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+OBJECTIVE: This retrospective chart review describes the epidemiology and clinical features of 40 patients with culture-proven Mycoplasma pneumoniae infections at King Abdulaziz University Hospital, Jeddah, Saudi Arabia.
+METHODS: Patients with positive M. pneumoniae cultures from respiratory specimens from January 1997 through December 1998 were identified through the Microbiology records.
+The infection affected all age groups but was most common in infants (32.5%) and pre-school children (22.5%).
+Twenty-four isolates (60%) were associated with pneumonia, 14 (35%) with upper respiratory tract infections, and 2 (5%) with bronchiolitis.
+Cough (82.5%), fever (75%), and malaise (58.8%) were the most common symptoms, and crepitations (60%), and wheezes (40%) were the most common signs.
+Immunocompromised patients were more likely than non-immunocompromised patients to present with pneumonia (8/9 versus 16/31, P = 0.05).
+Of the 24 patients with pneumonia, 14 (58.3%) had uneventful recovery, 4 (16.7%) recovered following some complications, 3 (12.5%) died because of M pneumoniae infection, and 3 (12.5%) died due to underlying comorbidities.
+CONCLUSION: our results were similar to published data except for the finding that infections were more common in infants and preschool children and that the mortality rate of pneumonia in patients with comorbidities was high.
+Inflammatory diseases of the respiratory tract are commonly associated with elevated production of nitric oxide (NO•) and increased indices of NO• -dependent oxidative stress.
+Although NO• is known to have anti-microbial, anti-inflammatory and anti-oxidant properties, various lines of evidence support the contribution of NO• to lung injury in several disease models.
+On the basis of biochemical evidence, it is often presumed that such NO• -dependent oxidations are due to the formation of the oxidant peroxynitrite, although alternative mechanisms involving the phagocyte-derived heme proteins myeloperoxidase and eosinophil peroxidase might be operative during conditions of inflammation.
+Because of the overwhelming literature on NO• generation and activities in the respiratory tract, it would be beyond the scope of this commentary to review this area comprehensively.
+Instead, it focuses on recent evidence and concepts of the presumed contribution of NO• to inflammatory diseases of the lung.
+Surfactant protein-D (SP-D) participates in the innate response to inhaled microorganisms and organic antigens, and contributes to immune and inflammatory regulation within the lung.
+SP-D is synthesized and secreted by alveolar and bronchiolar epithelial cells, but is also expressed by epithelial cells lining various exocrine ducts and the mucosa of the gastrointestinal and genitourinary tracts.
+SP-D, a collagenous calcium-dependent lectin (or collectin), binds to surface glycoconjugates expressed by a wide variety of microorganisms, and to oligosaccharides associated with the surface of various complex organic antigens.
+SP-D also specifically interacts with glycoconjugates and other molecules expressed on the surface of macrophages, neutrophils, and lymphocytes.
+In addition, SP-D binds to specific surfactant-associated lipids and can influence the organization of lipid mixtures containing phosphatidylinositol in vitro.
+Consistent with these diverse in vitro activities is the observation that SP-D-deficient transgenic mice show abnormal accumulations of surfactant lipids, and respond abnormally to challenge with respiratory viruses and bacterial lipopolysaccharides.
+The phenotype of macrophages isolated from the lungs of SP-D-deficient mice is altered, and there is circumstantial evidence that abnormal oxidant metabolism and/or increased metalloproteinase expression contributes to the development of emphysema.
+The expression of SP-D is increased in response to many forms of lung injury, and deficient accumulation of appropriately oligomerized SP-D might contribute to the pathogenesis of a variety of human lung diseases.
+Respiratory syncytial virus (RSV) and pneumonia virus of mice (PVM) are viruses of the family Paramyxoviridae, subfamily pneumovirus, which cause clinically important respiratory infections in humans and rodents, respectively.
+The respiratory epithelial target cells respond to viral infection with specific alterations in gene expression, including production of chemoattractant cytokines, adhesion molecules, elements that are related to the apoptosis response, and others that remain incompletely understood.
+Here we review our current understanding of these mucosal responses and discuss several genomic approaches, including differential display reverse transcription-polymerase chain reaction (PCR) and gene array strategies, that will permit us to unravel the nature of these responses in a more complete and systematic manner.
+Nidovirus subgenomic mRNAs contain a leader sequence derived from the 5′ end of the genome fused to different sequences (‘bodies’) derived from the 3′ end.
+Their generation involves a unique mechanism of discontinuous subgenomic RNA synthesis that resembles copy-choice RNA recombination.
+During this process, the nascent RNA strand is transferred from one site in the template to another, during either plus or minus strand synthesis, to yield subgenomic RNA molecules.
+Central to this process are transcription-regulating sequences (TRSs), which are present at both template sites and ensure the fidelity of strand transfer.
+Here we present results of a comprehensive co-variation mutagenesis study of equine arteritis virus TRSs, demonstrating that discontinuous RNA synthesis depends not only on base pairing between sense leader TRS and antisense body TRS, but also on the primary sequence of the body TRS.
+While the leader TRS merely plays a targeting role for strand transfer, the body TRS fulfils multiple functions.
+The sequences of mRNA leader–body junctions of TRS mutants strongly suggested that the discontinuous step occurs during minus strand synthesis.
+Recent evidence suggests that critically ill patients are able to tolerate lower levels of haemoglobin than was previously believed.
+It is our goal to show that transfusing to a level of 100 g/l does not improve mortality and other clinically important outcomes in a critical care setting.
+Although many questions remain, many laboratory and clinical studies, including a recent randomized controlled trial (RCT), have established that transfusing to normal haemoglobin concentrations does not improve organ failure and mortality in the critically ill patient.
+In addition, a restrictive transfusion strategy will reduce exposure to allogeneic transfusions, result in more efficient use of red blood cells (RBCs), save blood overall, and decrease health care costs.
+Heme oxygenase-1 (HO-1), an inducible stress protein, confers cytoprotection against oxidative stress in vitro and in vivo.
+In addition to its physiological role in heme degradation, HO-1 may influence a number of cellular processes, including growth, inflammation, and apoptosis.
+By virtue of anti-inflammatory effects, HO-1 limits tissue damage in response to proinflammatory stimuli and prevents allograft rejection after transplantation.
+The transcriptional upregulation of HO-1 responds to many agents, such as hypoxia, bacterial lipopolysaccharide, and reactive oxygen/nitrogen species.
+HO-1 and its constitutively expressed isozyme, heme oxygenase-2, catalyze the rate-limiting step in the conversion of heme to its metabolites, bilirubin IXα, ferrous iron, and carbon monoxide (CO).
+Remarkably, administration of CO at low concentrations can substitute for HO-1 with respect to anti-inflammatory and anti-apoptotic effects, suggesting a role for CO as a key mediator of HO-1 function.
+Chronic, low-level, exogenous exposure to CO from cigarette smoking contributes to the importance of CO in pulmonary medicine.
+The implications of the HO-1/CO system in pulmonary diseases will be discussed in this review, with an emphasis on inflammatory states.
+This report describes the design and implementation of the Real-time Outbreak and Disease Surveillance (RODS) system, a computer-based public health surveillance system for early detection of disease outbreaks.
+Hospitals send RODS data from clinical encounters over virtual private networks and leased lines using the Health Level 7 (HL7) message protocol.
+RODS automatically classifies the registration chief complaint from the visit into one of seven syndrome categories using Bayesian classifiers.
+It stores the data in a relational database, aggregates the data for analysis using data warehousing techniques, applies univariate and multivariate statistical detection algorithms to the data, and alerts users of when the algorithms identify anomalous patterns in the syndrome counts.
+RODS processes sales of over-the-counter health care products in a similar manner but receives such data in batch mode on a daily basis.
+RODS was used during the 2002 Winter Olympics and currently operates in two states—Pennsylvania and Utah.
+It has been and continues to be a resource for implementing, evaluating, and applying new methods of public health surveillance.
+Regulation of ornithine decarboxylase in vertebrates involves a negative feedback mechanism requiring the protein antizyme.
+The efficiency of the frameshift event reflects cellular polyamine levels creating the autoregulatory feedback loop.
+As shown here, the yeast antizyme gene and several newly identified antizyme genes from different nematodes also require a ribosomal frameshift event for their expression.
+The core element for this frameshifting is likely to have been present in the last common ancestor of yeast, nematodes and mammals.
+Heterogeneous nuclear ribonucleoprotein (hnRNP A1) is involved in pre-mRNA splicing in the nucleus and translational regulation in the cytoplasm.
+In the present study, we demonstrate that hnRNP A1 also participates in the transcription and replication of a cytoplasmic RNA virus, mouse hepatitis virus (MHV).
+Overexpression of hnRNP A1 accelerated the kinetics of viral RNA synthesis, whereas the expression in the cytoplasm of a dominant-negative hnRNP A1 mutant that lacks the nuclear transport domain significantly delayed it.
+The hnRNP A1 mutant caused a global inhibition of viral mRNA transcription and genomic replication, and also a preferential inhibition of the replication of defective-interfering RNAs.
+Similar to the wild-type hnRNP A1, the hnRNP A1 mutant complexed with an MHV polymerase gene product, the nucleocapsid protein and the viral RNA.
+However, in contrast to the wild-type hnRNP A1, the mutant protein failed to bind a 250 kDa cellular protein, suggesting that the recruitment of cellular proteins by hnRNP A1 is important for MHV RNA synthesis.
+For the first time, we demonstrate a systematic, high throughput approach to identification of UBA domain-interacting proteins from a proteome-wide perspective.
+Using the rabbit reticulocyte lysate in vitro expression cloning system, we have successfully identified eleven proteins that interact with p62’s UBA domain, and the majority of the eleven proteins are associated with neurodegenerative disorders, such as Alzheimer’s disease.
+Our approach provides an easy route to the characterization of UBA domain interacting proteins and its application will unfold the important roles that the UBA domain plays.
+We found that newly assembled virus particles accumulate in the vicinity of the microtubule-organizing centre in a microtubule- and dynein–dynactin complex-dependent fashion.
+Microtubules are required for efficient intracellular mature virus (IMV) formation and are essential for intracellular enveloped virus (IEV) assembly.
+As infection proceeds, the microtubule cytoskeleton becomes dramatically reorganized in a fashion reminiscent of overexpression of microtubule-associated proteins (MAPs).
+Consistent with this, we report that the vaccinia proteins A10L and L4R have MAP-like properties and mediate direct binding of viral cores to microtubules in vitro.
+In addition, vaccinia infection also results in severe reduction of proteins at the centrosome and loss of centrosomal microtubule nucleation efficiency.
+Further studies with vaccinia will provide insights into the role of microtubules during viral pathogenesis and regulation of centrosome function.
+INTRODUCTION: The pathogenicity of late respiratory infections with herpes simplex virus type 1 (HSV-1) in the critically ill is unclear.
+METHODS: In four critically ill patients with persistent pulmonary infiltrates of unknown origin and isolation of HSV-1 from tracheal aspirate or bronchoalveolar lavage fluid, at 7 (1–11) days after start of mechanical ventilatory support, a pulmonary leak index (PLI) for (67)Gallium ((67)Ga)-transferrin (upper limit of normal 14.1 × 10(-3)/min) was measured.
+CONCLUSIONS: The normal capillary permeability observed in the lungs argues against pathogenicity of HSV-1 in the critically ill, and favors that isolation of the virus reflects reactivation in the course of serious illness and immunodepresssion, rather than primary or superimposed infection in the lungs.
+BACKGROUND: Previous smallpox ring vaccination models based on contact tracing over a network suggest that ring vaccination would be effective, but have not explicitly included response logistics and limited numbers of vaccinators.
+METHODS: We developed a continuous-time stochastic simulation of smallpox transmission, including network structure, post-exposure vaccination, vaccination of contacts of contacts, limited response capacity, heterogeneity in symptoms and infectiousness, vaccination prior to the discontinuation of routine vaccination, more rapid diagnosis due to public awareness, surveillance of asymptomatic contacts, and isolation of cases.
+RESULTS: We found that even in cases of very rapidly spreading smallpox, ring vaccination (when coupled with surveillance) is sufficient in most cases to eliminate smallpox quickly, assuming that 95% of household contacts are traced, 80% of workplace or social contacts are traced, and no casual contacts are traced, and that in most cases the ability to trace 1–5 individuals per day per index case is sufficient.
+If smallpox is assumed to be transmitted very quickly to contacts, it may at times escape containment by ring vaccination, but could be controlled in these circumstances by mass vaccination.
+CONCLUSIONS: Small introductions of smallpox are likely to be easily contained by ring vaccination, provided contact tracing is feasible.
+Uncertainties in the nature of bioterrorist smallpox (infectiousness, vaccine efficacy) support continued planning for ring vaccination as well as mass vaccination.
+If initiated, ring vaccination should be conducted without delays in vaccination, should include contacts of contacts (whenever there is sufficient capacity) and should be accompanied by increased public awareness and surveillance.
+The base excision repair pathway is one of the most important cellular protection mechanisms that responds to oxidative DNA damage.
+METHODS: The above lesion-specific DNA repair enzymes were expressed in human alveolar epithelial cells (A549) using the pSF91.1 retroviral vector.
+Western blot analysis was performed to verify over-expression and assess endogenous expression under toxic and non-toxic conditions.
+Statistical analysis was performed using the paired Student's t test with significance being accepted for p < 0.05.
+RESULTS: Cell killing assays demonstrated cells over-expressing hMYH had improved survival to both increased oxygen and IR.
+Cell growth analysis of A549 cells under non-toxic conditions revealed cells over-expressing hMYH also grow at a slower rate.
+Western blot analysis demonstrated over-expression of each individual gene and did not result in altered endogenous expression of the others.
+However, it was observed that O(2 )toxicity did lead to a reduced endogenous expression of hNTH in A549 cells.
+CONCLUSION: Increased expression of the DNA glycosylase repair enzyme hMYH in A549 cells exposed to O(2 )and IR leads to improvements in cell survival.
+DNA repair through the base excision repair pathway may provide an alternative way to offset the damaging effects of O(2 )and its metabolites.
+1-methyladenine and 3-methylcytosine are repaired by oxidative demethylation and direct reversal of the methylated base back to its unmethylated form.
+Genes for AlkB homologues are widespread in nature, and Eukaryotes often have several genes coding for AlkB-like proteins.
+The function of the viral domain is unknown, but it has been suggested that it may be involved in protecting the virus against the post-transcriptional gene silencing (PTGS) system found in plants.
+We wanted to do a phylogenomic mapping of viral AlkB-like domains as a basis for analysing functional aspects of these domains, because this could have some relevance for understanding possible alternative roles of AlkB homologues e.g.
+RESULTS: Profile-based searches of protein sequence libraries showed that AlkB-like domains are found in at least 22 different single-stranded RNA positive-strand plant viruses, but mainly in a subgroup of the Flexiviridae family.
+Sequence analysis indicated that the AlkB domains probably are functionally conserved, and that they most likely have been integrated relatively recently into several viral genomes at geographically distinct locations.
+CONCLUSIONS: The AlkB domain found in viral genomes is most likely a conventional DNA/RNA repair domain that protects the viral RNA genome against methylating compounds from the environment.
+Lactococcus lactis, the model lactic acid bacterium (LAB), is a food grade and well-characterized Gram positive bacterium.
+It is a good candidate for heterologous protein delivery in foodstuff or in the digestive tract.
+Many heterologous proteins have already been produced in L. lactis but only few reports allow comparing production yields for a given protein either produced intracellularly or secreted in the medium.
+Here, we review several works evaluating the influence of the localization on the production yields of several heterologous proteins produced in L. lactis.
+The questions of size limits, conformation, and proteolysis are addressed and discussed with regard to protein yields.
+These data show that i) secretion is preferable to cytoplasmic production; ii) secretion enhancement (by signal peptide and propeptide optimization) results in increased production yield; iii) protein conformation rather than protein size can impair secretion and thus alter production yields; and iv) fusion of a stable protein can stabilize labile proteins.
+The new challenges now are the development of food grade systems and the identification and optimization of host factors affecting heterologous protein production not only in L. lactis, but also in other LAB species.
+Unfortunately, the location and length of horizontal transfers (HTs) are known for very few species.
+The usage of short oligonucleotides in a sequence (the so-called genomic signature) has been shown to be species-specific even in DNA fragments as short as 1 kb.
+Since DNA transfers originate from species with a signature different from those of the recipient species, the analysis of local variations of signature along recipient genome may allow for detecting exogenous DNA.
+The strategy consists in (i) scanning the genome with a sliding window, and calculating the corresponding local signature (ii) evaluating its deviation from the signature of the whole genome and (iii) looking for similar signatures in a database of genomic signatures.
+It has been observed that atypical regions make up ∼6% of each genome on the average.
+Among the species studied, Bacillus subtilis, Haemophilus Influenzae and Escherichia coli are investigated by many authors and give the opportunity to perform a thorough comparison of most of the bioinformatics methods used to detect HTs.
+Although oligonucleotide probes complementary to single nucleotide substitutions are commonly used in microarray-based screens for genetic variation, little is known about the hybridization properties of probes complementary to small insertions and deletions.
+It is necessary to define the hybridization properties of these latter probes in order to improve the specificity and sensitivity of oligonucleotide microarray-based mutational analysis of disease-related genes.
+Here, we compare and contrast the hybridization properties of oligonucleotide microarrays consisting of 25mer probes complementary to all possible single nucleotide substitutions and insertions, and one and two base deletions in the 9168 bp coding region of the ATM (ataxia telangiectasia mutated) gene.
+Over 68 different dye-labeled single-stranded nucleic acid targets representing all ATM coding exons were applied to these microarrays.
+We assess hybridization specificity by comparing the relative hybridization signals from probes perfectly matched to ATM sequences to those containing mismatches.
+Probes complementary to two base substitutions displayed the highest average specificity followed by those complementary to single base substitutions, single base deletions and single base insertions.
+In all the cases, hybridization specificity was strongly influenced by sequence context and possible intra- and intermolecular probe and/or target structure.
+Furthermore, single nucleotide substitution probes displayed the most consistent hybridization specificity data followed by single base deletions, two base deletions and single nucleotide insertions.
+Overall, these studies provide valuable empirical data that can be used to more accurately model the hybridization properties of insertion and deletion probes and improve the design and interpretation of oligonucleotide microarray-based resequencing and mutational analysis.
+Using differential display RT-PCR, we identified a gene of 2750 bp from human adult testis, named H-Lse, which encoded a putative protein of 523 amino acids and molecular weight of 58 kd with structural characteristics similar to that of mouse lysosome sialic-acid-specific 9-O-acetylesterase.
+Northern blot analysis showed a widespread distribution of H-Lse in various human tissues with high expression in the testis, prostate, and colon.
+In situ hybridization results showed that while H-Lse was not detected in embryonic testis, positive signals were found in spermatocytes but not spermatogonia in adult testis of human.
+The subcellular localization of H-Lse was visualized by green fluorescent protein (GFP) fused to the amino terminus of H-Lse, showing compartmentalization of H-Lse in large dense-core vesicles, presumably lysosomes, in the cytoplasm.
+The developmentally regulated and spermatogenic stage-specific expression of H-Lse suggests its possible involvement in the development of the testis and/or differentiation of germ cells.
+We examined the association of pain with mast cells in autopsy specimens of patients with painful chronic pancreatitis.
+We explored our hypothesis further using an experimental model of trinitrobenzene sulfonic acid (TNBS) -induced chronic pancreatitis in both wild type (WT) and mast cell deficient mice (MCDM).
+METHODS: Archival tissues with histological diagnoses of chronic pancreatitis were identified and clinical records reviewed for presence or absence of reported pain in humans.
+The presence of pain was assessed using von Frey Filaments (VFF) to measure abdominal withdrawal responses in both WT and MCDM mice with and without chronic pancreatitis.
+RESULTS: Humans with painful chronic pancreatitis demonstrated a 3.5-fold increase in pancreatic mast cells as compared with those with painless chronic pancreatitis.
+WT mice with chronic pancreatitis were significantly more sensitive as assessed by VFF pain testing of the abdomen when compared with MCDM.
+CONCLUSION: Humans with painful chronic pancreatitis have an increased number of pancreatic mast cells as compared with those with painless chronic pancreatitis.
+MCDM are less sensitive to mechanical stimulation of the abdomen after induction of chronic pancreatitis as compared with WT.
+Mast cells may play an important role in the pathogenesis of pain in chronic pancreatitis.
+In viruses, the recombination rate depends on the frequency of genetic exchange between different viral genomes within an infected host cell and on the frequency at which such co-infections occur.
+While the recombination rate has been recently evaluated in experimentally co-infected cell cultures for several viruses, direct quantification at the most biologically significant level, that of a host infection, is still lacking.
+We distributed four neutral markers along the viral genome, and co-inoculated host plants with marker-containing and wild-type viruses.
+On average, over 50% of viral genomes recovered after a single host infection were recombinants, clearly indicating that recombination is very frequent in this virus.
+Estimates of the recombination rate show that all regions of the genome are equally affected by this process.
+Assuming that ten viral replication cycles occurred during our experiment—based on data on the timing of coat protein detection—the per base and replication cycle recombination rate was on the order of 2 × 10(−5) to 4 × 10(−5).
+This first determination of a virus recombination rate during a single multi-cellular host infection indicates that recombination is very frequent in the everyday life of this virus.
+Though we previously presented a model for how mRNA pseudoknots might activate the mechanism for −1 PRF, it did not address the question of the role that they may play in positioning the mRNA relative to the ribosome in this process [E. P. Plant, K. L. M. Jacobs, J. W. Harger, A. Meskauskas, J. L. Jacobs, J. L. Baxter, A. N. Petrov and J. D. Dinman (2003) RNA, 9, 168–174].
+A separate ‘torsional restraint’ model suggests that mRNA pseudoknots act to increase the fraction of ribosomes directed to pause with the upstream heptameric slippery site positioned at the ribosome's A- and P-decoding sites [J. D. Dinman (1995) Yeast, 11, 1115–1127].
+Here, experiments using a series of ‘pseudo-pseudoknots’ having different degrees of rotational freedom were used to test this model.
+The results of this study support the mechanistic hypothesis that −1 ribosomal frameshifting is enhanced by torsional resistance of the mRNA pseudoknot.
+Although efficient methods exist to assemble synthetic oligonucleotides into genes and genomes, these suffer from the presence of 1–3 random errors/kb of DNA.
+Here, we introduce a new method termed consensus shuffling and demonstrate its use to significantly reduce random errors in synthetic DNA.
+The DNA is fragmented, and mismatched fragments are removed upon binding to an immobilized mismatch binding protein (MutS).
+PCR assembly of the remaining fragments yields a new population of full-length sequences enriched for the consensus sequence of the input population.
+We show that two iterations of consensus shuffling improved a population of synthetic green fluorescent protein (GFPuv) clones from ∼60 to >90% fluorescent, and decreased errors 3.5- to 4.3-fold to final values of ∼1 error per 3500 bp.
+In addition, two iterations of consensus shuffling corrected a population of GFPuv clones where all members were non-functional, to a population where 82% of clones were fluorescent.
+While it is universally accepted that intact RNA constitutes the best representation of the steady-state of transcription, there is no gold standard to define RNA quality prior to gene expression analysis.
+In this report, we evaluated the reliability of conventional methods for RNA quality assessment including UV spectroscopy and 28S:18S area ratios, and demonstrated their inconsistency.
+We then used two new freely available classifiers, the Degradometer and RIN systems, to produce user-independent RNA quality metrics, based on analysis of microcapillary electrophoresis traces.
+Both provided highly informative and valuable data and the results were found highly correlated, while the RIN system gave more reliable data.
+The relevance of the RNA quality metrics for assessment of gene expression differences was tested by Q-PCR, revealing a significant decline of the relative expression of genes in RNA samples of disparate quality, while samples of similar, even poor integrity were found highly comparable.
+We discuss the consequences of these observations to minimize artifactual detection of false positive and negative differential expression due to RNA integrity differences, and propose a scheme for the development of a standard operational procedure, with optional registration of RNA integrity metrics in public repositories of gene expression data.
+The ratio between proteins P27 and replicase of Cocksfoot mottle virus (CfMV) is regulated via a −1 programmed ribosomal frameshift (−1 PRF).
+A minimal frameshift signal with a slippery U UUA AAC heptamer and a downstream stem–loop structure was inserted into a dual reporter vector and directed −1 PRF with an efficiency of 14.4 ± 1.9% in yeast and 2.4 ± 0.7% in bacteria.
+P27-encoding CfMV sequence flanking the minimal frameshift signal caused ∼2-fold increase in the −1 PRF efficiencies both in yeast and in bacteria.
+In addition to the expected fusion proteins, termination products ending putatively at the frameshift site were found in yeast cells.
+We propose that the amount of premature translation termination from control mRNAs played a role in determining the calculated −1PRF efficiency.
+Co-expression of CfMV P27 with the dual reporter vector containing the minimal frameshift signal reduced the production of the downstream reporter, whereas replicase co-expression had no pronounced effect.
+This finding allows us to propose that CfMV protein P27 may influence translation at the frameshift site but the mechanism needs to be elucidated.
+In Australia, compared with other developed countries the many and varied programs which comprise public health have continued to be funded poorly and unsystematically, particularly given the amount of publicly voiced political support.
+In 2003, the major public health policy developments in communicable disease control were in the fields of SARS, and vaccine funding, whilst the TGA was focused on the Pan Pharmaceutical crisis.
+The tertiary education sector was involved in the development of programs for training the public health workforce and new professional qualifications and competencies.
+The Abelson Report received support from overseas experts, providing a potential platform for calls to improve national funding for future Australian preventive programs; however, inconsistencies continued across all jurisdictions in their approaches to tackling national health priorities.
+Despite 2004 being an election year, public health policy was not visible, with the bulk of the public health funding available in the 2004/05 federal budget allocated to managing such emerging risks as avian flu.
+GIDEON (Global Infectious Diseases and Epidemiology Network) is a web-based computer program designed for decision support and informatics in the field of Geographic Medicine.
+The first of four interactive modules generates a ranked differential diagnosis based on patient signs, symptoms, exposure history and country of disease acquisition.
+The second module accesses detailed and current information regarding the status of 338 individual diseases in each of 220 countries.
+Over 50,000 disease images, maps and user-designed graphs may be downloaded for use in teaching and preparation of written materials.
+The third module is a comprehensive source on the use of 328 anti-infective drugs and vaccines, including a listing of over 9,500 international trade names.
+The fourth module can be used to characterize or identify any bacterium or yeast, based on laboratory phenotype.
+This debut editorial of Globalization and Health introduces the journal, briefly delineating its goals and objectives and outlines its scope of subject matter.
+'Open Access' publishing is expected to become an increasingly important format for peer reviewed academic journals and that Globalization and Health is 'Open Access' is appropriate.
+The rationale behind starting a journal dedicated to globalization and health is three fold: Firstly: Globalization is reshaping the social geography within which we might strive to create health or prevent disease.
+The determinants of health – be they a SARS virus or a predilection for fatty foods – have joined us in our global mobility.
+Driven by economic liberalization and changing technologies, the phenomenon of 'access' is likely to dominate to an increasing extent the unfolding experience of human disease and wellbeing.
+Secondly: Understanding globalization as a subject matter itself needs certain benchmarks and barometers of its successes and failings.
+It is a marker of social infrastructure and social welfare and as such can be used to either sound an alarm or give a victory cheer as our interconnectedness hurts and heals the populations we serve.
+And lastly: In as much as globalization can have an effect on health, it is also true that health and disease has an effect on globalization as exemplified by the existence of quarantine laws and the devastating economic effects of the AIDS pandemic.
+A balanced view would propose that the effects of globalization on health (and health systems) are neither universally good nor bad, but rather context specific.
+If the dialogue pertaining to globalization is to be directed or biased in any direction, then it must be this: that we consider the poor first.
+However, in most cases, the serine tRNAs responsible for this non-universal decoding (tRNA(Ser)CAG) accept in vitro not only serine, but also, to some extent, leucine.
+This finding was supported by the fact that the tRNA(Ser)CAGs possessing the leucylation activity always have m1G37, whereas that of Candida cylindracea, which possesses no leucylation activity, has A37.
+Quantification of defined aminoacetylated tRNAs in cells demonstrated that 3% of the tRNA(Ser)CAGs possessing m1G37 were, in fact, charged with leucine in vivo.
+A genetic approach using an auxotroph mutant of C.maltosa possessing this type of tRNA(Ser)CAG also suggested that the URA3 gene inactivated due to the translation of CUG as serine was rescued by a slight incorporation of leucine into the polypeptide, which demonstrated that the tRNA charged with multiple amino acids could participate in the translation.
+These findings provide the first evidence that two distinct amino acids are assigned by a single codon, which occurs naturally in the translation process of certain Candida species.
+At present, there is no doubt that RNA recombination is one of the major factors responsible for the generation of new RNA viruses and retroviruses.
+Unfortunately, up till now a unified model of genetic RNA recombination has not been formulated, mainly due to difficulties with the direct comparison of data obtained for different RNA-based viruses.
+To solve this problem, we have attempted to construct a universal system in which the recombination activity of various RNA sequences could be tested.
+To this end, we have used brome mosaic virus, a model (+)RNA virus of plants, for which the structural requirements of RNA recombination are well defined.
+The effectiveness of the new homomolecular system has been proven in an experiment involving two RNA sequences derived from the hepatitis C virus genome.
+In addition, comparison of the data obtained with the homomolecular system with those generated earlier using the heteromolecular one has provided new evidence that the mechanisms of homologous and non-homologous recombination are different and depend on the virus' mode of replication.
+During enteric infections, proteolysis of the reovirus outer capsid protein σ3 is mediated by pancreatic serine proteases.
+In addition to its normal role in microbial defense, aberrant expression of NE has been implicated in the pathology of acute respiratory distress syndrome (ARDS).
+Because reovirus replication in rodent lungs causes ARDS-like symptoms and induces an infiltration of neutrophils, we investigated the capacity of NE to promote reovirus virion uncoating.
+Treatment of U937 cells with the broad-spectrum cysteine-protease inhibitor E64 [trans-epoxysuccinyl-L-leucylamido-(4-guanidino)butane] and with agents that increase vesicular pH did not inhibit reovirus replication.
+Even when these inhibitors were used in combination, reovirus replicated to significant yields, indicating that an acid-independent non-cysteine protease was capable of mediating reovirus uncoating in U937 cell cultures.
+To identify the protease(s) responsible, U937 cells were treated with phorbol 12-myristate 13-acetate (PMA), an agent that induces cellular differentiation and results in decreased expression of acid-independent serine proteases, including NE and cathepsin (Cat) G. In the presence of E64, reovirus did not replicate efficiently in PMA-treated cells.
+To directly assess the role of NE in reovirus infection of U937 cells, we examined viral growth in the presence of N-Ala-Ala-Pro-Val chloromethylketone, a NE-specific inhibitor.
+Reovirus replication in the presence of E64 was significantly reduced by treatment of cells with the NE inhibitor.
+Incubation of virions with purified NE resulted in the generation of infectious subviron particles that did not require additional intracellular proteolysis.
+The fact that it does so in the presence of agents that raise vesicular pH supports a model in which the requirement for acidic pH during infection reflects the conditions required for optimal protease activity.
+The capacity of reovirus to exploit NE may impact viral replication in the lung and other tissues during natural infections.
+The influence of locked nucleic acid (LNA) residues on the thermodynamic properties of 2′-O-methyl RNA/RNA heteroduplexes is reported.
+Optical melting studies indicate that LNA incorporated into an otherwise 2′-O-methyl RNA oligonucleotide usually, but not always, enhances the stabilities of complementary duplexes formed with RNA.
+Several trends are apparent, including: (i) a 3′ terminal U LNA and 5′ terminal LNAs are less stabilizing than interior and other 3′ terminal LNAs; (ii) most of the stability enhancement is achieved when LNA nucleotides are separated by at least one 2′-O-methyl nucleotide; and (iii) the effects of LNA substitutions are approximately additive when the LNA nucleotides are separated by at least one 2′-O-methyl nucleotide.
+An equation is proposed to approximate the stabilities of complementary duplexes formed with RNA when at least one 2′-O-methyl nucleotide separates LNA nucleotides.
+The sequence dependence of 2′-O-methyl RNA/RNA duplexes appears to be similar to that of RNA/RNA duplexes, and preliminary nearest-neighbor free energy increments at 37°C are presented for 2′-O-methyl RNA/RNA duplexes.
+We built a computational Sequencing Analysis Pipeline (SAP) to guide decisions regarding the amount of genomic sequencing necessary to develop high-quality diagnostic DNA and protein signatures.
+SAP uses simulations to estimate the number of target genomes and close phylogenetic relatives (near neighbors or NNs) to sequence.
+We use SAP to assess whether draft data are sufficient or finished sequencing is required using Marburg and variola virus sequences.
+Simulations indicate that intermediate to high-quality draft with error rates of 10(−3)–10(−5) (∼8× coverage) of target organisms is suitable for DNA signature prediction.
+Low-quality draft with error rates of ∼1% (3× to 6× coverage) of target isolates is inadequate for DNA signature prediction, although low-quality draft of NNs is sufficient, as long as the target genomes are of high quality.
+For protein signature prediction, sequencing errors in target genomes substantially reduce the detection of amino acid sequence conservation, even if the draft is of high quality.
+In summary, high-quality draft of target and low-quality draft of NNs appears to be a cost-effective investment for DNA signature prediction, but may lead to underestimation of predicted protein signatures.
+BACKGROUND: Epitopes can be defined as the molecular structures bound by specific receptors, which are recognized during immune responses.
+The Immune Epitope Database and Analysis Resource (IEDB) project will catalog and organize information regarding antibody and T cell epitopes from infectious pathogens, experimental antigens and self-antigens, with a priority on NIAID Category A-C pathogens () and emerging/re-emerging infectious diseases.
+Both intrinsic structural and phylogenetic features, as well as information relating to the interactions of the epitopes with the host's immune system will be catalogued.
+DESCRIPTION: To effectively represent and communicate the information related to immune epitopes, a formal ontology was developed.
+The semantics of the epitope domain and related concepts were captured as a hierarchy of classes, which represent the general and specialized relationships between the various concepts.
+CONCLUSION: The IEDB's ontology is the first ontology specifically designed to capture both intrinsic chemical and biochemical information relating to immune epitopes with information relating to the interaction of these structures with molecules derived from the host immune system.
+We anticipate that the development of this type of ontology and associated databases will facilitate rigorous description of data related to immune epitopes, and might ultimately lead to completely new methods for describing and modeling immune responses.
+BACKGROUND: Salmonid fishes are among the most widely studied model fish species but reports on systematic evaluation of reference genes in qRT-PCR studies is lacking.
+RESULTS: The stability of six potential reference genes was examined in eight tissues of Atlantic salmon (Salmo salar), to determine the most suitable genes to be used in quantitative real-time RT-PCR analyses.
+The relative transcription levels of genes encoding 18S rRNA, S20 ribosomal protein, β-actin, glyceraldehyde-3P-dehydrogenase (GAPDH), and two paralog genes encoding elongation factor 1A (EF1A(A )and EF1A(B)) were quantified in gills, liver, head kidney, spleen, thymus, brain, muscle, and posterior intestine in six untreated adult fish, in addition to a group of individuals that went through smoltification.
+Based on calculations performed with the geNorm VBA applet, which determines the most stable genes from a set of tested genes in a given cDNA sample, the ranking of the examined genes in adult Atlantic salmon was EF1A(B)>EF1A(A)>β-actin>18S rRNA>S20>GAPDH.
+When the same calculations were done on a total of 24 individuals from four stages in the smoltification process (presmolt, smolt, smoltified seawater and desmoltified freshwater), the gene ranking was EF1A(B)>EF1A(A)>S20>β-actin>18S rRNA>GAPDH.
+CONCLUSION: Overall, this work suggests that the EF1A(A )and EF1A(B )genes can be useful as reference genes in qRT-PCR examination of gene expression in the Atlantic salmon.
+BACKGROUND AND METHODS: Human metapneumovirus (hMPV) is a recently discovered respiratory virus associated with bronchiolitis, pneumonia, croup and exacerbations of asthma.
+Since respiratory viruses are frequently detected in patients with acute exacerbations of COPD (AE-COPD) it was our aim to investigate the frequency of hMPV detection in a prospective cohort of hospitalized patients with AE-COPD compared to patients with stable COPD and to smokers without by means of quantitative real-time RT-PCR.
+RESULTS: We analysed nasal lavage and induced sputum of 130 patients with AE-COPD, 65 patients with stable COPD and 34 smokers without COPD.
+HMPV was detected in 3/130 (2.3%) AE-COPD patients with a mean of 6.5 × 10(5 )viral copies/ml in nasal lavage and 1.88 × 10(5 )viral copies/ml in induced sputum.
+However it should be considered as a further possible viral trigger of AE-COPD because asymptomatic carriage is unlikely.
+BACKGROUND: The present study aimed to provide information on awareness of the attributable fraction of cancer causes among the Japanese general population.
+METHODS: A nationwide representative sample of 2,000 Japanese aged 20 or older was asked about their perception and level of concern about various environmental and genetic risk factors in relation to cancer prevention, as a part of an Omnibus Survey.
+RESULTS: Among 12 risk factor candidates, the attributable fraction of cancer-causing viral and bacterial infection was considered highest (51%), followed by that of tobacco smoking (43%), stress (39%), and endocrine-disrupting chemicals (37%).
+On the other hand, the attributable fractions of cancer by charred fish and meat (21%) and alcohol drinking (22%) were considered low compared with other risk factor candidates.
+As a whole, the subjects tended to respond with higher values than those estimated by epidemiologic evidence in the West.
+The attributable fraction of cancer speculated to be genetically determined was 32%, while 36% of cancer was considered preventable by improving lifestyle.
+CONCLUSION: Our results suggest that awareness of the attributable fraction of cancer causes in the Japanese general population tends to be dominated by cancer-causing infection, occupational exposure, air pollution and food additives rather than major lifestyle factors such as diet.
+BACKGROUND: Development of a practical gene point-of-care testing device (g-POCT device) requires innovative detection methods for demonstrating the results of the gene amplification reaction without the use of expensive equipment.
+We have studied a new method for the sequence-specific visual detection of minute amounts of nucleic acids using precipitation reaction by addition of cationic polymers to amplicons of Loop mediated isothermal Amplification (LAMP).
+RESULTS: Oligo DNA probes labeled with different fluorescent dyes were prepared for multiple nucleic acid templates, and the templates were amplified by the LAMP reactions under the existence of the probes.
+At completion of the LAMP reaction, an optimal amount of low molecular weight polyethylenimine (PEI) was added, resulting in the precipitation of the insoluble LAMP amplicon-PEI complex.
+The fluorescently labeled Oligo DNA probes hybridized to the LAMP product were incorporated into the precipitation, and the precipitate emitted fluorescence corresponding to the amplified nucleic acid templates.
+The color of emitted fluorescence can be detected easily by naked eye on a conventional UV illuminator.
+CONCLUSION: The presence or absence of minute amount of nucleic acid templates could be detected in a simple manner through visual assessment for the color of the LAMP amplicon-PEI complex precipitate.
+We conclude that this detection method may facilitate development of small and simple g-POCT device.
+Illicit drug abuse and HIV/AIDS have increased rapidly in the past 10 to 20 years in China.
+This paper reviews drug abuse in China, the HIV/AIDS epidemic and its association with injection drug use (IDU), and Chinese policies on illicit drug abuse and prevention of HIV/AIDS based on published literature and unpublished official data.
+As a major drug trans-shipment country with source drugs from the "Golden Triangle" and "Gold Crescent" areas in Asia, China has also become an increasingly important drug consuming market.
+The public security departments adopt "zero tolerance" approach to drug use, which conflict with harm reduction policies of the public health departments.
+Past experience in China suggests that cracking down on drug smuggling and prohibiting drug use alone can not prevent or solve all illicit drug related problems in the era of globalization.
+In recent years, the central government has outlined a series of pragmatic policies to encourage harm reduction programs; meanwhile, some local governments have not fully mobilized to deal with drug abuse and HIV/AIDS problems seriously.
+Strengthening government leadership at both central and local levels; scaling up methadone substitution and needle exchange programs; making HIV voluntary counseling and testing available and affordable to both urban and rural drug users; and increasing utilization of outreach and nongovernmental organizations are offered as additional strategies to help cope with China's HIV and drug abuse problem.
+Neutralization of West Nile virus (WNV) in vivo correlates with the development of an antibody response against the viral envelope (E) protein.
+Using random mutagenesis and yeast surface display, we defined individual contact residues of 14 newly generated monoclonal antibodies against domain III of the WNV E protein.
+Monoclonal antibodies that strongly neutralized WNV localized to a surface patch on the lateral face of domain III.
+One monoclonal antibody, E16, neutralized 10 different strains in vitro, and showed therapeutic efficacy in mice, even when administered as a single dose 5 d after infection.
+A humanized version of E16 was generated that retained antigen specificity, avidity and neutralizing activity.
+In postexposure therapeutic trials in mice, a single dose of humanized E16 protected mice against WNV-induced mortality, and may therefore be a viable treatment option against WNV infection in humans.
+SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nm1240) contains supplementary material, which is available to authorized users.
+BACKGROUND: Current national preparedness plans require local health departments to play an integral role in responding to an influenza pandemic, a major public health threat that the World Health Organization has described as "inevitable and possibly imminent".
+To understand local public health workers' perceptions toward pandemic influenza response, we surveyed 308 employees at three health departments in Maryland from March – July 2005, on factors that may influence their ability and willingness to report to duty in such an event.
+RESULTS: The data suggest that nearly half of the local health department workers are likely not to report to duty during a pandemic.
+The stated likelihood of reporting to duty was significantly greater for clinical (Multivariate OR: 2.5; CI 1.3–4.7) than technical and support staff, and perception of the importance of one's role in the agency's overall response was the single most influential factor associated with willingness to report (Multivariate OR: 9.5; CI 4.6–19.9).
+CONCLUSION: The perceived risk among public health workers was shown to be associated with several factors peripheral to the actual hazard of this event.
+These risk perception modifiers and the knowledge gaps identified serve as barriers to pandemic influenza response and must be specifically addressed to enable effective local public health response to this significant threat.
+BACKGROUND: As a number of commentators have noted, SARS exposed the vulnerabilities of our health care systems and governance structures.
+Health care professionals (HCPs) and hospital systems that bore the brunt of the SARS outbreak continue to struggle with the aftermath of the crisis.
+Indeed, HCPs – both in clinical care and in public health – were severely tested by SARS.
+Unprecedented demands were placed on their skills and expertise, and their personal commitment to their profession was severely tried.
+Many were exposed to serious risk of morbidity and mortality, as evidenced by the World Health Organization figures showing that approximately 30% of reported cases were among HCPs, some of whom died from the infection.
+Despite this challenge, professional codes of ethics are silent on the issue of duty to care during communicable disease outbreaks, thus providing no guidance on what is expected of HCPs or how they ought to approach their duty to care in the face of risk.
+DISCUSSION: In the aftermath of SARS and with the spectre of a pandemic avian influenza, it is imperative that we (re)consider the obligations of HCPs for patients with severe infectious diseases, particularly diseases that pose risks to those providing care.
+It is of pressing importance that organizations representing HCPs give clear indication of what standard of care is expected of their members in the event of a pandemic.
+In this paper, we address the issue of special obligations of HCPs during an infectious disease outbreak.
+We argue that there is a pressing need to clarify the rights and responsibilities of HCPs in the current context of pandemic flu preparedness, and that these rights and responsibilities ought to be codified in professional codes of ethics.
+Finally, we present a brief historical accounting of the treatment of the duty to care in professional health care codes of ethics.
+SUMMARY: An honest and critical examination of the role of HCPs during communicable disease outbreaks is needed in order to provide guidelines regarding professional rights and responsibilities, as well as ethical duties and obligations.
+With this paper, we hope to open the social dialogue and advance the public debate on this increasingly urgent issue.
+The anticancer potential of catechins derived from green tea is not well understood, in part because catechin-related growth suppression and/or apoptosis appears to vary with the type and stage of malignancy as well as with the type of catechin.
+This in vitro study examined the biological effects of epicatechin (EC), epigallocatechin (EGC), EC 3-gallate (ECG) and EGC 3-gallate (EGCG) in cell lines from human gender-specific cancers.
+Cell lines developed from organ-confined (HH870) and metastatic (DU145) prostate cancer, and from moderately (HH450) and poorly differentiated (HH639) epithelial ovarian cancer were grown with or without EC, EGC, ECG or EGCG.
+When untreated cells reached confluency, viability and doubling time were measured for treated and untreated cells.
+Whereas EC treatment reduced proliferation of HH639 cells by 50%, EGCG suppressed proliferation of all cell lines by 50%.
+ECG was even more potent: it inhibited DU145, HH870, HH450 and HH639 cells at concentrations of 24, 27, 29 and 30 µM, whereas EGCG inhibited DU145, HH870, HH450 and HH639 cells at concentrations 89, 45, 62 and 42 µM.
+When compared with EGCG, ECG more effectively suppresses the growth of prostate cancer and epithelial ovarian cancer cell lines derived from tumors of patients with different stages of disease.
+An exacerbation is an event defined in terms of subjective descriptors or symptoms, namely dyspnoea, cough and sputum that worsen sufficiently to warrant a change in medical management.
+There is a need for reliable markers that reflect the pathological mechanisms that underlie exacerbation severity and that can be used as a surrogate to assess treatment effects in clinical studies.
+Little is known as to how existing study variables and suggested markers change in both the stable and exacerbation phases of COPD.
+In an attempt to find the best surrogates for exacerbations, we have reviewed the literature to identify which of these markers change in a consistent manner with the severity of the exacerbation event.
+METHODS: We have searched standard databases between 1966 to July 2004 using major keywords and terms.
+Studies that provided demographics, spirometry, potential markers, and clear eligibility criteria were included in this study.
+Central tendencies and dispersions for all the variables and markers reported and collected by us were first tabulated according to sample size and ATS/ERS 2004 Exacerbation Severity Levels I to III criteria.
+Due to the possible similarity of patients in Levels II and III, the data was also redefined into categories of exacerbations, namely out-patient (Level I) and in-patient (Levels II & III combined).
+For both approaches, we performed a fixed effect meta-analysis on each of the reported variables.
+Arterial carbon dioxide tension and breathing rate were statistically different between all levels of exacerbation severity and between in out- and in-patient settings.
+Most other measures showed weak relationships with either level or setting, or they had insufficient data to permit meta-analysis.
+CONCLUSION: Arterial carbon dioxide and breathing rate varied in a consistent manner with exacerbation severity and patient setting.
+Many other measures showed weak correlations that should be further explored in future longitudinal studies or assessed using suggested mathematical modelling techniques.
+BACKGROUND: The main limitation in performing genome-wide gene-expression profiling is the assay of low-expression genes.
+Approaches with high throughput and high sensitivity for assaying low-expression transcripts are urgently needed for functional genomic studies.
+Combination of the suppressive subtractive hybridization (SSH) and cDNA microarray techniques using the subtracted cDNA clones as probes printed on chips has greatly improved the efficiency for fishing out the differentially expressed clones and has been used before.
+However, it remains tedious and inefficient sequencing works for identifying genes including the great number of redundancy in the subtracted amplicons, and sacrifices the original advantages of high sensitivity of SSH in profiling low-expression transcriptomes.
+RESULTS: We modified the previous combination of SSH and microarray methods by directly using the subtracted amplicons as targets to hybridize the pre-made cDNA microarrays (named as "SSH/microarray").
+mRNA prepared from three pairs of hepatoma and non-hepatoma liver tissues was subjected to the SSH/microarray assays, as well as directly to regular cDNA microarray assays for comparison.
+As compared to the original SSH and microarray combination assays, the modified SSH/microarray assays allowed for much easier inspection of the subtraction efficiency and identification of genes in the subtracted amplicons without tedious and inefficient sequencing work.
+On the other hand, 5015 of the 9376 genes originally filtered out by the regular cDNA microarray assays because of low expression became analyzable by the SSH/microarray assays.
+Moreover, the SSH/microarray assays detected about ten times more (701 vs. 69) HCC differentially expressed genes (at least a two-fold difference and P < 0.01), particularly for those with rare transcripts, than did the regular cDNA microarray assays.
+The differential expression was validated in 9 randomly selected genes in 18 pairs of hepatoma/non-hepatoma liver tissues using quantitative RT-PCR.
+The SSH/microarray approaches resulted in identifying many differentially expressed genes implicated in the regulation of cell cycle, cell death, signal transduction and cell morphogenesis, suggesting the involvement of multi-biological processes in hepato-carcinogenesis.
+CONCLUSION: The modified SSH/microarray approach is a simple but high-sensitive and high-efficient tool for differentially profiling the low-expression transcriptomes.
+The development of DNA microarray technology a decade ago led to the establishment of functional genomics as one of the most active and successful scientific disciplines today.
+With the ongoing development of immunomic microarray technology—a spatially addressable, large-scale technology for measurement of specific immunological response—the new challenge of functional immunomics is emerging, which bears similarities to but is also significantly different from functional genomics.
+Immunonic data has been successfully used to identify biological markers involved in autoimmune diseases, allergies, viral infections such as human immunodeficiency virus (HIV), influenza, diabetes, and responses to cancer vaccines.
+This review intends to provide a coherent vision of this nascent scientific field, and speculate on future research directions.
+We discuss at some length issues such as epitope prediction, immunomic microarray technology and its applications, and computation and statistical challenges related to functional immunomics.
+Based on the recent discovery of regulation mechanisms in T cell responses, we envision the use of immunomic microarrays as a tool for advances in systems biology of cellular immune responses, by means of immunomic regulatory network models.
+BACKGROUND: Because smallpox (variola major) may be used as a biological weapon, we reviewed outbreaks in post-World War II Europe and North America in order to understand smallpox transmission patterns.
+METHODS: A systematic review was used to identify papers from the National Library of Medicine, Embase, Biosis, Cochrane Library, Defense Technical Information Center, WorldCat, and reference lists of included publications.
+The median for the effective first generation reproduction rate (initial R) was 2 (range 0–38).
+Outbreaks with few hospitalized patients had low initial R values (median of 1) and were prolonged if not initially recognized (median of 3 generations); outbreaks with mostly hospitalized patients had higher initial R values (median 12) and were shorter (median of 3 generations).
+Index cases with an atypical presentation of smallpox were less likely to have been diagnosed with smallpox; outbreaks in which the index case was not correctly diagnosed were larger (median of 27.5 cases) and longer (median of 3 generations) compared to outbreaks in which the index case was correctly diagnosed (median of 3 cases and 1 generation).
+CONCLUSION: Patterns of spread during Smallpox outbreaks varied with circumstances, but early detection and implementation of control measures is a most important influence on the magnitude of outbreaks.
+The majority of outbreaks studied in Europe and North America were controlled within a few generations if detected early.
+BACKGROUND: Case definitions have been recognized to be important elements of public health surveillance systems.
+They are to assure comparability and consistency of surveillance data and have crucial impact on the sensitivity and the positive predictive value of a surveillance system.
+METHODS: We conducted a Round-Robin test by asking all 425 local health departments (LHD) and the 16 state health departments (SHD) in Germany to classify a selection of 68 case examples using case definitions.
+By multivariate analysis we investigated factors linked to classification agreement with a gold standard, which was defined by an expert panel.
+RESULTS: A total of 7870 classifications were done by 396 LHD (93%) and all SHD.
+Polio case examples had the lowest reporting precision, salmonellosis case examples the highest (OR = 0.008; CI: 0.005–0.013).
+Case definitions with a check-list format of clinical criteria resulted in higher reporting precision than case definitions with a narrative description (OR = 3.08; CI: 2.47–3.83).
+CONCLUSION: Our findings led to a systematic revision of the German case definitions and build the basis for general recommendations for the creation of case definitions.
+These include, among others, that testable yes/no criteria in a check-list format is likely to improve reliability, and that software used for data transmission should be designed in strict accordance with the case definitions.
+The findings of this study are largely applicable to case definitions in many other countries or international networks as they share the same structural and editorial characteristics of the case definitions evaluated in this study before their revision.
+Ventilator associated pneumonia (VAP) is the leading cause of morbidity and mortality in intensive care units.
+The incidence of VAP varies from 7% to 70% in different studies and the mortality rates are 20–75% according to the study population.
+Aspiration of colonized pathogenic microorganisms on the oropharynx and gastrointestinal tract is the main route for the development of VAP.
+On the other hand, the major risk factor for VAP is intubation and the duration of mechanical ventilation.
+Diagnosis remains difficult, and studies showed the importance of early initiation of appropriate antibiotic for prognosis.
+VAP causes extra length of stay in hospital and intensive care units and increases hospital cost.
+BACKGROUND: A major outbreak of human enterovirus 71-associated hand, foot and mouth disease in Sarawak in 1997 marked the beginning of a series of outbreaks in the Asia Pacific region.
+Some of these outbreaks had unusually high numbers of fatalities and this generated much fear and anxiety in the region.
+METHODS: We established a sentinel surveillance programme for hand, foot and mouth disease in Sarawak, Malaysia, in March 1998, and the observations of the first 7 years are described here.
+RESULTS: During this period Sarawak had two outbreaks of human enterovirus 71, in 2000 and 2003.
+The predominant strains circulating in the outbreaks of 1997, 2000 and 2003 were all from genogroup B, but the strains isolated during each outbreak were genetically distinct from each other.
+Human enterovirus 71 outbreaks occurred in a cyclical pattern every three years and Coxsackievirus A16 co-circulated with human enterovirus 71.
+Although vesicles were most likely to yield an isolate, this sample was not generally available from most cases and obtaining throat swabs was thus found to be the most efficient way to obtain virological information.
+CONCLUSION: Knowledge of the epidemiology of human enterovirus 71 transmission will allow public health personnel to predict when outbreaks might occur and to plan interventions in an effective manner in order to reduce the burden of disease.
+Live-virus vaccines activate both humoral and cell-mediated immunity, require only a single boosting, and generally provide longer immune protection than killed or subunit vaccines.
+However, growth of live-virus vaccines must be attenuated to minimize their potential pathogenic effects, and mechanisms of attenuation by conventional serial-transfer viral adaptation are not well-understood.
+New methods of attenuation based on rational engineering of viral genomes may offer a potentially greater control if one can link defined genetic modifications to changes in virus growth.
+To begin to establish such links between genotype and growth phenotype, we developed a computer model for the intracellular growth of vesicular stomatitis virus (VSV), a well-studied, nonsegmented, negative-stranded RNA virus.
+Our model incorporated established regulatory mechanisms of VSV while integrating key wild-type infection steps: hijacking of host resources, transcription, translation, and replication, followed by assembly and release of progeny VSV particles.
+Generalization of the wild-type model to allow for genome rearrangements matched the experimentally observed attenuation ranking for recombinant VSV strains that altered the genome position of their nucleocapsid gene.
+Finally, our simulations captured previously reported experimental results showing how altering the positions of other VSV genes has the potential to attenuate the VSV growth while overexpressing the immunogenic VSV surface glycoprotein.
+Such models will facilitate the engineering of new live-virus vaccines by linking genomic manipulations to controlled changes in virus gene-expression and growth.
+RNA interference (RNAi) is a powerful method for specific gene silencing which may also lead to promising novel therapeutic strategies.
+It is mediated through small interfering RNAs (siRNAs) which sequence-specifically trigger the cleavage and subsequent degradation of their target mRNA.
+One critical factor is the ability to deliver intact siRNAs into target cells/organs in vivo.
+This review highlights the mechanism of RNAi and the guidelines for the design of optimal siRNAs.
+It gives an overview of studies based on the systemic or local application of naked siRNAs or the use of various nonviral siRNA delivery systems.
+One promising avenue is the the complexation of siRNAs with the polyethylenimine (PEI), which efficiently stabilizes siRNAs and, upon systemic administration, leads to the delivery of the intact siRNAs into different organs.
+The antitumorigenic effects of PEI/siRNA-mediated in vivo gene-targeting of tumor-relevant proteins like in mouse tumor xenograft models are described.
+BACKGROUND: The hormonal control of oocyte maturation and ovulation as well as the molecular mechanisms of nuclear maturation have been thoroughly studied in fish.
+In contrast, the other molecular events occurring in the ovary during post-vitellogenesis have received far less attention.
+METHODS: Nylon microarrays displaying 9152 rainbow trout cDNAs were hybridized using RNA samples originating from ovarian tissue collected during late vitellogenesis, post-vitellogenesis and oocyte maturation.
+A supervised clustering analysis was performed using only differentially expressed genes in order to identify gene clusters exhibiting similar expression profiles.
+In addition, specific genes were selected and their preovulatory ovarian expression was analyzed using real-time PCR.
+Among those genes, 90 were up-regulated at the time of oocyte maturation while 220 exhibited an opposite pattern.
+After clustering analysis, 90 clones belonging to 3 gene clusters exhibiting the most remarkable expression patterns were kept for further analysis.
+Using real-time PCR analysis, we observed a strong up-regulation of ion and water transport genes such as aquaporin 4 (aqp4) and pendrin (slc26).
+Furthermore, angiotensin-converting-enzyme 2 (ace2), coagulation factor V (cf5), adam 22, and the chemokine cxcl14 genes exhibited a sharp up-regulation at the time of oocyte maturation.
+Finally, ovarian aromatase (cyp19a1) exhibited a dramatic down-regulation over the post-vitellogenic period while a down-regulation of Cytidine monophosphate-N-acetylneuraminic acid hydroxylase (cmah) was observed at the time of oocyte maturation.
+CONCLUSION: We showed the over or under expression of more that 300 genes, most of them being previously unstudied or unknown in the fish preovulatory ovary.
+In addition, the strong up-regulation of aqp4 and slc26 genes prior to ovulation suggests their participation in the oocyte hydration process occurring at that time.
+Furthermore, among the most up-regulated clones, several genes such as cxcl14, ace2, adam22, cf5 have pro-inflammatory, vasodilatory, proteolytics and coagulatory functions.
+The identity and expression patterns of those genes support the theory comparing ovulation to an inflammatory-like reaction.
+BACKGROUND: EpiFlex is a flexible, easy to use computer model for a single computer, intended to be operated by one user who need not be an expert.
+Its purpose is to study in-silico the epidemic behavior of a wide variety of diseases, both known and theoretical, by simulating their spread at the level of individuals contracting and infecting others.
+To understand the system fully, this paper must be read together in conjunction with study of the software and its results.
+EpiFlex is evaluated using results from modeling influenza A epidemics and comparing them with a variety of field data sources and other types of modeling.
+EpiFlex is an object-oriented Monte Carlo system, allocating entities to correspond to individuals, disease vectors, diseases, and the locations that hosts may inhabit.
+Populations are composed of demographic groups, each of which has a cycle of movement between locations.
+These results suggest that field research to study such phenomena, while expensive, should be worthwhile.
+CONCLUSION: Since EpiFlex shows all stages of disease progression, detailed insight into the progress of epidemics is possible.
+EpiFlex shows the characteristic multimodality and apparently random variation characteristic of real world data, but does so as an emergent property of a carefully constructed model of disease dynamics and is not simply a stochastic system.
+BACKGROUND: All states require some kind of testing for newborns, but the policies are far from standardized.
+In some states, newborn screening may include genetic tests for a wide range of targets, but the costs and complexities of the newer genetic tests inhibit expansion of newborn screening.
+We describe the development and technical evaluation of a multiplex platform that may foster increased newborn genetic screening.
+Each step is performed in the same reaction vessel, and the test is completed in ~3 h. For site-specific labeling and room-temperature decoding, we use an additional base pair constructed from isoguanosine and isocytidine.
+We used the method to test for mutations within the cystic fibrosis transmembrane conductance regulator (CFTR) gene.
+RESULTS: In the retrospective study, 99.1% of samples were correctly genotyped with no incorrect calls made.
+In the perspective study, 95% of the samples were correctly genotyped for all targets, and there were no incorrect calls.
+CONCLUSIONS: The unique genetic multiplexing platform was successfully able to test for 31 targets within the CFTR gene and provides accurate genotype assignments in a clinical setting.
+Programmed ribosomal frameshifting provides a mechanism to decode information located in two overlapping reading frames by diverting a proportion of translating ribosomes into a second open reading frame (ORF).
+The result is the production of two proteins: the product of standard translation from ORF1 and an ORF1–ORF2 fusion protein.
+Such programmed frameshifting is commonly utilized as a gene expression mechanism in viruses that infect eukaryotic cells and in a subset of cellular genes.
+RNA secondary structures, consisting of pseudoknots or stem–loops, located downstream of the shift site often act as cis-stimulators of frameshifting.
+Here, we demonstrate for the first time that antisense oligonucleotides can functionally mimic these RNA structures to induce +1 ribosomal frameshifting when annealed downstream of the frameshift site, UCC UGA.
+Antisense-induced shifting of the ribosome into the +1 reading frame is highly efficient in both rabbit reticulocyte lysate translation reactions and in cultured mammalian cells.
+The efficiency of antisense-induced frameshifting at this site is responsive to the sequence context 5′ of the shift site and to polyamine levels.
+The standard rules of genetic translational decoding are altered in specific genes by different events that are globally termed recoding.
+In Archaea recoding has been unequivocally determined so far only for termination codon readthrough events.
+We study here the mechanism of expression of a gene encoding for a α-l-fucosidase from the archaeon Sulfolobus solfataricus (fucA1), which is split in two open reading frames separated by a −1 frameshifting.
+The expression in Escherichia coli of the wild-type split gene led to the production by frameshifting of full-length polypeptides with an efficiency of 5%.
+Mutations in the regulatory site where the shift takes place demonstrate that the expression in vivo occurs in a programmed way.
+Further, we identify a full-length product of fucA1 in S.solfataricus extracts, which translate this gene in vitro by following programmed −1 frameshifting.
+This is the first experimental demonstration that this kind of recoding is present in Archaea.
+However, because viruses replicate obligatorily inside cells, and considering that evolution may be driven by a principle of economy of scale, it is reasonable to surmise that many viruses have evolved the ability to co-opt cell-encoded proteins to provide needed surrogate functions.
+An in silico survey of viral sequence databases reveals that most positive-strand and double-stranded RNA viruses have ORFs for RNA helicases.
+Here, we review in brief the notion that the human immunodeficiency virus (HIV-1) has adopted the ability to use one or more cellular RNA helicases for its replicative life cycle.
+BACKGROUND: Phage display is widely used in basic research such as the exploration of protein-protein interaction sites and networks, and applied research such as the development of new drugs, vaccines, and diagnostics.
+Research on new algorithms that assist and automate phage display based epitope mapping has attracted many groups.
+Most of the existing tools have not been implemented as an online service until now however, making it less convenient for the community to access, utilize, and evaluate them.
+RESULTS: We present MIMOX, a free web tool that helps to map the native epitope of an antibody based on one or more user supplied mimotopes and the antigen structure.
+In the first section, MIMOX provides a simple interface for ClustalW to align a set of mimotopes.
+It also provides a simple statistical method to derive the consensus sequence and embeds JalView as a Java applet to view and manage the alignment.
+In the second section, MIMOX can map a single mimotope or a consensus sequence of a set of mimotopes, on to the corresponding antigen structure and search for all of the clusters of residues that could represent the native epitope.
+NACCESS is used to evaluate the surface accessibility of the candidate clusters; and Jmol is embedded to view them interactively in their 3D context.
+Initial case studies show that MIMOX can reproduce mappings from existing tools such as FINDMAP and 3DEX, as well as providing novel, rational results.
+CONCLUSION: A web-based tool called MIMOX has been developed for phage display based epitope mapping.
+As a publicly available online service in this area, it is convenient for the community to access, utilize, and evaluate, complementing other existing programs.
+In multiple sclerosis lesions, remyelination typically fails with repeated or chronic demyelinating episodes and results in neurologic disability.
+Acute demyelination models in rodents typically exhibit robust spontaneous remyelination that prevents appropriate evaluation of strategies for improving conditions of insufficient remyelination.
+In the current study, we used a mouse model of chronic demyelination induced by continuous ingestion of 0.2% cuprizone for 12 weeks.
+Fibroblast growth factor 2 (FGF2) expression was persistently increased in the corpus callosum of chronically demyelinated mice as compared with nonlesioned mice.
+We used FGF2(−/−)mice to determine whether removal of endogenous FGF2 promoted remyelination of chronically demyelinated areas.
+Importantly, in contrast to wild-type mice, the FGF2(−/−)mice spontaneously remyelinated completely during the recovery period after chronic demyelination.
+FGF2 genotype did not alter the density of oligodendrocyte progenitor cells or proliferating cells after chronic demyelination.
+These findings indicate that attenuating FGF2 created a sufficiently permissive lesion environment for endogenous cells to effectively remyelinate viable axons even after chronic demyelination.
+There is an increasing recognition that detailed nucleic acid sequence information will be useful and even required in the diagnosis, treatment and surveillance of many significant pathogens.
+Because generating detailed information about pathogens leads to significantly larger amounts of data, it is necessary to develop automated analysis methods to reduce analysis time and to standardize identification criteria.
+This is especially important for multiple pathogen assays designed to reduce assay time and costs.
+In this paper, we present a successful algorithm for detecting pathogens and reporting the maximum level of detail possible using multi-pathogen resequencing microarrays.
+The algorithm filters the sequence of base calls from the microarray and finds entries in genetic databases that most closely match.
+Taxonomic databases are then used to relate these entries to each other so that the microorganism can be identified.
+Although developed using a resequencing microarray, the approach is applicable to any assay method that produces base call sequence information.
+The success and continued development of this approach means that a non-expert can now perform unassisted analysis of the results obtained from partial sequence data.
+Accuracy in translation of the genetic code into proteins depends upon correct tRNA–mRNA recognition in the context of the ribosome.
+In human [Formula: see text] three modified bases are present in the anticodon stem–loop—2-methylthio-N6-threonylcarbamoyladenosine at position 37 (ms(2)t(6)A37), 5-methoxycarbonylmethyl-2-thiouridine at position 34 (mcm(5)s(2)U34) and pseudouridine (ψ) at position 39—two of which, ms(2)t(6)A37 and mcm(5)s(2)U34, are required to achieve wild-type binding activity of wild-type human [Formula: see text] [C. Yarian, M. Marszalek, E. Sochacka, A. Malkiewicz, R. Guenther, A. Miskiewicz and P. F. Agris (2000) Biochemistry, 39, 13390–13395].
+Molecular dynamics simulations of nine tRNA anticodon stem–loops with different combinations of nonstandard bases were performed.
+The ms(2)t(6) modification at position 37 is required for maintenance of this structure and reduces solvent accessibility of U36.
+Ms(2)t(6)A37 generally hydrogen bonds across the loop and may prevent U36 from rotating into solution.
+A water molecule does coordinate to ψ39 most of the simulation time but weakly, as most of the residence lifetimes are <40 ps.
+Here we describe a novel endonuclease IV (Endo IV) based assay utilizing a substrate that mimics the abasic lesions that normally occur in double-stranded DNA.
+The three component substrate is characterized by single-stranded DNA target, an oligonucleotide probe, separated from a helper oligonucleotide by a one base gap.
+The oligonucleotide probe contains a non-fluorescent quencher at the 5′ end and fluorophore attached to the 3′ end through a special rigid linker.
+Fluorescence of the oligonucleotide probe is efficiently quenched by the interaction of terminal dye and quencher when not hybridized.
+Upon hybridization of the oligonucleotide probe and helper probe to their complementary target, the phosphodiester linkage between the rigid linker and the 3′ end of the probe is efficiently cleaved, generating a fluorescent signal.
+In this study, the use of the Endo IV assay as a post-PCR amplification detection system is demonstrated.
+BACKGROUND: Planning for the next pandemic influenza outbreak is underway in hospitals across the world.
+The global SARS experience has taught us that ethical frameworks to guide decision-making may help to reduce collateral damage and increase trust and solidarity within and between health care organisations.
+Good pandemic planning requires reflection on values because science alone cannot tell us how to prepare for a public health crisis.
+The ethical framework was developed with expertise from clinical, organisational and public health ethics and validated through a stakeholder engagement process.
+The incorporation of ethics into pandemic planning can be helped by senior hospital administrators sponsoring its use, by having stakeholders vet the framework, and by designing or identifying decision review processes.
+We discuss the merits and limits of an applied ethical framework for hospital decision-making, as well as the robustness of the framework.
+SUMMARY: The need for reflection on the ethical issues raised by the spectre of a pandemic influenza outbreak is great.
+Our efforts to address the normative aspects of pandemic planning in hospitals have generated interest from other hospitals and from the governmental sector.
+The framework will require re-evaluation and refinement and we hope that this paper will generate feedback on how to make it even more robust.
+INTRODUCTION: Acute respiratory distress syndrome (ARDS) has heterogeneous etiologies, rapid progressive change and a high mortality rate.
+To improve the outcome of ARDS, accurate diagnosis is essential to the application of effective early treatment.
+The present study investigated the clinical effects and safety of open lung biopsy (OLB) in patients with early-stage ARDS of suspected non-infectious origin.
+METHODS: We undertook a retrospective study of 41 patients with early-stage ARDS (defined as one week or less after intubation) who underwent OLB in two medical intensive care units of a tertiary care hospital from 1999 to 2005.
+The average ratio of arterial partial pressure of oxygen (PaO(2)) to fraction of inspired oxygen (FiO(2)) was 116 ± 43 mmHg (mean ± SD) at biopsy.
+The treatment alteration rate was higher in patients with nonspecific diagnoses than in patients with specific diagnoses (p = 0.0024).
+Overall mortality was 50% (21/41) and was not influenced by age, gender, pre-OLB oxygenation, complication rate, pathological results, and alteration of treatment.
+The survival rate for immunocompromised patients was better than that for immunocompetent patients (71% versus 33%; p = 0.0187) in this study.
+CONCLUSION: Our retrospective study suggests that OLB was a useful and acceptably safe diagnostic procedure in some selected patients with early-stage ARDS.
+The distribution of multi-host pathogens over their host range conditions their population dynamics and structure.
+Also, host co-infection by different pathogens may have important consequences for the evolution of hosts and pathogens, and host-pathogen co-evolution.
+Hence it is of interest to know if the distribution of pathogens over their host range is random, or if there are associations between hosts and pathogens, or between pathogens sharing a host.
+To analyse these issues we propose indices for the observed patterns of host infection by pathogens, and for the observed patterns of co-infection, and tests to analyse if these patterns conform to randomness or reflect associations.
+Applying these tests to the prevalence of five plant viruses on 21 wild plant species evidenced host-virus associations: most hosts and viruses were selective for viruses and hosts, respectively.
+Interestingly, the more host-selective viruses were the more prevalent ones, suggesting that host specialisation is a successful strategy for multi-host pathogens.
+The developed indices and tests provide the tools to analyse how strong and common are these associations among different groups of pathogens, which will help to understand and model the population biology of multi-host pathogens.
+BACKGROUND: Contact tracing plays an important role in the control of emerging infectious diseases, but little is known yet about its effectiveness.
+Here we deduce from a generic mathematical model how effectiveness of tracing relates to various aspects of time, such as the course of individual infectivity, the (variability in) time between infection and symptom-based detection, and delays in the tracing process.
+With these insights we explain why contact tracing was and will be effective for control of smallpox and SARS, only partially effective for foot-and-mouth disease, and likely not effective for influenza.
+METHODS AND FINDINGS: We investigate contact tracing in a model of an emerging epidemic that is flexible enough to use for most infections.
+We consider isolation of symptomatic infecteds as the basic scenario, and express effectiveness as the proportion of contacts that need to be traced for a reproduction ratio smaller than 1.
+We obtain general results for special cases, which are interpreted with respect to the likely success of tracing for influenza, smallpox, SARS, and foot-and-mouth disease epidemics.
+CONCLUSIONS: We conclude that (1) there is no general predictive formula for the proportion to be traced as there is for the proportion to be vaccinated; (2) variability in time to detection is favourable for effective tracing; (3) tracing effectiveness need not be sensitive to the duration of the latent period and tracing delays; (4) iterative tracing primarily improves effectiveness when single-step tracing is on the brink of being effective.
+BACKGROUND: The time delay between the start of an influenza pandemic and its subsequent initiation in other countries is highly relevant to preparedness planning.
+We quantify the distribution of this random time in terms of the separate components of this delay, and assess how the delay may be extended by non-pharmaceutical interventions.
+Efforts that reduce the disease reproduction number in the source region below two and severe travel restrictions are most effective for delaying a local epidemic, and under favourable circumstances, could add several months to the delay.
+On the other hand, the model predicts that border screening for symptomatic infection, wearing a protective mask during travel, promoting early presentation of cases arising among arriving passengers and moderate reduction in travel volumes increase the delay only by a matter of days or weeks.
+CONCLUSIONS: The delay until an epidemic of pandemic strain influenza is imported into an at-risk country is largely determined by the course of the epidemic in the source region and the number of travelers attempting to enter the at-risk country, and is little affected by non-pharmaceutical interventions targeting these travelers.
+Short of preventing international travel altogether, eradicating a nascent pandemic in the source region appears to be the only reliable method of preventing country-to-country spread of a pandemic strain of influenza.
+Prophylaxis with high doses of neutralizing antibody typically offers protection against challenge with viruses producing acute infections.
+In this study, we have investigated the ability of the neutralizing human monoclonal antibody, KZ52, to protect against Ebola virus in rhesus macaques.
+Four rhesus macaques were given 50 mg/kg of neutralizing human monoclonal antibody KZ52 intravenously 1 d before challenge with 1,000 plaque-forming units of Ebola virus, followed by a second dose of 50 mg/kg antibody 4 d after challenge.
+Passive transfer of the neutralizing human monoclonal antibody not only failed to protect macaques against challenge with Ebola virus but also had a minimal effect on the explosive viral replication following infection.
+We show that the inability of antibody to impact infection was not due to neutralization escape.
+It appears that Ebola virus has a mechanism of infection propagation in vivo in macaques that is uniquely insensitive even to high concentrations of neutralizing antibody.
+BACKGROUND: Recent international and national events have brought critical attention to the Canadian public health system and how prepared the system is to respond to various types of contemporary public health threats.
+This article describes the study design and methods being used to conduct a systems-level analysis of public health preparedness in the province of Alberta, Canada.
+The project is being funded under the Health Research Fund, Alberta Heritage Foundation for Medical Research.
+METHODS/DESIGN: We use an embedded, multiple-case study design, integrating qualitative and quantitative methods to measure empirically the degree of inter-organizational coordination existing among public health agencies in Alberta, Canada.
+We situate our measures of inter-organizational network ties within a systems-level framework to assess the relative influence of inter-organizational ties, individual organizational attributes, and institutional environmental features on public health preparedness.
+The relative contribution of each component is examined for two potential public health threats: pandemic influenza and West Nile virus.
+DISCUSSION: The organizational dimensions of public health preparedness depend on a complex mix of individual organizational characteristics, inter-agency relationships, and institutional environmental factors.
+Our study is designed to discriminate among these different system components and assess the independent influence of each on the other, as well as the overall level of public health preparedness in Alberta.
+While all agree that competent organizations and functioning networks are important components of public health preparedness, this study is one of the first to use formal network analysis to study the role of inter-agency networks in the development of prepared public health systems.
+Inflammation in the middle ear mucosa, which can be provoked by different primary factors such as bacterial and viral infection, local allergic reactions and reflux, is the crucial event in the pathogenesis of otitis media with effusion (OME).
+Unresolved acute inflammatory responses or defective immunoregulation of middle inflammation can promote chronic inflammatory processes and stimulate the chronic condition of OME.
+Cytokines are the central molecular regulators of middle ear inflammation and can switch the acute phase of inflammation in the chronic stage and induce molecular-pathological processes leading to the histopathological changes accompanying OME.
+In this review we present cytokines identified in otitis media, immunoregulatory [interleukin (IL)-2, IL-10, transforming growth factor-beta]) and allergy associated (IL-4, IL-5, granulocyte-macrophage colony-stimulating factor), as crucial molecular regulators, responsible for chronic inflammation in the middle ear and the chronic condition of OME.
+Cognitive dysfunction is common in critically ill patients, not only during the acute illness but also long after its resolution.
+A large number of pathophysiologic mechanisms are thought to underlie critical illness-associated cognitive dysfunction, including neuro-transmitter abnormalities and occult diffuse brain injury.
+Markers that could be used to evaluate the influence of specific mechanisms in individual patients include serum anticholinergic activity, certain brain proteins, and tissue sodium concentration determination via high-resolution three-dimensional magnetic resonance imaging.
+Although recent therapeutic advances in this area are exciting, they are still too immature to influence patient care.
+Additional research is needed if we are to understand better the relative contributions of specific mechanisms to the development of critical illness-associated cognitive dysfunction and to determine whether these mechanisms might be amenable to treatment or prevention.
+Understanding transcription factor (TF) mediated control of gene expression remains a major challenge at the interface of computational and experimental biology.
+We introduce a simple strategy that dramatically improves robustness and accuracy of computational binding site prediction.
+First, we evaluate the rate of recurrence of computational TFBS predictions by commonly used sampling procedures.
+Additionally, we find that positional clustering increases robustness to long or imperfectly selected input sequences.
+Positional clustering can also be used as a mechanism to integrate results from multiple sampling approaches for improvements in accuracy over each one alone.
+Finally, we predict and validate regulatory sequences partially responsible for transcriptional control of the mammalian type A γ-aminobutyric acid receptor (GABA(A)R) subunit genes.
+Positional clustering is useful for improving computational binding site predictions, with potential application to improving our understanding of mammalian gene expression.
+In particular, predicted regulatory mechanisms in the mammalian GABA(A)R subunit gene family may open new avenues of research towards understanding this pharmacologically important neurotransmitter receptor system.
+BACKGROUND: With the increased occurrence of outbreaks of H5N1 worldwide there is concern that the virus could enter commercial poultry farms with severe economic consequences.
+METHODOLOGY/PRINCIPAL FINDINGS: We analyse data from four recent outbreaks of highly pathogenic avian influenza (HPAI) in commercial poultry to estimate the farm-to-farm reproductive number for HPAI.
+The reproductive number is a key measure of the transmissibility of HPAI at the farm level because it can be used to evaluate the effectiveness of the control measures.
+In these outbreaks the mean farm-to-farm reproductive number prior to controls ranged from 1.1 to 2.4, with the maximum farm-based reproductive number in the range 2.2 to 3.2.
+Enhanced bio-security, movement restrictions and prompt isolation of the infected farms in all four outbreaks substantially reduced the reproductive number, but it remained close to the threshold value 1 necessary to ensure the disease will be eradicated.
+CONCLUSIONS/SIGNIFICANCE: Our results show that depending on the particular situation in which an outbreak of avian influenza occurs, current controls might not be enough to eradicate the disease, and therefore a close monitoring of the outbreak is required.
+The method we used for estimating the reproductive number is straightforward to implement and can be used in real-time.
+BACKGROUND: Planning public health responses against pandemic influenza relies on predictive models by which the impact of different intervention strategies can be evaluated.
+Research has to date rather focused on producing predictions for certain localities or under specific conditions, than on designing a publicly available planning tool which can be applied by public health administrations.
+Here, we provide such a tool which is reproducible by an explicitly formulated structure and designed to operate with an optimal combination of the competing requirements of precision, realism and generality.
+RESULTS: InfluSim is a deterministic compartment model based on a system of over 1,000 differential equations which extend the classic SEIR model by clinical and demographic parameters relevant for pandemic preparedness planning.
+It allows for producing time courses and cumulative numbers of influenza cases, outpatient visits, applied antiviral treatment doses, hospitalizations, deaths and work days lost due to sickness, all of which may be associated with economic aspects.
+The software is programmed in Java, operates platform independent and can be executed on regular desktop computers.
+CONCLUSION: InfluSim is an online available software which efficiently assists public health planners in designing optimal interventions against pandemic influenza.
+It can reproduce the infection dynamics of pandemic influenza like complex computer simulations while offering at the same time reproducibility, higher computational performance and better operability.
+Here we focus on individual defences, by presenting a genome-wide analysis of immunity in a social insect, the honey bee Apis mellifera.
+We present honey bee models for each of four signalling pathways associated with immunity, identifying plausible orthologues for nearly all predicted pathway members.
+When compared to the sequenced Drosophila and Anopheles genomes, honey bees possess roughly one-third as many genes in 17 gene families implicated in insect immunity.
+We suggest that an implied reduction in immune flexibility in bees reflects either the strength of social barriers to disease, or a tendency for bees to be attacked by a limited set of highly coevolved pathogens.
+Covalent binding of ubiquitin or Ubls to substrate proteins can be reversed by specific hydrolases.
+One particular set of cysteine proteases, the CE clan, which targets ubiquitin and Ubls, has homologs in eukaryotes, prokaryotes, and viruses.
+FINDINGS: We have cloned and analyzed the E. coli protein elaD, which is distantly related to eukaryotic CE clan members of the ULP/SENP protease family that are specific for SUMO and Nedd8.
+Previously misannotated as a putative sulfatase/phosphatase, elaD is an efficient and specific deubiquitinating enzyme in vitro.
+Interestingly, elaD is present in all intestinal pathogenic E. coli strains, but conspicuously absent from extraintestinal pathogenic strains (ExPECs).
+Further homologs of this protease can be found in Acanthamoeba Polyphaga Mimivirus, and in Alpha-, Beta-and Gammaproteobacteria.
+CONCLUSION: The expression of ULP/SENP-related hydrolases in bacteria therefore extends to plant pathogens and medically relevant strains of Escherichia coli, Legionella pneumophila, Rickettsiae, Chlamydiae, and Salmonellae, in which the elaD ortholog sseL has recently been identified as a virulence factor with deubiquitinating activity.
+As a counterpoint, our phylogenetic and functional examination reveals that ancient eukaryotic ULP/SENP proteases also have the potential of ubiquitin-specific hydrolysis, suggesting an early common origin of this peptidase clan.
+A common overlapping site on the N-terminal IgV-like domain of human carcinoembryonic antigen (CEA)-related cell adhesion molecules (CEACAMs) is targeted by several important human respiratory pathogens.
+These include Neisseria meningitidis (Nm) and Haemophilus influenzae (Hi) that can cause disseminated or persistent localized infections.
+To define the precise structural features that determine the binding of distinct pathogens with CEACAMs, we have undertaken molecular modelling and mutation of the receptor molecules at previously implicated key target residues required for bacterial binding.
+These include Ser-32, Tyr-34, Val-39, Gln-44 and Gln-89, in addition to Ile-91, the primary docking site for the pathogens.
+Most, but not all, of these residues located adjacent to each other in a previous N-domain model of human CEACAM1, which was based on REI, CD2 and CD4.
+In the current studies, we have refined this model based on the mouse CEACAM1 crystal structure, and observe that all of the above residues form an exposed continuous binding region on the N-domain.
+Examination of the model also suggested that substitution of two of these residues 34 and 89 could affect the accessibility of Ile-91 for ligand binding.
+By introducing selected mutations at the positions 91, 34 and 89, we confirmed the primary importance of Ile-91 in all bacterial binding to CEACAM1 despite the inter- and intraspecies structural differences between the bacterial CEACAM-binding ligands.
+The studies further indicated that the efficiency of binding was significantly enhanced for specific strains by mutations such as Y34F and Q89N, which also altered the hierarchy of Nm versus Hi strain binding.
+These studies imply that distinct polymorphisms in human epithelial CEACAMs have the potential to decrease or increase the risk of infection by the receptor-targeting pathogens.
+The immune reconstitution inflammatory syndrome (IRIS) in HIV-infected patients initiating antiretroviral therapy (ART) results from restored immunity to specific infectious or non-infectious antigens.
+A paradoxical clinical worsening of a known condition or the appearance of a new condition after initiating therapy characterizes the syndrome.
+Potential mechanisms for the syndrome include a partial recovery of the immune system or exuberant host immunological responses to antigenic stimuli.
+The overall incidence of IRIS is unknown, but is dependent on the population studied and its underlying opportunistic infectious burden.
+The infectious pathogens most frequently implicated in the syndrome are mycobacteria, varicella zoster, herpesviruses, and cytomegalovirus (CMV).
+No single treatment option exists and depends on the underlying infectious agent and its clinical presentation.
+Prospective cohort studies addressing the optimal screening and treatment of opportunistic infections in patients eligible for ART are currently being conducted.
+These studies will provide evidence for the development of treatment guidelines in order to reduce the burden of IRIS.
+We review the available literature on the pathogenesis and epidemiology of IRIS, and present treatment options for the more common infectious manifestations of this diverse syndrome and for manifestations associated with a high morbidity.
+BACKGROUND: Effective influenza surveillance requires new methods capable of rapid and inexpensive genomic analysis of evolving viral species for pandemic preparedness, to understand the evolution of circulating viral species, and for vaccine strain selection.
+We have developed one such approach based on previously described broad-range reverse transcription PCR/electrospray ionization mass spectrometry (RT-PCR/ESI-MS) technology.
+METHODS AND PRINCIPAL FINDINGS: Analysis of base compositions of RT-PCR amplicons from influenza core gene segments (PB1, PB2, PA, M, NS, NP) are used to provide sub-species identification and infer influenza virus H and N subtypes.
+Using this approach, we detected and correctly identified 92 mammalian and avian influenza isolates, representing 30 different H and N types, including 29 avian H5N1 isolates.
+Further, direct analysis of 656 human clinical respiratory specimens collected over a seven-year period (1999–2006) showed correct identification of the viral species and subtypes with >97% sensitivity and specificity.
+Base composition derived clusters inferred from this analysis showed 100% concordance to previously established clades.
+Ongoing surveillance of samples from the recent influenza virus seasons (2005–2006) showed evidence for emergence and establishment of new genotypes of circulating H3N2 strains worldwide.
+Mixed viral quasispecies were found in approximately 1% of these recent samples providing a view into viral evolution.
+CONCLUSION/SIGNIFICANCE: Thus, rapid RT-PCR/ESI-MS analysis can be used to simultaneously identify all species of influenza viruses with clade-level resolution, identify mixed viral populations and monitor global spread and emergence of novel viral genotypes.
+Despite intensive ongoing research, key aspects of the spatial-temporal evolution of the 2001 foot and mouth disease (FMD) epidemic in Great Britain (GB) remain unexplained.
+Here we develop a Markov Chain Monte Carlo (MCMC) method for estimating epidemiological parameters of the 2001 outbreak for a range of simple transmission models.
+We make the simplifying assumption that infectious farms were completely observed in 2001, equivalent to assuming that farms that were proactively culled but not diagnosed with FMD were not infectious, even if some were infected.
+We estimate how transmission parameters varied through time, highlighting the impact of the control measures on the progression of the epidemic.
+We demonstrate statistically significant evidence for assortative contact patterns between animals of the same species.
+Predictive risk maps of the transmission potential in different geographic areas of GB are presented for the fitted models.
+Pneumonia virus of mice (PVM; family Paramyxoviridae, subfamily Pneumovirinae) is a natural respiratory pathogen of rodent species and an important new model for the study of severe viral bronchiolitis and pneumonia.
+However, despite high virus titers typically detected in infected mouse lung tissue in vivo, cell lines used routinely for virus propagation in vitro are not highly susceptible to PVM infection.
+We have evaluated several rodent and primate cell lines for susceptibility to PVM infection, and detected highest virus titers from infection of the mouse monocyte-macrophage RAW 264.7 cell line.
+Additionally, virus replication in RAW 264.7 cells induces the synthesis and secretion of proinflammatory cytokines relevant to respiratory virus disease, including tumor necrosis factor-α (TNF-α), interferon-β (IFN-β), macrophage inflammatory proteins 1α and 1β (MIP-1α and MIP-1β) and the functional homolog of human IL-8, mouse macrophage inflammatory peptide-2 (MIP-2).
+Identification and characterization of a rodent cell line that supports the replication of PVM and induces the synthesis of disease-related proinflammatory mediators will facilitate studies of molecular mechanisms of viral pathogenesis that will complement and expand on findings from mouse model systems.
+BACKGROUND: Since 2001, state and local health departments in the United States (US) have accelerated efforts to prepare for high-impact public health emergencies.
+One component of these activities has been the development and conduct of exercise programs to assess capabilities, train staff and build relationships.
+This paper summarizes lessons learned from tabletop exercises about public health emergency preparedness and about the process of developing, conducting, and evaluating them.
+METHODS: We developed, conducted, and evaluated 31 tabletop exercises in partnership with state and local health departments throughout the US from 2003 to 2006.
+Participant self evaluations, after action reports, and tabletop exercise evaluation forms were used to identify aspects of the exercises themselves, as well as public health emergency responses that participants found more or less challenging, and to highlight lessons learned about tabletop exercise design.
+RESULTS: Designing the exercises involved substantial collaboration with representatives from participating health departments to assure that the scenarios were credible, focused attention on local preparedness needs and priorities, and were logistically feasible to implement.
+During execution of the exercises, nearly all health departments struggled with a common set of challenges relating to disease surveillance, epidemiologic investigations, communications, command and control, and health care surge capacity.
+In contrast, performance strengths were more varied across participating sites, reflecting specific attributes of individual health departments or communities, experience with actual public health emergencies, or the emphasis of prior preparedness efforts.
+CONCLUSION: The design, conduct, and evaluation of the tabletop exercises described in this report benefited from collaborative planning that involved stakeholders from participating health departments and exercise developers and facilitators from outside the participating agencies.
+While these exercises identified both strengths and vulnerabilities in emergency preparedness, additional work is needed to develop reliable metrics to gauge exercise performance, inform follow-up action steps, and to develop re-evaluation exercise designs that assess the impact of post-exercise interventions.
+BACKGROUND: The wide use of Affymetrix microarray in broadened fields of biological research has made the probeset annotation an important issue.
+a probeset is precisely linked to a gene, and probeset intensity is interpreted as gene expression.
+The increased knowledge that one gene may have multiple transcript variants clearly brings up the necessity of updating this gene-level annotation to a refined transcript-level.
+RESULTS: Through performing rigorous alignments of the Affymetrix probe sequences against a comprehensive pool of currently available transcript sequences, and further linking the probesets to the International Protein Index, we generated transcript-level or protein-level annotation tables for two popular Affymetrix expression arrays, Mouse Genome 430A 2.0 Array and Human Genome U133A Array.
+Application of our new annotations in re-examining existing expression data sets shows increased expression consistency among synonymous probesets and strengthened expression correlation between interacting proteins.
+CONCLUSION: By refining the standard Affymetrix annotation of microarray probesets from the gene level to the transcript level and protein level, one can achieve a more reliable interpretation of their experimental data, which may lead to discovery of more profound regulatory mechanism.
+The thiol-disulfide oxidoreductase thioredoxin-1 (Trx1) is known to be secreted by leukocytes and to exhibit cytokine-like properties.
+Extracellular effects of Trx1 require a functional active site, suggesting a redox-based mechanism of action.
+However, specific cell surface proteins and pathways coupling extracellular Trx1 redox activity to cellular responses have not been identified so far.
+Using a mechanism-based kinetic trapping technique to identify disulfide exchange interactions on the intact surface of living lymphocytes, we found that Trx1 catalytically interacts with a single principal target protein.
+This target protein was identified as the tumor necrosis factor receptor superfamily member 8 (TNFRSF8/CD30).
+We demonstrate that the redox interaction is highly specific for both Trx1 and CD30 and that the redox state of CD30 determines its ability to engage the cognate ligand and transduce signals.
+Thus, we conclude that receptor–ligand signaling interactions can be selectively regulated by an extracellular redox catalyst.
+BACKGROUND: The family of ubiquitin-like molecules (UbLs) comprises several members, each of which has sequence, structural, or functional similarity to ubiquitin.
+ISG15 is a homolog of ubiquitin in vertebrates and is strongly upregulated following induction by type I interferon.
+ISG15 can be covalently attached to proteins, analogous to ubiquitination and with actual support of ubiquitin conjugating factors.
+Specific proteases are able to reverse modification with ubiquitin or UbLs by hydrolyzing the covalent bond between their C-termini and substrate proteins.
+The tail regions of ubiquitin and ISG15 are identical and we therefore hypothesized that promiscuous deubiquitinating proteases (DUBs) might exist, capable of recognizing both ubiquitin and ISG15.
+RESULTS: We have cloned and expressed 22 human DUBs, representing the major clades of the USP protease family.
+Utilizing suicide inhibitors based on ubiquitin and ISG15, we have identified USP2, USP5 (IsoT1), USP13 (IsoT3), and USP14 as ISG15-reactive proteases, in addition to the bona fide ISG15-specific protease USP18 (UBP43).
+USP14 is a proteasome-associated DUB, and its ISG15 isopeptidase activity increases when complexed with the proteasome.
+CONCLUSIONS: By evolutionary standards, ISG15 is a newcomer among the UbLs and it apparently not only utilizes the conjugating but also the deconjugating machinery of its more established relative ubiquitin.
+Functional overlap between these two posttranslational modifiers might therefore be more extensive than previously appreciated and explain the rather innocuous phenotype of ISG15 null mice.
+The rapidly growing understanding of human genetic pathways, including those that mediate cancer biology and drug response, leads to an increasing need for extensive and reliable mutation screening on a population or on a single patient basis.
+Here we describe s-RT-MELT, a novel technology that enables highly expanded enzymatic mutation scanning in human samples for germline or low-level somatic mutations, or for SNP discovery.
+GC-clamp-containing PCR products from interrogated and wild-type samples are hybridized to generate mismatches at the positions of mutations over one or multiple sequences in-parallel.
+Mismatches are converted to double-strand breaks using a DNA endonuclease (Surveyor™) and oligonucleotide tails are enzymatically attached at the position of mutations.
+Subsequently, melting curve analysis, on conventional or nano-technology real-time PCR platforms, detects the samples that contain mutations in a high-throughput and closed-tube manner.
+We apply s-RT-MELT in the screening of p53 and EGFR mutations in cell lines and clinical samples and demonstrate its advantages for rapid, multiplexed mutation scanning in cancer and for genetic variation screening in biology and medicine.
+To identify malaria antigens for vaccine development, we selected α-helical coiled coil domains of proteins predicted to be present in the parasite erythrocytic stage.
+Indeed the 95 chemically synthesized peptides were all specifically recognized by human immune sera, though at various prevalence.
+Peptide specific antibodies were obtained both by affinity-purification from malaria immune sera and by immunization of mice.
+These antibodies did not show significant cross reactions, i.e., they were specific for the original peptide, reacted with native parasite proteins in infected erythrocytes and several were active in inhibiting in vitro parasite growth.
+Thus, we demonstrate that the bioinformatics/chemical synthesis approach described here can lead to the rapid identification of molecules which target biologically active antibodies, thus identifying suitable vaccine candidates.
+This strategy can be, in principle, extended to vaccine discovery in a wide range of other pathogens.
+Influenza A viruses are hosted by numerous avian and mammalian species, which have shaped their evolution into distinct lineages worldwide.
+The viral genome consists of eight RNA segments that are frequently exchanged between different viruses via a process known as genetic reassortment.
+Specialized bioinformatic tools to analyze reassortment are not available, which hampers progress in understanding its role in host range, virulence and transmissibility of influenza viruses.
+To meet this need, we have developed a nomenclature to name influenza A genotypes and implemented a web server, FluGenome (http://www.flugenome.org/), for the assignment of lineages and genotypes.
+FluGenome provides functions for the user to interrogate the database in different modalities and get detailed reports on lineages and genotypes.
+These features make FluGenome unique in its ability to automatically detect genotype differences attributable to reassortment events in influenza A virus evolution.
+BACKGROUND: Influenza pandemic preparedness plans are currently developed and refined on national and international levels.
+Much attention has been given to the administration of antiviral drugs, but contact reduction can also be an effective part of mitigation strategies and has the advantage to be not limited per se.
+The effectiveness of these interventions depends on various factors which must be explored by sensitivity analyses, based on mathematical models.
+METHODS: We use the freely available planning tool InfluSim to investigate how pharmaceutical and non-pharmaceutical interventions can mitigate an influenza pandemic.
+In particular, we examine how intervention schedules, restricted stockpiles and contact reduction (social distancing measures and isolation of cases) determine the course of a pandemic wave and the success of interventions.
+RESULTS: A timely application of antiviral drugs combined with a quick implementation of contact reduction measures is required to substantially protract the peak of the epidemic and reduce its height.
+because of parsimonious use of a limited stockpile) result in much more pessimistic outcomes and can even lead to the paradoxical effect that the stockpile is depleted earlier compared to early distribution of antiviral drugs.
+The protraction of the pandemic wave is essential to win time while waiting for vaccine development and production.
+However, it is the height of the peak of an epidemic which can easily overtax general practitioners, hospitals or even whole public health systems, causing bottlenecks in basic and emergency medical care.
+Over the past 15 years, DNA vaccines have gone from a scientific curiosity to one of the most dynamic research field and may offer new alternatives for the control of parasitic diseases such as leishmaniasis and Chagas disease.
+We review here some of the advances and challenges for the development of DNA vaccines against these diseases.
+Many studies have validated the concept of using DNA vaccines for both protection and therapy against these protozoan parasites in a variety of mouse models.
+The challenge now is to translate what has been achieved in these models into veterinary or human vaccines of comparable efficacy.
+Also, genome-mining and new antigen discovery strategies may provide new tools for a more rational search of novel vaccine candidates.
+Reproduction numbers, defined as averages of the number of people infected by a typical case, play a central role in tracking infectious disease outbreaks.
+The aim of this paper is to develop methods for estimating reproduction numbers which are simple enough that they could be applied with limited data or in real time during an outbreak.
+I present a new estimator for the individual reproduction number, which describes the state of the epidemic at a point in time rather than tracking individuals over time, and discuss some potential benefits.
+Then, to capture more of the detail that micro-simulations have shown is important in outbreak dynamics, I analyse a model of transmission within and between households, and develop a method to estimate the household reproduction number, defined as the number of households infected by each infected household.
+This method is validated by numerical simulations of the spread of influenza and measles using historical data, and estimates are obtained for would-be emerging epidemics of these viruses.
+I argue that the household reproduction number is useful in assessing the impact of measures that target the household for isolation, quarantine, vaccination or prophylactic treatment, and measures such as social distancing and school or workplace closures which limit between-household transmission, all of which play a key role in current thinking on future infectious disease mitigation.
+Understanding the mechanisms that help promote protective immune responses to pathogens is a major challenge in biomedical research and an important goal for the design of innovative therapeutic or vaccination strategies.
+While natural killer (NK) cells can directly contribute to the control of viral replication, whether, and how, they may help orchestrate global antiviral defense is largely unknown.
+To address this question, we took advantage of the well-defined molecular interactions involved in the recognition of mouse cytomegalovirus (MCMV) by NK cells.
+By using congenic or mutant mice and wild-type versus genetically engineered viruses, we examined the consequences on antiviral CD8 T cell responses of specific defects in the ability of the NK cells to control MCMV.
+This system allowed us to demonstrate, to our knowledge for the first time, that NK cells accelerate CD8 T cell responses against a viral infection in vivo.
+Moreover, we identify the underlying mechanism as the ability of NK cells to limit IFN-α/β production to levels not immunosuppressive to the host.
+This is achieved through the early control of cytomegalovirus, which dramatically reduces the activation of plasmacytoid dendritic cells (pDCs) for cytokine production, preserves the conventional dendritic cell (cDC) compartment, and accelerates antiviral CD8 T cell responses.
+Conversely, exogenous IFN-α administration in resistant animals ablates cDCs and delays CD8 T cell activation in the face of NK cell control of viral replication.
+Collectively, our data demonstrate that the ability of NK cells to respond very early to cytomegalovirus infection critically contributes to balance the intensity of other innate immune responses, which dampens early immunopathology and promotes optimal initiation of antiviral CD8 T cell responses.
+Thus, the extent to which NK cell responses benefit the host goes beyond their direct antiviral effects and extends to the prevention of innate cytokine shock and to the promotion of adaptive immunity.
+We conducted a study in the summer of 2004 at county fairs in the Midwest to investigate the role poultry exhibits have in spreading avian pathogens to humans.
+A nearly invisible powder (pathogen surrogate) that fluoresces under UV light was surreptitiously sprinkled each day on 1 show bird at each of 2 fairs.
+A UV light box was used to daily examine the hands of 94 poultry-exhibit participants (blinded regarding UV box results) for up to 4 days during the poultry shows.
+Eight (8.5%) of 94 participants had evidence of fluorescent powder contamination (95% confidence interval 2.76%–14.26%).
+This contamination and infrequent handwashing practices suggest that county fairs are a possible venue for animal-to-human pathogen transmission.
+The human APOBEC3G protein is an innate anti-viral factor that can dominantly inhibit the replication of some endogenous and exogenous retroviruses.
+Here, long-term co-culture experiments were used to show that porcine endogenous retrovirus (PERV) transmission from pig to human cells is reduced to nearly undetectable levels by expressing human APOBEC3G in virus-producing pig kidney cells.
+Inhibition occurred by a deamination-independent mechanism, likely after particle production but before the virus could immortalize by integration into human genomic DNA.
+PERV inhibition did not require the DNA cytosine deaminase activity of APOBEC3G and, correspondingly, APOBEC3G-attributable hypermutations were not detected.
+In contrast, over-expression of the sole endogenous APOBEC3 protein of pigs failed to interfere significantly with PERV transmission.
+Together, these data constitute the first proof-of-principle demonstration that APOBEC3 proteins can be used to fortify the innate anti-viral defenses of cells to prevent the zoonotic transmission of an endogenous retrovirus.
+These studies suggest that human APOBEC3G-transgenic pigs will provide safer, PERV-less xenotransplantation resources and that analogous cross-species APOBEC3-dependent restriction strategies may be useful for thwarting other endogenous as well as exogenous retrovirus infections.
+Serological analysis showed wide cross-reactivity of this virus with sera produced to H5N1 HPAI viruses isolated earlier in South-East Asia.
+CONCLUSION: Assuming all obtained data we can conclude that basic model parameters were characterized and virus A/duck/Tuva/01/06 can be used to evaluate anti-influenza vaccines and therapeutics.
+Predicting RNA secondary structure is often the first step to determining the structure of RNA.
+Prediction approaches have historically avoided searching for pseudoknots because of the extreme combinatorial and time complexity of the problem.
+Here, an algorithm utilizing structure mapping and thermodynamics is introduced for RNA pseudoknot prediction that finds the minimum free energy and identifies information about the flexibility of the RNA.
+The heuristic approach takes advantage of the 5′ to 3′ folding direction of many biological RNA molecules and is consistent with the hierarchical folding hypothesis and the contact order model.
+Mapping methods are used to build and analyze the folded structure for pseudoknots and to add important 3D structural considerations.
+The results of this study suggest that many functional RNA sequences are optimized for proper folding.
+They also suggest directions we can proceed in the future to achieve even better results.
+Arginine-rich cell-penetrating peptides (CPPs) are promising transporters for intracellular delivery of antisense morpholino oligomers (PMO).
+Here, we determined the effect of L-arginine, D-arginine and non-α amino acids on cellular uptake, splice-correction activity, cellular toxicity and serum binding for 24 CPP−PMOs.
+Insertion of 6-aminohexanoic acid (X) or β-alanine (B) residues into oligoarginine R(8) decreased the cellular uptake but increased the splice-correction activity of the resulting compound, with a greater increase for the sequences containing more X residues.
+Up to 60 μM, only the conjugates with ⩾ 5 Xs exhibited time- and concentration-dependent toxicity.
+High concentration of serum significantly decreased the uptake and splice-correction activity of oligoarginine conjugates, but had much less effect on the conjugates containing X or B.
+In summary, incorporation of X/B into oligoarginine enhanced the antisense activity and serum-binding profile of CPP−PMO.
+Toxicity of X/B-containing conjugates was affected by the number of Xs, treatment time and concentration.
+More active, stable and less toxic CPPs can be designed by optimizing the position and number of R, D-R, X and B residues.
+We've always wanted to save the world from the scourges of virus infection by developing better drugs and vaccines.
+But fully understanding the intricacies of virus-host interactions, the first step in achieving this goal, requires the ability to view the process on a grand scale.
+The advent of high-throughput technologies, such as DNA microarrays and mass spectrometry, provided the first opportunities to obtain such a view.
+Here we describe our efforts to use these tools to focus on the changes in cellular gene expression and protein abundance that occur in response to virus infection.
+By examining these changes in a comprehensive manner, we have been able to discover exciting new insights into innate immunity, interferon and cytokine signaling, and the strategies used by viruses to overcome these cellular defenses.
+The synthesis and characterization of isotopomer tandem nucleic acid mass tag–peptide nucleic acid (TNT–PNA) conjugates is described along with their use as electrospray ionisation-cleavable (ESI-Cleavable) hybridization probes for the detection and quantification of target DNA sequences by electrospray ionisation tandem mass spectrometry (ESI-MS/MS).
+ESI-cleavable peptide TNT isotopomers were introduced into PNA oligonucleotide sequences in a total synthesis approach.
+These conjugates were evaluated as hybridization probes for the detection and quantification of immobilized synthetic target DNAs using ESI-MS/MS.
+In these experiments, the PNA portion of the conjugate acts as a hybridization probe, whereas the peptide TNT is released in a collision-based process during the ionization of the probe conjugate in the electrospray ion source.
+The cleaved TNT acts as a uniquely resolvable marker to identify and quantify a unique target DNA sequence.
+The method should be applicable to a wide variety of assays requiring highly multiplexed, quantitative DNA/RNA analysis, including gene expression monitoring, genetic profiling and the detection of pathogens.
+Aberrant expression of DNA polymerase β, a key enzyme involved in base excision repair, leads to genetic instability and carcinogenesis.
+Pol β expression has been previously shown to be regulated at the level of transcription, but there is also evidence of post-transcriptional regulation, since rat transcripts undergo alternative polyadenylation, and the resulting 3′UTR contain at least one regulatory element.
+Data presented here indicate that RNA of the short 3′UTR folds to form a strong secondary structure (hairpin).
+Further studies led to the identification of a protein factor, which binds to this element—the anti-apoptotic, cytoskeleton-related protein Hax-1.
+The results of in vitro binding analysis indicate that the formation of the RNA–protein complex is significantly impaired by disruption of the hairpin motif.
+We demonstrate that Hax-1 binds to Pol β mRNA exclusively in the form of a dimer.
+Biochemical analysis revealed the presence of Hax-1 in mitochondria, but also in the nuclear matrix, which, along with its transcript-binding properties, suggests that Hax-1 plays a role in post-transcriptional regulation of expression of Pol β.
+The 'global public good' (GPG) concept has gained increasing attention, in health as well as development circles.
+However, it has suffered in finding currency as a general tool for global resource mobilisation, and is at risk of being attached to almost anything promoting development.
+Second, it identifies two key areas, health R&D and communicable disease control, in which the GPG concept is clearly relevant and considers the extent to which it has been applied.
+We point out that that, while there have been many new initiatives, it is not clear that additional resources from non-traditional sources have been forthcoming.
+Yet achieving this is, in effect, the entire purpose of applying the GPG concept in global health.
+Moreover, the proliferation of disease-specific programs associated with GPG reasoning has tended to promote vertical interventions at the expense of more general health sector strengthening.
+Third, we examine two major global health policy initiatives, the Global Fund against AIDS, Tuberculosis and Malaria (GFATM) and the bundling of long-standing international health goals in the form of Millennium Development Goals (MDG), asking how the GPG perspective has contributed to defining objectives and strategies.
+We conclude that both initiatives are best interpreted in the context of traditional development assistance and, one-world rhetoric aside, have little to do with the challenge posed by GPGs for health.
+The paper concludes by considering how the GPG concept can be more effectively used to promote global health.
+The development of paediatric intensive care has contributed to the improved survival of critically ill children.
+Physical and psychological sequelae and consequences for quality of life (QoL) in survivors might be significant, as has been determined in adult intensive care unit (ICU) survivors.
+Awareness of sequelae due to the original illness and its treatment may result in changes in treatment and support during and after the acute phase.
+To determine the current knowledge on physical and psychological sequelae and the quality of life in survivors of paediatric intensive care, we undertook a computerised comprehensive search of online databases for studies reporting sequelae in survivors of paediatric intensive care.
+Studies reporting sequelae in paediatric survivors of cardiothoracic surgery and trauma were excluded, as were studies reporting only mortality.
+Distinct physical and psychological sequelae in patients have been determined and seemed to interfere with quality of life.
+We conclude that paediatric intensive care survivors and their parents have physical and psychological sequelae affecting quality of life.
+Further well-designed prospective studies evaluating sequelae of the original illness and its treatment are warranted.
+BACKGROUND: With the development of new technology, it has recently become practical to resequence the genome of a bacterium after experimental manipulation.
+It is critical though to know the accuracy of the technique used, and to establish confidence that all of the mutations were detected.
+RESULTS: In order to evaluate the accuracy of genome resequencing using the microarray-based Comparative Genome Sequencing service provided by Nimblegen Systems Inc., we resequenced the E. coli strain W3110 Kohara using MG1655 as a reference, both of which have been completely sequenced using traditional sequencing methods.
+CGS detected 7 of 8 small sequence differences, one large deletion, and 9 of 12 IS element insertions present in W3110, but did not detect a large chromosomal inversion.
+In addition, we confirmed that CGS also detected 2 SNPs, one deletion and 7 IS element insertions that are not present in the genome sequence, which we attribute to changes that occurred after the creation of the W3110 lambda clone library.
+CONCLUSION: CGS is an effective way to detect multiple mutations present in one bacterium relative to another, and while highly cost-effective, is prone to certain errors.
+Mutations occurring in repeated sequences or in sequences with a high degree of secondary structure may go undetected.
+It is also critical to follow up on regions of interest in which SNPs were not called because they often indicate deletions or IS element insertions.
+BACKGROUND: Despite the seriousness of dengue-related disease, with an estimated 50–100 million cases of dengue fever and 250,000–500,000 cases of dengue hemorrhagic fever/dengue shock syndrome each year, a clear understanding of dengue pathogenesis remains elusive.
+Because of the lack of a disease model in animals and the complex immune interaction in dengue infection, the study of host response and immunopathogenesis is difficult.
+The development of genomics technology, microarray and high throughput quantitative PCR have allowed researchers to study gene expression changes on a much broader scale.
+We therefore used this approach to investigate the host response in dengue virus-infected cell lines and in patients developing dengue fever.
+METHODOLOGY/PRINCIPAL FINDINGS: Using microarray and high throughput quantitative PCR method to monitor the host response to dengue viral replication in cell line infection models and in dengue patient blood samples, we identified differentially expressed genes along three major pathways; NF-κB initiated immune responses, type I interferon (IFN) and the ubiquitin proteasome pathway.
+Among the most highly upregulated genes were the chemokines IP-10 and I-TAC, both ligands of the CXCR3 receptor.
+Increased expression of IP-10 and I-TAC in the peripheral blood of ten patients at the early onset of fever was confirmed by ELISA.
+A highly upregulated gene in the IFN pathway, viperin, was overexpressed in A549 cells resulting in a significant reduction in viral replication.
+The upregulation of genes in the ubiquitin-proteasome pathway prompted the testing of proteasome inhibitors MG-132 and ALLN, both of which reduced viral replication.
+CONCLUSION/SIGNIFICANCE: Unbiased gene expression analysis has identified new host genes associated with dengue infection, which we have validated in functional studies.
+We showed that some parts of the host response can be used as potential biomarkers for the disease while others can be used to control dengue viral replication, thus representing viable targets for drug therapy.
+BACKGROUND: Although the impact of pathogens on the evolution of the mammalian immune system is still under debate, proteins, which both regulate immune responses and serve as cellular receptors for pathogens should be at the forefront of pathogen-driven host evolution.
+The CEA (carcinoembryonic antigen) gene family codes for such proteins and indeed shows tremendous species-specific variation between human and rodents.
+Since little is known about the CEA gene family in other lineages of placental mammals, we expected to gain new insights into the evolution of the rapidly diverging CEA family by analyzing the CEA family of the dog.
+We found that the gene coding for the ITIM-bearing immunoregulatory molecule CEACAM1 gave rise to a recent expansion of the canine CEA gene family by gene duplication, similar to that previously found in humans and mice.
+However, while the murine and human CEACAMs (carcinoembryonic antigen-related cell adhesion molecules) are predominantly secreted and GPI-anchored, respectively, in the dog, most of the CEACAMs represent ITAM-bearing transmembrane proteins.
+One of these proteins, CEACAM28, exhibits nearly complete sequence identity with the ligand-binding N domain of CEACAM1, but antagonizing signaling motifs in the cytoplasmic tail.
+Comparison of nonsynonymous and synonymous substitutions indicates that the CEACAM28 N domain is under the strongest purifying selection of all canine CEACAM1-related CEACAMs.
+In addition, CEACAM28 shows a similar expression pattern in resting immune cells and tissues as CEACAM1.
+CONCLUSION: Thus, CEACAM1 and CEACAM28 are the first paired immune receptors identified within the CEA gene family, which are expressed on T cells and are most likely involved in the fine-tuning of T cell responses.
+The direction of gene conversion accompanied by purifying selection and expression in immune cells suggests the possibility that CEACAM28 evolved in response to selective pressure imposed by species-specific pathogens.
+The nucleolus reveals the functional organization of the nucleus in which the compartmentation of the different steps of ribosome biogenesis is observed whereas the nucleolar machineries are in permanent exchange with the nucleoplasm and other nuclear bodies.
+After mitosis, nucleolar assembly is a time and space regulated process controlled by the cell cycle.
+In addition, by generating a large volume in the nucleus with apparently no RNA polymerase II activity, the nucleolus creates a domain of retention/sequestration of molecules normally active outside the nucleolus.
+The nucleolus is also a sensor of stress due to the redistribution of the ribosomal proteins in the nucleoplasm by nucleolus disruption.
+The nucleolus plays several crucial functions in the nucleus: in addition to its function as ribosome factory of the cells it is a multifunctional nuclear domain, and nucleolar activity is linked with several pathologies.
+The leaves of Lagerstroemia speciosa (Lythraceae), a Southeast Asian tree more commonly known as banaba, have been traditionally consumed in various forms by Philippinos for treatment of diabetes and kidney related diseases.
+In the 1990s, the popularity of this herbal medicine began to attract the attention of scientists worldwide.
+Since then, researchers have conducted numerous in vitro and in vivo studies that consistently confirmed the antidiabetic activity of banaba.
+Using tumor cells as a cell model, corosolic acid was isolated from the methanol extract of banaba and shown to be an active compound.
+More recently, a different cell model and the focus on the water soluble fraction of the extract led to the discovery of other compounds.
+The ellagitannin Lagerstroemin was identified as an effective component of the banaba extract responsible for the activity.
+In a different approach, using 3T3-L1 adipocytes as a cell model and a glucose uptake assay as the functional screening method, Chen et al.
+Coupling HPLC fractionation with a glucose uptake assay, gallotannins were identified in the banaba extract as components responsible for the activity, not corosolic acid.
+A comparison of published data with results obtained for PGG indicates that PGG has a significantly higher glucose transport stimulatory activity than Lagerstroemin.
+have also shown that PGG exhibits anti-adipogenic properties in addition to stimulating the glucose uptake in adipocytes.
+The combination of glucose uptake and anti-adipogenesis activity is not found in the current insulin mimetic drugs and may indicate a great therapeutic potential of PGG.
+BACKGROUND: With a heightened increase in concern for an influenza pandemic we sought to better understand the 1918 Influenza pandemic, the most devastating epidemic of the previous century.
+METHODOLOGY/PRINCIPAL FINDINGS: We use data from several communities in Maryland, USA as well as two ships that experienced well-documented outbreaks of influenza in 1918.
+Using a likelihood-based method and a nonparametric method, we estimate the serial interval and reproductive number throughout the course of each outbreak.
+This analysis shows the basic reproductive number to be slightly lower in the Maryland communities (between 1.34 and 3.21) than for the enclosed populations on the ships (R(0) = 4.97, SE = 3.31).
+Additionally the effective reproductive number declined to sub epidemic levels more quickly on the ships (within around 10 days) than in the communities (within 30–40 days).
+The mean serial interval for the ships was consistent (3.33, SE = 5.96 and 3.81, SE = 3.69), while the serial intervals in the communities varied substantially (between 2.83, SE = 0.53 and 8.28, SE = 951.95).
+CONCLUSIONS/SIGNIFICANCE: These results illustrate the importance of considering the population dynamics when making statements about the epidemiological parameters of Influenza.
+The methods that we employ for estimation of the reproductive numbers and the serial interval can be easily replicated in other populations and with other diseases.
+INTRODUCTION: Exogenous surfactant is used to treat acute respiratory failure in children, although the benefits and harms in this setting are not clear.
+The objective of the present systematic review is to assess the effect of exogenous pulmonary surfactant on all-cause mortality in children mechanically ventilated for acute respiratory failure.
+METHODS: We searched the MEDLINE, EMBASE, CINAHL and Ovid Healthstar databases, the bibliographies of included trials and review articles, conference proceedings and trial registries.
+We included prospective, randomized, controlled trials of pulmonary surfactant that enrolled intubated and mechanically ventilated children with acute respiratory failure.
+Surfactant use reduced mortality (relative risk = 0.7, 95% confidence interval = 0.4 to 0.97, P = 0.04), was associated with increased ventilator-free days (weighted mean difference = 2.5 days, 95% confidence interval = 0.3 to 4.6 days, P = 0.02) and reduced the duration of ventilation (weighted mean difference = 2.3 days, 95% confidence interval = 0.1 to 4.4 days, P = 0.04).
+CONCLUSION: Surfactant use decreased mortality, was associated with more ventilator-free days and reduced the duration of ventilation.
+Influenza A viruses have a wide host range for infection, from wild waterfowl to poultry to humans.
+Recently, the cross-species transmission of avian influenza A, particularly subtype H5N1, has highlighted the importance of the non-human subtypes and their incidence in the human population has increased over the past decade.
+During cross-species transmission, human disease can range from the asymptomatic to mild conjunctivitis to fulminant pneumonia and death.
+With these cases, however, the risk for genetic change and development of a novel virus increases, heightening the need for public health and hospital measures.
+This review discusses the epidemiology, host range, human disease, outcome, treatment, and prevention of cross-transmission of avian influenza A into humans.
+Worst case scenarios for pandemic influenza planning in the US involve over 700,000 patients requiring mechanical ventilation.
+UK planning predicts a 231% occupancy of current level 3 (intensive care unit) bed capacity.
+Critical care planners need to recognise that mortality is likely to be high and the risk to healthcare workers significant.
+Contingency planning should, therefore, be multi-faceted, involving a robust health command structure, the facility to expand critical care provision in terms of space, equipment and staff and cohorting of affected patients in the early stages.
+It should also be recognised that despite this expansion of critical care, demand will exceed supply and a process for triage needs to be developed that is valid, reproducible, transparent and consistent with distributive justice.
+We advocate the development and validation of physiological scores for use as a triage tool, coupled with candid public discussion of the process.
+BACKGROUND: Avian influenza threatens public health worldwide because it is usually associated with severe illness and, consequently, a higher risk of death.
+A total of 21 human cases were identified, 12 of which were confirmed by the National Institute for Medical Research.
+This study aims to evaluate the efforts at the avian influenza outbreak control in the Van-Dogubeyazit region in 2006 through the experiences of health personnel.
+METHODS: We conducted in-depth interviews with seventeen key informants who took active roles during the avian influenza outbreak in East Turkey during the first months of 2006.
+We gathered information about the initial responses, the progress and management of the outbreak control, and the reactions of the health professionals and the public.
+The findings of the study are reported according to the topics that appeared through thematic analysis of the interview transcripts.
+RESULTS: Following the first suspected avian influenza cases, a Van Crisis Coordination Committee was formed as the coordinating and decision-making body and played an important role in the appropriate timing of decisions.
+The health and agriculture services could not be well coordinated owing to the lack of integrated planning in preparation for outbreak and of integrated surveillance programs.
+Traditional poultry practice together with the low socio-economic status of the people and the lack of health care access in the region seemed to be a major risk for animal to animal and animal to human transmission.
+The strengths and weaknesses of the present health system – primary health care services, national surveillance and notification systems, human resource and management – affected the inter organizational coordination during the outbreak.
+Open communication between the government and the public played an important part in overcoming difficulties.
+CONCLUSION: Although there were problems during the avian influenza outbreak in Turkey, the rapid responses of the central and regional health authorities and the performance of the health workers were the key points in controlling the epidemic.
+The lessons from this outbreak should provide an opportunity for integrating the preparation plans of the health and agricultural organizations, and for revising the surveillance system and enhancing the role of the primary health care services in controlling epidemic disease.
+Developing successful strategies based on knowledge and experience may play a valuable role in delaying an avian influenza pandemic.
+BACKGROUND: The European Influenza Surveillance Scheme (EISS) has collected clinical and virological data on influenza since 1996 in an increasing number of countries.
+The EISS dataset was used to characterise important epidemiological features of influenza activity in Europe during eight winters (1999–2007).
+The following questions were addressed: 1) are the sentinel clinical reports a good measure of influenza activity?
+3) is there a west-east and/or south-north course of peak activity ('spread') of influenza in Europe?
+METHODS: Influenza activity was measured by collecting data from sentinel general practitioners (GPs) and reports by national reference laboratories.
+The sentinel reports were first evaluated by comparing them to the laboratory reports and were then used to assess the timing and spread of influenza activity across Europe during eight seasons.
+RESULTS: We found a good match between the clinical sentinel data and laboratory reports of influenza collected by sentinel physicians (overall match of 72% for +/- 1 week difference).
+We also found a moderate to good match between the clinical sentinel data and laboratory reports of influenza from non-sentinel sources (overall match of 60% for +/- 1 week).
+There were no statistically significant differences between countries using ILI (influenza-like illness) or ARI (acute respiratory disease) as case definition.
+When looking at the peak-weeks of clinical activity, the average length of an influenza season in Europe was 15.6 weeks (median 15 weeks; range 12–19 weeks).
+Plotting the peak weeks of clinical influenza activity reported by sentinel GPs against the longitude or latitude of each country indicated that there was a west-east spread of peak activity (spread) of influenza across Europe in four winters (2001–2002, 2002–2003, 2003–2004 and 2004–2005) and a south-north spread in three winters (2001–2002, 2004–2005 and 2006–2007).
+CONCLUSION: We found that: 1) the clinical data reported by sentinel physicians is a valid indicator of influenza activity; 2) the length of influenza activity across the whole of Europe was surprisingly long, ranging from 12–19 weeks; 3) in 4 out of the 8 seasons, there was a west-east spread of influenza, in 3 seasons a south-north spread; not associated with type of dominant virus in those seasons.
+The burden of infection in industrialized countries has prompted considerable effort to improve the outcomes of patients with sepsis.
+This has been formalized through the Surviving Sepsis Campaign 'bundles', derived from the recommendations of 11 professional societies, which have promoted global improvement in those practices whose primary goal it is to reduce sepsis-related death.
+However, difficulties remain in implementing all of the procedures recommended by the experts, despite the apparent pragmatism of those procedures.
+We summarize the main proposals made by the Surviving Sepsis Campaign and focus on the difficulties associated with making a proper diagnosis and supplying adequate treatment promptly to septic patients.
+One of the primary organs affected by sepsis is the lung, presenting as the Acute Respiratory Distress Syndrome (ARDS).
+Organ damage in sepsis involves an alteration in gene expression, making gene transfer a potential therapeutic modality.
+This work examines the feasibility of applying simian virus 40 (SV40) vectors for pulmonary gene therapy.
+SV40 vectors carrying the luciferase reporter gene (SV/luc) were administered intratracheally immediately after sepsis induction.
+Sham operated (SO) as well as 2CLP rats given intratracheal PBS or adenovirus expressing luciferase served as controls.
+Luc transduction was evaluated by in vivo light detection, immunoassay and luciferase mRNA detection by RT-PCR in tissue harvested from septic rats.
+Vector abundance and distribution into alveolar cells was evaluated using immunostaining for the SV40 VP1 capsid protein as well as by double staining for VP1 and for the surfactant protein C (proSP-C).
+Immunostaining for T-lymphocytes was used to evaluate the cellular immune response induced by the vector.
+RESULTS: Luc expression measured by in vivo light detection correlated with immunoassay from lung tissue harvested from the same rats.
+CONCLUSION: In the present study we have demonstrated efficient uptake and expression of an SV40 vector in the lungs of animals with sepsis-induced ARDS.
+These vectors appear to be capable of in vivo transduction of alveolar type II cells and may thus become a future therapeutic tool.
+BACKGROUND: We previously identified unusual variants of Moloney and Friend ecotropic mouse gammaretroviruses that have altered host range and are cytopathic in cells of the wild mouse species Mus dunni.
+Cytopathicity was attributed to different amino acid substitutions at the same critical env residue involved in receptor interaction: S82F in the Moloney variant Spl574, and S84A in the Friend mouse leukemia virus F-S MLV.
+Because M. dunni cells carry a variant CAT-1 cell surface virus receptor (dCAT-1), we examined the role of this receptor variant in cytopathicity and host range.
+RESULTS: We expressed dCAT-1 or mCAT-1 of NIH 3T3 origin in cells that are not normally infectible with ecotropic MLVs and evaluated the transfectants for susceptibility to virus infection and to virus-induced syncytium formation.
+The dCAT-1 transfectants, but not the mCAT-1 transfectants, were susceptible to virus-induced cytopathicity, and this cytopathic response was accompanied by the accumulation of unintegrated viral DNA.
+The dCAT-1 transfectants, however, did not also reproduce the relative resistance of M. dunni cells to Moloney MLV, and the mCAT-1 transfectants did not show the relative resistance of NIH 3T3 cells to Spl574.
+Western analysis, use of glycosylation inhibitors and mutagenesis to remove receptor glycosylation sites identified a possible role for cell-specific glycosylation in the modulation of virus entry.
+CONCLUSION: Virus entry and virus-induced syncytium formation using the CAT-1 receptor are mediated by a small number of critical amino acid residues in receptor and virus Env.
+Virus entry is modulated by glycosylation of cellular proteins, and this effect is cell and virus-specific.
+HIV-1 uses a programmed -1 ribosomal frameshift to synthesize the precursor of its enzymes, Gag-Pol.
+The frameshift efficiency that is critical for the virus replication, is controlled by an interaction between the ribosome and a specific structure on the viral mRNA, the frameshift stimulatory signal.
+The rate of cap-dependent translation initiation is known to be altered by the TAR RNA structure, present at the 5′ and 3′ end of all HIV-1 mRNAs.
+We investigated here whether changes in translation initiation caused by TAR affect HIV-1 frameshift efficiency.
+CD4+ T cells and 293T cells were transfected with a dual-luciferase construct where the firefly luciferase expression depends upon the HIV-1 frameshift.
+Translation initiation was altered by adding TAR in cis or trans of the reporter mRNA.
+We show that HIV-1 frameshift efficiency correlates negatively with changes in the rate of translation initiation caused by TAR and mediated by PKR.
+A model is presented where changes in the rate of initiation affect the probability of frameshifting by altering the distance between elongating ribosomes on the mRNA, which influences the frequency of encounter between these ribosomes and the frameshift stimulatory signal.
+BACKGROUND: With international concern over emerging infectious diseases (EID) and bioterrorist attacks, public health is being required to have early outbreak detection systems.
+A disease surveillance team was organized to establish a hospital emergency department-based syndromic surveillance system (ED-SSS) capable of automatically transmitting patient data electronically from the hospitals responsible for emergency care throughout the country to the Centers for Disease Control in Taiwan (Taiwan-CDC) starting March, 2004.
+This report describes the challenges and steps involved in developing ED-SSS and the timely information it provides to improve in public health decision-making.
+METHODS: Between June 2003 and March 2004, after comparing various surveillance systems used around the world and consulting with ED physicians, pediatricians and internal medicine physicians involved in infectious disease control, the Syndromic Surveillance Research Team in Taiwan worked with the Real-time Outbreak and Disease Surveillance (RODS) Laboratory at the University of Pittsburgh to create Taiwan's ED-SSS.
+The system was evaluated by analyzing daily electronic ED data received in real-time from the 189 hospitals participating in this system between April 1, 2004 and March 31, 2005.
+RESULTS: Taiwan's ED-SSS identified winter and summer spikes in two syndrome groups: influenza-like illnesses and respiratory syndrome illnesses, while total numbers of ED visits were significantly higher on weekends, national holidays and the days of Chinese lunar new year than weekdays (p < 0.001).
+It also identified increases in the upper, lower, and total gastrointestinal (GI) syndrome groups starting in November 2004 and two clear spikes in enterovirus-like infections coinciding with the two school semesters.
+Using ED-SSS for surveillance of influenza-like illnesses and enteroviruses-related infections has improved Taiwan's pandemic flu preparedness and disease control capabilities.
+CONCLUSION: Taiwan's ED-SSS represents the first nationwide real-time syndromic surveillance system ever established in Asia.
+The system can be adapted to other cultural and language environments for better global surveillance of infectious diseases and international collaboration.
+BACKGROUND: Cytotoxic T cell (CTL) cross-reactivity is believed to play a pivotal role in generating immune responses but the extent and mechanisms of CTL cross-reactivity remain largely unknown.
+Several studies suggest that CTL clones can recognize highly diverse peptides, some sharing no obvious sequence identity.
+The emerging realization in the field is that T cell receptors (TcR) recognize multiple distinct ligands.
+PRINCIPAL FINDINGS: First, we analyzed peptide scans of the HIV epitope SLFNTVATL (SFL9) and found that TCR specificity is position dependent and that biochemically similar amino acid substitutions do not drastically affect recognition.
+Inspired by this, we developed a general model of TCR peptide recognition using amino acid similarity matrices and found that such a model was able to predict the cross-reactivity of a diverse set of CTL epitopes.
+With this model, we were able to demonstrate that seemingly distinct T cell epitopes, i.e., ones with low sequence identity, are in fact more biochemically similar than expected.
+Additionally, an analysis of HIV immunogenicity data with our model showed that CTLs have the tendency to respond mostly to peptides that do not resemble self-antigens.
+CONCLUSIONS: T cell cross-reactivity can thus, to an extent greater than earlier appreciated, be explained by amino acid similarity.
+The results presented in this paper will help resolving some of the long-lasting discussions in the field of T cell cross-reactivity.
+BACKGROUND: Human rhinoviruses (HRVs) are the most frequently detected pathogens in acute respiratory tract infections (ARTIs) and yet little is known about the prevalence, recurrence, structure and clinical impact of individual members.
+During 2007, the complete coding sequences of six previously unknown and highly divergent HRV strains were reported.
+To catalogue the molecular and clinical features distinguishing the divergent HRV strains, we undertook, for the first time, in silico analyses of all available polyprotein sequences and performed retrospective reviews of the medical records of cases in which variants of the prototype strain, HRV-QPM, had been detected.
+METHODOLOGY/PRINCIPLE FINDINGS: Genomic analyses revealed that the six divergent strains, residing within a clade we previously called HRV A2, had the shortest polyprotein of all picornaviruses investigated.
+Structure-based amino acid alignments identified conserved motifs shared among members of the genus Rhinovirus as well as substantive deletions and insertions unique to the divergent strains.
+Deletions mostly affected regions encoding proteins traditionally involved in antigenicity and serving as HRV and HEV receptor footprints.
+Because the HRV A2 strains cannot yet be cultured, we created homology models of predicted HRV-QPM structural proteins.
+In silico comparisons confirmed that HRV-QPM was most closely related to the major group HRVs.
+HRV-QPM was most frequently detected in infants with expiratory wheezing or persistent cough who had been admitted to hospital and required supplemental oxygen.
+CONCLUSIONS: The divergent strains did not meet classification requirements for any existing species of the genus Rhinovirus or Enterovirus.
+HRV A2 strains should be partitioned into at least one new species, putatively called Human rhinovirus C, populated by members detected with high frequency, from individuals with respiratory symptoms requiring hospital admission.
+In spite of protective ventilatory strategies, Acute Lung Injury (ALI) remains associated with high morbidity and mortality.
+One reason for the lack of therapeutic options might be that ALI is a co-morbid event associated with a diverse family of diseases and, thus, may be the result of distinct pathological processes.
+Among them, activated neutrophil- (PMN-) induced tissue injury and epithelial cell apoptosis mediated lung damage represent two potentially important candidate pathomechanisms that have been put forward.
+Several approaches have been undertaken to test these hypotheses, with substantial success in the treatment of experimental forms of ALI.
+With this in mind, we will summarize these two current hypotheses of ALI briefly, emphasizing the role of apoptosis in regulating PMN and/or lung epithelial cell responses.
+In addition, the contribution that Fas-mediated inflammation may play as a potential biological link between lung cell apoptosis and PMN recruitment will be considered, as well as the in vivo application of small interfering RNA (siRNA) as a novel approach to the inhibition of ALI and its therapeutic implications.
+RNA–RNA recombination is an important pathway in virus evolution and has been described for many viruses.
+Here, we show that the small movement protein (2b) was able to promote selection of RNA 1/2–RNA 3 recombinants within a chimeric virus having RNAs 1 and 2 from cucumber mosaic virus, and RNA 3 from the related tomato aspermy virus, along with heterologous 2b genes.
+The source of the 2b also determined the selection of the acceptor RNA and the crossover site, as well as affecting the rate of selection of the recombinant RNAs.
+A 163-nt tandem repeat in RNA 3 significantly affected the rate of selection of the recombinant RNA, while a single nucleotide within the repeat affected the crossover site.
+The recombination occurred in a non-random manner, involved no intermediates and probably was generated via a copy-choice mechanism during (+) strand RNA synthesis.
+BACKGROUND: The construction of complex spatial simulation models such as those used in network epidemiology, is a daunting task due to the large amount of data involved in their parameterization.
+Such data, which frequently resides on large geo-referenced databases, has to be processed and assigned to the various components of the model.
+All this just to construct the model, then it still has to be simulated and analyzed under different epidemiological scenarios.
+This workflow can only be achieved efficiently by computational tools that can automate most, if not all, these time-consuming tasks.
+In this paper, we present a simulation software, Epigrass, aimed to help designing and simulating network-epidemic models with any kind of node behavior.
+RESULTS: A Network epidemiological model representing the spread of a directly transmitted disease through a bus-transportation network connecting mid-size cities in Brazil.
+Results show that the topological context of the starting point of the epidemic is of great importance from both control and preventive perspectives.
+CONCLUSION: Epigrass is shown to facilitate greatly the construction, simulation and analysis of complex network models.
+The output of model results in standard GIS file formats facilitate the post-processing and analysis of results by means of sophisticated GIS software.
+Primary biliary cirrhosis (PBC) is an autoimmune disease characterized by intrahepatic bile duct destruction and the production of anti-mitochondrial antibodies (AMA).
+The absence of an animal model has been a striking impedance in defining the molecular basis of disease.
+Previous work has suggested that SJL/J mice immunize with the pyruvate dehydrogenase complex (PDC-E2), the major mitochondrial autoantigen of PBC, leads to the development of lymphoid cell infiltration in portal tracts and a model system coined autoimmune cholangitis.
+We hypothesized that this pathology would be augmented if immunization occurred in the presence of IFN-γ injections.
+More importantly, the livers from mice immunized with PDC-E2 and/or those immunized with α-casein all displayed lymphoid cell infiltration to the portal tracts, irrespective of bile duct size.
+Indeed, there was no significant difference between the experimental and the control groups by histologic analysis.
+BACKGROUND: La Crosse virus (LACV), family Bunyaviridae, was first identified as a human pathogen in 1960 after its isolation from a 4 year-old girl with fatal encephalitis in La Crosse, Wisconsin.
+LACV is a major cause of pediatric encephalitis in North America and infects up to 300,000 persons each year of which 70–130 result in severe disease of the central nervous system (CNS).
+As an initial step in the establishment of useful animal models to support vaccine development, we examined LACV infectivity, pathogenesis, and immunogenicity in both weanling mice and rhesus monkeys.
+RESULTS: Following intraperitoneal inoculation of mice, LACV replicated in various organs before reaching the CNS where it replicates to high titer causing death from neurological disease.
+The peripheral site where LACV replicates to highest titer is the nasal turbinates, and, presumably, LACV can enter the CNS via the olfactory neurons from nasal olfactory epithelium.
+The mouse infectious dose(50 )and lethal dose(50 )was similar for LACV administered either intranasally or intraperitoneally.
+LACV was highly infectious for rhesus monkeys and infected 100% of the animals at 10 PFU.
+CONCLUSION: In mice, LACV likely gains access to the CNS via the blood stream or via olfactory neurons.
+The ability to efficiently infect mice intranasally raises the possibility that LACV might use this route to infect its natural hosts.
+Rhesus monkeys are susceptible to LACV infection and develop strong neutralizing antibody responses after inoculation with as little as 10 PFU.
+Mice and rhesus monkeys are useful animal models for LACV vaccine immunologic testing although the rhesus monkey model is not optimal.
+Measles virus is a negative‐sense, single‐stranded RNA virus within theMononegavirales order,which includes several human pathogens, including rabies, Ebola, Nipah, and Hendra viruses.
+Themeasles virus nucleoprotein consists of a structured N‐terminal domain, and of an intrinsically disordered C‐terminal domain, N(TAIL) (aa 401–525), which undergoes induced folding in the presence of the C‐terminal domain (XD, aa 459–507) of the viral phosphoprotein.
+With in N(TAIL), an α‐helical molecular recognition element (α‐MoRE, aa 488–499) involved in binding to P and in induced folding was identified and then observed in the crystal structure of XD.
+Using small‐angle X‐ray scattering, we have derived a low‐resolution structural model of the complex between XD and N(TAIL), which shows that most of N(TAIL) remains disordered in the complex despite P‐induced folding within the α‐MoRE.
+The model consists of an extended shape accommodating the multiple conformations adopted by the disordered N‐terminal region of N(TAIL), and of a bulky globular region, corresponding to XD and to the C terminus of N(TAIL) (aa 486–525).
+Using surface plasmon resonance, circular dichroism, fluorescence spectroscopy, and heteronuclear magnetic resonance, we show that N(TAIL) has an additional site (aa 517–525) involved in binding to XD but not in the unstructured‐to‐structured transition.
+This work provides evidence that intrinsically disordered domains can establish complex interactions with their partners, and can contact them through multiple sites that do not all necessarily gain regular secondary structure.
+BACKGROUND: Several public health strategic interventions are required for effective prevention and control of avian influenza (AI) and it is necessary to create a communication plan to keep families adequately informed on how to avoid or reduce exposure.
+This investigation determined the knowledge, attitudes, and behaviors relating to AI among an adult population in Italy.
+METHODS: From December 2005 to February 2006 a random sample of 1020 adults received a questionnaire about socio-demographic characteristics, knowledge of transmission and prevention about AI, attitudes towards AI, behaviors regarding use of preventive measures and food-handling practices, and sources of information about AI.
+Those in higher socioeconomic classes were more likely to identify the modes of transmission and the animals' vehicles for AI.
+Those older, who knew the modes of transmission and the animals' vehicles for AI, and who still need information, were more likely to know that washing hands soap before and after touching raw poultry meat and using gloves is recommended to avoid spreading of AI through food.
+The risk of being infected was significantly higher in those from lower socioeconomic classes, if they did not know the definition of AI, if they knew that AI could be transmitted by eating and touching raw eggs and poultry foods, and if they did not need information.
+Compliance with the hygienic practices during handling of raw poultry meat was more likely in those who perceived to be at higher risk, who knew the hygienic practices, who knew the modes of transmission and the animals' vehicles for AI, and who received information from health professionals and scientific journals.
+CONCLUSION: Respondents demonstrate no detailed understanding of AI, a greater perceived risk, and a lower compliance with precautions behaviors and health educational strategies are strongly needed.
+BACKGROUND: Knowledge about the complete genome constellation of seasonal influenza A viruses from different countries is valuable for monitoring and understanding of the evolution and migration of strains.
+Few complete genome sequences of influenza A viruses from Europe are publicly available at the present time and there have been few longitudinal genome studies of human influenza A viruses.
+We have studied the evolution of circulating human H3N2, H1N1 and H1N2 influenza A viruses from 1999 to 2006, we analysed 234 Danish human influenza A viruses and characterised 24 complete genomes.
+RESULTS: H3N2 was the prevalent strain in Denmark during the study period, but H1N1 dominated the 2000–2001 season.
+After years of little genetic change in the H1N1 viruses the 2005–2006 season presented H1N1 of greater variability than before.
+This indicates that H1N1 viruses are evolving and that H1N1 soon is likely to be the prevalent strain again.
+The evolution has been stochastic, influenced by small "jumps" in genetic distance rather than constant drift, especially with the introduction of the Fujian-like viruses in 2002–2003.
+The evolution of H3N2 viruses have also been influenced by gene reassortments between lineages from different seasons.
+The antigenic site B in H3N2 HA was the preferred site for genetic change during the study period probably because the site A has been masked by glycosylations.
+Substitutions at CTL-epitopes in the genes coding for the neuraminidase (NA), polymerase acidic protein (PA), matrix protein 1 (M1), non-structural protein 1 (NS1) and especially the nucleoprotein (NP) were observed.
+The N-linked glycosylation pattern varied during the study period and the H3N2 isolates from 2004 to 2006 were highly glycosylated with ten predicted sequons in HA, the highest amount of glycosylations observed in this study period.
+CONCLUSION: The present study is the first to our knowledge to characterise the evolution of complete genomes of influenza A H3N2, H1N1 and H1N2 isolates from Europe over a time period of seven years from 1999 to 2006.
+More precise knowledge about the circulating strains may have implications for predicting the following season strains and thereby better matching the vaccine composition.
+BACKGROUND: AIDS, SARS, and the recent epidemics of the avian-flu have all served to remind us the debate over the limits of the moral duty to care.
+It is important to first consider the question of whether or not the "duty to treat" might be subject to contextual constraints.
+The purpose of this study was to investigate the opinions and beliefs held by both physicians and dentists regarding the occupational risks of infectious diseases, and to analyze the argument that the notion of "presumed consent" on the part of professionals may be grounds for supporting the duty to treat.
+METHODS: For this cross-sectional survey, the study population was selected from among physicians and dentists in Ankara.
+RESULTS: In total, 79.6% of the participants said that they either had some degree of knowledge about the risks when they chose their profession or that they learned of the risks later during their education and training.
+Of the participants, 5.2% said that they would not have chosen this profession if they had been informed of the risks.
+It was found that 57% of the participants believed that there is a standard level of risk, and 52% of the participants stated that certain diseases would exceed the level of acceptable risk unless specific protective measures were implemented.
+CONCLUSION: If we use the presumed consent argument to establish the duty of the HCW to provide care, we are confronted with problems ranging over the difficulty of choosing a profession autonomously, the constant level of uncertainty present in the medical profession, the near-impossibility of being able to evaluate retrospectively whether every individual was informed, and the seemingly inescapable problem that this practice would legitimize, and perhaps even foster, discrimination against patients with certain diseases.
+Our findings suggest that another problem can be added to the list: one-fifth of the participants in this study either lacked adequate knowledge of the occupational risks when they chose the medical profession or were not sufficiently informed of these risks during their faculty education and training.
+Furthermore, in terms of the moral duty to provide care, it seems that most HCWs are more concerned about the availability of protective measures than about whether they had been informed of a particular risk beforehand.
+For all these reasons, the presumed consent argument is not persuasive enough, and cannot be used to justify the duty to provide care.
+It is therefore more useful to emphasize justifications other than presumed consent when defining the duty of HCWs to provide care, such as the social contract between society and the medical profession and the fact that HCWs have a greater ability to provide medical aid.
+BACKGROUND: Here we describe a new technical solution for optimization of Pichia pastoris shake flask cultures with the example of production of stable human type II collagen.
+Production of recombinant proteins in P. pastoris is usually performed by controlling gene expression with the strong AOX1 promoter, which is induced by addition of methanol.
+Optimization of processes using the AOX1 promoter in P. pastoris is generally done in bioreactors by fed-batch fermentation with a controlled continuous addition of methanol for avoiding methanol toxification and carbon/energy starvation.
+The development of feeding protocols and the study of AOX1-controlled recombinant protein production have been largely made in shake flasks, although shake flasks have very limited possibilities for measurement and control.
+RESULTS: By applying on-line pO(2 )monitoring we demonstrate that the widely used pulse feeding of methanol results in long phases of methanol exhaustion and consequently low expression of AOX1 controlled genes.
+The presented solution applies a wireless feeding unit which can be flexibly positioned and allows the use of computer-controlled feeding profiles.
+By using the human collagen II as an example we show that a quasi-continuous feeding profile, being the simplest way of a fed-batch fermentation, results in a higher production level of human collagen II.
+Moreover, the product has a higher proteolytic stability compared to control cultures due to the increased expression of human collagen prolyl 4-hydroxylase as monitored by mRNA and protein levels.
+CONCLUSION: The recommended standard protocol for methanol addition in shake flasks using pulse feeding is non-optimal and leads to repeated long phases of methanol starvation.
+The presented wireless feeding unit, together with an on-line monitoring system offers a flexible, simple, and low-cost solution for initial optimization of the production in shake flasks which can be performed in parallel.
+By this way the fed-batch strategy can be applied from the early screening steps also in laboratories which do not have access to high-cost and complicated bioreactor systems.
+While foreign pathogens and their products have long been known to activate the innate immune system, the recent recognition of a group of endogenous molecules that serve a similar function has provided a framework for understanding the overlap between the inflammatory responses activated by pathogens and injury.
+These endogenous molecules, termed alarmins, are normal cell constituents that can be released into the extracellular milieu during states of cellular stress or damage and subsequently activate the immune system.
+One nuclear protein, High mobility group box-1 (HMGB1), has received particular attention as fulfilling the functions of an alarmin by being involved in both infectious and non-infectious inflammatory conditions.
+Once released, HMGB1 signals through various receptors to activate immune cells involved in the immune process.
+Although initial studies demonstrated HMGB1 as a late mediator of sepsis, recent findings indicate HMGB1 to have an important role in models of non-infectious inflammation, such as autoimmunity, cancer, trauma, and ischemia reperfusion injury.
+Furthermore, in contrast to its pro-inflammatory functions, there is evidence that HMGB1 also has restorative effects leading to tissue repair and regeneration.
+The complex functions of HMGB1 as an archetypical alarmin are outlined here to review our current understanding of a molecule that holds the potential for treatment in many important human conditions.
+Previous studies have reported the clinical usefulness of reverse transcription-polymerase chain reaction (RT-PCR) detection of thyroglobulin (TG) mRNA in the peripheral blood of patients with differentiated thyroid carcinoma.
+To evaluate this usefulness, we measured TG mRNA in the peripheral blood of patients diagnosed with thyroid carcinoma after total thyroidectomy by real-time quantitative RT-PCR using glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA as an internal control.
+Surprisingly, we detected TG mRNA in all samples obtained after total thyroidectomy, including those from 4 medullary carcinomas.
+Further, there was no statistical difference in expression levels of TG mRNA in the patients with or without metastasis, and no significant correlation was found between serum TG concentrations and the expression levels of TG mRNA.
+These results give rise to a question regarding the clinical applications of not only RT-PCR detection but also quantitative measurement of TG mRNA in peripheral blood.
+BACKGROUND: Jena Virus (JV), a bovine Norovirus, causes enteric disease in cattle and represents a potential model for the study of enteric norovirus infection and pathogenesis.
+The positive sense RNA genome of JV is organised into ORF1 (non-structural proteins), ORF2 (major capsid protein) and ORF3 (minor capsid protein).
+The lack of a cell culture system for studying JV replication has meant that work to date has relied upon in vitro systems to study non-structural protein synthesis and processing.
+PRINCIPAL FINDINGS: Only two of the three major ORF1 proteins were identified (p110 and 2C) following in vitro translation of JV RNA, the N-term protein was not detected.
+The N-term encoding genomic sequence (5′GS) was tested for IRES-like function in a bi-cistronic system and displayed no evidence of IRES-like activity.
+The site of translation initiation in JV was determined to be at the predicted nucleotide 22.
+Following the insertion of an epitope within the 5′GS the JV N-term protein was identified in vitro and within RNA transfected cells.
+CONCLUSIONS: The in vitro transcription/translation system is currently the best system for analysing protein synthesis and processing in JV.
+Unlike similarly studied human noroviruses JV initially did not appear to express the N-terminal protein, presenting the possibility that the encoding RNA sequence had a regulatory function, most likely involved in translation initiation in an IRES-like manner.
+This was not the case and, following determination of the site of translation initiation the N-term protein was detected using an epitope tag, both in vitro and in vivo.
+Although slightly larger than predicted the N-term protein was detected in a processed form in vivo, thus not only demonstrating initial translation of the ORF1 polyprotein but also activity of the viral protease.
+BACKGROUND: There are sparse data on whether non-pharmaceutical interventions can reduce the spread of influenza.
+We implemented a study of the feasibility and efficacy of face masks and hand hygiene to reduce influenza transmission among Hong Kong household members.
+METHODOLOGY/PRINCIPAL FINDINGS: We conducted a cluster randomized controlled trial of households (composed of at least 3 members) where an index subject presented with influenza-like-illness of <48 hours duration.
+After influenza was confirmed in an index case by the QuickVue Influenza A+B rapid test, the household of the index subject was randomized to 1) control or 2) surgical face masks or 3) hand hygiene.
+Nose and throat swabs were collected from index subjects and all household contacts at each home visit and tested by viral culture.
+The primary outcome measure was laboratory culture confirmed influenza in a household contact; the secondary outcome was clinically diagnosed influenza (by self-reported symptoms).
+We randomized 198 households and completed follow up home visits in 128; the index cases in 122 of those households had laboratory-confirmed influenza.
+There were 21 household contacts with laboratory confirmed influenza corresponding to a secondary attack ratio of 6%.
+The laboratory-based or clinical secondary attack ratios did not significantly differ across the intervention arms.
+CONCLUSIONS/SIGNIFICANCE: The secondary attack ratios were lower than anticipated, and lower than reported in other countries, perhaps due to differing patterns of susceptibility, lack of significant antigenic drift in circulating influenza virus strains recently, and/or issues related to the symptomatic recruitment design.
+BACKGROUND: Fast changes in human demographics worldwide, coupled with increased mobility, and modified land uses make the threat of emerging infectious diseases increasingly important.
+Currently there is worldwide alert for H5N1 avian influenza becoming as transmissible in humans as seasonal influenza, and potentially causing a pandemic of unprecedented proportions.
+Here we show how epidemiological surveillance data for emerging infectious diseases can be interpreted in real time to assess changes in transmissibility with quantified uncertainty, and to perform running time predictions of new cases and guide logistics allocations.
+METHODOLOGY/PRINCIPAL FINDINGS: We develop an extension of standard epidemiological models, appropriate for emerging infectious diseases, that describes the probabilistic progression of case numbers due to the concurrent effects of (incipient) human transmission and multiple introductions from a reservoir.
+The model is cast in terms of surveillance observables and immediately suggests a simple graphical estimation procedure for the effective reproductive number R (mean number of cases generated by an infectious individual) of standard epidemics.
+For emerging infectious diseases, which typically show large relative case number fluctuations over time, we develop a Bayesian scheme for real time estimation of the probability distribution of the effective reproduction number and show how to use such inferences to formulate significance tests on future epidemiological observations.
+CONCLUSIONS/SIGNIFICANCE: Violations of these significance tests define statistical anomalies that may signal changes in the epidemiology of emerging diseases and should trigger further field investigation.
+We apply the methodology to case data from World Health Organization reports to place bounds on the current transmissibility of H5N1 influenza in humans and establish a statistical basis for monitoring its evolution in real time.
+BACKGROUND: Foot-and-mouth disease (FMD) is a highly contagious disease of livestock that causes severe economic loss in susceptible cloven-hoofed animals.
+Although the traditional inactivated vaccine has been proved effective, it may lead to a new outbreak of FMD because of either incomplete inactivation of FMDV or the escape of live virus from vaccine production workshop.
+Thus, it is urgent to develop a novel FMDV vaccine that is safer, more effective and more economical than traditional vaccines.
+METHODOLOGY AND PRINCIPAL FINDINGS: A recombinant silkworm baculovirus Bm-P12A3C which contained the intact P1-2A and 3C protease coding regions of FMDV Asia 1/HNK/CHA/05 was developed.
+Indirect immunofluorescence test and sandwich-ELISA were used to verify that Bm-P12A3C could express the target cassette.
+Expression products from silkworm were diluted to 30 folds and used as antigen to immunize cattle.
+After challenge with virulent homologous virus, four of the five animals were completely protected, and clinical symptoms were alleviated and delayed in the remaining one.
+Furthermore, a PD(50) (50% bovine protective dose) test was performed to assess the bovine potency of the subunit vaccine.
+CONCLUSION: The results suggest that this strategy might be used to develop the new subunit FMDV vaccine.
+In networks, nodes may preferentially contact other nodes with similar (assortatively mixed) or dissimilar (disassortatively mixed) numbers of contacts.
+Different patterns of contact support different epidemic dynamics, potentially affecting the efficacy of control measures such as contact tracing, which aims to identify and isolate nodes with infectious contacts.
+We used stochastic simulations to investigate the effects of mixing patterns on epidemic dynamics and contact-tracing efficacy.
+For uncontrolled epidemics, outbreaks occur at lower infection rates for more assortatively mixed networks, with faster initial epidemic growth rate and shorter epidemic duration than for disassortatively mixed networks.
+Contact tracing performs better for assortative mixing where epidemic size is large and tracing rate low, but it performs better for disassortative mixing at higher contact rates.
+For assortatively mixed networks, disease spreads first to highly connected nodes, but this is balanced by contact tracing quickly identifying these same nodes.
+The converse is true for disassortative mixing, where both disease and tracing are less likely to target highly connected nodes.
+For small epidemics, contact tracing is more effective on disassortative networks due to the greater resilience of assortative networks to link removal.
+Multi-step contact tracing is more effective than single-step tracing for assortative mixing, but this effect is smaller for disassortatively mixed networks.
+BACKGROUND: Although primary health care, and in particular, general practice will be at the frontline in the response to pandemic influenza, there are no frameworks to guide systematic planning for this task or to appraise available plans for their relevance to general practice.
+We aimed to develop a framework that will facilitate planning for general practice, and used it to appraise pandemic plans from Australia, England, USA, New Zealand and Canada.
+METHODOLOGY/PRINCIPAL FINDINGS: We adapted the Haddon matrix to develop the framework, populating its cells through a multi-method study that incorporated the peer-reviewed and grey literature, interviews with general practitioners, practice nurses and senior decision-makers, and desktop simulation exercises.
+We used the framework to analyse 89 publicly-available jurisdictional plans at similar managerial levels in the five countries.
+The framework identifies four functional domains: clinical care for influenza and other needs, public health responsibilities, the internal environment and the macro-environment of general practice.
+Most plans either ignored or were sketchy about non-influenza clinical needs, and about the contribution of general practice to public health beyond surveillance.
+Collaborations between general practices were addressed in few plans, and inter-relationships with the broader health system, even less frequently.
+CONCLUSIONS: This is the first study to provide a framework to guide general practice planning for pandemic influenza.
+Engaging general practice effectively in planning is challenging, particularly where governance structures for primary health care are weak.
+Organisms exposed to reactive oxygen species, generated endogenously during respiration or by environmental conditions, undergo oxidative stress.
+Stress response can either repair the damage or activate one of the programmed cell death (PCD) mechanisms, for example apoptosis, and finally end in cell death.
+One striking characteristic, which accompanies apoptosis in both vertebrates and yeast, is a fragmentation of cellular DNA and mammalian apoptosis is often associated with degradation of different RNAs.
+We show that in yeast exposed to stimuli known to induce apoptosis, such as hydrogen peroxide, acetic acid, hyperosmotic stress and ageing, two large subunit ribosomal RNAs, 25S and 5.8S, became extensively degraded with accumulation of specific intermediates that differ slightly depending on cell death conditions.
+This process is most likely endonucleolytic, is correlated with stress response, and depends on the mitochondrial respiratory status: rRNA is less susceptible to degradation in respiring cells with functional defence against oxidative stress.
+In addition, RNA fragmentation is independent of two yeast apoptotic factors, metacaspase Yca1 and apoptosis-inducing factor Aif1, but it relies on the apoptotic chromatin condensation induced by histone H2B modifications.
+These data describe a novel phenotype for certain stress- and ageing-related PCD pathways in yeast.
+Viruses adapt to their hosts by evading defense mechanisms and taking over cellular metabolism for their own benefit.
+Alterations in cell metabolism as well as side-effects of antiviral responses contribute to symptoms development and virulence.
+Sometimes, a virus may spill over from its usual host species into a novel one, where usually will fail to successfully infect and further transmit to new host.
+However, in some cases, the virus transmits and persists after fixing beneficial mutations that allow for a better exploitation of the new host.
+Here we report results from an evolution experiment in which a plant virus was allowed to infect and evolve on a naïve host.
+After 17 serial passages, the viral genome has accumulated only five changes, three of which were non-synonymous.
+An amino acid substitution in the viral VPg protein was responsible for the appearance of symptoms, whereas one substitution in the viral P3 protein the epistatically contributed to exacerbate severity.
+DNA microarray analyses show that the evolved and ancestral viruses affect the global patterns of host gene expression in radically different ways.
+A major difference is that genes involved in stress and pathogen response are not activated upon infection with the evolved virus, suggesting that selection has favored viral strategies to escape from host defenses.
+BACKGROUND: Human metapneumovirus (hMPV) infection can cause acute lower respiratory tract illness in infants, the immunocompromised, and the elderly.
+Using a variant of hMPV/NL/1/00 that does not require trypsin supplementation for growth in tissue culture, we deleted the M2-2 gene and evaluated the replication of rhMPV/ΔM2-2 virus in vitro and in vivo.
+RESULTS: In vitro studies showed that the ablation of M2-2 increased the propensity for insertion of U nucleotides in poly-U tracts of the genomic RNA.
+In addition, viral transcription was up-regulated although the level of genomic RNA remained comparable to rhMPV.
+In vivo, rhMPV/ΔM2-2 was attenuated compared to rhMPV in the lungs and nasal turbinates of hamsters.
+Hamsters immunized with one dose of rhMPV/ΔM2-2 were protected from challenge with 10(6 )PFU of wild type (wt) hMPV/NL/1/00.
+CONCLUSION: Our results suggest that hMPV M2-2 alters regulation of transcription and influences the fidelity of the polymerase complex during viral genome replication.
+In the hamster model, rhMPVΔM2-2 is attenuated and protective suggesting that deletion of M2-2 may result in a potential live vaccine candidate.
+A more thorough knowledge of the hMPV polymerase complex and the role of M2-2 during hMPV replication are being studied as we develop a potential live hMPV vaccine candidate that lacks M2-2 expression.
+Diseases of mucosal inflammation represent important causes of morbidity and mortality, and have led to intense research efforts to understand the factors that lead to their development.
+It is well accepted that a breakdown of the normally impermeant epithelial barrier of the intestine, the lung, and the kidney is associated with the development of inflammatory disease in these organs, yet significant controversy exists as to how this breakdown actually occurs, and how such a breakdown may lead to inflammation.
+In this regard, much work has focused upon the role of the epithelium as an “innocent bystander,” a target of a leukocyte-mediated inflammatory cascade that leads to its destruction in the mucosal inflammatory process.
+However, recent evidence from a variety of laboratories indicates that the epithelium is not merely a passive component in the steps that lead to mucosal inflammation, but is a central participant in the process.
+In addressing this controversy, we and others have determined that epithelial cells express Toll-like receptors (TLRs) of the innate immune system, and that activation of TLRs by endogenous and exogenous ligands may play a central role in determining the balance between a state of “mucosal homeostasis,” as is required for optimal organ function, and “mucosal injury,” leading to mucosal inflammation and barrier breakdown.
+In particular, activation of TLRs within intestinal epithelial cells leads to the development of cellular injury and impairment in mucosal repair in the pathogenesis of intestinal inflammation, while activation of TLRs in the lung and kidney may participate in the development of pneumonitis and nephritis respectively.
+Recent work in support of these concepts is extensively reviewed, while essential areas of further study that are required to determine the significance of epithelial TLR signaling during states of health and disease are outlined.
+BACKGROUND: Protein ubiquitination and/or degradation by the ubiquitin/proteasome system (UPS) have been recognized as critical mechanisms in the regulation of numerous essential cellular functions.
+Using murine cardiomyocytes, we have previously demonstrated that the UPS plays a key role in the replication of coxsackievirus B3 (CVB3), an important human pathogen associated with various diseases.
+To further elucidate the underlying mechanisms, we examined the interplay between the UPS and CVB3, focusing on the role of ubiquitination in viral lifecycle.
+METHODOLOGY/PRINCIPAL FINDINGS: As assessed by in situ hybridization, Western blot, and plaque assay, we showed that proteasome inhibition decreased CVB3 RNA replication, protein synthesis, and viral titers in HeLa cells.
+However, we found viral infection led to an accumulation of protein-ubiquitin conjugates, accompanied by a decreased protein expression of free ubiquitin, implicating an important role of ubiquitination in the UPS-mediated viral replication.
+Using small-interfering RNA, we demonstrated that gene-silencing of ubiquitin significantly reduced viral titers, possibly through downregulation of protein ubiquitination and subsequent alteration of protein function and/or degradation.
+Inhibition of deubiquitinating enzymes apparently enhances the inhibitory effects of proteasome inhibitors on CVB3 replication.
+Finally, by immunoprecipitation, we showed that coxsackieviral polymerase 3D was post-translationally modified by ubiquitination and such modification might be a prerequisite for its function in transcriptional regulation of viral genome.
+CONCLUSION: Coxsackievirus infection promotes protein ubiquitination, contributing to effective viral replication, probably through ubiquitin modification of viral polymerase.
+Face-masks worn by the general population could be an accessible and affordable intervention, if effective when worn under routine circumstances.
+METHODOLOGY: We assessed transmission reduction potential provided by personal respirators, surgical masks and home-made masks when worn during a variety of activities by healthy volunteers and a simulated patient.
+PRINCIPAL FINDINGS: All types of masks reduced aerosol exposure, relatively stable over time, unaffected by duration of wear or type of activity, but with a high degree of individual variation.
+Personal respirators were more efficient than surgical masks, which were more efficient than home-made masks.
+Outward protection (mask wearing by a mechanical head) was less effective than inward protection (mask wearing by healthy volunteers).
+CONCLUSIONS/SIGNIFICANCE: Any type of general mask use is likely to decrease viral exposure and infection risk on a population level, in spite of imperfect fit and imperfect adherence, personal respirators providing most protection.
+Masks worn by patients may not offer as great a degree of protection against aerosol transmission.
+CD133 (prominin-1), a 5-transmembrane glycoprotein, has recently been considered to be an important marker that represents the subset population of cancer stem-like cells.
+Herein we report the isolation of CD133-positive cells (LC-CD133(+)) and CD133-negative cells (LC-CD133(−)) from tissue samples of ten patients with non-small cell lung cancer (LC) and five LC cell lines.
+LC-CD133(+) displayed higher Oct-4 expressions with the ability to self-renew and may represent a reservoir with proliferative potential for generating lung cancer cells.
+Furthermore, LC-CD133(+), unlike LC-CD133(−), highly co-expressed the multiple drug-resistant marker ABCG2 and showed significant resistance to chemotherapy agents (i.e., cisplatin, etoposide, doxorubicin, and paclitaxel) and radiotherapy.
+The treatment of Oct-4 siRNA with lentiviral vector can specifically block the capability of LC-CD133(+) to form spheres and can further facilitate LC-CD133(+) to differentiate into LC-CD133(−).
+In addition, knock-down of Oct-4 expression in LC-CD133(+) can significantly inhibit the abilities of tumor invasion and colony formation, and increase apoptotic activities of caspase 3 and poly (ADP-ribose) polymerase (PARP).
+Finally, in vitro and in vivo studies further confirm that the treatment effect of chemoradiotherapy for LC-CD133(+) can be improved by the treatment of Oct-4 siRNA.
+In conclusion, we demonstrated that Oct-4 expression plays a crucial role in maintaining the self-renewing, cancer stem-like, and chemoradioresistant properties of LC-CD133(+).
+Future research is warranted regarding the up-regulated expression of Oct-4 in LC-CD133(+) and malignant lung cancer.
+Germ-free piglets were orally infected with virulent rotavirus to collect jejunal mucosal scrapings at 12 and 18 hours post infection (two piglets per time point).
+IFN-gamma mRNA expression was stimulated in the mucosa of all four infected piglets, indicating that they all responded to the rotavirus infection.
+RNA pools prepared from two infected piglets were used to compare whole mucosal gene expression at 12 and 18 hpi to expression in uninfected germ-free piglets (n = 3) using a porcine intestinal cDNA microarray.
+Northern blot analysis of a selected group of genes confirmed the data of the microarray.
+Genes were functionally clustered in interferon-regulated genes, proliferation/differentiation genes, apoptosis genes, cytoskeleton genes, signal transduction genes, and enterocyte digestive, absorptive, and transport genes.
+Down-regulation of the transport gene cluster reflected in part the loss of rotavirus-infected enterocytes from the villous tips.
+Data mining suggested that several genes were regulated in lower- or mid-villus immature enterocytes and goblet cells, probably to support repair of the damaged epithelial cell layer at the villous tips.
+Furthermore, up-regulation was observed for IFN-γ induced guanylate binding protein 2, a protein that effectively inhibited VSV and EMCV replication in vitro (Arch Virol 150:1213–1220, 2005).
+This protein may play a role in the small intestine’s innate defense against enteric viruses like rotavirus.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00705-008-0118-6) contains supplementary material, which is available to authorized users.
+BACKGROUND: Enteric outbreaks associated with child care centres (CCC) have been well documented internationally and in Canada.
+The current literature focuses on identifying potential risk factors for introduction and transmission of enteric disease, but does not examine why these risk factors happen, how the risk is understood and managed by the staff of CCCs, or what challenges they experience responding to enteric illness.
+The purpose of this study was to explore the understanding, knowledge and actions of CCC staff regarding enteric illness and outbreaks, and to identify challenges that staff encounter while managing them.
+Staff used in-depth knowledge of the children, the centre and their personal experiences to assist in making decisions related to enteric illness.
+The decisions and actions may differ from guidance provided by public health officials, particularly when faced with challenges related to time, money, staffing and parents.
+CONCLUSION: CCC staff relied on experience and judgment in coordination with public health information to assist decision-making in the management of enteric illness and outbreaks.
+Advice and guidance from public health officials to CCC staff needs to be consistent yet flexible so that it may be adapted in a variety of situations and meet regulatory and public health requirements.
+Precise dating of viral subtype divergence enables researchers to correlate divergence with geographic and demographic occurrences.
+When historical data are absent (that is, the overwhelming majority), viral sequence sampling on a time scale commensurate with the rate of substitution permits the inference of the times of subtype divergence.
+Currently, researchers use two strategies to approach this task, both requiring strong conditions on the molecular clock assumption of substitution rate.
+As the underlying structure of the substitution rate process at the time of subtype divergence is not understood and likely highly variable, we present a simple method that estimates rates of substitution, and from there, times of divergence, without use of an assumed molecular clock.
+We accomplish this by blending estimates of the substitution rate for triplets of dated sequences where each sequence draws from a distinct viral subtype, providing a zeroth-order approximation for the rate between subtypes.
+As an example, we calculate the time of divergence for three genes among influenza subtypes A-H3N2 and B using subtype C as an outgroup.
+We show a time of divergence approximately 100 years ago, substantially more recent than previous estimates which range from 250 to 3800 years ago.
+Sepsis remains the most common cause of death in intensive care units in the USA, with a current estimate of at least 750,000 cases per year, and 215,000 deaths annually.
+Despite extensive research still we do not quite understand the cellular and molecular mechanisms that are involved in triggering and propagation of septic injury.
+Endotoxin (lipopolysaccharide from Gram-negative bacteria, or LPS) has been implicated as a major cause of this syndrome.
+In humans, inflammatory responses to LPS result in the release of cytokines and other cell mediators from monocytes and macrophages, which can cause fever, shock, organ failure and death.
+A number of different approaches have been investigated to try to treat and/or prevent the septic shock associated with infections caused by Gram-negative bacteria, including blockage of one or more of the cytokines induced by LPS.
+Recently several novel amphipathic compounds have been developed as direct LPS antagonists at the LPS receptor, TLR4.
+This review article will outline the current knowledge on the TLR4-LPS synthesis and discuss the signaling, in vitro pre-clinical and in vivo clinical evaluation of TLR4 antagonists and their potential use in sepsis and a variety of diseases such as atherosclerosis as well as hepatic and renal malfunction.
+BACKGROUND: Dengue virus pathogenesis is not yet fully understood and the identification of patients at high risk for developing severe disease forms is still a great challenge in dengue patient care.
+During the present study, we evaluated prospectively the potential of cytokines present in plasma from patients with dengue in stratifying disease severity.
+METHODS: Seventeen-cytokine multiplex fluorescent microbead immunoassay was used for the simultaneous detection in 59 dengue patients.
+GLM models using bimodal or Gaussian family were determined in order to associate cytokines with clinical manifestations and laboratory diagnosis.
+RESULTS: IL-1β, IFN-γ, IL-4, IL-6, IL-13, IL-7 and GM-CSF were significantly increased in patients with severe clinical manifestations (severe dengue) when compared to mild disease forms (mild dengue).
+CONCLUSION: Our data demonstrated that the use of a multiple cytokine assay platform was suitable for identifying distinct cytokine profiles associated with the dengue clinical manifestations and severity.
+MIP-β is indicated for the first time as a good prognostic marker in contrast to IFN-γ that was associated with disease severity.
+We fitted a statistical model to these data; the shape of the curve strongly suggests that the process of virus discovery is far from complete.
+We generated a 95% credible interval for the pool of as yet undiscovered virus species of 38–562.
+We extrapolated the curve and generated an estimate of 10–40 new species to be discovered by 2020.
+Although we cannot predict the level of health threat that these new viruses will present, we conclude that novel virus species must be anticipated in public health planning.
+More systematic virus discovery programmes, covering both humans and potential animal reservoirs of human viruses, should be considered.
+BACKGROUND: Two problems complicate the study of selection in viral genomes: Firstly, the presence of genes in overlapping reading frames implies that selection in one reading frame can bias our estimates of neutral mutation rates in another reading frame.
+Secondly, the high mutation rates we are likely to encounter complicate the inference of a reliable alignment of genomes.
+To address these issues, we develop a model that explicitly models selection in overlapping reading frames.
+We then integrate this model into a statistical alignment framework, enabling us to estimate selection while explicitly dealing with the uncertainty of individual alignments.
+We show that in this way we obtain un-biased selection parameters for different genomic regions of interest, and can improve in accuracy compared to using a fixed alignment.
+RESULTS: We run a series of simulation studies to gauge how well we do in selection estimation, especially in comparison to the use of a fixed alignment.
+We show that the standard practice of using a ClustalW alignment can lead to considerable biases and that estimation accuracy increases substantially when explicitly integrating over the uncertainty in inferred alignments.
+We even manage to compete favourably for general evolutionary distances with an alignment produced by GenAl.
+CONCLUSION: We propose that marginalizing over all alignments, as opposed to using a fixed one, should be considered in any parametric inference from divergent sequence data for which the alignments are not known with certainty.
+Moreover, we discover in HIV2 that double coding regions appear to be under less stringent selection than single coding ones.
+Additionally, there appears to be evidence for differential selection, where one overlapping reading frame is under positive and the other under negative selection.
+Phylogenetic studies investigated this phenomenon but have lacked sequences from more subtropical and tropical regions, particularly from Southeast Asia.
+METHODOLOGY/PRINCIPAL FINDINGS: 281 complete hemagglutinin (HA) and neuraminidase (NA) sequences were obtained from influenza A(H3N2) viruses, collected over 10 years (1997–2006) from Hong Kong.
+These dated sequences were analyzed with influenza A(H3N2) vaccine strain sequences (Syd/5/97, Mos/10/99, Fuj/411/02, Cal/7/04) and 315 other publicly available dated sequences from elsewhere, worldwide.
+In addition, the NA sequence alignment was inspected for the presence of any naturally occurring, known, neuraminidase inhibitor (NAI) resistance-associated amino acid mutations (R292K and E119V).
+Before 2001, the Hong Kong HA and NA sequences clustered more closely with the older vaccine sequences (Syd/5/97, Mos/10/99) than did sequences from elsewhere.
+After 2001, this trend reversed with significant clusters containing HA and NA sequences from different locations, isolated at different times, suggesting that viral migration may account for much of the influenza A(H3N2) seasonality during this 10-year period.
+However, at least one example from Hong Kong was found suggesting that in some years, influenza A(H3N2) viruses may persist in the same location, perhaps continuing to circulate, sub-clinically, at low levels between seasons, to re-emerge in the influenza season the following year, relatively unchanged.
+None of these Hong Kong influenza A(H3N2) NA sequences contained any of the known NAI-resistance associated mutations.
+CONCLUSIONS/SIGNIFICANCE: The seasonality of influenza A(H3N2) may be largely due to global migration, with similar viruses appearing in different countries at different times.
+However, occasionally, some viruses may remain within a single location and continue to circulate within that population, to re-emerge during the next influenza season, with relatively little genetic change.
+Naturally occurring NAI resistance mutations were absent or, at least, very rare in this population.
+Fatal human respiratory disease associated with the 1918 pandemic influenza virus and potentially pandemic H5N1 viruses is characterized by severe lung pathology, including pulmonary edema and extensive inflammatory infiltrate.
+Here, we quantified the cellular immune response to infection in the mouse lung by flow cytometry and demonstrate that mice infected with highly pathogenic (HP) H1N1 and H5N1 influenza viruses exhibit significantly high numbers of macrophages and neutrophils in the lungs compared to mice infected with low pathogenic (LP) viruses.
+Mice infected with the 1918 pandemic virus and a recent H5N1 human isolate show considerable similarities in overall lung cellularity, lung immune cell sub-population composition and cellular immune temporal dynamics.
+Interestingly, while these similarities were observed, the HP H5N1 virus consistently elicited significantly higher levels of pro-inflammatory cytokines in whole lungs and primary human macrophages, revealing a potentially critical difference in the pathogenesis of H5N1 infections.
+These results together show that infection with HP influenza viruses such as H5N1 and the 1918 pandemic virus leads to a rapid cell recruitment of macrophages and neutrophils into the lungs, suggesting that these cells play a role in acute lung inflammation associated with HP influenza virus infection.
+In addition, primary macrophages and dendritic cells were also susceptible to 1918 and H5N1 influenza virus infection in vitro and in infected mouse lung tissue.
+Genome-wide scans for positively selected genes (PSGs) in mammals have provided insight into the dynamics of genome evolution, the genetic basis of differences between species, and the functions of individual genes.
+However, previous scans have been limited in power and accuracy owing to small numbers of available genomes.
+Here we present the most comprehensive examination of mammalian PSGs to date, using the six high-coverage genome assemblies now available for eutherian mammals.
+The increased phylogenetic depth of this dataset results in substantially improved statistical power, and permits several new lineage- and clade-specific tests to be applied.
+Of ∼16,500 human genes with high-confidence orthologs in at least two other species, 400 genes showed significant evidence of positive selection (FDR<0.05), according to a standard likelihood ratio test.
+As in previous studies, the identified PSGs were enriched for roles in defense/immunity, chemosensory perception, and reproduction, but enrichments were also evident for more specific functions, such as complement-mediated immunity and taste perception.
+A novel Bayesian analysis of the possible “selection histories” of each gene indicated that most PSGs have switched multiple times between positive selection and nonselection, suggesting that positive selection is often episodic.
+A detailed analysis of Affymetrix exon array data indicated that PSGs are expressed at significantly lower levels, and in a more tissue-specific manner, than non-PSGs.
+Genes that are specifically expressed in the spleen, testes, liver, and breast are significantly enriched for PSGs, but no evidence was found for an enrichment for PSGs among brain-specific genes.
+This study provides additional evidence for widespread positive selection in mammalian evolution and new genome-wide insights into the functional implications of positive selection.
+BACKGROUND: Since 1999, the expansion of the West Nile virus (WNV) epizooty has led public health authorities to build and operate surveillance systems in North America.
+These systems are very useful to collect data, but cannot be used to forecast the probable spread of the virus in coming years.
+Such forecasts, if proven reliable, would permit preventive measures to be put into place at the appropriate level of expected risk and at the appropriate time.
+It is within this context that the Multi-Agent GeoSimulation approach has been selected to develop a system that simulates the interactions of populations of mosquitoes and birds over space and time in relation to the spread and transmission of WNV.
+This simulation takes place in a virtual mapping environment representing a large administrative territory (e.g.
+province, state) and carried out under various climate scenarios in order to simulate the effects of vector control measures such as larviciding at scales of 1/20 000 or smaller.
+RESULTS: After setting some hypotheses, a conceptual model and system architecture were developed to describe the population dynamics and interactions of mosquitoes (genus Culex) and American crows, which were chosen as the main actors in the simulation.
+Based on a mathematical compartment model used to simulate the population dynamics, an operational prototype was developed for the Southern part of Quebec (Canada).
+The system allows users to modify the parameters of the model, to select various climate and larviciding scenarios, to visualize on a digital map the progression (on a weekly or daily basis) of the infection in and around the crows' roosts and to generate graphs showing the evolution of the populations.
+CONCLUSION: In all likelihood this system might be used to support short term decision-making related to WNV vector control measures, including the use of larvicides, according to climatic scenarios.
+Once fully calibrated in several real-life contexts, this promising approach opens the door to the study and management of other zoonotic diseases such as Lyme disease.
+The emergence of alternative medicines for AIDS in Asia and Africa was discussed at a satellite symposium and the parallel session on alternative and traditional treatments of the AIDSImpact meeting, held in Marseille, in July 2007.
+These medicines are heterogeneous, both in their presentation and in their geographic and cultural origin.
+The sessions focused on the role of these medications in selected resource poor settings in Africa and Asia now that access to anti-retroviral therapy is increasing.
+The aims of the sessions were to (1) identify the actors involved in the diffusion of these alternative medicines for HIV/AIDS, (2) explore uses and forms, and the way these medicines are given legitimacy, (3) reflect on underlying processes of globalisation and cultural differentiation, and (4) define priority questions for future research in this area.
+This article presents the insights generated at the meeting, illustrated with some findings from the case studies (Uganda, Senegal, Benin, Burkina Faso, China and Indonesia) that were presented.
+These case studies reveal the wide range of actors who are involved in the marketing and supply of alternative medicines.
+The efficacy claims of alternative medicines often reinforce a biomedical paradigm for HIV/AIDS, and fit with a healthy living ideology promoted by AIDS care programs and support groups.
+The AIDSImpact session concluded that more interdisciplinary research is needed on the experience of people living with HIV/AIDS with these alternative medicines, and on the ways in which these products interact (or not) with anti-retroviral therapy at pharmacological as well as psychosocial levels.
+H5N1 highly pathogenic avian influenza (HPAI) viruses have seriously affected the Asian poultry industry since their recurrence in 2003.
+The viruses pose a threat of emergence of a global pandemic influenza through point mutation or reassortment leading to a strain that can effectively transmit among humans.
+In this study, we present phylogenetic evidences for the interlineage reassortment among H5N1 HPAI viruses isolated from humans, cats, and birds in Indonesia, and identify the potential genetic parents of the reassorted genome segments.
+Parsimony analyses of viral phylogeography suggest that the reassortant viruses may have originated from greater Jakarta and surroundings, and subsequently spread to other regions in the West Java province.
+In addition, Bayesian methods were used to elucidate the genetic diversity dynamics of the reassortant strain and one of its genetic parents, which revealed a more rapid initial growth of genetic diversity in the reassortant viruses relative to their genetic parent.
+These results demonstrate that interlineage exchange of genetic information may play a pivotal role in determining viral genetic diversity in a focal population.
+Moreover, our study also revealed significantly stronger diversifying selection on the M1 and PB2 genes in the lineages preceding and subsequent to the emergence of the reassortant viruses, respectively.
+We discuss how the corresponding mutations might drive the adaptation and onward transmission of the newly formed reassortant viruses.
+Gammaherpesvirus infections usually result in either a productive lytic infection, characterized by expression of all viral genes and rapid cell lysis, or latent infection, characterized by limited viral gene expression and no cell lysis.
+Here, we report characterization of endothelial cell infection with murine gammaherpesvirus 68 (γHV68), a virus phylogenetically related and biologically similar to the human gammaherpesviruses.
+Endothelial cells supported γHV68 replication in vitro, but were unique in that a significant proportion of the cells escaped lysis, proliferated, and remained viable in culture for an extended time.
+Upon infection, endothelial cells became non-adherent and altered in size, complexity, and cell-surface protein expression.
+These cells were uniformly infected and expressed the lytic transcription program based on detection of abundant viral gene transcripts, GFP fluorescence from the viral genome, and viral surface protein expression.
+Additionally, endothelial cells continued to produce new infectious virions as late as 30 days post-infection.
+The outcome of this long-term infection was promoted by the γHV68 v-cyclin, because in the absence of the v-cyclin, viability was significantly reduced following infection.
+Importantly, infected primary endothelial cells also demonstrated increased viability relative to infected primary fibroblasts, and this increased viability was dependent on the v-cyclin.
+The extended viability and virus production of infected endothelial cells indicated that endothelial cells provided a source of prolonged virus production and identify a cell-type specific adaptation of gammaherpesvirus replication.
+While infected endothelial cells would likely be cleared in a healthy individual, persistently infected endothelial cells could provide a source of continued virus replication in immune-compromised individuals, a context in which gammaherpesvirus-associated pathology frequently occurs.
+Based on current genome sequence analyses, we found that synonymous codon usage variations in the protein-coding genes of begomoviruses are mainly influenced by mutation bias.
+Base composition analysis suggested that the codon usage bias of AV1 and BV1 genes is significant and their expressions are high.
+Fourteen codons were determined as translational optimal ones according to the comparison of codon usage patterns between highly and lowly expressed genes.
+Interestingly the codon usages between begomoviruses from the Old and the New Worlds are apparently different, which supports the idea that the bipartite begomoviruses of the New World might originate from bipartite ones of the Old World, whereas the latter evolve from the Old World monopartite begomoviruses.
+BACKGROUND: Diffuse alveolar haemorrhage (DAH) is a serious pulmonary complication characterised by a high mortality rate and the absence of specific treatment.
+The intrapulmonary administration of activated recombinant factor VII (rFVIIa) in DAH was recently published in six patients by Heslet et al with an efficient hemostatic effect.
+METHODS: Two cases of DAH were admitted to the ICU after presenting abrupt desaturation, tachypnea, cough and haemoptysis, requiring orotracheal intubation and mechanical ventilation.
+The diagnosis was achieved by the bloody return during the bronchoalveolar lavage, during the procedure rFVIIa (50 μg/Kg in 50 ml of isotonic saline) was administered via the bronchoscope.
+Prior to intrapulmonary administration of rFVIIa, the FiO(2 )was 1, which was reduced to 0.4 24 hours later.
+After the intervention both cases progressed fast and was discharged from the ICU with no further episodes of bleeding.
+Local intrabronchial deposition of DAH with rFVIIa has been shown to be effective in controlling life-threatening DAH.
+In the case described above, no thrombotic complications were observed following the intrapulmonary administration of rFVIIa.
+Pore-forming toxins (PFTs) constitute the single largest class of proteinaceous bacterial virulence factors and are made by many of the most important bacterial pathogens.
+We find that the endoplasmic reticulum unfolded protein response (UPR) is activated upon exposure to PFTs both in Caenorhabditis elegans and in mammalian cells.
+Activation of the UPR is protective in vivo against PFTs since animals that lack either the ire-1-xbp-1 or the atf-6 arms of the UPR are more sensitive to PFT than wild-type animals.
+Loss of the UPR leads to a normal response against unrelated toxins or a pathogenic bacterium, indicating its PFT-protective role is specific.
+The p38 mitogen-activated protein (MAPK) kinase pathway has been previously shown to be important for cellular defenses against PFTs.
+We find here that the UPR is one of the key downstream targets of the p38 MAPK pathway in response to PFT since loss of a functional p38 MAPK pathway leads to a failure of PFT to properly activate the ire-1-xbp-1 arm of the UPR.
+The UPR-mediated activation and response to PFTs is distinct from the canonical UPR-mediated response to unfolded proteins both in terms of its activation and functional sensitivities.
+These data demonstrate that the UPR, a fundamental intracellular pathway, can operate in intrinsic cellular defenses against bacterial attack.
+BACKGROUND: Studies of wild animals responding to their native parasites are essential if we are to understand how the immune system functions in the natural environment.
+While immune defence may bring increased survival, this may come at a resource cost to other physiological traits, including reproduction.
+Here, we tested the hypothesis that wild common shrews (Sorex araneus), which produce large numbers of offspring during the one breeding season of their short life span, forgo investment in immunity and immune system maintenance, as increased longevity is unlikely to bring further opportunities for mating.
+In particular, we predicted that adult shrews, with shorter expected lifespans, would not respond as effectively as young animals to infection.
+METHODOLOGY/PRINCIPAL FINDINGS: We examined haemolymphatic tissues from wild-caught common shrews using light and transmission electron microscopy, applied in conjunction with immunohistology.
+We compared composition and function of these tissues in shrews of different ages, and the extent and type of inflammatory reactions observed in response to natural parasitic infections.
+All ages seemed able to mount systemic, specific immune responses, but adult shrews showed some signs of lymphatic tissue exhaustion: lymphatic follicles in adults (n = 21) were both smaller than those in sub-adults (n = 18; Wald = 11.1, p<0.05) and exhibited greater levels of depletion (Wald = 13.3, p<0.05).
+CONCLUSIONS/SIGNIFICANCE: Contrary to our expectations, shrews respond effectively to their natural parasites, and show little indication of immunosenescence as adults.
+The pancreas of Aselli, a unique lymphoid organ, may aid in providing efficient immune responses through the storage of large numbers of plasma cells.
+This may allow older animals to react effectively to previously encountered parasites, but infection by novel agents, and eventual depletion of plasma cell reserves, could both still be factors in the near-synchronous mortality of adult shrews observed shortly after breeding.
+Epitope enhancement can elicit more potent T cell responses and can subsequently lead to a stronger memory pool; however, the molecular basis of such enhancement is unclear.
+We used the consensus peptide-binding motif for the Major Histocompatibility Complex molecule H-2K(b) to design a heteroclitic version of the mouse hepatitis virus-specific subdominant S598 determinant.
+We demonstrate that a single amino acid substitution at a secondary anchor residue (Q to Y at position 3) increased the stability of the engineered determinant in complex with H-2K(b).
+The structural basis for this enhanced stability was associated with local alterations in the pMHC conformation as a result of the Q to Y substitution.
+Recombinant viruses encoding this engineered determinant primed CTL responses that also reacted to the wildtype epitope with significantly higher functional avidity, and protected against selection of virus mutated at a second CTL determinant and consequent disease progression in persistently infected mice.
+Collectively, our findings provide a basis for the enhanced immunogenicity of an engineered determinant that will serve as a template for guiding the development of heteroclitic T cell determinants with applications in prevention of CTL escape in chronic viral infections as well as in tumor immunity.
+BACKGROUND AND AIMS: Hepatitis C Virus (HCV)-related liver disease progresses more rapidly in individuals co-infected with Human Immunodeficiency Virus-1 (HIV), although the underlying immunologic mechanisms are unknown.
+We examined whether HIV-specific T-cells are identified in the liver of HCV/HIV co-infected individuals and promote liver inflammation through bystander immune responses.
+METHODS: Ex-vivo intra-hepatic lymphocytes from HCV mono-infected and HCV/HIV co-infected individuals were assessed for immune responses to HIV and HCV antigens by polychromatic flow cytometry.
+RESULTS: HCV/HIV liver biopsies had similar frequencies of lymphocytes but lower percentages of CD4(+) T-cells compared to HCV biopsies.
+In co-infection, intra-hepatic HIV-specific CD8(+) and CD4(+) T-cells producing IFN-γ and TNF-α were detected and were comparable in frequency to those that were HCV-specific.
+In both mono- and co-infected individuals, intra-hepatic HCV-specific T-cells were poorly functional compared to HIV-specific T-cells.
+In co-infection, HAART was not associated with a reconstitution of intra-hepatic CD4(+) T-cells and was associated with reduction in both HIV and HCV-specific intra-hepatic cytokine responses.
+CONCLUSION: The accumulation of functional HIV-specific T-cells in the liver during HCV/HIV co-infection may represent a bystander role for HIV in inducing faster progression of liver disease.
+INTRODUCTION: Hemophagocytic syndrome (HFS) is a potentially lethal disorder due to an uncontrolled immune response to a triggering agent.
+Our objective is to raise the importance of HFS early diagnosis by presenting a representative case.
+CASE PRESENTATION: A sixteen-year-old girl with Still disease diagnosis developed a progressive multiorgan failure including acute respiratory distress (ARDS), anemia and thrombopenia, elevated liver enzymes, renal failure, coagulopathy with hypofibrinogenemia, and acute phase reactants elevation despite broad-spectrum antibiotics.
+She received intensive care support therapy including mechanical ventilation and specific therapy according to HLH 2004 protocol, with a very good response.
+Copy number variations (CNVs) in the human genome are conventionally detected using high-throughput scanning technologies, such as comparative genomic hybridization and high-density single nucleotide polymorphism (SNP) microarrays, or relatively low-throughput techniques, such as quantitative polymerase chain reaction (PCR).
+All these approaches are limited in resolution and can at best distinguish a twofold (or 50%) difference in copy number.
+We have developed a new technology to study copy numbers using a platform known as the digital array, a nanofluidic biochip capable of accurately quantitating genes of interest in DNA samples.
+We have evaluated the digital array's performance using a model system, to show that this technology is exquisitely sensitive, capable of differentiating as little as a 15% difference in gene copy number (or between 6 and 7 copies of a target gene).
+We have also analyzed commercial DNA samples for their CYP2D6 copy numbers and confirmed that our results were consistent with those obtained independently using conventional techniques.
+In a screening experiment with breast cancer and normal DNA samples, the ERBB2 gene was found to be amplified in about 35% of breast cancer samples.
+The use of the digital array enables accurate measurement of gene copy numbers and is of significant value in CNV studies.
+BACKGROUND: Hospital preparedness is critical for the early detection and management of public health emergency (PHE).
+Understanding the current status of PHE preparedness is the first step in planning to enhance hospitals' capacities for emergency response.
+The objective of this study is to understand the current status of hospital PHE preparedness in China.
+METHODS: Four hundred hospitals in four city and provinces of China were surveyed using a standardized questionnaire.
+Data related to hospital demographic data; PHE preparation; response to PHE in community; stockpiles of drugs and materials; detection and identification of PHE; procedures for medical treatment; laboratory diagnosis and management; staff training; and risk communication were collected and analyzed.
+Of the valid responses, 264 (85.2%) hospitals had emergency plans; 93.3% had command centres and personnel for PHE; 22.9% included community organisations during the training for PHE; 97.4% could transport needed medical staff to a PHE; 53.1% had evaluated stockpiles of drugs; 61.5% had evaluated their supply systems; 55.5% had developed surveillance systems; and 74.6% could monitor the abnormity(See in appendix).
+Physicians in 80.2% of the analyzed hospitals reported up-to-date knowledge of their institution's PHE protocol.
+Of the 318 respondents, 97.4% followed strict laboratory regulations, however, only about 33.5% had protocols for suspected samples.
+Furthermore, only 59.0% could isolate and identify salmonella and staphylococcus and less than 5% could isolate and identify human H5N1 avian flu and SARS.
+Staff training or drill programs were reported in 94.5% of the institutions; 50.3% periodically assessed the efficacy of staff training; 45% had experts to provide psychological counselling; 12.1% had provided training for their medical staff to assess PHE-related stress.
+All of the above capacities related to the demographic characteristics of hospitals and will be discussed in-depth in this paper.
+CONCLUSION: Our survey suggested that, at the time of the survey, hospital preparedness for PHE in China was at an early stage of development.
+Comprehensive measures should be taken to enhance hospital capacity in the prevention and management of PHE.
+BACKGROUND: Female endoparasitic ichneumonid wasps inject virus-like particles into their caterpillar hosts to suppress immunity.
+These particles are classified as ichnovirus virions and resemble ascovirus virions, which are also transmitted by parasitic wasps and attack caterpillars.
+Polydnavirus DNA consists of wasp DNA replicated by the wasp from its genome, which also directs particle synthesis.
+Structural similarities between ascovirus and ichnovirus particles and the biology of their transmission suggest that ichnoviruses evolved from ascoviruses, although molecular evidence for this hypothesis is lacking.
+RESULTS: Here we show that a family of unique pox-D5 NTPase proteins in the Glypta fumiferanae ichnovirus are related to three Diadromus pulchellus ascovirus proteins encoded by ORFs 90, 91 and 93.
+A new alignment technique also shows that two proteins from a related ichnovirus are orthologs of other ascovirus virion proteins.
+CONCLUSION: Our results provide molecular evidence supporting the origin of ichnoviruses from ascoviruses by lateral transfer of ascoviral genes into ichneumonid wasp genomes, perhaps the first example of symbiogenesis between large DNA viruses and eukaryotic organisms.
+We also discuss the limits of this evidence through complementary studies, which revealed that passive lateral transfer of viral genes among polydnaviral, bacterial, and wasp genomes may have occurred repeatedly through an intimate coupling of both recombination and replication of viral genomes during evolution.
+The impact of passive lateral transfers on evolutionary relationships between polydnaviruses and viruses with large double-stranded genomes is considered in the context of the theory of symbiogenesis.
+route with Ad5 expressing Ebola Zaire glycoprotein (Ad5-ZGP) fully protected naïve mice against lethal challenge with Ebola.
+The frequency of IFN-γ+ CD8+ T cells was reduced by 80% and by 15% in animals vaccinated by the I.M.
+Pre-existing immunity did not compromise the frequency of IFN-γ+ CD8+ T cells (3.9±1% naïve vs. 3.6±1% pre-existing immunity, PEI) nor anti-Ebola neutralizing antibody (NAB, 40±10 reciprocal dilution, both groups).
+immunization was not compromised by pre-existing immunity to Ad5 (146±14, naïve vs. 120±16 SFC/million MNCs, PEI).
+Mice given the modified vaccine did not survive challenge and had reduced levels of IFN-γ+ CD8+ T cells 10 days after administration (0.3±0.3% PEG vs. 1.7±0.5% unmodified).
+These results provide some insight about the degree of T and B cell mediated immunity necessary for protection against Ebola virus and suggest that modification of the virus capsid can influence the type of immune response elicited by an Ad5-based vaccine.
+Government disease control measures were put in place to control, contain, and eradicate the disease; these measures included movement restrictions and quarantining of properties.
+This study was conducted to assess the psycho-social impacts of this disease, and this paper reports the prevalence of, and factors influencing, psychological distress during this outbreak.
+METHODS: Data were collected using an online survey, with a link directed to the affected population via a number of industry groups.
+Psychological distress, as determined by the Kessler 10 Psychological Distress Scale, was the main outcome measure.
+Extremely high levels of non-specific psychological distress were reported by respondents in this study, with 34% reporting high psychological distress (K10 > 22), compared to levels of around 12% in the Australian general population.
+Analysis, using backward stepwise binary logistic regression analysis, revealed that those living in high risk infection (red) zones (OR = 2.00; 95% CI: 1.57–2.55; p < 0.001) and disease buffer (amber) zones (OR = 1.83; 95% CI: 1.36–2.46; p < 0.001) were at much greater risk of high psychological distress than those living in uninfected (white zones).
+Although prevalence of high psychological distress was greater in infected EI zones and States, elevated levels of psychological distress were experienced in horse-owners nationally.
+Statistical analysis indicated that certain groups were more vulnerable to high psychological distress; specifically younger people, and those with lower levels of formal educational qualifications.
+Respondents whose principal source of income was from horse-related industry were more than twice as likely to have high psychological distress than those whose primary source of income was not linked to horse-related industry (OR = 2.23; 95% CI: 1.82–2.73; p < 0.001).
+CONCLUSION: Although, methodologically, this study had good internal validity, it has limited generalisability because it was not possible to identify, bound, or sample the target population accurately.
+However, this study is the first to collect psychological distress data from an affected population during such a disease outbreak and has potential to inform those involved in assessing the potential psychological impacts of human infectious diseases, such as pandemic influenza.
+The type I interferon (IFN) system is a first line of defense against viral infections.
+So far, the interferon antagonistic activity of influenza A viruses was mainly observed on the level of IFNβ gene induction via action of the viral non-structural protein 1 (NS1).
+Here we present data indicating that influenza A viruses not only suppress IFNβ gene induction but also inhibit type I IFN signaling through a mechanism involving induction of the suppressor of cytokine signaling-3 (SOCS-3) protein.
+Our study was based on the observation that in cells that were infected with influenza A virus and subsequently stimulated with IFNα/β, phosphorylation of the signal transducer and activator of transcription protein 1 (STAT1) was strongly reduced.
+This impaired STAT1 activation was not due to the action of viral proteins but rather appeared to be induced by accumulation of viral 5′ triphosphate RNA in the cell.
+Closer examination revealed that SOCS-3 but not SOCS-1 mRNA levels increase in an RNA- and nuclear factor kappa B (NF-κB)-dependent but type I IFN-independent manner early in the viral replication cycle.
+This direct viral induction of SOCS-3 mRNA and protein expression appears to be relevant for suppression of the antiviral response since in SOCS-3 deficient cells a sustained phosphorylation of STAT1 correlated with elevated expression of type I IFN-dependent genes.
+As a consequence, progeny virus titers were reduced in SOCS-3 deficient cells or in cells were SOCS-3 expression was knocked-down by siRNA.
+These data provide the first evidence that influenza A viruses suppress type I IFN signaling on the level of JAK/STAT activation.
+The inhibitory effect is at least in part due to the induction of SOCS-3 gene expression, which results in an impaired antiviral response.
+The early systemic production of interferon (IFN)-αβ is an essential component of the antiviral host defense mechanisms, but is also thought to contribute to the toxic side effects accompanying gene therapy with adenoviral vectors.
+By comparing the responses of normal, myeloid (m)DC- and plasmacytoid (p)DC-depleted mice and by measuring IFN-αβ mRNA expression in different organs and cells types, we show that in vivo, Ads elicit strong and rapid IFN-αβ production, almost exclusively in splenic mDCs.
+Using knockout mice, various strains of Ads (wild type, mutant and UV-inactivated) and MAP kinase inhibitors, we demonstrate that the Ad-induced IFN-αβ response does not require Toll-like receptors (TLR), known cytosolic sensors of RNA (RIG-I/MDA-5) and DNA (DAI) recognition and interferon regulatory factor (IRF)-3, but is dependent on viral endosomal escape, signaling via the MAP kinase SAPK/JNK and IRF-7.
+Furthermore, we show that Ads induce IFN-αβ and IL-6 in vivo by distinct pathways and confirm that IFN-αβ positively regulates the IL-6 response.
+Finally, by measuring TNF-α responses to LPS in Ad-infected wild type and IFN-αβR(−/−) mice, we show that IFN-αβ is the key mediator of Ad-induced hypersensitivity to LPS.
+These findings indicate that, like endosomal TLR signaling in pDCs, TLR-independent virus recognition in splenic mDCs can also produce a robust early IFN-αβ response, which is responsible for the bulk of IFN-αβ production induced by adenovirus in vivo.
+The signaling requirements are different from known TLR-dependent or cytosolic IFN-αβ induction mechanisms and suggest a novel cytosolic viral induction pathway.
+The hypersensitivity to components of the microbial flora and invading pathogens may in part explain the toxic side effects of adenoviral gene therapy and contribute to the pathogenesis of adenoviral disease.
+BACKGROUND: The hemorrhagic shock and encephalopathy syndrome (HSES) is a devastating disease that affects young children.
+METHODS: We examined the clinical, biological and radiological findings of 8 patients (4 months to 9 years old) who met the HSES criteria.
+RESULTS: Although cerebral edema, disseminated intravascular coagulopathy (DIC), and multiple organ failure were seen in all 8 cases during their clinical courses, brain computed tomography (CT) scans showed normal or only slight edema in 5 patients upon admission.
+However, they all had severe metabolic acidosis, which persisted even after 3 hours (median base excess (BE), -7.6 mmol/L).
+CONCLUSION: CT scan, platelet count, hemoglobin level and renal function upon admission are not useful for an early diagnosis of HSES.
+However, the elevated liver enzymes and CK upon admission, hypotension in the early stage after admission with refractory acid-base disturbance to fluid resuscitation and vasopressor infusion are useful markers for an early HSES diagnosis and helpful to indicate starting intensive neurological treatment.
+Computational methods for determining the secondary structure of RNA sequences from given alignments are currently either based on thermodynamic folding, compensatory base pair substitutions or both.
+However, there is currently no approach that combines both sources of information in a single optimization problem.
+Here, we present a model that formally integrates both the energy-based and evolution-based approaches to predict the folding of multiple aligned RNA sequences.
+We have implemented an extended version of Pfold that identifies base pairs that have high probabilities of being conserved and of being energetically favorable.
+The consensus structure is predicted using a maximum expected accuracy scoring scheme to smoothen the effect of incorrectly predicted base pairs.
+Parameter tuning revealed that the probability of base pairing has a higher impact on the RNA structure prediction than the corresponding probability of being single stranded.
+Our implementation, PETfold, was tested on a set of 46 well-curated Rfam families and its performance compared favorably to that of Pfold and RNAalifold.
+Studies of gene fusions in solid tumors are not as extensive as in hematological malignancies due to several technical and analytical problems associated with tumor heterogeneity.
+Nevertheless, there is a growing interest in the role of fusion genes in common epithelial tumors after the discovery of recurrent TMPRSS2:ETS fusions in prostate cancer.
+Among all of the reported fusion partners in the ETS gene family, TMPRSS2:ERG is the most prevalent one.
+Here, we present a simple and sensitive microarray-based assay that is able to simultaneously determine multiple fusion variants with a single RT–PCR in impure RNA specimens.
+The assay detected TMPRSS2:ERG fusion transcripts with a detection sensitivity of <10 cells in the presence of more than 3000 times excess normal RNA, and in primary prostate tumors having no >1% of cancer cells.
+The ability to detect multiple transcript variants in a single assay is critically dependent on both the primer and probe designs.
+The assay should facilitate clinical and basic studies for fusion gene screening in clinical specimens, as it can be readily adapted to include multiple gene loci.
+Redirecting the splicing machinery through the hybridization of high affinity, RNase H- incompetent oligonucleotide analogs such as phosphoramidate morpholino oligonucleotides (PMO) might lead to important clinical applications.
+Chemical conjugation of PMO to arginine-rich cell penetrating peptides (CPP) such as (R-Ahx-R)(4) (with Ahx standing for 6-aminohexanoic acid) leads to sequence-specific splicing correction in the absence of endosomolytic agents in cell culture at variance with most conventional CPPs.
+Importantly, (R-Ahx-R)(4)–PMO conjugates are effective in mouse models of various viral infections and Duchenne muscular dystrophy.
+Unfortunately, active doses in some applications might be close to cytotoxic ones thus presenting challenge for systemic administration of the conjugates in those clinical settings.
+Structure–activity relationship studies have thus been undertaken to unravel CPP structural features important for the efficient nuclear delivery of the conjugated PMO and limiting steps in their internalization pathway.
+Affinity for heparin (taken as a model heparan sulfate), hydrophobicity, cellular uptake, intracellular distribution and splicing correction have been monitored.
+Spacing between the charges, hydrophobicity of the linker between the Arg-groups and Arg-stereochemistry influence splicing correction efficiency.
+A significant correlation between splicing correction efficiency, affinity for heparin and ability to destabilize model synthetic vesicles has been observed but no correlation with cellular uptake has been found.
+Efforts will have to focus on endosomal escape since it appears to remain the limiting factor for the delivery of these splice-redirecting ON analogs.
+Two cardinal manifestations of viral immunity are efficient clearance of acute infection and the capacity to vaccinate against secondary viral exposure.
+For noroviruses, the contributions of T cells to viral clearance and vaccination have not been elucidated.
+We report here that both CD4 and CD8 T cells are required for efficient clearance of primary murine norovirus (MNV) infection from the intestine and intestinal lymph nodes.
+Systemic vaccination with the MNV capsid protein also effectively protected against mucosal challenge, while vaccination with the capsid protein of the distantly related human Lordsdale virus provided partial protection.
+Fully effective vaccination required a broad immune response including CD4 T cells, CD8 T cells, and B cells, but the importance of specific immune cell types varied between the intestine and intestinal lymph nodes.
+Perforin, but not interferon gamma, was required for clearance of MNV infection by adoptively transferred T lymphocytes from vaccinated hosts.
+These studies prove the feasibility of both mucosal and systemic vaccination against mucosal norovirus infection, demonstrate tissue specificity of norovirus immune cells, and indicate that efficient vaccination strategies should induce potent CD4 and CD8 T cell responses.
+Antiviral agents have been hailed to hold considerable promise for the treatment and prevention of emerging viral diseases like H5N1 avian influenza and SARS.
+However, antiviral drugs are not completely harmless, and the conditions under which individuals are willing to participate in a large-scale antiviral drug treatment program are as yet unknown.
+Throughout we compare the antiviral control strategy that is optimal from the public health perspective with the control strategy that would evolve if individuals make their own, rational decisions.
+To this end we investigate the conditions under which a large-scale antiviral control program can prevent an epidemic, and we analyze at what point in an unfolding epidemic the risk of infection starts to outweigh the cost of antiviral treatment.
+This enables investigation of how the optimal control strategy is moulded by the efficacy of antiviral drugs, the risk of mortality by antiviral prophylaxis, and the transmissibility of the pathogen.
+Our analyses show that there can be a strong incentive for an individual to take less antiviral drugs than is optimal from the public health perspective.
+In particular, when public health asks for early and aggressive control to prevent or curb an emerging pathogen, for the individual antiviral drug treatment is attractive only when the risk of infection has become non-negligible.
+It is even possible that from a public health perspective a situation in which everybody takes antiviral drugs is optimal, while the process of individual choice leads to a situation where nobody is willing to take antiviral drugs.
+Avian influenza virus (H5N1) can be transmitted to humans, resulting in a severe or fatal disease.
+The aim of this study was to evaluate the immune cross-reactivity between human and avian influenza (H5N1) strains in healthy donors vaccinated for seasonal influenza A (H1N1)/(H3N2).
+A small frequency of CD4 T cells specific for subtype H5N1 was detected in several persons at baseline, and seasonal vaccine administration enhanced the frequency of such reactive CD4 T cells.
+We also observed that seasonal vaccination is able to raise neutralizing immunity against influenza (H5N1) in a large number of donors.
+N1 may possibly be a target for both cellular and humoral cross-type immunity, but additional experiments are needed to clarify this point.
+These findings highlight the possibility of boosting cross-type cellular and humoral immunity against highly pathogenic avian influenza A virus subtype H5N1 by seasonal influenza vaccination.
+Studies have reported human bocavirus (HBoV) in children with respiratory tract infections (RTIs), but only occasionally in adults.
+We searched for HBoV DNA in nasopharyngeal aspirates (NPAs) from adults with exacerbations of chronic bronchitis or pneumonia, from children hospitalized for acute RTIs, and from asymptomatic children during the winter of 2002–2003 in Canada.
+HBoV was detected in NPAs of 1 (0.8%) of 126 symptomatic adults, 31 (13.8%) of 225 symptomatic children, and 43 (43%) of 100 asymptomatic children undergoing elective surgery.
+Another virus was detected in 22 (71%) of the 31 HBoV-positive NPAs from symptomatic children.
+The pathogenic role of HBoV in RTIs is uncertain because it was frequently detected in symptomatic and asymptomatic children and was commonly found with other viruses in symptomatic children.
+We explored how different socioeconomic and racial/ethnic groups in the United States might fare in an influenza pandemic on the basis of social factors that shape exposure, vulnerability to influenza virus, and timeliness and adequacy of treatment.
+Our purpose is not to establish the precise magnitude of disparities likely to occur; rather, it is to call attention to avoidable disparities that can be expected in the absence of systematic attention to differential social risks in pandemic preparedness plans.
+Policy makers at the federal, state, and local levels should consider potential sources of socioeconomic and racial/ethnic disparities during a pandemic and formulate specific plans to minimize these disparities.
+A key step in these projects is estimating the time, cost, and personnel required for obtaining an accurate and complete map.
+Here, we model the cost of interaction map completion across a spectrum of experimental designs.
+We show that current efforts may require up to 20 independent tests covering each protein pair to approach completion.
+We explore designs for reducing this cost substantially, including prioritization of protein pairs, probability thresholding, and interaction prediction.
+The best designs lower cost by four-fold overall and >100-fold in early stages of mapping.
+We demonstrate the best strategy in an ongoing project in Drosophila, in which we map 450 high-confidence interactions using 47 microtiter plates, versus thousands of plates expected using current designs.
+This study provides a framework for assessing the feasibility of interaction mapping projects and for future efforts to increase their efficiency.
+BACKGROUND: Influenza pneumonia causes high mortality every year, and pandemic episodes kill millions of people.
+Influenza-related mortality has been variously ascribed to an ineffective host response that fails to limit viral replication, an excessive host inflammatory response that results in lung injury and impairment of gas exchange, or to bacterial superinfection.
+We sought to determine whether lung inflammation promoted or impaired host survival in influenza pneumonia.
+METHODS AND FINDINGS: To distinguish among these possible causes of influenza-related death, we induced robust lung inflammation by exposing mice to an aerosolized bacterial lysate prior to challenge with live virus.
+The treatment induced expression of the inflammatory cytokines IL-6 and TNF in bronchoalveolar lavage fluid 8- and 40-fold greater, respectively, than that caused by lethal influenza infection.
+Yet, this augmented inflammation was associated with striking resistance to host mortality (0% vs 90% survival, p = 0.0001) and reduced viral titers (p = 0.004).
+When mice were repeatedly exposed to the bacterial lysate, as would be clinically desirable during an influenza epidemic, there was no tachyphylaxis of the induced viral resistance.
+When the bacterial lysate was administered after the viral challenge, there was still some mortality benefit, and when ribavirin was added to the aerosolized bacterial lysate, host survival was synergistically improved (0% vs 93.3% survival, p<0.0001).
+CONCLUSIONS: Together, these data indicate that innate immune resistance to influenza can be effectively stimulated, and suggest that ineffective rather than excessive inflammation is the major cause of mortality in influenza pneumonia.
+The lack of tumor specificity remains a major drawback for effective chemotherapies and results in dose-limiting toxicities.
+However, a ligand-mediated drug delivery system should be able to render chemotherapy more specific to tumor cells and less toxic to normal tissues.
+In this study, we isolated a novel peptide ligand from a phage-displayed peptide library that bound to non-small cell lung cancer (NSCLC) cell lines.
+Both the targeting phage and the synthetic peptide recognized the surgical specimens of NSCLC with a positive rate of 75% (27 of 36 specimens).
+In severe combined immunodeficiency (SCID) mice bearing NSCLC xenografts, the targeting phage specifically bound to tumor masses.
+The tumor homing ability of the targeting phage was inhibited by the cognate synthetic peptide, but not by a control or a WTY-mutated peptide.
+When the targeting peptide was coupled to liposomes carrying doxorubicin or vinorelbine, the therapeutic index of the chemotherapeutic agents and the survival rates of mice with human lung cancer xenografts markedly increased.
+Furthermore, the targeting liposomes increased drug accumulation in tumor tissues by 5.7-fold compared with free drugs and enhanced cancer cell apoptosis resulting from a higher concentration of bioavailable doxorubicin.
+The current study suggests that this tumor-specific peptide may be used to create chemotherapies specifically targeting tumor cells in the treatment of NSCLC and to design targeted gene transfer vectors or it may be used one in the diagnosis of this malignancy.
+Circulating levels of immune mediators and growth factors were analyzed from patients infected during the first Singaporean Chikungunya fever outbreak in early 2008 to establish biomarkers associated with infection and/or disease severity.
+METHODS AND FINDINGS: Adult patients with laboratory-confirmed Chikungunya fever infection, who were referred to the Communicable Disease Centre/Tan Tock Seng Hospital during the period from January to February 2008, were included in this retrospective study.
+Among the patients, the most common clinical features were fever (100%), arthralgia (90%), rash (50%) and conjunctivitis (40%).
+Profiles of 30 cytokines, chemokines, and growth factors were able to discriminate the clinical forms of Chikungunya from healthy controls, with patients classified as non-severe and severe disease.
+Statistical analysis showed that an increase in IL-1β, IL-6 and a decrease in RANTES were associated with disease severity.
+CONCLUSIONS: This is the first comprehensive report on the production of cytokines, chemokines, and growth factors during acute Chikungunya virus infection.
+Using these biomarkers, we were able to distinguish between mild disease and more severe forms of Chikungunya fever, thus enabling the identification of patients with poor prognosis and monitoring of the disease.
+Rift Valley fever virus (RVFV) (genus Phlebovirus, family Bunyaviridae) is a negative-stranded RNA virus with a tripartite genome.
+RVFV is transmitted by mosquitoes and causes fever and severe hemorrhagic illness among humans, and fever and high rates of abortions in livestock.
+A nonstructural RVFV NSs protein inhibits the transcription of host mRNAs, including interferon-β mRNA, and is a major virulence factor.
+The present study explored a novel function of the RVFV NSs protein by testing the replication of RVFV lacking the NSs gene in the presence of actinomycin D (ActD) or α-amanitin, both of which served as a surrogate of the host mRNA synthesis suppression function of the NSs.
+In the presence of the host-transcriptional inhibitors, the replication of RVFV lacking the NSs protein, but not that carrying NSs, induced double-stranded RNA-dependent protein kinase (PKR)–mediated eukaryotic initiation factor (eIF)2α phosphorylation, leading to the suppression of host and viral protein translation.
+RVFV NSs promoted post-transcriptional downregulation of PKR early in the course of the infection and suppressed the phosphorylated eIF2α accumulation.
+These data suggested that a combination of RVFV replication and NSs-induced host transcriptional suppression induces PKR-mediated eIF2α phosphorylation, while the NSs facilitates efficient viral translation by downregulating PKR and inhibiting PKR-mediated eIF2α phosphorylation.
+Thus, the two distinct functions of the NSs, i.e., the suppression of host transcription, including that of type I interferon mRNAs, and the downregulation of PKR, work together to prevent host innate antiviral functions, allowing efficient replication and survival of RVFV in infected mammalian hosts.
+Different extraction methods were also tested for their effects on the bioactivities of the medicinal plants.
+METHODS: Eight plants, namely Herba Polygonis Hydropiperis (Laliaocao), Folium Murraya Koenigii (Jialiye), Rhizoma Arachis Hypogea (Huashenggen), Herba Houttuyniae (Yuxingcao), Epipremnum pinnatum (Pashulong), Rhizoma Typhonium Flagelliforme (Laoshuyu), Cortex Magnoliae Officinalis (Houpo) and Rhizoma Imperatae (Baimaogen) were investigated for their potential antimicrobial and antioxidant properties.
+RESULTS: Extracts of Cortex Magnoliae Officinalis had the strongest activities against M. Smegmatis, C. albicans, B. subtilis and S. aureus.
+Boiled extracts of Cortex Magnoliae Officinalis, Folium Murraya Koenigii, Herba Polygonis Hydropiperis and Herba Houttuyniae demonstrated greater antioxidant activities than other tested medicinal plants.
+CONCLUSION: Among the eight tested medicinal plants, Cortex Magnoliae Officinalis showed the highest antimicrobial and antioxidant activities.
+Background: Herpes family viruses can cause central nervous system inflammatory changes that can present with symptoms indistinguishable from schizophrenia and therefore are of interest in schizophrenia research.
+As part of a larger research program, we conducted a hypothesis-generating case-control study of selected herpes virus antibodies among individuals discharged from the US military with schizophrenia and pre- and postdiagnosis sera.
+Methods: Cases (n = 180) were servicemembers hospitalized and discharged from military service with schizophrenia.
+We used microplate enzyme immunoassay to measure immunoglobulin G (IgG) antibody levels to 6 herpes viruses in pre- and postdiagnosis specimens.
+Conditional logistic regression was used, and the measure of association was the hazard ratio (HR).
+Results: Overall, we found a significant association between human herpes virus type 6 and schizophrenia, with an HR of 1.17 (95% confidence interval [CI] = 1.04, 1.32).
+Women and blacks had significant negative associations with herpes simplex virus type 2 and cytomegalovirus; among blacks, there was a significant positive association with herpes simplex virus type 1.
+Among men, there was a HHV-6 temporal effect with an HR of 1.41 (95% CI = 1.02, 1.96) for sera drawn 6–12 months before diagnosis.
+Our study is based on a larger population than most previous studies and used serum specimens collected before onset of illness.
+This study adds to the body of knowledge and provides testable hypotheses for follow-on studies.
+Seasonal variation in smallpox transmission is one of the most pressing ecological questions and is relevant to bioterrorism preparedness.
+In addition to time series analyses of reported data, an estimation and spectral analysis of the effective reproduction number at calendar time t, R(t), were made.
+Meteorological variables were extracted from a report in India from 1890–1921 and compared with smallpox mortality as well as R(t).
+Annual cycles of smallpox transmission were clearly shown not only in monthly reports but also in the estimates of R(t).
+Both mortality and R(t) revealed significant negative association (P < .01) and correlation (P < .01), respectively, with humidity.
+These findings suggest that smallpox transmission greatly varies with season and is most likely enhanced by dry weather.
+Chinese journals in epidemiology, preventive medicine and public health contain much that is of potential international interest.
+This article therefore provides an overview of the contemporary scene in Chinese biomedical journal publication, Chinese bibliographic databases and Chinese journals in epidemiology, preventive medicine and public health.
+The challenge of switching to English as the medium of publication, the development of publishing bibliometric data from Chinese databases, the prospect of an Open Access publication model in China, the issue of language bias in literature reviews and the quality of Chinese journals are discussed.
+Laribacter hongkongensis is a newly discovered Gram-negative bacillus of the Neisseriaceae family associated with freshwater fish–borne gastroenteritis and traveler's diarrhea.
+The complete genome sequence of L. hongkongensis HLHK9, recovered from an immunocompetent patient with severe gastroenteritis, consists of a 3,169-kb chromosome with G+C content of 62.35%.
+Genome analysis reveals different mechanisms potentially important for its adaptation to diverse habitats of human and freshwater fish intestines and freshwater environments.
+The gene contents support its phenotypic properties and suggest that amino acids and fatty acids can be used as carbon sources.
+The extensive variety of transporters, including multidrug efflux and heavy metal transporters as well as genes involved in chemotaxis, may enable L. hongkongensis to survive in different environmental niches.
+Genes encoding urease, bile salts efflux pump, adhesin, catalase, superoxide dismutase, and other putative virulence factors—such as hemolysins, RTX toxins, patatin-like proteins, phospholipase A1, and collagenases—are present.
+Proteomes of L. hongkongensis HLHK9 cultured at 37°C (human body temperature) and 20°C (freshwater habitat temperature) showed differential gene expression, including two homologous copies of argB, argB-20, and argB-37, which encode two isoenzymes of N-acetyl-L-glutamate kinase (NAGK)—NAGK-20 and NAGK-37—in the arginine biosynthesis pathway.
+NAGK-20 also had a lower optimal temperature for enzymatic activities and was inhibited by arginine probably as negative-feedback control.
+Similar duplicated copies of argB are also observed in bacteria from hot springs such as Thermus thermophilus, Deinococcus geothermalis, Deinococcus radiodurans, and Roseiflexus castenholzii, suggesting that similar mechanisms for temperature adaptation may be employed by other bacteria.
+Genome and proteome analysis of L. hongkongensis revealed novel mechanisms for adaptations to survival at different temperatures and habitats.
+Malignant mesothelioma is a fatal asbestos-associated malignancy originating from the lining cells (mesothelium) of the pleural and peritoneal cavities, as well as the pericardium and the tunica vaginalis.
+The exact prevalence is unknown but it is estimated that mesotheliomas represent less than 1% of all cancers.
+Breathlessness due to a pleural effusion without chest pain is reported in about 30% of patients.
+A chest wall mass, weight loss, sweating, abdominal pain and ascites (due to peritoneal involvement) are less common presentations.
+Mesothelioma is directly attributable to occupational asbestos exposure with a history of exposure in over 90% of cases.
+There is also evidence that mesothelioma may result from both para-occupational exposure and non-occupational "environmental" exposure.
+Idiopathic or spontaneous mesothelioma can also occur in the absence of any exposure to asbestos, with a spontaneous rate in humans of around one per million.
+A combination of accurate exposure history, along with examination radiology and pathology are essential to make the diagnosis.
+The most helpful CT findings suggesting malignant pleural disease are 1) a circumferential pleural rind, 2) nodular pleural thickening, 3) pleural thickening of > 1 cm and 4) mediastinal pleural involvement.
+Involvement of a multidisciplinary team is recommended to ensure prompt and appropriate management, using a framework of radiotherapy, chemotherapy, surgery and symptom palliation with end of life care.
+Life expectancy in malignant mesothelioma is poor, with a median survival of about one year following diagnosis.
+BACKGROUND: The anticipated extent of antiviral use during an influenza pandemic can have adverse consequences for the development of drug resistance and rationing of limited stockpiles.
+The strategic use of drugs is therefore a major public health concern in planning for effective pandemic responses.
+METHODS: We employed a mathematical model that includes both sensitive and resistant strains of a virus with pandemic potential, and applies antiviral drugs for treatment of clinical infections.
+Using estimated parameters in the published literature, the model was simulated for various sizes of stockpiles to evaluate the outcome of different antiviral strategies.
+RESULTS: We demonstrated that the emergence of highly transmissible resistant strains has no significant impact on the use of available stockpiles if treatment is maintained at low levels or the reproduction number of the sensitive strain is sufficiently high.
+However, moderate to high treatment levels can result in a more rapid depletion of stockpiles, leading to run-out, by promoting wide-spread drug resistance.
+We applied an antiviral strategy that delays the onset of aggressive treatment for a certain amount of time after the onset of the outbreak.
+Our results show that if high treatment levels are enforced too early during the outbreak, a second wave of infections can potentially occur with a substantially larger magnitude.
+However, a timely implementation of wide-scale treatment can prevent resistance spread in the population, and minimize the final size of the pandemic.
+CONCLUSION: Our results reveal that conservative treatment levels during the early stages of the outbreak, followed by a timely increase in the scale of drug-use, will offer an effective strategy to manage drug resistance in the population and avoid run-out.
+For a 1918-like strain, the findings suggest that pandemic plans should consider stockpiling antiviral drugs to cover at least 20% of the population.
+Rabies has been eliminated from domestic dog populations in Western Europe and North America, but continues to kill many thousands of people throughout Africa and Asia every year.
+A quantitative understanding of transmission dynamics in domestic dog populations provides critical information to assess whether global elimination of canine rabies is possible.
+We report extensive observations of individual rabid animals in Tanzania and generate a uniquely detailed analysis of transmission biology, which explains important epidemiological features, including the level of variation in epidemic trajectories.
+We found that the basic reproductive number for rabies, R(0), is very low in our study area in rural Africa (∼1.2) and throughout its historic global range (<2).
+This finding provides strong support for the feasibility of controlling endemic canine rabies by vaccination, even near wildlife areas with large wild carnivore populations.
+However, we show that rapid turnover of domestic dog populations has been a major obstacle to successful control in developing countries, thus regular pulse vaccinations will be required to maintain population-level immunity between campaigns.
+Nonetheless our analyses suggest that with sustained, international commitment, global elimination of rabies from domestic dog populations, the most dangerous vector to humans, is a realistic goal.
+BACKGROUND: The most common method of GMO detection is based upon the amplification of GMO-specific DNA amplicons using the polymerase chain reaction (PCR).
+Here we have applied the loop-mediated isothermal amplification (LAMP) method to amplify GMO-related DNA sequences, 'internal' commonly-used motifs for controlling transgene expression and event-specific (plant-transgene) junctions.
+RESULTS: We have tested the specificity and sensitivity of the technique for use in GMO studies.
+Results show that detection of 0.01% GMO in equivalent background DNA was possible and dilutions of template suggest that detection from single copies of the template may be possible using LAMP.
+CONCLUSION: This work shows that GMO detection can be carried out using LAMP for routine screening as well as for specific events detection.
+Moreover, the sensitivity and ability to amplify targets, even with a high background of DNA, here demonstrated, highlights the advantages of this isothermal amplification when applied for GMO detection.
+BACKGROUND: Sustained outbreaks of highly pathogenic avian influenza (HPAI) H5N1 in avian species increase the risk of reassortment and adaptation to humans.
+The ability to contain its spread in chickens would reduce this threat and help maintain the capacity for egg-based vaccine production.
+While vaccines offer the potential to control avian disease, a major concern of current vaccines is their potency and inability to protect against evolving avian influenza viruses.
+METHODOLOGY / PRINCIPAL FINDINGS: The ability of DNA vaccines encoding hemagglutinin (HA) proteins from different HPAI H5N1 serotypes was evaluated for its ability to elicit neutralizing antibodies and to protect against homologous and heterologous HPAI H5N1 strain challenge in mice and chickens after DNA immunization by needle and syringe or with a pressure injection device.
+These vaccines elicited antibodies that neutralized multiple strains of HPAI H5N1 when given in combinations containing up to 10 HAs.
+The response was dose-dependent, and breadth was determined by the choice of the influenza virus HA in the vaccine.
+Monovalent and trivalent HA vaccines were tested first in mice and conferred protection against lethal H5N1 A/Vietnam/1203/2004 challenge 68 weeks after vaccination.
+In chickens, protection was observed against heterologous strains of HPAI H5N1 after vaccination with a trivalent H5 serotype DNA vaccine with doses as low as 5 µg DNA given twice either by intramuscular needle injection or with a needle-free device.
+CONCLUSIONS/SIGNIFICANCE: DNA vaccines offer a generic approach to influenza virus immunization applicable to multiple animal species.
+In addition, the ability to substitute plasmids encoding different strains enables rapid adaptation of the vaccine to newly evolving field isolates.
+A Cucumber green mottle mosaic virus (CGMMV) was used to present a truncated dengue virus type 2 envelope (E) protein binding region from amino acids 379 to 423 (EB4).
+The EB4 gene was inserted at the terminal end of the CGMMV coat protein (CP) open reading frame (ORF).
+Read-through sequences of TMV or CGMMV, CAA-UAG-CAA-UUA, or AAA-UAG-CAA-UUA were, respectively, inserted in between the CP and the EB4 genes.
+The chimeric clones, pRT, pRG, and pCG+FSRTRE, were transcribed into full-length capped recombinant CGMMV transcripts.
+Only constructs with the wild-type CGMMV read-through sequence yielded infectious viruses following infection of host plant, muskmelon (Cucumis melo) leaves.
+The ratio of modified to unmodified CP for the read-through expression clone developed was also found to be approximately 1:1, higher than what has been previously reported.
+It was also observed that infectivity was not affected by differences in pI between the chimera and its wild counterpart.
+Analysis of recombinant viruses after 21-days-postinculation (dpi) revealed that deletions occurred resulting in partial reversions of the viral population to near wild type and suggesting that this would be the limiting harvest period for obtaining true to type recombinants with this construct.
+Control of norovirus outbreaks relies on enhanced hygiene measures, such as handwashing, surface cleaning, using disposable paper towels, and using separate toilets for sick and well persons.
+We analyzed norovirus outbreaks in 7 camps at an international scouting jamboree in the Netherlands during 2004.
+Implementation of hygiene measures coincided with an 84.8% (95% predictive interval 81.2%–86.6%) reduction in reproduction number.
+This reduction was unexpectedly large but still below the reduction needed to contain a norovirus outbreak.
+Even more stringent control measures are required to break the chain of transmission of norovirus.
+SP-A is expressed by alveolar epithelial cells type II as well as by a portion of non small cell lung carcinomas (NSCLC).
+SP-A is a major player in the pulmonary cytokine-network and moreover has been described to act in the pulmonary host defense.
+By the use of cell culture or animal models the functional properties have been repeatedly shown in many aspects, often bearing surprising properties which strongly indicate the physiological importance of SP-A.
+To date SP-A is recognized as a molecule essential for pulmonary development, structure and function.
+This article gives an overview about the state of knowledge on SP-A focused in applications for human pulmonary disorders and points out the importance for pathology-orientated research approaches using immunohistochemistry or in situ hybridization as promising methods to further elucidate the role of this molecule in adult lung diseases.
+Proteolytic processing of one of the precursors, AtPSK4, was demonstrated by cleavage of a preproAtPSK4–myc transgene product to AtPSK4–myc.
+The processing of proAtPSK4 was dependent on AtSBT1.1, a subtilisin-like serine protease, encoded by one of 56 subtilase genes in Arabidopsis.
+The gene encoding AtSBT1.1 was up-regulated following the transfer of root explants to tissue culture, suggesting that activation of the proteolytic machinery that cleaves proAtPSK4 is dependent on AtSBT1.1 expression.
+We also demonstrated that a fluorogenic peptide representing the putative subtilase recognition site in proAtPSK4 is cleaved in vitro by affinity-purified AtSBT1.1.
+An alanine scan through the recognition site peptide indicated that AtSBT1.1 is fairly specific for the AtPSK4 precursor.
+Thus, this peptide growth factor, which promotes callus formation in culture, is proteolytically cleaved from its precursor by a specific plant subtilase encoded by a gene that is up-regulated during the process of transfering root explants to tissue culture.
+One of the important fields to apply computational tools for domain boundaries prediction is structural biology.
+They can be used to design protein constructs that must be expressed in a stable and functional form and must produce diffraction-quality crystals.
+However, prediction of protein domain boundaries on the basis of amino acid sequences is still very problematical.
+It is observed that the statistical significance of most of the predictions is rather poor.
+Nevertheless, when the right number of domains is correctly predicted, domain boundaries are predicted within very few residues from their real location.
+It can be concluded that prediction methods cannot be used yet as routine tools in structural biology, though some of them are rather promising.
+BioSense is a US national system that uses data from health information systems for automated disease surveillance.
+We studied 4 time-series algorithm modifications designed to improve sensitivity for detecting artificially added data.
+To test these modified algorithms, we used reports of daily syndrome visits from 308 Department of Defense (DoD) facilities and 340 hospital emergency departments (EDs).
+At a constant alert rate of 1%, sensitivity was improved for both datasets by using a minimum standard deviation (SD) of 1.0, a 14–28 day baseline duration for calculating mean and SD, and an adjustment for total clinic visits as a surrogate denominator.
+Stratifying baseline days into weekdays versus weekends to account for day-of-week effects increased sensitivity for the DoD data but not for the ED data.
+These enhanced methods may increase sensitivity without increasing the alert rate and may improve the ability to detect outbreaks by using automated surveillance system data.
+The ability of pathogens to escape the host's immune response is crucial for the establishment of persistent infections and can influence virulence.
+Although distinctive recombination patterns have been described in many viral pathogens, little is known about the influence of biases in the recombination process itself relative to selective forces acting on newly formed recombinants.
+Understanding these influences is important for determining how recombination contributes to pathogen genome and proteome evolution.
+Most previous research on recombination-driven protein evolution has focused on relatively simple proteins, usually in the context of directed evolution experiments.
+Here, we study recombination in the envelope gene of HIV-1 between primary isolates belonging to subtypes that recombine naturally in the HIV/AIDS pandemic.
+By characterizing the early steps in the generation of recombinants, we provide novel insights into the evolutionary forces that shape recombination patterns within viral populations.
+Specifically, we show that the combined effects of mechanistic processes that determine the locations of recombination breakpoints across the HIV-1 envelope gene, and purifying selection acting against dysfunctional recombinants, can explain almost the entire distribution of breakpoints found within this gene in nature.
+These constraints account for the surprising paucity of recombination breakpoints found in infected individuals within this highly variable gene.
+Thus, the apparent randomness of HIV evolution via recombination may in fact be relatively more predictable than anticipated.
+In addition, the dominance of purifying selection in localized areas of the HIV genome defines regions where functional constraints on recombinants appear particularly strong, pointing to vulnerable aspects of HIV biology.
+Transmission of avian influenza viruses from bird to human is a rare event even though avian influenza viruses infect the ciliated epithelium of human airways in vitro and ex vivo.
+Using an in vitro model of human ciliated airway epithelium (HAE), we demonstrate that while human and avian influenza viruses efficiently infect at temperatures of the human distal airways (37°C), avian, but not human, influenza viruses are restricted for infection at the cooler temperatures of the human proximal airways (32°C).
+These data support the hypothesis that avian influenza viruses, ordinarily adapted to the temperature of the avian enteric tract (40°C), rarely infect humans, in part due to differences in host airway regional temperatures.
+Previously, a critical residue at position 627 in the avian influenza virus polymerase subunit, PB2, was identified as conferring temperature-dependency in mammalian cells.
+Here, we use reverse genetics to show that avianization of residue 627 attenuates a human virus, but does not account for the different infection between 32°C and 37°C.
+To determine the mechanism of temperature restriction of avian influenza viruses in HAE at 32°C, we generated recombinant human influenza viruses in either the A/Victoria/3/75 (H3N2) or A/PR/8/34 (H1N1) genetic background that contained avian or avian-like glycoproteins.
+Two of these viruses, A/Victoria/3/75 with L226Q and S228G mutations in hemagglutinin (HA) and neuraminidase (NA) from A/Chick/Italy/1347/99 and A/PR/8/34 containing the H7 and N1 from A/Chick/Italy/1347/99, exhibited temperature restriction approaching that of wholly avian influenza viruses.
+These data suggest that influenza viruses bearing avian or avian-like surface glycoproteins have a reduced capacity to establish productive infection at the temperature of the human proximal airways.
+This temperature restriction may limit zoonotic transmission of avian influenza viruses and suggests that adaptation of avian influenza viruses to efficient infection at 32°C may represent a critical evolutionary step enabling human-to-human transmission.
+BACKGROUND: At present, we have very limited ability to compare public health activity across jurisdictions and countries, or even to ascertain differences in what is considered to be a public health activity.
+Existing standardised health classifications do not capture important dimensions of public health, which include its functions, the methods and interventions used to achieve these, the health issues and determinants of health that public health activities address, the resources and infrastructure they use, and the settings in which they occur.
+A classification that describes these dimensions will promote consistency in collecting and reporting information about public health programs, expenditure, workforce and performance.
+METHODS: We used open-source Protégé software and published procedures to construct an ontology of public health, which forms the basis of the classification.
+We reviewed existing definitions of public health, descriptions of public health functions and classifications to develop the scope, domain, and multidimensional class structure of the ontology.
+These were then refined through a series of consultations with public health experts from across Australia, culminating in an initial classification framework.
+RESULTS: The public health classification consists of six top-level classes: public health 'Functions'; 'Health Issues'; 'Determinants of Health'; 'Settings'; 'Methods' of intervention; and 'Resources and Infrastructure'.
+Existing classifications (such as the international classifications of diseases, disability and functioning and external causes of injuries) can be used to further classify large parts of the classes 'Health Issues', 'Settings' and 'Resources and Infrastructure', while new subclass structures are proposed for the classes of public health 'Functions', 'Determinants of Health' and 'Interventions'.
+It will facilitate the organisation of information so that it can be used to address questions relating to any of these dimensions, either singly or in combination.
+However, the selection of siRNA-resistant viruses is a major concern in the use of RNAi as antiviral therapeutics.
+In this study, we conducted a lentiviral vector with a H1-short hairpin RNA (shRNA) expression cassette to deliver small interfering RNAs (siRNAs) into mammalian cells.
+Using this vector that also expresses enhanced green fluorescence protein (EGFP) as surrogate marker, stable shRNA-expressing cell lines were successfully established and the inhibition efficiencies of rationally designed siRNAs targeting to conserved regions of influenza A virus genome were assessed.
+The results showed that a siRNA targeting influenza M2 gene (siM2) potently inhibited viral replication.
+The siM2 was not only effective for H1N1 virus but also for highly pathogenic avian influenza virus H5N1.
+In addition to its M2 inhibition, the siM2 also inhibited NP mRNA accumulation and protein expression.
+A long term inhibition effect of the siM2 was demonstrated and the emergence of siRNA-resistant mutants in influenza quasispecies was not observed.
+Taken together, our study suggested that M2 gene might be an optimal RNAi target for antiviral therapy.
+These findings provide useful information for the development of RNAi-based prophylaxis and therapy for human influenza virus infection.
+BACKGROUND: There are increasing reports of severe clinical cases exclusively associated with Plasmodium vivax infections.
+PATIENTS: Two different patients presented at the Hospital Clinic in Barcelona with P. vivax malaria episodes.
+Two other patients with mild symptoms presented to the "Centro de Pesquisa em Medicina Tropical", also in the Brazilian Amazon (Rondônia) in 2000.
+METHODS: To exclude the possibility that the patient's severe symptoms were due to Plasmodium falciparum, a nested PCR was performed.
+Quantitative real-time PCR was performed to compare the transcript levels of two main transporters likely to be involved in chloroquine resistance in P. vivax, namely the P. vivax chloroquine resistance transporter, pvcrt-o, and the P. vivax multidrug resistance transporter, pvmdr 1.
+In addition, it was found that parasites obtained from the severe patient had up to 2.9-fold increase in pvmdr1 levels and up to 21.9-fold increase in pvcrt-o levels compared to expression levels of parasites from the other patients with mild symptoms.
+CONCLUSION: This is the first clinical case of severe disease exclusively associated with vivax malaria in Spain.
+Moreover, these findings suggest that clinical severity could be associated with increased expression levels of parasite genes likely involved in chloroquine resistance.
+It is necessary to further explore the potential of pvmdr1 and particularly pvcrt-o expression levels as molecular markers of severe disease in P. vivax.
+BACKGROUND: Prevention of mother-to-child transmission has been considered as not a simple intervention but a comprehensive set of interventions requiring capable health workers.
+Viet Nam's extensive health care system reaches the village level, but still HIV-infected mothers and children have received inadequate health care services for prevention of mother-to-child transmission.
+We report here the health workers' perceptions on factors that lead to their failure to give good quality prevention of mother-to-child transmission services.
+METHODS: Semistructured interviews with 53 health workers and unstructured observations in nine health facilities in Hanoi were conducted.
+Selection of respondents was based on their function, position and experience in the development or implementation of prevention of mother-to-child transmission policies/programmes.
+RESULTS: Factors that lead to health workers' failure to give good quality services for prevention of mother-to-child transmission include their own fear of HIV infection; lack of knowledge on HIV and counselling skills; or high workloads and lack of staff; unavailability of HIV testing at commune level; shortage of antiretroviral drugs; and lack of operational guidelines.
+A negative attitude during counselling and provision of care, treating in a separate area and avoidance of providing service at all were seen by health workers as the result of fear of being infected, as well as distrust towards almost all HIV-infected patients because of the prevailing association with antisocial behaviours.
+Additionally, the fragmentation of the health care system into specialized vertical pillars, including a vertical programme for HIV/AIDS, is a major obstacle to providing a continuum of care.
+CONCLUSION: Many hospital staff were not being able to provide good care or were even unwilling to provide appropriate care for HIV-positive pregnant women The study suggests that the quality of prevention of mother-to-child transmission service could be enhanced by improving communication and other skills of health workers, providing them with greater support and enhancing their motivation.
+Development of a practical strategy is needed to strengthen and adapt the referral system to meet the needs of patients.
+BACKGROUND: Proteolytic processing of the Lassa virus envelope glycoprotein precursor GP-C by the host proprotein convertase site 1 protease (S1P) is a prerequisite for the incorporation of the subunits GP-1 and GP-2 into viral particles and, hence, essential for infectivity and virus spread.
+Therefore, we tested in this study the concept of using S1P as a target to block efficient virus replication.
+METHODOLOGY/PRINCIPAL FINDING: We demonstrate that stable cell lines inducibly expressing S1P-adapted α(1)-antitrypsin variants inhibit the proteolytic maturation of GP-C. Introduction of the S1P recognition motifs RRIL and RRLL into the reactive center loop of α(1)-antitrypsin resulted in abrogation of GP-C processing by endogenous S1P to a similar level observed in S1P-deficient cells.
+Moreover, S1P-specific α(1)-antitrypsins significantly inhibited replication and spread of a replication-competent recombinant vesicular stomatitis virus expressing the Lassa virus glycoprotein GP as well as authentic Lassa virus.
+Inhibition of viral replication correlated with the ability of the different α(1)-antitrypsin variants to inhibit the processing of the Lassa virus glycoprotein precursor.
+CONCLUSIONS/SIGNIFICANCE: Our data suggest that glycoprotein cleavage by S1P is a promising target for the development of novel anti-arenaviral strategies.
+The improvement of prevention and treatment of viral infections and their associated diseases remains one of the main public health challenges.
+Towards this goal, deciphering virus–host molecular interactions opens new perspectives to understand the biology of infection and for the design of new antiviral strategies.
+Indeed, modelling of an infection network between viral and cellular proteins will provide a conceptual and analytic framework to efficiently formulate new biological hypothesis at the proteome scale and to rationalize drug discovery.
+Therefore, we present the first release of VirHostNet (Virus–Host Network), a public knowledge base specialized in the management and analysis of integrated virus–virus, virus–host and host–host interaction networks coupled to their functional annotations.
+VirHostNet integrates an extensive and original literature-curated dataset of virus–virus and virus–host interactions (2671 non-redundant interactions) representing more than 180 distinct viral species and one of the largest human interactome (10 672 proteins and 68 252 non-redundant interactions) reconstructed from publicly available data.
+The VirHostNet Web interface provides appropriate tools that allow efficient query and visualization of this infected cellular network.
+Rfam is a collection of RNA sequence families, represented by multiple sequence alignments and covariance models (CMs).
+The primary aim of Rfam is to annotate new members of known RNA families on nucleotide sequences, particularly complete genomes, using sensitive BLAST filters in combination with CMs.
+tRNA and rRNA) provide the majority of the sequence annotations, whilst the majority of Rfam families (e.g.
+snoRNAs and miRNAs) have a limited taxonomic range and provide a limited number of annotations.
+To evaluate genotypic diversity and identify forces shaping picornavirus evolution, we screened persons with respiratory illnesses by using rhinovirus-specific or generic real-time PCR assays.
+We then sequenced the 5′ untranslated region, capsid protein VP1, and protease precursor 3CD regions of virus-positive samples.
+We identified and completed the genome sequence of a new enterovirus genotype associated with respiratory symptoms and acute otitis media, confirming the close relationship between rhinoviruses and enteroviruses and the need to detect both viruses in respiratory specimens.
+Finally, we identified recombinants among circulating rhinoviruses and mapped their recombination sites, thereby demonstrating that rhinoviruses can recombine in their natural host.
+BACKGROUND: Rapid and cost-effective methods for HIV-1 diagnosis and viral load monitoring would greatly enhance the clinical management of HIV-1 infected adults and children in limited-resource settings.
+Recent recommendations to treat perinatally infected infants within the first year of life are feasible only if early diagnosis is routinely available.
+Dried blood spots (DBS) on filter paper are an easy and convenient way to collect and transport blood samples.
+A rapid and cost effective method to diagnose and quantify HIV-1 from DBS is urgently needed to facilitate early diagnosis of HIV-1 infection and monitoring of antiretroviral therapy.
+METHODS AND FINDINGS: We have developed a real-time LightCycler (rtLC) PCR assay to detect and quantify HIV-1 from DBS.
+HIV-1 RNA extracted from DBS was amplified in a one-step, single-tube system using primers specific for long-terminal repeat sequences that are conserved across all HIV-1 clades.
+SYBR Green dye was used to quantify PCR amplicons and HIV-1 RNA copy numbers were determined from a standard curve generated using serially diluted known copies of HIV-1 RNA.
+This assay detected samples across clades, has a dynamic range of 5 log(10), and %CV <8% up to 4 log(10) dilution.
+Plasma HIV-1 RNA copy numbers obtained using this method correlated well with the Roche Ultrasensitive (r = 0.91) and branched DNA (r = 0.89) assays.
+The rtLC DBS assay was 2.5 fold rapid as well as 40-fold cheaper when compared to commercial assays.
+CONCLUSIONS: The accuracy, reliability, genotype inclusivity and affordability, along with the small volumes of blood required for the assay suggest that the rtLC DBS assay will be useful for early diagnosis and monitoring of pediatric HIV-1 infection in resource-limited settings.
+BACKGROUND: Epidemiological interventions aim to control the spread of infectious disease through various mechanisms, each carrying a different associated cost.
+METHODOLOGY: We describe a flexible statistical framework for generating optimal epidemiological interventions that are designed to minimize the total expected cost of an emerging epidemic while simultaneously propagating uncertainty regarding the underlying disease model parameters through to the decision process.
+The strategies produced through this framework are adaptive: vaccination schedules are iteratively adjusted to reflect the anticipated trajectory of the epidemic given the current population state and updated parameter estimates.
+CONCLUSIONS: Using simulation studies based on a classic influenza outbreak, we demonstrate the advantages of adaptive interventions over non-adaptive ones, in terms of cost and resource efficiency, and robustness to model misspecification.
+Multiple organ dysfunction syndrome (MODS) occurs in response to major insults such as sepsis, severe haemorrhage, trauma, major surgery and pancreatitis.
+Overwhelming inflammation, immunoparesis, occult oxygen debt and other mechanisms have been investigated, and – despite many unanswered questions – therapies targeting these mechanisms have been developed.
+Unfortunately, only a few interventions, usually those targeting multiple mechanisms at the same time, have appeared to be beneficial.
+It functions at the intersection of several systems, including inflammation, coagulation, haemodynamics, fluid and electrolyte balance, and cell migration.
+In this review we describe this signalling system, giving special attention to what is known about it in critically ill patients and its potential as a target for therapy.
+In this work, we study the consequences of sequence variations of the "2009 H1N1" (swine or Mexican flu) influenza A virus strain neuraminidase for drug treatment and vaccination.
+We find that it is phylogenetically more closely related to European H1N1 swine flu and H5N1 avian flu rather than to the H1N1 counterparts in the Americas.
+Homology-based 3D structure modeling reveals that the novel mutations are preferentially located at the protein surface and do not interfere with the active site.
+The latter is the binding cavity for 3 currently used neuraminidase inhibitors: oseltamivir (Tamiflu(®)), zanamivir (Relenza(®)) and peramivir; thus, the drugs should remain effective for treatment.
+However, the antigenic regions of the neuraminidase relevant for vaccine development, serological typing and passive antibody treatment can differ from those of previous strains and already vary among patients.
+BACKGROUND: Anatid herpesvirus 1 (AHV-1) is an alphaherpesvirus associated with latent infection and mortality in ducks and geese and is currently affecting the world-wide waterfowl production severely.
+Here we describe a fluorescent quantitative real-time PCR (FQ-PCR) method developed for fast measurement of AHV-1 DNA based on TaqMan MGB technology.
+RESULTS: The detection limit of the assay was 1 × 10(1 )standard DNA copies, with a sensitivity of 2 logs higher than that of the conventional gel-based PCR assay targeting the same gene.
+The real-time PCR was reproducible, as shown by satisfactory low intra-assay and inter-assay coefficients of variation.
+CONCLUSION: The high sensitivity, specificity, simplicity and reproducibility of the AHV-1 fluorogenic PCR assay, combined with its wide dynamic range and high throughput, make this method suitable for a broad spectrum of AHV-1 etiologically related application.
+Reverse transcriptase (RT) of human immunodeficiency virus (HIV)-1 plays a key role in initiating viral replication and is an important target for developing anti-HIV drugs.
+Our previous study showed that two mutations (Y271A and I274A) in the turn RT (Gln(269)-Arg(277)) abrogated viral replication, but the replication capacity and RT activity was discordant.
+In this study, we further investigated why alanine substitutions at these two sites would affect viral replication.
+We found that both RT activity and RT protein were almost undetectable in viral particles of these two mutants, although the Pr160(gag-pol) mutants were properly expressed, transported and incorporated.
+Using protease inhibition assay, we demonstrated a correlation between the degradation of the RT mutants and the activity of viral protease.
+Our native gel analysis indicated that the mutations at 271 and 274 amino acids might cause conformational changes, leading to the formation of higher order oligomers instead of dimers, resulting in increased protein instability and susceptibility to viral protease.
+Thus, residues 271 and 274 are critical to RT stability and resistance to viral protease.
+The conservation of the two amino acid residues among different strains of HIV-1 lent further support to this conclusion.
+The CVTree web server (http://tlife.fudan.edu.cn/cvtree) presented here is a new implementation of the whole genome-based, alignment-free composition vector (CV) method for phylogenetic analysis.
+It is more efficient and user-friendly than the previously published version in the 2004 web server issue of Nucleic Acids Research.
+The development of whole genome-based alignment-free CV method has provided an independent verification to the traditional phylogenetic analysis based on a single gene or a few genes.
+This new implementation attempts to meet the challenge of ever increasing amount of genome data and includes in its database more than 850 prokaryotic genomes which will be updated monthly from NCBI, and more than 80 fungal genomes collected manually from several sequencing centers.
+Users can upload their own sequences to find their phylogenetic position among genomes selected from the server's; inbuilt database.
+In addition to standard phylogenetic trees, users can also choose to output trees whose monophyletic branches are collapsed to various taxonomic levels.
+This feature is particularly useful for comparing phylogeny with taxonomy when dealing with thousands of genomes.
+BACKGROUND: Glioblastoma is the most frequent and most malignant primary brain tumor with a poor prognosis.
+The translation of therapeutic strategies for glioblastoma from the experimental phase into the clinic has been limited by insufficient animal models, which lack important features of human tumors.
+Lentiviral gene therapy is an attractive therapeutic option for human glioblastoma, which we validated in a clinically relevant animal model.
+METHODOLOGY/PRINCIPAL FINDINGS: We used a rodent xenograft model that recapitulates the invasive and angiogenic features of human glioblastoma to analyze the transduction pattern and therapeutic efficacy of lentiviral pseudotyped vectors.
+Both, lymphocytic choriomeningitis virus glycoprotein (LCMV-GP) and vesicular stomatitis virus glycoprotein (VSV-G) pseudotyped lentiviral vectors very efficiently transduced human glioblastoma cells in vitro and in vivo.
+In contrast, pseudotyped gammaretroviral vectors, similar to those evaluated for clinical therapy of glioblastoma, showed inefficient gene transfer in vitro and in vivo.
+Both pseudotyped lentiviral vectors transduced cancer stem-like cells characterized by their CD133-, nestin- and SOX2-expression, the ability to form spheroids in neural stem cell medium and to express astrocytic and neuronal differentiation markers under serum conditions.
+In a therapeutic approach using the suicide gene herpes simplex virus thymidine kinase (HSV-1-tk) fused to eGFP, both lentiviral vectors mediated a complete remission of solid tumors as seen on MRI resulting in a highly significant survival benefit (p<0.001) compared to control groups.
+In all recurrent tumors, surviving eGFP-positive tumor cells were found, advocating prodrug application for several cycles to even enhance and prolong the therapeutic effect.
+CONCLUSIONS/SIGNIFICANCE: In conclusion, lentiviral pseudotyped vectors are promising candidates for gene therapy of glioma in patients.
+The inefficient gene delivery by gammaretroviral vectors is in line with the results obtained in clinical therapy for GBM and thus confirms the high reproducibility of the invasive glioma animal model for translational research.
+An oligonucleotide array (microarray) incorporating 13,000 elements representing selected strains of hepatitis A virus (HAV), human coxsackieviruses A and B (CVA and CVB), genogroups I and II of Norovirus (NV), and human rotavirus (RV) gene segments 3,4,10, and 11 was designed based on the principle of tiling.
+Each oligonucleotide was 29 bases long, starting at every 5th base of every sequence, resulting in an overlap of 24 bases in two consecutive oligonucleotides.
+The applicability of the array for virus identification was examined using PCR amplified products from multiple HAV and CV strains.
+PCR products labeled with biotin were hybridized to the array, and the biotin was detected using a brief reaction with Cy3-labeled streptavidin, the array subjected to laser scanning, and the hybridization data plotted as fluorescence intensity against each oligonucleotide in the array.
+The combined signal intensities of all probes representing a particular strain of virus were calculated and plotted against all virus strains identified on a linear representation of the array.
+The profile of the total signal intensity identified the strain that is most likely represented in the amplified cDNA target.
+The results obtained with HAV and CV indicated that the hybridization profile thus generated can be used to identify closely related viral strains.
+This represents a significant improvement over current methods for virus identification using PCR amplification and amplicon sequencing.
+Multiple sclerosis (MS) with onset in childhood offers a unique opportunity to study the infectious background of this disease but the immune reactions against infectious agents in such children have only recently been investigated.
+These and other epidemiological studies strongly implicate involvement of one or more infectious agents in the aetiology of MS, with Epstein-Barr virus (EBV) being the prime candidate.
+Rather than being the actual cause of MS, it is more probable that these agents are involved in the development of immunoregulatory pathways.
+These pathways, if disturbed by hygiene-related factors including an altered sequence of infections, may generate and maintain a deficit within the immunological network that facilitates, to particular early events in the development of MS, preceding the onset of MS disease by years or a decade.
+A framework that can serve as a guide for further epidemiological, immunologic and molecular biologic investigations is formulated.
+This approach may shed light on the complex natural history of MS and may lead to rational preventive and therapeutic strategies.
+It is possible that, in the future, MS could be prevented by vaccination against EBV in early childhood; the framework is of relevance to the design of an appropriate type of vaccine.
+BACKGROUND: Human rhinoviruses (HRVs) are a highly prevalent cause of acute respiratory infection in children.
+They are classified into at least three species, HRV-A, HRV-B and HRV-C, which are characterized by sequencing the 5′ untranslated region (UTR) or the VP4/VP2 region of the genome.
+Given the increased interest for novel HRV strain identification and their worldwide distribution, we have carried out clinical and molecular diagnosis of HRV strains in a 2-year study of children with acute respiratory infection visiting one district hospital in Shanghai.
+METHODOLOGY/FINDINGS: We cloned and sequenced a 924-nt fragment that covered part of the 5′UTR and the VP4/VP2 capsid genes.
+Two samples were co-infected with HRV-A and HRV-B or HRV-C. By comparative analysis of the VP4/VP2 sequences of the 66 HRVs, we showed a high diversity of strains in HRV-A and HRV-B species, and a prevalence of 51.5% of strains that belonged to the recently identified HRV-C species.
+When analyzing a fragment of the 5′ UTR, we characterized at least two subspecies of HRV-C: HRV-Cc, which clustered differently from HRV-A and HRV-B, and HRV-Ca, which resulted from previous recombination in this region with sequences related to HRV-A.
+The full-length sequence of one strain of each HRV-Ca and HRV-Cc subspecies was obtained for comparative analysis.
+We confirmed the close relationship of their structural proteins but showed apparent additional recombination events in the 2A gene and 3′UTR of the HRV-Ca strain.
+Double or triple infections with HRV-C and respiratory syncytial virus and/or bocavirus were diagnosed in 33.3% of the HRV-infected patients, but no correlation with severity of clinical outcome was observed.
+CONCLUSION: Our study showed a high diversity of HRV strains that cause bronchitis and pneumonia in children.
+A predominance of HRV-C over HRV-A and HRV-B was observed, and two subspecies of HRV-C were identified, the diversity of which seemed to be related to recombination with former HRV-A strains.
+None of the HRV-C strains appeared to have a higher clinical impact than HRV-A or HRV-B on respiratory compromise.
+INTRODUCTION: The precise role of cytomegalovirus (CMV) infection in contributing to outcomes in critically ill immunocompetent patients has not been fully defined.
+METHODS: Studies in which critically ill immunocompetent adults were monitored for CMV infection in the intensive care unit (ICU) were reviewed.
+RESULTS: CMV infection occurs in 0 to 36% of critically ill patients, mostly between 4 and 12 days after ICU admission.
+Prolonged mechanical ventilation (21 to 39 days vs. 13 to 24 days) and duration of ICU stay (33 to 69 days vs. 22 to 48 days) correlated significantly with a higher risk of CMV infection.
+Mortality rates in patients with CMV infection were higher in some but not all studies.
+Whether CMV produces febrile syndrome or end-organ disease directly in these patients is not known.
+CONCLUSIONS: CMV infection frequently occurs in critically ill immunocompetent patients and may be associated with poor outcomes.
+Further studies are warranted to identify subsets of patients who are likely to develop CMV infection and to determine the impact of antiviral agents on clinically meaningful outcomes in these patients.
+INTRODUCTION: Respiratory syncytial virus (RSV) lower respiratory tract disease is characterised by narrowing of the airways resulting in increased airway resistance, air-trapping and respiratory acidosis.
+The objective of this prospective cross-over study was to determine the effects of mechanical ventilation with heliox 60/40 versus conventional gas on respiratory system resistance, air-trapping and CO2 removal.
+METHODS: Mechanically ventilated, sedated and paralyzed infants with proven RSV were enrolled within 24 hours after paediatric intensive care unit (PICU)admission.
+At T = 0, respiratory system mechanics including respiratory system compliance and resistance, and peak expiratory flow rate were measured with the AVEA ventilator.
+The measurements were repeated at each interval (after 30 minutes of ventilation with heliox, after 30 minutes of ventilation with nitrox and again after 30 minutes of ventilation with heliox).
+Air-trapping (defined by relative change in end-expiratory lung volume) was determined by electrical impedance tomography (EIT) at each interval.
+This was not accompanied by an improved CO2 elimination, decreased peak expiratory flow rate or decreased end-expiratory lung volume.
+BACKGROUND: Cyclooxygenase-2 (COX-2) is over-expressed in colorectal cancer (CRC), rendering tumour cells resistant to apoptosis.
+Selective COX-2 inhibition is effective in CRC prevention, although having adverse cardiovascular effects, thus focus has shifted to downstream pathways.
+In vitro and in vivo regulation of DRAK2 (DAP kinase-related apoptosis-inducing kinase 2 or STK17β, an apoptosis-inducing kinase) by COX-2 was validated by qRT-PCR.
+RESULTS: Inhibition of COX-2 induced apoptosis and enhanced DRAK2 expression in HCA7 cells (4.4-fold increase at 4 h by qRT-PCR, P=0.001), an effect prevented by co-administration of PGE(2).
+DRAK2 levels were suppressed in a panel of human colorectal tumours (n=10) compared to normal mucosa, and showed inverse correlation with COX-2 expression (R=−0.68, R(2)=0.46, P=0.03).
+Administration of the selective COX-2 inhibitor rofecoxib to patients with CRC (n=5) induced DRAK2 expression in tumours (2.5-fold increase, P=0.01).
+In vitro silencing of DRAK2 by RNAi enhanced CRC cell survival following COX-2 inhibitor treatment.
+CONCLUSION: DRAK2 is a serine–threonine kinase implicated in the regulation of apoptosis and is negatively regulated by COX-2 in vitro and in vivo, suggesting a novel mechanism for the effect of COX-2 on cancer cell survival.
+BACKGROUND: The Picornaviridae family contains a number of important pathogenic viruses, among which the recently reclassified human parechoviruses (HPeVs).
+Understanding the evolutionary history of HPeV could answer questions such as how long the circulating lineages last shared a common ancestor and how the evolution of this viral species is shaped by its population dynamics.
+Using both strict and relaxed clock Bayesian phylogenetics we investigated 1) the substitutions rates of the structural P1 and capsid VP1 regions and 2) evolutionary timescale of currently circulating HPeV lineages.
+RESULTS: Our estimates reveal that human parechoviruses exhibit high substitution rates for both structural P1 and capsid VP1 regions, respectively 2.21 × 10(-3 )(0.48 – 4.21 × 10(-3)) and 2.79 × 10(-3 )(2.05 – 3.66 × 10(-3)) substitutions per site per year.
+By employing a constant population size coalescent prior, the date of the most recent common ancestor was estimated to be at around 1600 (1427–1733).
+In addition, by looking at the frequency of synonymous and non-synonymous substitutions within the VP1 gene we show that purifying selection constitutes the dominating evolutionary force leading to strong amino acid conservation.
+CONCLUSION: In conclusion, our estimates provide a timescale for the evolution of HPeVs and suggest that genetic diversity of current circulating HPeV types has arisen about 400 years ago.
+China’s first HIV infection was officially reported in 1985 and by the end of 1996, there may have been up to 200,000 people affected nationwide.
+China may soon have the largest HIV-infected population in the world, possibly 6 million cases by 2005.
+With infection rates rising at about 30% per year, it is feared this figure might exceed 10 million by 2010.
+Although the Chinese government was initially slow to accept the problem, in the late 1990s definite changes began occurring.
+In 2003 Premier Wen Jiabao publicly shook the hand of an AIDS patient and his government promised to introduce a range of free HIV-related services.
+Unfortunately, there will still be many obstacles in controlling the epidemic and preventing further spread of this disease.
+Without doubt, China faces a serious predicament in the new millennium, and one which will pose numerous challenges for preventive medicine.
+The use of animals as sentinels of human disease revolves around the concept of nidality.
+That is, an agent of disease occupies a particular ecologic niche and alterations in that niche will change the function of that agent relative to traditional host-agent-environment relationships.
+Nidus is defined as a nest or breeding place, particularly a place where microbes such as bacteria, fungi, viruses, as well as other organisms and larger parasites, are located and multiply.
+Application of the concept of nidality and development of prevention strategies has most frequently been associated with military campaigns and interruption of tick-borne infections.
+Modern usage of the phrase “one-medicine” was popularized in the United States and Europe by Calvin Schwabe and the concept is attributed to Rudolph Virchow.
+It is applied today to the study of zoonotic disease and interventions in rural agricultural communities that share close living arrangements between people and their families, their pastoral work environment, and the animals for which they care.
+Integration of the two concepts of one-medicine and nidality provides an opportunity to apply a systems approach (i.e.
+general systems theory) to dealing with emerging zoonotic diseases in today’s global agricultural and industrial settings.
+The incidence and frequency of epidemic transmission of zoonotic diseases, both known and newly recognized, has increased dramatically in the past 30 years.
+It is thought that this dramatic disease emergence is primarily the result of the social, demographic, and environmental transformation that has occurred globally since World War II.
+Investigating emerging zoonotic pathogens as an ecological phenomenon can provide significant insights as to why some of these pathogens have jumped species and caused major epidemics in humans.
+A review of concepts and theory from biological ecology and of causal factors in disease emergence previously described suggests a general model of global zoonotic disease emergence.
+The model links demographic and societal factors to land use and land cover change whose associated ecological factors help explain disease emergence.
+The scale and magnitude of these changes are more significant than those associated with climate change, the effects of which are largely not yet understood.
+Unfortunately, the complex character and non-linear behavior of the human-natural systems in which host-pathogen systems are embedded makes specific incidences of disease emergence or epidemics inherently difficult to predict.
+Employing a complex systems analytical approach, however, may show how a few key ecological variables and system properties, including the adaptive capacity of institutions, explains the emergence of infectious diseases and how an integrated, multi-level approach to zoonotic disease control can reduce risk.
+This paper explores the possibilities for global governance effectively dealing with the international transmission of disease.
+First, zoonotic regulation and control pose a special case for public health agencies, and this paper proposes a propositional model for an effective public health stance.
+Second, globalization dynamics are briefly reviewed in terms of an emerging consensus on the need for global governance in public health.
+Third, a brief examination of global governance modalities suggests that a strong global governance case has distinct limitations (despite its possible justification); an exploration of contemporary directions in global governance follows.
+Finally, the paper examines the phenomenon of contemporary zoonotic control within the conditions of an effective regulatory regime.
+Imidazoline receptors were first proposed by Bousquet et al., when they studied antihypertensive effect of clonidine.
+A strong candidate for I1R, known as imidazoline receptor antisera-selected protein (IRAS), has been cloned from human hippocampus.
+To elucidate the functional and structure properties of I1R, we developed the newly monoclonal antibody against the N-terminal hIRAS region including the PX domain (10–120aa) through immunization of BALB/c mice with the NusA-IRAS fusion protein containing an IRAS N-terminal (10–120aa).
+Stable hybridoma cell lines were established and monoclonal antibodies specifically recognized full-length IRAS proteins in their native state by immunoblotting and immunoprecipitation.
+Monoclonal antibodies stained in a predominantly punctate cytoplasmic pattern when applied to IRAS-transfected HEK293 cells by indirect immunofluorescence assays and demonstrated excellent reactivity in flow immunocytometry.
+These monoclonal antibodies will provide powerful reagents for the further investigation of hIRAS protein functions.
+30 years before the discovery of the pfcrt gene, altered cellular drug accumulation in drug-resistant malarial parasites had been well documented.
+Heme released from catabolized hemoglobin was thought to be a key target for quinoline drugs, and additional modifications to quinoline drug structure in order to improve activity against chloroquine-resistant malaria were performed in a few laboratories.
+However, parasite cell culture methods were still in their infancy, assays for drug susceptibility were not well standardized, and the power of malarial genetics was decades away.
+The last 10 years have witnessed explosive progress in elucidation of the biochemistry of chloroquine resistance.
+During migratory movements, birds carry pathogens that can be transmitted between species at breeding, wintering, and stopover places where numerous birds of various species are concentrated.
+We consider the area of the Camargue (southern France) as an example to highlight how ad hoc information already available on birds’ movements, abundance, and diversity can help assess the introduction and transmission risk for birdborne diseases in the western Mediterranean wetlands.
+Avian influenza and West Nile viruses are used as examples because birds are central to the epidemiology of these viruses.
+INTRODUCTION: Autoimmune hemolytic anemia in children younger than 2 years of age is usually characterized by a severe course, with a mortality rate of approximately 10%.
+The prolonged immunosuppression following specific treatment may be associated with a high risk of developing severe infections.
+Recently, the use of monoclonal antibodies (rituximab) has allowed sustained remissions to be obtained in the majority of pediatric patients with refractory autoimmune hemolytic anemia.
+CASE PRESENTATION: We describe the case of an 8-month-old Caucasian girl affected by a severe form of autoimmune hemolytic anemia, which required continuous steroid treatment for 16 months.
+Thereafter, she received 4 weekly doses of rituximab (375 mg/m(2)/dose) associated with steroid therapy, which was then tapered over the subsequent 2 weeks.
+One month after the last dose of rrituximab, she presented with recurrence of severe hemolysis and received two more doses of rrituximab.
+The patient remained in clinical remission for 7 months, before presenting with a further relapse.
+An alternative heavy immunosuppressive therapy was administered combining cyclophosphamide 10 mg/kg/day for 10 days with methylprednisolone 40 mg/kg/day for 5 days, which was then tapered down over 3 weeks.
+While still on steroid therapy, the patient developed an interstitial pneumonia with Acute Respiratory Distress Syndrome, which required immediate admission to the intensive care unit where extracorporeal membrane oxygenation therapy was administered continuously for 37 days.
+At 16-month follow-up, the patient is alive and in good clinical condition, with no organ dysfunction, free from any immunosuppressive treatment and with a normal Hb level.
+CONCLUSIONS: This case shows that aggressive combined immunosuppressive therapy may lead to a sustained complete remission in children with refractory autoimmune hemolytic anemia.
+However, the severe life-threatening complication presented by our patient indicates that strict clinical monitoring must be vigilantly performed, that antimicrobial prophylaxis should always be considered and that experienced medical and nursing staff must be available, to deliver highly specialized supportive salvage therapies, if necessary, during intensive care monitoring.
+Maintenance of endoplasmic reticulum (ER) function is achieved in part through Ire1 (inositol-requiring enzyme 1), a transmembrane protein activated by protein misfolding in the ER.
+The cytoplasmic nuclease domain of Ire1 cleaves the messenger RNA (mRNA) encoding XBP-1 (X-box–binding protein 1), enabling splicing and production of this active transcription factor.
+We recently showed that Ire1 activation independently induces the rapid turnover of mRNAs encoding membrane and secreted proteins in Drosophila melanogaster cells through a pathway we call regulated Ire1-dependent decay (RIDD).
+In this study, we show that mouse fibroblasts expressing wild-type Ire1 but not an Ire1 variant lacking nuclease activity also degrade mRNAs in response to ER stress.
+Using a second variant of Ire1 that is activated by a small adenosine triphosphate analogue, we show that although XBP-1 splicing can be artificially induced in the absence of ER stress, RIDD appears to require both Ire1 activity and ER stress.
+Our data suggest that cells use a multitiered mechanism by which different conditions in the ER lead to distinct outputs from Ire1.
+DNA sequences seen in the normal character-based representation appear to have a formidable mixing of the four nucleotides without any apparent order.
+Nucleotide frequencies and distributions in the sequences have been studied extensively, since the simple rule given by Chargaff almost a century ago that equates the total number of purines to the pyrimidines in a duplex DNA sequence.
+While it is difficult to trace any relationship between the bases from studies in the character representation of a DNA sequence, graphical representations may provide a clue.
+These novel representations of DNA sequences have been useful in providing an overview of base distribution and composition of the sequences and providing insights into many hidden structures.
+We report here our observation based on a graphical representation that the intra-purine and intra-pyrimidine differences in sequences of conserved genes generally follow a quadratic distribution relationship and show that this may have arisen from mutations in the sequences over evolutionary time scales.
+From this hitherto undescribed relationship for the gene sequences considered in this report we hypothesize that such relationships may be characteristic of these sequences and therefore could become a barrier to large scale sequence alterations that override such characteristics, perhaps through some monitoring process inbuilt in the DNA sequences.
+Such relationship also raises the possibility of intron sequences playing an important role in maintaining the characteristics and could be indicative of possible intron-late phenomena.
+Objective To assess the acceptability of pre-pandemic influenza vaccination among healthcare workers in public hospitals in Hong Kong and the effect of escalation in the World Health Organization’s alert level for an influenza pandemic.
+Design Repeated cross sectional studies using self administered, anonymous questionnaires Setting Surveys at 31 hospital departments of internal medicine, paediatrics, and emergency medicine under the Hong Kong Hospital Authority from January to March 2009 and in May 2009 Participants 2255 healthcare workers completed the questionnaires in the two studies.
+Main outcome measures Stated willingness to accept pre-pandemic influenza vaccination (influenza A subtypes H5N1 or H1N1) and its associating factors.
+Results The overall willingness to accept pre-pandemic H5N1 vaccine was only 28.4% in the first survey, conducted at WHO influenza pandemic alert phase 3.
+No significant changes in the level of willingness to accept pre-pandemic H5N1 vaccine were observed despite the escalation to alert phase 5.
+The willingness to accept pre-pandemic H1N1 vaccine was 47.9% among healthcare workers when the WHO alert level was at phase 5.
+The most common reasons for an intention to accept were “wish to be protected” and “following health authority’s advice.” The major barriers identified were fear of side effects and doubts about efficacy.
+More than half of the respondents thought nurses should be the first priority group to receive the vaccines.
+The strongest positive associating factors were history of seasonal influenza vaccination and perceived risk of contracting the infection.
+Conclusions The willingness to accept pre-pandemic influenza vaccination was low, and no significant effect was observed with the change in WHO alert level.
+Further studies are required to elucidate the root cause of the low intention to accept pre-pandemic vaccination.
+Herpesviruses constitute a family of large DNA viruses widely spread in vertebrates and causing a variety of different diseases.
+They possess dsDNA genomes ranging from 120 to 240 kbp encoding between 70 to 170 open reading frames.
+We previously reported the protein interaction networks of two herpesviruses, varicella-zoster virus (VZV) and Kaposi's sarcoma-associated herpesvirus (KSHV).
+In this study, we systematically tested three additional herpesvirus species, herpes simplex virus 1 (HSV-1), murine cytomegalovirus and Epstein-Barr virus, for protein interactions in order to be able to perform a comparative analysis of all three herpesvirus subfamilies.
+We identified 735 interactions by genome-wide yeast-two-hybrid screens (Y2H), and, together with the interactomes of VZV and KSHV, included a total of 1,007 intraviral protein interactions in the analysis.
+Whereas a large number of interactions have not been reported previously, we were able to identify a core set of highly conserved protein interactions, like the interaction between HSV-1 UL33 with the nuclear egress proteins UL31/UL34.
+Interactions were conserved between orthologous proteins despite generally low sequence similarity, suggesting that function may be more conserved than sequence.
+By combining interactomes of different species we were able to systematically address the low coverage of the Y2H system and to extract biologically relevant interactions which were not evident from single species.
+Polymorphism of angiotensin converting enzyme (ACE) gene is reported to be associated with ischemic heart disease, hypertrophic cardiomyopathy, and idiopathic dilated cardiomyopathy.
+In this study, we investigated the relationship between Kawasaki disease and insertion/deletion polymorphism of ACE gene.
+ACE genotype was evaluated from each of the subjects' DNA fragments through polymerase chain reaction (PCR).
+Frequencies of ACE genotypes (DD, ID, II) were 12.7%, 60.0%, 27.3% in Kawasaki group, and 41.9%, 30.2%, 27.9% in control group respectively, indicating low rate of DD and high rate of ID genotype among Kawasaki patients (p<0.01).
+Comparing allelic (I, D) frequencies, I allele was more prevalent in Kawasaki group than in control group (57.3% vs. 43.0%, p<0.05).
+In Kawasaki group, both genotype and allelic frequencies were not statistically different between those with coronary dilatations and those without.
+ACE gene I/D polymorphism is thought to be associated with Kawasaki disease but not with the development of coronary dilatations.
+A number of paramyxoviruses are responsible for acute respiratory infections in children, elderly and immuno-compromised individuals, resulting in airway inflammation and exacerbation of chronic diseases like asthma.
+To understand the molecular pathogenesis of these infections, we searched for cellular targets of the virulence protein C of human parainfluenza virus type 3 (hPIV3-C).
+We found that hPIV3-C interacts directly through its C-terminal domain with STAT1 and GRB2, whereas C proteins from measles or Nipah viruses failed to do so.
+Binding to STAT1 explains the previously reported capacity of hPIV3-C to block type I interferon signaling, but the interaction with GRB2 was unexpected.
+This adaptor protein bridges Epidermal Growth Factor (EGF) receptor to MAPK/ERK pathway, a signaling cascade recently found to be involved in airway inflammatory response.
+We report that either hPIV3 infection or transient expression of hPIV3-C both increase cellular response to EGF, as assessed by Elk1 transactivation and phosphorylation levels of ERK1/2, 40S ribosomal subunit protein S6 and translation initiation factor 4E (eIF4E).
+Altogether, our data provide molecular basis to explain the role of hPIV3-C as a virulence factor and determinant of pathogenesis and demonstrate that Paramyxoviridae have evolved a single virulence factor to block type I interferon signaling and to boost simultaneous cellular response to growth factors.
+The innate immune system responds to unique molecular signatures that are widely conserved among microbes but that are not normally present in host cells.
+Compounds that stimulate innate immune pathways may be valuable in the design of novel adjuvants, vaccines, and other immunotherapeutics.
+The cyclic dinucleotide cyclic-di–guanosine monophosphate (c-di-GMP) is a recently appreciated second messenger that plays critical regulatory roles in many species of bacteria but is not produced by eukaryotic cells.
+In vivo and in vitro studies have previously suggested that c-di-GMP is a potent immunostimulatory compound recognized by mouse and human cells.
+We provide evidence that c-di-GMP is sensed in the cytosol of mammalian cells via a novel immunosurveillance pathway.
+The potency of cytosolic signaling induced by c-di-GMP is comparable to that induced by cytosolic delivery of DNA, and both nucleic acids induce a similar transcriptional profile, including triggering of type I interferons and coregulated genes via induction of TBK1, IRF3, nuclear factor κB, and MAP kinases.
+However, the cytosolic pathway that senses c-di-GMP appears to be distinct from all known nucleic acid–sensing pathways.
+Our results suggest a novel mechanism by which host cells can induce an inflammatory response to a widely produced bacterial ligand.
+BACKGROUND: Processing by γ-secretase of many type-I membrane protein substrates triggers signaling cascades by releasing intracellular domains (ICDs) that, following nuclear translocation, modulate the transcription of different genes regulating a diverse array of cellular and biological processes.
+Because the list of γ-secretase substrates is growing quickly and this enzyme is a cancer and Alzheimer's disease therapeutic target, the mapping of γ-secretase activity susceptible gene transcription is important for sharpening our view of specific affected genes, molecular functions and biological pathways.
+METHODOLOGY/PRINCIPAL FINDINGS: To identify genes and molecular functions transcriptionally affected by γ-secretase activity, the cellular transcriptomes of Chinese hamster ovary (CHO) cells with enhanced and inhibited γ-secretase activity were analyzed and compared by cDNA microarray.
+The functional clustering by FatiGO of the 1,981 identified genes revealed over- and under-represented groups with multiple activities and functions.
+Single genes with the most pronounced transcriptional susceptibility to γ-secretase activity were evaluated by real-time PCR.
+Among the 21 validated genes, the strikingly decreased transcription of PTPRG and AMN1 and increased transcription of UPP1 potentially support data on cell cycle disturbances relevant to cancer, stem cell and neurodegenerative diseases' research.
+The mapping of interactions of proteins encoded by the validated genes exclusively relied on evidence-based data and revealed broad effects on Wnt pathway members, including WNT3A and DVL3.
+Intriguingly, the transcription of TERA, a gene of unknown function, is affected by γ-secretase activity and was significantly altered in the analyzed human Alzheimer's disease brain cortices.
+CONCLUSIONS/SIGNIFICANCE: Investigating the effects of γ-secretase activity on gene transcription has revealed several affected clusters of molecular functions and, more specifically, 21 genes that hold significant potential for a better understanding of the biology of γ-secretase and its roles in cancer and Alzheimer's disease pathology.
+As a key factor in endemic and epidemic dynamics, the geographical distribution of viruses has been frequently interpreted in the light of their genetic histories.
+Unfortunately, inference of historical dispersal or migration patterns of viruses has mainly been restricted to model-free heuristic approaches that provide little insight into the temporal setting of the spatial dynamics.
+The introduction of probabilistic models of evolution, however, offers unique opportunities to engage in this statistical endeavor.
+Here we introduce a Bayesian framework for inference, visualization and hypothesis testing of phylogeographic history.
+By implementing character mapping in a Bayesian software that samples time-scaled phylogenies, we enable the reconstruction of timed viral dispersal patterns while accommodating phylogenetic uncertainty.
+Standard Markov model inference is extended with a stochastic search variable selection procedure that identifies the parsimonious descriptions of the diffusion process.
+In addition, we propose priors that can incorporate geographical sampling distributions or characterize alternative hypotheses about the spatial dynamics.
+We describe how Bayesian phylogeography compares with previous parsimony analysis in the investigation of the influenza A H5N1 origin and H5N1 epidemiological linkage among sampling localities.
+Analysis of rabies in West African dog populations reveals how virus diffusion may enable endemic maintenance through continuous epidemic cycles.
+From these analyses, we conclude that our phylogeographic framework will make an important asset in molecular epidemiology that can be easily generalized to infer biogeogeography from genetic data for many organisms.
+The model repository (MREP) is a relational database management system (RDBMS) developed under the auspices of models of infectious disease agent study (MIDAS).
+The purpose of the MREP is to organize and catalog the models, results, and suggestions for using the MIDAS and to store them in a way to allow users to run models from an access-controlled disease MREP.
+The MREP contains source and object code of disease models developed by infectious disease modelers and tested in a production environment.
+Different versions of models used to describe various aspects of the same disease are housed in the repository.
+Models are linked to their developers and different versions of the codes are tied to Subversion, a version control tool.
+An additional element of the MREP will be to house, manage, and control access to a disease model results warehouse, which consists of output generated by the models contained in the MREP.
+The result tables and files are linked to the version of the model and the input parameters that collectively generated the results.
+The result tables are warehoused in a relational database that permits them to be easily identified, categorized, and downloaded.
+One aim for an HIV vaccine is to elicit neutralizing antibodies (Nab) that can limit replication of genetically diverse viruses and prevent establishment of a new infection.
+Thus, identifying the strengths and weaknesses of Nab during the early stages of natural infection could prove useful in achieving this goal.
+Here we demonstrate that viral escape readily occurred despite the development of high titer autologous Nab in two subjects with acute/early subtype C infection.
+To provide a detailed portrayal of the escape pathways, Nab resistant variants identified at multiple time points were used to create a series of envelope (Env) glycoprotein chimeras and mutants within the background of a corresponding newly transmitted Env.
+In one subject, Nab escape was driven predominantly by changes in the region of gp120 that extends from the beginning of the V3 domain to the end of the V5 domain (V3V5).
+However, Nab escape pathways in this subject oscillated and at times required cooperation between V1V2 and the gp41 ectodomain.
+This V1V2-dependent escape pathway was retained over time, and its utility was reflected in the virus's ability to escape from two distinct monoclonal antibodies (Mabs) derived from this same patient via introduction of a single potential N-linked glycosylation site in V2.
+Spatial representation of the sequence changes in gp120 suggested that selective pressure acted upon the same regions of Env in these two subjects, even though the Env domains that drove escape were different.
+Together the findings argue that a single mutational pathway is not sufficient to confer escape in early subtype C HIV-1 infection, and support a model in which multiple strategies, including potential glycan shifts, direct alteration of an epitope sequence, and cooperative Env domain conformational masking, are used to evade neutralization.
+BACKGROUND: UDP-GlcNAc 2-epimerase/ManNAc 6-kinase, GNE, is a bi-functional enzyme that plays a key role in sialic acid biosynthesis.
+GNE is the only human protein that contains a kinase domain belonging to the ROK (repressor, ORF, kinase) family.
+PRINCIPAL FINDINGS: We solved the structure of the GNE kinase domain in the ligand-free state.
+The protein exists predominantly as a dimer in solution, with small populations of monomer and higher-order oligomer in equilibrium with the dimer.
+Crystal packing analysis reveals the existence of a crystallographic hexamer, and that the kinase domain dimerizes through the C-lobe subdomain.
+Mapping of disease-related missense mutations onto the kinase domain structure revealed that the mutation sites could be classified into four different groups based on the location – dimer interface, interlobar helices, protein surface, or within other secondary structural elements.
+CONCLUSIONS: The crystal structure of the kinase domain of GNE provides a structural basis for understanding disease-causing mutations and a model of hexameric wild type full length enzyme.
+ENHANCED VERSION: This article can also be viewed as an enhanced version in which the text of the article is integrated with interactive 3D representations and animated transitions.
+Instructions for the installation and use of the web plugin are available in Text S1.
+For Lyme disease, disease suppression has been demonstrated by a dilution effect, whereby increasing species diversity decreases disease prevalence in host populations.
+To test the dilution effect in another disease, we examined 17 ecological variables associated with prevalence of the directly transmitted Sin Nombre virus (genus Hantavirus, etiologic agent of hantavirus pulmonary syndrome) in its wildlife host, the deer mouse (Peromyscus maniculatus).
+Only species diversity was statistically linked to infection prevalence: as species diversity decreased, infection prevalence increased.
+The increase was moderate, but prevalence increased exponentially at low levels of diversity, a phenomenon described as zoonotic release.
+BACKGROUND: Little is known about how optimism/pessimism and health-related quality of life compare across cultures.
+METHODS: Three samples of pregnant women in their final trimester were recruited from China, Ghana, and the United States (U.S.).
+Participants completed a survey that included the Life Orientation Test - Revised (LOT-R, an optimism/pessimism measure), the Short Form 12 (SF-12, a quality of life measure), and questions addressing health and demographic factors.
+A three-country set was created for analysis by matching women on age, gestational age at enrollment, and number of previous pregnancies.
+Multivariate regression analysis was used to create a model to identify those variables most strongly associated with optimism/pessimism.
+RESULTS: LOT-R scores varied significantly across cultures in these samples, with Ghanaian pregnant women being the most optimistic and least pessimistic and Chinese pregnant women being the least optimistic overall and the least pessimistic in subscale analysis.
+Four key variables predicted approximately 20% of the variance in overall optimism scores: country of origin (p = .006), working for money (p = .05); level of education (p = .002), and ever being treated for emotional issues with medication (p < .001).
+Quality of life scores also varied by country in these samples, with the most pronounced difference occurring in the vitality measure.
+U.S. pregnant women reported far lower vitality scores than both Chinese and Ghanaian pregnant women in our sample.
+CONCLUSION: This research raises important questions regarding what it is about country of origin that so strongly influences optimism/pessimism among pregnant women.
+Further research is warranted exploring underlying conceptualization of optimism/pessimism and health related quality of life across countries.
+The diagnosis of rabies is routinely based on clinical and epidemiological information, especially when exposures are reported in rabies-endemic countries.
+Diagnostic tests using conventional assays that appear to be negative, even when undertaken late in the disease and despite the clinical diagnosis, have a tendency, at times, to be unreliable.
+These tests are rarely optimal and entirely dependent on the nature and quality of the sample supplied.
+In the course of the past three decades, the application of molecular biology has aided in the development of tests that result in a more rapid detection of rabies virus.
+Currently, there are a number of molecular tests that can be used to complement conventional tests in rabies diagnosis.
+Indeed the challenges in the 21st century for the development of rabies diagnostics are not of a technical nature; these tests are available now.
+The challenges in the 21st century for diagnostic test developers are two-fold: firstly, to achieve internationally accepted validation of a test that will then lead to its acceptance by organisations globally.
+Secondly, the areas of the world where such tests are needed are mainly in developing regions where financial and logistical barriers prevent their implementation.
+Although developing countries with a poor healthcare infrastructure recognise that molecular-based diagnostic assays will be unaffordable for routine use, the cost/benefit ratio should still be measured.
+Adoption of rapid and affordable rabies diagnostic tests for use in developing countries highlights the importance of sharing and transferring technology through laboratory twinning between the developed and the developing countries.
+Importantly for developing countries, the benefit of molecular methods as tools is the capability for a differential diagnosis of human diseases that present with similar clinical symptoms.
+These barriers are not insurmountable and it is our expectation that if such tests are accepted and implemented where they are most needed, they will provide substantial improvements for rabies diagnosis and surveillance.
+The advent of molecular biology and new technological initiatives that combine advances in biology with other disciplines will support the development of techniques capable of high throughput testing with a low turnaround time for rabies diagnosis.
+Abstract Wild ducks are the main reservoir of influenza A viruses that can be transmitted to domestic poultry and mammals, including humans.
+Of the 16 hemagglutinin (HA) subtypes of influenza A viruses, only the H5 and H7 subtypes cause highly pathogenic (HP) influenza in the natural hosts.
+These duck species can shed and spread virus from both the respiratory and intestinal tracts while showing few or no disease signs.
+While the HP Asian H5N1 viruses are 100% lethal for chickens and other gallinaceous poultry, the absence of disease signs in some duck species has led to the concept that ducks are the “Trojan horses” of H5N1 in their surreptitious spread of virus.
+An important unresolved issue is whether the HP H5N1 viruses are maintained in the wild duck population of the world.
+Here, we review the ecology and pathobiology of ducks infected with influenza A viruses and ducks’ role in the maintenance and spread of HP H5N1 viruses.
+We also identify the key questions about the role of ducks that must be resolved in order to understand the emergence and control of pandemic influenza.
+It is generally accepted that wild duck species can spread HP H5N1 viruses, but there is insufficient evidence to show that ducks maintain these viruses and transfer them from one generation to the next.
+Clinical manifestations range from inapparent infections and fevers to fatal encephalitis but the factors that determine disease severity are currently undefined.
+TBEV is characteristically a hemagglutinating (HA) virus; the ability to agglutinate erythrocytes tentatively reflects virion receptor/fusion activity.
+However, for the past few years many atypical HA-deficient strains have been isolated from patients and also from the natural European host tick, Ixodes persulcatus.
+By analysing the sequences of HA-deficient strains we have identified 3 unique amino acid substitutions (D67G, E122G or D277A) in the envelope protein, each of which increases the net charge and hydrophobicity of the virion surface.
+Therefore, we genetically engineered virus mutants each containing one of these 3 substitutions; they all exhibited HA-deficiency.
+Unexpectedly, each genetically modified non-HA virus demonstrated increased TBEV reproduction in feeding Ixodes ricinus, not the recognised tick host for these strains.
+Moreover, virus transmission efficiency between infected and uninfected ticks co-feeding on mice was also intensified by each substitution.
+We propose that the emergence of atypical Siberian HA-deficient TBEV strains in Europe is linked to their molecular adaptation to local ticks.
+This process appears to be driven by the selection of single mutations that change the virion surface thus enhancing receptor/fusion function essential for TBEV entry into the unfamiliar tick species.
+As the consequence of this adaptive mutagenesis, some of these mutations also appear to enhance the ability of TBEV to cross the human blood-brain barrier, a likely explanation for fatal encephalitis.
+Future research will reveal if these emerging Siberian TBEV strains continue to disperse westwards across Europe by adaptation to the indigenous tick species and if they are associated with severe forms of TBE.
+Symptoms of drug-associated interstitial lung disease (ILD) are nonspecific and can be difficult to distinguish from a number of illnesses that commonly occur in patients with non-small-cell lung cancer (NSCLC) on therapy.
+Identification of drug involvement and differentiation from other illnesses is problematic, although radiological manifestations and clinical tests enable many of the alternative causes of symptoms in advanced NSCLC to be excluded.
+In lung cancer patients, high-resolution computed tomography (HRCT) is more sensitive than a chest radiograph in evaluating the severity and progression of parenchymal lung disease.
+Indeed, the use of HRCT imaging has led to the recognition of many distinct patterns of lung involvement and, along with clinical signs and symptoms, helps to predict both outcome and response to treatment.
+Primary biliary cirrhosis (PBC) is an immune-mediated chronic cholestatic liver disease with a slowly progressive course.
+Without treatment, most patients eventually develop fibrosis and cirrhosis of the liver and may need liver transplantation in the late stage of disease.
+PBC primarily affects women (female preponderance 9–10:1) with a prevalence of up to 1 in 1,000 women over 40 years of age.
+Common symptoms of the disease are fatigue and pruritus, but most patients are asymptomatic at first presentation.
+The diagnosis is based on sustained elevation of serum markers of cholestasis, i.e., alkaline phosphatase and gamma-glutamyl transferase, and the presence of serum antimitochondrial antibodies directed against the E2 subunit of the pyruvate dehydrogenase complex.
+Histologically, PBC is characterized by florid bile duct lesions with damage to biliary epithelial cells, an often dense portal inflammatory infiltrate and progressive loss of small intrahepatic bile ducts.
+Although the insight into pathogenetic aspects of PBC has grown enormously during the recent decade and numerous genetic, environmental, and infectious factors have been disclosed which may contribute to the development of PBC, the precise pathogenesis remains enigmatic.
+When administered at adequate doses of 13–15 mg/kg/day, up to two out of three patients with PBC may have a normal life expectancy without additional therapeutic measures.
+The mode of action of UDCA is still under discussion, but stimulation of impaired hepatocellular and cholangiocellular secretion, detoxification of bile, and antiapoptotic effects may represent key mechanisms.
+One out of three patients does not adequately respond to UDCA therapy and may need additional medical therapy and/or liver transplantation.
+This review summarizes current knowledge on the clinical, diagnostic, pathogenetic, and therapeutic aspects of PBC.
+16S rRNA gene is one of the preferred targets for resolving species phylogenesis issues in microbiological-related contexts.
+However, the identification of single-nucleotide variations capable of distinguishing a sequence among a set of homologous ones can be problematic.
+Here we present ORMA (Oligonucleotide Retrieving for Molecular Applications), a set of scripts for discriminating positions search and for performing the selection of high-quality oligonucleotide probes to be used in molecular applications.
+First, a new set of probe pairs on cyanobacteria 16S rRNA sequences of 18 different species was compared to that of a previous study.
+Then, a set of LDR probe pairs for the discrimination of 13 pathogens contaminating bovine milk was evaluated.
+The software determined more than 100 candidate probe pairs per dataset, from more than 300 16S rRNA sequences, in less than 5 min.
+Results demonstrated how ORMA improved the performance of the LDR assay on cyanobacteria, correctly identifying 12 out of 14 samples, and allowed the perfect discrimination among the 13 milk pathogenic-related species.
+ORMA represents a significant improvement from other contexts where enzyme-based techniques have been employed on already known mutations of a single base or on entire subsequences.
+BACKGROUND: The outbreak of the pandemic flu, Influenza A H1N1 (Swine Flu) in early 2009, provided a major challenge to health services around the world.
+Previous pandemics have led to stockpiling of goods, the victimisation of particular population groups, and the cancellation of travel and the boycotting of particular foods (e.g.
+We examined initial behavioural and attitudinal responses towards Influenza A, H1N1 ("Swine flu") in the six days following the WHO pandemic alert level 5, and regional differences in these responses.
+METHODS: 328 respondents completed a cross-sectional Internet or paper-based questionnaire study in Malaysia (N = 180) or Europe (N = 148).
+Measures assessed changes in transport usage, purchase of preparatory goods for a pandemic, perceived risk groups, indicators of anxiety, assessed estimated mortality rates for seasonal flu, effectiveness of seasonal flu vaccination, and changes in pork consumption RESULTS: 26% of the respondents were 'very concerned' about being a flu victim (42% Malaysians, 5% Europeans, p < .001).
+36% reported reduced public transport use (48% Malaysia, 22% Europe, p < .001), 39% flight cancellations (56% Malaysia, 17% Europe, p < .001).
+face masks: 8% Malaysia, 7% Europe), 41% Malaysia (15% Europe) intended to do so (p < .001).
+63% of Europeans, 19% of Malaysians had discussed the pandemic with friends (p < .001).
+Groups seen as at 'high risk' of infection included the immune compromised (mentioned by 87% respondents), pig farmers (70%), elderly (57%), prostitutes/highly sexually active (53%), and the homeless (53%).
+In data collected only in Europe, 64% greatly underestimated the mortality rates of seasonal flu, 26% believed seasonal flu vaccination gave protection against swine flu.
+3% had purchased anti-viral drugs for use at home, while 32% intended to do so if the pandemic worsened.
+CONCLUSION: Initial responses to Influenza A show large regional differences in anxiety, with Malaysians more anxious and more likely to reduce travel and to buy masks and food.
+Particular groups (homosexuals, prostitutes, the homeless) are perceived as at greater risk, potentially leading to increased prejudice during a pandemic.
+Europeans underestimated mortality of seasonal flu, and require more information about the protection given by seasonal flu inoculation.
+INTRODUCTION: Human herpesvirus 6 (HHV-6) has been recognized as a potentially significant pathogen in hemopoietic stem cell transplant (HSCT) recipients.
+Different clinical manifestations have been described, including fever, skin rash, bone marrow suppression, and encephalitis.
+MATERIALS AND METHODS: A retrospective review of a group of 26 adult recipients of allogeneic HSCTs was conducted.
+Serum samples taken before transplant were examined for the presence of specific anti-HHV-6 IgM and IgG antibodies.
+After transplantation, quantitative real-time PCR was used to determine viral load in plasma samples from days 0–80 post-transplant.
+RESULTS: HHV-6 DNA was detected in plasma samples in 8 (30%) of the 26 recipients between days 18 and 40 after transplantation.
+All of them developed fever of unknown origin and over 50% had graft-versus-host disease features.
+CONCLUSIONS: There is a high frequency of detectable HHV-6 viral load in stem cell transplant recipients in Poland.
+Further investigation to monitor HHV-6 reactivation in graft recipients will be important to improve outcome for these patients.
+Here we introduce a culture system for the isolation, passaging and amplification of avian tracheal epithelial (ATE) cells.
+The ATE medium, which contains chicken embryo extract and fetal bovine serum, supports the growth of ciliated cells, goblet cells and basal cells from chicken tracheas on fibronectin- or matrigel-coated dishes.
+We further show that ATE cells support the replication and spread of infectious bronchitis virus (IBV).
+We also demonstrate that glycosaminoglycan had no effect on infection of the cells by IBV.
+Taken together, these findings suggest that primary ATE cells provide a novel cell culture system for the amplification of IBV and the in vitro characterization of viral cytopathogenesis.
+BACKGROUND: In natural cat populations, Feline Immunodeficiency Virus (FIV) is transmitted through bites between individuals.
+Factors such as the density of cats within the population or the sex-ratio can have potentially strong effects on the frequency of fight between individuals and hence appear as important population risk factors for FIV.
+METHODOLOGY/PRINCIPAL FINDINGS: To study such population risk factors, we present data on FIV prevalence in 15 cat populations in northeastern France.
+We investigate five key social factors of cat populations; the density of cats, the sex-ratio, the number of males and the mean age of males and females within the population.
+We overcome the problem of dependence in the infective status data using sexually-structured dynamic stochastic models.
+Only the age of males and females had an effect (p = 0.043 and p = 0.02, respectively) on the male-to-female transmission rate.
+Due to multiple tests, it is even likely that these effects are, in reality, not significant.
+Finally we show that, in our study area, the data can be explained by a very simple model that does not invoke any risk factor.
+CONCLUSION: Our conclusion is that, in host-parasite systems in general, fluctuations due to stochasticity in the transmission process are naturally very large and may alone explain a larger part of the variability in observed disease prevalence between populations than previously expected.
+Finally, we determined confidence intervals for the simple model parameters that can be used to further aid in management of the disease.
+We describe a Multiplex Primer Prediction (MPP) algorithm to build multiplex compatible primer sets to amplify all members of large, diverse and unalignable sets of target sequences.
+The MPP algorithm is scalable to larger target sets than other available software, and it does not require a multiple sequence alignment.
+We applied it to questions in viral detection, and demonstrated that there are no universally conserved priming sequences among viruses and that it could require an unfeasibly large number of primers (∼3700 18-mers or ∼2000 10-mers) to generate amplicons from all sequenced viruses.
+We then designed primer sets separately for each viral family, and for several diverse species such as foot-and-mouth disease virus (FMDV), hemagglutinin (HA) and neuraminidase (NA) segments of influenza A virus, Norwalk virus, and HIV-1.
+We empirically demonstrated the application of the software with a multiplex set of 16 short (10 nt) primers designed to amplify the Poxviridae family to produce a specific amplicon from vaccinia virus.
+Activation of the type I interferon (IFN) pathway by small interfering RNA (siRNA) is a major contributor to the off-target effects of RNA interference in mammalian cells.
+While IFN induction complicates gene function studies, immunostimulation by siRNAs may be beneficial in certain therapeutic settings.
+Various forms of siRNA, meeting different compositional and structural requirements, have been reported to trigger IFN activation.
+The consensus is that intracellularly expressed short-hairpin RNAs (shRNAs) are less prone to IFN activation because they are not detected by the cell-surface receptors.
+Here we identify a shRNA that potently activates the IFN pathway in human cells in a sequence- and 5′-triphosphate-dependent manner.
+In addition to suppressing its intended mRNA target, expression of the shRNA results in dimerization of interferon regulatory factor-3, activation of IFN promoters and secretion of biologically active IFNs into the extracellular medium.
+Delivery by lentiviral vector transduction did not avoid IFN activation by this and another, unrelated shRNA.
+We also demonstrated that retinoic-acid-inducible gene I, and not melanoma differentiation associated gene 5 or toll-like receptor 3, is the cytoplasmic sensor for intracellularly expressed shRNAs that trigger IFN activation.
+Cellular uptake of therapeutic oligonucleotides and subsequent intracellular trafficking to their target sites represents the major technical hurdle for the biological effectiveness of these potential drugs.
+Among the different available non-viral systems like cationic polymers, cationic liposomes and polymeric nanoparticles, cell-penetrating peptides (CPPs) represent an attractive concept to bypass the problem of poor membrane permeability of these charged macromolecules.
+While uptake per se in most cases does not represent the main obstacle of nucleic acid delivery in vitro, it becomes increasingly apparent that intracellular trafficking is the bottleneck.
+As a consequence, in order to optimize a given delivery system, a side-by-side analysis of nucleic acid cargo internalized and the corresponding biological effect is required to determine the overall efficacy.
+In this review, we will concentrate on peptide-mediated delivery of siRNAs and steric block oligonucleotides and discuss different methods for quantitative assessment of the amount of cargo taken up and how to correlate those numbers with biological effects by applying easy to handle reporter systems.
+To illustrate current limitations of non-viral nucleic acid delivery systems, we present own data as an example and discuss options of how to enhance trafficking of molecules entrapped in cellular compartments.
+Pregnancy-associated malaria (PAM) is caused by Plasmodium falciparum-infected erythrocytes (IEs) that bind to chondroitin sulphate A (CSA) in the placenta by PAM-associated clonally variant surface antigens (VSA).
+Pregnancy-specific VSA (VSA(PAM)), which include the PfEMP1 variant VAR2CSA, are targets of IgG-mediated protective immunity to PAM.
+Here, we report an investigation of the specificity of naturally acquired immunity to PAM, using eight human monoclonal IgG1 antibodies that react exclusively with intact CSA-adhering IEs expressing VSA(PAM).
+Four reacted in Western blotting with high-molecular-weight (> 200 kDa) proteins, while seven reacted with either the DBL3-X or the DBL5-ε domains of VAR2CSA expressed either as Baculovirus constructs or on the surface of transfected Jurkat cells.
+We used a panel of recombinant antigens representing DBL3-X domains from P. falciparum field isolates to evaluate B-cell epitope diversity among parasite isolates, and identified the binding site of one monoclonal antibody using a chimeric DBL3-X construct.
+Our findings show that there is a high-frequency memory response to VSA(PAM), indicating that VAR2CSA is a primary target of naturally acquired PAM-specific protective immunity, and demonstrate the value of human monoclonal antibodies and conformationally intact recombinant antigens in VSA characterization.
+BACKGROUND: Since late April, 2009, a novel influenza virus A (H1N1), generally referred to as the “swine flu,” has spread around the globe and infected hundreds of thousands of people.
+During the first few days after the initial outbreak in Mexico, extensive media coverage together with a high degree of uncertainty about the transmissibility and mortality rate associated with the virus caused widespread concern in the population.
+The spread of an infectious disease can be strongly influenced by behavioral changes (e.g., social distancing) during the early phase of an epidemic, but data on risk perception and behavioral response to a novel virus is usually collected with a substantial delay or after an epidemic has run its course.
+METHODOLOGY/PRINCIPAL FINDINGS: Here, we report the results from an online survey that gathered data (n = 6,249) about risk perception of the Influenza A(H1N1) outbreak during the first few days of widespread media coverage (April 28 - May 5, 2009).
+We find that after an initially high level of concern, levels of anxiety waned along with the perception of the virus as an immediate threat.
+Intriguingly, principal component analysis revealed strong clustering of anxiety about swine flu, bird flu and terrorism.
+All three of these threats receive a great deal of media attention and their fundamental uncertainty is likely to generate an inordinate amount of fear vis-a-vis their actual threat.
+Of particular interest, we find that affective variables, such as self-reported anxiety over the epidemic, mediate the likelihood that respondents will engage in protective behavior.
+Understanding how protective behavior such as social distancing varies and the specific factors that mediate it may help with the design of epidemic control strategies.
+Through the use of a normal form coordinate transform, we are able to analytically derive the stochastic center manifold along with the associated, reduced set of stochastic evolution equations.
+Therefore, the solution of this reduced stochastic dynamical system yields excellent agreement, both in amplitude and phase, with the solution of the original stochastic system for a temporal scale that is orders of magnitude longer than the typical relaxation time.
+This new method allows for improved time series prediction of the number of infectious cases when modeling the spread of disease in a population.
+Numerical solutions of the fluctuations of the SEIR model are considered in the infinite population limit using a Langevin equation approach, as well as in a finite population simulated as a Markov process.
+In this study, focusing on cardiac catheterization services, Euclidean, Manhattan, and the less widely known Minkowski distance metrics are used to estimate distances from patient residence to hospital.
+Distance metrics typically produce less accurate estimates than actual measurements, but each metric provides a single model of travel over a given network.
+Distances estimated with each metric are contrasted with road distance and travel time measurements, and an optimized Minkowski distance is implemented in spatial analytical modeling.
+METHODS: Road distance and travel time are calculated from the postal code of residence of each patient undergoing cardiac catheterization to the pertinent hospital.
+Distance estimates and distance measurements are then compared using descriptive statistics and visual mapping methods.
+The optimized Minkowski metric is implemented, via the spatial weight matrix, in a spatial regression model identifying socio-economic factors significantly associated with cardiac catheterization.
+RESULTS: The Minkowski coefficient that best approximates road distance is 1.54; 1.31 best approximates travel time.
+The latter is also a good predictor of road distance, thus providing the best single model of travel from patient's residence to hospital.
+The Euclidean metric and the optimal Minkowski metric are alternatively implemented in the regression model, and the results compared.
+CONCLUSION: Road distance and travel time measurements are the most accurate estimates, but cannot be directly implemented in spatial analytical modeling.
+Euclidean distance tends to underestimate road distance and travel time; Manhattan distance tends to overestimate both.
+The optimized Minkowski distance partially overcomes their shortcomings; it provides a single model of travel over the network.
+The method is flexible, suitable for analytical modeling, and more accurate than the traditional metrics; its use ultimately increases the reliability of spatial analytical models.
+Concerns have been raised regarding the availability of National Institute for Occupational Safety and Health (NIOSH)-certified N95 filtering facepiece respirators (FFRs) during an influenza pandemic.
+One possible strategy to mitigate a respirator shortage is to reuse FFRs following a biological decontamination process to render infectious material on the FFR inactive.
+However, little data exist on the effects of decontamination methods on respirator integrity and performance.
+This study evaluated five decontamination methods [ultraviolet germicidal irradiation (UVGI), ethylene oxide, vaporized hydrogen peroxide (VHP), microwave oven irradiation, and bleach] using nine models of NIOSH-certified respirators (three models each of N95 FFRs, surgical N95 respirators, and P100 FFRs) to determine which methods should be considered for future research studies.
+Following treatment by each decontamination method, the FFRs were evaluated for changes in physical appearance, odor, and laboratory performance (filter aerosol penetration and filter airflow resistance).
+Additional experiments (dry heat laboratory oven exposures, off-gassing, and FFR hydrophobicity) were subsequently conducted to better understand material properties and possible health risks to the respirator user following decontamination.
+However, this study did not assess the efficiency of the decontamination methods to inactivate viable microorganisms.
+The remainder of the FFR samples that had been decontaminated had expected levels of filter aerosol penetration and filter airflow resistance.
+The scent of bleach remained noticeable following overnight drying and low levels of chlorine gas were found to off-gas from bleach-decontaminated FFRs when rehydrated with deionized water.
+UVGI, ethylene oxide (EtO), and VHP were found to be the most promising decontamination methods; however, concerns remain about the throughput capabilities for EtO and VHP.
+Methanolic extracts of 41 plant species belonging to 27 families used in the traditional medicine in Nepal have been investigated for in vitro antiviral activity against Herpes simplex virus type 1 (HSV-1) and influenza virus A by dye uptake assay in the systems HSV-1/Vero cells and influenza virus A/MDCK cells.
+The extracts of Astilbe rivularis, Bergenia ciliata, Cassiope fastigiata and Thymus linearis showed potent anti-herpes viral activity.
+The extracts of Allium oreoprasum, Androsace strigilosa, Asparagus filicinus, Astilbe rivularis, Bergenia ciliata and Verbascum thapsus exhibited strong anti-influenza viral activity.
+Only the extracts of A. rivularis and B. ciliata demonstrated remarkable activity against both viruses.
+BACKGROUND: The HIV epidemic poses significant challenges to the low income countries in sub Saharan Africa (SSA), affecting the attrition rate among health care workers, their level of motivation, and absenteeism from work.
+Little is known about how to deal with deterioration of human resources in the health care systems.
+This study aimed to predict the intention to provide surgical treatment to HIV infected patients among medical- and dental students in Tanzania and Sudan using an extended version of the Theory of Planned Behaviour (TPB).
+METHODS: Four hundred and seventy five medical- and dental students at the University of Dar es Salaam (mean age, 25 yr) and 642 dental students attending 6 public and private dental faculties in Khartoum (mean age 21.7 yr) completed self-administered TPB questionnaires in 2005 and 2007, respectively.
+RESULTS: Both Tanzanian and Sudanese students demonstrated strong intentions to provide care for people with HIV and AIDS.
+Stepwise linear regression revealed that the TPB accounted for 51% (43% in Tanzania and Sudan) of the variance in intention across study sites.
+After having controlled for country and past behaviour, the TPB in terms of attitudes, subjective norms and perceived behavioural control accounted for 34% and moral norms for an additional 2,3% of the explainable variance in intention.
+Across both study sites, attitudes were the strongest predictor of intention followed in descending order by subjective norms, moral norms and perceived behavioural control.
+CONCLUSION: The TPB is applicable to students' care delivery intentions in the context of HIV and AIDS across the two SSA countries investigated.
+It is suggested that attitudes, subjective norms, moral norms and perceived behavioural control are key factors in students' willingness to treat AIDS and HIV infected patients and should be targets of interventions aimed at improving the quality of health care delivery in this context.
+Acute lung injury (ALI) that clinically manifests as acute respiratory distress syndrome is caused by an uncontrolled systemic inflammatory response resulting from clinical events including sepsis, major surgery and trauma.
+Innate immunity is activated through families of related pattern recognition receptors (PRRs), which recognize conserved microbial motifs or pathogen-associated molecular patterns (PAMPs).
+Recently, NACHT–leucine-rich repeat (LRR) receptors and retinoic acid–inducible gene–like receptors have been added to the list.
+It is now understood that in addition to recognizing infectious stimuli, both Toll-like receptors and NACHT-LRR receptors can also respond to endogenous molecules released in response to stress, trauma and cell damage.
+It has been clinically observed for a long time that infectious and noninfectious insults initiate inflammation, so confirmation of overlapping receptor-signal pathways of activation between PAMPs and DAMPs is no surprise.
+Modification of PRR pathways is likely to be a logical therapeutic target for ALI/acute respiratory distress syndrome.
+In felids, feline leukemia virus (FeLV) infection results in a variety of outcomes that range from abortive (virus readily eliminated and never detectable) to progressive infection (persistent viremia and viral shedding).
+Naïve cats exposed to faeces of persistently infected cats seroconverted, indicating infection, but remained negative for provirus and p27 antigen in blood.
+FeLV provirus was found in some tissues but not in the bone marrow, infection of which is usually considered a necessary stage for disease progression.
+To investigate the impact of low FeLV doses on young cats and to test the hypothesis that low dose exposure may lead to an unknown pathogenesis of infection without involvement of the bone marrow, 21 cats were infected oronasally with variable viral doses.
+The immune response was monitored by measuring FeLV whole virus and p45 antibodies; and feline oncornavirus-associated cell membrane antigen (FOCMA) assay.
+One cat showed regressive infection (transient antigenemia, persistent provirus-positivity, and seroconversion) with provirus only found in some organs at sacrifice.
+In 7 of the 20 remaining cats FOCMA assay positivity was the only sign of infection, while all other tests were negative.
+Overall, the results show that FeLV low dose exposure can result in seroconversion during a presumed abortive infection.
+Therefore, commonly used detection methods do not detect all FeLV-infected animals, possibly leading to an underestimation of the prevalence of infection.
+Peptidases are important in pathological conditions such as Alzheimer's disease, tumour and parasite invasion, and for processing viral polyproteins.
+The MEROPS database is an Internet resource containing information on peptidases, their substrates and inhibitors.
+The database now includes details of cleavage positions in substrates, both physiological and non-physiological, natural and synthetic.
+There are 39 118 cleavages in the collection; including 34 606 from a total of 10 513 different proteins and 2677 cleavages in synthetic substrates.
+At least one substrate cleavage is known for 45% of the 2415 different peptidases recognized in the MEROPS database.
+The website now has three new displays: two showing peptidase specificity as a logo and a frequency matrix, the third showing a dynamically generated alignment between each protein substrate and its most closely related homologues.
+Many of the proteins described in the literature as peptidase substrates have been studied only in vitro.
+On the assumption that a physiologically relevant cleavage site would be conserved between species, the conservation of every site in terms of peptidase preference has been examined and a number have been identified that are not conserved.
+Some sites are identified that are very poorly conserved where cleavage is more likely to be fortuitous than of physiological relevance.
+This data-set is freely available via the Internet and is a useful training set for algorithms to predict substrates for peptidases and cleavage positions within those substrates.
+The data may also be useful for the design of inhibitors and for engineering novel specificities into peptidases.
+BACKGROUND: Flavivirus infected cells produce infectious virions and subviral particles, both of which are formed by the assembly of prM and E envelope proteins and are believed to undergo the same maturation process.
+Dengue recombinant subviral particles have been produced in cell cultures with either modified or chimeric proteins but not using the native forms of prM and E. METHODOLOGY/PRINCIPAL FINDINGS: We have used a codon optimization strategy to obtain an efficient expression of native viral proteins and production of recombinant subviral particles (RSPs) for all four dengue virus (DV) serotypes.
+A stable HeLa cell line expressing DV1 prME was established (HeLa-prME) and RSPs were analyzed by immunofluorescence and transmission electron microscopy.
+We found that E protein is mainly present in the endoplasmic reticulum (ER) where assembly of RSPs could be observed.
+Biochemical characterization of DV1 RSPs secretion revealed both prM protein cleavage and homodimerization of E proteins before their release into the supernatant, indicating that RSPs undergo a similar maturation process as dengue virus.
+Pulse chase experiment showed that 8 hours are required for the secretion of DV1 RSPs.
+We have used HeLa-prME to develop a semi-quantitative assay and screened a human siRNA library targeting genes involved in membrane trafficking.
+Knockdown of 23 genes resulted in a significant reduction in DV RSP secretion, whereas for 22 others we observed an increase of RSP levels in cell supernatant.
+CONCLUSIONS/SIGNIFICANCE: Our data describe the efficient production of RSPs containing native prM and E envelope proteins for all dengue serotypes.
+Dengue RSPs and corresponding producing cell lines are safe and novel tools that can be used in the study of viral egress as well as in the development of vaccine and drugs against dengue virus.
+BACKGROUND: On June 11, 2009, the World Health Organization declared phase 6 of the novel influenza A/H1N1 pandemic.
+Although by the end of September 2009, the novel virus had been reported from all continents, the impact in most countries of the northern hemisphere has been limited.
+The return of the virus in a second wave would encounter populations that are still nonimmune and not vaccinated yet.
+We modelled the effect of control strategies to reduce the spread with the goal to defer the epidemic wave in a country where it is detected in a very early stage.
+METHODOLOGY/PRINCIPAL FINDINGS: We constructed a deterministic SEIR model using the age distribution and size of the population of Germany based on the observed number of imported cases and the early findings for the epidemiologic characteristics described by Fraser (Science, 2009).
+We propose a two-step control strategy with an initial effort to trace, quarantine, and selectively give prophylactic treatment to contacts of the first 100 to 500 cases.
+In the second step, the same measures are focused on the households of the next 5,000 to 10,000 cases.
+As a result, the peak of the epidemic could be delayed up to 7.6 weeks if up to 30% of cases are detected.
+Necessary doses of antivirals would be less than the number of treatment courses for 0.1% of the population.
+In a sensitivity analysis, both case detection rate and the variation of R0 have major effects on the resulting delay.
+CONCLUSIONS/SIGNIFICANCE: Control strategies that reduce the spread of the disease during the early phase of a pandemic wave may lead to a substantial delay of the epidemic.
+Since prophylactic treatment is only offered to the contacts of the first 10,000 cases, the amount of antivirals needed is still very limited.
+BACKGROUND: Expression of the minor virion structural protein VP2 of the calicivirus murine norovirus (MNV) is believed to occur by the unusual mechanism of termination codon-dependent reinitiation of translation.
+In this process, following translation of an upstream open reading frame (ORF) and termination at the stop codon, a proportion of 40S subunits remain associated with the mRNA and reinitiate at the AUG of a downstream ORF, which is typically in close proximity.
+Consistent with this, the VP2 start codon (AUG) of MNV overlaps the stop codon of the upstream VP1 ORF (UAA) in the pentanucleotide UAA UG.
+PRINCIPAL FINDINGS: Here, we confirm that MNV VP2 expression is regulated by termination-reinitiation and define the mRNA sequence requirements.
+Efficient reintiation is dependent upon 43 nt of RNA immediately upstream of the UAA UG site.
+Chemical and enzymatic probing revealed that the RNA in this region is not highly structured and includes an essential stretch of bases complementary to 18S rRNA helix 26 (Motif 1).
+The relative position of Motif 1 with respect to the UAA UG site impacts upon the efficiency of the process.
+Termination-reinitiation in MNV was also found to be relatively insensitive to the initiation inhibitor edeine.
+Similar to other viruses that use this strategy, base-pairing between mRNA and rRNA is likely to play a role in tethering the 40S subunit to the mRNA following termination at the VP1 stop codon.
+Our data also indicate that accurate recognition of the VP2 ORF AUG is not a pre-requisite for efficient reinitiation of translation in this system.
+Ribosomal frameshifting on viral RNAs relies on the mechanical properties of structural elements, often pseudoknots and more rarely stem-loops, that are unfolded by the ribosome during translation.
+In human immunodeficiency virus (HIV)-1 type B a long hairpin containing a three-nucleotide bulge is responsible for efficient frameshifting.
+This three-nucleotide bulge separates the hairpin in two domains: an unstable lower stem followed by a GC-rich upper stem.
+Toeprinting and chemical probing assays suggest that a hairpin-like structure is retained when ribosomes, initially bound at the slippery sequence, were allowed multiple EF-G catalyzed translocation cycles.
+After the first, and single step of translocation of deacylated tRNA to the 30 S P site, movement of the mRNA stem-loop in the 5′ direction is halted, which is consistent with the notion that the downstream secondary structure resists unfolding.
+Mechanical stretching of the hairpin using optical tweezers only allows clear identification of unfolding of the upper stem at a force of 12.8 ± 1.0 pN.
+This suggests that the lower stem is unstable and may indeed readily unfold in the presence of a translocating ribosome.
+Are pathogens in outdoor air a health issue at present or will they become a problem in the future?
+A working group called AirPath - Outdoor Environments and Human Pathogens in Air was set up in 2007 at University College London, UK with the aim of opening new discussion and creating a research network to investigate the science and impacts of outdoor pathogens.
+Our objective in this paper is to review and discuss the following areas: What is the source of human pathogens in outdoor air?
+How do we prepare for the anticipated challenges of environmental change and new and emerging diseases?
+We think that this work can benefit the wider research community and policy makers by providing a concise overview of various research aspects and considerations which may be important to their work.
+BACKGROUND: Individual strategies in pandemic preparedness plans may not reduce the impact of an influenza pandemic.
+METHODS: We searched modeling publications through PubMed and associated references from 1990 to 30 September 2009.
+Inclusion criteria were modeling papers quantifying the effectiveness of combination strategies, both pharmaceutical and non-pharmaceutical.
+Four studies examined combination strategies on a global scale, 14 on single countries, and one on a small community.
+Stochastic individual-based modeling was used in nine studies, stochastic meta-population modeling in five, and deterministic compartmental modeling in another five.
+As part of combination strategies, vaccination was explored in eight studies, antiviral prophylaxis and/or treatment in 16, area or household quarantine in eight, case isolation in six, social distancing measures in 10 and air travel restriction in six studies.
+Two studies suggested a high probability of successful influenza epicenter containment with combination strategies under favorable conditions.
+During a pandemic, combination strategies delayed spread, reduced overall number of cases, and delayed and reduced peak attack rate more than individual strategies.
+Global cooperative strategies, including redistribution of antiviral drugs, were effective in reducing the global impact and attack rates of pandemic influenza.
+They include pharmaceutical (antiviral agents, antibiotics and vaccines) and non-pharmaceutical interventions (case isolation, quarantine, personal hygiene measures, social distancing and travel restriction).
+Excess wintertime mortality related to pneumonia has been noted for over a century, but the seasonality of invasive pneumococcal disease (IPD) has been described relatively recently and is poorly understood.
+Improved understanding of environmental influence on disease seasonality has taken on new urgency due to global climate change.
+METHODS: We evaluated 602 cases of IPD reported in Philadelphia County, Pennsylvania, from 2002 to 2007.
+Poisson regression models incorporating seasonal smoothers were used to identify associations between weekly weather patterns and case counts.
+Associations between acute (day-to-day) environmental fluctuations and IPD occurrence were evaluated using a case-crossover approach.
+Effect modification across age and sex strata was explored, and meta-regression models were created using stratum-specific estimates for effect.
+RESULTS: IPD incidence was greatest in the wintertime, and spectral decomposition revealed a peak at 51.0 weeks, consistent with annual periodicity.
+After adjustment for seasonality, yearly increases in reporting, and temperature, weekly incidence was found to be associated with clear-sky UV index (IRR per unit increase in index: 0.70 [95% CI 0.54-0.91]).
+At shorter time scales, only an association with increases in ambient sulphur oxides was linked to disease risk (OR for highest tertile of exposure 0.75, 95% CI 0.60 to 0.93).
+The major predictor of IPD in Philadelphia is extended periods of low UV radiation, which may explain observed wintertime seasonality.
+The mechanism of action of diminished light exposure on disease occurrence may be due to direct effects on pathogen survival or host immune function via altered 1,25-(OH)(2)-vitamin-D metabolism.
+These findings may suggest less diminution in future IPD risk with climate change than would be expected if wintertime seasonality was driven by temperature.
+BACKGROUND: Recent studies have suggested that autophagy is utilized by cells as a protective mechanism against Listeria monocytogenes infection.
+METHODOLOGY/PRINCIPAL FINDINGS: However we find autophagy has no measurable role in vacuolar escape and intracellular growth in primary cultured bone marrow derived macrophages (BMDMs) deficient for autophagy (atg5(−/−)).
+Nevertheless, we provide evidence that the pore forming activity of the cholesterol-dependent cytolysin listeriolysin O (LLO) can induce autophagy subsequent to infection by L. monocytogenes.
+Infection of BMDMs with L. monocytogenes induced microtubule-associated protein light chain 3 (LC3) lipidation, consistent with autophagy activation, whereas a mutant lacking LLO did not.
+Infection of BMDMs that express LC3-GFP demonstrated that wild-type L. monocytogenes was encapsulated by LC3-GFP, consistent with autophagy activation, whereas a mutant lacking LLO was not.
+Bacillus subtilis expressing either LLO or a related cytolysin, perfringolysin O (PFO), induced LC3 colocalization and LC3 lipidation.
+Further, LLO-containing liposomes also recruited LC3-GFP, indicating that LLO was sufficient to induce targeted autophagy in the absence of infection.
+CONCLUSIONS/SIGNIFICANCE: We propose that membrane damage, such as that caused by LLO, triggers bacterial-targeted autophagy, although autophagy does not affect the fate of wild-type intracellular L. monocytogenes in primary BMDMs.
+The major histocompatibility complex (MHC) class I B gene/allelic repertoire was investigated in a pedigreed population of cynomolgus macaques of mixed Indonesian/Malaysian origin.
+The Mafa-B alleles detected in this cohort are mostly specific for a given geographic area, and only a small number of alleles appears to be shared with other populations.
+In contrast to humans, the B locus in Old World monkeys displays extensive copy number variation.
+The Mafa-B and previously defined -A gene combinations segregate in families and thus allowed the definition of extended haplotypes.
+In many cases it was possible to assign a particular Mafa-I allele to one of these Mafa-A/B haplotypes as well.
+The presence of a large number of stable haplotypes in this cohort of animals, which was pedigreed for up to eight generations, looks promising for developing discriminative MHC typing tools that are less cumbersome.
+Furthermore, the discovery of 53 unreported Mafa-B sequences expands the lexicon of alleles significantly, and may help in understanding the complex organisation of the macaque B region.
+In vitro cytotoxicity testing has become an integral aspect of drug discovery because it is a convenient, costeffective, and predictive means of characterizing the toxic potential of new chemical entities.
+The early and routine implementation of this testing is testament to its prognostic importance for humans.
+Although a plethora of assay chemistries and methods exist for 96-well formats, few are practical and sufficiently sensitive enough for application in high throughput screening (HTS).
+Here we briefly describe a handful of the currently most robust and validated HTS assays for accurate and efficient assessment of cytotoxic risk.
+We also provide guidance for successful HTS implementation and discuss unique merits and detractions inherent in each method.
+Lastly, we discuss the advantages of combining specific HTS compatible assays into multi-parametric, same-well formats.
+INTRODUCTION: Macrophage activating syndrome is a severe, potentially life-threatening condition that may accompany Still's disease.
+It is characterized by fever, hepatosplenomegaly, lymphadenopathy, severe cytopenia, serious liver dysfunction, coagulopathy and neurologic involvement.
+The principal treatment for patients with this syndrome includes etoposide 150 mg/2 M twice a week for two weeks, dexamethasone 10 mg/2 M for two weeks and cyclosporine 3 mg/kg to 5 mg/kg for a longer period.
+CASE PRESENTATION: We describe the case of a 15-year-old Iraqi girl with Still's disease who developed macrophage activating syndrome with acute respiratory distress syndrome that required resuscitation and mechanical ventilation.
+Two weeks after cyclosporine was discontinued, however, she was readmitted with an acute relapse of macrophage activating syndrome manifested by spiking fever, arthralgias, maculopapular rash and leukocytosis.
+This time the patient recovered following the reintroduction of treatment with cyclosporine and the addition of mycophenolate mofetil (Cellcept).
+We recommend continuing this medication for several weeks following the patient's clinical recovery in order to prevent macrophage activating syndrome relapses.
+We report a case of a 16-yr-old female with fever, sore throat, productive cough, malaise and the presence of lung consolidation with multiple abscesses on radiographic examination.
+After a detailed diagnostic work-up the diagnosis of community acquired Acinetobacter pneumonia with multiple lung abscesses was made.
+The Acinetobacter stain was susceptible to a variety of antimicrobial agents and the patient's condition improved rapidly.
+The presence of lung abscesses due to Acinetobacter infection is an extremely uncommon manifestation of the disease.
+This case underlines the emergent role which these, often multi-drug resistant, bacteria may play in the future, perhaps in community infections as well.
+BACKGROUND: Mycobacterium tuberculosis (MTB) is a major cause of morbidity and mortality in the world.
+To combat against this pathogen, immune cells release cytokines including tumor necrosis factor-α (TNF-α), which is pivotal in the development of protective granulomas.
+Our previous results showed that Bacillus Calmette Guerin (BCG), a mycobacterium used as a model to investigate the immune response against MTB, stimulates the induction of TNF-α via mitogen-activated protein kinase (MAPK) in human blood monocytes.
+Since MAPK phosphatase-1 (MKP-1) is known to regulate MAPK activities, we examined whether MKP-1 plays a role in BCG-induced MAPK activation and cytokine expression.
+Our results demonstrated that following exposure to BCG, there was an increase in the expression of MKP-1.
+Additionally, the induction of MKP-1 was regulated by p38 MAPK and extracellular signal-regulated kinase 1 and 2 (ERK1/2).
+Surprisingly, when MKP-1 expression was blocked by its specific siRNA, there was a significant decrease in the levels of phospho-MAPK (p38 MAPK and ERK1/2) and TNF-α inducible by BCG.
+CONCLUSIONS: Since TNF-α is pivotal in granuloma formation, the results indicated an unexpected positive function of MKP-1 against mycobacterial infection as opposed to its usual phosphatase activity.
+Mammalian sperm become fertile after completing capacitation, a process associated with cholesterol loss and changes in the biophysical properties of the sperm membranes that prepares the sperm to undergo the acrosome reaction.
+Different laboratories have hypothesized that cholesterol efflux can influence the extent and/or movement of lipid raft microdomains.
+In a previous study, our laboratory investigated the identity of sperm proteins putatively associated with rafts.
+After extraction with Triton X-100 and ultracentrifugation in sucrose gradients, proteins distributing to the light buoyant-density fractions were cored from polyacrylamide gels and microsequenced.
+In this study, a subset of these proteins (TEX101, basigin, hexokinase 1, facilitated glucose transporter 3, IZUMO, and SPAM1) and other molecules known to be enriched in membrane rafts (caveolin 2, flotillin 1, flotillin 2, and the ganglioside GM3) were selected to investigate their localization in the sperm and their behavior during capacitation and the acrosome reaction.
+These molecules localize to multiple sperm domains, including the acrosomal cap (IZUMO, caveolin 2, and flotillin 2), equatorial segment (GM3), cytoplasmic droplet (TEX101), midpiece (basigin, facilitated glucose transporter 3, and flotillin 2), and principal piece (facilitated glucose transporter 3).
+Some of these markers modified their immunofluorescence pattern after sperm incubation under capacitating conditions, and these changes correlated with the occurrence of the acrosome reaction.
+While GM3 and caveolin 2 were not detected after the acrosome reaction, flotillin 2 was found in the equatorial segment of acrosome-reacted sperm, and IZUMO distributed along the sperm head, reaching the post- and para-acrosomal areas.
+Taking into consideration the requirement of the acrosome reaction for sperm to become fusogenic, these results suggest that membrane raft dynamics may have a role in sperm-egg membrane interaction.
+Since the inception of global gene expression profiling platforms in the mid-1990s, there has been a significant increase in publications of differentially expressed genes in the process of epileptogenesis.
+In particular for mesial temporal lobe epilepsy, the presence of a latency period between the first manifestation of seizures to chronic epilepsy provides the opportunity for therapeutic interventions at the molecular biology level.
+Using global expression profiling techniques, approximately 2000 genes have been published demonstrating differential expression in mesial temporal epilepsy.
+The majority of these changes, however, are specific to laboratory or experimental conditions with only 53 genes demonstrating changes in more than two publications.
+To this end, we review the current status of gene expression profiling in epileptogenesis and suggest standard guidelines to be followed for greater accuracy and reproducibility of results.
+[Image: see text] RNA pseudoknots have important functions, and thermodynamic stability is a key to predicting pseudoknots in RNA sequences and to understanding their functions.
+Traditional methods, such as UV melting and differential scanning calorimetry, for measuring RNA thermodynamics are restricted to temperature ranges around the melting temperature for a pseudoknot.
+Here, we report RNA pseudoknot free energy changes at 37 °C measured by fluorescence competition assays.
+Adenoviruses replicate primarily in the host cell nucleus, and it is well established that adenovirus infection affects the structure and function of host cell nucleoli in addition to coding for a number of nucleolar targeted viral proteins.
+Here we used unbiased proteomics methods, including high throughput mass spectrometry coupled with stable isotope labeling by amino acids in cell culture (SILAC) and traditional two-dimensional gel electrophoresis, to identify quantitative changes in the protein composition of the nucleolus during adenovirus infection.
+By contrast, SILAC-based approaches identified 351 proteins with 24 proteins showing at least a 2-fold change after infection.
+Of those, four were previously reported to have aberrant localization and/or functional relevance during adenovirus infection.
+In total, 15 proteins identified as changing in amount by proteomics methods were examined in infected cells using confocal microscopy.
+Comparing our data with the effects of actinomycin D on the nucleolar proteome revealed that adenovirus infection apparently specifically targets a relatively small subset of nucleolar antigens at the time point examined.
+BACKGROUND: The isolation of human monoclonal antibodies (mAbs) that neutralize a broad spectrum of primary HIV-1 isolates and the characterization of the human neutralizing antibody B cell response to HIV-1 infection are important goals that are central to the design of an effective antibody-based vaccine.
+METHODS AND FINDINGS: We immortalized IgG(+) memory B cells from individuals infected with diverse clades of HIV-1 and selected on the basis of plasma neutralization profiles that were cross-clade and relatively potent.
+Culture supernatants were screened using various recombinant forms of the envelope glycoproteins (Env) in multiple parallel assays.
+We isolated 58 mAbs that were mapped to different Env surfaces, most of which showed neutralizing activity.
+One mAb in particular (HJ16) specific for a novel epitope proximal to the CD4 binding site on gp120 selectively neutralized a multi-clade panel of Tier-2 HIV-1 pseudoviruses, and demonstrated reactivity that was comparable in breadth, but distinct in neutralization specificity, to that of the other CD4 binding site-specific neutralizing mAb b12.
+A second mAb (HGN194) bound a conserved epitope in the V3 crown and neutralized all Tier-1 and a proportion of Tier-2 pseudoviruses tested, irrespective of clade.
+A third mAb (HK20) with broad neutralizing activity, particularly as a Fab fragment, recognized a highly conserved epitope in the HR-1 region of gp41, but showed striking assay-dependent selectivity in its activity.
+CONCLUSIONS: This study reveals that by using appropriate screening methods, a large proportion of memory B cells can be isolated that produce mAbs with HIV-1 neutralizing activity.
+Three of these mAbs show unusual breadth of neutralization and therefore add to the current panel of HIV-1 neutralizing antibodies with potential for passive protection and template-based vaccine design.
+‘Recoding’ is a term used to describe non-standard read-out of the genetic code, and encompasses such phenomena as programmed ribosomal frameshifting, stop codon readthrough, selenocysteine insertion and translational bypassing.
+Although only a small proportion of genes utilize recoding in protein synthesis, accurate annotation of ‘recoded’ genes lags far behind annotation of ‘standard’ genes.
+In order to address this issue, provide a service to researchers in the field, and offer training data for developers of gene-annotation software, we have gathered together known cases of recoding within the Recode database.
+It provides access to detailed information on genes known to utilize translational recoding and allows complex search queries, browsing of recoding data and enhanced visualization of annotated sequence elements.
+At present, the Recode-2 database stores information on approximately 1500 genes that are known to utilize recoding in their expression—a factor of approximately three increase over the previous version of the database.
+Large collections of protein-encoding open reading frames (ORFs) established in a versatile recombination-based cloning system have been instrumental to study protein functions in high-throughput assays.
+Such ‘ORFeome’ resources have been developed for several organisms but in virology, plasmid collections covering a significant fraction of the virosphere are still needed.
+In this perspective, we present ViralORFeome 1.0 (http://www.viralorfeome.com), an open-access database and management system that provides an integrated set of bioinformatic tools to clone viral ORFs in the Gateway® system.
+ViralORFeome provides a convenient interface to navigate through virus genome sequences, to design ORF-specific cloning primers, to validate the sequence of generated constructs and to browse established collections of virus ORFs.
+Most importantly, ViralORFeome has been designed to manage all possible variants or mutants of a given ORF so that the cloning procedure can be applied to any emerging virus strain.
+A subset of plasmid constructs generated with ViralORFeome platform has been tested with success for heterologous protein expression in different expression systems at proteome scale.
+ViralORFeome should provide our community with a framework to establish a large collection of virus ORF clones, an instrumental resource to determine functions, activities and binding partners of viral proteins.
+Primary influenza pneumonia has a high mortality rate during pandemics, not only in immunocompromised individuals and patients with underlying comorbid conditions, but also in young healthy adults.
+Clinicians should maintain a high index of suspicion for this diagnosis in patients presenting with influenza-like symptoms that progress quickly (2 to 5 days) to respiratory distress and extensive pulmonary involvement.
+The sensitivity of rapid diagnostic techniques in identifying infections with the pandemic 2009 H1N1v influenza strain is currently suboptimal.
+The most reliable real-time reverse transcriptase-polymerase chain reaction molecular testing is available in limited clinical settings.
+Despite 6 months of pandemic circulation, most novel H1N1v pandemic strains remain susceptible to oseltamivir.
+Ensuring an appropriate oxygenation and ventilation strategy, as well as prompt initiation of antiviral therapy, is essential in management.
+BACKGROUND: Clearly air travel, by transporting infectious individuals from one geographic location to another, significantly affects the rate of spread of influenza A (H1N1).
+However, the possibility of within-flight transmission of H1N1 has not been evaluated; although it is known that smallpox, measles, tuberculosis, SARS and seasonal influenza can be transmitted during commercial flights.
+Here we present the first quantitative risk assessment to assess the potential for within-flight transmission of H1N1.
+METHODS: We model airborne transmission of infectious viral particles of H1N1 within a Boeing 747 using methodology from the field of quantitative microbial risk assessment.
+RESULTS: The risk of catching H1N1 will essentially be confined to passengers travelling in the same cabin as the source case.
+Not surprisingly, we find that the longer the flight the greater the number of infections that can be expected.
+We calculate that H1N1, even during long flights, poses a low to moderate within-flight transmission risk if the source case travels First Class.
+Specifically, 0-1 infections could occur during a 5 hour flight, 1-3 during an 11 hour flight and 2-5 during a 17 hour flight.
+However, within-flight transmission could be significant, particularly during long flights, if the source case travels in Economy Class.
+Specifically, two to five infections could occur during a 5 hour flight, 5-10 during an 11 hour flight and 7-17 during a 17 hour flight.
+If the aircraft is only partially loaded, under certain conditions more infections could occur in First Class than in Economy Class.
+During a 17 hour flight, a greater number of infections would occur in First Class than in Economy if the First Class Cabin is fully occupied, but Economy class is less than 30% full.
+CONCLUSIONS: Our results provide insights into the potential utility of air travel restrictions on controlling influenza pandemics in the winter of 2009/2010.
+They show travel by one infectious individual, rather than causing a single outbreak of H1N1, could cause several simultaneous outbreaks.
+These results imply that, during a pandemic, quarantining passengers who travel in Economy on long-haul flights could potentially be an important control strategy.
+Notably, our results show that quarantining passengers who travel First Class would be unlikely to be an effective control strategy.
+The innate immune response is essential for controlling West Nile virus (WNV) infection but how this response is propagated and regulates adaptive immunity in vivo are not defined.
+Herein, we show that IPS-1, the central adaptor protein to RIG-I-like receptor (RLR) signaling, is essential for triggering of innate immunity and for effective development and regulation of adaptive immunity against pathogenic WNV.
+IPS-1(−/−) mice exhibited increased susceptibility to WNV infection marked by enhanced viral replication and dissemination with early viral entry into the CNS.
+Infection of cultured bone-marrow (BM) derived dendritic cells (DCs), macrophages (Macs), and primary cortical neurons showed that the IPS-1-dependent RLR signaling was essential for triggering IFN defenses and controlling virus replication in these key target cells of infection.
+Intriguingly, infected IPS-1(−/−) mice displayed uncontrolled inflammation that included elevated systemic type I IFN, proinflammatory cytokine and chemokine responses, increased numbers of inflammatory DCs, enhanced humoral responses marked by complete loss of virus neutralization activity, and increased numbers of virus-specific CD8+ T cells and non-specific immune cell proliferation in the periphery and in the CNS.
+This uncontrolled inflammatory response was associated with a lack of regulatory T cell expansion that normally occurs during acute WNV infection.
+Thus, the enhanced inflammatory response in the absence of IPS-1 was coupled with a failure to protect against WNV infection.
+Our data define an innate/adaptive immune interface mediated through IPS-1-dependent RLR signaling that regulates the quantity, quality, and balance of the immune response to WNV infection.
+BACKGROUND: Zoonotic malaria caused by Plasmodium knowlesi is an important, but newly recognized, human pathogen.
+For the first time, post-mortem findings from a fatal case of knowlesi malaria are reported here.
+CASE PRESENTATION: A formerly healthy 40 year-old male became symptomatic 10 days after spending time in the jungle of North Borneo.
+Four days later, he presented to hospital in a state of collapse and died within two hours.
+He was hyponatraemic and had elevated blood urea, potassium, lactate dehydrogenase and amino transferase values; he was also thrombocytopenic and eosinophilic.
+Blood for malaria parasites indicated hyperparasitaemia and single species P. knowlesi infection was confirmed by nested-PCR.
+Macroscopic pathology of the brain and endocardium showed multiple petechial haemorrhages, the liver and spleen were enlarged and lungs had features consistent with ARDS.
+Microscopic pathology showed sequestration of pigmented parasitized red blood cells in the vessels of the cerebrum, cerebellum, heart and kidney without evidence of chronic inflammatory reaction in the brain or any other organ examined.
+The kidney had evidence of acute tubular necrosis and endothelial cells in heart sections were prominent.
+CONCLUSIONS: The overall picture in this case was one of systemic malaria infection that fit the WHO classification for severe malaria.
+Post-mortem findings in this case were unexpectedly similar to those that define fatal falciparum malaria, including cerebral pathology.
+There were important differences including the absence of coma despite petechial haemorrhages and parasite sequestration in the brain.
+These results suggest that further study of knowlesi malaria will aid the interpretation of, often conflicting, information on malaria pathophysiology in humans.
+On June 11, 2009, the World Health Organization declared the outbreak of novel influenza A (H1N1) a pandemic.
+With limited supplies of antivirals and vaccines, countries and individuals are looking at other ways to reduce the spread of pandemic (H1N1) 2009, particularly options that are cost effective and relatively easy to implement.
+Recent experiences with the 2003 SARS and 2009 H1N1 epidemics have shown that people are willing to wear facemasks to protect themselves against infection; however, little research has been done to quantify the impact of using facemasks in reducing the spread of disease.
+We construct and analyze a mathematical model for a population in which some people wear facemasks during the pandemic and quantify impact of these masks on the spread of influenza.
+To estimate the parameter values used for the effectiveness of facemasks, we used available data from studies on N95 respirators and surgical facemasks.
+The results show that if N95 respirators are only 20% effective in reducing susceptibility and infectivity, only 10% of the population would have to wear them to reduce the number of influenza A (H1N1) cases by 20%.
+We can conclude from our model that, if worn properly, facemasks are an effective intervention strategy in reducing the spread of pandemic (H1N1) 2009.
+The basic reproduction number, R(0), a summary measure of the transmission potential of an infectious disease, is estimated from early epidemic growth rate, but a likelihood-based method for the estimation has yet to be developed.
+The present study corrects the concept of the actual reproduction number, offering a simple framework for estimating R(0) without assuming exponential growth of cases.
+The proposed method is applied to the HIV epidemic in European countries, yielding R(0) values ranging from 3.60 to 3.74, consistent with those based on the Euler-Lotka equation.
+Recent events clearly illustrate a continued vulnerability of large populations to infectious diseases, which is related to our changing human-constructed and natural environments.
+A single person with multidrug-resistant tuberculosis in 2007 provided a wake-up call to the United States and global public health infrastructure, as the health professionals and the public realized that today’s ease of airline travel can potentially expose hundreds of persons to an untreatable disease associated with an infectious agent.
+Ease of travel, population increase, population displacement, pollution, agricultural activity, changing socioeconomic structures, and international conflicts worldwide have each contributed to infectious disease events.
+Today, however, nothing is larger in scale, has more potential for long-term effects, and is more uncertain than the effects of climate change on infectious disease outbreaks, epidemics, and pandemics.
+We discuss advances in our ability to predict these events and, in particular, the critical role that satellite imaging could play in mounting an effective response.
+To improve diagnostic methods, we conducted immunoglobulin (Ig) G and IgM enzyme immunoassays with recombinant virus–like particles of HBoV as antigen.
+Acute-phase and follow-up serum samples from 258 wheezing children and single serum samples from 115 healthy adults in Finland were examined.
+Of 48 children with serologically diagnosed acute HBoV infections, 45 were viremic and 35 had virus in nasopharyngeal aspirates (NPAs).
+Of 39 HBoV NPA PCR–positive children co-infected with another virus, 64% had a serologically verified HBoV infection.
+HBoV caused illness of longer duration than rhinovirus and of equal severity to that of respiratory syncytial virus.
+Accurate HBoV diagnosis requires serologic analysis or PCR of serum; PCR of NPAs alone is insufficient.
+While colocalization of HIV-1 envelope with lipid rich microenvironment have been shown in T cells, the significance of viral proteins modulating envelope association in such microdomains in plasma membrane enriched in glycosylphosphatidylinositol-anchored proteins in primary CD4(+ )T cells that are natural targets of HIV-1 is poorly understood.
+Here we show that in primary CD4(+ )T cells that are natural targets of HIV-1 in vivo, Gag modulates HIV-1 envelope association with GM1 ganglioside and CD59 rich cellular compartments as well as with detergent resistant membranes.
+Our data strengthen evidence that Gag-Env interaction is important in envelope association with lipid rafts containing GPI-anchored proteins for efficient assembly onto mature virions resulting in productive infection of primary CD4(+ )T cells.
+The influenza A nucleoprotein (NP) is an attractive target for avian flu vaccine development because of its high conversancy in the evolutionary chain of the virus.
+Here we identified two novel HLA-A*0201 restricted NP epitopes, named H5N1 NP373-381 AMDSNTLEL (NP373) and NP458-466 FQGRGVFEL (NP458), using computational bioinformatic analysis.
+The NP peptides showed a high binding affinity to HLA-A*0201 on T2 cells, and were able to induce the activation of the cytotoxic T cells in the human peripheral blood mononuclear cells.
+We examined the potential of using NP373 and NP458 peptide sequences supplemented with a single-chain trimer as potential DNA vaccine candidates in an HHD transgenic mouse model.
+A gene gun delivery system was used for administrating the vaccine candidates into the animals.
+The results from cytotoxicity and ELISPOT assays indicated that a significant amount of IFN-γ was secreted by the T cells of the vaccinated mice, and the T cells were able to eliminate the corresponding peptide-loaded T2 cells.
+The discovery of these novel immunogenic NP peptides provides valuable information for avian flu vaccine design and construction.
+Beginning in 2003, highly pathogenic avian influenza (HPAI) H5N1 virus spread across Southeast Asia, causing unprecedented epidemics.
+Thailand was massively infected in 2004 and 2005 and continues today to experience sporadic outbreaks.
+While research findings suggest that the spread of HPAI H5N1 is influenced primarily by trade patterns, identifying the anthropogenic risk factors involved remains a challenge.
+In this study, we investigated which anthropogenic factors played a role in the risk of HPAI in Thailand using outbreak data from the “second wave” of the epidemic (3 July 2004 to 5 May 2005) in the country.
+We first performed a spatial analysis of the relative risk of HPAI H5N1 at the subdistrict level based on a hierarchical Bayesian model.
+The results confirmed the role of free-grazing ducks and rice-cropping intensity but showed a weak association with fighting cock density.
+The results also revealed a set of anthropogenic factors significantly linked with the risk of HPAI.
+High risk was associated strongly with densely populated areas, short distances to a highway junction, and short distances to large cities.
+These findings highlight a new explanatory pattern for the risk of HPAI and indicate that, in addition to agro-environmental factors, anthropogenic factors play an important role in the spread of H5N1.
+To limit the spread of future outbreaks, efforts to control the movement of poultry products must be sustained.
+BACKGROUND: The genetic contributions to human common disorders and mouse genetic models of disease are complex and often overlapping.
+In common human diseases, unlike classical Mendelian disorders, genetic factors generally have small effect sizes, are multifactorial, and are highly pleiotropic.
+Moreover, phenotypic descriptions in the literature in both human and mouse are often poorly characterized and difficult to compare directly.
+METHODS: In this report, human genetic association results from the literature are summarized with regard to replication, disease phenotype, and gene specific results; and organized in the context of a systematic disease ontology.
+These disease gene sets are then compared individually and in large groups through dendrogram analysis and hierarchical clustering analysis.
+RESULTS: Human disease and mouse phenotype gene sets are shown to group into disease and phenotypically relevant groups at both a coarse and fine level based on gene sharing.
+CONCLUSION: This analysis provides a systematic and global perspective on the genetics of common human disease as compared to itself and in the context of mouse genetic models of disease.
+Combination of peginterferon and ribavirin is the current therapy for chronic hepatitis C infection (HCV).
+Interstitial pneumonitis is a rare side-effect of HCV therapy and is an important cause of dose reduction or discontinuation, impairing success of antiviral therapy.
+We performed a review of the literature in order to present diagnostic modalities and possible treatments for pneumonitis and to offer guidelines.
+First we performed a literature search via PubMed and Web of Science interface and second we searched three drug toxicity databases.
+We systematically analyzed all case reports with respect to clinical manifestations, type of treatment, and outcome.
+A literature search revealed 19 articles, containing 25 case descriptions, while we traced 33 cases from the drug toxicity databases.
+Pneumonitis presented with any of the combination of fever, dyspnea, and cough and can arise with any type of (conventional or pegylated) interferon.
+Interferon-induced pneumonitis during HCV treatment is a severe complication and should be recognized in order to prevent further pulmonary damage and/or death.
+BACKGROUND: Back in 1987, the World Health Organization (WHO) concluded that the screening of international travellers was an ineffective way to prevent the spread of HIV.
+However, some countries still restrict the entrance and/or residency of foreigners with an HIV infection.
+HIV-related travel restrictions have serious implications for individual and public health, and violate internationally recognized human rights.
+In this study, we reviewed the current situation regarding HIV-related travel restrictions in the 53 countries of the WHO European Region.
+METHODS: We retrieved the country-specific information chiefly from the Global Database on HIV Related Travel Restrictions at hivtravel.org.
+We simplified and standardized the database information to enable us to create an overview and compare countries.
+Where data was outdated, unclear or contradictory, we contacted WHO HIV focal points in the countries or appropriate non-governmental organizations.
+The United States Bureau of Consular Affairs website was also used to confirm and complement these data.
+RESULTS: Our review revealed that there are no entry restrictions for people living with HIV in 51 countries in the WHO European Region.
+In 11 countries, foreigners living with HIV applying for long-term stays will not be granted a visa.
+These countries are: Andorra, Armenia, Cyprus (denies access for non-European Union citizens), Hungary, Kazakhstan, Moldova, the Russian Federation, Tajikistan, Turkmenistan, Ukraine and Uzbekistan.
+In Uzbekistan, an HIV-positive foreigner cannot even enter the country, and in Georgia, we were not able to determine whether there were any HIV-related travel restrictions due to a lack of information.
+CONCLUSIONS: In 32% of the countries in the European Region, either there are some kind of HIV-related travel restrictions or we were unable to determine if such restrictions are in force.
+However, there is no evidence that denying HIV-positive foreigners access to a country is effective in protecting public health.
+In the meantime, a joint effort is needed to draw attention to the continuing discrimination and stigmatization of people living with HIV that takes place in those European Region countries where such laws and policies are still in force.
+The rapid emergence and subsequent spread of the novel 2009 Influenza A/H1N1 virus (2009 H1N1) has prompted the World Health Organization to declare the first pandemic of the 21(st) century, highlighting the threat of influenza to public health and healthcare systems.
+Widespread resistance to both classes of influenza antivirals (adamantanes and neuraminidase inhibitors) occurs in both pandemic and seasonal viruses, rendering these drugs to be of marginal utility in the treatment modality.
+Worldwide, virtually all 2009 H1N1 and seasonal H3N2 strains are resistant to the adamantanes (rimantadine and amantadine), and the majority of seasonal H1N1 strains are resistant to oseltamivir, the most widely prescribed neuraminidase inhibitor (NAI).
+To address the need for more effective therapy, we evaluated the in vitro activity of a triple combination antiviral drug (TCAD) regimen composed of drugs with different mechanisms of action against drug-resistant seasonal and 2009 H1N1 influenza viruses.
+Amantadine, ribavirin, and oseltamivir, alone and in combination, were tested against amantadine- and oseltamivir-resistant influenza A viruses using an in vitro infection model in MDCK cells.
+Our data show that the triple combination was highly synergistic against drug-resistant viruses, and the synergy of the triple combination was significantly greater than the synergy of any double combination tested (P<0.05), including the combination of two NAIs.
+Surprisingly, amantadine and oseltamivir contributed to the antiviral activity of the TCAD regimen against amantadine- and oseltamivir-resistant viruses, respectively, at concentrations where they had no activity as single agents, and at concentrations that were clinically achievable.
+Our data demonstrate that the TCAD regimen composed of amantadine, ribavirin, and oseltamivir is highly synergistic against resistant viruses, including 2009 H1N1.
+The TCAD regimen overcomes baseline drug resistance to both classes of approved influenza antivirals, and thus may represent a highly active antiviral therapy for seasonal and pandemic influenza.
+INTRODUCTION: Multicentric Castleman's Disease (MCD), a lymphoproliferative disorder associated with Human Herpes Virus-8 (HHV-8) infection, is increasing in incidence amongst HIV patients.
+A number of small studies have demonstrated the efficacy of the anti-CD20 monoclonal antibody, rituximab, in treating this condition.
+CASE PRESENTATION: We report the case of a 46 year old Zambian woman who presented with pyrexia, diarrhoea and vomiting, confusion, lymphadenopathy, and renal failure.
+She rapidly developed multiple organ failure following the initiation of treatment of MCD with rituximab.
+After 21 days on the ICU she returned to the haematology medical ward, and was discharged in remission from her disease after 149 days in hospital.
+CONCLUSION: Rituximab, the efficacy of which has thus far been examined predominantly in patients outside the ICU, in conjunction with extensive organ support was effective treatment for MCD with associated multiple organ failure.
+There is, to our knowledge, only one other published report of its successful use in an ICU setting, where it was combined with cyclophosphamide, adriamycin and prednisolone.
+Reports such as ours support the notion that critically unwell patients with HIV and haematological disease can benefit from intensive care.
+In this study, specific sequences within three genes (3D, VP4 and 2B) of the foot-and-mouth disease virus (FMDV) genome were determined to be effective RNAi targets.
+Small interfering RNA (siRNA)-expressing plasmids (p3D-NT19, p3D-NT56, pVP4-NT19, pVP4-NT65 and p2B-NT25) were constructed to express siRNA targeting 3D, VP4 and 2B, respectively.
+The antiviral potential of these siRNA for various FMDV isolates was investigated in baby hamster kidney (BHK-21) cells and suckling mice.
+The results show that these siRNA inhibited virus yield 10- to 300-fold for different FMDV isolates of serotype O and serotype Asia I at 48 h post infection in BHK-21 cells compared to control cells.
+Twenty percent to 40% of the animals that received a single siRNA dose survived 5 days post infection with serotype O or serotype Asia I.
+We used an attenuated Salmonella choleraesuis (C500) vaccine strain, to carry the plasmid that expresses siRNA directed against the polymerase gene 3D (p3D-NT56) of FMDV.
+The results indicate that 100% of the animals treated with 5 × 10(9) CFU of p3D-NT56/S.
+In this case report, the authors describe a thirty-five year old immunocompetent male presenting with severe respiratory distress requiring intubation.
+The morphology and sensitivity pattern of the organism found in the bronchoalveolar lavage fluid and blood culture were consistent with MRSA.
+The patient's stay in the hospital was complicated by acute renal failure due to rhabdomyolysis with CPK levels of 9995 U/L.
+This case brings to light that CA-MRSA is becoming a problem in developing nations where antibiotics are frequently used empirically with little laboratory guidance.
+The envelope of HSV-1 contains a number of glycoproteins, four of which are essential for virus entry.
+Virus particles lacking gB, gD, gH or gL are entry-defective, although these viruses retain the ability to bind to the plasma membrane via the remaining glycoproteins.
+Soluble forms of gD have been shown to trigger the nuclear translocation of the NF-κB transcriptional complex in addition to stimulating the production of Type I interferon.
+By taking advantage of the entry-defective phenotype of glycoprotein-deficient HSV-1 virus particles, the results presented here show that binding of virions to cellular receptors on the plasma membrane is sufficient to stimulate a change in cellular gene expression.
+Preliminary microarray studies, validated by quantitative real-time PCR, identified the differential expression of cellular genes associated with the NF-κB, PI3K/Akt, Jak/Stat and related Jak/Src pathways by virions lacking gB or gH but not gD.
+Gene induction occurred at a few particles per cell, corresponding to physiological conditions during primary infection.
+Reporter assay studies determined that NF-κB transcriptional activity is stimulated within an hour of HSV-1 binding, peaks between two and three hours post-binding and declines to background levels by five hours after induction.
+The immediate, transient nature of these signalling events suggests that HSV-1 glycoproteins, particularly gD, may alter the cellular environment pre-entry so as to condition the cell for viral replication.
+BACKGROUND: Influenza immunisation for healthcare workers is encouraged to protect their often vulnerable patients but also due to a perceived higher risk for influenza.
+We aimed to compare the risk of influenza infection in healthcare workers in acute hospital care with that in non-healthcare workers over the same season.
+METHODS: We conducted a prospective, multicentre cohort study during the 2006/07 influenza season in Berlin, Germany.
+Recruited participants gave serum samples before and after the season, and completed questionnaires to determine their relevant exposures and possible confounding factors.
+The main outcome measure was serologically confirmed influenza infection (SCII), defined as a fourfold or greater rise in haemagglutination inhibition antibody titres to a circulating strain of influenza (with post-season titre at least 1:40).
+Weekly mobile phone text messages were used to prompt participants to report respiratory illnesses during the influenza season.
+RESULTS: We recruited 250 hospital healthcare workers (mean age 35.7 years) and 486 non-healthcare workers (mean age 39.2 years) from administrative centres, blood donors and colleges.
+Being a healthcare worker was not a risk factor for SCII (relative risk 1.1, p = 0.70).
+The final multivariate model had three significant factors: living with children (odds ratio [OR] 3.7, p = 0.005), immunization (OR 0.50, p = 0.02), and - among persons living in households without children - ownership of a car (OR 3.0, p = 0.02).
+Living with three or more children (OR 13.8, p < 0.01) was a greater risk than living with one or two children (OR 5.3, p = 0.02).
+Healthcare workers were at slightly higher risk of reporting any respiratory infection than controls (adjusted OR 1.3, p = 0.04, n = 850).
+CONCLUSIONS: Our results suggest that healthcare workers in hospitals do not have a higher risk of influenza than non-healthcare workers, although their risk of any respiratory infection is slightly raised.
+It is both time-consuming and costly to determine compound-protein interactions or potential drug-target interactions by experiments alone.
+As a complement, the in silico prediction methods can provide us with very useful information in a timely manner.
+METHODS/PRINCIPAL FINDINGS: To realize this, drug compounds are encoded with functional groups and proteins encoded by biological features including biochemical and physicochemical properties.
+The optimal feature selection procedures are adopted by means of the mRMR (Maximum Relevance Minimum Redundancy) method.
+Instead of classifying the proteins as a whole family, target proteins are divided into four groups: enzymes, ion channels, G-protein- coupled receptors and nuclear receptors.
+Thus, four independent predictors are established using the Nearest Neighbor algorithm as their operation engine, with each to predict the interactions between drugs and one of the four protein groups.
+As a result, the overall success rates by the jackknife cross-validation tests achieved with the four predictors are 85.48%, 80.78%, 78.49%, and 85.66%, respectively.
+CONCLUSION/SIGNIFICANCE: Our results indicate that the network prediction system thus established is quite promising and encouraging.
+An efficient −1 programmed ribosomal frameshifting (PRF) signal requires an RNA slippery sequence and a downstream RNA stimulator, and the hairpin-type pseudoknot is the most common stimulator.
+hTPK-DU177, a pseudoknot derived from human telomerase RNA, shares structural similarities with several −1 PRF pseudoknots and is used to dissect the roles of distinct structural features in the stimulator of −1 PRF.
+Structure-based mutagenesis on hTPK-DU177 reveals that the −1 PRF efficiency of this stimulator can be modulated by sequential removal of base–triple interactions surrounding the helical junction.
+Further analysis of the junction-flanking base triples indicates that specific stem–loop interactions and their relative positions to the helical junction play crucial roles for the −1 PRF activity of this pseudoknot.
+Intriguingly, a bimolecular pseudoknot approach based on hTPK-DU177 reveals that continuing triplex structure spanning the helical junction, lacking one of the loop-closure features embedded in pseudoknot topology, can stimulate −1 PRF.
+Therefore, the triplex structure is an essential determinant for the DU177 pseudoknot to stimulate −1 PRF.
+Furthermore, it suggests that −1 PRF, induced by an in-trans RNA via specific base–triple interactions with messenger RNAs, can be a plausible regulatory function for non-coding RNAs.
+In July 1962, the author joined the Food Research Institute (FRI), then at the University of Chicago, to become its food virologist.
+There was a limited record of waterborne viral disease outbreaks at the time; recorded data on foodborne outbreaks were fewer still.
+Laboratory environmental (water and wastewater) virology was in its infancy, and food virology was in gestation.
+Detection of viruses was most often attempted by inoculation of primary primate cell cultures, with observation for plaque formation or cytopathic effects.
+Environmental and food samples had to be liquefied if not already in liquid form; clarified to remove solids, bacteria, and fungi; and concentrated to a volume that could be tested in cell culture.
+The FRI group was the World Health Organization’s Collaborating Center for Food Virology for many years.
+Other topics studied were virus inactivation as functions of temperature, time, matrix, disinfectants, and microbial action; peroral and ex-vivo infectivity; and the suitability of various virus surrogates for environmental monitoring and inactivation experiments.
+When it was found that inactivated virus often gave the same RT-PCR signal as that of infectious virus, sample treatments were sought, which would prevent false-positive test results.
+Many laboratories around the world have taken up food and environmental virology since 1962, with the result that a dedicated journal has been launched.
+Groundnut bud necrosis virus (GBNV), a member of genus Tospovirus in the family Bunyaviridae, infects a large number of leguminosae and solanaceae plants in India.
+With a view to elucidate the function of nonstructural protein, NSs encoded by the small RNA genome (S RNA), the NSs protein of GBNV- tomato (Karnataka) [1] was over-expressed in E. coli and purified by Ni-NTA chromatography.
+Further, this activity was metal ion dependent and was inhibited by adenosine 5′ (β, γ imido) triphosphate, an ATP analog.
+Interestingly, in addition to the NTPase and dATPase activities, the rNSs exhibited ATP independent 5′ RNA/DNA phosphatase activity that was completely inhibited by AMP.
+The 5′ α phosphate could be removed from ssDNA, ssRNA, dsDNA and dsRNA thus confirming that rNSs has a novel 5′ α phosphatase activity.
+K189A mutation in the Walker motif A (GxxxxGKT) resulted in complete loss of ATPase activity, but the 5′ phosphatase activity was unaffected.
+On the other hand, D159A mutation in the Walker motif B (DExx) resulted in partial loss of both the activities.
+These results demonstrate for the first time that NSs is a bifunctional enzyme, which could participate in viral movement, replication or in suppression of the host defense mechanism.
+BACKGROUND: To describe the characteristics of patients with tuberculosis (TB) requiring intensive care and to identify the factors that predicts in-hospital mortality in a city of a developing country with intermediate-to-high TB endemicity.
+Early intensive care unit admission and ventilator-associated pneumonia were independently associated with the in-hospital mortality.
+CONCLUSIONS: In this study we found a high mortality rate in TB patients requiring intensive care, especially in those with an early ICU admission.
+Efforts to develop a broadly protective vaccine against the highly pathogenic avian influenza A (HPAI) H5N1 virus have focused on highly conserved influenza gene products.
+The viral nucleoprotein (NP) and ion channel matrix protein (M2) are highly conserved among different strains and various influenza A subtypes.
+Here, we investigate the relative efficacy of NP and M2 compared to HA in protecting against HPAI H5N1 virus.
+In mice, previous studies have shown that vaccination with NP and M2 in recombinant DNA and/or adenovirus vectors or with adjuvants confers protection against lethal challenge in the absence of HA.
+However, we find that the protective efficacy of NP and M2 diminishes as the virulence and dose of the challenge virus are increased.
+To explore this question in a model relevant to human disease, ferrets were immunized with DNA/rAd5 vaccines encoding NP, M2, HA, NP+M2 or HA+NP+M2.
+Therefore, while gene-based vaccination with NP and M2 may provide moderate levels of protection against low challenge doses, it is insufficient to confer protective immunity against high challenge doses of H5N1 in ferrets.
+These immunogens may require combinatorial vaccination with HA, which confers protection even against very high doses of lethal viral challenge.
+The tracing of potentially infectious contacts has become an important part of the control strategy for many infectious diseases, from early cases of novel infections to endemic sexually transmitted infections.
+Here, we make use of mathematical models to consider the case of partner notification for sexually transmitted infection, however these models are sufficiently simple to allow more general conclusions to be drawn.
+We show that, when contact network structure is considered in addition to contact tracing, standard “mass action” models are generally inadequate.
+To consider the impact of mutual contacts (specifically clustering) we develop an improvement to existing pairwise network models, which we use to demonstrate that ceteris paribus, clustering improves the efficacy of contact tracing for a large region of parameter space.
+We also develop stochastic simulations for comparison, using simple re-wiring methods that allow the generation of appropriate comparator networks.
+In this way we contribute to the general theory of network-based interventions against infectious disease.
+Though, when host physiology is disrupted, this commensal-host interaction can degenerate and lead to an opportunistic infection.
+We developed a C. albicans cell surface protein microarray to profile the immunoglobulin G response during commensal colonization and candidemia.
+The antibody response from the sera of patients with candidemia and our negative control groups indicate that the immunocompetent host exists in permanent host-pathogen interplay with commensal C. albicans.
+We identified a set of thirteen cell surface antigens capable of distinguishing acute candidemia from healthy individuals and uninfected hospital patients with commensal colonization.
+Interestingly, a large proportion of these cell surface antigens are involved in either oxidative stress or drug resistance.
+In addition, we identified 33 antigenic proteins that are enriched in convalescent sera of the candidemia patients.
+Intriguingly, we found within this subset an increase in antigens associated with heme-associated iron acquisition.
+These findings have important implications for the mechanisms of C. albicans colonization as well as the development of systemic infection.
+Due to their rapid and widespread development, DNA vaccines have entered into a variety of human clinical trials for vaccines against various diseases including cancer.
+Evidence that DNA vaccines are well tolerated and have an excellent safety profile proved to be of advantage as many clinical trials combines the first phase with the second, saving both time and money.
+It is clear from the results obtained in clinical trials that such DNA vaccines require much improvement in antigen expression and delivery methods to make them sufficiently effective in the clinic.
+Similarly, it is clear that additional strategies are required to activate effective immunity against poorly immunogenic tumor antigens.
+Engineering vaccine design for manipulating antigen presentation and processing pathways is one of the most important aspects that can be easily handled in the DNA vaccine technology.
+Several approaches have been investigated including DNA vaccine engineering, co-delivery of immunomodulatory molecules, safe routes of administration, prime-boost regimen and strategies to break the immunosuppressive networks mechanisms adopted by malignant cells to prevent immune cell function.
+Combined or single strategies to enhance the efficacy and immunogenicity of DNA vaccines are applied in completed and ongoing clinical trials, where the safety and tolerability of the DNA platform are substantiated.
+In this review on DNA vaccines, salient aspects on this topic going from basic research to the clinic are evaluated.
+Efficient delivery of siRNA to specific cell populations in vivo remains a formidable challenge to its successful therapeutic application.
+We describe a novel siRNA-based approach – synthetically linking siRNA to an oligonucleotide TLR9 agonist – that targets and silences genes in TLR9(+) myeloid cells and B cells, both of which are key components of the tumor microenvironment.
+Because Stat3 in tumor-associated immune cells suppresses antitumor immune responses and hinders TLR9-induced immune stimulation, we tested CpG-Stat3siRNA conjugates for anti-tumor effects.
+When injected locally at the tumor site or systemically through an intravenous route, the CpG-Stat3siRNA conjugates access tumor-associated dendritic cells, macrophages and B cells, inhibit Stat3 expression, leading to activation of tumor-associated immune cells, and ultimately potent anti-tumor immune responses.
+Our findings demonstrate the potential of TLR agonist-siRNA conjugates for targeted gene silencing coupled with TLR stimulation and immune activation in the tumor microenvironment.
+BACKGROUND: Rift Valley fever virus (RVFV), a member of the genus Phlebovirus within the family Bunyaviridae, is a negative-stranded RNA virus with a tripartite genome.
+RVFV is transmitted by mosquitoes and causes fever and severe hemorrhagic illness among humans, while in livestock it causes fever and high abortion rates.
+METHODOLOGY/PRINCIPAL FINDINGS: Sequence analysis showed that a wild-type RVFV ZH501 preparation consisted of two major viral subpopulations, with a single nucleotide heterogeneity at nucleotide 847 of M segment (M847); one had a G residue at M847 encoding glycine in a major viral envelope Gn protein, while the other carried A residue encoding glutamic acid at the corresponding site.
+Two ZH501-derived viruses, rZH501-M847-G and rZH501-M847-A, carried identical genomic sequences, except that the former and the latter had G and A, respectively, at M847 were recovered by using a reverse genetics system.
+Intraperitoneal inoculation of rZH501-M847-A into mice caused a rapid and efficient viral accumulation in the sera, livers, spleens, kidneys and brains, and killed most of the mice within 8 days, whereas rZH501-M847-G caused low viremia titers, did not replicate as efficiently as did rZH501-M847-A in these organs, and had attenuated virulence to mice.
+Remarkably, as early as 2 days postinfection with rZH501-M847-G, the viruses carrying A at M847 emerged and became the major virus population thereafter, while replicating viruses retained the input A residue at M847 in rZH501-M847-A-infected mice.
+CONCLUSIONS/SIGNIFICANCE: These data demonstrated that the single nucleotide substitution in the Gn protein substantially affected the RVFV mouse virulence and that a virus population carrying the virulent viral genotype quickly emerged and became the major viral population within a few days in mice that were inoculated with the attenuated virus.
+Influenza A (H5N1) viruses are strong candidates for causing the next influenza pandemic if they acquire the ability for efficient human-to-human transmission.
+A major public health goal is to make efficacious vaccines against these viruses by using novel approaches, including cell-culture system, reverse genetics, and adjuvant development.
+Important consideration for the strategy includes preparation of vaccines from a currently circulating strain to induce broad-spectrum immunity toward newly emerged human H5 strains.
+This strategy would be a good solution early in a pandemic until an antigenically matched and approved vaccine is produced.
+The concept of therapeutic vaccines (e.g., antidisease vaccine) directed at diminishing the cytokine storm frequently seen in subtype H5N1–infected persons is underscored.
+Better understanding of host–virus interaction is essential to identify tools to produce effective vaccines against influenza (H5N1).
+The dynamics of infectious diseases spread via direct person-to-person transmission (such as influenza, smallpox, HIV/AIDS, etc.)
+Understanding how such community structure affects epidemics may provide insights for preventing the spread of disease between communities by changing the structure of the contact network through pharmaceutical or non-pharmaceutical interventions.
+We use empirical and simulated networks to investigate the spread of disease in networks with community structure.
+We find that community structure has a major impact on disease dynamics, and we show that in networks with strong community structure, immunization interventions targeted at individuals bridging communities are more effective than those simply targeting highly connected individuals.
+Because the structure of relevant contact networks is generally not known, and vaccine supply is often limited, there is great need for efficient vaccination algorithms that do not require full knowledge of the network.
+We developed an algorithm that acts only on locally available network information and is able to quickly identify targets for successful immunization intervention.
+The algorithm generally outperforms existing algorithms when vaccine supply is limited, particularly in networks with strong community structure.
+Understanding the spread of infectious diseases and designing optimal control strategies is a major goal of public health.
+Social networks show marked patterns of community structure, and our results, based on empirical and simulated data, demonstrate that community structure strongly affects disease dynamics.
+BACKGROUND: Human CEACAM1 is a cell-cell adhesion molecule with multiple functions including insulin clearance in the liver, vasculogenesis in endothelial cells, lumen formation in the mammary gland, and binding of certain human pathogens.
+PRINCIPAL FINDINGS: Three genomic BAC clones containing the human CEACAM1 gene were microinjected into pronuclei of fertilized FVB mouse oocytes.
+The embryos were implanted in the oviducts of pseudopregnant females and allowed to develop to term.
+DNA from newborn mice was evaluated by PCR for the presence of the human CEACAM1 gene.
+Using this assay, one out of five PCR positive lines was positive for human CEACAM1 expression and showed stable transmission to the F1 generation with the expected transmission frequency (0.5) for heterozygotes.
+Liver, lung, intestine, kidney, mammary gland, and prostate were strongly positive for the dual expression of both murine and human CEACAM1 and mimic that seen in human tissue.
+Peripheral blood and bone marrow granulocytes stained strongly for human CEACAM1 and bound Neisseria Opa proteins similar to that in human neutrophils.
+CONCLUSION: These transgenic animals may serve as a model for the binding of human pathogens to human CEACAM1.
+Practical algorithms for RNA structure prediction including restricted classes of pseudoknots suffer from high runtime and poor accuracy for longer sequences.
+A heuristic approach is to search for promising pseudoknot candidates in a sequence and verify those.
+We present a novel pseudoknot detection method called DotKnot that extracts stem regions from the secondary structure probability dot plot and assembles pseudoknot candidates in a constructive fashion.
+We show that the conventional probability dot plot makes a wide class of pseudoknots including those with bulged stems manageable in an explicit fashion.
+DotKnot is an efficient method for long sequences, which finds pseudoknots with higher accuracy compared to other known prediction algorithms.
+The United States is the world’s largest wildlife importer, and imported wild animals represent a potential source of zoonotic pathogens.
+Using data on mammals imported during 2000–2005, we assessed their potential to host 27 selected risk zoonoses and created a risk assessment that could inform policy making for wildlife importation and zoonotic disease surveillance.
+The most widespread agents of risk zoonoses were rabies virus (in 78 genera of mammals), Bacillus anthracis (57), Mycobacterium tuberculosis complex (48), Echinococcus spp.
+Genera capable of harboring the greatest number of risk zoonoses were Canis and Felis (14 each), Rattus (13), Equus (11), and Macaca and Lepus (10 each).
+These findings demonstrate the myriad opportunities for zoonotic pathogens to be imported and suggest that, to ensure public safety, immediate proactive changes are needed at multiple levels.
+Newcastle Disease Virus (NDV) is a pathogenic strain of avian paramyxovirus (aPMV-1) that is among the most serious of disease threats to the poultry industry worldwide.
+Viral diversity is high in aPMV-1; eight genotypes are recognized based on phylogenetic reconstruction of gene sequences.
+Modified live vaccines have been developed to decrease the economic losses caused by this virus.
+Vaccines derived from avirulent genotype II strains were developed in the 1950s and are in use globally, whereas Australian strains belonging to genotype I were developed as vaccines in the 1970s and are used mainly in Asia.
+In this study, we evaluated the consequences of attenuated live virus vaccination on the evolution of aPMV-1 genotypes.
+There was phylogenetic incongruence among trees based on individual genes and complete coding region of 54 full length aPMV-1 genomes, suggesting that recombinant sequences were present in the data set.
+Subsequently, five recombinant genomes were identified, four of which contained sequences from either genotype I or II.
+The population history of vaccine-related genotype II strains was distinct from other aPMV-1 genotypes; genotype II emerged in the late 19(th) century and is evolving more slowly than other genotypes, which emerged in the 1960s.
+Additionally, genotype I and II viruses, which are circulating in the presence of homotypic vaccine pressure, have unique selection profiles compared to nonvaccine-related strains.
+Collectively, these data show that vaccination with live attenuated viruses has changed the evolution of aPMV-1 by maintaining a large effective population size of a vaccine-related genotype, allowing for coinfection and recombination of vaccine and wild type strains, and by applying unique selective pressures on viral glycoproteins.
+The filoviruses, Marburg and Ebola, are non-segmented negative-strand RNA viruses causing severe hemorrhagic fever with high mortality rates in humans and nonhuman primates.
+The sequence of events that leads to release of filovirus particles from cells is poorly understood.
+Two contrasting mechanisms have been proposed, one proceeding via a “submarine-like” budding with the helical nucleocapsid emerging parallel to the plasma membrane, and the other via perpendicular “rocket-like” protrusion.
+Here we have infected cells with Marburg virus under BSL-4 containment conditions, and reconstructed the sequence of steps in the budding process in three dimensions using electron tomography of plastic-embedded cells.
+Budding proceeds via lateral association of intracellular nucleocapsid along its whole length with the plasma membrane, followed by rapid envelopment initiated at one end of the nucleocapsid, leading to a protruding intermediate.
+After prolonged infection, increased vesiculation of the plasma membrane correlates with changes in shape and infectivity of released viruses.
+They reconcile the contrasting models of filovirus budding and allow us to describe the sequence of events taking place during budding and release of Marburg virus.
+We propose that this represents a general sequence of events also followed by other filamentous and rod-shaped viruses.
+Therefore, unique molecules expressed on tumor endothelial cells can function as targets for the antiangiogenic therapy of cancer.
+Current efforts are focusing on developing therapeutic agents capable of specifically targeting cancer cells and tumor-associated microenvironments including tumor blood vessels.
+One recognized strategy for improving the therapeutic effectiveness of conventional chemotherapeutics is to encapsulate anticancer drugs into targeting liposomes that bind to the cell surface receptors expressed on tumor-associated endothelial cells.
+These anti-angiogenic drug delivery systems could be used to target both tumor blood vessels as well as the tumor cells, themselves.
+This article reviews the mechanisms and advantages of various present and potential methods using peptide-conjugated liposomes to specifically destroy tumor blood vessels in anticancer therapy.
+The earliest immune responses activated in acute human immunodeficiency virus type 1 infection (AHI) exert a critical influence on subsequent virus spread or containment.
+During this time frame, components of the innate immune system such as macrophages and DCs, NK cells, β-defensins, complement and other anti-microbial factors, which have all been implicated in modulating HIV infection, may play particularly important roles.
+A proteomics-based screen was performed on a cohort from whom samples were available at time points prior to the earliest positive HIV detection.
+The ability of selected factors found to be elevated in the plasma during AHI to inhibit HIV-1 replication was analyzed using in vitro PBMC and DC infection models.
+Analysis of unique plasma donor panels spanning the eclipse and viral expansion phases revealed very early alterations in plasma proteins in AHI.
+Induction of acute phase protein serum amyloid A (A-SAA) occurred as early as 5–7 days prior to the first detection of plasma viral RNA, considerably prior to any elevation in systemic cytokine levels.
+Furthermore, a proteolytic fragment of alpha–1-antitrypsin (AAT), termed virus inhibitory peptide (VIRIP), was observed in plasma coincident with viremia.
+Both A-SAA and VIRIP have anti-viral activity in vitro and quantitation of their plasma levels indicated that circulating concentrations are likely to be within the range of their inhibitory activity.
+Our results provide evidence for a first wave of host anti-viral defense occurring in the eclipse phase of AHI prior to systemic activation of other immune responses.
+Insights gained into the mechanism of action of acute-phase reactants and other innate molecules against HIV and how they are induced could be exploited for the future development of more efficient prophylactic vaccine strategies.
+A shortcoming of most correlation distance methods based on the composition vectors without alignment developed for phylogenetic analysis using complete genomes is that the “distances” are not proper distance metrics in the strict mathematical sense.
+In this paper we propose two new correlation-related distance metrics to replace the old one in our dynamical language approach.
+Four genome datasets are employed to evaluate the effects of this replacement from a biological point of view.
+We find that the two proper distance metrics yield trees with the same or similar topologies as/to those using the old “distance” and agree with the tree of life based on 16S rRNA in a majority of the basic branches.
+Hence the two proper correlation-related distance metrics proposed here improve our dynamical language approach for phylogenetic analysis.
+BACKGROUND: The highly pathogenic avian influenza (HPAI) virus H5N1 causes multi-organ disease and death in poultry, resulting in significant economic losses in the poultry industry.
+In addition, it poses a major public health threat as it can be transmitted directly from infected poultry to humans with very high (60%) mortality rate.
+Effective vaccination against HPAI H5N1 would protect commercial poultry and would thus provide an important control measure by reducing the likelihood of bird-to-bird and bird-to-human transmission.
+METHODOLOGY/PRINCIPAL FINDINGS: In the present study we evaluated the vaccine potential of recombinant soluble trimeric subtype 5 hemagglutinin (sH5(3)) produced in mammalian cells.
+The secreted, purified sH5(3) was biologically active as demonstrated by its binding to ligands in a sialic acid-dependent manner.
+It was shown to protect chickens, in a dose-dependent manner, against a lethal challenge with H5N1 after a single vaccination.
+Protected animals did not shed challenge virus as determined by a quantitative RT-PCR on RNA isolated from trachea and cloaca swabs.
+CONCLUSIONS/SIGNIFICANCE: Our results demonstrate that sH5(3) constitutes an attractive vaccine antigen for protection of chickens and mammals against HPAI H5N1.
+As these recombinant soluble hemagglutinin preparations can be produced with high yields and with relatively short lead time, they enable a rapid response to circulating and potentially pandemic influenza viruses.
+To help clinicians triage adults with acute respiratory illness, a scoring system for influenza-like illness (ILI) was implemented at Hospital Civil de Guadalajara, Mexico.
+METHODS: A medical history, laboratory and radiology results were collected on emergency room (ER) patients with acute respiratory illness to calculate an ILI-score.
+Patients were evaluated for admission by their ILI-score and clinicians' assessment of risk for developing complications.
+Nasal and throat swabs were collected from intermediate and high-risk patients for influenza testing by RT-PCR.
+The disposition and ILI-score of those oseltamivir-treated versus untreated, clinical characteristics of 2009 pandemic influenza A (H1N1) patients versus test-negative patients were compared by Pearson's Χ(2), Fisher's Exact, and Wilcoxon rank-sum tests.
+RESULTS: Of 1840 ER patients, 230 were initially hospitalized (mean ILI-score = 15), and the rest were discharged, including 286 ambulatory patients given oseltamivir (median ILI-score = 11), and 1324 untreated (median ILI-score = 5).
+Fourteen (1%) untreated patients returned, and 3 were hospitalized on oseltamivir (median ILI-score = 19).
+Of 371 patients tested by RT-PCR, 104 (28%) had pandemic influenza and 42 (11%) had seasonal influenza A detected.
+Twenty (91%) of 22 imaged hospitalized pandemic influenza patients had bilateral infiltrates compared to 23 (38%) of 61 imaged hospital test-negative patients (p<0.001).
+One patient with confirmed pandemic influenza presented 6 days after symptom onset, required mechanical ventilation, and died.
+CONCLUSIONS: The triaging system that used an ILI-score complimented clinicians' judgment of who needed oseltamivir and inpatient care and helped hospital staff manage a surge in demand for services.
+In April 2009, a new influenza A (H1N1 2009) virus emerged that rapidly spread around the world.
+While current variants of this virus have caused widespread disease, particularly in vulnerable groups, there remains the possibility that future variants may cause increased virulence, drug resistance or vaccine escape.
+Early detection of these virus variants may offer the chance for increased containment and potentially prevention of the virus spread.
+We have developed and field-tested a resequencing kit that is capable of interrogating all eight segments of the 2009 influenza A(H1N1) virus genome and its variants, with added focus on critical regions such as drug-binding sites, structural components and mutation hotspots.
+The accompanying base-calling software (EvolSTAR) introduces novel methods that utilize neighbourhood hybridization intensity profiles and substitution bias of probes on the microarray for mutation confirmation and recovery of ambiguous base queries.
+Our results demonstrate that EvolSTAR is highly accurate and has a much improved call rate.
+The high throughput and short turn-around time from sample to sequence and analysis results (30 h for 24 samples) makes this kit an efficient large-scale evolutionary biosurveillance tool.
+BACKGROUND: The unpredictable nature of the potentially devastating impact of 2009 pH1N1 influenza pandemic highlights the need for pandemic preparedness planning, where modeling studies could be most useful for simulations of possible future scenarios.
+METHODS: A compartmental model with pre-symptomatic and asymptomatic influenza infections is proposed which incorporates age groups as well as intervention measures such as age-specific vaccination, in order to study spread of influenza in a community.
+RESULTS: We derive the basic reproduction number and other effective reproduction numbers under various intervention measures.
+For illustration, we make use of the Pneumonia and Influenza (P&I) mortality data and vaccination data of the very young (age 0-2) and the very old (age >64) during 2004-2005 Taiwan winter influenza season to fit our model and to compute the relevant reproduction numbers.
+The reproduction number for this winter flu season is estimated to be slightly above one (~1.0001).
+CONCLUSIONS: Comparatively large errors in fitting the P&I mortality data of the elderly (>64) were observed shortly after winter school closings in January, which may indicate the impact of younger, more active age groups transmitting influenza to other age groups outside of the school settings; in particular, to the elderly in the households.
+Pre-symptomatic infections seemed to have little effect on the model fit, while asymptomatic infection by asymptomatic infectives has a more pronounced impact on the model fit for the elderly mortality, perhaps indicating a larger role in disease transmission by asymptomatic infection.
+Simulations indicate that the impact of vaccination on the disease incidence might not be fully revealed in the change (or the lack thereof) in the effective reproduction number with interventions, but could still be substantial.
+The estimated per contact transmission probability for susceptible elderly is significantly higher than that of any other age group, perhaps highlighting the vulnerability of the elderly due to close contacts with their caretakers from other age groups.
+The relative impact of targeting the very young and the very old for vaccination was weakened by their relative inactivity, thus giving evidence of the lack of impact of vaccinating these two groups on the overall transmissibility of the disease in the community.
+INTRODUCTION: Extracorporeal Life Support (ECLS) and extracorporeal membrane oxygenation (ECMO) have been indicated as treatment for acute respiratory and/or cardiac failure.
+Here we describe our first year experience of in-hospital ECLS activity, the operative algorithm and the protocol for centralization of adult patients from district hospitals.
+METHODS: At a tertiary referral trauma center (Careggi Teaching Hospital, Florence, Italy), an ECLS program was developed from 2008 by the Emergency Department and Heart and Vessel Department ICUs.
+The ECLS team consists of an intensivist, a cardiac surgeon, a cardiologist and a perfusionist, all trained in ECLS technique.
+ECMO support was applied in case of severe acute respiratory distress syndrome (ARDS) not responsive to conventional treatments.
+The use of veno-arterial (V-A) ECLS for cardiac support was reserved for cases of cardiac shock refractory to standard treatment and cardiac arrests not responding to conventional resuscitation.
+RESULTS: A total of 21 patients were treated with ECLS during the first year of activity.
+In one case of post-traumatic ARDS, V-A ECLS support permitted multiple organ donation after cerebral death was confirmed.
+Patients treated with V-A ECLS due to cardiogenic shock (N = 4) had a survival rate of 50%.
+CONCLUSIONS: In our centre, an ECLS Service was instituted over a relatively limited period of time.
+A strict collaboration between different specialists can be regarded as a key feature to efficiently implement the process.
+It is widely feared that a novel, highly pathogenic, human transmissible influenza virus may evolve that could cause the next global pandemic.
+Mitigating the spread of such an influenza pandemic would require not only the timely administration of antiviral drugs to those infected, but also the implementation of suitable intervention policies for stunting the spread of the virus.
+Towards this end, mathematical modelling and simulation studies are crucial as they allow us to evaluate the predicted effectiveness of the various intervention policies before enforcing them.
+Diagnosis plays a vital role in the overall pandemic management framework by detecting and distinguishing the pathogenic strain from the less threatening seasonal strains and other influenza-like illnesses.
+This allows treatment and intervention to be deployed effectively, given limited antiviral supplies and other resources.
+However, the time required to design a fast and accurate testkit for novel strains may limit the role of diagnosis.
+Herein, we aim to investigate the cost and effectiveness of different diagnostic methods using a stochastic agent-based city-scale model, and then address the issue of whether conventional testing approaches, when used with appropriate intervention policies, can be as effective as fast testkits in containing a pandemic outbreak.
+We found that for mitigation purposes, fast and accurate testkits are not necessary as long as sufficient medication is given, and are generally recommended only when used with extensive contact tracing and prophylaxis.
+Additionally, in the event of insufficient medication and fast testkits, the use of slower, conventional testkits together with proper isolation policies while waiting for the diagnostic results can be an equally effective substitute.
+Rotavirus-induced immune responses, especially the T and B cell responses, have been extensively characterized; however, little is known about innate immune mechanisms involved in the control of rotavirus infection.
+Although increased levels of systemic type I interferon (IFNα and β) correlate with accelerated resolution of rotavirus disease, multiple rotavirus strains, including rhesus rotavirus (RRV), have been demonstrated to antagonize type I IFN production in a variety of epithelial and fibroblast cell types through several mechanisms, including degradation of multiple interferon regulatory factors by a viral nonstructural protein.
+This report demonstrates that stimulation of highly purified primary human peripheral plasmacytoid dendritic cells (pDCs) with either live or inactivated RRV induces substantial IFNα production by a subset of pDCs in which RRV does not replicate.
+Characterization of pDC responses to viral stimulus by flow cytometry and Luminex revealed that RRV replicates in a small subset of human primary pDCs and, in this RRV-permissive small subset, IFNα production is diminished.
+pDC activation and maturation were observed independently of viral replication and were enhanced in cells in which virus replicates.
+Production of IFNα by pDCs following RRV exposure required viral dsRNA and surface proteins, but neither viral replication nor activation by trypsin cleavage of VP4.
+These results demonstrate that a minor subset of purified primary human peripheral pDCs are permissive to RRV infection, and that pDCs retain functionality following RRV stimulus.
+Additionally, this study demonstrates trypsin-independent infection of primary peripheral cells by rotavirus, which may allow for the establishment of extraintestinal viremia and antigenemia.
+Importantly, these data provide the first evidence of IFNα induction in primary human pDCs by a dsRNA virus, while simultaneously demonstrating impaired IFNα production in primary human cells in which RRV replicates.
+Rotavirus infection of primary human pDCs provides a powerful experimental system for the study of mechanisms underlying pDC-mediated innate immunity to viral infection and reveals a potentially novel dsRNA-dependent pathway of IFNα induction.
+BACKGROUND: Over the past decade there has been increasing interest in the use of lactic acid bacteria as mucosal delivery vehicles for vaccine antigens, microbicides and therapeutics.
+We investigated the mechanism by which a mucosal vaccine based in recombinant lactic acid bacteria breaks the immunological tolerance of the gut in order to elicit a protective immune response.
+METHODOLOGY/PRINCIPAL FINDINGS: We analyzed how the lipid modification of OspA affects the localization of the antigen in our delivery vehicle using a number of biochemistry techniques.
+Furthermore, we examined how OspA-expressing L. plantarum breaks the oral tolerance of the gut by stimulating human intestinal epithelial cells, peripheral blood mononuclear cells and monocyte derived dendritic cells and measuring cytokine production.
+We show that the leader peptide of OspA targets the protein to the cell envelope of L. plantarum, and it is responsible for protein export across the membrane.
+Further, we show that lipidated-OspA-expressing L. plantarum does not induce secretion of the pro-inflammatory cytokine IL-8 by intestinal epithelial cells.
+In addition, it breaks oral tolerance of the gut via Th1/Th2 cell mediated immunity, as shown by the production of pro- and anti-inflammatory cytokines by human dendritic cells, and by the production of IgG2a and IgG1 antibodies, respectively.
+CONCLUSIONS/SIGNIFICANCE: Lipid modification of OspA expressed in L. plantarum modulates the immune response to this antigen through a Th1/Th2 immune response.
+BACKGROUND: Myeloperoxidase (MPO), an important element of the microbicidal activity of neutrophils, generates hypochlorous acid (HOCl) from H(2)O(2 )and chloride, which is released into body fluids.
+Besides its direct microbicidal activity, HOCl can react with amino acid residues and HOCl-modified proteins can be detected in vivo.
+FINDINGS: This report is based on binding studies of HOCl-modified serum albumins to HIV-1 gp120 and three different neutralization assays using infectious virus.
+The binding studies were carried out by surface plasmon resonance spectroscopy and by standard ELISA techniques.
+Virus neutralization assays were carried out using HIV-1 NL4-3 virus and recombinant strains with CXCR4 and CCR5 coreceptor usage.
+Our data demonstrate that HOCl-modified mouse-, bovine- and human serum albumins all bind to the HIV-1 NL4-3 gp120 (LAV) glycoprotein in contrast to non-modified albumin.
+Binding of HOCl-modified albumin to gp120 correlated to the blockade of CD4 as well as that of V3 loop specific monoclonal antibody binding.
+In neutralization experiments, HOCl-modified serum albumins inhibited replication and syncytium formation of the X4- and R5-tropic NL4-3 isolates in a dose dependent manner.
+CONCLUSIONS: Our data indicate that HOCl-modified serum albumin veils the binding site for CD4 and the V3 loop on gp120.
+Such masking of the viral gp120/gp41 envelope complex might be a simple but promising strategy to inactivate HIV-1 and therefore prevent infection when HOCl-modified serum albumin is applied, for example, as a topical microbicide.
+Previous studies suggest that human pregnancy specific beta-1-glycoproteins (PSGs) play immunomodulatory roles during pregnancy; however, other possible functions of PSGs have yet to be explored.
+We have observed that PSGs induce transforming growth factor beta 1 (TGFB1), which among its other diverse functions inhibits T-cell function and has proangiogenic properties.
+The present study investigates a potential role for PSG1, the most abundant PSG in maternal serum, as a possible inducer of proangiogenic growth factors known to play an important role in establishment of the vasculature at the maternal-fetal interface.
+To this end, we measured TGFB1, vascular endothelial growth factors (VEGFs) A and C, and placental growth factor (PGF) protein levels in several cell types after PSG1 treatment.
+In addition, tube formation and wound healing assays were performed to investigate a possible direct interaction between PSG1 and endothelial cells.
+PSG1 induced up-regulation of both TGFB1 and VEGFA in human monocytes, macrophages, and two human extravillous trophoblast cell lines.
+We did not observe induction of VEGFC or PGF by PSG1 in any of the cells tested.
+Site-directed mutagenesis was performed to map the essential regions within the N-domain of PSG1 required for functional activity.
+We found that the aspartic acid at position 95, previously believed to be required for binding of PSGs to cells, is not required for PSG1 activity but that the amino acids implicated in the formation of a salt bridge within the N-domain are essential for PSG1 function.
+Viral fusogenic envelope proteins are important targets for the development of inhibitors of viral entry.
+We report an approach for the computational design of peptide inhibitors of the dengue 2 virus (DENV-2) envelope (E) protein using high-resolution structural data from a pre-entry dimeric form of the protein.
+By using predictive strategies together with computational optimization of binding “pseudoenergies”, we were able to design multiple peptide sequences that showed low micromolar viral entry inhibitory activity.
+The two most active peptides, DN57opt and 1OAN1, were designed to displace regions in the domain II hinge, and the first domain I/domain II beta sheet connection, respectively, and show fifty percent inhibitory concentrations of 8 and 7 µM respectively in a focus forming unit assay.
+The antiviral peptides were shown to interfere with virus:cell binding, interact directly with the E proteins and also cause changes to the viral surface using biolayer interferometry and cryo-electron microscopy, respectively.
+These peptides may be useful for characterization of intermediate states in the membrane fusion process, investigation of DENV receptor molecules, and as lead compounds for drug discovery.
+BACKGROUND: The threat of recurring influenza pandemics caused by new viral strains and the occurrence of escape mutants necessitate the search for potent therapeutic targets.
+The dependence of viruses on cellular factors provides a weak-spot in the viral multiplication strategy and a means to interfere with viral multiplication.
+RESULTS: Using a motif-based search strategy for antiviral targets we identified caveolin-1 (Cav-1) as a putative cellular interaction partner of human influenza A viruses, including the pandemic influenza A virus (H1N1) strains of swine origin circulating from spring 2009 on.
+The influence of Cav-1 on human influenza A/PR/8/34 (H1N1) virus replication was determined in inhibition and competition experiments.
+RNAi-mediated Cav-1 knock-down as well as transfection of a dominant-negative Cav-1 mutant results in a decrease in virus titre in infected Madin-Darby canine kidney cells (MDCK), a cell line commonly used in basic influenza research as well as in virus vaccine production.
+To understand the molecular basis of the phenomenon we focussed on the putative caveolin-1 binding domain (CBD) located in the lumenal, juxtamembranal portion of the M2 matrix protein which has been identified in the motif-based search.
+The data suggest, that Cav-1 modulates influenza virus A replication presumably based on M2/Cav-1 interaction.
+CONCLUSION: As Cav-1 is involved in the human influenza A virus life cycle, the multifunctional protein and its interaction with M2 protein of human influenza A viruses represent a promising starting point for the search for antiviral agents.
+BACKGROUND: The Pr55(gag) (Gag) polyprotein of HIV serves as a scaffold for virion assembly and is thus essential for progeny virion budding and maturation.
+Gag localizes to the plasma membrane (PM) and membranes of late endosomes, allowing for release of infectious virus directly from the cell membrane and/or upon exocytosis.
+Upon activation, CD4+ T cells, the primary target of HIV infection, express the class II transcriptional activator (CIITA) and therefore the MHC class II isotype, HLA-DR.
+Similar to Gag, HLA-DR localizes to the PM and at the membranes of endosomes and specialized vesicular MHC class II compartments (MIICs).
+In HIV producer cells, transient HLA-DR expression induces intracellular Gag accumulation and impairs virus release.
+METHODOLOGY/PRINCIPAL FINDINGS: Here we demonstrate that both stable and transient expression of CIITA in HIV producer cells does not induce HLA-DR-associated intracellular retention of Gag, but does increase the infectivity of virions.
+However, neither of these phenomena is due to recapitulation of the class II antigen presentation pathway or CIITA-mediated transcriptional activation of virus genes.
+Interestingly, we demonstrate that CIITA, apart from its transcriptional effects, acts cytoplasmically to enhance Pr160(gag-pol) (Gag-Pol) levels and thereby the viral protease and Gag processing, accounting for the increased infectivity of virions from CIITA-expressing cells.
+CONCLUSIONS/SIGNIFICANCE: This study demonstrates that CIITA enhances HIV Gag processing, and provides the first evidence of a novel, post-transcriptional, cytoplasmic function for a well-known transactivator.
+Sedimentation velocity analytical ultracentrifugation has become a very popular technique to study size distributions and interactions of macromolecules.
+Recently, a method termed two-dimensional spectrum analysis (2DSA) for the determination of size-and-shape distributions was described by Demeler and colleagues (Eur Biophys J 2009).
+It is based on novel ideas conceived for fitting the integral equations of the size-and-shape distribution to experimental data, illustrated with an example but provided without proof of the principle of the algorithm.
+In the present work, we examine the 2DSA algorithm by comparison with the mathematical reference frame and simple well-known numerical concepts for solving Fredholm integral equations, and test the key assumptions underlying the 2DSA method in an example application.
+While the 2DSA appears computationally excessively wasteful, key elements also appear to be in conflict with mathematical results.
+A prevailing hypothesis is that the highly pathogenic virus isolates cause a severe cytokinemia precipitating acute respiratory distress syndrome and multiple organ dysfunction syndrome.
+Cynomolgus macaques (Macaca fascicularis) infected with a human highly pathogenic avian influenza (HPAI) H5N1 virus isolate (A/Vietnam/1203/2004) or reassortants of human influenza virus A/Texas/36/91 (H1N1) containing genes from the 1918 pandemic influenza A (H1N1) virus developed severe pneumonia within 24 h postinfection.
+However, virus spread beyond the lungs was only detected in the H5N1 group, and signs of extrapulmonary tissue reactions, including microglia activation and sustained up-regulation of inflammatory markers, most notably hypoxia inducible factor-1α (HIF-1α), were largely limited to this group.
+It is now accepted that an overwhelming inflammatory response is the cause of human deaths from avian H5N1 influenza infection.
+With this in mind we sought to examine the literature for examples of complementary and alternative medicines that reduce inflammation, and to place the results of this search in the context of our own work in a mouse model of influenza disease, using a pharmaceutical agent with anti-inflammatory properties.
+Two Chinese herbs, Angelica sinensis (Dang Gui) and Salvia miltiorrhiza (Danshen), have been recently shown to protect mice during lethal experimental sepsis via inhibition of the novel inflammatory cytokine High Mobility Group Box 1 protein (HMGB1).
+Biochanin A, a ligand of the peroxisome proliferator activated receptors (PPAR) alpha and gamma and the active isoflavone in Trifolium pratense (red clover), has anti-inflammatory properties, and thus could be used as an influenza treatment.
+This is of great interest since we have recently shown that gemfibrozil, a drug used to treat hyperlipidemia in humans and a synthetic ligand of PPAR alpha, significantly reduces the mortality associated with influenza infections in mice.
+The inflammation-modulating abilities of these natural agents should be considered in light of what is now known about the mechanisms of fatal influenza, and tested as potential candidates for influenza treatments in their own right, or as adjunct treatments to antivirals.
+BACKGROUND: In mid-June 2009 the State of Victoria in Australia appeared to have the highest notification rate of pandemic (H1N1) 2009 influenza in the world.
+We hypothesise that this was because community transmission of pandemic influenza was already well established in Victoria at the time testing for the novel virus commenced.
+In contrast, this was not true for the pandemic in other parts of Australia, including Western Australia (WA).
+METHODS: We used data from detailed case follow-up of patients with confirmed infection in Victoria and WA to demonstrate the difference in the pandemic curve in two Australian states on opposite sides of the continent.
+We modelled the pandemic in both states, using a susceptible-infected-removed model with Bayesian inference accounting for imported cases.
+Only 5% of the first 100 Victorian cases were not locally acquired and three of these were brothers in one family.
+By contrast, 53% of the first 102 cases in WA were associated with importation from Victoria.
+Using plausible model input data, estimation of the effective reproductive number for the Victorian epidemic required us to invoke an earlier date for commencement of transmission to explain the observed data.
+CONCLUSION: Strong circumstantial evidence, supported by modelling, suggests community transmission of pandemic influenza was well established in Victoria, but not in WA, at the time testing for the novel virus commenced in Australia.
+The virus is likely to have entered Victoria and already become established around the time it was first identified in the US and Mexico.
+OBJECTIVE: To describe detailed clinical and radiological features of the pandemic H1N1 2009 influenza viral infection among healthy young males in a semi-closed institutionalized setting.
+MATERIALS AND METHODS: A total of 18 patients confirmed with the pandemic H1N1 2009 influenza virus infection from July 18 to July 30, 2009 were enrolled in this study.
+RESULTS: All patients presented with high fever (> 38.0℃), with accompanying symptoms of cough, rhinorrhea, sore throat, myalgia and diarrhea, and increased C-reactive protein (CRP) values with no leukocytosis nor elevated erythrocyte sedimentation rate (ESR).
+All patients, including one patient who progressed into acute respiratory distress syndrome, were treated with oseltamivir phosphate and quickly recovered from their symptoms.
+Chest radiographs showed abnormalities of small nodules and lobar consolidation in only two out of 18 patients.
+However, six of 12 patients who underwent thin-section CT examinations showed abnormal findings for small ground-glass opacities (GGOs) in addition to poorly-defined nodules with upper lobe predominance.
+CONCLUSION: In a population of healthy young adults, elevated CRP with normal ESR and white blood cell levels combined with GGOs and nodules on thin-section CT scans may indicate early signs of infection by the pandemic H1N1 2009 influenza virus.
+Acid dependent infection of Hela and Vero cells by BTV-10 occurs from within early-endosomes following virus uptake by clathrin-mediated endocytosis (Forzan et al., 2007: J Virol 81: 4819–4827).
+Here we report that BTV-1 infection of BHK cells is also dependent on a low endosomal pH; however, virus entry and infection were not inhibited by dominant-negative mutants of Eps15, AP180 or the ‘aa’ splice variant of dynamin-2, which were shown to inhibit clathrin-mediated endocytosis.
+In addition, infection was not inhibited by depletion of cellular cholesterol, which suggests that virus entry is not mediated by a lipid-raft dependent process such as caveolae-mediated endocytosis.
+Although virus entry and infection were not inhibited by the dominant-negative dynamin-2 mutant, entry was inhibited by the general dynamin inhibitor, dynasore, indicating that virus entry is dynamin dependent.
+During entry, BTV-1 co-localised with LAMP-1 but not with transferrin, suggesting that virus is delivered to late-endosomal compartments without first passing through early-endosomes.
+BTV-1 entry and infection were inhibited by EIPA and cytochalasin-D, known macropinocytosis inhibitors, and during entry virus co-localised with dextran, a known marker for macropinocytosis/fluid-phase uptake.
+Our results extend earlier observations with BTV-10, and show that BTV-1 can infect BHK cells via an entry mechanism that is clathrin and cholesterol-independent, but requires dynamin, and shares certain characteristics in common with macropinocytosis.
+Reovirus infection leads to apoptosis in both cultured cells and the murine central nervous system (CNS).
+NF-κB-driven transcription of proapoptotic cellular genes is required for the effector phase of the apoptotic response.
+Although both extrinsic death-receptor signaling pathways and intrinsic pathways involving mitochondrial injury are implicated in reovirus-induced apoptosis, mechanisms by which either of these pathways are activated and their relationship to NF-κB signaling following reovirus infection are unknown.
+To understand how reovirus integrates host signaling circuits to induce apoptosis, we examined proapoptotic signaling following infection of Bid-deficient cells.
+Although reovirus growth was not affected by the absence of Bid, cells lacking Bid failed to undergo apoptosis.
+Furthermore, we found that NF-κB activation is required for Bid cleavage and subsequent proapoptotic signaling.
+To examine the functional significance of Bid-dependent apoptosis in reovirus disease, we monitored fatal encephalitis caused by reovirus in the presence and absence of Bid.
+Survival of Bid-deficient mice was significantly enhanced in comparison to wild-type mice following either peroral or intracranial inoculation of reovirus.
+These findings define a role for NF-κB-dependent cleavage of Bid in the cell death program initiated by viral infection and link Bid to viral virulence.
+BACKGROUND: Although pulsed electromagnetic fields (PEMFs) are used to treat delayed unions and nonunions, their mechanisms of action are not completely clear.
+QUESTIONS/PURPOSES: We asked (1) whether PEMFs affect gene expression in human osteoblastlike cells (MG63) in vitro, and (2) whether and to what extent stimulation by PEMFs induce cell proliferation and differentiation in MG-63 cultures.
+One group was treated with PEMFs for 18 hours whereas the second was maintained in the same culture condition without PEMFs (control).
+Gene expression was evaluated throughout cDNA microarray analysis containing 19,000 genes spanning a substantial fraction of the human genome.
+RESULTS: PEMFs induced the upregulation of important genes related to bone formation (HOXA10, AKT1), genes at the transductional level (CALM1, P2RX7), genes for cytoskeletal components (FN1, VCL), and collagenous (COL1A2) and noncollagenous (SPARC) matrix components.
+However, PEMF induced downregulation of genes related to the degradation of extracellular matrix (MMP-11, DUSP4).
+Our data suggest specific mechanisms of the observed clinical effect of PEMFs, and thus specific approaches for use in regenerative medicine.
+This article aims to open up the biographical black box of three experts working in the boundary zone between science, policy and public debate.
+A biographical-narrative approach is used to analyse the roles played by the virologists Albert Osterhaus, Roel Coutinho and Jaap Goudsmit in policy and public debate.
+These figures were among the few leading virologists visibly active in the Netherlands during the revival of infectious diseases in the 1980s.
+Osterhaus and Coutinho in particular are still the key figures today, as demonstrated during the outbreak of novel influenza A (H1N1).
+This article studies the various political and communicative challenges and dilemmas encountered by these three virologists, and discusses the way in which, strategically or not, they handled those challenges and dilemmas during the various stages of the field’s recent history.
+Important in this respect is their pursuit of a public role that is both effective and credible.
+We will conclude with a reflection on the H1N1 pandemic, and the historical and biographical ties between emerging governance arrangements and the experts involved in the development of such arrangements.
+Among 641 feces samples from children and adults the most commonly detected bocaviruses species were HBoV2>HBoV3>HBoV4>HBoV1 with HBoV2 prevalence of 21% and 26% in Nigerian and Tunisian children.
+HBoV3 and HBoV4 species combined were found in 12/192 cases of non-polio acute flaccid paralysis (AFP) from Tunisia and Nigeria and 0/96 healthy Tunisian contacts (p=0.01).
+Evidence of extensive recombination at the NP1 and VP1 gene boundary between and within species was found.
+The multiple species and high degree of genetic diversity seen among the human bocaviruses found in feces relative to the highly homogeneous HBoV1 suggest that this world-wide distributed respiratory pathogen may have recently evolved from an enteric bocavirus, perhaps after acquiring an expanded tropism favoring the respiratory track.
+Elucidating the possible role of the newly identified enteric bocaviruses in human diseases including AFP and diarrhea will require further epidemiological studies.
+In order to establish an infection, viruses need to either suppress or escape from host immune defense systems.
+Recent immunological research has focused on innate immunity as the first line of host defense, especially pattern recognition molecules such as Toll-like receptors (TLRs), RIG-I-like receptors (RLRs), and NOD-like receptors (NLRs).
+Various microbial components are recognized by their vague and common molecular shapes so-called, pathogen-associated molecular patterns (PAMPs).
+PAMPs induce inflammatory reactions mediated by the activation of the transcription factor, NF-κB, and by interferons, which lead to an antiviral immune response.
+Viruses have the capacity to suppress or escape from this pattern recognition molecule-mediated antimicrobial response in various ways.
+In this paper, we review the various strategies used by viruses to modulate the pattern recognition molecule-mediated innate immune response.
+BACKGROUND: Pneumonia is a leading infectious disease killer worldwide, yet the burden in China is not well understood as much of the data is published in the non-English literature.
+METHODOLOGY/PRINCIPAL FINDINGS: We systematically reviewed the Chinese- and English-language literature for studies with primary data on pneumonia incidence and mortality in mainland China.
+For children <5 years, incidence ranged from 0.06–0.27 episodes per person-year and mortality ranged from 184–1,223 deaths per 100,000 population.
+Overall incidence and mortality were stable or decreased over the study period and were higher in rural compared to urban areas.
+CONCLUSIONS/SIGNIFICANCE: Pneumonia continues to be a major public health challenge in young children in China, and estimates of pneumonia incidence and mortality vary widely.
+Reliable surveillance data and new prevention efforts may be needed to achieve and document additional declines, especially in areas with higher incidence and mortality such as rural settings.
+Genetic robustness affords maintenance of phenotype despite mutational input, necessarily involving the role of epistasis.
+Environmental robustness is phenotypic constancy in the face of environmental variation, where epistasis may be uninvolved.
+Here we discuss genetic and environmental robustness, from the standpoint of infectious disease evolution, and suggest that robustness may be a unifying principle for understanding how different disease agents evolve.
+We focus especially on viruses with RNA genomes due to their importance in the evolution of emerging diseases and as model systems to test robustness theory.
+We present new data on adaptive constraints for a model RNA virus challenged to evolve in response to UV radiation.
+We also draw attention to other infectious disease systems where robustness theory may prove useful for bridging evolutionary biology and biomedicine, especially the evolution of antibiotic resistance in bacteria, immune evasion by influenza, and malaria parasite infections.
+Cystic fibrosis (CF) lung disease is characterized by massive neutrophil granulocyte influx in the airways, their activation and eventually apoptosis.
+We investigated on the presence and phenotype of MPs in the sputum, a rich non-invasive source of inflammation biomarkers, of acute and stable CF adult patients.
+METHODS: Spontaneous sputum, obtained from 21 CF patients (10 acute and 11 stable) and 7 patients with primary ciliary dyskinesia (PCD), was liquefied with Sputasol.
+MPs were counted, visualized by electron microscopy, and identified in the supernatants of treated sputum by cytofluorimetry and immunolabelling for leukocyte (CD11a), granulocyte (CD66b), and monocyte-macrophage (CD11b) antigens.
+RESULTS: Electron microscopy revealed that sputum MPs were in the 100-500 nm range and did not contain bacteria, confirming microbiological tests.
+Levels of CD11a(+)-and CD66b(+)-, but not CD11b(+)-MPs were significantly higher in CF than in PCD, without differences between acute and stable patients.
+CONCLUSIONS: In summary, MPs are detectable in sputa obtained from CF patients and are predominantly of granulocyte origin.
+This novel isolation method for MPs from sputum opens a new opportunity for the study of lung pathology in CF.
+Adenoviral (Ad) vectors have been used for a variety of vaccine applications including cancer and infectious diseases.
+Traditionally, Ad-based vaccines are designed to express antigens through transgene expression of a given antigen.
+In order to circumvent the need for antigen expression via transgene incorporation, the “antigen capsid-incorporation” strategy has been developed and used for Ad-based vaccine development in the context of a few diseases.
+This strategy embodies the incorporation of antigenic peptides within the capsid structure of viral vectors.
+The major capsid protein hexon has been utilized for these capsid incorporation strategies due to hexon's natural role in the generation of anti-Ad immune response and its numerical representation within the Ad virion.
+Using this strategy, we have developed the means to incorporate heterologous peptide epitopes specifically within the major surface-exposed domains of the Ad capsid protein hexon.
+Our study herein focuses on generation of multivalent vaccine vectors presenting HIV antigens within the Ad capsid protein hexon, as well as expressing an HIV antigen as a transgene.
+These novel vectors utilize HVR2 as an incorporation site for a twenty-four amino acid region of the HIV membrane proximal ectodomain region (MPER), derived from HIV glycoprotein gp41 (gp41).
+Furthermore, vaccinations with these vectors, which present HIV antigens at HVR2, elicit a HIV epitope-specific humoral immune response.
+INTRODUCTION: The impact of model of end stage liver disease (MELD) score on postoperative morbidity and mortality is still elusive, especially for high MELD.
+There are reports of poorer patient outcome in transplant candidates with high MELD score, others though report no influence of MELD score on outcome and survival.
+METHODS: We retrospectively analyzed data of 144 consecutive liver transplant recipients over a 72-month period in our transplant unit, from January 2003 until December 2008 and performed uni- and multivariate analysis for morbidity and mortality, in particular to define the influence of MELD to these parameters.
+RESULTS: This study identified MELD score greater than 23 as an independent risk factor of morbidity represented by intensive care unit (ICU) stay longer than 10 days (odds ratio 7.0) but in contrast had no negative impact on mortality.
+Furthermore, we identified transfusion of more than 7 units of red blood cells as independent risk factor for mortality (hazard ratio 7.6) and for prolonged ICU stay (odds ratio [OR] 7.8) together with transfusion of more than 10 units of fresh frozen plasma (OR 11.6).
+Postoperative renal failure is a strong predictor of morbidity (OR 7.9) and postoperative renal replacement therapy was highly associated with increased mortality (hazard ratio 6.8), as was hepato renal syndrome prior to transplantation (hazard ratio 13.2).
+CONCLUSIONS: This study identified MELD score greater than 23 as an independent risk factor of morbidity represented by ICU stay longer than 10 days but in contrast had no negative impact on mortality.
+This finding supports the transplantation of patients with high MELD score but only with knowledge of increased morbidity.
+Traditionally viewed as important in the regulation of blood pressure, the renin-angiotensin system - and specifically the angiotensin-converting enzyme (ACE)-angiotensin (Ang) II-AT(1 )receptor axis - may play a prominent role to promote inflammation and fibrosis.
+ACE2, a new component of the renin-angiotensin system, has emerged as a key enzyme that selectively degrades Ang II and generates Ang-(1-7), a bioactive peptide with anti-inflammatory and anti-fibrotic actions.
+Takahashi and colleagues demonstrate circulating titers of inhibitory autoantibodies against ACE2 in patients with systemic sclerosis.
+The current study reveals a potentially novel mechanism to attenuate the catalytic activity of ACE2, thereby promoting the actions of Ang II.
+By performing two cross-sectional questionnaire surveys during winter 2009 and winter 2010 among European travellers to resource-limited destinations, we aimed to investigate knowledge, attitudes and practices (KAP) regarding seasonal influenza vaccination.
+METHODS: Questionnaires were distributed in the waiting room to the visitors of the University of Zurich Centre for Travel' Health (CTH) in January and February 2009 and January 2010 prior to travel health counselling (CTH09 and CTH10).
+Differences in proportions were compared using the Chi-square test and the significance level was set at p ≤ 0.05.
+RESULTS: With a response rate of 96.6%, 906 individuals were enrolled and 868 (92.5%) provided complete data.
+Only 43 (14.2%) participants were vaccinated against pandemic influenza A/H1N1, mostly having received both vaccines simultaneously, the seasonal and pandemic one.
+Job-related purposes (44, 37%), age > 64 yrs (25, 21%) and recommendations of the family physician (27, 22.7%) were the most often reported reasons for being vaccinated.
+In the multiple logistic regression analyses of the pooled data increasing age (OR = 1.03, 95% CI 1.01 - 1.04), a business trip (OR = 0.39, 95% CI 0.17 - 0.92) and seasonal influenza vaccination in the previous winter seasons (OR = 12.91, 95% CI 8.09 - 20.58) were independent predictors for seasonal influenza vaccination in 2009 or 2010.
+Influenza vaccination recommended by the family doctor (327, 37.7%), travel to regions with known high risk of influenza (305, 35.1%), and influenza vaccination required for job purposes (233, 26.8%) were most frequently mentioned to consider influenza vaccination.
+CONCLUSIONS: Risk perception and vaccination coverage concerning seasonal and pandemic influenza was very poor among travellers to resource-limited destinations when compared to traditional at-risk groups.
+BACKGROUND: Production of native antigens for serodiagnosis of helminthic infections is laborious and hampered by batch-to-batch variation.
+For serodiagnosis of echinococcosis, especially cystic disease, most screening tests rely on crude or purified Echinococcus granulosus hydatid cyst fluid.
+To resolve limitations associated with native antigens in serological tests, the use of standardized and highly pure antigens produced by chemical synthesis offers considerable advantages, provided appropriate diagnostic sensitivity and specificity is achieved.
+METHODOLOGY/PRINCIPAL FINDINGS: Making use of the growing collection of genomic and proteomic data, we applied a set of bioinformatic selection criteria to a collection of protein sequences including conceptually translated nucleotide sequence data of two related tapeworms, Echinococcus multilocularis and Echinococcus granulosus.
+Our approach targeted alpha-helical coiled-coils and intrinsically unstructured regions of parasite proteins potentially exposed to the host immune system.
+From 6 proteins of E. multilocularis and 5 proteins of E. granulosus, 45 peptides between 24 and 30 amino acids in length were designed.
+These peptides were chemically synthesized, spotted on microarrays and screened for reactivity with sera from infected humans.
+This candidate derived from Echinococcus multilocularis antigen B8/1 and showed strong reactivity to sera from patients infected either with E. multilocularis or E. granulosus.
+CONCLUSIONS/SIGNIFICANCE: This study provides proof of principle for the discovery of diagnostically relevant peptides by bioinformatic selection complemented with screening on a high-throughput microarray platform.
+Our data showed that a single peptide cannot provide sufficient diagnostic sensitivity whereas pooling several peptide antigens improved sensitivity; thus combinations of several peptides may lead the way to new diagnostic tests that replace, or at least complement conventional immunodiagnosis of echinococcosis.
+Emergence of a new influenza strain leads to a rapid global spread of the virus due to minimal antibody immunity.
+Pre-existing CD8(+) T-cell immunity directed towards conserved internal viral regions can greatly ameliorate the disease.
+However, mutational escape within the T cell epitopes is a substantial issue for virus control and vaccine design.
+Although mutations can result in a loss of T cell recognition, some variants generate cross-reactive T cell responses.
+In this study, we used reverse genetics to modify the influenza NP(336–374) peptide at a partially-solvent exposed residue (N->A, NPN3A mutation) to assess the availability, effectiveness and mechanism underlying influenza-specific cross-reactive T cell responses.
+The engineered virus induced a diminished CD8(+) T cell response and selected a narrowed T cell receptor (TCR) repertoire within two Vβ regions (Vβ8.3 and Vβ9).
+This can be partially explained by the H-2D(b)NPN3A structure that showed a loss of several contacts between the NPN3A peptide and H-2D(b), including a contact with His155, a position known to play an important role in mediating TCR-pMHC-I interactions.
+Despite these differences, common cross-reactive TCRs were detected in both the naïve and immune NPN3A-specific TCR repertoires.
+However, while the NPN3A epitope primes memory T-cells that give an equivalent recall response to the mutant or wild-type (wt) virus, both are markedly lower than wt->wt challenge.
+Such decreased CD8(+) responses elicited after heterologous challenge resulted in delayed viral clearance from the infected lung.
+Furthermore, mice first exposed to the wt virus give a poor, low avidity response following secondary infection with the mutant.
+Thus, the protective efficacy of cross-reactive CD8(+) T cells recognising mutant viral epitopes depend on peptide-MHC-I structural interactions and functional avidity.
+Our study does not support vaccine strategies that include immunization against commonly selected cross-reactive variants with mutations at partially-solvent exposed residues that have characteristics comparable to NPN3A.
+The objective of this study was to develop a symptom scoring system for use in clinical studies that differentiates children with cold symptoms who have an identifiable viral etiology for their upper respiratory tract infection (URI) from those in whom no virus is detected.
+Nasal swabs for PCR testing for identification of respiratory viruses were obtained on children aged 2–11 y at baseline and when parents thought their child was developing a cold.
+Parental-recorded severity of specific symptoms in children with and without a documented viral URI were compared.
+Nasal swabs were obtained on 108 children whose parents reported their child was developing a cold.
+Symptom measures that best differentiated children with a viral etiology from those without were significant runny nose and significant cough on days 1–4 of the illness.
+A URI symptom score was developed based on these symptoms, with a sensitivity of 81.4%, specificity of 61.9%, and accuracy of 73.3%.
+Our URI symptom score provided a more accurate method for identifying children with viral URIs for clinical studies.
+BACKGROUND: It is a commonly accepted belief that cancer cells modify their transcriptional state during the progression of the disease.
+We propose that the progression of cancer cells towards malignant phenotypes can be efficiently tracked using high-throughput technologies that follow the gradual changes observed in the gene expression profiles by employing Shannon's mathematical theory of communication.
+Methods based on Information Theory can then quantify the divergence of cancer cells' transcriptional profiles from those of normally appearing cells of the originating tissues.
+The relevance of the proposed methods can be evaluated using microarray datasets available in the public domain but the method is in principle applicable to other high-throughput methods.
+METHODOLOGY/PRINCIPAL FINDINGS: Using melanoma and prostate cancer datasets we illustrate how it is possible to employ Shannon Entropy and the Jensen-Shannon divergence to trace the transcriptional changes progression of the disease.
+We establish how the variations of these two measures correlate with established biomarkers of cancer progression.
+The Information Theory measures allow us to identify novel biomarkers for both progressive and relatively more sudden transcriptional changes leading to malignant phenotypes.
+At the same time, the methodology was able to validate a large number of genes and processes that seem to be implicated in the progression of melanoma and prostate cancer.
+CONCLUSIONS/SIGNIFICANCE: We thus present a quantitative guiding rule, a new unifying hallmark of cancer: the cancer cell's transcriptome changes lead to measurable observed transitions of Normalized Shannon Entropy values (as measured by high-througput technologies).
+At the same time, tumor cells increment their divergence from the normal tissue profile increasing their disorder via creation of states that we might not directly measure.
+This unifying hallmark allows, via the the Jensen-Shannon divergence, to identify the arrow of time of the processes from the gene expression profiles, and helps to map the phenotypical and molecular hallmarks of specific cancer subtypes.
+The deep mathematical basis of the approach allows us to suggest that this principle is, hopefully, of general applicability for other diseases.
+Human societies are organized in complex webs that are constantly reshaped by a social dynamic which is influenced by the information individuals have about others.
+Similarly, epidemic spreading may be affected by local information that makes individuals aware of the health status of their social contacts, allowing them to avoid contact with those infected and to remain in touch with the healthy.
+Here we study disease dynamics in finite populations in which infection occurs along the links of a dynamical contact network whose reshaping may be biased based on each individual's health status.
+We adopt some of the most widely used epidemiological models, investigating the impact of the reshaping of the contact network on the disease dynamics.
+We derive analytical results in the limit where network reshaping occurs much faster than disease spreading and demonstrate numerically that this limit extends to a much wider range of time scales than one might anticipate.
+Specifically, we show that from a population-level description, disease propagation in a quickly adapting network can be formulated equivalently as disease spreading on a well-mixed population but with a rescaled infectiousness.
+We find that for all models studied here – SI, SIS and SIR – the effective infectiousness of a disease depends on the population size, the number of infected in the population, and the capacity of healthy individuals to sever contacts with the infected.
+Importantly, we indicate how the use of available information hinders disease progression, either by reducing the average time required to eradicate a disease (in case recovery is possible), or by increasing the average time needed for a disease to spread to the entire population (in case recovery or immunity is impossible).
+Ca(2+) plays a pivotal role in the physiology and biochemistry of prokaryotic and mammalian organisms.
+Viruses also utilize the universal Ca(2+) signal to create a specific cellular environment to achieve coexistence with the host, and to propagate.
+When methods such as the grafting approach are developed in conjunction with prediction algorithms we are better able to probe continuous Ca(2+)-binding sites that have been previously underrepresented due to the limitation of conventional methodology.
+BACKGROUND: Based on clinical representation of disease symptoms multiple sclerosis (MScl) patients can be divided into two major subtypes; relapsing remitting (RR) MScl (85–90%) and primary progressive (PP) MScl (10–15%).
+Proteomics analysis of cerebrospinal fluid (CSF) has detected a number of proteins that were elevated in MScl patients.
+Here we specifically aimed to differentiate between the PP and RR subtypes of MScl by comparing CSF proteins.
+METHODOLOGY/PRINCIPAL FINDINGS: CSF samples (n = 31) were handled according to the same protocol for quantitative mass spectrometry measurements we reported previously.
+In the comparison of PP MScl versus RR MScl we observed a number of differentially abundant proteins, such as protein jagged-1 and vitamin D-binding protein.
+Protein jagged-1 was over three times less abundant in PP MScl compared to RR MScl.
+These two proteins were validated by independent techniques (western blot and ELISA) as differentially abundant in the comparison between both MScl types.
+CONCLUSIONS/SIGNIFICANCE: The main finding of this comparative study is the observation that the proteome profiles of CSF in PP and RR MScl patients overlap to a large extent.
+Protein jagged-1 is a ligand for multiple Notch receptors and involved in the mediation of Notch signaling.
+It is suggested in literature that the Notch pathway is involved in the remyelination of MScl lesions.
+Aberration of normal homeostasis of Vitamin D, of which approximately 90% is bound to vitamin D-binding protein, has been widely implicated in MScl for some years now.
+Vitamin D directly and indirectly regulates the differentiation, activation of CD4+ T-lymphocytes and can prevent the development of autoimmune processes, and so it may be involved in neuroprotective elements in MScl.
+Interstitial lung disease (ILD) in infants and children comprises a large spectrum of rare respiratory disorders that are mostly chronic and associated with high morbidity and mortality.
+Typical features of ILD include dyspnea, diffuse infiltrates on chest radiographs, and abnormal pulmonary function tests with restrictive ventilatory defect and/or impaired gas exchange.
+Many pathological situations can impair gas exchange and, therefore, may contribute to progressive lung damage and ILD.
+Consequently, diagnosis approach needs to be structured with a clinical evaluation requiring a careful history paying attention to exposures and systemic diseases.
+Several classifications for ILD have been proposed but none is entirely satisfactory especially in children.
+The present article reviews current concepts of pathophysiological mechanisms, etiology and diagnostic approaches, as well as therapeutic strategies.
+The following diagnostic grouping is used to discuss the various causes of pediatric ILD: 1) exposure-related ILD; 2) systemic disease-associated ILD; 3) alveolar structure disorder-associated ILD; and 4) ILD specific to infancy.
+An overall favorable response to corticosteroid therapy is observed in around 50% of cases, often associated with sequelae such as limited exercise tolerance or the need for long-term oxygen therapy.
+BACKGROUND: Controlling the pandemic spread of newly emerging diseases requires rapid, targeted allocation of limited resources among nations.
+Critical, early control steps would be greatly enhanced if the key risk factors can be identified that accurately predict early disease spread immediately after emergence.
+METHODOLOGY/PRINCIPAL FINDINGS: Here, we examine the role of travel, trade, and national healthcare resources in predicting the emergence and initial spread of 2009 A/H1N1 influenza.
+We find that incorporating national healthcare resource data into our analyses allowed a much greater capacity to predict the international spread of this virus.
+In countries with lower healthcare resources, the reporting of 2009 A/H1N1 cases was significantly delayed, likely reflecting a lower capacity for testing and reporting, as well as other socio-political issues.
+We also report substantial international trade in live swine and poultry in the decade preceding the pandemic which may have contributed to the emergence and mixed genotype of this pandemic strain.
+However, the lack of knowledge of recent evolution of each H1N1 viral gene segment precludes the use of this approach to determine viral origins.
+CONCLUSIONS/SIGNIFICANCE: We conclude that strategies to prevent pandemic influenza virus emergence and spread in the future should include: 1) enhanced surveillance for strains resulting from reassortment in traded livestock; 2) rapid deployment of control measures in the initial spreading phase to countries where travel data predict the pathogen will reach and to countries where lower healthcare resources will likely cause delays in reporting.
+Our results highlight the benefits, for all parties, when higher income countries provide additional healthcare resources for lower income countries, particularly those that have high air traffic volumes.
+In particular, international authorities should prioritize aid to those poorest countries where both the risk of emerging infectious diseases and air traffic volume is highest.
+This strategy will result in earlier detection of pathogens and a reduction in the impact of future pandemics.
+BACKGROUND: Standard epidemiological theory claims that in structured populations competition between multiple pathogen strains is a deterministic process which is mediated by the basic reproduction number ([Image: see text]) of the individual strains.
+A new theory based on analysis, simulation and empirical study challenges this predictor of success.
+PRINCIPAL FINDINGS: We show that the quantity [Image: see text] is a valid predictor in structured populations only when size is infinite.
+In this article we show that when population size is finite the dynamics of infection by multi-strain pathogens is a stochastic process whose outcome can be predicted by evolutionary entropy, S, an information theoretic measure which describes the uncertainty in the infectious age of an infected parent of a randomly chosen new infective.
+This statistical parameter determines the duration of infection and thus provides a quantitative index of the pathogenicity of a strain.
+Standard epidemiological theory based on [Image: see text] as a measure of selective advantage is the limit as the population size tends to infinity of the entropic selection theory.
+The standard model is an approximation to the entropic selection theory whose validity increases with population size.
+CONCLUSION: An epidemiological analysis based on entropy is shown to explain empirical observations regarding the emergence of less pathogenic strains of human influenza during the antigenic drift phase.
+Furthermore, we exploit the entropy perspective to discuss certain epidemiological patterns of the current H1N1 swine 'flu outbreak.
+The proteomes that make up the collection of proteins in contemporary organisms evolved through recombination and duplication of a limited set of domains.
+These protein domains are essentially the main components of globular proteins and are the most principal level at which protein function and protein interactions can be understood.
+An important aspect of domain evolution is their atomic structure and biochemical function, which are both specified by the information in the amino acid sequence.
+With the present and still increasing wealth of sequences and annotation data brought about by genomics, new evolutionary relationships are constantly being revealed, unknown structures modeled and phylogenies inferred.
+Such investigations not only help predict the function of newly discovered proteins, but also assist in mapping unforeseen pathways of evolution and reveal crucial, co-evolving inter- and intra-molecular interactions.
+In turn this will help us describe how protein domains shaped cellular interaction networks and the dynamics with which they are regulated in the cell.
+Additionally, these studies can be used for the design of new and optimized protein domains for therapy.
+In this review, we aim to describe the basic concepts of protein domain evolution and illustrate recent developments in molecular evolution that have provided valuable new insights in the field of comparative genomics and protein interaction networks.
+BACKGROUND: The proteasome inhibitor bortezomib represents an important advance in the treatment of multiple myeloma (MM).
+Bortezomib inhibits the activity of the 26S proteasome and induces cell death in a variety of tumor cells; however, the mechanism of cytotoxicity is not well understood.
+METHODOLOGY/PRINCIPAL FINDINGS: We investigated the differential phosphoproteome upon proteasome inhibition by using stable isotope labeling by amino acids in cell culture (SILAC) in combination with phosphoprotein enrichment and LC-MS/MS analysis.
+In total 233 phosphoproteins were identified and 72 phosphoproteins showed a 1.5-fold or greater change upon bortezomib treatment.
+The phosphoproteins with expression alterations encompass all major protein classes, including a large number of nucleic acid binding proteins.
+Site-specific phosphopeptide quantitation revealed that Ser38 phosphorylation on stathmin increased upon bortezomib treatment, suggesting new mechanisms associated to bortezomib-induced apoptosis in MM cells.
+Further studies demonstrated that stathmin phosphorylation profile was modified in response to bortezomib treatment and the regulation of stathmin by phosphorylation at specific Ser/Thr residues participated in the cellular response induced by bortezomib.
+CONCLUSIONS/SIGNIFICANCE: Our systematic profiling of phosphorylation changes in response to bortezomib treatment not only advanced the global mechanistic understanding of the action of bortezomib on myeloma cells but also identified previously uncharacterized signaling proteins in myeloma cells.
+Many zoonotic, novel infectious diseases in humans appear as sporadic infections with spatially and temporally restricted outbreaks, as seen with influenza A(H5N1).
+Here we use simple mathematical models to describe different adaptation scenarios with particular reference to spatial heterogeneity within the human population.
+We present analytical expressions for the probability of emergence per introduction, as well as the waiting time to a successful emergence event.
+Furthermore, we derive general analytical results for the statistical properties of emergence events, including the probability distribution of outbreak sizes.
+We compare our analytical results with a stochastic model, which has previously been studied computationally.
+Our results suggest that, for typical connection strengths between communities, spatial heterogeneity has only a weak effect on outbreak size distributions, and on the risk of emergence per introduction.
+For example, if [Image: see text] or larger, any village connected to a large city by just ten commuters a day is, effectively, just a part of the city when considering the chances of emergence and the outbreak size distribution.
+We present empirical data on commuting patterns and show that the vast majority of communities for which such data are available are at least this well interconnected.
+For plausible parameter ranges, the effects of spatial heterogeneity are likely to be dominated by the evolutionary biology of host adaptation.
+BACKGROUND: An unusually high number of severe pneumonia cases with considerable mortality is being observed with the pandemic H1N1 2009 virus infections globally.
+In India, all mild as well as critically ill cases were admitted and treated in the government hospitals during the initial phase of the pandemic.
+METHODOLOGY: The role of viral load and host factors in the pathogenesis were assessed by examining 26 mild (MP), 15 critically ill patients (CIP) and 20 healthy controls from Pune, India.
+Viral load and cytokines/chemokine levels were determined from the plasma and lung aspirates of the patients.
+Gene profiling was done for both cells in the lung aspirates and PBMCs using TaqMan Low Density arrays.
+Sequential lung samples from CIP showed lower viral loads questioning association of viral replication with the severity.
+Anti-rpH1N1-09-HA-IgG titres were significantly higher in critically ill patients and both categories circulated exclusively IgG1 isotype.
+The disease severity correlated with increased plasma levels of IL1RA, IL2, IL6, CCL3, CCL4 and IL10.
+Majority of the immune-function genes were down-regulated in the PBMCs and up-regulated in the cells from lung aspirates of critically ill patients.
+No distinct pattern differentiating fatal and surviving patients was observed when sequential samples were examined for various parameters.
+BACKGROUND: Passive transfer of antibodies not only provides immediate short-term protection against disease, but also can be exploited as a therapeutic tool.
+However, the ‘humanization’ of murine monoclonal antibodies (mAbs) is a time-consuming and expensive process that has the inherent drawback of potentially altering antigenic specificity and/or affinity.
+The immortalization of human B cells represents an alternative for obtaining human mAbs, but relies on the availability of biological samples from vaccinated individuals or convalescent patients.
+In this work we describe a novel approach to generate fully human mAbs by combining a humanized mouse model with a new B cell immortalization technique.
+METHODOLOGY/PRINCIPAL FINDINGS: After transplantation with CD34(+)CD38(−) human hematopoietic progenitor cells, BALB/c Rag2(−/−)IL-2Rγc(−/−) mice acquire a human immune system and harbor B cells with a diverse IgM repertoire.
+“Human Immune System” mice were then immunized with two commercial vaccine antigens, tetanus toxoid and hepatitis B surface antigen.
+Sorted human CD19(+)CD27(+) B cells were retrovirally transduced with the human B cell lymphoma (BCL)-6 and BCL-XL genes, and subsequently cultured in the presence of CD40-ligand and IL-21.
+We recovered stable B cell clones that produced IgM specific for tetanus toxoid and the hepatitis B surface antigen, respectively.
+CONCLUSION/SIGNIFICANCE: This work provides the proof-of-concept for the usefulness of this novel method based on the immunization of humanized mice for the rapid generation of human mAbs against a wide range of antigens.
+The close phylogenetic relationship between humans and non-human primates makes non-human primates an irreplaceable model for the study of human infectious diseases.
+In this study, we describe the development of a large-scale automatic multi-functional isolation chamber for use with medium-sized laboratory animals carrying infectious diseases.
+The isolation chamber, including the transfer chain, disinfection chain, negative air pressure isolation system, animal welfare system, and the automated system, is designed to meet all biological safety standards.
+To create an internal chamber environment that is completely isolated from the exterior, variable frequency drive blowers are used in the air-intake and air-exhaust system, precisely controlling the filtered air flow and providing an air-barrier protection.
+A double door transfer port is used to transfer material between the interior of the isolation chamber and the outside.
+A peracetic acid sterilizer and its associated pipeline allow for complete disinfection of the isolation chamber.
+All of the isolation chamber parameters can be automatically controlled by a programmable computerized menu, allowing for work with different animals in different-sized cages depending on the research project.
+The large-scale multi-functional isolation chamber provides a useful and safe system for working with infectious medium-sized laboratory animals in high-level bio-safety laboratories.
+Proteomics is the large-scale study of the structure and function of proteins in complex biological sample.
+Such an approach has the potential value to understand the complex nature of the organism.
+Current proteomic tools allow large-scale, high-throughput analyses for the detection, identification, and functional investigation of proteome.
+Advances in protein fractionation and labeling techniques have improved protein identification to include the least abundant proteins.
+In addition, proteomics has been complemented by the analysis of posttranslational modifications and techniques for the quantitative comparison of different proteomes.
+However, the major limitation of proteomic investigations remains the complexity of biological structures and physiological processes, rendering the path of exploration paved with various difficulties and pitfalls.
+The quantity of data that is acquired with new techniques places new challenges on data processing and analysis.
+This article provides a brief overview of currently available proteomic techniques and their applications, followed by detailed description of advantages and technical challenges.
+Autopsy studies have shown that human highly pathogenic avian influenza virus (H5N1) can infect multiple human organs other than just the lungs, and that possible causes of organ damage are either viral replication and/or dysregulation of cytokines and chemokines.
+In this study, a full autopsy including 5 organ systems was conducted on a confirmed H5N1 human fatal case (male, 42 years old) within 18 hours of death.
+In addition to the respiratory system (lungs, bronchus and trachea), virus was isolated from cerebral cortex, cerebral medullary substance, cerebellum, brain stem, hippocampus ileum, colon, rectum, ureter, aortopulmonary vessel and lymph-node.
+Real time RT-PCR evidence showed that matrix and hemagglutinin genes were positive in liver and spleen in addition to positive tissues with virus isolation.
+Immunohistochemistry and in-situ hybridization stains showed accordant evidence of viral infection with real time RT-PCR except bronchus.
+Quantitative RT-PCR suggested that a high viral load was associated with increased host responses, though the viral load was significantly different in various organs.
+Overall, the pathogenesis of HPAI H5N1 virus was associated both with virus replication and with immunopathologic lesions.
+In addition, immune cells cannot be excluded from playing a role in dissemination of the virus in vivo.
+BACKGROUND: Whether information sources influence health protective behaviours during influenza pandemics or other emerging infectious disease epidemics is uncertain.
+METHODOLOGY: Data from cross-sectional telephone interviews of 1,001 Hong Kong adults in June, 2009 were tested against theory and data-derived hypothesized associations between trust in (formal/informal) information, understanding, self-efficacy, perceived susceptibility and worry, and hand hygiene and social distancing using Structural Equation Modelling with multigroup comparisons.
+PRINCIPAL FINDINGS: Trust in formal (government/media) information about influenza was associated with greater reported understanding of A/H1N1 cause (β = 0.36) and A/H1N1 prevention self-efficacy (β = 0.25), which in turn were associated with more hand hygiene (β = 0.19 and β = 0.23, respectively).
+Trust in informal (interpersonal) information was negatively associated with perceived personal A/H1N1 susceptibility (β = −0.21), which was negatively associated with perceived self-efficacy (β = −0.42) but positively associated with influenza worry (β = 0.44).
+Trust in informal information was positively associated with influenza worry (β = 0.16) which was in turn associated with greater social distancing (β = 0.36).
+Multigroup comparisons showed gender differences regarding paths from trust in formal information to understanding of A/H1N1 cause, trust in informal information to understanding of A/H1N1 cause, and understanding of A/H1N1 cause to perceived self-efficacy.
+CONCLUSIONS/SIGNIFICANCE: Trust in government/media information was more strongly associated with greater self-efficacy and handwashing, whereas trust in informal information was strongly associated with perceived health threat and avoidance behaviour.
+Yersinia pestis is the etiologic agent of plague that has killed more than 200 million people throughout the recorded history of mankind.
+Antibiotics may provide little immediate relief to patients who have a high bacteremia or to patients infected with an antibiotic resistant strain of plague.
+Two virulent factors of Y. pestis are the capsid F1 protein and the low-calcium response (Lcr) V-protein or V-antigen that have been proven to be the targets for both active and passive immunization.
+There are mouse monoclonal antibodies (mAbs) against the F1- and V-antigens that can passively protect mice in a murine model of plague; however, there are no anti-Yersinia pestis monoclonal antibodies available for prophylactic or therapeutic treatment in humans.
+We identified one anti-F1-specific human mAb (m252) and two anti-V-specific human mAb (m253, m254) by panning a naïve phage-displayed Fab library against the F1- and V-antigens.
+M252 bound weakly to peptides located at the F1 N-terminus where a protective mouse anti-F1 mAb also binds.
+M253 bound strongly to a V-antigen peptide indicating a linear epitope; m254 did not bind to any peptide from a panel of 53 peptides suggesting that its epitope may be conformational.
+M252 showed better protection than m253 and m254 against a Y, pestis challenge in a plague mouse model.
+These antibodies can be further studied to determine their potential as therapeutics or prophylactics in Y. pestis infection in humans.
+Triggering receptor expressed on myeloid cells (TREM)-1 is a neutrophil and monocyte receptor up-regulated during infection.
+The aim of this study was to evaluate the diagnostic accuracy of TREM-1 and of C-reactive protein (CRP) from patients with lung infiltrates to discern community acquired lung infections.
+METHODS: 68 patients admitted to a medical ward with acute respiratory illness were enrolled in the study.
+Neutrophil and monocyte TREM-1 expression were measured by flow cytometry, sTREM-1 by an enzyme immunoassay and C-reactive protein by nephelometry.
+RESULTS: 34 patients were diagnosed with bacterial community acquired pneumonia (group A) and 34 with non-bacterial pulmonary disease (group B).
+A cut-off of 19.53 pg/ml of sTREM-1 with sensitivity 82.6% and specificity 63% to discriminate between infectious and non-infectious pulmonary infiltrates was found.
+CONCLUSION: TREM-1 myeloid expression and sTREM-1 are reliable markers of bacterial infection among patients with pulmonary infiltrates; sTREM-1 is a predictor of final outcome.
+The ongoing emergence of human infections originating from wildlife highlights the need for better knowledge of the microbial community in wildlife species where traditional diagnostic approaches are limited.
+Here we evaluate the microbial biota in healthy mule deer (Odocoileus hemionus) by analyses of lymph node meta-transcriptomes.
+cDNA libraries from five individuals and two pools of samples were prepared from retropharyngeal lymph node RNA enriched for polyadenylated RNA and sequenced using Roche-454 Life Sciences technology.
+Protein-coding and 16S ribosomal RNA (rRNA) sequences were taxonomically profiled using protein and rRNA specific databases.
+Representatives of all bacterial phyla were detected in the seven libraries based on protein-coding transcripts indicating that viable microbiota were present in lymph nodes.
+Residents of skin and rumen, and those ubiquitous in mule deer habitat dominated classifiable bacterial species.
+Based on detection of both rRNA and protein-coding transcripts, we identified two new proteobacterial species; a Helicobacter closely related to Helicobacter cetorum in the Helicobacter pylori/Helicobacter acinonychis complex and an Acinetobacter related to Acinetobacter schindleri.
+Among viruses, a novel gamma retrovirus and other members of the Poxviridae and Retroviridae were identified.
+We additionally evaluated bacterial diversity by amplicon sequencing the hypervariable V6 region of 16S rRNA and demonstrate that overall taxonomic diversity is higher with the meta-transcriptomic approach.
+These data provide the most complete picture to date of the microbial diversity within a wildlife host.
+Our research advances the use of meta-transcriptomics to study microbiota in wildlife tissues, which will facilitate detection of novel organisms with pathogenic potential to human and animals.
+Flaviviruses bud into the endoplasmic reticulum and are transported through the secretory pathway, where the mildly acidic environment triggers particle rearrangement and allows furin processing of the prM protein to pr and M. The peripheral pr peptide remains bound to virus at low pH and inhibits virus-membrane interaction.
+Upon exocytosis, the release of pr at neutral pH completes virus maturation to an infectious particle.
+Together this evidence suggests that pr may shield the flavivirus fusion protein E from the low pH environment of the exocytic pathway.
+Here we developed an in vitro system to reconstitute the interaction of dengue virus (DENV) pr with soluble truncated E proteins.
+At low pH recombinant pr bound to both monomeric and dimeric forms of E and blocked their membrane insertion.
+Alanine substitution of E H244, a highly conserved histidine residue in the pr-E interface, blocked pr-E interaction and reduced release of DENV virus-like particles.
+Folding, membrane insertion and trimerization of the H244A mutant E protein were preserved, and particle release could be partially rescued by neutralization of the low pH of the secretory pathway.
+Thus, pr acts to silence flavivirus fusion activity during virus secretion, and this function can be separated from the chaperone activity of prM.
+The sequence conservation of key residues involved in the flavivirus pr-E interaction suggests that this protein-protein interface may be a useful target for broad-spectrum inhibitors.
+CD200, a type I membrane glycoprotein, plays an important role in prevention of inflammatory disorders, graft rejection, autoimmune diseases and spontaneous fetal loss.
+A truncated CD200 (CD200(tr)) resulting from alternative splicing has been identified and characterized as a functional antagonist to full-length CD200.
+In this study, we identified an exonic splicing enhancer (ESE) located in exon 2, which is a putative binding site for a splicing regulatory protein SF2/ASF.
+Direct binding of SF2/ASF to the ESE site was confirmed by RNA electrophoretic mobility shift assay (EMSA).
+Knockdown of expression of SF2/ASF resulted in the same splicing pattern as seen after deletion or mutation of the ESE, whereas overexpression of SF2/ASF increased expression of the full-length CD200.
+In vivo studies showed that viral infection reversed the alternative splicing pattern of CD200 with increased expression of SF2/ASF and the full-length CD200.
+Taken together, our data suggest for the first time that SF2/ASF regulates the function of CD200 by controlling CD200 alternative splicing, through direct binding to an ESE located in exon 2 of CD200.
+BACKGROUND: Neuraminidase inhibitors are thought to be efficacious in reducing the time to alleviation of symptoms in outpatients with seasonal influenza.
+The objective of this study was to compare the short-term virological efficacy of oseltamivir-zanamivir combination versus each monotherapy plus placebo.
+METHODS AND FINDINGS: We conducted a randomized placebo-controlled trial with 145 general practitioners throughout France during the 2008–2009 seasonal influenza epidemic.
+Adult outpatients presenting influenza-like illness for less than 36 hours and a positive influenza A rapid test diagnosis were randomized to oseltamivir 75 mg orally twice daily plus zanamivir 10 mg by inhalation twice daily (OZ), oseltamivir plus inhaled placebo (O), or zanamivir plus oral placebo (Z).
+Treatment efficacy was assessed virologically according to the proportion of patients with nasal influenza reverse transcription (RT)-PCR below 200 copies genome equivalent (cgeq)/µl at day 2 (primary outcome), and clinically to the time to alleviation of symptoms until day 14.
+Overall 541 patients (of the 900 planned) were included (OZ, n = 192; O, n = 176; Z, n = 173), 49% male, mean age 39 years.
+In the intention-to-treat analysis conducted in the 447 patients with RT-PCR-confirmed influenza A, 46%, 59%, and 34% in OZ (n = 157), O (n = 141), and Z (n = 149) arms had RT-PCR<200 cgeq/µl (−13.0%, 95% confidence interval [CI] −23.1 to −2.9, p = 0.025; +12.3%, 95% CI 2.39–22.2, p = 0.028 for OZ/O and OZ/Z comparisons).
+Mean day 0 to day 2 viral load decrease was 2.14, 2.49, and 1.68 log(10) cgeq/µl (p = 0.060, p = 0.016 for OZ/O and OZ/Z).
+Median time to alleviation of symptoms was 4.0, 3.0, and 4.0 days (+1.0, 95% CI 0.0–4.0, p = 0.018; +0.0, 95% CI −3.0 to 3.0, p = 0.960 for OZ/O and OZ/Z).
+Nausea and/or vomiting tended to be more frequent in the combination arm (OZ, n = 13; O, n = 4; and Z, n = 5 patients, respectively).
+CONCLUSIONS: In adults with seasonal influenza A mainly H3N2 virus infection, the oseltamivir-zanamivir combination appeared less effective than oseltamivir monotherapy, and not significantly more effective than zanamivir monotherapy.
+Despite the theoretical potential for the reduction of the emergence of antiviral resistance, the lower effectiveness of this combination calls for caution in its use in clinical practice.
+The initial clinical presentation can mimic other pediatric inflammatory conditions, which often leads to significant delays in diagnosis and appropriate therapy.
+EXPERIMENTAL DESIGN: We profiled the urine peptidome to analyze a set of 102 urine samples, from patients with SJIA, Kawasaki disease (KD), febrile illnesses (FI), and healthy controls.
+A set of 91 plasma samples, from SJIA flare and quiescent patients, were profiled using a customized antibody array against 43 proteins known to be involved in inflammatory and protein catabolic processes.
+RESULTS: We identified a 17-urine-peptide biomarker panel that could effectively discriminate SJIA patients at active, quiescent, and remission disease states, and patients with active SJIA from confounding conditions including KD and FI.
+Targeted sequencing of these peptides revealed that they fall into several tight clusters from seven different proteins, suggesting disease-specific proteolytic activities.
+The antibody array plasma profiling identified an SJIA plasma flare signature consisting of tissue inhibitor of metalloproteinase-1 (TIMP1), interleukin (IL)-18, regulated upon activation, normal T cell expressed and secreted (RANTES), P-Selectin, MMP9, and L-Selectin.
+CONCLUSIONS AND CLINICAL RELEVANCE: The urine peptidomic and plasma protein analyses have the potential to improve SJIA care and suggest that SJIA urine peptide biomarkers may be an outcome of inflammation-driven effects on catabolic pathways operating at multiple sites.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s12014-010-9058-8) contains supplementary material, which is available to authorized users.
+Replication of plus-strand RNA viruses depends on host factors that are recruited into viral replicase complexes.
+Previous studies showed that eukaryotic translation elongation factor (eEF1A) is one of the resident host proteins in the highly purified tombusvirus replicase complex.
+Using a random library of eEF1A mutants, we identified one mutant that decreased and three mutants that increased Tomato bushy stunt virus (TBSV) replication in a yeast model host.
+Additional in vitro assays with whole cell extracts prepared from yeast strains expressing the eEF1A mutants demonstrated several functions for eEF1A in TBSV replication: facilitating the recruitment of the viral RNA template into the replicase complex; the assembly of the viral replicase complex; and enhancement of the minus-strand synthesis by promoting the initiation step.
+These roles for eEF1A are separate from its canonical role in host and viral protein translation, emphasizing critical functions for this abundant cellular protein during TBSV replication.
+Here we propose a method to calculate the minimal amount of genomic information needed to construct organism (effective information) as a measure of organismal complexity, by using permutation and combination formulas and Shannon's information concept.
+RESULTS: The results demonstrate that the calculated information correlates quite well with the intuitive organismal phenotypic complexity defined by traditional taxonomy and evolutionary theory.
+From viruses to human beings, the effective information gradually increases, from thousands of bits to hundreds of millions of bits.
+The simpler the organism is, the less the information; the more complex the organism, the more the information.
+CONCLUSIONS: The effective information can be used as a quantitative measure of phenotypic complexity of living organisms and also as an estimate of functional fraction of genome.
+REVIEWERS: This article was reviewed by Dr. Lavanya Kannan (nominated by Dr. Arcady Mushegian), Dr. Chao Chen, and Dr. ED Rietman (nominated by Dr. Marc Vidal).
+To assess whether certain environmental factors temporally associated with the onset of juvenile idiopathic inflammatory myopathies (JIIMs) differ between phenotypes.
+Physicians completed questionnaires regarding documented infections, medications, immunizations and an open-ended question about other noted exposures within 6 months before illness onset for 285 patients with probable or definite JIIM.
+Sixty per cent of JIIM patients had a reported exposure within 6 months before illness onset.
+Most patients (62%) had one recorded exposure, 26% had two and 12% had three to five exposures.
+Patients older than the median age at diagnosis, those with a longer delay to diagnosis and those with anti-signal recognition particle autoantibodies had a higher frequency of documented exposures [odds ratios (ORs) 95% CI 3.4, 31].
+Infections were the most common exposure and represented 44% of the total number of reported exposures.
+Non-infectious exposures included medications (18%), immunizations (11%), stressful life events (11%) and unusual sun exposure (7%).
+Exposures varied by age at diagnosis, race, disease course and the presence of certain myositis autoantibodies.
+The JIIMs may be related to multiple exposures and these appear to vary among phenotypes.
+Although vaccines pose the best means of preventing influenza infection, strain selection and optimal implementation remain difficult due to antigenic drift and a lack of understanding global spread.
+Detecting viral movement by sequence analysis is complicated by skewed geographic and seasonal distributions in viral isolates.
+We propose a probabilistic method that accounts for sampling bias through spatiotemporal clustering and modeling regional and seasonal transmission as a binomial process.
+Analysis of H3N2 not only confirmed East-Southeast Asia as a source of new seasonal variants, but also increased the resolution of observed transmission to a country level.
+Network analysis suggested China and Hong Kong as the origins of new seasonal H3N2 strains and the United States as a region where increased vaccination would maximally disrupt global spread of the virus.
+These techniques provide a promising methodology for the analysis of any seasonal virus, as well as for the continued surveillance of influenza.
+BACKGROUND: The 2009 pandemic of influenza A (H1N1) infection has alerted many governments to make preparedness plan to control the spread of influenza A (H1N1) infection.
+Vaccination for influenza is one of the most important primary preventative measures to reduce the disease burden.
+Our study aims to assess the willingness of nurses who work for the community nursing service (CNS) in Hong Kong on their acceptance of influenza A (H1N1) influenza vaccination.
+METHODS: 401 questionnaires were posted from June 24, 2009 to June 30, 2009 to community nurses with 67% response rate.
+Results of the 267 respondents on their willingness to accept influenza A (H1N1) vaccine were analyzed.
+RESULTS: Twenty-seven percent of respondents were willing to accept influenza vaccination if vaccines were available.
+Having been vaccinated for seasonable influenza in the previous 12 months were significantly independently associated with their willingness to accept influenza A (H1N1) vaccination (OR = 4.03; 95% CI: 2.03-7.98).
+CONCLUSIONS: Similar to previous findings conducted in hospital healthcare workers and nurses, we confirmed that the willingness of community nurses to accept influenza A (H1N1) vaccination is low.
+Future studies that evaluate interventions to address nurses' specific concerns or interventions that aim to raise the awareness among nurses on the importance of influenza A (H1N1) vaccination to protect vulnerable patient populations is needed.
+BACKGROUND: Management of emerging infectious diseases such as the 2009 influenza pandemic A (H1N1) poses great challenges for real-time mathematical modeling of disease transmission due to limited information on disease natural history and epidemiology, stochastic variation in the course of epidemics, and changing case definitions and surveillance practices.
+FINDINGS: The Richards model and its variants are used to fit the cumulative epidemic curve for laboratory-confirmed pandemic H1N1 (pH1N1) infections in Canada, made available by the Public Health Agency of Canada (PHAC).
+The model is used to obtain estimates for turning points in the initial outbreak, the basic reproductive number (R(0)), and for expected final outbreak size in the absence of interventions.
+Confirmed case data were used to construct a best-fit 2-phase model with three turning points.
+R(0 )was estimated to be 1.30 (95% CI 1.12-1.47) for the first phase (April 1 to May 4) and 1.35 (95% CI 1.16-1.54) for the second phase (May 4 to June 19).
+Hospitalization data were also used to fit a 1-phase model with R(0 )= 1.35 (1.20-1.49) and a single turning point of June 11.
+CONCLUSIONS: Application of the Richards model to Canadian pH1N1 data shows that detection of turning points is affected by the quality of data available at the time of data usage.
+Using a Richards model, robust estimates of R(0 )were obtained approximately one month after the initial outbreak in the case of 2009 A (H1N1) in Canada.
+BACKGROUND: Japanese encephalitis (JE), caused by a mosquito-borne flavivirus, is endemic to the entire south-east Asian and adjoining regions.
+Currently no therapeutic interventions are available for JE, thereby making it one of the most dreaded encephalitides in the world.
+An effective way to counter the virus would be to inhibit viral replication by using anti-sense molecules directed against the viral genome.
+Octaguanidinium dendrimer-conjugated Morpholino (or Vivo-Morpholino) are uncharged anti-sense oligomers that can enter cells of living organisms by endocytosis and subsequently escape from endosomes into the cytosol/nuclear compartment of cells.
+We hypothesize that Vivo-Morpholinos generated against specific regions of 3′ or 5′ untranslated regions of JEV genome, when administered in an experimental model of JE, will have significant antiviral and neuroprotective effect.
+METHODOLOGY/PRINCIPAL FINDINGS: Mice were infected with JEV (GP78 strain) followed by intraperitoneal administration of Morpholinos (5 mg/kg body weight) daily for up to five treatments.
+Survivability of the animals was monitored for 15 days (or until death) following which they were sacrificed and their brains were processed either for immunohistochemical staining or protein extraction.
+Plaque assay and immunoblot analysis performed from brain homogenates showed reduced viral load and viral protein expression, resulting in greater survival of infected animals.
+Cytokine bead array showed reduction in the levels of proinflammatory cytokines in brain following Morpholino treatment, which were elevated after infection.
+Oxidative stress was reduced and certain stress-related signaling molecules were found to be positively modulated following Morpholino treatment.
+In vitro studies also showed that there was decrease in infective viral particle production following Morpholino treatment.
+CONCLUSIONS/SIGNIFICANCE: Administration of Vivo-Morpholino effectively resulted in increased survival of animals and neuroprotection in a murine model of JE.
+Background: The natural history and consequences of severe H1N1 influenza infection among cancer patients are not yet fully characterized.
+We describe eight cases of H1N1 infection in cancer patients admitted to the intensive care unit of a referral cancer center.
+Patients and methods: Clinical data from all patients admitted with acute respiratory failure due to novel viral H1N1 infection were reviewed.
+Lung tissue was submitted for viral and bacteriological analyses by real-time RT-PCR, and autopsy was conducted on all patients who died.
+There were five patients with solid organ tumors (62.5%) and three with hematological malignancies (37.5%).
+Lung tissue analysis was performed in all patients and showed diffuse alveolar damage in most patients.
+Conclusions: H1N1 viral infection in patients with cancer can cause severe illness, resulting in acute respiratory distress syndrome and death.
+Background and objective: The ‘attack rate’ of asthma following viral lower respiratory tract infections (LRTI) is about 3–4 fold higher than that of the general population; however, the majority of children who develop viral LRTI during infancy do not develop asthma, and asthma incidence has been observed to continuously decrease with age.
+Thus, we do not understand how viral LRTI either predispose or serve as a marker of children to develop asthma.
+The Tennessee Children's Respiratory Initiative has been established as a longitudinal prospective investigation of infants and their biological mothers.
+The primary goals are to investigate both the acute and the long‐term health consequences of varying severity and aetiology of clinically significant viral respiratory tract infections on early childhood outcomes.
+Methods: Over four respiratory viral seasons, 2004–2008, term, non‐low birth weight previously healthy infants and their biological mothers were enrolled during an infant's acute viral respiratory illness.
+Results: This report describes the study objectives, design and recruitment results of the over 650 families enrolled in this longitudinal investigation.
+The Tennessee Children's Respiratory Initiative is additionally unique because it is designed in parallel with a large retrospective birth cohort of over 95 000 mother–infant dyads with similar objectives to investigate the role of respiratory viral infection severity and aetiology in the development of asthma.
+Conclusions: Future reports from this cohort will help to clarify the complex relationship between infant respiratory viral infection severity, aetiology, atopic predisposition and the subsequent development of early childhood asthma and atopic diseases.
+Simian retrovirus type-1 uses programmed ribosomal frameshifting to control expression of the Gag-Pol polyprotein from overlapping gag and pol open-reading frames.
+The frameshifting signal consists of a heptanucleotide slippery sequence and a downstream-located 12-base pair pseudoknot.
+The solution structure of this pseudoknot, previously solved by NMR [Michiels,P.J., Versleijen,A.A., Verlaan,P.W., Pleij,C.W., Hilbers,C.W.
+Biol., 310, 1109–1123] has a classical H-type fold and forms an extended triple helix by interactions between loop 2 and the minor groove of stem 1 involving base–base and base–sugar contacts.
+A mutational analysis was performed to test the functional importance of the triple helix for −1 frameshifting in vitro.
+Changing bases in L2 or base pairs in S1 involved in a base triple resulted in a 2- to 5-fold decrease in frameshifting efficiency.
+The in vitro effects were well reproduced in vivo, although the effect of enlarging L2 was more dramatic in vivo.
+Although the ribosome is mainly comprised of rRNA and many of its critical functions occur through RNA–RNA interactions, distinct domains of ribosomal proteins also participate in switching the ribosome between different conformational/functional states.
+Prior studies demonstrated that two extended domains of ribosomal protein L3 form an allosteric switch between the pre- and post-translocational states.
+Missing was an explanation for how the movements of these domains are communicated among the ribosome's functional centers.
+Here, a third domain of L3 called the basic thumb, that protrudes roughly perpendicular from the W-finger and is nestled in the center of a cagelike structure formed by elements from three separate domains of the large subunit rRNA is investigated.
+Mutagenesis of basically charged amino acids of the basic thumb to alanines followed by detailed analyses suggests that it acts as a molecular clamp, playing a role in allosterically communicating the ribosome's tRNA occupancy status to the elongation factor binding region and the peptidyltransferase center, facilitating coordination of their functions through the elongation cycle.
+The observation that these mutations affected translational fidelity, virus propagation and cell growth demonstrates how small structural changes at the atomic scale can propagate outward to broadly impact the biology of cell.
+One of the main problems in nucleic acid-based techniques for detection of infectious agents, such as influenza viruses, is that of nucleic acid sequence variation.
+DNA probes, 70-nt long, some including the nucleotide analog deoxyribose-Inosine (dInosine), were analyzed for hybridization tolerance to different amounts and distributions of mismatching bases, e.g.
+Microsphere-linked 70-mer probes were hybridized in 3M TMAC buffer to biotinylated single-stranded (ss) DNA for subsequent analysis in a Luminex® system.
+When mismatches interrupted contiguous matching stretches of 6 nt or longer, it had a strong impact on hybridization.
+Contiguous matching stretches are more important than the same number of matching nucleotides separated by mismatches into several regions.
+dInosine, but not 5-nitroindole, substitutions at mismatching positions stabilized hybridization remarkably well, comparable to N (4-fold) wobbles in the same positions.
+In contrast to shorter probes, 70-nt probes with judiciously placed dInosine substitutions and/or wobble positions were remarkably mismatch tolerant, with preserved specificity.
+An algorithm, NucZip, was constructed to model the nucleation and zipping phases of hybridization, integrating both local and distant binding contributions.
+It predicted hybridization more exactly than previous algorithms, and has the potential to guide the design of variation-tolerant yet specific probes.
+We study the effect of migration between coupled populations, or patches, on the stability properties of multistrain disease dynamics.
+The epidemic model used in this work displays a Hopf bifurcation to oscillations in a single, well-mixed population.
+It is shown numerically that migration between two non-identical patches stabilizes the endemic steady state, delaying the onset of large amplitude outbreaks and reducing the total number of infections.
+This result is motivated by analyzing generic Hopf bifurcations with different frequencies and with diffusive coupling between them.
+Stabilization of the steady state is again seen, indicating that our observation in the full multistrain model is based on qualitative characteristics of the dynamics rather than on details of the disease model.
+OBJECTIVE: The World Health organization received reports of 478 laboratory-confirmed cases of influenza A (H5N1) from 15 countries between November 2003 and February 2010.
+Determining an association between the clinical factors at the time of hospital admission and prognosis may be useful for timely and adequate consultation and treatment.
+It has been difficult to obtain these clinical factors adjusted with other confounding factors, such as age and sex, as published studies of H5N1 virus infection usually reported only a few cases.
+METHODS: Five case reports (36 patients <18 years of age) of H5N1 infection from four countries published between 2004 and 2009 were assessed based on available individual clinical data.
+Using the pooled data for all patients, we investigated the associations between patients’ prognosis and available laboratory findings, such as white blood cell (WBC) counts, platelet (PLT) counts, and serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) by adjusting for age and/or sex.
+RESULTS: The linear regression analysis revealed that mortality was negatively associated with WBC and PLT counts adjusted with age and sex.
+Increased log AST tended to be associated with a poor prognosis (p = 0.054), but there was no significant association between survival and log ALT level.
+CONCLUSIONS: Both decreased WBC and PLT counts can be considered to be common predictors of poor prognosis in H5N1 influenza patients <18 years of age.
+Programmed ribosomal frameshifting is a translational recoding mechanism commonly used by RNA viruses to express two or more proteins from a single mRNA at a fixed ratio.
+An essential element in this process is the presence of an RNA secondary structure, such as a pseudoknot or a hairpin, located downstream of the slippery sequence.
+Here, we have tested the efficiency of RNA oligonucleotides annealing downstream of the slippery sequence to induce frameshifting in vitro.
+Antisense oligonucleotides bearing locked nucleid acid (LNA) modifications also proved to be efficient frameshift-stimulators in contrast to DNA oligonucleotides.
+The number, sequence and location of LNA bases in an otherwise DNA oligonucleotide have to be carefully manipulated to obtain optimal levels of frameshifting.
+Our data favor a model in which RNA stability at the entrance of the ribosomal tunnel is the major determinant of stimulating slippage rather than a specific three-dimensional structure of the stimulating RNA element.
+High-resolution structures reveal that yeast ribosomal protein L11 and its bacterial/archael homologs called L5 contain a highly conserved, basically charged internal loop that interacts with the peptidyl-transfer RNA (tRNA) T-loop.
+Chemical protection of wild-type ribosome shows that that the P-site loop is inherently flexible, i.e.
+it is extended into the ribosomal P-site when this is unoccupied by tRNA, while it is retracted into the terminal loop of 25S rRNA Helix 84 when the P-site is occupied.
+To further analyze the function of this structure, a series of mutants within the P-site loop were created and analyzed.
+A mutant that favors interaction of the P-site loop with the terminal loop of Helix 84 promoted increased affinity for peptidyl-tRNA, while another that favors its extension into the ribosomal P-site had the opposite effect.
+The two mutants also had opposing effects on binding of aa-tRNA to the ribosomal A-site, and downstream functional effects were observed on translational fidelity, drug resistance/hypersensitivity, virus maintenance and overall cell growth.
+These analyses suggest that the L11 P-site loop normally helps to optimize ribosome function by monitoring the occupancy status of the ribosomal P-site.
+To date, at least 900 different microRNA (miRNA) genes have been discovered in the human genome.
+These short, single-stranded RNA molecules originate from larger precursor molecules that fold to produce hairpin structures, which are subsequently processed by ribonucleases Drosha/Pasha and Dicer to form mature miRNAs.
+MiRNAs play role in the posttranscriptional regulation of about one third of human genes, mainly via degradation of target mRNAs.
+Whereas the target mRNAs are often involved in the regulation of diverse physiological processes ranging from developmental timing to apoptosis, miRNAs have a strong potential to regulate fundamental biological processes also in the lung compartment.
+However, the knowledge of the role of miRNAs in physiological and pathological conditions in the lung is still limited.
+This review, therefore, summarizes current knowledge of the mechanism, function of miRNAs and their contribution to lung development and homeostasis.
+Besides the involvement of miRNAs in pulmonary physiological conditions, there is evidence that abnormal miRNA expression may lead to pathological processes and development of various pulmonary diseases.
+Next, the review describes current state-of-art on the miRNA expression profiles in smoking-related diseases including lung cancerogenesis, in immune system mediated pulmonary diseases and fibrotic processes in the lung.
+From the current research it is evident that miRNAs may play role in the posttranscriptional regulation of key genes in human pulmonary diseases.
+Further studies are, therefore, necessary to explore miRNA expression profiles and their association with target mRNAs in human pulmonary diseases.
+BACKGROUND: Key to the control of pandemic influenza are surveillance systems that raise alarms rapidly and sensitively.
+We develop a method that uses historical syndromic influenza data from the existing surveillance system 'SERVIS' (Scottish Enhanced Respiratory Virus Infection Surveillance) for influenza-like illness (ILI) in Scotland.
+METHODS: We develop an algorithm based on the weekly case ratio (WCR) of reported ILI cases to generate an alarm for pandemic influenza.
+From the seasonal influenza data from 13 Scottish health boards, we estimate the joint probability distribution of the country-level WCR and the number of health boards showing synchronous increases in reported influenza cases over the previous week.
+Pandemic cases are sampled with various case reporting rates from simulated pandemic influenza infections and overlaid with seasonal SERVIS data from 2001 to 2007.
+Using this combined time series we test our method for speed of detection, sensitivity and specificity.
+Also, the 2008-09 SERVIS ILI cases are used for testing detection performances of the three methods with a real pandemic data.
+RESULTS: We compare our method, based on our simulation study, to the moving-average Cumulative Sums (Mov-Avg Cusum) and ILI rate threshold methods and find it to be more sensitive and rapid.
+For 1% case reporting and detection specificity of 95%, our method is 100% sensitive and has median detection time (MDT) of 4 weeks while the Mov-Avg Cusum and ILI rate threshold methods are, respectively, 97% and 100% sensitive with MDT of 5 weeks.
+Although the threshold method maintains its sensitivity of 100% with MDT of 5 weeks, sensitivity of Mov-Avg Cusum declines to 92% with increased MDT of 6 weeks.
+For a two-fold decrease in the case reporting rate (0.5%) and 99% specificity, the WCR and threshold methods, respectively, have MDT of 5 and 6 weeks with both having sensitivity close to 100% while the Mov-Avg Cusum method can only manage sensitivity of 77% with MDT of 6 weeks.
+However, the WCR and Mov-Avg Cusum methods outperform the ILI threshold method by 1 week in retrospective detection of the 2009 pandemic in Scotland.
+CONCLUSIONS: While computationally and statistically simple to implement, the WCR algorithm is capable of raising alarms, rapidly and sensitively, for influenza pandemics against a background of seasonal influenza.
+Although the algorithm was developed using the SERVIS data, it has the capacity to be used at other geographic scales and for different disease systems where buying some early extra time is critical.
+Leptospirosis is a widespread zoonotic infection that primarily affects residents of tropical regions, but causes infections in animals and humans in temperate regions as well.
+The agents of leptospirosis comprise several members of the genus Leptospira, which also includes non-pathogenic, saprophytic species.
+Leptospirosis can vary in severity from a mild, non-specific illness to severe disease that includes multi-organ failure and widespread endothelial damage and hemorrhage.
+To begin to investigate how pathogenic leptospires affect endothelial cells, we compared the responses of two endothelial cell lines to infection by pathogenic versus non-pathogenic leptospires.
+Microarray analyses suggested that pathogenic L. interrogans and non-pathogenic L. biflexa triggered changes in expression of genes whose products are involved in cellular architecture and interactions with the matrix, but that the changes were in opposite directions, with infection by L. biflexa primarily predicted to increase or maintain cell layer integrity, while L. interrogans lead primarily to changes predicted to disrupt cell layer integrity.
+The pathogenic L. interrogans, however, did result in significant disruption of endothelial cell layers as assessed by microscopy and the ability of the bacteria to cross the cell layers.
+This disruption of endothelial layer integrity was abrogated by addition of the endothelial protective drug lisinopril at physiologically relevant concentrations.
+These results suggest that, through adhesion of L. interrogans to endothelial cells, the bacteria may disrupt endothelial barrier function, promoting dissemination of the bacteria and contributing to severe disease manifestations.
+In addition, supplementing antibiotic therapy with lisinopril or derivatives with endothelial protective activities may decrease the severity of leptospirosis.
+Human adenovirus 5 (AdHu5) vectors are robust vaccine platforms however the presence of naturally-acquired neutralizing antibodies may reduce vector efficacy and potential for re-administration.
+This study evaluates immune responses and protection following vaccination with a replication-incompetent porcine adenovirus 3 (PAV3) vector as an alternative vaccine to AdHu5 using an avian influenza H5N1 disease model.
+Vaccine efficacy was evaluated in BALB/c mice following vaccination with different doses of the PAV3 vector expressing an optimized A/Hanoi/30408/2005 H5N1 hemagglutinin antigen (PAV3-HA) and compared with an AdHu5-HA control.
+PAV3-HA rapidly generated antibody responses, with significant neutralizing antibody titers on day 21, and stronger cellular immune responses detected on day 8, compared to AdHu5-HA.
+The PAV3-HA vaccine, administered 8 days before challenge, demonstrated improved survival and lower virus load.
+Evaluation of long-term vaccine efficacy at 12 months post-vaccination showed better protection with the PAV3-HA than with the AdHu5-HA vaccine.
+Importantly, as opposed to AdHu5, PAV3 vector was not significantly neutralized by human antibodies pooled from over 10,000 individuals.
+Overall, PAV3-based vector is capable of mediating swift, strong immune responses and offer a promising alternative to AdHu5.
+We have previously demonstrated that antigens chemically coupled to the surface of liposomes consisting of unsaturated fatty acids were cross-presented by antigen-presenting cells (APCs) to CD8(+) T cells, and that this process resulted in the induction of antigen-specific cytotoxic T lymphocytes.
+In the present study, the mechanism by which the liposome-coupled antigens were cross-presented to CD8(+) T cells by APCs was investigated.
+Confocal laser scanning microscopic analysis demonstrated that antigens coupled to the surface of unsaturated-fatty-acid-based liposomes received processing at both MHC class I and class II compartments, while most of the antigens coupled to the surface of saturated-fatty-acid-based liposomes received processing at the class II compartment.
+In addition, flow cytometric analysis demonstrated that antigens coupled to the surface of unsaturated-fatty-acid-liposomes were taken up by APCs even in a 4°C environment; this was not true of saturated-fatty-acid-liposomes.
+When two kinds of inhibitors, dimethylamiloride (DMA) and cytochalasin B, which inhibit pinocytosis and phagocytosis by APCs, respectively, were added to the culture of APCs prior to the antigen pulse, DMA but not cytochalasin B significantly reduced uptake of liposome-coupled antigens.
+Further analysis of intracellular trafficking of liposomal antigens using confocal laser scanning microscopy revealed that a portion of liposome-coupled antigens taken up by APCs were delivered to the lysosome compartment.
+In agreement with the reduction of antigen uptake by APCs, antigen presentation by APCs was significantly inhibited by DMA, and resulted in the reduction of IFN-γ production by antigen-specific CD8(+) T cells.
+These results suggest that antigens coupled to the surface of liposomes consisting of unsaturated fatty acids might be pinocytosed by APCs, loaded onto the class I MHC processing pathway, and presented to CD8(+) T cells.
+Thus, these liposome-coupled antigens are expected to be applicable for the development of vaccines that induce cellular immunity.
+Recommended treatment of chronic hepatitis B with interferon-α and/or nucleos(t)ide analogues does not lead to a satisfactory result.
+Induction of HBV-specific T cells by therapeutic vaccination or immunotherapies may be an innovative strategy to overcome virus persistence.
+Vaccination with commercially available HBV vaccines in patients did not result in effective control of HBV infection, suggesting that new formulations of therapeutic vaccines are needed.
+The woodchuck (Marmota monax) is a useful preclinical model for developing the new therapeutic approaches in chronic hepadnaviral infections.
+Several innovative approaches combining antiviral treatments with nucleos(t)ide analogues, DNA vaccines, and protein vaccines were tested in the woodchuck model.
+In this paper we summarize the available data concerning therapeutic immunization and gene therapy using recombinant viral vectors approaches in woodchucks, which show encouraging results.
+In addition, we present potential innovations in immunomodulatory strategies to be evaluated in this animal model.
+The purpose of this study was to use an immmunosense approach to develop a foundation for development of vaccines to protect humans with the HLA-A03 supertype.
+Three peptides had been identified with high binding scores for HLA-A03 supertypes using bioinformatic algorhythms, high measured binding affinity for HLA-A03 supertype molecules, and ability to elicit IFN-γ production by human HLA-A03 supertype peripheral blood CD8(+ )T cells from seropositive but not seronegative persons.
+RESULTS: Herein, when these peptides were administered with the universal CD4(+)T cell epitope PADRE (AKFVAAWTLKAAA) and formulated as lipopeptides, or administered with GLA-SE either alone, or with Pam(2)Cys added, we found we successfully created preparations that induced IFN-γ and reduced parasite burden in HLA-A*1101(an HLA-A03 supertype allele) transgenic mice.
+GLA-SE is a novel emulsified synthetic TLR4 ligand that is known to facilitate development of T Helper 1 cell (TH1) responses.
+Then, so our peptides would include those expressed in tachyzoites, bradyzoites and sporozoites from both Type I and II parasites, we used our approaches which had identified the initial peptides.
+We identified additional peptides using bioinformatics, binding affinity assays, and study of responses of HLA-A03 human cells.
+Lastly, we found that immunization of HLA-A*1101 transgenic mice with all the pooled peptides administered with PADRE, GLA-SE, and Pam(2)Cys is an effective way to elicit IFN-γ producing CD8(+ )splenic T cells and protection.
+Immunizations included the following peptides together: KSFKDILPK (SAG1(224-232)); AMLTAFFLR (GRA6(164-172)); RSFKDLLKK (GRA7(134-142)); STFWPCLLR (SAG2C(13-21)); SSAYVFSVK((SPA250-258)); and AVVSLLRLLK(SPA(89-98)).
+This immunization elicited robust protection, measured as reduced parasite burden using a luciferase transfected parasite, luciferin, this novel, HLA transgenic mouse model, and imaging with a Xenogen camera.
+CONCLUSIONS: Toxoplasma gondii peptides elicit HLA-A03 restricted, IFN-γ producing, CD8(+ )T cells in humans and mice.
+It also defines novel adjuvants for newly identified peptides for vaccines to prevent toxoplasmosis in those with HLA-A03 supertype alleles.
+Influenza A viruses belong to the best studied viruses, however no effective prevention against influenza infection has been developed.
+The emerging of still new escape variants of influenza A viruses causing epidemics and periodic worldwide pandemics represents a threat for human population.
+Therefore, current, hot task of influenza virus research is to look for a way how to get us closer to a universal vaccine.
+Combination of chosen conserved antigens inducing cross-protective antibody response with epitopes activating also cross-protective cytotoxic T-cells would offer an attractive strategy for improving protection against drift variants of seasonal influenza viruses and reduces the impact of future pandemic strains.
+Antigenically conserved fusion-active subunit of hemagglutinin (HA2 gp) and ectodomain of matrix protein 2 (eM2) are promising candidates for preparation of broadly protective HA2- or eM2-based vaccine that may aid in pandemic preparedness.
+Overall protective effect could be achieved by contribution of epitopes recognized by cytotoxic T-lymphocytes (CTL) that have been studied extensively to reach much broader control of influenza infection.
+We describe known adaptive immune mechanisms mediated by influenza specific B- and T-cells involved in the anti-influenza immune defense together with the contribution of innate immunity.
+We discuss the mechanisms of neutralization of influenza infection mediated by antibodies, the role of CTL in viral elimination and new approaches to develop epitope based vaccine inducing cross-protective influenza virus-specific immune response.
+S-palmitoylation describes the reversible attachment of fatty acids (predominantly palmitate) onto cysteine residues via a labile thioester bond.
+This posttranslational modification impacts protein functionality by regulating membrane interactions, intracellular sorting, stability, and membrane micropatterning.
+Several recent findings have provided a tantalizing insight into the regulation and spatiotemporal dynamics of protein palmitoylation.
+In mammalian cells, the Golgi has emerged as a possible super-reaction center for the palmitoylation of peripheral membrane proteins, whereas palmitoylation reactions on post-Golgi compartments contribute to the regulation of specific substrates.
+In addition to palmitoylating and depalmitoylating enzymes, intracellular palmitoylation dynamics may also be controlled through interplay with distinct posttranslational modifications, such as phosphorylation and nitrosylation.
+Children and young adults of reproductive age have emerged as groups that are highly vulnerable to the current 2009 H1N1 pandemic.
+The sex of an individual is a fundamental factor that can influence exposure, susceptibility and immune responses to influenza.
+Worldwide, the incidence, disease burden, morbidity and mortality rates following exposure to the 2009 H1N1 influenza virus differ between males and females and are often age-dependent.
+Pregnancy and differences in the presentation of various risk factors contribute to the worse outcome of infection in women.
+Finally, sex-specific genetic and hormonal differences may contribute to the severity of influenza and the clearance of viral infection.
+The contribution of sex and gender to influenza can only be determined by a greater consideration of these factors in clinical and epidemiological studies and increased research into the biological basis underlying these differences.
+Fast viral adaptation and the implication of this rapid evolution in the emergence of several new infectious diseases have turned this issue into a major challenge for various research domains.
+Indeed, viruses are involved in the development of a wide range of pathologies and understanding how viruses and host cells interact in the context of adaptation remains an open question.
+In order to provide insights into the complex interactions between viruses and their host organisms and namely in the acquisition of novel functions through exchanges of genetic material, we developed the PhEVER database.
+This database aims at providing accurate evolutionary and phylogenetic information to analyse the nature of virus–virus and virus–host lateral gene transfers.
+PhEVER (http://pbil.univ-lyon1.fr/databases/phever) is a unique database of homologous families both (i) between sequences from different viruses and (ii) between viral sequences and sequences from cellular organisms.
+PhEVER integrates extensive data from up-to-date completely sequenced genomes (2426 non-redundant viral genomes, 1007 non-redundant prokaryotic genomes, 43 eukaryotic genomes ranging from plants to vertebrates) and offers a clustering of proteins into homologous families containing at least one viral sequences, as well as alignments and phylogenies for each of these families.
+Public access to PhEVER is available through its webpage and through all dedicated ACNUC retrieval systems.
+Quantitative methods for analyzing outbreak data and estimating key parameters to characterize the spread of the outbreak, including the reproductive number and the serial interval, often assume that the data collected is complete.
+In reality reporting delays, undetected cases or lack of sensitive and specific tests to diagnose disease lead to reporting errors in the case counts.
+Here we provide insight on the impact that such reporting errors might have on the estimation of these key parameters.
+RESULTS: We show that when the proportion of cases reported is changing through the study period, the estimates of key epidemiological parameters are biased.
+Using data from the Influenza A/H1N1 outbreak in La Gloria, Mexico, we provide estimates of these parameters, accounting for possible reporting errors, and show that they can be biased by as much as 33%, if reporting issues are not accounted for.
+CONCLUSIONS: Failure to account for missing data can lead to misleading and inaccurate estimates of epidemic parameters.
+BACKGROUND: Cases of H1N1 and other pulmonary infections evolve to acute respiratory failure and death when co‐infections or lung injury predominate over the immune response, thus requiring early diagnosis to improve treatment.
+OBJECTIVE: To perform a detailed histopathological analysis of the open lung biopsy specimens from five patients with ARDS with confirmed H1N1.
+Immunophenotyping was used to characterize macrophages, natural killer, T and B cells, and expression of cytokines and iNOS.
+RESULTS: The pathological features observed were necrotizing bronchiolitis, diffuse alveolar damage, alveolar hemorrhage and abnormal immune response.
+CONCLUSIONS: Viral‐like particles can be successfully demonstrated in lung tissue by ultrastructural examination, without confirmation of the virus by RT‐PCR on nasopharyngeal aspirates.
+Bronchioles and epithelium, rather than endothelium, are probably the primary target of infection, and diffuse alveolar damage the consequence of the effect of airways obliteration and dysfunction on innate immunity, suggesting that treatment should be focused on epithelial repair.
+BACKGROUND: Since the first outbreak of a respiratory illness caused by H1N1 virus in Mexico, several reports have described the need of intensive care or extracorporeal membrane oxygenation (ECMO) assistance in young and often healthy patients.
+Here we describe our experience in H1N1-induced ARDS using both ventilation strategy and ECMO assistance.
+METHODS: Following Italian Ministry of Health instructions, an Emergency Service was established at the Careggi Teaching Hospital (Florence, Italy) for the novel pandemic influenza.
+From Sept 09 to Jan 10, all patients admitted to our Intensive Care Unit (ICU) of the Emergency Department with ARDS due to H1N1 infection were studied.
+H1N1 infection was confirmed by PCR assayed on pharyngeal swab, subglottic aspiration and bronchoalveolar lavage.
+RESULTS: A total of 12 patients were studied: 7 underwent ECMO treatment, and 5 responded to protective mechanical ventilation.
+In our series, PCR from bronchoalveolar lavage had a 100% sensitivity compared to 75% from pharyngeal swab samples.
+The routine use of LUS limited the number of chest X-ray examinations and decreased transportation to radiology for CT-scan, increasing patient safety and avoiding the transitory disconnection from ventilator.
+In three cases, bleeding from vascular access sites due to heparin infusion required blood transfusions.
+CONCLUSIONS: In our experience, early ECMO assistance resulted safe and feasible, considering the life threatening condition, in H1N1-induced ARDS.
+The 2009 pandemic H1N1 influenza pandemic demonstrated the global health threat of reassortant influenza strains.
+Herein, we report a detailed analysis of plasmablast and monoclonal antibody responses induced by pandemic H1N1 infection in humans.
+Unlike antibodies elicited by annual influenza vaccinations, most neutralizing antibodies induced by pandemic H1N1 infection were broadly cross-reactive against epitopes in the hemagglutinin (HA) stalk and head domain of multiple influenza strains.
+Based on these observations, we postulate that the plasmablasts producing these broadly neutralizing antibodies were predominantly derived from activated memory B cells specific for epitopes conserved in several influenza strains.
+Antibodies generated potently protected and rescued mice from lethal challenge with pandemic H1N1 or antigenically distinct influenza strains, making them excellent therapeutic candidates.
+BACKGROUND: The cane toad, Bufo (Chaunus) marinus, is one of the most notorious vertebrate pests introduced into Australia over the last 200 years and, so far, efforts to identify a naturally occurring B. marinus-specific pathogen for use as a biological control agent have been unsuccessful.
+We explored an alternative approach that entailed genetically modifying a pathogen with broad host specificity so that it no longer caused disease, but carried a gene to disrupt the cane toad life cycle in a species specific manner.
+METHODOLOGY/PRINCIPAL FINDINGS: The adult beta globin gene was selected as the model gene for proof of concept of autoimmunity as a biocontrol method for cane toads.
+A previous report showed injection of bullfrog tadpoles with adult beta globin resulted in an alteration in the form of beta globin expressed in metamorphs as well as reduced survival.
+In B. marinus we established for the first time that the switch from tadpole to adult globin exists.
+The effect of injecting B. marinus tadpoles with purified recombinant adult globin protein was then assessed using behavioural (swim speed in tadpoles and jump length in metamorphs), developmental (time to metamorphosis, weight and length at various developmental stages, protein profile of adult globin) and genetic (adult globin mRNA levels) measures.
+Further, globin delivery using Bohle iridovirus, an Australian ranavirus isolate belonging to the Iridovirus family, did not reduce the survival of metamorphs or alter the form of beta globin expressed in metamorphs.
+CONCLUSIONS/SIGNIFICANCE: While we were able to show for the first time that the switch from tadpole to adult globin does occur in B. marinus, we were not able to induce autoimmunity and disrupt metamorphosis.
+Eosinophil granulocytes reside in respiratory mucosa including lungs, in the gastro-intestinal tract, and in lymphocyte associated organs, the thymus, lymph nodes and the spleen.
+In parasitic infections, atopic diseases such as atopic dermatitis and asthma, the numbers of the circulating eosinophils are frequently elevated.
+Although, eosinophils were identified more than hundred years ago, their roles in homeostasis and in disease still remain unclear.
+The most prominent feature of the eosinophils are their large secondary granules, each containing four basic proteins, the best known being the eosinophil cationic protein (ECP).
+This protein has been developed as a marker for eosinophilic disease and quantified in biological fluids including serum, bronchoalveolar lavage and nasal secretions.
+Elevated ECP levels are found in T helper lymphocyte type 2 (atopic) diseases such as allergic asthma and allergic rhinitis but also occasionally in other diseases such as bacterial sinusitis.
+ECP is a ribonuclease which has been attributed with cytotoxic, neurotoxic, fibrosis promoting and immune-regulatory functions.
+ECP regulates mucosal and immune cells and may directly act against helminth, bacterial and viral infections.
+The levels of ECP measured in disease in combination with the catalogue of known functions of the protein and its polymorphisms presented here will build a foundation for further speculations of the role of ECP, and ultimately the role of the eosinophil.
+BACKGROUND: It is speculated that the 2009 pandemic H1N1 influenza virus might fall into a seasonal pattern during the current post-pandemic period with more severe clinical presentation for high-risk groups identified during the 2009 pandemic.
+Hence the extent of likely excess healthcare needs during this period must be fully considered.
+We will make use of the historical healthcare record in Taiwan during and after the 1918 influenza pandemic to ascertain the scope of potential excess healthcare burden during the post-pandemic period.
+METHODS: To establish the healthcare needs after the initial wave in 1918, the yearly healthcare records (hospitalizations, outpatients, etc.)
+in Taiwan during 1918-1920 are compared with the corresponding data from the adjacent "baseline" years of 1916, 1917, 1921, and 1922 to estimate the excess healthcare burden during the initial outbreak in 1918 and in the years immediately after.
+RESULTS: In 1918 the number of public hospital outpatients exceeded the yearly average of the baseline years by 20.11% (95% CI: 16.43, 25.90), and the number of hospitalizations exceeded the corresponding yearly average of the baseline years by 12.20% (10.59, 14.38), while the excess number of patients treated by the public medics was statistically significant at 32.21% (28.48, 39.82) more than the yearly average of the baseline years.
+For 1920, only the excess number of hospitalizations was statistically significant at 19.83% (95% CI: 17.21, 23.38) more than the yearly average of the baseline years.
+CONCLUSIONS: Considerable extra burden with significant loss of lives was reported in 1918 by both the public medics system and the public hospitals.
+In comparison, only a substantial number of excess hospitalizations in the public hospitals was reported in 1920, indicating that the population was relatively unprepared for the first wave in 1918 and did not fully utilize the public hospitals.
+Moreover, comparatively low mortality was reported by the public hospitals and the public medics during the second wave in 1920 even though significantly more patients were hospitalized, suggesting that there had been substantially less fatal illnesses among the hospitalized patients during the second wave.
+Immunoassays are important tools for the rapid detection and identification of pathogens, both clinically and in the research laboratory.
+An immunoassay with the potential for the detection of influenza was developed and tested using hemagglutinin (HA), a commonly studied glycoprotein found on the surface of influenza virions.
+Gold nanoparticles were synthesized, which present multiple peptide epitopes, including the HA epitope, in order to increase the gravimetric response achieved with the use of a QCM immunosensor for influenza.
+Specifically, epitopes associated with HA and FLAG peptides were affixed to gold nanoparticles by a six-mer PEG spacer between the epitope and the terminal cysteine.
+The PEG spacer was shown to enhance the probability for interaction with antibodies by increasing the distance the epitope extends from the gold surface.
+These nanoparticles were characterized using thermogravimetric analysis, transmission electron microscopy, matrix-assisted laser desorption/ionization-time of flight, and (1)H nuclear magnetic resonance analysis.
+Anti-FLAG and anti-HA antibodies were adhered to the surface of a QCM, and the response of each antibody upon exposure to HA, FLAG, and dual functionalized nanoparticles was compared with binding of Au–tiopronin nanoparticles and H5 HA proteins from influenza virus (H5N1).
+Results demonstrate that the immunoassay was capable of differentiating between nanoparticles presenting orthogonal epitopes in real-time with minimal nonspecific binding.
+The detection of H5 HA protein demonstrates the logical extension of using these nanoparticle mimics as a safe positive control in the detection of influenza, making this a vital step in improving influenza detection methodology.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00216-010-4419-8) contains supplementary material, which is available to authorized users.
+BACKGROUND: Aplastic anemia (AA) is a serious and rare disorder characterized by a hypocellular bone marrow.
+Hepatitis associated aplastic anemia (HAAA) is a variant of aplastic anemia in which aplastic anemia follows an acute attack of hepatitis.
+Several reports have noted an association between HGV and hepatitis-associated aplastic anemia besides other hepatitis causing viruses.
+CASE PRESENTATION: A female girl of age 11 year with a history of loose motion for one month, vomiting for last 15 days and poor oral intake for last few days is reported here.
+The physical examination presents fever, pallor whereas bleeding, hepatomegaly, Splenomegaly and bruising were absent, abdominal ultrasonography confirmed the absence of hepatomegaly, Splenomegaly and lymphodenopathy.
+The laboratory investigation parameters were: haemoglobin 6.2 g/L, total leucocytes count 1.51, neutrophils 0.47%, absolute reticulocyte count 0.5%, Monocytes 0.16%, red cell count 3.2 mil/uL, Picked cell volume (PCV) 30.13%, Mean Corpuscular Volume (MCV) 78 fL, Mean Corpuscular Hemoglobin (MCH) 26.3 pg.
+Serologic and molecular tests for hepatitis A, B, C, D, E, TTV, B19 were negative, whereas HGV RNA PCR test was found positive for hepatitis G virus.
+The bone marrow aspirate and trephine biopsy examination revealed hypo- cellularity, erythropoiesis, myelopoiesis and megakaryopoiesis.
+CONCLUSION: HAAA is an uncommon but severe condition, which may occur following idiopathic cases of acute hepatitis.
+In patients presenting with pancytopenia after an episode of acute hepatitis, the definitive diagnosis should be considered and confirmed by RT-PCR and if possible by bone marrow biopsy.
+Quantifying the frequency of travel and length of journeys in well-defined population is therefore critical for predicting the likely speed and pattern of spread of emerging infectious diseases, such as a new influenza pandemic.
+Here we present the results of a large population survey undertaken in 2007 in two areas of China: Shenzhen city in Guangdong province, and Huangshan city in Anhui province.
+In each area, 10,000 randomly selected individuals were interviewed, and data on regular and occasional journeys collected.
+Travel behaviour was examined as a function of age, sex, economic status and home location.
+Travel patterns in the economically developed Shenzhen region are shown to resemble those in developed and economically advanced middle income countries with a significant fraction of the population commuting over distances in excess of 50 km.
+Conversely, in the less developed rural region of Anhui, travel was much more local, with very few journeys over 30 km.
+Travel patterns in both populations were well-fitted by a gravity model with a lognormal kernel function.
+The results provide the first quantitative information on human travel patterns in modern China, and suggest that a pandemic emerging in a less developed area of rural China might spread geographically sufficiently slowly for containment to be feasible, while spatial spread in the more economically developed areas might be expected to be much more rapid, making containment more difficult.
+The 1918 pandemic provides an opportunity to elucidate spatial determinants of spread on a large scale.
+To better characterize the spread of the 1918 major wave, we fitted a range of city-to-city transmission models to mortality data collected for 246 population centres in England and Wales and 47 cities in the US.
+Using a gravity model for city-to-city contacts, we explored the effect of population size and distance on the spread of disease and tested assumptions regarding density dependence in connectivity between cities.
+We employed Bayesian Markov Chain Monte Carlo methods to estimate parameters of the model for population, infectivity, distance and density dependence.
+For England and Wales, a model that estimated the degree of density dependence in connectivity between cities was preferable by deviance information criterion comparison.
+Early in the major wave, long distance infective interactions predominated, with local infection events more likely as the epidemic became widespread.
+For the US, with fewer more widely dispersed cities, statistical power was lacking to estimate population size dependence or the degree of density dependence, with the preferred model depending on distance only.
+We find that parameters estimated from the England and Wales dataset can be applied to the US data with no likelihood penalty.
+Refolding of viral class-1 membrane fusion proteins from a native state to a trimer-of-hairpins structure promotes entry of viruses into cells.
+Here we present the structure of the bovine leukaemia virus transmembrane glycoprotein (TM) and identify a group of asparagine residues at the membrane-distal end of the trimer-of-hairpins that is strikingly conserved among divergent viruses.
+Our data indicate that, through electrostatic interactions with a chloride ion, the asparagine residues promote assembly and profoundly stabilize the fusion-active structures that are required for viral envelope-mediated membrane fusion.
+Moreover, the BLV TM structure also reveals a charge-surrounded hydrophobic pocket on the central coiled coil and interactions with basic residues that cluster around this pocket are critical to membrane fusion and form a target for peptide inhibitors of envelope function.
+Charge-surrounded pockets and electrostatic interactions with small ions are common among class-1 fusion proteins, suggesting that small molecules that specifically target such motifs should prevent assembly of the trimer-of-hairpins and be of value as therapeutic inhibitors of viral entry.
+We describe difficult weaning after prolonged mechanical ventilation in three tracheostomized children affected by respiratory virus infection.
+The strategy for weaning was the decrease of ventilation support combining pressure control ventilation (PCV) with increasing periods of continuous positive airway pressure + pressure support ventilation (CPAP + PSV) and then CPAP + PSV with increasing intervals of T-piece.
+They presented acute respiratory distress syndrome on admission with high requirements of mechanical ventilation (MV).
+Intervening factors in the capabilities and loads of the respiratory system were considered and optimized.
+Initiation of translation of the full-length messenger RNA of HIV-1, which generates the viral structural proteins and enzymes, is cap-dependent but can also use an internal ribosome entry site (IRES) located in the 5′ untranslated region.
+Our aim was to define, through a mutational analysis, regions of HIV-1 IRES that are important for its activity.
+A dual-luciferase reporter construct where the Renilla luciferase (Rluc) translation is cap-dependent while the firefly luciferase (Fluc) translation depends on HIV-1 IRES was used.
+The Fluc/Rluc ratio was measured in lysates of Jurkat T cells transfected with the dual-luciferase plasmid bearing either the wild-type or a mutated IRES.
+Deletions or mutations in three regions decreased the IRES activity but deletion or mutations of a stem-loop preceding the primer binding site increased the IRES activity.
+The wild-type IRES activity, but not that of an IRES with a mutated stem-loop, was increased when cells were treated with agents that induce oxidative stress.
+Such stress is known to be caused by HIV-1 infection and we propose that this stem-loop is involved in a switch that stimulates the IRES activity in cells infected with HIV-1, supporting the suggestion that the IRES activity is up-regulated in the course of HIV-1 replication cycle.
+Termination-dependent reinitiation is used to co-ordinately regulate expression of the M1 and BM2 open-reading frames (ORFs) of the dicistronic influenza B segment 7 RNA.
+The start codon of the BM2 ORF overlaps the stop codon of the M1 ORF in the pentanucleotide UAA UG and ∼10% of ribosomes terminating at the M1 stop codon reinitiate translation at the overlapping AUG. BM2 synthesis requires the presence of, and translation through, 45 nt of RNA immediately upstream of the UAA UG, known as the ‘termination upstream ribosome binding site’ (TURBS).
+This region may tether ribosomal 40S subunits to the mRNA following termination and a short region of the TURBS, motif 1, with complementarity to helix 26 of 18S rRNA has been implicated in this process.
+Here, we provide further evidence for a direct interaction between mRNA and rRNA using antisense oligonucleotide targeting and functional analysis in yeast cells.
+The TURBS also binds initiation factor eIF3 and we show here that this protein stimulates reinitiation from both wild-type and defective TURBS when added exogenously, perhaps by stabilising ribosome-mRNA interactions.
+Further, we show that the position of the TURBS with respect to the UAA UG overlap is crucial, and that termination too far downstream of the 18S complementary sequence inhibits the process, probably due to reduced 40S tethering.
+However, in reporter mRNAs where the restart codon alone is moved downstream, termination-reinitiation is inhibited but not abolished, thus the site of reinitiation is somewhat flexible.
+Reinitiation on distant AUGs is not inhibited in eIF4G-depleted RRL, suggesting that the tethered 40S subunit can move some distance without a requirement for linear scanning.
+Real-time PCR techniques are now commonly used for the detection of viral genomes in various human specimens and require for validation both external and internal controls (ECs and ICs).
+In particular, ICs added to clinical samples are necessary to monitor the extraction, reverse transcription, and amplification steps in order to detect false-negative results resulting from PCR-inhibition or errors in the technical procedure.
+Here, we performed a large scale evaluation of the use of bacteriophages as ICs in routine molecular diagnosis.
+This allowed to propose simple standardized procedures (i) to design specific ECs for both DNA and RNA viruses and (ii) to use T4 (DNA) or MS2 (RNA) phages as ICs in routine diagnosis.
+Subsequently, T4 and MS2 ICs were evaluated in routine real-time PCR or RT-PCR virological diagnostic tests, using a series of 8,950 clinical samples (representing 36 distinct specimen types) sent to our laboratory for the detection of a variety of DNA and RNA viruses.
+The frequency of inefficient detection of ICs was analyzed according to the nature of the sample.
+Inhibitors of enzymatic reactions were detected at high frequency in specific sample types such as heparinized blood and bone marrow (>70%), broncho-alveolar liquid (41%) and stools (36%).
+The use of T4 and MS2 phages as ICs proved to be cost-effective, flexible and adaptable to various technical procedures of real-time PCR detection in virology.
+It represents a valuable strategy for enhancing the quality of routine molecular diagnosis in laboratories that use in-house designed diagnostic systems, which can conveniently be associated to the use of specific synthetic ECs.
+The high rate of inhibitors observed in a variety of specimen types should stimulate the elaboration of improved technical protocols for the extraction and amplification of nucleic acids.
+BACKGROUND: Resistance to the neuraminidase inhibitor oseltamivir can be conferred by a well-characterized mutation in the neuraminidase gene, H275Y.
+In human H1N1 viruses that circulated in the first years of the 21st century, this mutation carried a fitness cost and resistant viruses were rare.
+We examined whether the H275Y mutation affected neuraminidase enzyme activity or replication of the pandemic influenza virus.
+METHODS: Using reverse genetics we engineered the H275Y mutation into the neuraminidase of a 2009 pandemic H1N1 virus and assessed the ability of this enzyme to desialylate mono- and multivalent substrates.
+The growth kinetics of wild-type and mutant viruses were assessed in Madin–Darby canine kidney (MDCK) and fully differentiated human airway epithelial (HAE) cells.
+RESULTS: The presence of H275Y was associated with a 1.3-fold decrease in the affinity of the neuraminidase for a monovalent substrate and a 4-fold compromise in desialylation of multivalent substrate.
+This was associated with a fitness cost to viral replication in vitro, which only became apparent during competitive replication in the mucus-rich HAE culture system.
+CONCLUSIONS: The neuraminidase protein of pandemic influenza isolates tolerates the H275Y mutation and this mutation confers resistance to oseltamivir.
+However, unlike seasonal H1N1 viruses isolated since 2007, the mutation is not associated with any fitness advantage and thus is unlikely to predominate without further antigenic drift, compensating mutations or intense selection pressure.
+BACKGROUND: Infections caused by community-associated strains of methicillin-resistant Staphylococcus aureus (CA-MRSA) are associated with a marked and prolonged host inflammatory response.
+In a sepsis simulation model, we tested whether the anesthetic ketamine inhibits the macrophage TNF response to antibiotic-exposed CA-MRSA bacteria via its antagonism of N-methyl-D-aspartate (NMDA) receptors.
+RAW264.7 cells were stimulated for 18 hrs with 10(5 )to 10(7 )CFU/mL inocula of either of two prototypical CA-MRSA isolates, USA300 strain LAC and USA400 strain MW2, in the presence of either vancomycin or daptomycin.
+One hour before bacterial stimulation, ketamine was added with or without MK-801 (dizocilpine, a chemically unrelated non-competitive NMDA receptor antagonist), APV (D-2-amino-5-phosphono-valerate, a competitive NMDA receptor antagonist), NMDA, or combinations of these agents.
+RESULTS: RAW264.7 cells exposed to either LAC or MW2 in the presence of daptomycin secreted less TNF than in the presence of vancomycin.
+The addition of ketamine inhibited macrophage TNF secretion after stimulation with either of the CA-MRSA isolates (LAC, MW2) in the presence of either antibiotic.
+The NMDA inhibitors, MK-801 and APV, also suppressed macrophage TNF secretion after stimulation with either of the antibiotic-exposed CA-MRSA isolates, and the effect was not additive or synergistic with ketamine.
+The addition of NMDA substrate augmented TNF secretion in response to the CA-MRSA bacteria, and the addition of APV suppressed the effect of NMDA in a dose-dependent fashion.
+CONCLUSIONS: Ketamine inhibits TNF secretion by MRSA-stimulated RAW264.7 macrophages and the mechanism likely involves NMDA receptor antagonism.
+APVs are distributed worldwide and cause disease in domestic, pet and wild birds of many species.
+APVs are transmitted by aerosols and biting insects, particularly mosquitoes and arthropods and are usually named after the bird species from which they were originally isolated.
+The virus species Fowlpox virus (FWPV) causes disease in poultry and associated mortality is usually low, but in flocks under stress (other diseases, high production) mortality can reach up to 50%.
+APVs are also major players in viral vaccine vector development for diseases in human and veterinary medicine.
+Abortive infection in mammalian cells (no production of progeny viruses) and their ability to accommodate multiple gene inserts are some of the characteristics that make APVs promising vaccine vectors.
+Although abortive infection in mammalian cells conceivably represents a major vaccine bio-safety advantage, molecular mechanisms restricting APVs to certain hosts are not yet fully understood.
+This review summarizes the current knowledge relating to APVs, including classification, morphogenesis, host-virus interactions, diagnostics and disease, and also highlights the use of APVs as recombinant vaccine vectors.
+This study aimed at substantiating the associations of the apolipoproein M gene (APOM) with type 2 diabetes (T2D) as well as with metabolic traits in Hong Kong Chinese.
+In addition, APOM gene function was further characterized to elucidate its activity in cholesterol metabolism.
+Five SNPs were confirmed in our study cohort of 1234 T2D and 606 control participants.
+We chose rs707922 to tag this LD region for down stream association analyses and characterized the function of this SNP at molecular level.
+No association between APOM and T2D susceptibility was detected in our Hong Kong Chinese cohort.
+Interestingly, the C allele of rs805297 was significantly associated with T2D duration of longer than 10 years (OR = 1.245, p = 0.015).
+The rs707922 TT genotype was significantly associated with elevated plasma total- and LDL- cholesterol levels (p = 0.006 and p = 0.009, respectively) in T2D patients.
+Molecular analyses of rs707922 lead to the discoveries of a novel transcript APOM5 as well as the cryptic nature of exon 5 of the gene.
+Ectopic expression of APOM5 transcript confirmed rs707922 allele-dependent activity of the transcript in modifying cholesterol homeostasis in vitro.
+In conclusion, the results here did not support APOM as a T2D susceptibility gene in Hong Kong Chinese.
+However, in T2D patients, a subset of APOM SNPs was associated with disease duration and metabolic traits.
+Further molecular analysis proved the functional activity of rs707922 in APOM expression and in regulation of cellular cholesterol content.
+BACKGROUND: Early detection of lung cancer is known to improve the chances of successful treatment.
+Conventional X-ray imaging is based purely on absorption resulting in very low contrast when imaging soft tissues without contrast agents.
+METHODS: In this study, a recently emerged imaging technique, in-line X-ray phase contrast imaging (IL-XPCI) was used.
+We applied IL-XPCI to observe the lungs in an intact mouse for the purpose of defining quantitatively the micro-structures in lung.
+FINDINGS: The three-dimensional model of the lung was successfully established, which provided an excellent view of lung airways.
+We highlighted the use of IL-XPCI in the visualization and assessment of alveoli which had rarely been studied in three dimensions (3D).
+These parameters were of great importance in the diagnosis of diseases related to alveolus and alveolar scar.
+CONCLUSION: Our results indicated that IL-XPCI had the ability to represent complex anatomical structures in lung.
+This offered a new perspective on the diagnosis of respiratory disease and may guide future work in the study of respiratory mechanism on the alveoli level.
+A fundamental goal of biology is to understand how novel phenotypes evolved through changes in existing genes.
+The Dictyostelia or social amoebas represent a simple form of multicellularity, where starving cells aggregate to build fruiting structures.
+This review summarizes efforts to provide a framework for investigating the genetic changes that generated novel morphologies in the Dictyostelia.
+The foundation is a recently constructed molecular phylogeny of the Dictyostelia, which was used to examine trends in the evolution of novel forms and in the divergence of genes that shape these forms.
+There is a major trend towards the formation of large unbranched fruiting bodies, which is correlated with the use of cyclic AMP (cAMP) as a secreted signal to coordinate cell aggregation.
+The role of cAMP in aggregation arose through co‐option of a pathway that originally acted to coordinate fruiting body formation.
+The genotypic changes that caused this innovation and the role of dynamic cAMP signaling in defining fruiting body size and pattern throughout social amoeba evolution are discussed.
+Plastid transformation is becoming more popular and an alternative to nuclear gene transformation because of various advantages like high protein levels, the feasibility of expressing multiple proteins from polycistronic mRNAs, and gene containment through the lack of pollen transmission.
+In addition to model plant tobacco, many transplastomic crop plants have been generated which possess higher resistance to biotic and abiotic stresses and molecular pharming.
+In this mini review, we will discuss the features of the plastid DNA and advantages of plastid transformation.
+We will also present some examples of transplastomic plants developed so far through plastid engineering, and the various applications of plastid transformation.
+Reactive oxygen species and thiol antioxidants, including glutathione (GSH), regulate innate immunity at various levels.
+This review outlines the redox-sensitive steps of the cellular mechanisms implicated in inflammation and host defense against infection, and describes how GSH is not only important as an antioxidant but also as a signaling molecule.
+Most reviews are biased by an oversimplified picture where “bad” free radicals cause all sorts of diseases and “good” antioxidants protect from them and prevent oxidative stress.
+While this may be the case in certain fields (eg, toxicology), the role of thiols (the topic of this review) in immunity certainly requires wearing scientist’s goggles and being prepared to accept a more complex picture.
+This review aims at describing the role of GSH in the lung in the context of immunity and inflammation.
+The second part focuses on GSH metabolism/levels in pathology, the third on the role of GSH in innate immunity and inflammation, and the fourth gives 4 examples describing the importance of GSH in the response to infections.
+BACKGROUND: More than a year after an influenza pandemic was declared in June 2009, the World Health Organization declared the pandemic to be over.
+DISCUSSION: We argue that, despite the enormous effort made to control the pandemic, it is now time to acknowledge that many of the population-based public health interventions may not have been well considered.
+In particular no border screening measures would have detected prodromal or asymptomatic infections, and asymptomatic infections with pandemic influenza were common.
+School closures, when they were partial or of short duration, would not have interrupted spread of the virus in school-aged children, the group with the highest rate of infection worldwide.
+In most countries where they were available, neuraminidase inhibitors were not distributed quickly enough to have had an effect at the population level, although they will have benefited individuals, and prophylaxis within closed communities will have been effective.
+A pandemic specific vaccine will have protected the people who received it, although in most countries only a small minority was vaccinated, and often a small minority of those most at risk.
+The pandemic vaccine was generally not available early enough to have influenced the shape of the first pandemic wave and it is likely that any future pandemic vaccine manufactured using current technology will also be available too late, at least in one hemisphere.
+SUMMARY: Border screening, school closure, widespread anti-viral prophylaxis and a pandemic-specific vaccine were unlikely to have been effective during a pandemic which was less severe than anticipated in the pandemic plans of many countries.
+Similar responses would be even less likely to be effective in a more severe pandemic.
+We agree with the recommendation from the World Health Organisation that pandemic preparedness plans need review.
+BACKGROUND: Computational models play an increasingly important role in the assessment and control of public health crises, as demonstrated during the 2009 H1N1 influenza pandemic.
+Much research has been done in recent years in the development of sophisticated data-driven models for realistic computer-based simulations of infectious disease spreading.
+However, only a few computational tools are presently available for assessing scenarios, predicting epidemic evolutions, and managing health emergencies that can benefit a broad audience of users including policy makers and health institutions.
+RESULTS: We present "GLEaMviz", a publicly available software system that simulates the spread of emerging human-to-human infectious diseases across the world.
+The GLEaMviz tool comprises three components: the client application, the proxy middleware, and the simulation engine.
+The simulation engine leverages on the Global Epidemic and Mobility (GLEaM) framework, a stochastic computational scheme that integrates worldwide high-resolution demographic and mobility data to simulate disease spread on the global scale.
+The GLEaMviz design aims at maximizing flexibility in defining the disease compartmental model and configuring the simulation scenario; it allows the user to set a variety of parameters including: compartment-specific features, transition values, and environmental effects.
+The output is a dynamic map and a corresponding set of charts that quantitatively describe the geo-temporal evolution of the disease.
+The multi-platform client, which can be installed on the user's local machine, is used to set up simulations that will be executed on the server, thus avoiding specific requirements for large computational capabilities on the user side.
+CONCLUSIONS: The user-friendly graphical interface of the GLEaMviz tool, along with its high level of detail and the realism of its embedded modeling approach, opens up the platform to simulate realistic epidemic scenarios.
+These features make the GLEaMviz computational tool a convenient teaching/training tool as well as a first step toward the development of a computational tool aimed at facilitating the use and exploitation of computational models for the policy making and scenario analysis of infectious disease outbreaks.
+Given her story and that of her World War II colleagues, the topic of nursing heroism in the 21(st )century could not be more germane.
+DISCUSSION: Is heroism a legitimate part of nursing, or are nurses simply 'just doing their job' even when facing extreme personal danger?
+I propose that nursing heroism deserves a broader appreciation and that within the term lie many hidden, 'unsung' or 'unrecorded' heroisms.
+I also challenge the critiques of heroism that would condemn it as part of a 'militarisation' of nursing.
+Finally, I argue that nursing needs to be more open in celebrating our heroes and the transformative power of nursing achievements.
+SUMMARY: The language of heroism may sound quaint by 21(st )Century standards but nursing heroism is alive and well in the best of our contemporary nursing ethos and practice.
+Copy number variation is common in the human genome with many regions, overlapping thousands of genes, now known to be deleted or amplified.
+Aneuploidies and other forms of chromosomal imbalance have a wide range of adverse phenotypes and are a common cause of birth defects resulting in significant morbidity and mortality.
+“Normal” copy number variants (CNVs) embedded within the regions of chromosome imbalance may affect the clinical outcomes by altering the local copy number of important genes or regulatory regions: this could alleviate or exacerbate certain phenotypes.
+In this way CNVs may contribute to the clinical variability seen in many disorders caused by chromosomal abnormalities, such as the congenital heart defects (CHD) seen in ~40% of Down’s syndrome (DS) patients.
+Investigation of CNVs may therefore help to pinpoint critical genes or regulatory elements, elucidating the molecular mechanisms underlying these conditions, also shedding light on the aetiology of such phenotypes in people without major chromosome imbalances, and ultimately leading to their improved detection and treatment.
+Hepatitis-associated aplastic anemia (HAAA) is an uncommon but distinct variant of aplastic anemia in which pancytopenia appears two to three months after an acute attack of hepatitis.
+The etiology of this syndrome is proposed to be attributed to various hepatitis and non hepatitis viruses.
+Several hepatitis viruses such as HAV, HBV, HCV, HDV, HEV and HGV have been associated with this set of symptoms.
+Viruses other than the hepatitis viruses such as parvovirus B19, Cytomegalovirus, Epstein bar virus, Transfusion Transmitted virus (TTV) and non-A-E hepatitis virus (unknown viruses) has also been documented to develop the syndrome.
+Considerable evidences including the clinical features, severe imbalance of the T cell immune system and effective response to immunosuppressive therapy strongly present HAAA as an immune mediated mechanism.
+Besides hepatitis and non hepatitis viruses and immunopathogenesis phenomenon as causative agents of the disorder, telomerase mutation, a genetic factor has also been predisposed for the development of aplastic anemia.
+Diagnosis includes clinical manifestations, blood profiling, viral serological markers testing, immune functioning and bone marrow hypocellularity examination.
+Patients presenting the features of HAAA have been mostly treated with bone marrow or hematopoietic cell transplantation from HLA matched donor, and if not available then by immunosuppressive therapy.
+New therapeutic approaches involve the administration of steroids especially the glucocorticoids to augment the immunosuppressive therapy response.
+Pancytopenia following an episode of acute hepatitis response better to hematopoietic cell transplantation than immunosuppressive therapy.
+We examined general population decision-making for pH1N1 vaccination using a modified Theory of Planned Behaviour (TBP).
+METHODOLOGY: We conducted a longitudinal study, collecting data before and after the introduction of pH1N1 vaccine in Hong Kong.
+Structural equation modeling (SEM) tested if a modified TPB had explanatory utility for vaccine uptake among adults.
+PRINCIPAL FINDINGS: Among 896 subjects who completed both the baseline and the follow-up surveys, 7% (67/896) reported being “likely/very likely/certain” to be vaccinated (intent) but two months later only 0.8% (7/896) reported having received pH1N1 vaccination.
+Perception of low risk from pH1N1 (60%) and concerns regarding adverse effects of the vaccine (37%) were primary justifications for avoiding pH1N1 vaccination.
+Greater perceived vaccine benefits (β = 0.15), less concerns regarding vaccine side-effects (β = −0.20), greater adherence to social norms of vaccination (β = 0.39), anticipated higher regret if not vaccinated (β = 0.47), perceived higher self-efficacy for vaccination (β = 0.12) and history of seasonal influenza vaccination (β = 0.12) were associated with higher intention to receive the pH1N1 vaccine, which in turn predicted self-reported vaccination uptake (β = 0.30).
+Social norm (β = 0.70), anticipated regret (β = 0.19) and vaccination intention (β = 0.31) were positively associated with, and accounted for 70% of variance in vaccination planning, which, in turn subsequently predicted self-reported vaccination uptake (β = 0.36) accounting for 36% of variance in reported vaccination behaviour.
+CONCLUSIONS/SIGNIFICANCE: Perceived low risk from pH1N1 and perceived high risk from pH1N1 vaccine inhibited pH1N1 vaccine uptake.
+Both the TPB and the additional components contributed to intended vaccination uptake but social norms and anticipated regret predominantly associated with vaccination intention and planning.
+Vaccination planning is a more significant proximal determinant of uptake of pH1N1 vaccine than is intention.
+The mechanisms of dengue virus (DENV) pathogenesis are little understood because we have no models of disease; only humans develop symptoms (dengue fever, DF, or dengue hemorrhagic fever, DHF) and research has been limited to studies involving patients.
+DENV is very diverse: there are four antigenic groups (serotypes) and three to five genetic groups (genotypes) within each serotype.
+Thus, it has been difficult to evaluate the relative virulence or transmissibility of each DENV genotype; both of these factors are important determinants of epidemiology and their measurement is complex because the natural cycle of this disease involves human-mosquito-human transmission.
+Although epidemiological and evolutionary studies have pointed to viral factors in determining disease outcome, only recently developed models could prove the importance of specific viral genotypes in causing severe epidemics and their potential to spread to other continents.
+These new models involve infection of primary human cell cultures, “humanized” mice and field-collected mosquitoes; also, new mathematical models can estimate the impact of viral replication, human immunity and mosquito transmission on epidemic behavior.
+DENV evolution does not seem to be rapid and the transmission and dispersal of stable, replication-fit genotypes has been more important in the causation of more severe epidemics.
+Controversy regarding viral determinants of DENV pathogenesis and epidemiology will continue until virulence and transmissibility can be measured under various conditions.
+Tylosema esculentum (marama) beans and tubers are used as food, and traditional medicine against diarrhoea in Southern Africa.
+Rotaviruses (RVs) are a major cause of diarrhoea among infants, young children, immunocompromised people, and domesticated animals.
+Our work is first to determine anti-RV activity of marama bean and tuber ethanol and water extracts; in this case on intestinal enterocyte cells of human infant (H4), adult pig (CLAB) and adult bovine (CIEB) origin.
+Marama cotyledon ethanolic extract (MCE) and cotyledon water extract (MCW) without RV were not cytotoxic to all cells tested, while seed coat and tuber extracts showed variable levels of cytotoxicity.
+(≥0.1 mg/mL), seed coat extract (MSCE) and seed coat water extract (MSCW) (0.01 to 0.001 mg/mL), especially ethanolic, significantly increased cell survival and enhanced survival to cytopathic effects of RV by at least 100% after in vitro co- and pre-incubation treatments.
+All marama extracts used significantly enhanced nitric oxide release from H4 cells and enhanced TER (Ω/cm(2)) of enterocyte barriers after coincubation with RV.
+Marama cotyledon and seed coat extracts inhibited virion infectivity possibly through interference with replication due to accumulation of nitric oxide.
+Infectious disease treatments, both pharmaceutical and vaccine, face three universal challenges: the difficulty of targeting treatments to high-risk ‘superspreader’ populations who drive the great majority of disease spread, behavioral barriers in the host population (such as poor compliance and risk disinhibition), and the evolution of pathogen resistance.
+Here, we describe a proposed intervention that would overcome these challenges by capitalizing upon Therapeutic Interfering Particles (TIPs) that are engineered to replicate conditionally in the presence of the pathogen and spread between individuals — analogous to ‘transmissible immunization’ that occurs with live-attenuated vaccines (but without the potential for reversion to virulence).
+Building on analyses of HIV field data from sub-Saharan Africa, we construct a multi-scale model, beginning at the single-cell level, to predict the effect of TIPs on individual patient viral loads and ultimately population-level disease prevalence.
+Our results show that a TIP, engineered with properties based on a recent HIV gene-therapy trial, could stably lower HIV/AIDS prevalence by ∼30-fold within 50 years and could complement current therapies.
+In contrast, optimistic antiretroviral therapy or vaccination campaigns alone could only lower HIV/AIDS prevalence by <2-fold over 50 years.
+The TIP's efficacy arises from its exploitation of the same risk factors as the pathogen, allowing it to autonomously penetrate superspreader populations, maintain efficacy despite behavioral disinhibition, and limit viral resistance.
+While demonstrated here for HIV, the TIP concept could apply broadly to many viral infectious diseases and would represent a new paradigm for disease control, away from pathogen eradication but toward robust disease suppression.
+The antigenic structure of the membrane protein hemagglutinin (HA) from the 2009 A(H1N1) influenza virus was dissected with a high-throughput screening method using complex antisera.
+The approach involves generating yeast cell libraries displaying a pool of random peptides of controllable lengths on the cell surface, followed by one round of fluorescence-activated cell sorting (FACS) against antisera from mouse, goat and human, respectively.
+The amino acid residue frequency appearing in the antigenic peptides at both the primary sequence and structural level was determined and used to identify “hot spots” or antigenically important regions.
+Moreover, five antigenic regions were identified, of which all but one are located in the conserved HA stem region that is responsible for membrane fusion.
+Our findings are corroborated by several recent studies on cross-neutralizing H1 subtype antibodies that recognize the HA stem region.
+The antigenic peptides identified may provide clues for creating peptide vaccines with better accessibility to memory B cells and better induction of cross-neutralizing antibodies than the whole HA protein.
+The scheme used in this study enables a direct mapping of the antigenic regions of viral proteins recognized by antisera, and may be useful for dissecting the antigenic structures of other viral proteins.
+The complement system was discovered a century ago as a potent defense cascade of innate immunity.
+After its first description, continuous experimental and clinical research was performed, and three canonical pathways of activation were established.
+Upon activation by traumatic or surgical tissue damage, complement reveals beneficial functions of pathogen and danger defense by sensing and clearing injured cells.
+However, the latest research efforts have provided a more distinct insight into the complement system and its clinical subsequences.
+Complement has been shown to play a significant role in the pathogenesis of various inflammatory processes such as sepsis, multiorgan dysfunction, ischemia/reperfusion, cardiovascular diseases and many others.
+The three well-known activation pathways of the complement system have been challenged by newer findings that demonstrate direct production of central complement effectors (for example, C5a) by serine proteases of the coagulation cascade.
+In particular, thrombin is capable of producing C5a, which not only plays a decisive role on pathogens and infected/damaged tissues, but also acts systemically.
+In the case of uncontrolled complement activation, “friendly fire” is generated, resulting in the destruction of healthy host tissue.
+Therefore, the traditional research that focuses on a mainly positive-acting cascade has now shifted to the negative effects and how tissue damage originated by the activation of the complement can be contained.
+In a translational approach including structure-function relations of this ancient defense system, this review provides new insights of complement-mediated clinical relevant diseases and the development of complement modulation strategies and current research aspects.
+The emergence of a novel strain of H1N1 influenza virus in Mexico in 2009, and its subsequent worldwide spread, has focused attention to the question of optimal deployment of mass vaccination campaigns.
+Here, we use three relatively simple models to address three issues of primary concern in the targeting of any vaccine.
+The advantages of such simple models are that the underlying assumptions and effects of individual parameters are relatively clear, and the impact of uncertainty in the parametrization can be readily assessed in the early stages of an outbreak.
+In particular, we examine whether targeting risk-groups, age-groups or spatial regions could be optimal in terms of reducing the predicted number of cases or severe effects; and how these targeted strategies vary as the epidemic progresses.
+We examine the conditions under which it is optimal to initially target vaccination towards those individuals within the population who are most at risk of severe effects of infection.
+Using age-structured mixing matrices, we show that targeting vaccination towards the more epidemiologically important age groups (5–14 year olds and then 15–24 year olds) leads to the greatest reduction in the epidemic growth and hence reduces the total number of cases.
+Finally, we consider how spatially targeting the vaccine towards regions of country worst affected could provide an advantage.
+We discuss how all three of these priorities change as both the speed at which vaccination can be deployed and the start of the vaccination programme is varied.
+It could be argued that epidemiology in particular has embraced the potential of network theory more than any other discipline.
+Here we review the growing body of research concerning the spread of infectious diseases on networks, focusing on the interplay between network theory and epidemiology.
+The review is split into four main sections, which examine: the types of network relevant to epidemiology; the multitude of ways these networks can be characterised; the statistical methods that can be applied to infer the epidemiological parameters on a realised network; and finally simulation and analytical methods to determine epidemic dynamics on a given network.
+Given the breadth of areas covered and the ever-expanding number of publications, a comprehensive review of all work is impossible.
+Instead, we provide a personalised overview into the areas of network epidemiology that have seen the greatest progress in recent years or have the greatest potential to provide novel insights.
+As such, considerable importance is placed on analytical approaches and statistical methods which are both rapidly expanding fields.
+In 2007, the A/Brisbane/59/2007 (H1N1) seasonal influenza virus strain acquired the oseltamivir-resistance mutation H275Y in its neuraminidase (NA) gene.
+Although previous studies had demonstrated that this mutation impaired the replication capacity of the influenza virus in vitro and in vivo, the A/Brisbane/59/2007 H275Y oseltamivir-resistant mutant completely out-competed the wild-type (WT) strain and was, in the 2008–2009 influenza season, the primary A/H1N1 circulating strain.
+Using a combination of plaque and viral yield assays, and a simple mathematical model, approximate values were extracted for two basic viral kinetics parameters of the in vitro infection.
+In the ST6GalI-MDCK cell line, the latent infection period (i.e., the time for a newly infected cell to start releasing virions) was found to be 1–3 h for the WT strain and more than 7 h for the H275Y mutant.
+The infecting time (i.e., the time for a single infectious cell to cause the infection of another one) was between 30 and 80 min for the WT, and less than 5 min for the H275Y mutant.
+These results, though preliminary, suggest that the increased fitness success of the A/Brisbane/59/2007 H275Y mutant may be due to increased infectivity compensating for an impaired or delayed viral release, and are consistent with recent evidence for the mechanistic origins of fitness reduction and recovery in NA expression.
+The method applied here can reconcile seemingly contradictory results from the plaque and yield assays as two complementary views of replication kinetics, with both required to fully capture a strain's fitness.
+globigii (BG) as a simulant for biological warfare (BW) agents, knowledge of its genome composition is limited.
+Furthermore, the ability to differentiate signatures of deliberate adaptation and selection from natural variation is lacking for most bacterial agents.
+We characterized a lineage of BGwith a long history of use as a simulant for BW operations, focusing on classical bacteriological markers, metabolic profiling and whole-genome shotgun sequencing (WGS).
+RESULTS: Archival strains and two “present day” type strains were compared to simulant strains on different laboratory media.
+Several of the samples produced multiple colony morphotypes that differed from that of an archival isolate.
+To trace the microevolutionary history of these isolates, we obtained WGS data for several archival and present-day strains and morphotypes.
+The genome of B. atrophaeus is, on average, 86% identical to B. subtilis on the nucleotide level.
+WGS of variants revealed that several strains were mixed but highly related populations and uncovered a progressive accumulation of mutations among the “military” isolates.
+Metabolic profiling and microscopic examination of bacterial cultures revealed enhanced growth of “military” isolates on lactate-containing media, and showed that the “military” strains exhibited a hypersporulating phenotype.
+CONCLUSIONS: Our analysis revealed the genomic and phenotypic signatures of strain adaptation and deliberate selection for traits that were desirable in a simulant organism.
+Together, these results demonstrate the power of whole-genome and modern systems-level approaches to characterize microbial lineages to develop and validate forensic markers for strain discrimination and reveal signatures of deliberate adaptation.
+BACKGROUND: In Plasmodium falciparum malaria endemic areas placental malaria (PM) is an important complication of malaria.
+The recurrence of malaria in primigravidae women irrespective of acquired protection during childhood is caused by the interaction between the parasite-expressed VAR2CSA antigen and chondroitin sulfate A (CSA) in the placental intervillous space and lack of protective antibodies.
+Ideally, a vaccine against PM will induce antibody-mediated immune responses that block the adhesion of infected erythrocytes (IE) in the placenta.
+PRINCIPAL FINDINGS: We have previously shown that antibodies raised in rat against individual domains of VAR2CSA can block IE binding to CSA.
+In this study we have immunized mice, rats and rabbits with each individual domain and the full-length protein corresponding to the FCR3 VAR2CSA variant.
+We found there is an inherently higher immunogenicity of C-terminal domains compared to N-terminally located domains.
+This was irrespective of whether antibodies were induced against single domains or the full-length protein.
+Species-specific antibody responses were also found, these were mainly directed against single domains and not the full-length VAR2CSA protein.
+Non-binding inhibitory antibodies reacted highly against the C-terminal end of the VAR2CSA molecule especially the highly polymorphic DBL6ε domain.
+Differential species-specific induction of antibody responses may allow for more direct analysis of functional versus non-functional B-cell epitopes.
+BACKGROUND: Most guidelines have been proposing, for more than 15 years, a β-lactam combined with either a quinolone or a macrolide as empirical, first-line therapy of severe community acquired pneumonia (CAP) requiring ICU admission.
+Our goal was to evaluate the outcome of patients with severe CAP, focusing on the impact of new rather than old fluoroquinolones combined with β-lactam in the empirical antimicrobial treatments.
+METHODS: Retrospective study of consecutive patients admitted in a 16-bed general intensive care unit (ICU), between January 1996 and January 2009, for severe (Pneumonia Severity Index > or = 4) community-acquired pneumonia due to non penicillin-resistant Streptococcus pneumoniae and treated with a β-lactam combined with a fluoroquinolone.
+RESULTS: We included 70 patients of whom 38 received a β-lactam combined with ofloxacin or ciprofloxacin and 32 combined with levofloxacin.
+Three independent factors associated with decreased survival in ICU were identified: septic shock on ICU admission (AOR = 10.6; 95% CI 2.87-39.3; p = 0.0004), age > 70 yrs.
+(AOR = 4.88; 95% CI 1.41-16.9; p = 0.01) and initial treatment with a β-lactam combined with ofloxacin or ciprofloxacin (AOR = 4.1; 95% CI 1.13-15.13; p = 0.03).
+CONCLUSION: Our results suggest that, when combined to a β-lactam, levofloxacin is associated with lower mortality than ofloxacin or ciprofloxacin in severe pneumococcal community-acquired pneumonia.
+This research examines whether maternal optimism/pessimism is associated with unplanned Cesarean section deliveries in China.
+A sample of 227 mostly primiparous women in the third trimester of pregnancy was surveyed in a large tertiary care hospital in Beijing, China.
+However, when optimism and pessimism were entered into a regression model together, optimism was no longer statistically significant.
+Pessimism remained significant, even when adjusting for clinical factors such as previous abortion, previous miscarriage, pregnancy complications, infant gestational age, infant birthweight, labor duration, birth complications, and self-rated difficulty of the pregnancy.
+This research suggests that maternal mindset during pregnancy has a role in mode of delivery.
+The purpose of this study is to evaluate in vitro gene delivery mediated by asialofetuin-appended cationic liposomes (AF-liposomes) associating cyclodextrins (CyD/AF-liposomes) as a hepatocyte-selective nonviral vector.
+Of various CyDs, AF-liposomes associated with plasmid DNA (pDNA) and γ-cyclodextrin (γ-CyD) (pDNA/γ-CyD/AF-liposomes) showed the highest gene transfer activity in HepG2 cells without any significant cytotoxicity.
+In addition, γ-CyD enhanced the encapsulation ratio of pDNA with AF-liposomes, and also increased gene transfer activity as the entrapment ratio of pDNA into AF-liposomes was increased.
+γ-CyD stabilized the liposomal membrane of AF-liposomes and inhibited the release of calcein from AF-liposomes.
+The stabilizing effect of γ-CyD may be, at least in part, involved in the enhancing gene transfer activity of pDNA/γ-CyD/AF-liposomes.
+Therefore, these results suggest the potential use of γ-CyD for an enhancer of transfection efficiency of AF-liposomes.
+BACKGROUND: Beside their established function in shaping cell architecture, some cell polarity proteins were proposed to participate to lymphocyte migration, homing, scanning, as well as activation following antigen receptor stimulation.
+Although PALS1 is a central component of the cell polarity network, its expression and function in lymphocytes remains unknown.
+Here we investigated whether PALS1 is present in T cells and whether it contributes to T Cell-Receptor (TCR)-mediated activation.
+METHODOLOGY/PRINCIPAL FINDINGS: By combining RT-PCR and immunoblot assays, we found that PALS1 is constitutively expressed in human T lymphocytes as well as in Jurkat T cells.
+We further provide evidence that PALS1 depletion selectively hindered TCR-driven activation of the transcription factor NF-κB.
+CONCLUSIONS: The cell polarity protein PALS1 is expressed in T lymphocytes and participates to the optimal activation of NF-κB following TCR stimulation.
+BACKGROUND: Swine origin influenza A/H1N1 infection (H1N1) emerged in early 2009 and rapidly spread to humans.
+For most infected individuals, symptoms were mild and self-limited; however, a small number developed a more severe clinical syndrome characterized by profound respiratory failure with hospital mortality ranging from 10 to 30%.
+While supportive care and neuraminidase inhibitors are the main treatment for influenza, data from observational and interventional studies suggest that the course of influenza can be favorably influenced by agents not classically considered as influenza treatments.
+Multiple observational studies have suggested that HMGCoA reductase inhibitors (statins) can exert a class effect in attenuating inflammation.
+The Collaborative H1N1 Adjuvant Treatment (CHAT) Pilot Trial sought to investigate the feasibility of conducting a trial during a global pandemic in critically ill patients with H1N1 with the goal of informing the design of a larger trial powered to determine impact of statins on important outcomes.
+METHODS/DESIGN: A multi-national, pilot randomized controlled trial (RCT) of once daily enteral rosuvastatin versus matched placebo administered for 14 days for the treatment of critically ill patients with suspected, probable or confirmed H1N1 infection.
+We propose to randomize 80 critically ill adults with a moderate to high index of suspicion for H1N1 infection who require mechanical ventilation and have received antiviral therapy for ≤ 72 hours.
+We propose several approaches to informed consent including a priori consent from the substitute decision maker (SDM), waived and deferred consent.
+The primary outcome of the CHAT trial is the proportion of eligible patients enrolled in the study.
+Secondary outcomes will evaluate adherence to medication administration regimens, the proportion of primary and secondary endpoints collected, the number of patients receiving open-label statins, consent withdrawals and the effect of approved consent models on recruitment rates.
+DISCUSSION: Several aspects of study design including the need to include central randomization, preserve allocation concealment, ensure study blinding compare to a matched placebo and the use novel consent models pose challenges to investigators conducting pandemic research.
+Moreover, study implementation requires that trial design be pragmatic and initiated in a short time period amidst uncertainty regarding the scope and duration of the pandemic.
+Influenza A virus (IAV) enters host cells upon binding of its hemagglutinin glycoprotein to sialylated host cell receptors.
+Whereas dynamin-dependent, clathrin-mediated endocytosis (CME) is generally considered as the IAV infection pathway, some observations suggest the occurrence of an as yet uncharacterized alternative entry route.
+By manipulating entry parameters we established experimental conditions that allow the separate analysis of dynamin-dependent and -independent entry of IAV.
+Whereas entry of IAV in phosphate-buffered saline could be completely inhibited by dynasore, a specific inhibitor of dynamin, a dynasore-insensitive entry pathway became functional in the presence of fetal calf serum.
+Under these conditions entry could be fully blocked by combined treatment with dynasore and the amiloride derivative EIPA, the hallmark inhibitor of macropinocytosis, whereas either drug alone had no effect.
+The sensitivity of the dynamin-independent entry pathway to inhibitors or dominant-negative mutants affecting actomyosin dynamics as well as to a number of specific inhibitors of growth factor receptor tyrosine kinases and downstream effectors thereof all point to the involvement of macropinocytosis in IAV entry.
+Consistently, IAV particles and soluble FITC-dextran were shown to co-localize in cells in the same vesicles.
+Thus, in addition to the classical dynamin-dependent, clathrin-mediated endocytosis pathway, IAV enters host cells by a dynamin-independent route that has all the characteristics of macropinocytosis.
+BACKGROUND: One of the early events in midgut epithelial cells of Aedes aegypti mosquitoes is the dynamic reorganization of rough endoplasmic reticulum (RER) whorl structures coincident with the onset of blood meal digestion.
+Based on our previous studies showing that feeding on an amino acid meal induces TOR signaling in Ae.
+aegypti, we used proteomics and RNAi to functionally identify midgut epithelial cell proteins that contribute to RER whorl formation.
+aegypti mosquitoes were maintained on sugar alone (unfed), or fed an amino acid meal, and then midgut epithelial cells were analyzed by electron microscopy and protein biochemistry.
+The size and number of RER whorls in midgut epithelial cells were found to decrease significantly after feeding, and several KDEL-containing proteins were shown to have altered expression levels.
+LC-MS/MS mass spectrometry was used to analyze midgut microsomal proteins isolated from unfed and amino acid fed mosquitoes, and of the 127 proteins identified, 8 were chosen as candidate whorl forming proteins.
+Three candidate proteins were COPI coatomer subunits (alpha, beta, beta'), all of which appeared to be present at higher levels in microsomal fractions from unfed mosquitoes.
+Using RNAi to knockdown alpha-COPI expression, electron microscopy revealed that both the size and number of RER whorls were dramatically reduced in unfed mosquitoes, and moreover, that extended regions of swollen RER were prevalent in fed mosquitoes.
+Lastly, while a deficiency in alpha-COPI had no effect on early trypsin protein synthesis or secretion 3 hr post blood meal (PBM), expression of late phase proteases at 24 hr PBM was completely blocked.
+CONCLUSIONS: alpha-COPI was found to be required for the formation of RER whorls in midgut epithelial cells of unfed Aa.
+Human embryonic stem cells differentiated under mesoderm-inducing conditions have important therapeutic properties in sepsis-induced lung injury in mice.
+1 hour after cecal ligation and puncture significantly reduced lung inflammation and edema as well as production of tumor necrosis factor-α and interferon-γ in lungs compared with controls, whereas interleukin-10 production remained elevated.
+The protection was ascribed to d7EB cell interaction with lung resident CD11b+ cells, and was correlated with the ability of d7EB cells to reduce it also reduced production of proinflammatory cytokines by CD11+ cells, and to endothelial NO synthase–derived NO by d7EB cells, leading to inhibition of inducible macrophage-type NO synthase activation in CD11b+ cells.
+The protective progenitor cells were positive for the endothelial and hematopoietic lineage marker angiotensin converting enzyme (ACE).
+Only the ACE+ fraction modulated the proinflammatory profile of CD11b+ cells and reduced mortality in septic mice.
+These findings suggest that an ACE+ subset of human embryonic stem cell–derived progenitor cells has a highly specialized anti-inflammatory function that ameliorates sepsis-induced lung inflammation and reduces mortality.
+Lack of life-long immunity against influenza viruses represents a major global health care problem with profound medical and economic consequences.
+A greater understanding of the broad-spectrum “heterosubtypic” neutralizing human antibody (BnAb) response to influenza should bring us closer toward a universal influenza vaccine.
+Serum samples obtained from 77 volunteers in an H5N1 vaccine study were analyzed for cross-reactive antibodies (Abs) against both subtype hemagglutinins (HAs) and a highly conserved pocket on the HA stem of Group 1 viruses.
+Cross-reactive Abs in commercial intravenous immunoglobulin were affinity purified using H5-coupled beads followed by step-wise monoclonal antibody competition or acid elution.
+Enzyme-linked immunosorbent assays were used to quantify cross-binding, and neutralization activity was determined with HA-pseudotyped viruses.
+Prevaccination serum samples have detectable levels of heterosubtypic HA binding activity to both Group 1 and 2 influenza A viruses, including subtypes H5 and H7, respectively, to which study subjects had not been vaccinated.
+Two different populations of Broadly neutralizing Abs (BnAbs) were purified from intravenous immunoglobulin by H5 beads: ∼0.01% of total immunoglobulin G can bind to HAs from both Group 1 and 2 and neutralize H1N1 and H5N1 viruses; ∼0.001% is F10-like Abs directed against the HA stem pocket on Group 1 viruses.
+These data—to our knowledge, for the first time—quantitatively show the presence, albeit at low levels, of two populations of heterosubtypic BnAbs against influenza A in human serum.
+These observations warrant further investigation to determine their origin, host polymorphism(s) that may affect their expression levels and how to boost these BnAb responses by vaccination to reach sustainable protective levels.
+Studying membrane active peptides or protein fragments within the lipid bilayer environment is particularly challenging in the case of synthetically modified, labeled, artificial, or recently discovered native structures.
+For such samples the localization and orientation of the molecular species or probe within the lipid bilayer environment is the focus of research prior to an evaluation of their dynamic or mechanistic behavior.
+X-ray scattering is a powerful method to study peptide/lipid interactions in the fluid, fully hydrated state of a lipid bilayer.
+For one, the lipid response can be revealed by observing membrane thickening and thinning as well as packing in the membrane plane; at the same time, the distinct positions of peptide moieties within lipid membranes can be elucidated at resolutions of up to several angstroms by applying heavy-atom labeling techniques.
+In this study, we describe a generally applicable X-ray scattering approach that provides robust and quantitative information about peptide insertion and localization as well as peptide/lipid interaction within highly oriented, hydrated multilamellar membrane stacks.
+To this end, we have studied an artificial, designed β-helical peptide motif in its homodimeric and hairpin variants adopting different states of oligomerization.
+These peptide lipid complexes were analyzed by grazing incidence diffraction (GID) to monitor changes in the lateral lipid packing and ordering.
+In addition, we have applied anomalous reflectivity using synchrotron radiation as well as in-house X-ray reflectivity in combination with iodine-labeling in order to determine the electron density distribution ρ(z) along the membrane normal (z axis), and thereby reveal the hydrophobic mismatch situation as well as the position of certain amino acid side chains within the lipid bilayer.
+In the case of multiple labeling, the latter technique is not only applicable to demonstrate the peptide’s reconstitution but also to generate evidence about the relative peptide orientation with respect to the lipid bilayer.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00249-010-0645-4) contains supplementary material, which is available to authorized users.
+Nipah virus (NiV) was first recognized in 1998 in a zoonotic disease outbreak associated with highly lethal febrile encephalitis in humans and a predominantly respiratory disease in pigs.
+Periodic deadly outbreaks, documentation of person-to-person transmission, and the potential of this virus as an agent of agroterror reinforce the need for effective means of therapy and prevention.
+The VLPs were composed of all the three viral proteins as designed, and their intracellular processing also appeared similar to NiV virions.
+The size, morphology and surface composition of the VLPs were consistent with the parental virus, and importantly, they retained their antigenic potential.
+Finally, these particles, formulated without adjuvant, were able to induce neutralizing antibody response in Balb/c mice.
+These findings indicate vaccine potential of these particles and will be the basis for undertaking future protective efficacy studies in animal models of NiV disease.
+PURPOSE: To generate and characterize a specific monoclonal antibody (mAb) against recombinant human RANK receptor and to develop an antiresorptive strategy using this mAb as an osteoclast-targeting platform that selectively targets osteoclast cells whilst delivering an attached (i.e.
+METHODS: Using hybridoma technology, we generated a specific monoclonal antibody (mAb) against recombinant human RANK receptor and characterized by SDS PAGE, ELISA, Western Blot and immunocytochemistry, then synthesized osteoclast-targeting bioconjugates of salmon calcitonin (sCT) using this antibody by generating thiol groups on mAb using 2-Iminothiolane and subsequently reacting them with sCT-PEG-MAL synthesised from sCT and NHS-PEG-MAL.
+To test the efficacy of the conjugate in vitro, osteoclasts were generated from precursor RAW 264.7 cells by dosing with the cytokines macrophage-colony-stimulating factor (M-CSF), and RANK Ligand (RANKL) and TRAP activity assay, Resorption Pit Assay, TRAP staining were performed.
+Cytotoxicity of the mAb-sCT conjugate was also evaluated in RAW 264.7 cells; sCT bioactivity and CTR binding potential were evaluated by in vitro intracellular cAMP stimulation assay in human T47D breast cancer cells.
+RESULTS: Generation of antibody against human RANK receptor was confirmed by SDS PAGE, ELISA and Western Blot.
+Successful conjugation of the antibody with sCT was confirmed by SDS PAGE and ELISA.Multinucleated osteoclast formation was confirmed by staining for tartrate-resistant acid phosphatase (TRAP).
+Conjugate functionality was confirmed by TRAP activity and Resorption Pit assay, showing the inhibitory effect on osteoclast differentiation.
+CONCLUSIONS: Our strategy offers the potential for a “universal” osteoclast-targeting platform—one that targets the RANK receptor on osteoclast cells by simply altering the conjugated cargo in order to affect the specific regulation of osteoclast cells.
+New Delhi metallo-beta-lactamase (NDM-1) is an enzyme that makes bacteria resistant to a broad range of beta-lactam antibiotic drugs.
+With such a structural frame, two enzyme-ligand complexes were derived by respectively docking Imipenem and Meropenem (two typical beta-lactam antibiotic drugs) to the NDM-1 receptor.
+It was revealed from the NDM-1/Imipenem complex that the antibiotic drug was hydrolyzed while sitting in a binding pocket of NDM-1 formed by nine residues.
+And for the case of NDM-1/Meropenem complex, the antibiotic drug was hydrolyzed in a binding pocket formed by twelve residues.
+All these constituent residues of the two binding pockets were explicitly defined and graphically labeled.
+It is anticipated that the findings reported here may provide useful insights for developing new antibiotic drugs to overcome the resistance problem.
+The family of type I interferons (IFN), which consists of several IFN-α and one IFN-β, are produced not only after stimulation by viruses, but also after infection with non-viral pathogens.
+IFN-β is the primary member of type I IFN that initiates a cascade of IFN-α production.
+Here we addressed the question which cells are responsible for IFN-β expression after infection with the intracellular pathogen Listeria monocytogenes by using a genetic approach.
+By means of newly established reporter mice, maximum of IFN-β expression was observed at 24 hours post infection in spleen and, surprisingly, 48 hours post infection in colonized cervical and inguinal lymph nodes.
+Colonization of lymph nodes was independent of the type I IFN signaling, as well as bacterial dose and strain.
+Using cell specific reporter function and conditional deletions we could define cells expressing LysM as the major IFN-β producers, with cells formerly defined as Tip-DCs being the highest.
+Neutrophilic granulocytes, dendritic cells and plasmacytoid dendritic cells did not significantly contribute to type I IFN production.
+Although first discovered in viruses, previous studies have identified operational −1 ribosomal frameshifting (−1 RF) signals in eukaryotic genomic sequences, and suggested a role in mRNA stability.
+Here, four yeast −1 RF signals are shown to promote significant mRNA destabilization through the nonsense mediated mRNA decay pathway (NMD), and genetic evidence is presented suggesting that they may also operate through the no-go decay pathway (NGD) as well.
+Ablation of the −1 RF signals or of NMD stabilizes this mRNA, and changes in −1 RF efficiency have opposing effects on the steady-state abundance of the EST2 mRNA.
+These results demonstrate that endogenous −1 RF signals function as mRNA destabilizing elements through at least two molecular pathways in yeast.
+Consistent with current evolutionary theory, phylogenetic analyses suggest that −1 RF signals are rapidly evolving cis-acting regulatory elements.
+Identification of high confidence −1 RF signals in ∼10% of genes in all eukaryotic genomes surveyed suggests that −1 RF is a broadly used post-transcriptional regulator of gene expression.
+BACKGROUND: Fully human monoclonal antibodies directed against specific pathogens have a high therapeutic potential, but are difficult to generate.
+METHODOLOGY/PRINCIPAL FINDINGS: Memory B cells were immortalized by expressing an inducible active mutant of the transcription factor Signal Transducer and Activator of Transcription 5 (STAT5).
+We obtained cloned B cell lines, which produced antibodies in the presence of interleukin 21 after turning off STAT5.
+CONCLUSIONS/SIGNIFICANCE: Here we describe a novel and relatively simple method of immortalizing antigen-specific human B cells for isolation of human monoclonal antibodies.
+These results show that STAT5 overexpression can be employed to isolate antigen specific antibodies from human memory B cells.
+Using random PCR amplification followed by plasmid subcloning and DNA sequencing, we detected bocavirus related sequences in 9 out of 17 porcine stool samples.
+Using primer walking, we sequenced the nearly complete genomes of two highly divergent bocaviruses we provisionally named porcine bocavirus 1 isolate H18 (PBoV1-H18) and porcine bocavirus 2 isolate A6 (PBoV2-A6) which differed by 51.8% in their NS1 protein.
+Phylogenetic analysis indicated that PBoV1-H18 was very closely related to a ∼2 Kb central region of a porcine bocavirus-like virus (PBo-LikeV) from Sweden described in 2009.
+PBoV2-A6 was very closely related to the porcine bocavirus genomes PBoV-1 and PBoV2 from China described in 2010.
+Among 340 fecal samples collected from different age, asymptomatic swine in five Chinese provinces, the prevalence of PBoV1-H18 and PBoV2-A6 related viruses were 45–75% and 55–70% respectively, with 30–47% of pigs co-infected.
+PBoV1-A6 related strains were highly conserved, while PBoV2-H18 related strains were more diverse, grouping into two genotypes corresponding to the previously described PBoV1 and PBoV2.
+Together with the recently described partial bocavirus genomes labeled V6 and V7, a total of three major porcine bocavirus clades have therefore been described to date.
+Further studies will be required to elucidate the possible pathogenic impact of these diverse bocaviruses either alone or in combination with other porcine viruses.
+BACKGROUND: Poliovirus, the causative agent of poliomyelitis, is a human enterovirus and a member of the family of Picornaviridae and among the most rapidly evolving viruses known.
+However, little information about synonymous codon usage pattern of polioviruses genome has been acquired to date.
+METHODS: The relative synonymous codon usage (RSCU) values, effective number of codon (ENC) values, nucleotide contents and dinucleotides were investigated and a comparative analysis of codon usage pattern for open reading frames (ORFs) among 48 polioviruses isolates including 31 of genotype 1, 13 of genotype 2 and 4 of genotype 3.
+RESULTS: The result shows that the overall extent of codon usage bias in poliovirus samples is low (mean ENC = 53.754 > 40).
+The general correlation between base composition and codon usage bias suggests that mutational pressure rather than natural selection is the main factor that determines the codon usage bias in those polioviruses.
+Depending on the RSCU data, it was found that there was a significant variation in bias of codon usage among three genotypes.
+Geographic factor also has some effect on the codon usage pattern (exists in the genotype-1 of polioviruses).
+No significant effect in gene length or vaccine derived polioviruses (DVPVs), wild viruses and live attenuated virus was observed on the variations of synonymous codon usage in the virus genes.
+The relative abundance of dinucleotide (CpG) in the ORFs of polioviruses are far below expected values especially in DVPVs and attenuated virus of polioviruses genotype 1.
+CONCLUSION: The information from this study may not only have theoretical value in understanding poliovirus evolution, especially for DVPVs genotype 1, but also have potential value for the development of poliovirus vaccines.
+BACKGROUND: Simian hemorrhagic fever virus (SHFV) has caused lethal outbreaks of hemorrhagic disease in captive primates, but its distribution in wild primates has remained obscure.
+Here, we describe the discovery and genetic characterization by direct pyrosequencing of two novel, divergent SHFV variants co-infecting a single male red colobus monkey from Kibale National Park, Uganda.
+METHODOLOGY/PRINCIPAL FINDINGS: The viruses were detected directly from blood plasma using pyrosequencing, without prior virus isolation and with minimal PCR amplification.
+The two new SHFV variants, SHFV-krc1 and SHFV-krc2 are highly divergent from each other (51.9% nucleotide sequence identity) and from the SHFV type strain LVR 42-0/M6941 (52.0% and 51.8% nucleotide sequence identity, respectively) and demonstrate greater phylogenetic diversity within SHFV than has been documented within any other arterivirus.
+Both new variants nevertheless have the same 3′ genomic architecture as the type strain, containing three open reading frames not present in the other arteriviruses.
+CONCLUSIONS/SIGNIFICANCE: These results represent the first documentation of SHFV in a wild primate and confirm the unusual 3′ genetic architecture of SHFV relative to the other arteriviruses.
+They also demonstrate a degree of evolutionary divergence within SHFV that is roughly equivalent to the degree of divergence between other arterivirus species.
+The presence of two such highly divergent SHFV variants co-infecting a single individual represents a degree of within-host viral diversity that exceeds what has previously been reported for any arterivirus.
+These results expand our knowledge of the natural history and diversity of the arteriviruses and underscore the importance of wild primates as reservoirs for novel pathogens.
+Avian influenza surveillance in Bangladesh has been passive, relying on poultry farmers to report suspected outbreaks of highly pathogenic H5N1 influenza.
+Here, the results of an active surveillance effort focusing on the live-bird markets are presented.
+Prevalence of influenza infection in the birds of the live bird markets is 23.0%, which is similar to that in poultry markets in other countries.
+Nearly all of the isolates (94%) were of the non-pathogenic H9N2 subtype, but viruses of the H1N2, H1N3, H3N6, H4N2, H5N1, and H10N7 subtypes were also observed.
+The highly pathogenic H5N1-subtype virus was observed at extremely low prevalence in the surveillance samples (0.08%), and we suggest that the current risk of infection for humans in the retail poultry markets in Bangladesh is negligible.
+However, the high prevalence of the H9 subtype and its potential for interaction with the highly pathogenic H5N1-subtype, i.e., reassortment and attenuation of host morbidity, highlight the importance of active surveillance of the poultry markets.
+BACKGROUND: Google Flu Trends was developed to estimate US influenza-like illness (ILI) rates from internet searches; however ILI does not necessarily correlate with actual influenza virus infections.
+METHODS AND FINDINGS: Influenza activity data from 2003–04 through 2007–08 were obtained from three US surveillance systems: Google Flu Trends, CDC Outpatient ILI Surveillance Network (CDC ILI Surveillance), and US Influenza Virologic Surveillance System (CDC Virus Surveillance).
+Pearson's correlation coefficients with 95% confidence intervals (95% CI) were calculated to compare surveillance data.
+An analysis was performed to investigate outlier observations and determine the extent to which they affected the correlations between surveillance data.
+Pearson's correlation coefficient describing Google Flu Trends and CDC Virus Surveillance over the study period was 0.72 (95% CI: 0.64, 0.79).
+The correlation between CDC ILI Surveillance and CDC Virus Surveillance over the same period was 0.85 (95% CI: 0.81, 0.89).
+Exclusion of the outlier observations did not substantially improve the correlation between Google Flu Trends and CDC Virus Surveillance (0.82; 95% CI: 0.76, 0.87) or CDC ILI Surveillance and CDC Virus Surveillance (0.86; 95%CI: 0.82, 0.90).
+CONCLUSIONS: This analysis demonstrates that while Google Flu Trends is highly correlated with rates of ILI, it has a lower correlation with surveillance for laboratory-confirmed influenza.
+Most of the outlier observations occurred during the 2003–04 influenza season that was characterized by early and intense influenza activity, which potentially altered health care seeking behavior, physician testing practices, and internet search behavior.
+While there has been much focus on T cell-mediated immune responses, limited knowledge exists on the role of mature B cells.
+We describe an approach, including a cell-based ELISA, to evaluate mature IgG antibody responses to melanoma from human peripheral blood B cells.
+We observed a significant increase in antibody responses from melanoma patients (n = 10) to primary and metastatic melanoma cells compared to healthy volunteers (n = 10) (P<0.0001).
+Interestingly, we detected a significant reduction in antibody responses to melanoma with advancing disease stage in our patient cohort (n = 21) (P<0.0001).
+Overall, 28% of melanoma patient-derived B cell cultures (n = 1,800) compared to 2% of cultures from healthy controls (n = 600) produced antibodies that recognized melanoma cells.
+These data demonstrate the presence of a mature systemic B cell response in melanoma patients, which is reduced with disease progression, adding to previous reports of tumor-reactive antibodies in patient sera, and suggesting the merit of future work to elucidate the clinical relevance of activating humoral immune responses to cancer.
+Abrogation is achieved by cleavage of both eIF4GI and eIF4GII by the viral protease 2A.
+Apart from the interference of poliovirus with cellular protein synthesis, other gene expression steps such as RNA and protein trafficking between nucleus and cytoplasm are also altered.
+Poliovirus 2A(pro) is capable of hydrolyzing components of the nuclear pore, thus preventing an efficient antiviral response by the host cell.
+Here, we compare in detail poliovirus 2A(pro) with other viral proteins (from picornaviruses and unrelated families) as regard to their activity on key host factors that control gene expression.
+It is possible that future analyses to determine the cellular proteins targeted by 2A(pro) will uncover other cellular functions ablated by poliovirus infection.
+Further understanding of the cellular proteins hydrolyzed by 2A(pro) will add further insight into the molecular mechanism by which poliovirus and other viruses interact with the host cell.
+During summer 2007 Italy has experienced an epidemic caused by Chikungunya virus – the first large outbreak documented in a temperate climate country – with approximately 161 laboratory confirmed cases concentrated in two bordering villages in North–Eastern Italy comprising 3,968 inhabitants.
+In this work we provide estimates of the transmission potential of the virus and we assess the efficacy of the measures undertaken by public health authorities to control the epidemic spread.
+To such aim, we developed a model describing the temporal dynamics of the competent vector, known as Aedes albopictus, explicitly depending on climatic factors, coupled to an epidemic transmission model describing the spread of the epidemic in both humans and mosquitoes.
+The cumulative number of notified cases predicted by the model was 185 on average (95% CI 117–278), in good agreement with observed data.
+The probability of observing a major outbreak after the introduction of an infective human case was estimated to be in the range of 32%–76%.
+We found that the basic reproduction number was in the range of 1.8–6 but it could have been even larger, depending on the density of mosquitoes, which in turn depends on seasonal meteorological effects, besides other local abiotic factors.
+These results confirm the increasing risk of tropical vector–borne diseases in temperate climate countries, as a consequence of globalization.
+However, our results show that an epidemic can be controlled by performing a timely intervention, even if the transmission potential of Chikungunya virus is sensibly high.
+BACKGROUND: Genetic polymorphisms in the gene encoding the β-adrenergic receptors (β-AR) have a pivotal role in the functions of the autonomic nervous system.
+Using heart rate variability (HRV) as an indicator of autonomic function, we present a bottom-up genotype–phenotype analysis to investigate the association between β-AR gene polymorphisms and heart rate dynamics.
+METHODS: A total of 221 healthy Han Chinese adults (59 males and 162 females, aged 33.6±10.8 years, range 19 to 63 years) were recruited and genotyped for three common β-AR polymorphisms: β(1)-AR Ser49Gly, β(2)-AR Arg16Gly and β(2)-AR Gln27Glu.
+We applied an information-based similarity (IBS) index to measure the pairwise dissimilarity of heart rate dynamics among study subjects.
+RESULTS: With the aid of agglomerative hierarchical cluster analysis, we categorized subjects into major clusters, which were found to have significantly different distributions of β(2)-AR Arg16Gly genotype.
+Furthermore, the non-randomness index, a nonlinear HRV measure derived from the IBS method, was significantly lower in Arg16 homozygotes than in Gly16 carriers.
+The non-randomness index was negatively correlated with parasympathetic-related HRV variables and positively correlated with those HRV indices reflecting a sympathovagal shift toward sympathetic activity.
+CONCLUSIONS: We demonstrate a bottom-up categorization approach combining the IBS method and hierarchical cluster analysis to detect subgroups of subjects with HRV phenotypes associated with β-AR polymorphisms.
+Our results provide evidence that β(2)-AR polymorphisms are significantly associated with the acceleration/deceleration pattern of heart rate oscillation, reflecting the underlying mode of autonomic nervous system control.
+Sialic acids (SAs) linked to galactose (Gal) in α2,3- and α2,6-configurations are the receptors for avian and human influenza viruses, respectively.
+We demonstrate that chicken tracheal ciliated cells express α2,3-linked SA, while goblet cells mainly express α2,6-linked SA.
+In addition, the plant lectin MAL-II, but not MAA/MAL-I, is bound to the surface of goblet cells, suggesting that SA2,3-linked oligosaccharides with Galβ1–3GalNAc subterminal residues are specifically present on the goblet cells.
+At a low multiplicity of infection (MOI) avian influenza virus H6N1 is exclusively detected in the ciliated cells, suggesting that the ciliated cell is the major target cell of the H6N1 virus.
+At a MOI of 1, ciliated, goblet and basal cells are all permissive to the AIV infection.
+This result clearly elucidates the receptor distribution for the avian influenza virus among chicken tracheal epithelial cells and illustrates a primary cell model for evaluating the cell tropisms of respiratory viruses in poultry.
+BACKGROUND: Viral zoonosis, the transmission of a virus from its primary vertebrate reservoir species to humans, requires ubiquitous cellular proteins known as receptor proteins.
+Zoonosis can occur not only through direct transmission from vertebrates to humans, but also through intermediate reservoirs or other environmental factors.
+Among them, the RNA viruses exhibit particularly high mutation rates and are especially problematic for this reason.
+Most zoonotic viruses are RNA viruses that change their envelope proteins to facilitate binding to various receptors of host species.
+In this study, we sought to predict zoonotic propensity through the analysis of receptor characteristics.
+We hypothesized that the major barrier to interspecies virus transmission is that receptor sequences vary among species--in other words, that the specific amino acid sequence of the receptor determines the ability of the viral envelope protein to attach to the cell.
+We then analysed these properties for similarities among receptors of different species and used a statistical discriminant analysis to predict the likelihood of transmission among species.
+CONCLUSIONS: This study is an attempt to predict zoonosis through simple computational analysis of receptor sequence differences.
+Our method may be useful in predicting the zoonotic potential of newly discovered viral strains.
+BACKGROUND: Molecular assays targeted to nucleic acid (NA) markers are becoming increasingly important to medical diagnostics.
+However, these are typically confined to wealthy, developed countries; or, to the national reference laboratories of developing-world countries.
+There are many infectious diseases that are endemic in low-resource settings (LRS) where the lack of simple, instrument-free, NA diagnostic tests is a critical barrier to timely treatment.
+One of the primary barriers to the practicality and availability of NA assays in LRS has been the complexity and power requirements of polymerase chain reaction (PCR) instrumentation (another is sample preparation).
+METHODOLOGY/PRINCIPAL FINDINGS: In this article, we investigate the hypothesis that an electricity-free heater based on exothermic chemical reactions and engineered phase change materials can successfully incubate isothermal NA amplification assays.
+We assess the heater's equivalence to commercially available PCR instruments through the characterization of the temperature profiles produced, and a minimal method comparison.
+CONCLUSIONS/SIGNIFICANCE: We demonstrate that an electricity-free heater based on exothermic chemical reactions and engineered phase change materials can successfully incubate isothermal NA amplification assays, and that the results of those assays are not significantly different from ones incubated in parallel in commercially available PCR instruments.
+These results clearly suggest the potential of the non-instrumented nucleic acid amplification (NINA) heater for molecular diagnostics in LRS.
+When combined with other innovations in development that eliminate power requirements for sample preparation, cold reagent storage, and readout, the NINA heater will comprise part of a kit that should enable electricity-free NA testing for many important analytes.
+Influenza A viruses are important pathogens that cause acute respiratory diseases and annual epidemics in humans.
+Macrophages recognize influenza A virus infection with their pattern recognition receptors, and are involved in the activation of proper innate immune response.
+Here, we have used high-throughput subcellular proteomics combined with bioinformatics to provide a global view of host cellular events that are activated in response to influenza A virus infection in human primary macrophages.
+We show that viral infection regulates the expression and/or subcellular localization of more than one thousand host proteins at early phases of infection.
+Our data reveals that there are dramatic changes in mitochondrial and nuclear proteomes in response to infection.
+We show that a rapid cytoplasmic leakage of lysosomal proteins, including cathepsins, followed by their secretion, contributes to inflammasome activation and apoptosis seen in the infected macrophages.
+Also, our results demonstrate that P2X(7) receptor and src tyrosine kinase activity are essential for inflammasome activation during influenza A virus infection.
+Finally, we show that influenza A virus infection is associated with robust secretion of different danger-associated molecular patterns (DAMPs) suggesting an important role for DAMPs in host response to influenza A virus infection.
+In conclusion, our high-throughput quantitative proteomics study provides important new insight into host-response against influenza A virus infection in human primary macrophages.
+Accumulating evidence shows that ACE2 provides protective effects in peripheral tissues and has great potential for the treatment of RAS-related diseases.
+However, in recent years, much more progress has been made on the studies of this carboxypeptidase in the central regulation of blood pressure and cardiovascular function in general.
+It has been shown that brain ACE2 interacts with the other components of the RAS (ACE, angiotensin II, and angiotensin II type 1 receptor), protects baroreflex and autonomic function, stimulates nitric oxide release, reduces oxidative stress, and prevents the development of or attenuates hypertension.
+These data support the critical role of ACE2 in the central regulation of cardiovascular function.
+This review summarizes recently published data on the central effects of ACE2 in the regulation of cardiovascular function.
+Therapeutic targeting of host cell factors required for virus replication rather than of pathogen components opens new perspectives to counteract virus infections.
+Anticipated advantages of this approach include a heightened barrier against the development of viral resistance and a broadened pathogen target spectrum.
+Myxoviruses are predominantly associated with acute disease and thus are particularly attractive for this approach since treatment time can be kept limited.
+To identify inhibitor candidates, we have analyzed hit compounds that emerged from a large-scale high-throughput screen for their ability to block replication of members of both the orthomyxovirus and paramyxovirus families.
+This has returned a compound class with broad anti-viral activity including potent inhibition of different influenza virus and paramyxovirus strains.
+After hit-to-lead chemistry, inhibitory concentrations are in the nanomolar range in the context of immortalized cell lines and human PBMCs.
+Antiviral activity is host-cell species specific and most pronounced in cells of higher mammalian origin, supporting a host-cell target.
+While the compound induces a temporary cell cycle arrest, host mRNA and protein biosynthesis are largely unaffected and treated cells maintain full metabolic activity.
+Viral replication is blocked at a post-entry step and resembles the inhibition profile of a known inhibitor of viral RNA-dependent RNA-polymerase (RdRp) activity.
+Direct assessment of RdRp activity in the presence of the reagent reveals strong inhibition both in the context of viral infection and in reporter-based minireplicon assays.
+In toto, we have identified a compound class with broad viral target range that blocks host factors required for viral RdRp activity.
+Viral adaptation attempts did not induce resistance after prolonged exposure, in contrast to rapid adaptation to a pathogen-directed inhibitor of RdRp activity.
+BACKGROUND: The scavenging ability of sufficient divalent metal ions is pivotal for pathogenic bacteria to survive in the host.
+ATP-binding cassette (ABC)-type metal transporters provide a considerable amount of different transition metals for bacterial growth.
+However, the function and structure of the TroA homologue from the epidemic Streptococcus suis isolates (SsTroA) have not been characterized.
+METHODOLOGY/PRINCIPAL FINDINGS: Here we determined the crystal structure of SsTroA from a highly pathogenic streptococcal toxic shock syndrome (STSS)-causing Streptococcus suis in complex with zinc.
+Both metals bind to SsTroA with nanomolar affinity and stabilize the protein against thermal unfolding.
+Zn(2+) and Mn(2+) induce distinct conformational changes in SsTroA compared with the apo form as confirmed by both circular dichroism (CD) and nuclear magnetic resonance (NMR) spectra.
+NMR data also revealed that Zn(2+)/Mn(2+) bind to SsTroA in either the same site or an adjacent region.
+Finally, we found that the folding of the metal-bound protein is more compact than the corresponding apoprotein.
+CONCLUSIONS/SIGNIFICANCE: Our findings reveal a mechanism for uptake of metal ions in S. suis and this mechanism provides a reasonable explanation as to how SsTroA operates in metal transport.
+Although the ecological importance of coinfection is increasingly recognized, analyses of microbial pathogen dynamics in wildlife usually focus on an ad hoc subset of the species present due to technological limitations on detection.
+Here we demonstrate the use of expression profiles for immunological genes (pattern recognition receptors, cytokines and transcription factors) as a means to identify, without preconception, the likelihood of important acute microbial infections in wildlife.
+Using a wood mouse population in the UK as a model we identified significant temporal clusters of individuals with extreme expression of immunological mediators across multiple loci, typical of an acute microbial infection.
+Animals in one cluster also had significantly higher individual macroparasite burdens than contemporaries with “normal” expression patterns.
+If the extreme transcriptional profiles observed are induced by an infectious agent then this implicates macroparasites as a possible player in mediating individual susceptibility or resilience to infection.
+The form of survey described here, combined with next generation nucleic acids sequencing methods for the broad detection of microbial infectious agents in individuals with anomalous immunological transcriptional profiles, could be a powerful tool for revealing unrecognized, ecologically important infectious agents circulating in wildlife populations.
+To gain a better understanding of the relationship between perkinsids, dinoflagellates and other alveolates, we analyzed the nuclear-encoded spliced-leader (SL) RNA and mitochondrial genes, intron prevalence, and multi-protein phylogenies.
+In contrast to the canonical 22-nt SL found in dinoflagellates (DinoSL), P. marinus has a shorter (21-nt) and a longer (22-nt) SL with slightly different sequences than DinoSL.
+The major SL RNA transcripts range in size between 80–83 nt in P. marinus, and ∼83 nt in P. chesapeaki, significantly larger than the typical ≤56-nt dinoflagellate SL RNA.
+In most of the phylogenetic trees based on 41 predicted protein sequences, P. marinus branched at the base of the dinoflagellate clade that included the ancient taxa Oxyrrhis and Amoebophrya, sister to the clade of apicomplexans, and in some cases clustered with apicomplexans as a sister to the dinoflagellate clade.
+mitochondrial cytochrome B and cytochrome C oxidase subunit I genes and their cDNAs revealed no mRNA editing, but these transcripts can only be translated when frameshifts are introduced at every AGG and CCC codon as if AGGY codes for glycine and CCCCU for proline.
+These results, along with the presence of the numerous uncharacterized ‘marine alveolate group I' and Perkinsus-like lineages separating perkinsids from core dinoflagellates, expand support for the affiliation of the genus Perkinsus with an independent lineage (Perkinsozoa) positioned between the phyla of Apicomplexa and Dinoflagellata.
+The presence of turkey astrovirus (TAstV) was monitored in meat-type turkey flocks in Poland in 2008.
+Clinical samples (10 individual faecal swabs/flock) from 77 flocks aged 1-19 weeks were collected from different regions of the country.
+RT-PCR experiments were performed for detection and molecular characterization of TAstV using four sets of primers within the RdRp gene (ORF1b).
+TAstV type 2 was associated with 30 of 77 infections (38.9%), either alone or in mixed infections; TAstV type 1 was detected in 9 of 77 flocks (11.6%), either alone or in mixed infections; ANV was detected only in one flock (1.29%) by sequence analysis during this study.
+Some of Polish TAstV-2 strains were genetically related to the North American isolates; however, most of them formed a distinct subgroup of “European” isolates, suggesting their separate origin or evolution.
+Additionally, due to the high variability of the TAstV sequences, the most suitable method for TAstV typing seems to be sequencing.
+Animal experiments indicated that when H1N1 virus infected early hosts, it showed strong CD4(+), CD8(+), and CD4(+)CD25(+ )T cell reactions.
+The aim of this study was to investigate the dynamic fluctuations of the peripheral blood lymphocyte subgroups in patients infected with H1N1 swine-origin influenza A virus (S-OIV).
+METHODS: The frequency of T cells, B cells, natural killer (NK) cells, and regulatory T cells (Treg) in 36 severe H1N1 and 40 moderate H1N1 patients were detected at different periods by flow cytometry.
+In parallel, serum cytokines were detected by enzyme-linked immunosorbent assay and C-reactive protein (CRP) was analyzed through an image-type automatic biochemical analyzer.
+In addition, 20 healthy volunteers, who were not infected with 2009 H1N1 virus, were selected as controls.
+RESULTS: The frequency of NK cells were decreased in all cases and CD19(+ )B cells were increased in severe cases than those of the controls.
+At 1-2d from onset, the frequency of CD4(+ )and CD4(+)CD25(+ )T cells in moderate cases was higher than in the severe cases.
+Serum cytokines, specifically IL-2, IL-4, IL-6, IL-10, and IFN-γ exhibited no significant change both in the moderate and the severe cases during the whole monitoring process.
+In the early stage of the disease, serum CRP levels in the severe and moderate groups were significantly higher than that in the control group.
+CONCLUSIONS: Patients showed different lymphocyte subgroup distributions between mild and severe cases, which might affect the incidence and development of 2009 H1N1.
+We evaluated the association between receipt of inactivated influenza vaccine during pregnancy and prematurity and small for gestational age (SGA) births.
+METHODS AND FINDINGS: We conducted a cohort analysis of surveillance data from the Georgia (United States) Pregnancy Risk Assessment Monitoring System.
+Among 4,326 live births between 1 June 2004 and 30 September 2006, maternal influenza vaccine information was available for 4,168 (96.3%).
+The primary intervention evaluated in this study was receipt of influenza vaccine during any trimester of pregnancy.
+The main outcome measures were prematurity (gestational age at birth <37 wk) and SGA (birth weight <10th percentile for gestational age).
+Infants who were born during the putative influenza season (1 October–31 May) and whose mothers were vaccinated against influenza during pregnancy were less likely to be premature compared to infants of unvaccinated mothers born in the same period (adjusted odds ratio [OR] = 0.60; 95% CI, 0.38–0.94).
+The magnitude of association between maternal influenza vaccine receipt and reduced likelihood of prematurity increased during the period of at least local influenza activity (adjusted OR = 0.44; 95% CI, 0.26–0.73) and was greatest during the widespread influenza activity period (adjusted OR = 0.28; 95% CI, 0.11–0.74).
+Compared with newborns of unvaccinated women, newborns of vaccinated mothers had 69% lower odds of being SGA (adjusted OR = 0.31; 95% CI, 0.13–0.75) during the period of widespread influenza activity.
+CONCLUSIONS: This study demonstrates an association between immunization with the inactivated influenza vaccine during pregnancy and reduced likelihood of prematurity during local, regional, and widespread influenza activity periods.
+Moreover, during the period of widespread influenza activity there was an association between maternal receipt of influenza vaccine and reduced likelihood of SGA birth.
+The Philippines is experiencing a low but slowly growing prevalence of HIV, with a UN estimate of 6,000–11,000 cases out of a population of 91 million, and a 150% increase in new cases in 2008 compared to previous years.
+Earlier education programmes employed non-formal educational training techniques in the southern Philippines to target high-risk groups such as female sex workers and their establishment managers; the effort was expanded to target males in the community.
+In comparison, as of 2009, Taiwan has an estimated 40,000 cases of HIV/AIDS in a population of 23 million.
+It experienced a major increase in HIV infection among injecting drug users, from 77 newly reported cases in 2003 to 2,381 such cases in 2007.
+This article compares and contrasts the response to the epidemic in each country, describing non-formal educational programmes targeted and tailored to specific high-risk populations.
+High-altitude pulmonary edema (HAPE) is a life-threatening disease of high altitude that often affects nonacclimatized apparently healthy individuals who rapidly ascend to high altitude.
+Early detection, early diagnosis, and early treatment are essential to maintain the safety of people who ascend to high altitude, such as construction workers and tourists.
+In this paper, I discuss various methods and criteria that can be used for the early diagnosis and prediction of HAPE.
+My objective is to improve the understanding of HAPE and to highlight the need for prevention, early diagnosis, and early treatment of HAPE to improve the safety of individuals ascending to high altitude.
+Honey bees (Apis mellifera) play a critical role in global food production as pollinators of numerous crops.
+Recently, honey bee populations in the United States, Canada, and Europe have suffered an unexplained increase in annual losses due to a phenomenon known as Colony Collapse Disorder (CCD).
+Epidemiological analysis of CCD is confounded by a relative dearth of bee pathogen field studies.
+To identify what constitutes an abnormal pathophysiological condition in a honey bee colony, it is critical to have characterized the spectrum of exogenous infectious agents in healthy hives over time.
+We conducted a prospective study of a large scale migratory bee keeping operation using high-frequency sampling paired with comprehensive molecular detection methods, including a custom microarray, qPCR, and ultra deep sequencing.
+We established seasonal incidence and abundance of known viruses, Nosema sp., Crithidia mellificae, and bacteria.
+Ultra deep sequence analysis further identified four novel RNA viruses, two of which were the most abundant observed components of the honey bee microbiome (∼10(11) viruses per honey bee).
+Our results demonstrate episodic viral incidence and distinct pathogen patterns between summer and winter time-points.
+Peak infection of common honey bee viruses and Nosema occurred in the summer, whereas levels of the trypanosomatid Crithidia mellificae and Lake Sinai virus 2, a novel virus, peaked in January.
+BACKGROUND: The wintertime co-occurrence of peaks in influenza and invasive pneumococcal disease (IPD) is well documented, but how and whether wintertime peaks caused by these two pathogens are causally related is still uncertain.
+We aimed to investigate the relationship between influenza infection and IPD in Ontario, Canada, using several complementary methodological tools.
+METHODS AND FINDINGS: We evaluated a total number of 38,501 positive influenza tests in Central Ontario and 6,191 episodes of IPD in the Toronto/Peel area, Ontario, Canada, between 1 January 1995 and 3 October 2009, reported through population-based surveillance.
+We assessed the relationship between the seasonal wave forms for influenza and IPD using fast Fourier transforms in order to examine the relationship between these two pathogens over yearly timescales.
+We also used three complementary statistical methods (time-series methods, negative binomial regression, and case-crossover methods) to evaluate the short-term effect of influenza dynamics on pneumococcal risk.
+Annual periodicity with wintertime peaks could be demonstrated for IPD, whereas periodicity for influenza was less regular.
+As for long-term effects, phase and amplitude terms of pneumococcal and influenza seasonal sine waves were not correlated and meta-analysis confirmed significant heterogeneity of influenza, but not pneumococcal phase terms.
+A short-term association between IPD and influenza could be demonstrated for 1-week lags in both case-crossover (odds ratio [95% confidence interval] for one case of IPD per 100 influenza cases = 1.10 [1.02–1.18]) and negative binomial regression analysis (incidence rate ratio [95% confidence interval] for one case of IPD per 100 influenza cases = 1.09 [1.05–1.14]).
+CONCLUSIONS: Our data support the hypothesis that influenza influences bacterial disease incidence by enhancing short-term risk of invasion in colonized individuals.
+The absence of correlation between seasonal waveforms, on the other hand, suggests that bacterial disease transmission is affected to a lesser extent.
+Following intracranial inoculation, neurovirulent mouse hepatitis virus (MHV) strains induce acute inflammation, demyelination and axonal loss in the CNS.
+Prior studies using recombinant MHV strains that differ only in the spike gene, which encodes a glycoprotein involved in virus-host cell attachment, demonstrated that spike mediates anterograde axonal transport of virus to the spinal cord.
+A demyelinating MHV strain induces optic neuritis, but whether this is due to retrograde axonal transport of viral particles to the retina, or if it is due to traumatic disruption of retinal ganglion cell axons during intracranial inoculation is not known.
+Using recombinant isogenic MHV strains, we examined the ability of recombinant MHV to induce optic neuritis by retrograde spread from the brain through the optic nerve into the eye following intracranial inoculation.
+Recombinant demyelinating MHV induced macrophage infiltration of optic nerves, demyelination and axonal loss whereas optic neuritis and axonal injury were minimal in mice infected with the non-demyelinating MHV strain that differs in the spike gene.
+Thus, optic neuritis was dependent on a spike glycoprotein-mediated mechanism of viral antigen transport along retinal ganglion cell axons.
+These data indicate that MHV spreads by retrograde axonal transport to the eye and that targeting spike protein interactions with axonal transport machinery is a potential therapeutic strategy for CNS viral infections and associated diseases.
+BACKGROUND: Apical membrane antigen 1 (AMA1) is one of the best-studied blood-stage malaria vaccine candidates.
+When an AMA1 vaccine was tested in a malaria naïve population, it induced functionally active antibodies judged by Growth Inhibition Assay (GIA).
+However, the same vaccine failed to induce higher growth-inhibitory activity in adults living in a malaria endemic area.
+Vaccination did induce functionally active antibodies in malaria-exposed children with less than 20% inhibition in GIA at baseline, but not in children with more than that level of baseline inhibition.
+METHODS: Total IgGs were purified from plasmas collected from the pediatric trial before and after immunization and pools of total IgGs were made.
+Another set of total IgGs was purified from U.S. adults immunized with AMA1 (US-total IgG).
+From these total IgGs, AMA1-specific and non-AMA1 IgGs were affinity purified and the functional activity of these IgGs was evaluated by GIA.
+RESULTS: AMA1-specific IgGs from malaria-exposed children and U.S. vaccinees showed similar growth-inhibitory activity at the same concentrations.
+When mixed with U.S.-total IgG, non-AMA1 IgGs from children showed an interference effect in GIA.
+The non-AMA1 IgGs did not compete with anti-AMA1 antibody in U.S.-total IgG in the competition ELISA.
+CONCLUSION: Children living in a malaria endemic area have a fraction of IgGs that interferes with the biological activity of anti-AMA1 antibody as judged by GIA.
+While the mechanism of interference is not resolved in this study, these results suggest it is not caused by direct competition between non-AMA1 IgG and AMA1 protein.
+This study indicates that anti-malaria IgGs induced by natural exposure may interfere with the biological effect of antibody induced by an AMA1-based vaccine in the target population.
+SUMMARY: We have determined the structure of the core capsid of an unusual variant of hepatitis B virus, genotype G (HBV/G) at 14 Å resolution, using cryo-electron microscopy.
+HBV/G is novel in that it has a unique 36- bp insertion downstream of the core gene start codon.
+This results in a twelve amino acid insertion at the N-terminal end of the core protein, and two stop codons in the precore region that prevent the expression of HBeAg.
+HBV/G replication in patients is associated with co-infection with another genotype of HBV, suggesting that HBV/G may have reduced replication efficiency in vivo.
+We localized the N-terminal insertion in HBV/G and show that it forms two additional masses on the core surface adjacent to each of the dimer-spikes and have modelled the structure of the additional residues within this density.
+We show that the position of the insertion would not interfere with translocation of nucleic acids through the pores to the core interior compartment.
+However, the insertion may partially obscure several residues on the core surface that are known to play a role in envelopment and secretion of virions, or that could affect structural rearrangements that may trigger envelopment after DNA second-strand synthesis.
+Humans who experience a primary dengue virus (DENV) infection develop antibodies that preferentially neutralize the homologous serotype responsible for infection.
+Dengue cross-reactive, non-neutralizing antibodies can enhance infection of Fc receptor bearing cells and, potentially, exacerbate disease.
+The actual binding sites of human antibody on the DENV particle are not well defined.
+We characterized the specificity and neutralization potency of polyclonal serum antibodies and memory B-cell derived monoclonal antibodies (hMAbs) from 2 individuals exposed to primary DENV infections.
+Moreover, many hMAbs bound to the viral pre-membrane protein and other sites on the virus that were not preserved when the viral envelope protein was produced as a soluble, recombinant antigen (rE protein).
+Nonetheless, by modifying the screening procedure to detect rare antibodies that bound to rE, we were able to isolate and map human antibodies that strongly neutralized the homologous serotype of DENV.
+Our MAbs results indicate that, in these two individuals exposed to primary DENV infections, a small fraction of the total antibody response was responsible for virus neutralization.
+BACKGROUND: Highly refined surveillance data on the 2009 A/H1N1 influenza pandemic are crucial to quantify the spatial and temporal characteristics of the pandemic.
+Here we provide a quantitative description of the age-specific morbidity pandemic patterns across administrative areas of Peru.
+METHODS: We used daily cases of influenza-like-illness, tests for A/H1N1 influenza virus infections, and laboratory-confirmed A/H1N1 influenza cases reported to the epidemiological surveillance system of Peru's Ministry of Health from May 1 to December 31, 2009.
+We analyzed the geographic spread of the pandemic waves and their association with the winter school vacation period, demographic factors, and absolute humidity.
+We also estimated the reproduction number and quantified the association between the winter school vacation period and the age distribution of cases.
+RESULTS: The national pandemic curve revealed a bimodal winter pandemic wave, with the first peak limited to school age children in the Lima metropolitan area, and the second peak more geographically widespread.
+The reproduction number was estimated at 1.6–2.2 for the Lima metropolitan area and 1.3–1.5 in the rest of Peru.
+We found a significant association between the timing of the school vacation period and changes in the age distribution of cases, while earlier pandemic onset was correlated with large population size.
+CONCLUSIONS: Our results indicate substantial spatial variation in pandemic patterns across Peru, with two pandemic waves of varying timing and impact by age and region.
+Moreover, the Peru data suggest a hierarchical transmission pattern of pandemic influenza A/H1N1 driven by large population centers.
+The higher reproduction number of the first pandemic wave could be explained by high contact rates among school-age children, the age group most affected during this early wave.
+Routine screening of lung transplant recipients and hospital patients for respiratory virus infections allowed to identify human rhinovirus (HRV) in the upper and lower respiratory tracts, including immunocompromised hosts chronically infected with the same strain over weeks or months.
+Phylogenetic analysis of 144 HRV-positive samples showed no apparent correlation between a given viral genotype or species and their ability to invade the lower respiratory tract or lead to protracted infection.
+By contrast, protracted infections were found almost exclusively in immunocompromised patients, thus suggesting that host factors rather than the virus genotype modulate disease outcome, in particular the immune response.
+Complete genome sequencing of five chronic cases to study rhinovirus genome adaptation showed that the calculated mutation frequency was in the range observed during acute human infections.
+Analysis of mutation hot spot regions between specimens collected at different times or in different body sites revealed that non-synonymous changes were mostly concentrated in the viral capsid genes VP1, VP2 and VP3, independent of the HRV type.
+In an immunosuppressed lung transplant recipient infected with the same HRV strain for more than two years, both classical and ultra-deep sequencing of samples collected at different time points in the upper and lower respiratory tracts showed that these virus populations were phylogenetically indistinguishable over the course of infection, except for the last month.
+Specific signatures were found in the last two lower respiratory tract populations, including changes in the 5′UTR polypyrimidine tract and the VP2 immunogenic site 2.
+These results highlight for the first time the ability of a given rhinovirus to evolve in the course of a natural infection in immunocompromised patients and complement data obtained from previous experimental inoculation studies in immunocompetent volunteers.
+Mesenchymal stem cells (MSCs) have the capacity to proliferate and differentiate into multiple connective tissue lineages, which include cartilage, bone, and fat.
+Cartilage differentiation and chondrocyte maturation are required for normal skeletal development, but the intracellular pathways regulating this process remain largely unclear.
+This study was designed to identify novel genes that might help clarify the molecular mechanisms of chondrogenesis.
+Chondrogenesis was induced by culturing human bone marrow (BM) derived MSCs in micromass pellets in the presence of defined medium for 3, 7, 14 or 21 days.
+Using an ABI microarray system, we determined the differential gene expression profiles of differentiated chondrocytes and BM-MSCs.
+To verify gene expression profiles determined by microarray analysis, the expression levels of 10 genes with high fold changes were confirmed by RT-PCR.
+Gene expression patterns of 9 genes (Hrad6B, annexinA2, BMP-7, contactin-1, peroxiredoxin-1, heat shock transcription factor-2, synaptotagmin IV, serotonin receptor-7, Axl) in RT-PCR were similar to the microarray gene expression patterns.
+Twenty-seven nanopeptides derived from the matrix (M) protein of porcine reproductive and respiratory syndrome virus (PRRSV) were screened for their ability to elicit a recall interferon-γ (IFN-γ) response from the splenocytes of BALB/c mice following DNA vaccination and a booster vaccination with recombinant vaccinia virus rWR-PRRSV-M. We identified two peptides (amino acid residues K(93)FITSRCRL and F(57)GYMTFVHF) as CD8(+ )cytotoxic T lymphocyte (CTL) epitopes.
+These peptides elicited significant numbers of IFN-γ secreting cells, compared with other M nonapeptides and one irrelevant nonapeptide.
+Bioinformatics analysis showed that the former is an H-2K(d)-restricted CTL epitope, and the latter is an H-2D(d)-restricted CTL epitope.
+Multiple amino acid sequence alignment among different PRRSV M sequences submitted to GenBank indicated that these two CTL epitopes are strongly conserved, and they should therefore be considered for further research on the mechanisms of cellular immune responses to PRRSV.
+Protein component modifications caused by mitochondrial DNA (mtDNA) depletion are related to a wide range of human diseases; however, little is known about how nuclear-encoded mitochondrial proteins (mt proteome) changes under such dysfunctional states.
+In this study, we investigated the systemic alterations of mtDNA-depleted (ρ(0)) mitochondria by using network analysis of gene expression data.
+By modularizing the quantified proteomics data into protein functional networks, systemic properties of mitochondrial dysfunction were analyzed.
+We discovered that up-regulated and down-regulated proteins were organized into two predominant subnetworks that exhibited distinct biological processes.
+The down-regulated network modules are involved in typical mitochondrial functions, while up-regulated proteins are responsible for mtDNA repair and regulation of mt protein expression and transport.
+Furthermore, comparisons of proteome and transcriptome data revealed that ρ(0) cells attempted to compensate for mtDNA depletion by modulating the coordinated expression/transport of mt proteins.
+Our results demonstrate that mt protein composition changed to remodel the functional organization of mitochondrial protein networks in response to dysfunctional cellular states.
+Human mt protein functional networks provide a framework for understanding how cells respond to mitochondrial dysfunctions.
+They regulate the permeability and polarity of cell layers and create compartments in cell membranes.
+There are 27 claudins known, and expression of different claudins is responsible for changes in the electrolyte and solute permeability in cells layers.
+Studies have shown that claudins and tight junctions also protect multicellular organisms from infections and that some infectious agents may use claudins as targets to invade and weaken the host's defense.
+Since their expression is associated with specific tumor types or with specific locations of tumors to a certain degree, they can, in a restricted sense, also be used as tumor markers.
+However, the regulation of claudin expression is complex involving growth factors and integrins, protein kinases, proto-oncogens and transcription factors.
+BACKGROUND: Human bocavirus (HBoV) is a newly identified viral pathogen, and its clinical epidemiology and significance in respiratory infections have not yet been completely elucidated.
+We investigated the prevalence of HBoV infection and the association between viral (HBoV) load and clinical features of the infection in patients of all age-groups.
+METHODS: Nasopharyngeal aspirates from patients with symptoms of respiratory infection were tested for presence of HBoV by using real-time polymerase chain reaction.
+HBoV-positive patients were categorized into low- and high-viral-load groups using 1.0×10(6) copies/mL as the threshold value of viral load.
+RESULTS: Detection rate of HBoV was 4.8% (N=93) in a total of 1,926 samples with peak incidence of infection being observed in patients aged 6-12 months.
+HBoV infection was more frequently observed in young children, especially, in children aged less than 5 yr, and the HBoV load decreased with increase in age.
+HBoV was codetected with other respiratory viruses in 17 (18.3%) of the 93 HBoV-positive patients and 15 patients (88.2%) belonged to the low-viral-load group.
+Patients infected with HBoV alone showed a higher viral load than those patients in whom HBoV was codetected with other respiratory viruses (median load, 3.78×10(5) copies/mL vs. 1.94×10(4) copies/mL, P=0.014).
+Higher pulse rate (P=0.007) and respiratory rate (P=0.021) were observed in patients with a high-viral-load.
+CONCLUSIONS: Our results suggest that HBoV may be the causative agent of respiratory infection in the high-viral-load group.
+OBJECTIVE: To explore the characteristics of seasonal distribution of active systemic lupus erythematosus (SLE) and the influences of meteorological factors including temperature and humidity on active systemic lupus erythematosus.
+METHODS: The characteristics of seasonal distribution of active SLE and its correlation with meteorological factors were retrospectively analyzed in 640 patients living in the city of Zhanjiang, China and had active SLE between January 1997 and December 2006.
+RESULTS: In winter, when there are weaker ultraviolet (UV) rays, the ratio of patients with active SLE to total inpatients was 3.89 ‰, which is significantly higher than in other seasons with stronger UV rays, including 2.17 ‰ in spring, 1.87 ‰ in summer and 2.12 ‰ in autumn.
+The number of patients with active SLE had significant negative correlation with mean temperature and was not significantly related to mean humidity.
+BACKGROUND: Allogeneic bone marrow transplantation (allo-BMT) is a potentially curative therapy for a variety of hematologic diseases, but benefits, including graft-versus-tumor (GVT) activity are limited by graft-versus-host-disease (GVHD).
+Carcinoembryonic antigen related cell adhesion molecule 1 (Ceacam1) is a transmembrane glycoprotein found on epithelium, T cells, and many tumors.
+It regulates a variety of physiologic and pathological processes such as tumor biology, leukocyte activation, and energy homeostasis.
+METHODS: We studied Ceacam1 as a regulator of GVHD and GVT after allogeneic bone marrow transplantation (allo-BMT) in mouse models.
+In vivo, Ceacam1(−/−) T cells caused increased GVHD mortality and GVHD of the colon, and greater numbers of donor T cells were positive for activation markers (CD25(hi), CD62L(lo)).
+Additionally, Ceacam1(−/−) CD8 T cells had greater expression of the gut-trafficking integrin α(4)β(7), though both CD4 and CD8 T cells were found increased numbers in the gut post-transplant.
+Ceacam1(−/−) recipients also experienced increased GVHD mortality and GVHD of the colon, and alloreactive T cells displayed increased activation.
+Additionally, Ceacam1(−/−) mice had increased mortality and decreased numbers of regenerating small intestinal crypts upon radiation exposure.
+Conversely, Ceacam1-overexpressing T cells caused attenuated target-organ and systemic GVHD, which correlated with decreased donor T cell numbers in target tissues, and mortality.
+Finally, graft-versus-tumor survival in a Ceacam1(+) lymphoma model was improved in animals receiving Ceacam1(−/−) vs. control T cells.
+CONCLUSIONS: We conclude that Ceacam1 regulates T cell activation, GVHD target organ damage, and numbers of donor T cells in lymphoid organs and GVHD target tissues.
+Because of its expression on both the donor graft and host tissues, this suggests that targeting Ceacam1 may represent a potent strategy for the regulation of GVHD and GVT after allogeneic transplantation.
+The inhibitory receptor programmed death-1 (PD-1) has the capacity to maintain peripheral tolerance and limit immunopathological damage; however, its precise role in fulminant viral hepatitis (FH) has yet to be described.
+Here, we investigated the functional mechanisms of PD-1 as related to FH pathogenesis induced by the murine hepatitis virus strain-3 (MHV-3).
+High levels of PD-1-positive CD4(+), CD8(+) T cells, NK cells and macrophages were observed in liver, spleen, lymph node and thymus tissues following MHV-3 infection.
+PD-1-deficient mice exhibited significantly higher expression of the effector molecule which initiates fibrinogen deposition, fibrinogen-like protein 2 (FGL2), than did their wild-type (WT) littermates.
+Fluorescence double-staining revealed that FGL2 and PD-1 were not co-expressed on the same cells, while quantitative RT-PCR demonstrated that higher levels of IFN-γ and TNF-α mRNA transcription occurred in PD-1-deficient mice in response to MHV-3 infection.
+Conversely, in vivo blockade of IFN-γ and TNF-α led to efficient inhibition of FGL2 expression, greatly attenuated the development of tissue lesions, and ultimately reduced mortality.
+Thus, the up-regulation of FGL2 in PD-1-deficient mice was determined to be mediated by IFN-γ and TNF-α.
+Taken together, our results suggest that PD-1 signaling plays an essential role in decreasing the immunopathological damage induced by MHV-3 and that manipulation of this signal might be a useful strategy for FH immunotherapy.
+Machupo virus (MACV) is a highly pathogenic New World arenavirus that causes hemorrhagic fever in humans.
+MACV, as well as other pathogenic New World arenaviruses, enter cells after their GP1 attachment glycoprotein binds to their cellular receptor, transferrin receptor 1 (TfR1).
+TfR1 residues essential for this interaction have been described, and a co-crystal of MACV GP1 bound to TfR1 suggests GP1 residues important for this association.
+We created MACV GP1 variants and tested their effect on TfR1 binding and virus entry to evaluate the functional significance of some of these and additional residues in human and simian cells.
+We found residues R111, D123, Y122, and F226 to be essential, D155, and P160 important, and D114, S116, D140, and K169 expendable for the GP1-TfR1 interaction and MACV entry.
+Several MACV GP1 residues that are critical for the interaction with TfR1 are conserved among other New World arenaviruses, indicating a common basis of receptor interaction.
+Pathogenicity islands (PAIs), a distinct type of genomic island (GI), play important roles in the rapid adaptation and increased virulence of pathogens.
+89K is a newly identified PAI in epidemic Streptococcus suis isolates that are related to the two recent large-scale outbreaks of human infection in China.
+However, its mechanism of evolution and contribution to the epidemic spread of S. suis 2 remain unknown.
+In this study, the potential for mobilization of 89K was evaluated, and its putative transfer mechanism was investigated.
+The precise excision is mediated by an 89K-borne integrase through site-specific recombination, with help from an excisionase.
+The 89K excision intermediate acts as a substrate for lateral transfer to non-89K S. suis 2 recipients, where it reintegrates site-specifically into the target site.
+The conjugal transfer of 89K occurred via a GI type IV secretion system (T4SS) encoded in 89K, at a frequency of 10(−6) transconjugants per donor.
+This is the first demonstration of horizontal transfer of a Gram-positive PAI mediated by a GI-type T4SS.
+We propose that these genetic events are important in the emergence, pathogenesis and persistence of epidemic S. suis 2 strains.
+The size of von Willebrand factor (VWF), controlled by ADAMTS13-dependent proteolysis, is associated with its hemostatic activity.
+These include coagulation factor VIII, platelet glycoprotein 1bα, and heparin sulfate, which accelerate the cleavage of VWF.
+Conversely, thrombospondin-1 decreases the rate of VWF proteolysis by ADAMTS13 by competing with ADAMTS13 for the A3 domain of VWF.
+To investigate whether murine monoclonal antibodies (mAbs) against human VWF affect the susceptibility of VWF to proteolysis by ADAMTS13 in vitro, eight mAbs to different domains of human VWF were used to evaluate the effects on VWF cleavage by ADAMTS13 under fluid shear stress and static/denaturing conditions.
+Additionally, the epitope of anti-VWF mAb (SZ34) was mapped using recombinant proteins in combination with enzyme-linked immunosorbent assay and Western blot analysis.
+The results indicate that mAb SZ34 inhibited proteolytic cleavage of VWF by ADAMTS13 in a concentration-dependent manner under fluid shear stress, but not under static/denaturing conditions.
+The binding epitope of SZ34 mAb is located between A1555 and G1595 in the central A2 domain of VWF.
+These data show that an anti-VWF mAb against the VWF-A2 domain (A1555-G1595) reduces the proteolytic cleavage of VWF by ADAMTS13 under shear stress, suggesting the role of this region in interaction with ADAMTS13.
+Effective control of this disease needs sensitive, specific, and quick diagnostic tools at each tier of control strategy.
+In this paper we have outlined various diagnostic approaches from old to new generation in a nutshell.
+Presently FMD diagnosis is being carried out using techniques such as Virus Isolation (VI), Sandwich-ELISA (S-ELISA), Liquid-Phase Blocking ELISA (LPBE), Multiplex-PCR (m-PCR), and indirect ELISA (DIVA), and real time-PCR can be used for detection of antibody against nonstructural proteins.
+Nucleotide sequencing for serotyping, microarray as well as recombinant antigen-based detection, biosensor, phage display, and nucleic-acid-based diagnostic are on the way for rapid and specific detection of FMDV.
+Canine rabies, responsible for most human rabies deaths, is a serious global public health concern.
+This zoonosis is entirely preventable, but by focusing solely upon rabies prevention in humans, this “incurable wound” persists at high costs.
+Although preventing human deaths through canine rabies elimination is feasible, dog rabies control is often neglected, because dogs are not considered typical economic commodities by the animal health sector.
+Here, we demonstrate that the responsibility of managing rabies falls upon multiple sectors, that a truly integrated approach is the key to rabies elimination, and that considerable progress has been made to this effect.
+Achievements include the construction of global rabies networks and organizational partnerships; development of road maps, operational toolkits, and a blueprint for rabies prevention and control; and opportunities for scaling up and replication of successful programs.
+Progress must continue towards overcoming the remaining challenges preventing the ultimate goal of rabies elimination.
+BACKGROUND: Neurons and astrocytes are generated from common neural precursors, yet neurogenesis precedes astrocyte formation during embryogenesis.
+The mechanisms of neural development underlying suppression and de-suppression of differentiation- related genes for cell fate specifications are not well understood.
+METHODOLOGY/PRINCIPAL FINDINGS: By using an in vitro system in which NTera-2 cells were induced to differentiate into an astrocyte-like lineage, we revealed a novel role for Sin3A in maintaining the suppression of GFAP in NTera-2 cells.
+Sin3A coupled with MeCP2 bound to the GFAP promoter and their occupancies were correlated with repression of GFAP transcription.
+The repression by Sin3A and MeCP2 may be an essential mechanism underlying the inhibition of cell differentiation.
+Upon commitment toward an astrocyte-like lineage, Sin3A- MeCP2 departed from the promoter and activated STAT3 simultaneously bound to the promoter and exon 1 of GFAP; meanwhile, olig2 was exported from nuclei to the cytoplasm.
+This suggested that a three-dimensional or higher-order structure was provoked by STAT3 binding between the promoter and proximal coding regions.
+STAT3 then recruited CBP/p300 to exon 1 and targeted the promoter for histone H3K9 and H3K14 acetylation.
+The CBP/p300-mediated histone modification further facilitates chromatin remodeling, thereby enhancing H3K4 trimethylation and recruitment of RNA polymerase II to activate GFAP gene transcription.
+CONCLUSIONS/SIGNIFICANCE: These results provide evidence that exchange of repressor and activator complexes and epigenetic modifications are critical strategies for cellular differentiation and lineage-specific gene expression.
+BACKGROUND: To develop the first international instrument to measure fertility quality of life (FertiQoL) in men and women experiencing fertility problems, to evaluate the preliminary psychometric properties of this new tool and to translate FertiQoL into multiple languages.
+METHOD: We conducted a survey, both online and in fertility clinics in USA, Australia/New Zealand, Canada and UK.
+RESULTS: FertiQoL consists of 36 items that assess core (24 items) and treatment-related quality of life (QoL) (10 items) and overall life and physical health (2 items).
+Cronbach reliability statistics for the Core and Treatment FertiQoL (and subscales) were satisfactory and in the range of 0.72 and 0.92.
+Sensitivity analyses showed that FertiQoL detected expected relations between QoL and gender, parity and support-seeking.
+FertiQoL was translated into 20 languages by the same translation team with each translation verified by local bilingual fertility experts.
+CONCLUSIONS: FertiQoL is a reliable measure of the impact of fertility problems and its treatment on QoL.
+BACKGROUND: The first case of 2009 pandemic influenza A (H1N1) virus infection was documented in our Hospital on 10th August 2009.
+Upon admission 12/44 had local patchy shadowing in their chest x-ray and additionally antibiotic regimen was added to these patients as pneumonia was suspected based on clinical evidence.
+Lung function was evaluated with forced vital capacity, forced expiratory volume in 1 sec and diffused carbon monoxide upon discharge and every 3 months, until 6 months of observation was completed after discharge.
+The purpose of this retrospective cohort study was to evaluate whether influenza A (H1N1) had an impact on the respiratory capacity of the infected patients.
+CONCLUSIONS: An improvement of pulmonary function tests was observed between the first two measurements, implicating an inflammatory pathogenesis of influenza A (H1N1) to the respiratory tract.
+All patients had a mild clinical course and their respiratory capacity was stable between the second and third measurement, suggesting that the duration of respiratory inflammation was two months.
+The major physiological function of milk is the transport of amino acids, carbohydrates, lipids and minerals to mammalian offspring.
+Caseins, the major milk proteins, are secreted in the form of a micelle consisting of protein and calcium-phosphate.
+We have analysed the role of the milk protein α-casein by inactivating the corresponding gene in mice.
+Absence of α-casein protein significantly curtails secretion of other milk proteins and calcium-phosphate, suggesting a role for α-casein in the establishment of casein micelles.
+In contrast, secretion of albumin, which is not synthesized in the mammary epithelium, into milk is not reduced.
+α-Casein deficiency severely delays pup growth during lactation and results in a life-long body size reduction compared to control animals, but has only transient effects on physical and behavioural development of the pups.
+The results also confirm lactation as a critical window of metabolic programming and suggest milk protein concentration as a decisive factor in determining adult body weight.
+[Image: see text] Force–distance measurements have been used to examine differences in the interaction of the dendritic cell glycan-binding receptor DC-SIGN and the closely related endothelial cell receptor DC-SIGNR (L-SIGN) with membranes bearing glycan ligands.
+The results demonstrate that upon binding to membrane-anchored ligand, DC-SIGNR undergoes a conformational change similar to that previously observed for DC-SIGN.
+The results also validate a model for the extracellular domain of DC-SIGNR derived from crystallographic studies.
+Force measurements were performed with DC-SIGNR variants that differ in the length of the neck that result from genetic polymorphisms, which encode different numbers of the 23-amino acid repeat sequences that constitute the neck.
+The findings are consistent with an elongated, relatively rigid structure of the neck repeat observed in crystals.
+In addition, differences in the lengths of DC-SIGN and DC-SIGNR extracellular domains with equivalent numbers of neck repeats support a model in which the different dispositions of the carbohydrate-recognition domains in DC-SIGN and DC-SIGNR result from variations in the sequences of the necks.
+During a lytic gammaherpesvirus infection, host gene expression is severely restricted by the global degradation and altered 3′ end processing of mRNA.
+This host shutoff phenotype is orchestrated by the viral SOX protein, yet its functional significance to the viral lifecycle has not been elucidated, in part due to the multifunctional nature of SOX.
+Using an unbiased mutagenesis screen of the murine gammaherpesvirus 68 (MHV68) SOX homolog, we isolated a single amino acid point mutant that is selectively defective in host shutoff activity.
+Incorporation of this mutation into MHV68 yielded a virus with significantly reduced capacity for mRNA turnover.
+Unexpectedly, the MHV68 mutant showed little defect during the acute replication phase in the mouse lung.
+Instead, the virus exhibited attenuation at later stages of in vivo infections suggestive of defects in both trafficking and latency establishment.
+Specifically, mice intranasally infected with the host shutoff mutant accumulated to lower levels at 10 days post infection in the lymph nodes, failed to develop splenomegaly, and exhibited reduced viral DNA levels and a lower frequency of latently infected splenocytes.
+These results highlight for the first time the importance of global mRNA degradation during a gammaherpesvirus infection and link an exclusively lytic phenomenon with downstream latency establishment.
+With time, this problem will only become more severe as population density in urban centers grows.
+Social interactions play a very important role in determining how infectious diseases spread, and organization of people along social lines gives rise to non-spatial networks in which the infections spread.
+Infection networks are different for diseases with different transmission modes, but are likely to be identical or highly similar for diseases that spread the same way.
+Hence, infection networks estimated from common infections can be useful to contain epidemics of a more severe disease with the same transmission mode.
+Here we present a proof-of-concept study demonstrating the effectiveness of epidemic mitigation based on such estimated infection networks.
+We first generate artificial social networks of different sizes and average degrees, but with roughly the same clustering characteristic.
+We then start SIR epidemics on these networks, censor the simulated incidences, and use them to reconstruct the infection network.
+We then efficiently fragment the estimated network by removing the smallest number of nodes identified by a graph partitioning algorithm.
+Finally, we demonstrate the effectiveness of this targeted strategy, by comparing it against traditional untargeted strategies, in slowing down and reducing the size of advancing epidemics.
+BACKGROUND: The recent emergence of a novel strain of influenza virus with pandemic potential underscores the need for quality surveillance and laboratory services to contribute to the timely detection and confirmation of public health threats.
+To provide a framework for strengthening disease surveillance and response capacities in African countries, the World Health Organization Regional Headquarters for Africa (AFRO) developed Integrated Disease Surveillance and Response (IDSR) aimed at improving national surveillance and laboratory systems.
+IDSR emphasizes the linkage of information provided by public health laboratories to the selection of relevant, appropriate and effective public health responses to disease outbreaks.
+METHODS: We reviewed the development of Rwanda's National Reference Laboratory (NRL) to understand essential structures involved in creating a national public health laboratory network.
+We reviewed documents describing the NRL's organization and record of test results, conducted site visits, and interviewed health staff in the Ministry of Health and in partner agencies.
+We purposefully sought to identify success factors as well as challenges inherent in developing a national public health laboratory system.
+RESULTS: Among the identified success factors were: a structured governing framework for public health surveillance; political commitment to promote leadership for stronger laboratory capacities in Rwanda; defined roles and responsibilities for each level; coordinated approaches between technical and funding partners; collaboration with external laboratories; and use of performance results in advocacy with national stakeholders.
+CONCLUSIONS: Rwanda's experience with collaborative partnerships contributed to creation of a functional public health laboratory network.
+BACKGROUND: Increasing robustness via improvement of resistance to pathogens is a major selection objective in livestock breeding.
+As resistance traits are difficult or impossible to measure directly, potential indirect criteria are measures of immune traits (ITs).
+Our underlying hypothesis is that levels of ITs with no focus on specific pathogens define an individual's immunocompetence and thus predict response to pathogens in general.
+Since variation in ITs depends on genetic, environmental and probably epigenetic factors, our aim was to estimate the relative importance of genetics.
+In this report, we present a large genetic survey of innate and adaptive ITs in pig families bred in the same environment.
+METHODOLOGY/PRINCIPAL FINDINGS: Fifty four ITs were studied on 443 Large White pigs vaccinated against Mycoplasma hyopneumoniae and analyzed by combining a principal component analysis (PCA) and genetic parameter estimation.
+ITs include specific and non specific antibodies, seric inflammatory proteins, cell subsets by hemogram and flow cytometry, ex vivo production of cytokines (IFNα, TNFα, IL6, IL8, IL12, IFNγ, IL2, IL4, IL10), phagocytosis and lymphocyte proliferation.
+While six ITs had heritabilities that were weak or not significantly different from zero, 18 and 30 ITs had moderate (0.1<h2≤0.4) or high (h2>0.4) heritability values, respectively.
+Phenotypic and genetic correlations between ITs were weak except for a few traits that mostly include cell subsets.
+CONCLUSIONS/SIGNIFICANCE: Our results demonstrate that variation in many innate and adaptive ITs is genetically controlled in swine, as already reported for a smaller number of traits by other laboratories.
+A limited redundancy of the traits was also observed confirming the high degree of complementarity between innate and adaptive ITs.
+Our data provide a genetic framework for choosing ITs to be included as selection criteria in multitrait selection programmes that aim to improve both production and health traits.
+INTRODUCTION: Acute respiratory failure has been one of the most important causes of death in intensive care units, and certain aspects of its pulmonary pathology are currently unknown.
+OBJECTIVES: The objective was to describe the demographic data, etiology, and pulmonary histopathological findings of different diseases in the autopsies of patients with acute respiratory failure.
+METHOD: Autopsies of 4,710 patients with acute respiratory failure from 1990 to 2008 were reviewed, and the following data were obtained: age, sex, and major associated diseases.
+The pulmonary histopathology was categorized as diffuse alveolar damage, pulmonary edema, alveolar hemorrhage, and lymphoplasmacytic interstitial pneumonia.
+The odds ratio of the concordance between the major associated diseases and specific autopsy findings was calculated using logistic regression.
+A multivariate analysis showed a significant and powerful association between diffuse alveolar damage and bronchopneumonia, HIV/AIDS, sepsis, and septic shock, between liver cirrhosis and pulmonary embolism, between pulmonary edema and acute myocardial infarction, between dilated cardiomyopathy and cancer, between alveolar hemorrhage and bronchopneumonia and pulmonary embolism, and between lymphoplasmacytic interstitial pneumonia and HIV/AIDS and liver cirrhosis.
+The most prevalent pulmonary histopathological pattern was diffuse alveolar damage, which was associated with different inflammatory conditions.
+Further studies are necessary to elucidate the complete pathophysiological mechanisms involved with each disease and the development of acute respiratory failure.
+Natural killer (NK) cells are equipped to innately produce the cytokine gamma interferon (IFN-γ) in part because they basally express high levels of the signal transducer and activator of transcription 4 (STAT4).
+Type 1 interferons (IFNs) have the potential to activate STAT4 and promote IFN-γ expression, but concurrent induction of elevated STAT1 negatively regulates access to the pathway.
+As a consequence, it has been difficult to detect type 1 IFN stimulation of NK cell IFN-γ during viral infections in the presence of STAT1 and to understand the evolutionary advantage for maintaining the pathway.
+The studies reported here evaluated NK cell responses following infections with lymphocytic choriomeningitis virus (LCMV) in the compartment handling the earliest events after infection, the peritoneal cavity.
+The production of type 1 IFNs, both IFN-α and IFN-β, was shown to be early and of short duration, peaking at 30 h after challenge.
+NK cell IFN-γ expression was detected with overlapping kinetics and required activating signals delivered through type 1 IFN receptors and STAT4.
+It took place under conditions of high STAT4 levels but preceded elevated STAT1 expression in NK cells.
+Interestingly, increases in STAT1 were delayed in NK cells compared to other peritoneal exudate cell (PEC) populations.
+Taken together, the studies demonstrate a novel mechanism for stimulating IFN-γ production and elucidate a biological role for type 1 IFN access to STAT4 in NK cells.
+The epithelial-mesenchymal transition (EMT) of renal epithelial cells (RTECs) has pivotal roles in the development of renal fibrosis.
+Although the interaction of lymphocyte function-associated antigen 1 (LFA-1) on leukocytes and its ligand, intracellular adhesion molecule 1 (ICAM-1), plays essential roles in most inflammatory reactions, its pathogenetic role in the EMT of RTECs remains to be clarified.
+In the present study, we investigated the effect of the interaction of LFA-1 on peripheral blood mononuclear cells (PBMCs) and ICAM-1 on HK-2 cells after stimulation with TGF-β(1) on the EMT of RTECs.
+After co-culture of PBMCs and HK-2 cells pre-stimulated with TGF-β(1) (0.1 ng/ml) (HK-2-TGF-β(1) (0.1)), the expression of the active form of LFA-1 increased on PBMCs; however, total LFA-1 expression did not change.
+The expression of the active form of LFA-1 on PBMCs did not increase after co-culture with not CCL3 but CXCL12 knockdown HK-2-TGF-β(1) (0.1).
+The expression of epithelial cell junction markers (E-cadherin and occludin) further decreased and that of mesenchymal markers (vimentin and fibronectin) further increased in HK-2-TGF-β(1) (0.1) after co-culture with PBMCs for 24 hrs (HK-2-TGF-β(1) (0.1)-PBMCs).
+Although the migration and invasion of HK-2 cells induced full EMT by a high dose (10.0 ng/ml) and long-term (72–96 hrs) TGF-β(1) stimulation increased, that of HK-2-TGF-β(1) (0.1)-PBMCs did not increase.
+These results suggested that HK-2 cells stimulated with TGF-β(1) induced conformational activation of LFA-1 on PBMCs by increased CXCL12.
+Then, the direct interaction of LFA-1 on PBMCs and ICAM-1 on HK-2 cells activated ERK1/2 signaling to accelerate the part of EMT of HK-2 cells induced by TGF-β(1.)
+The biodynamics of ultrasmall and small superparamagnetic iron oxide (USPIO and SPIO, respectively) particles that were injected intraperitoneally into 36 C57BL/6 mice were investigated chronologically.
+Their distribution was studied histologically at six time points by measuring iron-positive areas (μm(2)) in organ sections stained with Prussian blue.
+The uptake of the differently sized particles was also compared by cultured murine macrophages (J774.1).
+Iron-positive areas in the liver were significantly larger in the mice injected with USPIO than those injected with SPIO at the first three time points (P < 0.05).
+The amount of USPIO in the lung parenchyma around the airway was larger than that of SPIO at four time points (P < 0.05); distribution to the lymph nodes was not significantly different.
+The amount of iron was significantly larger in SPIO- than USPIO-treated cultured cells (P < 0.05).
+In conclusion, it is suggested that intra peritoneally injected USPIO particles could be used more quickly than SPIO to make Kupffer images of the liver and that both agents could help get lymph node images of similar quality.
+A common technique used for sensitive and specific diagnostic virus detection in clinical samples is PCR that can identify one or several viruses in one assay.
+However, a diagnostic microarray containing probes for all human pathogens could replace hundreds of individual PCR-reactions and remove the need for a clear clinical hypothesis regarding a suspected pathogen.
+We have established such a diagnostic platform for random amplification and subsequent microarray identification of viral pathogens in clinical samples.
+We show that Phi29 polymerase-amplification of a diverse set of clinical samples generates enough viral material for successful identification by the Microbial Detection Array, demonstrating the potential of the microarray technique for broad-spectrum pathogen detection.
+We conclude that this method detects both DNA and RNA virus, present in the same sample, as well as differentiates between different virus subtypes.
+Human cytomegalovirus (HCMV), a herpesvirus, is a ubiquitously distributed pathogen that causes severe disease in immunosuppressed patients and infected newborns.
+However, current vaccine efforts are hampered by the lack of information on protective immune responses against HCMV.
+Characterizing the B-cell response in healthy infected individuals could aid in the design of optimal vaccines and therapeutic antibodies.
+To address this problem, we determined, for the first time, the B-cell repertoire against glycoprotein B (gB) of HCMV in different healthy HCMV seropositive individuals in an unbiased fashion.
+HCMV gB represents a dominant viral antigenic determinant for induction of neutralizing antibodies during infection and is also a component in several experimental HCMV vaccines currently being tested in humans.
+Our findings have revealed that the vast majority (>90%) of gB-specific antibodies secreted from B-cell clones do not have virus neutralizing activity.
+Most neutralizing antibodies were found to bind to epitopes not located within the previously characterized antigenic domains (AD) of gB.
+To map the target structures of these neutralizing antibodies, we generated a 3D model of HCMV gB and used it to identify surface exposed protein domains.
+Domain I, located between amino acids (aa) 133–343 of gB and domain II, a discontinuous domain, built from residues 121–132 and 344–438.
+Analysis of a larger panel of human sera from HCMV seropositive individuals revealed positivity rates of >50% against domain I and >90% against domain II, respectively.
+In accordance with previous nomenclature the domains were designated AD-4 (Dom II) and AD-5 (Dom I), respectively.
+Collectively, these data will contribute to optimal vaccine design and development of antibodies effective in passive immunization.
+The Chikungunya virus infection zones have now quickly spread from Africa to parts of Asia, North America and Europe.
+Originally thought to trigger a disease of only mild symptoms, recently Chikungunya virus caused large-scale fatalities and widespread economic loss that was linked to recent virus genetic mutation and evolution.
+Due to the paucity of information on Chikungunya immunological progression, we investigated the serum levels of 13 cytokines/chemokines during the acute phase of Chikungunya disease and 6- and 12-month post-infection follow-up from patients of the Italian outbreak.
+We found that CXCL9/MIG, CCL2/MCP-1, IL-6 and CXCL10/IP-10 were significantly raised in the acute phase compared to follow-up samples.
+Furthermore, IL-1β, TNF-α, Il-12, IL-10, IFN-γ and IL-5 had low initial acute phase levels that significantly increased at later time points.
+These data give insight into Chikungunya disease establishment and subsequent convalescence, which is imperative to the treatment and containment of this quickly evolving and frequently re-emerging disease.
+The basic reproductive ratio, R (0), is one of the fundamental concepts in mathematical biology.
+It is a threshold parameter, intended to quantify the spread of disease by estimating the average number of secondary infections in a wholly susceptible population, giving an indication of the invasion strength of an epidemic: if R (0) < 1, the disease dies out, whereas if R (0) > 1, the disease persists.
+R (0) has been widely used as a measure of disease strength to estimate the effectiveness of control measures and to form the backbone of disease-management policy.
+Diseases can persist with R (0) < 1, while diseases with R (0) > 1 can die out.
+We show that the same model of malaria gives many different values of R (0), depending on the method used, with the sole common property that they have a threshold at 1.
+We also survey estimated values of R (0) for a variety of diseases, and examine some of the alternatives that have been proposed.
+If R (0) is to be used, it must be accompanied by caveats about the method of calculation, underlying model assumptions and evidence that it is actually a threshold.
+Subtype specificity of influenza A virus (IAV) is determined by its two surface glycoproteins, hemagglutinin (HA) and neuraminidase (NA).
+The epidemic strains of H1N1 IAV change frequently and cause annual seasonal epidemics as well as occasional pandemics, such as the notorious 1918 influenza pandemic.
+The recent introduction of pandemic A/H1N1 IAV (H1N1pdm virus) into humans re-emphasizes the public health concern about H1N1 IAV.
+Several studies have identified conserved epitopes within specific HA subtypes that can be used for diagnostics.
+In this study, linear epitopes on the H1N1pdm viral HA protein were identified by peptide scanning using libraries of overlapping peptides against convalescent sera from H1N1pdm patients.
+One epitope, P5 (aa 58–72) was found to be immunodominant in patients and to evoke high titer antibodies in mice.
+Multiple sequence alignments and in silico coverage analysis showed that this epitope is highly conserved in influenza H1 HA [with a coverage of 91.6% (9,860/10,767)] and almost completely absent in other subtypes [with a coverage of 3.3% (792/23,895)].
+This previously unidentified linear epitope is located outside the five well-recognized antigenic sites in HA.
+A peptide ELISA method based on this epitope was developed and showed high correlation (χ(2) = 51.81, P<0.01, Pearson correlation coefficient R = 0.741) with a hemagglutination inhibition test.
+The highly conserved H1 subtype-specific immunodominant epitope may form the basis for developing novel assays for sero-diagnosis and active surveillance against H1N1 IAVs.
+In Sindbis, Venezuelan equine encephalitis and related alphaviruses, the polymerase is translated as a fusion with other non-structural proteins via readthrough of a UGA stop codon.
+Surprisingly, earlier work reported that the signal for efficient readthrough comprises a single cytidine residue 3′-adjacent to the UGA.
+However, analysis of variability at synonymous sites revealed strikingly enhanced conservation within the ∼150 nt 3′-adjacent to the UGA, and RNA folding algorithms revealed the potential for a phylogenetically conserved stem–loop structure in the same region.
+Mutational analysis of the predicted structure demonstrated that the stem–loop increases readthrough by up to 10-fold.
+The same computational analysis indicated that similar RNA structures are likely to be relevant to readthrough in certain plant virus genera, notably Furovirus, Pomovirus, Tobravirus, Pecluvirus and Benyvirus, as well as the Drosophilia gene kelch.
+These results suggest that 3′ RNA stimulatory structures feature in a much larger proportion of readthrough cases than previously anticipated, and provide a new criterion for assessing the large number of cellular readthrough candidates that are currently being revealed by comparative sequence analysis.
+Liposomes are versatile (sub)micron-sized membrane vesicles that can be used for a variety of applications, including drug delivery and in vivo imaging but they also represent excellent models for artificial membranes or cells.
+Several studies have demonstrated that in vitro transcription and translation can take place inside liposomes to obtain compartmentalized production of functional proteins within the liposomes (Kita et al.
+To show proof-of-concept for this artificial cell-based platform, a bacterial in vitro transcription and translation system together with a gene construct encoding the model antigen β-galactosidase were entrapped inside multilamellar liposomes.
+Vaccination studies in mice showed that such antigen-expressing immunostimulatory liposomes (AnExILs) elicited higher specific humoral immune responses against the produced antigen (β-galactosidase) than control vaccines (i.e.
+In conclusion, AnExILs present a new platform for DNA-based vaccines which combines antigen production, adjuvanticity and delivery in one system and which offer several advantages over existing vaccine formulations.
+We included randomized clinical trials testing Xiaoyaosan against placebo, antidepressants, or combined with antidepressants against antidepressants alone.
+Study selection, data extraction, quality assessment, and data analyses were conducted according to the Cochrane standards.
+26 randomized trials (involving 1837 patients) were included and the methodological quality was evaluated as generally low.
+The pooled results showed that Xiaoyaosan combined with antidepressants was more effective in comprehensive effect, the score of HAMD and the score of SDS compared with antidepressants alone.
+However, due to poor methodological quality in the majority of included trials, the potential benefit from Xiaoyaosan need to be confirmed in rigorous trials and the design and reporting of trials should follow international standards.
+Healthcare workers (HCWs) are at high risk of acquiring infectious diseases and may be among the first to contract emerging infections.
+This study aims to explore European HCWs' perceptions and attitudes towards monitoring their absence and symptom reports for surveillance of newly circulating infections.
+Forty-nine hospital-based HCWs from 12 hospitals were recruited to six focus groups; two each in England and Hungary and one each in Germany and Greece.
+They were concerned that a lack of monitoring and guidelines for infectious HCWs posed a risk to staff and patients and felt employers failed to take a positive interest in their health.
+Staffing demands and loss of income were noted as pressures to attend work when unwell.
+In the UK, Hungary and Greece participants felt monitoring staff absence and the routine disclosure of symptoms could be appropriate provided the effectiveness and efficiency of such a system were demonstrable.
+All HCWs highlighted the need for knowledge and structural improvements for timelier recognition of emerging infections.
+CONCLUSIONS: Monitoring absence and infectious disease symptom reports among HCWs may be a feasible means of surveillance for emerging infections in some settings.
+The prediction of antibody-protein (antigen) interactions is very difficult due to the huge variability that characterizes the structure of the antibodies.
+Experimental data indicate that many antibodies react with a panel of distinct epitopes (positive reaction).
+The Challenge 1 of DREAM5 aims at understanding whether there exists rules for predicting the reactivity of a peptide/epitope, i.e., its capability to bind to human antibodies.
+DREAM 5 provided a training set of peptides with experimentally identified high and low reactivities to human antibodies.
+On the basis of this training set, the participants to the challenge were asked to develop a predictive model of reactivity.
+A test set was then provided to evaluate the performance of the model implemented so far.
+We developed a logistic regression model to predict the peptide reactivity, by facing the challenge as a machine learning problem.
+The initial features have been generated on the basis of the available knowledge and the information reported in the dataset.
+We also developed a method, based on a clustering approach, able to “in-silico” generate a list of positive and negative new peptide sequences, as requested by the DREAM5 “bonus round” additional challenge.
+The paper describes the developed model and its results in terms of reactivity prediction, and highlights some open issues concerning the propensity of a peptide to react with human antibodies.
+BACKGROUND: Despite the launch of the national plan for measles elimination, in Italy, immunization coverage remains suboptimal and outbreaks continue to occur.
+Two measles outbreaks, occurred in Lazio region during 2006-2007, were investigated to identify sources of infection, transmission routes, and assess operational implications for elimination of the disease.
+METHODS: Data were obtained from several sources, the routine infectious diseases surveillance system, field epidemiological investigations, and molecular genotyping of virus by the national reference laboratory.
+RESULTS: Overall 449 cases were reported, sustained by two different stereotypes overlapping for few months.
+Serotype D4 was likely imported from Romania by a Roma/Sinti family and subsequently spread to the rest of the population.
+Pockets of low vaccine coverage individuals (Roma/Sinti communities, high school students) facilitated the reintroduction of serotypes not endemic in Italy and facilitated the measles infection to spread.
+CONCLUSIONS: Communities with low vaccine coverage represent a more serious public health threat than do sporadic susceptible individuals.
+The successful elimination of measles will require additional efforts to immunize low vaccine coverage population groups, including hard-to-reach individuals, adolescents, and young adults.
+An enhanced surveillance systems, which includes viral genotyping to document chains of transmission, is an essential tool for evaluating strategy to control and eliminate measles
+Positive-strand RNA virus replication involves viral proteins and cellular proteins at nearly every replication step.
+Brome mosaic virus (BMV) is a well-established model for dissecting virus-host interactions and is one of very few viruses whose RNA replication, gene expression and encapsidation have been reproduced in the yeast Saccharomyces cerevisiae.
+Previously, our laboratory identified ∼100 non-essential host genes whose loss inhibited or enhanced BMV replication at least 3-fold.
+However, our isolation of additional BMV-modulating host genes by classical genetics and other results underscore that genes essential for cell growth also contribute to BMV RNA replication at a frequency that may be greater than that of non-essential genes.
+To systematically identify novel, essential host genes affecting BMV RNA replication, we tested a collection of ∼900 yeast strains, each with a single essential gene promoter replaced by a doxycycline-repressible promoter, allowing repression of gene expression by adding doxycycline to the growth medium.
+Using this strain array of ∼81% of essential yeast genes, we identified 24 essential host genes whose depleted expression reproducibly inhibited or enhanced BMV RNA replication.
+Relevant host genes are involved in ribosome biosynthesis, cell cycle regulation and protein homeostasis, among other cellular processes.
+BMV 2a(Pol) levels were significantly increased in strains depleted for a heat shock protein (HSF1) or proteasome components (PRE1 and RPT6), suggesting these genes may affect BMV RNA replication by directly or indirectly modulating 2a(Pol) localization, post-translational modification or interacting partners.
+Investigating the diverse functions of these newly identified essential host genes should advance our understanding of BMV-host interactions and normal cellular pathways, and suggest new modes of virus control.
+INTRODUCTION: Myocarditis is rarely reported as an extra-pulmonary manifestation of influenza while pregnancy is a rare cause of cardiomyopathy.
+Pregnancy was identified as a major risk factor for increased mortality and morbidity due to H(1)N(1 )influenza in the pandemic of 2009 to 2010.
+However, to the best of our knowledge there are no previous reports in the literature linking H(1)N(1 )with myocarditis in pregnancy.
+CASE PRESENTATION: We report the cases of two pregnant Caucasian women (aged 29 and 30), with no pre-existing illness, presenting with respiratory manifestations of H(1)N(1 )influenza virus infection in their third trimester.
+One woman developed acute respiratory distress syndrome, almost reaching the point of requiring extra-corporeal membrane oxygenation, and subsequently developed persistent cardiomyopathy; the other recovered without any long-term consequence.
+CONCLUSIONS: While it is not possible to ascertain retrospectively if myocarditis was caused by either infection with H(1)N(1 )virus or as a result of pregnancy (in the absence of endomyocardial biopsies), the significant association with myocardial involvement in both women demonstrates the increased risk of exposure to H(1)N(1 )influenza virus in pregnant women.
+This highlights the need for health care providers to increase awareness amongst caregivers to target this 'at risk' group aggressively with vaccination and prompt treatment.
+Since proteins aggregate to perform function, and since protein-protein interaction (PPI) networks model these aggregations, one would expect to uncover new biology from PPI network topology.
+Hence, using PPI networks to predict protein function and role of protein pathways in disease has received attention.
+A debate remains open about whether network properties of “biologically central (BC)” genes (i.e., their protein products), such as those involved in aging, cancer, infectious diseases, or signaling and drug-targeted pathways, exhibit some topological centrality compared to the rest of the proteins in the human PPI network.
+To help resolve this debate, we design new network-based approaches and apply them to get new insight into biological function and disease.
+We hypothesize that BC genes have a topologically central (TC) role in the human PPI network.
+We design a new centrality measure to capture complex wirings of proteins in the network that identifies as TC those proteins that reside in dense extended network neighborhoods.
+Also, we use the notion of domination and find dominating sets (DSs) in the PPI network, i.e., sets of proteins such that every protein is either in the DS or is a neighbor of the DS.
+Clearly, a DS has a TC role, as it enables efficient communication between different network parts.
+We find statistically significant enrichment in BC genes of TC nodes and outperform the existing methods indicating that genes involved in key biological processes occupy topologically complex and dense regions of the network and correspond to its “spine” that connects all other network parts and can thus pass cellular signals efficiently throughout the network.
+To our knowledge, this is the first study that explores domination in the context of PPI networks.
+Human African Trypanosomiasis (HAT) also called sleeping sickness is caused by subspecies of the parasitic hemoflagellate Trypanosoma brucei that mostly occurs in sub-Saharan Africa.
+The current chemotherapy of the human trypanosomiases relies on only six drugs, five of which have been developed more than 30 years ago, have undesirable toxic side effects and most of them show drug-resistance.
+Though development of new anti-trypanosomal drugs seems to be a priority area research in this area has lagged far behind.
+The given review mainly focus upon the recent synthetic and computer based approaches made by various research groups for the development of newer anti-trypanosomal analogues which may have improved efficacy and oral bioavailability than the present ones.
+The given paper also attempts to investigate the relationship between the various physiochemical parameters and anti-trypanosomal activity that may be helpful in development of potent anti-trypanosomal agents against sleeping sickness.
+BACKGROUND: Nucleolar localization sequences (NoLSs) are short targeting sequences responsible for the localization of proteins to the nucleolus.
+Given the large number of proteins experimentally detected in the nucleolus and the central role of this subnuclear compartment in the cell, NoLSs are likely to be important regulatory elements controlling cellular traffic.
+Although many proteins have been reported to contain NoLSs, the systematic characterization of this group of targeting motifs has only recently been carried out.
+RESULTS: Here, we describe NoD, a web server and a command line program that predicts the presence of NoLSs in proteins.
+Using the web server, users can submit protein sequences through the NoD input form and are provided with a graphical output of the NoLS score as a function of protein position.
+While the web server is most convenient for making prediction for just a few proteins, the command line version of NoD can return predictions for complete proteomes.
+Through stringent independent testing of the predictor using available experimentally validated NoLS-containing eukaryotic and viral proteins, the NoD sensitivity and positive predictive value were estimated to be 71% and 79% respectively.
+CONCLUSIONS: NoD is the first tool to provide predictions of nucleolar localization sequences in diverse eukaryotes and viruses.
+However, little is known about what psychosocial factors might influence people's decision to adopt such preventive behavior.
+This study aims to explore risk perception and other factors associated with handwashing and wearing face masks to prevent AI.
+METHODOLOGY/PRINCIPAL FINDINGS: An interviewer-administered survey was conducted among 352 traditional market workers and shoppers in Taiwan between December 2009 and January 2010.
+Gender interactive effect was also found among participants with a senior high-school education, with males being less likely to engage in the recommended AI preventive behavior than their female counterparts (AOR = 0.34).
+CONCLUSIONS/SIGNIFICANCE: Specific information concerning AI risk perception was associated with the recommended AI preventive behavior.
+In particular, having correct knowledge about the fatality rate of AI and being informed of severe cases and local outbreaks of AI were linked to increased AI preventive behavior.
+These results also have practical implications for prevention and policy-making to more effectively promote the recommended AI preventive behavior in the public.
+Emerging infectious diseases (EID) are currently the major threat to public health worldwide and most EID events have involved zoonotic infectious agents.
+Central Africa in general and Gabon in particular are privileged areas for the emergence of zoonotic EIDs.
+Indeed, human incursions in Gabonese forests for exploitation purposes lead to intensified contacts between humans and wildlife thus generating an increased risk of emergence of zoonotic diseases.
+The most notorious are dengue, yellow fever, ebola, marburg, Rift Valley fever and chikungunya viruses.
+Potential EID due to wildlife in Gabon are thereby plentiful and need to be inventoried.
+The Gabonese Public Health system covers geographically most of the country allowing a good access to sanitary information and efficient monitoring of emerging diseases.
+However, access to treatment and prevention is better in urban areas where medical structures are more developed and financial means are concentrated even though the population is equally distributed between urban and rural areas.
+In spite of this, Gabon could be a good field for investigating the emergence or re-emergence of zoonotic EID.
+Indeed Gabonese health research structures such as CIRMF, advantageously located, offer high quality researchers and facilities that study pathogens and wildlife ecology, aiming toward a better understanding of the contact and transmission mechanisms of new pathogens from wildlife to human, the emergence of zoonotic EID and the breaking of species barriers by pathogens.
+BACKGROUND: China is a country that is most seriously affected by hemorrhagic fever with renal syndrome (HFRS) with 90% of HFRS cases reported globally.
+Therefore, there is an urgent need for monitoring and predicting HFRS incidence to make the control of HFRS more effective.
+In this study, we applied a stochastic autoregressive integrated moving average (ARIMA) model with the objective of monitoring and short-term forecasting HFRS incidence in China.
+Subsequently, the fitted ARIMA model was applied to obtain the fitted HFRS incidence from 1978 to 2008 and contrast with corresponding observed values.
+To assess the validity of the proposed model, the mean absolute percentage error (MAPE) between the observed and fitted HFRS incidence (1978-2008) was calculated.
+Finally, the fitted ARIMA model was used to forecast the incidence of HFRS of the years 2009 to 2011.
+RESULTS: The goodness-of-fit test of the optimum ARIMA (0,3,1) model showed non-significant autocorrelations in the residuals of the model (Ljung-Box Q statistic = 5.95,P = 0.3113).
+The fitted values made by ARIMA (0,3,1) model for years 1978-2008 closely followed the observed values for the same years, with a mean absolute percentage error (MAPE) of 12.20%.
+The forecast values from 2009 to 2011 were 0.69, 0.86, and 1.21per 100,000 population, respectively.
+CONCLUSION: ARIMA models applied to historical HFRS incidence data are an important tool for HFRS surveillance in China.
+This study shows that accurate forecasting of the HFRS incidence is possible using an ARIMA model.
+If predicted values from this study are accurate, China can expect a rise in HFRS incidence.
+Intradermal (ID) vaccination can offer improved immunity and simpler logistics of delivery, but its use in medicine is limited by the need for simple, reliable methods of ID delivery.
+ID injection by the Mantoux technique requires special training and may not reliably target skin, but is nonetheless used currently for BCG and rabies vaccination.
+Scarification using a bifurcated needle was extensively used for smallpox eradication, but provides variable and inefficient delivery into the skin.
+Recently, ID vaccination has been simplified by introduction of a simple-to-use hollow microneedle that has been approved for ID injection of influenza vaccine in Europe.
+Vaccines can also be injected into skin using needle-free devices, such as jet injection, which is receiving renewed clinical attention for ID vaccination.
+Projectile delivery using powder and gold particles (i.e., gene gun) have also been used clinically for ID vaccination.
+Building off the scarification approach, a number of preclinical studies have examined solid microneedle patches for use with vaccine coated onto metal microneedles, encapsulated within dissolving microneedles or added topically to skin after microneedle pretreatment, as well as adapting tattoo guns for ID vaccination.
+Finally, technologies designed to increase skin permeability in combination with a vaccine patch have been studied through the use of skin abrasion, ultrasound, electroporation, chemical enhancers, and thermal ablation.
+The prospects for bringing ID vaccination into more widespread clinical practice are encouraging, given the large number of technologies for ID delivery under development.
+INTRODUCTION: Mechanical ventilation (MV) of mice is increasingly required in experimental studies, but the conditions that allow stable ventilation of mice over several hours have not yet been fully defined.
+The aim of the present study was to establish experimental conditions that keep these parameters within their physiological range over a period of 6 h. For this purpose, we also examined the effects of frequent short recruitment manoeuvres (RM) in healthy mice.
+METHODS: Mice were ventilated at low tidal volume V(T) = 8 mL/kg or high tidal volume V(T) = 16 mL/kg and a positive end-expiratory pressure (PEEP) of 2 or 6 cmH(2)O. RM were performed every 5 min, 60 min or not at all.
+Blood pressure (BP), electrocardiogram (ECG), heart frequency (HF), oxygen saturation and body temperature were monitored.
+Blood gases, neutrophil-recruitment, microvascular permeability and pro-inflammatory cytokines in bronchoalveolar lavage (BAL) and blood serum as well as histopathology of the lung were examined.
+Ventilation without RM worsened lung mechanics due to alveolar collapse, leading to impaired gas exchange.
+Microvascular permeability was highest in atelectatic lungs, whereas neutrophil-recruitment and structural changes were strongest in lungs ventilated with high tidal volume.
+The cytokines IL-6 and KC, but neither TNF nor IP-10, were elevated in the BAL and serum of all ventilated mice and were reduced by recurrent RM.
+CONCLUSIONS: Recurrent RM maintain lung mechanics in their physiological range during low tidal volume ventilation of healthy mice by preventing atelectasis and reduce the development of pulmonary inflammation.
+The RNA guanylyltransferase (GTase) is involved in the synthesis of the (m7)Gppp-RNA cap structure found at the 5′ end of eukaryotic mRNAs.
+GTases are members of the covalent nucleotidyl transferase superfamily, which also includes DNA and RNA ligases.
+GTases catalyze a two-step reaction in which they initially utilize GTP as a substrate to form a covalent enzyme-GMP intermediate.
+The GMP moiety is then transferred to the diphosphate end of the RNA transcript in the second step of the reaction to form the Gppp-RNA structure.
+In the current study, we used a combination of virtual database screening, homology modeling, and biochemical assays to search for novel GTase inhibitors.
+Using this approach, we demonstrate that mycophenolic acid (MPA) can inhibit the GTase reaction by preventing the catalytic transfer of the GMP moiety onto an acceptor RNA.
+As such, MPA represents a novel type of inhibitor against RNA guanylyltransferases that inhibits the second step of the catalytic reaction.
+Moreover, we show that the addition of MPA to S. cerevisiae cells leads to a reduction of capped mRNAs.
+Finally, biochemical assays also demonstrate that MPA can inhibit DNA ligases through inhibition of the second step of the reaction.
+The biological implications of these findings for the MPA-mediated inhibition of members of the covalent nucleotidyl superfamily are discussed.
+BACKGROUND: Clinical presentation, diagnosis, management and outcome of molecularly defined congenital pulmonary alveolar proteinosis (PAP) due to mutations in the GM-CSF receptor are not well known.
+Whole lung lavages were performed with a new catheter balloon technique, feasible in small sized airways.
+Because of some interstitial inflammation in the lung biopsy and to further improve the condition, empirical therapy with systemic steroids and azathioprin, and inhaled and subcutaneous GMCSF, were used.
+Based on clinical measures, total protein and lipid recovered by whole lung lavages, all these treatments were without benefit.
+Recently the novel homozygous stop mutation p.Ser25X of the GMCSF receptor alpha chain was identified in the patient.
+This mutation leads to a lack of functional GMCSF receptor and a reduced response to GMCSF stimulation of CD11b expression of mononuclear cells of the patient.
+Subsequently a very intense treatment with monthly lavages was initiated, resulting for the first time in complete resolution of partial respiratory insufficiency and a significant improvement of the overall somato-psychosocial condition of the child.
+CONCLUSIONS: The long term management from early childhood into young adolescence of severe alveolar proteinosis due to GMCSF receptor deficiency requires a dedicated specialized team to perform technically demanding whole lung lavages and cope with complications.
+We initiated a nation-wide three-year surveillance of children who were admitted to a paediatric intensive care unit (PICU) with severe seasonal influenza.
+METHODS: From October 2005 to July 2008, active surveillance was performed using an established reporting system for rare diseases (ESPED) including all paediatric hospitals in Germany.
+Cases to be reported were hospitalized children < 17 years of age with laboratory-confirmed influenza treated in a PICU or dying in hospital.
+RESULTS: Twenty severe influenza-associated cases were reported from 14 PICUs during three pre-pandemic influenza seasons (2005-2008).
+The median age of the patients (12 males/8 females) was 7.5 years (range 0.1-15 years).
+In 14 (70%) patients, the infection had been caused by influenza A and in five (25%) by influenza B; in one child (5%) the influenza type was not reported.
+Patients spent a median of 19 (IQR 12-38) days in the hospital and a median of 11 days (IQR 6-18 days) in the PICU; 10 (50%) needed mechanical ventilation.
+Most frequent diagnoses were influenza-associated pneumonia (60%), bronchitis/bronchiolitis (30%), encephalitis/encephalopathy (25%), secondary bacterial pneumonia (25%), and ARDS (25%).
+Eleven (55%) children had chronic underlying medical conditions, including 8 (40%) with chronic pulmonary diseases.
+Two influenza A- associated deaths were reported: i) an 8-year old boy with pneumococcal encephalopathy following influenza infection died from cerebral edema, ii) a 14-year-old boy with asthma bronchiale, cardiac malformation and Addison's disease died from cardiac and respiratory failure.
+For nine (45%) patients, possibly permanent sequelae were reported (3 neurological, 3 pulmonary, 3 other sequelae).
+CONCLUSIONS: Influenza-associated pneumonia and secondary bacterial infections are relevant complications of seasonal influenza in Germany.
+This may be either due to the weak to moderate seasonal influenza activity during the years 2005 to 2008 or due to under-diagnosis of influenza by physicians.
+Fifty% of the observed severe cases might have been prevented by following the recommendations for vaccination of risk groups in Germany.
+BACKGROUND: There was a pandemic influenza around the world in 2009 including South Korea since last pandemic occurred four decades ago.
+METHODS: We evaluated the epidemiologic characteristics of all the subjects infected with the 2009 H1N1 influenza A virus (2,971 patients, ≤ 15 years of age), and the clinical and laboratory findings of the inpatients (217 patients, 80 had pneumonia) between 1 September 2009 and 31 January 2010 in a single hospital throughout the epidemic.
+Two hundred and five patients (94.5%) received oseltamivir within 48 h of fever onset, and 97% of inpatients defervesced within 48 h of medication.
+The group with pneumonia included more males than females, and had higher leukocytes counts with lower lymphocyte differentials than the group without pneumonia.
+The white blood cell count and lymphocyte differential were associated with the severity of pneumonia.
+CONCLUSION: Children of all ages affected with even rates of infection, but males were predominant in pneumonia patients.
+Our results suggest that the mechanism of lung injury in 2009 H1N1 virus infection may be associated with the host immune response.
+BACKGROUND: Acute lung injury (ALI) is a serious respiratory disorder for which therapy is primarily supportive once infection is excluded.
+Surgical lung biopsy may rule out other diagnoses, but has not been generally useful for therapy decisions or prognosis in this setting.
+Importantly, tissue and peripheral blood eosinophilia, the hallmarks of steroid-responsive acute eosinophilic pneumonia, are not commonly linked with ALI.
+We hypothesized that occult eosinophilic pneumonia may explain better outcomes for some patients with ALI.
+METHODS: Immunohistochemistry using a novel monoclonal antibody recognizing eosinophil peroxidase (EPX-mAb) was used to assess intrapulmonary eosinophil accumulation/degranulation.
+Lung biopsies from ALI patients (n = 20) were identified following review of a pathology database; 45% of which (i.e., 9/20) displayed classical diffuse alveolar damage (ALI-DAD).
+Controls were obtained from uninvolved tissue in patients undergoing lobectomy for lung cancer (n = 10).
+Serial biopsy sections were stained with hematoxylin and eosin (H&E) and subjected to EPX-mAb immunohistochemistry.
+RESULTS: EPX-mAb immunohistochemistry provided a >40-fold increased sensitivity to detect eosinophils in the lung relative to H&E stained sections.
+This increased sensitivity led to the identification of higher numbers of eosinophils in ALI patients compared with controls; differences using H&E staining alone were not significant.
+Clinical assessments showed that lung infiltrating eosinophil numbers were higher in ALI patients that survived hospitalization compared with non-survivors.
+CONCLUSION: The enhanced sensitivity of EPX-mAb immunohistochemistry uniquely identified eosinophil accumulation/degranulation in patients with ALI relative to controls.
+These observations suggest that EPX-mAb immunohistochemistry may represent a diagnostic biomarker identifying a subset of ALI patients with improved clinical outcomes.
+Influenza A virus segment 2 mRNA expresses three polypeptides: PB1, PB1-F2 and PB1-N40, from AUGs 1, 4 and 5 respectively.
+Two short open reading frames (sORFs) initiated by AUGs 2 and 3 are also present.
+To understand translational regulation in this system, we systematically mutated AUGs 1–4 and monitored polypeptide synthesis from plasmids and recombinant viruses.
+This identified sORF2 as a key regulatory element with opposing effects on PB1-F2 and PB1-N40 expression.
+We propose a model in which AUGs 1–4 are accessed by leaky ribosomal scanning, with sORF2 repressing synthesis of downstream PB1-F2.
+However, sORF2 also up-regulates PB1-N40 expression, most likely by a reinitiation mechanism that permits skipping of AUG4.
+Surprisingly, we also found that in contrast to plasmid-driven expression, viruses with improved AUG1 initiation contexts produced less PB1 in infected cells and replicated poorly, producing virions with elevated particle:PFU ratios.
+Analysis of the genome content of virus particles showed reduced packaging of the mutant segment 2 vRNAs.
+Overall, we conclude that segment 2 mRNA translation is regulated by a combination of leaky ribosomal scanning and reinitiation, and that the sequences surrounding the PB1 AUG codon are multifunctional, containing overlapping signals for translation initiation and for segment-specific packaging.
+BACKGROUND: Pro-coagulant membrane microvesicles (MV) derived from platelets and leukocytes are shed into the circulation following receptor-mediated activation, cell-cell interaction, and apoptosis.
+Experiments were designed to evaluate the time course and mechanism of direct interactions between platelets and leukocytes following acute activation of TLR4 by bacterial lipopolysaccharide (LPS).
+METHODOLOGY/PRINCIPAL FINDINGS: Blood from age-matched male and female wild type (WT) and TLR4 gene deleted (dTLR4) mice was incubated with ultra-pure E. coli LPS (500 ng/ml) for up to one hour.
+At designated periods, leukocyte antigen positive platelets, platelet antigen positive leukocytes and cell-derived MV were quantified by flow cytometry.
+Numbers of platelet- or leukocyte-derived MV did not increase within one hour following in vitro exposure of blood to LPS.
+However, with LPS stimulation numbers of platelets staining positive for both platelet- and leukocyte-specific antigens increased in blood derived from WT but not dTLR4 mice.
+Seven days after a single intravenous injection of LPS (500 ng/mouse or 20 ng/gm body wt) to WT mice, none of the platelets stained for leukocyte antigen.
+CONCLUSIONS/SIGNIFICANCE: Within one hour of exposure to LPS, leukocytes exchange surface antigens with platelets through TLR4 activation.
+In vivo, leukocyte expression of platelet antigen is retained after a single exposure to LPS following turn over of the platelet pool.
+Acute expression of leukocyte antigen on platelets within one hour of exposure to LPS and the sustained expression of platelet antigen on leukocytes following a single acute exposure to LPS in vivo explains, in part, associations of platelets and leukocytes in response to bacterial infection and changes in thrombotic propensity of the blood.
+This receptor recognizes MHC class I-like molecules expressed on the surface of infected cells and serves to augment T cell-mediated cytotoxicity.
+The role of NKG2D-mediated augmentation in the clearance of central nervous system viral infections has not been explored.
+Using the Theiler's murine encephalomyelitis virus model we found that NKG2D-positive CD8+ cytotoxic T cells enter the brain, that NKG2D ligands are expressed in the brain during acute infection, and that interruption of NKG2D ligand recognition via treatment with a function blocking antibody attenuates the efficacy of viral clearance from the central nervous system.
+Partetravirus is a recently described group of animal parvoviruses which include the human partetravirus, bovine partetravirus and porcine partetravirus (previously known as human parvovirus 4, bovine hokovirus and porcine hokovirus respectively).
+In this report, we describe the discovery and genomic characterization of partetraviruses in bovine and ovine samples from China.
+These partetraviruses were detected by PCR in 1.8% of bovine liver samples, 66.7% of ovine liver samples and 71.4% of ovine spleen samples.
+One of the bovine partetraviruses detected in the present samples is phylogenetically distinct from previously reported bovine partetraviruses and likely represents a novel genotype.
+The ovine partetravirus is a novel partetravirus and phylogenetically most related to the bovine partetraviruses.
+The genome organization is conserved amongst these viruses, including the presence of a putative transmembrane protein encoded by an overlapping reading frame in ORF2.
+Results from the present study provide further support to the classification of partetraviruses as a separate genus in Parvovirinae.
+Epidemiology and public health planning will increasingly rely on the analysis of genetic sequence data.
+In particular, genetic data coupled with dates and locations of sampled isolates can be used to reconstruct the spatiotemporal dynamics of pathogens during outbreaks.
+Although these approaches have proved useful for informing on the spread of pathogens, they do not aim at directly reconstructing the underlying transmission tree.
+Instead, phylogenetic models infer most recent common ancestors between pairs of isolates, which can be inadequate for densely sampled recent outbreaks, where the sample includes ancestral and descendent isolates.
+In this paper, we introduce a novel method based on a graph approach to reconstruct transmission trees directly from genetic data.
+Using simulated data, we show that our approach can efficiently reconstruct genealogies of isolates in situations where classical phylogenetic approaches fail to do so.
+We then illustrate our method by analyzing data from the early stages of the swine-origin A/H1N1 influenza pandemic.
+Using 433 isolates sequenced at both the hemagglutinin and neuraminidase genes, we reconstruct the likely history of the worldwide spread of this new influenza strain.
+The presented methodology opens new perspectives for the analysis of genetic data in the context of disease outbreaks.
+IFN-I have potent direct antiviral activities and also mediate a multiplicity of immunoregulatory functions, which can either promote or dampen antiviral adaptive immune responses.
+Plasmacytoid dendritic cells (pDCs) are the professional producers of IFN-I in response to many viruses, including all of the herpesviruses tested.
+There is strong evidence that pDCs could play a major role in the initial orchestration of both innate and adaptive antiviral immune responses.
+Depending on their activation pattern, pDC responses may be either protective or detrimental to the host.
+Here, we summarize and discuss current knowledge regarding pDC implication in the physiopathology of mouse and human herpesvirus infections, and we discuss how pDC functions could be manipulated in immunotherapeutic settings to promote health over disease.
+INTRODUCTION: To establish strategic priorities for the German national public health institute (RKI) and guide the institute's mid-term strategic decisions, we prioritized infectious pathogens in accordance with their importance for national surveillance and epidemiological research.
+METHODS: We used the Delphi process with internal (RKI) and external experts and a metric-consensus approach to score pathogens according to ten three-tiered criteria.
+Additional experts were invited to weight each criterion, leading to the calculation of a median weight by which each score was multiplied.
+We ranked the pathogens according to the total weighted score and divided them into four priority groups.
+Eighty-six experts participated in the weighting; “Case fatality rate” was rated as the most important criterion.
+Twenty-six pathogens were ranked in the highest priority group; among those were pathogens with internationally recognised importance (e.g., Human Immunodeficiency Virus, Mycobacterium tuberculosis, Influenza virus, Hepatitis C virus, Neisseria meningitides), pathogens frequently causing large outbreaks (e.g., Campylobacter spp.
+Other pathogens in the highest priority group included Helicobacter pylori, Respiratory Syncytial Virus, Varicella zoster virus and Hantavirus.
+DISCUSSION: While several pathogens from the highest priority group already have a high profile in national and international health policy documents, high scores for other pathogens (e.g., Helicobacter pylori, Respiratory syncytial virus or Hantavirus) indicate a possible under-recognised importance within the current German public health framework.
+The prioritization methodology has worked well; its modular structure makes it potentially useful for other settings.
+Type I interferons (IFN) comprise a family of cytokines that signal through a common cellular receptor to induce a plethora of genes with antiviral and other activities.
+Recombinant IFNs are used for the treatment of hepatitis C virus infection, multiple sclerosis, and certain malignancies.
+The capability of type I IFN to suppress virus replication and resultant cytopathic effects is frequently used to measure their bioactivity.
+In this study, an improved IFN assay is presented which is based on a recombinant vesicular stomatitis virus (VSV) replicon encoding two reporter proteins, firefly luciferase and green fluorescent protein.
+The vector lacks the essential envelope glycoprotein (G) gene of VSV and is propagated on a G protein-expressing transgenic cell line.
+Several mammalian and avian cells turned out to be susceptible to infection with the complemented replicon particles.
+When human fibroblasts were treated with serial dilutions of human IFN-β prior to infection, reporter expression was accordingly suppressed.
+This method was more sensitive and faster than a classical IFN bioassay based on VSV cytopathic effects.
+In addition, the antiviral activity of human IFN-λ (interleukin-29), a type III IFN, was determined on Calu-3 cells.
+The antiviral activities of canine, porcine, and avian type I IFN were analysed with cell lines derived from the corresponding species.
+This safe bioassay will be useful for the rapid and sensitive quantification of multi-species type I IFN and potentially other antiviral cytokines.
+Several new human monoclonal antibodies (mAbs) with a neutralizing potential across different subtypes have recently been described.
+Three mAbs, HJ16, HGN194 and HK20, were obtained from patients within the HIV-1 cohort of the Institute of Tropical Medicine (ITM).
+Here, we describe the selection and characterization of patient plasma and their mAbs, using a range of neutralization assays, including several peripheral blood mononuclear cell (PBMC) based assays and replicating primary viruses as well as cell line based assays and pseudoviruses (PV).
+The principal criterion for selection of patient plasma was the activity in an ‘extended incubation phase’ PBMC assay.
+Neutralizing Abs, derived from their memory B cells, were then selected by ELISA with envelope proteins as solid phase.
+The present study indicates that the strong profiles in the patients' plasma were not solely due to antibodies represented by the newly isolated mAbs.
+Although results from the various assays were divergent, they by and large indicate that neutralizing Abs to other epitopes of the HIV-1 envelope are present in the plasma and synergy between Abs may be important.
+Thus, the spectrum of the obtained mAbs does not cover the range of cross-reactivity seen in plasma in these carefully selected patients irrespective of which neutralization assay is used.
+Nevertheless, these mAbs are relevant for immunogen discovery because they bind to the recombinant glycoproteins to which the immune response needs to be targeted in vivo.
+gp350, the major envelope protein of Epstein-Barr-Virus, confers B-cell tropism to the virus by interacting with the B lineage marker CD21.
+These exosomes can be used for the targeted co-transfer of functional proteins to normal and malignant human B cells.
+We demonstrate here the co-transfer of functional CD154 protein on tailored gp350+ exosomes to malignant B blasts from patients with B chronic lymphocytic leukemia (B-CLL), rendering B blasts immunogenic to tumor-reactive autologous T cells.
+Intriguingly, engulfment of gp350+ exosomes by B-CLL cells and presentation of gp350-derived peptides also re-stimulated EBV-specific T cells and redirected the strong antiviral cellular immune response in patients to leukemic B cells.
+In essence, we show that gp350 alone confers B-cell tropism to exosomes and that these exosomes can be further engineered to simultaneously trigger virus- and tumor-specific immune responses.
+The simultaneous exploitation of gp350 as a tropism molecule for tailored exosomes and as a neo-antigen in malignant B cells provides a novel attractive strategy for immunotherapy of B-CLL and other B-cell malignancies.
+The orbivirus genome, composed of 10 segments of dsRNA, encodes 7 structural proteins (VP1–VP7) and 3 non-structural proteins (NS1–NS3).
+An open reading frame (ORF) that spans almost the entire length of genome segment-9 (Seg-9) encodes VP6 (the viral helicase).
+Western blotting and confocal fluorescence microscopy, using antibodies raised against recombinant NS4 from Bluetongue virus (BTV, which is insect-borne), or Great Island virus (GIV, which is tick-borne), demonstrate that these proteins are synthesised in BTV or GIV infected mammalian cells, respectively.
+NS4 forms aggregates throughout the cytoplasm as well as in the nucleus, consistent with identification of nuclear localisation signals within the NS4 sequence.
+Bioinformatic analyses indicate that NS4 contains coiled-coils, is related to proteins that bind nucleic acids, or are associated with membranes and shows similarities to nucleolar protein UTP20 (a processome subunit).
+Recombinant NS4 of GIV protects dsRNA from degradation by endoribonucleases of the RNAse III family, indicating that it interacts with dsRNA.
+However, BTV NS4, which is only half the putative size of the GIV NS4, did not protect dsRNA from RNAse III cleavage.
+NS4 was found to associate with lipid droplets in cells infected with BTV or GIV or transfected with a plasmid expressing NS4.
+BACKGROUND: As of 31(st) March 2010, more than 127,000 confirmed cases of 2009 pandemic influenza A (H1N1), including 800 deaths, were reported in mainland China.
+The distribution and characteristics of the confirmed cases in the initial phase of this pandemic in this country are largely unknown.
+The present study aimed to characterize the geographic distribution and patient characteristics of H1N1 infection in the 2009 pandemic as well as to identify potential risk factors associated with adverse patient outcome in China, through retrospective analyses of 885 hospitalized cases with confirmed H1N1 infection.
+METHODOLOGY/PRINCIPAL FINDINGS: The proportional hazards model was employed to detect risk factors for adverse outcome; the geo-statistical maps were used to characterize the distribution of all 2668 confirmed H1N1 patients throughout mainland China.
+The number of new cases increased slowly in May, 2009, but rapidly between June and August of the year.
+Confirmed cases were reported in 26 provinces; Beijing, Guangdong, Shanghai, Zhejiang and Fujian were the top five regions of the incidence of the virus infection.
+After being adjusted for gender, age, chronic pulmonary disease and other general symptoms, delay for more than two days before hospital admission (HR: 0.6; 95%CI: 0.5–0.7) and delayed onset of the H1N1-specific respiratory symptoms (HR: 0.3; 95%CI: 0.2–0.4) were associated with adverse patient outcome.
+CONCLUSIONS/SIGNIFICANCE: The 2009 pandemic influenza A affected east and southeast coastal provinces and most populous cities more severely than other regions in mainland China due to higher risk of high level traffic-, high population density-, and high population mobility-associated H1N1 transmission.The clinical symptoms were mild in the initial phase of infection.
+Delayed hospital admission and delayed appearance of respiratory symptoms were among the major risk factors for poor patient outcome.
+BACKGROUND: RNA viruses infecting a host usually exist as a set of closely related sequences, referred to as quasispecies.
+The genomic diversity of viral quasispecies is a subject of great interest, particularly for chronic infections, since it can lead to resistance to existing therapies.
+High-throughput sequencing is a promising approach to characterizing viral diversity, but unfortunately standard assembly software was originally designed for single genome assembly and cannot be used to simultaneously assemble and estimate the abundance of multiple closely related quasispecies sequences.
+RESULTS: In this paper, we introduce a new Viral Spectrum Assembler (ViSpA) method for quasispecies spectrum reconstruction and compare it with the state-of-the-art ShoRAH tool on both simulated and real 454 pyrosequencing shotgun reads from HCV and HIV quasispecies.
+Experimental results show that ViSpA outperforms ShoRAH on simulated error-free reads, correctly assembling 10 out of 10 quasispecies and 29 sequences out of 40 quasispecies.
+While ShoRAH has a significant advantage over ViSpA on reads simulated with sequencing errors due to its advanced error correction algorithm, ViSpA is better at assembling the simulated reads after they have been corrected by ShoRAH.
+Indeed, 7 most frequent sequences reconstructed by ViSpA from a real HCV dataset are viable (do not contain internal stop codons), and the most frequent sequence was within 1% of the actual open reading frame obtained by cloning and Sanger sequencing.
+On a real HIV dataset, ShoRAH correctly inferred only 2 quasispecies sequences with at most 4 mismatches whereas ViSpA correctly reconstructed 5 quasispecies with at most 2 mismatches, and 2 out of 5 sequences were inferred without any mismatches.
+We are currently exploring extensions applicable to the analysis of high-throughput sequencing data from bacterial metagenomic samples and ecological samples of eukaryote populations.
+ZEBOV primarily targets mononuclear phagocytes, which are activated upon infection and secrete mediators believed to trigger initial stages of pathogenesis.
+The characterization of the responses of target cells to ZEBOV infection may therefore not only further understanding of pathogenesis but also suggest possible points of therapeutic intervention.
+Gene expression profiles of primary human macrophages exposed to ZEBOV were determined using DNA microarrays and quantitative PCR to gain insight into the cellular response immediately after cell entry.
+Some, however, are inflammatory mediators known to be elevated during the acute phase of disease in the blood of ZEBOV-infected humans.
+This observation supports the hypothesis that virion binding or entry mediated by the spike glycoprotein (GP(1,2)) is the primary stimulus for an initial response.
+Indeed, ZEBOV virions, LPS, and virus-like particles consisting of only the ZEBOV matrix protein VP40 and GP(1,2) (VLP(VP40-GP)) triggered comparable responses in macrophages, including pro-inflammatory and pro-apoptotic signals.
+This suggests that GP(1,2) binding to macrophages plays an important role in the immediate cellular response.
+BACKGROUND: In contrast to seasonal influenza epidemics, where the majority of deaths occur amongst elderly, a considerable part of the 2009 pandemic influenza related deaths concerned relatively young people.
+In the Netherlands, all deaths associated with laboratory-confirmed influenza A(H1N1) 2009 virus infection had to be notified, both during the 2009-2010 pandemic season and the 2010-2011 influenza season.
+To assess whether and to what extent pandemic mortality patterns were reverting back to seasonal patterns, a retrospective analyses of all notified fatal cases associated with laboratory-confirmed influenza A(H1N1) 2009 virus infection was performed.
+METHODS: The notification database, including detailed information about the clinical characteristics of all notified deaths, was used to perform a comprehensive analysis of all deceased patients with a laboratory-confirmed influenza A(H1N1) 2009 virus infection.
+Characteristics of the fatalities with respect to age and underlying medical conditions were analysed, comparing the 2009-2010 pandemic and the 2010-2011 influenza season.
+RESULTS: A total of 65 fatalities with a laboratory-confirmed influenza A(H1N1) 2009 virus infection were notified in 2009-2010 and 38 in 2010-2011.
+During the pandemic season, the population mortality rates peaked in persons aged 0-15 and 55-64 years.
+In the 2010-2011 influenza season, peaks in mortality were seen in persons aged 0-15 and 75-84 years.
+During the 2010-2011 influenza season, the height of first peak was lower compared to that during the pandemic season.
+Underlying immunological disorders were more common in the pandemic season compared to the 2010-2011 season (p = 0.02), and cardiovascular disorders were more common in the 2010-2011 season (p = 0.005).
+CONCLUSIONS: The mortality pattern in the 2010-2011 influenza season still resembled the 2009-2010 pandemic season with a peak in relatively young age groups, but concurrently a clear shift toward seasonal patterns was seen, with a peak in mortality in the elderly, i.e.
+In the present study, we investigated the effects of a Chinese herbal formula on GPS in earthquake survivors with PTSD.
+A randomized, double-blind, placebo-controlled trial compared a Chinese herbal formula, Xiao-Tan-Jie-Yu-Fang (XTJYF), to placebo in 2008 Sichuan earthquake survivors with PTSD.
+Baseline-to-end-point score changes in the three global indices of the Symptom Checklist-90-Revised (SCL-90-R) and rates of response in the SCL global severity index (GSI) were the primary endpoints.
+A subanalysis of the nine SCL factors and the sleep quality score were secondary endpoints.
+Compared to placebo, the XTJYF group was significantly improved in all three SCL global indices (P = 0.001~0.028).
+More patients in the XTJYF group reported “much improved” than the placebo group (P = 0.001).
+The XTJYF group performed significantly better than control in five out of nine SCL factors (somatization, obsessive-compulsive behavior, depression, anxiety, and hostility (P = 0.001~0.036)), and in sleep quality score (P < 0.001).
+These findings suggest that XTJYF may be an effective and safe treatment option for improving GPS in patients with PTSD.
+BACKGROUND: On the base of our previous study we were observed relevant studies on the hypothesis that the antiviral activity of quercetin 7-rhamnoside (Q7R), a flavonoid, won't relate ability of its antioxidant.
+METHODS: We were investigated the effects of Q7R on the cytopathic effects (CPE) by CPE reduction assay.
+Production of DNA fragment and reactive oxygen species (ROS) induced by PEDV infection were studied using DNA fragmentation assay and flow cytometry.
+RESULTS: In the course of this study it was discovered that Q7R is an extremely potent compound against PEDV.
+The addition of Q7R to PEDV-infected Vero cells directly reduced the formation of a visible cytopathic effect (CPE).
+Antiviral activity of antioxidants such as NAC, pyrrolidine dithiocarbamate (PDTC), and the vitamin E derivative, trolox, were hardly noticed.
+CONCLUSIONS: We concluded that the inhibition of PEDV production by Q7R is not simply due to a general action as an antioxidants and is highly specific, as several other antioxidants (NAC, PDTC, trolox) are inactive against PEDV infection.
+Several arenaviruses can cause viral hemorrhagic fever, a severe disease with case-fatality rates in hospitalized individuals ranging from 15-30%.
+Because of limited prophylaxis and treatment options, new medical countermeasures are needed for these viruses classified by the National Institutes of Allergy and Infectious Diseases (NIAID) as top priority biodefense Category A pathogens.
+However, while cIFN-α has great therapeutic value, its utility for biodefense applications is hindered by its short in vivo half-life, mode and frequency of administration, and costly production.
+To address these limitations, we describe the use of DEF201, a replication-deficient adenovirus vector that drives the expression of cIFN-α, for pre- and post-exposure prophylaxis of acute arenaviral infection modeled in hamsters.
+Intranasal administration of DEF201 24 h prior to challenge with Pichindé virus (PICV) was highly effective at protecting animals from mortality and preventing viral replication and liver-associated disease.
+A significant protective effect was still observed with a single dosing of DEF201 given two weeks prior to PICV challenge.
+DEF201 was also efficacious when administered as a treatment 24 to 48 h post-virus exposure.
+The protective effect of DEF201 was largely attributed to the expression of cIFN-α, as dosing with a control empty vector adenovirus did not protect hamsters from lethal PICV challenge.
+Effective countermeasures that are highly stable, easily administered, and elicit long lasting protective immunity are much needed for arena and other viral infections.
+The DEF201 technology has the potential to address all of these issues and may serve as a broad-spectrum antiviral to enhance host defense against a number of viral pathogens.
+Reactive oxygen species (ROS) production by immunological cells is known to cause damage to pathogens.
+Increasing evidence accumulated in the last decade has shown, however, that ROS (and redox signals) functionally regulate different cellular pathways in the host-pathogen interaction.
+These especially affect (i) pathogen entry through protein redox switches and redox modification (i.e., intra- and interdisulfide and cysteine oxidation) and (ii) phagocytic ROS production via Nox family NADPH oxidase enzyme and the control of phagolysosome function with key implications for antigen processing.
+The protein disulfide isomerase (PDI) family of redox chaperones is closely involved in both processes and is also implicated in protein unfolding and trafficking across the endoplasmic reticulum (ER) and towards the cytosol, a thiol-based redox locus for antigen processing.
+Here, we summarise examples of the cellular association of host PDI with different pathogens and explore the possible roles of pathogen PDIs in infection.
+A better understanding of these complex regulatory steps will provide insightful information on the redox role and coevolutional biological process, and assist the development of more specific therapeutic strategies in pathogen-mediated infections.
+Initially thought as being non-immunogenic, recombinant AAVs have emerged as efficient vector candidates for treating monogenic diseases.
+It is now clear however that they induce potent immune responses against transgene products which can lead to destruction of transduced cells.
+Therefore, developing strategies to circumvent these immune responses and facilitate long-term expression of transgenic therapeutic proteins is a main challenge in gene therapy.
+We evaluated herein a strategy to inhibit the undesirable immune activation that follows muscle gene transfer by administration of CTLA-4/Ig to block the costimulatory signals required early during immune priming and by using gene transfer of PD-1 ligands to inhibit T cell functions at the tissue sites.
+We provide the proof of principle that this combination immunoregulatory therapy targeting two non-redundant checkpoints of the immune response, i.e., priming and effector functions, can improve persistence of transduced cells in experimental settings where cytotoxic T cells escape initial blockade.
+Therefore, CTLA-4/Ig plus PD-L1/2 combination therapy represents a candidate approach to circumvent the bottleneck of immune responses directed toward transgene products.
+Epstein-Barr virus (EBV) is a ubiquitous herpesvirus, and Kaposi’s sarcoma–associated herpesvirus (KSHV) has a restricted seroprevalence.
+Both viruses are associated with malignancies that have an increased frequency in individuals who are coinfected with human immunodeficiency virus type 1 (HIV-1).
+To obtain an overview of humoral immune responses to these viruses, we generated a protein array that displayed 174 EBV and KSHV polypeptides purified from yeast.
+Antibody responses to EBV and KSHV were examined in plasma from healthy volunteers and patients with B cell lymphoma or with AIDS-related Kaposi’s sarcoma or lymphoma.
+In addition to the commonly studied antigens, IgG responses were frequently detected to the tegument proteins KSHV ORF38 and EBV BBRF and BGLF2 and BNRF1 and to the EBV early lytic proteins BRRF1 and BORF2.
+The protein array provided a sensitive platform for global screening; identified new, frequently recognized viral antigens; and revealed a broader humoral response to EBV compared with KSHV in the same patients.
+−1 Programmed ribosomal frameshifting (PRF) in synthesizing the gag-pro precursor polyprotein of Simian retrovirus type-1 (SRV-1) is stimulated by a classical H-type pseudoknot which forms an extended triple helix involving base–base and base–sugar interactions between loop and stem nucleotides.
+Recently, we showed that mutation of bases involved in triple helix formation affected frameshifting, again emphasizing the role of the triple helix in −1 PRF.
+Here, we investigated the efficiency of hairpins of similar base pair composition as the SRV-1 gag-pro pseudoknot.
+Subsequent investigation of ∼30 different hairpin constructs revealed that next to thermodynamic stability, loop size and composition and stem irregularities can influence frameshifting.
+Interestingly, hairpins carrying the stable GAAA tetraloop were significantly less shifty than other hairpins, including those with a UUCG motif.
+Recent advances in high-throughput technologies have made it possible to generate both gene and protein sequence data at an unprecedented rate and scale thereby enabling entirely new “omics”-based approaches towards the analysis of complex biological processes.
+However, the amount and complexity of data that even a single experiment can produce seriously challenges researchers with limited bioinformatics expertise, who need to handle, analyze and interpret the data before it can be understood in a biological context.
+Thus, there is an unmet need for tools allowing non-bioinformatics users to interpret large data sets.
+We have recently developed a method, NNAlign, which is generally applicable to any biological problem where quantitative peptide data is available.
+This method efficiently identifies underlying sequence patterns by simultaneously aligning peptide sequences and identifying motifs associated with quantitative readouts.
+Here, we provide a web-based implementation of NNAlign allowing non-expert end-users to submit their data (optionally adjusting method parameters), and in return receive a trained method (including a visual representation of the identified motif) that subsequently can be used as prediction method and applied to unknown proteins/peptides.
+We have successfully applied this method to several different data sets including peptide microarray-derived sets containing more than 100,000 data points.
+Red blood cell (RBC) transfusion is a common intervention in intensive care unit (ICU) patients.
+Anemia is frequent in this population and is associated with poor outcomes, especially in patients with ischemic heart disease.
+Although blood transfusions are generally given to improve tissue oxygenation, they do not systematically increase oxygen consumption and effects on oxygen delivery are not always very impressive.
+Blood transfusion may be lifesaving in some circumstances, but many studies have reported increased morbidity and mortality in transfused patients.
+This review focuses on some important aspects of RBC transfusion in the ICU, including physiologic considerations, a brief description of serious infectious and noninfectious hazards of transfusion, and the effects of RBC storage lesions.
+Emphasis is placed on the importance of personalizing blood transfusion according to physiological endpoints rather than arbitrary thresholds.
+BACKGROUND: Neurally adjusted ventilatory assist (NAVA) is a new mode of mechanical ventilation controlled by diaphragmatic electrical signals.
+The electrical signals allow synchronization of ventilation to spontaneous breathing efforts of a child, as well as permitting pressure assistance proportional to the electrical signal.
+NAVA provides equally fine synchronization of respiratory support and pressure assistance varying with the needs of the child.
+NAVA has mainly been studied in children who underwent cardiac surgery during the period of weaning from a respirator.
+CASE PRESENTATION: We report here a series of 3 children (1 month, 3 years, and 28 days old) with severe respiratory distress due to RSV-related bronchiolitis requiring invasive mechanical ventilation with a high level of oxygen (FiO(2 )≥50%) for whom NAVA facilitated respiratory support.
+One of these children had diagnosis criteria for acute lung injury, another for acute respiratory distress syndrome.
+Establishment of NAVA provided synchronization of mechanical ventilatory support with the breathing efforts of the children.
+Respiratory rate and inspiratory pressure became extremely variable, varying at each cycle, while children were breathing easily and smoothly.
+All three children demonstrated less oxygen requirements after introducing NAVA (57 ± 6% to 42 ± 18%).
+This improvement was observed while peak airway pressure decreased (28 ± 3 to 15 ± 5 cm H(2)O).
+In one child, NAVA facilitated the management of acute respiratory distress syndrome with extensive subcutaneous emphysema.
+CONCLUSIONS: Our findings highlight the feasibility and benefit of NAVA in children with severe RSV-related bronchiolitis.
+NAVA provides a less aggressive ventilation requiring lower inspiratory pressures with good results for oxygenation and more comfort for the children.
+BACKGROUND: Vaccine development against malaria and other complex diseases remains a challenge for the scientific community.
+The recent elucidation of the genome, proteome and transcriptome of many of these complex pathogens provides the basis for rational vaccine design by identifying, on a proteome-wide scale, novel target antigens that are recognized by T cells and antibodies from exposed individuals.
+However, there is currently no algorithm to effectively identify important target antigens from genome sequence data; this is especially challenging for T cell targets.
+Furthermore, for some of these pathogens, such as Plasmodium, protein expression using conventional platforms has been problematic but cell-free in vitro transcription translation (IVTT) strategies have recently proved successful.
+Herein, we report a novel approach for proteome-wide scale identification of the antigenic targets of T cell responses using IVTT products.
+PRINCIPAL FINDINGS: We conducted a series of in vitro and in vivo experiments using IVTT proteins either unpurified, absorbed to carboxylated polybeads, or affinity purified through nickel resin or magnetic beads.
+In vitro studies in humans using CMV, EBV, and Influenza A virus proteins showed antigen-specific cytokine production in ELIspot and Cytometric Bead Array assays with cells stimulated with purified or unpurified IVTT antigens.
+In vitro and in vivo studies in mice immunized with the Plasmodium yoelii circumsporozoite DNA vaccine with or without IVTT protein boost showed antigen-specific cytokine production using purified IVTT antigens only.
+Overall, the nickel resin method of IVTT antigen purification proved optimal in both human and murine systems.
+CONCLUSIONS: This work provides proof of concept for the potential of high-throughput approaches to identify T cell targets of complex parasitic, viral or bacterial pathogens from genomic sequence data, for rational vaccine development against emerging and re-emerging diseases that pose a threat to public health.
+In all vertebrate animals, CD8(+) cytotoxic T lymphocytes (CTLs) are controlled by major histocompatibility complex class I (MHC-I) molecules.
+These are highly polymorphic peptide receptors selecting and presenting endogenously derived epitopes to circulating CTLs.
+The polymorphism of the MHC effectively individualizes the immune response of each member of the species.
+We have recently developed efficient methods to generate recombinant human MHC-I (also known as human leukocyte antigen class I, HLA-I) molecules, accompanying peptide-binding assays and predictors, and HLA tetramers for specific CTL staining and manipulation.
+We systematically transferred domains of the frequently expressed swine MHC-I molecule, SLA-1*0401, onto a HLA-I molecule (HLA-A*11:01), thereby generating recombinant human/swine chimeric MHC-I molecules as well as the intact SLA-1*0401 molecule.
+Biochemical peptide-binding assays and positional scanning combinatorial peptide libraries were used to analyze the peptide-binding motifs of these molecules.
+A pan-specific predictor of peptide–MHC-I binding, NetMHCpan, which was originally developed to cover the binding specificities of all known HLA-I molecules, was successfully used to predict the specificities of the SLA-1*0401 molecule as well as the porcine/human chimeric MHC-I molecules.
+These data indicate that it is possible to extend the biochemical and bioinformatics tools of the Human MHC Project to other vertebrate species.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00251-011-0555-3) contains supplementary material, which is available to authorized users.
+Following the 2009 H1N1 pandemic and ongoing sporadic avian-to-human transmission of H5N1 viruses, an emphasis has been placed on better understanding the determinants and pathogenesis of severe influenza infections.
+Much of the current literature has focused on viral genetics and its impact on host immunity as well as novel risk factors for severe infection (particularly within the H1N1 pandemic).
+An understanding of the host genetic determinants of susceptibility and severe respiratory illness, however, is currently lacking.
+By better defining the role of genetic variability in influenza infection and identifying key polymorphisms that impair the host immune response or correlate with protection, we will be able to better identify at-risk populations and new targets for therapeutic interventions and vaccines.
+This paper will summarize known immunogenetic factors associated with susceptibility or severity of both pH1N1 and H5N1 infections and will also identify genetic pathways and polymorphisms of high relevance for future study.
+OBJECTIVE: To test whether the incidence of common colds among college students in China is associated with ventilation rates and crowdedness in dormitories.
+METHODS: In Phase I of the study, a cross-sectional study, 3712 students living in 1569 dorm rooms in 13 buildings responded to a questionnaire about incidence and duration of common colds in the previous 12 months.
+In Phase II, air temperature, relative humidity and CO(2) concentration were measured for 24 hours in 238 dorm rooms in 13 buildings, during both summer and winter.
+RESULTS: In Phase I, 10% of college students reported an incidence of more than 6 common colds in the previous 12 months, and 15% reported that each infection usually lasted for more than 2 weeks.
+Students in 6-person dorm rooms were about 2 times as likely to have an incidence of common colds ≥6 times per year and a duration ≥2 weeks, compared to students in 3-person rooms.
+In Phase II, 90% of the measured dorm rooms had an out-to indoor air flow rate less than the Chinese standard of 8.3 L/s per person during the heating season.
+There was a dose-response relationship between out-to indoor air flow rate per person in dorm rooms and the proportion of occupants with annual common cold infections ≥6 times.
+A mean ventilation rate of 5 L/(s•person) in dorm buildings was associated with 5% of self reported common cold ≥6 times, compared to 35% at 1 L/(s•person).
+CONCLUSION: Crowded dormitories with low out-to indoor airflow rates are associated with more respiratory infections among college students.
+BACKGROUND: Numerous reports have described the epidemiological and clinical characteristics of influenza A (H1N1) 2009 infected patients.
+Therefore, this study explores the impact of bacterial coinfection on the clinical and laboratory parameters amongst H1N1 hospitalized patients.
+FINDINGS: This retrospective study involved hospitalized patients with laboratory-confirmed H1N1 infections (September 2009 to May 2010).
+Relevant clinical data and the detection of bacterial coinfection from respiratory or sterile site samples were obtained.
+Mycoplasma pneumoniae (n = 5) was the commonest bacteria followed by Staphylococcus aureus (n = 3).
+In univariate analysis, clinical factors associated with bacterial coinfection were age > 50 years (p = 0.02), presence of comorbidity (p = 0.04), liver impairment (p = 0.02), development of complications (p = 0.004) and supplemental oxygen requirement (p = 0.02).
+Leukocytosis (p = 0.02) and neutrophilia (p = 0.004) were higher in bacterial coinfected patients.
+Multivariate logistic regression analysis revealed that age > 50 years and combined complications were predictive of bacterial coinfection.
+CONCLUSIONS: Bacterial coinfection is not uncommon in H1N1 infected patients and is more frequently noted in the older aged patients and is associated with higher rates of complications.
+Also, as adjunct to clinical findings, clinicians need to have a higher index of suspicion if neutrophilia was identified at admission as it may denote bacterial coinfection.
+Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) confer substantial morbidity and mortality, and have no specific therapy.
+The accessibility of the distal lung epithelium via the airway route, and the relatively transient nature of ALI/ARDS, suggest that the disease may be amenable to gene-based therapies.
+Ongoing advances in our understanding of the pathophysiology of ALI/ARDS have revealed multiple therapeutic targets for gene-based approaches.
+Strategies to enhance or restore lung epithelial and/or endothelial cell function, to strengthen lung defense mechanisms against injury, to speed clearance of infection and to enhance the repair process following ALI/ARDS have all demonstrated promise in preclinical models.
+Despite three decades of gene therapy research, however, the clinical potential for gene-based approaches to lung diseases including ALI/ARDS remains to be realized.
+Multiple barriers to effective pulmonary gene therapy exist, including the pulmonary architecture, pulmonary defense mechanisms against inhaled particles, the immunogenicity of viral vectors and the poor transfection efficiency of nonviral delivery methods.
+Encouragingly, recent progress in overcoming these barriers offers hope for the successful translation of gene-based approaches for ALI/ARDS to the clinical setting.
+INTRODUCTION: During the first winter of exposure, the H1N1 2009 influenza virus placed considerable strain on intensive care unit (ICU) services in Australia and New Zealand (ANZ).
+We assessed the impact of the H1N1 2009 influenza virus on ICU services during the second (2010) winter, following the implementation of vaccination.
+METHODS: A prospective, cohort study was conducted in all ANZ ICUs during the southern hemisphere winter of 2010.
+RESULTS: From 1 June to 15 October 2010, there were 315 patients with confirmed influenza A, of whom 283 patients (90%) had H1N1 2009 (10.6 cases per million inhabitants; 95% confidence interval (CI), 9.4 to 11.9) which was an observed incidence of 33% of that in 2009 (P < 0.001).
+The maximum daily ICU occupancy was 2.4 beds (95% CI, 1.8 to 3) per million inhabitants in 2010 compared with 7.5 (95% CI, 6.5 to 8.6) in 2009, (P < 0.001).
+The onset of the epidemic in 2010 was delayed by five weeks compared with 2009.
+The clinical characteristics were similar in 2010 and 2009 with no difference in the age distribution, proportion of patients treated with mechanical ventilation, duration of ICU admission, or hospital mortality.
+Unlike 2009 the incidence of critical illness was significantly greater in New Zealand (18.8 cases per million inhabitants compared with 9 in Australia, P < 0.001).
+Of 170 patients with known vaccination status, 26 (15.3%) had been vaccinated against H1N1 2009.
+CONCLUSIONS: During the 2010 ANZ winter, the impact of H1N1 2009 on ICU services was still appreciable in Australia and substantial in New Zealand.
+INTRODUCTION: The intent of this study was to determine whether serum procalcitonin (PCT) levels are associated with prognosis, measured as organ dysfunctions and 28-day mortality, in patients with severe pneumonia.
+METHODS: This was a multicenter, observational study of critically ill adult patients with pneumonia requiring mechanical ventilation conducted in 10 academic hospitals in Canada, the United States, and Central Europe.
+RESULTS: We included 175 patients, 57 with community acquired pneumonia (CAP), 61 with ventilator associated pneumonia (VAP) and 57 with hospital acquired pneumonia (HAP).
+Initial PCT levels were higher in CAP than VAP patients (median (interquartile range: IQR); 2.4 (0.95 to 15.8) vs. 0.7 (0.3 to 2.15), ng/ml, P < 0.001) but not significantly different to HAP (2.2 (0.4 to 8.0) ng/ml).
+The 28-day ICU mortality rate for all patients was 18.3% with a median ICU length of stay of 16 days (range 1 to 142 days).
+Initial and maximum PCT levels correlated with maximum Sequential Organ Failure Assessment (SOFA) score r(2 )= 0.50 (95% CI: 0.38 to 0.61) and r(2 )= 0.57 (0.46 to 0.66), respectively.
+Receiver operating curve (ROC) analysis on discrimination of 28-day mortality showed areas under the curve (AUC) of 0.74, 0.70, and 0.69 for maximum PCT, initial PCT, and Acute Physiology and Chronic Health Evaluation (APACHE) II score, respectively.
+The optimal cut-off to predict mortality for initial PCT was 1.1 ng/ml (odds ratio: OD 7.0 (95% CI 2.6 to 25.2)) and that for maximum PCT was 7.8 ng/ml (odds ratio 5.7 (95% CI 2.5 to 13.1)).
+CONCLUSIONS: PCT is associated with the severity of illness in patients with severe pneumonia and appears to be a prognostic marker of morbidity and mortality comparable to the APACHE II score.
+Since 2007, many cases of fever, thrombocytopenia and leukopenia syndrome (FTLS) have emerged in Henan Province, China.
+However, only 8% (24/285) of samples collected from 2007 to 2010 tested positive for human granulocytic anaplasmosis (HGA), suggesting that other pathogens could be involved.
+Here, we used an unbiased metagenomic approach to screen and survey for microbes possibly associated with FTLS.
+BLASTx analysis of deduced protein sequences revealed that a novel bunyavirus (36% identity to Tehran virus, accession: HQ412604) was present only in sera from FTLS patients.
+A phylogenetic analysis further showed that, although closely related to Uukuniemi virus of the Phlebovirus genus, this virus was distinct.
+The candidate virus was examined for association with FTLS among samples collected from Henan province during 2007–2010.
+Of 95 patients for whom paired acute and convalescent sera were available, 73 had serologic evidence of infection, with 52 seroconversions and 21 exhibiting a 4-fold increase in antibody titer to the virus.
+The new virus was isolated from patient acute-phase serum samples and named Henan Fever Virus (HNF virus).
+Whole-genome sequencing confirmed that the virus was a novel bunyavirus with genetic similarity to known bunyaviruses, and was most closely related to the Uukuniemi virus (34%, 24%, and 29% of maximum identity, respectively, for segment L, M, S at maximum query coverage).
+After the release of the GenBank sequences of SFTSV, we found that they were nearly identical (>99% identity).
+INTRODUCTION: The immune responses in patients with novel A(H1N1) virus infection (nvA(H1N1)) are incompletely characterized.
+We investigated the profile of Th1 and Th17 mediators and interferon-inducible protein-10 (IP-10) in groups with severe and mild nvA(H1N1) disease and correlated them with clinical aspects.
+METHODS: Thirty-two patients hospitalized with confirmed nvA(H1N1) infection were enrolled in the study: 21 patients with nvA(H1N1)-acute respiratory distress syndrome (ARDS) and 11 patients with mild disease.
+One group of 20 patients with bacterial sepsis-ARDS and another group of 15 healthy volunteers were added to compare their cytokine levels with pandemic influenza groups.
+In the nvA(H1N1)-ARDS group, the serum cytokine samples were obtained on admission and 3 days later.
+RESULTS: In the nvA(H1N1)-ARDS group, obesity and lymphocytopenia were more common and IP-10, interleukin (IL)-12, IL-15, tumor necrosis factor (TNF)α, IL-6, IL-8 and IL-9 were significantly increased versus control.
+When comparing mild with severe nvA(H1N1) groups, IL-6, IL-8, IL-15 and TNFα were significantly higher in the severe group.
+In nonsurvivors versus survivors, IL-6 and IL-15 were increased on admission and remained higher 3 days later.
+A positive correlation of IL-6, IL-8 and IL-15 levels with C-reactive protein and with > 5-day interval between symptom onset and admission, and a negative correlation with the PaO(2):FiO(2 )ratio, were found in nvA(H1N1) groups.
+When comparing viral ARDS with bacterial ARDS, the level of IL-8, IL-17 and TNFα was significantly higher in bacterial ARDS and IL-12 was increased only in viral ARDS.
+CONCLUSIONS: In our critically ill patients with novel influenza A(H1N1) virus infection, the hallmarks of the severity of disease were IL-6, IL-15, IL-8 and TNFα.
+These cytokines, except TNFα, had a positive correlation with the admission delay and C-reactive protein, and a negative correlation with the PaO(2):FiO(2 )ratio.
+There are significant differences in the level of cytokines when comparing viral ARDS with bacterial ARDS.
+Idiopathic pulmonary fibrosis (IPF) is a dreadful, chronic, and irreversibly progressive fibrosing disease leading to death in all patients affected, and IPF acute exacerbations constitute the most devastating complication during its clinical course.
+IPF exacerbations are subacute/acute, clinically significant deteriorations of unidentifiable cause that usually transform the slow and more or less steady disease decline to the unexpected appearance of acute lung injury/acute respiratory distress syndrome (ALI/ARDS) ending in death.
+The histological picture is that of diffuse alveolar damage (DAD), which is the tissue counterpart of ARDS, upon usual interstitial pneumonia, which is the tissue equivalent of IPF.
+ALI/ARDS and acute interstitial pneumonia share with IPF exacerbations the tissue damage pattern of DAD.
+'Treatment' with high-dose corticosteroids with or without an immunosuppressant proved ineffective and represents the coup de grace for these patients.
+Provision of excellent supportive care and the search for and treatment of the 'underlying cause' remain the only options.
+Admission to an intensive care unit (ICU) is a particular clinical and ethical challenge because of the extremely poor outcome.
+INTRODUCTION: Genetic variability of the pulmonary surfactant proteins A and D may affect clearance of microorganisms and the extent of the inflammatory response.
+The genes of these collectins (SFTPA1, SFTPA2 and SFTPD) are located in a cluster at 10q21-24.
+The objective of this study was to evaluate the existence of linkage disequilibrium (LD) among these genes, and the association of variability at these genes with susceptibility and outcome of community-acquired pneumonia (CAP).
+RESULTS: The SFTPD aa11-C allele was significantly associated with lower SP-D serum levels, in a dose-dependent manner.
+Haplotypes SFTPA1 6A(2 )(P = 0.0009, odds ration (OR) = 0.78), SFTPA2 1A(0 )(P = 0.002, OR = 0.79), SFTPA1-SFTPA2 6A(2)-1A(0 )(P = 0.0005, OR = 0.77), and SFTPD-SFTPA1-SFTPA2 C-6A(2)-1A(0 )(P = 0.00001, OR = 0.62) were underrepresented in patients, whereas haplotypes SFTPA2 1A(10 )(P = 0.00007, OR = 6.58) and SFTPA1-SFTPA2 6A(3)-1A (P = 0.0007, OR = 3.92) were overrepresented.
+Similar results were observed in CAP due to pneumococcus, though no significant differences were now observed after Bonferroni corrections.
+1A(10 )and 6A-1A were associated with higher 28-day and 90-day mortality, and with multi-organ dysfunction syndrome (MODS) and acute respiratory distress syndrome (ARDS) respectively.
+CONCLUSIONS: Our study indicates that missense single nucleotide polymorphisms and haplotypes of SFTPA1, SFTPA2 and SFTPD are associated with susceptibility to CAP, and that several haplotypes also influence severity and outcome of CAP.
+BACKGROUND: The majority of influenza transmission occurs in homes, schools and workplaces, where many frequently touched communal items are situated.
+However the importance of transmission via fomites is unclear since few data exist on the survival of virus on commonly touched surfaces.
+We therefore measured the viability over time of two H1N1 influenza strains applied to a variety of materials commonly found in households and workplaces.
+METHODOLOGY AND PRINCIPAL FINDINGS: Influenza A/PuertoRico/8/34 (PR8) or A/Cambridge/AHO4/2009 (pandemic H1N1) viruses were inoculated onto a wide range of surfaces used in home and work environments, then sampled at set times following incubation at stabilised temperature and humidity.
+Virus genome was measured by RT-PCR; plaque assay (for PR8) or fluorescent focus formation (for pandemic H1N1) was used to assess the survival of viable virus.
+CONCLUSIONS/SIGNIFICANCE: The genome of either virus could be detected on most surfaces 24 h after application with relatively little drop in copy number, with the exception of unsealed wood surfaces.
+Live virus was recovered from most surfaces tested four hours after application and from some non-porous materials after nine hours, but had fallen below the level of detection from all surfaces at 24 h. We conclude that influenza A transmission via fomites is possible but unlikely to occur for long periods after surface contamination (unless re-inoculation occurs).
+In situations involving a high probability of influenza transmission, our data suggest a hierarchy of priorities for surface decontamination in the multi-surface environments of home and hospitals.
+INTRODUCTION: Media sensationalism on the H1N1 outbreak may have influenced decisional processes and clinical diagnosis.
+CASE PRESENTATION: We report two cases of patients who presented in 2009 with coexisting H1N1 virus and Legionella infections: a 69-year-old Caucasian man and a 71-year-old Caucasian woman.
+In our cases all the signs and symptoms, including vomiting, progressive respiratory disease leading to respiratory failure, refractory hypoxemia, leukopenia, lymphopenia, thrombocytopenia, and elevated levels of creatine kinase and hepatic aminotransferases, were consistent with critical illness due to 2009 H1N1 virus infection.
+Because the swine flu H1N1 pandemic occurred in Autumn in Italy, Legionnaires disease was to be highly suspected since the peak incidence usually occurs in early fall.
+We do think that our immediate suspicion of Legionella infection based on clinical history and X-ray abnormalities was fundamental for a successful resolution.
+CONCLUSION: Our two case reports suggest that patients with H1N1 should be screened for Legionella, which is not currently common practice.
+Emerging zoonoses threaten global health, yet the processes by which they emerge are complex and poorly understood.
+Nipah virus (NiV) is an important threat owing to its broad host and geographical range, high case fatality, potential for human-to-human transmission and lack of effective prevention or therapies.
+Here, we investigate the origin of the first identified outbreak of NiV encephalitis in Malaysia and Singapore.
+We analyse data on livestock production from the index site (a commercial pig farm in Malaysia) prior to and during the outbreak, on Malaysian agricultural production, and from surveys of NiV's wildlife reservoir (flying foxes).
+Our analyses suggest that repeated introduction of NiV from wildlife changed infection dynamics in pigs.
+Initial viral introduction produced an explosive epizootic that drove itself to extinction but primed the population for enzootic persistence upon reintroduction of the virus.
+This study refutes an earlier hypothesis that anomalous El Niño Southern Oscillation-related climatic conditions drove emergence and suggests that priming for persistence drove the emergence of a novel zoonotic pathogen.
+Thus, we provide empirical evidence for a causative mechanism previously proposed as a precursor to widespread infection with H5N1 avian influenza and other emerging pathogens.
+BACKGROUND: Examining professional assessments of a blood product recall/withdrawal and its implications for risk and public health, the paper introduces ideas about perceptions of minimal risk and its management.
+It also describes the context of publicly funded blood transfusion in Canada and the withdrawal event that is the basis of this study.
+METHODS: Interviews with 45 experts from administration, medicine, blood supply, laboratory services and risk assessment took place using a multi-level sampling framework in the aftermath of the recall.
+These experts either directly dealt with the withdrawal or were involved in the management of the blood supply at the national level.
+Analytically, data were interpreted to derive typifications to relate interview responses to risk management heuristics.
+RESULTS: While all those interviewed agreed on the importance of patient safety, differences in the ways in which the risk was contextualized and explicated were discerned.
+CONCLUSIONS: Expert assessments did not fully converge and it is possible that these different risk logics and discourses may affect the risk management process more generally, although not necessarily in a negative way.
+Patient safety is not to be compromised but management of blood risk in publicly funded systems may vary.
+Noninvasive positive pressure ventilation (NPPV) refers to the delivery of mechanical respiratory support without the use of endotracheal intubation (ETI).
+The present review focused on the effectiveness of NPPV in children > 1 month of age with acute respiratory failure (ARF) due to different conditions.
+Therefore, prompt recognition and treatment of pediatric patients with pending respiratory failure can be lifesaving.
+In recent years, NPPV has been proposed as a valuable alternative to invasive mechanical ventilation (IMV) in this acute setting.
+Several pediatric clinical studies, the majority of which were noncontrolled or case series and of small size, have suggested the effectiveness of NPPV in the treatment of ARF due to acute airway (upper or lower) obstruction or certain primary parenchymal lung disease, and in specific circumstances, such as postoperative or postextubation ARF, immunocompromised patients with ARF, or as a means to facilitate extubation.
+NPPV was well tolerated with rare major complications and was associated with improved gas exchange, decreased work of breathing, and ETI avoidance in 22-100% of patients.
+High FiO(2 )needs or high PaCO(2 )level on admission or within the first hours after starting NPPV appeared to be the best independent predictive factors for the NPPV failure in children with ARF.
+However, many important issues, such as the identification of the patient, the right time for NPPV application, and the appropriate setting, are still lacking.
+BACKGROUND: During the 2009 influenza A/H1N1v pandemic, children were identified as a specific "at risk" group.
+We conducted a multicentric study to describe pattern of influenza A/H1N1v infection among hospitalized children in Brussels, Belgium.
+METHODS: From July 1, 2009, to January 31, 2010, we collected epidemiological and clinical data of all proven (positive H1N1v PCR) and probable (positive influenza A antigen or culture) pediatric cases of influenza A/H1N1v infections, hospitalized in four tertiary centers.
+RESULTS: During the epidemic period, an excess of 18% of pediatric outpatients and emergency department visits was registered.
+Children over 2 years of age showed a higher propensity to be admitted to PICU (16% vs 1%, p = 0.002) and a higher mortality rate (4% vs 0%, p = 0.06).
+Infants less than 3 months old showed a milder course of infection, with few respiratory and neurological complications.
+Compared to other countries experiencing different health care systems, our Belgian cohort was younger and received less frequently antiviral therapy; disease course and mortality were however similar.
+Aberrant activation of caspase-6 has recently emerged as a major contributor to the pathogeneses of neurodegenerative disorders such as Alzheimer's and Huntington disease.
+Commercially available assays to measure caspase-6 activity commonly use the VEID peptide as a substrate.
+However these methods are not well suited to specifically assess caspase-6 activity in the presence of other, confounding protease activities, as often encountered in cell and tissue samples.
+Here we report the development of a method that overcomes this limitation by using a protein substrate, lamin A, which is highly specific for caspase-6 cleavage at amino acid 230.
+Using a neo-epitope antibody against cleaved lamin A, we developed an electrochemiluminescence-based ELISA assay that is suitable to specifically detect and quantify caspase-6 activity in highly apoptotic cell extracts.
+The method is more sensitive than VEID-based assays and can be adapted to a high-content imaging platform for high-throughput screening.
+This method should be useful to screen for and characterize caspase-6 inhibitor compounds and other interventions to decrease intracellular caspase-6 activity for applications in neurodegenerative disorders.
+Local epidemic curves during the 1918–1919 influenza pandemic were often characterized by multiple epidemic waves.
+We investigate the hypothesis that these waves were caused by people avoiding potentially infectious contacts—a behaviour termed ‘social distancing’.
+We estimate the effective disease reproduction number and from it infer the maximum degree of social distancing that occurred during the course of the multiple-wave epidemic in Sydney, Australia.
+We estimate that, on average across the city, people reduced their infectious contact rate by as much as 38%, and that this was sufficient to explain the multiple waves of this epidemic.
+The basic reproduction number, R(0), was estimated to be in the range of 1.6–2.0 with a preferred estimate of 1.8, in line with other recent estimates for the 1918–1919 influenza pandemic.
+The data are also consistent with a high proportion (more than 90%) of the population being initially susceptible to clinical infection, and the proportion of infections that were asymptomatic (if this occurs) being no higher than approximately 9%.
+The observed clinical attack rate of 36.6% was substantially lower than the 59% expected based on the estimated value of R(0), implying that approximately 22% of the population were spared from clinical infection.
+This reduction in the clinical attack rate translates to an estimated 260 per 100 000 lives having been saved, and suggests that social distancing interventions could play a major role in mitigating the public health impact of future influenza pandemics.
+The worldwide spread of H1N1 avian influenza and the increasing reports about its resistance to the current drugs have made a high priority for developing new anti-influenza drugs.
+Owing to its unique function in assisting viruses to bind the cellular surface, a key step for them to subsequently penetrate into the infected cell, hemagglutinin (HA) has become one of the main targets for drug design against influenza virus.
+To develop potent HA inhibitors, the ZINC fragment database was searched for finding the optimal compound with the core hopping technique.
+It has been shown through the subsequent molecular docking studies and molecular dynamic simulations that Neo6 not only assumes more favorable conformation at the binding pocket of HA but also has stronger binding interaction with its receptor.
+Accordingly, Neo6 may become a promising candidate for developing new and more powerful drugs for treating influenza.
+Or at the very least, the findings reported here may provide useful insights to stimulate new strategy in this area.
+The infection of viruses to a neighboring cell is considered to be beneficial in terms of evasion from host anti-virus defense systems.
+There are two pathways for viral infection to “right next door”: one is the virus transmission through cell-cell fusion by forming syncytium without production of progeny virions, and the other is mediated by virions without virus diffusion, generally designated cell-to-cell transmission.
+Influenza viruses are believed to be transmitted as cell-free virus from infected cells to uninfected cells.
+Here, we demonstrated that influenza virus can utilize cell-to-cell transmission pathway through apical membranes, by handover of virions on the surface of an infected cell to adjacent host cells.
+Live cell imaging techniques showed that a recombinant influenza virus, in which the neuraminidase gene was replaced with the green fluorescence protein gene, spreads from an infected cell to adjacent cells forming infected cell clusters.
+The cell-to-cell transmission was also blocked by amantadine, which inhibits the acidification of endosomes required for uncoating of influenza virus particles in endosomes, indicating that functional hemagglutinin and endosome acidification by M2 ion channel were essential for the cell-to-cell influenza virus transmission.
+Furthermore, in the cell-to-cell transmission of influenza virus, progeny virions could remain associated with the surface of infected cell even after budding, for the progeny virions to be passed on to adjacent uninfected cells.
+The evidence that cell-to-cell transmission occurs in influenza virus lead to the caution that local infection proceeds even when treated with neuraminidase inhibitors.
+HCV infection is a major cause of chronic liver disease and liver cancer in the United States.
+To address the pathogenesis caused by HCV infection, recent studies have focused on the direct cytopathic effects of individual HCV proteins, with the objective of identifying their specific roles in the overall pathogenesis.
+However, this approach precludes examination of the possible interactions between different HCV proteins and organelles.
+To obtain a better understanding of the various cytopathic effects of and cellular responses to HCV proteins, we used human hepatoma cells constitutively replicating HCV RNA encoding either the full-length polyprotein or the non-structural proteins, or cells constitutively expressing the structural protein core, to model the state of persistent HCV infection and examined the combination of various HCV proteins in cellular pathogenesis.
+Increased reactive oxygen species (ROS) generation in the mitochondria, mitochondrial injury and degeneration, and increased lipid accumulation were common among all HCV protein-expressing cells regardless of whether they expressed the structural or non-structural proteins.
+Expression of the non-structural proteins also led to increased oxidative stress in the cytosol, membrane blebbing in the endoplasmic reticulum, and accumulation of autophagocytic vacuoles.
+Alterations of cellular redox state, on the other hand, significantly changed the level of autophagy, suggesting a direct link between oxidative stress and HCV-mediated activation of autophagy.
+With the wide-spread cytopathic effects, cells with the full-length HCV polyprotein showed a modest antioxidant response and exhibited a significant increase in population doubling time and a concomitant decrease in cyclin D1.
+In contrast, cells expressing the non-structural proteins were able to launch a vigorous antioxidant response with up-regulation of antioxidant enzymes.
+The population doubling time and cyclin D1 level were also comparable to that of control cells.
+Finally, the cytopathic effects of core protein appeared to focus on the mitochondria without remarkable disturbances in the cytosol.
+Although random mutagenesis can be used to generate TS mutants, the procedure is laborious and unfeasible in multicellular organisms.
+To elucidate TS mechanisms, we used a machine learning method–logistic regression–to investigate a large number of sequence and structure features.
+We developed and tested 133 features, describing properties of either the mutation site or the mutation site neighborhood.
+The most predictive features suggest that TS mutations tend to occur at buried and rigid residues, and are located at conserved protein domains.
+The environment of a buried residue often determines the overall structural stability of a protein, thus may lead to reversible activity change upon temperature switch.
+Through a ten-fold cross-validation, we obtained the area under the curve of 0.91 for the model using both sequence and structure features.
+Testing on independent datasets suggested that the model predicted TS mutations with a 50% precision.
+In summary, our study elucidated the molecular basis of TS mutants and suggested the importance of neighborhood properties in determining TS mutations.
+In this way, TS mutants can be efficiently obtained through experimentally introducing the predicted mutations.
+BACKGROUND: High-quality review evidence is useful for informing and influencing public health policy and practice decisions.
+However, certain topic areas lack representation in terms of the quantity and quality of review literature available.
+The objectives of this paper are to identify the quantity, as well as quality, of review-level evidence available on the effectiveness of public health interventions for public health decision makers.
+METHODS: Searches conducted on http://www.health-evidence.ca produced an inventory of public health review literature in 21 topic areas.
+Gaps and areas of wealth in the review literature, as well as the proportion of reviews rated methodologically strong, moderate, or weak were identified.
+The top 10 topic areas of interest for registered users and visitors of http://www.health-evidence.ca were extracted from user profile data and Google Analytics.
+RESULTS: Registered users' top three interests included: 1) healthy communities, 2) chronic diseases, and 3) nutrition.
+The top three preferences for visitors included: 1) chronic diseases, 2) physical activity, and 3) addiction/substance use.
+All of the topic areas with many (301+) available reviews were of interest to registered users and/or visitors (mental health, physical activity, addiction/substance use, adolescent health, child health, nutrition, adult health, and chronic diseases).
+Conversely, the majority of registered users and/or visitors did not have preference for topic areas with few (≤ 150) available reviews (food safety and inspection, dental health, environmental health) with the exception of social determinants of health and healthy communities.
+Across registered users' and visitors' topic areas of preference, 80.2% of the reviews were of well-done methodological quality, with 43.5% of reviews having a strong quality rating and 36.7% a moderate review quality rating.
+CONCLUSIONS: In topic areas in which many reviews are available, higher level syntheses are needed to guide policy and practice.
+For other topic areas with few reviews, it is necessary to determine whether primary study evidence exists, or is needed, so that reviews can be conducted in the future.
+Considering that less than half of the reviews available on http://www.health-evidence.ca are of strong methodological quality, the quality of the review-level evidence needs to improve across the range of public health topic areas.
+The Nairoviruses are an important group of tick-borne viruses that includes pathogens of man (Crimean Congo hemorrhagic fever virus) and livestock animals (Dugbe virus, Nairobi sheep disease virus (NSDV)).
+NSDV is found in large parts of East Africa and the Indian subcontinent (where it is known as Ganjam virus).
+We have investigated the ability of NSDV to antagonise the induction and actions of interferon.
+Both pathogenic and apathogenic isolates could actively inhibit the induction of type 1 interferon, and also blocked the signalling pathways of both type 1 and type 2 interferons.
+Using transient expression of viral proteins or sections of viral proteins, these activities all mapped to the ovarian tumour-like protease domain (OTU) found in the viral RNA polymerase.
+Virus infection, or expression of this OTU domain in transfected cells, led to a great reduction in the incorporation of ubiquitin or ISG15 protein into host cell proteins.
+Point mutations in the OTU that inhibited the protease activity also prevented it from antagonising interferon induction and action.
+Interestingly, a mutation at a peripheral site, which had little apparent effect on the ability of the OTU to inhibit ubiquitination and ISG15ylation, removed the ability of the OTU to block the induction of type 1 and the action of type 2 interferons, but had a lesser effect on the ability to block type 1 interferon action, suggesting that targets other than ubiquitin and ISG15 may be involved in the actions of the viral OTU.
+The interest in broad-range anti-influenza A monoclonal antibodies (mAbs) has recently been strengthened by the identification of anti-hemagglutinin (HA) mAbs endowed with heterosubtypic neutralizing activity to be used in the design of “universal” prophylactic or therapeutic tools.
+However, the majority of the single mAbs described to date do not bind and neutralize viral isolates belonging to highly divergent subtypes clustering into the two different HA-based influenza phylogenetic groups: the group 1 including, among others, subtypes H1, H2, H5 and H9 and the group 2 including, among others, H3 subtype.
+Here, we describe a human mAb, named PN-SIA28, capable of binding and neutralizing all tested isolates belonging to phylogenetic group 1, including H1N1, H2N2, H5N1 and H9N2 subtypes and several isolates belonging to group 2, including H3N2 isolates from the first period of the 1968 pandemic.
+Therefore, PN-SIA28 is capable of neutralizing isolates belonging to subtypes responsible of all the reported pandemics, as well as other subtypes with pandemic potential.
+The region recognized by PN-SIA28 has been identified on the stem region of HA and includes residues highly conserved among the different influenza subtypes.
+A deep characterization of PN-SIA28 features may represent a useful help in the improvement of available anti-influenza therapeutic strategies and can provide new tools for the development of universal vaccinal strategies.
+It can be transmitted by mosquitoes, inhalation or physical contact with the body fluids of infected animals.
+The dynamics of RVFV infection and the cell types infected in vivo are poorly understood.
+METHODOLOGY/PRINCIPAL FINDINGS: RVFV strains expressing humanized Renilla luciferase (hRLuc) or green fluorescent protein (GFP) were generated and inoculated to susceptible Ifnar1-deficient mice.
+We investigated the tissue tropism in these mice and the nature of the target cells in vivo using whole-organ imaging and flow cytometry.
+Macrophages infiltrating various tissues, in particular the adipose tissue surrounding the pancreas also expressed the virus.
+The liver rapidly turned into the major luminescent organ and the mice succumbed to severe hepatitis.
+FACS analysis in RVFV-GFP-infected mice showed that the macrophages, dendritic cells and granulocytes were main target cells for RVFV.
+The crucial role of cells of the monocyte/macrophage/dendritic lineage during RVFV infection was confirmed by the slower viral dissemination, decrease in RVFV titers in blood, and prolonged survival of macrophage- and dendritic cell-depleted mice following treatment with clodronate liposomes.
+Upon dermal and nasal inoculations, the viral dissemination was primarily observed in the lymph node draining the injected ear and in the lungs respectively, with a significant increase in survival time.
+CONCLUSIONS/SIGNIFICANCE: These findings reveal the high levels of phagocytic cells harboring RVFV during viral infection in Ifnar1-deficient mice.
+They demonstrate that bioluminescent and fluorescent viruses can shed new light into the pathogenesis of RVFV infection.
+The use of reference genes is commonly accepted as the most reliable approach to normalize qRT-PCR and to reduce possible errors in the quantification of gene expression.
+The most suitable reference genes in sheep have been identified for a restricted range of tissues, but no specific data on whole blood are available.
+The aim of this study was to identify a set of reference genes for normalizing qRT-PCR from ovine whole blood.
+We designed 11 PCR assays for commonly employed reference genes belonging to various functional classes and then determined their expression stability in whole blood samples from control and disease-stressed sheep.
+SDHA and YWHAZ were considered the most suitable internal controls as they were stably expressed regardless of disease status according to both geNorm and NormFinder software; furthermore, geNorm indicated SDHA/HPRT, YWHAZ/GAPDH and SDHA/YWHAZ as the best reference gene combinations in control, disease-stressed and combined sheep groups, respectively.
+Our study provides a validated panel of optimal control genes which may be useful for the identification of genes differentially expressed by qRT-PCR in a readily accessible tissue, with potential for discovering new physiological and disease markers and as a tool to improve production traits (e.g., by identifying expression Quantitative Trait Loci).
+An additional outcome of the study is a set of intron-spanning primer sequences suitable for gene expression experiments employing SYBR Green chemistry on other ovine tissues and cells.
+BACKGROUND: Thermal imagers have been used in a number of disciplines to record animal surface temperatures and as a result detect temperature distributions and abnormalities requiring a particular course of action.
+Some work, with animals infected with foot-and-mouth disease virus, has suggested that the technique might be used to identify animals in the early stages of disease.
+In this study, images of 19 healthy cattle have been taken over an extended period to determine hoof and especially coronary band temperatures (a common site for the development of FMD lesions) and eye temperatures (as a surrogate for core body temperature) and to examine how these vary with time and ambient conditions.
+RESULTS: The results showed that under UK conditions an animal's hoof temperature varied from 10°C to 36°C and was primarily influenced by the ambient temperature and the animal's activity immediately prior to measurement.
+Eye temperatures were not affected by ambient temperature and are a useful indicator of core body temperature.
+CONCLUSIONS: Given the variation in temperature of the hooves of normal animals under various environmental conditions the use of a single threshold hoof temperature will be at best a modest predictive indicator of early FMD, even if ambient temperature is factored into the evaluation.
+OBJECTIVES: Our study had two objectives: a) to systematically identify all existing systematic reviews of Chinese herbal medicines (CHM) published in Cochrane Library; b) to assess the methodological quality of included reviews.
+METHODOLOGY/PRINCIPAL FINDINGS: We performed a systematic search of the Cochrane Database of Systematic Reviews (CDSR, Issue 5, 2010) to identify all reviews of CHM.
+Twenty-one of the included reviews had at least one Traditional Chinese Medicine (TCM) practitioner as its co-author.
+7 reviews didn't include any primary study, the remaining reviews (n = 51) included a median of 9 studies and 936 participants.
+The questions addressed by 39 reviews were broad in scope, in which 9 reviews combined studies with different herbal medicines.
+For OQAQ, the mean of overall quality score (item 10) was 5.05 (95% CI; 4.58-5.52).
+All reviews assessed the methodological quality of primary studies, 16% of included primary studies used adequate sequence generation and 7% used adequate allocation concealment.
+Of the 51 nonempty reviews, 23 reviews were reported as being inconclusive, while 27 concluded that there might be benefit of CHM, which was limited by the poor quality or inadequate quantity of included studies.
+58 reviews reported searching a median of seven electronic databases, while 10 reviews did not search any Chinese database.
+CONCLUSIONS: Now CDSR has included large numbers of CHM reviews, our study identified some areas which could be improved, such as almost half of included reviews did not have the participation of TCM practitioners and were not up-to-date according to Cochrane criteria, some reviews pooled the results of different herbal medicines and ignored the searching of Chinese databases.
+Multiple sclerosis (MS) is an autoimmune disease of the central nervous system, and CD4(+) T cells form the core immunopathogenic cascade leading to chronic inflammation.
+Traditionally, Th1 cells (interferon-γ-producing CD4(+) T cells) driven by interleukin 12 (IL12) were considered to be the encephalitogenic T cells in MS and experimental autoimmune encephalomyelitis (EAE), an animal model of MS.
+Currently, Th17 cells (Il17-producing CD4(+) T cells) are considered to play a fundamental role in the immunopathogenesis of EAE.
+This paper highlights the growing evidence that Th17 cells play the core role in the complex adaptive immunity of EAE/MS and discusses the roles of the associated immune cells and cytokines.
+These constitute the modern immunological basis for the development of novel clinical and preclinical immunomodulatory therapies for MS discussed in this paper.
+BACKGROUND: Online news reports are increasingly becoming a source for event-based early warning systems that detect natural disasters.
+Harnessing the massive volume of information available from multilingual newswire presents as many challanges as opportunities due to the patterns of reporting complex spatio-temporal events.
+RESULTS: In this article we study the problem of utilising correlated event reports across languages.
+We track the evolution of 16 disease outbreaks using 5 temporal aberration detection algorithms on text-mined events classified according to disease and outbreak country.
+Using ProMED reports as a silver standard, comparative analysis of news data for 13 languages over a 129 day trial period showed improved sensitivity, F1 and timeliness across most models using cross-lingual events.
+We report a detailed case study analysis for Cholera in Angola 2010 which highlights the challenges faced in correlating news events with the silver standard.
+CONCLUSIONS: The results show that automated health surveillance using multilingual text mining has the potential to turn low value news into high value alerts if informed choices are used to govern the selection of models and data sources.
+An implementation of the C2 alerting algorithm using multilingual news is available at the BioCaster portal http://born.nii.ac.jp/?page=globalroundup.
+Considerable progress has been made in the past few years in the development of therapeutic interventions that can reduce mortality in sepsis.
+However, encouraging physicians to put the results of new studies into practice is not always simple.
+A roundtable was thus convened to provide guidance for clinicians on the integration and implementation of new interventions into the intensive care unit (ICU).
+Five topics were selected that have been shown in randomized, controlled trials to reduce mortality: limiting the tidal volume in acute lung injury or acute respiratory distress syndrome, early goal-directed therapy, use of drotrecogin alfa (activated), use of moderate doses of steroids, and tight control of blood sugar.
+One of the principal investigators for each study was invited to participate in the roundtable.
+The discussions and questions that followed the presentation of data by each panel member enabled a consensus recommendation to be derived regarding when each intervention should be used.
+Furthermore, and importantly, the therapies are not mutually exclusive; many patients will need a combination of several approaches – an 'ICU package'.
+The present article provides guidelines from experts in the field on optimal patient selection and timing for each intervention, and provides advice on how to integrate new therapies into ICU practice, including protocol development, so that mortality rates from this disease process can be reduced.
+Host factors are recruited into viral replicase complexes to aid replication of plus-strand RNA viruses.
+In this paper, we show that deletion of eukaryotic translation elongation factor 1Bgamma (eEF1Bγ) reduces Tomato bushy stunt virus (TBSV) replication in yeast host.
+eEF1Bγ binds to the viral RNA and is one of the resident host proteins in the tombusvirus replicase complex.
+Additional in vitro assays with whole cell extracts prepared from yeast strains lacking eEF1Bγ demonstrated its role in minus-strand synthesis by opening of the structured 3′ end of the viral RNA and reducing the possibility of re-utilization of (+)-strand templates for repeated (-)-strand synthesis within the replicase.
+We also show that eEF1Bγ plays a synergistic role with eukaryotic translation elongation factor 1A in tombusvirus replication, possibly via stimulation of the proper positioning of the viral RNA-dependent RNA polymerase over the promoter region in the viral RNA template.These roles for translation factors during TBSV replication are separate from their canonical roles in host and viral protein translation.
+Mannose-binding lectin (MBL) is a pattern-recognition molecule, which functions as a first line of host defense.
+Pandemic H1N1 (pdmH1N1) influenza A virus caused massive infection in 2009 and currently circulates worldwide.
+Avian influenza A H9N2 (H9N2/G1) virus has infected humans and has the potential to be the next pandemic virus.
+Antiviral function and immunomodulatory role of MBL in pdmH1N1 and H9N2/G1 virus infection have not been investigated.
+In this study, MBL wild-type (WT) and MBL knockout (KO) murine models were used to examine the role of MBL in pdmH1N1 and H9N2/G1 virus infection.
+Our study demonstrated that in vitro, MBL binds to pdmH1N1 and H9N2/G1 viruses, likely via the carbohydrate recognition domain of MBL.
+Wild-type mice developed more severe disease, as evidenced by a greater weight loss than MBL KO mice during influenza virus infection.
+Furthermore, MBL WT mice had enhanced production of proinflammatory cytokines and chemokines compared with MBL KO mice, suggesting that MBL could upregulate inflammatory responses that may potentially worsen pdmH1N1 and H9N2/G1 virus infections.
+Our study provided the first in vivo evidence that MBL may be a risk factor during pdmH1N1 and H9N2/G1 infection by upregulating proinflammatory response.
+Seasonal influenza has considerable impact around the world, both economically and in mortality among risk groups, but there is considerable uncertainty as to the essential mechanisms and their parametrization.
+In this paper, we identify a number of characteristic features of influenza incidence time series in temperate regions, including ranges of annual attack rates and outbreak durations.
+By constraining the output of simple models to match these characteristic features, we investigate the role played by population heterogeneity, multiple strains, cross-immunity and the rate of strain evolution in the generation of incidence time series.
+Results indicate that an age-structured model with non-random mixing and co-circulating strains are both required to match observed time-series data.
+Our work gives estimates of the seasonal peak basic reproduction number, R(0), in the range 1.6–3.
+Estimates of R(0) are strongly correlated with the timescale for waning of immunity to current circulating seasonal influenza strain, which we estimate is between 3 and 8 years.
+While population heterogeneity and cross-immunity are required mechanisms, the degree of heterogeneity and cross-immunity is not tightly constrained.
+We discuss our findings in the context of other work fitting to seasonal influenza data.
+Amiodarone [2-butyl-3-(3′,5′-diiodo-4’α-diethylaminoethoxybenzoyl)-benzofuran] (AMD), a class III antiarrhythmic drug, is known to cause idiosyncratic hepatotoxic reactions in human patients.
+One hypothesis for the etiology of idiosyncratic adverse drug reactions is that a concurrent inflammatory stress results in decreased threshold for drug toxicity.
+To explore this hypothesis in an animal model, male Sprague-Dawley rats were treated with nonhepatotoxic doses of AMD or its vehicle and with saline vehicle or lipopolysaccharide (LPS) to induce low-level inflammation.
+Elevated alanine aminotransferase (ALT), aspartate aminotransferase, alkaline phosphatase, and gamma-glutamyltransferase activities as well as increased total bile acid concentrations in serum and midzonal hepatocellular necrosis were observed only in AMD/LPS-cotreated rats.
+The time interval between AMD and LPS administration was critical: AMD injected 16 h before LPS led to liver injury, whereas AMD injected 2–12 h before LPS failed to cause this response.
+The increase in ALT activity in AMD/LPS cotreatment showed a clear dose-response relationship with AMD as well as LPS.
+Serum concentration of tumor necrosis factor-alpha (TNF) was significantly increased by LPS and was slightly prolonged by AMD.
+In Hepac1c7 cells, addition of TNF potentiated the cytotoxicity of both AMD and its primary metabolite, mono-N-desethylamiodarone.
+In vivo inhibition of TNF signaling by etanercept attenuated the AMD/LPS-induced liver injury in rats.
+In summary, AMD treatment during modest inflammation induced severe hepatotoxicity in rats, and TNF contributed to the induction of liver injury in this animal model of idiosyncratic AMD-induced liver injury.
+Highly pathogenic avian influenza A (HPAI) H5N1 viruses are circulating among poultry populations in parts of Asia, Africa, and the Middle East, and have caused human infections with a high mortality rate.
+H5 subtype hemagglutinin (HA) has evolved into phylogenetically distinct clades and subclades based on viruses isolated from various avian species.
+It is, therefore, important to develop strategies to produce protective antibody responses against H5N1 viruses from multiple clades or antigenic groups.
+In the current study, we optimized the signal peptide design of DNA vaccines expressing HA antigens from H5N1 viruses.
+Cross reactivity analysis using sera from immunized rabbits showed that antibody responses elicited by a polyvalent formulation, including HA antigens from different clades, was able to elicit broad protective antibody responses against multiple key representative H5N1 viruses across different clades.
+Data presented in this report support the development of a polyvalent DNA vaccine strategy against the threat of a potential H5N1 influenza pandemic.
+Linear motifs are short, evolutionarily plastic components of regulatory proteins and provide low-affinity interaction interfaces.
+These compact modules play central roles in mediating every aspect of the regulatory functionality of the cell.
+They are particularly prominent in mediating cell signaling, controlling protein turnover and directing protein localization.
+Given their importance, our understanding of motifs is surprisingly limited, largely as a result of the difficulty of discovery, both experimentally and computationally.
+The Eukaryotic Linear Motif (ELM) resource at http://elm.eu.org provides the biological community with a comprehensive database of known experimentally validated motifs, and an exploratory tool to discover putative linear motifs in user-submitted protein sequences.
+The current update of the ELM database comprises 1800 annotated motif instances representing 170 distinct functional classes, including approximately 500 novel instances and 24 novel classes.
+Several older motif class entries have been also revisited, improving annotation and adding novel instances.
+Furthermore, addition of full-text search capabilities, an enhanced interface and simplified batch download has improved the overall accessibility of the ELM data.
+The motif discovery portion of the ELM resource has added conservation, and structural attributes have been incorporated to aid users to discriminate biologically relevant motifs from stochastically occurring non-functional instances.
+The bone marrow contains heterogeneous population of cells that are involved in the regeneration and repair of diseased organs, including the lungs.
+In this study, we isolated and characterized progenitor epithelial cells from the bone marrow of 4- to 5-week old germ-free pigs.
+Phenotypically, these cells expressed the stem cell markers octamer-binding transcription factor (Oct4) and stage-specific embryonic antigen-1 (SSEA-1), the alveolar stem cell marker Clara cell secretory protein (Ccsp), and the epithelial cell markers pan-cytokeratin (Pan-K), cytokeratin-18 (K-18), and occludin.
+When cultured in epithelial cell growth medium, the progenitor epithelial cells expressed type I and type II pneumocyte markers.
+Progenitor epithelial cells expressed sialic acid receptors utilized by avian and mammalian influenza viruses and were targets for influenza virus replication.
+Additionally, differentiated type II but not type I pneumocytes supported the replication of influenza virus.
+Our data indicate that we have identified a unique population of progenitor epithelial cells in the bone marrow that might have airway reconstitution potential and may be a useful model for cell-based therapies for infectious and non-infectious lung diseases.
+During this pandemic, development of drug resistance further complicated efforts to control and treat the widespread illness.
+This research utilizes traditional Chinese medicine Database@Taiwan (TCM Database@Taiwan) to screen for compounds that simultaneously target H1 and N1 to overcome current difficulties with virus mutations.
+Bioactivity of the de novo derivatives against N1 were validated by multiple machine learning prediction models.
+Ability of the de novo compounds to maintain CoMFA/CoMSIA contour and form key interactions implied bioactivity within H1 as well.
+Addition of a pyridinium fragment was critical to form stable interactions in H1 and N1 as supported by molecular dynamics (MD) simulation.
+Results from MD, hydrophobic interactions, and torsion angles are consistent and support the findings of docking.
+Multiple anchors and lack of binding to residues prone to mutation suggest that the TCM de novo derivatives may be resistant to drug resistance and are advantageous over conventional H1N1 treatments such as oseltamivir.
+These results suggest that the TCM de novo derivatives may be suitable candidates of dual-targeting drugs for influenza.
+BACKGROUND: Recent incidents, such as the SARS and influenza epidemics, have highlighted the need for readily available antiviral drugs.
+One important precursor currently used for the production of Relenza, an antiviral product from GlaxoSmithKline, is N-acetylneuraminic acid (NeuNAc).
+This substance has a considerably high market price despite efforts to develop cost-reducing (biotechnological) production processes.
+Hypocrea jecorina (Trichoderma reesei) is a saprophyte noted for its abundant secretion of hydrolytic enzymes and its potential to degrade chitin to its monomer N-acetylglucosamine (GlcNAc).
+Chitin is considered the second most abundant biomass available on earth and therefore an attractive raw material.
+RESULTS: In this study, we introduced two enzymes from bacterial origin into Hypocrea, which convert GlcNAc into NeuNAc via N-acetylmannosamine.
+This enabled the fungus to produce NeuNAc from the cheap starting material chitin in liquid culture.
+Furthermore, we expressed the two recombinant enzymes as GST-fusion proteins and developed an enzyme assay for monitoring their enzymatic functionality.
+Finally, we demonstrated that Hypocrea does not metabolize NeuNAc and that no NeuNAc-uptake by the fungus occurs, which are important prerequisites for a potential production strategy.
+CONCLUSIONS: This study is a proof of concept for the possibility to engineer in a filamentous fungus a bacterial enzyme cascade, which is fully functional.
+Furthermore, it provides the basis for the development of a process for NeuNAc production as well as a general prospective design for production processes that use saprophytes as whole-cell catalysts.
+Several viruses utilize programmed ribosomal frameshifting mediated by mRNA pseudoknots in combination with a slippery sequence to produce a well defined stochiometric ratio of the upstream encoded to the downstream-encoded protein.
+A correlation between the mechanical strength of mRNA pseudoknots and frameshifting efficiency has previously been found; however, the physical mechanism behind frameshifting still remains to be fully understood.
+Two-dimensional gel electrophoresis of pulse labelled proteins revealed that a significant fraction of the ribosomes were frameshifted but unable to pass the pseudoknot-like structures.
+Hence, pseudoknots can act as ribosomal roadblocks, prohibiting a significant fraction of the frameshifted ribosomes from reaching the downstream stop codon.
+The stronger the pseudoknot the larger the frameshifting efficiency and the larger its roadblocking effect.
+The maximal amount of full-length frameshifted product is produced from a structure where those two effects are balanced.
+BACKGROUND: Secretory phospholipase A2 (sPLA2) is a group of enzymes involved in lung tissue inflammation and surfactant catabolism.
+sPLA2 plays a role in adults affected by acute lung injury and seems a promising therapeutic target.
+Preliminary data allow foreseeing the importance of such enzyme in some critical respiratory diseases in neonates and infants, as well.
+Our study aim is to clarify the role of sPLA2 and its modulators in the pathogenesis and clinical severity of hyaline membrane disease, infection related respiratory failure, meconium aspiration syndrome and acute respiratory distress syndrome.
+METHODS/DESIGN: Multicentre, international, translational study, including several paediatric and neonatal intensive care units and one coordinating laboratory.
+Babies affected by the above mentioned conditions will be enrolled: broncho-alveolar lavage fluid, serum and whole blood will be obtained at definite time-points during the disease course.
+Laboratory researchers who perform the bench part of the study will be blinded to the clinical data.
+DISCUSSION: This study, thanks to its multicenter design, will clarify the role(s) of sPLA2 and its pathway in these diseases: sPLA2 might be the crossroad between inflammation and surfactant dysfunction.
+This may represent a crucial target for new anti-inflammatory therapies but also a novel approach to protect surfactant or spare it, improving alveolar stability, lung mechanics and gas exchange.
+BACKGROUND: In order to compare the transmissibility of the 2009 pH1N1 pandemic during successive waves of infections in summer and fall/winter in the Northern Hemisphere, and to assess the temporal changes during the course of the outbreak in relation to the intervention measures implemented, we analyze the epidemiological patterns of the epidemic in Taiwan during July 2009-March 2010.
+METHODS: We utilize the multi-phase Richards model to fit the weekly cumulative pH1N1 epidemiological data (numbers of confirmed cases and hospitalizations) as well as the daily number of classes suspended under a unique "325" partial school closing policy in Taiwan, in order to pinpoint the turning points of the summer and fall/winter waves, and to estimate the reproduction numbers R for each wave.
+RESULTS: Our analysis indicates that the summer wave had slowed down by early September when schools reopened for fall.
+However, a second fall/winter wave began in late September, approximately 4 weeks after the school reopened, peaking at about 2-3 weeks after the start of the mass immunization campaign in November.
+R is estimated to be in the range of 1.04-1.27 for the first wave, and between 1.01-1.05 for the second wave.
+CONCLUSIONS: Transmissibility of the summer wave in Taiwan during July-early September, as measured by R, was lower than that of the earlier spring outbreak in North America and Europe, as well as that of the winter outbreak in Southern Hemisphere.
+Furthermore, transmissibility during fall/winter in Taiwan was noticeably lower than that of the summer, which is attributable to population-level immunity acquired from the earlier summer wave and also to the intervention measures that were implemented prior to and during the fall/winter wave.
+Recent clinical and experimental studies have brought increasing evidence for activation of the innate immune system in contributing to the pathogenesis of trauma-induced sequelae and adverse outcome.
+As the "first line of defense", the complement system represents a potent effector arm of innate immunity, and has been implicated in mediating the early posttraumatic inflammatory response.
+Despite its generic beneficial functions, including pathogen elimination and immediate response to danger signals, complement activation may exert detrimental effects after trauma, in terms of mounting an "innocent bystander" attack on host tissue.
+Posttraumatic ischemia/reperfusion injuries represent the classic entity of complement-mediated tissue damage, adding to the "antigenic load" by exacerbation of local and systemic inflammation and release of toxic mediators.
+These pathophysiological sequelae have been shown to sustain the systemic inflammatory response syndrome after major trauma, and can ultimately contribute to remote organ injury and death.
+Numerous experimental models have been designed in recent years with the aim of mimicking the inflammatory reaction after trauma and to allow the testing of new pharmacological approaches, including the emergent concept of site-targeted complement inhibition.
+The present review provides an overview on the current understanding of the cellular and molecular mechanisms of complement activation after major trauma, with an emphasis of emerging therapeutic concepts which may provide the rationale for a "bench-to-bedside" approach in the design of future pharmacological strategies.
+It is a fundamentally important problem because the information thus obtained may benefit the understanding of many basic biological processes and provide useful clues for drug design.
+It was observed that the overall success rate obtained by the method via the 5-fold cross-validation test on a benchmark dataset consisting of 3,137 compounds was 77.97%, which is much higher than 10.45%, the corresponding success rate obtained by the random guesses.
+Besides, to deal with the situation that some compounds may be involved with more than one metabolic pathway class, the method presented here is featured by the capacity able to provide a series of potential metabolic pathway classes ranked according to the descending order of their likelihood for each of the query compounds concerned.
+Furthermore, our method was also applied to predict 5,549 compounds whose metabolic pathway classes are unknown.
+Interestingly, the results thus obtained are quite consistent with the deductions from the reports by other investigators.
+It is anticipated that, with the continuous increase of the chemical-chemical interaction data, the current method will be further enhanced in its power and accuracy, so as to become a useful complementary vehicle in annotating uncharacterized compounds for their biological functions.
+For over two decades, it has been widely accepted that the 10 segments of the dsRNA genome of BTV encode for 7 structural and 3 non-structural proteins.
+The non-structural proteins (NS1, NS2, NS3/NS3a) play different key roles during the viral replication cycle.
+In this study we show that BTV expresses a fourth non-structural protein (that we designated NS4) encoded by an open reading frame in segment 9 overlapping the open reading frame encoding VP6.
+NS4 is 77–79 amino acid residues in length and highly conserved among several BTV serotypes/strains.
+By reverse genetics, we showed that NS4 is dispensable for BTV replication in vitro, both in mammalian and insect cells, and does not affect viral virulence in murine models of bluetongue infection.
+Interestingly, NS4 conferred a replication advantage to BTV-8, but not to BTV-1, in cells in an interferon (IFN)-induced antiviral state.
+However, the BTV-1 NS4 conferred a replication advantage both to a BTV-8 reassortant containing the entire segment 9 of BTV-1 and to a BTV-8 mutant with the NS4 identical to the homologous BTV-1 protein.
+Collectively, this study suggests that NS4 plays an important role in virus-host interaction and is one of the mechanisms played, at least by BTV-8, to counteract the antiviral response of the host.
+In addition, the distinct nucleolar localization of NS4, being expressed by a virus that replicates exclusively in the cytoplasm, offers new avenues to investigate the multiple roles played by the nucleolus in the biology of the cell.
+Two intramolecular interactions, i.e., (1) hydrogen bond and (2) substituent effect, were analyzed and compared.
+For this purpose, the geometry of 4- and 5-X-substituted salicylaldehyde derivatives (X = NO(2), H or OH) was optimized by means of B3LYP/6-311 + G(d,p) and MP2/aug-cc-pVDZ methods.
+The results obtained allowed us to show that substituents (NO(2) or OH) in the para or meta position with respect to either OH or CHO in H-bonded systems interact more strongly than in the case of di-substituted species: 4- and 3-nitrophenol or 4- and 3-hydroxybenzaldehyde by ∼31%.
+The substituent effect due to the intramolecular charge transfer from the para-counter substituent (NO(2)) to the proton-donating group (OH) is ∼35% greater than for the interaction of para-OH with the proton-accepting group (CHO).
+The total energy of H-bonding for salicylaldehyde, and its derivatives, is composed of two contributions: ∼80% from the energy of H-bond formation and ∼20% from the energy associated with reorganization of the electron structure of the systems in question.
+[Figure: see text] ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00894-011-1044-1) contains supplementary material, which is available to authorized users.
+BACKGROUND: Acute respiratory distress syndrome (ARDS) induced by pandemic 2009 H1N1 influenza virus has been widely reported and was considered the main cause of death in critically ill patients with 2009 H1N1 infection.
+However, no animal model has been developed for ARDS caused by infection with 2009 H1N1 virus.
+METHODOLOGY PRINCIPAL FINDINGS: Mice were inoculated with A/swine/Shandong/731/2009 (SD/09), which was a 2009 H1N1 influenza variant with a G222D mutation in the hemagglutinin.
+Arterial blood gas, leukocyte count in the bronchial alveolar lavage fluid and blood, virus titers, and cytokine levels in the lung were measured at various times post-inoculation.
+Mice infected with SD/09 virus showed typical ARDS symptoms characterized by 60% lethality on days 8–10 post-inoculation, highly edematous lungs, inflammatory cellular infiltration, alveolar and interstitial edema, lung hemorrhage, progressive and severe hypoxemia, and elevated levels of proinflammatory cytokines and chemokines.
+CONCLUSIONS/SIGNIFICANCE: These results suggested that we successfully established an ARDS mouse model induced by a virulent 2009 H1N1 variant without previous adaptation, which may be of benefit for evaluating the pathogenesis or therapy of human ARDS caused by 2009 H1N1 virus.
+BACKGROUND: Multiple infections are common in natural host populations and interspecific parasite interactions are therefore likely within a host individual.
+As they may seriously impact the circulation of certain parasites and the emergence and management of infectious diseases, their study is essential.
+In the field, detecting parasite interactions is rendered difficult by the fact that a large number of co-infected individuals may also be observed when two parasites share common risk factors.
+To correct for these “false interactions”, methods accounting for parasite risk factors must be used.
+METHODOLOGY/PRINCIPAL FINDINGS: In the present paper we propose such a method for presence-absence data (i.e., serology).
+Our method enables the calculation of the expected frequencies of single and double infected individuals under the independence hypothesis, before comparing them to the observed ones using the chi-square statistic.
+The method is termed “the corrected chi-square.” Its robustness was compared to a pre-existing method based on logistic regression and the corrected chi-square proved to be much more robust for small sample sizes.
+Since the logistic regression approach is easier to implement, we propose as a rule of thumb to use the latter when the ratio between the sample size and the number of parameters is above ten.
+Applied to serological data for four viruses infecting cats, the approach revealed pairwise interactions between the Feline Herpesvirus, Parvovirus and Calicivirus, whereas the infection by FIV, the feline equivalent of HIV, did not modify the risk of infection by any of these viruses.
+CONCLUSIONS/SIGNIFICANCE: This work therefore points out possible interactions that can be further investigated in experimental conditions and, by providing a user-friendly R program and a tutorial example, offers new opportunities for animal and human epidemiologists to detect interactions of interest in the field, a crucial step in the challenge of multiple infections.
+CEACAM1 is a multifunctional Ig-like cell adhesion molecule expressed by epithelial cells in many organs.
+Here, we have isolated an anchorage dependent clone, designated 253T-NT that does not express detectable levels of CEACAM1.
+Stable transfection of 253-NT cells with a wild type CEACAM1-4S expression vector induced an anchorage independent growth in vitro and a tumorigenic phenotype in vivo.
+These phenotypes were used as quantifiable end points to examine the functionality of the CEACAM1-4S transmembrane domain.
+Examination of the CEACAM1 transmembrane domain showed N-terminal GXXXG dimerization sequences and C-terminal tyrosine residues shown in related studies to stabilize transmembrane domain helix-helix interactions.
+To examine the effects of transmembrane domain mutations, 253-NT cells were transfected with transmembrane domain mutants carrying glycine to leucine or tyrosine to valine substitutions.
+Results showed that mutation of transmembrane tyrosine residues greatly enhanced growth in vitro and in vivo.
+253-NT cells expressing CEACAM1-4S with both glycine to leucine and tyrosine to valine mutations displayed the growth-enhanced phenotype of tyrosine mutants.
+The dramatic effect of transmembrane domain mutations constitutes strong evidence that the transmembrane domain is an important determinant of CEACAM1-4S functionality and most likely by other proteins with transmembrane domains containing dimerization sequences and/or C-terminal tyrosine residues.
+Overstimulation of host lipid metabolism in the liver by HCV-encoded proteins during viral infection creates a favorable environment for virus propagation and pathogenesis.
+In this study, we hypothesize that targeting cellular enzymes acting as master regulators of lipid homeostasis could represent a powerful approach to developing a novel class of broad-spectrum antivirals against infection associated with human Flaviviridae viruses such as hepatitis C virus (HCV), whose assembly and pathogenesis depend on interaction with lipid droplets (LDs).
+One such master regulator of cholesterol metabolic pathways is the host subtilisin/kexin-isozyme-1 (SKI-1) – or site-1 protease (S1P).
+SKI-1/S1P plays a critical role in the proteolytic activation of sterol regulatory element binding proteins (SREBPs), which control expression of the key enzymes of cholesterol and fatty-acid biosynthesis.
+Here we report the development of a SKI-1/S1P-specific protein-based inhibitor and its application to blocking the SREBP signaling cascade.
+The inhibitory mechanism is associated with a dramatic reduction in the abundance of neutral lipids, LDs, and the LD marker: adipose differentiation-related protein (ADRP)/perilipin 2.
+Importantly, we confirm that SKI-1/S1P is a key host factor for HCV infection by using a specific active, site-directed, small-molecule inhibitor of SKI-1/S1P: PF-429242.
+Our studies identify SKI-1/S1P as both a novel regulator of the HCV lifecycle and as a potential host-directed therapeutic target against HCV infection and liver steatosis.
+With identification of an increasing number of human viruses that use host LDs for infection, our results suggest that SKI-1/S1P inhibitors may allow development of novel broad-spectrum biopharmaceuticals that could lead to novel indirect-acting antiviral options with the current standard of care.
+Dendritic cells (DCs) initiate immune responses by transporting antigens and migrating to lymphoid tissues to initiate T-cell responses.
+DCs are located in the mucosal surfaces that are involved in human immunodeficiency virus (HIV) transmission and they are probably among the earliest targets of HIV-1 infection.
+DCs have an important role in viral transmission and dissemination, and HIV-1 has evolved different strategies to evade DC antiviral activity.
+High mobility group box 1 (HMGB1) is a DNA-binding nuclear protein that can act as an alarmin, a danger signal to alert the innate immune system for the initiation of host defense.
+It is the prototypic damage-associated molecular pattern molecule, and it can be secreted by innate cells, including DCs and natural killer (NK) cells.
+The fate of DCs is dependent on a cognate interaction with NK cells, which involves HMGB1 expressed at NK–DC synapse.
+HMGB1 is essential for DC maturation, migration to lymphoid tissues and functional type-1 polarization of naïve T cells.
+This review highlights the latest advances in our understanding of the impact of HIV on the interactions between HMGB1 and DCs, focusing on the mechanisms of HMGB1-dependent viral dissemination and persistence in DCs, and discussing the consequences on antiviral innate immunity, immune activation and HIV pathogenesis.
+BACKGROUND: Bacterial meningitis is an infectious disease with high rates of mortality and high frequency of severe sequelae.
+Early identification of causative bacterial and viral pathogens is important for prompt and proper treatment of meningitis and for prevention of life-threatening clinical outcomes.
+In the present study, we evaluated the value of the Seeplex Meningitis ACE Detection kit (Seegene Inc., Korea), a newly developed multiplex PCR kit employing dual priming oligonucleotide methods, for diagnosing acute meningitis.
+METHODS: Analytical sensitivity of the kit was studied using reference strains for each pathogen targeted by the kit, while it's analytical specificity was studied using the human genome DNA and 58 clinically well-identified reference strains.
+For clinical validation experiment, we used 27 control cerebrospinal fluid (CSF) samples and 78 clinical CSF samples collected from patients at the time of diagnosis of acute meningitis.
+RESULTS: The lower detection limits ranged from 10(1) copies/µL to 5×10(1) copies/µL for the 12 viral and bacterial pathogens targeted.
+CONCLUSIONS: The Seeplex Meningitis ACE Detection kit showed high sensitivity, specificity, and detection rate for the identification of pathogens in clinical CSF samples.
+As far as taxonomy is concerned, color may help observing various species’ characteristics in correlation with classification.
+However, choosing the number of subclasses to display is often a complex task: on the one hand, assigning a limited number of colors to taxa of interest hides the structure imbedded in the subtrees of the taxonomy; on the other hand, differentiating a high number of taxa by giving them specific colors, without considering the underlying taxonomy, may lead to unreadable results since relationships between displayed taxa would not be supported by the color code.
+In the present paper, an automatic color coding scheme is proposed to visualise the levels of taxonomic relationships displayed as overlay on any kind of data plot.
+To achieve this goal, a dimensionality reduction method allows displaying taxonomic “distances” onto a Euclidean two-dimensional space.
+The resulting map is projected onto a 2D color space (the Hue, Saturation, Brightness colorimetric space with brightness set to 1).
+Proximity in the taxonomic classification corresponds to proximity on the map and is therefore materialised by color proximity.
+As a result, each species is related to a color code showing its position in the taxonomic tree.
+The so called ColorPhylo displays taxonomic relationships intuitively and can be combined with any biological result.
+Many of the cellular mechanisms underlying host responses to pathogens have been well conserved during evolution.
+As a result, Drosophila can be used to deconstruct many of the key events in host-pathogen interactions by using a wealth of well-developed molecular and genetic tools.
+In this review, we aim to emphasize the great leverage provided by the suite of genomic and classical genetic approaches available in flies for decoding details of host-pathogen interactions; these findings can then be applied to studies in higher organisms.
+We first briefly summarize the general strategies by which Drosophila resists and responds to pathogens.
+We then focus on how recently developed genome-wide RNA interference (RNAi) screens conducted in cells and flies, combined with classical genetic methods, have provided molecular insight into host-pathogen interactions, covering examples of bacteria, fungi and viruses.
+Finally, we discuss novel strategies for how flies can be used as a tool to examine how specific isolated virulence factors act on an intact host.
+Structural data on the arrangement, stoichiometry and organisation of the component molecules of filoviruses has until now been lacking, partially due to the need to work under level 4 biological containment.
+METHODOLOGY AND PRINCIPAL FINDINGS: We have investigated the structure of Ebola virus using a combination of cryo-electron microscopy, cryo-electron tomography, sub-tomogram averaging, and single particle image processing.
+Here we report the three-dimensional structure and architecture of Ebola virus and establish that multiple copies of the RNA genome can be packaged to produce polyploid virus particles, through an extreme degree of length polymorphism.
+We show that the helical Ebola virus inner nucleocapsid containing RNA and nucleoprotein is stabilized by an outer layer of VP24-VP35 bridges.
+Elucidation of the structure of the membrane-associated glycoprotein in its native state indicates that the putative receptor-binding site is occluded within the molecule, while a major neutralizing epitope is exposed on its surface proximal to the viral envelope.
+The matrix protein VP40 forms a regular lattice within the envelope, although its contacts with the nucleocapsid are irregular.
+CONCLUSIONS: The results of this study demonstrate a modular organization in Ebola virus that accommodates a well-ordered, symmetrical nucleocapsid within a flexible, tubular membrane envelope.
+Using a series of theoretical methods like pharmacophore modeling, database screening, molecular docking and Density Functional Theory (DFT) calculations, an investigation for identification of novel chymase inhibitors, and to specify the key factors crucial for the binding and interaction between chymase and inhibitors is performed.
+A highly correlating (r = 0.942) pharmacophore model (Hypo1) with two hydrogen bond acceptors, and three hydrophobic aromatic features is generated.
+Finally, three structurally diverse compounds with high GOLD fitness scores and interactions with key active site amino acids are identified as potent chymase hits.
+Moreover, DFT study is performed which confirms very clear trends between electronic properties and inhibitory activity (IC(50)) data thus successfully validating “Hypo1” by DFT method.
+Therefore, this research exertion can be helpful in the development of new potent hits for chymase.
+In addition, the combinational use of docking, orbital energies and molecular electrostatic potential analysis is also demonstrated as a good endeavor to gain an insight into the interaction between chymase and inhibitors.
+They are central to the immunological link that occurs when the mother transfers passive immunity to the offspring.
+Cattle provide a readily available immune rich colostrum and milk in large quantities, making those secretions important potential sources of immune products that may benefit humans.
+Immune milk is a term used to describe a range of products of the bovine mammary gland that have been tested against several human diseases.
+The use of colostrum or milk as a source of immunoglobulins, whether intended for the neonate of the species producing the secretion or for a different species, can be viewed in the context of the types of immunoglobulins in the secretion, the mechanisms by which the immunoglobulins are secreted, and the mechanisms by which the neonate or adult consuming the milk then gains immunological benefit.
+The stability of immunoglobulins as they undergo processing in the milk, or undergo digestion in the intestine, is an additional consideration for evaluating the value of milk immunoglobulins.
+This review summarizes the fundamental knowledge of immunoglobulins found in colostrum, milk, and immune milk.
+BACKGROUND: The purpose of this investigation was to compare the outcome of percutaneous radiofrequency thermal ablation therapy (PRFA) with surgical resection (SR) in the treatment of single and small hepatocellular carcinoma (HCC).
+METHODS: We conducted a retrospective cohort study on 231 treatment naive patients with a single HCC ≤ 3 cm who had received either curative PRFA (162 patients) or curative SR (69 patients).
+All patients were regularly followed up after treatment at our department with blood and radiologic tests.
+RESULTS: The 1-, 3- and 5-year overall survival rates after PRFA and SR were 95.4%, 79.6% and 63.1%, respectively in the PRFA group and 100%, 81.4% and 74.6%, respectively in the SR group.
+The corresponding recurrence free survival rates at 1, 3 and 5 years after PRFA and SR were 82.0%, 38.3% and 18.0%, respectively in the PRFA group and 86.0%, 47.2% and 26.0%, respectively in the SR group.
+In terms of overall survival and recurrence free survival, there were no significant differences between these two groups.
+In comparison of PRFA group patients with liver cirrhosis (LC) (n = 127) and SR group patients with LC (n = 50) and in comparison of PRFA group patients without LC (n = 35) and SR group patients without LC (n = 19), there were also no significant differences between two groups in terms of overall survival and recurrence free survival.
+In the multivariate analysis of the risk factors contributing to overall survival, serum albumin level was the sole significant factor.
+In the multivariate analysis of the risk factors contributing to recurrence free survival, presence of LC was the sole significant factor.
+The rate of serious adverse events in the SR group was significantly higher than that in the PRFA group (P = 0.023).
+Hospitalization length in the SR group was significantly longer than in the PRFA group (P = 0.013).
+CONCLUSIONS: PRFA is as effective as SR in the treatment of single and small HCC, and is less invasive than SR.
+Therefore, PRFA could be a first choice for the treatment of single and small HCC.
+Success requires better understanding of parents' perceptions of diseases and consequent decisions about vaccinations, however few studies have considered this from the theoretical perspectives of risk perception and decision-making under uncertainty.
+The aim of this study was to examine the utility of subjective risk perception and decision-making theories to provide a better understanding of the differences between immunisers' and non-immunisers' health beliefs and behaviours.
+METHODS: In a qualitative study we conducted semi-structured in-depth interviews with 45 Australian parents exploring their experiences and perceptions of disease severity and susceptibility.
+Using scenarios about 'a new strain of flu' we explored how risk information was interpreted.
+RESULTS: We found that concepts of dread, unfamiliarity, and uncontrollability from the subjective perception of risk and ambiguity, optimistic control and omission bias from explanatory theories of decision-making under uncertainty were useful in understanding why immunisers, incomplete immunisers and non-immunisers interpreted severity and susceptibility to diseases and vaccine risk differently.
+Participants believed that the risks of diseases and complications from diseases are not equally spread throughout the community, therefore, when listening to reports of epidemics, it is not the number of people who are affected but the familiarity or unfamiliarity of the disease and the characteristics of those who have had the disease that prompts them to take preventive action.
+Almost all believed they themselves would not be at serious risk of the 'new strain of flu' but were less willing to take risks with their children's health.
+CONCLUSION: This study has found that health messages about the risks of disease which are communicated as though there is equality of risk in the population may be unproductive as these messages are perceived as unbelievable or irrelevant.
+The findings from this study have implications beyond the issue of childhood vaccinations as we grapple with communicating risks of new epidemics, and indeed may usefully contribute to the current debate especially in the UK of how these theories of risk and decision-making can be used to 'nudge' other health behaviours.
+Viral vectors have been available in various fields such as medical and biological research or gene therapy applications.
+Targeting vectors pseudotyped with distinct viral envelope proteins that influence cell tropism and transfection efficiency are useful tools not only for examining entry mechanisms or cell tropisms but also for vaccine vector development.
+A recombinant VSV lacking its own envelope (G) gene has been used to produce a pseudotype or recombinant VSV possessing the envelope proteins of heterologous viruses.
+These viruses possess a reporter gene instead of a VSV G gene in their genome, and therefore it is easy to evaluate their infectivity in the study of viral entry, including identification of viral receptors.
+Furthermore, advantage can be taken of a property of the pseudotype VSV, which is competence for single-round infection, in handling many different viruses that are either difficult to amplify in cultured cells or animals or that require specialized containment facilities.
+Here we describe procedures for producing pseudotype or recombinant VSVs and a few of the more prominent examples from envelope viruses, such as hepatitis C virus, Japanese encephalitis virus, baculovirus, and hemorrhagic fever viruses.
+Swine influenza is an acute respiratory disease in pigs caused by swine influenza virus (SIV).
+Importantly, pigs have long been considered “mixing vessels” that generate novel influenza viruses with pandemic potential, a constant threat to public health.
+Since its emergence in 2009 and subsequent pandemic spread, the pandemic (H1N1) 2009 (H1N1pdm) has been detected in pig farms, creating the risk of generating new reassortants and their possible infection of humans.
+Proinflammatory and antiviral cytokine responses are considered correlated with the intensity of clinical signs, and swine macrophages are found to be indispensible in effective clearance of SIV from pig lungs.
+In this study, we report a unique pattern of cytokine responses in swine macrophages infected with H1N1pdm.
+The roles of mitogen-activated protein (MAP) kinases in the regulation of the host responses were examined.
+We found that proinflammatory cytokines IL-6, IL-8, IL-10, and TNF-α were significantly induced and their induction was ERK1/2-dependent.
+IFN-β and IFN-inducible antiviral Mx and 2′5′-OAS were sharply induced, but the inductions were effectively abolished when ERK1/2 was inhibited.
+Induction of CCL5 (RANTES) was completely inhibited by inhibitors of ERK1/2 and JNK1/2, which appeared also to regulate FasL and TNF-α, critical for apoptosis in pig macrophages.
+We found that NFκB was activated in H1N1pdm-infected cells, but the activation was suppressed when ERK1/2 was inhibited, indicating there is cross-talk between MAP kinase and NFκB responses in pig macrophages.
+Our data suggest that MAP kinase may activate NFκB through the induction of RIG-1, which leads to the induction of IFN-β in swine macrophages.
+Understanding host responses and their underlying mechanisms may help identify venues for effective control of SIV and assist in prevention of future influenza pandemics.
+Genome structural annotation, i.e., identification and demarcation of the boundaries for all the functional elements in a genome (e.g., genes, non-coding RNAs, proteins and regulatory elements), is a prerequisite for systems level analysis.
+Current genome annotation programs do not identify all of the functional elements of the genome, especially small non-coding RNAs (sRNAs).
+Whole genome transcriptome analysis is a complementary method to identify “novel” genes, small RNAs, regulatory regions, and operon structures, thus improving the structural annotation in bacteria.
+In particular, the identification of non-coding RNAs has revealed their widespread occurrence and functional importance in gene regulation, stress and virulence.
+However, very little is known about non-coding transcripts in Histophilus somni, one of the causative agents of Bovine Respiratory Disease (BRD) as well as bovine infertility, abortion, septicemia, arthritis, myocarditis, and thrombotic meningoencephalitis.
+In this study, we report a single nucleotide resolution transcriptome map of H. somni strain 2336 using RNA-Seq method.
+The RNA-Seq based transcriptome map identified 94 sRNAs in the H. somni genome of which 82 sRNAs were never predicted or reported in earlier studies.
+We also identified 38 novel potential protein coding open reading frames that were absent in the current genome annotation.
+The transcriptome map allowed the identification of 278 operon (total 730 genes) structures in the genome.
+When compared with the genome sequence of a non-virulent strain 129Pt, a disproportionate number of sRNAs (∼30%) were located in genomic region unique to strain 2336 (∼18% of the total genome).
+This observation suggests that a number of the newly identified sRNAs in strain 2336 may be involved in strain-specific adaptations.
+Molecular determinants of ion channel tetramerization are well characterized, but those involved in heteromeric channel assembly are less clearly understood.
+Cyclic nucleotide-gated (CNG) channels from rod photoreceptors exhibit a 3:1 stoichiometry of CNGA1 and CNGB1 subunits that tunes the channels for their specialized role in phototransduction.
+Here we show, using electrophysiology, fluorescence, biochemistry, and X-ray crystallography, that the mechanism for this controlled assembly is the formation of a parallel 3-helix coiled-coil domain of the carboxy-terminal leucine zipper region of CNGA1 subunits, constraining the channel to contain three CNGA1 subunits, followed by preferential incorporation of a single CNGB1 subunit.
+Deletion of the carboxy-terminal leucine zipper domain relaxed the constraint and permitted multiple CNGB1 subunits in the channel.
+The X-ray crystal structures of the parallel 3-helix coiled-coil domains of CNGA1 and CNGA3 subunits were similar, suggesting that a similar mechanism controls the stoichiometry of cone CNG channels.
+SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/ncomms1466) contains supplementary material, which is available to authorized users.
+BACKGROUND: Environmental factors have been associated with transmission and survival of influenza viruses but no studies have ever explored the role of environmental factors on severity of influenza infection.
+METHODS: We applied a Poisson regression model to the mortality data of two Chinese metropolitan cities located within the subtropical zone, to calculate the influenza associated excess mortality risks during the periods with different levels of temperature and humidity.
+RESULTS: The results showed that high absolute humidity (measured by vapor pressure) was significantly (p < 0.05) associated with increased risks of all-cause and cardiorespiratory deaths, but not with increased risks of pneumonia and influenza deaths.
+The association between absolute humidity and mortality risks was found consistent among the two cities.
+An increasing pattern of influenza associated mortality risks was also found across the strata of low to high relative humidity, but the results were less consistent for temperature.
+CONCLUSIONS: These findings highlight the need for people with chronic cardiovascular and respiratory diseases to take extra caution against influenza during hot and humid days in the subtropics and tropics.
+BACKGROUND: Immunocompromised patients, such as systemic lupus erythematosus (SLE) sufferers have an increased risk of mortality, following influenza infection.
+In the recent pandemic, influenza A H1NI virus caused 18449 deaths, mainly because of adult respiratory distress syndrome or bacterial co-infections.
+CASE PRESENTATION: In this case report, an SLE patient with viral-induced septic shock, without overt pulmonary involvement, is discussed.
+The patient was administered oseltamivir and supportive treatment, including wide-spectrum antibiotics, vasopressors and steroids, according to the guidelines proposed for bacterial sepsis and septic shock.
+She finally survived and experienced a lupus flare soon after intensive care unit (ICU) discharge.
+CONCLUSIONS: To our knowledge, this is the first case to report severe septic shock from influenza A/H1N1 virus, without overt pulmonary involvement.
+BACKGROUND: During the initial containment phase of influenza A/H1N1 2009, close contacts of cases were traced to provide antiviral prophylaxis within 48 h after exposure and to alert them on signs of disease for early diagnosis and treatment.
+Passengers seated on the same row, two rows in front or behind a patient infectious for influenza, during a flight of ≥ 4 h were considered close contacts.
+This study evaluates the timeliness of flight-contact tracing (CT) as performed following national and international CT requests addressed to the Center of Infectious Disease Control (CIb/RIVM), and implemented by the Municipal Health Services of Schiphol Airport.
+METHODS: Elapsed days between date of flight arrival and the date passenger lists became available (contact details identified - CI) was used as proxy for timeliness of CT.
+In a retrospective study, dates of flight arrival, onset of illness, laboratory diagnosis, CT request and identification of contacts details through passenger lists, following CT requests to the RIVM for flights landed at Schiphol Airport were collected and analyzed.
+In 17 out of 21 requests, contact details were obtained within 7 days after arrival (81%).
+The average delay between arrival and CI was 3,9 days (range 2-7), mainly caused by delay in diagnosis of the index patient after arrival (2,6 days).
+CONCLUSION: CT for influenza A/H1N1 2009 among flight passengers was not successful for timely provision of prophylaxis.
+CT had little additional value for alerting passengers for disease symptoms, as this information already was provided during and after the flight.
+Public health authorities should take into account patient delays in seeking medical advise and laboratory confirmation in relation to maximum time to provide postexposure prophylaxis when deciding to install contact tracing measures.
+A variety of mechanisms have been suggested as the means by which infections can initiate and/or exacerbate autoimmune diseases.
+One mechanism is molecular mimicry, where a foreign antigen shares sequence or structural similarities with self-antigens.
+However, structural relatedness between pathogen and self does not account for T cell activation in a number of autoimmune diseases.
+A proposed mechanism that could have been misinterpreted for molecular mimicry is the expression of dual T cell receptors (TCR) on a single T cell.
+These T cells have dual reactivity to both foreign and self-antigens leaving the host vulnerable to foreign insults capable of triggering an autoimmune response.
+In this review, we briefly discuss what is known about molecular mimicry followed by a discussion of the current understanding of dual TCRs.
+Finally, we discuss three mechanisms, including molecular mimicry, dual TCRs, and chimeric TCRs, by which dual reactivity of the T cell may play a role in autoimmune diseases.
+BACKGROUND: Sentinel surveillance for severe acute respiratory infections in hospitals and influenza-like illness in ambulatory clinics is recommended to assist in global pandemic influenza preparedness.
+Healthcare utilization patterns will affect the generalizability of data from sentinel sites and the potential to use them to estimate burden of disease.
+The objective of this study was to measure healthcare utilization patterns in Guatemala to inform the establishment of a sentinel surveillance system for influenza and other respiratory infections, and allow estimation of disease burden.
+METHODS: We used a stratified, two-stage cluster survey sample to select 1200 households from the Department of Santa Rosa.
+Trained interviewers screened household residents for self-reported pneumonia in the last year and influenza-like illness (ILI) in the last month and asked about healthcare utilization for each illness episode.
+RESULTS: We surveyed 1131 (94%) households and 5449 residents between October and December 2006 and identified 323 (6%) cases of pneumonia and 628 (13%) cases of ILI.
+Treatment for pneumonia outside the home was sought by 92% of the children <5 years old and 73% of the persons aged five years and older.
+For both children <5 years old (53%) and persons aged five years and older (31%) who reported pneumonia, private clinics were the most frequently reported source of care.
+For ILI, treatment was sought outside the home by 81% of children <5 years old and 65% of persons aged five years and older.
+Government ambulatory clinics were the most frequently sought source of care for ILI both for children <5 years old (41%) and persons aged five years and older (36%).
+CONCLUSIONS: Sentinel surveillance for influenza and other respiratory infections based in government health facilities in Guatemala will significantly underestimate the burden of disease.
+Adjustment for healthcare utilization practices will permit more accurate estimation of the incidence of influenza and other respiratory pathogens in the community.
+The resurgence of the malaria eradication agenda and the increasing number of severe manifestation reports has contributed to a renewed interested in the Plasmodium vivax infection.
+It is the most geographically widespread parasite causing human malaria, with around 2.85 billion people living under risk of infection.
+The Brazilian Amazon region reports more than 50% of the malaria cases in Latin America and since 1990 there is a marked predominance of this species, responsible for 85% of cases in 2009.
+However, only a few complicated cases of P. vivax have been reported from this region.
+A systematic review of the Brazilian indexed and non-indexed literature on complicated cases of vivax malaria was performed including published articles, masters' dissertations, doctoral theses and national congresses' abstracts.
+The following information was retrieved: patient characteristics (demographic, presence of co-morbidities and, whenever possible, associated genetic disorders); description of each major clinical manifestation.
+As a result, 27 articles, 28 abstracts from scientific events' annals and 13 theses/dissertations were found, only after 1987.
+Most of the reported information was described in small case series and case reports of patients from all the Amazonian states, and also in travellers from Brazilian non-endemic areas.
+The more relevant clinical complications were anaemia, thrombocytopaenia, jaundice and acute respiratory distress syndrome, present in all age groups, in addition to other more rare clinical pictures.
+Clinical atypical cases of malaria are more frequent than published in the indexed literature, probably due to a publication bias.
+In the Brazilian Amazon (considered to be a low to moderate intensity area of transmission), clinical data are in accordance with the recent findings of severity described in diverse P. vivax endemic areas (especially anaemia in Southeast Asia), however in this region both children and adults are affected.
+Despite reduction in cardiovascular (CV) events and end-organ damage with the current pharmacologic strategies, CV disease remains the primary cause of death in the world.
+Pharmacological therapies based on the renin angiotensin system (RAS) blockade are used extensively for the treatment of hypertension, heart failure, and CV remodeling but in spite of their success the prevalence of end-organ damage and residual risk remain still high.
+Novel approaches must be discovered for a more effective treatment of residual CV remodeling and risk.
+The ACE2/Ang-(1–9) axis is a new and important target to counterbalance the vasoconstrictive/proliferative RAS axis.
+Ang-(1–9) is hydrolyzed slower than Ang-(1–7) and is able to bind the Ang II type 2 receptor.
+We review here the current experimental evidence suggesting that activation of the ACE2/Ang-(1–9) axis protects the heart and vessels (and possibly the kidney) from adverse cardiovascular remodeling in hypertension as well as in heart failure.
+The infection cycle of viruses creates many opportunities for the exchange of genetic material with the host.
+We searched for unexpected sequence similarity among the 900,000 viral proteins and all proteins from cellular organisms.
+About 5% of the 12,000 statistical models archived in Pfam are composed of viral-metazoan proteins.
+In about half of Pfam families, we provide indirect support for the directionality from the host to the virus.
+The other families are either wrongly annotated or reflect an extensive sequence exchange between the viruses and their hosts.
+In about 75% of cross-taxa Pfam families, the viral proteins are significantly shorter than their metazoan counterparts.
+The tendency for shorter viral proteins relative to their related host proteins accounts for the acquisition of only a fragment of the host gene, the elimination of an internal domain and shortening of the linkers between domains.
+We postulate that the trimmed proteins act by interfering with the fundamental function of the host including intracellular signaling, post-translational modification, protein-protein interaction networks and cellular trafficking.
+Bioterrorism is defined as the intentional use of biological, chemical, nuclear, or radiological agents to cause disease, death, or environmental damage.
+Early recognition of a bioterrorist attack is of utmost importance to minimize casualties and initiate appropriate therapy.
+The range of agents that could potentially be used as weapons is wide, however, only a few of these agents have all the characteristics making them ideal for that purpose.
+Many of the chemical and biological weapons can cause neurological symptoms and damage the nervous system in varying degrees.
+The main challenge is to be cognizant of the clinical syndromes and to be able to differentiate diseases caused by bioterrorism from naturally occurring disorders.
+This review provides an overview of the biological and chemical warfare agents, with a focus on neurological manifestation and an approach to treatment from a perspective of neurological critical care.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s13311-011-0097-2) contains supplementary material, which is available to authorized users.
+Angiotensin (Ang)-(1–7) is now recognized as a biologically active component of the renin-angiotensin system (RAS).
+The discovery of the angiotensin-converting enzyme homologue ACE2 revealed important metabolic pathways involved in the Ang-(1–7) synthesis.
+This enzyme can form Ang-(1–7) from Ang II or less efficiently through hydrolysis of Ang I to Ang-(1–9) with subsequent Ang-(1–7) formation.
+Additionally, it is well established that the G protein-coupled receptor Mas is a functional ligand site for Ang-(1–7).
+The axis formed by ACE2/Ang-(1–7)/Mas represents an endogenous counter regulatory pathway within the RAS whose actions are opposite to the vasoconstrictor/proliferative arm of the RAS constituted by ACE/Ang II/AT(1) receptor.
+In this review we will discuss recent findings concerning the biological role of the ACE2/Ang-(1–7)/Mas arm in the cardiovascular and pulmonary system.
+Also, we will highlight the initiatives to develop potential therapeutic strategies based on this axis.
+Much of our understanding of ssRNA conformational behavior is limited to structures in which ssRNA directly engages in tertiary interactions or is recognized by proteins.
+Little is known about the structural and dynamic behavior of free ssRNAs at atomic resolution.
+Here, we report the collaborative application of nuclear magnetic resonance (NMR) and replica exchange molecular dynamics (REMD) simulations to characterize the 12 nt ssRNA tail derived from the prequeuosine riboswitch.
+NMR carbon spin relaxation data and residual dipolar coupling measurements reveal a flexible yet stacked core adopting an A-form-like conformation, with the level of order decreasing toward the terminal ends.
+An A-to-C mutation within the polyadenine tract alters the observed dynamics consistent with the introduction of a dynamic kink.
+Pre-ordering of the tail may increase the efficacy of ligand binding above that achieved by a random-coil ssRNA.
+The REMD simulations recapitulate important trends in the NMR data, but suggest more internal motions than inferred from the NMR analysis.
+Our study unmasks a previously unappreciated level of complexity in ssRNA, which we believe will also serve as an excellent model system for testing and developing computational force fields.
+BACKGROUND: Community-acquired pneumonia (CAP) is considered the most important cause of death from infectious disease in developed countries.
+A lack of specific and valid pathophysiologic severity markers affect early and effective sepsis therapy.
+HMGB-1, sRAGE and RAGE have been involved in sepsis and their potential as severity markers has been proposed.
+The aim of this study was to evaluate HMGB-1, RAGE and sRAGE levels in patients with CAP-associated sepsis and determine their possible association with clinical outcome.
+METHOD: We evaluated 33 patients with CAP-associated sepsis admitted to the emergency room and followed in the medical wards.
+Severity assessment scores (CURB-65, PSI, APACHE II, SOFA) and serologic markers (HMGB-1, RAGE, sRAGE) were evaluated on admission.
+RESULTS: Thirty patients with a diagnosis of CAP-associated sepsis were enrolled in the study within 24 hours after admission.
+Fourteen (46.6%) had pandemic (H1N1) influenza A virus, 2 (6.6%) had seasonal influenza A and 14 other diagnoses.
+ARDS was observed in 17 (56.6%) and a total of 22 patients had severe sepsis on admission (73%).
+The SOFA score showed the greatest difference between surviving and non-surviving groups (P = .003) with similar results in ARDS patients (P = .005).
+sRAGE levels tended to be higher in non-surviving (P = .058) and ARDS patients (P = .058).
+Logistic regression modeling demonstrated that SOFA (P = .013) and sRAGE (P = .05) were the only variables that modified the probability of a fatal outcome.
+CONCLUSION: The association of elevated sRAGE with a fatal outcome suggests that it may have an independent causal effect in CAP.
+SOFA scores were the only clinical factor with the ability to identify surviving and ARDS patients.
+Dengue virus is an emerging infectious agent that infects an estimated 50–100 million people annually worldwide, yet current diagnostic practices cannot detect an etiologic pathogen in ∼40% of dengue-like illnesses.
+Metagenomic approaches to pathogen detection, such as viral microarrays and deep sequencing, are promising tools to address emerging and non-diagnosable disease challenges.
+In this study, we used the Virochip microarray and deep sequencing to characterize the spectrum of viruses present in human sera from 123 Nicaraguan patients presenting with dengue-like symptoms but testing negative for dengue virus.
+We utilized a barcoding strategy to simultaneously deep sequence multiple serum specimens, generating on average over 1 million reads per sample.
+We then implemented a stepwise bioinformatic filtering pipeline to remove the majority of human and low-quality sequences to improve the speed and accuracy of subsequent unbiased database searches.
+By deep sequencing, we were able to detect virus sequence in 37% (45/123) of previously negative cases.
+Other samples contained sequences with similarity to sequences from viruses in the Herpesviridae, Flaviviridae, Circoviridae, Anelloviridae, Asfarviridae, and Parvoviridae families.
+In some cases, the putative viral sequences were virtually identical to known viruses, and in others they diverged, suggesting that they may derive from novel viruses.
+These results demonstrate the utility of unbiased metagenomic approaches in the detection of known and divergent viruses in the study of tropical febrile illness.
+We cloned the β-glucuronidase gene (AtGUS) from Aspergillus terreus Li-20 encoding 657 amino acids (aa), which can transform glycyrrhizin into glycyrrhetinic acid monoglucuronide (GAMG) and glycyrrhetinic acid (GA).
+Based on sequence alignment, the C-terminal non-conservative sequence showed low identity with those of other species; thus, the partial sequence AtGUS(-3t) (1–592 aa) was amplified to determine the effects of the non-conservative sequence on the enzymatic properties.
+At the similar optimum temperature (55°C) and pH (AtGUS-E, 6.6; AtGUS(-3t)-E, 7.0) conditions, the thermal stability of AtGUS(-3t)-E was enhanced at 65°C, and the metal ions Co(2+), Ca(2+) and Ni(2+) showed opposite effects on AtGUS-E and AtGUS(-3t)-E, respectively.
+Furthermore, Km of AtGUS(-3t)-E (1.95 mM) was just nearly one-seventh that of AtGUS-E (12.9 mM), whereas the catalytic efficiency of AtGUS(-3t)-E was 3.2 fold higher than that of AtGUS-E (7.16 vs. 2.24 mM s(−1)), revealing that the truncation of non-conservative sequence can significantly improve the catalytic efficiency of AtGUS.
+Conformational analysis illustrated significant difference in the secondary structure between AtGUS-E and AtGUS(-3t)-E by circular dichroism (CD).
+The results showed that the truncation of the non-conservative sequence could preferably alter and influence the stability and catalytic efficiency of enzyme.
+Recently, other animals such as pigs and some species of fruit bats have also been shown to be susceptible to these viruses.
+While having a preference for some cell types such as hepatocytes, endothelial cells, dendritic cells, monocytes, and macrophages, filoviruses are known to be pantropic in infection of primates.
+The envelope glycoprotein (GP) is responsible for both receptor binding and fusion of the virus envelope with the host cell membrane.
+It has been demonstrated that filovirus GP interacts with multiple molecules for entry into host cells, whereas none of the cellular molecules so far identified as a receptor/co-receptor fully explains filovirus tissue tropism and host range.
+Available data suggest that the mucin-like region (MLR) on GP plays an important role in attachment to the preferred target cells, whose infection is likely involved in filovirus pathogenesis, whereas the MLR is not essential for the fundamental function of the GP in viral entry into cells in vitro.
+Further studies elucidating the mechanisms of cellular entry of filoviruses may shed light on the development of strategies for prophylaxis and treatment of Ebola and Marburg hemorrhagic fevers.
+Porcine reproductive and respiratory syndrome virus (PRRSV) can subvert early innate immunity, which leads to ineffective antimicrobial responses.
+Overcoming immune subversion is critical for developing vaccines and other measures to control this devastating swine virus.
+The overall goal of this work was to enhance innate and adaptive immunity following vaccination through the expression of interferon (IFN) genes by the PRRSV genome.
+We have constructed a series of recombinant PRRS viruses using an infectious PRRSV cDNA clone (pCMV-P129).
+Coding regions of exogenous genes, which included Renilla luciferase (Rluc), green and red fluorescent proteins (GFP and DsRed, respectively) and several interferons (IFNs), were constructed and expressed through a unique subgenomic mRNA placed between ORF1b and ORF2 of the PRRSV infectious clone.
+The constructs, which expressed Rluc, GFP, DsRed, efficiently produced progeny viruses and mimicked the parental virus in both MARC-145 cells and porcine macrophages.
+In contrast, replication of IFN-expressing viruses was attenuated, similar to the level of replication observed after the addition of exogenous IFN.
+Furthermore, the IFN expressing viruses inhibited the replication of a second PRRS virus co-transfected or co-infected.
+Inhibition by the different IFN subtypes corresponded to their anti-PRRSV activity, i.e., IFNω5 ° IFNα1 > IFN-β > IFNδ3.
+In summary, the indicator-expressing viruses provided an efficient means for real-time monitoring of viral replication thus allowing high‑throughput elucidation of the role of host factors in PRRSV infection.
+This was shown when they were used to clearly demonstrate the involvement of tumor susceptibility gene 101 (TSG101) in the early stage of PRRSV infection.
+In addition, replication‑competent IFN-expressing viruses may be good candidates for development of modified live virus (MLV) vaccines, which are capable of reversing subverted innate immune responses and may induce more effective adaptive immunity against PRRSV infection.
+Replication of plus-strand RNA viruses depends on recruited host factors that aid several critical steps during replication.
+In this paper, we show that an essential translation factor, Ded1p DEAD-box RNA helicase of yeast, directly affects replication of Tomato bushy stunt virus (TBSV).
+To separate the role of Ded1p in viral protein translation from its putative replication function, we utilized a cell-free TBSV replication assay and recombinant Ded1p.
+The in vitro data show that Ded1p plays a role in enhancing plus-strand synthesis by the viral replicase.
+We also find that Ded1p is a component of the tombusvirus replicase complex and Ded1p binds to the 3′-end of the viral minus-stranded RNA.
+The data obtained with wt and ATPase deficient Ded1p mutants support the model that Ded1p unwinds local structures at the 3′-end of the TBSV (−)RNA, rendering the RNA compatible for initiation of (+)-strand synthesis.
+Interestingly, we find that Ded1p and glyceraldehyde-3-phosphate dehydrogenase (GAPDH), which is another host factor for TBSV, play non-overlapping functions to enhance (+)-strand synthesis.
+Altogether, the two host factors enhance TBSV replication synergistically by interacting with the viral (−)RNA and the replication proteins.
+In addition, we have developed an in vitro assay for Flock house virus (FHV), a small RNA virus of insects, that also demonstrated positive effect on FHV replicase activity by the added Ded1p helicase.
+Thus, two small RNA viruses, which do not code for their own helicases, seems to recruit a host RNA helicase to aid their replication in infected cells.
+BACKGROUND: The spread of infectious diseases in wildlife populations is influenced by patterns of between-host contacts.
+Habitat “hotspots” - places attracting a large numbers of individuals or social groups - can significantly alter contact patterns and, hence, disease propagation.
+Research on the importance of habitat hotspots in wildlife epidemiology has primarily focused on how inter-individual contacts occurring at the hotspot itself increase disease transmission.
+However, in territorial animals, epidemiologically important contacts may primarily occur as animals cross through territories of conspecifics en route to habitat hotspots.
+Here, we investigate the importance of these contacts in the case where infectious individuals keep visiting the hotspots and in the case where these individuals are not able to travel to the hotspot any more.
+METHODOLOGY AND PRINCIPAL FINDINGS: We developed a simulation epidemiological model to investigate both cases in a scenario when transmission at the hotspot does not occur.
+We find that (i) hotspots still exacerbate epidemics, (ii) when infectious individuals do not travel to the hotspot, the most vulnerable individuals are those residing at intermediate distances from the hotspot rather than nearby, and (iii) the epidemiological vulnerability of a population is the highest when the number of hotspots is intermediate.
+CONCLUSIONS AND SIGNIFICANCE: By altering animal movements in their vicinity, habitat hotspots can thus strongly increase the spread of infectious diseases, even when disease transmission does not occur at the hotspot itself.
+Interestingly, when animals only visit the nearest hotspot, creating additional artificial hotspots, rather than reducing their number, may be an efficient disease control measure.
+The Interferon induced transmembrane proteins (IFITM) are a family of transmembrane proteins that is known to inhibit cell invasion of viruses such as HIV-1 and influenza.
+We show that the IFITM genes are a subfamily in a larger family of transmembrane (TM) proteins that we call Dispanins, which refers to a common 2TM structure.
+We mined the Dispanins in 36 eukaryotic species, covering all major eukaryotic groups, and investigated their evolutionary history using Bayesian and maximum likelihood approaches to infer a phylogenetic tree.
+We identified ten human genes that together with the known IFITM genes form the Dispanin family.
+We show that the Dispanins first emerged in eukaryotes in a common ancestor of choanoflagellates and metazoa, and that the family later expanded in vertebrates where it forms four subfamilies (A–D).
+Interestingly, we also find that the family is found in several different phyla of bacteria and propose that it was horizontally transferred to eukaryotes from bacteria in the common ancestor of choanoflagellates and metazoa.
+In conclusion, we introduce a novel family, the Dispanins, together with a nomenclature based on the evolutionary origin.
+Given the wide variation in socio-economic conditions, health system capacity across the region is likely to impact to varying degrees on pandemic mitigation operations.
+We aimed to estimate and compare the resource gaps, and potential mortalities associated with those gaps, for responding to pandemic influenza within and between six territories in Asia.
+METHODS AND FINDINGS: We collected health system resource data from Cambodia, Indonesia (Jakarta and Bali), Lao PDR, Taiwan, Thailand and Vietnam.
+We applied a mathematical transmission model to simulate a “mild-to-moderate” pandemic influenza scenario to estimate resource needs, gaps, and attributable mortalities at province level within each territory.
+The results show that wide variations exist in resource capacities between and within the six territories, with substantial mortalities predicted as a result of resource gaps (referred to here as “avoidable” mortalities), particularly in poorer areas.
+Severe nationwide shortages of mechanical ventilators were estimated to be a major cause of avoidable mortalities in all territories except Taiwan.
+Estimates of resource gaps and avoidable mortalities were highly sensitive to model parameters defining the transmissibility and clinical severity of the pandemic scenario.
+However, geographic patterns observed within and across territories remained similar for the range of parameter values explored.
+CONCLUSIONS: The findings have important implications for where (both geographically and in terms of which resource types) investment is most needed, and the potential impact of resource mobilization for mitigating the disease burden of an influenza pandemic.
+Effective mobilization of resources across administrative boundaries could go some way towards minimizing avoidable deaths.
+The mammalian tick-borne flavivirus group (MTBFG) contains viruses associated with important human and animal diseases such as encephalitis and hemorrhagic fever.
+In contrast to mosquito-borne flaviviruses where recombination events are frequent, the evolutionary dynamic within the MTBFG was believed to be essentially clonal.
+This assumption was challenged with the recent report of several homologous recombinations within the Tick-borne encephalitis virus (TBEV).
+We performed a thorough analysis of publicly available genomes in this group and found no compelling evidence for the previously identified recombinations.
+However, our results show for the first time that demonstrable recombination (i.e., with large statistical support and strong phylogenetic evidences) has occurred in the MTBFG, more specifically within the Louping ill virus lineage.
+Putative parents, recombinant strains and breakpoints were further tested for statistical significance using phylogenetic methods.
+We investigated the time of divergence between the recombinant and parental strains in a Bayesian framework.
+The recombination was estimated to have occurred during a window of 282 to 76 years before the present.
+By unravelling the temporal setting of the event, we adduce hypotheses about the ecological conditions that could account for the observed recombination.
+BACKGROUND: To date, the use of traditional nucleic acid amplification tests (NAAT) for detection of HIV-1 DNA or RNA has been restricted to laboratory settings due to time, equipment, and technical expertise requirements.
+The availability of a rapid NAAT with applicability for resource-limited or point-of-care (POC) settings would fill a great need in HIV diagnostics, allowing for timely diagnosis or confirmation of infection status, as well as facilitating the diagnosis of acute infection, screening and evaluation of infants born to HIV-infected mothers.
+Isothermal amplification methods, such as reverse-transcription, loop-mediated isothermal amplification (RT-LAMP), exhibit characteristics that are ideal for POC settings, since they are typically quicker, easier to perform, and allow for integration into low-tech, portable heating devices.
+METHODOLOGY/SIGNIFICANT FINDINGS: In this study, we evaluated the HIV-1 RT-LAMP assay using portable, non-instrumented nucleic acid amplification (NINA) heating devices that generate heat from the exothermic reaction of calcium oxide and water.
+The NINA heating devices exhibited stable temperatures throughout the amplification reaction and consistent amplification results between three separate devices and a thermalcycler.
+The performance of the NINA heaters was validated using whole blood specimens from HIV-1 infected patients.
+CONCLUSION: The RT-LAMP isothermal amplification method used in conjunction with a chemical heating device provides a portable, rapid and robust NAAT platform that has the potential to facilitate HIV-1 testing in resource-limited settings and POC.
+The design and management of an orthopaedic bone bank is a complex process in which medical organisation and legislation intertwine.
+Neither in the Netherlands, nor in any other European country, there are official guidelines for the organisation and management of an orthopaedic bone bank.
+In the Netherlands, the recently modified ‘law of security and quality for using human materials’ (WVKL) dictates requirements for technical and organisational aspects for the use of human tissue and cells.
+The bone bank procedures include a thorough questionnaire for donor selection, extensive serological, bacteriological and histopathological examination, as well as standard procedures for registration, processing, preservation, storage and distribution of bone allografts.
+This article describes the organisation of an accredited bone bank and can be used as a proposition for an official guideline or can be useful as an example for other orthopaedic bone banks in Europe.
+The recognition of pathogen-derived structures by C-type lectins and the chemotactic activity mediated by the CCL2/CCR2 axis are critical steps in determining the host immune response to fungi.
+The present study was designed to investigate whether the presence of single nucleotide polymorphisms (SNPs) within DC-SIGN, Dectin-1, Dectin-2, CCL2 and CCR2 genes influence the risk of developing Invasive Pulmonary Aspergillosis (IPA).
+Twenty-seven SNPs were selected using a hybrid functional/tagging approach and genotyped in 182 haematological patients, fifty-seven of them diagnosed with proven or probable IPA according to the 2008 EORTC/MSG criteria.
+Association analysis revealed that carriers of the Dectin-1 (rs3901533 T/T) and Dectin-1 (rs7309123 G/G) genotypes and DC-SIGN (rs4804800 G), DC-SIGN (rs11465384 T), DC-SIGN (7248637 A) and DC-SIGN (7252229 C) alleles had a significantly increased risk of IPA infection (OR = 5.59 95%CI 1.37–22.77; OR = 4.91 95%CI 1.52–15.89; OR = 2.75 95%CI 1.27–5.95; OR = 2.70 95%CI 1.24–5.90; OR = 2.39 95%CI 1.09–5.22 and OR = 2.05 95%CI 1.00–4.22, respectively).
+There was also a significantly increased frequency of galactomannan positivity among patients carrying the Dectin-1 (rs3901533_T) allele and Dectin-1 (rs7309123_G/G) genotype.
+In addition, healthy individuals with this latter genotype showed a significantly decreased level of Dectin-1 mRNA expression compared to C-allele carriers, suggesting a role of the Dectin-1 (rs7309123) polymorphism in determining the levels of Dectin-1 and, consequently, the level of susceptibility to IPA infection.
+SNP-SNP interaction (epistasis) analysis revealed significant interactions models including SNPs in Dectin-1, Dectin-2, CCL2 and CCR2 genes, with synergistic genetic effects.
+Although these results need to be further validated in larger cohorts, they suggest that Dectin-1, DC-SIGN, Dectin-2, CCL2 and CCR2 genetic variants influence the risk of IPA infection and might be useful in developing a risk-adapted prophylaxis.
+Nipah virus (NiV) is a recently emerged zoonotic Paramyxovirus that causes regular outbreaks in East Asia with mortality rate exceeding 75%.
+To better understand virus-host interaction, we analyzed the transcriptome profile of NiV infection in primary human umbilical vein endothelial cells.
+We further assessed some of the obtained results by in vitro and in vivo methods in a hamster model and in brain samples from NiV-infected patients.
+We found that NiV infection strongly induces genes involved in interferon response in endothelial cells.
+Among the top ten upregulated genes, we identified the chemokine CXCL10 (interferon-induced protein 10, IP-10), an important chemoattractant involved in the generation of inflammatory immune response and neurotoxicity.
+In NiV-infected hamsters, which develop pathology similar to what is seen in humans, expression of CXCL10 mRNA was induced in different organs with kinetics that followed NiV replication.
+Finally, we showed intense staining for CXCL10 in the brain of patients who succumbed to lethal NiV infection during the outbreak in Malaysia, confirming induction of this chemokine in fatal human infections.
+This study sheds new light on NiV pathogenesis, indicating the role of CXCL10 during the course of infection and suggests that this chemokine may serve as a potential new marker for lethal NiV encephalitis.
+While influenza viruses are a common respiratory pathogen, sporadic reports of conjunctivitis following human infection demonstrates the ability of this virus to cause disease outside of the respiratory tract.
+The ocular surface represents both a potential site of virus replication and a portal of entry for establishment of a respiratory infection.
+However, the properties which govern ocular tropism of influenza viruses, the mechanisms of virus spread from ocular to respiratory tissue, and the potential differences in respiratory disease initiated from different exposure routes are poorly understood.
+Here, we established a ferret model of ocular inoculation to explore the development of virus pathogenicity and transmissibility following influenza virus exposure by the ocular route.
+We found that multiple subtypes of human and avian influenza viruses mounted a productive virus infection in the upper respiratory tract of ferrets following ocular inoculation, and were additionally detected in ocular tissue during the acute phase of infection.
+H5N1 viruses maintained their ability for systemic spread and lethal infection following inoculation by the ocular route.
+Replication-independent deposition of virus inoculum from ocular to respiratory tissue was limited to the nares and upper trachea, unlike traditional intranasal inoculation which results in virus deposition in both upper and lower respiratory tract tissues.
+Despite high titers of replicating transmissible seasonal viruses in the upper respiratory tract of ferrets inoculated by the ocular route, virus transmissibility to naïve contacts by respiratory droplets was reduced following ocular inoculation.
+These data improve our understanding of the mechanisms of virus spread following ocular exposure and highlight differences in the establishment of respiratory disease and virus transmissibility following use of different inoculation volumes and routes.
+Some researchers believe that interactions between HIV-1 Gag-Pol molecules trigger the activation of embedded PR (which mediates Gag and Gag-Pol cleavage), and that Gag-Pol assembly domains outside of PR may contribute to PR activation by influencing PR dimer interaction in a Gag-Pol context.
+To determine if the enhancement of PR dimer interaction facilitates PR activation, we placed single or tandem repeat leucine zippers (LZ) at the PR C-terminus, and looked for a correlation between enhanced Gag processing efficiency and increased Gag-PR-LZ multimerization capacity.
+We found significant reductions in virus-like particles (VLPs) produced by HIV-1 mutants, with LZ fused to the end of PR as a result of enhanced Gag cleavage efficiency.
+Since VLP production can be restored to wt levels following PR activity inhibition, this assembly defect is considered PR activity-dependent.
+We also found a correlation between the LZ enhancement effect on Gag cleavage and enhanced Gag-PR multimerization.
+The results suggest that PR dimer interactions facilitated by forced Gag-PR multimerization lead to premature Gag cleavage, likely a result of premature PR activation.
+Our conclusion is that placement of a heterologous dimerization domain downstream of PR enhances PR-mediated Gag cleavage efficiency, implying that structural conformation, rather than the primary sequence outside of PR, is a major determinant of HIV-1 PR activation.
+Accurate identification of new AFPs is important in understanding ice-protein interactions and creating novel ice-binding domains in other proteins.
+In this paper, an accurate method, called AFP_PSSM, has been developed for predicting antifreeze proteins using a support vector machine (SVM) and position specific scoring matrix (PSSM) profiles.
+This is the first study in which evolutionary information in the form of PSSM profiles has been successfully used for predicting antifreeze proteins.
+Tested by 10-fold cross validation and independent test, the accuracy of the proposed method reaches 82.67% for the training dataset and 93.01% for the testing dataset, respectively.
+The aim of this study is to measure the reliability and external validity of AMSTAR by applying it to a sample of TCM systematic reviews.
+We tested the agreement, reliability, construct validity, and feasibility of AMSTAR through comparisons with OQAQ.
+The interrater agreement of the individual items of AMSTAR was moderate with a mean kappa of 0.50 (95% CI: 0.26, 0.73).
+The ICC for AMSTAR against OQAQ (total score of 9 items, excluding item 10) was 0.87 (95% CI: 0.76, 0.93).
+Although there is room for improvement on few items, the new tool is reliable, valid, and easy to use for methodological quality assessment of systematic reviews on TCM.
+Alveolar macrophages (AM) are one of the key cell types for initiating inflammatory and immune responses to influenza virus in the lung.
+However, the genome-wide changes in response to influenza infection in AM have not been defined.
+We performed gene profiling of human AM in response to H1N1 influenza A virus PR/8 using Affymetrix HG-U133 Plus 2.0 chips and verified the changes at both mRNA and protein levels by real-time RT-PCR and ELISA.
+To understand the local cellular response, we also evaluated the impact of paracrine factors on virus-induced chemokine and cytokine secretion.
+In addition, we investigated the changes in the expression of macrophage receptors and uptake of pathogens after PR/8 infection.
+Although macrophages fail to release a large amount of infectious virus, we observed a robust induction of type I and type III interferons and several cytokines and chemokines following influenza infection.
+Inhibition of TNF and/or IL-1β activity significantly decreased the secretion of the proinflammatory chemokines CCL5 and CXCL8 by over 50%.
+PR/8 infection also significantly decreased mRNA levels of macrophage receptors including C-type lectin domain family 7 member A (CLEC7A), macrophage scavenger receptor 1 (MSR1), and CD36, and reduced uptake of zymosan.
+Targeting local components of innate immune response might provide a strategy for controlling influenza A infection-induced proinflammatory response in vivo.
+INTRODUCTION: Chlamydophila pneumoniae is a respiratory pathogen known to infect the upper and lower respiratory tracts.
+CASE PRESENTATION: A previously healthy 62-year-old Caucasian man was admitted to our hospital for acute respiratory failure.
+Serum samples obtained every week starting from the day of admission showed clear-cut seroconversion for C. pneumoniae antibodies.
+Despite maximal ventilatory support (high positive end expiratory pressure, fraction of inspired oxygen of 1.0, nitric oxide inhalation, neuromuscular blocking agents and prone positioning), our patient remained severely hypoxemic, which led us to initiate an extracorporeal membrane oxygenation treatment.
+Our patient was extubated on day 18 and discharged from our Intensive Care Unit on day 20.
+CONCLUSION: We describe the first published case of acute respiratory distress syndrome due to C. pneumoniae infection successfully treated by extracorporeal membrane oxygenation, a very useful tool in this syndrome.
+A quick and specific method for the definite diagnosis of Chlamydophila infection should be developed.
+To identify environmental sites commonly contaminated by avian influenza virus A (H5N1) in live-bird markets in Indonesia, we investigated 83 markets in 3 provinces in Indonesia.
+At each market, samples were collected from up to 27 poultry-related sites to assess the extent of contamination.
+A questionnaire was used to ascertain types of birds in the market, general infrastructure, and work practices.
+Thirty-nine (47%) markets showed contamination with avian influenza virus in >1 of the sites sampled.
+Risk factors were slaughtering birds in the market and being located in West Java province.
+Protective factors included daily removal of waste and zoning that segregated poultry-related work flow areas.
+These results can aid in the design of evidence-based programs concerning environmental sanitation, food safety, and surveillance to reduce the risk for avian influenza virus A (H5N1) transmission in live-bird markets.
+We describe the epidemiology of influenza virus infections in refugees in a camp in rural Southeast Asia during May–October 2009, the first 6 months after identification of pandemic (H1N1) 2009 in Thailand.
+Influenza A viruses were detected in 20% of patients who had influenza-like illness and in 23% of those who had clinical pneumonia.
+Seasonal influenza A (H1N1) was the predominant virus circulating during weeks 26–33 (June 25–August 29) and was subsequently replaced by the pandemic strain.
+A review of passive surveillance for acute respiratory infection did not show an increase in acute respiratory tract infection incidence associated with the arrival of pandemic (H1N1) 2009 in the camp.
+In addition, the natural history of pediatric dengue early in illness in a community-based setting has not been well-defined.
+METHODS: Data from the multi-year, ongoing Pediatric Dengue Cohort Study of approximately 3,800 children aged 2–14 years in Managua, Nicaragua, were used to examine the frequency of clinical signs and symptoms by day of illness and to generate models for the association of signs and symptoms during the early phase of illness and over the entire course of illness with testing dengue-positive.
+Odds ratios (ORs) and 95% confidence intervals were calculated using generalized estimating equations (GEE) for repeated measures, adjusting for age and gender.
+RESULTS: One-fourth of children who tested dengue-positive did not meet the WHO case definition for suspected dengue.
+The frequency of signs and symptoms varied by day of illness, dengue status, and disease severity.
+Multivariable GEE models showed increased odds of testing dengue-positive associated with fever, headache, retro-orbital pain, myalgia, arthralgia, rash, petechiae, positive tourniquet test, vomiting, leukopenia, platelets ≤150,000 cells/mL, poor capillary refill, cold extremities and hypotension.
+Estimated ORs tended to be higher for signs and symptoms over the course of illness compared to the early phase of illness.
+CONCLUSIONS: Day-by-day analysis of clinical signs and symptoms together with longitudinal statistical analysis showed significant associations with testing dengue-positive and important differences during the early phase of illness compared to the entire course of illness.
+These findings stress the importance of considering day of illness when developing prediction algorithms for real-time clinical management.
+Although the pandemic is now over, the virus has emerged as the predominant strain in the current seasonal influenza phase in the northern hemisphere.
+The A H1N1 influenza is a novel strain of the influenza A virus and is widely known as swine flu.
+The virus contains a mixture of genetic material from human, pig and bird flu virus.
+It is a new variety of flu which people have not had much immunity to.
+Much has been learnt from the Pandemic of 2009/2010 but the messages about vaccination and treatment seem to be taken slowly by the clinical profession.
+Most people affected by the virus, including pregnant women, suffer a mild viral illness, and make a full recovery.
+Current experience shows that the age group experiencing increased morbidity and mortality rates are in those under 65 years of age.
+Pregnant women, because of their altered immunity and physiological adaptations, are at higher risk of developing pulmonary complications, especially in the second and third trimesters.
+In the United Kingdom, twelve maternal deaths were reported to be associated with the H1N1 virus during the pandemic and clear avoidable factors were identified (Modder, Review of Maternal Deaths in the UK related to A H1N1 2009 influenza (CMACE).
+The pregnancy outcomes were also poor for women who were affected by the virus with a fivefold increase in the perinatal mortality rate and threefold increase in the preterm delivery rate (Yates et al.
+There continues to be a low uptake of the flu vaccine and commencement of antiviral treatment for pregnant women.
+Comprehensive microbiological testing will be a core function of the Pneumonia Etiology Research for Child Health (PERCH) project.
+The development stage of PERCH provided the time and resources necessary for us to conduct a comprehensive review of the current state of respiratory diagnostics.
+These efforts allowed us to articulate the unique requirements of PERCH, establish that molecular methods would be central to our testing strategy, and focus on a short list of candidate platforms.
+This process also highlighted critical challenges in the general design and interpretation of diagnostic evaluation studies, particularly in the field of respiratory infections.
+Although our final molecular diagnostic platform was ultimately selected on the basis of operational and strategic considerations determined by the specific context of PERCH, our review highlighted several conceptual and practical challenges in respiratory diagnostics that have broader relevance for the performance and interpretation of pneumonia research studies.
+In the field of herpesvirus research, the exact molecular mechanism by which such viruses reactivate from latency remains elusive.
+Kaposi's sarcoma-associated herpesvirus (KSHV) primarily exists in a latent state, while only 1–3% of cells support lytic infection at any specific time.
+KSHV reactivation from latency is an exceedingly intricate process mediated by the integration of viral and cellular factors.
+Previously, our lab has described early growth response-1 (Egr-1) as an essential component for the KSHV reactivation process via its ability to mediate transcription of KSHV ORF50, the gene encoding for replication and transcription activator (RTA), a viral component known to control the switch from latent to lytic infection.
+In here, electrophoretic mobility shift assays (EMSA) and chromatin immunoprecipitation (ChIP) experiments revealed that Egr-1 binds KSHV ORF50 promoter (ORF50P) in at least two different GC-rich binding domains.
+Expression profiles of cellular egr-1 and KSHV-encoded ORF50 follow a similar pattern during de novo KSHV infection.
+Over-expressing Egr-1, a signaling component downstream of Raf>MEK>ERK1/2, in KSHV-infected cells activates KSHV lytic replication.
+Through performing more physiologically relevant experiments, we analyzed the effect of a dietary supplement containing resveratrol on KSHV-infected cells.
+Our results, for the first time, demonstrate resveratrol to act in lowering ERK1/2 activity and expression of Egr-1 in KSHV-infected cells, resulting in the suppression of virus reactivation from latency.
+Taken together, these findings will undoubtedly contribute to future studies on not only combating KSHV related disease conditions, but also on other herpesviruses-induced pathogenesis.
+BACKGROUND: To date, only a small portion of the genetic variation for primary open-angle glaucoma (POAG), the major type of glaucoma, has been elucidated.
+METHODS AND PRINCIPAL FINDINGS: We examined our two data sets of the genome-wide association studies (GWAS) derived from a total of 2,219 Japanese subjects.
+First, we performed a GWAS by analyzing 653,519 autosomal common single-nucleotide polymorphisms (SNPs) in 833 POAG patients and 686 controls.
+As a result, five variants that passed the Bonferroni correction were identified in CDKN2B-AS1 on chromosome 9p21.3, which was already reported to be a significant locus in the Caucasian population.
+Moreover, we combined the data set with our previous GWAS data set derived from 411 POAG patients and 289 controls by the Mantel-Haenszel test, and all of the combined variants showed stronger association with POAG (P<5.8×10(−10)).
+We then subdivided the case groups into two subtypes based on the value of intraocular pressure (IOP)—POAG with high IOP (high pressure glaucoma, HPG) and that with normal IOP (normal pressure glaucoma, NPG)—and performed the GWAS using the two data sets, as the prevalence of NPG in Japanese is much higher than in Caucasians.
+The results suggested that the variants from the same CDKN2B-AS1 locus were likely to be significant for NPG patients.
+CONCLUSIONS AND SIGNIFICANCE: In this study, we successfully identified POAG-associated variants in the CDKN2B-AS1 locus using a Japanese population, i.e., variants originally reported as being associated with the Caucasian population.
+Although we cannot rule out that the significance could be due to the differences in sample size between HPG and NPG, the variants could be associated specifically with the vulnerability of the optic nerve to IOP, which is useful for investigating the etiology of glaucoma.
+INTRODUCTION: The aim of the study was to demonstrate Interleukin-18 (IL-18) expression in keratinocytes from psoriatic lesions in comparison to keratinocytes from uninvolved skin and to study the change of expression after therapeutic interventions.
+Two were taken from the lesional psoriatic skin and from uninvolved skin before starting treatment.
+A third lesional skin biopsy was taken at the end of two months' treatment course.
+RESULTS: Of all 16 studied patients significantly increased IL-18 expression was noted in keratinocytes from psoriatic lesions before and after treatment when compared to keratinocytes from uninvolved skin (P = 0.001 and 0.002 respectively).
+The IL-18 expression in the skin lesions after treatment was significantly lower than lesional skin before treatment (P = 0.023).
+In psoriatic skin lesions of all studied patients IL-18 expression was significantly correlated with disease duration (r = 0.40 and P = 0.01) and clinical severity of psoriasis (r = 0.72 and P = 0.001).
+CONCLUSIONS: Increased IL-18 expression in keratinocytes from psoriatic lesions of our patients and its correlation with disease duration and severity supported the concept which views psoriasis as a T-cell-mediated autoimmune disease.
+This could establish therapeutic and preventive approaches for psoriasis that ultimately lead to improved outcomes for patients.
+We provide experimental evidence of a replication enhancer element (REE) within the capsid gene of tick-borne encephalitis virus (TBEV, genus Flavivirus).
+Thermodynamic and phylogenetic analyses predicted that the REE folds as a long stable stem–loop (designated SL6), conserved among all tick-borne flaviviruses (TBFV).
+Homologous sequences and potential base pairing were found in the corresponding regions of mosquito-borne flaviviruses, but not in more genetically distant flaviviruses.
+To investigate the role of SL6, nucleotide substitutions were introduced which changed a conserved hexanucleotide motif, the conformation of the terminal loop and the base-paired dsRNA stacking.
+Substitutions were made within a TBEV reverse genetic system and recovered mutants were compared for plaque morphology, single-step replication kinetics and cytopathic effect.
+Point mutations in the conserved hexanucleotide motif of the terminal loop caused moderate virus attenuation.
+Thus, although not essential for growth in tissue culture, the SL6 REE acts to up-regulate virus replication.
+We hypothesize that this modulatory role may be important for TBEV survival in nature, where the virus circulates by non-viraemic transmission between infected and non-infected ticks, during co-feeding on local rodents.
+Our recent studies showed that Listeria monocytogenes limits immune detection and IFN-β synthesis via deacetylation of its peptidoglycan, which renders the bacterium resistant to lysozyme degradation.
+Here, we examined signaling requirements for the massive IFN-β production resulting from the infection of murine macrophages with a mutant strain of L. monocytogenes, ΔpgdA, which is unable to modify its peptidoglycan.
+We report the identification of unconventional signaling pathways to the IFN-β gene, requiring TLR2 and bacterial internalization.
+Induction of IFN-β was independent of the Mal/TIRAP adaptor protein but required TRIF and the transcription factors IRF3 and IRF7.
+They operated in both resident and inflammatory macrophages derived from the peritoneal cavity, but not in bone marrow-derived macrophages.
+The novelty of our findings thus lies in the first description of TLR2 and TRIF as two critical components leading to the induction of the IFN-β gene and in uncovering that individual macrophage populations adopt different strategies to link pathogen recognition signals to IFN-β gene expression.
+Recent drug discovery efforts have utilized high throughput screening (HTS) of large chemical libraries to identify compounds that modify the activity of discrete molecular targets.
+The molecular target approach to drug screening is widely used in the pharmaceutical and biotechnology industries, because of the amount of knowledge now available regarding protein structure that has been obtained by computer simulation.
+The molecular target approach requires that the structure of target molecules, and an understanding of their physiological functions, is known.
+As an alternative, the phenotypic- or pathway-screening approach to drug discovery is gaining popularity, particularly in the academic sector.
+This approach not only provides the opportunity to identify promising drug candidates, but also enables novel information regarding biological pathways to be unveiled.
+Of the various reporter genes that can be used in such assays, those encoding secreted proteins enable the screening of hit molecules in both living cells and animals.
+Cell- and animal-based screens enable simultaneous evaluation of drug metabolism or toxicity with biological activity.
+Therefore, drug candidates identified in these screens may have increased biological efficacy and a lower risk of side effects in humans.
+Airway epithelial ion transport regulates the homeostasis of airway surface liquid, essential for airway mucosal immunity and lung host defense.
+Here, air-liquid interface cultures of Calu-3 epithelial cells were basolaterally exposed to physiologically relevant concentrations of ethanol (0, 25, 50 and 100 mM) for 24 hours and adenosine-stimulated ion transport was measured by Ussing chamber.
+The ion currents activated by adenosine were chloride conductance mediated by cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP-activated chloride channel.
+Alloxazine, a specific inhibitor for A(2B) adenosine receptor (A(2B)AR), largely abolished the adenosine-stimulated chloride transport, suggesting that A(2B)AR is a major receptor responsible for regulating the chloride transport of the cells.
+Moreover, ethanol-suppression of the chloride secretion was able to be restored by cAMP analogs or by inhibitors to block cAMP degradation.
+These results imply that ethanol exposure dysregulates CFTR-mediated chloride transport in airways by suppression of adenosine-A(2B)AR-cAMP signaling pathway, which might contribute to alcohol-associated lung infections.
+The azurophilic granules of human neutrophils contain four α-defensins called human neutrophil peptides (HNPs 1–4).
+HNPs are tridisulfide-linked antimicrobial peptides involved in the intracellular killing of organisms phagocytosed by neutrophils.
+The peptides are produced as inactive precursors (proHNPs) which are processed to active microbicides by as yet unidentified convertases.
+ProHNP1 was expressed in E. coli and the affinity-purified propeptide isolated as two species, one containing mature HNP1 sequence with native disulfide linkages (“folded proHNP1”) and the other containing non-native disulfide linked proHNP1 conformers (misfolded proHNP1).
+Native HNP1, liberated by CNBr treatment of folded proHNP1, was microbicidal against Staphylococcus aureus, but the peptide derived from misfolded proHNP1 was inactive.
+We hypothesized that neutrophil elastase (NE), proteinase 3 (PR3) or cathepsin G (CG), serine proteases that co-localize with HNPs in azurophil granules, are proHNP1 activating convertases.
+Folded proHNP1 was converted to mature HNP1 by both NE and PR3, but CG generated an HNP1 variant with an N-terminal dipeptide extension.
+NE and PR3 cleaved folded proHNP1 to produce a peptide indistinguishable from native HNP1 purified from neutrophils, and the microbicidal activities of in vitro derived and natural HNP1 peptides were equivalent.
+Thus, NE and PR3 possess proHNP1 convertase activity that requires the presence of the native HNP1 disulfide motif for high fidelity activation of the precursor in vitro.
+We earlier established a model of a persistent viral CNS infection using two week old immunologically normal (genetically unmodified) mice and recombinant measles virus (MV).
+Using this model infection we investigated the role of regulatory T cells (Tregs) as regulators of the immune response in the brain, and assessed whether the persistent CNS infection can be modulated by manipulation of Tregs in the periphery.
+CD4(+) CD25(+) Foxp3(+) Tregs were expanded or depleted during the persistent phase of the CNS infection, and the consequences for the virus-specific immune response and the extent of persistent infection were analyzed.
+Virus-specific CD8(+) T cells predominantly recognising the H-2D(b)-presented viral hemagglutinin epitope MV-H(22–30) (RIVINREHL) were quantified in the brain by pentamer staining.
+application of the superagonistic anti-CD28 antibody D665 inducing transient immunosuppression caused increased virus replication and spread in the CNS.
+In contrast, depletion of Tregs using diphtheria toxin (DT) in DEREG (depletion of regulatory T cells)-mice induced an increase of virus-specific CD8(+) effector T cells in the brain and caused a reduction of the persistent infection.
+These data indicate that manipulation of Tregs in the periphery can be utilized to regulate virus persistence in the CNS.
+BACKGROUND: Numerous cases of swine-origin 2009 H1N1 influenza A virus (H1N1)-associated acute respiratory distress syndrome (ARDS) bridged by extracorporeal membrane oxygenation (ECMO) therapy have been reported; however, complication rates are high.
+We present our experience with H1N1-associated ARDS and successful bridging of lung function using superimposed high-frequency jet ventilation (SHFJV) in combination with continuous positive airway pressure/assisted spontaneous breathing (CPAP/ASB).
+METHODS: We admitted five patients with H1N1 infection and ARDS to our intensive care unit.
+In all patients, successful oxygenation was achieved by SHFJV (PaO(2)/FiO(2 )ratio 105-306 mmHg within 24 h).
+SHFJV could be stopped after 39, 40, 72, 100, or 240 h. Concomitant pulmonary herpes simplex virus (HSV) infection was observed in all patients.
+The other three patients relapsed and died within 7 weeks mainly due to combined HSV infection and in two cases reoccurring H1N1 infection.
+CONCLUSIONS: SHFJV represents an alternative to bridge lung function successfully and improve oxygenation in the critically ill.
+The first human virus in the genus Cardiovirus was described in 2007 and named Saffold virus (SAFV).
+Cardioviruses can cause severe infections of the myocardium and central nervous system in animals, but SAFV has not yet been convincingly associated with disease in humans.
+To study a possible association between SAFV and infections in the human central nervous system, we designed a real-time PCR for SAFV and tested cerebrospinal fluid (CSF) samples from children <4 years of age.
+SAFV was detected in 2 children: in the CSF and a fecal sample from 1 child with monosymptomatic ataxia caused by cerebellitis; and in the CSF, blood, and myocardium of another child who died suddenly with no history of illness.
+We estimated the attack rate of pandemic (H1N1) 2009 and assessed risk factors for infection among close contacts quarantined in Beijing, People’s Republic of China.
+The first 613 confirmed cases detected between May 16 and September 15, 2009, were investigated; 7,099 close contacts were located and quarantined.
+The attack rate of confirmed infection in close contacts was 2.4% overall, ranging from 0.9% among aircraft passengers to >5% among household members.
+Risk factors for infection among close contacts were younger age, being a household member of an index case-patient, exposure during the index case-patient’s symptomatic phase, and longer exposure.
+Among close contacts with positive test results at the start of quarantine, 17.2% had subclinical infection.
+Having contact with a household member and younger age were the major risk factors for acquiring pandemic (H1N1) 2009 influenza virus infection.
+Dengue virus causes ∼50–100 million infections per year and thus is considered one of the most aggressive arthropod-borne human pathogen worldwide.
+During its replication, dengue virus induces dramatic alterations in the intracellular membranes of infected cells.
+Using high-resolution mass spectrometry of mosquito cells, we show that this membrane remodeling is directly linked to a unique lipid repertoire induced by dengue virus infection.
+Specifically, 15% of the metabolites detected were significantly different between DENV infected and uninfected cells while 85% of the metabolites detected were significantly different in isolated replication complex membranes.
+Furthermore, we demonstrate that intracellular lipid redistribution induced by the inhibition of fatty acid synthase, the rate-limiting enzyme in lipid biosynthesis, is sufficient for cell survival but is inhibitory to dengue virus replication.
+Lipids that have the capacity to destabilize and change the curvature of membranes as well as lipids that change the permeability of membranes are enriched in dengue virus infected cells.
+Several sphingolipids and other bioactive signaling molecules that are involved in controlling membrane fusion, fission, and trafficking as well as molecules that influence cytoskeletal reorganization are also up regulated during dengue infection.
+These observations shed light on the emerging role of lipids in shaping the membrane and protein environments during viral infections and suggest membrane-organizing principles that may influence virus-induced intracellular membrane architecture.
+We compared the prevalence of 8 polymorphisms in the tumor necrosis factor and mannose-binding lectin genes among 105 children and young adults with fatal influenza with US population estimates and determined in subanalyses whether these polymorphisms were associated with sudden death and bacterial co-infection among persons with fatal influenza.
+No differences were observed in genotype prevalence or minor allele frequencies between persons with fatal influenza and the reference sample.
+Fatal cases with low-producing MBL2 genotypes had a 7-fold increased risk for invasive methicillin-resistant Staphylococcus aureus (MRSA) co-infection compared with fatal cases with high- and intermediate-producing MBL2 genotypes (odds ratio 7.1, 95% confidence interval 1.6–32.1).
+Limited analysis of 2 genes important to the innate immune response found no association between genetic variants and fatal influenza infection.
+Among children and young adults who died of influenza, low-producing MBL2 genotypes may have increased risk for MRSA co-infection.
+BACKGROUND: 2009 pandemic H1N1 (pH1N1) influenza posed an increased risk of severe illness among pregnant women.
+Data on risk factors associated with death of pregnant women and neonates with pH1N1 infections are limited outside of developed countries.
+METHODS: Retrospective observational study in 394 severe or critical pregnant women admitted to a hospital with pH1N1 influenza from Sep. 1, 2009 to Dec. 31, 2009. rRT-PCR testing was used to confirm infection.
+Univariable logistic analysis and multivariate logistic regression analysis were used to investigate the potential factors on admission that might be associated with the maternal and neonatal mortality.
+RESULTS: 394 pregnant women were included, 286 were infected with pH1N1 in the third trimester.
+A PaO(2)/FiO(2 )≤ 200 (odds ratio (OR), 27.16; 95% confidence interval (CI), 2.64-279.70) and higher BMI (i.e.
+≥ 30) on admission (OR, 1.26; 95% CI, 1.09 to 1.47) were independent risk factors for maternal death.
+Among 186 patients who received mechanical ventilation, 83 patients were treated with non-invasive ventilation (NIV) and 38 were successful with NIV.
+The death rate was lower among patients who initially received NIV than those who were initially intubated (24/83, 28.9% vs 43/87, 49.4%; p = 0.006).
+CONCLUSIONS: Severe hypoxemia and higher BMI on admission were associated with adverse outcomes for pregnant women.
+Preterm delivery was a risk factor for neonatal death among pregnant women with pH1N1 influenza infection.
+Xenotropic murine leukemia virus-related virus (XMRV) is a gammaretrovirus that was originally identified from human prostate cancer patients and subsequently linked to chronic fatigue syndrome.
+Recent studies showed that XMRV is a recombinant mouse retrovirus; hence, its association with human diseases has become questionable.
+Here, we demonstrated that XMRV envelope (Env)-mediated pseudoviral infection is not blocked by lysosomotropic agents and cellular protease inhibitors, suggesting that XMRV entry is not pH-dependent.
+The full length XMRV Env was unable to induce syncytia formation and cell-cell fusion, even in cells overexpressing the viral receptor, XPR1.
+However, truncation of the C-terminal 21 or 33 amino acid residues in the cytoplasmic tail (CT) of XMRV Env induced substantial membrane fusion, not only in the permissive 293 cells but also in the nonpermissive CHO cells that lack a functional XPR1 receptor.
+The increased fusion activities of these truncations correlated with their enhanced SU shedding into culture media, suggesting conformational changes in the ectodomain of XMRV Env.
+Noticeably, further truncation of the CT of XMRV Env proximal to the membrane-spanning domain severely impaired the Env fusogenicity, as well as dramatically decreased the Env incorporations into MoMLV oncoretroviral and HIV-1 lentiviral vectors resulting in greatly reduced viral transductions.
+Collectively, our studies reveal that XMRV entry does not require a low pH or low pH-dependent host proteases, and that the cytoplasmic tail of XMRV Env critically modulates membrane fusion and cell entry.
+Our data also imply that additional cellular factors besides XPR1 are likely to be involved in XMRV entry.
+The substantial winter influenza peak in temperate climates has lead to the hypothesis that cold and/or dry air is a causal factor in influenza variability.
+We examined the relationship between cold and/or dry air and daily influenza and pneumonia mortality in the cold season in the New York metropolitan area from 1975–2002.
+We conducted a retrospective study relating daily pneumonia and influenza mortality for New York City and surroundings from 1975–2002 to daily air temperature, dew point temperature (a measure of atmospheric humidity), and daily air mass type.
+We identified high mortality days and periods and employed temporal smoothers and lags to account for the latency period and the time between infection and death.
+Unpaired t-tests were used to compare high mortality events to non-events and nonparametric bootstrapped regression analysis was used to examine the characteristics of longer mortality episodes.
+We found a statistically significant (p = 0.003) association between periods of low dew point temperature and above normal pneumonia and influenza mortality 17 days later.
+The duration (r = −0.61) and severity (r = −0.56) of high mortality episodes was inversely correlated with morning dew point temperature prior to and during the episodes.
+Weeks in which moist polar air masses were common (air masses characterized by low dew point temperatures) were likewise followed by above normal mortality 17 days later (p = 0.019).
+This research supports the contention that cold, dry air may be related to influenza mortality and suggests that warning systems could provide enough lead time to be effective in mitigating the effects.
+BACKGROUND: Social networks are often highly skewed, meaning that the vast majority of the population has only few contacts whereas a small minority has a large number of contacts.
+These highly connected individuals may play an important role in case of an infectious disease outbreak.
+METHODS: We propose a novel strategy of finding and immunizing highly connected individuals and evaluate this strategy by computer simulations, using a stochastic, individual-and network-based simulation approach.
+A small random sample of the population is asked to list their acquaintances, and those who are mentioned most frequently are offered vaccination.
+RESULTS: Asking only 10% of the population for 10 acquaintances each and vaccinating the most frequently named people strongly diminishes the magnitude of an outbreak which would otherwise have exhausted the available isolation units and gone out of control.
+Omitting a few of them because of unsuccessful vaccination jeopardizes the overall success, unless non-immunized individuals are taken under surveillance.
+CONCLUSIONS: The strategy proposed in this paper is particularly successful because it attacks the very point from which the transmission network draws its strength: the highly connected individuals.
+Current preparedness and containment plans for smallpox and other infectious diseases may benefit from such knowledge.
+BACKGROUND: There is an urgent need to understand how the provision of information influences individual risk perception and how this in turn shapes the evolution of epidemics.
+Emerging infectious diseases, such as the recent swine flu epidemic, may be particular hotspots for a media-fueled rush to vaccination; conversely, seasonal diseases may receive little media attention, despite their high mortality rate, due to their perceived lack of newness.
+METHODS: We formulate a deterministic transmission and vaccination model to investigate the effects of media coverage on the transmission dynamics of influenza.
+The compartmental model includes the effect of media coverage on reporting the number of infections as well as the number of individuals successfully vaccinated.
+RESULTS: A threshold parameter (the basic reproductive ratio) is analytically derived and used to discuss the local stability of the disease-free steady state.
+The impact of costs that can be incurred, which include vaccination, education, implementation and campaigns on media coverage, are also investigated using optimal control theory.
+A simplified version of the model with pulse vaccination shows that the media can trigger a vaccinating panic if the vaccine is imperfect and simplified messages result in the vaccinated mixing with the infectives without regard to disease risk.
+Simplified understandings of disease epidemiology, propogated through media soundbites, may make the disease significantly worse.
+BACKGROUND: Buruli ulcer (BU) caused by Mycobacterium ulcerans (M. ulcerans) has emerged as an important public health problem in several rural communities in sub-Saharan Africa.
+Early diagnosis and prompt treatment are important in preventing disfiguring complications associated with late stages of the disease progression.
+Presently there is no simple and rapid test that is appropriate for early diagnosis and use in the low-resource settings where M. ulcerans is most prevalent.
+METHODOLOGY: We compared conventional and pocket warmer loop mediated isothermal amplification (LAMP) methods (using a heat block and a pocket warmer respectively as heat source for amplification reaction) for the detection of M. ulcerans in clinical specimens.
+The effect of purified and crude DNA preparations on the detection rate of the LAMP assays were also investigated and compared with that of IS2404 PCR, a reference assay for the detection of M. ulcerans.
+PRINCIPAL FINDINGS: The lower detection limit of both LAMP methods at 60°C was 300 copies of IS2404 and 30 copies of IS2404 for the conventional LAMP at 65°C.
+When purified DNA extracts were used, both the conventional LAMP and IS2404 PCR concordantly detected 21 positive cases, while the pocket warmer LAMP detected 19 cases.
+Nine of 30 samples were positive by both the LAMP assays as well as IS2404 PCR when crude extracts of clinical specimens were used.
+CONCLUSION/SIGNIFICANCE: The LAMP method can be used as a simple and rapid test for the detection of M. ulcerans in clinical specimens.
+However, obtaining purified DNA, as well as generating isothermal conditions, remains a major challenge for the use of the LAMP method under field conditions.
+With further improvement in DNA extraction and amplification conditions, the pwLAMP could be used as a point of care diagnostic test for BU
+Dengue virus (DENV) is a major mosquito-borne pathogen infecting up to 100 million people each year; so far no effective treatment or vaccines are available.
+Recently, highly cross-reactive and infection-enhancing pre-membrane (prM)-specific antibodies were found to dominate the anti-DENV immune response in humans, raising concern over vaccine candidates that contain native dengue prM sequences.
+In this study, we have isolated a broadly cross-reactive prM-specific antibody, D29, during a screen with a non-immunized human Fab-phage library against the four serotypes of DENV.
+The antibody is capable of restoring the infectivity of virtually non-infectious immature DENV (imDENV) in FcγR-bearing K562 cells.
+Remarkably, D29 also cross-reacted with a cryptic epitope on the envelope (E) protein located to the DI/DII junction as evidenced by site-directed mutagenesis.
+This cryptic epitope, while inaccessible to antibody binding in a native virus particle, may become exposed if E is not properly folded.
+These findings suggest that generation of anti-prM antibodies that enhance DENV infection may not be completely avoided even with immunization strategies employing E protein alone or subunits of E proteins.
+Previous genetic studies have identified certain candidate genes associated with susceptibility to KD and coronary artery lesions.
+The aim of this study was to investigate CLEC5A (C-type lectin domain family 5) genetic polymorphisms with regards to the susceptibility and outcome of KD.
+A total of 1045 subjects (381 KD patients and 664 controls) were enrolled to identify 4 tagging single-nucleotide polymorphisms (tSNPs) of CLEC5A (rs1285968, rs11770855, rs1285935, rs1285933) by using the TaqMan Allelic Discrimination Assay.
+The Hardy-Weinberg equilibrium was assessed in cases and controls, and genetic effects were evaluated by the chi-square test.
+No significant associations were noted between the genotypes and allele frequency of the 4 CLEC5A tSNPs between controls and patients.
+In the patients, polymorphisms of CLEC5A showed no significant association with coronary artery lesion formation and intravenous immunoglobulin treatment response.
+This study showed for the first time that polymorphisms of CLEC5A are not associated with susceptibility to KD, coronary artery lesion formation, and intravenous immunoglobulin treatment response in a Taiwanese population.
+Influenza viruses are among the most important human pathogens and are responsible for annual epidemics and sporadic, potentially devastating pandemics.
+The humoral immune response plays an important role in the defense against these viruses, providing protection mainly by producing antibodies directed against the hemagglutinin (HA) glycoprotein.
+However, their high genetic variability allows the virus to evade the host immune response and the potential protection offered by seasonal vaccines.
+The emergence of resistance to antiviral drugs in recent years further limits the options available for the control of influenza.
+In this study, we describe a human monoclonal antibody (PN-SIA49) that recognizes a highly conserved epitope located on the stem region of the HA and able to neutralize a broad spectrum of influenza viruses belonging to different subtypes (H1, H2 and H5).
+Furthermore, we describe its protective activity in mice after lethal challenge with H1N1 and H5N1 viruses suggesting a potential application in the treatment of influenza virus infections.
+In September 2001, the Hawaii Department of Health was notified of an unusual febrile illness in a resident with no travel history; dengue fever was confirmed.
+During the investigation, 1,644 persons with locally acquired denguelike illness were evaluated, and 122 (7%) laboratory-positive dengue infections were identified; dengue virus serotype 1 was isolated from 15 patients.
+In 3 instances autochthonous infections were linked to a person who reported denguelike illness after travel to French Polynesia.
+Aedes albopictus was present in all communities surveyed on Oahu, Maui, Molokai, and Kauai; no Ae.
+This outbreak underscores the importance of maintaining surveillance and control of potential disease vectors even in the absence of an imminent disease threat.
+BACKGROUND: This research was a part of a contestable rapid response initiative launched by the Health Research Council of New Zealand and the Ministry of Health in response to the 2009 influenza A pandemic.
+The aim was to provide health authorities in New Zealand with evidence-based practical information to guide the development and delivery of effective health messages for H1N1 and other health campaigns.
+This study contributed to the initiative by providing qualitative data about community responses to key health messages in the 2009 and 2010 H1N1 campaigns, the impact of messages on behavioural change and the differential impact on vulnerable groups in New Zealand.
+METHODS: Qualitative data were collected on community responses to key health messages in the 2009 and 2010 Ministry of Health H1N1 campaigns, the impact of messages on behaviour and the differential impact on vulnerable groups.
+Eight focus groups were held in the winter of 2010 with 80 participants from groups identified by the Ministry of Health as vulnerable to the H1N1 virus, such as people with chronic health conditions, pregnant women, children, Pacific Peoples and Māori.
+Because this study was part of a rapid response initiative, focus groups were selected as the most efficient means of data collection in the time available.
+RESULTS: Thematic analysis of data identified four major themes: personal and community risk, building community strategies, responsibility and information sources.
+People wanted messages about specific actions that they could take to protect themselves and their families and to mitigate any consequences.
+They wanted transparent and factual communication where both good and bad news is conveyed by people who they could trust.
+CONCLUSIONS: The responses from all groups endorsed the need for community based risk management including information dissemination.
+Engaging with communities will be essential to facilitate preparedness and build community resilience to future pandemic events.
+This research provides an illustration of the complexities of how people understand and respond to health messages related to the H1N1 pandemic.
+The importance of the differences identified in the analysis is not the differences per se but highlight problems with a "one size fits all" pandemic warning strategy.
+An important determinant of a pathogen's success is the rate at which it is transmitted from infected to susceptible hosts.
+Although there are anecdotal reports that methicillin-resistant Staphylococcus aureus (MRSA) clones vary in their transmissibility in hospital settings, attempts to quantify such variation are lacking for common subtypes, as are methods for addressing this question using routinely-collected MRSA screening data in endemic settings.
+Here we present a method to quantify the time-varying transmissibility of different subtypes of common bacterial nosocomial pathogens using routine surveillance data.
+The method adapts approaches for estimating reproduction numbers based on the probabilistic reconstruction of epidemic trees, but uses relative hazards rather than serial intervals to assign probabilities to different sources for observed transmission events.
+The method is applied to data collected as part of a retrospective observational study of a concurrent MRSA outbreak in the United Kingdom with dominant endemic MRSA clones (ST22 and ST36) and an Asian ST239 MRSA strain (ST239-TW) in two linked adult intensive care units, and compared with an approach based on a fully parametric transmission model.
+The results provide support for the hypothesis that the clones responded differently to an infection control measure based on the use of topical antiseptics, which was more effective at reducing transmission of endemic clones.
+They also suggest that in one of the two ICUs patients colonized or infected with the ST239-TW MRSA clone had consistently higher risks of transmitting MRSA to patients free of MRSA.
+These findings represent some of the first quantitative evidence of enhanced transmissibility of a pandemic MRSA lineage, and highlight the potential value of tailoring hospital infection control measures to specific pathogen subtypes.
+Sapovirus is a genus of caliciviruses that are known to cause enteric disease in humans and animals.
+There is considerable genetic diversity among the sapoviruses, which are classified into different genogroups based on phylogenetic analysis of the full-length capsid protein sequence.
+While several mammalian species, including humans, pigs, minks, and dogs, have been identified as animal hosts for sapoviruses, there were no reports of sapoviruses in bats in spite of their biological diversity.
+In this report, we present the results of a targeted surveillance study in different bat species in Hong Kong.
+Five of the 321 specimens from the bat species, Hipposideros pomona, were found to be positive for sapoviruses by RT-PCR.
+Complete or nearly full-length genome sequences of approximately 7.7 kb in length were obtained for three strains, which showed similar organization of the genome compared to other sapoviruses.
+Interestingly, they possess many genomic features atypical of most sapoviruses, like high G+C content and minimal CpG suppression.
+Phylogenetic analysis of the viral proteins suggested that the bat sapovirus descended from an ancestral sapovirus lineage and is most closely related to the porcine sapoviruses.
+Codon usage analysis showed that the bat sapovirus genome has greater codon usage bias relative to other sapovirus genomes.
+In summary, we report the discovery and genomic characterization of the first bat calicivirus, which appears to have evolved under different conditions after early divergence from other sapovirus lineages.
+The angiotensin converting enzymes (ACEs) are the key catalytic components of the renin-angiotensin system, mediating precise regulation of blood pressure by counterbalancing the effects of each other.
+Inhibition of ACE has been shown to improve pathology in cardiovascular disease, whilst ACE2 is cardioprotective in the failing heart.
+However, the mechanisms by which ACE2 mediates its cardioprotective functions have yet to be fully elucidated.
+Here we demonstrate that both ACE and ACE2 bind integrin subunits, in an RGD-independent manner, and that they can act as cell adhesion substrates.
+Furthermore, we present evidence that soluble ACE2 (sACE2) is capable of suppressing integrin signalling mediated by FAK.
+In addition, sACE2 increases the expression of Akt, thereby lowering the proportion of the signalling molecule phosphorylated Akt.
+These results suggest that ACE2 plays a role in cell-cell interactions, possibly acting to fine-tune integrin signalling.
+Hence the expression and cleavage of ACE2 at the plasma membrane may influence cell-extracellular matrix interactions and the signalling that mediates cell survival and proliferation.
+As such, ectodomain shedding of ACE2 may play a role in the process of pathological cardiac remodelling.
+Interferon alpha (IFNα) therapy, despite good efficacy in curing HCV infection, leads to major side effects, in particular inducement of a strong peripheral T-cell lymphocytopenia.
+We here analyze the early consequences of IFNα therapy on both thymic function and peripheral T-cell homeostasis in patients in the acute or chronic phase of HCV-infection as well as in HIV/HCV co-infected patients.
+The evolution of T-cell subsets and T-cell homeostasis were estimated by flow cytometry while thymic function was measured through quantification of T-cell receptor excision circles (TREC) and estimation of intrathymic precursor T-cell proliferation during the first four months following the initiation of IFNα therapy.
+Beginning with the first month of therapy, a profound lymphocytopenia was observed for all T-cell subsets, including naïve T-cells and recent thymic emigrants (RTE), associated with inhibition of intrathymic precursor T-cell proliferation.
+This was neither a consequence of higher consumption of the cytokine nor due to its neutralization by soluble CD127.
+Decrease in IL-7 plasma concentration under IFNα therapy correlated with the decline in HCV viral load, thymic activity and RTE concentration in blood.
+These data demonstrate that IFNα-based therapy rapidly impacts on thymopoiesis and, consequently, perturbs T-cell homeostasis.
+Such a side effect might be detrimental for the continuation of IFNα therapy and may lead to an increased level of infectious risk, in particular in HIV/HCV co-infected patients.
+Altogether, this study suggests the therapeutic potential of IL-7 in the maintenance of peripheral T-cell homeostasis in IFNα-treated patients.
+BACKGROUND: Respiratory syncytial virus (RSV) is a major cause of severe lower respiratory tract diseases in infancy and early childhood.
+The attachment glycoprotein (G) of RSV is a potentially important target for protective antiviral immune responses.
+Recombinant baculovirus has been recently emerged as a new vaccine vector, since it has intrinsic immunostimulatory properties and good bio-safety profile.
+METHODS: We have constructed a recombinant baculovirus-based RSV vaccine, Bac-RSV/G, displaying G glycoprotein, and evaluated immunogenicity and protective efficacy by intranasal immunization of BALB/c mice with Bac-RSV/G.
+In addition to humoral immunity, G-specific Th17- as well as Th1-type T-cell responses were detected in the lungs of Bac-RSV/G-immune mice upon RSV challenge.
+Neither lung eosinophilia nor vaccine-induced weight loss was observed upon Bac-RSV/G immunization and subsequent RSV infection.
+CONCLUSION: Our data demonstrate that intranasal administration of baculovirus-based Bac-RSV/G vaccine is efficient for the induction of protection against RSV and represents a promising prophylactic vaccination regimen.
+Recently identified hantaviruses harbored by shrews and moles (order Soricomorpha) suggest that other mammals having shared ancestry may serve as reservoirs.
+To investigate this possibility, archival tissues from 213 insectivorous bats (order Chiroptera) were analyzed for hantavirus RNA by RT-PCR.
+Following numerous failed attempts, hantavirus RNA was detected in ethanol-fixed liver tissue from two banana pipistrelles (Neoromicia nanus), captured near Mouyassué village in Côte d'Ivoire, West Africa, in June 2011.
+Phylogenetic analysis of partial L-segment sequences using maximum-likelihood and Bayesian methods revealed that the newfound hantavirus, designated Mouyassué virus (MOUV), was highly divergent and basal to all other rodent- and soricomorph-borne hantaviruses, except for Nova virus in the European common mole (Talpa europaea).
+Full genome sequencing of MOUV and further surveys of other bat species for hantaviruses, now underway, will provide critical insights into the evolution and diversification of hantaviruses.
+In this study we propose a novel bacterial vaccine strategy where non-pathogenic bacteria are complemented with traits desirable for the induction of protective immunity.
+To illustrate the proof of principle of this novel vaccination strategy, we use the model organism of intracellular immunity Listeria.
+We introduced a, low copy number BAC-plasmid harbouring the virulence gene cluster (vgc) of L. monocytogenes (Lm) into the non-pathogenic L. innocua (L.inn) strain and examined for its ability to induce protective cellular immunity.
+The resulting strain (L.inn::vgc) was attenuated for virulence in vivo and showed a strongly reduced host detrimental inflammatory response compared to Lm.
+Like Lm, L.inn::vgc induced the production of Type I Interferon's and protection was mediated by Listeria-specific CD8(+) T cells.
+Rational vaccine design whereby avirulent strains are equipped with the capabilities to induce protection but lack detrimental inflammatory effects offer great promise towards future studies using non-pathogenic bacteria as vectors for vaccination.
+BACKGROUND: The Manila clam (Ruditapes philippinarum) is a worldwide cultured bivalve species with important commercial value.
+Because knowledge of the molecular mechanisms of the immune response in bivalves, especially clams, is scarce and fragmentary, we sequenced RNA from immune-stimulated R. philippinarum hemocytes by 454-pyrosequencing to identify genes involved in their immune defense against infectious diseases.
+METHODOLOGY AND PRINCIPAL FINDINGS: High-throughput deep sequencing of R. philippinarum using 454 pyrosequencing technology yielded 974,976 high-quality reads with an average read length of 250 bp.
+The reads were assembled into 51,265 contigs and the 44.7% of the translated nucleotide sequences into protein were annotated successfully.
+The 35 most frequently found contigs included a large number of immune-related genes, and a more detailed analysis showed the presence of putative members of several immune pathways and processes like the apoptosis, the toll like signaling pathway and the complement cascade.
+We have found sequences from molecules never described in bivalves before, especially in the complement pathway where almost all the components are present.
+CONCLUSIONS: This study represents the first transcriptome analysis using 454-pyrosequencing conducted on R. philippinarum focused on its immune system.
+Our results will provide a rich source of data to discover and identify new genes, which will serve as a basis for microarray construction and the study of gene expression as well as for the identification of genetic markers.
+The discovery of new immune sequences was very productive and resulted in a large variety of contigs that may play a role in the defense mechanisms of Ruditapes philippinarum.
+Data from all reported cases of 2009 pandemic influenza A (H1N1) were obtained from the China Information System for Disease Control and Prevention.
+The impact of travel-related risk factors on invasion of the disease was analyzed using survival analysis, and climatic factors related to local transmission were identified using multilevel Poisson regression, both at the county level.
+The results showed that the epidemic spanned a large geographic area, with the most affected areas being in western China.
+Significant differences in incidence were found among age groups, with incidences peaking in school-age children.
+Proximity to airports and being intersected by national highways or freeways but not railways were variables associated with the presence of the disease in a county.
+Lower temperature and lower relative humidity were the climatic factors facilitating local transmission after correction for the effects of school summer vacation and public holidays, as well as population density and the density of medical facilities.
+These findings indicate that interventions focused on domestic travel, population density, and climatic factors could play a role in mitigating the public health impact of future influenza pandemics.
+APMV-1 (Newcastle disease virus) is the only well-characterized serotype, because of the high morbidity, mortality, and economic loss caused by highly virulent strains.
+Very little is known about the pathogenesis, replication, virulence, and tropism of the other APMV serotypes.
+Here, this was evaluated for prototypes strains of APMV serotypes 2–9 in cell culture and in chickens and ducks.
+In chicken DF1 cells, APMV-3 replicated with an efficiency approaching that of APMV-1, while APMV-2 and -5 replicated to lower, intermediate titers and the others were much lower.
+Mean death time (MDT) assay in chicken eggs and intracerebral pathogenicity index (ICPI) test in 1-day-old SPF chicks demonstrated that APMV types 2–9 were avirulent.
+Evaluation of replication in primary neuronal cells in vitro as well as in the brains of 1-day-old chicks showed that, among types 2–9, only APMV-3 was neurotropic, although this virus was not neurovirulent.
+Following intranasal infection of 1-day-old and 2-week-old chickens, replication of APMV types 2–9 was mostly restricted to the respiratory tract, although APMV-3 was neuroinvasive and neurotropic (but not neurovirulent) and also was found in the spleen.
+Experimental intranasal infection of 3-week-old mallard ducks with the APMVs did not produce any clinical signs (even for APMV-1) and exhibited restricted viral replication of the APMVs (including APMV-1) to the upper respiratory tract regardless of their isolation source, indicating avirulence of APMV types 1–9 in mallard ducks.
+The link between the presence of a furin cleavage site in the F protein, syncytium formation, systemic spread, and virulence that has been well-established with APMV-1 pathotypes was not evident with the other APMV serotypes.
+BACKGROUND: Analysis of codon usage can reveal much about the molecular evolution of the viruses.
+Nevertheless, little information about synonymous codon usage pattern of porcine circovirus (PCV) genome in the process of its evolution is available.
+In this study, to give a new understanding on the evolutionary characteristics of PCV and the effects of natural selection from its host on the codon usage pattern of the virus, Patterns and the key determinants of codon usage in PCV were examined.
+METHODS: We carried out comprehensive analysis on codon usage pattern in the PCV genome, by calculating relative synonymous codon usage (RSCU), effective number of codons (ENC), dinucleotides and nucleic acid content of the PCV genome.
+RESULTS: PCV genomes have relatively much lower content of GC and codon preference, this result shows that nucleotide constraints have a major impact on its synonymous codon usage.
+The results of the correspondence analysis indicate codon usage patterns of PCV of various genotypes, various subgenotypes changed greatly, and significant differences in codon usage patterns of Each virus of Circoviridae.There is much comparability between PCV and its host in their synonymous codon usage, suggesting that the natural selection pressure from the host factor also affect the codon usage patterns of PCV.
+In particular, PCV genotype II is in synonymous codon usage more similar to pig than to PCV genotype I, which may be one of the most important molecular mechanisms of PCV genotype II to cause disease.
+The calculations results of the relative abundance of dinucleotides indicate that the composition of dinucleotides also plays a key role in the variation found in synonymous codon usage in PCV.
+Furthermore, geographic factors, the general average hydrophobicity and the aromaticity may be related to the formation of codon usage patterns of PCV.
+CONCLUSION: The results of these studies suggest that synonymous codon usage pattern of PCV genome are the result of interaction between mutation pressure and natural selection from its host.
+The information from this study may not only have theoretical value in understanding the characteristics of synonymous codon usage in PCV genomes, but also have significant value for the molecular evolution of PCV.
+BACKGROUND: Dengue virus (DENV) is a significant public health threat in tropical and subtropical regions of the world.
+A therapeutic antibody against the viral envelope (E) protein represents a promising immunotherapy for disease control.
+METHODOLOGY/PRINCIPAL FINDINGS: We generated seventeen novel mouse monoclonal antibodies (mAbs) with high reactivity against E protein of dengue virus type 2 (DENV-2).
+The mAbs were further dissected using recombinant E protein domain I-II (E-DI-II) and III (E-DIII) of DENV-2.
+Using plaque reduction neutralization test (PRNT) and mouse protection assay with lethal doses of DENV-2, we identified four serotype-specific mAbs that had high neutralizing activity against DENV-2 infection.
+Of the four, E-DIII targeting mAb DB32-6 was the strongest neutralizing mAb against diverse DENV-2 strains.
+Using phage display and virus-like particles (VLPs) we found that residue K310 in the E-DIII A-strand was key to mAb DB32-6 binding E-DIII.
+We successfully converted DB32-6 to a humanized version that retained potency for the neutralization of DENV-2 and did not enhance the viral infection.
+The DB32-6 showed therapeutic efficacy against mortality induced by different strains of DENV-2 in two mouse models even in post-exposure trials.
+CONCLUSIONS/SIGNIFICANCE: We used novel epitope mapping strategies, by combining phage display with VLPs, to identify the important A-strand epitopes with strong neutralizing activity.
+This study introduced potential therapeutic antibodies that might be capable of providing broad protection against diverse DENV-2 infections without enhancing activity in humans.
+An emerging picture of the nature of immune systems across animal phyla reveals both conservatism of some features and the appearance among and within phyla of novel, lineage-specific defense solutions.
+Factors influencing this macroevolutionary (above the species level) pattern of novelty are considered and include adoption of different life styles, life histories, and body plans; a general advantage of being distinctive with respect to immune defenses; and the responses required to cope with parasites, many of which afflict hosts in a lineage-specific manner.
+This large-scale pattern of novelty implies that immunological phenomena can affect microevolutionary processes (at the population level within species) that can eventually lead to macroevolutionary events such as speciation, radiations, or extinctions.
+Immunologically based phenomena play a role in favoring intraspecific diversification, specialization and host specificity of parasites, and mechanisms are discussed whereby this could lead to parasite speciation.
+Host switching – the acquisition of new host species by parasites – is a major mechanism that drives parasite diversity and is frequently involved in disease emergence.
+It is also one that can be favored by reductions in immune competence of new hosts.
+Mechanisms involving immune phenomena favoring intraspecific diversification and speciation of host species are also discussed.
+A macroevolutionary perspective on immunology is invaluable in today’s world, including the need to study a broader range of species with distinctive immune systems.
+Many of these species are faced with extinction, another macroevolutionary process influenced by immune phenomena.
+A potentially fatal complication of influenza infection is the development of pneumonia, caused either directly by the influenza virus, or by secondary bacterial infection.
+Pneumonia related to the 2009 influenza A pandemic was found to be underestimated by commonly used pneumonia severity scores in many cases, and to be rapidly progressive, leading to respiratory failure.
+Confirmation of pandemic H1N1 influenza A infection can only be made by real-time reverse-transcriptase polymerase chain reaction (rRT-PCR) or viral culture.
+Decisions to administer antiviral medications for influenza treatment or chemoprophylaxis should be based upon clinical and epidemiological factors, and should not be delayed by confirmatory laboratory testing results.
+deviation = 0.018 Å), and the N- and C-bound benzene rings are inclined to this plane [dihedral angles = 21.45 (10) and 6.96 (10)°, respectively] and form a dihedral angle of 20.42 (10)° with each other.
+Supra­molecular layers are formed in the crystal structure via C—H⋯O and C—H⋯N inter­actions, and these are assembled into double layers by C—H⋯π and π–π inter­actions between the pyrazole and C-bound benzene rings [ring centroid–centroid distance = 3.6476 (12) Å].
+The double layers stack along the a axis being connected by π–π inter­actions between the N- and C-bound benzene rings [ring centroid–centroid distance = 3.7718 (12) Å].
+MEDI-565 (also known as MT111) is a bispecific T-cell engager (BiTE®) antibody in development for the treatment of patients with cancers expressing carcinoembryonic antigen (CEA).
+MEDI-565 binds CEA on cancer cells and CD3 on T cells to induce T-cell mediated killing of cancer cells.
+To understand the molecular basis of human CEA recognition by MEDI-565 and how polymorphisms and spliced forms of CEA may affect MEDI-565 activity, we mapped the epitope of MEDI-565 on CEA using mutagenesis and homology modeling approaches.
+We found that MEDI-565 recognized a conformational epitope in the A2 domain comprised of amino acids 326–349 and 388–410, with critical residues F(326), T(328), N(333), V(388), G(389), P(390), E(392), I(408), and N(410).
+Two non-synonymous single-nucleotide polymorphisms (SNPs) (rs10407503, rs7249230) were identified in the epitope region, but they are found at low homozygosity rates.
+Searching the National Center for Biotechnology Information GenBank® database, we further identified a single, previously uncharacterized mRNA splice variant of CEA that lacks a portion of the N-terminal domain, the A1 and B1 domains, and a large portion of the A2 domain.
+Real-time quantitative polymerase chain reaction analysis of multiple cancers showed widespread expression of full-length CEA in these tumors, with less frequent but concordant expression of the CEA splice variant.
+Because the epitope was largely absent from the CEA splice variant, MEDI-565 did not bind or mediate T-cell killing of cells solely expressing this form of CEA.
+In addition, the splice variant did not interfere with MEDI-565 binding or activity when co-expressed with full-length CEA.
+Thus MEDI-565 may broadly target CEA-positive tumors without regard for expression of the short splice variant of CEA.
+Together our data suggest that MEDI-565 activity will neither be impacted by SNPs nor by a splice variant of CEA.
+Most of current strategies for antiviral therapeutics target the virus specifically and directly, but an alternative approach to drug discovery might be to enhance the immune response to a broad range of viruses.
+Based on clinical observation in humans and successful genetic strategies in experimental models, we reasoned that an improved interferon (IFN) signaling system might better protect against viral infection.
+Here we aimed to identify small molecular weight compounds that might mimic this beneficial effect and improve antiviral defense.
+Accordingly, we developed a cell-based high-throughput screening (HTS) assay to identify small molecules that enhance the IFN signaling pathway components.
+The assay is based on a phenotypic screen for increased IFN-stimulated response element (ISRE) activity in a fully automated and robust format (Z′>0.7).
+Application of this assay system to a library of 2240 compounds (including 2160 already approved or approvable drugs) led to the identification of 64 compounds with significant ISRE activity.
+From these, we chose the anthracycline antibiotic, idarubicin, for further validation and mechanism based on activity in the sub-µM range.
+We found that idarubicin action to increase ISRE activity was manifest by other members of this drug class and was independent of cytotoxic or topoisomerase inhibitory effects as well as endogenous IFN signaling or production.
+We also observed that this compound conferred a consequent increase in IFN-stimulated gene (ISG) expression and a significant antiviral effect using a similar dose-range in a cell-culture system inoculated with encephalomyocarditis virus (EMCV).
+The antiviral effect was also found at compound concentrations below the ones observed for cytotoxicity.
+Taken together, our results provide proof of concept for using activators of components of the IFN signaling pathway to improve IFN efficacy and antiviral immune defense as well as a validated HTS approach to identify small molecules that might achieve this therapeutic benefit.
+The rapid emergence of AIDS in humans during the period between 1980 and 2000 has led to extensive efforts to understand more fully similar etiologic agents of chronic and progressive acquired immunodeficiency disease in several mammalian species.
+Lentiviruses that have gene sequence homology with human immunodeficiency virus (HIV) have been found in different species (including sheep, goats, horses, cattle, cats, and several Old World monkey species).
+Lentiviruses, comprising a genus of the Retroviridae family, cause persistent infection that can lead to varying degrees of morbidity and mortality depending on the virus and the host species involved.
+Feline immunodeficiency virus (FIV) causes an immune system disease in domestic cats (Felis catus) involving depletion of the CD4+ population of T lymphocytes, increased susceptibility to opportunistic infections, and sometimes death.
+This is a brief overview of the current state of knowledge of this large and ancient group of viruses (FIVs) in South America.
+Early literature studies manifested that Shenfu injection (SFI) is one of the most commonly used traditional Chinese patent medicine for HF in China.
+An extensive search was performed within 6 English and Chinese electronic database up to November 2011.
+Compared with routine treatment and/or device support, SFI combined with routine treatment and/or device support showed better effect on clinical effect rate, mortality, heart rate, NT-proBNP and 6-minute walk distance.
+Results in ultrasonic cardiography also showed that SFI combined with routine treatment improved heart function of HF patients.
+Adverse events were reported in thirteen trails with thirteen specific symptoms, while no serious adverse effect was reported.
+However, further rigorously designed RCTs are warranted because of insufficient methodological rigor in the majority of included trials.
+Influenza A virus (H1N1), which arose in 2009, constituted the fourth pandemic after the cases of 1918, 1957, and 1968.
+This new variant was formed by a triple reassortment, with genomic segments from swine, avian, and human influenza origins.
+The objective of this study was to analyze sequences of hemagglutinin (n=2038) and neuraminidase (n=1273) genes, in order to assess the extent of diversity among circulating 2009-2010 strains, estimate if these genes evolved through positive, negative, or neutral selection models of evolution during the pandemic phase, and analyze the worldwide percentage of detection of important amino acid mutations that could enhance the viral performance, such as transmissibility or resistance to drugs.
+A continuous surveillance by public health authorities will be critical to monitor the appearance of new influenza variants, especially in animal reservoirs such as swine and birds, in order to prevent the potential animal-human transmission of viruses with pandemic potential.
+BACKGROUND: In view of the close relationship of Portugal with African countries, particularly former Portuguese colonies, the diagnosis of malaria is not a rare thing.
+When a traveller returns ill from endemic areas, malaria should be the number one suspect.
+World Health Organization treatment guidelines recommend that adults with severe malaria should be admitted to an intensive care unit (ICU).
+METHODS: Severe cases of malaria in patients admitted to an ICU were reviewed retrospectively (1990-2011) and identification of variables associated with in-ICU mortality performed.
+Malaria prediction score (MPS), malaria score for adults (MSA), simplified acute physiology score (SAPSII) and a score based on WHO's malaria severe criteria were applied.
+Comparing the four scores, the SAPS II and the WHO score were the most sensitive to death prediction.
+In the univariate analysis, death was associated with the SAPS II score, cerebral malaria, acute renal and respiratory failure, DIC, spontaneous bleeding, acidosis and hypoglycaemia.
+Age, partial immunity to malaria, delay in malaria diagnosis and the level of parasitaemia were not associated with death in this cohort.
+SAPS II and the WHO score are good predictors of mortality in malaria patients, but other specific scores deserve to be studied prospectively.
+High-dose intravenous immunoglobulin (IVIG) is the most effective therapy for KD to reduce the prevalence of coronary artery lesion (CAL) formation.
+Recently, the α2, 6 sialylated IgG was reported to interact with a lectin receptor, specific intracellular adhesion molecule-3 grabbing nonintegrin homolog-related 1 (SIGN-R1) in mice and dendritic cell-specific intercellular adhesion molecule-3 grabbing nonintegrin (DC-SIGN) in human, and to trigger an anti-inflammatory cascade.
+This study was conducted to investigate whether the polymorphism of DC-SIGN (CD209) promoter −336 A/G (rs4804803) is responsible for susceptibility and CAL formation in KD patients using Custom TaqMan SNP Genotyping Assays.
+A total of 521 subjects (278 KD patients and 243 controls) were investigated to identify an SNP of rs4804803, and they were studied and showed a significant association between the genotypes and allele frequency of rs4804803 in control subjects and KD patients (P = 0.004 under the dominant model).
+However, the promoter variant of DC-SIGN gene was not associated with the occurrence of IVIG resistance, CAL formation in KD.
+The G allele of DC-SIGN promoter −336 (rs4804803) is a risk allele in the development of KD.
+Interferon protects mice from vesicular stomatitis virus (VSV) infection and pathogenesis; however, it is not known which of the numerous interferon-stimulated genes (ISG) mediate the antiviral effect.
+A prominent family of ISGs is the interferon-induced with tetratricopeptide repeats (Ifit) genes comprising three members in mice, Ifit1/ISG56, Ifit2/ISG54 and Ifit3/ISG49.
+Intranasal infection with a low dose of VSV is not lethal to wild-type mice and all three Ifit genes are induced in the central nervous system of the infected mice.
+We tested their potential contributions to the observed protection of wild-type mice from VSV pathogenesis, by taking advantage of the newly generated knockout mice lacking either Ifit2 or Ifit1.
+We observed that in Ifit2 knockout (Ifit2 (−/−)) mice, intranasal VSV infection was uniformly lethal and death was preceded by neurological signs, such as ataxia and hind limb paralysis.
+In contrast, wild-type and Ifit1 (−/−) mice were highly protected and survived without developing such disease.
+However, when VSV was injected intracranially, virus replication and survival were not significantly different between wild-type and Ifit2(−/−) mice.
+When administered intranasally, VSV entered the central nervous system through the olfactory bulbs, where it replicated equivalently in wild-type and Ifit2 (−/−) mice and induced interferon-β.
+However, as the infection spread to other regions of the brain, VSV titers rose several hundred folds higher in Ifit2 (−/−) mice as compared to wild-type mice.
+This was not caused by a broadened cell tropism in the brains of Ifit2 (−/−) mice, where VSV still replicated selectively in neurons.
+Surprisingly, this advantage for VSV replication in the brains of Ifit2(−/−) mice was not observed in other organs, such as lung and liver.
+Pathogenesis by another neurotropic RNA virus, encephalomyocarditis virus, was not enhanced in the brains of Ifit2 (−/−) mice.
+Our study provides a clear demonstration of tissue-, virus- and ISG-specific antiviral action of interferon.
+Noroviruses are the principal cause of epidemic gastroenteritis worldwide with GII.4 strains accounting for 80% of infections.
+The major capsid protein of GII.4 strains is evolving rapidly, resulting in new epidemic strains with altered antigenic potentials.
+To test if antigenic drift may contribute to GII.4 persistence, human memory B cells were immortalized and the resulting human monoclonal antibodies (mAbs) characterized for reactivity to a panel of time-ordered GII.4 virus-like particles (VLPs).
+Reflecting the complex exposure history of the volunteer, human anti-GII.4 mAbs grouped into three VLP reactivity patterns; ancestral (1987–1997), contemporary (2004–2009), and broad (1987–2009).
+NVB 97 specifically bound and blocked only contemporary GII.4 VLPs, while NBV 111 and 43.9 exclusively reacted with and blocked variants of the GII.4.2006 Minerva strain.
+Two, NVB 37.10 and 61.3, also detected other genogroup II VLPs by EIA but did not block any VLP interactions with carbohydrate ligands.
+NVB 71.4 cross-neutralized the panel of time-ordered GII.4 VLPs, as measured by VLP-carbohydrate blockade assays.
+Using mutant VLPs designed to alter predicted antigenic epitopes, two evolving, GII.4-specific, blockade epitopes were mapped.
+Amino acids 294–298 and 368–372 were required for binding NVB 114, 111 and 43.9 mAbs.
+Amino acids 393–395 were essential for binding NVB 97, supporting earlier correlations between antibody blockade escape and carbohydrate binding variation.
+These data inform VLP vaccine design, provide a strategy for expanding the cross-blockade potential of chimeric VLP vaccines, and identify an antibody with broadly neutralizing therapeutic potential for the treatment of human disease.
+Moreover, these data support the hypothesis that GII.4 norovirus evolution is heavily influenced by antigenic variation of neutralizing epitopes and consequently, antibody-driven receptor switching; thus, protective herd immunity is a driving force in norovirus molecular evolution.
+Nucleic acid sensing by cells is a key feature of antiviral responses, which generally result in type-I Interferon production and tissue protection.
+However, detection of double-stranded RNAs in virus-infected cells promotes two concomitant and apparently conflicting events.
+The dsRNA-dependent protein kinase (PKR) phosphorylates translation initiation factor 2-alpha (eIF2α) and inhibits protein synthesis, whereas cytosolic DExD/H box RNA helicases induce expression of type I-IFN and other cytokines.
+We demonstrate that the phosphatase-1 cofactor, growth arrest and DNA damage-inducible protein 34 (GADD34/Ppp1r15a), an important component of the unfolded protein response (UPR), is absolutely required for type I-IFN and IL-6 production by mouse embryonic fibroblasts (MEFs) in response to dsRNA.
+GADD34 expression in MEFs is dependent on PKR activation, linking cytosolic microbial sensing with the ATF4 branch of the UPR.
+The importance of this link for anti-viral immunity is underlined by the extreme susceptibility of GADD34-deficient fibroblasts and neonate mice to Chikungunya virus infection.
+Here, we characterized this process relative to (1) specific 18S and 28S ribosomal RNA cleavage sites and (2) identity of specific upstream signaling elements in this pathway.
+Capillary electrophoresis indicated that DON at concentrations as low as 200 ng/ml evoked selective rRNA cleavage after 6 h and that 1000 ng/ml caused cleavage within 2 h. Northern blot analysis revealed that DON exposure induced six rRNA cleavage fragments from 28S rRNA and five fragments from 18S rRNA.
+When selective kinase inhibitors were used to identify potential upstream signals, RNA-activated protein kinase (PKR), hematopoietic cell kinase (Hck), and p38 were found to be required for rRNA cleavage, whereas c-Jun N-terminal kinase and extracellular signal-regulated kinase were not.
+Furthermore, rRNA fragmentation was suppressed by the p53 inhibitors pifithrin-α and pifithrin-μ as well as the pan caspase inhibitor Z-VAD-FMK.
+DON activated caspases 3, 8, and 9, thus suggesting the possible coinvolvement of both extrinsic and intrinsic apoptotic pathways in rRNA cleavage.
+Satratoxin G (SG), anisomycin, and ricin also induced specific rRNA cleavage profiles identical to those of DON, suggesting that ribotoxins might share a conserved rRNA cleavage mechanism.
+Taken together, DON-induced rRNA cleavage is likely to be closely linked to apoptosis activation and appears to involve the sequential activation of PKR/Hck →p38→p53→caspase 8/9→caspase 3.
+The PLEX-ID/Flu assay has been recently developed to enable the detection and typing of influenza viruses based on the RT-PCR/electrospray ionization mass spectrometry technology.
+This novel assay was evaluated for typing performance on 201 positive influenza A or B nasopharyngeal swab specimens (NPS) detected by real-time RT-PCR during the 2010-2011 season.
+The PLEX-ID/Flu assay detected and characterized 91.3% and 95.3% of all influenza A and B samples, respectively.
+All non-typeable influenza A and B specimens by the assay showed low viral loads with threshold cycle values ≥ 33.
+Taken together, and although our results need to be confirmed by further prospective studies, the PLEX-ID/Flu assay detected positively and gave a typing result for 93% of all NPS detected positively by real-time RT-PCR, thus suggesting a potential role for influenza virus surveillance among other techniques.
+Magnetic resonance imaging (MRI) can detect atherosclerotic lesions containing accumulations of ultrasmall superparamagnetic iron oxides (USPIO).
+Positing that improved USPIO with a higher affinity for atherosclerotic plaques would yield better plaque images, we performed MRI and histologic studies to compare the uptake of dextran- and mannan–dextran-coated USPIO (D-USPIO and DM-USPIO, respectively) by the atherosclerotic walls of rabbits.
+We intravenously injected atherosclerotic rabbits with DM-USPIO (n = 5) or D-USPIO (n = 5).
+The doses delivered were 0.08 (dose 1) (n = 1), 0.4 (dose 2) (n = 1), or 0.8 (dose 3) (n = 3) mmol iron/Kg.
+The dose 3 rabbits underwent in vivo contrast-enhanced magnetic resonance angiography (MRA) before and 5 days after USPIO administration.
+Afterwards, all animals were euthanized, the aortae were removed and subjected to in vitro MRI study.
+The signal-to-noise ratio (SNR) of the aortic wall in the same region of interest (ROI) was calculated in both in vivo and in vitro studies.
+Histological assessment through measurement of iron-positive regions in Prussian blue-stained specimens showed that iron-positive regions were significantly larger in rabbits injected with DM- rather than D-USPIO (P < 0.05) for all doses.
+In vivo MRA showed that the SNR-reducing effect of DM- was greater than that of D-USPIO (P < 0.05).
+With in vitro MRI scans, SNR was significantly lower in rabbits treated with dose 2 of DM-USPIO compared with D-USPIO treatment (P < 0.05), and it tended to be lower at dose 3 (P < 0.1).
+In conclusion, we suggest that DM-USPIO is superior to D-USPIO for the study of atherosclerotic lesions in rabbits.
+Following influenza infection, natural killer (NK) cells function as interim effectors by suppressing viral replication until CD8 T cells are activated, proliferate, and are mobilized within the respiratory tract.
+Here, in a murine model of influenza, we show that virally-induced IL-15 facilitates the trafficking of NK cells into the lung airways.
+Blocking IL-15 delays NK cell entry to the site of infection and results in a disregulated control of early viral replication.
+By the same principle, viral control by NK cells can be therapeutically enhanced via intranasal administration of exogenous IL-15 in the early days post influenza infection.
+In addition to controlling early viral replication, this IL-15-induced mobilization of NK cells to the lung airways has important downstream consequences on adaptive responses.
+Primarily, depletion of responding NK1.1+ NK cells is associated with reduced immigration of influenza-specific CD8 T cells to the site of infection.
+Together this work suggests that local deposits of IL-15 in the lung airways regulate the coordinated innate and adaptive immune responses to influenza infection and may represent an important point of immune intervention.
+To determine whether frontline health care workers (HCWs) are at greater risk for contracting pandemic (H1N1) 2009 than nonclinical staff, we conducted a study of 231 HCWs and 215 controls.
+Overall, 79 (17.7%) of 446 had a positive antibody titer by hemagglutination inhibition, with 46 (19.9%) of 231 HCWs and 33 (15.3%) of 215 controls positive (OR 1.37, 95% confidence interval 0.84–2.22).
+Of 87 participants who provided a second serum sample, 1 showed a 4-fold rise in antibody titer; of 45 patients who had a nose swab sample taken during a respiratory illness, 7 had positive results.
+Higher numbers of children in a participant’s family and working in an intensive care unit were risk factors for infection; increasing age, working at hospital 2, and wearing gloves were protective factors.
+This highly exposed group of frontline HCWs was no more likely to contract pandemic (H1N1) 2009 influenza infection than nonclinical staff, which suggests that personal protective measures were adequate in preventing transmission.
+Angiotensin-converting enzyme 2 (ACE2) is expressed in the kidney and may be a renoprotective enzyme, since it converts angiotensin (Ang) II to Ang-(1-7).
+We measured urinary ACE2 activity and protein levels in renal transplant patients (age 54 yrs, 65% male, 38% diabetes, n = 100) and healthy controls (age 45 yrs, 26% male, n = 50), and determined factors associated with elevated urinary ACE2 in the patients.
+Urinary ACE2 levels were significantly higher in transplant patients compared to controls (p = 0.003 for ACE2 activity, and p≤0.001 for ACE2 protein by ELISA or western analysis).
+Transplant patients with diabetes mellitus had significantly increased urinary ACE2 activity and protein levels compared to non-diabetics (p<0.001), while ACE2 mRNA levels did not differ.
+Urinary ACE activity and protein were significantly increased in diabetic transplant subjects, while ACE mRNA levels did not differ from non-diabetic subjects.
+After adjusting for confounding variables, diabetes was significantly associated with urinary ACE2 activity (p = 0.003) and protein levels (p<0.001), while female gender was associated with urinary mRNA levels for both ACE2 and ACE.
+These data indicate that urinary ACE2 is increased in renal transplant recipients with diabetes, possibly due to increased shedding from tubular cells.
+Epitope mapping from affinity-selected peptides has become popular in epitope prediction, and correspondingly many Web-based tools have been developed in recent years.
+To address this problem, we employed an ensemble approach to incorporate two popular Web tools, MimoPro and Pep-3D-Search, together for taking advantages offered by both methods so as to give users more options for their specific purposes of epitope-peptide mapping.
+The combined operation of Union finds as many associated peptides as possible from both methods, which increases sensitivity in finding potential epitopic regions on a given antigen surface.
+The combined operation of Intersection achieves to some extent the mutual verification by the two methods and hence increases the likelihood of locating the genuine epitopic region on a given antigen in relation to the interacting peptides.
+The Consistency between Intersection and Union is an indirect sufficient condition to assess the likelihood of successful peptide-epitope mapping.
+On average from 27 tests, the combined operations of PepMapper outperformed either MimoPro or Pep-3D-Search alone.
+Autophagy is a catabolic pathway conserved among eukaryotes that allows cells to rapidly eliminate large unwanted structures such as aberrant protein aggregates, superfluous or damaged organelles, and invading pathogens.
+The hallmark of this transport pathway is the sequestration of the cargoes that have to be degraded in the lysosomes by double-membrane vesicles called autophagosomes.
+Recent studies, however, have highlighted the capacity of this pathway to exclusively eliminate specific structures and thus better fulfil the catabolic necessities of the cell.
+We are just starting to unveil the regulation and mechanism of these selective types of autophagy, but what it is already clearly emerging is that structures targeted to destruction are accurately enwrapped by autophagosomes through the action of specific receptors and adaptors.
+In this paper, we will briefly discuss the impact that the selective types of autophagy have had on our understanding of autophagy.
+BACKGROUND: Liver fluke infection of livestock causes economic losses of over US$ 3 billion worldwide per annum.
+There are currently no commercial vaccines, and only one drug with significant efficacy against adult worms and juveniles.
+A liver fluke vaccine is deemed essential as short-lived chemotherapy, which is prone to resistance, is an unsustainable option in both developed and developing countries.
+A new form of glutathione transferase (GST) family, Sigma class GST, closely related to a leading Schistosome vaccine candidate (Sm28), has previously been revealed by proteomics in the liver fluke but not functionally characterised.
+METHODOLOGY/PRINCIPAL FINDINGS: In this manuscript we show that a purified recombinant form of the F. hepatica Sigma class GST possesses prostaglandin synthase activity and influences activity of host immune cells.
+Immunocytochemistry and western blotting have shown the protein is present near the surface of the fluke and expressed in eggs and newly excysted juveniles, and present in the excretory/secretory fraction of adults.
+We have assessed the potential to use F. hepatica Sigma class GST as a vaccine in a goat-based vaccine trial.
+No significant reduction of worm burden was found but we show significant reduction in the pathology normally associated with liver fluke infection.
+CONCLUSIONS/SIGNIFICANCE: We have shown that F. hepatica Sigma class GST has likely multi-functional roles in the host-parasite interaction from general detoxification and bile acid sequestration to PGD synthase activity.
+BACKGROUND: Because of the high global prevalence of latent TB infection (LTBI), a key challenge in endemic settings is distinguishing patients with active TB from patients with overlapping clinical symptoms without active TB but with co-existing LTBI.
+Plasma proteomic fingerprinting can resolve this difficulty by providing a molecular snapshot defining disease state that can be used to develop point-of-care diagnostics.
+METHODS: Plasma and clinical data were obtained prospectively from patients attending community TB clinics in Peru and from household contacts.
+Statistical pattern recognition methods were used to define mass spectral patterns that distinguished patients with active TB from symptomatic controls with or without LTBI.
+RESULTS: 156 patients with active TB and 110 symptomatic controls (patients with respiratory symptoms without active TB) were investigated.
+Active TB patients were distinguishable from undifferentiated symptomatic controls with accuracy of 87% (sensitivity 84%, specificity 90%), from symptomatic controls with LTBI (accuracy of 87%, sensitivity 89%, specificity 82%) and from symptomatic controls without LTBI (accuracy 90%, sensitivity 90%, specificity 92%).
+CONCLUSIONS: We show that active TB can be distinguished accurately from LTBI in symptomatic clinic attenders using a plasma proteomic fingerprint.
+Translation of biomarkers derived from this study into a robust and affordable point-of-care format will have significant implications for recognition and control of active TB in high prevalence settings.
+No direct evidence indicates that these new viruses arose as a result of recombination between genotype C and D or a result of convergence.
+In this study, we search for evidence of intra-individual recombination in the family cluster cases with co-circulation of genotype C, D and C/D recombinants.
+We studied 68 individuals from 15 families with HBV infections in 2006, identified individuals with mixed HBV genotype co-infections by restriction fragment length polymorphism and proceeded with cloning and DNA sequencing.
+One individual (Y2) had a triple infection of HBV genotype C, D and C/D recombinant in 2006, but only genotype D in 2007.
+Further clonal analysis of this patient indicated that the C/D recombinant was not identical to previously isolated CD1 or CD2, but many novel recombinants with C2, D1 and CD1 were simultaneously found.
+All parental strains could recombine with each other to form new recombinant in this patient.
+Also, as the recombinant nature of HBV precludes the possibility of a simple phylogenetic taxonomy, a new standard may be required for classifying HBV sequences.
+Wet markets are common in many parts of the world and may promote the emergence, spread and maintenance of livestock pathogens, including zoonoses.
+A survey was conducted in order to assess the potential of Vietnamese and Cambodian live bird markets (LBMs) to sustain circulation of highly pathogenic avian influenza virus subtype H5N1 (HPAIV H5N1).
+Thirty Vietnamese and 8 Cambodian LBMs were visited, and structured interviews were conducted with the market managers and 561 Vietnamese and 84 Cambodian traders.
+Multivariate and cluster analysis were used to construct a typology of traders based on their poultry management practices.
+As a result of those practices and large poultry surplus (unsold poultry reoffered for sale the following day), some poultry traders were shown to promote conditions favorable for perpetuating HPAIV H5N1 in LBMs.
+More than 80% of these traders operated in LBMs located in the most densely populated areas, Ha Noi and Phnom Penh.
+The profiles of sellers operating at a given LBM could be reliably predicted using basic information about the location and type of market.
+Consequently, LBMs with the largest combination of risk factors for becoming virus reservoirs could be easily identified, potentially allowing control strategies to be appropriately targeted.
+These findings are of particular relevance to resource-scarce settings with extensively developed LBM systems, commonly found in South-East Asia.
+Detection of genogroup II (GII) norovirus (NoV) RNA from adult pigs in Japan and Europe and GII NoV antibodies in US swine raises public health concerns about zoonotic transmission of porcine NoVs to humans, although no NoVs have been detected in US swine.
+To detect porcine NoVs and to investigate their genetic diversity and relatedness to human NoVs, 275 fecal samples from normal US adult swine were screened by reverse transcription–polymerase chain reaction with calicivirus universal primers.
+Six samples were positive for NoV. Based on sequence analysis of 3 kb on the 3´ end of 5 porcine NoVs, 3 genotypes in GII and a potential recombinant were identified.
+One genotype of porcine NoVs was genetically and antigenically related to human NoVs and replicated in gnotobiotic pigs.
+These results raise concerns of whether subclinically infected adult swine may be reservoirs of new human NoVs or if porcine/human GII recombinants could emerge.
+BACKGROUND: Elevation of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) is prominent in acute dengue illness.
+The World Health Organization (WHO) 2009 dengue guidelines defined AST or ALT≥1000 units/liter (U/L) as a criterion for severe dengue.
+We aimed to assess the clinical relevance and discriminatory value of AST or ALT for dengue hemorrhagic fever (DHF) and severe dengue.
+METHODOLOGY/PRINCIPAL FINDINGS: We retrospectively studied and classified polymerase chain reaction positive dengue patients from 2006 to 2008 treated at Tan Tock Seng Hospital, Singapore according to WHO 1997 and 2009 criteria for dengue severity.
+Median AST and ALT values were significantly higher with increasing dengue severity by both WHO 1997 and 2009 criteria.
+However, they were poorly discriminatory between non-severe and severe dengue (e.g., AST area under the receiver operating characteristic [ROC] curve = 0.62; 95% confidence interval [CI]: 0.57–0.67) and between dengue fever (DF) and DHF (AST area under the ROC curve = 0.56; 95% CI: 0.52–0.61).
+There was significant overlap in AST and ALT values among patients with dengue with or without warning signs and severe dengue, and between those with DF and DHF.
+CONCLUSIONS: Although aminotransferase levels increased in conjunction with dengue severity, AST or ALT values did not discriminate between DF and DHF or non-severe and severe dengue.
+Mesenchymal stem cells (MSCs) spontaneously fuse with somatic cells in vivo, albeit rarely, and the fusion products are capable of tissue-specific function (mature trait) or proliferation (immature trait), depending on the microenvironment.
+That stem cells can be programmed, or somatic cells reprogrammed, in this fashion suggests that stem cell fusion holds promise as a therapeutic approach for the repair of damaged tissues, especially tissues not readily capable of functional regeneration, such as the myocardium.
+In an attempt to increase the frequency of stem cell fusion and, in so doing, increase the potential for cardiac tissue repair, we expressed the fusogen of the vesicular stomatitis virus (VSV-G) in human MSCs.
+We found VSV-G expressing MSCs (vMSCs) fused with cardiomyocytes (CMs) and these fusion products adopted a CM-like phenotype and morphology in vitro.
+In vivo, vMSCs delivered to damaged mouse myocardium via a collagen patch were able to home to the myocardium and fuse to cells within the infarct and peri-infarct region of the myocardium.
+This study provides a basis for the investigation of the biological impact of fusion of stem cells with CMs in vivo and illustrates how viral fusion proteins might better enable such studies.
+Owing to their unique functions in regulating glucose, lipid and cholesterol metabolism, PPARs (peroxisome proliferator-activated receptors) have drawn special attention for developing drugs to treat type-2 diabetes.
+By combining the lipid benefit of PPAR-alpha agonists (such as fibrates) with the glycemic advantages of the PPAR-gamma agonists (such as thiazolidinediones), the dual PPAR agonists approach can both improve the metabolic effects and minimize the side effects caused by either agent alone, and hence has become a promising strategy for designing effective drugs against type-2 diabetes.
+In this study, by means of the powerful “core hopping” and “glide docking” techniques, a novel class of PPAR dual agonists was discovered based on the compound GW409544, a well-known dual agonist for both PPAR-alpha and PPAR-gamma modified from the farglitazar structure.
+It was observed by molecular dynamics simulations that these novel agonists not only possessed the same function as GW409544 did in activating PPAR-alpha and PPAR-gamma, but also had more favorable conformation for binding to the two receptors.
+It was further validated by the outcomes of their ADME (absorption, distribution, metabolism, and excretion) predictions that the new agonists hold high potential to become drug candidates.
+Or at the very least, the findings reported here may stimulate new strategy or provide useful insights for discovering more effective dual agonists for treating type-2 diabetes.
+Since the “core hopping” technique allows for rapidly screening novel cores to help overcome unwanted properties by generating new lead compounds with improved core properties, it has not escaped our notice that the current strategy along with the corresponding computational procedures can also be utilized to find novel and more effective drugs for treating other illnesses.
+BACKGROUND: The H1N1 influenza pandemic strain has been associated with a poor prognosis in hospitalized patients.
+METHODS: A total of 813 patients hospitalized with H1N1 influenza in 36 hospitals (nationwide) in Spain were analysed.
+Detailed histories of variables preceding hospital admission were obtained by interview, validating data on medications and vaccine with their attending physicians.
+As definition of poor outcome, the endpoints of death and admission to intensive care were combined; and as a further outcome, length of stay was used.
+The variables significantly associated with a poor outcome were diabetes (OR = 2.21, 95% CI = 1.21–4.02), corticosteroid therapy (OR = 3.37, 95% CI = 1.39–8.20) and use of histamine-2 receptor antagonists (OR = 2.68, 95% CI = 1.14–6.36), while the use of neuraminidase inhibitors (OR = 0.57, 95% CI = 0.34–0.94) was protective.
+Neuraminidase inhibitors within the first 2 days after the influenza onset reduced hospital stay by a mean of 1.9 days (95% CI = 4.7–6.6).
+CONCLUSIONS: The use of neuraminidase inhibitors decreases the length of hospital stay and admission to intensive care and/or death.
+We describe the first reported transmission to a human of simian foamy virus (SFV) from a free-ranging population of nonhuman primates in Asia.
+The transmission of an exogenous retrovirus, SFV, from macaques (Macaca fascicularis) to a human at a monkey temple in Bali, Indonesia, was investigated with molecular and serologic techniques.
+Antibodies to SFV were detected by Western blotting of serum from 1 of 82 humans tested.
+SFV DNA was detected by nested polymerase chain reaction (PCR) from the blood of the same person.
+Cloning and sequencing of PCR products confirmed the virus's close phylogenetic relationship to SFV isolated from macaques at the same temple.
+This study raises concerns that persons who work at or live around monkey temples are at risk for infection with SFV.
+BACKGROUND: In order to identify novel chemical classes of β-secretase (BACE-1) inhibitors, an alternative scoring protocol, Principal Component Analysis (PCA), was proposed to summarize most of the information from the original scoring functions and re-rank the results from the virtual screening against BACE-1.
+METHOD: Given a training set (50 BACE-1 inhibitors and 9950 inactive diverse compounds), three rank-based virtual screening methods, individual scoring, conventional consensus scoring and PCA, were judged by the hit number in the top 1% of the ranked list.
+The docking poses were generated by Surflex, five scoring functions (Surflex_Score, D_Score, G_Score, ChemScore, and PMF_Score) were used for pose extraction.
+For each pose group, twelve scoring functions (Surflex_Score, D_Score, G_Score, ChemScore, PMF_Score, LigScore1, LigScore2, PLP1, PLP2, jain, Ludi_1, and Ludi_2) were used for the pose rank.
+For a test set, 113,228 chemical compounds (Sigma-Aldrich® corporate chemical directory) were docked by Surflex, then ranked by the same three ranking methods motioned above to select the potential active compounds for experimental test.
+RESULTS: For the training set, the PCA approach yielded consistently superior rankings compared to conventional consensus scoring and single scoring.
+For the test set, the top 20 compounds according to conventional consensus scoring were experimentally tested, no inhibitor was found.
+Then, we relied on PCA scoring protocol to test another different top 20 compounds and two low micromolar inhibitors (S450588 and 276065) were emerged through the BACE-1 fluorescence resonance energy transfer (FRET) assay.
+CONCLUSION: The PCA method extends the conventional consensus scoring in a quantitative statistical manner and would appear to have considerable potential for chemical screening applications.
+The term epidemic (from the Greek epi [on] plus demos [people]), first used by Homer, took its medical meaning when Hippocrates used it as the title of one of his famous treatises.
+At that time, epidemic was the name given to a collection of clinical syndromes, such as coughs or diarrheas, occurring and propagating in a given period at a given location.
+Successive epidemics of plague in the Middle Ages contributed to the definition of an epidemic as the propagation of a single, well-defined disease.
+Its most recent semantic evolution dates from the last quarter of the 20th century, and this evolution is likely to continue in the future.
+Cytokine expression patterns of T cells can be regulated by pre-commitment to stable effector phenotypes, further modification of moderately stable phenotypes, and quantitative changes in cytokine production in response to acute signals.
+We showed previously that the epidermal growth factor family member Amphiregulin is expressed by T cell receptor-activated mouse CD4 T cells, particularly Th2 cells, and helps eliminate helminth infection.
+Here we report a detailed analysis of the regulation of Amphiregulin expression by human T cell subsets.
+Signaling through the T cell receptor induced Amphiregulin expression by most or all T cell subsets in human peripheral blood, including naive and memory CD4 and CD8 T cells, Th1 and Th2 in vitro T cell lines, and subsets of memory CD4 T cells expressing several different chemokine receptors and cytokines.
+In these different T cell types, Amphiregulin synthesis was inhibited by an antagonist of protein kinase A, a downstream component of the cAMP signaling pathway, and enhanced by ligands that increased cAMP or directly activated protein kinase A. Prostaglandin E2 and adenosine, natural ligands that stimulate adenylyl cyclase activity, also enhanced Amphiregulin synthesis while reducing synthesis of most other cytokines.
+Thus, in contrast to mouse T cells, Amphiregulin synthesis by human T cells is regulated more by acute signals than pre-commitment of T cells to a particular cytokine pattern.
+This may be appropriate for a cytokine more involved in repair than attack functions during most inflammatory responses.
+Allogeneic stem cell transplant for multiple myeloma (MM) is one treatment associated with long-term disease-free survival.
+The high incidence of treatment-related mortality and relapses, however, are important reasons for controversy about the role of allografting in the management of MM.
+We reviewed our results of allografting for MM spanning a period of 34 years in order to better define long-term outcomes and identify areas of progress as well as areas requiring improvement.
+A total of 278 patients received allogeneic marrow or PBSCs after high-dose myeloablative (N=144) or reduced intensity, non-myeloablative (N=134) regimens.
+In multivariable analysis, adjusting for differences in patient groups, reduced intensity/non-myeloablative transplants were associated with significantly less acute GVHD, lower transplant mortality, better PFS and overall survival.
+In multivariable analysis of patients receiving only non-myeloablative transplants, decreased overall survival and PFS were associated with relapse after a prior autograft and a β2 microglobulin >4.0.
+Antiviral defense in the liver during acute infection with the hepatotropic virus murine cytomegalovirus (MCMV) involves complex cytokine and cellular interactions.
+However, the mechanism of viral sensing in the liver that promotes these cytokine and cellular responses has remained unclear.
+Studies here were undertaken to investigate the role of nucleic acid-sensing Toll-like receptors (TLRs) in initiating antiviral immunity in the liver during infection with MCMV.
+We examined the host response of UNC93B1 mutant mice, which do not signal properly through TLR3, TLR7 and TLR9, to acute MCMV infection to determine whether liver antiviral defense depends on signaling through these molecules.
+Infection of UNC93B1 mutant mice revealed reduced production of systemic and liver proinflammatory cytokines including IFN-α, IFN-γ, IL-12 and TNF-α when compared to wild-type.
+UNC93B1 deficiency also contributed to a transient hepatitis later in acute infection, evidenced by augmented liver pathology and elevated systemic alanine aminotransferase levels.
+Moreover, viral clearance was impaired in UNC93B1 mutant mice, despite intact virus-specific CD8+ T cell responses in the liver.
+Altogether, these results suggest a combined role for nucleic acid-sensing TLRs in promoting early liver antiviral defense during MCMV infection.
+BACKGROUND: Rabbit haemorrhagic disease virus (RHDV), as the pathogeny of Rabbit haemorrhagic disease, can cause a highly infectious and often fatal disease only affecting wild and domestic rabbits.
+Recent researches revealed that it, as one number of the Caliciviridae, has some specialties in its genome, its reproduction and so on.
+RESULTS: In this report, we firstly analyzed its genome and two open reading frameworks (ORFs) from this aspect of codon usage bias.
+Our researches indicated that mutation pressure rather than natural is the most important determinant in RHDV with high codon bias, and the codon usage bias is nearly contrary between ORF1 and ORF2, which is maybe one of factors regulating the expression of VP60 (encoding by ORF1) and VP10 (encoding by ORF2).
+Furthermore, negative selective constraints on the RHDV whole genome implied that VP10 played an important role in RHDV lifecycle.
+CONCLUSIONS: We conjectured that VP10 might be beneficial for the replication, release or both of virus by inducing infected cell apoptosis initiate by RHDV.
+According to the results of the principal component analysis for ORF2 of RSCU, we firstly separated 30 RHDV into two genotypes, and the ENC values indicated ORF1 and ORF2 were independent among the evolution of RHDV.
+BACKGROUND: Entomological surveys of Simulium vectors are an important component in the criteria used to determine if Onchocerca volvulus transmission has been interrupted and if focal elimination of the parasite has been achieved.
+However, because infection in the vector population is quite rare in areas where control has succeeded, large numbers of flies need to be examined to certify transmission interruption.
+The efficiency of this process is limited by the size of the pools that may be screened, which is in turn determined by the constraints imposed by the biochemistry of the assay.
+The current method of DNA purification from pools of vector black flies relies upon silica adsorption.
+This method can be applied to screen pools containing a maximum of 50 individuals (from the Latin American vectors) or 100 individuals (from the African vectors).
+METHODOLOGY/PRINCIPAL FINDINGS: We have evaluated an alternative method of DNA purification for pool screening of black flies which relies upon oligonucleotide capture of Onchocerca volvulus genomic DNA from homogenates prepared from pools of Latin American and African vectors.
+The oligonucleotide capture assay was shown to reliably detect one O. volvulus infective larva in pools containing 200 African or Latin American flies, representing a two-four fold improvement over the conventional assay.
+The capture assay requires an equivalent amount of technical time to conduct as the conventional assay, resulting in a two-four fold reduction in labor costs per insect assayed and reduces reagent costs to $3.81 per pool of 200 flies, or less than $0.02 per insect assayed.
+CONCLUSIONS/SIGNIFICANCE: The oligonucleotide capture assay represents a substantial improvement in the procedure used to detect parasite prevalence in the vector population, a major metric employed in the process of certifying the elimination of onchocerciasis.
+T cell epitopes can be used for the accurate monitoring of avian influenza virus (AIV) immune responses and the rational design of vaccines.
+No T cell epitopes have been previously identified in the H5N1 AIV virus nucleoprotein (NP) in chickens.
+For the first time, this study used homology modelling techniques to construct three-dimensional structures of the peptide-binding domains of chicken MHC class Ι molecules for four commonly encountered unique haplotypes, i.e., B4, B12, B15, and B19.
+H5N1 AIV NP was computationally parsed into octapeptides or nonapeptides according to the peptide-binding motifs of MHC class I molecules of the B4, B12, B15 and B19 haplotypes.
+Seventy-five peptide sequences were modelled and their MHC class I molecule-binding abilities were analysed by molecular docking.
+Twenty-five peptides (Ten for B4, six for B12, two for B15, and seven for B19) were predicted to be potential T cell epitopes in chicken.
+Nine of these peptides and one unrelated peptide were manually synthesized and their T cell responses were tested in vitro.
+Spleen lymphocytes were collected from SPF chickens that had been immunised with a NP-expression plasmid, pCAGGS-NP, and they were stimulated using the synthesized peptides.
+The secretion of chicken IFN-γ and the proliferation of CD8(+) T cells were tested using an ELISA kit and flow cytometry, respectively.
+The significant secretion of chicken IFN-γ and proliferation of CD8(+) T lymphocytes increased by 13.7% and 11.9% were monitored in cells stimulated with peptides NP(89–97) and NP(198–206), respectively.
+The results indicate that peptides NP(89–97) (PKKTGGPIY) and NP(198–206) (KRGINDRNF) are NP T cell epitopes in chicken of certain haplotypes.
+The method used in this investigation is applicable to predicting T cell epitopes for other antigens in chicken, while this study also extends our understanding of the mechanisms of the immune response to AIV in chicken.
+The zoonotic potential of paramyxoviruses is particularly demonstrated by their broad host range like the highly pathogenic Hendra and Nipah viruses originating from bats.
+But while so far all bat-borne paramyxoviruses have been identified in fruit bats across Africa, Australia, South America, and Asia, we describe the detection and characterization of the first paramyxoviruses in free-ranging European bats.
+Moreover, we examined the possible impact of paramyxovirus infection on individual animals by comparing histo-pathological findings and virological results.
+Organs from deceased insectivorous bats of various species were sampled in Germany and tested for paramyxovirus RNA in parallel to a histo-pathological examination.
+Nucleic acids of three novel paramyxoviruses were detected, two viruses in phylogenetic relationship to the recently proposed genus Jeilongvirus and one closely related to the genus Rubulavirus.
+Two infected animals revealed subclinical pathological changes within their kidneys, suggestive of a similar pathogenesis as the one described in fruit bats experimentally infected with Hendra virus.
+Our findings indicate the presence of bat-born paramyxoviruses in geographic areas free of fruit bat species and therefore emphasize a possible virus–host co-evolution in European bats.
+Since these novel viruses are related to the very distinct genera Rubulavirus and Jeilongvirus, a similarly broad genetic diversity among paramyxoviruses in other Microchiroptera compared to Megachiroptera can be assumed.
+Given that the infected bats were either found in close proximity to heavily populated human habitation or areas of intensive agricultural use, a potential risk of the emergence of zoonotic paramyxoviruses in Europe needs to be considered.
+Lipid rafts are membrane domains, more ordered than the bulk membrane and enriched in cholesterol and sphingolipids.
+In addition to their normal functions, including membrane trafficking, ligand binding (including viruses), axonal development and maintenance of synaptic integrity, rafts have also been implicated in the pathogenesis of several neurodegenerative diseases including Alzheimer’s disease (AD).
+Lipid rafts promote interaction of the amyloid precursor protein (APP) with the secretase (BACE-1) responsible for generation of the amyloid β peptide, Aβ.
+In addition, such major lipid raft components as cholesterol and GM1 ganglioside have been directly implicated in pathogenesis of the disease.
+Perturbation of lipid raft integrity can also affect various signaling pathways leading to cellular death and AD.
+In this review, we discuss modulation of APP cleavage by lipid rafts and their components, while also looking at more recent findings on the role of lipid rafts in signaling events.
+BACKGROUND: Four species of human bocaviruses (HBoV1-4) have been identified based on phylogenetic analysis since its first report in 2005.
+HBoV1 has been associated with respiratory disease, whereas HBoV2-4 are mainly detected in enteric infections.
+Although the prevalence of HBoVs in humans has been studied in some regions, it has not been well addressed globally.
+METHODOLOGY/PRINCIPAL FINDINGS: Cross-reactivity of anti-VP2 antibodies was detected between HBoV1, 2, 3, and 4 in mouse and human serum.
+The prevalence of specific anti-VP2 IgG antibodies against HBoV1-4 was determined in different age groups of healthy individuals aged 0-70 years old in Beijing, China, using a competition ELISA assay based on virus-like particles of HBoV1-4.
+The seroprevalence of HBoV1-4 was 50%, 36.9%, 28.7%, and 0.8%, respectively, in children aged 0-14 years (n = 244); whereas the seroprevalence of HBoV1-4 was 66.9%, 49.3%, 38.7% and 1.4%, respectively, in healthy adults (≥15 years old; n = 142).
+The seropositive rate of HBoV1 was higher than that of HBoV2, HBoV3, and HBoV4 in individuals older than 0.5 years.
+Furthermore, IgG seroconversion of HBoV1 (10/31, 32.3%), HBoV2 (8/31, 25.8%), and HBoV3 (2/31, 6.5%) was found in paired sera collected from children with respiratory tract infections who were positive for HBoV1 according to PCR analysis.
+CONCLUSIONS/SIGNIFICANCE: Our data indicate that HBoV1 is more prevalent than HBoV2, HBoV3, and HBoV4 in the population we sampled in Beijing, China, suggesting that HBoV species may play differential roles in disease.
+Human respiratory syncytial virus (RSV) sometimes causes acute and severe lower respiratory tract illness in infants and young children.
+RSV strongly upregulates proinflammatory cytokines and the platelet-activating factor (PAF) receptor, which is a receptor for Streptococcus pneumoniae, in the pulmonary epithelial cell line A549.
+Clarithromycin (CAM), which is an antimicrobial agent and is also known as an immunomodulator, significantly suppressed RSV-induced production of interleukin-6, interleukin-8, and regulated on activation, normal T-cell expressed and secreted (RANTES).
+CAM also suppressed RSV-induced PAF receptor expression and adhesion of fluorescein-labeled S. pneumoniae cells to A549 cells.
+The RSV-induced S. pneumoniae adhesion was thought to be mediated by the host cell's PAF receptor.
+CAM, which exhibits antimicrobial and immunomodulatory activities, was found in this study to suppress the RSV-induced adhesion of respiratory disease-causing bacteria, S. pneumoniae, to host cells.
+Porcine reproductive and respiratory syndrome virus (PRRSV) is not only a poor inducer of type I interferon but also inhibits the efficient induction of type I interferon by porcine transmissible gastroenteritis virus (TGEV) and synthetic dsRNA molecules, Poly I:C. However, the mechanistic basis by which PRRSV interferes with the induction of type I interferon in its natural host cells remains less well defined.
+The purposes of this review are to summarize the key findings in supporting the post-transcriptional control of type I interferon in its natural host cells and to propose the possible role of translational control in the regulation of type I interferon induction by PRRSV.
+Antenatally, the pregnant patient is more likely to be admitted with diseases non-specific to pregnancy, such as pneumonia.
+Pregnancy-specific diseases resulting in ICU admission include obstetric hemorrhage, pre-eclampsia/eclampsia, HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome, amniotic fluid embolus syndrome, acute fatty liver of pregnancy, and peripartum cardiomyopathy.
+Alternatively, critical illness may result from pregnancy-induced worsening of pre-existing diseases (for example, valvular heart disease, myasthenia gravis, and kidney disease).
+Pregnancy can also predispose women to diseases seen in the non-pregnant population, such as acute respiratory distress syndrome (for example, pneumonia and aspiration), sepsis (for example, chorioamnionitis and pyelonephritis) or pulmonary embolism.
+The pregnant patient may also develop conditions co-incidental to pregnancy such as trauma or appendicitis.
+Hemorrhage, particularly postpartum, and hypertensive disorders of pregnancy remain the most frequent indications for ICU admission.
+The physiologic changes in pregnancy and the presence of a second, dependent, patient may necessitate adjustments to therapeutic and supportive strategies.
+The fetus is generally robust despite maternal illness, and therapeutically what is good for the mother is generally good for the fetus.
+Prognosis following pregnancy-related critical illness is generally better than for age-matched non-pregnant critically ill patients.
+INTRODUCTION: Our aims in this study were to report changes in the ratio of alveolar dead space to tidal volume (VD(alv)/V(T)) in the prone position (PP) and to test whether changes in partial pressure of arterial CO(2 )(PaCO(2)) may be more relevant than changes in the ratio of partial pressure of arterial O(2 )to fraction of inspired O(2 )(PaO(2)/FiO(2)) in defining the respiratory response to PP.
+We also aimed to validate a recently proposed method of estimation of the physiological dead space (VD(physiol)/V(T)) without measurement of expired CO(2).
+METHODS: Thirteen patients with a PaO(2)/FiO(2 )ratio < 100 mmHg were included in the study.
+Plateau pressure (Pplat), positive end-expiratory pressure (PEEP), blood gas analysis and expiratory CO(2 )were recorded with patients in the supine position and after 3, 6, 9, 12 and 15 hours in the PP.
+Responders to PP were defined after 15 hours of PP either by an increase in PaO(2)/FiO(2 )ratio > 20 mmHg or by a decrease in PaCO(2 )> 2 mmHg.
+RESULTS: PP induced a decrease in Pplat, PaCO(2 )and VD(alv)/V(T )ratio and increases in PaO(2)/FiO(2 )ratios and compliance of the respiratory system (Crs).
+Changes in VD(alv)/V(T )were correlated with changes in Crs, but not with changes in PaO(2)/FiO(2 )ratios.
+When the response was defined by PaO(2)/FiO(2 )ratio, no significant differences in Pplat, PaCO(2 )or VD(alv)/V(T )alterations between responders (n = 7) and nonresponders (n = 6) were observed.
+When the response was defined by PaCO(2), four patients were differently classified, and responders (n = 7) had a greater decrease in VD(alv)/V(T )ratio and in Pplat and a greater increase in PaO(2)/FiO(2 )ratio and in Crs than nonresponders (n = 6).
+Estimated VD(physiol)/V(T )ratios significantly underestimated measured VD(physiol)/V(T )ratios (concordance correlation coefficient 0.19 (interquartile ranges 0.091 to 0.28)), whereas changes during PP were more reliable (concordance correlation coefficient 0.51 (0.32 to 0.66)).
+The respiratory response to PP appeared more relevant when PaCO(2 )rather than the PaO(2)/FiO(2 )ratio was used.
+INTRODUCTION: Most cases of the 2009 influenza A (H1N1) infection are self-limited, but occasionally the disease evolves to a severe condition needing hospitalization.
+Here we describe the evolution of the respiratory compromise, ventilatory management and laboratory variables of patients with diffuse viral pneumonitis caused by pandemic 2009 influenza A (H1N1) admitted to the ICU.
+METHOD: This was a multicenter, prospective inception cohort study including adult patients with acute respiratory failure requiring mechanical ventilation (MV) admitted to 20 ICUs in Argentina between June and September of 2009 during the influenza A (H1N1) pandemic.
+In a standard case-report form, we collected epidemiological characteristics, results of real-time reverse-transcriptase--polymerase-chain-reaction viral diagnostic tests, oxygenation variables, acid-base status, respiratory mechanics, ventilation management and laboratory tests.
+RESULTS: During the study period 178 patients with diffuse viral pneumonitis requiring MV were admitted.
+They were 44 ± 15 years of age, with Acute Physiology And Chronic Health Evaluation II (APACHE II) scores of 18 ± 7, and most frequent comorbidities were obesity (26%), previous respiratory disease (24%) and immunosuppression (16%).
+Non-invasive ventilation (NIV) was applied in 49 (28%) patients on admission, but 94% were later intubated.
+Acute respiratory distress syndrome (ARDS) was present throughout the entire ICU stay in the whole group (mean PaO(2)/FIO(2 )170 ± 25).
+Tidal-volumes used were 7.8 to 8.1 ml/kg (ideal body weight), plateau pressures always remained < 30 cmH(2)O, without differences between survivors and non-survivors; and mean positive end-expiratory pressure (PEEP) levels used were between 8 to 12 cm H(2)O.
+Rescue therapies, like recruitment maneuvers (8 to 35%), prone positioning (12 to 24%) and tracheal gas insufflation (3%) were frequently applied.
+At all time points, pH, platelet count, lactate dehydrogenase assay (LDH) and Sequential Organ Failure Assessment (SOFA) differed significantly between survivors and non-survivors.
+CONCLUSIONS: These patients had severe, hypoxemic respiratory failure compatible with ARDS that persisted over time, frequently requiring rescue therapies to support oxygenation.
+Persistence of thrombocytopenia, acidosis and leukocytosis, and high LDH levels found in non-survivors during the course of the disease might be novel prognostic findings.
+BACKGROUND: The sequence of the pathogen Mycobacterium tuberculosis (Mtb) strain H37Rv has been available for over a decade, but the biology of the pathogen remains poorly understood.
+Genome sequences from other Mtb strains and closely related bacteria present an opportunity to apply the power of comparative genomics to understand the evolution of Mtb pathogenesis.
+We conducted a comparative analysis using 31 genomes from the Tuberculosis Database (TBDB.org), including 8 strains of Mtb and M. bovis, 11 additional Mycobacteria, 4 Corynebacteria, 2 Streptomyces, Rhodococcus jostii RHA1, Nocardia farcinia, Acidothermus cellulolyticus, Rhodobacter sphaeroides, Propionibacterium acnes, and Bifidobacterium longum.
+RESULTS: Our results highlight the functional importance of lipid metabolism and its regulation, and reveal variation between the evolutionary profiles of genes implicated in saturated and unsaturated fatty acid metabolism.
+By analyzing sequence conservation and gene expression data, we identify nearly 400 conserved noncoding regions.
+These include 37 predicted promoter regulatory motifs, of which 14 correspond to previously validated motifs, as well as 50 potential noncoding RNAs, of which we experimentally confirm the expression of four.
+CONCLUSIONS: Our analysis of protein evolution highlights gene families that are associated with the adaptation of environmental Mycobacteria to obligate pathogenesis.
+Our analysis reinforces recent findings suggesting that small noncoding RNAs are more common in Mycobacteria than previously expected.
+Our data provide a foundation for understanding the genome and biology of Mtb in a comparative context, and are available online and through TBDB.org.
+The anaphase-promoting complex (APC) is an E3 ubiquitin ligase which controls ubiquitination and degradation of multiple cell cycle regulatory proteins.
+During infection, human cytomegalovirus (HCMV), a widespread pathogen, not only phosphorylates the APC coactivator Cdh1 via the multifunctional viral kinase pUL97, it also promotes degradation of APC subunits via an unknown mechanism.
+Using a proteomics approach, we found that a recently identified HCMV protein, pUL21a, interacted with the APC.
+Importantly, we determined that expression of pUL21a was necessary and sufficient for proteasome-dependent degradation of APC subunits APC4 and APC5.
+We have identified the proline-arginine amino acid pair at residues 109–110 in pUL21a to be critical for its ability to bind and regulate the APC.
+A point mutant virus in which proline-arginine were mutated to alanines (PR-AA) grew at wild-type levels.
+However, a double mutant virus in which the viral ability to regulate the APC was abrogated by both PR-AA point mutation and UL97 deletion was markedly more attenuated compared to the UL97 deletion virus alone.
+This suggests that these mutations are synthetically lethal, and that HCMV exploits two viral factors to ensure successful disruption of the APC to overcome its restriction on virus infection.
+This study reveals the HCMV protein pUL21a as a novel APC regulator and uncovers a unique viral mechanism to subvert APC activity.
+Over the years, a vast array of information concerning the interactions of viruses with their hosts has been collected.
+However, recent advances in proteomics and other system biology techniques suggest these interactions are far more complex than anticipated.
+One particularly interesting and novel aspect is the analysis of cellular proteins incorporated into mature virions.
+Though sometimes considered purification contaminants in the past, their repeated detection by different laboratories suggests that a number of these proteins are bona fide viral components, some of which likely contribute to the viral life cycles.
+It highlights the common cellular functions of these proteins, their potential implications for host–pathogen interactions, discusses technical limitations, the need for complementing methods and probes potential future research avenues.
+Dendritic cell–specific ICAM-3 grabbing-nonintegrin (DC-SIGN, also known as CD209) is an HIV-1 receptor that enhances its transmission to T cells and is expressed on placental macrophages.
+METHODS AND FINDINGS: We have investigated the association between DC-SIGN genetic variants and risk of MTCT of HIV-1 among Zimbabwean infants and characterized the impact of the associated mutations on DC-SIGN expression and interaction with HIV-1.
+DC-SIGN promoter (p-336C and p-201A) and exon 4 (198Q and 242V) variants were all significantly associated with increased risk of intrauterine (IU) HIV-1 infection.
+Promoter variants decreased DC-SIGN expression both in vitro and in placental CD163(+) macrophages (Hofbauer cells) of HIV-1 unexposed infants but not of HIV-1 exposed infants.
+The exon 4 protein-modifying mutations increased HIV-1 capture and transmission to T cells in vitro.
+CONCLUSION: This study provides compelling evidence to support an important role of DC-SIGN in IU HIV-1 infection.
+Hendra virus (HeV) infection in humans is characterized by an influenza like illness, which may progress to pneumonia or encephalitis and lead to death.
+The pathogenesis of HeV infection is poorly understood, and the lack of a mouse model has limited the opportunities for pathogenetic research.
+In this project we reassessed the role of mice as an animal model for HeV infection and found that mice are susceptible to HeV infection after intranasal exposure, with aged mice reliably developing encephalitic disease.
+This is supported by evidence for the development of encephalitis in the absence of viremia and the sequential distribution of viral antigen along pathways of olfaction in the brain of intranasally challenged animals.
+In our studies mice developed transient lower respiratory tract infection without progressing to viremia and systemic vasculitis that is common to other animal models.
+These studies report a new animal model of HeV encephalitis that will allow more detailed studies of the neuropathogenesis of HeV infection, particularly the mode of viral spread and possible sequestration within the central nervous system; investigation of mechanisms that moderate the development of viremia and systemic disease; and inform the development of improved treatment options for human patients.
+Many proteins are induced in the plant defense response to biotic stress or mechanical wounding.
+In this study, we resolved the crystal structures of IPO in its apo form and in complex with carbohydrates such as methyl α-D-mannopyranoside (Me-Man), methyl α-D-glucopyranoside (Me-Glc), and methyl α-D-galactopyranoside (Me-Gal) in different space groups.
+The packing diagrams indicated that IPO might represent a compact tetrameric association in the JRL family.
+The protomer of IPO showed a canonical β-prism fold with 12 strands of β-sheets but with 2 additional short β-strands at the N terminus.
+A truncated IPO (ΔN10IPO) by removing the 2 short β-strands of the N terminus was used to reveal its role in a tetrameric association.
+Isothermal titration calorimetry determined the binding constants (K(A)) of IPO and ΔN10IPO against various carbohydrates.
+In contrast, ΔN10IPO showed high binding ability to Me-Man and Me-Glc but could not bind to Me-Gal.
+Our structural and functional analysis of IPO revealed that its compact tetrameric association and carbohydrate binding polyspecificity could be regulated by the 2 additional N-terminal β-strands.
+Together with the Gag protein, the Env glycoprotein is a major retroviral structural protein and is essential for forming infectious virus particles.
+Env is synthesized, processed, and transported to certain microdomains at the plasma membrane and takes advantage of the same host machinery for its trafficking as that used by cellular glycoproteins.
+Incorporation of Env into progeny virions is probably mediated by the interaction between Env and Gag, in some cases with the additional involvement of certain host factors.
+Although several general models have been proposed to explain the incorporation of retroviral Env glycoproteins into virions, the actual mechanism for this process is still unclear, partly because structural data on the Env protein cytoplasmic tail is lacking.
+This paper presents the current understanding of the synthesis, trafficking, and virion incorporation of retroviral Env proteins.
+Immunized mammals are a wide source of hyperimmune sera used in different approaches, including diagnosis and the study of host-parasite interactions.
+Unfortunately, mammalian antibodies present limitations for its production, such as the necessity for animal bleeding, low yield, interference with rheumatoid factor, complement activation and affinity to Fc mammalian receptors.
+IgY antibodies avoid those limitations; therefore they could be an alternative to be applied in T. gondii model.
+METHODOLOGY/PRINCIPAL FINDINGS: In this study we immunized hens with soluble tachyzoite antigens of T. gondii (STAg) and purified egg yolk antibodies (IgY) by an inexpensive and simple method, with high yield and purity degree.
+IgY anti-STAg antibodies presented high avidity and were able to recognize a broad range of parasite antigens, although some marked differences were observed in reactivity profile between antibodies produced in immunized hens and mice.
+We also show that IgY antibodies were suitable to detect T. gondii forms in paraffin-embedded sections and culture cell monolayers.
+CONCLUSIONS/SIGNIFICANCE: Due to its cost-effectiveness, high production yield and varied range of possible applications, polyclonal IgY antibodies are useful tools for studies involving T. gondii.
+BACKGROUND: Alpha-momorcharin (α-MMC) and momordica anti-HIV protein (MAP30) derived from Momordica charantia L. have been confirmed to possess antitumor and antivirus activities due to their RNA-N-glycosidase activity.
+METHODOLOGY/PRINCIPAL FINDINGS: In this article, a novel purification strategy for the two main type I ribosome-inactivating proteins (RIPs), α-MMC and MAP30, was successfully developed for laboratory-scale preparation.
+Using this dramatic method, 200 mg of α-MMC and about 120 mg of MAP30 was obtained in only one purification process from 200 g of Momordica charantia seeds.
+The homogeneity and some other properties of the two proteins were assessed by gradient SDS-PAGE, electrospray ionization quadruple mass spectrometry, and N-terminal sequence analysis as well as Western blot.
+Homogeneous mono-, di-, or tri-PEGylated proteins were characterized by matrix-assisted laser desorption ionization-time of flight mass spectrometry.
+The analysis of antitumor and antivirus activities indicated that the serial PEGylated RIPs preserved moderate activities on JAR choriocarcinoma cells and herpes simplex virus-1.
+Furthermore, both PEGylated proteins showed about 60%–70% antitumor and antivirus activities, and at the same time decreased 50%–70% immunogenicity when compared with their unmodified counterparts.
+CONCLUSION/SIGNIFICANCE: α-MMC and MAP30 obtained from this novel purification strategy can meet the requirement of a large amount of samples for research.
+Their chemical modification can solve the problem of strong immunogenicity and meanwhile preserve moderate activities.
+All these findings suggest the potential application of PEGylated α-MMC and PEGylated MAP30 as antitumor and antivirus agents.
+According to these results, PEGylated RIPs can be constructed with nanomaterials to be a targeting drug that can further decrease immunogenicity and side effects.
+Through nanotechnology we can make them low-release drugs, which can further prolong their half-life period in the human body.
+Knowing when, and to what extent co-extracted inhibitors interfere with molecular RNA diagnostic assays is of utmost importance.
+The QIAamp Viral RNA Mini Kit (A); MagNA Pure LC2.0 Automatic extractor (B); KingFisher (C); and NucliSENS EasyMag (D) RNA extraction systems were evaluated for extraction efficiency and co-purification of inhibitors from stool suspensions.
+Real-Time Reverse Transcriptase Polymerase Chain Reaction (rRT-PCR) of MS-2 coliphage spiked into each system’s lysis buffer served as an external control for both.
+Cycle thresholds (Cts) of the MS2 were determined for RNA extracted from stool suspensions containing unknown (n = 93) or varying amounts of inhibitors (n = 92).
+Stool suspensions from the latter group were also used to determine whether MS-2 and enterovirus rRT-PCR inhibitions were correlated.
+Specifically 23 RNA extracts from stool suspensions were spiked with enterovirus RNA after extraction and 13 of these stool suspension were spiked with intact enterovirus before extraction.
+Inhibition was noted in 12 (13.0%), 26 (28.3%), 7 (7.6%), and 7 (7.6%) of the first 93 RNA extracts, and 58 (63.0%), 55 (59.8%), 37 (40.2%) and 30 (32.6%) of the second 92 extracts for A, B, C, and D, respectively.
+Furthermore, enterovirus rRT-PCR inhibition correlated with MS2 rRT-PCR inhibition for added enterovirus RNA or virus particles.
+In conclusion, rRT-PCR for MS-2 RNA is a good predictor of inhibition of enterovirus RNA extracted from stool suspensions.
+EasyMag performed the best, however all four extraction methods were suitable provided that external controls identified problematic samples.
+BACKGROUND: In the present study, the whole human genome oligo microarray was employed to investigate the gene expression profile in symptomatic pulmonary embolism (PE).
+METHODS: Twenty patients with PE and 20 age and gender matched patients without PE as controls were enrolled into the present study in the same period.
+The diagnosis of PE was based on the clinical manifestations and findings on imaging examinations.
+Statistical analysis was performed with t test following analysis of very small samples of repeated measurements and Gene Ontology (GO) analysis.
+Genomic data only found increased mRNA expression of a small amount of coagulation factors in PE patients.
+In the PE group, anticoagulant proteins, Fibrinolytic system and proteins related to platelet functions only played partial roles in the pathogenesis of PE.
+Gene Ontology analysis showed the genes with down-regulated expressions mainly explain the compromised T cell immunity.
+CONCLUSION: The damage to vascular endothelial cells is not necessary in the pathogenesis of VTE, and only a fraction of factors involved in the shared coagulation cascade are activated.
+Genomic results may provide a new clue for clinical diagnosis, treatment and prevention of VTE.
+As a result, we have gained detailed mechanistic knowledge on enzymatic removal of tRNA introns catalyzed by endonuclease and ligase proteins.
+In addition to the elucidation of tRNA processing, these studies facilitated the discovery of additional functions of RNA ligases such as RNA repair and non-conventional mRNA splicing events.
+Recently, the identification of a new type of RNA ligases in bacteria, archaea, and humans closed a long-standing gap in the field of tRNA processing.
+This review summarizes past and recent findings in the field of tRNA splicing with a focus on RNA ligation as it preferentially occurs in archaea and humans.
+In addition to providing an integrated view of the types and phyletic distribution of RNA ligase proteins known to date, this survey also aims at highlighting known and potential accessory biological functions of RNA ligases.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00018-012-0944-2) contains supplementary material, which is available to authorized users.
+Molecular imaging has gained attention as a possible approach for the study of the progression of inflammation and disease dynamics.
+Herein we used [(18)F]-2-deoxy-2-fluoro-D-glucose ([(18)F]-FDG) as a radiotracer for PET imaging coupled with CT (FDG-PET/CT) to gain insight into the spatiotemporal progression of the inflammatory response of ferrets infected with a clinical isolate of a pandemic influenza virus, H1N1 (H1N1pdm).
+The thoracic regions of mock- and H1N1pdm-infected ferrets were imaged prior to infection and at 1, 2, 3 and 6 days post-infection (DPI).
+On 1 DPI, FDG-PET/CT imaging revealed areas of consolidation in the right caudal lobe which corresponded with elevated [(18)F]-FDG uptake (maximum standardized uptake values (SUVMax), 4.7–7.0).
+By days 2 and 3, consolidation (CT) and inflammation ([(18)F]-FDG) appeared in the left caudal lobe.
+By 6 DPI, CT images showed extensive areas of patchy ground-glass opacities (GGO) and consolidations with the largest lesions having high SUVMax (6.0–7.6).
+Viral shedding and replication were detected in most nasal, throat and rectal swabs and nasal turbinates and lungs on 1, 2 and 3 DPI, but not on day 7, respectively.
+In conclusion, molecular imaging of infected ferrets revealed a progressive consolidation on CT with corresponding [(18)F]-FDG uptake.
+Strong positive correlations were measured between SUVMax and bronchiolitis-related pathologic scoring (Spearman’s ρ = 0.75).
+Importantly, the extensive areas of patchy GGO and consolidation seen on CT in the ferret model at 6 DPI are similar to that reported for human H1N1pdm infections.
+In summary, these first molecular imaging studies of lower respiratory infection with H1N1pdm show that FDG-PET can give insight into the spatiotemporal progression of the inflammation in real-time.
+The dynamics and the factors causing outbreaks of these diseases can be better understood using mathematical models, which are fit to data.
+Here we investigate the dynamics of a Hepatitis E outbreak in the Kitgum region of northern Uganda during 2007 to 2009.
+First, we use the data to determine that [Image: see text] is approximately 2.25 for the outbreak.
+Secondly, we use a model to estimate that the critical level of latrine and bore hole coverages needed to eradicate the epidemic is at least [Image: see text] and [Image: see text] respectively.
+Lastly, we further investigate the relationship between the co-infection factor for malaria and Hepatitis E on the value of [Image: see text] for Hepatitis E. Taken together, these results provide us with a better understanding of the dynamics and possible causes of Hepatitis E outbreaks.
+Human bocavirus (HBoV)s, which are associated with respiratory infections, have also frequently been detected in stool samples in cases of gastroenteritis, and a tentative association between HBoVs, and in particular type-2 HBoVs, and gastroenteritis has previously been made.
+The aim of this study was to determine the role of HBoVs in gastroenteritis, using archived DNA samples from the case-control Infectious Intestinal Disease Study (IID).
+DNA extracted from stool samples from 2,256 cases and 2,124 controls were tested for the presence of HBoV DNA.
+All samples were screened in a real time PCR pan-HBoV assay, and positive samples were then tested in genotype 1 to 3-specific assays.
+HBoV was detected in 7.4% but no significantly different prevalence was observed between cases and controls.
+In the genotype-specific assays 106 of the 324 HBoV-positive samples were genotyped, with HBoV-1 predominantly found in controls whilst HBoV-2 was more frequently associated with cases of gastroenteritis (p<0.01).
+A significant proportion of HBoV positives could not be typed using the type specific assays, 67% of the total positives, and this was most likely due to low viral loads being present in the samples.
+However, the distribution of the untyped HBoV strains was no different between cases and controls.
+In conclusion, HBoVs, including HBoV-2 do not appear to be a significant cause of gastroenteritis in the UK population.
+Human leukotriene A4 hydrolase (hLTA4H), which is the final and rate-limiting enzyme of arachidonic acid pathway, converts the unstable epoxide LTA4 to a proinflammatory lipid mediator LTB4 through its hydrolase function.
+The LTA4H is a bi-functional enzyme that also exhibits aminopeptidase activity with a preference over arginyl tripeptides.
+Various mutations including E271Q, R563A, and K565A have completely or partially abolished both the functions of this enzyme.
+The crystal structures with these mutations have not shown any structural changes to address the loss of functions.
+Molecular dynamics simulations of LTA4 and tripeptide complex structures with functional mutations were performed to investigate the structural and conformation changes that scripts the observed differences in catalytic functions.
+The observed protein-ligand hydrogen bonds and distances between the important catalytic components have correlated well with the experimental results.
+This study also confirms based on the structural observation that E271 is very important for both the functions as it holds the catalytic metal ion at its location for the catalysis and it also acts as N-terminal recognition residue during peptide binding.
+The comparison of binding modes of substrates revealed the structural changes explaining the importance of R563 and K565 residues and the required alignment of substrate at the active site.
+The results of this study provide valuable information to be utilized in designing potent hLTA4H inhibitors as anti-inflammatory agents.
+Exhaled breath condensate (EBC) is increasingly being used as a non-invasive method for disease diagnosis and environmental exposure assessment.
+By using hydrophobic surface, ice, and droplet scavenging, a simple impaction and condensing based collection method is reported here.
+Human subjects were recruited to exhale toward the device for 1, 2, 3, and 4 min.
+The exhaled breath quickly formed into tiny droplets on the hydrophobic surface, which were subsequently scavenged into a 10 µL rolling deionized water droplet.
+The collected EBC was further analyzed using culturing, DNA stain, Scanning Electron Microscope (SEM), polymerase chain reaction (PCR) and colorimetry (VITEK 2) for bacteria and viruses.
+Experimental data revealed that bacteria and viruses in EBC can be rapidly collected using the method developed here, with an observed efficiency of 100 µL EBC within 1 min.
+Culturing, DNA stain, SEM, and qPCR methods all detected high bacterial concentrations up to 7000 CFU/m(3) in exhaled breath, including both viable and dead cells of various types.
+Sphingomonas paucimobilis and Kocuria variants were found dominant in EBC samples using VITEK 2 system.
+SEM images revealed that most bacteria in exhaled breath are detected in the size range of 0.5–1.0 µm, which is able to enable them to remain airborne for a longer time, thus presenting a risk for airborne transmission of potential diseases.
+Different from other devices restricted solely to condensation, the developed method can be easily achieved both by impaction and condensation in a laboratory and could impact current practice of EBC collection.
+Nonetheless, the reported work is a proof-of-concept demonstration, and its performance in non-invasive disease diagnosis such as bacterimia and virus infections needs to be further validated including effects of its influencing matrix.
+The relationship between knowledge, risk perceptions, health belief towards seasonal influenza and vaccination and the vaccination behaviours of nurses was explored.
+Qualified nurses attending continuing professional education courses at a large London university between 18 April and 18 October 2010 were surveyed (522/672; response rate 77·7%).
+Of these, 82·6% worked in hospitals; 37·0% reported receiving seasonal influenza vaccination in the previous season and 44·9% reported never being vaccinated during the last 5 years.
+All respondents were categorized using two-step cluster analyses into never, occasionally, and continuously vaccinated groups.
+Nurses vaccinated the season before had higher scores of knowledge and risk perception compared to the unvaccinated (P<0·001).
+Nurses never vaccinated had the lowest scores of knowledge and risk perception compared to other groups (P<0·001).
+Demyelination and axonal degeneration are determinants of progressive neurological disability in patients with multiple sclerosis (MS).
+Cells resident within the central nervous system (CNS) are active participants in development, progression and subsequent control of autoimmune disease; however, their individual contributions are not well understood.
+Astrocytes, the most abundant CNS cell type, are highly sensitive to environmental cues and are implicated in both detrimental and protective outcomes during autoimmune demyelination.
+Experimental autoimmune encephalomyelitis (EAE) was induced in transgenic mice expressing signaling defective dominant-negative interferon gamma (IFN-γ) receptors on astrocytes to determine the influence of inflammation on astrocyte activity.
+Inhibition of IFN-γ signaling to astrocytes did not influence disease incidence, onset, initial progression of symptoms, blood brain barrier (BBB) integrity or the composition of the acute CNS inflammatory response.
+Nevertheless, increased demyelination at peak acute disease in the absence of IFN-γ signaling to astrocytes correlated with sustained clinical symptoms.
+Following peak disease, diminished clinical remission, increased mortality and sustained astrocyte activation within the gray matter demonstrate a critical role of IFN-γ signaling to astrocytes in neuroprotection.
+The CNS infiltrating leukocyte composition was not altered; however, decreased IL-10 and IL-27 correlated with sustained disease.
+These data indicate that astrocytes play a critical role in limiting CNS autoimmune disease dependent upon a neuroprotective signaling pathway mediated by engagement of IFN-γ receptors.
+PrP(Sc) is believed to serve as a template for the conversion of PrP(C) to the abnormal isoform.
+This process requires contact between the two proteins and implies that there may be critical contact sites that are important for conversion.
+We hypothesized that antibodies binding to either PrP(c)or PrP(Sc) would hinder or prevent the formation of the PrP(C)–PrP(Sc) complex and thus slow down or prevent the conversion process.
+Two systems were used to analyze the effect of different antibodies on PrP(Sc) formation: (i) neuroblastoma cells persistently infected with the 22L mouse-adapted scrapie stain, and (ii) protein misfolding cyclic amplification (PMCA), which uses PrP(Sc) as a template or seed, and a series of incubations and sonications, to convert PrP(C) to PrP(Sc).
+The two systems yielded similar results, in most cases, and demonstrate that PrP-specific monoclonal antibodies (Mabs) vary in their ability to inhibit the PrP(C)–PrP(Sc) conversion process.
+Based on the numerous and varied Mabs analyzed, the inhibitory effect does not appear to be epitope specific, related to PrP(C) conformation, or to cell membrane localization, but is influenced by the targeted PrP region (amino vs carboxy).
+BACKGROUND: Miliary tuberculosis (TB) is an uncommon cause of acute respiratory distress syndrome (ARDS) with a high mortality.
+The aim of the present study was to evaluate the clinical characteristics, predictors and outcome of patients with ARDS caused by miliary TB.
+METHODS: A retrospective study was conducted among patients with a diagnosis of ARDS with miliary TB in four hospitals from 2006 to 2010.
+Medical records and laboratory examinations of these patients were taken during the first 24 h of admission.
+Duration of time to diagnosis, time from diagnosis to mechanical ventilation, and time to anti-tuberculosis therapy were significantly shorter in survivors than those in non-survivors.
+Diabetes mellitus (OR 5.431, 95%CI 1.471-20.049; P = 0.005), ALT (70-100U/L, OR 10.029, 95%CI 2.764-36.389; P = 0.001), AST (>94U/L,OR 8.034, 95%CI 2.200-29.341; P = 0.002), D-dimer (>1.6mg/L, OR 3.167, 95%CI 0.896-11.187; P = 0.042), hemoglobin (<90g/L, OR 14.824, 95%CI 3.713-59.179; P = 0.001), albumin (<25g/L, OR 15.896, 95%CI 3.975-63.566; P = 0.001) were independent predictors of ARDS development in the setting of miliary TB.
+CONCLUSIONS: Accurate diagnosis, early initiation of anti-tuberculosis therapy and mechanical ventilation are important for the outcome of patients with ARDS caused by miliary TB.
+DM, ALT, AST, D-dimer, hemoglobin, and albumin are independent predictors of ARDS development in patients with miliary TB.
+The characteristics of human genomics and cellular immune function between clinically symptomatic venous thromboembolism (VTE) and controls were systematically compared to explore the immunologic pathogenesis of VTE.
+Microarray assay showed the mRNA expressions of genes related to non-specific cellarer immune and cytokines were significantly down-regulated.
+Abnormal expressions of CD3+, CD4+, CD8+, NK marker CD16+56+, CD19 and aberrant CD4+/CD8+ ratio were detected in 54 among 56 patients.
+In PE patients, microarray assay revealed the imbalance in the expressions of genes related to the immune system.
+The expressions of genes related to non-specific immune cells and cytokines were markedly up-regulated and those associated with cellular immune were dramatically down-regulated.
+In VTE patients, cytological examination indicated the functions of NK cells were significantly compromised, and the antigen recognition and killing function of T cells markedly decreased.
+The consistence between genomic and cytological examination suggests the symptomatic VTE is closely associated with the infection and immune dysfunction.
+The genus Henipavirus in the family Paramyxoviridae contains two viruses, Hendra virus (HeV) and Nipah virus (NiV) for which pteropid bats act as the main natural reservoir.
+Each virus also causes serious and commonly lethal infection of people as well as various species of domestic animals, however little is known about the associated mechanisms of pathogenesis.
+Here, we report the isolation and characterization of a new paramyxovirus from pteropid bats, Cedar virus (CedPV), which shares significant features with the known henipaviruses.
+The genome size (18,162 nt) and organization of CedPV is very similar to that of HeV and NiV; its nucleocapsid protein displays antigenic cross-reactivity with henipaviruses; and it uses the same receptor molecule (ephrin- B2) for entry during infection.
+Preliminary challenge studies with CedPV in ferrets and guinea pigs, both susceptible to infection and disease with known henipaviruses, confirmed virus replication and production of neutralizing antibodies although clinical disease was not observed.
+In this context, it is interesting to note that the major genetic difference between CedPV and HeV or NiV lies within the coding strategy of the P gene, which is known to play an important role in evading the host innate immune system.
+Unlike HeV, NiV, and almost all known paramyxoviruses, the CedPV P gene lacks both RNA editing and also the coding capacity for the highly conserved V protein.
+Preliminary study indicated that CedPV infection of human cells induces a more robust IFN-β response than HeV.
+Influenza A virus infects 5–20% of the population annually, resulting in ∼35,000 deaths and significant morbidity.
+However, both of these approaches have limitations, as vaccines require yearly development and the rapid evolution of viral proteins gives rise to drug resistance.
+In consequence additional intervention strategies, that target host factors required for the viral life cycle, are under investigation.
+Here we employed arrayed whole-genome siRNA screening strategies to identify cell-autonomous molecular components that are subverted to support H1N1 influenza A virus infection of human bronchial epithelial cells.
+Integration across relevant public data sets exposed druggable gene products required for epithelial cell infection or required for viral proteins to deflect host cell suicide checkpoint activation.
+Pharmacological inhibition of representative targets, RGGT and CHEK1, resulted in significant protection against infection of human epithelial cells by the A/WS/33 virus.
+In addition, chemical inhibition of RGGT partially protected against H5N1 and the 2009 H1N1 pandemic strain.
+The observations reported here thus contribute to an expanding body of studies directed at decoding vulnerabilities in the command and control networks specified by influenza virulence factors.
+BACKGROUND: As important regulators of the immune system, the human Fcγ receptors (FcγRs) have been demonstrated to play important roles in the pathogenesis of various infectious diseases.
+The aim of the present study was to identify the association between FCGR polymorphisms and cryptococcal meningitis.
+METHODOLOGY/PRINCIPAL FINDINGS: In this case control genetic association study, we genotyped four functional polymorphisms in low-affinity FcγRs, including FCGR2A 131H/R, FCGR3A 158F/V, FCGR3B NA1/NA2, and FCGR2B 232I/T, in 117 patients with cryptococcal meningitis and 190 healthy controls by multiplex SNaPshot technology.
+In patients with cryptococcal meningitis, the FCGR2B 232I/I genotype was over-presented (OR = 1.652, 95% CI [1.02–2.67]; P = 0.039) and the FCGR2B 232I/T genotype was under-presented (OR = 0.542, 95% CI [0.33–0.90]; P = 0.016) in comparison with control group.
+In cryptococcal meningitis patients without predisposing factors, FCGR2B 232I/I genotype was also more frequently detected (OR = 1.958, 95% CI [1.05–3.66]; P = 0.033), and the FCGR2B 232I/T genotype was also less frequently detected (OR = 0.467, 95% CI [0.24–0.91]; P = 0.023) than in controls.
+No significant difference was found among FCGR2A 131H/R, FCGR3A 158F/V, and FCGR3B NA1/NA2 genotype frequencies between patients and controls.
+CONCLUSION/SIGNIFICANCE: We found for the first time associations between cryptococcal meningitis and FCGR2B 232I/T genotypes, which suggested that FcγRIIB might play an important role in the central nervous system infection by Cryptococcus in HIV-uninfected individuals.
+BACKGROUND: Non-HIV Pneumocystis pneumonia (PCP) can occur in immunosuppressed patients having malignancy or on immunosuppressive agents.
+To classify severity, the A-DROP scale proposed by the Japanese Respiratory Society (JRS), the CURB-65 score of the British Respiratory Society (BTS) and the Pneumonia Severity Index (PSI) of the Infectious Diseases Society of America (IDSA) are widely used in patients with community-acquired pneumonia (CAP) in Japan.
+To evaluate how correctly these conventional prognostic guidelines for CAP reflect the severity of non-HIV PCP, we retrospectively analyzed 21 patients with non-HIV PCP.
+METHODS: A total of 21 patients were diagnosed by conventional staining and polymerase chain reaction (PCR) for respiratory samples with chest x-ray and computed tomography (CT) findings.
+We compared the severity of 21 patients with PCP classified by A-DROP, CURB-65, and PSI.
+Also, patients’ characteristics, clinical pictures, laboratory results at first visit or admission and intervals from diagnosis to start of specific-PCP therapy were evaluated in both survivor and non-survivor groups.
+RESULTS: Based on A-DROP, 18 patients were classified as mild or moderate; respiratory failure developed in 15 of these 18 (83.3%), and 7/15 (46.7%) died.
+Based on CURB-65, 19 patients were classified as mild or moderate; respiratory failure developed in 16/19 (84.2%), and 8 of the 16 (50%) died.
+In contrast, PSI classified 14 as severe or extremely severe; all of the 14 (100%) developed respiratory failure and 8/14 (57.1%) died.
+The time between the initial visit and diagnosis, and the time between the initial visit and starting of specific-PCP therapy were statistically shorter in the survivor group than in the non-survivor group.
+CONCLUSIONS: Conventional prognostic guidelines for CAP could underestimate the severity of non-HIV PCP, resulting in a therapeutic delay resulting in high mortality.
+The most important factor to improve the mortality of non-HIV PCP is early diagnosis and starting of specific-PCP therapy as soon as possible.
+This study was conducted to analyze alterations in the human serum proteome as a consequence of infection by malaria parasites Plasmodium falciparum and P. vivax to obtain mechanistic insights about disease pathogenesis, host immune response, and identification of potential protein markers.
+Serum samples from patients diagnosed with falciparum malaria (FM) (n = 20), vivax malaria (VM) (n = 17) and healthy controls (HC) (n = 20) were investigated using multiple proteomic techniques and results were validated by employing immunoassay-based approaches.
+Specificity of the identified malaria related serum markers was evaluated by means of analysis of leptospirosis as a febrile control (FC).
+Compared to HC, 30 and 31 differentially expressed and statistically significant (p<0.05) serum proteins were identified in FM and VM respectively, and almost half (46.2%) of these proteins were commonly modulated due to both of the plasmodial infections.
+Functional pathway analysis involving the identified proteins revealed the modulation of different vital physiological pathways, including acute phase response signaling, chemokine and cytokine signaling, complement cascades and blood coagulation in malaria.
+A panel of identified proteins consists of six candidates; serum amyloid A, hemopexin, apolipoprotein E, haptoglobin, retinol-binding protein and apolipoprotein A-I was used to build statistical sample class prediction models.
+By employing PLS-DA and other classification methods the clinical phenotypic classes (FM, VM, FC and HC) were predicted with over 95% prediction accuracy.
+Individual performance of three classifier proteins; haptoglobin, apolipoprotein A-I and retinol-binding protein in diagnosis of malaria was analyzed using receiver operating characteristic (ROC) curves.
+The discrimination of FM, VM, FC and HC groups on the basis of differentially expressed serum proteins demonstrates the potential of this analytical approach for the detection of malaria as well as other human diseases.
+Clara cells are non-ciliated, secretory bronchiolar epithelial cells that serve to detoxify harmful inhaled substances.
+Clara cell secretory protein (CCSP) is specifically expressed in pulmonary Clara cells and is widely used as a Clara cell marker.
+In addition CCSP promoter is commonly used to direct gene expression into the lung in transgenic models.
+The discovery of CCSP immunoreactivity in plasma membranes of airway lining cells prompted us to explore the possibility of enriching Clara cells by flow cytometry.
+We established a novel and simple method for the isolation of CCSP-expressing cell Clara cells using a combination of mechanical and enzymatic dissociation followed by flow cytometry sorting technology.
+Notably, we found that several common stem cell markers including CD44, CD133, Sca-1 and Sox2 were expressed in CCSP(+) cells.
+Parallel studies in vivo confirmed that a small population of CCSP(−)expressing cells in mouse airways also demonstrates stem cell-like properties such as label retention and harboring rare bronchioalveolar stem cells (BASCs) in terminal bronchioles (TBs).
+We conclude that CCSP(+) cells exhibit a number of stem cell-like features including stem cell marker expression, bronchosphere colony formation and self-renewal ability.
+Clara cell isolation by flow cytometry sorting is a useful method for investigating the function of primary Clara cells in stem cell research and mouse models.
+BACKGROUND: Real-time PCR array for rapid detection of multiple viral pathogens should be highly useful in cases where the sample volume and the time of testing are limited, i.e.
+FINDINGS: We developed a real-time PCR array capable of simultaneously detecting eight human viral pathogens: human immunodeficiency virus types 1 and 2 (HIV-1 and -2), hepatitis B virus (HBV), hepatitis C virus (HCV), human T-cell leukemia virus-1 and -2 (HTLV-1 and -2), vaccinia virus (VACV) and West Nile virus (WNV).
+One hundred twenty (120) primers were designed using a combination of bioinformatics approaches, and, after experimental testing, 24 primer sets targeting eight viral pathogens were selected to set up the array with SYBR Green chemistry.
+The specificity and sensitivity of the virus-specific primer sets selected for the array were evaluated using analytical panels with known amounts of viruses spiked into human plasma.
+The array detected: 10 genome equivalents (geq)/ml of HIV-2 and HCV, 50 geq of HIV-1 (subtype B), HBV (genotype A) and WNV.
+It detected 100–1,000 geq/ml of plasma of HIV-1 subtypes (A – G), group N and CRF (AE and AG) isolates.
+Further evaluation with a panel consisting of 28 HIV-1 and HIV-2 clinical isolates revealed no cross-reactivity of HIV-1 or HIV-2 specific primers with another type of HIV.
+All 28 viral isolates were identified with specific primer sets targeting the most conserved genome areas.
+The PCR array correctly identified viral infections in a panel of 17 previously quantified clinical plasma samples positive for HIV-1, HCV or HBV at as low as several geq per PCR reaction.
+CONCLUSIONS: The viral array described here demonstrated adequate performance in the testing of donors’ clinical samples.
+Further improvement in its sensitivity for the broad spectrum of HIV-1 subtypes is under development.
+Symptoms of C. difficile infection range from mild diarrhea to pseudomembranous colitis, sometimes resulting in colectomy or death.
+Besides the genes encoding these toxins (tcdA and tcdB), the pathogenicity locus (PaLoc) also contains genes encoding a sigma factor (tcdR) and a putative anti-sigma factor (tcdC).
+The important role of TcdR as a sigma factor for toxin expression is undisputed, whereas the role of TcdC as an anti-sigma factor, inhibiting toxin expression, is currently the subject of debate.
+To clarify the role of TcdC in toxin expression, we generated an isogenic ClosTron-based mutant of tcdC in Clostridium difficile strain 630Δ Erm (CT::tcdC) and determined the transcription levels of the PaLoc genes and the expression levels of the toxins in the wild type strain and the tcdC mutant strain.
+We found only minor differences in transcription levels of the PaLoc genes between the wild type and CT::tcdC strains and total toxin levels did not significantly differ either.
+These results suggest that in C. difficile 630Δerm TcdC is not a major regulator of toxin expression under the conditions tested.
+Haemophagocytic syndrome is a life threatening complication of systemic infection resulting from an exaggerated immune response to a triggering agent.
+Prompt recognition and treatment of this disorder can abrogate otherwise high fatality associated with this disorder.
+A 2 year old girl presented with acute enteritis, developed prolonged fever and organomegaly complicated by multi-organ failure.
+In addition she had serological evidence of tubercular infection as well as a positive family history of tuberculosis.
+Our case illustrates the association of haemophagocytic syndrome with tuberculosis as well as the favourable response obtained with prompt diagnosis and treatment.
+Signaling by Bone Morphogenetic Proteins (BMP) has been implicated in early lung development, adult lung homeostasis and tissue-injury repair.
+However, the precise mechanism of action and the spatio-temporal pattern of BMP-signaling during these processes remains inadequately described.
+To address this, we have utilized a transgenic line harboring a BMP-responsive eGFP-reporter allele (BRE-eGFP) to construct the first detailed spatiotemporal map of canonical BMP-pathway activation during lung development, homeostasis and adult-lung injury repair.
+We demonstrate that during the pseudoglandular stage, when branching morphogenesis progresses in the developing lung, canonical BMP-pathway is active mainly in the vascular network and the sub-epithelial smooth muscle layer of the proximal airways.
+Activation of the BMP-pathway becomes evident in epithelial compartments only after embryonic day (E) 14.5 primarily in cells negative for epithelial-lineage markers, located in the proximal portion of the airway-tree, clusters adjacent to neuro-epithelial-bodies (NEBs) and in a substantial portion of alveolar epithelial cells.
+The pathway becomes activated in isolated E12.5 mesenchyme-free distal epithelial buds cultured in Matrigel suggesting that absence of reporter activity in these regions stems from a dynamic cross-talk between endoderm and mesenchyme.
+Epithelial cells with activated BMP-pathway are enriched in progenitors capable of forming colonies in three-dimensional Matrigel cultures.
+As lung morphogenesis approaches completion, eGFP-expression declines and in adult lung its expression is barely detectable.
+However, upon tissue-injury, either with naphthalene or bleomycin, the canonical BMP-pathways is re-activated, in bronchial or alveolar epithelial cells respectively, in a manner reminiscent to early lung development and in tissue areas where reparatory progenitor cells reside.
+Our studies illustrate the dynamic activation of canonical BMP-pathway during lung development and adult lung tissue-repair and highlight its involvement in two important processes, namely, the early development of the pulmonary vasculature and the management of epithelial progenitor pools both during lung development and repair of adult lung tissue-injury.
+BACKGROUND: Dengue virus (DENV) infection is the most common mosquito-borne viral disease threatening human health around the world.
+We previously reported that DENV serotype 2 (DENV-2) induced low levels of interferon regulatory factor 3 and NF-κB activation, thus leading to reduced production of IFN-β in the early phase of infection.
+Here, we determined whether DENV infection not only hampers type I IFN activation but also cytokine production triggered by Toll-like receptor (TLR) signaling.
+METHODOLOGY/PRINCIPAL FINDINGS: We used quantitative RT-PCR and found that only low levels of IFN-β and inflammatory cytokines such as interleukin 10 (IL-10), IL-12 and tumor necrosis factor α (TNFα) mRNA were detected in DENV-2–infected bone-marrow–derived dendritic cells.
+To elucidate the molecular mechanisms underlying this suppression event, we measured NF-κB activation by p65 nuclear translocation and luciferase reporter assay and found that NF-κB activation triggered by TLR ligands was blocked by DENV-2 infection.
+CONCLUSIONS/SIGNIFICANCE: To downregulate the host innate immunity, DENV-2 by itself is a weak inducer of type I IFN and cytokines, furthermore DENV-2 can also block the TLR-triggered ERK–NF-κB activation and cytokine production.
+During the last decade, the role of wildlife in emerging pathogen transmission to domestic animals has often been pointed out.
+Conversely, far less attention has been paid to pathogen transmission from domestic animals to wildlife.
+Here, we focus on the case of game restocking, which implies the release of millions of animals worldwide each year.
+We conducted a 2-year study in the Camargue (Southern France) to investigate the influence of hand-reared Mallard releases on avian influenza virus dynamics in surrounding wildlife.
+We sampled Mallards (cloacal swabs) from several game duck facilities in 2009 and 2010 before their release.
+A very high (99%) infection rate caused by an H10N7 strain was detected in the game bird facility we sampled in 2009.
+We did not detect this strain in shot ducks we sampled, neither during the 2008/2009 nor the 2009/2010 hunting seasons.
+The H10 and N7 segments we sequenced were clearly distinct from the Australian ones but they belonged to the same large cluster as the Egyptian ones.
+We did not observe any mutation linked to increased virulence, transmission to mammals, or antiviral resistance in the H10N7 strain we identified.
+Our results indicate that the potential role of hand-reared Mallards in influenza virus epizootics must be taken into account given the likely risk of viral exchange between game bird facilities and wild habitats, owing to duck rearing conditions.
+Measures implemented to limit transmission from wildlife to domestic animals as well as measures to control transmission from domestic animals to wild ones need to be equally reinforced.
+Human bocavirus 1 (HBoV1) has been identified as one of the etiological agents of wheezing in young children with acute respiratory-tract infections.
+In this study, we have obtained the sequence of a full-length HBoV1 genome (including both termini) using viral DNA extracted from a nasopharyngeal aspirate of an infected patient, cloned the full-length HBoV1 genome, and demonstrated DNA replication, encapsidation of the ssDNA genome, and release of the HBoV1 virions from human embryonic kidney 293 cells.
+The HBoV1 virions generated from this cell line-based production system exhibits a typical icosahedral structure of approximately 26 nm in diameter, and is capable of productively infecting polarized primary human airway epithelia (HAE) from the apical surface.
+Infected HAE showed hallmarks of lung airway-tract injury, including disruption of the tight junction barrier, loss of cilia and epithelial cell hypertrophy.
+Notably, polarized HAE cultured from an immortalized airway epithelial cell line, CuFi-8 (originally derived from a cystic fibrosis patient), also supported productive infection of HBoV1.
+Thus, we have established a reverse genetics system and generated the first cell line-based culture system for the study of HBoV1 infection, which will significantly advance the study of HBoV1 replication and pathogenesis.
+BACKGROUND: Although several therapeutic options have become available for patients with Cutaneous T-cell Lymphoma (CTCL), no therapy has been curative.
+METHODOLOGY/PRINCIPAL FINDINGS: In this study, a xenograft model of CTCL was established and a recombinant adeno-associated viral serotype 8 (AAV8) vector expressing a humanized single-chain variable fragment (scFv)-Fc fusion (scFvFc or “minibody”) of anti-CCR4 monoclonal antibody (mAb) h1567 was evaluated for curative treatment.
+Human CCR4(+) tumor-bearing mice treated once with intravenous infusion of AAV8 virions encoding the h1567 (AAV8-h1567) minibody showed anti-tumor activity in vivo and increased survival.
+The AAV8-h1567 minibody notably increased the number of tumor-infiltrating Ly-6G(+) FcγRIIIa(CD16A)(+) murine neutrophils in the tumor xenografts over that of AAV8-control minibody treated mice.
+Furthermore, in CCR4(+) tumor-bearing mice co-treated with AAV8-h1567 minibody and infused with human peripheral blood mononuclear cells (PBMCs), marked tumor infiltration of human CD16A(+) CD56(+) NK cells was observed.
+The h1567 minibody also induced in vitro ADCC activity through both mouse neutrophils and human NK cells.
+CONCLUSIONS/SIGNIFICANCE: Overall, our data demonstrate that the in vivo anti-tumor activity of h1567 minibody is mediated, at least in part, through CD16A(+) immune effector cell ADCC mechanisms.
+These data further demonstrate the utility of the AAV-minibody gene transfer system in the rapid evaluation of candidate anti-tumor mAbs and the potency of h1567 as a potential novel therapy for CTCL.
+BACKGROUND: Dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin related (DC-SIGNR) can bind to the human immunodeficiency virus-1 (HIV-1) gp120 envelope glycoprotein and is thus important for the host-pathogen interaction in HIV-1 infection.
+Studies of the association between the variable number tandem repeat (VNTR) polymorphism of the DC-SIGNR gene and HIV-1 susceptibility have produced controversial results.
+METHODS AND FINDINGS: We conducted a meta-analysis of the data contained in the literature to clarify these findings.
+In total, 10 studies consisting of 2683 HIV-1 patients and 3263 controls (2130 healthy controls and 1133 HIV-1 exposed but seronegative (HESN) controls) were included.
+Odds ratios (ORs) with 95% confidence intervals (95% CIs) were assessed in the main analyses.
+By dividing the controls into two groups, healthy controls and HIV-1 exposed but seronegative (HESN) controls, we explored different genetic models to detect any association between the VNTR polymorphism and predisposition to HIV-1 infection.
+The results showed that the 5-repeat allele carriers (OR = 0.84, 95% CI = 0.73–0.96) and the 5/5 homozygous (OR = 0.68, 95% CI = 0.50–0.93) had significantly reduced risk when using the HIV-1 exposed but seronegative (HESN) as controls.
+CONCLUSIONS: Our findings demonstrate that the VNTR polymorphism of the DC-SIGNR gene is associated with a moderate effect on host susceptibility to HIV-1 infection.
+Similar to the 32-bp deletion in the chemokine receptor-5 gene (CCR5Δ32), the DC-SIGNR VNTR 5-repeat allele might have a role in resistance to HIV infection, particularly in Asian populations.
+Both innate and adaptive immunity have been shown to be important in controlling Brucella infection.
+Toll-like receptors (TLRs) represent a group of pattern recognition receptors (PRRs) that play critical roles in the host innate immune response, as well as development of adaptive immunity.
+In the current report, we investigated the role of TLR signaling in the clearance of Brucella and development of adaptive immunity in TLR2(−/−), TLR4(−/−), or MyD88(−/−) mice following aerosol exposure to B. melitensis 16 M. Consistent with previous reports, MyD88 is required for efficient clearance of Brucella from all three organs (lung, spleen, and liver).
+The results reveal Th2-skewed immune responses in TLR2(−/−) mice late in infection and support a TLR2 requirement for efficient clearance of Brucella from the lungs, but not from the spleen or liver.
+Similarly, TLR4 is required for efficient clearance of Brucella from the lung, but exhibits a minor contribution to clearance from the spleen and no demonstrable contribution to clearance from the liver.
+Lymphocyte proliferation assays suggest that the TLRs are not involved in the development of cell-mediated memory response to Brucella antigen.
+Antibody detection reveals that TLR2 and 4 are required to generate early antigen-specific IgG, but not during the late stages of infection.
+TLR2 and 4 are only transiently required for IgM production and not at all for IgA production.
+In contrast, MyD88 is essential for antigen specific IgG production late in infection, but is not required for IgM generation over the course of infection.
+Surprisingly, despite the prominent role for MyD88 in clearance from all tissues, MyD88-knockout mice express significantly higher levels of serum IgA.
+These results confirm the important role of MyD88 in controlling infection in the spleen while providing evidence of a prominent contribution to protection in other tissues.
+In addition, although TLR4 and TLR2 contribute little to control of spleen infection, a significant contribution to clearance of lung infection is described.
+BACKGROUND: The 2009 pandemic influenza A (H1N1) (PIA) virus infected large parts of the pediatric population with a wide clinical spectrum and an initially unknown complication rate.
+The aims of our study were to define clinical characteristics and outcome of pandemic influenza A (H1N1) 2009-associated hospitalizations (PIAH) in children <18 years of age.
+All hospitalized cases of children <18 years of age with laboratory-confirmed pandemic influenza A (H1N1) 2009 in the region of Wuerzburg (Northern Bavaria, Germany) between July 2009 and March 2010 were identified.
+For these children a medical chart review was performed to determine their clinical characteristics and complications.
+RESULTS: Between July 2009 and March 2010, 94 PIAH (62% males) occurred in children <18 years of age, with a median age of 7 years (IQR: 3–12 years).
+Underlying diseases and predisposing factors were documented in 40 (43%) children; obesity (n = 12, 30%), asthma (n = 10, 25%) and neurologic disorders (n = 8, 20%) were most frequently reported.
+Six (6%) children were admitted to an intensive care unit, four of them with underlying chronic diseases.
+Antisense oligonucleotides (AOs) are currently the most promising therapeutic intervention for Duchenne muscular dystrophy (DMD).
+AOs modulate dystrophin pre-mRNA splicing, thereby specifically restoring the dystrophin reading frame and generating a truncated but semifunctional dystrophin protein.
+Challenges in the development of this approach are the relatively poor systemic AO delivery and inefficient dystrophin correction in affected non-skeletal muscle tissues, including the heart.
+We have previously reported impressive heart activity including high-splicing efficiency and dystrophin restoration following a single administration of an arginine-rich cell-penetrating peptide (CPPs) conjugated to a phosphorodiamidate morpholino oligonucleotide (PMO): Pip5e-PMO.
+Here, we report studies involving single dose administration (12.5 mg/kg) of derivatives of Pip5e-PMO, consecutively assigned as Pip6-PMOs.
+These peptide-PMOs comprise alterations to the central hydrophobic core of the Pip5e peptide and illustrate that certain changes to the peptide sequence improves its activity; however, partial deletions within the hydrophobic core abolish its efficiency.
+Our data indicate that the hydrophobic core of the Pip sequences is critical for PMO delivery to the heart and that specific modifications to this region can enhance activity further.
+OBJECTIVE: This study reports the clinical characteristics and outcome of HIV-associated Penicilliummarneffei infection in northern Vietnam.
+METHODS: We conducted a retrospective chart review of all patients with laboratory confirmed Penicilliummarneffei infection admitted to the National Hospital for Tropical Diseases in Hanoi, Vietnam, between July 2006 and September 2009.
+Common clinical features were fever (92.9%), skin lesions (82.6%), hepatomegaly (61.4%), lymphadenopathy (40.2%), weight loss (59.1%) and cough (49.6%).
+Initial treatment regimens were: itraconazole or ketoconazole capsule (77.2%), amphotericin B (20.5%), and fluconazole (1.6%).
+In-hospital mortality was 12.6% and showed no significant difference in patients treated with itraconazole (or ketoconazole) and amphotericin B (p = 0.43).
+CONCLUSION: The clinical features, treatments and outcomes of HIV-associated P. marneffei infection in northern Vietnam are similar to those reported in other endemic regions.
+More patients were treated with itraconazole than amphotericin B and no significant difference in treatment outcome was observed.
+It would be of clinical value to compare the efficacy of oral itraconazole and amphotericin B in a clinical trial.
+BACKGROUND: Emergency department visits quadrupled with the initial onset and surge during the 2009 H1N1 influenza pandemic in New York City from April to June 2009.
+This time period was unique in that >90% of the circulating virus was surveyed to be the novel 2009 H1N1 influenza A according to the New York City Department of Health.
+We describe our experience using lung ultrasound in a case series of patients with respiratory symptoms requiring chest X-ray during the initial onset and surge of the 2009 H1N1 influenza pandemic.
+METHODS: We describe a case series of patients from a prospective observational cohort study of lung ultrasound, enrolling patients requiring chest X-ray for suspected pneumonia that coincided with the onset and surge of the 2009 H1N1 influenza pandemic.
+RESULTS: Twenty pandemic 2009 H1N1 influenza patients requiring chest X-ray were enrolled during this time period.
+Lung ultrasound via modified Bedside Lung Ultrasound in Emergency protocol assisted in the identification of viral pneumonia (n = 15; 75%), viral pneumonia with superimposed bacterial pneumonia (n = 7; 35%), isolated bacterial pneumonia only (n = 1; 5%), and no findings of viral or bacterial pneumonia (n = 4; 20%) in this cohort of patients.
+Based on 54 observations, interobserver agreement for distinguishing viral from bacterial pneumonia using lung ultrasound was ĸ = 0.82 (0.63 to 0.99).
+Lung ultrasound may be useful during epidemics or pandemics of acute respiratory illnesses for rapid point-of-care triage and management of patients.
+Atherosclerosis is a chronic inflammatory disease and the acute clinical manifestations represent acute on chronic inflammation.
+Neutrophil gelatinase-associated lipocalin (NGAL) is found in the granules of human neutrophils, with many diverse functions.
+The aim of this study was to evaluate the hypothesis that levels NGAL in blood may reflect the inflammatory process in various stages of coronary artery disease.
+We studied 140 patients, with SA 40, UA 35, NSTEMI 40, and STEMI 25, and 20 healthy controls.
+Significant differences were observed in median serum-NGAL(ng/mL) between patients with SA (79.23 (IQR, 37.50–100.32)), when compared with UA (108.00 (68.34–177.59)), NSTEMI (166.49 (109.24–247.20)), and STEMI (178.63 (111.18–305.92)) patients and controls (50.31 (44.30–69.78)) with significant incremental value from SA to STEMI.
+We observed a positive and significant correlation between serum-NGAL and hs-CRP (spearman coefficient rho = 0.685, P < 0.0001) as well as with neutrophil counts (r = 0.511, P < 0.0001).
+In patients with coronary artery disease serum levels of NGAL increase and reflect the degree of inflammatory process.
+In patients with acute coronary syndromes, serum levels of NGAL have high negative predictive value and reflecting the inflammatory status could show the severity of coronary clinical syndrome.
+Activity-based protein profiling (ABPP) is a newly emerging technique that uses active site-directed probes to monitor the functional status of enzymes.
+More than 200 serine hydrolases have been identified, but little is known about their specific roles.
+Serine hydrolases are involved in a variety of physiological functions, including digestion, immune response, blood coagulation, and reproduction.
+ABPP has been used recently to investigate host–virus interactions and to understand the molecular pathogenesis of virus infections.
+Monitoring the altered serine hydrolases during viral infection gives insight into the catalytic activity of these enzymes that will help to identify novel targets for diagnostic and therapeutic application.
+This review presents the usefulness of ABPP in detecting and analyzing functional annotation of host cell serine hydrolases as a result of host–virus interaction.
+The quality of bacteriophage electron microscopy appears to be on a downward course since the 1980s.
+This coincides with the introduction of digital electron microscopes and a general lowering of standards, possibly due to the disappearance of several world-class electron microscopists The most important problem seems to be poor contrast.
+Phage parts, bacterial debris, and aberrant or damaged phage particles may be misdiagnosed as bacterial viruses.
+Digital electron microscopes often seem to be operated without magnification control because this is difficult and inconvenient.
+Journals are a last-ditch defense and have a heavy responsibility in selecting competent reviewers and rejecting, or not, unsatisfactory articles.
+Complementary and alternative medicine soughts and encompasses a wide range of approaches; its use begun in ancient China at the time of Xia dynasty and in India during the Vedic period, but thanks to its long-lasting curative effect, easy availability, natural way of healing, and poor side-effects it is gaining importance throughout the world in clinical practice.
+We conducted a review describing the effects and the limits of using herbal products in chronic liver disease, focusing our attention on those most known, such as quercetin or curcumin.
+We tried to describe their pharmacokinetics, biological properties, and their beneficial effects (as antioxidant role) in metabolic, alcoholic, and viral hepatitis (considering that oxidative stress is the common pathway of chronic liver diseases of different etiology).
+The main limit of applicability of CAM comes from the lacking of randomized, placebo-controlled clinical trials giving a real proof of efficacy of those products, so that anecdotal success and personal experience are frequently the driving force for acceptance of CAM in the population.
+BACKGROUND: Death records are a rich source of data, which can be used to assist with public surveillance and/or decision support.
+However, to use this type of data for such purposes it has to be transformed into a coded format to make it computable.
+Because the cause of death in the certificates is reported as free text, encoding the data is currently the single largest barrier of using death certificates for surveillance.
+Therefore, the purpose of this study was to demonstrate the feasibility of using a pipeline, composed of a detection rule and a natural language processor, for the real time encoding of death certificates using the identification of pneumonia and influenza cases as an example and demonstrating that its accuracy is comparable to existing methods.
+RESULTS: A Death Certificates Pipeline (DCP) was developed to automatically code death certificates and identify pneumonia and influenza cases.
+The pipeline used MetaMap to code death certificates from the Utah Department of Health for the year 2008.
+The output of MetaMap was then accessed by detection rules which flagged pneumonia and influenza cases based on the Centers of Disease and Control and Prevention (CDC) case definition.
+The output from the DCP was compared with the current method used by the CDC and with a keyword search.
+Recall, precision, positive predictive value and F-measure with respect to the CDC method were calculated for the two other methods considered here.
+The two different techniques compared here with the CDC method showed the following recall/ precision results: DCP: 0.998/0.98 and keyword searching: 0.96/0.96.
+Both the keyword and the DCP can run in interactive form with modest computer resources, but DCP showed superior performance.
+CONCLUSION: The pipeline proposed here for coding death certificates and the detection of cases is feasible and can be extended to other conditions.
+This method provides an alternative that allows for coding free-text death certificates in real time that may increase its utilization not only in the public health domain but also for biomedical researchers and developers.
+Rift Valley fever virus (RVFV), belongs to genus Phlebovirus of the family Bunyaviridae, causes high rates of abortion and fetal malformation in infected ruminants as well as causing neurological disorders, blindness, or lethal hemorrhagic fever in humans.
+RVFV is classified as a category A priority pathogen and a select agent in the U.S., and currently there are no therapeutics available for RVF patients.
+NSs protein, a major virulence factor of RVFV, inhibits host transcription including interferon (IFN)-β mRNA synthesis and promotes degradation of dsRNA-dependent protein kinase (PKR).
+NSs self-associates at the C-terminus 17 aa., while NSs at aa.210–230 binds to Sin3A-associated protein (SAP30) to inhibit the activation of IFN-β promoter.
+Thus, we hypothesize that NSs function(s) can be abolished by truncation of specific domains, and co-expression of nonfunctional NSs with intact NSs will result in the attenuation of NSs function by dominant-negative effect.
+6–30, 31–55, 56–80, 81–105, 106–130, 131–155, 156–180, 181–205, 206–230, 231–248 or 249–265 lack functions of IFN–β mRNA synthesis inhibition and degradation of PKR.
+Truncated NSs were less stable in infected cells, while nuclear localization was inhibited in NSs lacking either of aa.81–105, 106–130, 131–155, 156–180, 181–205, 206–230 or 231–248.
+Furthermore, none of truncated NSs had exhibited significant dominant-negative functions for NSs-mediated IFN-β suppression or PKR degradation upon co-expression in cells infected with RVFV.
+We also found that any of truncated NSs except for intact NSs does not interact with RVFV NSs even in the presence of intact C-terminus self-association domain.
+Our results suggest that conformational integrity of NSs is important for the stability, cellular localization and biological functions of RVFV NSs, and the co-expression of truncated NSs does not exhibit dominant-negative phenotype.
+As recently pointed out by the Institute of Medicine, the existing pandemic mitigation models lack the dynamic decision support capability.
+We develop a large-scale simulation-driven optimization model for generating dynamic predictive distribution of vaccines and antivirals over a network of regional pandemic outbreaks.
+The model incorporates measures of morbidity, mortality, and social distancing, translated into the cost of lost productivity and medical expenses.
+The performance of the strategy is compared to that of the reactive myopic policy, using a sample outbreak in Fla, USA, with an affected population of over four millions.
+The comparison is implemented at different levels of vaccine and antiviral availability and administration capacity.
+Sensitivity analysis is performed to assess the impact of variability of some critical factors on policy performance.
+The model is intended to support public health policy making for effective distribution of limited mitigation resources.
+Using peptide nanoparticle technology, we have designed two novel vaccine constructs representing M2e in monomeric (Mono-M2e) and tetrameric (Tetra-M2e) forms.
+Groups of specific pathogen free (SPF) chickens were immunized intramuscularly with Mono-M2e or Tetra-M2e with and without an adjuvant.
+Two weeks after the second boost, chickens were challenged with 107.2 EID50 of H5N2 low pathogenicity avian influenza (LPAI) virus.
+Vaccinated chickens exhibited increased M2e-specific IgG responses for each of the constructs as compared to a non-vaccinated group.
+However, the vaccine construct Tetra-M2e elicited a significantly higher antibody response when it was used with an adjuvant.
+On the other hand, virus neutralization assays indicated that immune protection is not by way of neutralizing antibodies.
+The level of protection was evaluated using quantitative real time PCR at 4, 6, and 8 days post-challenge with H5N2 LPAI by measuring virus shedding from trachea and cloaca.
+The Tetra-M2e with adjuvant offered statistically significant (P < 0.05) protection against subtype H5N2 LPAI by reduction of the AI virus shedding.
+The results suggest that the self-assembling polypeptide nanoparticle shows promise as a potential platform for a development of a vaccine against AI.
+The aim of this study was to assess factors associated with increased risk perception of pandemic influenza in Australia.
+The sample consisted of 2081 Australian adults aged 16 years and older who completed a short three item pandemic influenza question module which was incorporated into the NSW Health Adult Population Health Survey during the first quarter of 2007.
+After adjusting for covariates, multivariate analysis indicated that those living in rural regions were significantly more likely to perceive a high risk that a pandemic influenza would occur, while those with poor self-rated health perceived both a high likelihood of pandemic and high concern that self/family would be directly affected were such an event to occur.
+Those who spoke a language other than English at home and those on low incomes and younger people (16–24 years) were significantly more likely to have changed the way they lived their lives due to the possibility of pandemic influenza, compared to those who spoke only English at home, middle-high income earners, and older age groups, respectively.
+This data provides an Australian population baseline against which the risk perceptions of demographic subgroups regarding the current, and potential future pandemics, can be compared and monitored.
+The 2003-2004 H5N1 highly pathogenic avian influenza (HPAI) outbreaks in Japan were the first such outbreaks in 79 years in Japan.
+Knowledge of the transmission route responsible for the HPAI outbreaks in these countries remains elusive.
+Our studies strongly suggested that field and laboratory studies focusing on mechanical transmission by blow flies should be considered to control H5N1 avian influenza outbreaks, in particular in epidemic areas, where there are high densities of different fly species throughout the year.
+In this paper, we review these field and laboratory entomological studies and discuss the possibility of blow flies transmitting H5N1 viruses.
+BACKGROUND: Prior to the availability of the specific pandemic vaccine, strategies to mitigate the impact of the disease typically involved antiviral treatment and “non-pharmaceutical” community interventions.
+However, compliance with these strategies is linked to risk perceptions, perceived severity and perceived effectiveness of the strategies.
+In 2010, we undertook a study to examine the knowledge, attitudes, risk perceptions, practices and barriers towards influenza and infection control strategies amongst domestic and international university students.
+METHODS: A study using qualitative methods that incorporated 20 semi-structured interviews was undertaken with domestic and international undergraduate and postgraduate university students based at one university in Sydney, Australia.
+Participants were invited to discuss their perceptions of influenza (seasonal vs. pandemic) in terms of perceived severity and impact, and attitudes towards infection control measures including hand-washing and the use of social distancing, isolation or cough etiquette.
+RESULTS: While participants were generally knowledgeable about influenza transmission, they were unable to accurately define what ‘pandemic influenza’ meant.
+While avian flu or SARS were mistaken as examples of past pandemics, almost all participants were able to associate the recent “swine flu” situation as an example of a pandemic event.
+Not surprisingly, it was uncommon for participants to identify university students as being at risk of catching pandemic influenza.
+Amongst those interviewed, it was felt that ‘students’ were capable of fighting off any illness.
+The participant’s nominated hand washing as the most feasible and acceptable compared with social distancing and mask use.
+CONCLUSIONS: Given the high levels of interaction that occurs in a university setting, it is really important that students are informed about disease transmission and about risk of infection.
+It may be necessary to emphasize that pandemic influenza could pose a real threat to them, that it is important to protect oneself from infection and that infection control measures can be effective.
+Microarrays have revolutionized the study of microbiology by providing a high-throughput method for examining thousands of genes with a single test and overcome the limitations of many culture-independent approaches.
+Functional gene arrays (FGA) probe a wide range of genes involved in a variety of functions of interest to microbial ecology (e.g., carbon degradation, N fixation, metal resistance) from many different microorganisms, cultured and uncultured.
+The most comprehensive FGA to date is the GeoChip array, which targets tens of thousands of genes involved in the geochemical cycling of carbon, nitrogen, phosphorus, and sulfur, metal resistance and reduction, energy processing, antibiotic resistance and contaminant degradation as well as phylogenetic information (gyrB).
+Since the development of GeoChips, many studies have been performed using this FGA and have shown it to be a powerful tool for rapid, sensitive, and specific examination of microbial communities in a high-throughput manner.
+As such, the GeoChip is well-suited for linking geochemical processes with microbial community function and structure.
+This technology has been used successfully to examine microbial communities before, during, and after in situ bioremediation at a variety of contaminated sites.
+These studies have expanded our understanding of biodegradation and bioremediation processes and the associated microorganisms and environmental conditions responsible.
+This review provides an overview of FGA development with a focus on the GeoChip and highlights specific GeoChip studies involving in situ bioremediation.
+The negative transcription regulator of the ica locus, TcaR, regulates proteins involved in the biosynthesis of poly-N-acetylglucosamine (PNAG).
+Previously, the 3D structure of TcaR in its apo form and its complex structure with several antibiotics have been analyzed.
+However, the detailed mechanism of multiple antibiotic resistance regulator (MarR) family proteins such as TcaR is unclear and only restricted on the binding ability of double-strand DNA (dsDNA).
+Here we show by electrophoretic mobility shift assay (EMSA), electron microscopy (EM), circular dichroism (CD), and Biacore analysis that TcaR can interact strongly with single-stranded DNA (ssDNA), thereby identifying a new role in MarR family proteins.
+Moreover, we show that TcaR preferentially binds 33-mer ssDNA over double-stranded DNA and inhibits viral ssDNA replication.
+In contrast, such ssDNA binding properties were not observed for other MarR family protein and TetR family protein, suggesting that the results from our studies are not an artifact due to simple charge interactions between TcaR and ssDNA.
+We anticipate that the results of this work will extend our understanding of MarR family protein and broaden the development of new therapeutic strategies for Staphylococci.
+The use of bioinformatics to integrate phenotypic and genomic data from mammalian models is well established as a means of understanding human biology and disease.
+Beyond direct biomedical applications of these approaches in predicting structure–function relationships between coding sequences and protein activities, comparative studies also promote understanding of molecular evolution and the relationship between genomic sequence and morphological and physiological specialization.
+Recently recognized is the potential of comparative studies to identify functionally significant regulatory regions and to generate experimentally testable hypotheses that contribute to understanding mechanisms that regulate gene expression, including transcriptional activity, alternative splicing and transcript stability.
+Functional tests of hypotheses generated by computational approaches require experimentally tractable in vitro systems, including cell cultures.
+Comparative sequence analysis strategies that use genomic sequences from a variety of evolutionarily diverse organisms are critical for identifying conserved regulatory motifs in the 5′-upstream, 3′-downstream and introns of genes.
+Genomic sequences and gene orthologues in the first aquatic vertebrate and protovertebrate organisms to be fully sequenced (Fugu rubripes, Ciona intestinalis, Tetraodon nigroviridis, Danio rerio) as well as in the elasmobranchs, spiny dogfish shark (Squalus acanthias) and little skate (Raja erinacea), and marine invertebrate models such as the sea urchin (Strongylocentrotus purpuratus) are valuable in the prediction of putative genomic regulatory regions.
+Data and tools resulting from these kinds of studies will contribute to understanding transcriptional regulation of biomedically important genes and provide new avenues for medical therapeutics and disease prevention.
+Contemporary basic research is rapidly revealing increasingly complex molecular regulatory networks which are often interconnected via key signal integrators.
+These connections among regulatory and catalytic networks often frustrate bioengineers as promising metabolic engineering strategies are bypassed by compensatory metabolic responses or cause unexpected, undesired outcomes such as apoptosis, product protein degradation or inappropriate post- translational modification.
+Therefore, for metabolic engineering to achieve greater success in mammalian cell culture processes and to become important for future applications such as gene therapy and tissue engineering, this technology must be enhanced to allow simultaneous, in cases conditional, reshaping of metabolic pathways to access difficult-to-attain cell states.
+Recent advances in this new territory of multigene metabolic engineering are intimately linked to the development of multicistronic expression technology which allows the simultaneous, and in some cases, regulated expression of several genes in mammalian cells.
+Here we review recent achievements in multicistronic expression technology in view of multigene metabolic engineering.
+Disabled Infectious Single Cycle (DISC) HSV-2 has been cultured in the complimentary cell line CR2 to provide high titre bulk material suitable for the purification of the virus as a live viral vaccine.
+CR2 cells are cultured on the microcarrier Cytodex-1 at 5 g l-1 in small scale (1 l) and larger scale (15 l) reactors.
+The cells are infected at an MOI of 0.01 pfu cell-1 and the culture harvested 60–72 h later.
+The infected cells are removed from the microcarriers by the addition of a hypotonic saline and the virus released by low-pressure disruption techniques.
+On 15 April and 17 April 2009, novel swineorigin influenza A (H1N1) virus was identifi ed in specimens obtained from two epidemiologically unlinked patients in the United States.
+The ongoing outbreak of novel H1N1 2009 influenza (swine influenza) has caused more than 3,99,232 laboratory confi rmed cases of pandemic influenza H1N1 and over 4735 deaths globally.
+This novel 2009 influenza virus designated as H1N1 A/swine/California/04/2009 virus is not zoonotic swine flu and is transmitted from person to person and has higher transmissibility then that of seasonal influenza viruses.
+In India the novel H1N1 virus infection has been reported from all over the country.
+A total of 68,919 samples from clinically suspected persons have been tested for influenza A H1N1 across the country and 13,330 (18.9%) of them have been found positive with 427 deaths.
+At the All India Institute of Medical Sciences, New Delhi India, we tested 1096 clinical samples for the presence of novel H1N1 influenza virus and seasonal influenza viruses.
+Of these 1096 samples, 194 samples (17.7%) were positive for novel H1N1 influenza virus and 197 samples (18%) were positive for seasonal influenza viruses.
+During outbreaks of emerging infectious diseases accurate and rapid diagnosis is critical for minimizing further spread through timely implementation of appropriate vaccines and antiviral treatment.
+Since the symptoms of novel H1N1 influenza infection are not specifi c, laboratory confi rmation of suspected cases is of prime importance.
+The last decade has seen the emergence of two new influenza A subtypes and they have become a cause of concern for the global community.
+These are the highly pathogenic H5N1 influenza A virus (H5N1) and the Pandemic 2009 influenza H1N1 virus.
+Since 2003 the H5N1 virus has caused widespread disease and death in poultry, mainly in south East Asia and Africa.
+In humans the number of cases infected with this virus is few but the mortality has been about 60%.
+The second influenza virus, the pandemic H1N1 2009, emerged in Mexico in March this year.
+This virus acquired the ability for sustained human to human spread and within a few months spread throughout the world and infected over 4 lakh individuals.
+The symptoms of infection with this virus are similar to seasonal influenza but it currently affecting younger individuals more often.
+Both these new influenza viruses are currently circulating and have different clinical and epidemiological characteristics.
+The 1918 influenza pandemic was one of the most virulent strains of influenza in history.
+Phylogenic evidence of the novel H1N1 strain of influenza discovered in Mexico last spring (2009) links it to the 1918 influenza strain.
+With information gained from analyzing viral genetics, public health records and advances in medical science we can confront the 2009 H1N1 influenza on a global scale.
+The paper analyses the causes and characteristics of a pandemic, and major issues in controlling the spread of the disease.
+Wide public vaccination and open communication between government and health sciences professionals will be an essential and vital component in managing the 2009 H1N1 pandemic and any future pandemics.
+Complex interactions between effector T cells and Foxp3(+) regulatory T cells (Treg) contribute to clinical outcomes in cancer, and autoimmune and infectious diseases.
+We and others have also shown that Tregs express T-bet and IFN-γ at sites of Th1 inflammation and that IL-12 induces IFN-γ production by Tregs in vitro.
+To investigate whether loss of immunosuppression occurs when IFN-γ is expressed by Tregs we treated mouse lymphocyte cultures with IL-12.
+We further showed that IL-12 increased IL-2R expression on Tconv and CD8 T cells, diminished its expression on Tregs and decreased IL-2 production by Tconv and CD8 T cells.
+Additionally, we showed that treatment with a second cytokine, IL-27, decreased IL-2 expression without augmenting Tconv and CD8 T cell proliferation.
+Together, these results show that IL-12 has multiple effects that modify the balance between Tregs and non-Tregs and support an important role for relative levels of IL-2R but not for IFN-γ expression in IL-12-mediated reversal of Treg immunosuppression.
+BACKGROUND: Tumor necrosis factor (TNF) and TNF receptor superfamily (TNFR)-mediated immune response play an essential role in the pathogenesis of severe sepsis.
+Studies examining associations of TNF and lymphotoxin-α (LTA) single nucleotide polymorphisms (SNPs) with severe sepsis have produced conflicting results.
+The objective of this study was to investigate whether genetic variation in TNF, LTA, TNFRSF1A and TNFRSF1B was associated with susceptibility to or death from severe sepsis in Chinese Han population.
+METHODOLOGY/PRINCIPAL FINDINGS: Ten SNPs in TNF, LTA, TNFRSF1A and TNFRSF1B were genotyped in samples of patients with severe sepsis (n = 432), sepsis (n = 384) and healthy controls (n = 624).
+Our results showed that rs1800629, a SNP in the promoter region of TNF, was significantly associated with risk for severe sepsis.
+The minor allele frequency of rs1800629 was significantly higher in severe sepsis patients than that in both healthy controls (P(adj) = 0.00046, odds ratio (OR)(adj) = 1.92) and sepsis patients (P(adj) = 0.002, OR(adj) = 1.56).
+Further, we investigated the correlation between rs1800629 genotypes and TNF-α concentrations in peripheral blood mononuclear cells (PBMCs) of healthy volunteers exposed to lipopolysaccharides (LPS) ex vivo, and the association between rs1800629 and TNF-α serum levels in severe sepsis patients.
+After exposure to LPS, the TNF-α concentration in culture supernatants of PBMCs was significantly higher in the subjects with AA+AG genotypes than that with GG genotype (P = 0.007).
+Moreover, in patients with severe sepsis, individuals with AA+AG genotypes had significantly higher TNF-α serum concentrations than those with GG genotype (P(adj) = 0.02).
+However, there were no significant associations between SNPs in the four candidate genes and 30 day mortality for patients with severe sepsis.
+CONCLUSIONS/SIGNIFICANCE: Our findings suggested that the functional TNF gene SNP rs1800629 was strongly associated with susceptibility to severe sepsis, but not with lethality in Chinese Han population.
+BACKGROUND: Anterior gradient homolog 2 (AGR2) is a functional protein with critical roles in a diverse range of biological systems, including vertebrate tissue development, inflammatory tissue injury responses, and cancer progression.
+Clinical studies have shown that the AGR2 protein is overexpressed in a wide range of human cancers, including carcinomas of the esophagus, pancreas, breast, prostate, and lung, making the protein as a potential cancer biomarker.
+However, the general biochemical functions of AGR2 in human cells remain undefined, and the signaling mechanisms that drive AGR2 to inhibit p53 are still not clearly illustrated.
+Therefore, it is of great interest to develop molecular probes specifically recognizing AGR2 for its detection and for the elucidation of AGR2-associated molecular mechanism.
+METHODOLOGY/PRINCIPAL FINDINGS: Through a bead-based and flow cytometry monitored SELEX technology, we have identified a group of DNA aptamers that can specifically bind to AGR2 with K(d) values in the nanomolar range after 14 rounds of selections.
+Aptamer C14B was chosen to further study, due to its high binding affinity and specificity.
+The optimized and shortened C14B1 has special G-rich characteristics, and the G-rich region of this binding motif was further characterized to reveal an intramolecular parallel G-quadruplex by CD spectroscopy and UV spectroscopy.
+Our experiments confirmed that the stability of the G-quadruplex structure was strongly dependent on the nature of the monovalent ions and the formation of G-quadruplex structure was also important for the binding capacity of C14B1 to the target.
+Furthermore, we have designed a kind of allosteric molecule beacon (aMB) probe for selective and sensitive detection of AGR2.
+CONCLUSION/SIGNIFICANCE: In this work, we have developed new aptamer probes for specific recognition of the AGR2.
+Structural study have identified that the binding motif of aptamer is an intramolecular parallel G-quadruplex structure and its structure and binding affinity are strongly dependent on the nature of the monovalent ion.
+This aptamer probe has great potential to serve as a useful tool for early diagnosis and prognosis of cancer and for fundamental research to elucidate the biochemical functions of AGR2.
+Dendritic cells (DCs) play an important role in orchestrating immune responses by either mediating protective immune responses or inducing antigen specific tolerance.
+Previous studies demonstrated that the fms-like tyrosine kinase 3 receptor (Flt3) and its ligand (Flt3L) play an essential role in the regulation of DC commitment and development.
+Here, we report a synergic effect between Flt3L and low-dose rapamycin (Rapa) in the protection of allograft rejction.
+It was found that Flt3L combined with Rapa significantly prolonged murine cardiac allograft survival time as compared with that of untreated recipients or recipients treated with Rapa or Flt3L alone.
+Mechanistic studies revealed that Flt3L combined with low-dose of Rapa induced the generation of tolerogenic DCs along with the production of CD25(+) Foxp3(+) regulatory T cells and IL-10 secretion.
+We also observed enhanced autophagy in the cardiac allograft, which could be another asset contributing to the enhanced allograft survival.
+All together, these data suggest that Flt3L combined with low-dose of Rapa could be an effective therapeutic approach to induce tolerance in clinical setting of transplantation.
+To study renalase's expression and distribution in renal tissues and cells, renalase coded DNA vaccine was constructed, and anti-renalase monoclonal antibodies were produced using DNA immunization and hybridoma technique, followed by further investigation with immunological testing and western blotting to detect the expression and distribution of renalase among the renal tissue and cells.
+Further studies with anti-renalase monoclonal antibody showed that renalase expressed in glomeruli, tubule, mesangial cells, podocytes, renal tubule epithelial cells and its cells supernatant.
+Renalase is wildly expressed in kidney, including glomeruli, tubule, mesangial cells, podocytes and tubule epithelial cells, and may be secreted by tubule epithelial cells primarily.
+In contrast to contamination by microbes and mycoplasma, which can be relatively easily detected, viral contamination present a serious threat because of the difficulty in detecting some viruses and the lack of effective methods of treating infected cell cultures.
+cytopathic effect)which are detectable by microscopy some viral contaminations result in the integration of the viral genome as provirus, this causes no visual evidence, by means of modification of the cellular morphology.
+Virus production from such cell lines, are potentially dangerous for other cell cultures (in research labs)by cross contaminations, or for operators and patients (in the case of the production of injectable biologicals) because of potential infection.
+The only way to keep cell cultures for research, development, and the biotech industry virus-free is the prevention of such contaminations.
+Cell cultures can become contaminated by the following means: firstly, they may already be contaminated as primary cultures (because the source of the cells was already infected), secondly, they were contaminated due to the use of contaminated raw materials, or thirdly, they were contaminated via an animal passage.
+This overview describes the problems and risks associated with viral contaminations in animal cell culture, describes the origins of these contaminations as well as the most important virsuses associated with viral contaminations in cell culture.
+In addition, ways to prevent viral contaminations as well as measures undertaken to avoid and assess risks for viral contaminations as performed in the biotech industry are briefly described.
+To efficiently infect humans, DENV must evade or inhibit fundamental elements of the innate immune system, namely the type I interferon response.
+DENV circumvents the host immune response by expressing proteins that antagonize the cellular innate immunity.
+We have recently documented the inhibition of type I IFN production by the proteolytic activity of DENV NS2B3 protease complex in human monocyte derived dendritic cells (MDDCs).
+In the present report we identify the human adaptor molecule STING as a target of the NS2B3 protease complex.
+We characterize the mechanism of inhibition of type I IFN production in primary human MDDCs by this viral factor.
+Conversely, mutated versions of STING that cannot be cleaved by the DENV NS2B3 protease induced higher levels of type I IFN after infection with DENV.
+Additionally, we show that DENV NS2B3 is not able to degrade the mouse version of STING, a phenomenon that severely restricts the replication of DENV in mouse cells, suggesting that STING plays a key role in the inhibition of DENV infection and spread in mice.
+Vaccines based on live viruses are attractive because they are immunogenic, cost-effective, and can be delivered by multiple routes.
+However, live virus vaccines also cause reactogenic side effects such as fever, myalgia, and injection site pain that have reduced their acceptance in the clinic.
+Several recent studies have linked vaccine-induced reactogenic side effects to production of the pro-inflammatory cytokine interleukin-1β (IL-1β) in humans.
+Our objective was therefore to determine whether IL-1β contributed to pathology after immunization with recombinant vesicular stomatitis virus (rVSV) vaccine vectors, and if so, to identify strategies by which IL-1β mediated pathology might be reduced without compromising immunogenicity.
+We found that an rVSV vaccine induced local and systemic production of IL-1β in vivo, and that accumulation of IL-1β correlated with acute pathology after rVSV immunization.
+rVSV-induced pathology was reduced in mice deficient in the IL-1 receptor Type I, but the IL-1R−/− mice were fully protected from lethal rechallenge with a high dose of VSV.
+This result demonstrated that IL-1 contributed to reactogenicity of the rVSV, but was dispensable for induction of protective immunity.
+The amount of IL-1β detected in mice deficient in either caspase-1 or the inflammasome adaptor molecule ASC after rVSV immunization was not significantly different than that produced by wild type animals, and caspase-1−/− and ASC−/− mice were only partially protected from rVSV-induced pathology.
+Those data support the idea that some of the IL-1β expressed in vivo in response to VSV may be activated by a caspase-1 and ASC-independent mechanism.
+Together these results suggest that rVSV vectors engineered to suppress the induction of IL-1β, or signaling through the IL-1R would be less reactogenic in vivo, but would retain their immunogenicity and protective capacity.
+Such rVSV would be highly desirable as either vaccine vectors or oncolytic therapies, and would likely be better tolerated in human vaccinees.
+How IAV balances the replication and transcription of its multiple genome segments is not understood.
+We developed a dual competition assay based on the co-transfection of firefly or Gaussia luciferase-encoding genome segments together with plasmids encoding IAV polymerase subunits and nucleoprotein.
+At limiting amounts of polymerase subunits, expression of the firefly luciferase segment was negatively affected by the presence of its Gaussia luciferase counterpart, indicative of competition between reporter genome segments.
+This competition could be relieved by increasing or decreasing the relative amounts of firefly or Gaussia reporter segment, respectively.
+The balance between the luciferase expression levels was also affected by the identity of the untranslated regions (UTRs) as well as segment length.
+In general it appeared that genome segments displaying inherent higher expression levels were more efficient competitors of another segment.
+When natural genome segments were tested for their ability to suppress reporter gene expression, shorter genome segments generally reduced firefly luciferase expression to a larger extent, with the M and NS segments having the largest effect.
+The balance between different reporter segments was most dramatically affected by the introduction of UTR panhandle-stabilizing mutations.
+Furthermore, only reporter genome segments carrying these mutations were able to efficiently compete with the natural genome segments in infected cells.
+This competition is probably most apparent early during infection, when limiting amounts of polymerases are present, and may contribute to the regulation of segment-specific replication and transcription.
+For a long time, oral disease is one of the major problems of the public health for its high prevalence and incidence throughout the world, which is especially true for low-income populations.
+These changes have significant impact on and have been reflected in oral disease trends in China.
+It focuses on changes in the nation's demographic profile, in the marketplace, the oral disease status and trends.
+The paper also suggests some possible measures and strategies for bettering oral health in future China.
+Little is known about the challenges faced in this setting with regard to critical care medicine.
+The aim of this study was to analyse and categorise the diagnosis and outcomes of 1,774 patients admitted to a hospital intensive care unit (ICU) in a low-income country over a 7-year period.
+We also assessed the country’s ICU bed capacity and described the challenges faced in dealing with critically ill patients in this setting.
+FINDINGS: A retrospective audit was conducted in a general ICU in a university hospital in Uganda.
+Demographic data, admission diagnosis, and ICU length of stay were recorded for the 1,774 patients who presented to the ICU in the period January 2003 to December 2009.
+Males accounted for 56.5% of the study population; 92.8% were indigenous, and 42.9% were referrals from upcountry units.
+The highest mortality rate (44%) was recorded in 2004 and the lowest (33.2%) in 2005.
+Sepsis, ARDS, traumatic brain injuries and HIV related conditions were the most frequent admission diagnoses.
+A telephonic survey determined that there are 33 adult ICU beds in the whole country.
+CONCLUSIONS: Mortality was 40.1%, with sepsis, head injury, acute lung injury and HIV/AIDS the most common admission diagnoses.
+Prioritising infectious diseases poses a challenge to ensuring that critical care is an essential part of the health care package in Uganda.
+We have developed a simple electrochemical biosensing strategy for the label-free diagnosis of hepatitis B virus (HBV) on a gold electrode surface.
+Gold-binding polypeptide (GBP) fused with single-chain antibody (ScFv) against HBV surface antigen (HBsAg), in forms of genetically engineered protein, was utilized.
+This GBP-ScFv fusion protein can directly bind onto the gold substrate with the strong binding affinity between the GBP and the gold surface, while the recognition site orients toward the sample for target binding at the same time.
+Furthermore, this one-step immobilization strategy greatly simplifies a fabrication process without any chemical modification as well as maintaining activity of biological recognition elements.
+This system allows specific immobilization of proteins and sensitive detection of targets, which were verified by surface plasmon resonance analysis and successfully applied to electrochemical cyclic voltammetry and impedance spectroscopy upto 0.14 ng/mL HBsAg.
+Although many studies provide strong evidence supporting the development of HCV virus-like particle (VLP)-based vaccines, the fact that heterologous viral vectors and/or multiple dosing regimes are required to induce protective immunity indicates that it is necessary to improve their immunogenicity.
+In this study, we have evaluated the use of an anionic self-adjuvanting lipopeptide containing the TLR2 agonist Pam(2)Cys (E(8)Pam(2)Cys) to enhance the immunogenicity of VLPs containing the HCV structural proteins (core, E1 and E2) of genotype 1a.
+While co-formulation of this lipopeptide with VLPs only resulted in marginal improvements in dendritic cell (DC) uptake, its ability to concomitantly induce DC maturation at very small doses is a feature not observed using VLPs alone or in the presence of an aluminium hydroxide-based adjuvant (Alum).
+Dramatically improved VLP and E2-specific antibody responses were observed in VLP+E(8)Pam(2)Cys vaccinated mice where up to 3 doses of non-adjuvanted or traditionally alum-adjuvanted VLPs was required to match the antibody titres obtained with a single dose of VLPs formulated with this lipopeptide.
+This result also correlated with significantly higher numbers of specific antibody secreting cells that was detected in the spleens of VLP+E(8)Pam(2)Cys vaccinated mice and greater ability of sera from these mice to neutralise the binding and uptake of VLPs by Huh7 cells.
+Moreover, vaccination of HLA-A2 transgenic mice with this formulation also induced better VLP-specific IFN-γ-mediated responses compared to non-adjuvanted VLPs but comparable levels to that achieved when coadministered with complete freund’s adjuvant.
+These results suggest overall that the immunogenicity of HCV VLPs can be significantly improved by the addition of this novel adjuvant by targeting their delivery to DCs and could therefore constitute a viable vaccine strategy for the treatment of HCV.
+BACKGROUND: As a result of rapidly growing human populations, intensification of livestock production and increasing exploitation of wildlife habitats for animal agriculture, the interface between wildlife, livestock and humans is expanding, with potential impacts on both domestic animal and human health.
+Wild animals serve as reservoirs for many viruses, which may occasionally result in novel infections of domestic animals and/or the human population.
+Given this background, we used metagenomics to investigate the presence of viral pathogens in sera collected from bushpigs (Potamochoerus larvatus), a nocturnal species of wild Suid known to move between national parks and farmland, in Uganda.
+RESULTS: Application of 454 pyrosequencing demonstrated the presence of Torque teno sus virus (TTSuV), porcine parvovirus 4 (PPV4), porcine endogenous retrovirus (PERV), a GB Hepatitis C–like virus, and a Sclerotinia hypovirulence-associated-like virus in sera from the bushpigs.
+PCR assays for each specific virus combined with Sanger sequencing revealed two TTSuV-1 variants, one TTSuV-2 variant as well as PPV4 in the serum samples and thereby confirming the findings from the 454 sequencing.
+CONCLUSIONS: Using a viral metagenomic approach we have made an initial analysis of viruses present in bushpig sera and demonstrated for the first time the presence of PPV4 in a wild African Suid.
+In this study, we used African green monkey kidney cells (Vero) and Ixodes scapularis tick cells (ISE6) to compare virus-induced changes in mammalian and arthropod cells.
+Using confocal microscopy, transmission electron microscopy (TEM), and electron tomography (ET), we examined viral protein distribution and the ultrastructural changes that occur during TBFV infection.
+Within host cells, flaviviruses cause complex rearrangement of cellular membranes for the purpose of virus replication.
+Virus infection was accompanied by a marked expansion in endoplasmic reticulum (ER) staining and markers for TBFV replication were localized mainly to the ER in both cell lines.
+TEM of Vero cells showed membrane-bound vesicles enclosed in a network of dilated, anastomosing ER cisternae.
+In acutely and persistently infected ISE6 cells, membrane proliferation and vesicles were also noted; however, the extent of membrane expansion and the abundance of vesicles were lower and no viral particles were observed.
+Tubular profiles were far more prevalent in persistently infected ISE6 cells than in acutely infected cells.
+By ET, tubular profiles, in persistently infected tick cells, had a cross-sectional diameter of 60–100 nm, reached up to 800 nm in length, were closed at the ends, and were often arranged in fascicle-like bundles, shrouded with ER membrane.
+Our experiments provide analysis of viral protein localization within the context of both mammalian and arthropod cell lines as well as both acute and persistent arthropod cell infection.
+Additionally, we show for the first time 3D flavivirus infection in a vector cell line and the first ET of persistent flavivirus infection.
+The remarkable advance in sequencing technology and the rising interest in medical and environmental microbiology, biotechnology, and synthetic biology resulted in a deluge of published microbial genomes.
+Yet, genome annotation, comparison, and modeling remain a major bottleneck to the translation of sequence information into biological knowledge, hence computational analysis tools are continuously being developed for rapid genome annotation and interpretation.
+Among the earliest, most comprehensive resources for prokaryotic genome analysis, the SEED project, initiated in 2003 as an integration of genomic data and analysis tools, now contains >5,000 complete genomes, a constantly updated set of curated annotations embodied in a large and growing collection of encoded subsystems, a derived set of protein families, and hundreds of genome-scale metabolic models.
+Until recently, however, maintaining current copies of the SEED code and data at remote locations has been a pressing issue.
+To allow high-performance remote access to the SEED database, we developed the SEED Servers (http://www.theseed.org/servers): four network-based servers intended to expose the data in the underlying relational database, support basic annotation services, offer programmatic access to the capabilities of the RAST annotation server, and provide access to a growing collection of metabolic models that support flux balance analysis.
+The SEED servers offer open access to regularly updated data, the ability to annotate prokaryotic genomes, the ability to create metabolic reconstructions and detailed models of metabolism, and access to hundreds of existing metabolic models.
+This work offers and supports a framework upon which other groups can build independent research efforts.
+Large integrations of genomic data represent one of the major intellectual resources driving research in biology, and programmatic access to the SEED data will provide significant utility to a broad collection of potential users.
+Circulative transmission of viruses in the Luteoviridae, such as cereal yellow dwarf virus (CYDV), requires a series of precisely orchestrated interactions between virus, plant, and aphid proteins.
+Natural selection has favored these viruses to be retained in the phloem to facilitate acquisition and transmission by aphids.
+We show that treatment of infected oat tissue homogenate with sodium sulfite reduces transmission of the purified virus by aphids.
+However, treated virions were not acquired by aphids through the hindgut epithelial cells and were not transmitted when injected directly into the hemocoel.
+Analysis of virus preparations using nanoflow liquid chromatography coupled to tandem mass spectrometry revealed a number of host plant proteins co-purifying with viruses, some of which were lost following sodium sulfite treatment.
+Using targeted mass spectrometry, we show data suggesting that several of the virus-associated host plant proteins accumulated to higher levels in aphids that were fed on CYDV-infected plants compared to healthy plants.
+We propose two hypotheses to explain these observations, and these are not mutually exclusive: (a) that sodium sulfite treatment disrupts critical virion-host protein interactions required for aphid transmission, or (b) that host infection with CYDV modulates phloem protein expression in a way that is favorable for virus uptake by aphids.
+Importantly, the genes coding for the plant proteins associated with virus may be examined as targets in breeding cereal crops for new modes of virus resistance that disrupt phloem-virus or aphid-virus interactions.
+INTRODUCTION: While there is much information about the burden of influenza A(H1N1)pdm09 in North America, little data exist on its burden in South America.
+METHODS: During April to December 2009, we actively searched for persons with severe acute respiratory infection and influenza-like illness (ILI) in three sentinel cities.
+We estimated the number of case-patients that would have tested positive for influenza by multiplying the number of untested case-patients by the proportion who tested positive.
+We estimated rates by dividing the estimated number of case-patients by the census population after adjusting for the proportion of case-patients with missing illness onset information and ILI case-patients who visited physicians multiple times for one illness event.
+RESULTS: We estimated that the influenza A(H1N1)pdm09 mortality rate per 100,000 person-years (py) ranged from 1.5 among persons aged 5–44 years to 5.6 among persons aged ≥65 years.
+A(H1N1)pdm09 hospitalization rates per 100,000 py ranged between 26.9 among children aged <5 years to 41.8 among persons aged ≥65 years.
+Influenza A(H1N1)pdm09 ILI rates per 100 py ranged between 1.6 among children aged <5 to 17.1 among persons aged 45–64 years.
+While 9 (53%) of 17 influenza A(H1N1)pdm09 decedents with available data had obesity and 7 (17%) of 40 had diabetes, less than 4% of surviving influenza A(H1N1)pdm09 case-patients had these pre-existing conditions (p≤0.001).
+CONCLUSION: Influenza A(H1N1)pdm09 caused a similar burden of disease in Argentina as in other countries.
+The bacterium is the causative agent of C. difficile infection (CDI), for which the symptoms can range from a mild diarrhea to potentially fatal pseudomembranous colitis and toxic megacolon.
+Endospore formation in Firmicutes, including C. difficile, is governed by the key regulator for sporulation, Spo0A.
+In Bacillus subtilis, this transcription factor is also directly or indirectly involved in various other cellular processes.
+Here, we report that C. difficile Spo0A shows a high degree of similarity to the well characterized B. subtilis protein and recognizes a similar binding sequence.
+We find that the laboratory strain C. difficile 630Δerm contains an 18bp-duplication near the DNA-binding domain compared to its ancestral strain 630.
+In vitro binding assays using purified C-terminal DNA binding domain of the C. difficile Spo0A protein demonstrate direct binding to DNA upstream of spo0A and sigH, early sporulation genes and several other putative targets.
+In vitro binding assays suggest that the gene encoding the major clostridial toxin TcdB may be a direct target of Spo0A, but supernatant derived from a spo0A negative strain was no less toxic towards Vero cells than that obtained from a wild type strain, in contrast to previous reports.
+These results identify for the first time direct (putative) targets of the Spo0A protein in C. difficile and make a positive effect of Spo0A on production of the large clostridial toxins unlikely.
+Human hepatitis B virus (HBV) infection and HBV-related diseases remain a major public health problem.
+The pre-S1 domain of the large envelope protein is a key determinant for receptor(s) binding.
+Here, by using near zero distance photo-cross-linking and tandem affinity purification, we revealed that the receptor-binding region of pre-S1 specifically interacts with sodium taurocholate cotransporting polypeptide (NTCP), a multiple transmembrane transporter predominantly expressed in the liver.
+Silencing NTCP inhibited HBV and HDV infection, while exogenous NTCP expression rendered nonsusceptible hepatocarcinoma cells susceptible to these viral infections.
+Moreover, replacing amino acids 157–165 of nonfunctional monkey NTCP with the human counterpart conferred its ability in supporting both viral infections.
+Two glycoproteins, hemagglutinin (HA) and neuraminidase (NA), on the surface of influenza viruses play crucial roles in transfaunation, membrane fusion and the release of progeny virions.
+To explore the distribution of N-glycosylation sites (glycosites) in these two glycoproteins, we collected and aligned the amino acid sequences of all the HA and NA subtypes.
+Two glycosites were located at HA0 cleavage sites and fusion peptides and were strikingly conserved in all HA subtypes, while the remaining glycosites were unique to their subtypes.
+Two to four conserved glycosites were found in the stalk domain of NA, but these are affected by the deletion of specific stalk domain sequences.
+Another highly conserved glycosite appeared at the top center of tetrameric global domain, while the others glycosites were distributed around the global domain.
+Here we present a detailed investigation of the distribution and the evolutionary pattern of the glycosites in the envelope glycoproteins of IVs, and further focus on the H5N1 virus and conclude that the glycosites in H5N1 have become more complicated in HA and less influential in NA in the last five years.
+Niclosamide is approved for human use against helminthic infections, and has anti-neoplastic and antiviral effects.
+Here, we show that niclosamide, which is a weak lipophilic acid inhibited infection with pH-dependent human rhinoviruses (HRV) and influenza virus.
+Structure-activity studies showed that antiviral efficacy and endolysosomal pH neutralization co-tracked, and acidification of the extracellular medium bypassed the virus entry block.
+Niclosamide did not affect the vacuolar H(+)-ATPase, but neutralized coated vesicles or synthetic liposomes, indicating a proton carrier mode-of-action independent of any protein target.
+This report demonstrates that physico-chemical interference with host pathways has broad range antiviral effects, and provides a proof of concept for the development of host-directed antivirals.
+Cholera toxin (CT) from Vibrio cholerae is responsible for the majority of the symptoms of the diarrheal disease cholera.
+CT is a heterohexameric protein complex with a 240-residue A subunit and a pentameric B subunit of identical 103-residue B polypeptides.
+The A subunit is proteolytically cleaved within a disulfide-linked loop to generate the A1 and A2 fragments.
+The B subunit of wild-type (wt) CT binds 5 cell surface ganglioside GM(1) (GM(1)) molecules, and the toxin-GM(1) complex traffics from the plasma membrane (PM) retrograde through endosomes and the Golgi apparatus to the endoplasmic reticulum (ER).
+Clustering of GM(1) by multivalent toxin binding can structurally remodel cell membranes in ways that may assist toxin uptake and retrograde trafficking.
+We have recently found, however, that CT may traffic from the PM to the ER by exploiting an endogenous glycosphingolipid pathway (A.
+Here we formally tested this idea by creating homogenous chimeric holotoxins with defined numbers of native GM(1) binding sites from zero (nonbinding) to five (wild type).
+We found that a single GM(1) binding site is sufficient for activity of the holotoxin.
+Therefore, remodeling of cell membranes by mechanisms that involve multivalent binding of toxin to GM(1) receptors is not essential for toxicity of CT.
+BACKGROUND: Serological studies for influenza infection and vaccine response often involve microneutralization and hemagglutination inhibition assays to evaluate neutralizing antibodies against human and avian influenza viruses, including H5N1.
+We have previously characterized lentiviral particles pseudotyped with H5-HA (H5pp) and validated an H5pp-based assay as a safe alternative for high-throughput serological studies in BSL-2 facilities.
+Here we show that H5-HAs from different clades do not always give rise to efficient production of H5pp and the underlying mechanisms are addressed.
+METHODOLOGY/FINDINGS: We have carried out mutational analysis to delineate the molecular determinants responsible for efficient packaging of HA from A/Cambodia/40808/2005 (H5Cam) and A/Anhui/1/2005 (H5Anh) into H5pp.
+Our results demonstrate that a single A134V mutation in the 130-loop of the receptor binding domain is sufficient to render H5Anh the ability to generate H5Anh-pp efficiently, whereas the reverse V134A mutation greatly hampers production of H5Cam-pp.
+Although protein expression in total cell lysates is similar for H5Anh and H5Cam, cell surface expression of H5Cam is detected at a significantly higher level than that of H5Anh.
+We further demonstrate by several independent lines of evidence that the behaviour of H5Anh can be explained by a stronger binding to sialic acid receptors implicating residue 134.
+CONCLUSIONS: We have identified a single A134V mutation as the molecular determinant in H5-HA for efficient incorporation into H5pp envelope and delineated the underlying mechanism.
+The reduced binding to sialic acid receptors as a result of the A134V mutation not only exerts a critical influence in pseudotyping efficiency of H5-HA, but has also an impact at the whole virus level.
+Because A134V substitution has been reported as a naturally occurring mutation in human host, our results may have implications for the understanding of human host adaptation of avian influenza H5N1 viruses.
+BACKGROUND: Exposure to particulate matter (PM) is a significant risk factor for increased cardiopulmonary morbidity and mortality.
+However, PM is proinflammatory to the endothelium and increases vascular permeability in vitro and in vivo via ROS generation.
+OBJECTIVES: We explored the role of tight junction proteins as targets for PM-induced loss of lung endothelial cell (EC) barrier integrity and enhanced cardiopulmonary dysfunction.
+METHODS: Changes in human lung EC monolayer permeability were assessed by Transendothelial Electrical Resistance (TER) in response to PM challenge (collected from Ft. McHenry Tunnel, Baltimore, MD, particle size >0.1 μm).
+RESULTS: PM exposure induced tight junction protein Zona occludens-1 (ZO-1) relocation from the cell periphery, which was accompanied by significant reductions in ZO-1 protein levels but not in adherens junction proteins (VE-cadherin and β-catenin).
+N-acetyl-cysteine (NAC, 5 mM) reduced PM-induced ROS generation in ECs, which further prevented TER decreases and atteneuated ZO-1 degradation.
+PM also mediated intracellular calcium mobilization via the transient receptor potential cation channel M2 (TRPM2), in a ROS-dependent manner with subsequent activation of the Ca(2+)-dependent protease calpain.
+Overexpression of ZO-1 attenuated PM-induced endothelial barrier disruption and vascular hyperpermeability in vivo and in vitro.
+CONCLUSIONS: These results demonstrate that PM induces marked increases in vascular permeability via ROS-mediated calcium leakage via activated TRPM2, and via ZO-1 degradation by activated calpain.
+Nicotinic acetylcholine receptor alpha7 expression was examined in the developing and adult auditory system using mice that were modified through homologous recombination to coexpress either GFP (alpha7GFP) or Cre (alpha7Cre), respectively.
+The expression of alpha7GFP is first detected at embryonic (E) day E13.5 in cells of the spiral prominence.
+By E14.5, sensory regions including the putative outer hair cells and Deiters' cells express alpha7GFP as do solitary efferent fibers.
+This pattern diminishes after E16.5 in a basal to apex progression, as Hensen's cells and cells of the spiral ligament acquire alpha7GFP expression.
+At birth and thereafter alpha7GFP also identifies a subset of spiral ganglion cells whose processes terminate on inner hair cells.
+In addition to cochlear structures, there is strong expression of alpha7GFP by cells of the central auditory pathways including the ventral posterior cochlear nucleus, lateral lemniscus, central inferior colliculus, and the medial geniculate nucleus.
+Our findings suggest that alpha7 expression by both neuronal and non-neuronal cells has the potential to impact multiple auditory functions through mechanisms that are not traditionally attributed to this receptor.
+BACKGROUND: Porcine reproductive and respiratory syndrome (PRRS) is one of the most significant swine diseases worldwide.
+Despite its relevance, serum biomarkers associated with early-onset viral infection, when clinical signs are not detectable and the disease is characterized by a weak anti-viral response and persistent infection, have not yet been identified.
+Surface-enhanced laser desorption ionization time of flight mass spectrometry (SELDI-TOF MS) is a reproducible, accurate, and simple method for the identification of biomarker proteins related to disease in serum.
+This work describes the SELDI-TOF MS analyses of sera of 60 PRRSV-positive and 60 PRRSV-negative, as measured by PCR, asymptomatic Large White piglets at weaning.
+Sera with comparable and low content of hemoglobin (< 4.52 μg/mL) were fractionated in 6 different fractions by anion-exchange chromatography and protein profiles in the mass range 1–200 kDa were obtained with the CM10, IMAC30, and H50 surfaces.
+RESULTS: A total of 200 significant peaks (p < 0.05) were identified in the initial discovery phase of the study and 47 of them were confirmed in the validation phase.
+A panel of 14 discriminatory peaks identified in fraction 1 (pH = 9), on the surface CM10, and acquired at low focus mass provided a serum protein profile diagnostic pattern that enabled to discriminate between PRRSV-positive and -negative piglets with a sensitivity and specificity of 77% and 73%, respectively.
+CONCLUSIONS: SELDI-TOF MS profiling of sera from PRRSV-positive and PRRSV-negative asymptomatic piglets provided a proteomic signature with large scale diagnostic potential for early identification of PRRSV infection in weaning piglets.
+Furthermore, SELDI-TOF protein markers represent a refined phenotype of PRRSV infection that might be useful for whole genome association studies.
+BACKGROUND: Analysis of human monoclonal antibodies (mAbs) developed from HIV-1 infected donors have enormously contributed to the identification of neutralization sensitive epitopes on the HIV-1 envelope glycoprotein.
+The third variable region (V3) is a crucial target on gp120, primarily due to its involvement in co-receptor (CXCR4 or CCR5) binding and presence of epitopes recognized by broadly neutralizing antibodies.
+METHODS: Thirty-three HIV-1 seropositive drug naive patients (18 males and 15 females) within the age range of 20–57 years (median = 33 years) were recruited in this study for mAb production.
+The mAbs were selected from EBV transformed cultures with conformationally constrained Cholera-toxin-B containing V3C (V3C-CTB) fusion protein.
+We tested the mAbs for their binding with HIV-1 derived proteins and peptides by ELISA and for neutralization against HIV-1 viruses by TZM-bl assays.
+RESULTS: We isolated three anti-V3 mAbs, 277, 903 and 904 from the cells of different individuals.
+The ELISA binding revealed a subtype-C and subtype-A specific binding of antibody 277 and 903 while mAb 904 exhibited cross reactivity also with subtype-B V3.
+The antibodies displayed high and low neutralizing activity against 2/5 tier 1 and 1/6 tier 2 viruses respectively.
+Overall, we observed a resistance of the tier 2 viruses to neutralization by the anti-V3 mAbs, despite the exposure of the epitopes recognized by these antibodies on two representative native viruses (Du156.12 and JRFL), suggesting that the affinity of mAb might equally be crucial for neutralization, as the epitope recognition.
+CONCLUSIONS: Our study suggests that the anti-V3 antibodies derived from subtype-C infected Indian patients display neutralization potential against tier 1 viruses while such activity may be limited against more resistant tier 2 viruses.
+Defining the fine epitope specificities of these mAbs and further experimental manipulations will be helpful in identification of epitopes, unique to clade C or shared with non-clade C viruses, in context of V3 region.
+As a new human immunodeficiency virus type 1 (HIV-1) vaccine approach, the live-attenuated measles virus (MV) Schwarz vaccine strain was genetically engineered to express the F4 antigen (MV1-F4).
+F4 is a fusion protein comprising HIV-1 antigens p17 and p24, reverse transcriptase and Nef.
+Cynomolgus macaques were intramuscularly immunized one or three times with the highest dose of MV1-F4 intended for clinical use, the reference (Schwarz) measles vaccine or saline, and monitored clinically for 11 or 85 days.
+Toxicological parameters included local and systemic clinical signs, organ weights, haematology, clinical and gross pathology and histopathology.
+Both vaccines were well tolerated, with no morbidity, clinical signs or gross pathological findings observed.
+Mean spleen weights were increased after three doses of either vaccine, which corresponded with increased numbers and/or sizes of germinal centers.
+Either vaccine virus replicated preferentially in secondary lymphoid organs and to a lesser extent in epithelium-rich tissues (e.g., intestine, urinary bladder and trachea) and the liver.
+At the expected peak of viremia, viral RNA was detected in some biological fluid samples from few animals immunized with either vaccine, but none of these samples contained infectious virus.
+In conclusion, no shedding of infectious viral particles was identified in cynomolgus monkeys after injection of MV1-F4 or Schwarz measles vaccines.
+Furthermore, no toxic effect in relation to the MV vaccination was found with these vaccines in this study.
+During the replication of human cytomegalovirus (HCMV) genome, the viral DNA polymerase subunit UL44 plays a key role, as by binding both DNA and the polymerase catalytic subunit it confers processivity to the holoenzyme.
+However, several lines of evidence suggest that UL44 might have additional roles during virus life cycle.
+To shed light on this, we searched for cellular partners of UL44 by yeast two-hybrid screenings.
+Intriguingly, we discovered the interaction of UL44 with Ubc9, an enzyme involved in the covalent conjugation of SUMO (Small Ubiquitin-related MOdifier) to cellular and viral proteins.
+We found that UL44 can be extensively sumoylated not only in a cell-free system and in transfected cells, but also in HCMV-infected cells, in which about 50% of the protein resulted to be modified at late times post-infection, when viral genome replication is accomplished.
+Mass spectrometry studies revealed that UL44 possesses multiple SUMO target sites, located throughout the protein.
+Remarkably, we observed that binding of UL44 to DNA greatly stimulates its sumoylation both in vitro and in vivo.
+In addition, we showed that overexpression of SUMO alters the intranuclear distribution of UL44 in HCMV-infected cells, and enhances both virus production and DNA replication, arguing for an important role for sumoylation in HCMV life cycle and UL44 function(s).
+These data report for the first time the sumoylation of a viral processivity factor and show that there is a functional interplay between the HCMV UL44 protein and the cellular sumoylation system.
+BACKGROUND: Exposure to mechanical ventilation enhances lung injury in response to various stimuli, such as bacterial endotoxin (LPS).
+The Fas/FasL system is a receptor ligand system that has dual pro-apoptotic and pro-inflammatory functions and has been implicated in the pathogenesis of lung injury.
+In this study we test the hypothesis that a functioning Fas/FasL system is required for the development of lung injury in mechanically ventilated mice.
+METHODS: C57BL/6 (B6) and Fas-deficient lpr mice were exposed to either intra-tracheal PBS followed by spontaneous breathing or intra-tracheal LPS followed by four hours mechanical ventilation with tidal volumes of 10 mL/kg, respiratory rate of 150 breaths per minute, inspired oxygen 0.21 and positive end expiratory pressure (PEEP) of 3 cm of water.
+RESULTS: Compared with the B6 mice, the lpr mice showed attenuation of the neutrophilic response as measured by decreased numbers of BAL neutrophils and lung myeloperoxidase activity.
+Interestingly, the B6 and lpr mice had similar concentrations of pro-inflammatory cytokines, including CXCL1 (KC), and similar measurements of permeability and apoptosis.
+However, the B6 mice showed greater deposition of anti-KC:KC immune complexes in the lungs, as compared with the lpr mice.
+CONCLUSIONS: We conclude that a functioning Fas/FasL system is required for full neutrophilic response to LPS in mechanically ventilated mice.
+Vertebrate interferon-induced transmembrane (IFITM) genes have been demonstrated to have extensive and diverse functions, playing important roles in the evolution of vertebrates.
+Despite observance of their functionality, the evolutionary dynamics of this gene family are complex and currently unknown.
+Here, we performed detailed evolutionary analyses to unravel the evolutionary history of the vertebrate IFITM family.
+A total of 174 IFITM orthologous genes and 112 pseudogenes were identified from 27 vertebrate genome sequences.
+The vertebrate IFITM family can be divided into immunity-related IFITM (IR-IFITM), IFITM5 and IFITM10 sub-families in phylogeny, implying origins from three different progenitors.
+In general, vertebrate IFITM genes are located in two loci, one containing the IFITM10 gene, and the other locus containing IFITM5 and various numbers of IR-IFITM genes.
+No gene duplication or positive selection was found in IFITM5 sub-family, implying the functional conservation of IFITM5 in vertebrate evolution, which is involved in bone formation.
+No IFITM5 locus was identified in the marmoset genome, suggesting a potential association with the tiny size of this monkey.
+Functional divergence was detected between the two groups, and five IFITM10-like genes from frog were dispersed into the two groups.
+Both gene duplication and positive selection were observed in aquatic vertebrate IFITM10-like genes, indicating that IFITM10 might be associated with the adaptation to aquatic environments.
+A large number of lineage- and species-specific gene duplications were observed in IR-IFITM sub-family and positive selection was detected in IR-IFITM of primates and rodents.
+Because primates have experienced a long history of viral infection, such rapid expansion and positive selection suggests that the evolution of primate IR-IFITM genes is associated with broad-spectrum antiviral activity.
+Health research programs targeting the population of Gabon and Equatorial Africa at the International Center for Medical Research in Franceville (CIRMF), Gabon, have evolved during the years since its inception in 1979 in accordance with emerging diseases.
+Since the reemergence of Ebola virus in Central Africa, the CIRMF “Emerging Viral Disease Unit” developed diagnostic tools and epidemiologic strategies and transfers of such technology to support the response of the National Public Health System and the World Health Organization to epidemics of Ebola virus disease.
+The Unit carries out a unique investigation program on the natural history of the filoviruses, emergence of epidemics, and Ebola virus pathogenesis.
+In addition, academic training is provided at all levels to regional and international students covering emerging conditions (host factors, molecular biology, genetics) that favor the spread of viral diseases.
+BACKGROUND/OBJECTIVE: Describing transmissibility parameters of past pandemics from diverse geographic sites remains critical to planning responses to future outbreaks.
+We characterize the transmissibility of influenza A(H1N1)pdm09 (hereafter pH1N1) in South Africa during 2009 by estimating the serial interval (SI), the initial effective reproductive number (initial R(t)) and the temporal variation of R(t).
+METHODS: We make use of data from a central registry of all pH1N1 laboratory-confirmed cases detected throughout South Africa.
+Whenever date of symptom onset is missing, we estimate it from the date of specimen collection using a multiple imputation approach repeated 100 times for each missing value.
+We apply a likelihood-based method (method 1) for simultaneous estimation of initial R(t) and the SI; estimate initial R(t) from SI distributions established from prior field studies (method 2); and the Wallinga and Teunis method (method 3) to model the temporal variation of R(t).
+During the period of exponential growth of the epidemic (June 21 to August 3, 2009), we simultaneously estimate a mean R(t) of 1.47 (95% CI: 1.30–1.72) and mean SI of 2.78 days (95% CI: 1.80–3.75) (method 1).
+Field studies found a mean SI of 2.3 days between primary cases and laboratory-confirmed secondary cases, and 2.7 days when considering both suspected and confirmed secondary cases.
+Incorporating the SI estimate from field studies using laboratory-confirmed cases, we found an initial R(t) of 1.43 (95% CI: 1.38–1.49) (method 2).
+The mean R(t) peaked at 2.91 (95% CI: 0.85–2.91) on June 21, as the epidemic commenced, and R(t)>1 was sustained until August 22 (method 3).
+CONCLUSIONS: Transmissibility characteristics of pH1N1 in South Africa are similar to estimates reported by countries outside of Africa.
+The authors contend that all-hazards, or capabilities-based planning, in which a set of core capabilities applicable to numerous types of events is developed, is a more efficient way to achieve general health care system emergency preparedness than scenario-based planning.
+Essentially, the core of what is necessary to plan for and respond to one kind of disaster (e.g.
+a biologic event) is also necessary for planning and responding to other types of disasters, allowing for improvements in planning and maximizing efficiencies.
+have advanced the science of health care emergency preparedness through their consideration of 490 measures to assess preparedness, a shorter set of validated preparedness measures would support the dual goals of accountability and improved outcomes and could provide the basis for determining which actions in the name of preparedness really matter.
+BACKGROUND: Critical illness due to 2009 H1N1 influenza has been characterized by respiratory complications, including acute lung injury (ALI) or acute respiratory distress syndrome (ARDS), and associated with high mortality.
+We studied the severity, outcomes, and hospital charges of patients with ALI/ARDS secondary to pandemic influenza A infection compared with ALI and ARDS from other etiologies.
+METHODS: A retrospective review was conducted that included patients admitted to the Cleveland Clinic MICU with ALI/ARDS and confirmed influenza A infection, and all patients admitted with ALI/ARDS from any other etiology from September 2009 to March 2010.
+An itemized list of individual hospital charges was obtained for each patient from the hospital billing office and organized by billing code into a database.
+Continuous data that were normally distributed are presented as the mean ± SD and were analyzed by the Student’s t test.
+The chi-square and Fisher exact tests were used to evaluate differences in proportions between patient subgroups.
+RESULTS: Forty-five patients were studied: 23 in the H1N1 group and 22 in the noninfluenza group.
+Mean ± SD age was similar (44 ± 13 and 51 ± 17 years, respectively, p = 0.15).
+H1N1 patients had lower APACHE III scores (66 ± 20 vs. 89 ± 32, p = 0.015) and had higher Pplat and PEEP on days 1, 3, and 14.
+SOFA scores over the first 2 weeks in the ICU indicate more severe organ failure in the noninfluenza group (p = 0.017).
+Hospital mortality was significantly higher in the noninfluenza group (77 vs. 39%, p = 0.016).
+The noninfluenza group tended to have higher overall charges, including significantly higher cost of blood products in the ICU.
+CONCLUSIONS: ALI/ARDS secondary to pandemic influenza infection is associated with more severe respiratory compromise but has lower overall acuity and better survival rates than ALI/ARDS due to other causes.
+Higher absolute charges in the noninfluenza group are likely due to underlying comorbid medical conditions.
+BACKGROUND: The gp90 protein of avian reticuloendotheliosis-associated virus (REV-A) is an important envelope glycoprotein, which is responsible for inducing protective antibody immune responses in animals.
+B-cell epitopes on the gp90 protein of REV have not been well studied and reported.
+METHODS AND RESULTS: This study describes the identification of a linear B-cell epitope on the gp90 protein by screening a phage-displayed 12-mer random peptide library with the neutralizing monoclonal antibody (mAb) A9E8 directed against the gp90.
+Further identification of the displayed B cell epitope was conducted using a set of truncated peptides expressed as GST fusion proteins and the Western blot results indicated that (213)SVQYHPL(219) was the minimal determinant of the linear B cell epitope recognized by the mAb A9E8.
+Moreover, an eight amino acid peptide SVQYHPLA was proven to be the minimal unit of the epitope with the maximal binding activity to mAb A9E8.
+The REV-A-positive chicken serum reacted with the minimal linear epitopes in Western blot, revealing the importance of the eight amino acids of the epitope in antibody-epitope binding activity.
+Furthermore, we found that the epitope is a common motif shared among REV-A and other members of REV group.
+CONCLUSIONS AND SIGNIFICANCE: We identified (213)SVQYHPL(219) as a gp90-specific linear B-cell epitope recognized by the neutralizing mAb A9E8.
+The results in this study may have potential applications in development of diagnostic techniques and epitope-based marker vaccines against REV-A and other viruses of the REV group.
+The mode of infection transmission has profound implications for effective containment by public health interventions.
+Although, “respiratory droplet” transmission was generally regarded as the primary mode of transmission, the relative importance of large ballistic droplets and fine particle aerosols that remain suspended in air for more than a few seconds was never resolved.
+This review examines evidence from the history of variolation, data on mucosal infection collected in the last decades of smallpox transmission, aerosol measurements, animal models, reports of smallpox lung among healthcare workers, and the epidemiology of smallpox regarding the potential importance of fine particle aerosol mediated transmission.
+I introduce briefly the term anisotropic infection to describe the behavior of Variola major in which route of infection appears to have altered the severity of disease.
+Many protozoan parasites have evolved a cyst lifecycle stage that provides it with increased protection from environmental degradation as well as endogenous host mechanisms of attack.
+In the case of Toxoplasma gondii, these cysts are predominantly found in the immune protected brain making clearance of the parasite more difficult and resulting in a lifelong infection.
+Currently, little is known about the nature of the immune response stimulated by the presence of these cysts or how they are able to propagate.
+Despite a dominant Th1 immune response during Toxoplasma infection there exists a population of alternatively activated macrophages (AAMØ) in the infected CNS.
+These cells are capable of cyst lysis via the production of AMCase as revealed by live imaging, and this chitinase is necessary for protective immunity within the CNS.
+These data demonstrate chitinase activity in the brain in response to a protozoan pathogen and provide a novel mechanism to facilitate cyst clearance during chronic infections.
+This study presents a novel computer-assisted detection (CAD) system for automatically detecting and precisely quantifying abnormal nodular branching opacities in chest computed tomography (CT), termed tree-in-bud (TIB) opacities by radiology literature.
+The developed CAD system in this study is based on 1) fast localization of candidate imaging patterns using local scale information of the images, and 2) Möbius invariant feature extraction method based on learned local shape and texture properties of TIB patterns.
+For fast localization of candidate imaging patterns, we use ball-scale filtering and, based on the observation of the pattern of interest, a suitable scale selection is used to retain only small size patterns.
+Once candidate abnormality patterns are identified, we extract proposed shape features from regions where at least one candidate pattern occupies.
+The comparative evaluation of the proposed method with commonly used CAD methods is presented with a dataset of 60 chest CTs (laboratory confirmed 39 viral bronchiolitis human parainfluenza CTs and 21 normal chest CTs).
+The quantitative results are presented as the area under the receiver operator characteristics curves and a computer score (volume affected by TIB) provided as an output of the CAD system.
+In addition, a visual grading scheme is applied to the patient data by three well-trained radiologists.
+Interobserver and observer–computer agreements are obtained by the relevant statistical methods over different lung zones.
+Experimental results demonstrate that the proposed CAD system can achieve high detection rates with an overall accuracy of 90.96%.
+Moreover, correlations of observer–observer [Formula: see text] , [Formula: see text] and observer–CAD agreements [Formula: see text] , [Formula: see text] validate the feasibility of the use of the proposed CAD system in detecting and quantifying TIB patterns.
+Whether mannose-binding lectin deficiency is associated with acute exacerbations of chronic obstructive pulmonary disease is debated.
+METHODS: Participants in a study designed to determine if azithromycin taken daily for one year decreased acute exacerbations had serum mannose-binding lectin concentrations measured at the time of enrollment.
+The prevalence of mannose-binding lectin deficiency ranged from 0.5% to 52.2%, depending on how deficiency was defined.
+No differences in the prevalence of deficiency were observed with respect to any demographic variable assessed, and no differences were observed in time to first exacerbation, rate of exacerbations, or percentage of subjects requiring hospitalization for exacerbations in those with deficiency versus those without, regardless of how deficiency was defined.
+CONCLUSION: In a large sample of subjects with chronic obstructive pulmonary disease selected for having an increased risk of experiencing an acute exacerbation of chronic obstructive pulmonary disease, only 1.9% had mannose-binding lectin concentrations below the normal range and we found no association between mannose-binding lectin concentrations and time to first acute exacerbation or frequency of acute exacerbations during one year of prospective follow-up.
+It has been nearly a century since the early description of microglia by Rio-Hortega; since then many more biological and pathological features of microglia have been recognized.
+Today, microglia are generally considered to be beneficial to homeostasis at the resting state through their abilities to survey the environment and phagocytose debris.
+However, when activated microglia assume diverse phenotypes ranging from fully inflamed, which involves the release of many pro-inflammatory cytokines, to alternatively activated, releasing anti-inflammatory cytokines or neurotrophins, the consequences to neurons can range from detrimental to supportive.
+Due to the different experimental sets and conditions, contradictory results have been obtained regarding the controversial question of whether microglia are “good” or “bad.” While it is well understood that the dual roles of activated microglia depend on specific situations, the underlying mechanisms have remained largely unclear, and the interpretation of certain findings related to diverse microglial phenotypes continues to be problematic.
+In this review we discuss the functions of microglia in neuronal survival and neurogenesis, the crosstalk between microglia and surrounding cells, and the potential factors that could influence the eventual manifestation of microglia.
+BACKGROUND: Salmonellosis in water buffalo (Bubalus bubalis) calves is a widespread disease characterized by severe gastrointestinal lesions, profuse diarrhea and severe dehydration, occasionally exhibiting a systemic course.
+Several Salmonella serovars seem to be able to infect water buffalo, but Salmonella isolates collected from this animal species have been poorly characterized.
+in water buffalo calves affected by lethal gastroenteritis was assessed, and a polyphasic characterization of isolated strains of S. Typhimurium was performed.
+RESULTS: The microbiological analysis of the intestinal contents obtained from 248 water buffalo calves affected by lethal gastroenteritis exhibited a significant prevalence of Salmonella spp.
+The 13 S. Typhimurium isolates were all associated with enterocolitis characterized by severe damage of the intestine, and only sporadically isolated with another possible causative agent responsible for gastroenteritis, such as Cryptosporidium spp., Rotavirus or Clostridium perfringens.
+Other Salmonella isolates were mostly isolated from minor intestinal lesions, and often (78% of cases) isolated with other microorganisms, mainly toxinogenic Escherichia coli (35%), Cryptosporidium spp.
+The S. Typhimurium strains were characterized by phage typing and further genotyped by polymerase chain reaction (PCR) detection of 24 virulence genes.
+Three monophasic S. Typhimurium (B:4,12:i:-) isolates were also found and characterized, displaying three different phage types and three different virulotypes.
+The molecular characterization was extended to the 7 S. Muenster and 7 S. Give isolates collected, indicating the existence of different virulotypes also within these serovars.
+Three representative strains of S. Typhimurium were tested in vivo in a mouse model of mixed infection.
+The most pathogenic strain was characterized by a high number of virulence factors and the presence of the locus agfA, coding for a thin aggregative fimbria.
+CONCLUSIONS: These results provide evidence that Salmonella is frequently associated with gastroenteritis in water buffalo calves, particularly S. Typhimurium.
+Moreover, the variety in the number and distribution of different virulence markers among the collected S. Typhimurium strains suggests that within this serovar there are different pathotypes potentially responsible for different clinical syndromes.
+BACKGROUND: Cerebral malaria (CM) and severe malarial anemia (SMA) are the most serious life-threatening clinical syndromes of Plasmodium falciparum infection in childhood.
+Therefore it is important to understand the pathology underlying the development of CM and SMA, as opposed to uncomplicated malaria (UM).
+Different host responses to infection are likely to be reflected in plasma proteome-patterns that associate with clinical status and therefore provide indicators of the pathogenesis of these syndromes.
+METHODS AND FINDINGS: Plasma and comprehensive clinical data for discovery and validation cohorts were obtained as part of a prospective case-control study of severe childhood malaria at the main tertiary hospital of the city of Ibadan, an urban and densely populated holoendemic malaria area in Nigeria.
+Plasma proteome-patterns accurately distinguished children with CM and with SMA from those with UM, and from healthy or severely ill malaria-negative children.
+CONCLUSIONS: We report that an accurate definition of the major childhood malaria syndromes can be achieved using plasma proteome-patterns.
+Our proteomic data can be exploited to understand the pathogenesis of the different childhood severe malaria syndromes.
+Motivation: Laboratory RNA structure determination is demanding and costly and thus, computational structure prediction is an important task.
+Single sequence methods for RNA secondary structure prediction are limited by the accuracy of the underlying folding model, if a structure is supported by a family of evolutionarily related sequences, one can be more confident that the prediction is accurate.
+Results: A comparative pseudoknot prediction method called DotKnot-PW is introduced based on structural comparison of secondary structure elements and H-type pseudoknot candidates.
+DotKnot-PW outperforms other methods from the literature on a hand-curated test set of RNA structures with experimental support.
+Availability: DotKnot-PW and the RNA structure test set are available at the web site http://dotknot.csse.uwa.edu.au/pw.
+The genetic similarity observed among species is normally attributed to the existence of a common ancestor.
+However, a growing body of evidence suggests that the exchange of genetic material is not limited to the transfer from parent to offspring but can also occur through horizontal transfer (HT).
+Transposable elements (TEs) are DNA fragments with an innate propensity for HT; they are mobile and possess parasitic characteristics that allow them to exist and proliferate within host genomes.
+However, horizontal transposon transfer (HTT) is not easily detected, primarily because the complex TE life cycle can generate phylogenetic patterns similar to those expected for HTT events.
+The increasingly large number of new genome projects, in all branches of life, has provided an unprecedented opportunity to evaluate the TE content and HTT events in these species, although a standardized method of HTT detection is required before trends in the HTT rates can be evaluated in a wide range of eukaryotic taxa and predictions about these events can be made.
+Thus, we propose a straightforward hypothesis test that can be used by TE specialists and nonspecialists alike to discriminate between HTT events and natural TE life cycle patterns.
+We also discuss several plausible explanations and predictions for the distribution and frequency of HTT and for the inherent biases of HTT detection.
+Finally, we discuss some of the methodological concerns for HTT detection that may result in the underestimation and overestimation of HTT rates during eukaryotic genome evolution.
+This study was to prepare a mannosylated lycorine lipid nano-emulsion formulation (M-LYC-OA-LNEs) for the aim of achieving tumor targeting delivery of lycorine (LYC) .
+The low lipophilicity of LYC made it hard to be dispersed into lipid nano-emulsions (LNEs).
+M-LYC-OA-LNEs and uncoated lycorine-oleic acid loaded lipid nano-emulsions (LYC-OA-LNEs) were prepared by solvent injection method and characterized by transmission electron microscopy (TEM), particle size, polydispersity index, zeta-potential and entrapment efficiency analysis.
+The in vitro cellular uptake and growth inhibition activity studies were performed on A549 cell lines.
+The cellular uptake study showed that coated LNEs were preferably taken up by A549 cells than uncoated LNEs.
+The effective test by MTT assay showed better growth inhibition activity of M-LYC-OA-LNEs on A549 cell lines when compared with LYC-OA-LNEs and blank LNEs.
+These results demonstrated that M-LYC-OA-LNEs could be a promising formulation for tumor targeting delivery of LYC with the potential of being applied in the diagnosis and treatment of cancer.
+BACKGROUND: The role of demographic factors, climatic conditions, school cycles, and connectivity patterns in shaping the spatio-temporal dynamics of pandemic influenza is not clearly understood.
+Here we analyzed the spatial, age and temporal evolution of the 2009 A/H1N1 influenza pandemic in Chile, a southern hemisphere country covering a long and narrow strip comprising latitudes 17°S to 56°S.
+METHODS: We analyzed the dissemination patterns of the 2009 A/H1N1 pandemic across 15 regions of Chile based on daily hospitalizations for severe acute respiratory disease and laboratory confirmed A/H1N1 influenza infection from 01-May to 31-December, 2009.
+We explored the association between timing of pandemic onset and peak pandemic activity and several geographical and demographic indicators, school vacations, climatic factors, and international passengers.
+We also estimated the reproduction number (R) based on the growth rate of the exponential pandemic phase by date of symptoms onset, estimated using maximum likelihood methods.
+RESULTS: While earlier pandemic onset was associated with larger population size, there was no association with connectivity, demographic, school or climatic factors.
+In contrast, there was a latitudinal gradient in peak pandemic timing, representing a 16-39-day lag in disease activity from the southern regions relative to the northernmost region (P < 0.001).
+Geographical differences in latitude of Chilean regions, maximum temperature and specific humidity explained 68.5% of the variability in peak timing (P = 0.01).
+In addition, there was a decreasing gradient in reproduction number from south to north Chile (P < 0.0001).
+The regional mean R estimates were 1.6-2.0, 1.3-1.5, and 1.2-1.3 for southern, central and northern regions, respectively, which were not affected by the winter vacation period.
+CONCLUSIONS: There was a lag in the period of most intense 2009 pandemic influenza activity following a South to North traveling pattern across regions of Chile, significantly associated with geographical differences in minimum temperature and specific humidity.
+The latitudinal gradient in timing of pandemic activity was accompanied by a gradient in reproduction number (P < 0.0001).
+Intensified surveillance strategies in colder and drier southern regions could lead to earlier detection of pandemic influenza viruses and improved control outcomes.
+BACKGROUND: Recombinatorial cloning using the Gateway(TM) technology has been the method of choice for high-throughput omics projects, resulting in the availability of entire ORFeomes in Gateway(TM) compatible vectors.
+The MultiSite Gateway(TM) system allows combining multiple genetic fragments such as promoter, ORF and epitope tag in one single reaction.
+To date, this technology has not been accessible in the yeast Saccharomyces cerevisiae, one of the most widely used experimental systems in molecular biology, due to the lack of appropriate destination vectors.
+RESULTS: Here, we present a set of three-fragment MultiSite Gateway(TM) destination vectors that have been developed for gene expression in S. cerevisiae and that allow the assembly of any promoter, open reading frame, epitope tag arrangement in combination with any of four auxotrophic markers and three distinct replication mechanisms.
+As an example of its applicability, we used yeast three-hybrid to provide evidence for the assembly of a ternary complex of plant proteins involved in jasmonate signalling and consisting of the JAZ, NINJA and TOPLESS proteins.
+CONCLUSION: Our vectors make MultiSite Gateway(TM) cloning accessible in S. cerevisiae and implement a fast and versatile cloning method for the high-throughput functional analysis of (heterologous) proteins in one of the most widely used model organisms for molecular biology research.
+Attachment of CDV hemagglutinin protein (CDV-H) to this receptor facilitates fusion and virus entry in cooperation with the fusion protein (CDV-F).
+We investigated whether CDV strains co-evolved in the large, homogeneous domestic dog population exhibited specialist traits, and strains adapted to the heterogeneous environment of smaller populations of different carnivores exhibited generalist traits.
+Comparison of amino acid sequences of the SLAM binding region revealed higher similarity between sequences from Canidae species than to sequences from other carnivore families.
+Using an in vitro assay, we quantified syncytia formation mediated by CDV-H proteins from dog and non-dog CDV strains in cells expressing dog, lion or cat SLAM.
+CDV-H proteins from dog strains produced significantly higher values with cells expressing dog SLAM than with cells expressing lion or cat SLAM.
+CDV-H proteins from strains of non-dog species produced similar values in all three cell types, but lower values in cells expressing dog SLAM than the values obtained for CDV-H proteins from dog strains.
+By experimentally changing one amino acid (Y549H) in the CDV-H protein of one dog strain we decreased expression of specialist traits and increased expression of generalist traits, thereby confirming its functional importance.
+A virus titer assay demonstrated that dog strains produced higher titers in cells expressing dog SLAM than cells expressing SLAM of non-dog hosts, which suggested possible fitness benefits of specialization post-cell entry.
+We provide in vitro evidence for the expression of specialist and generalist traits by CDV strains, and fitness trade-offs across carnivore host environments caused by antagonistic pleiotropy.
+Pentraxin 3 (PTX3) is a soluble pattern recognition receptor which is classified as a long-pentraxin in the pentraxin family.
+It is known to play an important role in innate immunity, inflammatory regulation, and female fertility.
+Neutrophils store PTX3 in neutrophil-specific granules and then the stored PTX3 is released and localizes in neutrophil extracellular traps (NETs).
+Although certain NET components have been identified, such as histones and anti-microbial proteins, the detailed mechanisms by which NETs localize, as well as capture and kill microbes, have not been fully elucidated.
+In severe infectious diseases such as sepsis, the circulating PTX3 concentration increases greatly (up to 100 ng/mL, i.e., up to 100-fold of the normal level).
+Even though it is clearly implied that PTX3 plays a protective role in sepsis and certain other disorders, the detailed mechanisms by which it does so remain unclear.
+A proteomic study of PTX3 ligands in septic patients revealed that PTX3 forms a complex with certain NET component proteins.
+This suggests a role for PTX3 in which it facilitates the efficiency of anti-microbial protein pathogen clearance by interacting with both pathogens and anti-microbial proteins.
+We discuss the possible relationships between PTX3 and NET component proteins in the host protection afforded by the innate immune response.
+The PTX3 complex has the potential to be a highly useful diagnostic marker of sepsis and other inflammatory diseases.
+In addition to its surface glycoprotein (GP(1,2)), Ebola virus (EBOV) directs the production of large quantities of a truncated glycoprotein isoform (sGP) that is secreted into the extracellular space.
+The generation of secreted antigens has been studied in several viruses and suggested as a mechanism of host immune evasion through absorption of antibodies and interference with antibody-mediated clearance.
+In this study, we immunized mice with DNA constructs expressing GP(1,2) and/or sGP, and demonstrate that sGP can efficiently compete for anti-GP(12) antibodies, but only from mice that have been immunized by sGP.
+We term this phenomenon “antigenic subversion”, and propose a model whereby sGP redirects the host antibody response to focus on epitopes which it shares with membrane-bound GP(1,2), thereby allowing it to absorb anti-GP(1,2) antibodies.
+Unexpectedly, we found that sGP can also subvert a previously immunized host's anti-GP(1,2) response resulting in strong cross-reactivity with sGP.
+This finding is particularly relevant to EBOV vaccinology since it underscores the importance of eliciting robust immunity that is sufficient to rapidly clear an infection before antigenic subversion can occur.
+Antigenic subversion represents a novel virus escape strategy that likely helps EBOV evade host immunity, and may represent an important obstacle to EBOV vaccine design.
+Nucleic acid amplification techniques are commonly used currently to diagnose viral diseases and manage patients with this kind of illnesses.
+These techniques have had a rapid but unconventional route of development during the last 30 years, with the discovery and introduction of several assays in clinical diagnosis.
+The increase in the number of commercially available methods has facilitated the use of this technology in the majority of laboratories worldwide.
+This technology has reduced the use of some other techniques such as viral culture based methods and serological assays in the clinical virology laboratory.
+Moreover, nucleic acid amplification techniques are now the methods of reference and also the most useful assays for the diagnosis in several diseases.
+The introduction of these techniques and their automation provides new opportunities for the clinical laboratory to affect patient care.
+The main objectives in performing nucleic acid tests in this field are to provide timely results useful for high-quality patient care at a reasonable cost, because rapid results are associated with improvements in patients care.
+The use of amplification techniques such as polymerase chain reaction, real-time polymerase chain reaction or nucleic acid sequence-based amplification for virus detection, genotyping and quantification have some advantages like high sensitivity and reproducibility, as well as a broad dynamic range.
+This review is an up-to-date of the main nucleic acid techniques and their clinical applications, and special challenges and opportunities that these techniques currently provide for the clinical virology laboratory.
+BACKGROUND: Swine influenza (H1N1) is a very contagious respiratory infection and World Health Organization (WHO) has raised the alert level to phase 6 (pandemic).
+The study of clinical and laboratory manifestations as well as radiologic imaging findings helps in its early diagnosis.
+OBJECTIVES: The aim of this study was to evaluate the imaging findings of patients with documented H1N1 infection referred to our center.
+PATIENTS AND METHODS: Thirty-one patients (16 men) with documented H1N1 infection were included in our study.
+The initial radiography obtained from the patients was reviewed regarding pattern (consolidation, ground glass, nodules and reticulation), distribution (focal, multifocal, and diffuse) and the lung zones involved.
+Seventeen (54.8%) patients had co-existing condition (eight respiratory, five cardiovascular, two immunodeficiency, two cancer, four others).
+The most common abnormality was consolidation (12/31; 38.7%) in the peripheral region (11/31; 35.5%) followed by peribronchovascular areas (10/31; 32.3%) which was most commonly observed in the lower zone.
+The patients admitted to the ICU were more likely to have two or more lung zones involved (P = 0.005).
+CONCLUSIONS: In patients with the novel swine flu infection, the most common radiographic abnormality observed was consolidation in the lower lung zones.
+Patients admitted to ICU were more likely to have two or more lung zones involved.
+In addition, retroviruses are widely used as tools to transfer genes of interest to target cells.
+Understanding the entry mechanism of retroviruses contributes to developments of novel therapeutic approaches against retrovirus-induced diseases and efficient exploitation of retroviral vectors.
+Entry of enveloped viruses into host cell cytoplasm is achieved by fusion between the viral envelope and host cell membranes at either the cell surface or intracellular vesicles.
+CD4-dependent human immunodeficiency virus (HIV) infection is thought to occur via endosomes, but endosome acidification is not necessary for the entry whereas entry of CD4-independent HIVs, which are thought to be prototypes of CD4-dependent viruses, is low pH dependent.
+Because endocytosis and endosome acidification are complicatedly controlled by cellular mechanisms, the retrovirus entry pathways may be different in different cell lines.
+Chronic hepatitis C, which is caused by infection with the hepatitis C virus (HCV), is a global health problem.
+Using a mouse model of hepatitis C, we examined the therapeutic effects of a recombinant vaccinia virus (rVV) that encodes an HCV protein.
+We generated immunocompetent mice that each expressed multiple HCV proteins via a Cre/loxP switching system and established several distinct attenuated rVV strains.
+The HCV core protein was expressed consistently in the liver after polyinosinic acid–polycytidylic acid injection, and these mice showed chronic hepatitis C-related pathological findings (hepatocyte abnormalities, accumulation of glycogen, steatosis), liver fibrosis, and hepatocellular carcinoma.
+Immunization with one rVV strain (rVV-N25), which encoded nonstructural HCV proteins, suppressed serum inflammatory cytokine levels and alleviated the symptoms of pathological chronic hepatitis C within 7 days after injection.
+Furthermore, HCV protein levels in liver tissue also decreased in a CD4 and CD8 T-cell-dependent manner.
+Consistent with these results, we showed that rVV-N25 immunization induced a robust CD8 T-cell immune response that was specific to the HCV nonstructural protein 2.
+We also demonstrated that the onset of chronic hepatitis in CN2-29((+/−))/MxCre((+/−)) mice was mainly attributable to inflammatory cytokines, (tumor necrosis factor) TNF-α and (interleukin) IL-6.
+Thus, our generated mice model should be useful for further investigation of the immunological processes associated with persistent expression of HCV proteins because these mice had not developed immune tolerance to the HCV antigen.
+HIV-1 Nef protein contributes essentially to the pathology of AIDS by a variety of protein-protein-interactions within the host cell.
+The versatile functionality of Nef is partially attributed to different conformational states and posttranslational modifications, such as myristoylation.
+Up to now, many interaction partners of Nef have been identified using classical yeast two-hybrid screens.
+Such screens rely on transcriptional activation of reporter genes in the nucleus to detect interactions.
+Thus, the identification of Nef interaction partners that are integral membrane proteins, membrane-associated proteins or other proteins that do not translocate into the nucleus is hampered.
+In the present study, a split-ubiquitin based yeast two-hybrid screen was used to identify novel membrane-localized interaction partners of Nef.
+The identified hits are GPM6B, GPM6A, BAP31, TSPAN7, CYB5B, CD320/TCblR, VSIG4, PMEPA1, OCIAD1, ITGB1, CHN1, PH4, CLDN10, HSPA9, APR-3, PEBP1 and B3GNT, which are involved in diverse cellular processes like signaling, apoptosis, neurogenesis, cell adhesion and protein trafficking or quality control.
+For a subfraction of the hereby identified proteins we present data supporting their direct interaction with HIV-1 Nef.
+We discuss the results with respect to many phenotypes observed in HIV infected cells and patients.
+The identified Nef interaction partners may help to further elucidate the molecular basis of HIV-related diseases.
+A recent resurgence of pertussis has raised public health concerns even in developed countries with high vaccination coverage.
+The aim of this study was to describe the clinical characteristics of infant pertussis, and to determine the relative importance of household transmission in Korea.
+We identified the demographic and clinical data from these patients and performed the diagnostic tests for pertussis in their household contacts.
+All infections occurred in infants younger than 6 months of age (mean age, 2.5 months) who had not completed the primary DTaP vaccination except for one patient.
+Infants without immunization history had a significant higher lymphocytosis and longer duration of hospital stay compared to those with immunization.
+Household members were responsible for pertussis transmission of infants in whom a source could be identified.
+The control of pertussis through booster vaccination with Tdap in family who is taking care of young infants is necessary in Korea.
+The study of cell-population heterogeneity in a range of biological systems, from viruses to bacterial isolates to tumor samples, has been transformed by recent advances in sequencing throughput.
+While the high-coverage afforded can be used, in principle, to identify very rare variants in a population, existing ad hoc approaches frequently fail to distinguish true variants from sequencing errors.
+We report a method (LoFreq) that models sequencing run-specific error rates to accurately call variants occurring in <0.05% of a population.
+Using simulated and real datasets (viral, bacterial and human), we show that LoFreq has near-perfect specificity, with significantly improved sensitivity compared with existing methods and can efficiently analyze deep Illumina sequencing datasets without resorting to approximations or heuristics.
+We also present experimental validation for LoFreq on two different platforms (Fluidigm and Sequenom) and its application to call rare somatic variants from exome sequencing datasets for gastric cancer.
+The spontaneous and reversible formation of foci and filaments that contain proteins involved in different metabolic processes is common in both the nucleus and the cytoplasm.
+Stress granules (SGs) and processing bodies (PBs) belong to a novel family of cellular structures collectively known as mRNA silencing foci that harbour repressed mRNAs and their associated proteins.
+SGs and PBs are highly dynamic and they form upon stress and dissolve thus releasing the repressed mRNAs according to changes in cell physiology.
+In spite of the growing relevance of these supramolecular aggregates to diverse cellular functions a reliable automated tool for their systematic analysis is lacking.
+Here we report a MATLAB Script termed BUHO for the high-throughput image analysis of cellular foci.
+We used BUHO to assess the number, size and distribution of distinct objects with minimal deviation from manually obtained parameters.
+BUHO successfully addressed the induction of both SGs and PBs in mammalian and insect cells exposed to different stress stimuli.
+We also used BUHO to assess the dynamics of specific mRNA-silencing foci termed Smaug 1 foci (S-foci) in primary neurons upon synaptic stimulation.
+Finally, we used BUHO to analyze the role of candidate genes on SG formation in an RNAi-based experiment.
+The role of PP1 is conserved in mammalian cells as judged by the effect of the PP1 inhibitor salubrinal, and involves dephosphorylation of the translation factor eIF2α.
+All these experiments were analyzed manually and by BUHO and the results differed in less than 5% of the average value.
+The automated analysis by this user-friendly method will allow high-throughput image processing in short times by providing a robust, flexible and reliable alternative to the laborious and sometimes unfeasible visual scrutiny.
+This study evaluates the effects of Sargassum pallidum polysaccharides (SPP) on the immune responses in a chicken model.
+The adjuvanticity of Sargassum pallidum polysaccharides in Newcastle disease (ND), infectious bronchitis (IB) and avian influenza (AI) was investigated by examining the antibody titers and lymphocyte proliferation following immunization in chickens.
+The chickens were administrated combined ND, IB and AI inactivated vaccines containing SPP at 10, 30 and 50 mg/mL, using an oil adjuvant vaccine as a control.
+The ND, IB and AI antibody titers and the lymphocyte proliferation were enhanced at 30 mg/mL SPP.
+In conclusion, an appropriate dose of SPP may be a safe and efficacious immune stimulator candidate that is suitable for vaccines to produce early and persistent prophylaxis.
+On 11 June 2009, the World Health Organization (WHO) declared that the world was in phase 6 of an influenza pandemic.
+In India, the first case of 2009 H1N1 influenza was reported on 16 May 2009 and by August 2010 (when the pandemic was declared over), 38 730 cases of 2009 H1N1 had been confirmed of which there were 2024 deaths.
+Here, we propose a conceptual model of the sources of health disparities in an influenza pandemic in India.
+Guided by a published model of the plausible sources of such disparities in the United States, we reviewed the literature for the determinants of the plausible sources of health disparities during a pandemic in India.
+Whereas causal factors can only be determined by testing the model when incidence and mortality data, collected in conjunction with socio-economic and geographic factors, become available, we put forth recommendations that policy makers can undertake to ensure that the pandemic preparedness plan includes a focus on social inequalities in India in order to prevent their exacerbation in a pandemic.
+A key priority in infectious disease research is to understand the ecological and evolutionary drivers of viral diseases from data on disease incidence as well as viral genetic and antigenic variation.
+We propose using a simulation-based, Bayesian method known as Approximate Bayesian Computation (ABC) to fit and assess phylodynamic models that simulate pathogen evolution and ecology against summaries of these data.
+We illustrate the versatility of the method by analyzing two spatial models describing the phylodynamics of interpandemic human influenza virus subtype A(H3N2).
+The first model captures antigenic drift phenomenologically with continuously waning immunity, and the second epochal evolution model describes the replacement of major, relatively long-lived antigenic clusters.
+Combining features of long-term surveillance data from the Netherlands with features of influenza A (H3N2) hemagglutinin gene sequences sampled in northern Europe, key phylodynamic parameters can be estimated with ABC.
+Goodness-of-fit analyses reveal that the irregularity in interannual incidence and H3N2's ladder-like hemagglutinin phylogeny are quantitatively only reproduced under the epochal evolution model within a spatial context.
+However, the concomitant incidence dynamics result in a very large reproductive number and are not consistent with empirical estimates of H3N2's population level attack rate.
+These results demonstrate that the interactions between the evolutionary and ecological processes impose multiple quantitative constraints on the phylodynamic trajectories of influenza A(H3N2), so that sequence and surveillance data can be used synergistically.
+ABC, one of several data synthesis approaches, can easily interface a broad class of phylodynamic models with various types of data but requires careful calibration of the summaries and tolerance parameters.
+A series of phenanthroquinolizidine alkaloids 1–24 were prepared and first evaluated for their antiviral activity against tobacco mosaic virus (TMV).
+The bioassay results showed that most of these compounds exhibited good to excellent in vivo anti-TMV activity, of which compounds 1, 2, 15 and 16 displayed significantly higher activity than (R)-antofine and commercial Ningnanmycin at the same test condition.
+The substituents on the phenanthrene moiety play an important role for maintaining high in vivo antiviral activity.
+The introduction of 6-hydroxyl, which is proposed to interact with TMV RNA, did increased anti-TMV activity.
+Introduction of hydroxy group at 15-position of phenanthroquinolizidine alkaloids increased activity for S-configuration but decreased activity for R-configuration.
+Present study provides fundamental support for development and optimization of phenanthroquinolizidine alkaloids as potential inhibitors of plant virus.
+The ability of influenza vaccines to elicit CD4(+) T cells and the relationship between induction of CD4(+) T cells and vaccine-induced neutralizing antibody responses has been controversial.
+The emergence of swine-origin 2009 pandemic influenza A virus subtype H1N1 (A[H1N1]pdm09) provided a unique opportunity to examine responses to an influenza vaccine composed of both novel and previously encountered antigens and to probe the relationship between B-cell and T-cell responses to vaccination.
+We tracked CD4(+) T-cell and antibody responses of human subjects vaccinated with monovalent subunit A(H1N1)pdm09 vaccine.
+The specificity and magnitude of the CD4(+) T-cell response was evaluated using cytokine enzyme-linked immunosorbent spot assays in conjugation with peptide pools representing distinct influenza virus proteins.
+Our studies revealed that vaccination induced readily detectable CD4(+) T cells specific for conserved portions of hemagglutinin (HA) and the internal viral proteins.
+Interestingly, expansion of HA-specific CD4(+) T cells was most tightly correlated with the antibody response.
+These results indicate that CD4(+) T-cell expansion may be a limiting factor in development of neutralizing antibody responses to pandemic influenza vaccines and suggest that approaches to facilitate CD4(+) T-cell recruitment may increase the neutralizing antibody produced in response to vaccines against novel influenza strains.
+BACKGROUND: The Australian state of Victoria, with 5.2 million residents, enforced home quarantine during a H1N1 pandemic in 2009.
+The objective of this study was to investigate the extent to which parents’ access to paid sick leave or paid carer’s leave was associated with (a) time taken off work to care for quarantined children, (b) household finances, and (c) compliance with quarantine recommendations.
+METHODS: We conducted an online and telephone survey of households recruited through 33 schools (85% of eligible schools), received 314 responses (27%), and analysed the subsample of 133 households in which all resident parents were employed.
+RESULTS: In 52% of households, parents took time off work to care for quarantined children.
+Households in which no resident parent had access to leave appeared to be less likely to take time off work (42% vs 58%, p=0.08) although this difference had only borderline significance.
+Among parents who did take time off work, those in households without access to leave were more likely to lose pay (73% vs 21%, p<0.001).
+Of the 26 households in which a parent lost pay due to taking time off work, 42% experienced further financial consequences such as being unable to pay a bill.
+CONCLUSIONS: Future pandemic plans should consider the economic costs borne by households and options for compensating quarantined families for income losses.
+To examine the impacts of a multi-city HIV prevention public health program (China Global Fund Round 5 Project) on condom use and HIV infection, we analyzed four yearly cross-sectional surveys from 2006 through 2009 among 20,843 men who have sex with men (MSM) in 16 Chinese cities.
+Self-reported condom use at last sex with a male partner increased from 58% in 2006 to 81% in 2009 (trend test, P<0.001).
+Multivariable logistic regression analysis showed that self-reported receipt of interventions was an independent predictor of increased condom use at last sex with a male partner over time (adjusted odds ratio [aOR], 1.63 in 2006 to 2.33 in 2009; P<0.001), and lower HIV prevalence (aOR, 1.08 in 2006 to 0.45 in 2009; P<0.001).
+HIV prevalence increased from 2006–2009 for participants with no self-reported receipt of interventions (2.1% in 2006 to 10.3% in 2009) and less so for those with interventions (2.4% to 4.7%).
+This Chinese public health program had positive impacts on both behaviors and disease rate among MSM population.
+Escalation of the coverage and intensity of effective interventions is needed for further increasing condom use and for reversing the rising trend of HIV epidemic.
+BACKGROUND: Some patients have a greater response to viral infection than do others having a similar level of viral replication.
+Hypercytokinemia is the principal immunopathological mechanism that contributes to a severer clinical course in cases of influenza A/H1N1.
+The benefit produced, or damage caused, by these cytokines in severe disease is not known.
+The genes that code for these molecules are polymorphic and certain alleles have been associated with susceptibility to various diseases.
+The objective of the present study was to determine whether there was an association between polymorphisms of TNF, LTA, IL1B, IL6, IL8, and CCL1 and the infection and severity of the illness caused by the pandemic A/H1N1 in Mexico in 2009.
+The cases were patients confirmed with real time PCR with infection by the A/H1N1 pandemic virus.
+The controls were patients with infection like to influenza and non-familial healthy contacts of the patients with influenza.
+The DNA samples were genotyped for polymorphisms TNF rs361525, rs1800629, and rs1800750; LTA rs909253; IL1B rs16944; IL6 rs1818879; IL8 rs4073; and CCL1 rs2282691.
+The logistic regression model was adjusted by age and severity of the illness in cases.
+RESULTS: Infection with the pandemic A/H1N1 virus was associated with the following genotypes: TNF rs361525 AA, OR = 27.00; 95% CI = 3.07–1248.77); LTA rs909253 AG (OR = 4.33, 95% CI = 1.82–10.32); TNF rs1800750 AA (OR = 4.33, 95% CI = 1.48–12.64); additionally, LTA rs909253 AG showed a limited statistically significant association with mortality (p = 0.06, OR = 3.13).
+Carriers of the TNF rs1800629 GA genotype were associated with high levels of blood urea nitrogen (p = 0.05); those of the TNF rs1800750 AA genotype, with high levels of creatine phosphokinase (p=0.05).
+The IL1B rs16944 AA genotype was associated with an elevated number of leukocytes (p <0.001) and the IL8 rs4073 AA genotype, with a higher value for P(a)O(2) mm Hg.
+CONCLUSION: The polymorphisms of genes involved in the inflammatory process contributed to the severity of the clinical behavior of infection by the pandemic influenza A/H1N1 virus.
+It interacts with diverse endogenous pathways and contributes to the maintenance of homeostasis, the modulation of adaptive immune responses, and the development of various pathologies.
+The potential usefulness, in both research and clinical settings, of compounds that detect or modulate complement activity has resulted in thousands of publications on complement-related innovations in fields such as drug discovery, disease diagnosis and treatment, and immunoassays, among others.
+This study highlights the distribution and publication trends of patents related to the complement system that were granted by the United States Patent and Trademark Office from 1976 to the present day.
+A comparison to complement-related documents published by the World Intellectual Property Organization is also included.
+More than half of the patents were found to focus on the discovery of inhibitors; interest in various inhibitor classes exhibited a remarkable transformation from chemical compounds early on to proteins and antibodies in more recent years.
+Among clinical applications, complement proteins and their modulators have been extensively patented for the diagnosis and treatment of eye diseases (especially age-related macular degeneration), graft rejection, cancer, sepsis, and a variety of other inflammatory and immune diseases.
+All of the patents discussed in this chapter, as well as those from other databases, are available from our newly constructed complement patent database: www.innateimmunity.us/patent.
+BACKGROUND: Production of human monoclonal antibodies that exhibit broadly neutralizing activity is needed for preventing HIV-1 infection, however only a few such antibodies have been generated till date.
+Further, the loss of unstable or slowly growing clones which may have unique binding specificities often occurs during cloning and propagation and the strongly positive clones are often lost.
+This has been avoided by the process described in this paper, wherein, by combining the strategy of EBV transformation and recombinant DNA technology, we constructed human single chain variable fragments (scFvs) against the third variable region (V3) of the clade C HIV-1 envelope.
+RESULTS: An antigen specific phage library of 7000 clones was constructed from the enriched V3- positive antibody secreting EBV transformed cells.
+By ligation of the digested scFv DNA into phagemid vector and bio panning against the HIV-1 consensus C and B V3 peptides followed by random selection of 40 clones, we identified 15 clones that showed V3 reactivity in phage ELISA.
+DNA fingerprinting analysis and sequencing showed that 13 out of the 15 clones were distinct.
+All the 13 anti-V3 scFvs showed cross-reactivity against both the clade C and B V3 peptides and did not show any reactivity against other unrelated peptides in ELISA.
+EBV transformation, followed by antigen selection of lines to identify specific binders, enabled the selection of phage from un-cloned lines for scFv generation, thus avoiding the problems of hybridoma technology.
+Moreover, as the clones were pretested for antigen binding, a comparatively small library sufficed for the selection of a considerable number of unique antigen binding phage.
+CONCLUSIONS: This strategy can be efficiently used and is cost effective for the generation of diverse recombinant antibodies.
+BACKGROUND: Although the wearing of face masks in public has not been recommended for preventing influenza, these devices are often worn in many Asian countries during the influenza season.
+In Japan, it is thought that such behavior may be an indicator of other positive hygiene practices.
+The aim of this study, therefore, was to determine if wearing a face mask in public is associated with other positive hygiene practices and health behaviors among Japanese adults.
+METHODS: We initially recruited around 3,000 Japanese individuals ranging from 20 to 69 years of age who were registered with a web survey company.
+Participants were asked to recall their personal hygiene practices during the influenza season of the previous year.
+Logistic regression analysis was then used to examine the associations between wearing a face mask in public and personal hygiene practices and health behaviors.
+RESULTS: A total of 3,129 persons responded to the survey, among whom 38% reported that they had worn a face mask in public during the previous influenza season.
+CONCLUSIONS: Overall, this study suggests that wearing a face mask in public may be associated with other personal hygiene practices and health behaviors among Japanese adults.
+Rather than preventing influenza itself, face mask use might instead be a marker of additional, positive hygiene practices and other favorable health behaviors in the same individuals.
+The control of infectious diseases such as swine influenza viruses (SwIV) plays an important role in food production both from the animal health and from the public health point of view.
+Probiotic microorganisms and other health improving food supplements have been given increasing attention in recent years, but, no information on the effects of probiotics on swine influenza virus is available.
+Here we address this question by assessing the inhibitory potential of the probiotic Enterococcus faecium NCIMB 10415 (E. faecium) on the replication of two porcine strains of influenza virus (H1N1 and H3N2 strain) in a continuous porcine macrophage cell line (3D4/21) and in MDBK cells.
+Cell cultures were treated with E. faecium at the non-toxic concentration of 1×10(6) CFU/ml in growth medium for 60 to 90 min before, during and after SwIV infection.
+After further incubation of cultures in probiotic-free growth medium, cell viability and virus propagation were determined at 48 h or 96 h post infection.
+The results obtained reveal an almost complete recovery of viability of SwIV infected cells and an inhibition of virus multiplication by up to four log units in the E. faecium treated cells.
+In both 3D4/21- and MDBK-cells a 60 min treatment with E. faecium stimulated nitric oxide (NO) release which is in line with published evidence for an antiviral function of NO.
+Furthermore, E. faecium caused a modified cellular expression of selected mediators of defence in 3D4-cells: while the expression of TNF-α, TLR-3 and IL-6 were decreased in the SwIV-infected and probiotic treated cells, IL-10 was found to be increased.
+Since we obtained experimental evidence for the direct adsorptive trapping of SwIV through E. faecium, this probiotic microorganism inhibits influenza viruses by at least two mechanisms, direct physical interaction and strengthening of innate defence at the cellular level.
+Anti-viral T cells are thought to regulate whether hepatitis C virus (HCV) and HIV infections result in viral control, asymptomatic persistence, or severe disease, though the reasons for these different outcomes remain unclear.
+Recent genetic evidence, however, has indicated a correlation between certain natural killer (NK) cell receptors and progression of both HIV and HCV infection(1–3), implying that NK cells are playing a role in these T cell-associated diseases.
+While direct NK cell-mediated lysis of virus-infected cells may contribute to anti-viral defense during some virus infections, especially murine cytomegalovirus (MCMV) infections in mice and perhaps HIV in humans(4–5), NK cells have also been suspected as having immunoregulatory functions.
+For instance, NK cells may indirectly regulate T cell responses by lysing MCMV-infected antigen-presenting cells(6–7).
+In contrast to MCMV, lymphocytic choromeningitis virus (LCMV) infection in mice seems resistant to any direct anti-viral effects of NK cells(5,8).
+Here the roles of NK cells in regulating T cell-dependent viral persistence and immunopathology were examined in mice infected with LCMV, an established model for HIV and HCV infections in humans.
+We describe a three-way interaction, whereby activated NK cells cytolytically eliminate activated CD4 T cells that affect CD8 T-cell function and exhaustion.
+At high virus dose NK cells prevented fatal pathology while enabling T-cell exhaustion and viral persistence, but at a medium dose NK cells paradoxically facilitated lethal T cell-mediated pathology.
+Thus, NK cells can act as rheostats, regulating CD4 T cell-mediated support for the anti-viral CD8 T cells that control viral pathogenesis and persistence.
+BACKGROUND: In Australia, the 2009 epidemic of influenza A(H1N1)pdm09 resulted in increased admissions to intensive care.
+The annual contribution of influenza to use of intensive care is difficult to estimate, as many people with influenza present without a classic influenza syndrome and laboratory testing may not be performed.
+We used a population-based approach to estimate and compare the impact of recent epidemics of seasonal and pandemic influenza.
+METHODS: For 2007 to 2010, time series describing health outcomes in various population groups were prepared from a database of all intensive care unit (ICU) admissions in the state of New South Wales, Australia.
+The Serfling approach, a time series method, was used to estimate seasonal patterns in health outcomes in the absence of influenza epidemics.
+The contribution of influenza was estimated by subtracting expected seasonal use from observed use during each epidemic period.
+RESULTS: The estimated excess rate of influenza-associated respiratory ICU admissions per 100,000 inhabitants was more than three times higher in 2007 (2.6/100,000, 95% CI 2.0 to 3.1) than the pandemic year, 2009 (0.76/100,000, 95% CI 0.04 to 1.48).
+In 2009, the highest excess respiratory ICU admission rate was in 17 to 64 year olds (2.9/100,000, 95% CI 2.2 to 3.6), while in 2007, the highest excess rate was in those aged 65 years or older (9.5/100,000, 95% CI 6.2 to 12.8).
+In 2009, the excess rate was 17/100,000 (95% CI 14 to 20) in Aboriginal people and 14/100,000 (95% CI 13 to 16) in pregnant women.
+CONCLUSION: While influenza was diagnosed more frequently and peak use of intensive care was higher during the epidemic of pandemic influenza in 2009, overall excess admissions to intensive care for respiratory illness was much greater during the influenza season in 2007.
+Thus, the impact of seasonal influenza on intensive care use may have previously been under-recognised.
+In 2009, high ICU use among young to middle aged adults was offset by relatively low use among older adults, and Aboriginal people and pregnant women were substantially over-represented in ICUs.
+Greater emphasis on prevention of serious illness in Aboriginal people and pregnant women should be a priority in pandemic planning.
+The unfolded protein response (UPR) is a stress-induced cyto-protective mechanism elicited towards an influx of large amount of proteins in the endoplasmic reticulum (ER).
+In the present study, we evaluated if AAV manipulates the UPR pathways during its infection.
+We first examined the role of the three major UPR axes, namely, endoribonuclease inositol-requiring enzyme-1 (IRE1α), activating transcription factor 6 (ATF6) and PKR-like ER kinase (PERK) in AAV infected cells.
+Total RNA from mock or AAV infected HeLa cells were used to determine the levels of 8 different ER-stress responsive transcripts from these pathways.
+We observed a significant up-regulation of IRE1α (up to 11 fold) and PERK (up to 8 fold) genes 12–48 hours after infection with self-complementary (sc)AAV2 but less prominent with single-stranded (ss)AAV2 vectors.
+Further studies demonstrated that scAAV1 and scAAV6 also induce cellular UPR in vitro, with AAV1 vectors activating the PERK pathway (3 fold) while AAV6 vectors induced a significant increase on all the three major UPR pathways [6–16 fold].
+These data suggest that the type and strength of UPR activation is dependent on the viral capsid.
+We then examined if transient inhibition of UPR pathways by RNA interference has an effect on AAV transduction.
+siRNA mediated silencing of PERK and IRE1α had a modest effect on AAV2 and AAV6 mediated gene expression (∼1.5–2 fold) in vitro.
+Furthermore, hepatic gene transfer of scAAV2 vectors in vivo, strongly elevated IRE1α and PERK pathways (2 and 3.5 fold, respectively).
+However, when animals were pre-treated with a pharmacological UPR inhibitor (metformin) during scAAV2 gene transfer, the UPR signalling and its subsequent inflammatory response was attenuated concomitant to a modest 2.8 fold increase in transgene expression.
+Collectively, these data suggest that AAV vectors activate the cellular UPR pathways and their selective inhibition may be beneficial during AAV mediated gene transfer.
+Hypoxia/hypoxia-inducible factor-1α (HIF-1α) regulates many important steps of the metastatic processes, especially epithelial-mesenchymal transition (EMT) that is one of the crucial mechanisms to cause early stage of tumor metastasis.
+To have a better understanding of the mechanism of hypoxia-regulated metastasis, various hypoxia/HIF-1α-regulated target genes are categorized into different classes including transcription factors, histone modifiers, enzymes, receptors, kinases, small GTPases, transporters, adhesion molecules, surface molecules, membrane proteins, and microRNAs.
+Different roles of these target genes are described with regards to their relationship to hypoxia-induced metastasis.
+We hope that this review will provide a framework for further exploration of hypoxia/HIF-1α-regulated target genes and a comprehensive view of the metastatic picture induced by hypoxia.
+By November 2012, approximately 28 clinical trials were approved to assess novel gene therapy agents.
+Viral infections such as herpetic keratitis caused by herpes simplex virus 1 (HSV-1) can cause serious complications that may lead to blindness.
+Recurrence of the disease is likely and cornea transplantation, therefore, might not be the ideal therapeutic solution.
+This paper will focus on the current situation of ocular gene therapy research against herpetic keratitis, including the use of viral and nonviral vectors, routes of delivery of therapeutic genes, new techniques, and key research strategies.
+Whereas the correction of inherited diseases was the initial goal of the field of gene therapy, here we discuss transgene expression, gene replacement, silencing, or clipping.
+Gene therapy of herpetic keratitis previously reported in the literature is screened emphasizing candidate gene therapy targets.
+Commonly adopted strategies are discussed to assess the relative advantages of the protective therapy using antiviral drugs and the common gene therapy against long-term HSV-1 ocular infections signs, inflammation and neovascularization.
+The disproportionate effects of the 2009 H1N1 pandemic on many Canadian Aboriginal communities have drawn attention to the vulnerability of these communities in terms of health outcomes in the face of emerging and reemerging infectious diseases.
+In alignment with the objectives of the Pandemic Influenza Outbreak Research Modelling (Pan-InfORM) team, a Canadian public health workshop was held at the Centre for Disease Modelling (CDM) to: (i) evaluate post-pandemic research findings; (ii) identify existing gaps in knowledge that have yet to be addressed through ongoing research and collaborative activities; and (iii) build upon existing partnerships within the research community to forge new collaborative links with Aboriginal health organizations.
+The workshop achieved its objectives in identifying main research findings and emerging information post pandemic, and highlighting key challenges that pose significant impediments to the health protection and promotion of Canadian Aboriginal populations.
+The health challenges faced by Canadian indigenous populations are unique and complex, and can only be addressed through active engagement with affected communities.
+The academic research community will need to develop a new interdisciplinary framework, building upon concepts from ‘Communities of Practice’, to ensure that the research priorities are identified and targeted, and the outcomes are translated into the context of community health to improve policy and practice.
+Schmallenberg virus (SBV) is an emerging orthobunyavirus of ruminants associated with outbreaks of congenital malformations in aborted and stillborn animals.
+Since its discovery in November 2011, SBV has spread very rapidly to many European countries.
+Here, we developed molecular and serological tools, and an experimental in vivo model as a platform to study SBV pathogenesis, tropism and virus-host cell interactions.
+Using a synthetic biology approach, we developed a reverse genetics system for the rapid rescue and genetic manipulation of SBV.
+We showed that SBV has a wide tropism in cell culture and “synthetic” SBV replicates in vitro as efficiently as wild type virus.
+We developed an experimental mouse model to study SBV infection and showed that this virus replicates abundantly in neurons where it causes cerebral malacia and vacuolation of the cerebral cortex.
+These virus-induced acute lesions are useful in understanding the progression from vacuolation to porencephaly and extensive tissue destruction, often observed in aborted lambs and calves in naturally occurring Schmallenberg cases.
+Indeed, we detected high levels of SBV antigens in the neurons of the gray matter of brain and spinal cord of naturally affected lambs and calves, suggesting that muscular hypoplasia observed in SBV-infected lambs is mostly secondary to central nervous system damage.
+Interestingly, we found a biological SBV clone that after passage in cell culture displays increased virulence in mice.
+We also found that a SBV deletion mutant of the non-structural NSs protein (SBVΔNSs) is less virulent in mice than wild type SBV.
+Attenuation of SBV virulence depends on the inability of SBVΔNSs to block IFN synthesis in virus infected cells.
+In conclusion, this work provides a useful experimental framework to study the biology and pathogenesis of SBV.
+Nine cases of diffuse cavernous hemangioma of the gravid uterus have been reported, most of which diffusely involved the myometrium.
+These vascular malformations are clinically significant, and may cause pronounced bleeding resulting in maternal or fetal demise.
+We here report the first case in which a thrombosed cavernous hemangioma of the myometrium resulted in a fatal pulmonary embolism in a post-partum woman.
+CASE PRESENTATION: A 25-year-old obese African-American woman who had one pregnancy and was delivered of twins by cesarean section was admitted 1 week after the successful delivery.
+The 12-day clinical course included ventilator-dependent respiratory failure, systemic hypertension, methicillin-resistant Staphylococcus aureus in the sputum, leukocytosis and asystole.
+The laboratory values were relevant for an increased prothrombin time, activated partial thromboplastin time, ferritin and a decrease in hemoglobin.
+At autopsy, a 400g spongy, hemorrhagic uterus with multiple cystic spaces measuring approximately 0.5 × 0.4cm filled with thrombi within the myometrium was identified.
+Immunohistological examination with a CD31 stain for vascular endothelium associated antigen confirmed several endothelium-lined vessels, some of which contained thrombi.
+A histological examination of the lungs revealed multiple fresh thromboemboli in small- and medium-sized pulmonary arteries in the right upper and lower lobes without organization, but with adjacent areas of fresh hemorrhagic infarction.
+CONCLUSION: This case underscores the importance of a high index of suspicion in a pregnant or post-partum woman presenting with respiratory symptoms.
+Thrombosis of the cavernous hemangiomas of the gravid or post-partum uterus is a rare entity.
+This case is of interest because it indicates that this condition can be fatally complicated by embolization of the thrombi in the cavernous myometrial hemangiomas.
+Although delivery by conservative methods, as well as cesarean section, is possible without resorting to hysterectomy, occasionally, the consequences could be fatal as in this case.
+BACKGROUND: Influenza A virus (IAV) is a member of the family Orthomyxoviridae and contains eight segments of a single-stranded RNA genome with negative polarity.
+The first influenza pandemic of this century was declared in April of 2009, with the emergence of a novel H1N1 IAV strain (H1N1pdm) in Mexico and USA.
+Understanding the extent and causes of biases in codon usage is essential to the understanding of viral evolution.
+A comprehensive study to investigate the effect of selection pressure imposed by the human host on the codon usage of an emerging, pandemic IAV strain and the trends in viral codon usage involved over the pandemic time period is much needed.
+RESULTS: We performed a comprehensive codon usage analysis of 310 IAV strains from the pandemic of 2009.
+When correspondence analysis (COA) on relative synonymous codon usage (RSCU) is applied, the distribution of IAV ORFs in the plane defined by the first two major dimensional factors showed that different strains are located at different places, suggesting that IAV codon usage also reflects an evolutionary process.
+CONCLUSIONS: A general association between codon usage bias, base composition and poor adaptation of the virus to the respective host tRNA pool, suggests that mutational pressure is the main force shaping H1N1 pdm IAV codon usage.
+A dynamic process is observed in the variation of codon usage of the strains enrolled in these studies.
+These results suggest a balance of mutational bias and natural selection, which allow the virus to explore and re-adapt its codon usage to different environments.
+Recoding of IAV taking into account codon bias, base composition and adaptation to host tRNA may provide important clues to develop new and appropriate vaccines.
+This study determined the burden of pediatric LRTIs on hospital settings in British Columbia and the benefits of prevention strategies as they relate to healthcare resource demand.
+METHODS: LRTI inpatient episodes for patients <19 years of age during 2008–2010 were extracted from the BC Discharge Abstract Database.
+Population projections were used to forecast LRTI hospitalizations and the effectiveness of public health initiatives to reduce the incidence of LRTIs to 2020 and 2030.
+RESULTS: During 2008–2010, LRTI as the primary diagnosis accounted for 32.0 and 75.9% hospitalizations for diseases of the respiratory system in children <19 years of age and infants <1 year of age, respectively.
+Infants <1 year of age accounted for 47 and 77% hospitalizations due to pediatric LRTIs and pediatric LRTI hospitalizations specifically due to respiratory syncytial virus (RSV), respectively.
+The average length of stay was 3.1 days for otherwise healthy infants <1 year of age and 9.1 days for high-risk infants (P <0.0001).
+Over the study timeframe, 19.6 acute care beds were required on average to care for pediatric LRTIs which increased to 64.0 beds at the peak of LRTI hospitalizations.
+Increases in LRTI bed-days of 5.5 and 16.2% among <19 year olds by 2020 and 2030, respectively, were predicted.
+Implementation of appropriate prevention strategies could cause 307 and 338 less LRTI hospitalizations in <19 year olds in 2020 and 2030, respectively.
+CONCLUSION: Pediatric LRTI hospitalizations require significant use of acute care infrastructure particularly between November and April.
+Population projections show the burden may increase in the next 20 years, but implementation of effective public health prevention strategies may contribute to reducing the acute care demand and to supporting efforts for overall pediatric healthcare sustainability.
+To evaluate the role of the F protein cleavage site in the replication and pathogenicity of avian paramyxoviruses (APMVs), we constructed a reverse genetics system for recovery of infectious recombinant APMV-4 from cloned cDNA.
+The recovered recombinant APMV-4 resembled the biological virus in growth characteristics in vitro and in pathogenicity in vivo.
+The F cleavage site sequence of APMV-4 (DIQPR↓F) contains a single basic amino acid, at the -1 position.
+Six mutant APMV-4 viruses were recovered in which the F protein cleavage site was mutated to contain increased numbers of basic amino acids or to mimic the naturally occurring cleavage sites of several paramyxoviruses, including neurovirulent and avirulent strains of NDV.
+The presence of a glutamine residue at the -3 position was found to be important for mutant virus recovery.
+In addition, cleavage sites containing the furin protease motif conferred increased replication and syncytium formation in vitro.
+However, analysis of viral pathogenicity in 9-day-old embryonated chicken eggs, 1-day-old and 2-week-old chickens, and 3-week-old ducks showed that none the F protein cleavage site mutations altered the replication, tropism, and pathogenicity of APMV-4, and no significant differences were observed among the parental and mutant APMV-4 viruses in vivo.
+Although parental and mutant viruses replicated somewhat better in ducks than in chickens, they all were highly restricted and avirulent in both species.
+These results suggested that the cleavage site sequence of the F protein is not a limiting determinant of APMV-4 pathogenicity in chickens and ducks.
+BACKGROUND: Historically, Pacific island countries and territories (PICTs) have been more severely affected by influenza pandemics than any other part of the world.
+We herein describe the emergence and epidemiologic characteristics of pandemic influenza H1N1 in PICTs from 2009 to 2010.
+METHODS: The World Health Organization gathered reports of influenza-like-illness and laboratory-confirmed pandemic H1N1 cases from all 23 Pacific island countries and territories, from April 2009 through August 2010.
+Data were gathered through weekly email reports from Pacific island countries and territories and through email or telephone follow-up.
+RESULTS: Pacific island countries and territories started detecting pandemic H1N1 cases in June 2009, firstly in French Polynesia, with the last new detection occurring in August 2009 in Tuvalu.
+No confirmed pandemic H1N1 cases were identified in Niue, Pitcairn and Tokelau; the latter instituted strict maritime quarantine.
+Pacific island countries and territories instituted a variety of mitigation measures, including arrival health screening.
+Despite being well-prepared, Pacific island countries and territories experienced significant morbidity and mortality, consistent with other indigenous and low-resource settings.
+For the first time, regional influenza-like-illness surveillance was conducted in the Pacific, allowing health authorities to monitor the pandemic’s spread and severity in real-time.
+INTRODUCTION: Even in developed economies infectious diseases remain the most common cause of illness in early childhood.
+Our current understanding of the epidemiology of these infections is limited by reliance on data from decades ago performed using low-sensitivity laboratory methods, and recent studies reporting severe, hospital-managed disease.
+METHODS AND ANALYSIS: The Observational Research in Childhood Infectious Diseases (ORChID) study is an ongoing study enrolling a dynamic birth cohort to document the community-based epidemiology of viral respiratory and gastrointestinal infections in early childhood.
+Women are recruited antenatally, and their healthy newborn is followed for the first 2 years of life.
+Parents keep a daily symptom diary for the study child, collect a weekly anterior nose swab and dirty nappy swab and complete a burden diary when a child meets pre-defined illness criteria.
+Primary analyses involves calculating incidence rates for acute respiratory illness (ARI) and acute gastroenteritis (AGE) for the cohort by age and seasonality.
+Control material from children when they are without symptoms will allow us to determine what proportion of ARIs and AGE can be attributed to specific pathogens.
+Secondary analyses will assess the incidence and shedding duration of specific respiratory and gastrointestinal pathogens.
+ETHICS AND DISSEMINATION: This study is approved by The Human Research Ethics Committees of the Children's Health Queensland Hospital and Health Service, the Royal Brisbane and Women's Hospital and The University of Queensland.
+BACKGROUND: The identification of new virus strains is important for the study of infectious disease, but current (or existing) molecular biology methods are limited since the target sequence must be known to design genome-specific PCR primers.
+Thus, we developed a new method for the discovery of unknown viruses based on the cDNA - random amplified polymorphic DNA (cDNA-RAPD) technique.
+Getah virus, belonging to the family Togaviridae in the genus Alphavirus, is a mosquito-borne enveloped RNA virus that was identified using the Virus-Discovery-cDNA RAPD (VIDISCR) method.
+RESULTS: A novel Getah virus was identified by VIDISCR from suckling mice exposed to mosquitoes (Aedes albopictus) collected in Yunnan Province, China.
+The non-structural protein gene, nsP3, the structural protein gene, the capsid protein gene, and the 3'-untranslated region (UTR) of the novel Getah virus isolate were cloned and sequenced.
+Nucleotide sequence identities of each gene were determined to be 97.1–99.3%, 94.9–99.4%, and 93.6–99.9%, respectively, when compared with the genomes of 10 other representative strains of Getah virus.
+CONCLUSIONS: The VIDISCR method was able to identify known virus isolates and a novel isolate of Getah virus from infected mice.
+Phylogenetic analysis indicated that the YN08 isolate was more closely related to the Hebei HB0234 strain than the YN0540 strain, and more genetically distinct from the MM2021 Malaysia primitive strain.
+Mizoribine monophosphate (MZP) is a specific inhibitor of the cellular inosine-5′-monophosphate dehydrogenase (IMPDH), the enzyme catalyzing the rate-limiting step of de novo guanine nucleotide biosynthesis.
+MZP is a highly potent antagonistic inhibitor of IMPDH that blocks the proliferation of T and B lymphocytes that use the de novo pathway of guanine nucleotide synthesis almost exclusively.
+In the present study, we investigated the ability of MZP to directly inhibit the human RNA capping enzyme (HCE), a protein harboring both RNA 5′-triphosphatase and RNA guanylyltransferase activities.
+HCE is involved in the synthesis of the cap structure found at the 5′ end of eukaryotic mRNAs, which is critical for the splicing of the cap-proximal intron, the transport of mRNAs from the nucleus to the cytoplasm, and for both the stability and translation of mRNAs.
+Our biochemical studies provide the first insight that MZP can inhibit the formation of the RNA cap structure catalyzed by HCE.
+In the presence of MZP, the RNA 5′-triphosphatase activity appears to be relatively unaffected while the RNA guanylyltransferase activity is inhibited, indicating that the RNA guanylyltransferase activity is the main target of MZP inhibition.
+Kinetic studies reveal that MZP is a non-competitive inhibitor that likely targets an allosteric site on HCE.
+Mizoribine also impairs mRNA capping in living cells, which could account for the global mechanism of action of this therapeutic agent.
+Together, our study clearly demonstrates that mizoribine monophosphate inhibits the human RNA guanylyltransferase in vitro and impair mRNA capping in cellulo.
+There is an increasing interest in the potential of exhaled biomarkers, such as volatile organic compounds (VOCs), to improve accurate diagnoses and management decisions in pulmonary diseases.
+The objective of this manuscript is to systematically review the current knowledge on exhaled VOCs with respect to their potential clinical use in asthma, lung cancer, chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF), and respiratory tract infections.
+A systematic literature search was performed in PubMed, EMBASE, Cochrane database, and reference lists of retrieved studies.
+Controlled, clinical, English-language studies exploring the diagnostic and monitoring value of VOCs in asthma, COPD, CF, lung cancer and respiratory tract infections were included.
+The collection and analysis of exhaled VOCs is non-invasive and could be easily applied in the broad range of patients, including subjects with severe disease and children.
+Various research groups demonstrated that VOCs profiles could accurately distinguish patients with a pulmonary disease from healthy controls.
+Pulmonary diseases seem to be characterized by a disease specific breath-print, as distinct profiles were found in patients with dissimilar diseases.
+Despite these promising findings, multiple challenges such as further standardization and validation of the diverse techniques need to be mastered before VOCs can be applied into clinical practice.
+A strategy for antiviral drug discovery is the elucidation and imitation of viral interference mechanisms.
+HIV-1 patients benefit from a coinfection with GB Virus C (GBV-C), since HIV-positive individuals with long-term GBV-C viraemia show better survival rates than HIV-1 patients without persisting GBV-C. A direct influence of GBV-C on HIV-1 replication has been shown in coinfection experiments.
+GBV-C is a human non-pathogenic member of the flaviviridae family that can replicate in T and B cells.
+In earlier work we have demonstrated that recombinant glycoprotein E2 of GBV-C and peptides derived from the E2 N-terminus interfere with HIV entry.
+Performing a virus-cell fusion assay and temperature-arrested HIV-infection kinetics, we provide evidence that the HIV-inhibitory E2 peptides interfere with late HIV-1 entry steps after the engagement of gp120 with CD4 receptor and coreceptor.
+Binding and competition experiments revealed that the N-terminal E2 peptides bind to the disulfide loop region of HIV-1 transmembrane protein gp41.
+In conjunction with computational analyses, we identified sequence similarities between the N-termini of GBV-C E2 and the HIV-1 glycoprotein gp120.
+This similarity appears to enable the GBV-C E2 N-terminus to interact with the HIV-1 gp41 disulfide loop, a crucial domain involved in the gp120-gp41 interface.
+Furthermore, the results of the present study provide initial proof of concept that peptides targeted to the gp41 disulfide loop are able to inhibit HIV fusion and should inspire the development of this new class of HIV-1 entry inhibitors.
+The brain is assumed to be a sterile organ in the absence of disease although the impact of immune disruption is uncertain in terms of brain microbial diversity or quantity.
+To investigate microbial diversity and quantity in the brain, the profile of infectious agents was examined in pathologically normal and abnormal brains from persons with HIV/AIDS [HIV] (n = 12), other disease controls [ODC] (n = 14) and in cerebral surgical resections for epilepsy [SURG] (n = 6).
+Deep sequencing of cerebral white matter-derived RNA from the HIV (n = 4) and ODC (n = 4) patients and SURG (n = 2) groups revealed bacterially-encoded 16 s RNA sequences in all brain specimens with α-proteobacteria representing over 70% of bacterial sequences while the other 30% of bacterial classes varied widely.
+Bacterial rRNA was detected in white matter glial cells by in situ hybridization and peptidoglycan immunoreactivity was also localized principally in glia in human brains.
+Analyses of amplified bacterial 16 s rRNA sequences disclosed that Proteobacteria was the principal bacterial phylum in all human brain samples with similar bacterial rRNA quantities in HIV and ODC groups despite increased host neuroimmune responses in the HIV group.
+Exogenous viruses including bacteriophage and human herpes viruses-4, -5 and -6 were detected variably in autopsied brains from both clinical groups.
+Brains from SIV- and SHIV-infected macaques displayed a profile of bacterial phyla also dominated by Proteobacteria but bacterial sequences were not detected in experimentally FIV-infected cat or RAG1(−/−) mouse brains.
+Intracerebral implantation of human brain homogenates into RAG1(−/−) mice revealed a preponderance of α-proteobacteria 16 s RNA sequences in the brains of recipient mice at 7 weeks post-implantation, which was abrogated by prior heat-treatment of the brain homogenate.
+Thus, α-proteobacteria represented the major bacterial component of the primate brain’s microbiome regardless of underlying immune status, which could be transferred into naïve hosts leading to microbial persistence in the brain.
+BACKGROUND: Swine influenza (SI) is an acute respiratory disease caused by swine influenza virus (SIV).
+The objective of this work was to study the acute phase proteins (APP) responses after coinfection of piglets with H1N1 swine influenza virus (SwH1N1) and Pasteurella multocida (Pm) in order to identify whether the individual APP response correlate with disease severity and whether APP could be used as markers of the health status of coinfected pigs.
+The mean level of antibodies against Pm dermonecrotoxin in infected piglets increase significantly from 7 dpi.
+The concentration of C-reactive protein (CRP) increased significantly at 1 dpi as compared to control pigs, and remained significantly higher to 3 dpi.
+Haptoglobin (Hp) was significantly elevated from 3 dpi to the end of study, while pig major acute phase protein (Pig-MAP) from 3 to 7 dpi.
+Positive correlations were found between serum concentration of Hp and SAA and lung scores, and between clinical score and concentrations of Pig-MAP and SAA.
+CONCLUSIONS: The results of current study confirmed that monitoring of APP may revealed ongoing infection, and in this way may be useful in selecting clinically healthy pigs (i.e.
+Present results corroborated our previous findings that SAA could be a potentially useful indicator in experimental infection studies (e.g.
+vaccine efficiency investigations) or as a marker for disease severity, because of correlation observed between its concentration in serum and disease severity (lung scores, clinical scores).
+The immune system rapidly responds to intracellular infections by detecting MHC class I restricted T-cell epitopes presented on infected cells.
+It was originally thought that viral peptides are liberated during constitutive protein turnover, but this conflicts with the observation that viral epitopes are detected within minutes of their synthesis even when their source proteins exhibit half-lives of days.
+The DRiPs hypothesis proposes that epitopes derive from Defective Ribosomal Products (DRiPs), rather than degradation of mature protein products.
+If this is a major source of DRiPs, this should be reflected in positional bias towards the N-terminus.
+By contrast, if downstream initiation is a major source of DRiPs, there should be positional bias towards the C-terminus.
+Here, we systematically assessed positional bias of epitopes in viral antigens, exploiting the large set of data available in the Immune Epitope Database and Analysis Resource.
+We show a statistically significant degree of positional skewing among epitopes; epitopes from both ends of antigens tend to be under-represented.
+Centric-skewing correlates with a bias towards class I binding peptides being over-represented in the middle, in parallel with a higher degree of evolutionary conservation.
+BACKGROUND: This study aimed to establish a suitable in vitro system for investigating effects of respiratory pathogens and toxins on lung tissue bioenergetics (cellular respiration and ATP content) and caspase activity.
+Lung fragments were then collected and incubated at 37°C in a continuously gassed (with 95% O(2):5% CO(2)) Minimal Essential Medium (MEM) or Krebs-Henseleit buffer.
+Phosphorescence O(2) analyzer that measured dissolved O(2) concentration as a function of time was used to monitor the rate of cellular mitochondrial O(2) consumption.
+The caspase-3 substrate N-acetyl-asp-glu-val-asp-7-amino-4-methylcoumarin (Ac-DEVD-AMC) was used to monitor intracellular caspase activity; cleaved AMC moieties (reflecting caspase activity) were separated on HPLC and detected by fluorescence.
+RESULTS: For Wistar rats, the values of k(c) and ATP for 0 < t ≤ 7 h (mean ± SD) were 0.15 ± 0.02 μM O(2) min(-1) mg(-1) (n = 18, coefficient of variation, Cv = 13%) and 131 ± 69 pmol mg(-1) (n = 16, Cv = 53%), respectively.
+The AMC peak areas remained relatively small despite a ~5-fold rise over 6 h. Good tissue preservation was evident despite time-dependent increases in apoptotic cells.
+Lung tissue bioenergetics, caspase activity and structure were deleterious in unoxygenated or intermittently oxygenated solutions.
+Incubating lung tissue in O(2) depleted MEM for 30 min or anesthesia by urethane had no effect on lung bioenergetics, but produced higher caspase activity.
+CONCLUSIONS: Lung tissue bioenergetics and structure could be maintained in vitro in oxygenated buffer for several hours and, thus, used as biomarkers for investigating respiratory pathogens or toxins.
+A virulent avian infectious bronchitis virus (IBV) was isolated from 30-day-old broiler chickens that exhibited respiratory symptoms, nephropathologic lesions, and a high proportion of deaths in the People’s Republic of China during 2005.
+Phylogenetic analysis showed that YN and most of the previously characterized IBV isolates found in China were phylogenetically classified into 2 main genetic clusters.
+The YN isolate caused severe lesions and resulted in deaths of 65% in experimental infections of 30-day-old specific-pathogen–free chickens.
+Tracheal and severe kidney lesions developed in all infected birds, confirming the ability of YN strain to induce both respiratory and renal disease.
+IBV antigens were detected by immunohistochemical analysis in the trachea, lung, kidney, and bursa, consistent with histopathologic observations, virus isolation, and reverse transcription PCR detection.
+We showed that YN IBV exhibits severe pathogenicity in chickens, and that similar viruses are prevalent in China.
+The Mekong Basin Disease Surveillance (MBDS) network was formally established in 2001 through a Memorandum of Understanding signed by six Ministers of Health of the countries in the Greater Mekong sub-region: Cambodia, China (Yunnan and Guangxi), Lao PDR, Myanmar, Thailand and Vietnam.
+The main areas of focus of the network are to: i) improve cross-border infectious disease outbreak investigation and response by sharing surveillance data and best practices in disease recognition and reporting, and by jointly responding to outbreaks; ii) develop expertise in epidemiological surveillance across the countries; and iii) enhance communication between the countries.
+Comprised of senior health officials, epidemiologists, health practitioners, and other professionals, the MBDS has grown and matured over the years into an entity based on mutual trust that can be sustained into the future.
+In this paper, we describe the development of MBDS, the way in which it operates today, and some of its achievements.
+We present key challenges the network has faced and lessons its members have learned about how to develop sufficient trust for health and other professionals to alert each other to disease threats across national borders and thereby more effectively combat these threats.
+In the new millennium, the centuries-old strategy of quarantine is becoming a powerful component of the public health response to emerging and reemerging infectious diseases.
+During the 2003 pandemic of severe acute respiratory syndrome, the use of quarantine, border controls, contact tracing, and surveillance proved effective in containing the global threat in just over 3 months.
+For centuries, these practices have been the cornerstone of organized responses to infectious disease outbreaks.
+However, the use of quarantine and other measures for controlling epidemic diseases has always been controversial because such strategies raise political, ethical, and socioeconomic issues and require a careful balance between public interest and individual rights.
+In a globalized world that is becoming ever more vulnerable to communicable diseases, a historical perspective can help clarify the use and implications of a still-valid public health strategy.
+The rapid advancement of genome technologies holds great promise for improving the quality and speed of clinical and public health laboratory investigations and for decreasing their cost.
+The latest generation of genome DNA sequencers can provide highly detailed and robust information on disease-causing microbes, and in the near future these technologies will be suitable for routine use in national, regional, and global public health laboratories.
+With additional improvements in instrumentation, these next- or third-generation sequencers are likely to replace conventional culture-based and molecular typing methods to provide point-of-care clinical diagnosis and other essential information for quicker and better treatment of patients.
+Provided there is free-sharing of information by all clinical and public health laboratories, these genomic tools could spawn a global system of linked databases of pathogen genomes that would ensure more efficient detection, prevention, and control of endemic, emerging, and other infectious disease outbreaks worldwide.
+To our knowledge, no previous study has reported the existence of bocavirus in Saudi Arabia.
+Swabs samples from 80 children with respiratory tract infections were examined for the presence of HBoV.
+The NP1 partial gene sequence from all patients showed that the circulated strains were related to HBoV-1 genotype.
+Interestingly, most of the HBoV1 infected cases were associated with high rates of co-infections with other viruses.
+During disease progression to AIDS, HIV-1 infected individuals become increasingly immunosuppressed and susceptible to opportunistic infections.
+It has also been demonstrated that multiple subsets of dendritic cells (DC), including DC-SIGN(+) cells, become significantly depleted in the blood and lymphoid tissues of AIDS patients, which may contribute to the failure in initiating effective host immune responses.
+It is also known that vast quantities of viral envelope protein gp120 are shed from maturing HIV-1 virions and form circulating immune complexes in the serum of HIV-1-infected individuals, but the pathological role of gp120 in HIV-1 pathogenesis remains elusive.
+Here we describe a previously unrecognized mechanism of DC death in chronic HIV-1 infection, in which ligation of DC-SIGN by gp120 sensitizes DC to undergo accelerated apoptosis in response to a variety of activation stimuli.
+The cultured monocyte-derived DC and also freshly-isolated DC-SIGN(+) blood DC that were exposed to either cross-linked recombinant gp120 or immune-complex gp120 in HIV(+) serum underwent considerable apoptosis after CD40 ligation or exposure to bacterial lipopolysaccharide (LPS) or pro-inflammatory cytokines such as TNFα and IL-1β.
+Furthermore, circulating DC-SIGN(+) DC that were isolated directly from HIV-1(+) individuals had actually been pre-sensitized by serum gp120 for activation-induced exorbitant apoptosis.
+Finally, we showed that accelerated DC apoptosis was a direct consequence of excessive activation of the pro-apoptotic molecule ASK-1 and transfection of siRNA against ASK-1 significantly prevented the activation-induced excessive DC death.
+Our study discloses a previously unknown mechanism of immune modulation by envelope protein gp120, provides new insights into HIV immunopathogenesis, and suggests potential therapeutic approaches to prevent DC depletion in chronic HIV infection.
+The alveolar epithelium serves as a barrier between organism and environment and functions as the first line of protection against potential respiratory pathogens.
+Alveolar type II (TII) cells have traditionally been considered the immune cells of the alveolar epithelium, as they possess immunomodulatory functions; however, the precise role of alveolar type I (TI) cells, which comprise ∼95% of the alveolar epithelial surface area, in lung immunity is not clear.
+We sought to determine if there was a difference in the response of TI and TII cells to lung injury and if TI cells could actively participate in the alveolar immune response.
+TI cells isolated via fluorescence activated cell sorting (FACS) from LPS-injured rats demonstrated greater fold-induction of multiple inflammatory mediators than TII cells isolated in the same manner from the same animals.
+Levels of the cytokines TNF-α, IL-6 and IL-1β from cultured primary rat TI cells after LPS stimulation were significantly increased compared to similarly studied primary rat TII cells.
+We found that contrary to published reports, cultured TII cells produce relatively small amounts of TNF-α, IL-6 and IL-1β after LPS treatment; the higher levels of cytokine expression from cultured TII cells reported in the literature were likely from macrophage contamination due to traditional non-FACS TII cell isolation methods.
+Co-culture of TII cells with macrophages prior to LPS stimulation increased TNF-α and IL-6 production to levels reported by other investigators for TII cells, however, co-culture of TI cells and macrophages prior to LPS treatment resulted in marked increases in TNF-α and IL-6 production.
+Taken together, these findings advocate a role for TI cells in the innate immune response and suggest that both TI and TII cells are active players in host defense mechanisms in the lung.
+RNA-dependent RNA polymerase (RdRp) is essential to viral replication and is therefore one of the primary targets of countermeasures against these dangerous infectious agents.
+Development of broad-spectrum therapeutics targeting polymerases has been hampered by the extreme sequence variability of these sequences.
+RdRps range in length from 400–800 residues, yet contain only ∼20 residues that are conserved in most species.
+In this study, we made structure-based comparisons that are independent of sequence composition using a recently developed algorithm.
+We identified residue-to-residue correspondences of multiple protein structures and created (two-dimensional) structure-based alignment maps of 37 polymerase structures that provide both sequence and structure details.
+Using these maps, we determined that ∼75% of each polymerase species consists of seven protein segments, each of which has high structural similarity to segments in other species, though they are widely divergent in sequence composition and order.
+We define each of these segments as a ‘homomorph’, and each includes (though most are much larger than) the well-known conserved polymerase motifs.
+All homomorphs contact the template tunnel or nucleoside triphosphate (NTP) entry tunnel and the exterior of the protein, suggesting they constitute a structural and functional skeleton common among the polymerases.
+BACKGROUND: Primary ciliary dyskinesia (PCD) is a rare congenital respiratory disorder characterized by abnormal ciliary motility leading to chronic airway infections.
+Qualitative evaluation of ciliary beat pattern based on digital high-speed videomicroscopy analysis has been proposed in the diagnosis process of PCD.
+Although this evaluation is easy in typical cases, it becomes difficult when ciliary beating is partially maintained.
+We compared quantitative parameters with the qualitative evaluation of ciliary beat pattern in patients in whom the diagnosis of PCD was confirmed or excluded.
+METHODS: Nasal nitric oxide measurement, nasal brushings and biopsies were performed prospectively in 34 patients with suspected PCD.
+In combination with qualitative analysis, 12 quantitative parameters of ciliary beat pattern were determined on high-speed videomicroscopy recordings of beating ciliated edges.
+The combination of ciliary ultrastructural abnormalities on transmission electron microscopy analysis with low nasal nitric oxide levels was the “gold standard” used to establish the diagnosis of PCD.
+RESULTS: This “gold standard” excluded PCD in 15 patients (non-PCD patients), confirmed PCD in 10 patients (PCD patients) and was inconclusive in 9 patients.
+Among the 12 parameters, the distance traveled by the cilium tip weighted by the percentage of beating ciliated edges presented 96% sensitivity and 95% specificity.
+In 9/10 PCD patients, quantitative analysis was concordant with the “gold standard”, while the qualitative evaluation was discordant with the “gold standard” in 3/10 cases.
+Among the patients with an inconclusive “gold standard”, the use of quantitative parameters supported PCD diagnosis in 4/9 patients (confirmed by the identification of disease-causing mutations in one patient) and PCD exclusion in 2/9 patients.
+CONCLUSIONS: When the beat pattern is normal or virtually immotile, the qualitative evaluation is adequate to study ciliary beating in patients suspected for PCD.
+However, when cilia are still beating but with moderate alterations (more than 40% of patients suspected for PCD), quantitative analysis is required to precise the diagnosis and can be proposed to select patients eligible for TEM.
+The reasons for the unusual age-specific mortality patterns of the 1918–1919 influenza pandemic remain unknown.
+Here we characterize pandemic-related mortality by single year of age in a unique statewide Kentucky data set and explore breakpoints in the age curves.
+Pandemic-associated excess mortality rates were calculated by subtracting observed rates during pandemic months from rates in previous years, separately for each single year of age and by sex.
+The age profile of excess mortality risk in fall 1918 was characterized by a maximum among infants, a minimum at ages 9–10 years, a maximum at ages 24–26 years, and a second minimum at ages 56–59 years.
+The observed mortality breakpoints in male and female cohorts born during 1859–1862, 1892–1894, and 1908–1909 did not coincide with known dates of historical pandemics.
+The atypical age mortality patterns of the 1918–1919 pandemic cannot be explained by military crowding, war-related factors, or prior immunity alone and likely result from a combination of unknown factors.
+The function of any given biological membrane is determined largely by the specific set of integral membrane proteins embedded in it, and the peripheral membrane proteins attached to the membrane surface.
+The activity of these proteins, in turn, can be modulated by the phospholipid composition of the membrane.
+The reconstitution of membrane proteins into a model membrane allows investigation of individual features and activities of a given cell membrane component.
+However, the activity of membrane proteins is often difficult to sustain following reconstitution, since the composition of the model phospholipid bilayer differs from that of the native cell membrane.
+This review will discuss the reconstitution of membrane protein activities in four different types of model membrane—monolayers, supported lipid bilayers, liposomes and nanodiscs, comparing their advantages in membrane protein reconstitution.
+Variation in the surrounding model environments for these four different types of membrane layer can affect the three-dimensional structure of reconstituted proteins and may possibly lead to loss of the proteins activity.
+We also discuss examples where the same membrane proteins have been successfully reconstituted into two or more model membrane systems with comparison of the observed activity in each system.
+Understanding of the behavioral changes for proteins in model membrane systems after membrane reconstitution is often a prerequisite to protein research.
+It is essential to find better solutions for retaining membrane protein activities for measurement and characterization in vitro.
+Defining the connections among neurons is critical to our understanding of the structure and function of the nervous system.
+Recombinant viruses engineered to transmit across synapses provide a powerful approach for the dissection of neuronal circuitry in vivo.
+We recently demonstrated that recombinant vesicular stomatitis virus (VSV) can be endowed with anterograde or retrograde transsynaptic tracing ability by providing the virus with different glycoproteins.
+Here we extend the characterization of the transmission and gene expression of recombinant VSV (rVSV) with the rabies virus glycoprotein (RABV-G), and provide examples of its activity relative to the anterograde transsynaptic tracer form of rVSV.
+rVSV with RABV-G was found to drive strong expression of transgenes and to spread rapidly from neuron to neuron in only a retrograde manner.
+Depending upon how the RABV-G was delivered, VSV served as a polysynaptic or monosynaptic tracer, or was able to define projections through axonal uptake and retrograde transport.
+In animals co-infected with rVSV in its anterograde form, rVSV with RABV-G could be used to begin to characterize the similarities and differences in connections to different areas.
+rVSV with RABV-G provides a flexible, rapid, and versatile tracing tool that complements the previously described VSV-based anterograde transsynaptic tracer.
+INTRODUCTION: Although pneumonia has been identified as the single most common risk factor for acute lung injury (ALI), we have a limited knowledge as to why ALI develops in some patients with pneumonia and not in others.
+The objective of this study was to determine frequency, risk factors, and outcome of ALI in patients with infectious pneumonia.
+METHODS: A retrospective cohort study of adult patients with microbiologically positive pneumonia, hospitalized at two Mayo Clinic Rochester hospitals between January 1, 2005, and December 31, 2007.
+In a subsequent nested case-control analysis, we evaluated the differences in prehospital and intrahospital exposures between patients with and without ALI/acute respiratory distress syndrome (ARDS) matched by specific pathogen, isolation site, gender, and closest age in a 1:1 manner.
+The occurrence of ALI was less frequent in bacterial (n = 99 of 412, 24%) compared with viral (n = 19 of 55, 35%), fungal (n = 39 of 95, 41%), and mixed isolates pneumonias (n = 14 of 34, 41%; P = 0.002).
+After adjusting for baseline severity of illness and comorbidities, patients in whom ALI developed had a markedly increased risk of hospital death (OR(adj )9.7; 95% CI, 6.0 to 15.9).
+In a nested case-control study, presence of shock (OR, 8.9; 95% CI, 2.8 to 45.9), inappropriate initial antimicrobial treatment (OR, 3.2; 95% CI, 1.3 to 8.5), and transfusions (OR, 4.8; 95% CI, 1.5 to 19.6) independently predicted ALI development.
+CONCLUSIONS: The development of ALI among patients hospitalized with infectious pneumonia varied among pulmonary pathogens and was associated with increased mortality.
+The objective of this study was to screen for antigens of the hepatitis C virus (HCV) to establish a new double antibody sandwich-lateral flow immunoassay (DAS-LFIA) method for testing the presence of anti-HCV antibodies in human serum or plasma.
+A series of different recombinant HCV proteins in Escherichia coli cells were constructed, expressed, purified and the new DAS-LFIA strip was developed.
+The sensitivity and specificity of new the DAS-LFIA strip were evaluated by detecting 23 HCV-positive sera, a set of quality control references for anti-HCV detection that contain known amounts of anti-HCV antibodies, and 8 HCV-negative sera.
+A total of 300 clinical serum samples was examined by both the new DAS-LFIA strip and enzyme-linked immunosorbent assay (ELISA).
+In conclusion, our new testing method is rapid, simple, sensitive and specifically detects the presence of anti-HCV antibodies in human serum or plasma.
+Although hepatitis C virus (HCV) affects approximately 130–170 million people worldwide, no vaccines are available.
+HCV is an important cause of chronic hepatitis, cirrhosis and hepatocellular carcinoma, leading to the need for liver transplantation.
+In this study, curcumin, a constituent used in traditional Chinese medicine, has been evaluated for its anti-HCV activity and mechanism, using a human hepatoma cell line containing the HCV genotype 1b subgenomic replicon.
+Below the concentration of 20% cytotoxicity, curcumin dose-dependently inhibited HCV replication by luciferase reporter gene assay, HCV RNA detection and HCV protein analysis.
+Under the same conditions, curcumin also dose-dependently induced heme oxygenase-1 with the highest induction at 24 h. Hemin, a heme oxygenase-1 inducer, also inhibited HCV protein expression in a dose-dependent manner.
+In addition to the heme oxygenase-1 induction, signaling molecule activities of AKT, extracellular signal-regulated kinases (ERK) and nuclear factor-κB (NF-κB) were inhibited by curcumin.
+Using specific inhibitors of PI3K-AKT, MEK-ERK and NF-κB, the results suggested that only PI3K-AKT inhibition is positively involved in curcumin-inhibited HCV replication.
+Although curcumin also inhibits ERK and NF-κB activities, it slightly increased the HCV protein expression.
+This result may provide information when curcumin is used as an adjuvant in anti-HCV therapy.
+BACKGROUND: During the early stages of a new influenza pandemic, travel restriction is an immediate and non-pharmaceutical means of retarding incidence growth.
+It extends the time frame of effective mitigation, especially when the characteristics of the emerging virus are unknown.
+In the present study, we used the 2009 influenza A pandemic as a case study to evaluate the impact of regulating air, sea, and land transport.
+METHODS: Hong Kong arrivals from 44 countries via air, sea, and land transports were imported into a discrete stochastic Susceptible, Exposed, Infectious and Recovered (SEIR) host-flow model.
+The model allowed a number of latent and infectious cases to pass the border, which constitutes a source of local disease transmission.
+We also modeled antiviral and hospitalization prevention strategies to compare the effectiveness of these control measures.
+RESULTS: Regarding air travel, the main route connected to the influenza source area should be targeted for travel restrictions; imposing a 99% air travel restriction delayed the epidemic peak by up to two weeks.
+Once the pandemic was established in China, the strong land connection between Hong Kong and China rendered Hong Kong vulnerable.
+Antivirals and hospitalization were found to be more effective on attack rate reductions than travel restrictions.
+Combined strategies (with 99% restriction on all transport modes) deferred the peak for long enough to establish a vaccination program.
+We also suggest regulating the extent of restriction and the transport mode, once restriction has been deemed necessary for pandemic control.
+Although travel restrictions have yet to gain social acceptance, they allow time for mitigation response when a new and highly intrusive virus emerges.
+INTRODUCTION: Influenza is easily overlooked in intensive care units (ICUs), particularly in patients with alternative causes of respiratory failure or in those who acquire influenza during their ICU stay.
+METHODS: We performed a prospective study of patients admitted to three adult ICUs of our hospital from December 2010 to February 2011.
+All tracheal aspirate (TA) samples sent to the microbiology department were systematically screened for influenza.
+We defined influenza as unsuspected if testing was not requested and the patient was not receiving empirical antiviral therapy after sample collection.
+Influenza was detected in 31 patients and was classified as unsuspected in 15 (48.4%) patients, and as hospital acquired in 13 (42%) patients.
+Suspected and unsuspected cases were compared, and significant differences were found for age (53 versus 69 median years), severe respiratory failure (68.8% versus 20%), surgery (6.3% versus 60%), median days of ICU stay before diagnosis (1 versus 4), nosocomial infection (18.8% versus 66.7%), cough (93.8% versus 53.3%), localized infiltrate on chest radiograph (6.3% versus 40%), median days to antiviral treatment (2 versus 9), pneumonia (93.8% versus 53.3%), and acute respiratory distress syndrome (75% versus 26.7%).
+Multivariate analysis showed admission to the surgical ICU (odds ratio (OR), 37.1; 95% confidence interval (CI), 2.1 to 666.6; P = 0.01) and localized infiltrate on chest radiograph (OR, 27.8; 95% CI, 1.3 to 584.1; P = 0.03) to be independent risk factors for unsuspected influenza.
+CONCLUSION: During the influenza season, almost one third of critical patients with suspected lower respiratory tract infection had influenza, and in 48.4%, the influenza was unsuspected.
+Lower respiratory samples from adult ICUs should be systematically screened for influenza during seasonal epidemics.
+INTRODUCTION: The specific burden imposed on Intensive Care Units (ICUs) during the A/H1N1 influenza 2009 pandemic has been poorly explored.
+An on-line screening registry allowed a daily report of ICU beds occupancy rate by flu infected patients (Flu-OR) admitted in French ICUs.
+METHODS: We conducted a prospective inception cohort study with results of an on-line screening registry designed for daily assessment of ICU burden.
+RESULTS: Among the 108 centers participating to the French H1N1 research network on mechanical ventilation (REVA) - French Society of Intensive Care (SRLF) registry, 69 ICUs belonging to seven large geographical areas voluntarily participated in a website screening-registry.
+The aim was to daily assess the ICU beds occupancy rate by influenza-infected and non-infected patients for at least three weeks.
+Three hundred ninety-one critically ill infected patients were enrolled in the cohort, representing a subset of 35% of the whole French 2009 pandemic cohort; 73% were mechanically ventilated, 13% required extra corporal membrane oxygenation (ECMO) and 22% died.
+The global Flu-OR in these ICUs was only 7.6%, but it exceeded a predefined 15% critical threshold in 32 ICUs for a total of 103 weeks.
+The peak ICU burden was poorly predicted by observations obtained at the level of large geographical areas.
+CONCLUSIONS: The peak Flu-OR during the pandemic significantly exceeded a 15% critical threshold in almost half of the ICUs, with an uneven distribution with time, geographical areas and between University and non-University hospitals.
+An on-line assessment of Flu-OR via a simple dedicated registry may contribute to better match resources and needs.
+INTRODUCTION: Community-acquired pneumonia (CAP) account for a high proportion of ICU admissions, with Streptococcus pneumoniae being the main pathogen responsible for these infections.
+However, little is known on the clinical features and outcomes of ICU patients with pneumococcal pneumonia.
+The aims of this study were to provide epidemiological data and to determine risk factors of mortality in patients admitted to ICU for severe S. pneumoniae CAP.
+Patients admitted for management of severe pneumococcal CAP were enrolled if they met the 2001 American Thoracic Society criteria for severe pneumonia, had life-threatening organ failure and had a positive microbiological sample for S. pneumoniae.
+RESULTS: Two hundred and twenty two patients were included, with a median SAPS II score reaching 47 [36-64].
+Acute respiratory failure (n = 154) and septic shock (n = 54) were their most frequent causes of ICU admission.
+Septic shock occurred in 170 patients (77%) and mechanical ventilation was required in 186 patients (84%); renal replacement therapy was initiated in 70 patients (32%).
+In multivariate analysis, independent risk factors for mortality were age (OR 1.05 (95% CI: 1.02-1.08)), male sex (OR 2.83 (95% CI: 1.16-6.91)) and renal replacement therapy (OR 3.78 (95% CI: 1.71-8.36)).
+New organisms and biological systems designed to satisfy human needs are among the aims of synthetic genomics and synthetic biology.
+Synthetic biology seeks to model and construct biological components, functions and organisms that do not exist in nature or to redesign existing biological systems to perform new functions.
+Synthetic genomics, on the other hand, encompasses technologies for the generation of chemically-synthesized whole genomes or larger parts of genomes, allowing to simultaneously engineer a myriad of changes to the genetic material of organisms.
+Engineering complex functions or new organisms in synthetic biology are thus progressively becoming dependent on and converging with synthetic genomics.
+While applications from both areas have been predicted to offer great benefits by making possible new drugs, renewable chemicals or clean energy, they have also given rise to concerns about new safety, environmental and socio-economic risks – stirring an increasingly polarizing debate.
+Here we intend to provide an overview on recent progress in biomedical and biotechnological applications of synthetic genomics and synthetic biology as well as on arguments and evidence related to their possible benefits, risks and governance implications.
+Choice of synonymous codons depends on nucleotide/dinucleotide composition of the genome (termed mutational pressure) and relative abundance of tRNAs in a cell (translational pressure).
+Mutational pressure is commonly simplified to genomic GC content; however mononucleotide and dinucleotide frequencies in different genomes or mRNAs may vary significantly, especially in RNA viruses.
+A series of in silico shuffling algorithms were developed to account for these features and analyze the relative impact of mutational pressure components on codon usage bias in RNA viruses.
+Total GC content was a poor descriptor of viral genome composition and causes of codon usage bias.
+Moreover, the choice between compatible amino acids (e.g., leucine and isoleucine) was strongly affected by genomic nucleotide composition.
+Together with mononucleotide composition bias, it could explain almost the entire codon usage bias in RNA viruses.
+On the other hand, strong dinucleotide content bias at codon position 3-1 found in some viruses had very little effect on codon usage.
+A hypothetical innate immunity sensor for CpG in RNA could partially explain the codon usage bias, but due to dependence of virus translation upon biased host translation machinery, experimental studies are required to further explore the source of dinucleotide bias in RNA viruses.
+BACKGROUND: Renal failure with following continuous renal replacement therapy is a major clinical problem in liver transplant recipients, with reported incidences of 3% to 20%.
+Little is known about the significance of postoperative acute renal failure or acute-on-chronic renal failure to postoperative outcome in liver transplant recipients.
+METHODS: In this post hoc analysis we compared the mortality rates of 135 consecutive liver transplant recipients over 6 years in our center subject to their renal baseline conditions and postoperative RRT.
+We classified the patients into 4 groups, according to their preoperative calculated Cockcroft formula and the incidence of postoperative renal replacement therapy.
+Data then were analyzed in regard to mortality rates and in addition to pre- and peritransplant risk factors.
+RESULTS: There was a significant difference in ICU mortality (p=.008), hospital mortality (p=.002) and cumulative survival (p<.0001) between the groups.
+The highest mortality rate occurred in the group with RRT and normal baseline kidney function (20% ICU mortality, 26.6% hospital mortality and 50% cumulative 1-year mortality, respectively).
+CONCLUSION: This study shows that in liver transplant recipient’s acute renal failure with postoperative RRT is associated with mortality and the mortality rate is higher than in patients with acute-on-chronic renal failure and postoperative renal replacement therapy.
+As a bioaerosol sampling standard, Andersen type impactor is widely used since its invention in 1950s, including the investigation of the anthrax attacks in the United States in 2001.
+However, its related problems such as impaction and desiccation stress as well as particle bounce have not been solved.
+Here, we improved its biological collection efficiencies by plating a mineral oil layer (100 µL) onto the agar plate.
+An Andersen six-stage sampler and a BioStage impactor were tested with mineral-oil-spread agar plates in collecting indoor and outdoor bacterial and fungal aerosols.
+The effects of sampling times (5, 10 and 20 min) were also studied using the BioStage impactor when sampling environmental bioaerosols as well as aerosolized Bacillus subtilis (G+) and Escherichia coli (G-).
+In addition, particle bounce reduction by mineral-oil-plate was also investigated using an optical particle counter (OPC).
+Experimental results revealed that use of mineral-oil-spread agar plate can substantially enhance culturable bioaerosol recoveries by Andersen type impactors (p-values<0.05).
+The recovery enhancement was shown to depend on bioaerosol size, type, sampling time and environment.
+In general, more enhancements (extra 20%) were observed for last stage of the Andersen six-stage samplers compared to the BioStage impactor for 10 min sampling.
+When sampling aerosolized B. subtilis, E. coli and environmental aerosols, the enhancement was shown to increase with increasing sampling time, ranging from 50% increase at 5 min to ∼100% at 20 min.
+OPC results indicated that use of mineral oil can effectively reduce the particle bounce with an average of 66% for 10 min sampling.
+Our work suggests that enhancements for fungal aerosols were primarily attributed to the reduced impaction stress, while for bacterial aerosols reduced impaction, desiccation and particle bounce played major roles.
+The developed technology can readily enhance the agar-based techniques including those high volume portable samplers for bioaerosol monitoring.
+BACKGROUND: Knowing the national disease burden of severe influenza in low-income countries can inform policy decisions around influenza treatment and prevention.
+METHODS AND FINDINGS: This method begins with calculating the hospitalized severe acute respiratory illness (SARI) incidence for children <5 years old and persons ≥5 years old from population-based surveillance in one province.
+This base rate of SARI is then adjusted for each province based on the prevalence of risk factors and healthcare-seeking behavior.
+The percentage of SARI with influenza virus detected is determined from provincial-level sentinel surveillance and applied to the adjusted provincial rates of hospitalized SARI.
+Rates of hospitalized and non-hospitalized influenza-associated SARI are applied to census data to calculate the national number of cases.
+The method was field-tested in Kenya, and validated in Guatemala, using data from August 2009–July 2011.
+In Kenya (2009 population 38.6 million persons), the annual number of hospitalized influenza-associated SARI cases ranged from 17,129–27,659 for children <5 years old (2.9–4.7 per 1,000 persons) and 6,882–7,836 for persons ≥5 years old (0.21–0.24 per 1,000 persons), depending on year and base rate used.
+In Guatemala (2011 population 14.7 million persons), the annual number of hospitalized cases of influenza-associated pneumonia ranged from 1,065–2,259 (0.5–1.0 per 1,000 persons) among children <5 years old and 779–2,252 cases (0.1–0.2 per 1,000 persons) for persons ≥5 years old, depending on year and base rate used.
+In both countries, the number of non-hospitalized influenza-associated cases was several-fold higher than the hospitalized cases.
+CONCLUSIONS: Influenza virus was associated with a substantial amount of severe disease in Kenya and Guatemala.
+BACKGROUND: Human T cell lymphotropic virus type 1 (HTLV-1) infection can lead to development of adult T cell leukemia/lymphoma (ATL) or HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in a subset of infected subjects.
+HTLV-1 basic leucine zipper factor (HBZ) gene has a critical role in HTLV-1 infectivity and the development of ATL and HAM/TSP.
+In this study, we examined antibody responses against HBZ in serum/plasma samples from 436 subjects including HTLV-1 seronegative donors, asymptomatic carriers (AC), ATL, and HAM/TSP patients using the luciferase immunoprecipitation system.
+RESULTS: Immunoreactivity against HBZ was detected in subsets of all HTLV-1-infected individuals but the test did not discriminate between AC, ATL and HAM/TSP.
+However, the frequency of detection of HBZ-specific antibodies in the serum of ATL patients with the chronic subtype was higher than in ATL patients with the lymphomatous subtype.
+Antibody responses against HBZ were also detected in cerebrospinal fluid of HAM/TSP patients with anti-HBZ in serum.
+Antibody responses against HBZ did not correlate with proviral load and HBZ mRNA expression in HAM/TSP patients, but the presence of an HBZ-specific response was associated with reduced CD4(+) T cell activation in HAM/TSP patients.
+CONCLUSIONS: This is the first report demonstrating humoral immune response against HBZ associated with HTLV-I infection.
+Genetic variation contributes to host responses and outcomes following infection by influenza A virus or other viral infections.
+Yet narrow windows of disease symptoms and confounding environmental factors have made it difficult to identify polymorphic genes that contribute to differential disease outcomes in human populations.
+Therefore, to control for these confounding environmental variables in a system that models the levels of genetic diversity found in outbred populations such as humans, we used incipient lines of the highly genetically diverse Collaborative Cross (CC) recombinant inbred (RI) panel (the pre-CC population) to study how genetic variation impacts influenza associated disease across a genetically diverse population.
+A wide range of variation in influenza disease related phenotypes including virus replication, virus-induced inflammation, and weight loss was observed.
+Many of the disease associated phenotypes were correlated, with viral replication and virus-induced inflammation being predictors of virus-induced weight loss.
+In order to identify how host genetic polymorphisms contribute to the observed variation in disease, we conducted quantitative trait loci (QTL) mapping.
+We identified several QTL contributing to specific aspects of the host response including virus-induced weight loss, titer, pulmonary edema, neutrophil recruitment to the airways, and transcriptional expression.
+Existing whole-genome sequence data was applied to identify high priority candidate genes within QTL regions.
+A key host response QTL was located at the site of the known anti-influenza Mx1 gene.
+We sequenced the coding regions of Mx1 in the eight CC founder strains, and identified a novel Mx1 allele that showed reduced ability to inhibit viral replication, while maintaining protection from weight loss.
+BACKGROUND: Asthma was the most common co-morbidity among patients hospitalized with pandemic influenza A(H1N1)pdm09 [pH1N1] infection.
+The objective was to compare characteristics of hospitalized pH1N1 patients with and without asthma and assess factors associated with severity among asthma patients.
+A case was defined as a person ≥ 2 years old hospitalized with laboratory-confirmed pH1N1.
+Persons with asthma were more likely to be 2–17 years old (39% vs. 30%, p = 0.04) and black (29% vs. 18%, p < 0.01), and have chronic obstructive pulmonary disease (13% vs. 9%, p = 0.04) but less likely to have pneumonia (37% vs. 47%, p = 0.05), need mechanical ventilation (13% vs. 23%, p = 0.02), and die (4% vs. 10%, p = 0.04) than those without asthma.
+Among patients with asthma, those admitted to an intensive care unit (ICU) or who died (n = 38) compared with survivors not admitted to an ICU (n = 99) were more likely to have pneumonia on admission (60% vs. 27%, p < 0.01) or acute respiratory distress syndrome (24% vs. 0%, p < 0.01) and less likely to receive influenza antiviral agents ≤ 2 days of admission (73% vs. 92%, p = 0.02).
+CONCLUSIONS: The majority of persons with asthma had an uncomplicated course; however, severe disease, including ICU admission and death, occurred in asthma patients who presented with pneumonia.
+Influenza antiviral agents should be started early in hospitalized patients with suspected influenza, including those with asthma.
+BACKGROUND: Relationship between the level of repetitiveness in genomic sequence and genome size has been investigated by making use of complete prokaryotic and eukaryotic genomes, but relevant studies have been rarely made in virus genomes.
+RESULTS: In this study, a total of 257 viruses were examined, which cover 90% of genera.
+The results showed that simple sequence repeats (SSRs) is strongly, positively and significantly correlated with genome size.
+Mono-, di- and tri- repeats are widely distributed in all virus genomes, tetra- SSRs as a common component consist in genomes which more than 100 kb in size; in the range of genome < 100 kb, genomes containing penta- and hexa- SSRs are not more than 50%.
+Principal components analysis (PCA) indicated that dinucleotide repeat affects the differences of SSRs most strongly among virus genomes.
+Results showed that SSRs tend to accumulate in larger virus genomes; and the longer genome sequence, the longer repeat units.
+We concluded that genome size is an important factor in affecting the occurrence of SSRs; hosts are also responsible for the variances of SSRs content to a certain degree.
+It is activated by long stretches of dsRNA and provides the first line of host defense against pathogens by inhibiting translation initiation in the infected cell.
+Many cellular and viral transcripts contain nucleoside modifications and/or tertiary structure that could affect PKR activation.
+We have previously demonstrated that a 5′-end triphosphate–a signature of certain viral and bacterial transcripts–confers the ability of relatively unstructured model RNA transcripts to activate PKR to inhibit translation, and that this activation is abrogated by certain modifications present in cellular RNAs.
+In order to understand the biological implications of native RNA tertiary structure and nucleoside modifications on PKR activation, we study here the heavily modified cellular tRNAs and the unmodified or the lightly modified mitochondrial tRNAs (mt-tRNA).
+We find that both a T7 transcript of yeast tRNA(Phe) and natively extracted total bovine liver mt-tRNA activate PKR in vitro, whereas native E. coli, bovine liver, yeast, and wheat tRNA(Phe) do not, nor do a variety of base- or sugar-modified T7 transcripts.
+These results are further supported by activation of PKR by a natively folded T7 transcript of tRNA(Phe) in vivo supporting the importance of tRNA modification in suppressing PKR activation in cells.
+We also examine PKR activation by a T7 transcript of the A14G pathogenic mutant of mt-tRNA(Leu), which is known to dimerize, and find that the misfolded dimeric form activates PKR in vitro while the monomeric form does not.
+Overall, the in vitro and in vivo findings herein indicate that tRNAs have an intrinsic ability to activate PKR and that nucleoside modifications and native RNA tertiary folding may function, at least in part, to suppress such activation, thus serving to distinguish self and non-self tRNA in innate immunity.
+OBJECTIVE: To evaluate the efficacy and tolerability of sorafenib combined with cryoablation in treating unresectable hepatocellular carcinoma (HCC).
+METHODS: Patients with unresectable advanced HCC received cryoablation and sorafenib at a dose of 400 mg twice daily in 4-week cycles on the same day of the cryoablation.
+Tumor response, median overall survival and the median time to radiological progression were calculated and the toxicity was evaluated.
+The Eastern Cooperative Oncology Group (ECOG) performance status scores were 0 (39.7%), 1 (55.1%), and 2 (5.1%).
+Nine (11.5%) patients were at Barcelona clinic liver cancer (BCLC) stage A, twenty-four (30.8%) patients were at stage B and 45 (57.7%) patients were at stage C. Five (6.4%) achieved partial responses, and 34 (43.6%) achieved stable disease.
+The median time to progression (TTP) for all enrolled patients was 6.6 months and the median overall survival (OS) was 12.2 months.
+CONCLUSION: Cryoablation combined with sorafenib demonstrates good efficacy and acceptable tolerability in treating unresectable advanced HCC patients.
+The exact role of CD8(+) T cells during Mycobacterium tuberculosis (Mtb) infection has been heavily debated, yet it is generally accepted that CD8(+) T cells contribute to protection against Mtb.
+In this study, however, we show that the Mtb-susceptible CBA/J mouse strain accumulates large numbers of CD8(+) T cells in the lung as infection progresses, and that these cells display a dysfunctional and immunosuppressive phenotype (PD-1(+), Tim-3(+), CD122(+)).
+CD8(+) T cell expansions from the lungs of Mtb-infected CBA/J mice were also capable of secreting the immunosuppressive cytokine interleukin-10 (IL-10), although in vivo CD8(+) T cell depletion did not significantly alter Mtb burden.
+Further analysis revealed that pulmonary CD8(+) T cells from Mtb-infected CBA/J mice were clonally expanded, preferentially expressing T cell receptor (TcR) Vβ chain 8 (8.2, 8.3) or Vβ 14.
+Although Vβ8(+) CD8(+) T cells were responsible for the majority of IL-10 production, in vivo depletion of Vβ8(+) did not significantly change the outcome of Mtb infection, which we hypothesize was a consequence of their dual IL-10/IFN-γ secreting profiles.
+Our data demonstrate that IL-10-secreting CD8(+) T cells can arise during chronic Mtb infection, although the significance of this T cell population in tuberculosis pathogenesis remains unclear.
+Here, we investigated whether a compound, polyethylenimine (PEI), which activates Toll-like receptor 5 (TLR5)-mediated NF-kB signaling pathways, could have an anti-radiation effect on a mouse model.
+First, a cell-based screening model for an agonist of TLR5-mediated NF-kB pathway was established and then validated by activation of TLR5-mediated NF-kB luciferase reporter activity with a known TLR5 agonist, flagellin.
+We found that PEI induced dose-dependent activation of the TLR5-mediated NF-kB pathway, indicating that PEI is indeed a TLR5 agonist.
+Furthermore, the anti-radiation effect of polyethylenimine was assessed using a γ-ray total body irradiation (TBI) mouse model.
+Compared with the irradiation control, both survival time and survival rate were significantly improved in mice that received either a low dose of polyethylenimine (P= 0.019) or a high dose of polyethylenimine (P< 0.001).
+We also observed a positive correlation between animal body weight and survival time in mice that received a low dose of polyethylenimine, a high dose of polyethylenimine and amifostine, over a period of 30 days, r= 0.42 (P< 0.02), 0.72 (P< 0.0001) and 0.95 (P< 0.0001), respectively, while a negative correlation between animal body weight and survival time was observed in the irradiation control (r= –0.89; P< 0.0001).
+These results indicate that polyethylenimine is a new TLR5 agonist with potential application in offering protection for patients receiving radiotherapy or in radiation-related accidents.
+Malaria is a reemerging disease in the countries where it was eradicated previously, whereas it is endemic in many countries including tropical countries.
+In India, malarial infection is on rise due to rapid urbanization and overcrowding in all major metropolitan cities.
+The incidence of morbidity and mortality due to malaria infection is increasing and could be attributed to drug resistance in strains of malarial parasite.
+Combining immune modulation strategies with anti-malarial drugs has a beneficial effect in an attempt to improve treatment for malaria.
+Along with clinical presentation and outcome of this parasitic infection, it is important to understand immunological disturbances associated with biological mechanisms underlying these actions in better understanding of pathogenesis of malarial infection.
+Immune and inflammatory responses in malarial infection are controlled and co-ordinated by various cytokines and chemokines.
+This review focuses on commonly seen immunological disturbances associated with malarial infection resulting in related humoral and cell mediated immune functions primarily with innate to subsequent adaptive immunity in tackling this parasitic infection.
+BACKGROUND: Recent focus on earlier detection of pathogen introduction in human and animal populations has led to the development of surveillance systems based on automated monitoring of health data.
+Real- or near real-time monitoring of pre-diagnostic data requires automated classification of records into syndromes–syndromic surveillance–using algorithms that incorporate medical knowledge in a reliable and efficient way, while remaining comprehensible to end users.
+METHODS: This paper describes the application of two of machine learning (Naïve Bayes and Decision Trees) and rule-based methods to extract syndromic information from laboratory test requests submitted to a veterinary diagnostic laboratory.
+RESULTS: High performance (F(1)-macro = 0.9995) was achieved through the use of a rule-based syndrome classifier, based on rule induction followed by manual modification during the construction phase, which also resulted in clear interpretability of the resulting classification process.
+An unmodified rule induction algorithm achieved an F(1-micro) score of 0.979 though this fell to 0.677 when performance for individual classes was averaged in an unweighted manner (F(1-macro)), due to the fact that the algorithm failed to learn 3 of the 16 classes from the training set.
+Decision Trees showed equal interpretability to the rule-based approaches, but achieved an F(1-micro) score of 0.923 (falling to 0.311 when classes are given equal weight).
+A Naïve Bayes classifier learned all classes and achieved high performance (F(1-micro) = 0.994 and F(1-macro) = .955), however the classification process is not transparent to the domain experts.
+CONCLUSION: The use of a manually customised rule set allowed for the development of a system for classification of laboratory tests into syndromic groups with very high performance, and high interpretability by the domain experts.
+Further research is required to develop internal validation rules in order to establish automated methods to update model rules without user input.
+RNA viruses are the causative agents for AIDS, influenza, SARS, and other serious health threats.
+Development of rapid and broadly applicable methods for complete viral genome sequencing is highly desirable to fully understand all aspects of these infectious agents as well as for surveillance of viral pandemic threats and emerging pathogens.
+In this study, we describe sequence-independent amplification for samples containing ultra-low amounts of viral RNA coupled with Illumina sequencing and de novo assembly optimized for viral genomes.
+With 5 million reads, we capture 96 to 100% of the viral protein coding region of HIV, respiratory syncytial and West Nile viral samples from as little as 100 copies of viral RNA.
+The methods presented here are scalable to large numbers of samples and capable of generating full or near full length viral genomes from clone and clinical samples with low amounts of viral RNA, without prior sequence information and in the presence of substantial host contamination.
+This review highlights the growing importance of protein epitope mimetics in the discovery of new biologically active molecules and their potential applications in drug and vaccine research.
+The focus is on folded β-hairpin mimetics, which are designed to mimic β-hairpin motifs in biologically important peptides and proteins.
+An ever-growing number of protein crystal structures reveal how β-hairpin motifs often play key roles in protein–protein and protein–nucleic acid interactions.
+This review illustrates how using protein structures as a starting point for small-molecule mimetic design can provide novel ligands as protein–protein interaction inhibitors, as protease inhibitors, and as ligands for chemokine receptors and folded RNA targets, as well as novel antibiotics to combat the growing health threat posed by the emergence of antibiotic-resistant bacteria.
+The β-hairpin antibiotics are shown to target a β-barrel outer membrane protein (LptD) in Pseudomonas sp., which is essential for the biogenesis of the outer cell membrane.
+Another exciting prospect is that protein epitope mimetics will be of increasing importance in synthetic vaccine design, in the emerging field of structural vaccinology.
+Crystal structures of protective antibodies bound to their pathogen-derived epitopes provide an ideal starting point for the design of synthetic epitope mimetics.
+The mimetics can be delivered to the immune system in a highly immunogenic format on the surface of synthetic virus-like particles.
+The scientific challenges in molecular design remain great, but the potential significance of success in this area is even greater.
+Among approximately 1000 adenoviruses from chimpanzees and bonobos studied recently, the Pan Adenovirus type 3 (PanAd3, isolated from a bonobo, Pan paniscus) has one of the best profiles for a vaccine vector, combining potent transgene immunogenicity with minimal pre-existing immunity in the human population.
+In this study, we inserted into a replication defective PanAd3 a transgene expressing a fusion protein of conserved influenza antigens nucleoprotein (NP) and matrix 1 (M1).
+We then studied antibody and T cell responses as well as protection from challenge infection in a mouse model.
+A single intranasal administration of PanAd3-NPM1 vaccine induced strong antibody and T cell responses, and protected against high dose lethal influenza virus challenge.
+Global climate change is expected to affect the frequency, intensity and duration of extreme water-related weather events such as excessive precipitation, floods, and drought.
+We conducted a systematic review to examine waterborne outbreaks following such events and explored their distribution between the different types of extreme water-related weather events.
+Four medical and meteorological databases (Medline, Embase, GeoRef, PubMed) and a global electronic reporting system (ProMED) were searched, from 1910 to 2010.
+Eighty-seven waterborne outbreaks involving extreme water-related weather events were identified and included, alongside 235 ProMED reports.
+Heavy rainfall and flooding were the most common events preceding outbreaks associated with extreme weather and were reported in 55·2% and 52·9% of accounts, respectively.
+Outbreaks following extreme water-related weather events were often the result of contamination of the drinking-water supply (53·7%).
+Extreme water-related weather events represent a risk to public health in both developed and developing countries, but impact will be disproportionate and likely to compound existing health disparities.
+The most severe manifestations of malaria (caused by Plasmodium falciparum) occur as a direct result of parasitemia following invasion of erythrocytes by post-liver blood-stage merozoites, and during subsequent cyto-adherence of infected erythrocytes to the vascular endothelium.
+However, the disproportionate epidemiologic clustering of severe malaria with aggressive forms of endemic diseases such as Kaposi’s sarcoma (KS), a neoplasm that is etiologically linked to infection with KS-associated herpesvirus (KSHV), underscores the significance of previously unexplored co-pathogenetic interactions that have the potential to modify the overall disease burden in co-infected individuals.
+Based on recent studies of the mechanisms that P. falciparum and KSHV have evolved to interact with their mutual human host, several new perspectives are emerging that highlight a surprising convergence of biological themes potentially underlying their associated co-morbidities.
+Against this background, ongoing studies are rapidly constructing a fascinating new paradigm in which the major host receptors that control parasite invasion (Basigin/CD147) and cyto-adherence (CD36) are, surprisingly, also important targets for exploitation by KSHV.
+In this article, we consider the major pathobiological implications of the co-option of Basigin/CD147 and CD36 signaling pathways by both P. falciparum and KSHV, not only as essential host factors for parasite persistence but also as important mediators of the pro-angiogenic phenotype within the virus-infected endothelial microenvironment.
+Consequently, the triangulation of interactions between P. falciparum, KSHV, and their mutual human host articulates a syndemic relationship that points to a conceptual framework for prevalence of aggressive forms of KS in malaria-endemic areas, with implications for the possibility of dual-use therapies against these debilitating infections in resource-limited parts of the world.
+NOA36/ZNF330 is an evolutionarily well-preserved protein present in the nucleolus and mitochondria of mammalian cells.
+We have previously reported that the pro-apoptotic activity of this protein is mediated by a characteristic cysteine-rich domain.
+We now demonstrate that the nucleolar localization of NOA36 is due to a highly-conserved nucleolar localization signal (NoLS) present in residues 1–33.
+This NoLS is a sequence containing three clusters of two or three basic amino acids.
+We fused the amino terminal of NOA36 to eGFP in order to characterize this putative NoLS.
+We show that a cluster of three lysine residues at positions 3 to 5 within this sequence is critical for the nucleolar localization.
+We also demonstrate that the sequence as found in human is capable of directing eGFP to the nucleolus in several mammal, fish and insect cells.
+Moreover, this NoLS is capable of specifically directing the cytosolic yeast enzyme polyphosphatase to the target of the nucleolus of HeLa cells, wherein its enzymatic activity was detected.
+This NoLS could therefore serve as a very useful tool as a nucleolar marker and for directing particular proteins to the nucleolus in distant animal species.
+BACKGROUND: The threat of emergence of a human-to-human transmissible strain of highly pathogenic influenza A(H5N1) is very real, and is reinforced by recent results showing that genetically modified A(H5N1) may be readily transmitted between ferrets.
+Public health authorities are hesitant in introducing social distancing interventions due to societal disruption and productivity losses.
+This study estimates the effectiveness and total cost (from a societal perspective, with a lifespan time horizon) of a comprehensive range of social distancing and antiviral drug strategies, under a range of pandemic severity categories.
+METHODS: An economic analysis was conducted using a simulation model of a community of ~30,000 in Australia.
+Data from the 2009 pandemic was used to derive relationships between the Case Fatality Rate (CFR) and hospitalization rates for each of five pandemic severity categories, with CFR ranging from 0.1% to 2.5%.
+RESULTS: For a pandemic with basic reproduction number R(0) = 1.8, adopting no interventions resulted in total costs ranging from $441 per person for a pandemic at category 1 (CFR 0.1%) to $8,550 per person at category 5 (CFR 2.5%).
+For severe pandemics of category 3 (CFR 0.75%) and greater, a strategy combining antiviral treatment and prophylaxis, extended school closure and community contact reduction resulted in the lowest total cost of any strategy, costing $1,584 per person at category 5.
+With low severity pandemics costs are dominated by productivity losses due to illness and social distancing interventions, whereas higher severity pandemic costs are dominated by healthcare costs and costs arising from productivity losses due to death.
+CONCLUSIONS: For pandemics in high severity categories the strategies with the lowest total cost to society involve rigorous, sustained social distancing, which are considered unacceptable for low severity pandemics due to societal disruption and cost.
+We previously demonstrated that mice immunized with CEP-modified albumin developed AMD-like degenerative changes in the outer retina.
+Here, we examined the kinetics of lesion development in immunized mice and the presence of macrophages within the interphotoreceptor matrix (IPM), between the retinal pigment epithelium and photoreceptor outer segments.
+We observed a significant and time-dependent increase in the number of macrophages in immunized mice relative to young age-matched controls prior to overt pathology.
+Moreover, when Ccr2-deficient mice were immunized, macrophages were not present in the IPM and no retinal lesions were observed, suggesting a deleterious role for these cells in our model.
+This work provides mechanistic evidence linking immune responses against oxidative damage with the presence of proinflammatory macrophages at sites of future AMD and experimentally demonstrates that manipulating immunity may be a target for modulating the development of AMD.
+BACKGROUND: Vincristine (VCR), which is a widely used antineoplastic drug, was integrated with a submicron-emulsion drug-delivery system to enhance the anticancer effect.
+METHODS: After the formation of a VCR-oleic acid ion-pair complex (VCR-OA), the VCR-OA-loaded submicron emulsion (VCR-OA-SME), prepared by classical high-pressure homogenization, was characterized and its in vitro anticancer effects were evaluated.
+The mean particle size, zeta potential, and encapsulation efficiency were 157.6 ± 12.6 nm, −26.5 ± 5.0 mV and 78.64% ± 3.44%, respectively.
+An in vitro release study of the VCR-OA-SME revealed that 12.4% of the VCR was released within the first 2 hours (initial burst-release phase) and the rest of the drug was detected in the subsequent sustained-release phase.
+Compared with VCR solution, the pharmacokinetic study of VCR-OA-SME showed relatively longer mean residence time (mean residence time [0–∞] increased from 187.19 to 227.56 minutes), higher maximum concentration (from 252.13 ng/mL to 533.34 ng/mL), and greater area under the curve (area under the curve [0–∞] from 11,417.77 μg/L/minute to 17,164.34 μg/L/minute.
+Moreover, the VCR-OA-SME exhibited higher cytotoxicity (P < 0.05) on tumor cells by inducing cell arrest in the G2/M phase or even apoptosis (P < 0.05).
+CONCLUSION: The VCR-OA-SME formulation in our study displayed great potential for an anticancer effect for VCR.
+Since the immune system is hardwired to protect the host, there is a possibility that cancers, regardless of their histological origins, endow themselves with a common and shared inflammatory cancer-associated molecular pattern (iCAMP) to promote oncoinflammation.
+METHODS AND FINDINGS: Genome-wide cDNA expression data was analyzed for 221 normal and 324 cancer specimens from 7 cancer types: breast, prostate, lung, colon, gastric, oral and pancreatic.
+A total of 96 inflammatory genes with consistent dysregulation were identified, including 44 up-regulated and 52 down-regulated genes.
+The iCAMP contains proteins whose roles in cancer have been implicated and others which are yet to be appreciated.
+The clinical significance of many iCAMP genes was confirmed in multiple independent cohorts of colon and ovarian cancer patients.
+In both cases, better prognosis correlated strongly with high CXCL13 and low level of GREM1, LOX, TNFAIP6, CD36, and EDNRA.
+An “Inflammatory Gene Integrated Score” was further developed from the combination of 18 iCAMP genes in ovarian cancer, which predicted overall survival.
+Noticeably, as a selective nuclear import protein whose immuno-regulatory function just begins to emerge, karyopherin alpha 2 (KPNA2) is uniformly up-regulated across cancer types.
+For the first time, the cancer-specific up-regulation of KPNA2 and its clinical significance were verified by tissue microarray analysis in colon and head-neck cancers.
+CONCLUSION: This work defines an inflammatory signature shared by seven epithelial cancer types and KPNA2 as a consistently up-regulated protein in cancer.
+Identification of iCAMP may not only serve as a novel biomarker for prognostication and individualized treatment of cancer, but also have significant biological implications.
+The nasal septa of fetal rabbits at 26 days of gestation were harvested by cesarean section of the does while under anesthesia and then exposed to Bordetella bronchiseptica or its lipopolysaccharide (LPS) for periods of 2 and 4 hours.
+Then, semithin sections (0.5 μm) were stained with toluidine blue and examined with indirect immunoperoxidase (IPI) and lectin histochemistry.
+The most frequent and statistically significant findings were as follows: (1) cell death and increased goblet cell activity when exposed to bacteria and (2) cell death, cytoplasmic vacuolation and infiltration of polymorphonuclear leukocytes when exposed to LPS.
+The lesions induced by the bacterium were more severe than with LPS alone, except for the cytoplasmic vacuolation in epithelial cells.
+IPI stained the ciliated border of the epithelium with the bacterium more intensely, while LPS lectin histochemistry preferentially labeled the cytoplasm of goblet cell.
+These data indicate that B. bronchiseptica and its LPS may have an affinity for specific glycoproteins that would act as adhesion receptors in both locations.
+BACKGROUND: In endemic countries such as Bangladesh, consequences of cholera place an enormous financial and social burden on patients and their families.
+Cholera vaccines not only provide health benefits to susceptible populations but also have effects on the earning capabilities and financial stability of the family.
+Community-based research and evaluations are necessary to understand perceptions about and practices of the community relating to cholera and oral cholera vaccines.
+This may help identify the ways in which such vaccines may be successfully introduced, and other preventive measures can be implemented.
+The present study assessed the knowledge of, attitudes toward, and preventive practices relating to cholera and oral cholera vaccine among an urban population residing in a high cholera-prone setting in Dhaka, Bangladesh.
+METHODS: This cross-sectional study was conducted in an area of high cholera prevalence in 15 randomly-selected clusters in Mirpur, Dhaka city.
+A study team collected data through a survey and in-depth interviews during December 2010–February 2011.
+RESULTS: Of 2,830 families included in the final analysis, 23% could recognize cholera as acute watery diarrhea and 16% had ever heard of oral cholera vaccine.
+About 54% of the respondents had poor knowledge about cholera-related issues while 97% had a positive attitude toward cholera and oral cholera vaccine.
+The findings showed a significant (p < 0.05) association between the respondents’ knowledge and sex, education, occupation, monthly overall household expenditure, attitudes and practice.
+In the adjusted model, male sex, having a lower monthly overall household expenditure, and having a less positive attitude toward cholera were the significant predictors to having poor knowledge.
+CONCLUSIONS: The findings suggest the strengthening of health education activities to improve knowledge on cholera, its prevention and treatment and information on cholera vaccination among high-risk populations.
+The data also underscore the potential of mass cholera vaccination to prevent and control cholera.
+Tumor necrosis factor-alpha (TNF-α) was reported as anticancer therapy due to its cytotoxic effect against an array of tumor cells.
+However, its undesirable responses of TNF-α on activating NF-κB signaling and pro-metastatic property limit its clinical application in treating cancers.
+Therefore, sensitizing agents capable of overcoming this undesirable effect must be valuable for facilitating the usage of TNF-α-mediated apoptosis therapy for cancer patients.
+Previously, saikosaponin-d (Ssd), a triterpene saponin derived from the medicinal plant, Bupleurum falcatum L. (Umbelliferae), showed to exhibit a variety of pharmacological activities such as antiinflammation, antibacteria, antivirus and anticancer.
+Recently, we found that Ssd could inhibit the activated T lymphocytes via suppression of NF-κB, NF-AT and AP-1 signaling.
+Here, we showed that Ssd significantly potentiated TNF-α-mediated cell death in HeLa and HepG2 cancer cells via suppression of TNF-α-induced NF-κB activation and its target genes expression involving cancer cell proliferation, invasion, angiogenesis and survival.
+Also, Ssd revealed a significant potency of abolishing TNF-α-induced cancer cell invasion and angiogenesis in HUVECs while inducing apoptosis via enhancing the loss of mitochondrial membrane potential in HeLa cells.
+Collectively, these findings indicate that Ssd has a significant potential to be developed as a combined adjuvant remedy with TNF-α for cancer patients.
+OBJECTIVES: The possible occurrence of a highly pathogenic influenza strain is of concern to health authorities worldwide.
+It is known that during past influenza pandemics developing countries have experienced considerably higher death rates compared with developed countries.
+Mathematical modelling studies to guide the development of such plans are largely focused on predicting pandemic influenza spread in developed nations.
+However, intervention strategies shown by modelling studies to be highly effective for developed countries give limited guidance as to the impact which an influenza pandemic may have on low-income countries given different demographics and resource constraints.
+To address this, an individual-based model of a Papua New Guinean (PNG) community was created and used to simulate the spread of a novel influenza strain.
+SETTING: The towns of Madang in PNG (population ∼35 000) and Albany (population ∼30 000) in Australia.
+OUTCOME MEASURES: Daily and cumulative illness attack rates in both models following introduction of a novel influenza strain into a naive population, for an unmitigated scenario and two social distancing intervention scenarios.
+RESULTS: The unmitigated scenario indicated an approximately 50% higher attack rate in PNG compared with the Australian model.
+The two social distancing-based interventions strategies were 60–70% less effective in a PNG setting compared with an Australian setting.
+CONCLUSIONS: This study provides further evidence that an influenza pandemic occurring in a low-income country such as PNG may have a greater impact than one occurring in a developed country, and that PNG-feasible interventions may be substantially less effective.
+The larger average household size in PNG, the larger proportion of the population under 18 and greater community-wide contact all contribute to this feature.
+The protective efficacy of DNA plasmids encoding avian infectious bronchitis virus (IBV) S1, N, or M protein was investigated in chickens.
+Chickens were inoculated monovalently (with plasmid pVAX1-16S1, pVAX1-16M, or pVAX1-16N alone) or multivalently (combination of the three different plasmids, pVAX1-16S1/M/N).
+Chickens were immunized with the multivalent DNA vaccine twice and then boosted with an inactivated vaccine once.
+Antibody titers of the chickens immunized with pVAX1-16S1/M/N were much higher than those of the monovalent groups (p < 0.01).
+The serum antibody titers in the prime-boost birds were significantly higher than those of the multivalent DNA vaccine group (p < 0.01) but not significantly different compared to the inactivated vaccine group at 49 days of age.
+Additionally, the prime-boost group also showed the highest level of IBV-specific cellular proliferation compared to the monovalent groups (p < 0.01) but no significant difference was found compared to the multivalent DNA vaccine group, and the prime-boost group completely protected from followed viral challenge.
+Most automated disease surveillance systems notify users of increases in the prevalence of reports in syndrome categories and allow users to view patient level data related to those increases.
+Occasionally, a more dynamic level of control is required to properly detect an emerging disease in a community.
+Dynamic querying features are invaluable when using existing surveillance systems to investigate outbreaks of newly emergent diseases or to identify cases of reportable diseases within data being captured for surveillance.
+The objective of the Advance Querying Tool (AQT) is to build a more flexible query interface for most web-based disease surveillance systems.
+This interface allows users to define and build their query as if they were writing a logical expression for a mathematical computation.
+It provides a flexible interface that accommodates both advanced and novice users, checks the validity of the expression as it is built, and marks errors for users.
+However, the lack of a safe and efficient oral delivery system restricts its clinical application.
+Here, we constructed alginic acid-coated chitosan nanoparticles (A.C.NPs) as an oral delivery carrier for a legumain DNA vaccine.
+DNA agarose electrophoresis data show that A.C.NPs protected DNA better from degradation in acidic solution (pH 1.5) than did chitosan nanoparticles (C.NPs).
+Furthermore, size distribution analysis showed that A.C.NPs tended to aggregate and form micrometer scale complexes in pH<2.7, while dispersing into nanoparticles with an increase in pH.
+Mice were intragastrically administrated A.C.NPs carrying EGFP plasmids and EGFP expression was detected in the intestinal Peyer’s patches.
+Full-length legumain plasmids were loaded into different delivery carriers, including C.NPs, attenuated Salmonella typhimurium and A.C.NPs.
+Our data indicate that tumor volume was significantly smaller in groups using A.C.NPs or attenuated Salmonella typhimurium as carriers.
+Furthermore, splenocytes co-cultured them with 4T1 cells pre-stimulated with CoCl(2), which influenced the translocation of legumain from cytoplasm to plasma membrane, showed a 4.7 and 2.3 folds increase in active cytotoxic T lymphocytes (CD3(+)/CD8(+)/CD25(+)) when treated with A.C.NPs carriers compared with PBS C.NPs.
+Our study suggests that C.NPs coated with alginic acid may be a safe and efficient tool for oral delivery of a DNA vaccine.
+Moreover, a legumain DNA vaccine delivered orally with A.C.NPs can effectively improve autoimmune response and protect against breast cancer in mice.
+Although berberine alkaloids (BAs) are reported to be with broad-spectrum antibacterial and antiviral activities, the interactions among BAs have not been elucidated.
+In the present study, methicillin-resistant Staphylococcus aureus (MRSA) was chosen as a model organism, and modified broth microdilution was applied for the determination of the fluorescence absorption values to calculate the anti-MRSA activity of BAs.
+We have initiated four steps to seek the optimal combination of BAs that are (1) determining the anti-MRSA activity of single BA, (2) investigating the two-component combination to clarify the interactions among BAs by checkerboard assay, (3) investigating the multicomponent combination to determine the optimal ratio by quadratic rotation-orthogonal combination design, and (4) in vivo and in vitro validation of the optimal combination.
+The synergetic combinations included “berberine and epiberberine,” “jatrorrhizine and palmatine” and “jatrorrhizine and coptisine”; the antagonistic combinations included “coptisine and epiberberine”.
+The optimal combination was berberine : coptisine : jatrorrhizine : palmatine : epiberberine = 0.702 : 0.863 : 1 : 0.491 : 0.526, and the potency of the optimal combination on cyclophosphamide-immunocompromised mouse model was better than the natural combinations of herbs containing BAs.
+Empiric quantification of human mobility patterns is paramount for better urban planning, understanding social network structure and responding to infectious disease threats, especially in light of rapid growth in urbanization and globalization.
+This need is of particular relevance for developing countries, since they host the majority of the global urban population and are disproportionally affected by the burden of disease.
+We used Global Positioning System (GPS) data-loggers to track the fine-scale (within city) mobility patterns of 582 residents from two neighborhoods from the city of Iquitos, Peru.
+We used ∼2.3 million GPS data-points to quantify age-specific mobility parameters and dynamic co-location networks among all tracked individuals.
+Only up to 38% of the tracked participants showed a regular and predictable mobility routine, a sharp contrast to the situation in the developed world.
+As a case study, we quantified the impact of spatially and temporally unstructured routines on the dynamics of transmission of an influenza-like pathogen within an Iquitos neighborhood.
+Temporally unstructured daily routines (e.g., not dominated by a single location, such as a workplace, where an individual repeatedly spent significant amount of time) increased an epidemic’s final size and effective reproduction number by 20% in comparison to scenarios modeling temporally structured contacts.
+Our findings provide a mechanistic description of the basic rules that shape human mobility within a resource-poor urban center, and contribute to the understanding of the role of fine-scale patterns of individual movement and co-location in infectious disease dynamics.
+More generally, this study emphasizes the need for careful consideration of human social interactions when designing infectious disease mitigation strategies, particularly within resource-poor urban environments.
+BACKGROUND: The clinical consequences of co-infection with two or more respiratory viruses are poorly understood.
+We sought to determine if co-infection with pandemic 2009–2010 influenza A H1N1 (pH1N1) and another respiratory virus was associated with worse clinical outcomes.
+METHODS: A retrospective cohort study was performed of all hospitalized patients with a positive respiratory viral panel (RVP) for two or more viruses within 72 hours of admission at our institution from October 2009 to December 2009.
+RESULTS: We identified 617 inpatients with a positive RVP sample with a single virus and 49 inpatients with a positive RVP sample for two viruses (i.e.
+Co-infected patients were significantly younger, more often had fever/chills, tachypnea, and they more often demonstrated interstitial opacities suggestive of viral pneumonia on the presenting chest radiograph (OR 7.5, 95% CI 3.4–16.5).
+The likelihood of death, length of stay, and requirement for intensive care unit level of care were similar in both groups, but patients with any respiratory virus co-infection were more likely to experience complications, particularly treatment for a secondary bacterial pneumonia (OR 6.8, 95% CI 3.3–14.2).
+Patients co-infected with pH1N1 and another respiratory virus were more likely to present with chest radiograph changes suggestive of a viral pneumonia, compared to mono-infection with pH1N1 (OR 16.9, 95% CI 4.5–62.7).
+By logistic regression using mono-infection with non-PH1N1 viruses as the reference group, co-infection with pH1N1 was the strongest independent predictor of treatment for a secondary bacterial pneumonia (OR 17.8, 95% CI 6.7–47.1).
+CONCLUSION: Patients with viral co-infection, particularly with pH1N1, were more likely to have chest radiograph features compatible with a viral pneumonia and complications during their hospital course, particularly treatment for secondary bacterial pneumonia.
+The high prevalence of type 2 diabetes mellitus in the world as well as the increasing reports about the adverse side effects of the existing diabetes treatment drugs have made developing new and effective drugs against the disease a very high priority.
+In this study, we report ten novel compounds found by targeting peroxisome proliferator-activated receptors (PPARs) using virtual screening and core hopping approaches.
+PPARs have drawn increasing attention for developing novel drugs to treat diabetes due to their unique functions in regulating glucose, lipid, and cholesterol metabolism.
+The reported compounds are featured with dual functions, and hence belong to the category of dual agonists.
+Compared with the single PPAR agonists, the dual PPAR agonists, formed by combining the lipid benefit of PPARα agonists (such as fibrates) and the glycemic advantages of the PPARγ agonists (such as thiazolidinediones), are much more powerful in treating diabetes because they can enhance metabolic effects while minimizing the side effects.
+This was observed in the studies on molecular dynamics simulations, as well as on absorption, distribution, metabolism, and excretion, that these novel dual agonists not only possessed the same function as ragaglitazar (an investigational drug developed by Novo Nordisk for treating type 2 diabetes) did in activating PPARα and PPARγ, but they also had more favorable conformation for binding to the two receptors.
+Moreover, the residues involved in forming the binding pockets of PPARα and PPARγ among the top ten compounds are explicitly presented, and this will be very useful for the in-depth conduction of mutagenesis experiments.
+It is anticipated that the ten compounds may become potential drug candidates, or at the very least, the findings reported here may stimulate new strategies or provide useful insights for designing new and more powerful dual-agonist drugs for treating type 2 diabetes.
+Respiratory Syncytial Virus (RSV) is a highly pathogenic member of the Paramyxoviridae that causes severe respiratory tract infections.
+Reports in the literature have indicated that to infect cells the incoming viruses either fuse their envelope directly with the plasma membrane or exploit clathrin-mediated endocytosis.
+To study the entry process in human tissue culture cells (HeLa, A549), we used fluorescence microscopy and developed quantitative, FACS-based assays to follow virus binding to cells, endocytosis, intracellular trafficking, membrane fusion, and infection.
+We found that immediately after binding to cells RSV activated a signaling cascade involving the EGF receptor, Cdc42, PAK1, and downstream effectors.
+This led to a series of dramatic actin rearrangements; the cells rounded up, plasma membrane blebs were formed, and there was a significant increase in fluid uptake.
+If these effects were inhibited using compounds targeting Na(+)/H(+) exchangers, myosin II, PAK1, and other factors, no infection was observed.
+The RSV was rapidly and efficiently internalized by an actin-dependent process that had all hallmarks of macropinocytosis.
+Rather than fusing with the plasma membrane, the viruses thus entered Rab5-positive, fluid-filled macropinosomes, and fused with the membranes of these on the average 50 min after internalization.
+To find an explanation for the endocytosis requirement, which is unusual among paramyxoviruses, we analyzed the fusion protein, F, and could show that, although already cleaved by a furin family protease once, it underwent a second, critical proteolytic cleavage after internalization.
+This cleavage by a furin-like protease removed a small peptide from the F1 subunits, and made the virus infectious.
+BACKGROUND: The way we formulate a mathematical model of an infectious disease to capture symptomatic and asymptomatic transmission can greatly influence the likely effectiveness of vaccination in the presence of vaccine effect for preventing clinical illness.
+The present study aims to assess the impact of model building strategy on the epidemic threshold under vaccination.
+METHODOLOGY/PRINCIPAL FINDINGS: We consider two different types of mathematical models, one based on observable variables including symptom onset and recovery from clinical illness (hereafter, the “observable model”) and the other based on unobservable information of infection event and infectiousness (the “unobservable model”).
+By imposing a number of modifying assumptions to the observable model, we let it mimic the unobservable model, identifying that the two models are fully consistent only when the incubation period is identical to the latent period and when there is no pre-symptomatic transmission.
+We also computed the reproduction numbers with and without vaccination, demonstrating that the data generating process of vaccine-induced reduction in symptomatic illness is consistent with the observable model only and examining how the effective reproduction number is differently calculated by two models.
+CONCLUSIONS: To explicitly incorporate the vaccine effect in reducing the risk of symptomatic illness into the model, it is fruitful to employ a model that directly accounts for disease progression.
+In mammals, carcinoembryonic antigen cell adhesion molecules (CEACAMs) and pregnancy-specific glycoproteins (PSGs) play important roles in the regulation of pathogen transmission, tumorigenesis, insulin signaling turnover, and fetal–maternal interactions.
+However, how these genes evolved and to what extent they diverged in humans remain to be investigated specifically.
+Based on syntenic mapping of chordate genomes, we reveal that diverging homologs with a prototypic CEACAM architecture–including an extracellular domain with immunoglobulin variable and constant domain-like regions, and an intracellular domain containing ITAM motif–are present from cartilaginous fish to humans, but are absent in sea lamprey, cephalochordate or urochordate.
+Interestingly, the CEACAM/PSG gene inventory underwent radical divergence in various vertebrate lineages: from zero in avian species to dozens in therian mammals.
+In addition, analyses of genetic variations in human populations showed the presence of various types of copy number variations (CNVs) at the CEACAM/PSG locus.
+These copy number polymorphisms have 3–80% frequency in select populations, and encompass single to more than six PSG genes.
+Furthermore, we found that CEACAM/PSG genes contain a significantly higher density of nonsynonymous single nucleotide polymorphism (SNP) compared to the chromosome average, and many CEACAM/PSG SNPs exhibit high population differentiation.
+Taken together, our study suggested that CEACAM/PSG genes have had a more dynamic evolutionary history in vertebrates than previously thought.
+Given that CEACAM/PSGs play important roles in maternal–fetal interaction and pathogen recognition, these data have laid the groundwork for future analysis of adaptive CEACAM/PSG genotype-phenotypic relationships in normal and complicated pregnancies as well as other etiologies.
+Cleft palate results from a mixture of genetic and environmental factors and occurs when the bilateral palatal shelves fail to fuse.
+The objective of this study was to search for new genes involved in mouse palate formation.
+Gene expression of murine embryonic palatal tissue was analyzed at various developmental stages before, during, and after palate fusion using GeneChip® microarrays.
+Ceacam1 was one of the highly up-regulated genes during palate formation, and this was confirmed by quantitative real-time PCR.
+Immunohistochemical staining showed that CEACAM1 was present in prefusion palatal epithelium and was degraded during fusion.
+To investigate the developmental role of CEACAM1, function-blocking antibody was added to embryonic mouse palate in organ culture.
+Epithelial cells persisted abnormally at the midline of the embryonic palate even on day E16.0, and palatal fusion was delayed in Ceacam1 (−/−) mice.
+TGFβ3 expression, apoptosis, and cell proliferation in palatal epithelium were not affected in the palate of Ceacam1(−/−)mice.
+These results suggest that CEACAM1 has roles in the initiation of palatal fusion via epithelial cell adhesion.
+We conducted an unbiased metagenomics survey using plasma from patients with chronic hepatitis B, chronic hepatitis C, autoimmune hepatitis (AIH), non-alcoholic steatohepatitis (NASH), and patients without liver disease (control).
+RNA and DNA libraries were sequenced from plasma filtrates enriched in viral particles to catalog virus populations.
+Hepatitis viruses were readily detected at high coverage in patients with chronic viral hepatitis B and C, but only a limited number of sequences resembling other viruses were found.
+The exception was a library from a patient diagnosed with hepatitis C virus (HCV) infection that contained multiple sequences matching GB virus C (GBV-C).
+Abundant GBV-C reads were also found in plasma from patients with AIH, whereas Torque teno virus (TTV) was found at high frequency in samples from patients with AIH and NASH.
+After taxonomic classification of sequences by BLASTn, a substantial fraction in each library, ranging from 35% to 76%, remained unclassified.
+These unknown sequences were assembled into scaffolds along with virus, phage and endogenous retrovirus sequences and then analyzed by BLASTx against the non-redundant protein database.
+Nearly the full genome of a heretofore-unknown circovirus was assembled and many scaffolds that encoded proteins with similarity to plant, insect and mammalian viruses.
+We re-evaluated these alignments with a profile hidden Markov method, HHblits, and observed inconsistencies in the target proteins reported by the different algorithms.
+This suggests that sequence alignments are insufficient to identify NCLDV proteins, especially when these alignments are only to small portions of the target protein.
+Nevertheless, we have now established a reliable protocol for the identification of viruses in plasma that can also be adapted to other patient samples such as urine, bile, saliva and other body fluids.
+The frequency and potential long-term effects of sport-related traumatic brain injuries (TBI) make it a major public health concern.
+The culture within contact sports, such as ice hockey, encourages aggression that puts youth at risk of TBI such as concussion.
+Newspaper reports play an important role in conveying and shaping the culture around health-related behaviors.
+We qualitatively studied reports about sport-related TBI in four major North American newspapers over the last quarter-century.
+We used the grounded-theory approach to identify major themes and then did a content analysis to compare the frequency of key themes between 1998–2000 and 2009–2011.
+The major themes were: perceptions of brain injury, aggression, equipment, rules and regulations, and youth hockey.
+Across the full study period, newspaper articles from Canada and America portrayed violence and aggression that leads to TBI both as integral to hockey and as an unavoidable risk associated with playing the game.
+They also condemned violence in ice hockey, criticized the administrative response to TBI, and recognized the significance of TBI.
+In Canada, aggression was reported more often recently and there was a distinctive shift in portraying protective equipment as a solution to TBI in earlier years to a potential contributing factor to TBI later in the study period.
+American newspapers gave a greater attention to ‘perception of risks’ and the role of protective equipment, and discussed TBI in a broader context in the recent time period.
+Newspapers from both countries showed similar recent trends in regards to a need for rule changes to curb youth sport-related TBI.
+Understanding this reporting is important for evaluating whether the dangers of sport-related TBI are being appropriately communicated by the media.
+Rift Valley fever virus (RVFV; genus Phlebovirus, family Bunyaviridae) is a mosquito-borne zoonotic pathogen which can cause hemorrhagic fever, neurological disorders or blindness in humans, and a high rate of abortion in ruminants.
+MP-12 strain, a live-attenuated candidate vaccine, is attenuated in the M- and L-segments, but the S-segment retains the virulent phenotype.
+MP-12 was manufactured as an Investigational New Drug vaccine by using MRC-5 cells and encodes a functional NSs gene, the major virulence factor of RVFV which 1) induces a shutoff of the host transcription, 2) inhibits interferon (IFN)-β promoter activation, and 3) promotes the degradation of dsRNA-dependent protein kinase (PKR).
+Although MP-12 lacking NSs works for DIVA, it does not replicate efficiently in type-I IFN-competent MRC-5 cells, while the use of type-I IFN-incompetent cells may negatively affect its genetic stability.
+To generate modified MP-12 vaccine candidates encoding a DIVA marker, while still replicating efficiently in MRC-5 cells, we generated recombinant MP-12 encoding Punta Toro virus Adames strain NSs (rMP12-PTNSs) or Sandfly fever Sicilian virus NSs (rMP12-SFSNSs) in place of MP-12 NSs.
+We have demonstrated that those recombinant MP-12 viruses inhibit IFN-β mRNA synthesis, yet do not promote the degradation of PKR.
+The rMP12-PTNSs, but not rMP12-SFSNSs, replicated more efficiently than recombinant MP-12 lacking NSs in MRC-5 cells.
+Mice vaccinated with rMP12-PTNSs or rMP12-SFSNSs induced neutralizing antibodies at a level equivalent to those vaccinated with MP-12, and were efficiently protected from wild-type RVFV challenge.
+The rMP12-PTNSs and rMP12-SFSNSs did not induce antibodies cross-reactive to anti-RVFV NSs antibody and are therefore applicable to DIVA.
+Thus, rMP12-PTNSs is highly efficacious, replicates efficiently in MRC-5 cells, and encodes a DIVA marker, all of which are important for vaccine development for Rift Valley fever.
+Large-scale Hand, Foot, and Mouth Disease (HFMD) outbreaks have frequently occurred in China since 2008, affecting more than one million children and causing several hundred children deaths every year.
+Among them, human enterovirus 71 (HEV71) and coxsackievirus A16 (CVA16) are the most common pathogens of HFMD.
+To rapidly detect HEV71 and CVA16, and ensure detection of all HEVs causing HFMD, two real-time hybridization probe-based RT-PCR assays were developed in this study.
+One is a multiplex real-time RT-PCR assay, which was developed to detect and differentiate HEV71 specifically from CVA16 directly from clinical specimens within 1–2 h, and the other is a broad-spectrum real-time RT-PCR assay, which targeted almost all HEVs.
+The experiments confirmed that the two assays have high sensitivity and specificity, and the sensitivity was up to 0.1 TCID(50)/ml for detection of HEVs, HEV71, and CVA16, respectively.
+A total of 213 clinical specimens were simultaneously detected by three kinds of assays, including the two real-time RT-PCR assays, direct conventional RT-PCR assay, and virus isolation assay on human rhabdomyosarcoma cells (RD cells).
+The total positive rate of both HEV71 and CVA16 was 69.48% with real-time RT-PCR assay, 47.42% with RT-PCR assay, and 34.58% with virus isolation assay.
+One HFMD clinical specimen was positive for HEV, but negative for HEV71 or CVA16, which was identified as Echovirus 11 (Echo11) by virus isolation, RT-PCR, and sequencing for the VP1 gene.
+The two real-time RT-PCR assays had been applied in 31 provincial HFMD labs to detect the pathogens of HFMD, which has contributed to the rapid identification of the pathogens in the early stages of HFMD outbreaks, and helped to clarify the etiologic agents of HFMD in China.
+Patrick Manson, a clinician-scientist serving in China (1866–1889), discovered that many tropical infectious diseases require a vector peculiar to warm climate for person to person transmission.
+These microfilariae undergo metamorphosis when ingested by the mosquito acting as the vector for the completion of their life cycle.
+Furthermore, he demonstrated the linkage between the lung fluke and endemic haemoptysis by finding operculated eggs in patients' sputa.
+He predicted that the miracidium from hatched eggs uses crustaceans, such as fresh-water snails found at tropical conditions, as the intermediate hosts in the life cycle of many trematodes.
+His vector hypothesis leads to vector control which is now the cornerstone for the World Health Organization's programme for the elimination/control of lymphatic filariasis, dracunculiasis and malaria.
+Before leaving China, he established the Alice Memorial Hospital, the Hong Kong College of Medicine for Chinese (the forerunner of the University of Hong Kong), and the Hong Kong Medical Society for medical service and education.
+He also incepted the Hong Kong Dairy Farm for supplying hygienic milk affordable by pregnant women, children and patients.
+Intrinsically disordered regions in eukaryotic proteomes contain key signaling and regulatory modules and mediate interactions with many proteins.
+Many viral proteomes encode disordered proteins and modulate host factors through the use of short linear motifs (SLiMs) embedded within disordered regions.
+However, the degree of viral protein disorder across different viruses is not well understood, so we set out to establish the constraints acting on viruses, in terms of their use of disordered protein regions.
+We surveyed predicted disorder across 2,278 available viral genomes in 41 families, and correlated the extent of disorder with genome size and other factors.
+Protein disorder varies strikingly between viral families (from 2.9% to 23.1% of residues), and also within families.
+However, this substantial variation did not follow the established trend among their hosts, with increasing disorder seen across eubacterial, archaebacterial, protists, and multicellular eukaryotes.
+For example, among large mammalian viruses, poxviruses and herpesviruses showed markedly differing disorder (5.6% and 17.9%, respectively).
+Viral families with smaller genome sizes have more disorder within each of five main viral types (ssDNA, dsDNA, ssRNA+, dsRNA, retroviruses), except for negative single-stranded RNA viruses, where disorder increased with genome size.
+However, surveying over all viruses, which compares tiny and enormous viruses over a much bigger range of genome sizes, there is no strong association of genome size with protein disorder.
+While a proportion of this may relate to base composition, to extent of gene overlap, and to genome size within viral types, there remain important additional family and virus-specific effects.
+Differing disorder strategies are likely to impact on how different viruses modulate host factors, and on how rapidly viruses can evolve novel instances of SLiMs subverting host functions, such as innate and acquired immunity.
+Amongst the Closteroviridae, Citrus tristeza virus (CTV) is almost unique in possessing a number of distinct and characterized strains, isolates of which produce a wide range of phenotype combinations among its different hosts.
+There is little understanding to connect genotypes to phenotypes, and to complicate matters more, these genotypes are found throughout the world as members of mixed populations within a single host plant.
+There is essentially no understanding of how combinations of genotypes affect symptom expression and disease severity.
+We know little about the evolution of the genotypes that have been characterized to date, little about the biological role of their diversity and particularly, about the effects of recombination.
+In this study we utilized an extensive array of CTV genomic information to classify the major genotypes, and to determine the major evolutionary processes that led to their formation and subsequent retention.
+Our analyses suggest that three major processes act on these genotypes: (1) ancestral diversification of the major CTV lineages, followed by (2) conservation and co-evolution of the major functional domains within, though not between CTV genotypes, and (3) extensive recombination between lineages that have given rise to new genotypes that have subsequently been retained within the global population.
+The effects of genotype diversity and host-interaction are discussed, as is a proposal for standardizing the classification of existing and novel CTV genotypes.
+Protein antigens usually have multiple epitopes, thus, there may be a plurality of antibodies binding to one antigen.
+Experiments show that some screened anti-human creatine kinase single chain antibodies (scFV) could assist in the folding and stabilizing of the enzyme, while others could not.
+We built the model of the single chain antibody (scFv-A4) that increased the stability of human creatine kinase (HCK) by the homology modeling method.
+Epitopes of human creatine kinase were predicted by computer and then the binding of scFv-A4 and HCK was modeled with computer.
+The calculation results were further combined with the peptide array membrane experiment results to obtain reliable models for the scFv-A4-HCK complex.
+Based on the above study we gave an explanation about how scFv-A4 could act as a macromolecular chaperone assisting the folding of HCK.
+This study provides an approach for predicting antigen-antibody binding mode and also a useful theoretical guidance for the study of antibodies' chaperone-like function.
+Retroviruses encode their genetic information with RNA molecules, and have a high genomic recombination rate which allows them to mutate more rapidly, thereby posting a higher risk to humans.
+One important way to help combat a pandemic of viral infectious diseases is early detection before large scale outbreaks occur.
+The polymerase chain reaction (PCR) and reverse transcription-PCR (RT-PCR) have been used to identify precisely different strains of some very closely related pathogens.
+However, isolation and detection of viral RNA in the field are difficult due to the unstable nature of viral RNA molecules.
+Consequently, performing in-the-field nucleic acid analysis to monitor the spread of viruses is financially and technologically challenging in remote and underdeveloped regions that are high-risk areas for outbreaks.
+A simplified rapid viral RNA extraction method is reported to meet the requirements for in-the-field viral RNA extraction and detection.
+The ability of this device to perform viral RNA extraction with subsequent RT-PCR detection of retrovirus is demonstrated.
+This inexpensive device has the potential to be distributed on a large scale to underdeveloped regions for early detection of retrovirus, with the possibility of reducing viral pandemic events.
+Upon recognition of viral components by pattern recognition receptors, such as the toll-like receptors (TLRs) and retinoic acid-inducible gene I (RIG-I)-like helicases, cells are activated to produce type I interferon (IFN) and proinflammatory cytokines.
+These pathways are tightly regulated by the host to prevent an inappropriate cellular response, but viruses can modulate these pathways to proliferate and spread.
+In this study, we revealed a novel mechanism in which hepatitis C virus (HCV) evades the immune surveillance system to proliferate by activating microRNA-21 (miR-21).
+We demonstrated that HCV infection upregulates miR-21, which in turn suppresses HCV-triggered type I IFN production, thus promoting HCV replication.
+Furthermore, we demonstrated that miR-21 targets two important factors in the TLR signaling pathway, myeloid differentiation factor 88 (MyD88) and interleukin-1 receptor-associated kinase 1 (IRAK1), which are involved in HCV-induced type I IFN production.
+Moreover, we identified a transcription factor, activating protein-1 (AP-1), which is partly responsible for miR-21 induction in response to HCV infection through PKCε/JNK/c-Jun and PKCα/ERK/c-Fos cascades.
+Taken together, our results indicate that miR-21 is upregulated during HCV infection and negatively regulates IFN-α signaling through MyD88 and IRAK1 and may be a potential therapeutic target for antiviral intervention.
+The RIG-I like receptor pathway is stimulated during RNA virus infection by interaction between cytosolic RIG-I and viral RNA structures that contain short hairpin dsRNA and 5′ triphosphate (5′ppp) terminal structure.
+In the present study, an RNA agonist of RIG-I was synthesized in vitro and shown to stimulate RIG-I-dependent antiviral responses at concentrations in the picomolar range.
+In human lung epithelial A549 cells, 5′pppRNA specifically stimulated multiple parameters of the innate antiviral response, including IRF3, IRF7 and STAT1 activation, and induction of inflammatory and interferon stimulated genes - hallmarks of a fully functional antiviral response.
+Evaluation of the magnitude and duration of gene expression by transcriptional profiling identified a robust, sustained and diversified antiviral and inflammatory response characterized by enhanced pathogen recognition and interferon (IFN) signaling.
+Bioinformatics analysis further identified a transcriptional signature uniquely induced by 5′pppRNA, and not by IFNα-2b, that included a constellation of IRF7 and NF-kB target genes capable of mobilizing multiple arms of the innate and adaptive immune response.
+Treatment of primary PBMCs or lung epithelial A549 cells with 5′pppRNA provided significant protection against a spectrum of RNA and DNA viruses.
+In C57Bl/6 mice, intravenous administration of 5′pppRNA protected animals from a lethal challenge with H1N1 Influenza, reduced virus titers in mouse lungs and protected animals from virus-induced pneumonia.
+Strikingly, the RIG-I-specific transcriptional response afforded partial protection from influenza challenge, even in the absence of type I interferon signaling.
+This systems approach provides transcriptional, biochemical, and in vivo analysis of the antiviral efficacy of 5′pppRNA and highlights the therapeutic potential associated with the use of RIG-I agonists as broad spectrum antiviral agents.
+There is an established consensus that it is primarily the adaptive arm of immunity, and the T cell subset in particular, that is most susceptible to the deleterious changes with age known as “immunosenescence”.
+Can we garner any clues as to why this might be by considering comparative immunology and the evolutionary emergence of adaptive and innate immunity?
+The immune system is assumed to have evolved to protect the organism against pathogens, but the way in which this is accomplished is different in the innate-vs-adaptive arms, and it is unclear why the latter is necessary.
+Are there special characteristics of adaptive immunity which might make the system more susceptible to age-associated dysfunction?
+Given recent accumulating findings that actually there are age-associated changes to innate immunity and that these are broadly similar in vertebrates and invertebrates, we suggest here that it is the special property of memory in the adaptive immune system which results in the accumulation of cells with a restricted receptor repertoire, dependent on the immunological history of the individual’s exposures to pathogens over the lifetime, and which is commonly taken as a hallmark of “immunosenescence”.
+However, we further hypothesize that this immunological remodelling per se does not necessarily convey a disadvantage to the individual (ie.
+Indeed, under certain circumstances, or potentially even as a rule, this adaptation to the individual host environment may confer an actual survival advantage.
+The renin-angiotensin system (RAS) in brain is a crucial regulator for physiological homeostasis and diseases of cerebrovascular system, such as ischemic stroke.
+Overactivation of brain Angiotensin-converting enzyme (ACE) - Angiotensin II (Ang II) - Angiotensin II type 1 receptor (AT(1)R) axis was found to be involved in the progress of hypertension, atherosclerosis and thrombogenesis, which increased the susceptibility to ischemic stroke.
+Besides, brain Ang II levels have been revealed to be increased in ischemic tissues after stroke, and contribute to neural damage through elevating oxidative stress levels and inducing inflammatory response in the ischemic hemisphere via AT(1)R. In recent years, new components of RAS have been discovered, including ACE2, Angiotensin-(1–7) [Ang-(1-7)] and Mas, which constitute ACE2-Ang-(1-7)-Mas axis.
+ACE2 converts Ang II to Ang-(1-7), and Ang-(1-7) binds with its receptor Mas, exerting benefical effects in cerebrovascular disease.
+Through interacting with nitric oxide and bradykinin, Ang-(1-7) could attenuate the development of hypertension and the pathologic progress of atherosclerosis.
+Besides, its antithrombotic activity also prevents thrombogenic events, which may contribute to reduce the risk of ischemic stroke.
+In addition, after ischemia insult, ACE2-Ang-(1-7)-Mas has been shown to reduce the cerebral infarct size and improve neurological deficits through its antioxidative and anti-inflammatory effects.
+Taken together, activation of the ACE2-Ang-(1-7)-Mas axis may become a novel therapeutic target in prevention and treatment of ischemia stroke, which deserves further investigations.
+BACKGROUND: Baicalein, a bioflavone present in the dry roots of Scutellaria baicalensis Georgi, is known to reduce eotaxin production in human fibroblasts.
+However, there are no reports of its anti-asthma activity or its effect on airway injury.
+METHODOLOGY/PRINCIPAL FINDINGS: In a standard experimental asthma model, male Balb/c mice that were sensitized with ovalbumin (OVA), treated with baicalein (10 mg/kg, ip) or a vehicle control, either during (preventive use) or after OVA challenge (therapeutic use).
+In an alternate model, baicalein was administered to male Balb/c mice which were given either IL-4 or IL-13 intranasally.
+Features of asthma were determined by estimating airway hyperresponsiveness (AHR), histopathological changes and biochemical assays of key inflammatory molecules.
+Airway injury was determined with apoptotic assays, transmission electron microscopy and assessing key mitochondrial functions.
+Furthermore, baicalein treatment significantly reduced 12/15-LOX activity, features of mitochondrial dysfunctions, and apoptosis of bronchial epithelia.
+CONCLUSION/SIGNIFICANCE: Our findings demonstrate that baicalein can attenuate important features of asthma, possibly through the reduction of airway injury and restoration of mitochondrial function.
+Alterations within the renal renin angiotensin system play a pivotal role in the development and progression of cardiovascular and renal disease.
+Angiotensin converting enzyme 2 (ACE2) is highly expressed in renal tubules and has been shown to be renoprotective in diabetes.
+The protease, a disintegrin and metalloprotease (ADAM) 17, is involved in the ectodomain shedding of several transmembrane proteins including ACE2.
+We investigated the effect of the insulin sensitizer, rosiglitazone, on albuminuria, renal ADAM17 protein expression and ACE2 shedding in db/db diabetic mice.
+Rosiglitazone treatment of db/db mice normalized hyperglycemia, attenuated renal injury and decreased urinary ACE2 and renal ADAM17 protein expression.
+Western blot analysis of urinary ACE2 demonstrated two prominent immunoreactive bands at approximately 70 & 90 kDa.
+The predominant immunoreactive band is approximately 20 kDa shorter than the one demonstrated for kidney lysate, indicating possible ectodomain shedding of active renal ACE2 in the urine.
+Therefore, it is tempting to speculate that renoprotection of rosiglitazone could be partially mediated via downregulation of renal ADAM17 and ACE2 shedding.
+In addition, there was a positive correlation between blood glucose, urinary albumin, plasma glucagon, and triglyceride levels with urinary ACE2 excretion.
+In conclusion, urinary ACE2 could be used as a sensitive biomarker of diabetic nephropathy and for monitoring the effectiveness of renoprotective medication.
+AIM: To identify the risk factors in children under five years of age for severe acute lower respiratory infections (ALRI), which are the leading cause of child mortality.
+We conducted a quality assessment of all eligible studies according to GRADE criteria and performed a meta-analysis to report the odds ratios for all risk factors identified in these studies.
+CONCLUSION: This study highlights the role of the above seven risk factors in the development of severe pneumonia in under-five children.
+Since these risk factors are potentially preventable, health policies targeted at reducing their prevalence provide a basis for decreasing the burden of childhood pneumonia.
+For many infectious disease processes such as emerging zoonoses and vaccine-preventable diseases, [Image: see text] and infections occur as self-limited stuttering transmission chains.
+A mechanistic understanding of transmission is essential for characterizing the risk of emerging diseases and monitoring spatio-temporal dynamics.
+Thus methods for inferring [Image: see text] and the degree of heterogeneity in transmission from stuttering chain data have important applications in disease surveillance and management.
+Previous researchers have used chain size distributions to infer [Image: see text], but estimation of the degree of individual-level variation in infectiousness (as quantified by the dispersion parameter, [Image: see text]) has typically required contact tracing data.
+Utilizing branching process theory along with a negative binomial offspring distribution, we demonstrate how maximum likelihood estimation can be applied to chain size data to infer both [Image: see text] and the dispersion parameter that characterizes heterogeneity.
+While the maximum likelihood value for [Image: see text] is a simple function of the average chain size, the associated confidence intervals are dependent on the inferred degree of transmission heterogeneity.
+As demonstrated for monkeypox data from the Democratic Republic of Congo, this impacts when a statistically significant change in [Image: see text] is detectable.
+In addition, by allowing for superspreading events, inference of [Image: see text] shifts the threshold above which a transmission chain should be considered anomalously large for a given value of [Image: see text] (thus reducing the probability of false alarms about pathogen adaptation).
+Our analysis of monkeypox also clarifies the various ways that imperfect observation can impact inference of transmission parameters, and highlights the need to quantitatively evaluate whether observation is likely to significantly bias results.
+Previous studies indicated that a 719-nt subgenomic minigenome (DENV-MINI) is an efficient template for translation and (−) strand RNA synthesis in vitro.
+We performed a detailed structural analysis of DENV-MINI RNA, combining chemical acylation techniques, Pb(2+) ion-induced hydrolysis and site-directed mutagenesis.
+Probing analyses identified tandem dumbbell structures (DBs) within the 3′ terminus spaced by single-stranded regions, internal loops and hairpins with embedded GNRA-like motifs.
+Analysis of conserved motifs and top loops (TLs) of these dumbbells, and their proposed interactions with downstream pseudoknot (PK) regions, predicted an H-type pseudoknot involving TL1 of the 5′ DB and the complementary region, PK2.
+As disrupting the TL1/PK2 interaction, via ‘flipping’ mutations of PK2, previously attenuated DENV replication, this pseudoknot may participate in regulation of RNA synthesis.
+In addition, our studies targeting elements of the 3′ DB and its complementary region PK1 indicated that communication between 5′–3′ terminal regions strongly depends on structure and sequence composition of the 5′ cyclization region.
+BACKGROUND: Cells of the innate immune system including monocytes and macrophages are the first line of defence against infections and are critical regulators of the inflammatory response.
+These cells express toll-like receptors (TLRs), innate immune receptors which govern tailored inflammatory gene expression patterns.
+Monocytes, which produce pro-inflammatory mediators, are readily recruited to the central nervous system (CNS) in neurodegenerative diseases.
+METHODS: This study explored the expression of receptors (CD11b, TLR2 and TLR4) on circulating monocyte-derived macrophages (MDMs) and peripheral blood mononuclear cells (PBMCs) isolated from healthy elderly adults who we classified as either IQ memory-consistent (high-performing, HP) or IQ memory-discrepant (low-performing, LP).
+RESULTS: The expression of CD11b, TLR4 and TLR2 was increased in MDMs from the LP group when compared to HP cohort.
+MDMs from both groups responded robustly to treatment with the TLR4 activator, lipopolysaccharide (LPS), in terms of cytokine production.
+INTERPRETATION: Overall these findings define differential receptor expression and cytokine profiles that occur in MDMs derived from a cohort of IQ memory-discrepant individuals.
+These changes are indicative of inflammation and may be involved in the prodromal processes leading to the development of neurodegenerative disease.
+The NSs proteins of bunyaviruses are the viral interferon antagonists, counteracting the host's antiviral response to infection.
+During high-multiplicity infection of cultured mammalian cells with Bunyamwera orthobunyavirus (BUNV), NSs is rapidly degraded after reaching peak levels of expression at 12hpi.
+Through the use of inhibitors this was shown to be the result of proteasomal degradation.
+A recombinant virus (rBUN4KR), in which all four lysine residues in NSs were replaced by arginine residues, expresses an NSs protein (NSs4KR) that is resistant to degradation, confirming that degradation is lysine-dependent.
+However, despite repeated attempts, no direct ubiquitylation of NSs in infected cells could be demonstrated.
+This suggests that degradation of NSs, although lysine-dependent, may be achieved through an indirect mechanism.
+Infection of cultured mammalian cells or mice indicated no disadvantage for the virus in having a non-degradable NSs protein: in fact rBUN4KR had a slight growth advantage over wtBUNV in interferon-competent cells, presumably due to the increased and prolonged presence of NSs.
+In cultured mosquito cells there was no difference in growth between wild-type BUNV and rBUN4KR, but surprisingly NSs4KR was not stabilised compared to the wild-type NSs protein.
+Strong downstream mRNA secondary (2°) structures, which must be unfolded for translation, can slow or even halt protein synthesis.
+Here we employ single molecule fluorescence resonance energy transfer to determine reaction rates for specific steps within the elongation cycle as the Escherichia coli ribosome encounters stem loop or pseudoknot mRNA 2° structures.
+Downstream stem-loops containing 100% G-C base pairs decrease the rates of both tRNA translocation within the ribosome and deacylated tRNA dissociation from the ribosomal exit (E) site.
+Downstream stem-loops or pseudoknots containing both G-C and A-U pairs also decrease the rate of tRNA dissociation, but they have little effect on tRNA translocation rate.
+Thus, somewhat surprisingly, unfolding of mRNA 2° structures is more closely coupled to E-site tRNA dissociation than to tRNA translocation.
+Influenza viruses are common respiratory pathogens in humans and can cause serious infection that leads to the development of pneumonia.
+In this study, the clinical and laboratory features of 36 patients from Turkey who are hospitalized in intensive care unit due to pandemic influenza A (H1N1) associated pneumonia and respiratory failure were retrospectively evaluated.
+Consolidation (36.1 %) and interstitial changes (30.6 %) were the most frequently identified findings on chest radiographs at the time of admission.
+Mortality occurred in 3 of 13 patients (23.1 %) with underlying disease, whilst it occurred in only 3 of 23 patients (13 %) who were previously healthy.
+A significant relationship was determined only between the presence of lymphopenia and acute respiratory distress syndrome and the need for intensive care treatment.
+The average time elapsed from the onset of the symptoms until admission was 8.67 ± 2.87 days for the patients died, and 6.0 ± 3.8 days for the patients survived.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s13337-012-0122-z) contains supplementary material, which is available to authorized users.
+BACKGROUND: The relationship between inducible nitric oxide synthatase activity and disease severity in leptospirosis is unclear.
+Nitric oxide is converted to nitrites and nitrates, thus nitrite and nitrate levels (NO(x)) in serum are considered surrogate markers for nitric oxide.
+We assessed the correlation of NO(x) with disease severity in patients with leptospirosis, compared with healthy controls and non-leptospirosis fever patients.
+METHODS: All patients admitted over a two-month period to the National Hospital, Colombo, Sri Lanka with a clinical picture suggestive of leptospirosis were included.
+Severe leptospirosis was defined by the presence of two or more of the following criteria: jaundice (bilirubin> 51.3 μmol/l), oliguria (urine output < 400 ml/day), serum creatinine> 133 μmol/l or blood urea > 25.5 mmol/l, or the presence of organ dysfunction.
+RESULTS: Forty patients were confirmed as having leptospirosis and 26 of them had severe disease.
+NO(x) levels were significantly higher in confirmed leptospirosis patients compared to healthy controls, MAT equivocal patients and non-leptospirosis fever patients (p<0.001).
+NO(x) concentrations were also significantly higher in patients with severe compared to mild leptospirosis (p<0.001).
+Once NO(x) levels were corrected for renal function, by using the ratio NO(x)/creatinine, NO(x) levels were actually significantly lower in patients with severe disease compared to other patients, and values were similar to those of healthy controls.
+CONCLUSIONS: We postulate that high NOx levels may be protective against severe leptospirosis, and that finding low NOx levels (when corrected for renal function) in patients with leptospirosis may predict the development of severe disease and organ dysfunction.
+The objective of study was to evaluate the incidence and mortality rates of disasters and mass casualty incidents (MCIs) over the past 10 yr in the administrative system of Korea administrative system and to examine their relationship with population characteristics.
+We calculated the nationwide incidence, as well as the crude mortality and injury incidence rates, of disasters and MCIs.
+The data were collected from the administrative database of the National Emergency Management Agency (NEMA) and from provincial fire departments from January 2000 to December 2009.
+Of these events, 115 and 3,079 cases were defined as disasters and MCIs that occurred in Korea, respectively.
+The incidence of technical disasters/MCIs was approximately 12.7 times greater than that of natural disasters/MCIs.
+Over the past 10 yr, the crude mortality rates for disasters and MCIs were 2.36 deaths per 100,000 persons and 6.78 deaths per 100,000 persons, respectively.
+The crude injury incidence rates for disasters and MCIs were 25.47 injuries per 100,000 persons and 152 injuries per 100,000 persons, respectively.
+The incidence and mortality of disasters/MCIs in Korea seem to be low compared to that of trend around the world.
+BACKGROUND: Mycoplasma pneumoniae is thought to be a common cause of respiratory tract infections (RTIs) in children.
+The diagnosis of M. pneumoniae RTIs currently relies on serological methods and/or the detection of bacterial DNA in the upper respiratory tract (URT).
+It is conceivable, however, that these diagnostic methods also yield positive results if M. pneumoniae is carried asymptomatically in the URT.
+Positive results from these tests may therefore not always be indicative of a symptomatic infection.
+We hypothesized that asymptomatic carriage in children exists and investigated whether colonization and symptomatic infection could be differentiated by current diagnostic methods.
+METHODS AND FINDINGS: This study was conducted at the Erasmus MC–Sophia Children's Hospital and the after-hours General Practitioners Cooperative in Rotterdam, The Netherlands.
+Asymptomatic children (n = 405) and children with RTI symptoms (n = 321) aged 3 mo to 16 y were enrolled in a cross-sectional study from July 1, 2008, to November 30, 2011.
+The primary objective was to differentiate between colonization and symptomatic infection with M. pneumoniae by current diagnostic methods, especially real-time PCR.
+M. pneumoniae DNA was detected in 21.2% (95% CI 17.2%–25.2%) of the asymptomatic children and in 16.2% (95% CI 12.2%–20.2%) of the symptomatic children (p = 0.11).
+A total of 202 children were tested for the presence of other bacterial and viral pathogens.
+Two or more pathogens were found in 56% (63/112) of the asymptomatic children and in 55.5% (50/90) of the symptomatic children.
+Finally, longitudinal sampling showed persistence of M. pneumoniae in the URT for up to 4 mo.
+Fifteen of the 21 asymptomatic children with M. pneumoniae and 19 of the 22 symptomatic children with M. pneumoniae in this longitudinal follow-up tested negative after 1 mo.
+CONCLUSIONS: Although our study has limitations, such as a single study site and limited sample size, our data indicate that the presence of M. pneumoniae in the URT is common in asymptomatic children.
+The current diagnostic tests for M. pneumoniae are unable to differentiate between asymptomatic carriage and symptomatic infection.
+The use of recombinant viral vectors expressing T. gondii antigens is a safe and efficient approach to induce immune response against the parasite and a valuable tool for vaccine development.
+We have previously protected mice from toxoplasmosis by immunizing the animals with an adenovirus expressing the protein SAG1 (AdSAG1) of T. gondii.
+One limitation of homologous vaccinations (sequential doses of the same vector) is induction of anti-vector immune response that blocks cell transduction, restricts transgene expression and, consequently, compromises the overall outcome of vaccination.
+One way to avert the effects of anti-vector response is to use different viruses in prime and boost (heterologous vaccination).
+Bearing this in mind, we generated a modified Vaccinia Virus Ankara encoding SAG1 (MVASAG1), to be tested as boost agent after prime with AdSAG1.
+Although minor differences were observed in the magnitude of the anti-SAG1 immune response induced by each vaccination protocol, the heterologous immunization with AdSAG1 followed by MVASAG1 resulted in improved capacity to control brain cyst formation in a model of chronic toxoplasmosis in C57BL/6 mice.
+Since Kaposi's sarcoma associated herpesvirus (KSHV) establishes a persistent infection in human B cells, B cells are a critical compartment for viral pathogenesis.
+RTA, the replication and transcription activator of KSHV, can either directly bind to DNA or use cellular DNA binding factors including CBF1/CSL as DNA adaptors.
+In addition, the viral factors LANA1 and vIRF4 are known to bind to CBF1/CSL and modulate RTA activity.
+To analyze the contribution of CBF1/CSL to reactivation in human B cells, we have successfully infected DG75 and DG75 CBF1/CSL knock-out cell lines with recombinant KSHV.219 and selected for viral maintenance by selective medium.
+Viral reactivation could be initiated in both B cell lines but viral genome replication was attenuated in CBF1/CSL deficient lines, which also failed to produce detectable levels of infectious virus.
+Induction of immediate early, early and late viral genes was impaired in CBF1/CSL deficient cells at multiple stages of the reactivation process but could be restored to wild-type levels by reintroduction of CBF1/CSL.
+To identify additional viral RTA target genes, which are directly controlled by CBF1/CSL, we analyzed promoters of a selected subset of viral genes.
+We show that the induction of the late viral genes ORF29a and ORF65 by RTA is strongly enhanced by CBF1/CSL.
+Orthologs of ORF29a in other herpesviruses are part of the terminase complex required for viral packaging.
+Our study demonstrates for the first time that in human B cells viral replication can be initiated in the absence of CBF1/CSL but the reactivation process is severely attenuated at all stages and does not lead to virion production.
+Thus, CBF1/CSL acts as a global hub which is used by the virus to coordinate the lytic cascade.
+Virus-induced apoptosis is thought to be the primary mechanism of cell death following reovirus infection.
+Induction of cell death following reovirus infection is initiated by the incoming viral capsid proteins during cell entry and occurs via NF-κB-dependent activation of classical apoptotic pathways.
+To investigate how signaling pathways initiated by T3D and T1L differ, we methodically analyzed cell death pathways activated by these two viruses in L929 cells.
+We found that T3D activates NF-κB, initiator caspases, and effector caspases to a significantly greater extent than T1L.
+Cell death following T3D infection resulted in a reduction in cellular ATP levels and was sensitive to inhibition of the kinase activity of receptor interacting protein 1 (RIP1).
+Based on the dispensability of caspases, a requirement for RIP1 kinase function, and the physiological status of infected cells, we conclude that reovirus can also induce an alternate, necrotic form of cell death described as necroptosis.
+We also found that induction of necroptosis requires synthesis of viral RNA or proteins, a step distinct from that necessary for the induction of apoptosis.
+Thus, our studies reveal that two different events in the reovirus replication cycle can injure host cells by distinct mechanisms.
+Sialic acids are structurally diverse nine-carbon ketosugars found mostly in humans and other animals as the terminal units on carbohydrate chains linked to proteins or lipids.
+The sialic acids function in cell-cell and cell-molecule interactions necessary for organismic development and homeostasis.
+They not only pose a barrier to microorganisms inhabiting or invading an animal mucosal surface, but also present a source of potential carbon, nitrogen, and cell wall metabolites necessary for bacterial colonization, persistence, growth, and, occasionally, disease.
+The explosion of microbial genomic sequencing projects reveals remarkable diversity in bacterial sialic acid metabolic potential.
+How bacteria exploit host sialic acids includes a surprisingly complex array of metabolic and regulatory capabilities that is just now entering a mature research stage.
+This paper attempts to describe the variety of bacterial sialometabolic systems by focusing on recent advances at the molecular and host-microbe-interaction levels.
+The hope is that this focus will provide a framework for further research that holds promise for better understanding of the metabolic interplay between bacterial growth and the host environment.
+An ability to modify or block this interplay has already yielded important new insights into potentially new therapeutic approaches for modifying or blocking bacterial colonization or infection.
+We construct a stochastic SIR model for influenza spreading on a D-dimensional lattice, which represents the dynamic contact network of individuals.
+The displacement from a site to a nearest neighbor empty site, allows individuals to change the number and identities of their contacts.
+The dynamics on the lattice is governed by an attractive interaction between individuals belonging to the same age-class.
+The parameters, which regulate the pattern dynamics, are fixed fitting the data on the age-dependent daily contact numbers, furnished by the Polymod survey.
+A simple SIR transmission model with a nearest neighbors interaction and some very basic adaptive mobility restrictions complete the model.
+The model is validated against the age-distributed Italian epidemiological data for the influenza A(H1N1) during the [Image: see text] season, with sensible predictions for the epidemiological parameters.
+For an appropriate topology of the lattice, we find that, whenever the accordance between the contact patterns of the model and the Polymod data is satisfactory, there is a good agreement between the numerical and the experimental epidemiological data.
+This result shows how rich is the information encoded in the average contact patterns of individuals, with respect to the analysis of the epidemic spreading of an infectious disease.
+Exosomes are small 30–100 nm membrane vesicles released from hematopoietic and non-hematopoietic cells and function to promote intercellular communication.
+They are generated through fusion of multivesicular bodies with the plasma membrane and release of interluminal vesicles.
+Previous studies from our laboratory demonstrated that macrophages infected with Mycobacterium release exosomes that promote activation of both innate and acquired immune responses; however, the components present on exosomes inducing these host responses were not defined.
+The present study used LC-MS/MS to identify 41 mycobacterial proteins present on exosomes released from M. tuberculosis-infected J774 cells.
+Further, since most of the mycobacterial proteins identified are actively secreted, we hypothesized that macrophages treated with M. tuberculosis culture filtrate proteins (CFP) would release exosomes containing mycobacterial proteins.
+We found 29 M. tuberculosis proteins in exosomes released from CFP-treated J774 cells, the majority of which were also present on exosomes isolated from M. tuberculosis-infected cells.
+The exosomes from CFP-treated J774 cells could promote macrophage and dendritic cell activation as well as activation of naïve T cells in vivo.
+These results suggest that exosomes containing M. tuberculosis antigens may be alternative approach to developing a tuberculosis vaccine.
+Epstein-Barr virus (EBV) is an oncogenic virus that is associated with the pathogenesis of several human lymphoid malignancies, including Hodgkin's lymphoma.
+Infection of normal resting B cells with EBV results in activation to lymphoblasts that are phenotypically similar to those generated by physiological stimulation with CD40L plus IL-4.
+One important difference is that infection leads to the establishment of permanently growing lymphoblastoid cell lines, whereas CD40L/IL-4 blasts have finite proliferation lifespans.
+To identify early events which might later determine why EBV infected blasts go on to establish transformed cell lines, we performed global transcriptome analyses on resting B cells and on EBV and CD40L/IL-4 blasts after 7 days culture.
+As anticipated there was considerable overlap in the transcriptomes of the two types of lymphoblasts when compared to the original resting B cells, reflecting common changes associated with lymphocyte activation and proliferation.
+Of interest to us was a subset of 255 genes that were differentially expressed between EBV and CD40L/IL-4 blasts.
+Genes which were more highly expressed in EBV blasts were substantially and significantly enriched for a set of interferon-stimulated genes which on further in silico analyses were found to be repressed by IL-4 in other cell contexts and to be up-regulated in micro-dissected malignant cells from Hodgkin's lymphoma biopsies when compared to their normal germinal center cell counterparts.
+We hypothesized that EBV and IL-4 were targeting and discordantly regulating a common set of genes.
+This was supported experimentally in our B cell model where IL-4 stimulation partially reversed transcriptional changes which follow EBV infection and it impaired the efficiency of EBV-induced B cell transformation.
+Taken together, these data suggest that the discordant regulation of interferon and IL-4 pathway genes by EBV that occurs early following infection of B cells has relevance to the development or maintenance of an EBV-associated malignancy.
+Transferrin Receptor (TfR1) is the cell-surface receptor that regulates iron uptake into cells, a process that is fundamental to life.
+We use evolutionary and functional analyses of TfR1 in the rodent clade, where two families of viruses bind this receptor, to mechanistically dissect how essential housekeeping genes like TFR1 successfully balance the opposing selective pressures exerted by host and virus.
+We find that while the sequence of rodent TfR1 is generally conserved, a small set of TfR1 residue positions has evolved rapidly over the speciation of rodents.
+We show that naturally occurring mutations at these positions block virus entry while simultaneously preserving iron-uptake functionalities, both in rodent and human TfR1.
+Thus, by constantly replacing the amino acids encoded at just a few residue positions, TFR1 divorces adaptation to ever-changing viruses from preservation of key cellular functions.
+These dynamics have driven genetic divergence at the TFR1 locus that now enforces species-specific barriers to virus transmission, limiting both the cross-species and zoonotic transmission of these viruses.
+Its zoonotic nature and wide-spread distribution in industrialized countries calls for a quick and reliable diagnostic tool.
+Thus, an approach is presented, which allows for the rapid screening of numerous cDNA derived expression clones to identify novel antigens.
+The deeper understanding of immunodominant proteins assists in the design of diagnostic tools and furthers the insight into the bacterium’s pathogenicity as well as revealing potential candidates for vaccination.
+We have successfully screened 1536 clones of an expression library to identify 22 proteins that have not been described as immunodominant before.
+After subcloning the corresponding 22 genes and expression of full-length proteins, we investigated the immunodominant character by microarrays and ELISA.
+Consequently, an eleven amino acid residue sequence TLIKELKRLGI was analyzed via alanine scan, which revealed the glycine residue to be significant for binding of the antibody.
+The innovative approach presented herein of generating cDNAs of prokaryotes in combination with a microarray platform rendering time-consuming purification steps obsolete has helped to illuminate novel immunodominant proteins of C.jejuni.
+The findings of a specific linear epitope pave the way for a plethora of future research and the potential use in diagnostic applications such as serological screenings.
+Moreover, the current approach is easily adaptable to other highly relevant bacteria making it a formidable tool for the future discovery of antigens and potential biomarkers.
+Consequently, it is desirable to simplify the identification of structural epitopes, as this would extend the spectrum of novel epitopes to be detected.
+Several approaches have been proposed for near real-time detection and prediction of the spread of influenza.
+These include search query data for influenza-related terms, which has been explored as a tool for augmenting traditional surveillance methods.
+In this paper, we present a method that uses Internet search query data from Baidu to model and monitor influenza activity in China.
+The objectives of the study are to present a comprehensive technique for: (i) keyword selection, (ii) keyword filtering, (iii) index composition and (iv) modeling and detection of influenza activity in China.
+Sequential time-series for the selected composite keyword index is significantly correlated with Chinese influenza case data.
+In addition, one-month ahead prediction of influenza cases for the first eight months of 2012 has a mean absolute percent error less than 11%.
+To our knowledge, this is the first study on the use of search query data from Baidu in conjunction with this approach for estimation of influenza activity in China.
+Circulating RNA may result from excessive cell damage or acute viral infection and can interact with vascular endothelial cells.
+Despite the obvious clinical implications associated with the presence of circulating RNA, its pathological effects on endothelial cells and the governing molecular mechanisms are still not fully elucidated.
+We analyzed the effects of double stranded RNA on primary human pulmonary artery endothelial cells (hPAECs).
+The effect of natural and synthetic double-stranded RNA (dsRNA) on hPAECs was investigated using trans-endothelial electric resistance, molecule trafficking, calcium (Ca(2+)) homeostasis, gene expression and proliferation studies.
+Furthermore, the morphology and mechanical changes of the cells caused by synthetic dsRNA was followed by in-situ atomic force microscopy, by vascular-endothelial cadherin and F-actin staining.
+This was reflected by morphological and mechanical changes and an increase in the permeability of the endothelial monolayer.
+Additionally, the proliferation rate of the cells in the presence of synthetic dsRNA was significantly decreased.
+Furthermore, we found that natural and synthetic dsRNA modulated Ca(2+) signaling in hPAECs by inhibiting the sarco-endoplasmic Ca(2+)-ATPase (SERCA) which is involved in the regulation of the intracellular Ca(2+) homeostasis and thus cell growth.
+Our data identify novel mechanisms by which dsRNA can disrupt endothelial barrier function and these may be relevant in inflammatory processes.
+A cost-effective and efficacious influenza vaccine for use in commercial poultry farms would help protect against avian influenza outbreaks.
+Current influenza vaccines for poultry are expensive and subtype specific, and therefore there is an urgent need to develop a universal avian influenza vaccine.
+We have constructed a live bacterial vaccine against avian influenza by expressing a conserved peptide from the ectodomain of M2 antigen (M2e) on the surface of Lactococcus lactis (LL).
+Chickens were vaccinated intranasally with the lactococcal vaccine (LL-M2e) or subcutaneously with keyhole-limpet-hemocyanin conjugated M2e (KLH-M2e).
+Vaccinated and nonvaccinated birds were challenged with high pathogenic avian influenza virus A subtype H5N2.
+Birds vaccinated with LL-M2e or KLH-M2e had median survival times of 5.5 and 6.0 days, respectively, which were significantly longer than non-vaccinated birds (3.5 days).
+Birds vaccinated subcutaneously with KLH-M2e had a lower mean viral burden than either of the other two groups.
+However, there was a significant correlation between the time of survival and M2e-specific serum IgG.
+The results of these trials show that birds in both vaccinated groups had significantly (P < 0.05) higher median survival times than non-vaccinated birds and that this protection could be due to M2e-specific serum IgG.
+This work presents a new approach with details on the integrated platform and hardware architecture for nanorobots application in epidemic control, which should enable real time in vivo prognosis of biohazard infection.
+The recent developments in the field of nanoelectronics, with transducers progressively shrinking down to smaller sizes through nanotechnology and carbon nanotubes, are expected to result in innovative biomedical instrumentation possibilities, with new therapies and efficient diagnosis methodologies.
+The use of integrated systems, smart biosensors, and programmable nanodevices are advancing nanoelectronics, enabling the progressive research and development of molecular machines.
+The use of nanobioelectronics as embedded systems is the natural pathway towards manufacturing methodology to achieve nanorobot applications out of laboratories sooner as possible.
+To demonstrate the practical application of medical nanorobotics, a 3D simulation based on clinical data addresses how to integrate communication with nanorobots using RFID, mobile phones, and satellites, applied to long distance ubiquitous surveillance and health monitoring for troops in conflict zones.
+Therefore, the current model can also be used to prevent and save a population against the case of some targeted epidemic disease.
+We have recently reported that calreticulin (CRT), a luminal resident protein, can be found in the sera of patients with rheumatoid arthritis and also that recombinant CRT (rCRT) exhibits extraordinarily strong immunological activities.
+We herein further demonstrate that rCRT fragments 18–412 (rCRT/18-412), rCRT/39-272, rCRT/120-308 and rCRT/120-250 can self-oligomerize in solution and are 50–100 fold more potent than native CRT (nCRT, isolated from mouse livers) in activating macrophages in vitro.
+We narrowed down the active site of CRT to residues 150–230, the activity of which also depends on dimerization.
+When rCRT/18-412 is fractionated into oligomers and monomers by gel filtration, the oligomers maintain most of their immunological activities in terms of activating macrophages in vitro and inducing specific antibodies in vivo, while the monomers were much less active by comparison.
+Additionally, rCRT/18-412 oligomers are much better than monomers in binding to, and uptake by, macrophages.
+We conclude that the immunologically active site of CRT maps between residues 198–230 and that soluble CRT could acquire potent immuno-pathological activities in microenvironments favoring its oligomerization.
+M36 is the first member of a novel class of potent HIV-1 entry inhibitors based on human engineered antibody domains (eAds).
+First, a panel of mimotopes was affinity-selected from a random peptide library and potential m36-binding residues were computationally predicted.
+Second, homology modeling of m36 and molecular docking of m36 onto gp120 revealed potentially important residues in gp120-m36 interactions.
+Taken together, m36 epitope comprising three discontinuous sites including six key gp120 residues (Site C1: Thr123 and Pro124; Site C3: Glu370 and Ile371; Site C4: Met426 and Trp427) were identified.
+In the 3D structure of gp120, the sites C1 and C4 are located in the bridging sheet and the site C3 is within the β15-α3 excursion, which play essential roles for the receptor- and coreceptor-binding and are major targets of neutralizing antibodies.
+Based on these results we propose a precise localization of the m36 epitope and suggest a mechanism of its broad inhibitory activity which could help in the development of novel HIV-1 therapeutics based on eAds.
+The concentrations of three bacteria/genera, Stenotrophomonas maltophilia, Streptomyces sp., and Mycobacterium sp., were measured in air and dust samples using quantitative PCR (QPCR).
+The concentrations of the bacteria measured in the air samples were not associated with any specific home characteristic based on multiple regression models.
+However, higher concentrations of S. maltophilia in the dust samples were associated with water damage, that is, with higher floor surface moisture and higher concentrations of moisture‐related mold species.
+had similar patterns and may be partially determined by human and animal occupants and outdoor sources of these bacteria.
+BACKGROUND: With concerns about the disastrous health and economic consequences caused by the influenza pandemic, comprehensively understanding the global host response to influenza virus infection is urgent.
+However, the precise role of miRNAs in the pathogenesis of influenza virus infection in humans, especially in critically ill patients is still unclear.
+METHODS: We identified cellular miRNAs involved in the host response to influenza virus infection by performing comprehensive miRNA profiling in peripheral blood mononuclear cells (PBMCs) from critically ill patients with swine-origin influenza pandemic H1N1 (2009) virus infection via miRNA microarray and quantitative reverse-transcription polymerase chain reaction (qRT-PCR) assays.
+Receiver operator characteristic (ROC) curve analysis was conducted and area under the ROC curve (AUC) was calculated to evaluate the diagnostic accuracy of severe H1N1 influenza virus infection.
+Furthermore, an integrative network of miRNA-mediated host-influenza virus protein interactions was constructed by integrating the predicted and validated miRNA-gene interaction data with influenza virus and host-protein-protein interaction information using Cytoscape software.
+RESULTS: Forty-one significantly differentially expressed miRNAs were found by miRNA microarray; nine were selected and validated by qRT-PCR.
+QRT-PCR assay and ROC curve analyses revealed that miR-31, miR-29a and miR-148a all had significant potential diagnostic value for critically ill patients infected with H1N1 influenza virus, which yielded AUC of 0.9510, 0.8951 and 0.8811, respectively.
+We subsequently constructed an integrative network of miRNA-mediated host-influenza virus protein interactions, wherein we found that miRNAs are involved in regulating important pathways, such as mitogen-activated protein kinase signaling pathway, epidermal growth factor receptor signaling pathway, and Toll-like receptor signaling pathway, during influenza virus infection.
+Some of differentially expressed miRNAs via in silico analysis targeted mRNAs of several key genes in these pathways.
+The mRNA expression level of tumor protein T53 and transforming growth factor beta receptor 1 were found significantly reduced in critically ill patients, whereas the expression of Janus kinase 2, caspase 3 apoptosis-related cysteine peptidase, interleukin 10, and myxovirus resistance 1 were extremely increased in critically ill patients.
+CONCLUSIONS: Our data suggest that the dysregulation of miRNAs in the PBMCs of H1N1 critically ill patients can regulate a number of key genes in the major signaling pathways associated with influenza virus infection.
+These differentially expressed miRNAs could be potential therapeutic targets or biomarkers for severe influenza virus infection.
+Compared to traditional testing strategies, nucleic acid amplification tests such as real-time PCR offer many advantages for the detection of human adenoviruses.
+To overcome fiscal challenges, a cost effective strategy was developed using a combination of homogenization and heat treatment with an “in-house” real-time PCR.
+In 196 swabs submitted for adenovirus detection, this crude extraction method showed performance characteristics equivalent to viral DNA obtained from a commercial nucleic acid extraction.
+In addition, the in-house real-time PCR outperformed traditional testing strategies using virus culture, with sensitivities of 100% and 69.2%, respectively.
+Overall, the combination of homogenization and heat treatment with a sensitive in-house real-time PCR provides accurate results at a cost comparable to viral culture.
+When a pathogen is rare in a host population, there is a chance that it will die out because of stochastic effects instead of causing a major epidemic.
+Yet no criteria exist to determine when the pathogen increases to a risky level, from which it has a large chance of dying out, to when a major outbreak is almost certain.
+We introduce such an outbreak threshold (T(0)), and find that for large and homogeneous host populations, in which the pathogen has a reproductive ratio R(0), on the order of 1/Log(R(0)) infected individuals are needed to prevent stochastic fade-out during the early stages of an epidemic.
+We also show how this threshold scales with higher heterogeneity and R(0) in the host population.
+BACKGROUND: In this study, we sequenced and phylogenetic analyses of the VP2 genes from twelve canine parvovirus (CPV) strains obtained from eleven domestic dogs and a giant panda (Ailuropoda melanoleuca) in China.
+RESULTS: Nucleotide and phylogenetic analysis of the capsid protein VP2 gene classified the CPV as a new CPV-2a type.
+Substitution of Gln for Arg at the conserved 370 residue in CPV presents an unusual variation in the new CPV-2a amino acid sequence of the giant panda and is further evidence for the continuing evolution of the virus.
+CONCLUSIONS: These findings extend the knowledge on CPV molecular epidemiology of particular relevance to wild carnivores.
+The identification of dystrophin and the causative role of mutations in this gene in Duchenne and Becker muscular dystrophies (D/BMD) was expected to lead to timely development of effective therapies.
+Despite over 20 years of research, corticosteroids remain the only available pharmacological treatment for DMD, although significant benefits and extended life have resulted from advances in the clinical care and management of DMD individuals.
+Effective treatment of DMD will require dystrophin restitution in skeletal, cardiac, and smooth muscles and nonmuscle tissues; however, modulation of muscle loss and regeneration has the potential to play an important role in altering the natural history of DMD, particularly in combination with other treatments.
+Emerging biological, molecular, and small molecule therapeutics are showing promise in ameliorating this devastating disease, and it is anticipated that regulatory environments will need to display some flexibility in order to accommodate the new treatment paradigms.
+Although heterotypic secondary infection with dengue virus (DENV) is associated with severe disease, the majority of secondary infections are mild or asymptomatic.
+In 2010, 108 DENV3-positive cases were enrolled in a pediatric hospital-based study in Managua, Nicaragua, with 61 primary and 47 secondary infections.
+We analyzed DENV-specific neutralization titers (NT(50)), IgM and IgG avidity, and antibody titer in serum samples collected during acute and convalescent phases and 3, 6, and 18 months post-infection.
+IgG avidity to DENV3 significantly increased between convalescent and 3-month time-points in primary DENV infections and between the acute and convalescent phase in secondary DENV infections.
+While avidity to DENV2, a likely previous infecting serotype, was initially higher than avidity to DENV3 in secondary DENV infections, the opposite relation was observed 3–18 months post-infection.
+We found significant correlations between IgM avidity and NT(50) in acute primary cases and between IgG avidity and NT(50) in secondary DENV infections.
+In summary, our findings indicate that IgM antibodies likely play a role in early control of DENV infections.
+IgG serum avidity to DENV, analyzed for the first time in longitudinal samples, switches from targeting mainly cross-reactive serotype(s) to the current infecting serotype over time.
+INTRODUCTION: The purpose of the study was to assess the long term outcome and quality of life of patients with acute respiratory distress syndrome (ARDS) receiving extracorporeal membrane oxygenation (ECMO) for refractory hypoxemia.
+METHODS: A retrospective observational study with prospective health related quality of life (HRQoL) assessment was conducted in ARDS patients who had ECMO as a rescue therapy for reversible refractory hypoxemia from January 2009 until April 2011 in a tertiary Australian centre.
+Survival and long-term quality of life assessment, using the Short-Form 36 (SF-36) and the EuroQol health related quality of life questionnaire (EQ5D) were assessed and compared to international data from other research groups.
+RESULTS: Twenty-one patients (mean age 36.3 years) with ARDS receiving ECMO for refractory hypoxemia were studied.
+Eighteen (86%) patients were retrieved from external intensive care units (ICUs) by a dedicated ECMO retrieval team.
+Of the 18 survivors, ten (56%) were discharged to other hospitals and 8 (44%) were discharged directly home.
+Sequelae and health related quality of life were evaluated for 15 of the 18 (71%) long-term survivors (assessment at median 8 months).
+Mean SF-36 scores were significantly lower across all domains compared to age and sex matched Australian norms.
+Mean SF-36 scores were lower (minimum important difference at least 5 points) than previously described ARDS survivors in the domains of general health, mental health, vitality and social function.
+Only 26% of survivors had returned to previous work levels at the time of follow-up.
+CONCLUSIONS: This ARDS cohort had a high survival rate (86%) after use of ECMO support for reversible refractory hypoxemia.
+Long term survivors had similar physical health but decreased mental health, general health, vitality and social function compared to other ARDS survivors and an unexpectedly poor return to work.
+Highly pathogenic avian influenza H5N1 viruses can result in poultry and occasionally in human mortality.
+Hemagglutinin (HA), a major envelope protein accounting for approximately 80% of spikes in influenza virus, is often used as a major antigen for subunit vaccine development.
+In this study, we conducted a systematic study of the immune response against influenza virus infection following immunization with recombinant HA proteins expressed in insect (Sf9) cells, insect cells that contain exogenous genes for elaborating N-linked glycans (Mimic) and mammalian cells (CHO).
+While the antibody titers are higher with the insect cell derived HA proteins, the neutralization and HA inhibition titers are much higher with the mammalian cell produced HA proteins.
+Recombinant HA proteins containing tri- or tetra-antennary complex, terminally sialylated and asialyated-galactose type N-glycans induced better protective immunity in mice to lethal challenge.
+The results are highly relevant to issues that should be considered in the production of fragment vaccines.
+BACKGROUND: This study was performed to compare the clinical characteristics and antibiotic susceptibilities of viridans streptococcal bacteremia (VSB) between febrile neutropenic adults and children with hematologic malignancies.
+METHODS: The consecutive medical records of neutropenic patients with hematologic malignancies who were admitted to the Catholic Blood and Marrow Transplantation Center between April 2009 and July 2012, and who were subsequently diagnosed with VSB were reviewed retrospectively.
+A comparison was made between the clinical and laboratory characteristics of adults and pediatric patients and also between patients with cefepime susceptible or not susceptible VSB.
+RESULTS: A total of 202 episodes (141 in adults, 61 in children) of VSB were identified.
+Among them, 26 (12.9%) cases had severe complications including four (2.0%) cases of death attributable to VSB.
+For antibacterial prophylaxis, most adults received ciprofloxacin (97.1%), but children more frequently received trimethoprim/sulfamethoxazole (86.9%).
+Oral mucositis (p = 0.005) and abdominal pain (p = 0.001) were found more frequently in adults, and cough was found more frequently in children (p = 0.004).
+The occurrence rates of severe complications and death attributable to VSB were not significantly different between adults and children.
+Susceptibility rate to cefepime was significantly higher in adults than children (85.7% vs. 66.1%, p = 0.002).
+CONCLUSIONS: There was no significant difference in clinical outcome between adults and children with VSB despite a difference in cefepime susceptibility.
+Many viral proteins have been shown to be sumoylated with corresponding regulatory effects on their protein function, indicating that this host cell modification process is widely exploited by viral pathogens to control viral activity.
+In addition to using sumoylation to regulate their own proteins, several viral pathogens have been shown to modulate overall host sumoylation levels.
+Given the large number of cellular targets for SUMO addition and the breadth of critical cellular processes that are regulated via sumoylation, viral modulation of overall sumoylation presumably alters the cellular environment to ensure that it is favorable for viral reproduction and/or persistence.
+Like some viruses, certain bacterial plant pathogens also target the sumoylation system, usually decreasing sumoylation to disrupt host anti-pathogen responses.
+The recent demonstration that Listeria monocytogenes also disrupts host sumoylation, and that this is required for efficient infection, extends the plant pathogen observations to a human pathogen and suggests that pathogen modulation of host sumoylation may be more widespread than previously appreciated.
+This review will focus on recent aspects of how pathogens modulate the host sumoylation system and how this benefits the pathogen.
+Hepatitis C virus (HCV) is among the most relevant causes of liver cirrhosis and hepatocellular carcinoma.
+The systematic investigation of viruses of small mammals could guide efforts to establish such models, while providing insight into viral evolutionary biology.
+We have assembled the so-far largest collection of small-mammal samples from around the world, qualified to be screened for bloodborne viruses, including sera and organs from 4,770 rodents (41 species); and sera from 2,939 bats (51 species).
+Three highly divergent rodent hepacivirus clades were detected in 27 (1.8%) of 1,465 European bank voles (Myodes glareolus) and 10 (1.9%) of 518 South African four-striped mice (Rhabdomys pumilio).
+Bats showed anti-HCV immunoblot reactivities but no virus detection, although the genetic relatedness suggested by the serologic results should have enabled RNA detection using the broadly reactive PCR assays developed for this study.
+210 horses and 858 cats and dogs were tested, yielding further horse-associated hepaciviruses but none in dogs or cats.
+The rodent viruses were equidistant to HCV, exceeding by far the diversity of HCV and the canine/equine hepaciviruses taken together.
+Quantitative RT-PCR, RNA in-situ hybridisation, and histopathology suggested hepatic tropism with liver inflammation resembling hepatitis C. Recombinant serology for two distinct hepacivirus lineages in 97 bank voles identified seroprevalence rates of 8.3 and 12.4%, respectively.
+Antibodies in bank vole sera neither cross-reacted with HCV, nor the heterologous bank vole hepacivirus.
+Co-occurrence of RNA and antibodies was found in 3 of 57 PCR-positive bank vole sera (5.3%).
+Our data enable new hypotheses regarding HCV evolution and encourage efforts to develop rodent surrogate models for HCV.
+Japanese encephalitis virus (JEV) non-structural protein 1 (NS1) contributes to virus replication and elicits protective immune responses during infection.
+JEV NS1-specific antibody responses could be a target in the differential diagnosis of different flavivirus infections.
+For epitope mapping of monoclonal antibodies, a set of 51 partially-overlapping peptides covering the entire NS1 protein were expressed with a GST-tag and then screened using monoclonal antibodies.
+By sequentially removing amino acid residues from the carboxy and amino terminal of peptides, the minimal units of the five linear epitopes were identified and confirmed using monoclonal antibodies.
+Five linear epitopes are located in amino acids residues (5)AIDITRK(11), (72)RDELNVL(78), (251)KSKHNRREGY(260), (269)DENGIVLD(276), and (341)DETTLVRS(348).
+Furthermore, it was found that the epitopes are highly conserved among JEV strains through sequence alignment.
+Notably, none of the homologous regions on NS1 proteins from other flaviviruses reacted with the MAbs when they were tested for cross-reactivity, and all five epitope peptides were not recognized by sera against West Nile virus or Dengue virus.
+These novel virus-specific linear B-cell epitopes of JEV NS1 would benefit the development of new vaccines and diagnostic assays.
+It is now used in the treatment of chronic myelogenous leukemia (CML) with resistance or intolerance to prior therapies, including imatinib.
+Here we report a novel effect of dasatinib on inducing the differentiation of acute myeloid leukemia (AML) cells through MEK/ERK-dependent activation of signal transducer and activator of transcription 1 (STAT1).
+We found that dasatinib could induce the differentiation of AML cells as demonstrated by the expression of differentiation marker CD11b, G0/G1 phase arrest and decreased ratio of nucleus to cytoplasm.
+Of note, dasatinib induced robust phosphorylation of STAT1 both at Tyr701 and Ser727 as well as the redistribution of STAT1 from the cytoplasm to the nucleus, thus leading to the transcription of STAT1-targeted genes.
+Knocking down STAT1 expression by shRNA significantly attenuated dasatinib-induced differentiation, indicating an important role of STAT1 in myeloid maturation.
+The phosporylation of MEK and ERK occurred rapidly upon dasatinib treatment and increased progressively as differentiation was induced.
+MEK inhibitors PD98059 and U0216 not only inhibited the phosphorylation of STAT1, but also abrogated dasatinib-induced myeloid differentiation, suggesting that MEK/ERK dependent phosphorylation of STAT1 might be indispensable for the differentiating effect of dasatinib in AML cells.
+Taken together, our study suggests that STAT1 is an important mediator in dasatinib-induced differentiation of AML cells, whose activation requires the activation of MEK/ERK cascades.
+The Pneumonia Etiology Research for Child Health (PERCH) project is the largest multicountry etiology study of childhood pneumonia since the Board on Science and Technology in International Development studies of the 1980s.
+However, it is not the only recent or ongoing pneumonia etiology study, and even with seven sites, it cannot capture all epidemiologic settings in the developing world.
+Funding providers, researchers and policymakers rely on the best available evidence to strategically plan programs, new research directions and interventions.
+We aimed to describe the current landscape of recent pneumonia etiology studies in children under 5 years of age in the developed and developing world, as ascertained by a literature review of relevant studies with data since the year 2000 and a survey of researchers in the field of childhood pneumonia.
+We collected information on the study population, study design, case definitions, laboratory samples and methods and identified pathogens.
+As of June 2010, our survey of researchers identified an additional 65 ongoing and recently completed child pneumonia etiology studies.
+However, the landscape analysis also reveals a multiplicity of case definitions, levels of clinician involvement, facility types, specimen collection, and laboratory techniques.
+It reinforces the need for the standardization of methods and analyses for present and future pneumonia etiology studies in order to optimize their cumulative potential to accurately describe the microbial causes of childhood pneumonia.
+INTRODUCTION: An infection by herpes zoster virus is a common and important cause of encephalitis.
+Herpes zoster virus encephalitis if not treated promptly can result in significant morbidity and mortality.
+The diagnosis of herpes zoster virus encephalitis is based on clinical history, examination, neuroradiological imaging (magnetic resonance imaging and/or computed tomography scan), cerebrospinal fluid analysis and identification of the pathogen in cerebrospinal fluid by polymerase chain reaction amplification and/or anti-herpes zoster virus immunoglobulin G antibody in cerebrospinal fluid.
+Although ischemic intracerebral infarcts in patients with herpes zoster virus encephalitis or vasculopathy are reported in the literature, multiple intracerebral hemorrhages as a complication of herpes zoster virus encephalitis in an immunocompetent individual are extremely rare.
+CASE PRESENTATION: A 40-year-old Indian man presented with an acute history of four episodes of seizures, fever, headache, drowsiness, focal neurological deficits and vesicular eruptions over the abdomen in a typical dermatomal distribution.
+Investigations (positive ratio between the cerebrospinal fluid/serum quotients for anti-herpes zoster virus immunoglobulin G and total immunoglobulin G antibodies) established its infective origin due to herpes zoster virus.
+CONCLUSION: Herpes zoster virus encephalitis or vasculopathy is a rare cause of multiple intracerebral hemorrhages and must be considered in the differential diagnosis of patients presenting with an acute history of fever, altered consciousness, and focal neurologic deficits with history of a typical herpetic rash.
+As a consequence of innate immune activation granulocytes and macrophages produce hypochlorite/hypochlorous acid (HOCl) via secretion of myeloperoxidase (MPO) to the outside of the cells, where HOCl immediately reacts with proteins.
+Most proteins that become altered by this system do not belong to the invading microorganism but to the host.
+While there is no doubt that the myeloperoxidase system is capable of directly inactivating HIV-1, we hypothesized that it may have an additional indirect mode of action.
+We show in this article that HOCl is able to chemically alter proteins and thus turn them into Idea-Ps (Idea-P = immune defence-altered protein), potent amyloid-like and SH-groups capturing antiviral weapons against HIV-1.
+HOCl-altered plasma proteins (Idea-PP) have the capacity to bind efficiently and with high affinity to the HIV-1 envelope protein gp120, and to its receptor CD4 as well as to the protein disulfide isomerase (PDI).
+Idea-PP was able to inhibit viral infection and replication in a cell culture system as shown by reduced number of infected cells and of syncytia, resulting in reduction of viral capsid protein p24 in the culture supernatant.
+HOCl-altered isolated proteins antithrombin III and human serum albumin, taken as representative examples of the whole pool of plasma proteins, were both able to exert the same activity of binding to gp120 and inhibition of viral proliferation.
+These data offer an opportunity to improve the understanding of the intricacies of host-pathogen interactions and allow the generation of the following hypothetical scheme: natural immune defense mechanisms generate by posttranslational modification of plasma proteins a potent virucidal weapon that immobilizes the virus as well as inhibits viral fusion and thus entry into the host cells.
+Furthermore simulation of this mechanism in vitro might provide an interesting new therapeutic approach against microorganisms.
+This study analyzed a heterologous prime-boost vaccine approach against HIV-1 using three different antigenically unrelated negative-stranded viruses (NSV) expressing HIV-1 Gag as vaccine vectors: rabies virus (RABV), vesicular stomatitis virus (VSV) and Newcastle disease virus (NDV).
+We hypothesized that this approach would result in more robust cellular immune responses than those achieved with the use of any of the vaccines alone in a homologous prime-boost regimen.
+Primed mice were rested for thirty-five days after which we administered a second immunization with the same or heterologous NSV-Gag viruses.
+The magnitude and quality of the Gag-specific CD8(+) T cells in response to these vectors post boost were measured.
+In addition, we performed challenge experiments using vaccinia virus expressing HIV-1 Gag (VV-Gag) thirty-three days after the boost inoculation.
+Our results showed that the choice of the vaccine used for priming was important for the detected Gag-specific CD8(+) T cell recall responses post boost and that NDV-Gag appeared to result in a more robust recall of CD8(+) T cell responses independent of the prime vaccine used.
+However, the different prime-boost strategies were not distinct for the parameters studied in the challenge experiments using VV-Gag but did indicate some benefits compared to single immunizations.
+Taken together, our data show that NSV vectors can individually stimulate HIV-Gag specific CD8(+) T cells that are effectively recalled by other NSV vectors in a heterologous prime-boost approach.
+These results provide evidence that RABV, VSV and NDV can be used in combination to develop vaccines needing prime-boost regimens to stimulate effective immune responses.
+Reversible phosphorylation is one of the major mechanisms of signal transduction, and signaling networks are critical regulators of cell growth and development.
+Towards this end, quantitative phosphoproteomics is emerging as a useful tool enabling large-scale determination of relative phosphorylation levels.
+However, phosphoproteomics differs from classical proteomics by a more extensive sampling limitation due to the limited number of detectable sites per protein.
+Here, we propose a comprehensive quantitative analysis pipeline customized for phosphoproteome data from interventional experiments for identifying key proteins in specific pathways, discovering the protein-protein interactions and inferring the signaling network.
+We also made an effort to partially compensate for the missing value problem, a chronic issue for proteomics studies.
+The dataset used for this study was generated using SILAC (Stable Isotope Labeling with Amino acids in Cell culture) technique with interventional experiments (kinase-dead mutations).
+The major components of the pipeline include phosphopeptide meta-analysis, correlation network analysis and causal relationship discovery.
+We have successfully applied our pipeline to interventional experiments identifying phosphorylation events underlying the transition to a filamentous growth form in Saccharomyces cerevisiae.
+We identified 5 high-confidence proteins from meta-analysis, and 19 hub proteins from correlation analysis (Pbi2p and Hsp42p were identified by both analyses).
+In addition, we tested four of our predicted proteins, Nth1p, Pbi2p, Pdr12p and Rcn2p, by interventional phenotypic experiments and all of them present differential invasive growth, providing prospective validation of our approach.
+This comprehensive pipeline presents a systematic way for discovering signaling networks using interventional phosphoproteome data and can suggest candidate proteins for further investigation.
+We anticipate the methodology to be applicable as well to other interventional studies via different experimental platforms.
+Reliable forecasts of influenza can aid in the control of both seasonal and pandemic outbreaks.
+This study represents the final step of a project aimed at using a combination of simulation, classification, statistical and optimization techniques to forecast the epidemic curve and infer underlying model parameters during an influenza outbreak.
+The method is used to forecast epidemics simulated over synthetic social networks representing Montgomery County in Virginia, Miami, Seattle and surrounding metropolitan regions.
+Depending on the synthetic network, the peak time could be predicted within a 95% CI as early as seven weeks before the actual peak.
+The peak infected and total infected were also accurately forecasted for Montgomery County in Virginia within the forecasting period.
+Forecasting of the epidemic curve for both seasonal and pandemic influenza outbreaks is a complex problem, however this is a preliminary step and the results suggest that more can be achieved in this area.
+Human rhinoviruses (HRVs), in the Enterovirus genus within the family Picornaviridae, are a highly prevalent cause of acute respiratory infection (ARI).
+Enteroviruses are genetically highly variable, and recombination between serotypes is known to be a major contribution to their diversity.
+This study analyzed parts of the viral genes spanning the 5′ non- coding region (NCR) through to the viral protein (VP) encoding sequences of 105 HRV field isolates from 51 outpatient cases of Acute Respiratory Infectious Network (ARINET) and 54 inpatient cases of severe lower respiratory infection (SLRI) surveillance, in order to identify recombination in field samples.
+When analyzing parts of the 5′NCR and VP4/VP2 encoding sequences, we found intra- and interspecies recombinants in field strains of HRV-A and -C. Nineteen cases of recombination events (18.1%) were found among 105 field strains.
+For HRV-A, there were five cases (4.8%) of intraspecies recombination events and three cases (2.8%) of interspecies recombination events.
+For HRV-C, there were four cases (3.8%) of intraspecies recombination events and seven cases (6.7%) of interspecies recombination events.
+Recombination events were significantly more frequently observed in the ARINET samples (18 cases) than in the SLRI samples (1 case; P< 0.0001).
+The recombination breakpoints were located in nucleotides (nt) 472–554, which comprise stem-loop 5 in the internal ribosomal entry site (IRES), based on the HRV-B 35 sequence (accession no.
+Our findings regarding genomic recombination in circulating HRV-A and -C strains suggest that recombination might play a role in HRV fitness and could be a possible determinant of disease severity caused by various HRV infections in patients with ARI.
+The tumor necrosis factor receptor (TNF-R)-associated factor (TRAF) family of intracellular proteins were originally identified as signaling adaptors that bind directly to the cytoplasmic regions of receptors of the TNF-R superfamily.
+The past decade has witnessed rapid expansion of receptor families identified to employ TRAFs for signaling.
+These include Toll-like receptors (TLRs), NOD-like receptors (NLRs), RIG-I-like receptors (RLRs), T cell receptor, IL-1 receptor family, IL-17 receptors, IFN receptors and TGFβ receptors.
+In addition to their role as adaptor proteins, most TRAFs also act as E3 ubiquitin ligases to activate downstream signaling events.
+TRAF-dependent signaling pathways typically lead to the activation of nuclear factor-κBs (NF-κBs), mitogen-activated protein kinases (MAPKs), or interferon-regulatory factors (IRFs).
+Compelling evidence obtained from germ-line and cell-specific TRAF-deficient mice demonstrates that each TRAF plays indispensable and non-redundant physiological roles, regulating innate and adaptive immunity, embryonic development, tissue homeostasis, stress response, and bone metabolism.
+Notably, mounting evidence implicates TRAFs in the pathogenesis of human diseases such as cancers and autoimmune diseases, which has sparked new appreciation and interest in TRAF research.
+This review presents an overview of the current knowledge of TRAFs, with an emphasis on recent findings concerning TRAF molecules in signaling and in human diseases.
+Whereas red blood cell transfusions have been used since the 19th century, plasma has only been available since 1941.
+It was originally mainly used as volume replacement, mostly during World War II and the Korean War.
+Over the years, its indication has shifted to correct coagulation factors deficiencies or to prevent bleeding.
+Currently, it remains a frequent treatment in the intensive care unit, both for critically ill adults and children.
+However, observational studies have shown that plasma transfusion fail to correct mildly abnormal coagulation tests.
+Furthermore, recent epidemiological studies have shown that plasma transfusions are associated with an increased morbidity and mortality in critically ill patients.
+Therefore, plasma, as any other treatment, has to be used when the benefits outweigh the risks.
+Based on observational data, most experts suggest limiting its use either to massively bleeding patients or bleeding patients who have documented abnormal coagulation tests, and refraining for transfusing plasma to nonbleeding patients whatever their coagulation tests.
+In this paper, we will review current evidence on plasma transfusions and discuss its indications.
+The COP9 signalosome (CSN), an evolutionally highly conserved protein complex composed of 8 unique subunits (CSN1 through CSN8) in higher eukaryotes, is purported to modulate protein degradation mediated by the ubiquitin-proteasome system (UPS) but this has not been demonstrated in a critical mitotic parenchymal organ of vertebrates.
+Hepatocyte-specific knockout of the Cops8 gene (HS-Csn8KO) was shown to cause massive hepatocyte apoptosis and liver malfunction but the underlying mechanism remains unclear.
+Here, we report that Csn8/CSN exerts profound impacts on hepatic UPS function and is critical to the stability of the pro-apoptotic protein Bim.
+Significant decreases in CIS (cytokine-inducible Src homology 2 domain-containing protein), a Bim receptor of a cullin2-based ubiquitin ligase, were found to co-exist with a marked increase of Bim proteins.
+Csn8 deficiency also significantly decreased 19S proteasome subunit Rpt5 and markedly increased high molecular weight neddylated and ubiquitinated proteins.
+The use of a surrogate UPS substrate further reveals severe impairment of UPS-mediated proteolysis in HS-Csn8KO livers.
+In addition to Bim, massive hepatocyte apoptosis in HS-Csn8KO livers is also associated with elevated expression of other members of the Bcl2 family, including pro-apoptotic Bax as well as anti-apoptotic Bcl2 and Bcl-XL.
+Hence, it is concluded that hepatic CSN8 deficiency impairs the UPS in the liver and the resultant Bim upregulation likely plays an important role in triggering hepatocyte apoptosis via sequestering Bcl2 away from Bax.
+Infection with influenza A virus, one of the most common life-threatening viruses, causes the accumulation of inflammatory cells in the lung, which is directly correlated with influenza-associated morbidity and mortality.
+In this study, we investigated the potential of lysozyme-treated Enterococcus faecalis FK-23 (LFK) to prevent influenza in influenza virus-infected mice.
+C57BL/6N mice were orally administered LFK and intranasally infected with influenza virus A/Puerto Rico/8/34 (H1N1) at lethal doses.
+After infection with influenza A virus, the survival rate of the LFK-administered mice was significantly higher than that of saline-administered mice.
+Staining of lung sections with hematoxylin-eosin, and cell counts of lung and bronchoalveolar lavage fluid showed that oral administration of LFK suppressed the excessive infiltration of leukocytes into the lung after viral infection.
+Expression levels of genes involved in matrix degradation, which are correlated with vascular permeability, were downregulated in LFK-administered mice.
+These findings suggest that stabilizing the integrity of the alveolar-capillary barrier by the administration of LFK improves survival rate.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/2193-1801-2-269) contains supplementary material, which is available to authorized users.
+BACKGROUND: Southeast Asia has been identified as a potential epicentre of emerging diseases with pandemic capacity, including highly pathogenic influenza.
+Cambodia in particular has the potential for high rates of avoidable deaths from pandemic influenza due to large gaps in health system resources.
+This study seeks to better understand the course and cost-of-illness for cases of highly pathogenic avian influenza in Cambodia.
+METHODS: We studied the 18 laboratory-confirmed cases of avian influenza subtype H5N1 identified in Cambodia between January 2005 and August 2011.
+Medical records for all patients were reviewed to extract information on patient characteristics, travel to hospital, time to admission, diagnostic testing, treatment and disease outcomes.
+Further data related to costs was collected through interviews with key informants at district and provincial hospitals, the Ministry of Health and non-governmental organisations.
+An ingredient-based approach was used to estimate the total economic cost for each study patient.
+Costing was conducted from a societal perspective and included both financial and opportunity costs to the patient or carer.
+RESULTS: Of the 18 patients studied, 11 (61%) were under the age of 18 years.
+The majority of patients (16, 89%) died, eight (44%) within 24 hours of hospital admission.
+There was an average delay of seven days between symptom onset and hospitalisation with patients travelling an average of 148 kilometres (8-476 km) to the admitting hospital.
+For the 16 patients who received all their treatment in Cambodia the average per patient cost of H5N1 influenza illness was US$300 of which 85.0% comprised direct medical provider costs, including diagnostic testing (41.2%), pharmaceuticals (28.4%), hospitalisation (10.4%), oxygen (4.4%) and outpatient consultations (0.6%).
+CONCLUSION: Cases of avian influenza in Cambodia were characterised by delays in hospitalisation, deficiencies in some aspects of treatment and a high fatality rate.
+The costs associated with medical care, particularly diagnostic testing and pharmaceutical therapy, were major contributors to the relatively high cost-of-illness.
+Various factors including heredity, environmental agent, innate and acquired immunity, and skin barrier function participate in the pathogenesis of AD.
+T -helper (Th) 2-dominant immunological milieu has been suggested in the acute phase of AD.
+Ag85B has strong Th1-type cytokine inducing activity, and is expected to ameliorate Th2 condition in allergic disease.
+Recently, we have established a novel functional virus vector; recombinant human parainfluenza type 2 virus vector (rhPIV2): highly expressive, replication-deficient, and very low-pathogenic vector.
+In this study, we investigated the efficacy of rhPIV2 engineered to express Ag85B (rhPIV2/Ag85B) in a mouse AD model induced by repeated oxazolone (OX) challenge.
+Ear swelling, dermal cell infiltrations and serum IgE level were significantly suppressed in the rhPIV2/Ag85B treated mouse group accompanied with elevated IFN-γ and IL-10 mRNA expressions, and suppressed IL-4, TNF-α and MIP-2 mRNA expressions.
+These results suggested that rhPIV2/Ag85B might be a potent therapeutic tool to control allergic disorders.
+This study aims to determine whether chronic stress is associated with poorer influenza-specific immune responses to influenza vaccines in Hong Kong Chinese elderly people.
+Subjects were recruited from government general out-patient clinics, non-government organizations, and public housing estates in Hong Kong.
+Participants include 55 caregivers of spouses with chronic conditions that impaired their activities of daily living and 61 age- and sex-matched non-caregivers.
+Blood samples were collected before vaccination, at 6 weeks, and at 12 weeks after vaccination.
+Lymphocyte subsets were analyzed for ratios and absolute counts, and cytokine concentration were measured by flow cytometry.
+Validated scales were used to assess psychological (depressive symptoms, perceived stress, and caregiver strain), social (multidimensional social support scale), and lifestyle factors (physical exercise, cigarette smoking, and alcohol consumption) at baseline prior to vaccination.
+Caregivers had statistically significant (p < 0.05) lower cell-mediated immune responses to influenza vaccination at 12 weeks when compared with those of the controls.
+Hong Kong Chinese elderly who experience chronic stress have a significantly lower cell-mediated immune response to influenza vaccination when compared with non-caregivers.
+In recent years, Hong Kong has invested in research infrastructure to appropriately respond to novel infectious disease epidemics.
+Research from Hong Kong made a strong contribution to the international response to the 2009 influenza A (H1N1) pandemic (pH1N1).
+Summarizing, describing, and reviewing Hong Kong’s response to the 2009 pandemic, this article aimed to identify key elements of a real‐time research response.
+A systematic search in PubMed and EMBASE for research into the infection dynamics and natural history, impact, or control of pH1N1 in Hong Kong.
+Transmissibility of pH1N1 was similar in Hong Kong to elsewhere, and only a small fraction of infections were associated with severe disease.
+School closures were effective in reducing pH1N1 transmission, oseltamivir was effective for treatment of severe cases while convalescent plasma therapy has the potential to mitigate future pandemics.
+There was a rapid and comprehensive research response to pH1N1 in Hong Kong, providing important information on the epidemiology of the novel virus with relevance internationally as well as locally.
+The scientific knowledge gained through these detailed studies of pH1N1 is now being used to revise and update pandemic plans.
+The experiences of the research response in Hong Kong could provide a template for the research response to future emerging and reemerging disease epidemics.
+Microglia remain quiescent, unable to perform effector and antigen presentation (APC) functions until activated by injury or infection, and have been suggested to represent the first line of defence for the CNS.
+Previous studies demonstrated that microglia can be persistently infected by neurotropic mouse hepatitis virus (MHV) which causes meningoencephalitis, myelitis with subsequent axonal loss, and demyelination and serve as a virus-induced model of human neurological disease multiple sclerosis (MS).
+Current studies revealed that MHV infection is associated with the pronounced activation of microglia during acute inflammation, as evidenced by characteristic changes in cellular morphology and increased expression of microglia-specific proteins, Iba1 (ionized calcium-binding adaptor molecule 1), which is a macrophage/microglia-specific novel calcium-binding protein and involved in membrane ruffling and phagocytosis.
+Experiments performed in ex vivo spinal cord slice culture and in vitro neonatal microglial culture confirmed direct microglial infection.
+Our results suggest that MHV can directly infect and activate microglia during acute inflammation, which in turn during chronic inflammation stage causes phagocytosis of myelin sheath leading to chronic inflammatory demyelination.
+Infection with hepatitis C virus (HCV) is etiologically involved in liver cirrhosis, hepatocellular carcinoma and B-cell lymphomas.
+It has been demonstrated previously that HCV non-structural protein 3 (NS3) is involved in cell transformation.
+In this study, a yeast two-hybrid screening experiment was conducted to identify cellular proteins interacting with HCV NS3 protein.
+Binding domains of HCV NS3 and cellular cdN proteins were also determined using the yeast two-hybrid system.
+Interactions between HCV NS3 and cdN proteins were further demonstrated by co-immunoprecipitation and confocal analysis in cultured cells.
+The cellular cdN activity was partially repressed by NS3 protein in both the transiently-transfected and the stably-transfected systems.
+Furthermore, HCV partially repressed the cdN activity while had no effect on its protein expression in the systems of HCV sub-genomic replicons and infectious HCV virions.
+Deoxyribonucleotidases are present in most mammalian cells and involve in the regulation of intracellular deoxyribonucleotides pools by substrate cycles.
+Thus, our results suggested that HCV partially reduced the cdN activity via its NS3 protein and this may in turn cause diseases.
+The HIV-1 pandemic continues to expand while no effective vaccine or cure is yet available.
+Existing therapies have managed to limit mortality and control viral proliferation, but are associated with side effects, do not cure the disease and are subject to development of resistance.
+We have previously shown that the dendritic cell immunoreceptor (DCIR), a C-type lectin receptor expressed on dendritic cells (DCs), acts as an attachment factor for HIV-1 to DCs and contributes to HIV-1 transmission to CD4(+) T lymphocytes (CD4TL).
+Directly involved in HIV-1 infection, DCIR is expressed in apoptotic or infected CD4TL and promotes trans-infection to bystander cells.
+Based on this structure, two surface accessible pockets containing the carbohydrate recognition domain and the EPS binding motif, respectively, were targeted for screening of chemicals that will disrupt normal interaction with HIV-1 particle.
+Preliminary screening using Raji-CD4-DCIR cells allowed identification of two inhibitors that decreased HIV-1 attachment and propagation.
+The impact of these inhibitors on infection of DCs and CD4TL was evaluated as well.
+The results of this study thus identify novel molecules capable of blocking HIV-1 transmission by DCs and CD4TL.
+Acute lung injury is characterized by intense neutrophilic lung inflammation and increased alveolar-capillary barrier permeability leading to severe hypoxemia, and is associated with high mortality despite improvements in supportive care.
+Zhang and colleagues tested the efficacy of adipose-derived stem cells in acute lung injury in mice.
+When adipose-derived stem cells were delivered to mice that had been challenged with lipopolysaccharide, they potently limited acute lung inflammation and injury in the mice, indicating that adipose-derived stem cells have therapeutic potential in acute lung injury in humans.
+Herein, we discuss the advantages and potential limitations of using adipose-derived stem cells as therapeutics for human acute lung injury.
+State-of-the-art monoclonal antibody (mAb) discovery methods that utilize surface display techniques in prokaryotic and eukaryotic cells require multiple steps of reformatting and switching of hosts to transition from display to expression.
+Here, we report for the first time, a method in Glyco-engineered Pichia pastoris that enables simultaneous surface display and secretion of full-length mAb molecules with human-like N-glycans using the same yeast cell.
+This paradigm takes advantage of homo-dimerization of the Fc portion of an IgG molecule to a surface-anchored "bait" Fc, which results in targeting functional “half” IgGs to the cell wall of Pichia pastoris without interfering with the secretion of full length mAb.
+We show the utility of this method in isolating high affinity, well-expressed anti-PCSK9 leads from a designed library that was created by mating yeasts containing either light chain or heavy chain IgG libraries.
+Coupled with Glyco-engineered Pichia pastoris , this method provides a powerful tool for the discovery and production of therapeutic human mAbs in the same host thus improving drug developability and potentially shortening the discovery time cycle.
+It remains largely mysterious how the genomes of non-enveloped eukaryotic viruses are transferred across a membrane into the host cell.
+Picornaviruses are simple models for such viruses, and initiate this uncoating process through particle expansion, which reveals channels through which internal capsid proteins and the viral genome presumably exit the particle, although this has not been clearly seen until now.
+Here we present the atomic structure of an uncoating intermediate for the major human picornavirus pathogen CAV16, which reveals VP1 partly extruded from the capsid, poised to embed in the host membrane.
+Together with previous low-resolution results, we are able to propose a detailed hypothesis for the ordered egress of the internal proteins, using two distinct sets of channels through the capsid, and suggest a structural link to the condensed RNA within the particle, which may be involved in triggering RNA release.
+BACKGROUND: Over the past two decades, international health policies focusing on the fight against the human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS), tuberculosis (TB), malaria, and those diseases that address maternal and child health problems, among others, have skewed disease control priorities in China and other Asian countries.
+Although these are important health problems, an epidemic of chronic, non-communicable diseases (NCDs) in China has accounted for a much greater burden of disease due to the ongoing rapid socioeconomic and demographic transition.
+DISCUSSION: Although NCDs currently account for more than 80% of the overall disease burden in China, they remain very low on the nation’s disease control priorities, attracting marginal investment from central and local governments.
+International organizations and national governments have recognized the devastating social and economic consequences caused by NCDs in low- and middle-income countries, including China.
+Yet, few donor-funded projects that address NCDs have been implemented in these countries over the past decade.
+Due to a lack of strong support from international organizations and national governments for fighting against NCDs, affected persons in China, especially the poor and those who live in rural and less developed regions, continue to have limited access to the needed care.
+Costs associated with frequent health facility visits and regular treatment have become a major factor in medical impoverishment in China.
+This article argues that although China's ongoing health system reform would provide a unique opportunity to tackle current public health problems, it may not be sufficient to address the emerging threat of NCDs unless targeted steps are taken to assure that adequate financial and human resources are mapped for effective control and management of NCDs in the country.
+SUMMARY: The Chinese government needs to develop a domestically-driven and evidence-based disease control policy and funding priorities that respond appropriately to the country’s current epidemiological transition, and rapid sociodemographic and lifestyle changes.
+Defining immunogenic domains of viral proteins capable of eliciting a protective immune response is crucial in the development of novel epitope-based prophylactic strategies.
+This is particularly important for the selective targeting of conserved regions shared among hypervariable viruses.
+Studying postinfection and postimmunization sera, as well as cloning and characterization of monoclonal antibodies (mAbs), still represents the best approach to identify protective epitopes.
+In particular, a protective mAb directed against conserved regions can play a key role in immunogen design and in human therapy as well.
+Experimental approaches aiming to characterize protective mAb epitopes or to identify T-cell-activating peptides are often burdened by technical limitations and can require long time to be correctly addressed.
+These algorithms are continually evolving, and their use to address the empirical research is widely increasing.
+Here, we review several strategies based on experimental techniques alone or addressed by in silico analysis that are frequently used to predict immunogens to be included in novel epitope-based vaccine approaches.
+We will list the main strategies aiming to design a new vaccine preparation conferring the protection of a neutralizing mAb combined with an effective cell-mediated response.
+However, in immunocompromised patients, it can cause systemic infection accompanied by complications such as pneumonia, encephalitis, and hepatitis.
+Although most of critically ill patients in intensive care unit (ICU) are immunologically compromised, they are usually not considered to be at risk for systemic VZV infection.
+We report two cases of systemic VZV infection occurring in critically ill patients in an ICU.
+One patient was a 69-year-old man with Streptococcus pneumoniae-induced purpurafulminans, and the other was a 75-year-old woman with severe acute pancreatitis.
+During the clinical course in the ICU, characteristic vesicles with umbilical fossa appeared diffusely and bilaterally on their face, trunk, and extremities.
+VZV-specific IgG levels were confirmed to be elevated compared to that of the pre-onset, and a diagnosis of recurrent VZV infection was made in both patients.
+The patients were treated at the same ICU but did not coincide with each other; therefore a cross-infection was unlikely.
+They were treated with intravenous acyclovir, but the latter patient eventually died of respiratory failure.
+VZV infection can cause a number of serious complications, and can lead to death in some patients.
+Early detection and proper treatment are needed to prevent the infection from spreading out and save the patients.
+It might be necessary to consider antiviral prophylaxis against VZV infection for a part of critically ill patients in ICU, although the effectiveness of this approach is yet to be established.
+The threat of bioterrorism and the possibility of accidental release have spawned a growth of interest in modeling the course of the release of a highly pathogenic agent.
+Studies focused on strategies to contain local outbreaks after their detection show that timely interventions with vaccination and contact tracing are able to halt transmission.
+Using a large-scale structured metapopulation model to simulate the global spread of smallpox after an intentional release event, we show that index cases and potential outbreaks can occur in different continents even before the detection of the pathogen release.
+These results have two major implications: i) intentional release of a highly pathogenic agent within a country will have global effects; ii) the release event may trigger outbreaks in countries lacking the health infrastructure necessary for effective containment.
+The presented study provides data with potential uses in defining contingency plans at the National and International level.
+To meet this need, an active surveillance program was conducted at pig farms throughout the midwestern United States.
+From June 2009 through December 2011, nasal swab samples were collected monthly from among 540 groups of growing pigs and tested for influenza A virus by real-time reverse transcription PCR.
+Of 16,170 samples, 746 were positive for influenza A virus; of these, 18.0% were subtype H1N1, 16.0% H1N2, 7.6% H3N2, and 14.5% (H1N1)pdm09.
+This active influenza A virus surveillance program provided quality data and increased the understanding of the current situation of circulating viruses in the midwestern US pig population.
+A Rift Valley fever (RVF) epidemic affecting animals on domestic livestock farms was reported in South Africa during January–August 2010.
+To determine the possible effect of environmental conditions and vaccination on RVF virus transmissibility, we estimated the effective reproduction number (R(e)) for the virus over the course of the epidemic by extending the Wallinga and Teunis algorithm with spatial information.
+R(e) reached its highest value in mid-February and fell below unity around mid-March, when vaccination coverage was 7.5%–45.7% and vector-suitable environmental conditions were maintained.
+The epidemic fade-out likely resulted first from the immunization of animals following natural infection or vaccination.
+The decline in vector-suitable environmental conditions from April onwards and further vaccination helped maintain R(e) below unity.
+Increased availability of vaccine use data would enable evaluation of the effect of RVF vaccination campaigns.
+Our contemporary political order is, in part, characterized by sovereign states acting either in opposition or cooperation with other sovereign states.
+This order is also characterized by transnational efforts to address transnational issues such as those featured so prominently in the area of global health, such as the spread of infectious disease, health worker migration and the movement of health-harming products.
+DISCUSSION: National security has become the dominant ethical frame underlying the health-based foreign policy of many states, despite the transnational nature of many contemporary health challenges.
+Implicit in this ethical frame is the version of humanity that dichotomizes between “us” and “them”.
+What has been left out of this discourse, for the most part, is the role that foreign policy can play in extending the responsibility of states to protect and promote health of the other, for the sake of the other.
+SUMMARY: The principal purpose of this paper is to review arguments for a cosmopolitan ethics of health-based foreign policy.
+I will argue that health-based foreign policy that is motivated by security interests is lacking both morally and practically to further global health goals.
+In other words, a cosmopolitan ethic is not only intrinsically superior as a moral ideal, but also has potential to contribute to utilitarian ends.
+This paper draws on the cosmopolitanism literature to build robust support for foreign policies that contribute to sustainable systems of global health governance.
+Using 1723 prospectively collected serum samples in southern Vietnam, we tested for antibodies to 5 avian influenza virus antigens, using a protein microarray.
+General-population antibody titers against subtype H7 virus are higher than antibody titers against subtype H5 and lower than titers against H9.
+Titers to avian influenza virus antigens increased with age and with geometric mean antibody titer to human influenza virus antigens.
+There were no titer differences between the urban and the rural location in our study.
+Cryptococcus is an emerging global health threat that is annually responsible for over 1,000,000 infections and one third of all AIDS patient deaths.
+Cryptococcosis is a disease resulting from the inhalation of the infectious propagules from the environment.
+The current and most frequently used animal infection models initiate infection via liquid suspension through intranasal instillation or intravenous injection.
+These models do not replicate the typically dry nature of aerosol exposure and may hinder our ability to decipher the initial events that lead to clearance or the establishment of infection.
+We have established a standardized aerosol model of murine infection for the human fungal pathogen Cryptococcus.
+Aerosolized cells were generated utilizing a Collison nebulizer in a whole-body Madison Chamber at different humidity conditions.
+The aerosols inside the chamber were sampled using a BioSampler to determine viable aerosol concentration and spray factor (ratio of viable aerosol concentration to total inoculum concentration).
+We have effectively delivered yeast and yeast-spore mixtures to the lungs of mice and observed the establishment of disease.
+We observed that growth conditions prior to exposure and humidity within the Madison Chamber during exposure can alter Cryptococcus survival and dose retained in mice.
+A dynamic model incorporating social distancing can provide a mechanism to consider complex scenarios to support decisions regarding antiviral stockpile size while considering uncertainty around behavioural interventions.
+We have examined the impact of social distancing measures on the demand for limited healthcare resources such as antiviral drugs from a central stockpile during a severe pandemic.
+METHODS: We used an existing age-structured model for pandemic influenza in Canada and biologically plausible scenarios for severe influenza transmission within the population.
+We incorporated data from published reports regarding stated intentions to change behaviour during a pandemic as well as the magnitude and duration of time that individuals expected to maintain the behavioural change.
+We ran simulations for all combinations of parameter values to identify the projected antiviral requirements in each scenario.
+RESULTS: With 12 weeks of distancing, the effect is relatively small for the lowest R0 of 1.6 with a projected stockpile to treat 25.6% being required (IQR = 21.7 – 28.7%) unless the proportion of people involved (81%) and magnitude of the behaviour change is large (69% reduction in contacts).
+If 24 weeks of distancing occurs, with only a low to moderate reduction in contacts (38% or less), it is not possible to bring treatment requirements below 20% regardless of what proportion of the population engages in distancing measures when transmissibility is high (R0 = 2.0; stockpile size = 31%, IQR = 29.2 – 33.5%).
+CONCLUSIONS: Our results demonstrate that the magnitude and duration of social distancing behaviours during a severe pandemic have an impact on the need for antiviral drugs.
+However, significant investments over a long period of time (>16 weeks) are required to decrease the need for antiviral treatment to below 10% of the total population for a highly transmissible viral strain (R0 > 1.8).
+Encouraging individuals to adopt behaviours that decrease their daily contact rate can help to control the spread of the virus until a vaccine becomes available however; relying on these measures to justify stockpiling fewer courses of treatment will not be sufficient in the case of a severe pandemic.
+Recombinant antibodies are highly specific detection probes in research, diagnostics, and have emerged over the last two decades as the fastest growing class of therapeutic proteins.
+An increasing variety of recombinant production systems have been developed, ranging from Gram-negative and positive bacteria, yeasts and filamentous fungi, insect cell lines, mammalian cells to transgenic plants and animals.
+Currently, almost all therapeutic antibodies are still produced in mammalian cell lines in order to reduce the risk of immunogenicity due to altered, non-human glycosylation patterns.
+However, recent developments of glycosylation-engineered yeast, insect cell lines, and transgenic plants are promising to obtain antibodies with “human-like” post-translational modifications.
+Furthermore, smaller antibody fragments including bispecific antibodies without any glycosylation are successfully produced in bacteria and have advanced to clinical testing.
+The first therapeutic antibody products from a non-mammalian source can be expected in coming next years.
+In this review, we focus on current antibody production systems including their usability for different applications.
+Vaccines for protection against respiratory infections should optimally induce a mucosal immune response in the respiratory tract in addition to a systemic immune response.
+However, current parenteral immunization modalities generally fail to induce mucosal immunity, while mucosal vaccine delivery often results in poor systemic immunity.
+In order to find an immunization strategy which satisfies the need for induction of both mucosal and systemic immunity, we compared local and systemic immune responses elicited by two mucosal immunizations, given either by the intranasal (IN) or the intrapulmonary (IPL) route, with responses elicited by a mucosal prime followed by a systemic boost immunization.
+The study was conducted in BALB/c mice and the vaccine formulation was an influenza subunit vaccine supplemented with GPI-0100, a saponin-derived adjuvant.
+While optimal mucosal antibody titers were obtained after two intrapulmonary vaccinations, optimal systemic antibody responses were achieved by intranasal prime followed by intramuscular boost.
+The latter strategy also resulted in the best T cell response, yet, it was ineffective in inducing nose or lung IgA.
+Successful induction of secretory IgA, IgG and T cell responses was only achieved with prime-boost strategies involving intrapulmonary immunization and was optimal when both immunizations were given via the intrapulmonary route.
+Our results underline that immunization via the lungs is particularly effective for priming as well as boosting of local and systemic immune responses.
+Recognition of microorganisms by pattern-recognition receptors (PRRs) is the primary component of innate immunity that is responsible for the maintenance of host–microbial interactions in intestinal mucosa.
+Dysregulation in host–commensal interactions has been implicated as the central pathogenesis of inflammatory bowel disease (IBD), which predisposes to developing colorectal cancer.
+Recent animal studies have begun to outline some unique physiology and pathology involving each PRR signaling in the intestine.
+The major roles played by PRRs in the gut appear to be the regulation of the number and the composition of commensal bacteria, epithelial proliferation, and mucosal permeability in response to epithelial injury.
+In addition, PRR signaling in lamina propria immune cells may be involved in induction of inflammation in response to invasion of pathogens.
+Because some PRR-deficient mice have shown variable susceptibility to colitis, the outcome of intestinal inflammation may be modified depending on PRR signaling in epithelial cells, immune cells, and the composition of commensal flora.
+Through recent findings in animal models of IBD, this review will discuss how abnormal PRR signaling may contribute to the pathogenesis of inflammation and inflammation-associated tumorigenesis in the intestine.
+SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/mi.2013.13) contains supplementary material, which is available to authorized users.
+More than a decade into the 21(st) century, the ability to effectively monitor community health status, as well as forecast, detect, and respond to disease outbreaks and other events of public health significance, remains a major challenge.
+As an issue that affects population health, economic stability, and global security, the public health surveillance enterprise warrants the attention of decision makers at all levels.
+Public health practitioners responsible for surveillance functions are best positioned to identify the key elements needed for creating and maintaining effective and sustainable surveillance systems.
+This paper presents the recommendations of the Sustainable Surveillance Workgroup convened by the International Society for Disease Surveillance (ISDS) to identify strategies for building, strengthening, and maintaining surveillance systems that are equipped to provide data continuity and to handle both established and new data sources and public health surveillance practices.
+Japanese encephalitis virus (JEV) causes acute central nervous system (CNS) disease in humans, in whom the clinical symptoms vary from febrile illness to meningitis and encephalitis.
+In this study, using a mouse model, we investigated the pathogenetic mechanisms that correlate with fatal JEV infection.
+Following extraneural infection with the JaOArS982 strain of JEV, infected mice exhibited clinical signs ranging from mild to fatal outcome.
+Comparison of the pathogenetic response between severe and mild cases of JaOArS982-infected mice revealed increased levels of TNF-α in the brains of severe cases.
+However, unexpectedly, the mortality rate of TNF-α KO mice was significantly increased compared with that of WT mice, indicating that TNF-α plays a protective role against fatal infection.
+Interestingly, there were no significant differences of viral load in the CNS between WT and TNF-α KO mice.
+Although these observations were also obtained in IL-10 KO mice, the mortality and enhanced inflammatory responses were more pronounced in TNF-α KO mice.
+Our findings therefore provide the first evidence that TNF-α has an immunoregulatory effect on pro-inflammatory cytokines in the CNS during JEV infection and consequently protects the animals from fatal disease.
+Thus, we propose that the increased level of TNF-α in severe cases was the result of severe disease, and secondly that immunopathological effects contribute to severe neuronal degeneration resulting in fatal disease.
+In future, further elucidation of the immunoregulatory mechanism of TNF-α will be an important priority to enable the development of effective treatment strategies for Japanese encephalitis.
+Targeting papain family cysteine proteases is one of the novel strategies in the development of chemotherapy for a number of diseases.
+Novel cysteine protease inhibitors derived from 1-pyridylimidazo[1,5-a]pyridine representing pharmacologically important class of compounds are being reported here for the first time.
+The derivatives were initially designed and screened in silico by molecular docking studies against papain to explore the possible mode of action.
+The molecular interaction between the compounds and cysteine protease (papain) was found to be very similar to the interactions observed with the respective epoxide inhibitor (E-64c) of papain.
+When characterized kinetically, these compounds show their K(i) and IC(50) values in the range of 13.75 to 99.30 µM and 13.40 to 96.50 µM, respectively.
+These inhibitors also inhibit the growth of clinically important different types of Gram positive and Gram negative bacteria having MIC(50) values in the range of 0.6–1.4 µg/ml.
+Based on Lipinski’s rule of Five, we also propose these compounds as potent antibacterial prodrugs.
+BACKGROUND: Estimates of parameters for disease transmission in large-scale infectious disease outbreaks are often obtained to represent large groups of people, providing an average over a potentially very diverse area.
+For control measures to be more effective, a measure of the heterogeneity of the parameters is desirable.
+METHODS: We propose a novel extension of a network-based approach to estimating the reproductive number.
+We apply this to the 2009 Influenza pandemic in South Africa to understand the spatial variability across provinces.
+We explore the use of five similarity matrices to illustrate their impact on the subsequent epidemic parameter estimates.
+RESULTS: When treating South Africa as a single entity with homogeneous transmission characteristics across the country, the basic reproductive number, R(0), (and imputation range) is 1.33 (1.31, 1.36).
+When fitting a new model for each province with no inter-province connections this estimate varies little (1.23-1.37).
+Using the proposed method with any of the four similarity measures yields an overall R(0) that varies little across the four new models (1.33 to 1.34).
+However, when allowed to vary across provinces, the estimated R(0) is greater than one consistently in only two of the nine provinces, the most densely populated provinces of Gauteng and Western Cape.
+CONCLUSIONS: Our results suggest that the spatial heterogeneity of influenza transmission was compelling in South Africa during the 2009 pandemic.
+While the cause of this fluctuation might be partially due to reporting differences, there is substantial evidence to warrant further investigation.
+One hundred and eighty febrile patients were analyzed in a prospective evaluation of Orientia tsutsugamushi and Rickettsia spp.
+By paired serology, 3.9% (7 of 180) and 6.1% (11 of 180) of patients were confirmed to have acute scrub or murine typhus, respectively.
+had high specificity (99.4% [95% confidence interval (CI): 96.8–100] and 100% [95% CI: 97.8–100], respectively).
+The PCR results were also compared with immunoglobulin M (IgM) immunofluorescence assay (IFA) on acute sera.
+For O. tsutsugamushi, PCR sensitivity was twice that of acute specimen IgM IFA (28.6% versus 14.3%; McNemar's P = 0.3).
+For Rickettsia spp., PCR was four times as sensitive as acute specimen IgM IFA (36.4% versus 9.1%; P = 0.08), although this was not statistically significant.
+Respiratory syncytial virus (RSV) is an important cause of respiratory tract disease in infants and the elderly.
+Here we describe the development of a safe and effective intranasal subunit vaccine that is based on recombinant fusion (F) protein bound to the surface of immunostimulatory bacterium-like particles (BLPs) derived from the food-grade bacterium Lactococcus lactis.
+Different variants of F were analyzed with respect to their conformation and reactivity with neutralizing antibodies, assuming that F proteins mimicking the metastable prefusion form of RSV F expose a more extensive and relevant epitope repertoire than F proteins corresponding to the postfusion structure.
+Our results indicate that the recombinant soluble ectodomain of RSV F readily adopts a postfusion conformation, generation of which cannot be prevented by C-terminal addition of a trimerization motif, but whose formation is prevented by mutation of the two furin cleavage sites in F. While the putative postfusion form of F is recognized well by the monoclonal antibody Palivizumab, this is much less so for the more potently neutralizing, prefusion-specific antibodies D25 and AM22.
+Both addition of the trimerization motif and mutation of the furin cleavage sites increased the reactivity of F with D25 and AM22, with the highest reactivity being observed for F proteins in which both these features were combined.
+Intranasal vaccination of mice or cotton rats with BLPs loaded with this latter prefusion-like F protein (BLP-F), resulted in the potent induction of F-specific immunoglobulins and in significantly decreased virus titers in the lungs upon RSV challenge.
+Moreover, and in contrast to animals vaccinated with formalin-inactivated RSV, animals that received BLP-F exhibited high levels of F-specific secretory IgA in the nose and RSV-neutralizing antibodies in sera, but did not show symptoms of enhanced disease after challenge with RSV.
+BACKGROUND: Timely information about disease severity can be central to the detection and management of outbreaks of acute respiratory infections (ARI), including influenza.
+We asked if two resources: 1) free text, and 2) structured data from an electronic medical record (EMR) could complement each other to identify patients with pneumonia, an ARI severity landmark.
+METHODS: A manual EMR review of 2747 outpatient ARI visits with associated chest imaging identified x-ray reports that could support the diagnosis of pneumonia (kappa score = 0.88 (95% CI 0.82∶0.93)), along with attendant cases with Possible Pneumonia (adds either cough, sputum, fever/chills/night sweats, dyspnea or pleuritic chest pain) or with Pneumonia-in-Plan (adds pneumonia stated as a likely diagnosis by the provider).
+The x-ray reports served as a reference to develop a text classifier using machine-learning software that did not require custom coding.
+To identify pneumonia cases, the classifier was combined with EMR-based structured data and with text analyses aimed at ARI symptoms in clinical notes.
+The x-ray report text classifier increased the positive predictive value of otherwise identical EMR-based case-detection algorithms by 20–70%, while retaining sensitivities of 58–75%.
+These performance gains were independent of the case definitions and of whether patients were admitted to the hospital or sent home.
+CONCLUSION: Specialized software development is not required for automated text analyses to help identify pneumonia patients.
+These results begin to map an efficient, replicable strategy through which EMR data can be used to stratify ARI severity.
+Turnip yellow mosaic virus (TYMV) - a member of the alphavirus-like supergroup of viruses - serves as a model system for positive-stranded RNA virus membrane-bound replication.
+TYMV encodes a precursor replication polyprotein that is processed by the endoproteolytic activity of its internal cysteine proteinase domain (PRO).
+We recently reported that PRO is actually a multifunctional enzyme with a specific ubiquitin hydrolase (DUB) activity that contributes to viral infectivity.
+Strikingly, PRO displays no homology to other processing proteinases from positive-stranded RNA viruses, including that of alphaviruses.
+Instead, the closest structural homologs of PRO are DUBs from the Ovarian tumor (OTU) family.
+In the crystal, one molecule's C-terminus inserts into the catalytic cleft of the next, providing a view of the N-terminal product complex in replication polyprotein processing.
+In addition to the catalytic cleft, at the exit of which the active site is unusually pared down and solvent-exposed, a key element in molecular recognition by PRO is a lobe N-terminal to the catalytic domain.
+Docking models and the activities of PRO and PRO mutants in a deubiquitylating assay suggest that this N-terminal lobe is also likely involved in PRO's DUB function.
+Our data thus establish that DUBs can evolve to specifically hydrolyze both iso- and endopeptide bonds with different sequences.
+This is achieved by the use of multiple specificity determinants, as recognition of substrate patches distant from the cleavage sites allows a relaxed specificity of PRO at the sites themselves.
+Our results thus shed light on how such a compact protein achieves a diversity of key functions in viral genome replication and host-pathogen interaction.
+The design of optimized nanoparticles offers a promising strategy to enable DNA vaccines to cross various physiological barriers for eliciting a specific and protective mucosal immunity via intranasal administration.
+Here, we reported a new designed nanoparticle system through incorporating anionic liposomes (AL) into chitosan/DNA (CS/DNA) complexes.
+With enhanced cellular uptake, the constructed AL/CS/DNA nanoparticles can deliver the anti-caries DNA vaccine pGJA-P/VAX into nasal mucosa.
+High DNA loading ability and effective DNA protection against nuclease were proved by gel electrophoresis.
+The surface charge of the AL/CS/DNA depended strongly on pH environment, enabling the intracellular release of loaded DNA via a pH-mediated manner.
+In comparison to the traditional CS/DNA system, our new design rendered a higher transfection efficiency and longer residence time of the AL/CS/DNA at nasal mucosal surface.
+These outstanding features enable the AL/CS/DNA to induce a significantly (p<0.01) higher level of secretory IgA (SIgA) than the CS/DNA in animal study, and a longer-term mucosal immunity.
+These results suggest that the developed nanoparticles offer a potential platform for DNA vaccine packaging and delivery for more efficient elicitation of mucosal immunity.
+Human rhinoviruses (HRVs) frequently cause mild upper respiratory tract infections and more severe disease manifestations such as bronchiolitis and asthma exacerbations.
+HRV species A and B contain 75 and 25 serotypes identified by cross-neutralization assays, although the use of such assays for routine HRV typing is hampered by the large number of serotypes, replacement of virus isolation by molecular methods in HRV diagnosis and the poor or absent replication of HRV species C in cell culture.
+To address these problems, we propose an alternative, genotypic classification of HRV-based genetic relatedness analogous to that used for enteroviruses.
+Nucleotide distances between 384 complete VP1 sequences of currently assigned HRV (sero)types identified divergence thresholds of 13, 12 and 13 % for species A, B and C, respectively, that divided inter- and intra-type comparisons.
+These were paralleled by 10, 9.5 and 10 % thresholds in the larger dataset of >3800 VP4 region sequences.
+Assignments based on VP1 sequences led to minor revisions of existing type designations (such as the reclassification of serotype pairs, e.g.
+A8/A95 and A29/A44, as single serotypes) and the designation of new HRV types A101–106, B101–103 and C34–C51.
+A protocol for assignment and numbering of new HRV types using VP1 sequences and the restriction of VP4 sequence comparisons to type identification and provisional type assignments is proposed.
+Genotypic assignment and identification of HRV types will be of considerable value in the future investigation of type-associated differences in disease outcomes, transmission and epidemiology.
+BACKGROUND: Penicillium marneffei is the most important thermal dimorphic fungus causing systemic mycosis in China and Southeast Asia.
+While miRNAs are increasingly recognized for their roles in post-transcriptional regulation of gene expression in animals and plants, miRNAs in fungi were less well studied and their potential roles in fungal dimorphism were largely unknown.
+Based on P. marneffei genome sequence, we hypothesize that miRNA-like RNAs (milRNAs) may be expressed in the dimorphic fungus.
+METHODOLOGY/PRINCIPAL FINDINGS: We attempted to identify milRNAs in P. marneffei in both mycelial and yeast phase using high-throughput sequencing technology.
+Sequence analysis revealed 24 potential milRNA candidates, including 17 candidates in mycelial and seven in yeast phase.
+Two genes, dcl-1 and dcl-2, encoding putative Dicer-like proteins and the gene, qde-2, encoding Argonaute-like protein, were identified in P. marneffei.
+Phylogenetic analysis showed that dcl-2 of P. marneffei was more closely related to the homologues in other thermal dimorphic pathogenic fungi than to Penicillium chrysogenum and Aspergillus spp., suggesting the co-evolution of dcl-2 among the thermal dimorphic fungi.
+Moreover, dcl-2 demonstrated higher mRNA expression levels in mycelial than yeast phase by 7 folds (P<0.001).
+Northern blot analysis confirmed the expression of two milRNAs, PM-milR-M1 and PM-milR-M2, only in mycelial phase.
+Using dcl-1(KO), dcl-2(KO), dcl(DKO) and qde-2(KO) deletion mutants, we showed that the biogenesis of both milRNAs were dependent on dcl-2 but not dcl-1 or qde-2.
+The mRNA expression levels of three predicted targets of PM-milR-M1 were upregulated in knockdown strain PM-milR-M1 (KD), supporting regulatory function of milRNAs.
+CONCLUSIONS/SIGNIFICANCE: Our findings provided the first evidence for differential expression of milRNAs in different growth phases of thermal dimorphic fungi and shed light on the evolution of fungal proteins involved in milRNA biogenesis and possible role of post-transcriptional control in governing thermal dimorphism.
+BACKGROUND: Necrotizing pneumonia attributed to Panton-Valentine leukocidin-positive Staphylococcus aureus has mainly been reported in otherwise healthy children and young adults, with a high mortality rate.
+The objectives of this study were to define the characteristics of patients with severe leukopenia at 48-h hospitalization and to update our data regarding mortality predicting factors in a larger population than we had previously described.
+The following data were collected: basic demographic information, medical history, signs and symptoms, radiological findings and laboratory results during the first 48 h of hospitalization.
+The study population was divided into 2 groups: (1) with severe leukopenia (leukocyte count ≤3,000 leukocytes/mL, n=62) and (2) without severe leukopenia (>3,000 leukocytes/mL, n=86).
+Death occurred in 75.8% of severe leukopenia cases with median survival time of 4 days, and in 16.3% of cases with leukocyte count >3,000/mL (P<0.001).
+Multivariate analysis indicated that the factors associated with severe leukopenia were influenza-like illness (adjusted odds ratio (aOR) 4.45, 95% CI (95% confidence interval) 1.67-11.88, P=0.003), airway bleeding (aOR 4.53, 95% CI 1.85-11.13, P=0.001) and age over 30 years (aOR 2.69, 95% CI 1.08-6.68, P=0.033).
+A personal history of furuncles appeared to be protective (OR 0.11, 95% CI 0.01-0.96, P=0.046).
+CONCLUSION: S. aureus-necrotizing pneumonia is still an extremely severe disease in patients with severe leukopenia.
+Some factors could distinguish these patients, allowing better initial identification to initiate adapted, rapid administration of appropriate therapy.
+BACKGROUND: The current study was conducted to establish animal models (including mouse and ferret) for the novel avian-origin H7N9 influenza virus.
+FINDINGS: A/Anhui/1/2013 (H7N9) virus was administered by intranasal instillation to groups of mice and ferrets, and animals developed typical clinical signs including body weight loss (mice and ferrets), ruffled fur (mice), sneezing (ferrets), and death (mice).
+Virus could also be detected in brain, liver, spleen, kidney, and intestine from inoculated mice, and in heart, liver, and olfactory bulb from inoculated ferrets.
+The inoculation of H7N9 could elicit seroconversion titers up to 1280 in ferrets and 160 in mice.
+Leukopenia, significantly reduced lymphocytes but increased neutrophils were also observed in mouse and ferret models.
+CONCLUSIONS: The mouse and ferret model enables detailed studies of the pathogenesis of this illness and lay the foundation for drug or vaccine evaluation.
+The noble gas helium has many applications owing to its distinct physical and chemical characteristics, namely: its low density, low solubility, and high thermal conductivity.
+Chiefly, the abundance of studies in medicine relating to helium are concentrated in its possibility of being used as an adjunct therapy in a number of respiratory ailments such as asthma exacerbation, COPD, ARDS, croup, and bronchiolitis.
+Helium gas, once believed to be biologically inert, has been recently shown to be beneficial in protecting the myocardium from ischemia by various mechanisms.
+Though neuroprotection of brain tissue has been documented, the mechanism by which it does so has yet to be made clear.
+Surgeons are exploring using helium instead of carbon dioxide to insufflate the abdomen of patients undergoing laparoscopic abdominal procedures due to its superiority in preventing respiratory acidosis in patients with comorbid conditions that cause carbon dioxide retention.
+Newly discovered applications in Pulmonary MRI radiology and imaging of organs in very fine detail using Helium Ion Microscopy has opened exciting new possibilities for the use of helium gas in technologically advanced fields of medicine.
+Understanding these processes at the molecular level requires homogeneous RNA samples for structural, biochemical and pharmacological studies.
+We previously devised a generic approach that allows efficient in vivo expression of recombinant RNA in Escherichia coli.
+We have investigated the potential of these tools in many applications, including the production of nuclease-sensitive RNAs encapsulated in viral protein pseudo-particles, the co-production of non-coding RNAs with chaperone proteins, the incorporation of a post-transcriptional RNA modification by co-production with the appropriate modifying enzyme and finally the production and purification of an RNA–His-tagged protein complex by nickel affinity chromatography.
+The new tools we report will pave the way to large-scale structural and molecular investigations of RNA function and interactions with proteins.
+Early diagnosis and management of influenza virus infection directly correlates with the effectiveness in disease control.
+Current molecular influenza virus tests were designed for use in diagnostic testing facilities, where sophisticated equipment and highly trained technicians are available.
+A longer turnaround time for the centralized testing than when testing near the sample source could delay the initiation of medical intervention, thereby reducing the efficacy of antiviral treatment.
+The new assay, the SAMBA (simple amplification-based assay) Flu duplex test, is a dipstick-based molecular assay developed to provide a simple, accurate, and cost-effective solution for the diagnosis of influenza A/B viruses intended for near-patient testing.
+The test presents an alternative format of influenza virus molecular testing that utilizes isothermal amplification and visual detection of nucleic acid on a test strip.
+The entire test procedure (extraction, amplification, and detection) is integrated into an enclosed semiautomated system.
+Analytically, the SAMBA Flu duplex test detects 95 and 85 copies of viral genomes for influenza A and B viruses, respectively, with no cross-reactivity observed against other common respiratory pathogens.
+The clinical performance was established by blind testing of 328 nasal/throat and nasopharyngeal swab specimens from the United Kingdom and Belgium and comparing the results with the quantitative reverse transcription-PCR method routinely used in two public health laboratories.
+The SAMBA Flu duplex test showed a clinical sensitivity and specificity of 100% and 97.9% for influenza virus A and 100% and 100% for influenza virus B.
+The test provides a new technology that could facilitate simple and timely identification of influenza virus infection, potentially resulting in more efficient control measures.
+Involved in many diseases such as cancer, diabetes, neurodegenerative, inflammatory and respiratory disorders, G-protein-coupled receptors (GPCRs) are among the most frequent targets of therapeutic drugs.
+It is time-consuming and expensive to determine whether a drug and a GPCR are to interact with each other in a cellular network purely by means of experimental techniques.
+Although some computational methods were developed in this regard based on the knowledge of the 3D (dimensional) structure of protein, unfortunately their usage is quite limited because the 3D structures for most GPCRs are still unknown.
+To overcome the situation, a sequence-based classifier, called “iGPCR-drug”, was developed to predict the interactions between GPCRs and drugs in cellular networking.
+In the predictor, the drug compound is formulated by a 2D (dimensional) fingerprint via a 256D vector, GPCR by the PseAAC (pseudo amino acid composition) generated with the grey model theory, and the prediction engine is operated by the fuzzy K-nearest neighbour algorithm.
+For the convenience of most experimental scientists, a step-by-step guide is provided on how to use the web-server to get the desired results without the need to follow the complicated math equations presented in this paper just for its integrity.
+The overall success rate achieved by iGPCR-drug via the jackknife test was 85.5%, which is remarkably higher than the rate by the existing peer method developed in 2010 although no web server was ever established for it.
+It is anticipated that iGPCR-Drug may become a useful high throughput tool for both basic research and drug development, and that the approach presented here can also be extended to study other drug – target interaction networks.
+Covalent post-translational modification of proteins by ubiquitin and ubiquitin-like factors has emerged as a general mechanism to regulate myriad intra-cellular processes.
+The addition and removal of ubiquitin or ubiquitin-like proteins from factors has recently been demonstrated as a key mechanism to modulate DNA damage response (DDR) pathways.
+It is thus, timely to evaluate the potential for ubiquitin pathway enzymes as DDR drug targets for therapeutic intervention.
+The synthetic lethal approach provides exciting opportunities for the development of targeted therapies to treat cancer: most tumours have lost critical DDR pathways, and thus rely more heavily on the remaining pathways, while normal tissues are still equipped with all DDR pathways.
+Here, we review key deubiquitylating enzymes (DUBs) involved in DDR pathways, and describe how targeting DUBs may lead to selective therapies to treat cancer patients.
+The clinical serial interval of an infectious disease is the time between date of symptom onset in an index case and the date of symptom onset in one of its secondary cases.
+It is a quantity which is commonly collected during a pandemic and is of fundamental importance to public health policy and mathematical modelling.
+In this paper we present a novel method for calculating the serial interval distribution for a Markovian model of household transmission dynamics.
+This allows the use of Bayesian MCMC methods, with explicit evaluation of the likelihood, to fit to serial interval data and infer parameters of the underlying model.
+We use simulated and real data to verify the accuracy of our methodology and illustrate the importance of accounting for household size.
+The output of our approach can be used to produce posterior distributions of population level epidemic characteristics.
+Cancer therapy has been characterized throughout history by ups and downs, not only due to the ineffectiveness of treatments and side effects, but also by hope and the reality of complete remission and cure in many cases.
+Within the therapeutic arsenal, alongside surgery in the case of solid tumors, are the antitumor drugs and radiation that have been the treatment of choice in some instances.
+In recent years, immunotherapy has become an important therapeutic alternative, and is now the first choice in many cases.
+Nanotechnology has recently arrived on the scene, offering nanostructures as new therapeutic alternatives for controlled drug delivery, for combining imaging and treatment, applying hyperthermia, and providing directed target therapy, among others.
+These therapies can be applied either alone or in combination with other components (antibodies, peptides, folic acid, etc.).
+Here, we present a review of the evolution of cancer treatments, starting with chemotherapy, surgery, radiation and immunotherapy, and moving on to the most promising cutting-edge therapies (gene therapy and nanomedicine).
+We offer an historical point of view that covers the arrival of these therapies to clinical practice and the market, and the promises and challenges they present.
+Flow cytometry-based analysis of lymphocyte division using carboxyfluorescein succinimidyl ester (CFSE) dye dilution permits acquisition of data describing cellular proliferation and differentiation.
+For example, CFSE histogram data enable quantitative insight into cellular turnover rates by applying mathematical models and parameter estimation techniques.
+However, analysis of CFSE proliferation assays is based on the premise that the label is halved in the two daughter cells.
+Importantly, asymmetry of protein distribution in lymphocyte division is a basic biological feature of cell division with the degree of the asymmetry depending on various factors.
+Here, we review the recent literature on asymmetric lymphocyte division and CFSE-based lymphocyte proliferation analysis.
+We suggest that division- and label-structured mathematical models describing CFSE-based cell proliferation should take into account asymmetry and time-lag in cell proliferation.
+Utilization of improved modeling algorithms will permit straightforward quantification of essential parameters describing the performance of activated lymphocytes.
+Viral particles were enriched from the feces of 51 wild urban pigeons (Columba livia) from Hong Kong and Hungary, their nucleic acids randomly amplified and then sequenced.
+We identified sequences from known and novel species from the viral families Circoviridae, Parvoviridae, Picornaviridae, Reoviridae, Adenovirus, Astroviridae, and Caliciviridae (listed in decreasing number of reads), as well as plant and insect viruses likely originating from consumed food.
+The near full genome of a new species of a proposed parvovirus genus provisionally called Aviparvovirus contained an unusually long middle ORF showing weak similarity to an ORF of unknown function from a fowl adenovirus.
+Picornaviruses found in both Asia and Europe that are distantly related to the turkey megrivirus and contained a highly divergent 2A1 region were named mesiviruses.
+All eleven segments of a novel rotavirus subgroup related to a chicken rotavirus in group G were sequenced and phylogenetically analyzed.
+This study provides an initial assessment of the enteric virome in the droppings of pigeons, a feral urban species with frequent human contact.
+Background: Only recently has the environment been clearly implicated in the risk of antibiotic resistance to clinical outcome, but to date there have been few documented approaches to formally assess these risks.
+Objective: We examined possible approaches and sought to identify research needs to enable human health risk assessments (HHRA) that focus on the role of the environment in the failure of antibiotic treatment caused by antibiotic-resistant pathogens.
+Methods: The authors participated in a workshop held 4–8 March 2012 in Québec, Canada, to define the scope and objectives of an environmental assessment of antibiotic-resistance risks to human health.
+We focused on key elements of environmental-resistance-development “hot spots,” exposure assessment (unrelated to food), and dose response to characterize risks that may improve antibiotic-resistance management options.
+Discussion: Various novel aspects to traditional risk assessments were identified to enable an assessment of environmental antibiotic resistance.
+These include a) accounting for an added selective pressure on the environmental resistome that, over time, allows for development of antibiotic-resistant bacteria (ARB); b) identifying and describing rates of horizontal gene transfer (HGT) in the relevant environmental “hot spot” compartments; and c) modifying traditional dose–response approaches to address doses of ARB for various health outcomes and pathways.
+Conclusions: We propose that environmental aspects of antibiotic-resistance development be included in the processes of any HHRA addressing ARB.
+Because of limited available data, a multicriteria decision analysis approach would be a useful way to undertake an HHRA of environmental antibiotic resistance that informs risk managers.
+Citation: Ashbolt NJ, Amézquita A, Backhaus T, Borriello P, Brandt KK, Collignon P, Coors A, Finley R, Gaze WH, Heberer T, Lawrence JR, Larsson DG, McEwen SA, Ryan JJ, Schönfeld J, Silley P, Snape JR, Van den Eede C, Topp E. 2013.
+The ongoing decline of honey bee health worldwide is a serious economic and ecological concern.
+However, information is limited on the biology of bee viruses and molecular interactions with their hosts.
+An experimental protocol to test these systems was developed, using injections of Israeli Acute Paralysis Virus (IAPV) into honey bee pupae reared ex-situ under laboratory conditions.
+Symptoms varied from complete cessation of development with no visual evidence of disease to rapid darkening of a part or the entire body.
+Considerable differences in IAPV titer dynamics were observed, suggesting significant variation in resistance to IAPV among and possibly within honey bee colonies.
+Gene expression analyses of three separate experiments suggest IAPV disruption of transcriptional homeostasis of several fundamental cellular functions, including an up-regulation of the ribosomal biogenesis pathway.
+They mirror a transcriptional survey of honey bees afflicted with Colony Collapse Disorder and thus support the hypothesis that viruses play a critical role in declining honey bee health.
+HRVs and other members of the HEV genus share many common features, including sense RNA genomes and partial nucleotide sequence identity.
+Samples from adults with acute respiratory infection (n = 291) who were treated in Sao Paulo Hospital (2001-2003) were tested using three assays.
+The first assay detected picornaviruses by RT-PCR and hybridization, the second detected rhinoviruses using RT-PCR/sequencing, and the third differentiated HRV from HEV using duplex semi-nested-RT-PCR.
+The picornavirus detection protocol was more sensitive but less specific than the rhinovirus detection protocols.
+The semi-nested protocol utilized in the present study was less sensitive and was not useful in differentiating HRV from HEV.
+Sequencing assays examining different genes would address the best strategy of confirming rhinovirus and enterovirus infections.
+Feline calicivirus (FCV) and feline herpesvirus type 1 (FHV-1) are the two primary causes of upper respiratory tract disease in cats.
+The aim of this study was to demonstrate the distribution of FCV and FHV-1 among the feline population of several counties in Rio Grande do Sul State, Brazil.
+To this end, conjunctival and nasal swabs were collected from 302 cats from different locations, including households, breeding catteries, veterinary clinics, animal hospitals and experimental research facilities.
+The virus isolation was performed in CRFK cells and, subsequently, the identification was confirmed by PCR.
+FCV alone was isolated from 52.7% (29/55) of the animals that tested positively, FHV-1 alone was isolated from 38.2% (21/55) of the animals that tested positively, and co-infection were detected in 9.1% (5/55) of the animals that tested positively.
+Virus detection was more prevalent in cats that were less than 1 year old, among animals that shared a living space with other cats, and females.
+The results suggest that a carrier state is common for both viruses in the evaluated population.
+A search for other causes of respiratory disease in that population is necessary; and further studies relating to the molecular characterization of viruses and vaccine efficacy are also necessary.
+Viruses are the major cause of lower respiratory tract infections in childhood and the main viruses involved are Human Respiratory Syncytial Virus (HRSV), Human Metapneumovirus (HMPV), Influenzavirus A and B (FLUA and FLUB), Human Parainfluenza Virus 1, 2 and 3 (HPIV1, 2 and 3) and Human Rhinovirus (HRV).
+The purposes of this study were to detect respiratory viruses in hospitalized children younger than six years and identify the influence of temperature and relative air humidity on the detected viruses.
+HRSV was detected in 29% (79/272) of the samples; HRV in 23.1% (63/272); HPIV3 in 5.1% (14/272); HMPV in 3.3% (9/272); HPIV1 in 2.9% (8/272); FLUB in 1.4% (4/272), FLUA in 1.1% (3/272), and HPIV2 in 0.3% (1/272).
+The highest detection rates occurred mainly in the spring 2004 and in the autumn 2005.
+It was observed that viral respiratory infections tend to increase as the relative air humidity decreases, showing significant association with monthly averages of minimal temperature and minimal relative air humidity.
+In conclusion, viral respiratory infections vary according to temperature and relative air humidity and viral respiratory infections present major incidences it coldest and driest periods.
+BACKGROUND: Contacts between patients, patients and health care workers (HCWs) and among HCWs represent one of the important routes of transmission of hospital-acquired infections (HAI).
+A detailed description and quantification of contacts in hospitals provides key information for HAIs epidemiology and for the design and validation of control measures.
+METHODS AND FINDINGS: We used wearable sensors to detect close-range interactions (“contacts”) between individuals in the geriatric unit of a university hospital.
+Contact events were measured with a spatial resolution of about 1.5 meters and a temporal resolution of 20 seconds.
+The study included 46 HCWs and 29 patients and lasted for 4 days and 4 nights.
+The number and duration of contacts varied between mornings, afternoons and nights, and contact matrices describing the mixing patterns between HCW and patients were built for each time period.
+38% of the contacts occurred between pairs of HCWs and 6 HCWs accounted for 42% of all the contacts including at least one patient, suggesting a population of individuals who could potentially act as super-spreaders.
+CONCLUSIONS: Wearable sensors represent a novel tool for the measurement of contact patterns in hospitals.
+The collected data can provide information on important aspects that impact the spreading patterns of infectious diseases, such as the strong heterogeneity of contact numbers and durations across individuals, the variability in the number of contacts during a day, and the fraction of repeated contacts across days.
+This variability is however associated with a marked statistical stability of contact and mixing patterns across days.
+Our results highlight the need for such measurement efforts in order to correctly inform mathematical models of HAIs and use them to inform the design and evaluation of prevention strategies.
+Lassa virus (LASV) is the causative agent of Lassa Fever and is responsible for several hundred thousand infections and thousands of deaths annually in West Africa.
+A live attenuated reassortant of MOPV and LASV, designated ML29, protects rodents and primates from LASV challenge and appears to be more attenuated than MOPV.
+To gain better insight into LASV-induced pathology and mechanism of attenuation we performed gene expression profiling in human peripheral blood mononuclear cells (PBMC) exposed to LASV and the vaccine candidate ML29.
+Although most PBMC are non-permissive for virus replication, they remain susceptible to signal transduction by virus particles.
+Total RNA was extracted and global gene expression was evaluated during the first 24 hours using high-density microarrays.
+LASV and ML29 elicited differential expression of interferon-stimulated genes (ISG), as well as genes involved in apoptosis, NF-kB signaling and the coagulation pathways.
+The remarkable differential expression of thrombomodulin, a key regulator of inflammation and coagulation, suggests its involvement with vascular abnormalities and mortality in Lassa fever disease.
+The mosquito-borne alphavirus, chikungunya virus (CHIKV), has recently reemerged, producing the largest epidemic ever recorded for this virus, with up to 6.5 million cases of acute and chronic rheumatic disease.
+There are currently no licensed vaccines for CHIKV and current anti-inflammatory drug treatment is often inadequate.
+Here we describe the isolation and characterization of two human monoclonal antibodies, C9 and E8, from CHIKV infected and recovered individuals.
+C9 was determined to be a potent virus neutralizing antibody and a biosensor antibody binding study demonstrated it recognized residues on intact CHIKV VLPs.
+Shotgun mutagenesis alanine scanning of 98 percent of the residues in the E1 and E2 glycoproteins of CHIKV envelope showed that the epitope bound by C9 included amino-acid 162 in the acid-sensitive region (ASR) of the CHIKV E2 glycoprotein.
+The ASR is critical for the rearrangement of CHIKV E2 during fusion and viral entry into host cells, and we predict that C9 prevents these events from occurring.
+When used prophylactically in a CHIKV mouse model, C9 completely protected against CHIKV viremia and arthritis.
+We also observed that when administered therapeutically at 8 or 18 hours post-CHIKV challenge, C9 gave 100% protection in a pathogenic mouse model.
+Given that targeting this novel neutralizing epitope in E2 can potently protect both in vitro and in vivo, it is likely to be an important region both for future antibody and vaccine-based interventions against CHIKV.
+Although, the IL-33 levels increased in sera of viral hepatitis patients in human, the cellular sources of IL-33 in viral hepatitis remained obscure.
+Therefore, we aimed to investigate the expression of IL-33 in murine fulminant hepatitis induced by a Toll like receptor (TLR3) viral mimetic, poly(I:C) or by pathogenic mouse hepatitis virus (L2-MHV3).
+The administration of poly(I:C) plus D-galactosamine (D-GalN) in mice led to acute liver injury associated with the induction of IL-33 expression in liver sinusoidal endothelial cells (LSEC) and vascular endothelial cells (VEC), while the administration of poly(I:C) alone led to hepatocyte specific IL-33 expression in addition to vascular IL-33 expression.
+The hepatocyte-specific IL-33 expression was down-regulated in NK-depleted poly(I:C) treated mice suggesting a partial regulation of IL-33 by NK cells.
+The CD1d KO (NKT deficient) mice showed hepatoprotection against poly(I:C)-induced hepatitis in association with increased number of IL-33 expressing hepatocytes in CD1d KO mice than WT controls.
+These results suggest that hepatocyte-specific IL-33 expression in poly(I:C) induced liver injury was partially dependent of NK cells and with limited role of NKT cells.
+In parallel, the L2-MHV3 infection in mice induced fulminant hepatitis associated with up-regulated IL-33 expression as well as pro-inflammatory cytokine microenvironment in liver.
+The LSEC and VEC expressed inducible expression of IL-33 following L2-MHV3 infection but the hepatocyte-specific IL-33 expression was only evident between 24 to 32h of post infection.
+In conclusion, the alarmin cytokine IL-33 was over-expressed during fulminant hepatitis in mice with LSEC, VEC and hepatocytes as potential sources of IL-33.
+OBJECTIVE: The present study aimed to analyze clinical features and factors associated with treatment outcomes of H7N9 influenza A virus infection.
+The clinical features of H7N9 infection were noted and factors associated with treatment outcomes were analyzed by univariate analyses.
+RESULTS: The average ages of patients in recovered and critical conditions were 67.0±10.83 years and 72.75±12.0 years, respectively.
+The duration of traditional Chinese medicine (TCM) therapy was longer in recovered patients than in critically ill patients (P = 0.01).
+Laboratory tests showed that levels of C-reactive protein, serum creatinine, and myoglobin were significantly higher in critically ill patients than in recovered patients (P = 0.011, 0.04, and 0.016, respectively).
+Meanwhile, levels of all T cell subsets examined including total CD3(+), CD4(+), CD8(+), and CD45(+) T cells were lower in critically ill patients than in recovered patients (P = 0.033, 0.059, 0.015, and 0.039, respectively).
+Logistic regression analysis demonstrated that C-reactive protein level, myoglobin level and TCM therapy duration were likely associated with treatment outcomes of H7N9 infection (P = 0.032, 0.041 and 0.017, respectively).
+C-reactive protein level, myoglobin level and TCM duration may be associated with treatment outcomes of H7N9 infection.
+INTRODUCTION: There was a growing need for practical guidelines for the most common OIs in Germany and Austria under consideration of the local epidemiological conditions.
+MATERIALS AND METHODS: The German and Austrian AIDS societies developed these guidelines between March 2010 and November 2011.
+A structured Medline research was performed for 12 diseases, namely Immune reconstitution inflammatory syndrome, Pneumocystis jiroveci pneumonia, cerebral toxoplasmosis, cytomegalovirus manifestations, candidiasis, herpes simplex virus infections, varizella zoster virus infections, progressive multifocal leucencephalopathy, cryptosporidiosis, cryptococcosis, nontuberculosis mycobacteria infections and tuberculosis.
+Due to the lack of evidence by randomized controlled trials, part of the guidelines reflects expert opinions.
+The German version was accepted by the German and Austrian AIDS Societies and was previously published by the Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften (AWMF; German Association of the Scientific Medical Societies).
+CONCLUSION: The review presented here is a translation of a short version of the German–Austrian Guidelines of opportunistic infections in HIV patients.
+They lead to a similar treatment of a heterogeneous group of patients in these countries.
+Recently, one of the interferon-induced transmembrane (IFITM) family proteins, IFITM3, has become an important target for the activity against influenza A (H1N1) virus infection.
+In this protein, a post-translational modification by fatty acids covalently attached to cysteine, termed S-palmitoylation, plays a crucial role for the antiviral activity.
+IFITM3 possesses three cysteine residues for the S-palmitoylation in the first transmembrane (TM1) domain and in the cytoplasmic (CP) loop.
+Because these cysteines are well conserved in the mammalian IFITM family proteins, the S-palmitoylation on these cysteines is significant for their functions.
+IFITM5 is another IFITM family protein and interacts with the FK506-binding protein 11 (FKBP11) to form a higher-order complex in osteoblast cells, which induces the expression of immunologically relevant genes.
+In this study, we investigated the role played by S-palmitoylation of IFITM5 in its interaction with FKBP11 in the cells, because this interaction is a key process for the gene expression.
+Our investigations using an established reporter, 17-octadecynoic acid (17-ODYA), and an inhibitor for the S-palmitoylation, 2-bromopalmitic acid (2BP), revealed that IFITM5 was S-palmitoylated in addition to IFITM3.
+Specifically, we found that cysteine residues in the TM1 domain and in the CP loop were S-palmitoylated in IFITM5.
+Then, we revealed by immunoprecipitation and western blot analyses that the interaction of IFITM5 with FKBP11 was inhibited in the presence of 2BP.
+The mutant lacking the S-palmitoylation site in the TM1 domain lost the interaction with FKBP11.
+Finally, we investigated bone nodule formation in osteoblast cells in the presence of 2BP, because IFITM5 was originally identified as a bone formation factor.
+Recent reports indicate that the replication of hepatitis C virus (HCV) depends on the GBF1-Arf1-COP-I pathway.
+We generated Huh-7-derived cell lines resistant to brefeldin A (BFA), which is an inhibitor of this pathway.
+The resistant cell lines could be sorted into two phenotypes regarding BFA-induced toxicity, inhibition of albumin secretion, and inhibition of HCV infection.
+Two cell lines were more than 100 times more resistant to BFA than the parental Huh-7 cells in these 3 assays.
+This resistant phenotype was correlated with the presence of a point mutation in the Sec7 domain of GBF1, which is known to impair the binding of BFA.
+Surprisingly, the morphology of the cis-Golgi of these cells remained sensitive to BFA at concentrations of the drug that allowed albumin secretion, indicating a dichotomy between the phenotypes of secretion and Golgi morphology.
+Cells of the second group were about 10 times more resistant than parental Huh-7 cells to the BFA-induced toxicity.
+The EC(50) for albumin secretion was only 1.5–1.8 fold higher in these cells than in Huh-7 cells.
+However their level of secretion in the presence of inhibitory doses of BFA was 5 to 15 times higher.
+Despite this partially effective secretory pathway in the presence of BFA, the HCV infection was almost as sensitive to BFA as in Huh-7 cells.
+This suggests that the function of GBF1 in HCV replication does not simply reflect its role of regulator of the secretory pathway of the host cell.
+Thus, our results confirm the involvement of GBF1 in HCV replication, and suggest that GBF1 might fulfill another function, in addition to the regulation of the secretory pathway, during HCV replication.
+Progeny particles of non-enveloped lytic parvoviruses were previously shown to be actively transported to the cell periphery through vesicles in a gelsolin-dependent manner.
+This process involves rearrangement and destruction of actin filaments, while microtubules become protected throughout the infection.
+Here the focus is on the intracellular egress pathway, as well as its impact on the properties and release of progeny virions.
+By colocalization with cellular marker proteins and specific modulation of the pathways through over-expression of variant effector genes transduced by recombinant adeno-associated virus vectors, we show that progeny PV particles become engulfed into COPII-vesicles in the endoplasmic reticulum (ER) and are transported through the Golgi to the plasma membrane.
+Besides known factors like sar1, sec24, rab1, the ERM family proteins, radixin and moesin play (an) essential role(s) in the formation/loading and targeting of virus-containing COPII-vesicles.
+These proteins also contribute to the transport through ER and Golgi of the well described analogue of cellular proteins, the secreted Gaussia luciferase in absence of virus infection.
+It is therefore likely that radixin and moesin also serve for a more general function in cellular exocytosis.
+Finally, parvovirus egress via ER and Golgi appears to be necessary for virions to gain full infectivity through post-assembly modifications (e.g.
+While not being absolutely required for cytolysis and progeny virus release, vesicular transport of parvoviruses through ER and Golgi significantly accelerates these processes pointing to a regulatory role of this transport pathway.
+In the model fungus Podospora anserina, the PaYIP3 gene encoding the orthologue of the Saccharomyces cerevisiae YIP3 Rab-GDI complex dissociation factor expresses two polypeptides, one of which, the long form, is produced through a programmed translation frameshift.
+Inactivation of PaYIP3 results in slightly delayed growth associated with modification in repartition of fruiting body on the thallus, along with reduced ascospore production on wood.
+Long and short forms of PaYIP3 are expressed in the mycelium, while only the short form appears expressed in the maturing fruiting body (perithecium).
+The frameshift has been conserved over the evolution of the Pezizomycotina, lasting for over 400 million years, suggesting that it has an important role in the wild.
+AIMS: To determine the role of CD13 as an adhesion molecule in trafficking of inflammatory cells to the site of injury in vivo and its function in wound healing following myocardial infarction induced by permanent coronary artery occlusion.
+METHODS AND RESULTS: Seven days post-permanent ligation, hearts from CD13 knockout (CD13(KO)) mice showed significant reductions in cardiac function, suggesting impaired healing in the absence of CD13.
+Mechanistically, CD13(KO) infarcts showed an increase in small, endothelial-lined luminal structures, but no increase in perfusion, arguing against an angiogenic defect in the absence of CD13.
+Cardiac myocytes of CD13(KO) mice showed normal basal contractile function, eliminating myocyte dysfunction as a mechanism of adverse remodelling.
+Conversely, immunohistochemical and flow cytometric analysis of CD13(KO) infarcts demonstrated a dramatic 65% reduction in infiltrating haematopoietic cells, including monocytes, macrophages, dendritic, and T cells, suggesting a critical role for CD13 adhesion in inflammatory trafficking.
+Accordingly, CD13(KO) infarcts also contained fewer myofibroblasts, consistent with attenuation of fibroblast differentiation resulting from the reduced inflammation, leading to adverse remodelling.
+CONCLUSION: In the ischaemic heart, while compensatory mechanisms apparently relieve potential angiogenic defects, CD13 is essential for proper trafficking of the inflammatory cells necessary to prime and sustain the reparative response, thus promoting optimal post-infarction healing.
+Multiple sclerosis (MS) is an inflammatory demyelinating disease of the human central nervous system (CNS).
+Neurotropic demyelinating strain of MHV (MHV-A59 or its isogenic recombinant strain RSA59) induces MS-like disease in mice mediated by microglia, along with a small population of T cells.
+The mechanism of demyelination is at least in part due to microglia-mediated myelin stripping, with some direct axonal injury.
+Immunization with myelin oligodendrocyte glycoprotein (MOG) induces experimental autoimmune encephalomyelitis (EAE), a mainly CD4(+) T-cell-mediated disease, although CD8(+) T cells may play a significant role in demyelination.
+It is possible that both autoimmune and nonimmune mechanisms such as direct viral toxicity may induce MS. Our study directly compares CNS pathology in autoimmune and viral-induced MS models.
+Mice with viral-induced and EAE demyelinating diseases demonstrated similar patterns and distributions of demyelination that accumulated over the course of the disease.
+Inflammation was restricted mainly to white matter at all times in EAE, whereas inflammation initially largely involved gray matter in acute MHV-induced disease and then is subsequently localized only in white matter in the chronic disease phase.
+The presence of dual mechanisms of demyelination may be responsible for the failure of immunosuppression to promote long-term remission in many MS patients.
+Although the canine transferrin receptor (TfR) was identified as a receptor for CPV infection, whether extracellular domain of TfR (called soluble TfR (sTfR)) possesses anti-CPV activities remains elusive.
+Here, we used the recombinant sTfR prepared from HEK293T cells with codon-optimized gene structure to investigate its anti-CPV activity both in vitro and in vivo.
+The prepared recombinant sTfR possessed a binding activity to both CPV and CPV VP2 capsid proteins and significantly inhibited CPV infection of cultured feline F81 cells and decreased the mortality of CPV-infected dogs, which indicates that the sTfR has the anti-CPV activity both in vitro and in vivo.
+Infection is normally confined to the upper respiratory tract but certain viral strains have evolved the ability to infect the lower respiratory tract, including the alveoli, leading to inflammation and a disease pattern of diffuse alveolar damage.
+Factors leading to this sequence of events are novel influenza strains, or strains that have viral proteins, in particular the NS1 protein that allow it to escape the innate immune system.
+There are three main barriers that prevent infection of pneumocytes - mucin, host defence lectins and cells such as macrophages.
+Though there has been much investment in antiviral drugs, it is proposed that more attention should be directed towards developing or utilizing compounds that enhance the ability of the innate immune system to combat viral infection.
+Influenza vaccines that target the highly variable surface glycoproteins hemagglutinin and neuraminidase cause inconvenience of having vaccination every year.
+In this study, we generated recombinant adenovirus (rAd) vaccine encoding nucleoprotein (NP) of A/PR/8/34 influenza virus, designated rAd/NP.
+BALB/c mice were immunized intranasally or sublingually with rAd/NP vaccine and subsequently challenged with lethal doses of heterologous as well as homologous influenza viruses.
+We found that intranasal immunization of rAd/NP elicited strong mucosal IgA responses as well as stronger CD8 T-cell responses toward immunodominant K(d)-restricted NP(147-155) epitope than sublingual immunization.
+Importantly, only single intranasal but not sublingual immunization of rAd/NP provides potent protection against both homologous and heterologous influenza virus challenges.
+These results suggest that recombinant rAd/NP could be a universal vaccine candidate for mucosal administration against influenza virus.
+BACKGROUND: The ribosomal RNA content of a sample collected from a woman with bacterial vaginosis (BV) was analysed to determine the active microbial community, and to identify potential targets for further screening.
+METHODOLOGY/PRINCIPAL FINDINGS: The sample from the BV patient underwent total RNA extraction, followed by physical subtraction of human rRNA and whole transcriptome amplification.
+Bacteria of the genus Prevotella (predominately P. amnii) constituted 36% of the 16S rRNA reads, followed by Megasphaera (19%), Leptotrichia/Sneathia (8%) and Fusobacterium (8%).
+Comparison of the abundances of several bacteria to quantitative PCR (qPCR) screening of extracted DNA revealed comparable relative abundances.
+This suggests a correlation between what was present and transcriptionally active in this sample: however distinct differences were seen when compared to the microbiome determined by 16S rRNA gene amplicon sequencing.
+To assess the presence of P. amnii in a larger pool of samples, 90 sexually active women were screened using qPCR.
+This bacterium was found to be strongly associated with BV (P<0.001, OR 23.3 (95%CI:2.9–190.7)) among the 90 women.
+CONCLUSIONS/SIGNIFICANCE: This study highlighted the potential of metatranscriptomics as a tool for characterising metabolically active microbiota and identifying targets for further screening.
+Prevotella amnii was chosen as an example target, being the most metabolically active species present in the single patient with BV, and was found to be detected at a high concentration by qPCR in 31% of cohort with BV, with an association with both oral and penile-vaginal sex.
+This paper is concerned with the modeling of infectious disease spread in a composite space-time domain under conditions of uncertainty.
+We focus on stochastic modeling that accounts for basic mechanisms of disease distribution and multi-sourced in situ uncertainties.
+Starting from the general formulation of population migration dynamics and the specification of transmission and recovery rates, the model studies the functional formulation of the evolution of the fractions of susceptible-infected-recovered individuals.
+The suggested approach is capable of: a) modeling population dynamics within and across localities, b) integrating the disease representation (i.e.
+susceptible-infected-recovered individuals) with observation time series at different geographical locations and other sources of information (e.g.
+hard and soft data, empirical relationships, secondary information), and c) generating predictions of disease spread and associated parameters in real time, while considering model and observation uncertainties.
+Molecular docking remains an important tool for structure-based screening to find new ligands and chemical probes.
+As docking ambitions grow to include new scoring function terms, and to address ever more targets, the reliability and extendability of the orientation sampling, and the throughput of the method, become pressing.
+Here we explore sampling techniques that eliminate stochastic behavior in DOCK3.6, allowing us to optimize the method for regularly variable sampling of orientations.
+This also enabled a focused effort to optimize the code for efficiency, with a three-fold increase in the speed of the program.
+This, in turn, facilitated extensive testing of the method on the 102 targets, 22,805 ligands and 1,411,214 decoys of the Directory of Useful Decoys - Enhanced (DUD-E) benchmarking set, at multiple levels of sampling.
+Encouragingly, we observe that as sampling increases from 50 to 500 to 2000 to 5000 to 20000 molecular orientations in the binding site (and so from about 1×10(10) to 4×10(10) to 1×10(11) to 2×10(11) to 5×10(11) mean atoms scored per target, since multiple conformations are sampled per orientation), the enrichment of ligands over decoys monotonically increases for most DUD-E targets.
+Meanwhile, including internal electrostatics in the evaluation ligand conformational energies, and restricting aromatic hydroxyls to low energy rotamers, further improved enrichment values.
+Several of the strategies used here to improve the efficiency of the code are broadly applicable in the field.
+Intrinsically disordered proteins (IDPs) were found to be widely associated with human diseases and may serve as potential drug design targets.
+Progress in drug design is usually achieved using experimental screening; however, the structural disorder of IDPs makes it difficult to characterize their interaction with ligands using experiments alone.
+To better understand the structure of IDPs and their interactions with small molecule ligands, we performed extensive simulations on the c-Myc(370–409) peptide and its binding to a reported small molecule inhibitor, ligand 10074-A4.
+We found that the conformational space of the apo c-Myc(370–409) peptide was rather dispersed and that the conformations of the peptide were stabilized mainly by charge interactions and hydrogen bonds.
+The ligand was found to bind to c-Myc(370–409) at different sites along the chain and behaved like a ‘ligand cloud’.
+In contrast to ligand binding to more rigid target proteins that usually results in a dominant bound structure, ligand binding to IDPs may better be described as ligand clouds around protein clouds.
+Nevertheless, the binding of the ligand and a non-ligand to the c-Myc(370–409) target could be clearly distinguished.
+The present study provides insights that will help improve rational drug design that targets IDPs.
+Cellular restriction factors, which render cells intrinsically resistant to viruses, potentially impose genetic barriers to cross-species transmission and emergence of viral pathogens in nature.
+To overcome APOBEC3G-mediated restriction, many lentiviruses encode Vif, a protein that targets APOBEC3G for degradation.
+This is interpreted as evidence that the primate APOBEC3G locus reflects a long-term evolutionary “arms-race” between retroviruses and their primate hosts.
+Here, we provide direct evidence that APOBEC3G has functioned as a barrier to cross-species transmission, selecting for viral resistance during emergence of the AIDS-causing pathogen SIVmac in captive colonies of Asian macaques in the 1970s.
+Specifically, we found that rhesus macaques have multiple, functionally distinct APOBEC3G alleles, and that emergence of SIVmac and simian AIDS required adaptation of the virus to evade APOBEC3G-mediated restriction.
+Our evidence includes the first comparative analysis of APOBEC3G polymorphism and function in both a reservoir and recipient host species (sooty mangabeys and rhesus macaques, respectively), and identification of adaptations unique to Vif proteins of the SIVmac lineage that specifically antagonize rhesus APOBEC3G alleles.
+By demonstrating that interspecies variation in a known restriction factor selected for viral counter-adaptations in the context of a documented case of cross-species transmission, our results lend strong support to the evolutionary “arms-race” hypothesis.
+Importantly, our study confirms that APOBEC3G divergence can be a critical determinant of interspecies transmission and emergence of primate lentiviruses, including viruses with the potential to infect and spread in human populations.
+Since 1997, several epizootic avian influenza viruses (AIVs) have been transmitted to humans, causing diseases and even deaths.
+The recent emergence of severe human infections with AIV (H7N9) in China has raised concerns about efficient interpersonal viral transmission, polygenic traits in viral pathogenicity and the management of newly emerging strains.
+The symptoms associated with viral infection are different in various AI strains: H5N1 and newly emerged H7N9 induce severe pneumonia and related complications in patients, while some H7 and H9 subtypes cause only conjunctivitis or mild respiratory symptoms.
+The virulence and tissue tropism of viruses as well as the host responses contribute to the pathogenesis of human AIV infection.
+Several preventive and therapeutic approaches have been proposed to combat AIV infection, including antiviral drugs such as M2 inhibitors, neuraminidase inhibitors, RNA polymerase inhibitors, attachment inhibitors and signal-transduction inhibitors etc.
+In this article, we summarize the recent progress in researches on the epidemiology, clinical features, pathogenicity determinants, and available or potential antivirals of AIV.
+The nature of influenza virus to randomly mutate and evolve into new types is an important challenge in the control of influenza infection.
+It is necessary to monitor virus evolution for a better understanding of the pandemic risk posed by certain variants as evidenced by the highly pathogenic avian influenza (HPAI) viruses.
+This has been clearly recognized in Egypt following the notification of the first HPAI H5N1 outbreak.
+The continuous circulation of the virus and the mass vaccination programme undertaken in poultry have resulted in a progressive genetic evolution and a significant antigenic drift near the major antigenic sites.
+In order to establish if vaccination is sufficient to provide significant intra- and interclade cross-protection, lentiviral pseudotypes derived from H5N1 HPAI viruses (A/Vietnam/1194/04, A/chicken/Egypt-1709-01/2007) and an antigenic drift variant (A/chicken/Egypt-1709-06-2008) were constructed and used in pseudotype-based neutralization assays (pp-NT).
+A panel of pseudotypes belonging to influenza Groups 1 and 2, with a combination of reporter systems, was also employed for testing avian sera in order to support further application of pp-NT as an alternative valid assay that can improve avian vaccination efficacy testing, vaccine virus selection, and the reliability of reference sera.
+APMV-1 (also called Newcastle disease virus, NDV) is attenuated in non-human primates and is being developed as a candidate human vaccine vector.
+In the present study, we evaluated nine different biologically- or recombinantly-derived APMV strains for the ability to replicate and cause disease in rhesus macaque model.
+Five of the viruses were: biologically-derived wild type (wt) APMV-2, -3, -5, -7 and -9.
+The remaining three viruses were versions of wt rAPMV-2, -4 and -7 in which the F cleavage site had been modified to be multi-basic.
+Rhesus macaques were inoculated intranasally and intratracheally and monitored for clinical disease, virus shedding from the upper and lower respiratory tract, and seroconversion.
+Very limited shedding was detected for wt rAPMV-4 and modified rAPMV-4, and only in a subset of animals.
+Shedding by the other viruses was detected in every infected animal, and usually from both the upper and lower respiratory tract.
+In particular, shedding over a number of days in every animal was observed for modified rAPMV-2, wt APMV-7, and modified rAPMV-7.
+Modification of the F protein cleavage site appeared to increase shedding by wt rAPMV-2 and marginally by wt rAPMV-4.
+All APMVs except wt APMV-5 induced a virus-specific serum antibody response in all infected animals.
+These results indicate that APMVs 2, 3, 4, 7, and 9 are competent to infect non-human primates, but are moderately-to-highly restricted, depending on the serotype.
+This suggests that they are not likely to significantly infect primates in nature, and represent promising attenuated candidates for vector development.
+The cellular entry of viruses represents a critical area of study, not only for viral tropism, but also because viral entry dictates the nature of the immune response elicited upon infection.
+Epidemic keratoconjunctivitis (EKC), caused by viruses within human adenovirus species D (HAdV-D), is a severe, ocular surface infection associated with corneal inflammation.
+Clathrin-mediated endocytosis has previously been shown to play a critical role in entry of other HAdV species into many host cell types.
+Herein, we show an essential role for cholesterol rich, lipid raft microdomains and caveolin-1, in the entry of HAdV-D37 into primary human corneal fibroblasts.
+When replenished with soluble cholesterol, the effect of MβCD was reversed, allowing productive viral infection.
+Src kinase activity was also increased in caveolin-1 rich endosomal fractions after infection, and Src phosphorylation and CXCL1 induction were both decreased in caveolin-1-/- mice corneas compared to wild type mice.
+siRNA knock down of caveolin-1 in corneal cells reduced chemokine induction upon viral infection, and caveolin-1-/- mouse corneas showed reduced cellular entry of HAdV-D37.
+As a control, HAdV-C2, a non-corneal pathogen, appeared to utilize the caveolar pathway for entry into A549 cells, but failed to infect corneal cells entirely, indicating virus and cell specific tropism.
+Immuno-electron microscopy confirmed the presence of caveolin-1 in HAdV-D37-containing vesicles during the earliest stages of viral entry.
+Collectively, these experiments indicate for the first time that HAdV-D37 uses a lipid raft mediated caveolin-1 associated pathway for entry into corneal cells, and connects the processes of viral entry with downstream proinflammatory cell signaling.
+Secondary infections with Streptococcus pneumoniae (SP) are frequently observed following influenza A virus (IAV) infection and have a substantial impact on global health.
+To investigate the effect of co-infection on human monocyte-derived dendritic cells (MDDCs) we analysed the expression of clinically important pro-inflammatory and immune-modulatory cytokines.
+IAV infection or treatment with supernatants from IAV-infected cell cultures resulted in priming of the DCs which subsequently influenced the production of IL-12p70, as well as IL-6, following SP infection.
+Co-infection of the same cell was not required but this effect was dependent on the time, dose and duration of the infections, as well as pathogen viability, bacterial uptake and endosome acidification.
+Finally, we showed that type I interferons were primarily responsible for the priming of IL-12p70 that was observed by infection with IAV.
+These results provide a probable mechanism for the elevated levels of particular cytokines observed in IAV and SP co-infected cell cultures with implications for the pathogenic outcome observed during in vivo infection.
+West Nile virus (WNV) appeared in the U.S. in 1999 and has since become endemic, with yearly summer epidemics causing tens of thousands of cases of serious disease over the past 14 years.
+Analysis of WNV strains isolated during the 2006–2007 epidemic seasons demonstrates that a new genetic variant had emerged coincidentally with an intense outbreak in Idaho during 2006.
+The isolates belonging to the new variant carry a 13 nt deletion, termed ID-Δ13, located at the variable region of the 3′UTR, and are genetically related.
+The analysis of deletions and insertions in the 3′UTR of two major lineages of WNV revealed the presence of conserved repeats and two indel motifs in the variable region of the 3′UTR.
+One human and two bird isolates from the Idaho 2006–2007 outbreaks were sequenced using Illumina technology and within-host variability was analyzed.
+Continued monitoring of new genetic variants is important for public health as WNV continues to evolve.
+Two types of Canine Adenovirus (CAVs), Canine Adenovirus type 1 (CAV-1), the virus which causes infectious canine hepatitis, and Canine Adenovirus type 2 (CAV-2), which causes canine infectious laryngotracheitis, have been found in dogs.
+In this study, blood samples taken from 111 dogs, which were admitted to the Internal Medicine Clinic of Selcuk University, Faculty of Veterinary Medicine, with clinical symptoms.
+Seventy-seven dogs were sampled from Isparta and Burdur dog shelters by random sampling, regardless of the clinical findings.
+Dogs showed a systemic disease, characterized by fever, diarrhea, vomiting, oculonasal discharge, conjunctivitis, severe moist cough, signs of pulmonary disease and dehydration.
+In serological studies, 188 serum samples were investigated on the presence of CAV antibodies by ELISA.
+Total 103 (103/188–54.7%) blood samples were detected to be positive for CAV antibodies by ELISA.
+Blood leukocyte samples from dogs were processed and inoculated onto confluent monolayers of MDCK cells using standard virological techniques.
+In an effort to circumvent resistance to rapamycin – an mTOR inhibitor - we searched for novel rapamycin-downstream-targets that may be key players in the response of cancer cells to therapy.
+We found that rapamycin, at nM concentrations, increased phosphorylation of eukaryotic initiation factor (eIF) 2α in rapamycin-sensitive and estrogen-dependent MCF-7 cells, but had only a minimal effect on eIF2α phosphorylation in the rapamycin-insensitive triple-negative MDA-MB-231 cells.
+Addition of salubrinal – an inhibitor of eIF2α dephosphorylation – decreased expression of a surface marker associated with capacity for self renewal, increased senescence and induced clonogenic cell death, suggesting that excessive phosphorylation of eIF2α is detrimental to the cells' survival.
+Treating cells with salubrinal enhanced radiation-induced increase in eIF2α phosphorylation and clonogenic death and showed that irradiated cells are more sensitive to increased eIF2α phosphorylation than non-irradiated ones.
+Similar to salubrinal - the phosphomimetic eIF2α variant - S51D - increased sensitivity to radiation, and both abrogated radiation-induced increase in breast cancer type 1 susceptibility gene, thus implicating enhanced phosphorylation of eIF2α in modulation of DNA repair.
+Indeed, salubrinal inhibited non-homologous end joining as well as homologous recombination repair of double strand breaks that were induced by I-SceI in green fluorescent protein reporter plasmids.
+In addition to its effect on radiation, salubrinal enhanced eIF2α phosphorylation and clonogenic death in response to the histone deacetylase inhibitor – vorinostat.
+Finally, the catalytic competitive inhibitor of mTOR - Ku-0063794 - increased phosphorylation of eIF2α demonstrating further the involvement of mTOR activity in modulating eIF2α phosphorylation.
+These experiments suggest that excessive phosphorylation of eIF2α decreases survival of cancer cells; making eIF2α a worthy target for drug development, with the potential to enhance the cytotoxic effects of established anti-neoplastic therapies and circumvent resistance to rapalogues and possibly to other drugs that inhibit upstream components of the mTOR pathway.
+BACKGROUND: Tracing persons who have been in contact with an infectious patient may be very effective in preventing the spread of communicable diseases.
+We have investigated the available evidence for contact tracing with a focus on public ground transport aiming to give guidance in what situations contact tracing should be considered.
+METHODS: Relevant infectious diseases suitable for contact tracing in ground transport and a set of disease-specific epidemiological criteria were defined through literature search and structured multistep expert consultations.
+We developed continuous scales for each criterion to be rated for its relevance to contact tracing in ground transport.
+We used the Delphi method with an international expert panel to position the values of criteria on the respective scales.
+RESULTS: The study led to the development of the ‘Contact Tracing-Risk Assessment Profile’ (CT-RAP), a decision-making instrument, taking into account pathogen-specific as well as situation-specific criteria.
+This report describes the methodology of this instrument and presents two examples of ready-to-use CT-RAP for tuberculosis and for meningococcal disease in public ground transport.
+DISCUSSION: The systematic and transparent use of the CT-RAP for tuberculosis and meningococcal disease is likely to facilitate reasonable, efficient and user-friendly decisions with respect to contact tracing.
+New CT-RAPs for additional pathogens and different settings such as schools and kindergartens are being planned.
+Recent gain-of-function studies in influenza A virus H5N1 strains revealed that as few as three amino-acid changes in the hemagglutinin protein confer the capacity for viral transmission between ferrets(1, 2).
+As transmission between ferrets is considered a surrogate indicator of transmissibility between humans, these studies raised concerns about the risks of gain-of-function influenza A virus research.
+In particular, we found that the microRNA miR-192 was expressed in primary human respiratory tract epithelial cells as well as mouse lungs but absent from the ferret respiratory tract.
+Incorporation of miR-192 target sites into influenza A virus did not prevent influenza replication and transmissibility in ferrets, but did attenuate influenza pathogenicity in mice.
+This molecular biocontainment approach should be applicable beyond influenza A virus to minimize the risk of experiments involving other pathogenic viruses.
+Although the first isolates were from Nigeria and other Congo basin countries, all reports over the past 20 years have been from southern Africa.
+Previous phylogenetic studies analyzed few isolates or used partial gene sequence for analysis since limited sequence information is available for MOKV and the isolates were distributed among various laboratories.
+The complete nucleoprotein, phosphoprotein, matrix and glycoprotein genes of 18 MOKV isolates in various laboratories were sequenced either using partial or full genome sequencing using pyrosequencing and a phylogenetic analysis was undertaken.
+The results indicated that MOKV isolates from the Republic of South Africa, Zimbabwe, Central African Republic and Nigeria clustered according to geographic origin irrespective of the genes used for phylogenetic analysis, similar to that observed with Lagos bat virus.
+A Bayesian Markov-Chain-Monte-Carlo- (MCMC) analysis revealed the age of the most recent common ancestor (MRCA) of MOKV to be between 279 and 2034 years depending on the genes used.
+Generally, all MOKV isolates showed a similar pattern at the amino acid sites considered influential for viral properties.
+BACKGROUND: No attention has been paid on comparing a set of genome sequences crossing genetic components and biological categories with far divergence over large size range.
+RESULTS: First, we create a method, GenomeFingerprinter, to unambiguously produce a set of three-dimensional coordinates from a sequence, followed by one three-dimensional plot and six two-dimensional trajectory projections, to illustrate the genome fingerprint of a given genome sequence.
+Second, we develop a set of concepts and tools, and thereby establish a method called the universal genome fingerprint analysis (UGFA).
+Particularly, we define the total genetic component configuration (TGCC) (including chromosome, plasmid, and phage) for describing a strain as a systematic unit, the universal genome fingerprint map (UGFM) of TGCC for differentiating strains as a universal system, and the systematic comparative genomics (SCG) for comparing a set of genomes crossing genetic components and biological categories.
+Third, we construct a method of quantitative analysis to compare two genomes by using the outcome dataset of genome fingerprint analysis.
+Specifically, we define the geometric center and its geometric mean for a given genome fingerprint map, followed by the Euclidean distance, the differentiate rate, and the weighted differentiate rate to quantitatively describe the difference between two genomes of comparison.
+Moreover, we demonstrate the applications through case studies on various genome sequences, giving tremendous insights into the critical issues in microbial genomics and taxonomy.
+CONCLUSIONS: We have created a method, GenomeFingerprinter, for rapidly computing, geometrically visualizing, intuitively comparing a set of genomes at genome fingerprint level, and hence established a method called the universal genome fingerprint analysis, as well as developed a method of quantitative analysis of the outcome dataset.
+These have set up the methodology of systematic comparative genomics based on the genome fingerprint analysis.
+The innate immune response to viruses is initiated when specialized cellular sensors recognize viral danger signals.
+Here we show that truncated forms of viral genomes that accumulate in infected cells potently trigger the sustained activation of the transcription factors IRF3 and NF-κB and the production type I IFNs through a mechanism independent of IFN signaling.
+We demonstrate that these defective viral genomes (DVGs) are generated naturally during respiratory infections in vivo even in mice lacking the type I IFN receptor, and their appearance coincides with the production of cytokines during infections with Sendai virus (SeV) or influenza virus.
+Remarkably, the hallmark antiviral cytokine IFNβ is only expressed in lung epithelial cells containing DVGs, while cells within the lung that contain standard viral genomes alone do not express this cytokine.
+Together, our data indicate that DVGs generated during viral replication are a primary source of danger signals for the initiation of the host immune response to infection.
+Chikungunya virus (CHIKV) is a mosquito-borne arthrogenic alphavirus that causes acute febrile illness in humans accompanied by joint pains and in many cases, persistent arthralgia lasting weeks to years.
+The re-emergence of CHIKV has resulted in numerous outbreaks in the eastern hemisphere, and threatens to expand in the foreseeable future.
+The present study reports the use of resazurin in a cell-based high-throughput assay, and an image-based high-content assay to identify and characterize inhibitors of CHIKV-infection in vitro.
+Thus, cell viability of HuH-7 cells infected with CHIKV in the presence of compounds was determined by measuring metabolic reduction of resazurin to identify inhibitors of CHIKV-associated cell death.
+A kinase inhibitor library of 4,000 compounds was screened against CHIKV infection of HuH-7 cells using the resazurin reduction assay, and the cell toxicity was also measured in non-infected cells.
+Seventy-two compounds showing ≥50% inhibition property against CHIKV at 10 µM were selected as primary hits.
+Four compounds having a benzofuran core scaffold (CND0335, CND0364, CND0366 and CND0415), one pyrrolopyridine (CND0545) and one thiazol-carboxamide (CND3514) inhibited CHIKV-associated cell death in a dose-dependent manner, with EC(50) values between 2.2 µM and 7.1 µM.
+Based on image analysis, these 6 hit compounds did not inhibit CHIKV replication in the host cell.
+However, CHIKV-infected cells manifested less prominent apoptotic blebs typical of CHIKV cytopathic effect compared with the control infection.
+Moreover, treatment with these compounds reduced viral titers in the medium of CHIKV-infected cells by up to 100-fold.
+In conclusion, this cell-based high-throughput screening assay using resazurin, combined with the image-based high content assay approach identified compounds against CHIKV having a novel antiviral activity - inhibition of virus-induced CPE - likely by targeting kinases involved in apoptosis.
+In recent years, transgenic technology has become more versatile and sophisticated, mainly because of the incorporation of recombinase-mediated conditional expression and targeted insertion, site-specific endonuclease-mediated genome editing, siRNA-mediated gene knockdown, various inducible gene expression systems, and fluorescent protein marking and tracking techniques.
+Site-specific recombinases (such as PhiC31) and engineered endonucleases (such as ZFN and Talen) have significantly enhanced our ability to target transgenes into specific genomic loci, but currently a great majority of transgenic mouse lines are continuingly being created using the conventional random insertion method.
+A major challenge for using this conventional method is that the genomic environment at the integration site has a substantial influence on the expression of the transgene.
+Although our understanding of such chromosomal position effects and our means to combat them are still primitive, adhering to some general guidelines can significantly increase the odds of successful transgene expression.
+This chapter first discusses the major problems associated with transgene expression, and then describes some of the principles for using plasmid and bacterial artificial chromosomes (BACs) for generating transgenic constructs.
+Finally, the strategies for conducting each of the major types of transgenic research are discussed, including gene overexpression, promoter characterization, cell-lineage tracing, mutant complementation, expression of double or multiple transgenes, siRNA knockdown, and conditional and inducible systems.
+Conventional vaccines have been extremely successful in preventing infections by pathogens expressing relatively conserved antigens through antibody‐mediated effector mechanisms.
+Thanks to vaccination some diseases have been eradicated and mortality due to infectious diseases has been significantly reduced.
+However, there are still many infections that are not preventable with vaccination, which represent a major cause of mortality worldwide.
+Some of these infections are caused by pathogens with a high degree of antigen variability that cannot be controlled only by antibodies, but require a mix of humoral and cellular immune responses.
+Novel technologies for antigen discovery, expression and formulation allow now for the development of vaccines that can better cope with pathogen diversity and trigger multifunctional immune responses.
+In addition, the application of new genomic assays and systems biology approaches in human immunology can help to better identify vaccine correlates of protection.
+The availability of novel vaccine technologies, together with the knowledge of the distinct human immune responses that are required to prevent different types of infection, should help to rationally design effective vaccines where conventional approaches have failed.
+The drug discovery process has been profoundly changed recently by the adoption of computational methods helping the design of new drug candidates more rapidly and at lower costs.
+In silico drug design consists of a collection of tools helping to make rational decisions at the different steps of the drug discovery process, such as the identification of a biomolecular target of therapeutical interest, the selection or the design of new lead compounds and their modification to obtain better affinities, as well as pharmacokinetic and pharmacodynamic properties.
+Among the different tools available, a particular emphasis is placed in this review on molecular docking, virtual high-throughput screening and fragment-based ligand design.
+Ubiquitination and deubiquitination have emerged as critical regulatory processes in the virus-triggered type I interferon (IFN) induction pathway.
+In this study, we carried out a targeted siRNA screen of 54 ubiquitin-specific proteases (USPs) and identified USP25 as a negative regulator of the virus-triggered type I IFN signaling pathway.
+Overexpression of USP25 inhibited virus-induced activation of IFN-β, interferon regulation factor 3 (IRF3) and nuclear factor-kappa B (NF-κB), as well as the phosphorylation of IRF3 and NF-κB subunit p65.
+In addition, detailed analysis demonstrated that USP25 cleaved lysine 48- and lysine 63-linked polyubiquitin chains in vitro and in vivo, and its deubiquitinating enzyme (DUB) activity, were dependent on a cysteine residue (Cys178) and a histidine residue (His607).
+USP25 mutants lacking DUB activity lost the ability to block virus-induced type I IFN to some degree.
+Mechanistically, USP25 deubiquitinated retinoic acid-inducible gene I (RIG-I), tumornecrosis factor (TNF) receptor-associated factor 2 (TRAF2), and TRAF6 to inhibit RIG-I-like receptor-mediated IFN signaling.
+Our findings suggest that USP25 is a novel DUB negatively regulating virus-induced type I IFN production.
+We investigated whether small RNA (sRNA) sequenced from field-collected mosquitoes and chironomids (Diptera) can be used as a proxy signature of viral prevalence within a range of species and viral groups, using sRNAs sequenced from wild-caught specimens, to inform total RNA deep sequencing of samples of particular interest.
+mosquitoes the apparently nearly complete genome of one previously undescribed virus related to chronic bee paralysis virus, and, from a pool of Ochlerotatus caspius and Oc.
+Crucially, several of the sequences detected were reconstructed from host organisms highly divergent from those in which related viruses have been previously isolated or discovered.
+It is clear that viral transmission and maintenance cycles in nature are likely to be significantly more complex and taxonomically diverse than previously expected.
+Since those functions are associated with the hippocampus, I analyzed the global gene expression data from post-mortem hippocampal tissue of 25 old (age ≥ 60 yrs) and 15 young (age ≤ 45 yrs) cognitively intact human subjects.
+By employing a rigorous, multi-method bioinformatic approach, I identified 36 genes that were the most significant in terms of differential expression; and by employing mathematical modeling, I demonstrated that 7 of the 36 genes were able to discriminate between the old and young subjects with high accuracy.
+Remarkably, 90% of the known genes from those 36 most significant genes are associated with either inflammation or immune system activation.
+This suggests that chronic inflammation and immune system over-activity may underlie the aging process of the human brain, and that potential anti-inflammatory treatments targeting those genes may slow down this process and alleviate its symptoms.
+BACKGROUND: Recent experimental studies provide evidence indicating that manipulation of the mononuclear phagocyte phenotype could be a feasible approach to alter the severity and persistence of pulmonary injury and fibrosis.
+The present work was designed to investigate the therapeutic potential of MR antagonism in bleomycin-induced acute lung injury and fibrosis.
+METHODOLOGY/PRINCIPAL FINDINGS: We first demonstrated the expression of MR in magnetic bead-purified Ly6G-/CD11b+ circulating monocytes and in alveolar macrophages harvested in bronchoalveolar lavage fluid (BALF) from C57BL/6 mice.
+Then, a pharmacological intervention study using spironolactone (20mg/kg/day by oral gavage) revealed that MR antagonism led to decreased inflammatory cell infiltration, cytokine production (downregulated monocyte chemoattractant protein-1, transforming growth factor β1, and interleukin-1β at mRNA and protein levels) and collagen deposition (decreased lung total hydroxyproline content and collagen positive area by Masson’ trichrome staining) in bleomycin treated (2.5mg/kg, via oropharyngeal instillation) male C57BL/6 mice.
+Moreover, serial flow cytometry analysis in blood, BALF and enzymatically digested lung tissue, revealed that spironolactone could partially inhibit bleomycin-induced circulating Ly6C(hi) monocyte expansion, and reduce alternative activation (F4/80+CD11c+CD206+) of mononuclear phagocyte in alveoli, whereas the phenotype of interstitial macrophage (F4/80+CD11c-) remained unaffected by spironolactone during investigation.
+CONCLUSIONS/SIGNIFICANCE: The present work provides the experimental evidence that spironolactone could attenuate bleomycin-induced acute pulmonary injury and fibrosis, partially via inhibition of MR-mediated circulating monocyte and alveolar macrophage phenotype switching.
+One of the hurdles to understanding the role of viral quasispecies in RNA virus cross-species transmission (CST) events is the need to analyze a densely sampled outbreak using deep sequencing in order to measure the amount of mutation occurring on a small time scale.
+In 2009, the California Department of Public Health reported a dramatic increase (350) in the number of gray foxes infected with a rabies virus variant for which striped skunks serve as a reservoir host in Humboldt County.
+To better understand the evolution of rabies, deep-sequencing was applied to 40 unpassaged rabies virus samples from the Humboldt outbreak.
+For each sample, approximately 11 kb of the 12 kb genome was amplified and sequenced using the Illumina platform.
+Average coverage was 17,448 and this allowed characterization of the rabies virus population present in each sample at unprecedented depths.
+Phylogenetic analysis of the consensus sequence data demonstrated that samples clustered according to date (1995 vs. 2009) and geographic location (northern vs. southern).
+A single amino acid change in the G protein distinguished a subset of northern foxes from a haplotype present in both foxes and skunks, suggesting this mutation may have played a role in the observed increased transmission among foxes in this region.
+Deep-sequencing data indicated that many genetic changes associated with the CST event occurred prior to 2009 since several nonsynonymous mutations that were present in the consensus sequences of skunk and fox rabies samples obtained from 20032010 were present at the sub-consensus level (as rare variants in the viral population) in skunk and fox samples from 1995.
+These results suggest that analysis of rare variants within a viral population may yield clues to ancestral genomes and identify rare variants that have the potential to be selected for if environment conditions change.
+The mechanisms by which human immunodeficiency virus type 1 (HIV-1) crosses mucosal surfaces to establish infection are unknown.
+We found that the combination of acidic pH and Env-specific IgG, including that from cervicovaginal and seminal fluids of HIV-1-infected individuals, augmented transcytosis across epithelial cells as much as 20-fold compared with Env-specific IgG at neutral pH or non-specific IgG at either pH.
+Enhanced transcytosis was observed with clinical HIV-1 isolates, including transmitted/founder strains, and was eliminated in Fc neonatal receptor (FcRn)-knockdown epithelial cells.
+However, the ratio of total:infectious virus was higher for neutralizing antibodies, indicating that they allowed transcytosis while blocking infectivity of transcytosed virus.
+Immunocytochemistry revealed abundant FcRn expression in columnar epithelia lining the human endocervix and penile urethra.
+Acidity and Env-specific IgG enhance transcytosis of virus across epithelial cells via FcRn and could facilitate translocation of virus to susceptible target cells following sexual exposure.
+The interferon-inducible transmembrane (IFITM) family of proteins has been shown to restrict a broad range of viruses in vitro and in vivo by halting progress through the late endosomal pathway.
+Further, single nucleotide polymorphisms (SNPs) in its sequence have been linked with risk of developing severe influenza virus infections in humans.
+The number of viruses restricted by this host protein has continued to grow since it was first demonstrated as playing an antiviral role; all of which enter cells via the endosomal pathway.
+We therefore sought to test the limits of antimicrobial restriction by Ifitm3 using a knockout mouse model.
+We showed that Ifitm3 does not impact on the restriction or pathogenesis of bacterial (Salmonella typhimurium, Citrobacter rodentium, Mycobacterium tuberculosis) or protozoan (Plasmodium berghei) pathogens, despite in vitro evidence.
+However, Ifitm3 is capable of restricting respiratory syncytial virus (RSV) in vivo either through directly restricting RSV cell infection, or by exerting a previously uncharacterised function controlling disease pathogenesis.
+This represents the first demonstration of a virus that enters directly through the plasma membrane, without the need for the endosomal pathway, being restricted by the IFITM family; therefore further defining the role of these antiviral proteins.
+Hantaan virus (HTNV) is a major zoonotic pathogen that causes hemorrhagic fever with renal syndrome (HFRS) in Asia, especially in China.
+Shaanxi province, which is located in northwest of China, is one of the areas in China most severely afflicted with HFRS epidemics annually.
+This study aims to establish a quantitative RT-PCR (qRT-PCR) assay to detect HTNV both in cell culture and clinical serum samples.
+We established a SYBR Green Ⅰ-based one-step qRT-PCR assay that targets the S segment of the HTNV genome for rapid detection and quantification.
+The HTNV cRNA standards were constructed by in vitro transcription, and the copy numbers of the HTNV cRNA were quantified.
+Standard curve was generated by determining the mean cycle threshold (Ct) values versus 10-fold serial dilutions of the HTNV cRNA over a range of 1×10(8) to 1×10(3) copies/μl.
+The standard curve had a reaction efficiency of 102.1%, a correlation coefficient (R(2)) of 0.998, and a slope of -3.273.
+The coefficient of variation (CV) of the intra- and inter-assays ranged from 0.68% to 3.00% and from 0.86% to 3.21%, respectively.
+The cycle intervals of the qRT-PCR assay between each dilution ranged from 2.9 to 3.8 cycles, and the lowest detection limit of the qRT-PCR assay was 10 copies/μl.
+The assay exhibited high specificity that was confirmed by melting curve analysis, and no cross reaction with the Seoul virus (SEOV) and other viruses (HBV, HCV and HIV) was observed.
+HTNV RNA was also detected in the 27 serum samples of clinical HFRS patients using the assay, and the HTNV RNA viral load ranged from 2.06×10(1) to 1.95×10(5) copies/μl.
+The SYBR Green Ⅰ-based one-step qRT-PCR assay is a sensitive, specific, reproducible, and simple method for detecting and quantifying HTNV in cell culture and clinical samples.
+Theiler’s murine encephalomyelitis is an experimentally virus-induced inflammatory demyelinating disease of the spinal cord, displaying clinical and pathological similarities to chronic progressive multiple sclerosis.
+The aim of this study was to identify pathways associated with chronic demyelination using an assumption-free combined microarray and immunohistology approach.
+Movement control as determined by rotarod assay significantly worsened in Theiler’s murine encephalomyelitis -virus-infected SJL/J mice from 42 to 196 days after infection (dpi).
+In the spinal cords, inflammatory changes were detected 14 to 196 dpi, and demyelination progressively increased from 42 to 196 dpi.
+The dominating changes as revealed by k-means and functional annotation clustering included up-regulations related to intrathecal antibody production and antigen processing and presentation via major histocompatibility class II molecules.
+A random forest machine learning algorithm revealed that down-regulated lipid and cholesterol biosynthesis, differentially expressed neurite morphogenesis and up-regulated toll-like receptor-4-induced pathways were intimately associated with demyelination as measured by immunohistology.
+Conclusively, although transcriptional changes were dominated by the adaptive immune response, the main pathways associated with demyelination included up-regulation of toll-like receptor 4 and down-regulation of cholesterol biosynthesis.
+Cholesterol biosynthesis is a rate limiting step of myelination and its down-regulation is suggested to be involved in chronic demyelination by an inhibition of remyelination.
+Equine lentivirus receptor 1 (ELR1) has been identified as the sole receptor for equine infectious anemia virus (EIAV) and is a member of the tumor necrosis factor receptor (TNFR) superfamily.
+In addition to the previously described membrane-associated form of ELR1, two other major alternative splicing variant mRNAs were identified in equine monocyte-derived macrophages (eMDMs).
+One major spliced species (ELR1-IN) contained an insertion of 153 nt, which resulted in a premature stop codon situated 561 nt upstream of the predicted membrane spanning domain.
+The other major species (ELR1-DE) has a deletion of 109 nt that causes a shift of the open reading frame and generates a stop codon 312 nt downstream.
+Because ELR1-DE presumably encodes a peptide of a mere 23 residues, only ELR1-IN was further analyzed.
+The expression of a soluble form of ELR1 (sELR1) by ELR1-IN was confirmed by Western blot and immunofluorescence analyses.
+Similar to ELR1, the transcription level of ELR1-IN varied among individual horses and at different time points in the same individuals.
+Pre-incubation of the recombinant sELR1 with EIAV significantly inhibited EIAV infection in equine macrophages, the primary in vivo target cell of the virus.
+Fetal equine dermal (FED) cells are susceptible to EIAV in vitro, and the replication of EIAV in FED cells transiently transfected with ELR1-IN was markedly reduced when compared with replication in cells transfected with the empty vector.
+Finally, the expression levels of both forms of the EIAV receptor were significantly regulated by infection with this virus.
+Taken together, our data indicate that sELR1 acts as a secreted cellular factor that inhibits EIAV infection in host cells.
+Although type I interferons (IFN-I) were initially defined as potent antiviral agents, they can also cause decreased host resistance to some bacterial and viral infections.
+The many antiviral functions of the IFN-I include direct suppression of viral replication and activation of the immune response against viruses.
+In addition to their antiviral effects, IFN-I are also protective against several extracellular bacterial infections, in part, by promoting the induction of TNF-α and nitric oxide.
+In contrast, there is a negative effect of IFN-I on host resistance during chronic infection with lymphocytic choriomeningitis virus (LCMV) and acute infections with intracellular bacteria.
+Blockade of IFN-I signaling removes the suppression and allows CD4 T-cell- and IFN-γ-mediated resolution of the infection.
+During acute intracellular bacterial infection, IFN-I suppress innate immunity by at least two defined mechanisms.
+Following Listeria infection, IFN-I promote the cell death of macrophages and lymphocytes, which leads to innate immune suppression.
+These divergent findings for the role of IFN-I on pathogen control emphasize the complexity of the interferons system and force more mechanistic evaluation of its role in pathogenesis.
+This review evaluates IFN-I during infection with an emphasis on work carried out IFN-I-receptor-deficient mice.
+Two species of the DNA virus Torque teno sus virus (TTSuV), TTSuV1 and TTSuV2, have become widely distributed in pig-farming countries in recent years.
+In this study, we performed a comprehensive analysis of synonymous codon usage bias in 41 available TTSuV2 coding sequences (CDS), and compared the codon usage patterns of TTSuV2 and TTSuV1.
+Values for the effective number of codons (ENC) indicated that the overall extent of codon usage bias in both TTSuV2 and TTSuV1 was not significant, the most frequently occurring codons had an A or C at the third codon position.
+Correspondence analysis (COA) was performed and TTSuV2 and TTSuV1 sequences were located in different quadrants of the first two major axes.
+A plot of the ENC revealed that compositional constraint was the major factor determining the codon usage bias for TTSuV2.
+In addition, hierarchical cluster analysis of 41 TTSuV2 isolates based on relative synonymous codon usage (RSCU) values suggested that there was no association between geographic distribution and codon bias of TTSuV2 sequences.
+Finally, the comparison of RSCU for TTSuV2, TTSuV1 and the corresponding host sequence indicated that the codon usage pattern of TTSuV2 was similar to that of TTSuV1.
+These conclusions provide important insight into the synonymous codon usage pattern of TTSuV2, as well as better understangding of the molecular evolution of TTSuV2 genomes.
+The infection dynamics of bovine respiratory syncytial virus (BRSV) were studied in randomly selected Norwegian dairy herds.
+The herds were classified as positive for BRSV if at least one animal between 150 and 365 days old tested positive for antibodies against BRSV, thereby representing herds that had most likely had the virus present during the previous year.
+The prevalence of positive herds at the first and second sampling was 34 per cent and at 41 per cent, respectively, but varied greatly between regions.
+Of the herds initially being negative, 42 per cent changed status to positive during the six months.
+This occurred at the same rate during summer as winter, but a higher rate of animals in the herds was positive if it took place during winter.
+This indicates that an effective strategy to lower the prevalence and the impact of BRSV could be to employ close surveillance and place a high biosecurity focus on the negative herds.
+The mammalian RIG-I-like receptors, RIG-I, MDA5 and LGP2, are a family of DExD/H box RNA helicases responsible for the cytoplasmic detection of viral RNA.
+These receptors detect a variety of RNA viruses, or DNA viruses that express unusual RNA species, many of which are responsible for a great number of severe and lethal diseases.
+Host innate sentinel proteins involved in pathogen recognition must rapidly evolve in a dynamic arms race with pathogens, and thus are subjected to long-term positive selection pressures to avoid potential infections.
+Using six codon-based Maximum Likelihood methods, we were able to identify specific codons under positive selection in each of these three genes.
+The highest number of positively selected codons was detected in MDA5, but a great percentage of these codons were located outside of the currently defined protein domains for MDA5, which likely reflects the imposition of both functional and structural constraints.
+Additionally, our results support LGP2 as being the least prone to evolutionary change, since the lowest number of codons under selection was observed for this gene.
+On the other hand, the preponderance of positively selected codons for RIG-I were detected in known protein functional domains, suggesting that pressure has been imposed by the vast number of viruses that are recognized by this RNA helicase.
+Furthermore, the RIG-I repressor domain, the region responsible for recognizing and binding to its RNA substrates, exhibited the strongest evidence of selective pressures.
+Branch-site analyses were performed and several species branches on the three receptor gene trees showed evidence of episodic positive selection.
+In conclusion, by looking for evidence of positive evolutionary selection on mammalian RIG-I-like receptor genes, we propose that a multitude of viruses have crafted the receptors biological function in host defense, specifically for the RIG-I gene, contributing to the innate species-specific resistance/susceptibility to diverse viral pathogens.
+BACKGROUND: Classical scrapie in sheep is a fatal neurodegenerative disease associated with the conversion PrP(C) to PrP(Sc).
+Much is known about genetic susceptibility, uptake and dissemination of PrP(Sc) in the body, but many aspects of prion diseases are still unknown.
+Different proteomic techniques have been used during the last decade to investigate differences in protein profiles between affected animals and healthy controls.
+We have investigated the protein profiles in serum of sheep with scrapie and healthy controls by SELDI-TOF-MS and LC-MS/MS.
+Latent Variable methods such as Principal Component Analysis, Partial Least Squares-Discriminant Analysis and Target Projection methods were used to describe the MS data.
+RESULTS: The serum proteomic profiles showed variable differences between the groups both throughout the incubation period and at the clinical end stage of scrapie.
+At the end stage, the target projection model separated the two groups with a sensitivity of 97.8%, and serum amyloid A was identified as one of the protein peaks that differed significantly between the groups.
+CONCLUSIONS: At the clinical end stage of classical scrapie, ten SELDI peaks significantly discriminated the scrapie group from the healthy controls.
+During the non-clinical incubation period, individual SELDI peaks were differently expressed between the groups at different time points.
+Investigations of differences in -omic profiles can contribute to new insights into the underlying disease processes and pathways, and advance our understanding of prion diseases, but comparison and validation across laboratories is difficult and challenging.
+Free vascularized fibular grafting (FVFG) has been reported to be an effective method of treating osteonecrosis of the femoral head (ONFH).
+This study evaluated whether postoperative maintenance doses of corticosteroids had an adverse effect on FVFG outcomes in patients with corticosteroid-induced ONFH.
+We retrospectively reviewed the records of 39 patients (67 hips) who had received maintenance doses of corticosteroids following FVFG.
+This group was matched to a group of patients who had not received corticosteroids treatment after operation.
+The mean follow-up duration was 5.4 years for the postoperative corticosteroid administration group (PCA group) and 5.0 years for the control group.
+At the latest follow-up, the average increase in Harris hip score was 11.1 ± 8.7 points for all hips in the PCA group and 12.6 ± 7.4 points for all hips in the control group (P > 0.05).
+In the PCA group, through radiographic evaluation, 49 hips were improved, 10 hips appeared unchanged, and 8 hips appeared worse.
+In the control group, 47 hips were improved, 13 hips appeared unchanged, and 7 hips appeared worse.
+The results suggested that postoperative maintenance doses of corticosteroids do not have an adverse effect on FVFG outcomes in patients with corticosteroid-induced ONFH.
+BACKGROUND: Genetic variants in the inhibiting FcγRIIB mediate anti-inflammatory responses and influence IVIG refractoriness (IVIG-R).
+However, these variants are rare in Asian and Hispanic populations so other genes in the pathway could be potentially involved.
+Further, DC-SIGN is a known receptor for sialylated Fc, the component responsible for the anti-inflammatory action of IVIG.
+Thus, we hypothesized that DC-SIGN would also be involved in the pathway of IVIG response in Kawasaki Disease (KD) patients.
+FINDINGS: A case-control approach was performed to examine the differential distribution of five single nucleotide polymorphisms (SNPs) in DC-SIGN promoter with IVIG-R among White (158 vs. 62), Asian (64 vs. 12) and Hispanic (55 vs. 20) KD patients.
+Distinct differences in allele frequency distributions of several variants in the DC-SIGN promoter were observed in the three ethnic groups.
+Further, Asians with the major allele “A” in rs2287886 were more likely (OR = 1.76, p = 0.04) to be IVIG non-responder, but this allele is a minor allele in other two ethnic groups, where the association was not apparent.
+CONCLUSIONS: DC-SIGN can potentially complement the role of FcγRIIB in the anti-inflammatory cascade involved in the IVIG response mechanism.
+BACKGROUND: Porcine reproductive and respiratory syndrome virus (PRRSV) is a RNA virus with high genetic variation.
+In this study, we developed a sensitive and specific zip nucleic acid probe-based real-time PCR assay to evaluate the viremia of natural PRRSV-infected pigs in Taiwan.
+These include 444 clinically healthy pigs and 133 symptomatic pigs were confirmed to have porcine respiratory disease complex (PRDC).
+RESULTS: Viremia was quantified in 79 of the 444 (17.8%) clinically healthy pigs and in 112 of the 133 (84.2%) PRDC cases.
+Viremias were significantly more common in pigs with PRDC compared with the clinically healthy pigs (P <0.0001).
+These results suggest that a high viral load is a major feature of PRRSV-affected pigs.
+CONCLUSIONS: ZNA probe-based real-time PCR can be a useful tool to diagnose symptomatic and asymptomatic PRRSV-infected pigs.
+The presence of this marker in a sample of animals with high PRRSV loads (>10(4.2) PRRSV genomes/μl of serum) seems to indicate that it correlates with the presence of PRDC in pigs.
+HNF1B is overexpressed in clear cell epithelial ovarian cancer, and we observed epigenetic silencing in serous epithelial ovarian cancer, leading us to hypothesize that variation in this gene differentially associates with epithelial ovarian cancer risk according to histological subtype.
+Here we comprehensively map variation in HNF1B with respect to epithelial ovarian cancer risk and analyse DNA methylation and expression profiles across histological subtypes.
+Different single-nucleotide polymorphisms associate with invasive serous (rs7405776 odds ratio (OR)=1.13, P=3.1 × 10(−10)) and clear cell (rs11651755 OR=0.77, P=1.6 × 10(−8)) epithelial ovarian cancer.
+Unmethylated, expressed HNF1B, primarily present in clear cell tumours, coincides with a CpG island methylator phenotype affecting numerous other promoters throughout the genome.
+Different variants in HNF1B associate with risk of serous and clear cell epithelial ovarian cancer; DNA methylation and expression patterns are also notably distinct between these subtypes.
+SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/ncomms2629) contains supplementary material, which is available to authorized users.
+Individual genes or regions are still commonly used to estimate the phylogenetic relationships among viral isolates.
+The genomic regions that can faithfully provide assessments consistent with those predicted with full-length genome sequences would be preferable to serve as good candidates of the phylogenetic markers for molecular epidemiological studies of many viruses.
+Here we employed a statistical method to evaluate the evolutionary relationships between individual viral genes and full-length genomes without tree construction as a way to determine which gene can match the genome well in phylogenetic analyses.
+This method was performed by calculation of linear correlations between the genetic distance matrices of aligned individual gene sequences and aligned genome sequences.
+We applied this method to the phylogenetic analyses of porcine circovirus 2 (PCV2), measles virus (MV), hepatitis E virus (HEV) and Japanese encephalitis virus (JEV).
+Phylogenetic trees were constructed for comparisons and the possible factors affecting the method accuracy were also discussed in the calculations.
+The results revealed that this method could produce results consistent with those of previous studies about the proper consensus sequences that could be successfully used as phylogenetic markers.
+And our results also suggested that these evolutionary correlations could provide useful information for identifying genes that could be used effectively to infer the genetic relationships.
+BACKGROUND: Accurate knowledge of incubation period is important to investigate and to control infectious diseases and their transmission, however statements of incubation period in the literature are often uncited, inconsistent, and/or not evidence based.
+METHODS: In a systematic review of the literature on five enteric viruses of public health importance, we found 256 articles with incubation period estimates, including 33 with data for pooled analysis.
+RESULTS: We fit a log-normal distribution to pooled data and found the median incubation period to be 4.5 days (95% CI 3.9-5.2 days) for astrovirus, 1.2 days (95% CI 1.1-1.2 days) for norovirus genogroups I and II, 1.7 days (95% CI 1.5-1.8 days) for sapovirus, and 2.0 days (95% CI 1.4-2.4 days) for rotavirus.
+CONCLUSIONS: Our estimates combine published data and provide sufficient quantitative detail to allow for these estimates to be used in a wide range of clinical and modeling applications.
+This can translate into improved prevention and control efforts in settings with transmission or the risk of transmission.
+BACKGROUND: Zoonoses are a growing international threat interacting at the human-animal-environment interface and call for transdisciplinary and multi-sectoral approaches in order to achieve effective disease management.
+The recent emergence of Lyme disease in Quebec, Canada is a good example of a complex health issue for which the public health sector must find protective interventions.
+Traditional preventive and control interventions can have important environmental, social and economic impacts and as a result, decision-making requires a systems approach capable of integrating these multiple aspects of interventions.
+This paper presents the results from a study of a multi-criteria decision analysis (MCDA) approach for the management of Lyme disease in Quebec, Canada.
+METHODS: MCDA models were developed to assess various prevention and control decision criteria pertinent to a comprehensive management of Lyme disease: a first model was developed for surveillance interventions and a second was developed for control interventions.
+Multi-criteria analyses were conducted under two epidemiological scenarios: a disease emergence scenario and an epidemic scenario.
+For the surveillance model, the three preferred interventions were: active surveillance of vectors by flagging or dragging, active surveillance of vectors by trapping of small rodents and passive surveillance of vectors of human origin.
+For the control interventions model, basic preventive communications, human vaccination and small scale landscaping were the three preferred interventions.
+Scenarios were found to only have a small effect on the group ranking of interventions in the control model.
+CONCLUSIONS: MCDA was used to structure key decision criteria and capture the complexity of Lyme disease management.
+This facilitated the identification of gaps in the scientific literature and enabled a clear identification of complementary interventions that could be used to improve the relevance and acceptability of proposed prevention and control strategy.
+Overall, MCDA presents itself as an interesting systematic approach for public health planning and zoonoses management with a “One Health” perspective.
+Many natural dietary products prevent or cure allergic inflammation; however, the ability of mixtures of these natural medicinals to suppress allergic skin inflammation is unknown.
+We examined the inhibitory effects of nonanatural products mixture (NPM-9), which provides immunoregulatory activation, on Th2-mediated skin allergic inflammation.
+Oral administration of NPM-9 in mice reduced ear thickness and specific IgE production in trimellitic anhydride- (TMA-)induced contact hypersensitivity (CHS).
+NPM-9 also suppressed IL-4 and IL-1β production in splenocytes but prevented only TMA-induced IL-1β production in inflamed ears.
+To characterize the mechanism of this effect, we examined NPM-9 immunosuppression on an OVA-induced Th2 allergic state.
+These data suggest that NPM-9 may be a useful therapeutic agent for allergic inflammatory diseases through its suppression of the Th2-mediated allergic response.
+The combined effect of hepatocyte growth factor (HGF) and Ang II on cardiomyocytes is unknown.
+The present study was designed to determine the effect of HGF on cardiomyocyte hypertrophy and to explore the combined effect of HGF and Ang II on cardiomyocyte hypertrophy.
+Cells were treated with Ang II (1 µM) alone, HGF (10 ng/mL) alone, and Ang II (1 µM) plus HGF (10 ng/mL) for 24, 48, and 72 h. The amount of [(3)H]-leucine incorporation was then measured to evaluate protein synthesis.
+The mRNA levels of β-myosin heavy chain and atrial natriuretic factor were determined by real-time PCR to evaluate the presence of fetal phenotypes of gene expression.
+Moreover, the combination of 1 µM Ang II and 10 ng/mL HGF clearly induced a combined pro-hypertrophy effect on cardiomyocytes.
+The present study demonstrates for the first time a novel, combined effect of HGF and Ang II in promoting cardiomyocyte hypertrophy.
+Japanese encephalitis virus (JEV) can cause severe central nervous disease with a high mortality rate.
+In this study, a cytopathic-effect-based, high-throughput screening assay was developed and applied to screen JEV inhibitors from Library of Pharmacologically Active Compounds 1280.
+The antiviral effects of three hit compounds including FGIN-1-27, cilnidipine, and niclosamide were evaluated in cells by western blotting, indirect immunofluorescence assay, and plaque reduction assay.
+A time-of-addition assay proved that all three compounds inhibited JEV at the stage of replication.
+The EC50s of FGIN-1-27, cilnidipine, and niclosamide were 3.21, 6.52, and 5.80 µM, respectively, while the selectivity indexes were 38.79, 30.67, and 7.49.
+GH and GH receptors are expressed throughout life, and GH elicits a diverse range of responses, including growth and altered metabolism.
+It is therefore important to understand the full spectrum of GH signaling pathways and cellular responses.
+We applied mass spectrometry-based phosphoproteomics combined with stable isotope labeling with amino acids in cell culture to identify proteins rapidly phosphorylated in response to GH in 3T3-F442A preadipocytes.
+We identified 132 phosphosites in 95 proteins that exhibited rapid (5 or 15 min) GH-dependent statistically significant increases in phosphorylation by more than or equal to 50% and 96 phosphosites in 46 proteins that were down-regulated by GH by more than or equal to 30%.
+regulatory Thr/Tyr in Erks 1 and 2, Tyr in signal transducers and activators of transcription (Stat) 5a and 5b, Ser939 in tuberous sclerosis protein (TSC) 2 or tuberin).
+Kyoto Encyclopedia of Genes and Genomes pathway analysis of GH-stimulated sites indicated enrichment in proteins associated with the insulin and mammalian target of rapamycin (mTOR) pathways, regulation of the actin cytoskeleton, and focal adhesions.
+Immunoblotting confirmed GH-stimulated phosphorylation of all seven novel GH-dependent sites tested [regulatory sites in proline-rich Akt substrate, 40 kDA (PRAS40), regulatory associated protein of mTOR, ATP-citrate lyase, Na(+)/H(+) exchanger-1, N-myc downstream regulated gene 1, and Shc]).
+The immunoblot results suggest that many, if not most, of the GH-stimulated phosphosites identified in this large-scale quantitative phosphoproteomics analysis, including sites in multiple proteins in the Akt/ mTOR complex 1 pathway, are phosphorylated in response to GH.
+Mink enteritis virus (MEV) is one of the most important viral pathogens in the mink industry.
+Recent studies have showed that microRNAs (miRNAs), small noncoding RNAs of length ranging from 18–23 nucleotides (nt) participate in host-pathogen interaction networks; however, whether or not miRNAs are involved in MEV infection has not been reported.
+Our study revealed that miRNA miR-181b inhibited replication of MEV in the feline kidney (F81) cell line by targeting the MEV non-structural protein 1 (NS1) messenger RNA (mRNA) coding region, resulting in NS1 translational repression, while MEV infection reduced miR-181b expression.
+This is the first description of cellular miRNAs modulating MEV infection in F81 cells, providing further insight into the mechanisms of viral infection, and may be useful in development of naturally-occurring miRNAs antiviral strategies.
+Vacuolating cytotoxin A (VacA) is one of the important virulence factors produced by H. pylori.
+VacA also causes cell death by mitochondrial damage, via signaling pathways that are not fully defined.
+Our aim was to determine whether endoplasmic reticulum (ER) stress is associated with VacA-induced mitochondrial dysfunction and apoptosis.
+We found that C/EBP homologous protein (CHOP), a key signaling protein of ER stress-induced apoptosis, was transcriptionally up-regulated following incubation of gastric epithelial cells with VacA.
+The effect of VacA on CHOP induction was significantly enhanced by co-incubation with ammonium chloride.
+Phosphorylation of eukaryotic initiation factor 2 (eIF2)-alpha, which is known to occur downstream of the ER stress sensor PKR-like ER-localized eIF2-alpha kinase (PERK) and to regulate CHOP expression, was also observed following incubation with VacA in the presence of ammonium chloride.
+Further studies showed that silencing of the PERK gene with siRNA attenuated VacA-mediated phosphorylation of eIF2-alpha, CHOP induction, expression of BH3-only protein Bim and Bax activation, and cell death induced by VacA with ammonium chloride, indicating that ER stress may lead to mitochondrial dysfunction during VacA-induced toxicity.
+Activation of ER stress and up-regulation of BH3-only proteins were also observed in human H. pylori-infected gastric mucosa.
+Collectively, this study reveals a possible association between VacA-induced apoptosis in gastric epithelial cells, and activation of ER stress in H. pylori-positive gastric mucosa.
+Dendritic cells (DCs) are critical to initiate the immune response and maintain tolerance, depending on different status and subsets.
+The expression profiles of microRNAs (miRNAs) in various DC subsets and haematopoietic stem cells (HSCs), which generate DCs, remain to be fully identified.
+Here we examine miRNomes of mouse bone marrow HSCs, immature DCs, mature DCs and IL-10/NO-producing regulatory DCs by deep sequencing.
+We identify numerous stage-specific miRNAs and histone modification in HSCs and DCs at different differentiation stages.
+miR-30b, significantly upregulated via a TGF-beta/Smad3-mediated epigenetic pathway in regulatory DCs, can target Notch1 to promote IL-10 and NO production, suggesting that miR-30b is a negative regulator of immune response.
+We also identify miRNomes of in vivo counterparts of mature DCs and regulatory DCs and systematically compare them with DCs cultured in vitro.
+These results provide a resource for studying roles of miRNAs in stem cell biology, development and functional regulation of DC subsets.
+Identification of microbial pathogens in clinical specimens is still performed by phenotypic methods that are often slow and cumbersome, despite the availability of more comprehensive genotyping technologies.
+We present an approach based on whole‐genome amplification and resequencing microarrays for unbiased pathogen detection.
+This 10 h process identifies a broad spectrum of bacterial and viral species and predicts antibiotic resistance and pathogenicity and virulence profiles.
+We successfully identify a variety of bacteria and viruses, both in isolation and in complex mixtures, and the high specificity of the microarray distinguishes between different pathogens that cause diseases with overlapping symptoms.
+The resequencing approach also allows identification of organisms whose sequences are not tiled on the array, greatly expanding the repertoire of identifiable organisms and their variants.
+We identify organisms by hybridization of their DNA in as little as 1–4 h. Using this method, we identified Monkeypox virus and drug‐resistant Staphylococcus aureus in a skin lesion taken from a child suspected of an orthopoxvirus infection, despite poor transport conditions of the sample, and a vast excess of human DNA.
+Our results suggest this technology could be applied in a clinical setting to test for numerous pathogens in a rapid, sensitive and unbiased manner.
+The human liver and lymph node sinusoidal endothelial cell C-type lectin (hLSECtin), a type II integral membrane protein, containing a Ca(2+)-dependent carbohydrate recognition domain (CRD), has a well-established biological activity, yet its three-dimensional structure is unknown due to low expression yields and aggregation into inclusion bodies.
+Previous study has demonstrated that the HIV-1 virus-encoded Tat peptide (‘YGRKKRRQRRR’) can increase the yields and the solubility of heterologous proteins.
+However, whether the Tat peptide could promote the high-yield and soluble expression of membrane proteins in Escherichia coli is not known.
+Therefore, the prokaryotic expression vector pET28b-Tat-hLSECtin-CRD (using pET28b and pET28b-hLSECtin-CRD as controls) was constructed, and transformed into E. coli BL21 (DE3) cells and induced with isopropyl-β-d-thiogalactoside (IPTG) followed with identifying by SDS-PAGE and Western blot.
+Subsequently, the bacterial subcellular structure, in which overexpressed the heterologous proteins Tat-hLSECtin-CRD and Tat-free hLSECtin-CRD, was analyzed by transmission electron microscope (TEM) respectively, and the mannose-binding activity of Tat-hLSECtin-CRD was also determined.
+Expectedly, the solubility of Tat-LSECtin-CRD significantly increased compared to Tat-free LSECtin-CRD (**p < 0.01) with prolonged time, and the Tat-LSECtin-CRD had a significant mannose-binding activity.
+The subcellular structure analysis indicated that the bacterial cells overexpressed Tat-hLSECtin-CRD exhibited denser region compared with controls, while dot denser region aggregated in the two ends of bacterial cells overexpressed Tat-free hLSECtin-CRD.
+This study provided a novel method for improving the soluble expression of membrane proteins in prokaryotic systems by fusion with the Tat peptide, which may be potentially expanded to the expression of other membrane proteins.
+We describe two donor splice site mutations, affecting dystrophin exons 16 and 45 that led to Duchenne muscular dystrophy (DMD), through catastrophic inactivation of the mRNA.
+These gene lesions unexpectedly resulted in the retention of the downstream introns, thereby increasing the length of the dystrophin mRNA by 20.2 and 36 kb, respectively.
+Splice-switching antisense oligomers targeted to exon 16 excised this in-frame exon and the following intron from the patient dystrophin transcript very efficiently in vitro, thereby restoring the reading frame and allowing synthesis of near-normal levels of a putatively functional dystrophin isoform.
+In contrast, targeting splice-switching oligomers to exon 45 in patient cells promoted only modest levels of an out-of-frame dystrophin transcript after transfection at high oligomer concentrations, whereas dual targeting of exons 44 and 45 or 45 and 46 resulted in more efficient exon skipping, with concomitant removal of intron 45.
+We suggest that other splice site mutations may need to be evaluated for oligomer interventions on a case-by-case basis.
+Cyclophilin A (CypA) is a ubiquitous cis-trans-prolyl isomerase with key roles in immunity and viral infection.
+CypA suppresses T-cell activation through cyclosporine (Cs) complexation and is required for effective HIV-1 replication in host cells.
+We show that CypA is acetylated in diverse human cell lines and use a synthetically evolved acetyl-lysyl-tRNA synthetase/tRNA(CUA) pair to produce recombinant acetylated CypA in E. coli.
+We determine atomic resolution structures of acetylated CypA and its complexes with Cs and HIV-1 capsid.
+Acetylation dramatically inhibits CypA catalysis of cis to trans isomerisation and stabilises cis rather than trans forms of the HIV-1 capsid.
+Furthermore, CypA acetylation antagonizes the immunosuppressive effects of Cs, by inhibiting the sequential steps of Cs binding and calcineurin inhibition.
+Our results reveal that acetylation regulates key functions of CypA in immunity and viral infection and provide a general set of mechanisms by which acetylation modulates interactions to regulate cell function.
+In our current study, a newer amine functionalized guar gum derivative was studied for its efficacy in colonic drug delivery.
+The Scanning Electron Microscopic study revealed spherical particles of sizes from 4.9 ± 3.8 μm to 6.9 ± 3.9 μm.
+The drug was encapsulated in amorphous form as observed from the powder X-Ray Diffraction studies.
+A cumulative drug release study was carried out in simulated gastric, intestinal, and colonic fluids.
+The cumulative drug release studies presented a burst release followed by a sustained release of the drug in simulated colonic fluid containing rat cecal contents.
+The drug-polymer ratio was optimised using a 3(2) factorial design by taking the amounts of glycyrrhizic acid (X(1)) and guar gum alkyl amine (X(2)) as the independant variables.
+The percent cumulative drug release at 240 mins (Q(240)), 720 mins (Q(720)), and at 1,440 mins (Q(1440)) were considered as the dependant variables.
+The efficacy of the optimized formulation was studied in a 2,4,6-trinitrobenzene sulfonic acid-induced rat colitis model.
+The tissue’s nitric oxide, malondialdehyde, and myeloperoxidase activities were found to be much lower in the microparticle-treated group compared to free drug-treated group.
+The histology of the colonic tissue from the treated group of animals revealed almost no infiltration of inflammatory cells in the tissue for the microparticle-treated group of animals.
+The synthesized amine derivative of guar gum was found to be better in vitro with a better in vivo efficacy in the colonic delivery of glycyrrhizic acid monoammonium salt and can be considered as a newer modified biopolymer for colonic drug delivery.
+Indeed, small RNA-mediated silencing or RNA interference (RNAi) is one of the earliest forms of antiviral immunity.
+Although it represents the main defense system against viruses in many organisms, the antiviral role of RNAi has not been clearly proven in higher vertebrates.
+However, it is well established that their response to viral infection relies on the recognition of viral RNAs by host pattern recognition receptors (PRRs) to trigger activation of the interferon pathway.
+In the present work, we report the existence of a novel small noncoding RNA population produced in mammalian cells upon RNA virus infection.
+Using Sindbis virus (SINV) as a prototypic arbovirus model, we profiled the small RNA population of infected cells in both human and African green monkey cell lines.
+Here, we provide evidence for the presence of discrete small RNAs of viral origin that are not associated with the RNA-induced silencing complex (RISC), that are highly expressed and detected by Northern blot analysis, and that accumulate as 21- to 28-nucleotide (nt) species during infection.
+We report that the cellular antiviral endoribonuclease RNase L cleaves the viral genome, producing in turn the small RNAs.
+Surprisingly, we uncovered the presence of a modification on the 3′-end nucleotide of SINV-derived viral small RNAs (SvsRNAs) that might be at the origin of their stability.
+Altogether, our findings show that stable modified small viral RNAs could represent a novel way to modulate host-virus interaction upon SINV infection.
+Infant mortality from viral infection remains a major global health concern: viruses causing acute infections in immunologically mature hosts often follow a more severe course in early life, with prolonged or persistent viral replication.
+Similarly, the WE strain of lymphocytic choriomeningitis virus (LCMV-WE) causes acute self-limiting infection in adult mice but follows a protracted course in infant animals, in which LCMV-specific CD8(+) T cells fail to expand and control infection.
+By disrupting type I IFNs signaling in adult mice or providing IFN-α supplementation to infant mice, we show here that the impaired early life T cell responses and viral control result from limited early type I IFN responses.
+We postulated that plasmacytoid dendritic cells (pDC), which have been identified as one major source of immediate-early IFN-I, may not exert adult-like function in vivo in the early life microenvironment.
+We tested this hypothesis by studying pDC functions in vivo during LCMV infection and identified a coordinated downregulation of infant pDC maturation, activation and function: despite an adult-like in vitro activation capacity of infant pDCs, the expression of the E2-2 pDC master regulator (and of critical downstream antiviral genes such as MyD88, TLR7/TLR9, NF-κB, IRF7 and IRF8) is downregulated in vivo at baseline and during LCMV infection.
+A similar pattern was observed in response to ssRNA polyU, a model ligand of the TLR7 viral sensor.
+This suggests that the limited T cell-mediated defense against early life viral infections is largely attributable to / regulated by infant pDC responses and provides incentives for novel strategies to supplement or stimulate immediate-early IFN-α responses.
+The most severely immunocompromised patients are those who have been diagnosed with a hematologic malignancy, solid organ tumor, or who have other conditions that require immunosuppressive therapies and/or solid organ or stem cell transplants.
+Medically attended patients with a positive clinical diagnosis of influenza were recruited prospectively and clinically evaluated.
+Evaluation of viral shedding, nasal and serum cytokines, clinical illness, and clinical outcomes were performed to compare severely immunocompromised individuals to nonimmunocompromised individuals with influenza infection.
+Immunocompromised patients with influenza had more severe disease/complications, longer viral shedding, and more antiviral resistance while demonstrating less clinical symptoms and signs on clinical assessment.
+Immunocompromised patients are at risk for more severe or complicated influenza induced disease, which may be difficult to prevent with existing vaccines and antiviral treatments.
+Specific issues to consider when managing a severely immunocompromised host include the development of asymptomatic shedding, multi-drug resistance during prolonged antiviral therapy, and the potential high risk of pulmonary involvement.
+BACKGROUND: Live-animal markets are a culturally important feature of meat distribution chains in many populations, yet they provide an opportunity for the maintenance and transmission of potentially emergent zoonotic pathogens.
+The ongoing human outbreak of avian H7N9 in China highlights the need for increased surveillance and control in these live-bird markets (LBMs).
+DISCUSSION: Closure of retail markets in affected areas rapidly decreased human cases to rare, sporadic occurrence, but little attention has been paid thus far to the role of upstream elements of the poultry distribution chain such as wholesale markets.
+This could partly explain why transmission in poultry populations has not been eliminated more broadly.
+We present surveillance data from both wholesale live-bird markets (wLBMs) and rLBMs in Shantou, China (from 2004–2006), and call on disease-dynamic theory to illustrate why closing rLBMs has only minor effects on the overall volume of transmission.
+We show that the length of time birds stay in rLBMs can severely limit transmission there, but that the system-wide effect may be reduced substantially by high levels of transmission upstream of retail markets.
+SUMMARY: Management plans that minimize transmission throughout the entire poultry supply chain are essential for minimizing exposure to the public.
+These include reducing stay-time of birds in markets to 1 day, standardizing poultry supply chains to limit transmission in pre-retail settings, and monitoring strains with epidemiological traits that pose a high risk of emergence.
+These actions will further limit human exposure to extant viruses and reduce the likelihood of the emergence of novel strains by decreasing the overall volume of transmission.
+Enterovirus 71 (EV71) is the major pathogen responsible for fatal hand, foot and mouth disease (HFMD).
+Our previous work reported on an EV71-infected rhesus monkey infant model that presented with histo-pathologic changes of the central nervous system (CNS) and lungs.
+This study is focused on the correlated modulation of gene expression in the peripheral blood mononuclear cells (PBMCs) from EV71-infected rhesus monkey infants.
+The expression of genes associated with immune inflammatory responses was up-regulated during the period from days 4 to 10 post-infection.
+The expression of two genes (TAC1 and IL17A), which play major roles in inflammatory reactions, was remarkably up-regulated during the infection period.
+Furthermore, a higher expression level of the TAC1 gene was identified in the CNS compared to the lungs, but a high expression level of the IL-17A gene was observed in the lungs and not in the CNS.
+The results of this study suggest at least two facts about EV71 infection, which are that: the TAC1 gene that encodes substance P and neurokinin-A is present in both PBMCs and the hypothalamus; and the up-regulation of IL-17A is sustained in the peripheral blood.
+The human signal-molecule-profiling database (HSMPD) is designed as a prospective medical database for translational bioinformatics (TBI).
+A HSMPD-oriented tool, called “signal-molecule-profiling (SMP) chip” was developed for data acquisition, which can be employed in the routine blood tests in hospitals; the results will be stored in the HSMPD system automatically.
+HSMPD system can provide data services for the TBI community, which generates a stable income to support the data acquisition.
+The small-scale experimental test was performed in the hospital to verify SMP chips and the demo HSMPD software.
+One hundred and eighty nine complete SMP records were collected, and the demo HSMPD system was also evaluated in the survey study on patients and doctors.
+The function of SMP chip was verified, whereas the demo HSMPD software needed to be improved.
+The survey study showed that patients would only accept free tests of SMP chips when they originally needed blood examinations.
+The study indicated that the construction of HSMPD relies on the self-motivated cooperation of the TBI community and the traditional healthcare system.
+The proposed roadmap potentially provides an executable solution to build the HSMPD without high costs.
+The identification of a specific immunogenic candidate that will effectively activate the appropriate pathway for neutralizing antibody production is fundamental for vaccine design.
+By using a monoclonal antibody (1H8) that neutralizes HCV in vitro, we have demonstrated here that 1H8 recognized an epitope mapped between residues A524 and W529 of the E2 protein.
+We also found that the epitope residues A524, P525, Y527 and W529 were crucial for antibody binding, while the residues T526, Y527 and W529 within the same epitope engaged in the interaction with the host entry factor CD81.
+Furthermore, we detected “1H8-like” antibodies, defined as those with amino acid-specificity similar to 1H8, in the plasma of patients with chronic HCV infection.
+The time course study of plasma samples from Patient H, a well-characterized case of post-transfusion hepatitis C, showed that “1H8-like” antibodies could be detected in a sample collected almost two years after the initial infection, thus confirming the immunogenicity of this epitope in vivo.
+The characterization of this neutralization epitope with a function in host entry factor CD81 interaction should enhance our understanding of antibody-mediated neutralization of HCV infections.
+BACKGROUND: The cynomolgus monkey (Macaca fascicularis) has been increasingly used as a non-human primate model in biomedical research.
+As establishing baseline thoracic radiography for the cynomolgus monkey is essential, we tested the hypothesis that age and sex may affect the thoracic radiography parameters of this species.
+METHODS: Here, 697 healthy cynomolgus monkeys were segregated by sex and age (three age groups: 25–36 months, 37–48 months, 49–60 months).
+The lung length (LL), maximal interior thoracic depth (TD), maximal interior thoracic breadth (TBr), cardiac silhouette breadth (CBr), cardiothoracic ratio (CR), right and left costophrenic angles (RCA and LCA), and right hilar height ratio (R-HHR) were assessed by chest film.
+Statistical analysis was applied to examine the effect of age, sex, and age × sex interactions.
+Both TD and TBr increased with age in both sexes, and both were significantly higher in males than in females in the group aged 49–60 months.
+CBr increased with age and was significantly higher in males than in females across all age groups.
+CR declined with age and was significantly higher in males than females across all age groups, and CR was similar or slightly higher relative to those previously found in other non-human primate species.
+As to the other parameters with no significant sex nor age-related differences, the R-HHR was greater than 1.00, and the angulation of bilateral costophrenic angles were sharp.
+CONCLUSIONS: The thoracic radiographic parameters for the healthy cynomolgus monkey presented here should prove useful in veterinary practice, research involving non-human primate models of respiratory or cardiovascular disorders, and morphological studies on cynomolgus monkeys.
+BACKGROUND: In 2009, pandemic H1N1 influenza virus (2009 H1N1) emerged worldwide, causing morbidity and mortality that disproportionately affected young adults.
+Upper respiratory infection (URI), largely due to adenovirus, is an endemic cause of morbidity in military training.
+METHODS: The Center for Advanced Molecular Detection evaluates epidemiology and rapid diagnostics of respiratory pathogens in trainees with URI.
+From May 1, 2009, to November 30, 2009, demographic, clinical, and PCR data from throat and nasal specimens for adenovirus and 2009 H1N1 were prospectively collected.
+RESULTS: 375 trainees with URI enrolled and were tested for both adenovirus and 2009 H1N1 by PCR (median age 20; 89% male).
+Males were more likely to have adenovirus and females more likely to have 2009 H1N1 (p = 0.047).
+Subjects with 2009 H1N1 presented an average of 1 week earlier in training, had shorter illness duration before enrollment, less sore throat, diarrhea, and fewer abnormal findings on throat exam.
+Subjects with 2009 H1N1 were less likely to have adenovirus than those without, despite persistently high frequencies of adenovirus detections during peak 2009 H1N1 weeks (15% vs. 83%, p < 0.01).
+Rates of hospitalization and pneumonia did not differ between the adenovirus, 2009 H1N1, or coinfected groups.
+CONCLUSION: Military trainees with 2009 H1N1 vs. adenovirus have differing clinical presentations, and males are more likely to have adenovirus.
+Despite high frequencies of adenovirus infection, coinfection with adenovirus and 2009 H1N1 is rare and apparently does not result in increased morbidity.
+Mesenchymal stem cells (MSCs) are multipotent, tissue-resident cells that can facilitate tissue regeneration and thus, show great promise as potential therapeutic agents.
+Functional MSCs have been isolated and characterized from a wide array of adult tissues and are universally identified by the shared expression of a core panel of MSCs markers.
+One of these markers is the multifunctional cell surface peptidase CD13 that has been shown to be expressed on human and murine MSCs from many tissues.
+To investigate whether this universal expression indicates a functional role for CD13 in MSC biology we isolated, expanded and characterized MSCs from bone marrow of wild type (WT) and CD13(KO) mice.
+Characterization of these cells demonstrated that both WT and CD13(KO) MSCs expressed the full complement of MSC markers (CD29, CD44, CD49e, CD105, Sca1), showed comparable proliferation rates and were capable of differentiating toward the adipogenic and osteogenic lineages.
+However, MSCs lacking CD13 were unable to differentiate into vascular cells, consistent with our previous characterization of CD13 as an angiogenic regulator.
+Compared to WT MSCs, adhesion and migration on various extracellular matrices of CD13(KO) MSCs were significantly impaired, which correlated with decreased phospho-FAK levels and cytoskeletal alterations.
+Crosslinking human MSCs with activating CD13 antibodies increased cell adhesion to endothelial monolayers and induced FAK activation in a time dependent manner.
+In agreement with these in vitro data, intramuscular injection of CD13(KO) MSCs in a model of severe ischemic limb injury resulted in significantly poorer perfusion, decreased ambulation, increased necrosis and impaired vascularization compared to those receiving WT MSCs.
+This study suggests that CD13 regulates FAK activation to promote MSC adhesion and migration, thus, contributing to MSC-mediated tissue repair.
+CD13 may present a viable target to enhance the efficacy of mesenchymal stem cell therapies.
+The renin-angiotensin-system (RAS) constitutes an important hormonal system in the physiological regulation of blood pressure.
+Indeed, dysregulation of the RAS may lead to the development of cardiovascular pathologies including kidney injury.
+Moreover, the blockade of this system by the inhibition of angiotensin converting enzyme (ACE) or antagonism of the angiotensin type 1 receptor (AT(1)R) constitutes an effective therapeutic regimen.
+It is now apparent with the identification of multiple components of the RAS that the system is comprised of different angiotensin peptides with diverse biological actions mediated by distinct receptor subtypes.
+The classic RAS can be defined as the ACE-Ang II-AT(1)R axis that promotes vasoconstriction, sodium retention, and other mechanisms to maintain blood pressure, as well as increased oxidative stress, fibrosis, cellular growth, and inflammation in pathological conditions.
+In contrast, the non-classical RAS composed of the ACE2-Ang-(1–7)-Mas receptor axis generally opposes the actions of a stimulated Ang II-AT(1)R axis through an increase in nitric oxide and prostaglandins and mediates vasodilation, natriuresis, diuresis, and oxidative stress.
+Thus, a reduced tone of the Ang-(1–7) system may contribute to these pathologies as well.
+Moreover, the non-classical RAS components may contribute to the effects of therapeutic blockade of the classical system to reduce blood pressure and attenuate various indices of renal injury.
+The review considers recent studies on the ACE2-Ang-(1–7)-Mas receptor axis regarding the precursor for Ang-(1–7), the intracellular expression and sex differences of this system, as well as an emerging role of the Ang1-(1–7) pathway in fetal programing events and cardiovascular dysfunction.
+Highly pathogenic avian influenza H5N1 (HPAI H5N1) viruses can infect mammals, including humans, causing severe systemic disease with the inhibition of the immune system and a high mortality rate.
+In conditions of lymphoid tissue depletion, the liver plays an important role in host defence against viruses.
+It has been shown that the virus persistence in the liver leads to the expression of proinflammatory cytokines (TNF-α, IL-6) and intracellular proteases (lysozyme, cathepsin D, and myeloperoxidase) by Kupffer cells.
+Defective antiviral response exacerbates destructive processes in the liver accelerating the development of liver failure.
+Reactive oxygen species (ROS) and reactive nitrogen species (RNS) produced by the oxidative burst in activated macrophages and neutrophils cause oxidative stressimplicated diseases.
+Quercetin is flavonoid that occurs naturally in plants and is widely used as a nutritional supplement due to its antioxidant and anti-inflammatory properties.
+In this study, we investigated antioxidant activities and mechanisms of action in zymosan-induced macrophages of quercetin and quercetin-related flavonoids such as quercitrin, isoquercitrin, quercetin 3-O-β-(2″-galloyl)-rhamnopyranoside (QGR) and quercetin 3-O-β-(2″-galloyl)-glucopyranoside (QGG) as well as gallic acid, a building moiety of QGR and QGG.
+QGR and QGG exhibited stronger antioxidant activities compared with quercetin, whereas quercitrin, isoquercitrin and gallic acid exhibited weak-tono antioxidant activities, assessed by 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging, superoxide production, superoxide scavenging, nitric oxide (NO) production, peroxynitrite (ONOO(−)) scavenging and myeloperoxidase (MPO) activity.
+Regarding mechanisms, the quercetincontaining flavonoids QGR and QGG differentially targeted compared with quercetin in the NF-κB signaling pathway that inhibited the DNA binding activity of the NF-κB complex without affecting the degradation and phosphorylation of IκBα and NF-κB phosphorylation.
+In addition, QGR and QGG inhibited CRE and activator protein (AP-1) transcriptional activity and JNK phosphorylation by inhibiting the cAMP/protein kinase A (PKA) and protein kinase C (PKC) signaling in a different manner than quercetin.
+Our results showed that although QGR and QGG exhibited stronger antioxidant activities than querce-tin in macrophages, their mechanisms of action in terms of the NF-κB, PKA and PKC signaling pathways were different.
+PQC is recognized for targeting the destruction of defective polypeptides, whereas regulated protein degradation mechanisms modulate the concentration of specific proteins in concert with physiological demands.
+For example, ion channel levels are physiologically regulated within tight limits, but a system-wide approach to define which degradative systems are involved is lacking.
+We focus on the Kir2.1 potassium channel because altered Kir2.1 levels lead to human disease and Kir2.1 restores growth on low-potassium medium in yeast mutated for endogenous potassium channels.
+Using this system, first we find that Kir2.1 is targeted for endoplasmic reticulum–associated degradation (ERAD).
+The most prominent gene family that emerges from this effort encodes members of endosomal sorting complex required for transport (ESCRT).
+ERAD and ESCRT also mediate Kir2.1 degradation in human cells, with ESCRT playing a more prominent role.
+BACKGROUND: Inflammation and remodeling of the small airways are major determinants of the progression and severity of COPD.
+The present study explored the correlation between sputum p38 mitogen-activated protein kinase (MAPK) activity and airway inflammation and reduction of lung function in the patients with chronic obstructive pulmonary disease (COPD).
+Sputum p38 MAPK activity was measured by Western blotting and sputum levels of CXCL8 and neutrophil, and lung function was measured.
+The correlation between p38MAPK activity and airway inflammation and reduction of lung function was analyzed.
+RESULT: Our results showed the significantly increased expression of phospho-p38 MAPK and CXCL8 in the sputum samples of the COPD patients.
+The p38 MAPK activity was remarkably correlated with the CXCL8 level and neutrophils infiltration in the airway, and the decline of lung function in the COPD patients.
+CONCLUSIONS: These findings suggest the pivotal role of p38 MAPK in the airway inflammation of COPD patients.
+BACKGROUND: Severe epidemics of enterovirus have occurred frequently in Malaysia, Singapore, Taiwan, Cambodia, and China, involving cases of pulmonary edema, hemorrhage and encephalitis, and an effective vaccine has not been available.
+The specific aim of this study was to understand the epidemiological characteristics of mild and severe enterovirus cases through integrated surveillance data.
+METHODS: All enterovirus cases in Taiwan over almost ten years from three main databases, including national notifiable diseases surveillance, sentinel physician surveillance and laboratory surveillance programs from July 1, 1999 to December 31, 2008 were analyzed.
+The Pearson’s correlation coefficient was applied for measuring the consistency of the trends in the cases between different surveillance systems.
+Cross correlation analysis in a time series model was applied for examining the capability to predict severe enterovirus infections.
+Poisson temporal, spatial and space-time scan statistics were used for identifying the most likely clusters of severe enterovirus outbreaks.
+The directional distribution method with two standard deviations of ellipse was applied to measure the size and the movement of the epidemic.
+RESULTS: The secular trend showed that the number of severe EV cases peaked in 2008, and the number of mild EV cases was significantly correlated with that of severe ones occurring in the same week [r = 0.553, p < 0.01].
+These severe EV cases showed significantly higher association with the weekly positive isolation rates of EV-71 than the mild cases [severe: 0.498, p < 0.01 vs. mild: 0.278, p < 0.01].
+In a time series model, the increase of mild EV cases was the significant predictor for the occurrence of severe EV cases.
+The directional distribution showed that both the mild and severe EV cases spread extensively during the peak.
+Before the detected spatio-temporal clusters in June 2008, the mild cases had begun to rise since May 2008, and the outbreak spread from south to north.
+CONCLUSIONS: Local public health professionals can monitor the temporal and spatial trends plus spatio-temporal clusters and isolation rate of EV-71 in mild and severe EV cases in a community when virus transmission is high, to provide early warning signals and to prevent subsequent severe epidemics.
+All TB deaths were classified into 2 groups (TB-related and non-TB-related), based on the underlying cause of death.
+The overall mortality rate was 12.3% (249 cases) and the mean age at death was 74 years; 17.3% (43 cases) of all TB deaths were TB-related.
+Most of the TB-related deaths occurred early (median survival: 20 days), and the patient died of septic shock.
+Malignancy, liver cirrhosis, renal failure, and miliary and pneumonic radiographic patterns were all independent predictors for all TB deaths.
+Managing TB as well as underlying comorbidities in a multidisciplinary approach is essential to improve the outcome of patients in an aging population.
+However, the clinical manifestations of patients with TB-related death vary; many progressed to fulminant septic shock requiring timely recognition with prompt treatment to prevent early death.
+The previous SARS outbreak in this country was accompanied by contradictory information, while worries about wide-spread influenza led to discrimination worldwide.
+Early understanding of public threat perceptions is therefore important for effective public health communication and intervention.
+Questions examined risk awareness and media use, beliefs about the emergence of the threat and those most at risk, anxiety about infection and preventive and avoidant behaviours.
+RESULTS: Results demonstrate moderate levels of anxiety but relatively high levels of trust towards government officials.
+Threat emergence was associated with hygiene levels, temperature change, floating pigs in the Huangpu River and migration to the city.
+CONCLUSIONS: Comparatively high levels of trust in Chinese government advice about H7N9 contrast positively with previous pandemic communications in China.
+Anxiety helped drive both recommended and non-recommended behaviours, with potentially important economic and social implications.
+However, the detail mechanism by which LPS contributes to the development of lung fibrosis is not clearly understood.
+To investigate the role of phosphatase and tensin homolog (PTEN), a PI3-K pathway suppressor, on LPS-induced lung fibroblast proliferation, differentiation, collagen secretion and activation of PI3-K, we transfected PTEN overexpression lentivirus into cultured mouse lung fibroblasts with or without LPS treatment to evaluate proliferation by MTT and Flow cytometry assays.
+Expression of PTEN, alpha-smooth muscle actin (alpha-SMA), glycogen synthase kinase 3 beta (GSK3beta) and phosphorylation of Akt were determined by Western-blot or real-time RT-PCR assays.
+The content of C-terminal propeptide of type I procollagen (PICP) in cell culture supernatants was examined by ELISA.
+RESULTS: We found that overexpression of PTEN effectively increased expression and phosphatase activity of PTEN, and concomitantly inhibited LPS-induced fibroblast proliferation, differentiation and collagen secretion.
+Phosphorylation of Akt and GSK3beta protein expression levels in the LPS-induced PTEN overexpression transfected cells were significantly lower than those in the LPS-induced non-transfected cells, which can be reversed by the PTEN inhibitor, bpV(phen).
+CONCLUSIONS: Collectively, our results show that overexpression and induced phosphatase activity of PTEN inhibits LPS-induced lung fibroblast proliferation, differentiation and collagen secretion through inactivation of PI3-K-Akt-GSK3beta signaling pathways, which can be abrogated by a selective PTEN inhibitor.
+Thus, expression and phosphatase activity of PTEN could be a potential therapeutic target for LPS-induced pulmonary fibrosis.
+Compared with PTEN expression level, phosphatase activity of PTEN is more crucial in affecting lung fibroblast proliferation, differentiation and collagen secretion.
+We have previously isolated several IgG rheumatoid factors (RFs) from patients with both rheumatoid arthritis and idiopathic thrombocytopenia purpura using phage display system.
+To study IgG RFs in patients with other autoimmune diseases, phage display antibody libraries from a hepatitis C virus infected patient with Sjögren's syndrome were constructed.
+The binding activity and specificity of RFL11 to IgG Fc fragment were comparable to those of RFs previously isolated.
+The analysis with existed RF-Fc complex structures indicated the homology model of RFL11 is similar to IgM RF61 complex with high binding affinity of about 6 × 10(−8) M. This effect resulted from longer complementarity-determining region (CDR) combining key somatic mutations.
+In the RFL11-Fc interfaces, the CDR-H3 loop forms a finger-like structure extending into the bottom of Fc pocket and resulting in strong ion and cation-pi interactions.
+Moreover, a process of antigen-driven maturation was proven by somatically mutated VH residues on H2 and H3 CDR loops in the interfaces.
+Taken together, these results suggested that high affinity IgG RFs can be generated in patients with Sjögren's syndrome and may play an important role in the pathogenesis of this autoimmune disease.
+Angiotensin-converting enzyme 2 (ACE2) is highly expressed in the kidney proximal tubule, where it cleaves angiotensin (Ang) II to Ang-(1-7).
+Urinary ACE2 levels increase in diabetes, suggesting that ACE2 may be shed from tubular cells.
+The aim of this study was to determine if ACE2 is shed from proximal tubular cells, to characterize ACE2 fragments, and to study pathways for shedding.
+Studies involved primary cultures of mouse proximal tubular cells, with ACE2 activity measured using a synthetic substrate, and analysis of ACE2 fragments by immunoblots and mass spectrometry.
+The culture media from mouse proximal tubular cells demonstrated a time-dependent increase in ACE2 activity, suggesting constitutive ACE2 shedding.
+ACE2 was detected in media as two bands at ∼90 kDa and ∼70 kDa on immunoblots.
+By contrast, full-length ACE2 appeared at ∼100 kDa in cell lysates or mouse kidney cortex.
+Mass spectrometry of the two deglycosylated fragments identified peptides matching mouse ACE2 at positions 18-706 and 18-577, respectively.
+The C-terminus of the 18-706 peptide fragment contained a non-tryptic site, suggesting that Met(706) is a candidate ACE2 cleavage site.
+Incubation of cells in high D-glucose (25 mM) (and to a lesser extent Ang II) for 48–72 h increased ACE2 activity in the media (p<0.001), an effect blocked by inhibition of a disintegrin and metalloproteinase (ADAM)17.
+These data indicate that two glycosylated ACE2 fragments are constitutively shed from mouse proximal tubular cells.
+The results suggest that proximal tubular shedding of ACE2 may increase in diabetes, which could enhance degradation of Ang II in the tubular lumen, and increase levels of Ang-(1-7).
+BACKGROUND: Peste des petits ruminants (PPR) is an economically important disease of small ruminants such as sheep and goats.
+The disease is characterized by severe pyrexia, oculo-nasal discharge, pneumonia, necrosis and ulceration of the mucous membrane and inflammation of the gastro-intestinal tract leading to severe diarrhea.
+A SYBR Green I based real time RT-PCR targeting the N gene of PPRV has not been established for PPRV detection.
+Thus, the objective of present study was to develop highly sensitive N gene target SYBR Green I real time RT-PCR for specific detection and quantification of PPRV in clinical samples.
+RESULTS: The assay exhibited high specificity as all the viruses which have clinical and structural similarities to PPRV including Canine distemper virus (CDV), Measles virus (MV), Bluetongue virus (BTV) and Newcastle disease virus (NDV) failed to show an amplification signal.
+The lower detection limit of the assay was 5.11 copies/μl (Ct value of 33.67 ± 0.5) and 0.001 TCID(50)/ml (Ct value of 34.7 ± 0.5) based on plasmid copy number and tissue culture infectivity titre.
+The coefficient of variation (CV) values for intra- and inter-assay variability were low, ranging from 0.32% - 2.31%, and 0.71% - 5.32%, respectively.
+To evaluate the performance of the newly developed assay, a total of 36 clinical samples suspected of PPR were screened for the presence of PPRV in parallel with conventional RT-PCR.
+The real time RT-PCR assay detected PPRV in 30 (83.3%) of clinical samples compared to 16 (44.4%) by conventional RT-PCR.
+CONCLUSIONS: The two-step SYBR Green I based real time RT-PCR assay reported here is highly sensitive, specific, reproducible and rapid for detection and quantification of PPRV nucleic acids.
+To gain insights into the pathogenesis of influenza A virus (IAV) infections, this study focused on characterizing the inflammatory network and identifying key proteins by combining high-throughput data and computational techniques.
+We constructed the cell-specific normal and inflammatory networks for H5N1 and H1N1 infections through integrating high-throughput data.
+We demonstrated that better discrimination between normal and inflammatory networks by network entropy than by other topological metrics.
+Moreover, we identified different dynamical interactions among TLR2, IL-1β, IL10 and NFκB between normal and inflammatory networks using optimization algorithm.
+Furthermore, we identified a complex, TNFSF10/HDAC4/HDAC5, which may play important roles in controlling inflammation, and demonstrated that changes in network entropy of this complex negatively correlated to those of three proteins: TNFα, NFκB and COX-2.
+These findings provide significant hypotheses for further exploring the molecular mechanisms of infectious diseases and developing control strategies.
+Hepatitis B virus (HBV) reactivation and recurrence are common in patients under immunosuppression and can be controlled by hepatitis B immunoglobulin, antivirals, and hepatitis B vaccine.
+However, the detailed analysis of HBV infection under immunosuppression is essential for the prophylaxis and therapy for HBV reactivation and recurrence.
+In this study, HBV replication and T cell responses were analyzed in a HBV-transfected mouse model under immunosuppressive therapy.
+During the treatment, HBV replication was at a high level in mice treated with dexamethasone, cyclosporine, and cyclophosphamide, whereas was terminated in mice treated with mycophenolate mofetil.
+After the withdrawal, HBV replication was at low or high levels in the dexamethasone-treated mice or in both cyclosporine- and cyclophosphamide-treated mice.
+The early withdrawal of cyclosporine allowed the recovery of suppressed T cell responses and led to subsequent HBV clearance, while the adoptive immune transfer to the mice with HBV persistence led to HBV suppression.
+Taken together, long-term HBV persistence under immunosuppression depends on the immunosuppressive drugs used and on the treatment duration and is mediated by the suppressed intrahepatic CD8 T cell response.
+These data may be helpful for individualized immunosuppressive therapy in patients with high risk of HBV reactivation and recurrence, and the mouse system is suitable for studying HBV reactivation and recurrence under immunosuppression.
+Here, we establish that the antimycotic heptaen, amphotericin B (AmphoB), prevents IFITM3-mediated restriction of IAV, thereby increasing viral replication.
+Consistent with its neutralization of IFITM3, a clinical preparation of AmphoB, AmBisome, reduces the majority of interferon’s protective effect against IAV in vitro.
+Mechanistic studies reveal that IFITM1 decreases host-membrane fluidity, suggesting both a possible mechanism for IFITM-mediated restriction and its negation by AmphoB.
+Notably, we reveal that mice treated with AmBisome succumbed to a normally mild IAV infection, similar to animals deficient in Ifitm3.
+Therefore, patients receiving antifungal therapy with clinical preparations of AmphoB may be functionally immunocompromised and thus more vulnerable to influenza, as well as other IFITM3-restricted viral infections.
+It is well established that RNA viruses exhibit higher rates of spontaneous mutation than DNA viruses and microorganisms.
+However, their mutation rates vary amply, from 10(−6) to 10(−4) substitutions per nucleotide per round of copying (s/n/r) and the causes of this variability remain poorly understood.
+In addition to differences in intrinsic fidelity or error correction capability, viral mutation rates may be dependent on host factors.
+Here, we assessed the effect of the cellular environment on the rate of spontaneous mutation of the vesicular stomatitis virus (VSV), which has a broad host range and cell tropism.
+Luria-Delbrück fluctuation tests and sequencing showed that VSV mutated similarly in baby hamster kidney, murine embryonic fibroblasts, colon cancer, and neuroblastoma cells (approx.
+Cell immortalization through p53 inactivation and oxygen levels (1–21%) did not have a significant impact on viral replication fidelity.
+This shows that previously published mutation rates can be considered reliable despite being based on a narrow and artificial set of laboratory conditions.
+Interestingly, we also found that VSV mutated approximately four times more slowly in various insect cells compared with mammalian cells.
+This may contribute to explaining the relatively slow evolution of VSV and other arthropod-borne viruses in nature.
+It has been suggested that resting of PBMC after thawing, that is, culturing them overnight in test medium, produces higher antigen-induced spot counts in ELISPOT assays.
+To evaluate the importance of overnight resting, we systematically tested cryopreserved PBMC from 25 healthy donors.
+CEF peptides (comprising CMV, EBV and flu antigens) were used to stimulate CD8 cells and mumps antigen to stimulate CD4 cells.
+The data show that resting significantly increased antigen-elicited T cell responses only for CEF high responder PBMC.
+For CEF low responders, and for mumps responders of either low- or high reactivity levels, resting had no statistically significant effect on the observed spot counts.
+Therefore, resting is not a generally applicable approach to improve ELISPOT assay performance, but can be recommended only for clinical subject cohorts and antigens for which it has a proven benefit.
+Because resting invariably leads to losing about half of the PBMC available for testing, and because doubling the PBMC numbers plated into the assay reliably doubles the antigen-induced spot counts, we suggest the latter approach as a simple and reliable alternative to resting for enhancing the performance of ELISPOT assays.
+Our data imply that resting is not required if PBMC were cryopreserved and thawed under conditions that minimize apoptosis of the cells.
+Therefore, this study should draw attention to the need to optimize freezing and thawing conditions for successful T cell work.
+This process is activated above basal levels upon cell intrinsic or environmental stress and dysregulation of autophagy has been linked to various human diseases, including those caused by viral infection.
+Many viruses have evolved strategies to directly interfere with autophagy, presumably to facilitate their replication or to escape immune detection.
+However, in some cases, modulation of autophagy appears to be a consequence of the virus disturbing the cell’s metabolic signaling networks.
+Here, we summarize recent advances in research at the interface of autophagy and viral infection, paying special attention to strategies that human tumor viruses have evolved.
+OBJECTIVE: Sepsis is an inflammatory syndrome caused by infection, and both its incidence and mortality are high.
+Because interferon-gamma (IFN-γ) plays an important role in inflammation, this work assessed IFN-γ single nucleotide polymorphism (SNPs) that may be associated with sepsis.
+METHODS: A total of 196 patients with pneumonia-induced sepsis and 213 age- and sex-matched healthy volunteers participated in our study from July 2012 to July 2013 in Guangzhou, China.
+Clinical pathology was assessed in subgroups defined based on clinical criteria, APACHE II (acute physiology and chronic health evaluation) and SOFA (sepsis-related organ failure assessment) scores and discharge rate.
+Four functional SNPs, −1616T/C (rs2069705), −764G/C (rs2069707), +874A/T (rs2430561) and +3234C/T (rs2069718), were genotyped by Snapshot in both sepsis patients and healthy controls.
+Pearson’s chi-square test or Fisher’s exact test were used to analyze the distribution of the SNPs, and the probability values (P values), odds ratios (OR) and 95% confidence intervals (CIs) were calculated.
+RESULTS: No mutations in the IFN-γ −764G/C SNP were detected among the participants in our study.
+The −1616 TC+TT, +874 AT+AA genotype and the TAC haplotype were significantly associated with sepsis susceptibility, while the CTT haplotype was associated with protection against sepsis incidence.
+Genotype of −1616 TT wasn’t only protective against severity of sepsis, but also against higher APACHE II and SOFA scores as +874 AA and +3234 CC.
+CONCLUSION: Our results suggest that functional IFN-γ SNPs and their haplotypes are associated with pneumonia-induced sepsis.
+BACKGROUND: The aim of this study is to give a description of the road traffic injuries (RTIs) characteristics of floating migrant population by comparing with those of local residents in a harbor city of China.
+METHODS: A population-based descriptive study was carried out between 2007 and 2010 with RTI patient records from the Fifth Center Hospital of Tianjin.
+Inpatient diagnoses of RTI patients were defined using the International Classification of Diseases, Tenth Revision (ICD-10) codes.
+We analyzed the demographics and general characteristics of RTI patients that were in the hospital during the four years.
+In order to compare the group differences between local resident patients and floating migrant patients, the distribution of their ages, diagnoses, severity of injuries, duration of inpatient stays, hospitalization cost were analyzed.
+RESULTS: People between the ages of 16 and 55 were the most likely to suffer RTIs.
+The floating migrant patients between the ages of 16 and 45 had a higher incidence of accidents, while local resident patients between 46 and 55 had a higher incidence of accidents.
+Compared to local resident patients, floating migrant patients were more vulnerable to open injuries and severe traffic injuries.
+With the severity of injuries ranked from mild to severe, floating migrant patients had lower duration of inpatient stay, but higher hospitalization costs compared to local resident patients.
+CONCLUSIONS: Floating migrant patients had a different age distribution, severity of injuries, diseases, inpatient duration and hospitalization cost compared with local resident patients.
+Compared to local resident patients, floating migrants had a higher risk to RTIs and were more vulnerable to severer traffic accidents at lower ages.
+Surface disinfectants are part of broader preventive strategies preventing the transmission of bacteria, fungi and viruses in medical institutions.
+To evaluate their virucidal efficacy, these products must be tested with appropriate model viruses with different physico-chemical properties under conditions representing practical application in hospitals.
+Furthermore, different putative model viruses like adenovirus type 5 (AdV-5) and different animal parvoviruses were evaluated with respect to their tenacity and practicability in laboratory handling.
+To evaluate the robustness of the method, some of the viruses were tested in parallel in different laboratories in a multi-center study.
+Different biocides, which are common active ingredients of surface disinfectants, were used in the test.
+After drying on stainless steel discs as the carrier, model viruses were exposed to different concentrations of three alcohols, peracetic acid (PAA) or glutaraldehyde (GDA), with a fixed exposure time of 5 minutes.
+All parvoviruses exhibited a similar stability with respect to GDA, while AdV-5 was more susceptible.
+For PAA, the porcine parvovirus was more sensitive than the other parvoviruses, and again, AdV-5 presented a higher susceptibility than the parvoviruses.
+All parvoviruses were resistant to alcohols, while AdV-5 was only stable when treated with 2-propanol.
+The analysis of the results of the multi-center study showed a high reproducibility of this test system.
+In conclusion, two viruses with different physico-chemical properties can be recommended as appropriate model viruses for the evaluation of the virucidal efficacy of surface disinfectants: AdV-5, which has a high clinical impact, and murine parvovirus (MVM) with the highest practicability among the parvoviruses tested.
+During spring-summer 2009, several observational studies from Canada showed increased risk of medically-attended, laboratory-confirmed A(H1N1)pdm09 illness among prior recipients of 2008–09 trivalent inactivated influenza vaccine (TIV).
+In a randomized placebo-controlled ferret study, we tested whether prior receipt of 2008–09 TIV may have directly influenced A(H1N1)pdm09 illness.
+Thirty-two ferrets (16/group) received 0.5 mL intra-muscular injections of the Canadian-manufactured, commercially-available, non-adjuvanted, split 2008–09 Fluviral or PBS placebo on days 0 and 28.
+Four ferrets per group were randomly selected for sacrifice at day 5 post-challenge (Ch+5) and the rest followed until Ch+14.
+Sera were tested for antibody to vaccine antigens and A(H1N1)pdm09 by hemagglutination inhibition (HI), microneutralization (MN), nucleoprotein-based ELISA and HA1-based microarray assays.
+Clinical characteristics and nasal virus titers were recorded pre-challenge then post-challenge until sacrifice when lung virus titers, cytokines and inflammatory scores were determined.
+Antibody rise to vaccine antigens was evident by ELISA and HA1-based microarray but not by HI or MN assays; virus challenge raised antibody to A(H1N1)pdm09 by all assays in both groups.
+Beginning at Ch+2, vaccinated animals experienced greater loss of appetite and weight than placebo animals, reaching the greatest between-group difference in weight loss relative to baseline at Ch+5 (7.4% vs. 5.2%; p = 0.01).
+At Ch+5 vaccinated animals had higher lung virus titers (log-mean 4.96 vs. 4.23pfu/mL, respectively; p = 0.01), lung inflammatory scores (5.8 vs. 2.1, respectively; p = 0.051) and cytokine levels (p>0.05).
+While they cannot be considered conclusive to explain human observations, these ferret findings are consistent with direct, adverse effect of prior 2008–09 TIV receipt on A(H1N1)pdm09 illness.
+Since there is no causative treatment of SIV, we tested if probiotic Enterococcus (E.) faecium NCIMB 10415 or zinc (Zn) oxide as feed supplements provide beneficial effects upon SIV infection in piglets.
+Seventy-two weaned piglets were fed three different diets containing either E. faecium or different levels of Zn (2500 ppm, Zn(high); 50 ppm, Zn(low)).
+Half of the piglets were vaccinated intramuscularly (VAC) twice with an inactivated trivalent SIV vaccine, while all piglets were then infected intranasally with H3N2 SIV.
+Significantly higher weekly weight gains were observed in the E. faecium group before virus infection, and piglets in Zn(high) and E. faecium groups gained weight after infection while those in the control group (Zn(low)) lost weight.
+Using ELISA, we found significantly higher H3N2-specific antibody levels in the E. faecium+VAC group 2 days before and at the day of challenge infection as well as at 4 and 6 days after challenge infection.
+Higher hemagglutination inhibition (HI) titers were also observed in the Zn(high)+VAC and E. faecium+VAC groups at 0, 1 and 4 days after infection.
+However, there were no significant differences in virus shedding and lung lesions between the dietary groups.
+Using flow cytometry analysis significantly higher activated T helper cells and cytotoxic T lymphocyte percentages in the PBMCs were detected in the Zn(high) and E. faecium groups at single time points after infection compared to the Zn(low) control group, but no prolonged effect was found.
+In the BAL cells no influence of dietary supplementation on immune cell percentages could be detected.
+Our results suggest that feeding high doses of zinc oxide and particularly E. faecium could beneficially influence humoral immune responses after vaccination and recovery from SIV infection, but not affect virus shedding and lung pathology.
+BACKGROUND: A key goal for HIV-1 envelope immunogen design is the induction of cross-reactive neutralizing antibodies (nAbs).
+As AIDS vaccine recipients will not be exposed to strains exactly matching any immunogens due to multiple HIV-1 quasispecies circulating in the human population worldwide, heterologous SHIV challenges are essential for realistic vaccine efficacy testing in primates.
+We assessed whether polyclonal IgG, isolated from rhesus monkeys (RMs) with high-titer nAbs (termed SHIVIG), could protect RMs against the R5-tropic tier-2 SHIV-2873Nip, which was heterologous to the viruses or HIV-1 envelopes that had elicited SHIVIG.
+RESULTS: SHIVIG demonstrated binding to HIV Gag, Tat, and Env of different clades and competed with the broadly neutralizing antibodies b12, VRC01, 4E10, and 17b.
+Although SHIVIG neutralized SHIV-2873Nip in vitro, this polyclonal IgG preparation failed to prevent acquisition after repeated intrarectal low-dose virus challenges, but at a dose of 400 mg/kg, it significantly lowered peak viremia (P = 0.001).
+Unexpectedly, single-genome analysis revealed a higher number of transmitted variants at the low dose of 25 mg/kg, implying increased acquisition at low SHIVIG levels.
+In vitro, SHIVIG demonstrated complement-mediated Ab-dependent enhancement of infection (C’-ADE) at concentrations similar to those observed in plasmas of RMs treated with 25 mg/kg of SHIVIG.
+CONCLUSION: Our primate model data suggest a dual role for polyclonal anti-HIV-1 Abs depending on plasma levels upon virus encounter.
+A profound understanding of the viral population in key animal species acting as reservoirs represents an important step towards this goal.
+Bats harbor diverse viruses, some of which are of particular interest because they cause severe human diseases.
+However, little is known about the diversity of the global population of viruses found in bats (virome).
+We determined the viral diversity of five different French insectivorous bat species (nine specimens in total) in close contact with humans.
+Sequence-independent amplification, high-throughput sequencing with Illumina technology and a dedicated bioinformatics analysis pipeline were used on pooled tissues (brain, liver and lungs).
+Comparisons of the sequences of contigs and unassembled reads provided a global taxonomic distribution of virus-related sequences for each sample, highlighting differences both within and between bat species.
+Many viral families were present in these viromes, including viruses known to infect bacteria, plants/fungi, insects or vertebrates, the most relevant being those infecting mammals (Retroviridae, Herpesviridae, Bunyaviridae, Poxviridae, Flaviviridae, Reoviridae, Bornaviridae, Picobirnaviridae).
+In particular, we detected several new mammalian viruses, including rotaviruses, gammaretroviruses, bornaviruses and bunyaviruses with the identification of the first bat nairovirus.
+These observations demonstrate that bats naturally harbor viruses from many different families, most of which infect mammals.
+They may therefore constitute a major reservoir of viral diversity that should be analyzed carefully, to determine the role played by bats in the spread of zoonotic viral infections.
+White plague (WP)-like diseases of tropical corals are implicated in reef decline worldwide, although their etiological cause is generally unknown.
+Studies thus far have focused on bacterial or eukaryotic pathogens as the source of these diseases; no studies have examined the role of viruses.
+Using a combination of transmission electron microscopy (TEM) and 454 pyrosequencing, we compared 24 viral metagenomes generated from Montastraea annularis corals showing signs of WP-like disease and/or bleaching, control conspecific corals, and adjacent seawater.
+No bacteria were visually identified within diseased coral tissues, but viral particles and sequence similarities to eukaryotic circular Rep-encoding single-stranded DNA viruses and their associated satellites (SCSDVs) were abundant in WP diseased tissues.
+In contrast, sequence similarities to SCSDVs were not found in any healthy coral tissues, suggesting SCSDVs might have a role in WP disease.
+Furthermore, Herpesviridae gene signatures dominated healthy tissues, corroborating reports that herpes-like viruses infect all corals.
+Nucleocytoplasmic large DNA virus (NCLDV) sequences, similar to those recently identified in cultures of Symbiodinium (the algal symbionts of corals), were most common in bleached corals.
+This finding further implicates that these NCLDV viruses may have a role in bleaching, as suggested in previous studies.
+This study determined that a specific group of viruses is associated with diseased Caribbean corals and highlights the potential for viral disease in regional coral reef decline.
+A 23-year-old healthy male volunteer took part in a clinical trial in which the volunteer took chloroquine chemoprophylaxis and received three intradermal doses at four-week intervals of aseptic, purified Plasmodium falciparum sporozoites to induce protective immunity against malaria.
+Fifty-nine days after the last administration of sporozoites and 32 days after the last dose of chloroquine the volunteer underwent controlled human malaria infection (CHMI) by the bites of five P. falciparum-infected mosquitoes.
+Eleven days post-CHMI a thick blood smear was positive (6 P. falciparum/μL blood) and treatment was initiated with atovaquone/proguanil (Malarone®).
+On the second day of treatment, day 12 post-CHMI, troponin T, a marker for cardiac tissue damage, began to rise above normal, and reached a maximum of 1,115 ng/L (upper range of normal = 14 ng/L) on day 16 post-CHMI.
+The volunteer had one ~20 minute episode of retrosternal chest pain and heavy feeling in his left arm on day 14 post-CHMI.
+ECG at the time revealed minor repolarization disturbances, and cardiac MRI demonstrated focal areas of subepicardial and midwall delayed enhancement of the left ventricle with some oedema and hypokinesia.
+Troponin T levels were normal within 16 days and the volunteer recovered without clinical sequelae.
+Follow-up cardiac MRI at almost five months showed normal function of both ventricles and disappearance of oedema.
+With the exception of a throat swab that was positive for rhinovirus on day 14 post-CHMI, no other tests for potential aetiologies of the myocarditis were positive.
+A number of possible aetiological factors may explain or have contributed to this case of myocarditis including, i) P. falciparum infection, ii) rhinovirus infection, iii) unidentified pathogens, iv) hyper-immunization (the volunteer received six travel vaccines between the last immunization and the CHMI), v) atovaquone/proguanil treatment, or vi) a combination of these factors.
+Though normally feeding as single cells, nutrient stress triggers the collection of amoebas into colonies that form delicately shaped fruiting structures in which the cells differentiate into spores and up to three cell types to support the spore mass.
+Cyclic adenosine monophosphate (cAMP) plays a very dominant role in controlling morphogenesis and cell differentiation in the model species Dictyostelium discoideum.
+Secreted cAMP also controls gene expression at different developmental stages, while intracellular cAMP is extensively used to transduce the effect of other stimuli that control the developmental program.
+In this review, I present an overview of the different roles of cAMP in the model D. discoideum and I summarize studies aimed to resolve how these roles emerged during Dictyostelid evolution.
+The study analyses the role of long-distance travel behaviours on the large-scale spatial spreading of directly transmitted infectious diseases, focusing on two different travel types in terms of the travellers travelling to a specific group or not.
+For this purpose, we have formulated and analysed a metapopulation model in which the individuals in each subpopulation are organised into a scale-free contact network.
+The long-distance travellers between the subpopulations will temporarily change the network structure of the destination subpopulation through the “merging effects (MEs),��� which indicates that the travellers will be regarded as either connected components or isolated nodes in the contact network.
+The results show that the presence of the MEs has constantly accelerated the transmission of the diseases and aggravated the outbreaks compared to the scenario in which the diversity of the long-distance travel types is arbitrarily discarded.
+Sensitivity analyses show that these results are relatively constant regarding a wide range variation of several model parameters.
+Our study has highlighted several important causes which could significantly affect the spatiotemporal disease dynamics neglected by the present studies.
+The genome sequences of new viruses often contain many “orphan” or “taxon-specific” proteins apparently lacking homologs.
+However, because viral proteins evolve very fast, commonly used sequence similarity detection methods such as BLAST may overlook homologs.
+We analyzed a data set of proteins from RNA viruses characterized as “genus specific” by BLAST.
+More powerful methods developed recently, such as HHblits or HHpred (available through web-based, user-friendly interfaces), could detect distant homologs of a quarter of these proteins, suggesting that these methods should be used to annotate viral genomes.
+In-depth manual analyses of a subset of the remaining sequences, guided by contextual information such as taxonomy, gene order, or domain cooccurrence, identified distant homologs of another third.
+Thus, a combination of powerful automated methods and manual analyses can uncover distant homologs of many proteins thought to be orphans.
+We expect these methodological results to be also applicable to cellular organisms, since they generally evolve much more slowly than RNA viruses.
+As an application, we reanalyzed the genome of a bee pathogen, Chronic bee paralysis virus (CBPV).
+We could identify homologs of most of its proteins thought to be orphans; in each case, identifying homologs provided functional clues.
+We discovered that CBPV encodes a domain homologous to the Alphavirus methyltransferase-guanylyltransferase; a putative membrane protein, SP24, with homologs in unrelated insect viruses and insect-transmitted plant viruses having different morphologies (cileviruses, higreviruses, blunerviruses, negeviruses); and a putative virion glycoprotein, ORF2, also found in negeviruses.
+When bound to the envelope of viruses, factor H (FH), a soluble regulator of complement activation, contributes to the protection against a potent immune defense mechanism, the complement-mediated lysis (CML).
+For a proof of concept, we developed a construct consisting of recombinant bifunctional single-chain variable fragment (scFv) based on a monoclonal antibody against Friend murine leukemia virus (F-MuLV) envelope protein gp70, which was coupled to specific binding domains (short consensus repeats 19-20; SCR1920) of FH.
+We used Pichia pastoris as expression system in common shake flasks and optimized expression in high density bench top fermentation.
+The recombinant scFv-SCR significantly enhanced CML of F-MuLV in vitro implying that FH binding to the viral surface was impaired by the scFv-SCR.
+A few studies have emerged on epidemiology of multidrug resistant organisms in tertiary care settings in the Arabian Gulf.
+To describe the epidemiology of multi-drug resistant organisms (MDRO) at Sultan Qaboos University Hospital, a tertiary hospital in Oman.
+A retrospective review of MDRO records has been conducted throughout the period from January 2012 till December 2012.
+Organisms were identified and tested by an automated identification and susceptibility system, and the antibiotic susceptibility testing was confirmed by the disk diffusion method.
+Out of the total of 29,245 admissions, there have been 315 patients registered as MDRO patients giving an overall prevalence rate of 10.8 (95% CI 9.3, 12.4) MDRO cases per 1000 admissions.
+In addition, the prevalence rate of MDRO isolates was 11.2 (95% CI 9.7, 12.9) per 1000 admissions.
+Overall, increasing trends in prevalence rates of MDRO patients and MDRO isolates were observed throughout the study period.
+Continuous monitoring of antimicrobial susceptibility and strict adherence to infection prevention guidelines are essential to prevent proliferation of MDRO.
+BACKGROUND: China's one-child-per-couple policy, introduced in 1979, led to profound demographic changes for nearly a quarter of the world's population.
+Several decades later, the consequences include decreased fertility rates, population aging, decreased household sizes, changes in family structure, and imbalanced sex ratios.
+The epidemiology of communicable diseases may have been affected by these changes since the transmission dynamics of infectious diseases depend on demographic characteristics of the population.
+Of particular interest is influenza because China and Southeast Asia lie at the center of a global transmission network of influenza.
+Is it possible that the pronounced demographic changes that have occurred in China have affected influenza transmission?
+METHODS AND FINDINGS: To address this question, we developed a continuous-time, stochastic, individual-based simulation model for influenza transmission.
+With this model, we simulated 30 years of influenza transmission and compared influenza transmission rates in populations with and without the one-child policy control.
+We found that the average annual attack rate is reduced by 6.08% (SD 2.21%) in the presence of the one-child policy compared to a population in which no demographic changes occurred.
+There was no discernible difference in the secondary attack rate, −0.15% (SD 1.85%), between the populations with and without a one-child policy.
+We also forecasted influenza transmission over a ten-year time period in a population with a two-child policy under a hypothesis that a two-child-per-couple policy will be carried out in 2015, and found a negligible difference in the average annual attack rate compared to the population with the one-child policy.
+CONCLUSIONS: This study found that the average annual attack rate is slightly lowered in a population with a one-child policy, which may have resulted from a decrease in household size and the proportion of children in the population.
+Since late 2010, the outbreak of porcine epidemic diarrhea (PED) in China has resulted in the deaths of millions of suckling piglets.
+In this study, partial spike (S), ORF3, and membrane (M) genes amplified from these variants were sequenced and analyzed.
+The results showed that the variants could be clustered into one to three subgroups and suggested that S genes were variable, while M genes were relatively conserved.
+Moreover, in comparison with the vaccine strain CV777, sequence alignment analyses revealed that the S genes of the newly isolated strains contained several mutations at the aa level.
+It is possible that these mutations have changed the hydrophobicity of the S protein and influenced the viral antigenicity and virulence.
+Interestingly, homology analyses based on ORF3 demonstrated that the isolates had an intact opening reading frame (ORF), which were different from the attenuated DR13 strain.
+Additionally, the high degree of variation in the genes, particularly S genes, might provide an explanation for the poor immunity and rapid spread of the disease.
+These unique motifs have been extensively studied on the DNA level; however, exploration of the biological roles of G4s at the RNA level is just emerging.
+Here we show that G4 RNA when introduced within coding regions are capable of stimulating −1 ribosomal frameshifting (−1 FS) in vitro and in cultured cells.
+Systematic manipulation of the loop length between each G-tract revealed that the −1 FS efficiency positively correlates with G4 stability.
+Further, we demonstrated that the G4s can stimulate +1 FS and stop codon readthrough as well.
+BACKGROUND: We surveyed the emergency medical system (EMS) in Taiwan to provide information to policymakers responsible for decisions regarding the redistribution of national medical resources.
+METHODS: A systematic sampling method was used to randomly sample a representative database from the National Health Insurance (NHI) database in Taiwan, during the period from 2000 to 2004.
+RESULTS: We identified 10,124, 10,408, 11,209, 10,686, and 11,914 emergency room visits in 2000, 2001, 2002, 2003, and 2004, respectively.
+There were more males than females, and the majority of adults were younger than 50 years.
+Diagnose of injury/poisoning was the most frequently noted diagnostic category in emergency departments (EDs) in Taiwan.
+There were 13,196 (24.3%) and 2,952 (5.4%) patients with 2 and 3 concomitant diagnoses, respectively.
+There was a significant association between advanced age and the existence of multiple diagnoses (P < 0.001).
+With the exception of the ill-defined symptoms/signs/conditions, the two most frequent diagnoses were diseases of the circulatory system and diseases of the respiratory system in patients aged 65 years or older.
+On average, treatment-associated expenditure and drug-associated expenditure in Taiwan EDs averaged NT$1,155 ($35.0) and NT$190 ($5.8), respectively, which was equal to 64.5% and 10.6% of the total ED-associated cost.
+General ED medical expenditure increased with patient age; the increased cost ratio due to age was estimated at 8% per year (P < 0.001).
+CONCLUSIONS: The frequency of major health problems diagnosed at ED visits varied by age: more complicated complaints and multiple diagnoses were more frequent in older patients.
+In Taiwan, the ED system remains overloaded, possibly because of the low cost of an ED visit.
+Enterovirus 71 (EV-71) is the main etiological agent of hand, foot and mouth disease (HFMD).
+Recent EV-71 outbreaks in Asia-Pacific were not limited to mild HFMD, but were associated with severe neurological complications such as aseptic meningitis and brainstem encephalitis, which may lead to cardiopulmonary failure and death.
+This review highlights the potential antiviral agents targeting EV-71 attachment, entry, uncoating, translation, polyprotein processing, virus-induced formation of membranous RNA replication complexes, and RNA-dependent RNA polymerase.
+The strategies for antiviral development include target-based synthetic compounds, anti-rhinovirus and poliovirus libraries screening, and natural compound libraries screening.
+The continued effort to develop antiviral agents for treatment is crucial in the absence of a vaccine.
+The quantitative real-time polymerase chain reaction (qRT-PCR) is one of the most widely used methods to study gene expression profiles, and it requires appropriate normalization for accurate and reliable results.
+Although several genes are commonly used as reference genes (such as GAPDH, ACTB, and 18S rRNA), they are also regulated and can be expressed at varying levels.
+In this study, we evaluated twelve well-known reference genes to identify the most suitable housekeeping gene for normalization of qRT-PCR in human lumbar vertebral endplate with Modic changes, by using the geNorm, NormFinder, and BestKeeper algorithms.
+Our results showed that the rarely-used SDHA was the most stable single reference gene, and a combination of three, SDHA, B2M, and LDHA, was the most suitable gene set for normalization in all samples.
+In addition, the commonly-used genes, GAPDH, ACTB and 18S rRNA, were all inappropriate as internal standards.
+The rankings of reference genes for the three types of Modic change differed, although SDHA and RPL13A uniformly ranked in the first and last position, respectively.
+Further simulated expression analysis validated that the arbitrary use of a reference gene could lead to the misinterpretation of data.
+Our study confirmed the necessity of exploring the expression stability of potential reference genes in each specific tissue and experimental situation before quantitative evaluation of gene expression by qRT-PCR.
+BACKGROUND: Using microarray analysis, this study showed up-regulation of toll-like receptors 1, 2, 4, 7, 8, NF-κB, TNF, p38-MAPK, and MHC molecules in human peripheral blood mononuclear cells following infection with Plasmodium falciparum.
+METHODS: This analysis reports herein further studies based on time-course microarray analysis with focus on malaria-induced host immune response.
+RESULTS: The results show that in early malaria, selected immune response-related genes were up-regulated including α β and γ interferon-related genes, as well as genes of IL-15, CD36, chemokines (CXCL10, CCL2, S100A8/9, CXCL9, and CXCL11), TRAIL and IgG Fc receptors.
+During acute febrile malaria, up-regulated genes included α β and γ interferon-related genes, IL-8, IL-1b IL-10 downstream genes, TGFB1, oncostatin-M, chemokines, IgG Fc receptors, ADCC signalling, complement-related genes, granzymes, NK cell killer/inhibitory receptors and Fas antigen.
+When viewed in terms of immune response type, malaria infection appeared to induce a mixed TH1 response, in which α and β interferon-driven responses appear to predominate over the more classic IL-12 driven pathway.
+In addition, TH17 pathway also appears to play a significant role in the immune response to P. falciparum.
+Gene markers of TH17 (neutrophil-related genes, TGFB1 and IL-6 family (oncostatin-M)) and THαβ (IFN-γ and NK cytotoxicity and ADCC gene) immune response were up-regulated.
+Initiation of THαβ immune response was associated with an IFN-αβ response, which ultimately resulted in moderate-mild IFN-γ achieved via a pathway different from the more classic IL-12 TH1 pattern.
+CONCLUSIONS: Based on these observations, this study speculates that in P. falciparum infection, THαβ/TH17 immune response may predominate over ideal TH1 response.
+BACKGROUND: The pig faecal virome, which comprises the community of viruses present in pig faeces, is complex and consists of pig viruses, bacteriophages, transiently passaged plant viruses and other minor virus species.
+Here, the effect of the probiotic bacterium Enterococcus faecium (E. faecium) NCIMB 10415 on the pig faecal virome composition was analysed in a pig feeding trial with sows and their piglets, which received either the probiotic bacterium or not.
+RESULTS: From 8 pooled faecal samples derived from the feeding trial, DNA and RNA virus particles were prepared and subjected to process-controlled Next Generation Sequencing resulting in 390,650 sequence reads.
+The percentage of detected mammalian virus sequences was highest (55–77%) in the samples of the youngest piglets and lowest (8–10%) in the samples of the sows.
+In contrast, the percentage of bacteriophage sequences increased from 22–44% in the youngest piglets to approximately 90% in the sows.
+The dominating mammalian viruses differed remarkably among 12 day-old piglets (kobuvirus), 54 day-old piglets (boca-, dependo- and pig stool-associated small circular DNA virus [PigSCV]) and the sows (PigSCV, circovirus and “circovirus-like” viruses CB-A and RW-A).
+In addition, the Shannon index, which reflects the diversity of sequences present in a sample, was generally higher for the sows as compared to the piglets.
+No consistent differences in the virome composition could be identified between the viromes of the probiotic bacterium-treated group and the control group.
+CONCLUSION: The analysis indicates that the pig faecal virome shows a high variability and that its general composition is mainly dependent on the age of the pigs.
+Changes caused by feeding with the probiotic bacterium E. faecium could not be demonstrated using the applied metagenomics method.
+The phosphoprotein (P) gene of most Paramyxovirinae encodes several proteins in overlapping frames: P and V, which share a common N-terminus (PNT), and C, which overlaps PNT.
+Overlapping genes are of particular interest because they encode proteins originated de novo, some of which have unknown structural folds, challenging the notion that nature utilizes only a limited, well-mapped area of fold space.
+We predicted that all C proteins have a similar organization: a variable, disordered N-terminus and a conserved, α-helical C-terminus.
+We confirmed this predicted organization by biophysically characterizing recombinant C proteins from Tupaia paramyxovirus (measles group) and human parainfluenza virus 1 (Sendai group).
+We also found that the C of the measles and Nipah groups have statistically significant sequence similarity, indicating a common origin.
+Although the C of the Sendai group lack sequence similarity with them, we speculate that they also have a common origin, given their similar genomic location and structural organization.
+Since C is dispensable for viral replication, unlike PNT, we hypothesize that C may have originated de novo by overprinting PNT in the ancestor of Paramyxovirinae.
+Intriguingly, in measles virus and Nipah virus, PNT encodes STAT1-binding sites that overlap different regions of the C-terminus of C, indicating they have probably originated independently.
+This arrangement, in which the same genetic region encodes simultaneously a crucial functional motif (a STAT1-binding site) and a highly constrained region (the C-terminus of C), seems paradoxical, since it should severely reduce the ability of the virus to adapt.
+The fact that it originated twice suggests that it must be balanced by an evolutionary advantage, perhaps from reducing the size of the genetic region vulnerable to mutations.
+MnmEG catalyzes two different modification reactions, which add an aminomethyl (nm) or carboxymethylaminomethyl (cmnm) group to position 5 of the anticodon wobble uridine using ammonium or glycine, respectively.
+In [Image: see text] and [Image: see text], however, cmnm(5) appears as the final modification, whereas in the remaining tRNAs, the MnmEG products are converted into 5-methylaminomethyl (mnm(5)) through the two-domain, bi-functional enzyme MnmC.
+MnmC(o) transforms cmnm(5) into nm(5), whereas MnmC(m) converts nm(5) into mnm(5), thus producing an atypical network of modification pathways.
+We investigate the activities and tRNA specificity of MnmEG and the MnmC domains, the ability of tRNAs to follow the ammonium or glycine pathway and the effect of mnmC mutations on growth.
+We demonstrate that the two MnmC domains function independently of each other and that [Image: see text] and [Image: see text] are substrates for MnmC(m), but not MnmC(o).
+Synthesis of mnm(5)s(2)U by MnmEG-MnmC in vivo avoids build-up of intermediates in [Image: see text].
+Strikingly, the net output of the MnmEG pathways in vivo depends on growth conditions and tRNA species.
+Since 2001, when Human metapneumovirus (HMPV) was isolated in the Netherlands, the virus has been detected in several continents.
+HMPV plays an important role in respiratory tract infections in individuals of all ages particularly in children.
+This study was aimed at estimating the prevalence of HMPV in patients with community-acquired lower respiratory infection in Upper Egypt and characterizing the circulating Egyptian HMPV strains for the first time.
+From 2005 to 2008, respiratory samples from 520 patients were analyzed for the presence of HMPV by real-time RT-PCR.
+Nucleotide sequence identity within lineage B1 was 98.8%–99.7% and higher than that in lineage B2 (94.3%–100%).
+White spot syndrome virus (WSSV) is the most devastating virosis threatening the shrimp culture industry worldwide.
+Variations of environmental factors in shrimp culture ponds usually lead to the outbreak of white spot syndrome (WSS).
+In order to know the molecular mechanisms of WSS outbreak induced by temperature variation and the biological changes of the host at the initial stage of WSSV acute infection, RNA-Seq technology was used to analyze the differentially expressed genes (DEGs) in shrimp with a certain amount of WSSV cultured at 18°C and shrimp whose culture temperature were raised to 25°C.
+To analyze whether the expression changes of the DEGs were due to temperature rising or WSSV proliferation, the expression of selected DEGs was analyzed by real-time PCR with another shrimp group, namely Group T, as control.
+At the initial stage of WSSV acute infection, DEGs related to energy production were up-regulated, whereas most DEGs related to cell cycle and positive regulation of cell death and were down-regulated.
+Triose phosphate isomerase, enolase and alcohol dehydrogenase involved in glycosis were up-regulated, while pyruvate dehydrogenase, citrate synthase and isocitrate dehydrogenase with NAD as the coenzyme involved in TCA pathway were down-regulated.
+Also genes involved in host DNA replication, including DNA primase, DNA topoisomerase and DNA polymerase showed down-regulated expression.
+Several interesting genes including crustin genes, acting binding or inhibiting protein genes, a disintegrin and metalloproteinase domain-containing protein 9 (ADAM9) gene and a GRP 78 gene were also analyzed.
+Understanding the interactions between hosts and WSSV at the initial stage of acute infection will not only help to get a deep insight into the pathogenesis of WSSV but also provide clues for therapies.
+Chikungunya virus (CHIKV) is an arthropod-borne virus of the family Togaviridae that is transmitted to humans by Aedes spp.
+In the present study, we report the patterns of synonymous codon usage in 141 CHIKV genomes by calculating several codon usage indices and applying multivariate statistical methods.
+Relative synonymous codon usage (RSCU) analysis showed that the preferred synonymous codons were G/C and A-ended.
+A comparative analysis of RSCU between CHIKV and its hosts showed that codon usage patterns of CHIKV are a mixture of coincidence and antagonism.
+Similarity index analysis showed that the overall codon usage patterns of CHIKV have been strongly influenced by Pan troglodytes and Aedes albopictus during evolution.
+The overall codon usage bias was low in CHIKV genomes, as inferred from the analysis of effective number of codons (ENC) and codon adaptation index (CAI).
+Our data suggested that although mutation pressure dominates codon usage in CHIKV, patterns of codon usage in CHIKV are also under the influence of natural selection from its hosts and geography.
+To the best of our knowledge, this is first report describing codon usage analysis in CHIKV genomes.
+The findings from this study are expected to increase our understanding of factors involved in viral evolution, and fitness towards hosts and the environment.
+We investigated the sensitivity of human rotavirus rapid antigen detection (RAD) kits, RT-PCR and next-generation DNA sequencing (NGS) for detection of bovine group A rotavirus (RVA).
+The Dipstick ‘Eiken’ Rota (Dipstick) showed the highest sensitivity out of the seven RAD kits against all selected strains in limited dilution analyses, which was consistent with the results for equine rotavirus previously reported.
+NGS using thirteen RT-PCR-negative fecal samples revealed that all samples yielded RVA reads and especially that two of them covered all 11 genome segments.
+The NGS would be sensitive and useful for analysis of less dependent on specific primers and screening of genotypes.
+PURPOSE: Advances in supportive care and ventilator management for acute respiratory distress syndrome (ARDS) have resulted in declines in short-term mortality, but risks of death after survival to hospital discharge have not been well described.
+Our objective was to quantify the difference between short-term and long-term mortality in ARDS and to identify risk factors for death and causes of death at 1 year among hospital survivors.
+METHODS: This multi-intensive care unit, prospective cohort included patients with ARDS enrolled between January 2006 and February 2010.
+We determined the clinical characteristics associated with in-hospital and 1-year mortality among hospital survivors and utilized death certificate data to identify causes of death.
+RESULTS: Of 646 patients hospitalized with ARDS, mortality at 1 year was substantially higher (41 %, 95 % CI 37–45 %) than in-hospital mortality (24 %, 95 % CI 21–27 %), P < 0.0001.
+Among 493 patients who survived to hospital discharge, the 110 (22 %) who died in the subsequent year were older (P < 0.001) and more likely to have been discharged to a nursing home, other hospital, or hospice compared to patients alive at 1 year (P < 0.001).
+Important predictors of death among hospital survivors were comorbidities present at the time of ARDS, and not living at home prior to admission.
+ARDS-related measures of severity of illness did not emerge as independent predictors of mortality in hospital survivors.
+CONCLUSIONS: Despite improvements in short-term ARDS outcomes, 1-year mortality is high, mostly because of the large burden of comorbidities, which are prevalent in patients with ARDS.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00134-013-3186-3) contains supplementary material, which is available to authorized users.
+Angiotensin II (Ang-II), the final product of this pathway, is known for its vasoconstrictive and proliferative effects.
+Angiotensin-converting enzyme 2 (ACE2), a newly discovered homolog of ACE, plays a key role as the central negative regulator of the RAS.
+It diverts the generation of vasoactive Ang-II into the vasodilatory and growth inhibiting peptide angiotensin(1–7) [Ang(1–7)], thereby providing counter-regulatory responses to neurohormonal activation.
+There is substantial experimental evidence evaluating the role of ACE2/Ang(1–7) in hypertension, heart failure, and atherosclerosis.
+In this review, we aim to focus on the conceptual facts of the ACE2-Ang(1–7) axis with regards to clinical implications and therapeutic targets in cardiovascular disorders, with emphasis on the potential therapeutic role in cardiovascular diseases.
+The comprehensive information of small molecules and their biological activities in the PubChem database allows chemoinformatic researchers to access and make use of large-scale biological activity data to improve the precision of drug profiling.
+A Quantitative Structure–Activity Relationship approach, for classification, was used for the prediction of active/inactive compounds relatively to overall biological activity, antitumor and antibiotic activities using a data set of 1804 compounds from PubChem.
+Using the best classification models for antibiotic and antitumor activities a data set of marine and microbial natural products from the AntiMarin database were screened—57 and 16 new lead compounds for antibiotic and antitumor drug design were proposed, respectively.
+All compounds proposed by our approach are classified as non-antibiotic and non-antitumor compounds in the AntiMarin database.
+Recently several of the lead-like compounds proposed by us were reported as being active in the literature.
+BACKGROUND: Canine parvovirus 2 (CPV 2) is a major infectious cause of mortality in puppies.
+Soon after CPV was first recognized in the late 1970s, the original virus, CPV 2, was replaced in the canine population by strains carrying minor antigenic variants (termed 2a, 2b, and 2c) of the VP2 gene that could be distinguished using monoclonal antibodies and molecular analyses.
+METHODS: In this study, 28 isolates of CPV 2 from 144 dogs with suspected CPV infection were obtained from northern, central, and southern Taiwan from 2008 to 2012 and screened by PCR.
+The 28 isolates were sequenced, and a phylogenetic analysis of the VP2 gene was performed.
+RESULTS: Of the 28 Taiwanese CPV 2 isolates, 15 were identified as new CPV 2a, and 13 were identified as new CPV 2b.
+Compared to the reference CPV 2a, all 15 of the CPV 2a sequences collected in this study contain an Ile324 mutation caused by a TAT to ATT mutation at nucleotides 970–972 of the VP2 gene.
+CONCLUSION: Our VP2 sequence data revealed that both types are currently prevalent CPV 2 field strains circulating in Taiwan, and a unique Ile324 VP2 mutation was found in our Taiwanese CPV 2a isolates and recent Asian isolates.
+Failure to incorporate the beliefs and attitudes of the public into theoretical models of preparedness has been identified as a weakness in strategies to mitigate infectious disease outbreaks.
+We administered a cross-sectional telephone survey to a representative sample (n = 443) of the Swedish adult population to examine whether self-reported intentions to improve personal hygiene and increase social distancing during influenza outbreaks could be explained by trust in official information, self-reported health (SF-8), sociodemographic factors, and determinants postulated in protection motivation theory, namely threat appraisal and coping appraisal.
+The interviewees were asked to make their appraisals for two scenarios: a) an influenza with low case fatality and mild lifestyle impact; b) severe influenza with high case fatality and serious disturbances of societal functions.
+The proportion that reported intentions to take deliberate actions to improve personal hygiene during outbreaks ranged between 45–85%, while less than 25% said that they intended to increase social distancing.
+We conclude that coping appraisal was the explanatory factor most frequently included in statistical models explaining self-reported intentions to carry out non-pharmaceutical health actions in the Swedish outlined context, and that variations in threat appraisal played a smaller role in these models despite scientific uncertainties surrounding a recent mass vaccination campaign.
+The concept that adult tissue, including bone marrow (BM), contains early-development cells with broader differentiation potential has again been recently challenged.
+In response, we would like to review the accumulated evidence from several independent laboratories that adult tissues, including BM, harbor a population of very rare stem cells that may cross germ layers in their differentiation potential.
+These dormant, early-development cells that our group described as very small embryonic-like stem cells (VSELs) most likely overlap with similar populations of stem cells that have been identified in adult tissues by other investigators as the result of various experimental strategies and have been given various names.
+Moreover, they display several epiblast/germline markers that suggest their embryonic origin and developmental deposition in adult BM.
+Moreover, at the molecular level, changes in expression of parentally imprinted genes (for example, Igf2–H19) and resistance to insulin/insulin-like growth factor signaling (IIS) regulates their quiescent state in adult tissues.
+In several emergency situations related to organ damage, VSELs can be activated and mobilized into peripheral blood, and in appropriate animal models they contribute to tissue organ/regeneration.
+Interestingly, their number correlates with lifespan in mice, and they may also be involved in some malignancies.
+VSELs have been successfully isolated in several laboratories; however, some investigators experience problems with their isolation.
+OBJECTIVE: To examine the efficiency of the Hong Kong hospitalisation system based on hospitalisation days.
+METHODS: A decomposition method was used to determine the effects on total hospitalisation days during the period 2000–2010 of the following three factors: (i) hospitalisation rate per person; (ii) the number of visits per patient; and (iii) the mean duration of stay per visit.
+MAIN OUTCOME MEASURES: The decomposition method provides empirical measures of how the three factors contributed to the change in total hospitalisation days during the period 2000–2010 and identifies the most effective way to contain increases in hospitalisation days.
+RESULTS: The results of decomposition analysis show that the decrease in mean duration of stay per visit (reducing from 6.83 to 4.58 days) is the most important factor in the reduction in the total number of hospitalisation days, despite increases in total population size (from 6.7 to 7.0 million), the number of individual hospital admissions (from 583 000 to 664 000) and the number of episodes (from 1.2 to 1.4 million) from 2000 to 2010.
+The decline in the mean duration of stay per visit contributed 200.6% to this reduction but was offset by −51.1% due to a slight growth in the number of visits per patient and by −49.4% as a result of changed hospitalisation rates per person.
+CONCLUSIONS: Better management of the duration of stay of per visit without compromising patient satisfaction levels or the quality of service is the most important factor for controlling increases in health expenditure in Hong Kong.
+Ebola virus (EBOV) entry requires the virion surface-associated glycoprotein (GP) that is composed of a trimer of heterodimers (GP1/GP2).
+The GP1 subunit contains two heavily glycosylated domains, the glycan cap and the mucin-like domain (MLD).
+The glycan cap contains only N-linked glycans, whereas the MLD contains both N- and O-linked glycans.
+Site-directed mutagenesis was performed on EBOV GP1 to systematically disrupt N-linked glycan sites to gain an understanding of their role in GP structure and function.
+All 15 N-glycosylation sites of EBOV GP1 could be removed without compromising the expression of GP.
+The loss of these 15 glycosylation sites significantly enhanced pseudovirion transduction in Vero cells, which correlated with an increase in protease sensitivity.
+Interestingly, exposing the receptor-binding domain (RBD) by removing the glycan shield did not allow interaction with the endosomal receptor, NPC1, indicating that the glycan cap/MLD domains mask RBD residues required for binding.
+The effects of the loss of GP1 N-linked glycans on Ca(2+)-dependent (C-type) lectin (CLEC)-dependent transduction were complex, and the effect was unique for each of the CLECs tested.
+Surprisingly, EBOV entry into murine peritoneal macrophages was independent of GP1 N-glycans, suggesting that CLEC-GP1 N-glycan interactions are not required for entry into this important primary cell.
+Finally, the removal of all GP1 N-glycans outside the MLD enhanced antiserum and antibody sensitivity.
+In total, our results provide evidence that the conserved N-linked glycans on the EBOV GP1 core protect GP from antibody neutralization despite the negative impact the glycans have on viral entry efficiency.
+Cell-penetrating peptide-mediated delivery of phosphorodiamidate morpholino oligomers (PMOs) has shown great promise for exon-skipping therapy of Duchenne Muscular Dystrophy (DMD).
+Pip6a-PMO, a recently developed conjugate, is particularly efficient in a murine DMD model, although mechanisms responsible for its increased biological activity have not been studied.
+Here, we evaluate the cellular trafficking and the biological activity of Pip6a-PMO in skeletal muscle cells and primary cardiomyocytes.
+Our results indicate that Pip6a-PMO is taken up in the skeletal muscle cells by an energy- and caveolae-mediated endocytosis.
+Interestingly, its cellular distribution is different in undifferentiated and differentiated skeletal muscle cells (vesicular versus nuclear).
+Likewise, Pip6a-PMO mainly accumulates in cytoplasmic vesicles in primary cardiomyocytes, in which clathrin-mediated endocytosis seems to be the pre-dominant uptake pathway.
+These differences in cellular trafficking correspond well with the exon-skipping data, with higher activity in myotubes than in myoblasts or cardiomyocytes.
+These differences in cellular trafficking thus provide a possible mechanistic explanation for the variations in exon-skipping activity and restoration of dystrophin protein in heart muscle compared with skeletal muscle tissues in DMD models.
+Overall, Pip6a-PMO appears as the most efficient conjugate to date (low nanomolar EC(50)), even if limitations remain from endosomal escape.
+Crimean-Congo Haemorrhagic Fever (CCHF) is a severe tick-borne disease, endemic in many countries in Africa, the Middle East, Eastern Europe and Asia.
+There is no approved vaccine available, and preclinical protection in vivo by an experimental vaccine has not been demonstrated previously.
+In the present study, the attenuated poxvirus vector, Modified Vaccinia virus Ankara, was used to develop a recombinant candidate vaccine expressing the CCHF virus glycoproteins.
+Cellular and humoral immunogenicity was confirmed in two mouse strains, including type I interferon receptor knockout mice, which are susceptible to CCHF disease.
+This vaccine protected all recipient animals from lethal disease in a challenge model adapted to represent infection via a tick bite.
+Histopathology and viral load analysis of protected animals confirmed that they had been exposed to challenge virus, even though they did not exhibit clinical signs.
+Although astrogliosis and microglia activation are characteristic features of multiple sclerosis (MS) and other central nervous system (CNS) lesions the exact functions of these events are not fully understood.
+Animal models help to understand the complex interplay between the different cell types of the CNS and uncover general mechanisms of damage and repair of myelin sheaths.
+The so called cuprizone model is a toxic model of demyelination in the CNS white and gray matter, which lacks an autoimmune component.
+Cuprizone induces apoptosis of mature oligodendrocytes that leads to a robust demyelination and profound activation of both astrocytes and microglia with regional heterogeneity between different white and gray matter regions.
+Although not suitable to study autoimmune mediated demyelination, this model is extremely helpful to elucidate basic cellular and molecular mechanisms during de- and particularly remyelination independently of interactions with peripheral immune cells.
+Phagocytosis and removal of damaged myelin seems to be one of the major roles of microglia in this model and it is well known that removal of myelin debris is a prerequisite of successful remyelination.
+Using the cuprizone model we could demonstrate that there is an important crosstalk between astrocytes and microglia.
+In this review we focus on the role of glial reactions and interaction in the cuprizone model.
+Advantages and limitations of as well as its potential therapeutic relevance for the human disease MS are critically discussed in comparison to other animal models.
+Glioblastoma multiforme (GBM) is the most frequent and most devastating of the primary central nervous system tumors, with few patients living beyond 2 years postdiagnosis.
+The damage caused by the disease and our treatments for the patients often leave them physically and cognitively debilitated.
+Generally, GBMs appear after very short clinical histories and are discovered by imaging (using magnetic resonance imaging [MRI]), and the diagnosis is validated by pathology, following surgical resection.
+The treatment response and diagnosis of tumor recurrence are also tracked by MRI, but there are numerous problems encountered with these monitoring modalities, such as ambiguous interpretation and forms of pseudoprogression.
+Diagnostic, prognostic, and predictive biomarkers would be an immense boon in following treatment schemes and in determining recurrence, which often requires an invasive intracranial biopsy to verify imaging data.
+Extracellular vesicles (EVs) are stable, membrane-enclosed, virus-sized particles released from either the cell surface or from endosomal pathways that lead to the systemic release of EVs into accessible biofluids, such as serum/plasma, urine, cerebrospinal fluid, and saliva.
+EVs carry a wide variety of proteins, nucleic acids, lipids, and other metabolites, with many common features but with enough individuality to be able to identify the cell of origin of the vesicles.
+These components, if properly interrogated, could allow for the identification of tumor-derived EVs in biofluids, indicating tumor progression, relapse, or treatment failure.
+That knowledge would allow clinicians to continue with treatment regimens that were actually effective or to change course if the therapies were failing.
+Here, we review the features of GBM EVs, in terms of EV content and activities that may lead to the use of EVs as serially accessible biomarkers for diagnosis and treatment response in neuro-oncology.
+[Image: see text] The life cycle of the human immunodeficiency virus type 1 (HIV-1) has an absolute requirement for ribosomal frameshifting during protein translation in order to produce the polyprotein precursor of the viral enzymes.
+While an RNA stem-loop structure (the “HIV-1 Frameshift Stimulating Signal”, or HIV-1 FSS) controls the frameshift efficiency and has been hypothesized as an attractive therapeutic target, developing compounds that selectively bind this RNA and interfere with HIV-1 replication has proven challenging.
+Building on our prior discovery of a “hit” molecule able to bind this stem-loop, we now report the development of compounds displaying high affinity for the HIV-1 FSS.
+These compounds are able to enhance frameshifting more than 50% in a dual-luciferase assay in human embryonic kidney cells, and they strongly inhibit the infectivity of pseudotyped HIV-1 virions.
+Several studies have confirmed that SOCS3 is increased in asthmatic patients, and SOCS3 expression is correlated with disease severity.
+The objective of this study was to evaluate if delivering of SOCS3 short interfering RNA (siRNA) intranasally in lungs could be a good therapeutic approach in an asthma chronic mouse model.
+Our results showed that intranasal treatment with SOCS3-siRNA led to an improvement in the eosinophil count and the normalization of hyperresponsiveness to methacholine.
+Concomitantly, this treatment resulted in an improvement in mucus secretion, a reduction in lung collagen, which are prominent features of airway remodeling.
+The mechanism implies JAK/STAT and RhoA/Rho-kinase signaling pathway, because we found a decreasing in STAT3 phosphorylation status and down regulation of RhoA/Rho-kinase protein expression.
+Type 1 interferons (IFN) protect the host against viruses by engaging a cognate receptor (consisting of IFNAR1/IFNAR2 chains) and inducing downstream signaling and gene expression.
+However, inflammatory stimuli can trigger IFNAR1 ubiquitination and downregulation thereby attenuating IFN effects in vitro.
+Presented here results demonstrate that inability to stimulate IFNAR1 ubiquitination in the Ifnar1(SA) knock-in mice renders them highly susceptible to numerous inflammatory syndromes including acute and chronic pancreatitis, and autoimmune and toxic hepatitis.
+Ifnar1(SA) mice (or their bone marrow-receiving wild type animals) display persistent immune infiltration of inflamed tissues, extensive damage and gravely inadequate tissue regeneration.
+Pharmacologic stimulation of IFNAR1 ubiquitination is protective against from toxic hepatitis and fulminant generalized inflammation in wild type but not Ifnar1(SA) mice.
+These results suggest that endogenous mechanisms that trigger IFNAR1 ubiquitination for limiting the inflammation-induced tissue damage can be purposely mimicked for therapeutic benefits.
+The homologous p10 fusion-associated small transmembrane (FAST) proteins of the avian (ARV) and Nelson Bay (NBV) reoviruses are the smallest known viral membrane fusion proteins, and are virulence determinants of the fusogenic reoviruses.
+The small size of FAST proteins is incompatible with the paradigmatic membrane fusion pathway proposed for enveloped viral fusion proteins.
+Understanding how these diminutive viral fusogens mediate the complex process of membrane fusion is therefore of considerable interest, from both the pathogenesis and mechanism-of-action perspectives.
+Using chimeric ARV/NBV p10 constructs, the 36–40-residue ectodomain was identified as the major determinant of the differing fusion efficiencies of these homologous p10 proteins.
+Syncytiogenesis assays, thiol-specific surface biotinylation, and liposome lipid mixing assays identified an ∼25-residue, N-terminal motif that dictates formation of a cystine loop fusion peptide in both ARV and NBV p10.
+Surface immunofluorescence staining, FRET analysis and cholesterol depletion/repletion studies determined the cystine loop motif is connected through a two-residue linker to a 13-residue membrane-proximal ectodomain region (MPER).
+The MPER constitutes a second, independent motif governing reversible, cholesterol-dependent assembly of p10 multimers in the plasma membrane.
+Results further indicate that: (1) ARV and NBV homomultimers segregate to distinct, cholesterol-dependent microdomains in the plasma membrane; (2) p10 homomultimerization and cholesterol-dependent microdomain localization are co-dependent; and (3) the four juxtamembrane MPER residues present in the multimerization motif dictate species-specific microdomain association and homomultimerization.
+The p10 ectodomain therefore constitutes a remarkably compact, multifunctional fusion module that directs syncytiogenic efficiency and species-specific assembly of p10 homomultimers into cholesterol-dependent fusion platforms in the plasma membrane.
+Metal-based drugs with extensive clinical applications hold great promise for the development of cancer chemotherapeutic agents.
+In the last few decades, Schiff bases and their complexes have become well known for their extensive biological potential.
+In the present study, we examined the antiproliferative effect of a copper (II) complex on HT-29 colon cancer cells.
+The Cu(BrHAP)(2 ) Schiff base compound demonstrated a potent antiproliferative effect in HT-29 cells, with an IC(50 )value of 2.87 μg/ml after 72 h of treatment.
+HT-29 cells treated with Cu (II) complexes underwent apoptosis death, as exhibited by a progressive elevation in the proportion of the G(1 ) cell population.
+At a concentration of 6.25 μg/ml, the Cu(BrHAP)(2 ) compound caused significant elevation in ROS production following perturbation of mitochondrial membrane potential and cytochrome c release, as assessed by the measurement of fluorescence intensity in stained cells.
+Furthermore, the activation of caspases 3/7 and 9 was part of the Cu (II) complex-induced apoptosis, which confirmed the involvement of mitochondrial-mediated apoptosis.
+Taken together, these results imply that the Cu(BrHAP)(2 ) compound is a potential candidate for further in vivo and clinical colon cancer studies to develop novel chemotherapeutic agents derived from metal-based agents.
+The disease is caused by the PRRS virus (PRRSV), an Arterivirus which is a highly mutating RNA virus.
+Widely used modified live PRRSV vaccines have failed to prevent PRRS outbreaks and reinfections; moreover, safety of the live virus vaccines is questionable.
+Therefore, we attempted to strengthen the immunogenicity of inactivated/killed PRRSV vaccine antigens (KAg), especially in the pig respiratory system, through: 1) entrapping the KAg in biodegradable poly(lactic-co-glycolic acid) nanoparticles (NP-KAg); 2) coupling the NP-KAg with a potent mucosal adjuvant, whole cell lysate of Mycobacterium tuberculosis (M. tb WCL); and 3) delivering the vaccine formulation twice intranasally to growing pigs.
+We have previously shown that a single dose of NP-KAg partially cleared the challenged heterologous PRRSV.
+Recently, we reported that NP-KAg coupled with unentrapped M. tb WCL significantly cleared the viremia of challenged heterologous PRRSV.
+Since PRRSV is primarily a lung disease, our goal in this study was to investigate lung viral load and various immune correlates of protection at the lung mucosal surfaces and its parenchyma in vaccinated heterologous PRRSV-challenged pigs.
+Our results indicated that out of five different vaccine-adjuvant formulations, the combination of NP-KAg and unentrapped M. tb WCL significantly cleared detectable replicating infective PRRSV with a tenfold reduction in viral RNA load in the lungs, associated with substantially reduced gross and microscopic lung pathology.
+Immunologically, strong humoral (enhanced virus neutralization titers by high avidity antibodies) and cell-mediated immune responses (augmented population of interferon-γ secreting CD4(+) and CD8(+) lymphocytes and reduced secretion of immunosuppressive cytokines) in the lungs were observed.
+In conclusion, combination of NP-KAg and soluble M. tb WCL elicits broadly cross-protective anti-PRRSV immunity in the pig respiratory system.
+Respiratory syncytial virus (RSV) lower respiratory tract disease (LRD) is a life-threatening complication in hematopoietic cell transplant (HCT) recipients.
+Lymphopenia has been associated with an increased risk of progression from upper respiratory tract infection (URI) to LRD.
+This study retrospectively analyzed the significance of lymphocyte engraftment dynamics, lung function, smoking history, corticosteroids, antiviral treatment, viral subtypes, and RSV-specific neutralizing antibodies for the progression to LRD in 181 HCT recipients with RSV URI.
+In multivariable models, smoking history, conditioning with high-dose total body irradiation, and an absolute lymphocyte count (ALC) ≤100/mm(3) at the time of URI onset were significantly associated with disease progression.
+Pre- and posttransplant donor and posttransplant recipient RSV subtype-specific neutralizing antibody levels, RSV viral subtypes, and corticosteroids also were not significantly associated with LRD progression.
+Host and transplant related factors appear to determine the risk of progression to LRD more than viral factors.
+Dysfunctional cell-mediated immunity appears to be important in the pathogenesis of progressive RSV disease after HCT.
+BACKGROUND: Growing evidence exists for soluble Angiotensin Converting Enzyme-2 (sACE2) as a biomarker in definitive heart failure (HF), but there is little information about changes in sACE2 activity in hypertension with imminent heart failure and in reverse remodeling.
+METHODS, FINDINGS: Patients with systolic HF (NYHAII-IV, enrolled for cardiac resynchronisation therapy, CRT, n = 100) were compared to hypertensive patients (n = 239) and to a healthy cohort (n = 45) with preserved ejection fraction (EF>50%) in a single center prospective clinical study.
+Biochemical (ACE and sACE2 activity, ACE concentration) and echocardiographic parameters (EF, left ventricular end-diastolic (EDD) and end-systolic diameter (ESD) and dP/dt) were measured.
+sACE2 activity negatively correlated with EF and positively with ESD and EDD in all patient's populations, while it was independent in the healthy cohort.
+sACE2 activity was already increased in the hypertensive group, where signs for imminent heart failure (slightly decreased EF and barely increased NT-proBNP levels) were detected.
+sACE2 activities further increased in patients with definitive heart failure (EF<50%), while sACE2 activities decreased with the improvement of the heart failure after CRT (reverse remodeling).
+Serum angiotensin converting enzyme (ACE) concentrations were lower in the diseased populations, but did not show a strong correlation with the echocardiographic parameters.
+CONCLUSIONS: Soluble ACE2 activity appears to be biomarker in heart failure, and in hypertension, where heart failure may be imminent.
+HMGB1 is a nuclear component involved in nucleosome stabilization and transcription regulation, but extracellularly it is able to serve as a potential late mediator of lethality.
+In the present study, we explored inflammation-promoting activity of HMGB1 and blockade of extracellular release of HMGB1 by glycyrrhizin (GL) in LPS/GalN-triggered mouse liver injury.
+At 1 to 10 h after LPS/GalN-treatment, mice were anesthetized to collect blood from heart puncture, and serum transaminase and HMGB1 were evaluated.
+At 8 h nuclear immunoreactive products were remarkably reduced and extracellular HMGB1 expression was found exclusively in the pericentral foci.
+The treatment with GL significantly down-regulated the serum levels of ALT, AST, and HMGB1 in addition to the strong inhibition of tissue injury and extracellular immunoreactivity to HMGB1 and to acetylated-lysine.
+Furthermore, GL brought about a significant decrease in the number of apoptotic hepatocytes labeled with TUNEL-method.
+On the basis of these results, three apoptosis-associated genes were identified with microarray analysis and real-time PCR.
+The ChIP-assay revealed the binding of HMGB1 protein to Gsto1 promoter sequence in LPS/GalN-treated mice and the remarkable decrease in combined HMGB1 protein by GL.
+The current findings claim that a single injection of LPS/GalN might stimulate apoptosis of hepatocytes through the binding of HMGB1 protein to Gsto1 promoter region and that GL-treatment might prevent the apoptosis and inflammatory infiltrates caused with LPS/GalN-injection by disturbing the binding of HMGB1 protein to Gsto1 promoter sequence.
+INTRODUCTION: Worldwide, three Influenza-A virus subtypes (H1N1, H1N2 and H3N2) in swine are major public health issues.
+This study aimed at determining the prevalence and correlates of Influenza-A viruses circulating in piggery workers and pigs in Oke-aro and Goshen communities in Lagos, Nigeria.
+METHODS: Nasal swabs were taken from 197 consenting piggery workers and 281 randomly selected pigs to determine the prevalence of Influenza-A (H1, H3, H5) using Reverse Transcriptase Polymerase Chain Reaction test (gene M).
+An interviewer administered questionnaire was used to collect information on demography, Influenza-A related symptoms experienced, personal hygiene and management practices from the piggery workers.
+RESULTS: All piggery workers and pigs’ nasal swabs tested negative for Influenza-A viruses, hence, association could not be tested.
+Nineteen percent had history of headache; 14.0% had catarrh and cough; 4.0% had sore-throat; 5.0% had diarrhea; while 48.0% had muscle pain at the time of data collection.
+CONCLUSION: Piggery workers and pigs in study area were free of Influenza-A (H1, H3, H5) viruses.
+The 2′,5′-oligoadenylate (2-5A) synthetase (OAS)-RNase L system is a mechanism for restricting viral infections during the interferon antiviral response.
+Here, we investigated a potential role for the OAS-RNase L system in the restriction of retrotransposons.
+Expression of wild type (WT) and a constitutively active form of RNase L (NΔ385), but not a catalytically inactive RNase L mutant (R667A), impaired the mobility of engineered human LINE-1 (L1) and mouse intracisternal A-type particle retrotransposons in cultured human cells.
+Furthermore, WT RNase L, but not an inactive RNase L mutant (R667A), reduced L1 RNA levels and subsequent expression of the L1-encoded proteins (ORF1p and ORF2p).
+Consistently, confocal immunofluorescent microscopy demonstrated that WT RNase L, but not RNase L R667A, prevented formation of L1 cytoplasmic foci.
+Finally, siRNA-mediated depletion of endogenous RNase L in a human ovarian cancer cell line (Hey1b) increased the levels of L1 retrotransposition by ∼2-fold.
+Together, these data suggest that RNase L might function as a suppressor of structurally distinct retrotransposons.
+BACKGROUND: The first case of human infection with avian influenza A (H7N9) virus was identified in March, 2013 and the new H7N9 virus infected 134 patients and killed 45 people in China as of September 30, 2013.
+Family clusters with confirmed or suspected the new H7N9 virus infection were previously reported, but the family cluster of H7N9 virus infection in Shandong Province was first reported.
+CASE PRESENTATION: A 36-year-old man was admitted to Zaozhuang City Hospital with progressive respiratory distress and suspicion of impending acute respiratory distress syndrome on April 21.
+The second case, the first case’s 4 year old son, was admitted to the same hospital on April 28 with fever and multiple patchy shadows in the bilateral lungs.
+Both of the two cases were confirmed to infect with H7N9 virus by the results of real-time reverse transcriptase-polymerase-chain reaction (rRT-PCR), virus isolation and serum antibody titer.
+At the same time, one environment samples was detected positive for H7N9 virus in the living poultry market in Zaozhuang.
+The homologous analysis of the full genome sequence indicated that both viruses from the patients were almost genetically identical.
+The field epidemiology investigation showed that the two cases had no recognized exposure to poultry, but had the exposure to the environment.
+The second case had substantial unprotected close exposure to his ill father and developed symptoms seven days after his last contact with his father.
+After surgery, the index case and his son were discharged on May 16 and May 6, respectively.
+11 close contacts of both patients were identified and tested negative both the throat swabs and the serum antibody.
+CONCLUSION: The infection of the index case probably resulted from contact with environmentally contaminated material.
+For the son, the probable infection source was from the index case during unprotected exposure, but the possibility from the environment or other sources could not be completely ruled out.
+Deep sequencing allows for a rapid, accurate characterization of microbial DNA and RNA sequences in many types of samples.
+Deep sequencing (also called next generation sequencing or NGS) is being developed to assist with the diagnosis of a wide variety of infectious diseases.
+In this study, seven frozen brain samples from deceased subjects with recent encephalitis were investigated.
+This analysis successfully identified measles virus sequences in two brain samples and herpes simplex virus type-1 sequences in three brain samples.
+These results were concordant with pathogen-specific PCR and partially concordant with prior neuropathological examinations, demonstrating that deep sequencing can accurately identify viral infections in frozen brain tissue.
+Nuclear receptors (NRs) are closely associated with various major diseases such as cancer, diabetes, inflammatory disease, and osteoporosis.
+During the process of developing drugs against these diseases by targeting NRs, we are often facing a problem: Given a NR and chemical compound, can we identify whether they are really in interaction with each other in a cell?
+In the predictor, the drug compound concerned was formulated by a 256-D (dimensional) vector derived from its molecular fingerprint, and the NR by a 500-D vector formed by incorporating its sequential evolution information and physicochemical features into the general form of pseudo amino acid composition, and the prediction engine was operated by the SVM (support vector machine) algorithm.
+Compared with the existing prediction methods in this area, iNR-Drug not only can yield a higher success rate, but is also featured by a user-friendly web-server established at http://www.jci-bioinfo.cn/iNR-Drug/, which is particularly useful for most experimental scientists to obtain their desired data in a timely manner.
+It is anticipated that the iNR-Drug server may become a useful high throughput tool for both basic research and drug development, and that the current approach may be easily extended to study the interactions of drug with other targets as well.
+We assessed the public and philanthropic investments awarded to UK institutions for respiratory infectious disease research to identify areas of underinvestment.
+We aimed to identify projects and categorise them by pathogen, disease and position along the research and development value chain.
+PRIMARY AND SECONDARY OUTCOME MEASURES: The total amount spent and number of studies with a focus on several different respiratory pathogens or diseases, and to correlate these against the global burden of disease; also the total amount spent and number of studies relating to the type of science, the predominant funder in each category and the mean and median award size.
+Despite high burden, there was relatively little investment in vaccine-preventable diseases including diphtheria (£0.1 million, 0.03%), measles (£5.0 million, 1.2%) and drug-resistant tuberculosis.
+There were 802 preclinical studies (67.3%) receiving £273 million (65.2%), while implementation research received £81 million (19.3%) across 274 studies (23%).
+The high global burden of pneumonia-related disease warrants greater investment than it has historically received.
+Other priority areas include antimicrobial resistance (particularly within tuberculosis), economics and proactive investments for emerging infectious threats.
+Chemokine CXCL-8 plays a central role in human immune response by binding to and activate its cognate receptor CXCR1, a member of the G-protein coupled receptor (GPCR) family.
+The full-length structure of CXCR1 is modeled by combining the structures of previous NMR experiments with those from homology modeling.
+Molecular docking is performed to search favorable binding sites of monomeric and dimeric CXCL-8 with CXCR1 and a mutated form of it.
+The receptor-ligand complex is embedded into a lipid bilayer and used in multi ns molecular dynamics (MD) simulations.
+A multi-steps binding mode is proposed: (i) the N-loop of CXCL-8 initially binds to the N-terminal domain of receptor CXCR1 driven predominantly by electrostatic interactions; (ii) hydrophobic interactions allow the N-terminal Glu-Leu-Arg (ELR) motif of CXCL-8 to move closer to the extracellular loops of CXCR1; (iii) electrostatic interactions finally dominate the interaction between the N-terminal ELR motif of CXCL-8 and the EC-loops of CXCR1.
+The detailed binding process may help to facilitate the discovery of agonists and antagonists for rational drug design.
+Cytotoxic T cells (CTLs) play a key role in the control of Hepatitis B virus (HBV) infection and viral clearance.
+However, most of identified CTL epitopes are derived from HBV of genotypes A and D, and few have been defined in virus of genotypes B and C which are more prevalent in Asia.
+As HBV core protein (HBc) is the most conservative and immunogenic component, in this study we used an overlapping 9-mer peptide pool covering HBc to screen and identify specific CTL epitopes.
+Finally, we show that mutations in HBc141–149 epitope are associated with viral parameters and disease progression in HBV infected patients.
+Our data therefore provide insights into the structure characteristics of this unconventional epitope binding to MHC-I molecules, as well as epitope specific CTL activity that orchestrate T cell response and immune evasion in HBV infected patients.
+To develop a safe and effective mucosal vaccine against pathogenic influenza viruses, we constructed recombinant Lactobacillus casei strains that express conserved matrix protein 2 with (pgsA-CTA1-sM2/L.
+The surface localization of the fusion protein was verified by cellular fractionation analyses, flow cytometry and immunofluorescence microscopy.
+Oral and nasal inoculations of recombinant L. casei into mice resulted in high levels of serum immunoglobulin G (IgG) and mucosal IgA.
+However, the conjugation of cholera toxin subunit A1 induced more potent mucosal, humoral and cell-mediated immune responses.
+In a challenge test with 10 MLD(50) of A/EM/Korea/W149/06(H5N1), A/Puerto Rico/8/34(H1N1), A/Aquatic bird /Korea/W81/2005(H5N2), A/Aquatic bird/Korea/W44/2005(H7N3), and A/Chicken/Korea/116/2004(H9N2) viruses, the recombinant pgsA-CTA1-sM2/L.
+These results indicate that mucosal immunization with recombinant L. casei expressing CTA1-conjugated sM2 protein on its surface is an effective means of eliciting protective immune responses against diverse influenza subtypes.
+Nairobi sheep disease virus (NSDV) of the genus Nairovirus causes a haemorrhagic gastroenteritis in sheep and goats with mortality up to 90%; the virus is found in East and Central Africa, and in India, where the virus is called Ganjam virus.
+NSDV is closely related to the human pathogen Crimean-Congo haemorrhagic fever virus, which also causes a haemorrhagic disease.
+As with other nairoviruses, replication of NSDV takes place in the cytoplasm and the new virus particles bud into the Golgi apparatus; however, the effect of viral replication on cellular compartments has not been studied extensively.
+We have found that the overall structure of the endoplasmic reticulum (ER), the ER-Golgi intermediate compartment and the Golgi were unaffected by infection with NSDV.
+However, we observed that NSDV infection led to the loss of protein disulphide isomerase (PDI), an oxidoreductase present in the lumen of the endoplasmic reticulum (ER) and which assists during protein folding, from the ER.
+Further investigation showed that NSDV-infected cells have high levels of PDI at their surface, and PDI is also secreted into the culture medium of infected cells.
+Analysis of infected cells and expression of individual viral glycoproteins indicated that the NSDV PreGn glycoprotein is involved in redistribution of these soluble ER oxidoreductases.
+It has been suggested that extracellular PDI can activate integrins and tissue factor, which are involved respectively in pro-inflammatory responses and disseminated intravascular coagulation, both of which manifest in many viral haemorrhagic fevers.
+The discovery of enhanced PDI secretion from NSDV-infected cells may be an important finding for understanding the mechanisms underlying the pathogenicity of haemorrhagic nairoviruses.
+Influenza A virus is a dreadful pathogen of animals and humans, causing widespread infection and severe morbidity and mortality.
+It is essential to characterize the influenza A virus-host interaction and develop efficient counter measures against the viral infection.
+Recently, it has been shown that autophagy is a critical mechanism underlying the interaction between influenza A virus and its host.
+Autophagy can be induced by the infection with influenza A virus, which is considered as a necessary process for the viral proliferation, including the accumulation of viral elements during the replication of influenza A virus.
+On the other hand, influenza A virus can inhibit the autophagic formation via interaction with the autophagy-related genes (Atg) and signaling pathways.
+In addition, autophagy is involved in the influenza virus-regulated cell deaths, leading to significant changes in host apoptosis.
+Interestingly, the high pathogenic strains of influenza A virus, such as H5N1, stimulate autophagic cell death and appear to interplay with the autophagy in distinct ways as compared with low pathogenic strains.
+The implementation of expanded newborn screening programs reduced mortality and morbidity in medium-chain acyl-CoA dehydrogenase deficiency (MCADD) caused by mutations in the ACADM gene.
+Here we established a comprehensive experimental setup to analyze the structural consequences of eight ACADM missense mutations (p.Ala52Val, p.Tyr67His, p.Tyr158His, p.Arg206Cys, p.Asp266Gly, p.Lys329Glu, p.Arg334Lys, p.Arg413Ser) identified after newborn screening and linked the corresponding protein misfolding phenotype to the site of side-chain replacement with respect to the domain.
+With fever being the crucial risk factor for metabolic decompensation of patients with MCADD, special emphasis was put on the analysis of structural and functional derangements related to thermal stress.
+Based on protein conformation, thermal stability and kinetic stability, the molecular phenotype in MCADD depends on the structural region that is affected by missense-induced conformational changes with the central β-domain being particularly prone to structural derangement and destabilization.
+Since systematic classification of conformational derangements induced by ACADM mutations may be a helpful tool in assessing the clinical risk of patients, we scored the misfolding phenotype of the variants in comparison to p.Lys329Glu (K304E), the classical severe mutation, and p.Tyr67His (Y42H), discussed to be mild.
+Experiments assessing the impact of thermal stress revealed that mutations in the ACADM gene lower the temperature threshold at which MCAD loss-of-function occurs.
+Consequently, increased temperature as it occurs during intercurrent infections, significantly increases the risk of further conformational derangement and loss of function of the MCAD enzyme explaining the life-threatening clinical courses observed during fever episodes.
+The emergence of novel respiratory pathogens can challenge the capacity of key health care resources, such as intensive care units, that are constrained to serve only specific geographical populations.
+An ability to predict the magnitude and timing of peak incidence at the scale of a single large population would help to accurately assess the value of interventions designed to reduce that peak.
+However, current disease-dynamic theory does not provide a clear understanding of the relationship between: epidemic trajectories at the scale of interest (e.g.
+Here, we used a spatially-explicit stochastic meta-population model of arbitrary spatial resolution to determine the effect of resolution on model-derived epidemic trajectories.
+We simulated an influenza-like pathogen spreading across theoretical and actual population densities and varied our assumptions about mobility using Latin-Hypercube sampling.
+Even though, by design, cumulative attack rates were the same for all resolutions and mobilities, peak incidences were different.
+Clear thresholds existed for all tested populations, such that models with resolutions lower than the threshold substantially overestimated population-wide peak incidence.
+The effect of resolution was most important in populations which were of lower density and lower mobility.
+With the expectation of accurate spatial incidence datasets in the near future, our objective was to provide a framework for how to use these data correctly in a spatial meta-population model.
+If underlying interactions between pathogens and spatially heterogeneous populations are represented at this resolution or higher, accurate predictions of peak incidence for city-scale epidemics are feasible.
+Laboratory testing is the single highest-volume medical activity, making it useful to ask how well one can anticipate whether a given test result will be high, low, or within the reference interval (“normal”).
+We analyzed 10 years of electronic health records—a total of 69.4 million blood tests—to see how well standard rule-mining techniques can anticipate test results based on patient age and gender, recent diagnoses, and recent laboratory test results.
+We evaluated rules according to their positive and negative predictive value (PPV and NPV) and area under the receiver-operator characteristic curve (ROC AUCs).
+Using a stringent cutoff of PPV and/or NPV≥0.95, standard techniques yield few rules for sendout tests but several for in-house tests, mostly for repeat laboratory tests that are part of the complete blood count and basic metabolic panel.
+Most rules were clinically and pathophysiologically plausible, and several seemed clinically useful for informing pre-test probability of a given result.
+But overall, rules were unlikely to be able to function as a general substitute for actually ordering a test.
+It was found that high-affinity anti-DNA antibodies were one of the major components of the intrathecal IgG response in multiple sclerosis (MS) patients [Williamson et al., PNAS, 2001].
+Recently we have shown that IgGs from the sera of MS patients are active in the hydrolysis of DNA.
+Here we have shown, for the first time, that average concentration of total proteins (132-fold), total IgGs (194-fold) and anti-DNA antibodies (200-fold) in the sera is significantly higher than that in the cerebrospinal fluid (CSF) of fifteen MS patients.
+The relative activities of total protein from sera and CSFs varied remarkably from patient to patient.
+It was surprising that the specific DNase activity of the total protein of CSF reparations were 198-fold higher than the serum ones.
+Electrophoretically and immunologically homogeneous IgGs were obtained by sequential affinity chromatography of the CSF proteins on protein G-Sepharose and FPLC gel filtration.
+We present first evidence showing that IgGs from CSF not only bind but efficiently hydrolyze DNA and that average specific DNase activity of homogeneous antibodies from CSF is unpredictably ∼49-fold higher than that from the sera of the same MS patients.
+We suggest that DNase IgGs of CSF may promote important neuropathologic mechanisms in this chronic inflammatory disorder and MS pathogenesis development.
+The interferon-inducible restriction factor tetherin (also known as CD317, BST-2 or HM1.24) has emerged as a key component of the antiviral immune response.
+Initially, tetherin was shown to restrict replication of various enveloped viruses by inhibiting the release of budding virions from infected cells.
+More recently, it has become clear that tetherin also acts as a pattern recognition receptor inducing NF-κB-dependent proinflammatory gene expression in virus infected cells.
+Whereas the ability to restrict virion release is highly conserved among mammalian tetherin orthologs and thus probably an ancient function of this protein, innate sensing seems to be an evolutionarily recent activity.
+The potent and broad antiviral activity of tetherin is reflected by the fact that many viruses evolved means to counteract this restriction factor.
+A continuous arms race with viruses has apparently driven the evolution of different isoforms of tetherin with different functional properties.
+Interestingly, tetherin has also been implicated in cellular processes that are unrelated to immunity, such as the organization of the apical actin network and membrane microdomains or stabilization of the Golgi apparatus.
+In this review, I summarize our current knowledge of the different functions of tetherin and describe the molecular strategies that viruses have evolved to antagonize or evade this multifunctional host restriction factor.
+Replication of plus-strand RNA viruses depends on recruited host factors that aid several critical steps during replication.
+Several of the co-opted host factors bind to the viral RNA, which plays multiple roles, including mRNA function, as an assembly platform for the viral replicase (VRC), template for RNA synthesis, and encapsidation during infection.
+It is likely that remodeling of the viral RNAs and RNA-protein complexes during the switch from one step to another requires RNA helicases.
+In this paper, we have discovered a second group of cellular RNA helicases, including the eIF4AIII-like yeast Fal1p and the DDX5-like Dbp3p and the orthologous plant AtRH2 and AtRH5 DEAD box helicases, which are co-opted by tombusviruses.
+Unlike the previously characterized DDX3-like AtRH20/Ded1p helicases that bind to the 3′ terminal promoter region in the viral minus-strand (−)RNA, the other class of eIF4AIII-like RNA helicases bind to a different cis-acting element, namely the 5′ proximal RIII(−) replication enhancer (REN) element in the TBSV (−)RNA.
+We show that the binding of AtRH2 and AtRH5 helicases to the TBSV (−)RNA could unwind the dsRNA structure within the RIII(−) REN.
+This unique characteristic allows the eIF4AIII-like helicases to perform novel pro-viral functions involving the RIII(−) REN in stimulation of plus-strand (+)RNA synthesis.
+We also show that AtRH2 and AtRH5 helicases are components of the tombusvirus VRCs based on co-purification experiments.
+We propose that eIF4AIII-like helicases destabilize dsRNA replication intermediate within the RIII(−) REN that promotes bringing the 5′ and 3′ terminal (−)RNA sequences in close vicinity via long-range RNA-RNA base pairing.
+This newly formed RNA structure promoted by eIF4AIII helicase together with AtRH20 helicase might facilitate the recycling of the viral replicases for multiple rounds of (+)-strand synthesis, thus resulting in asymmetrical viral replication.
+While viruses must evade autophagocytic destruction, some viruses can also subvert autophagy for their own benefit.
+The ability of influenza A virus (IAV) to evade autophagy depends on the Matrix 2 (M2) ion-channel protein.
+We show that the cytoplasmic tail of IAV M2 interacts directly with the essential autophagy protein LC3 and promotes LC3 relocalization to the unexpected destination of the plasma membrane.
+The M2 LIR is required for LC3 redistribution to the plasma membrane in virus-infected cells.
+Mutations in M2 that abolish LC3 binding interfere with filamentous budding and reduce virion stability.
+This strategy may facilitate transmission of infection between organisms by enhancing the stability of viral progeny.
+Glycyrrhizin has a role in immune regulation in the central nervous system, but its impact on sciatic nerve injury had not previously been reported.
+In this study, a BALB/c mouse model of sciatic nerve injury was used to explore the role of glycyrrhizin in sciatic nerve repair and its underlying mechanism.
+Glycyrrhizin with intragastric gavage of 10 and 20 mg/kg weight per day (mid- and high-dose, respectively) inhibited p75 neurotrophin receptor (p75NTR) expression at the protein and mRNA levels versus the 5 mg/kg (low-dose) group and control (0.9% NaCl solution) at one, two, four and eight weeks following sciatic nerve injury, and simultaneously improved the action potential amplitude and motor nerve conductive velocity.
+Combined Marsland, Glees and Erikson’s silver stain and Luxol fast blue staining results indicated that high- and mid-dose glycyrrhizin promoted improved sciatic nerve myelination compared with the low-dose or control groups eight weeks after injury.
+Immunofluorescence staining demonstrated that glycyrrhizin had an inhibitory effect to a certain degree on local hypertrophic scar and inflammatory responses in the mouse model.
+In conclusion, glycyrrhizin can promote sciatic nerve regeneration and functional repair, in which doses of 10 and 20 mg/kg per day are more effective than lower doses, and such regeneration is associated with the downregulation of p75NTR.
+[Image: see text] Active immunization is an effective means of blocking the pharmacodynamic effects of drugs and holds promise as a treatment for heroin addiction.
+Previously, we demonstrated the efficacy of our first-generation vaccine in blocking heroin self-administration in rats, however, many vaccine components can be modified to further improve performance.
+Mice immunized via subcutaneous (sc) injection exhibited inferior anti-heroin titers compared to intraperitoneal (ip) and sc/ip coadministration injection routes.
+Addition of TLR9 agonist cytosine-guanine oligodeoxynucleotide 1826 (CpG ODN 1826) to the original alum adjuvant elicited superior antibody titers and opioid affinities compared to alum alone.
+To thoroughly assess vaccine efficacy, full dose–response curves were generated for heroin-induced analgesia in both hot plate and tail immersion tests.
+Mice treated with CpG ODN 1826 exhibited greatly shifted dose–response curves (10–13-fold vs unvaccinated controls) while non-CpG ODN vaccine groups did not exhibit the same robust effect (2–7-fold shift for ip and combo, 2–3-fold shift for sc).
+Our results suggest that CpG ODN 1826 is a highly potent adjuvant, and injection routes should be considered for development of small molecule–protein conjugate vaccines.
+Lastly, this study has established a new standard for assessing drugs of abuse vaccines, wherein a full dose–response curve should be performed in an appropriate behavioral task.
+The possibility of using variable domain heavy-chain antibodies (VHH antibodies) as diagnostic tools for dengue virus (DENV) type 2 NS1 protein was investigated and compared with the use of conventional monoclonal antibodies.
+After successful expression of DENV type 2 NS1 protein, the genes of VHH antibodies against NS1 protein were biopanned from a non-immune llama library by phage display.
+Sequence analysis of the VHH antibodies revealed novel and long complementarity determining regions 3 (CDR3).
+Epitope mapping was performed via a phage display peptide library using purified VHH and monoclonal antibodies as targets.
+Interestingly, the same region of NS1, which comprises amino acids (224)HWPKPHTLW(232), was conserved for both kinds of antibodies displaying the consensus motif histidine-tryptophan-tryptophan or tryptophan-proline-tryptophan.
+The two types of antibodies were used to prepare rapid diagnostic kits based on immunochromatographic assay.
+The VHH antibody immobilized rapid diagnostic kit showed better sensitivity and specificity than the monoclonal antibody immobilized rapid diagnostic kit, which might be due to the long CDR3 regions of the VHH antibodies and their ability to bind to the pocket and cleft of the targeted antigen.
+This demonstrates that VHH antibodies are likely to be an option for developing point-of-care tests against DENV infection.
+BACKGROUND: Recent studies have demonstrated that mesenchymal stem cells (MSCs) modulate the immune response and reduce lung injury in animal models.
+Currently, no clinical studies of the effects of MSCs in acute respiratory distress syndrome (ARDS) exist.
+The objectives of this study were first to examine the possible adverse events after systemic administration of allogeneic adipose-derived MSCs in ARDS patients and second to determine potential efficacy of MSCs on ARDS.
+METHODS: Twelve adult patients meeting the Berlin definition of acute respiratory distress syndrome with a PaO(2)/FiO(2) ratio of < 200 were randomized to receive allogeneic adipose-derived MSCs or placebo in a 1:1 fashion.
+Patients received one intravenous dose of 1 × 10(6) cells/kg of body weight or saline.
+Acute lung injury biomarkers, including IL-6, IL-8 and surfactant protein D (SP-D), were examined to determine the effects of MSCs on lung injury and inflammation.
+RESULTS: There were no infusion toxicities or serious adverse events related to MSCs administration and there were no significant differences in the overall number of adverse events between the two groups.
+Length of hospital stay, ventilator-free days and ICU-free days at day 28 after treatment were similar.
+In the MSCs group, serum SP-D levels at day 5 were significantly lower than those at day 0 (p = 0.027) while the changes in IL-8 levels were not significant.
+The IL-6 levels at day 5 showed a trend towards lower levels as compared with day 0, but this trend was not statistically significant (p = 0.06).
+CONCLUSIONS: Administration of allogeneic adipose-derived MSCs appears to be safe and feasible in the treatment of ARDS.
+However, the clinical effect with the doses of MSCs used is weak, and further optimization of this strategy will probably be required to reach the goal of reduced alveolar epithelial injury in ARDS.
+Although patient cohort studies have shown the production of CHIKV specific antibodies, the fine specificity of the antibody response against CHIKV is not completely defined.
+More importantly, its close relation to humans will allow the study of chronic infection and further identify important CHIKV targets.
+In this study, serum samples from CHIKV-infected macaques collected at different time-points post infection were used to characterize the antibody production pattern and kinetics.
+Results revealed that anti-CHIKV antibodies were neutralizing and the E2 glycoprotein, Capsid, nsP1, nsP3 and nsP4 proteins were targets of the anti-CHIKV antibody response in macaques.
+Furthermore, linear B-cell epitopes recognized by these anti-CHIKV antibodies were identified, and mapped to their structural localization.
+This characterizes the specificity of anti-CHIKV antibody response in macaques and further demonstrates the importance of the different regions in CHIKV-encoded proteins in the adaptive immune response.
+Information from this study provides critical knowledge that will aid in the understanding of CHIKV infection and immunity, vaccine design, and pre-clinical efficacy studies.
+Translational medicine is a roller coaster with occasional brilliant successes and a large majority of failures.
+Lost in Translation 1 (‘LiT1’), beginning in the 1950s, was a golden era built upon earlier advances in experimental physiology, biochemistry and pharmacology, with a dash of serendipity, that led to the discovery of many new drugs for serious illnesses.
+LiT2 saw the large-scale industrialization of drug discovery using high-throughput screens and assays based on affinity for the target molecule.
+The links between drug development and university sciences and medicine weakened, but there were still some brilliant successes.
+In LiT3, the coverage of translational medicine expanded from molecular biology to drug budgets, with much greater emphasis on safety and official regulation.
+Compared with R&D expenditure, the number of breakthrough discoveries in LiT3 was disappointing, but monoclonal antibodies for immunity and inflammation brought in a new golden era and kinase inhibitors such as imatinib were breakthroughs in cancer.
+The pharmaceutical industry is trying to revive the LiT1 approach by using phenotypic assays and closer links with academia.
+LiT4 faces a data explosion generated by the genome project, GWAS, ENCODE and the ‘omics’ that is in danger of leaving LiT4 in a computerized cloud.
+Industrial laboratories are filled with masses of automated machinery while the scientists sit in a separate room viewing the results on their computers.
+Big Data will need Big Thinking in LiT4 but with so many unmet medical needs and so many new opportunities being revealed there are high hopes that the roller coaster will ride high again.
+The choice of an adequate level of response relies upon available knowledge of the spatial and temporal parameters governing pathogen spread, affecting, amongst others, the predicted severity of the epidemic.
+Yet, when a new pathogen is introduced into an alien environment, such information is often lacking or of no use, and epidemiological parameters must be estimated from the first observations of the epidemic.
+This poses a challenge to epidemiologists: how quickly can the parameters of an emerging disease be estimated?
+We investigate these issues using a unique, spatially and temporally resolved dataset for the invasion of a plant disease, Asiatic citrus canker in urban Miami.
+We use epidemiological models, Bayesian Markov-chain Monte Carlo, and advanced spatial statistical methods to analyse rates and extent of spread of the disease.
+The spatial scale of spread is approximately constant over time and can be estimated rapidly with great precision (although the evidence for long-range transmission is inconclusive).
+In contrast, the rate of infection is characterised by strong monthly fluctuations that we associate with extreme weather events.
+Uninformed predictions from the early stages of the epidemic, assuming complete ignorance of the future environmental drivers, fail because of the unpredictable variability of the infection rate.
+Conversely, predictions improve dramatically if we assume prior knowledge of either the main environmental trend, or the main environmental events.
+A contrast emerges between the high detail attained by modelling in the spatiotemporal description of the epidemic and the bottleneck imposed on epidemic prediction by the limits of meteorological predictability.
+We argue that identifying such bottlenecks will be a fundamental step in future modelling of weather-driven epidemics.
+The progressive loss of muscle mass characteristic of many muscular dystrophies impairs the efficacy of most of the gene and molecular therapies currently being pursued for the treatment of those disorders.
+It is becoming increasingly evident that a therapeutic application, to be effective, needs to target not only mature myofibers, but also muscle progenitors cells or muscle stem cells able to form new muscle tissue and to restore myofibers lost as the result of the diseases or during normal homeostasis so as to guarantee effective and lost lasting effects.
+Correction of the genetic defect using oligodeoxynucleotides (ODNs) or engineered nucleases holds great potential for the treatment of many of the musculoskeletal disorders.
+The encouraging results obtained by studying in vitro systems and model organisms have set the groundwork for what is likely to become an emerging field in the area of molecular and regenerative medicine.
+Furthermore, the ability to isolate and expand from patients various types of muscle progenitor cells capable of committing to the myogenic lineage provides the opportunity to establish cell lines that can be used for transplantation following ex vivo manipulation and expansion.
+The purpose of this article is to provide a perspective on approaches aimed at correcting the genetic defect using gene editing strategies and currently under development for the treatment of Duchenne muscular dystrophy (DMD), the most sever of the neuromuscular disorders.
+Emphasis will be placed on describing the potential of using the patient own stem cell as source of transplantation and the challenges that gene editing technologies face in the field of regenerative biology.
+Parainfluenza virus (PIV) commonly infects patients following hematopoietic cell transplantation (HCT), frequently causing lower respiratory tract disease (LRTD).
+The definition of LRTD significantly differs among studies evaluating the impact of PIV after HCT.
+We retrospectively evaluated 544 HCT recipients with laboratory-confirmed PIV and classified LRTD into 3 groups: possible (PIV detection in upper respiratory tract with new pulmonary infiltrates with/without LRTD symptoms), probable (PIV detection in lung with LRTD symptoms without new pulmonary infiltrates), and proven (PIV detection in lung with new pulmonary infiltrates with/without LRTD symptoms).
+Probabilities of 90-day survival after LRTD were 87%, 58%, and 45% in possible, probable, and proven cases, respectively.
+Patients with probable and proven LRTD had significantly worse survival than those with upper respiratory tract infection (probable: hazard ratio [HR], 5.87 [P < .001]; proven: HR, 9.23 [P < .001]), whereas possible LRTD did not (HR, 1.49 [P = .27]).
+Among proven/probable cases, oxygen requirement at diagnosis, low monocyte counts, and high-dose steroid use (>2 mg/kg/day) were associated with high mortality in multivariable analysis.
+PIV LRTD with viral detection in lungs (proven/probable LRTD) was associated with worse outcomes than was PIV LRTD with viral detection in upper respiratory samples alone (possible LRTD).
+This new classification should impact clinical trial design and permit comparability of results among centers.
+AIM: To demonstrate the gene expression profiles mediated by hepatitis B virus X protein (HBx), we characterized the molecular features of pathogenesis associated with HBx in a human liver cell model.
+METHODS: We examined gene expression profiles in L-O2-X cells, an engineered L-O2 cell line that constitutively expresses HBx, relative to L-O2 cells using an Agilent 22 K human 70-mer oligonucleotide microarray representing more than 21,329 unique, well-characterized Homo sapiens genes.
+Western blot analysis and RNA interference (RNAi) targeting HBx mRNA validated the overexpression of proliferating cell nuclear antigen (PCNA) and Bcl-2 in L-O2-X cells.
+Meanwhile, the BrdU incorporation assay was used to test cell proliferation mediated by upregulated cyclooxygenase-2 (COX-2).
+RESULTS: The microarray showed that the expression levels of 152 genes were remarkably altered; 82 of the genes were upregulated and 70 genes were downregulated in L-O2-X cells.
+The altered genes were associated with signal transduction pathways, cell cycle, metastasis, transcriptional regulation, immune response, metabolism, and other processes.
+Furthermore, we found that COX-2 upregulation in L-O2-X cells enhanced proliferation using the BrdU incorporation assay, whereas indomethacin (an inhibitor of COX-2) abolished the promotion.
+CONCLUSION: Our findings provide new evidence that HBx is able to regulate many genes that may be involved in the carcinogenesis.
+These regulated genes mediated by HBx may serve as molecular targets for the prevention and treatment of hepatocellular carcinoma.
+Pulmonary fibrosis (PF) is a common complication in those interstitial lung diseases patients, which will result in poor prognosis and short survival.
+Traditional therapeutic methods such as glucocorticoid and cytotoxic drugs are insufficient for treating PF and may cause severe side effects.
+Recent studies showed that traditional Chinese herbal abstraction such as Tanshinone IIA (TIIA) was displayed significant anti-PF effects in animal models.
+The results showed that BLM resulted in severe PF and alveolar inflammation; together with significant elevation of transforming growth factor-β 1 (TGF-β1).
+Angiotensin-converting enzyme 2 (ACE-2) together with angiotensin-(1-7) [ANG-(1-7)] were both greatly reduced after BLM administration.
+TIIA treatment notably attenuated BLM induced PF and inflammation, decreased expression of TGF-β1 and reversed ACE-2 and ANG-(1-7) production in rat lungs.
+Thus we may draw the conclusion that TIIA may exert protective effects on BLM induced PF in rats, and the ACE-2/ANG-(1-7) axis may ascribe to those protective effects.
+Studies of the domestic cat have contributed to many scientific advances, including the present understanding of the mammalian cerebral cortex.
+A practical capability for cat transgenesis is needed to realize the distinctive potential of research on this neurobehaviorally complex, accessible species for advancing human and feline health.
+For example, humans and cats are afflicted with pandemic AIDS lentiviruses that are susceptible to species-specific restriction factors.
+Here we introduced genes encoding such a factor, rhesus macaque TRIMCyp, and eGFP, into the cat germline.
+This capability to experimentally manipulate the genome of an AIDS-susceptible species can be used to test the potential of restriction factors for HIV gene therapy and to build models of other infectious and noninfectious diseases.
+SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nmeth.1703) contains supplementary material, which is available to authorized users.
+BACKGROUND: Mice lacking the type I interferon receptor (IFNAR(−/−) mice) reproduce relevant aspects of Crimean-Congo hemorrhagic fever (CCHF) in humans, including liver damage.
+We aimed at characterizing the liver pathology in CCHF virus-infected IFNAR(−/−) mice by immunohistochemistry and employed the model to evaluate the antiviral efficacy of ribavirin, arbidol, and T-705 against CCHF virus.
+METHODOLOGY/PRINCIPAL FINDINGS: CCHF virus-infected IFNAR(−/−) mice died 2–6 days post infection with elevated aminotransferase levels and high virus titers in blood and organs.
+Main pathological alteration was acute hepatitis with extensive bridging necrosis, reactive hepatocyte proliferation, and mild to moderate inflammatory response with monocyte/macrophage activation.
+Ribavirin, arbidol, and T-705 suppressed virus replication in vitro by ≥3 log units (IC(50) 0.6–2.8 µg/ml; IC(90) 1.2–4.7 µg/ml).
+Ribavirin [100 mg/(kg×d)] did not increase the survival rate of IFNAR(−/−) mice, but prolonged the time to death (p<0.001) and reduced the aminotransferase levels and the virus titers.
+Animals treated with T-705 at 1 h [15, 30, and 300 mg/(kg×d)] or up to 2 days [300 mg/(kg×d)] post infection survived, showed no signs of disease, and had no virus in blood and organs.
+CONCLUSIONS/SIGNIFICANCE: Activated hepatic macrophages and monocyte-derived cells may play a role in the proinflammatory cytokine response in CCHF.
+Its in vivo efficacy exceeds that of the current standard drug for treatment of CCHF, ribavirin.
+The high incidence of emerging infectious diseases has highlighted the importance of effective immunization strategies, especially the stochastic algorithms based on local available network information.
+Present stochastic strategies are mainly evaluated based on classical network models, such as scale-free networks and small-world networks, and thus are insufficient.
+Three frequently referred stochastic immunization strategies—acquaintance immunization, community-bridge immunization, and ring vaccination—were analyzed in this work.
+The optimal immunization ratios for acquaintance immunization and community-bridge immunization strategies were investigated, and the effectiveness of these three strategies in controlling the spreading of epidemics were analyzed based on realistic social contact networks.
+The results show all the strategies have decreased the coverage of the epidemics compared to baseline scenario (no control measures).
+However the effectiveness of acquaintance immunization and community-bridge immunization are very limited, with acquaintance immunization slightly outperforming community-bridge immunization.
+Ring vaccination significantly outperforms acquaintance immunization and community-bridge immunization, and the sensitivity analysis shows it could be applied to controlling the epidemics with a wide infectivity spectrum.
+The effectiveness of several classical stochastic immunization strategies was evaluated based on realistic contact networks for the first time in this study.
+Genetic information regarding the leader (L) and complete capsid-coding (P1) region of FMD serotype A and O viruses prevalent on the African continent is lacking.
+Here, we present the complete L-P1 sequences for eight serotype A and nine serotype O viruses recovered from FMDV outbreaks in East and West Africa over the last 33 years.
+Phylogenetic analysis of the P1 and capsid-coding regions revealed that the African isolates grouped according to serotype, and certain clusters were indicative of transboundary as well as intra-regional spread of the virus.
+However, similar analysis of the L region revealed random groupings of isolates from serotypes O and A.
+Comparisons between the phylogenetic trees derived from the structural coding regions and the L region pointed to a possibility of genetic recombination.
+The intertypic nucleotide and amino acid variation of all the isolates in this study supported results from previous studies where the externally located 1D was the most variable whilst the internally located 1A was the most conserved, which likely reflects the selective pressures on these proteins.
+Amino acids identified previously as important for FMDV structure and functioning were found to be highly conserved.
+The information gained from this study will contribute to the construction of structurally designed FMDV vaccines in Africa.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00705-013-1838-9) contains supplementary material, which is available to authorized users.
+Current human papillomavirus (HPV) major capsid protein L1 virus-like particles (VLPs)-based vaccines in clinic induce strong HPV type-specific neutralizing antibody responses.
+To develop pan-HPV vaccines, here, we show that the fusion protein E3R4 consisting of three repeats of HPV16 L2 aa 17–36 epitope (E3) and a modified human IgG1 Fc scaffold (R4) induces cross-neutralizing antibodies and protective immunity against divergent HPV types.
+E3R4 was expressed as a secreted protein in baculovirus expression system and could be simply purified by one step Protein A affinity chromatography with the purity above 90%.
+Vaccination of E3R4 formulated with Freunds adjuvant not only induced cross-neutralizing antibodies against HPV pseudovirus types 16, 18, 45, 52, 58, 6, 11 and 5 in mice, but also protected mice against vaginal challenges with HPV pseudovirus types 16, 45, 52, 58, 11 and 5 for at least eleven months after the first immunization.
+Moreover, vaccination of E3R4 formulated with FDA approved adjuvant alum plus monophosphoryl lipid A also induced cross-neutralizing antibodies against HPV types 16, 18 and 6 in rabbits.
+Thus, our results demonstrate that delivery of L2 antigen as a modified Fc-fusion protein may facilitate pan-HPV vaccine development.
+Blood parasites of the sub-genus Haemoproteus have been reported in seabirds, in particular in species in the Suliformes order.
+These parasites are transmitted by hippoboscid flies of the genus Olfersia; strong specificity has been suggested between the vector and its vertebrate host.
+We investigated the prevalence of Haemoproteus infection in Suliformes and hippoboscid flies in two oceanic islands of the Western Indian Ocean: Europa and Tromelin.
+In total, 209 blood samples were collected from great frigatebirds (Fregata minor), masked boobies (Sula dactylatra) and red-footed boobies (Sula sula).
+Seventeen frigatebirds and one fly collected on Europa tested positive for the presence of Haemoproteus parasites by polymerase chain reaction.
+Phylogenetic analyses based on partial sequences of the Cytochrome b gene showed that parasites were closely related to Haemoproteus iwa reported from frigatebirds in the Pacific Ocean and in the Caribbean.
+Plasmodium was also detected in a frigatebird on Europa; however, its placement on the phylogenetic tree could not be resolved.
+We provide strong support for transmission of blood parasites in seabirds in the Western Indian Ocean and suggest that migrations between the Pacific and the Indian oceans could favor the large-scale distribution of Haemoproteus iwa in frigatebird populations.
+BACKGROUND: Acute respiratory failure (ARF) and severe sepsis (SS) are possible complications in patients with community-acquired pneumonia (CAP).
+The aim of the study was to evaluate prevalence, characteristics, risk factors and impact on mortality of hospitalized patients with CAP according to the presence of ARF and SS on admission.
+METHODS: This was a multicenter, observational, prospective study of consecutive CAP patients admitted to three hospitals in Italy, Spain, and Scotland between 2008 and 2010.
+Three groups of patients were identified: those with neither ARF nor SS (Group A), those with only ARF (Group B) and those with both ARF and SS (Group C) on admission.
+RESULTS: Among the 2,145 patients enrolled, 45% belonged to Group A, 36% to Group B and 20% to Group C. Patients in Group C were more severe than patients in Group B.
+Isolated ARF was correlated with age (p < 0.001), COPD (p < 0.001) and multilobar infiltrates (p < 0.001).
+The contemporary occurrence of ARF and SS was associated with age (p = 0.002), residency in nursing home (p = 0.007), COPD (p < 0.001), multilobar involvement (p < 0.001) and renal disease (p < 0.001).
+4.2% of patients in Group A died, 9.3% in Group B and 26% in Group C, p < 0.001.
+After adjustment, the presence of only ARF had an OR for in-hospital mortality of 1.85 (p = 0.011) and the presence of both ARF and SS had an OR of 6.32 (p < 0.001).
+CONCLUSIONS: The identification of ARF and SS on hospital admission can help physicians in classifying CAP patients into three different clinical phenotypes.
+Innate immunity involves direct interactions between the host and microorganisms, both pathogenic and symbiotic, so natural selection is expected to strongly influence genes involved in these processes.
+Population genetics investigates the impact of past natural selection events on the genome of present-day human populations, and it complements immunological as well as clinical and epidemiological genetic studies.
+Recent data show that the impact of selection on the different families of innate immune receptors and their downstream signalling molecules varies considerably.
+This Review discusses these findings and highlights how they help to delineate the relative functional importance of innate immune pathways, which can range from being essential to being redundant.
+The IL-13/TGF-β(1) interaction has previously been identified as a key pathway orchestrating fibrosis in different inflammatory immune disorders.
+Here we investigate if this pathway is also responsible for allograft fibrosis and if interference with the IL-13/TGF-β(1) interaction prevents allograft fibrosis.
+METHODS: FVB or control DBA/1 donor hearts were transplanted heterotopically into DBA/1 recipient mice and hearts were explanted at day 60 and 100 post-transplantation.
+Cardiac tissue was examined by Masson’s trichrome staining and immunohistochemistry for CD4, CD8, CD11b, IL-13, Fas ligand, matrix metalloproteinase (MMP)-1, MMP-13, β2-microglobulin, and Gremlin-1.
+IL-13 and TGF-β(1) levels were determined by enzyme-linked immunosorbent assay (ELISA) and the amount of collagen was quantified using a Sircol assay; IL-13Rα(2) expression was detected by Western blotting.
+Additionally, a PCR array of RNA isolated from the allografts was performed to analyze expression of multiple genes involved in fibrosis.
+The allogeneic grafts were infiltrated by significantly increased numbers of CD4(+) (P <0.0001), CD8(+) (P <0.0001), and CD11b(+) cells (P = 0.0065) by day 100.
+Furthermore, elevated IL-13 levels (P = 0.0003) and numbers of infiltrating IL-13(+) cells (P = 0.0037), together with an expression of IL-13Rα(2), were detected only within allografts.
+The expression of IL-13 and IL-13Rα(2) resulted in significantly increased TGF-β(1) levels (P <0.0001), higher numbers of CD11b(high)Gr1(intermediate)TGF-β(1)(+) cells, and elevated cardiac collagen deposition (P = 0.0094).
+The allograft fibrosis found in these experiments was accompanied by upregulation of multiple profibrotic genes, which was confirmed by immunohistochemical stainings of allograft tissue.
+Blockage of the IL-13/TGF-β(1) interaction by IL-13Rα(2) siRNA led to lower numbers of CD11b(high)Gr1(intermediate)TGF-β(1)(+), CD4(+), CD8(+), and CD11b(+) cells, and prevented collagen deposition (P = 0.0018) within these allografts.
+CONCLUSIONS: IL-13 signaling via IL-13Rα(2) induces TGF-β(1) and causes allograft fibrosis in a murine model of chronic transplant rejection.
+Thus, IL-13Rα(2) may be exploitable as a future target to reduce allograft fibrosis in organ transplantation.
+BACKGROUND: The usefulness of bronchoalveolar lavage (BAL) fluid cellular analysis in pneumonia has not been adequately evaluated.
+This study investigated the ability of cellular analysis of BAL fluid to differentially diagnose bacterial pneumonia from viral pneumonia in adult patients who are admitted to intensive care unit.
+METHODS: BAL fluid cellular analysis was evaluated in 47 adult patients who underwent bronchoscopic BAL following less than 24 hours of antimicrobial agent exposure.
+The abilities of BAL fluid total white blood cell (WBC) counts and differential cell counts to differentiate between bacterial and viral pneumonia were evaluated using receiver operating characteristic (ROC) curve analysis.
+RESULTS: Bacterial pneumonia (n = 24) and viral pneumonia (n = 23) were frequently associated with neutrophilic pleocytosis in BAL fluid.
+BAL fluid median total WBC count (2,815/µL vs. 300/µL, P<0.001) and percentage of neutrophils (80.5% vs. 54.0%, P = 0.02) were significantly higher in the bacterial pneumonia group than in the viral pneumonia group.
+In ROC curve analysis, BAL fluid total WBC count showed the best discrimination, with an area under the curve of 0.855 (95% CI, 0.750–0.960).
+BAL fluid total WBC count ≥510/µL had a sensitivity of 83.3%, specificity of 78.3%, positive likelihood ratio (PLR) of 3.83, and negative likelihood ratio (NLR) of 0.21.
+When analyzed in combination with serum procalcitonin or C-reactive protein, sensitivity was 95.8%, specificity was 95.7%, PLR was 8.63, and NLR was 0.07.
+BAL fluid total WBC count ≥510/µL was an independent predictor of bacterial pneumonia with an adjusted odds ratio of 13.5 in multiple logistic regression analysis.
+CONCLUSIONS: Cellular analysis of BAL fluid can aid early differential diagnosis of bacterial pneumonia from viral pneumonia in critically ill patients.
+BACKGROUND: Hemorrhagic fever with renal syndrome (HFRS) has become an important public health concern because of the high incidence and mortality rates, and limited treatment and vaccination.
+Until now, clinical studies on characteristics and outcomes in critical patients with HFRS have been limited.
+The aim of this study was to observe the clinical characteristics and cumulative proportions surviving and explore the predictive effects and risk factors for prognosis.
+The patients enrolled were treated in the centre for infectious diseases, Tangdu Hospital, between January 2008 and August 2012.
+The clinical characteristics between the survivors and non-survivors were compared by Student’s t-test or Chi-square test.
+The predictive effects of prognosis in clinical and laboratory parameters were analyzed by receiver operating characteristic (ROC) curves.
+The cumulative proportions surviving at certain intervals in the critical patients were observed by Kaplan-Meier survival analysis.
+RESULTS: Of the 75 patients enrolled, the cumulative proportion surviving was 70.7% at the second week interval, with a 28-day mortality rate of 36.3%.
+The non-survivors tended to have higher frequencies of agitation, dyspnea, conjunctival hemorrhage, coma, cardiac failure, acute respiratory distress syndrome (ARDS) and encephalopathy (P < .05).
+ARDS, conjunctival hemorrhage and coma were risk factors for death in the critical patients with HFRS.
+The non-survivors were found to have lower serum creatinine (Scr) levels (P < .001) and higher incidences of prolonged prothrombin time (PT) (P = .006), activated partial thromboplastin time (APTT) (P = .003) and elevated white blood cells (WBC) levels (P = .005), and the laboratory parameters mentioned above reached statistical significance for predicting prognosis (P < .05).
+CONCLUSION: The high fatality in critical patients with HFRS underscores the importance of clinicians’ alertness to the occurrence of potentially fatal complications and changes in biochemical status to ensure that timely and systematically supportive treatment can be initiated when necessary.
+As a modulator of the immune pathway, it indirectly controls the amount of antimicrobial peptides.
+Evolutionary questions are crucial to understanding the conservation and functioning of the biochemical pathways like the Tollip-mediated one.
+Through an analysis of 36 sequences of the Tollip protein from different animal taxa, downloaded from Kyoto Encyclopedia of Genes and Genomes (KEGG) databank, we inferred diverse evolutionary parameters, such as molecular selection and structure conservation, by analyzing residue by residue, beyond the canonical parameters to this type of study, as maximum likelihood trees.
+In primates, the protein is becoming more unstable, just the opposite is observed in the arthropod group.
+The most interesting finding was the concentration of positively selected residues at amino terminal ends.
+Some observed topological incongruences in maximum likelihood trees of complete and curated Tollip data sets could be explained through horizontal transfers, evidenced by recombination detection.
+These results suggest that there is more to be researched and understood about this protein.
+BACKGROUND: School closure is a non-pharmaceutical intervention that was considered in many national pandemic plans developed prior to the start of the influenza A(H1N1)pdm09 pandemic, and received considerable attention during the event.
+Here, we retrospectively review and compare national and local experiences with school closures in several countries during the A(H1N1)pdm09 pandemic.
+Our intention is not to make a systematic review of country experiences; rather, it is to present the diversity of school closure experiences and provide examples from national and local perspectives.
+METHODS: Data were gathered during and following a meeting, organized by the European Centres for Disease Control, on school closures held in October 2010 in Stockholm, Sweden.
+The twelve participating countries and administrative regions (Bulgaria, China, France, Hong Kong Special Administrative Region (SAR), Italy, Japan, New Zealand, Serbia, South Africa, Thailand, United Kingdom, and United States) provided data.
+RESULTS: Our review highlights the very diverse national and local experiences on school closures during the A(H1N1)pdm09 pandemic.
+The processes including who was in charge of making recommendations and who was in charge of making the decision to close, the school-based control strategies, the extent of school closures, the public health tradition of responses and expectations on school closure varied greatly between countries.
+Our review also discusses the many challenges associated with the implementation of this intervention and makes recommendations for further practical work in this area.
+CONCLUSIONS: The single most important factor to explain differences observed between countries may have been the different public health practises and public expectations concerning school closures and influenza in the selected countries.
+Age-related macular degeneration (AMD) is the leading cause of vision loss in the elderly throughout the industrialized world.
+Its most prominent pathologic features are lesions involving the retinal pigment epithelium (RPE) the Bruch's membrane, the degeneration of photoreceptors, and, in the most aggressive cases, choroidal neovascularization.
+Genetic associations between the risk of developing AMD and polymorphism within components of the complement system, as well as chemokine receptors expressed on microglial cells and macrophages, have linked retinal degeneration and choroidal neovascularization to innate immunity (inflammation).
+In addition to inflammation, players of the adaptive immunity including cytokines, chemokines, antibodies, and T cells have been detected in animal models of AMD and in patients suffering from this pathology.
+These observations suggest that adaptive immunity might play a role in different processes associated with AMD such as RPE atrophy, neovascularization, and retinal degeneration.
+To this date however, the exact roles (if any) of autoantibodies and T cells in AMD remain unknown.
+In this review we discuss the potential effects of adaptive immune responses in AMD pathogenesis.
+The influenza virus surface glycoprotein hemagglutinin (HA) is responsible for viral attachment to sialic acid-containing host cell receptors and it facilitates the initial stage of viral infection.
+In the present study, we isolated an RNA aptamer specific to the glycosylated receptor-binding domain of the HA protein (gHA1) after 12 cycles of the systematic evolution of ligands by exponential enrichment procedure (SELEX), and we then investigated if the selected aptamer suppresses viral infection in host cells.
+Nitrocellulose filter binding and enzyme-linked immunosorbent assay (ELISA) experiments revealed that 1 RNA aptamer, HA12-16, bound specifically to the gHA1 protein.
+Cell viability assay showed that the HA12-16 RNA aptamer suppressed viral infection in host cells by enhancing cell viability.
+Immunofluorescence microscopic analysis further demonstrated that the HA12-16 RNA aptamer suppresses viral attachment to host cells by neutralizing the receptor-binding site of influenza virus HA.
+These results indicate that the isolated RNA aptamer can be developed as an antiviral reagent against influenza through appropriate therapeutic formulation.
+The growing concern over climate and other drivers that may increase infectious disease threats to future generations has stimulated a review of the surveillance systems and environmental data sources that might be used to assess future health impacts from climate change in Europe.
+We present an overview of organizations, agencies and institutions that are responsible for infectious disease surveillance in Europe.
+We describe the surveillance systems, tracking tools, communication channels, information exchange and outputs in light of environmental and climatic drivers of infectious diseases.
+Many of the environmental data sets have a relatively uniform quality across EU Member States because they are based on satellite measurements or EU funded FP6 or FP7 projects with full EU coverage.
+Case-reporting systems for surveillance of infectious diseases should include clear and consistent case definitions and reporting formats that are geo-located at an appropriate resolution.
+This will allow linkage to environmental, social and climatic sources that will enable risk assessments, future threat evaluations, outbreak management and interventions to reduce disease burden.
+Reporter genes inserted into viral genomes enable the easy and rapid quantification of virus replication, which is instrumental to efficient in vitro screening of antiviral compounds or in vivo analysis of viral spread and pathogenesis.
+Based on a published design, we have generated several replication competent influenza A viruses carrying either fluorescent proteins or Gaussia luciferase.
+Reporter activity could be readily quantified in infected cultures, but the virus encoding Gaussia luciferase was more stable than viruses bearing fluorescent proteins and was therefore analyzed in detail.
+Quantification of Gaussia luciferase activity in the supernatants of infected culture allowed the convenient and highly sensitive detection of viral spread, and enzymatic activity correlated with the number of infectious particles released from infected cells.
+Furthermore, the Gaussia luciferase encoding virus allowed the sensitive quantification of the antiviral activity of the neuraminidase inhibitor (NAI) zanamivir and the host cell interferon-inducible transmembrane (IFITM) proteins 1–3, which are known to inhibit influenza virus entry.
+Finally, the virus was used to demonstrate that influenza A virus infection is sensitive to a modulator of endosomal cholesterol, in keeping with the concept that IFITMs inhibit viral entry by altering cholesterol levels in the endosomal membrane.
+In sum, we report the characterization of a novel influenza A reporter virus, which allows fast and sensitive detection of viral spread and its inhibition, and we show that influenza A virus entry is sensitive to alterations of endosomal cholesterol levels.
+CASE PRESENTATION: We report an unusual case of avascular necrosis of the hip in a 41-year-old woman from Thailand presenting with hip pain.
+A pelvic X-ray revealed necrosis of the right femoral head and histological analysis of the punctuated nodules showed a reaction of foreign body granulomas.
+CONCLUSIONS: This case report emphasizes that orthopedic surgeons treating patients with necrosis of the hip joint in combination with palpable granulomas in the gluteal region have to be aware of silicone augmentation and its potential complications before planning a hip replacement.
+The Hymenocallis littoralis, an ornamental and medicinal plant, had been traditionally used for wound healing.
+In the present study, an analytical method using HPLC with ultraviolet detection was developed for the quantification of lycorine in the extracts of different parts of wild plant and tissue culture samples of H. littoralis.
+The method was found to be accurate, repeatable, and sensitive for the quantification of minute amount of lycorine present in the samples.
+The highest lycorine content was found in the bulb extract (2.54 ± 0.02 μg/mg) whereas the least was in the root extract (0.71 ± 0.02 μg/mg) of the wild plants.
+Few callus culture samples had high content of lycorine, comparable to that of wild plants.
+The results showed that plant growth regulators, 2,4-dichlorophenoxyacetic acid (2,4-D) alone at 4.5 μM (2.58 ± 0.38 μg/mg) or a combination of 2,4-D at 9.00 μM with 4.5 μM of 6-benzylaminopurine (BAP), were the optimum concentrations for the production of high lycorine (2.45 ± 0.15 μg/mg) content in callus culture.
+The present analytical method could be of value for routine quantification of lycorine in the tissue culture production and standardization of the raw material or extracts of H. littoralis.
+There is a pressing need for more effective and selective therapies for cancer and other diseases.
+Consequently, much effort is being devoted to the development of alternative experimental approaches based on selective systems, which are designed to be specifically directed against target cells.
+However, they do not reach clinical trials because of their low delivery, poor specificity or their incapacity to bypass the plasma membrane.
+Putting all these together, research is sailing in the direction of the design of systems with the capacity to transport new drugs into a target cell.
+Some CPPs show cell type specificity while others require modifications or form part of more sophisticated drug delivery systems.
+In this review article we summarize several strategies for directed drug delivery involving CPPs that have been reported in the literature.
+Advanced nucleic acid-based technologies are powerful research tools for novel virus discovery but need to be standardized for broader applications such as virus detection in biological products and clinical samples.
+We have used well-characterized retrovirus stocks to evaluate the limit of detection (LOD) for broad-range PCR with electrospray ionization mass spectrometry (PCR/ESI-MS or PLEX-ID), RT-PCR assays, and virus microarrays.
+The results indicated that in the absence of background cellular nucleic acids, PLEX-ID and RT-PCR had a similar LOD for xenotropic murine retrovirus-related virus (XMRV; 3.12 particles per µL) whereas sensitivity of virus detection was 10-fold greater using virus microarrays.
+When virus was spiked into a background of cellular nucleic acids, the LOD using PLEX-ID remained the same, whereas virus detection by RT-PCR was 10-fold less sensitive, and no virus could be detected by microarrays.
+Expected endogenous retrovirus (ERV) sequences were detected in cell lines tested and known species-specific viral sequences were detected in bovine serum and porcine trypsin.
+A follow-up strategy was developed using PCR amplification, nucleotide sequencing, and bioinformatics to demonstrate that an RD114-like retrovirus sequence that was detected by PLEX-ID in canine cell lines (Madin-Darby canine kidney (MDCK) and Cf2Th canine thymus) was due to defective, endogenous gammaretrovirus-related sequences.
+The recent discovery of genetically distinct hantaviruses in multiple species of shrews and moles prompted a further exploration of their host diversification by analyzing frozen, ethanol-fixed and RNAlater(®)-preserved archival tissues and fecal samples from 533 bats (representing seven families, 28 genera and 53 species in the order Chiroptera), captured in Asia, Africa and the Americas in 1981–2012, using RT-PCR.
+Hantavirus RNA was detected in Pomona roundleaf bats (Hipposideros pomona) (family Hipposideridae), captured in Vietnam in 1997 and 1999, and in banana pipistrelles (Neoromicia nanus) (family Vespertilionidae), captured in Côte d’Ivoire in 2011.
+Phylogenetic analysis, based on the full-length S- and partial M- and L-segment sequences using maximum likelihood and Bayesian methods, demonstrated that the newfound hantaviruses formed highly divergent lineages, comprising other recently recognized bat-borne hantaviruses in Sierra Leone and China.
+The detection of bat-associated hantaviruses opens a new era in hantavirology and provides insights into their evolutionary origins.
+Some, but not all, previous studies have reported that low interferon responses in patients with asthma increase the risk for virus-induced exacerbations.
+OBJECTIVE: We sought to determine the relationship between lower airway inflammatory biomarkers, specifically interferon gene expression, and the severity or presence of an exacerbation in asthmatics experiencing a naturally occurring viral infection.
+METHODS: Sputum samples were analyzed from subjects in an asthma exacerbation study who experienced a confirmed viral infection.
+Subjects were monitored for daily symptoms, medication use, and peak expiratory flow rate until baseline.
+RESULTS: IFN-γ expression was significantly greater in patients with asthma exacerbations compared to non-exacerbating patients (p=0.002).
+IFN-α1, IFN-β1, and IFN-γ mRNA levels correlated with the peak Asthma Index (r=0.58, p<0.001; r=0.57, p=0.001; and r=0.51, p=0.004, respectively).
+Additionally, IL-13, IL-10 and eosinophil major basic protein mRNA levels were greater in patients with asthma exacerbations compared to non-exacerbating patients (p=0.03, p=0.06, and p=0.02, respectively), and IL-13 mRNA correlated with the peak Asthma Index (p=0.006).
+CONCLUSIONS: Our findings indicate that asthma exacerbations are associated with increased rather than decreased expression of interferons early in the course of infection.
+These findings raise the possibility that excessive virus-induced interferon production during acute infections can contribute to airway inflammation and exacerbations of asthma.
+Hand, foot and mouth disease caused by enterovirus 71(EV71) leads to the majority of neurological complications and death in young children.
+While putative inactivated vaccines are only now undergoing clinical trials, no specific treatment options exist yet.
+To date, only a single universally neutralizing monoclonal antibody against a conserved linear epitope of VP1 has been identified.
+Other enteroviruses have been shown to possess major conformational neutralizing epitopes on both the VP2 and VP3 capsid proteins.
+Hence, we attempted to isolate such neutralizing antibodies against conformational epitopes for their potential in the treatment of infection as well as differential diagnosis and vaccine optimization.
+Here we describe a universal neutralizing monoclonal antibody that recognizes a conserved conformational epitope of EV71 which was mapped using escape mutants.
+Eight escape mutants from different subgenogroups (A, B2, B4, C2, C4) were rescued; they harbored three essential mutations either at amino acid positions 59, 62 or 67 of the VP3 protein which are all situated in the “knob” region.
+The escape mutant phenotype could be mimicked by incorporating these mutations into reverse genetically engineered viruses showing that P59L, A62D, A62P and E67D abolish both monoclonal antibody binding and neutralization activity.
+Pigs are often colonized by more than one bacterial and/or viral species during respiratory tract infections.
+Actinobacillus pleuropneumoniae (App) and porcine reproductive and respiratory syndrome virus (PRRSV) are pathogens that are frequently involved in PRDC.
+The main objective of this project was to study the in vitro interactions between these two pathogens and the host cells in the context of mixed infections.
+To fulfill this objective, PRRSV permissive cell lines such as MARC-145, SJPL, and porcine alveolar macrophages (PAM) were used.
+A pre-infection with PRRSV was performed at 0.5 multiplicity of infection (MOI) followed by an infection with App at 10 MOI.
+Incubation of SJPL and PAM cells with an App cell-free culture supernatant is also sufficient to significantly block PRRSV infection.
+This antiviral activity is not due to LPS but rather by small molecular weight, heat-resistant App metabolites (<1 kDa).
+The antiviral activity was also observed in SJPL cells infected with swine influenza virus but to a much lower extent compared to PRRSV.
+More importantly, the PRRSV antiviral activity of App was also seen with PAM, the cells targeted by the virus in vivo during infection in pigs.
+The antiviral activity might be due, at least in part, to the production of interferon γ.
+The use of in vitro experimental models to study viral and bacterial co-infections will lead to a better understanding of the interactions between pathogens and their host cells, and could allow the development of novel prophylactic and therapeutic tools.
+Aberrant glycosylation of cell surface glycoprotein due to specific alterations of glycosyltransferase activity is usually associated with invasion and metastasis of cancer, particularly of gastric carcinomas.
+Polypeptide N-acetylgalactosaminyltransferase 2 (ppGalNAc-T2), which catalyzes initiation of mucin-type O-glycosylation, is also involved in tumor migration and invasion.
+However, a comprehensive understanding of how ppGalNAc-T2 correlates with the metastasic potential of human gastric cancer is not currently available.
+In the present study, ppGalNAc-T2 was detected in a variety of human poorly differentiated tumor cells, and expression appeared to be higher in SGC7901 gastric cancer cells.
+In addition, we investigated the potential effects of ppGalNAc-T2 on growth and metastasis-associated behavior in SGC7901 cells after stable transfection with ppGalNAc-T2 sense and antisense vectors.
+We found that cell proliferation, adhesion and invasion were decreased in ppGalNAc-T2 overexpressed cells but increased in ppGalNAc-T2 downregulated cells.
+Further investigation indicated that overexpression of ppGalNAc-T2 is involved in the inhibition of matrix metalloproteinase (MMP)-2 expression at both the protein and mRNA levels, which may be associated with ppGalNAc-T2 suppressing the expression of transforming growth factor (TGF)-β1.
+Our data show the effect of ppGalNAc-T2 on proliferation, adhesion or invasion of SGC7901 gastric cancer cells, suggesting that ppGalNAc-T2 may exert anti-proliferative and anti-metastatic activity through the decrease of MMP-2 and TGF-β1.
+These results indicate that ppGalNAc-T2 may be used as a novel therapeutic target for human gastric cancer treatment.
+This in vitro study assessed the antimicrobial properties of a novel octasilver salt of Sucrose Octasulfate (IASOS) as well as of an innovative vaginal gel containing IASOS (SilSOS Femme), against bacterial and yeast pathogens isolated from human clinical cases of symptomatic vaginal infections.
+In BHI and LAPT culture media, different ionic silver concentrations and different pHs were tested.
+IASOS exerted a strong antimicrobial activity towards all the pathogens tested in both culture media.
+The results demonstrated that salts and organic compounds present in the culture media influenced IASOS efficacy only to a moderate extent.
+Whereas comparable MBCs (Minimal Bactericidal Concentrations) were observed for G. vaginalis (10 mg/L Ag(+)), E. coli and E. aerogenes (25 mg/L Ag(+)) in both media, higher MBCs were found for S. aureus and S. agalactiae in LAPT cultures (50 mg/L Ag(+) versus 25 mg/L Ag(+)).
+Nevertheless, in both media at the highest ionic silver concentrations (50–200 mg/L Ag(+)), a significant 34–52% drop in Candida growth was observed.
+pH differently affected the antimicrobial properties of IASOS against bacteria or yeasts; however, a stronger antimicrobial activity at pH higher than the physiological pH was generally observed.
+It can be therefore concluded that IASOS exerts a bactericidal action against all the tested bacteria and a clear fungistatic action against C. albicans.
+The antimicrobial activity of the whole vaginal gel SilSOS Femme further confirmed the antimicrobial activity of IASOS.
+On the Thai-Myanmar border, all pregnant women are followed systematically with active weekly malaria screening.
+Over a 27-year period of providing antenatal care, 48,983 have been prospectively followed until pregnancy outcome (miscarriage or delivery) and 4,298 women have had P. vivax detected at least once.
+The initial patient presentation was of uncomplicated P. vivax (0.5% parasitaemia) in a term, multigravida woman who responded rapidly to oral artesunate and mefloquine treatment, clearing her blood stage parasites within 48 hours.
+The patient appeared well, was ambulatory and due to be discharged but became unwell with acute respiratory distress syndrome (ARDS) requiring ventilation three days (67 hours) into treatment.
+Despite induction and delivery of a stillborn foetus, ventilatory requirements increased and the patient died on day 7.
+Sensitive detection with nested PCR confirmed only the presence of P. vivax species and concomitant infections such as tuberculosis and human immunodeficiency virus (HIV) were also ruled out.
+The contemporaneous treatment of acute uncomplicated P. vivax and the onset of ARDS on day 3 in this patient implies a possible but unconfirmed association with death in this patient.
+Assuming this death was caused by P. vivax, the risk of ARDS-related maternal mortality in this setting did not differ significantly between Plasmodium falciparum and P. vivax (0.24 per 1,000 (1/4,158) versus 0.23 per 1,000 (1/4,298), contrary to the increased risk of maternal mortality from P. falciparum compared to P. vivax, 2.89 per 1,000 (12/4,158) versus 0.23 per 1,000 (1/4,298), P = 0.003.
+OBJECTIVE: To reconstruct the local HIV-1 transmission network from 1996 to 2011 and use network data to evaluate and guide efforts to interrupt transmission.
+METHODS: We analyzed HIV-1 pol sequence data to infer a partial local transmission network among 478 recently HIV-1 infected persons and 170 of their sexual and social contacts in San Diego, California.
+A transmission network score (TNS) was developed to estimate the risk of HIV transmission from a newly diagnosed individual to a new partner and target prevention interventions.
+RESULTS: HIV-1 pol sequences from 339 individuals (52.3%) were highly similar to sequences from at least one other participant (i.e., clustered).
+A high TNS (top 25%) was significantly correlated with baseline risk behaviors (number of unique sexual partners and insertive unprotected anal intercourse (p = 0.014 and p = 0.0455, respectively) and predicted risk of transmission (p<0.0001).
+Retrospective analysis of antiretroviral therapy (ART) use, and simulations of ART targeted to individuals with the highest TNS, showed significantly reduced network level HIV transmission (p<0.05).
+CONCLUSIONS: Sequence data from an HIV-1 screening program focused on recently infected persons and their social and sexual contacts enabled the characterization of a highly connected transmission network.
+The network-based risk score (TNS) was highly correlated with transmission risk behaviors and outcomes, and can be used identify and target effective prevention interventions, like ART, to those at a greater risk for HIV-1 transmission.
+The nonstructural protein 2 (NSP2) is considered to be one of crucial viral proteins in the replication and pathogenesis of porcine reproductive and respiratory syndrome virus (PRRSV).
+In the present study, the host cellular proteins that interact with the NSP2 of PRRSV were immunoprecipitated with anti-Myc antibody from the MARC-145 cells infected by a recombinant PRRSV with 3xMyc tag insertion in its NSP2-coding region, and then 285 cellular proteins interacting with NSP2 were identified by LC-MS/MS.
+The Gene Ontology and enriched KEGG Pathway bioinformatics analyses indicated that the identified proteins could be assigned to different subcellular locations and functional classes.
+Functional analysis of the interactome profile highlighted cellular pathways associated with infectious disease, translation, immune system, nervous system and signal transduction.
+Two interested cellular proteins–BCL2-associated athanogene 6 (BAG6) and apoptosis-inducing factor 1 (AIF1) which may involve in transporting of NSP2 to Endoplasmic reticulum (ER) or PRRSV-driven apoptosis were validated by Western blot.
+The interactome data between PRRSV NSP2 and cellular proteins contribute to the understanding of the roles of NSP2 in the replication and pathogenesis of PRRSV, and also provide novel cellular target proteins for elucidating the associated molecular mechanisms of the interaction of host cellular proteins with viral proteins in regulating the viral replication.
+We have established a mouse model, in which ocular infection with a recombinant HSV-1 that expresses murine IL-2 constitutively (HSV-IL-2) causes CNS demyelination in different strains of mice.
+This model differs from most other models in that it represents a mixture of viral and immune triggers.
+In the present study, we directly compared MOG(35–55), MBP(35–47), and PLP(190–209) models of EAE with our HSV-IL-2-induced MS model.
+Mice with HSV-IL-2-induced and MOG-induced demyelinating diseases demonstrated a similar pattern and distribution of demyelination in their brain, spinal cord, and optic nerves.
+In contrast, no demyelination was detected in the optic nerves of MBP- and PLP-injected mice.
+IFN-β injections significantly reduced demyelination in brains of all groups, in the spinal cords of the MOG and MBP groups, and completely blocked it in the spinal cords of the PLP and HSV-IL-2 groups as well as in optic nerves of MOG and HSV-IL-2 groups.
+In contrast to IFN-β treatment, IL-12p70 protected the HSV-IL-2 group from demyelination, while IL-4 was not effective at all in preventing demyelination.
+MOG-injected mice showed clinical signs of paralysis and disease-related mortality whereas mice in the other treatment groups did not.
+Collectively, the results indicate that the HSV-IL-2 model and the MOG model complement each other and, together, provide unique insights into the heterogeneity of human MS.
+The aim of this essay is to elaborate philosophical and ethical underpinnings of posthumous diagnosis of famous historical figures based on literary and artistic products, or commonly called retrospective diagnosis.
+It discusses ontological and epistemic challenges raised in the humanities and social sciences, and attempts to systematically reply to their criticisms from the viewpoint of clinical medicine, philosophy of medicine, particularly the ontology of disease and the epistemology of diagnosis, and medical ethics.
+The ontological challenge focuses on the doubt about the persistence of a disease over historical time, whereas the epistemic challenge disputes the inaccessibility of scientific verification of a diagnosis in the past.
+I argue that the critics are in error in conflating the taxonomy of disease (nosology) and the act of diagnosing a patient.
+Medical diagnosis is fundamentally a hypothesis-construction and an explanatory device that can be generated under various degrees of uncertainty and limited amount of information.
+It is not an apodictic judgment (true or false) as the critics presuppose, but a probabilistic (Bayesian) judgment with varying degrees of plausibility under uncertainty.
+In order to avoid this confusion, I propose that retrospective diagnosis of a historical figure be syndromic without identifying underlying disease, unless there is justifiable reason for such specification.
+Moreover it should be evaluated not only from the viewpoint of medical science but also in a larger context of the scholarship of the humanities and social sciences by its overall plausibility and consistency.
+On the other hand, I will endorse their concerns regarding the ethics and professionalism of retrospective diagnosis, and call for the need for situating such a diagnosis in an interdisciplinary scope and the context of the scholarship of the historical figure.
+I will then enumerate several important caveats for interdisciplinary retrospective diagnosis using an example of the retrospective diagnosis of Socrates for his life-long intermittent neurologic symptoms.
+Finally, I will situate the present argument in a larger context of the major debate among the historians of medicine and paleopathologists, and discuss the similarities and differences.
+BACKGROUND: Positive traits, such as life satisfaction, optimism, and core self-evaluation (CSE), have garnered increasing attention from researchers and professionals.
+OBJECTIVE: This study examines the effect of dispositional optimism on life satisfaction and primarily verified the mediator role of CSEs.
+METHODS: Six hundred thirty college students from two general universities completed a questionnaire packet containing life orientation test–revised (LOT–R), core self-evaluations, and satisfaction with life scale.
+RESULTS: Results revealed that dispositional optimism and core self-evaluations were significantly correlated with life satisfaction.
+SEM indicated that core self-evaluations partially mediated the effect of dispositional optimism on life satisfaction.
+The final model also revealed significant paths from optimism and pessimism to life satisfaction through core-self evaluations.
+CONCLUSION: The findings extended prior studies and shed light on how dispositional optimism influences life satisfaction.
+This study provides valuable evidence on how to promote the life satisfaction of human beings in positive psychology.
+Background: The extent to which climate change may affect human health by increasing risk from vector-borne diseases has been under considerable debate.
+Objectives: We quantified potential effects of future climate change on the basic reproduction number (R(0)) of the tick vector of Lyme disease, Ixodes scapularis, and explored their importance for Lyme disease risk, and for vector-borne diseases in general.
+Methods: We applied observed temperature data for North America and projected temperatures using regional climate models to drive an I. scapularis population model to hindcast recent, and project future, effects of climate warming on R(0).
+Modeled R(0) increases were compared with R(0) ranges for pathogens and parasites associated with variations in key ecological and epidemiological factors (obtained by literature review) to assess their epidemiological importance.
+Results: R(0) for I. scapularis in North America increased during the years 1971–2010 in spatio-temporal patterns consistent with observations.
+Increased temperatures due to projected climate change increased R(0) by factors (2–5 times in Canada and 1.5–2 times in the United States), comparable to observed ranges of R(0) for pathogens and parasites due to variations in strains, geographic locations, epidemics, host and vector densities, and control efforts.
+Conclusions: Climate warming may have co-driven the emergence of Lyme disease in northeastern North America, and in the future may drive substantial disease spread into new geographic regions and increase tick-borne disease risk where climate is currently suitable.
+Our findings highlight the potential for climate change to have profound effects on vectors and vector-borne diseases, and the need to refocus efforts to understand these effects.
+Estimated effects of projected climate change on the basic reproductive number of the Lyme disease vector Ixodes scapularis.
+Balkan endemic nephropathy (BEN) is a familial chronic tubulointerstitial disease with insidious onset and slow progression leading to terminal renal failure.
+The results of molecular biological investigations propose that BEN is a multifactorial disease with genetic predisposition to environmental risk agents.
+Exome sequencing of 22 000 genes with Illumina Nextera Exome Enrichment Kit was performed on 22 DNA samples (11 Bulgarian patients and 11 Serbian patients).
+The frequency of all annotated genetic variants with deleterious/damaging effect was compared with those of European populations.
+Then we focused on nonannotated variants (with no data available about them and not found in healthy Bulgarian controls).
+There is no statistically significant difference between annotated variants in BEN patients and European populations.
+From nonannotated variants with more than 40% frequency in both patients' groups, we nominated 3 genes with possible deleterious/damaging variants—CELA1, HSPG2, and KCNK5.
+Mutant genes (CELA1, HSPG2, and KCNK5) in BEN patients encode proteins involved in basement membrane/extracellular matrix and vascular tone, tightly connected to process of angiogenesis.
+We suggest that an abnormal process of angiogenesis plays a key role in the molecular pathogenesis of BEN.
+Response surface methodology using a face-centered cube design was used to describe and predict spore inactivation of Bacillus anthracis ∆Sterne and Bacillus thuringiensis Al Hakam spores after exposure of six spore-contaminated materials to hot, humid air.
+For each strain/material pair, an attempt was made to fit a first or second order model.
+All three independent predictor variables (temperature, relative humidity, and time) were significant in the models except that time was not significant for B. thuringiensis Al Hakam on nylon.
+Modeling was unsuccessful for wiring insulation and wet spores because there was complete spore inactivation in the majority of the experimental space.
+In cases where a predictive equation could be fit, response surface plots with time set to four days were generated.
+The survival of highly purified Bacillus spores can be predicted for most materials tested when given the settings for temperature, relative humidity, and time.
+Glycyrrhizic acid (GA) is a triterpene glycoside found in the roots of licorice plants (Glycyrrhiza glabra).
+GA is the most important active ingredient in the licorice root, and possesses a wide range of pharmacological and biological activities.
+GA coupled with glycyrrhetinic acid and 18-beta-glycyrrhetic acid was developed in China or Japan as an anti-inflammatory, antiviral, and antiallergic drug for liver disease.
+This review summarizes the current biological activities of GA and its medical applications in liver diseases.
+The pharmacological actions of GA include inhibition of hepatic apoptosis and necrosis; anti-inflammatory and immune regulatory actions; antiviral effects; and antitumor effects.
+This paper will be a useful reference for physicians and biologists researching GA and will open the door to novel agents in drug discovery and development from Chinese herbs.
+With additional research, GA may be more widely used in the treatment of liver diseases or other conditions.
+Background: Upper respiratory tract infections (URTIs) account for at least half of all acute illnesses.
+Specific antiviral therapy has not been developed against most respiratory viruses thought to cause URTIs.
+The pharmacologic action of glycyrrhizin has been shown to produce anti-inflammatory activity, modulation of the immune system, inhibition of virus growth, and inactivation of viruses.
+Objective: The aim of this study was to assess the tolerability, efficacy, and cost of glycyrrhizin in improving the severity and duration of signs and symptoms of URTIs.
+The primary end point was tolerability, and the secondary and points included improvement in signs and symptoms of URTI and cost.
+Methods: Members of the Japanese Maritime Self-Defense Force (SDF) treated for URTIs from January 2002 to May 2002 in the SDF Etajima Hospital (Hiroshima, Japan) were eligible for this prospective, randomized, double-blind, controlled, parallel-group, alternate-day treatment assignment study.
+All patients in this study fulfilled the following enrollment criteria: admitted to the hospital on the first arrival day as an outpatient; fever (body temperature <38.0°C) with signs and symptoms of URTI (headache, sore throat, rhinorrhea, pharyngitis); and had not received antibiotics or oseltamivir phosphate for 4 weeks before the study.
+Patients who were admitted on an even day received an IV drip infusion of 40 mL of glycyrrhizin (0.2%) and 500 mL of lactated Ringer's solution daily during hospitalization (glycyrrhizin group).
+Patients who were admitted on an odd day received an IV drip infusion of 500 mL/d of lactated Ringer's solution only (control group).
+Adverse effects were assessed by the physicians during hospitalization, using patient interview and laboratory analysis.
+Results: Forty-one consecutive patients entered the study; 15 patients (15 men, 0 women; mean [SD] age, 25.2 [1.5] years) were assigned to the glycyrrhizin group and 269 patients (24 men, 2 women; mean [SD] age, 22.6 [0.9] years) were assigned to the control group.
+The mean duration of hospitalization was shorter (P = 0.01), the mean maximum body temperature 24 to 48 hours after admission was less (P = 0.05), and the cost of therapy (P = 0.03) was less in the glycyrrhizin group than the control group.
+Conclusions: In this study of hospitalized patients with URTIs, glycyrrhizin therapy was associated with a shorter hospitalization, lower-grade fever, and lower cost of therapy compared with controls, showing that it may be beneficial to patients with URTIs without acute bacterial infections.
+BACKGROUND: Various pathways have been implicated in the pathogenesis of heart failure (HF) with preserved ejection fraction (HFPEF).
+Inflammation in response to comorbid conditions, such as hypertension and diabetes, may play a proportionally larger role in HFPEF as compared to HF with reduced ejection fraction (HFREF).
+METHODS AND RESULTS: This study investigated inflammation mediated by the tumor necrosis factor-alpha (TNFα) axis in community-based cohorts of HFPEF patients (n = 100), HFREF patients (n = 100) and healthy controls (n = 50).
+Enzyme-linked immunosorbent assays were used to investigate levels of TNFα, its two receptors (TNFR1 and TNFR2), and a non-TNFα cytokine, interleukin-6 (IL-6), in plasma derived from peripheral blood samples.
+Plasma levels of TNFα and TNFR1 were significantly elevated in HFPEF relative to controls, while levels of TNFR2 were significantly higher in HFPEF than both controls and HFREF.
+TNFα, TNFR1 and TNFR2 were each significantly associated with at least two of the following: age, estimated glomerular filtration rate, hypertension, diabetes, smoking, peripheral vascular disease or history of atrial fibrillation.
+TNFR2 levels were also significantly associated with increasing grade of diastolic dysfunction and severity of symptoms in HFPEF.
+CONCLUSIONS: Inflammation mediated through TNFα and its receptors, TNFR1 and TNFR2, may represent an important component of a comorbidity-induced inflammatory response that partially drives the pathophysiology of HFPEF.
+The objective of this study was to determine serum malondialdehyde (MDA) levels during the first week of follow up, whether such levels are associated with severity during the first week and whether non-surviving patients showed higher MDA levels than survivors during the first week.
+Serum levels of MDA were measured in 328 patients (215 survivors and 113 non-survivors) with severe sepsis at days one, four and eight of diagnosis, and in 100 healthy controls.
+Cox regression analysis was applied to determine the independent contribution of serum MDA levels on the prediction of 30-day and 6-month mortality.
+Hazard ratio (HR) and 95% confidence intervals (CI) were calculated as measures of the clinical impact of the predictor variables.
+RESULTS: We found higher serum MDA in septic patients at day one (p < 0.001), day four (p < 0.001) and day eight (p < 0.001) of diagnosis than in healthy controls.
+Serum MDA was lower in surviving than non-surviving septic patients at day one (p < 0.001), day four (p < 0.001) and day eight (p < 0.001).
+Serum MDA levels were positively correlated with lactic acid and SOFA during the first week.
+Finally, serum MDA levels were associated with 30-day mortality (HR = 1.05; 95% CI = 1.02-1.09; p = 0.005) and six-month mortality (hazard ratio (HR) = 1.05; 95% CI = 1.02-1.09; p = 0.003) after controlling for lactic acid levels, acute physiology and chronic health evaluation (APACHE)-II, diabetes mellitus, bloodstream infection and chronic renal failure.
+CONCLUSIONS: To our knowledge, this is the largest series providing data on the oxidative state in septic patients to date.
+The novel finding is that high serum MDA levels sustained throughout the first week of follow up were associated with severity and mortality in septic patients.
+INTRODUCTION: The aim of this study was to investigate the kinetics of immunoglobulin M (IgM) during the different stages of sepsis.
+METHODS: In this prospective multicenter study, blood sampling for IgM measurement was done within the first 24 hours from diagnosis in 332 critically ill patients; in 83 patients this was repeated upon progression to more severe stages.
+Among these 83 patients, 30 patients with severe sepsis progressed into shock and IgM was monitored daily for seven consecutive days.
+Peripheral blood mononuclear cells (PBMCs) were isolated from 55 patients and stimulated for IgM production.
+RESULTS: Serum IgM was decreased in septic shock compared to patients with systemic inflammatory response syndrome (SIRS) and patients with severe sepsis.
+Paired comparisons at distinct time points of the sepsis course showed that IgM was decreased only when patients deteriorated from severe sepsis to septic shock.
+Serial measurements in these patients, beginning from the early start of vasopressors, showed that the distribution of IgM over time was significantly greater for survivors than for non-survivors.
+Production of IgM by PBMCs was significantly lower at all stages of sepsis compared with healthy controls.
+CONCLUSIONS: Specific changes of circulating IgM occur when patients with severe sepsis progress into septic shock.
+INTRODUCTION: Nuclear factor (NF)-κB is central to the pathogenesis of inflammation in acute lung injury, but also to inflammation resolution and repair.
+We wished to determine whether overexpression of the NF-κB inhibitor IκBα could modulate the severity of acute and prolonged pneumonia-induced lung injury in a series of prospective randomized animal studies.
+METHODS: Adult male Sprague-Dawley rats were randomized to undergo intratracheal instillation of (a) 5 × 10(9 )adenoassociated virus (AAV) vectors encoding the IκBα transgene (5 × 10(9 )AAV-IκBα); (b) 1 × 10(10 )AAV-IκBα; (c) 5 × 10(10 )AAV-IκBα; or (d) vehicle alone.
+After intratracheal inoculation with Escherichia coli, the severity of the lung injury was measured in one series over a 4-hour period (acute pneumonia), and in a second series after 72 hours (prolonged pneumonia).
+Additional experiments examined the effects of IκBα and null-gene overexpression on E. coli-induced and sham pneumonia.
+RESULTS: In acute pneumonia, IκBα dose-dependently decreased lung injury, improving arterial oxygenation and lung static compliance, reducing alveolar protein leak and histologic injury, and decreasing alveolar IL-1β concentrations.
+Benefit was maximal at the intermediate (1 × 10(10)) IκBα vector dose; however, efficacy was diminished at the higher (5 × 10(10)) IκBα vector dose.
+In contrast, IκBα worsened prolonged pneumonia-induced lung injury, increased lung bacterial load, decreased lung compliance, and delayed resolution of the acute inflammatory response.
+CONCLUSIONS: Inhibition of pulmonary NF-κB activity reduces early pneumonia-induced injury, but worsens injury and bacterial load during prolonged pneumonia.
+INTRODUCTION: Community acquired pneumonia (CAP) is the most common infectious reason for admission to the Intensive Care Unit (ICU).
+Phenotypic data was recorded using a robust clinical database allowing a contemporary analysis of the clinical characteristics, microbiology, outcomes and independent risk factors in patients with severe CAP admitted to ICUs across Europe.
+A Cox Proportional Hazards (PH) model was used to identify variables independently associated with 28-day and six-month mortality.
+Streptococcus pneumoniae was the commonest organism isolated (28% of cases) with no organism identified in 36%.
+Independent risk factors associated with an increased risk of death at six months included APACHE II score (hazard ratio, HR, 1.03; confidence interval, CI, 1.01-1.05), bilateral pulmonary infiltrates (HR1.44; CI 1.11-1.87) and ventilator support (HR 3.04; CI 1.64-5.62).
+Haematocrit, pH and urine volume on day one were all associated with a worse outcome.
+CONCLUSIONS: The mortality rate in patients with severe CAP admitted to European ICUs was 27% at six months.
+Ventilator support, the presence of diffuse pulmonary infiltrates, lower haematocrit, urine volume and pH on admission were independent predictors of a worse outcome.
+INTRODUCTION: Community-acquired pneumonia (CAP) requiring intensive care unit (ICU) treatment commonly causes acute respiratory failure with high mortality.
+Kallistatin, an endogenous tissue kallikrein inhibitor, has been reported to be protective in various human diseases.
+The aim of this study was to assess the correlations of kallistatin with other biomarkers and to determine whether kallistatin levels have a prognostic value in severe CAP.
+METHODS: Plasma samples and clinical data were prospectively collected from 54 patients with severe CAP requiring ICU admission.
+Plasma kallistatin, kallikrein, and other biomarkers of inflammation (tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, IL-8, C-reactive protein (CRP)), and anti-coagulation (protein C, anti-thrombin III) were measured on days 1 and 4 of ICU admission.
+Lower day 1 kallistatin levels showed a strong trend toward increased mortality (P = 0.018) and higher day 1 CURB-65 scores (P = 0.004).
+Plasma kallistatin levels on day 1 of ICU admission were significantly decreased in patients who developed septic shock (P = 0.017) and who had acute respiratory distress syndrome (P = 0.044).
+In addition, kallistatin levels were positively correlated with anti-thrombin III and protein C and inversely correlated with IL-1β, IL-6, and CRP levels.
+In a multivariate logistic regression analysis, higher day 1 CURB-65 scores were independent predictors of mortality (odds ratio = 29.9; P = 0.009).
+Also, higher day 1 kallistatin levels were independently associated with a decreased risk of death (odds ratio, 0.1) with a nearly significant statistical difference (P = 0.056).
+Furthermore, we found that a cutoff level of 6.5 μg/ml of day 1 kallistatin determined by receiver operating characteristic curves could be used to distinguish between patients who survived in 60 days and those who did not.
+CONCLUSIONS: These results suggest that kallistatin may serve as a novel marker for severe CAP prognosis and may be involved in the pathogenesis of CAP through antiinflammatory and anticoagulation effects.
+Extracorporeal membrane oxygenation (ECMO) can support gas exchange in patients failing conventional mechanical ventilation, but its role is still controversial.
+Studies reporting on 10 or more patients with H1N1 infection treated with ECMO were included.
+Baseline, procedural, outcome and validity data were systematically appraised and pooled, when appropriate, with random-effect methods.
+RESULTS: From 1,196 initial citations, 8 studies were selected, including 1,357 patients with confirmed/suspected H1N1 infection requiring intensive care unit admission, 266 (20%) of whom were treated with ECMO.
+Patients had a median Sequential Organ Failure Assessment (SOFA) score of 9, and had received mechanical ventilation before ECMO implementation for a median of two days.
+ECMO was implanted before inter-hospital patient transfer in 72% of cases and in most patients (94%) the veno-venous configuration was used.
+Outcomes were highly variable among the included studies, with in-hospital or short-term mortality ranging between 8% and 65%, mainly depending on baseline patient features.
+Random-effect pooled estimates suggested an overall in-hospital mortality of 28% (95% confidence interval 18% to 37%; I(2 )= 64%).
+Despite this, prolonged support (more than one week) is required in most cases, and subjects with severe comorbidities or multiorgan failure remain at high risk of in-hospital death.
+INTRODUCTION: Veno-venous extracorporeal membrane oxygenation (vvECMO) can be a life-saving therapy in patients with severe acute lung failure refractory to conventional therapy.
+The aim of this study was to assess published models for prediction of mortality following vvECMO and optimize an alternative model.
+METHODS: Established mortality risk scores were validated to assess their usefulness in 304 adult patients undergoing vvECMO for refractory lung failure at the University Medical Center Regensburg from 2008 to 2013.
+A parsimonious prediction model was developed based on variables available before ECMO initiation using logistic regression modelling.
+We then assessed whether addition of variables available one day after ECMO implementation enhanced mortality prediction.
+RESULTS: In the present study population, existing mortality prediction tools for vvECMO patients showed suboptimal performance.
+Evaluated before vvECMO initiation, a logistic prediction model comprising age, immunocompromised state, artificial minute ventilation, pre-ECMO serum lactate and hemoglobin concentrations showed best mortality prediction in our patients (area under curve, AUC: 0.75).
+Additional information about norepinephrine dosage, fraction of inspired oxygen, C-reactive protein and fibrinogen concentrations the first day following ECMO initiation further improved discrimination (AUC: 0.79, P = 0.03) and predictive ability (likelihood ratio test, P < 0.001).
+When classifying patients as lower (<40%) or higher (>80%) risk based on their predicted mortality, the pre-ECMO and day1-on-ECMO models had negative/positive predictive values of 76%/82% and 82%/81%, respectively.
+CONCLUSIONS: While pre-ECMO mortality prediction remains a challenge due to large patient heterogeneity, evaluation one day after ECMO initiation may improve the ability to separate lower- and higher-risk patients.
+Our findings support the clinical perception that chronic health condition, high comorbidity and reduced functional reserves are strongly related to survival during and following ECMO support.
+Renewed evaluation the first day after ECMO initiation may provide enhanced guidance for further handling of ECMO patients.
+Despite the usefulness of prediction models, thorough clinical evaluation should always represent the cornerstone in decision for ECMO.
+Over the last two decades, considerable progress has been made in the understanding of disease mechanisms and infection control strategies related to infections, particularly pneumonia, in critically ill patients.
+Patient-centered and preventative strategies assume paramount importance in this era of limited health-care resources, in which effective targeted therapy is required to achieve the best outcomes.
+Risk stratification using severity scores and inflammatory biomarkers is a promising strategy for identifying sick patients early during their hospital stay.
+Cooperation, education, and interaction between multiple disciplines in the intensive care unit are required to limit the spread of resistant pathogens and to improve care.
+In this review, we summarize findings from major publications over the last year in the field of respiratory infections in critically ill patients, putting an emphasis on a newer understanding of pathogenesis, use of biomarkers, and antibiotic stewardship and examining new treatment options and preventive strategies.
+INTRODUCTION: Secretory phospholipase A2 is supposed to play a role in acute lung injury but no data are available for pediatric acute respiratory distress syndrome (ARDS).
+It is not clear which enzyme subtypes are secreted and what the relationships are between enzyme activity, biophysical and biochemical parameters, and clinical outcomes.
+We aimed to measure the enzyme and identify its subtypes and to study its biochemical and biophysical effect.
+METHODS: Bronchoalveolar lavage was performed in 24 infants with ARDS and 14 controls with no lung disease.
+Samples were assayed for secretory phospholipase A2 and molecules related to its activity and expression.
+RESULTS: Tumor necrosis factor-α (814 (506-2,499) vs. 287 (111-1,315) pg/mL; P = 0.04), enzyme activity (430 (253-600) vs. 149 (61-387) IU/mL; P = 0.01), free fatty acids (4.3 (2.8-8.6) vs. 2 (0.8-4.6) mM; P = 0.026), and minimum surface tension (25.6 ± 6.1 vs. 18 ± 1.8 mN/m; P = 0.006) were higher in ARDS than in controls.
+Phospholipids are lower in ARDS than in controls (76.5 (54-100) vs. 1,094 (536-2,907) μg/mL; P = 0.0001).
+Three enzyme subtypes were identified (-IIA, -V, -X), although in lower quantities in controls; another subtype (-IB) was mainly detected in ARDS.
+Significant correlations exist between enzyme activity, free fatty acids (ρ = 0.823; P < 0.001), and surface tension (ρ = 0.55; P < 0.028).
+Correlations also exist with intensive care stay (ρ = 0.54; P = 0.001), PRISM-III(24 )(ρ = 0.79; P< 0.001), duration of ventilation (ρ = 0.53; P = 0.002), and oxygen therapy (ρ = 0.54; P = 0.001).
+CONCLUSIONS: Secretory phospholipase A2 activity is raised in pediatric ARDS and constituted of four subtypes.
+We sought to determine whether this survival gain extends to the high-risk subgroup of patients with cirrhosis.
+METHODS: Cirrhotic patients with septic shock admitted to a medical intensive care unit (ICU) during two consecutive periods (1997-2004 and 2005-2010) were retrospectively studied.
+RESULTS: Forty-seven and 42 cirrhotic patients presented with septic shock in 1997-2004 and 2005-2010, respectively.
+The recent period differed from the previous one by implementation of adjuvant treatments of septic shock including albumin infusion as fluid volume therapy, low-dose glucocorticoids, and intensive insulin therapy.
+ICU and hospital survival markedly improved over time (40% in 2005-2010 vs. 17% in 1997-2004, P = 0.02 and 29% in 2005-2010 vs. 6% in 1997-2004, P = 0.009, respectively).
+Furthermore, this survival gain in the latter period was sustained for 6 months (survival rate 24% in 2005-2010 vs. 6% in 1997-2004, P = 0.06).
+After adjustment with age, the liver disease stage (Child-Pugh score), and the critical illness severity score (SOFA score), ICU admission between 2005 and 2010 remained an independent favorable prognostic factor (odds ratio (OR) 0.09, 95% confidence interval (CI) 0.02-0.4, P = 0.004).
+The stage of the underlying liver disease was also independently associated with hospital mortality (Child-Pugh score: OR 1.42 per point, 95% CI 1.06-1.9, P = 0.018).
+CONCLUSIONS: In the light of advances in management of both cirrhosis and septic shock, survival of such patients substantially increased over recent years.
+The stage of the underlying liver disease and the related therapeutic options should be included in the decision-making process for ICU admission.
+INTRODUCTION: Bleeding is the most frequent complication in patients receiving venoarterial or venovenous extracorporeal membrane oxygenation (ECMO).
+We describe our experience with rFVIIa for refractory bleeding in this setting and review the cases reported in the literature.
+METHODS: Clinical characteristics, demographics, bleeding, thrombotic complications, mortality, and rFVIIa administration were retrospectively collected for analysis from the electronic charts of the 15 patients in our intensive care unit who received rFVIIa while being given ECMO from January 2006 to March 2011.
+RESULTS: Fifteen patients received rFVIIa for persistent bleeding under venoarterial (n = 11) or venovenous (n = 4) ECMO.
+Bleeding dramatically decreased in 14 patients, without a major thrombotic event, except in one patient in whom a major stroke could not be ruled out.
+Two circuits were changed within the 48 hours after rFVIIa administration for clots in the membrane and decreased oxygenation but without massive clotting.
+CONCLUSIONS: rFVIIa use for intractable hemorrhaging in patients receiving ECMO controlled bleeding, without major thrombotic events, and with 60% dying.
+Hence, its use warrants discussion, and clinicians should be aware of the possibility of potentially life-threatening systemic thrombosis, emboli, or circuit clotting.
+BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is a life-saving bridging procedure in patients with severe acute respiratory distress syndrome (ARDS).
+Official indications for ECMO are unclear for immunocompromised and HIV-positive patients affected by severe hypoxemia.
+However, the care of patients with HIV infection has advanced since the introduction of highly active antiretroviral therapy (HAART), with increased life expectancy and decreased mortality.
+CASE PRESENTATION: Three HIV-infected patients with AIDS were admitted to ICU and were treated with ECMO: a 21 years old Caucasian female with congenital HIV infection presented with Pneumocystis jirovecii pneumonia (PJP); a 38 years old Caucasian female with HIV-HCV infection and L. pneumophila pneumonia; a 24 years old Caucasian male with fever, cough weight loss and PJP pneumonia.
+Two patients were alive, with a good immunovirological profile and they went back to their previous quality of life.
+A multidisciplinary critical team is needed to individualize the use of ECMO in immunocompromised patients, including those with HIV infection.
+Intracranial infection of the neurotropic JHM strain of mouse hepatitis virus (JHMV) into the central nervous system (CNS) of susceptible strains of mice results in an acute encephalomyelitis, accompanied by viral replication in glial cells and robust infiltration of virus-specific T cells that contribute to host defense through cytokine secretion and cytolytic activity.
+Mice surviving the acute stage of disease develop an immune-mediated demyelinating disease, characterized by viral persistence in white matter tracts and a chronic neuroinflammatory response dominated by T cells and macrophages.
+Chemokines and their corresponding chemokine receptors are dynamically expressed throughout viral infection of the CNS, influencing neuroinflammation by regulating immune cell infltration and glial biology.
+This review is focused upon the pleiotropic chemokine receptor CXCR2 and its effects upon neutrophils and oligodendrocytes during JHMV infection and a number of other models of CNS inflammation.
+Hendra virus causes sporadic but typically fatal infection in horses and humans in eastern Australia.
+Fruit-bats of the genus Pteropus (commonly known as flying-foxes) are the natural host of the virus, and the putative source of infection in horses; infected horses are the source of human infection.
+Effective treatment is lacking in both horses and humans, and notwithstanding the recent availability of a vaccine for horses, exposure risk mitigation remains an important infection control strategy.
+This study sought to inform risk mitigation by identifying spatial and environmental risk factors for equine infection using multiple analytical approaches to investigate the relationship between plausible variables and reported Hendra virus infection in horses.
+Spatial autocorrelation (Global Moran’s I) showed significant clustering of equine cases at a distance of 40 km, a distance consistent with the foraging ‘footprint’ of a flying-fox roost, suggesting the latter as a biologically plausible basis for the clustering.
+Getis-Ord Gi* analysis identified multiple equine infection hot spots along the eastern Australia coast from far north Queensland to central New South Wales, with the largest extending for nearly 300 km from southern Queensland to northern New South Wales.
+Geographically weighted regression (GWR) showed the density of P. alecto and P. conspicillatus to have the strongest positive correlation with equine case locations, suggesting these species are more likely a source of infection of Hendra virus for horses than P. poliocephalus or P. scapulatus.
+The density of horses, climate variables and vegetation variables were not found to be a significant risk factors, but the residuals from the GWR suggest that additional unidentified risk factors exist at the property level.
+Further investigations and comparisons between case and control properties are needed to identify these local risk factors.
+The mammalian genome has evolved to encode a battery of mechanisms, to mitigate a progression in the life cycle of an invasive viral pathogen.
+Although apparently disadvantaged by their dependence on the host biosynthetic processes, an immensely faster rate of evolution provides viruses with an edge in this conflict.
+In this review, I have discussed the potential anti-virus activity of inositol-requiring enzyme 1 (IRE1), a well characterized effector of the cellular homeostatic response to an overloading of the endoplasmic reticulum (ER) protein-folding capacity.
+IRE1, an ER-membrane-resident ribonuclease (RNase), upon activation catalyses regulated cleavage of select protein-coding and non-coding host RNAs, using an RNase domain which is homologous to that of the known anti-viral effector RNaseL.
+The latter operates as part of the Oligoadenylate synthetase OAS/RNaseL system of anti-viral defense mechanism.
+Protein-coding RNA substrates are differentially treated by the IRE1 RNase to either augment, through cytoplasmic splicing of an intron in the Xbp1 transcript, or suppress gene expression.
+This referred suppression of gene expression is mediated through degradative cleavage of a select cohort of cellular RNA transcripts, initiating the regulated IRE1-dependent decay (RIDD) pathway.
+The review first discusses the anti-viral mechanism of the OAS/RNaseL system and evasion tactics employed by different viruses.
+This is followed by a review of the RIDD pathway and its potential effect on the stability of viral RNAs.
+I conclude with a comparison of the enzymatic activity of the two RNases followed by deliberations on the physiological consequences of their activation.
+BACKGROUND: Improving accuracy and efficiency of computational methods that predict pseudoknotted RNA secondary structures is an ongoing challenge.
+Existing methods based on free energy minimization tend to be very slow and are limited in the types of pseudoknots that they can predict.
+Incorporating known structural information can improve prediction accuracy; however, there are not many methods for prediction of pseudoknotted structures that can incorporate structural information as input.
+There is even less understanding of the relative robustness of these methods with respect to partial information.
+Iterative HFold takes as input a pseudoknot-free structure, and produces a possibly pseudoknotted structure whose energy is at least as low as that of any (density-2) pseudoknotted structure containing the input structure.
+Iterative HFold leverages strengths of earlier methods, namely the fast running time of HFold, a method that is based on the hierarchical folding hypothesis, and the energy parameters of HotKnots V2.0.
+Our experimental evaluation on a large data set shows that Iterative HFold is robust with respect to partial information, with average accuracy on pseudoknotted structures steadily increasing from roughly 54% to 79% as the user provides up to 40% of the input structure.
+Iterative HFold also has significantly better accuracy than IPknot on our HK-PK and IP-pk168 data sets.
+CONCLUSIONS: Iterative HFold is a robust method for prediction of pseudoknotted RNA secondary structures, whose accuracy with more than 5% information about true pseudoknot-free structures is better than that of IPknot, and with about 35% information about true pseudoknot-free structures compares well with that of HotKnots V2.0 while being significantly faster.
+BACKGROUND: The envelope (E) of dengue virus (DENV) is the major target of neutralizing antibodies and vaccine development.
+Recent reports of infection enhancement by anti-prM monoclonal antibodies (mAbs) suggest anti-prM responses could be potentially harmful.
+Previously, we studied a series of C-terminal truncation constructs expressing DENV type 4 prM/E or E proteins and found the ectodomain of E protein alone could be recognized by all 12 mAbs tested, suggesting E protein ectodomain as a potential subunit immunogen without inducing anti-prM response.
+The characteristics of DENV E protein ectodomain in the absence of prM protein remains largely unknown.
+METHODOLOGY/PRINCIPAL FINDINGS: In this study, we investigated the expression, membrane association, glycosylation pattern, secretion and particle formation of E protein ectodomain of DENV4 in the presence or absence of prM protein.
+E protein ectodomain associated with membrane in or beyond trans-Golgi and contained primarily complex glycans, whereas full-length E protein associated with ER membrane and contained high mannose glycans.
+In the absence of prM protein, E protein ectodomain can secrete as well as form particles of approximately 49 nm in diameter, as revealed by sucrose gradient ultracentrifugation with or without detergent and electron microscopy.
+Mutational analysis revealed that the secretion of E protein ectodomain was affected by N-linked glycosylation and could be restored by treatment with ammonia chloride.
+CONCLUSIONS/SIGNIFICANCE: Considering the enhancement of DENV infectivity by anti-prM antibodies, our findings provide new insights into the expression and secretion of E protein ectodomain in the absence of prM protein and contribute to future subunit vaccine design.
+Programmed ribosomal -1 frameshifting is a non-standard decoding process occurring when ribosomes encounter a signal embedded in the mRNA of certain eukaryotic and prokaryotic genes.
+This signal has a mandatory component, the frameshift motif: it is either a Z_ZZN tetramer or a X_XXZ_ZZN heptamer (where ZZZ and XXX are three identical nucleotides) allowing cognate or near-cognate repairing to the -1 frame of the A site or A and P sites tRNAs.
+Depending on the signal, the frameshifting frequency can vary over a wide range, from less than 1% to more than 50%.
+The present study combines experimental and bioinformatics approaches to carry out (i) a systematic analysis of the frameshift propensity of all possible motifs (16 Z_ZZN tetramers and 64 X_XXZ_ZZN heptamers) in Escherichia coli and (ii) the identification of genes potentially using this mode of expression amongst 36 Enterobacteriaceae genomes.
+While motif efficiency varies widely, a major distinctive rule of bacterial -1 frameshifting is that the most efficient motifs are those allowing cognate re-pairing of the A site tRNA from ZZN to ZZZ.
+The outcome of the genomic search is a set of 69 gene clusters, 59 of which constitute new candidates for functional utilization of -1 frameshifting.
+BACKGROUND: Recent studies have shown that influenza is associated with significant disease burden in many countries in the tropics, but until recently national surveillance for influenza was not conducted in most countries in Africa.
+METHODS: In 2007, the Kenyan Ministry of Health with technical support from the CDC-Kenya established a national sentinel surveillance system for influenza.
+At 11 hospitals, for every hospitalized patient with severe acute respiratory illness (SARI), and for the first three outpatients with influenza-like illness (ILI) per day, we collected both nasopharyngeal and oropharyngeal swabs.
+Influenza A-positive specimens were subtyped for H1, H3, H5, and (beginning in May 2009) A(H1N1)pdm09.
+RESULTS: From July 1, 2007 through June 30, 2013, we collected specimens from 24,762 SARI and 14,013 ILI patients.
+For SARI and ILI case-patients, the median ages were 12 months and 16 months, respectively, and 44% and 47% were female.
+In all, 2,378 (9.6%) SARI cases and 2,041 (14.6%) ILI cases were positive for influenza viruses.
+Of all influenza-positive specimens, 78% were influenza A, 21% were influenza B, and 1% were influenza A/B coinfections.
+CONCLUSIONS: During six years of surveillance in Kenya, influenza was associated with nearly 10 percent of hospitalized SARI cases and one-sixth of outpatient ILI cases.
+Most influenza-associated SARI and ILI cases were in children <2 years old; interventions to reduce the burden of influenza, such as vaccine, could consider young children as a priority group.
+Hypertension is a major risk factor for stroke, coronary events, heart and renal failure, and the renin-angiotensin system (RAS) plays a major role in its pathogenesis.
+Within the RAS, angiotensin converting enzyme (ACE) converts angiotensin (Ang) I into the vasoconstrictor Ang II.
+An “alternate” arm of the RAS now exists in which ACE2 counterbalances the effects of the classic RAS through degradation of Ang II, and generation of the vasodilator Ang 1-7.
+The ACE2 gene maps to a quantitative trait locus on the X chromosome in three strains of genetically hypertensive rats, suggesting that ACE2 may be a candidate gene for hypertension.
+It is hypothesized that disruption of tissue ACE/ACE2 balance results in changes in blood pressure, with increased ACE2 expression protecting against increased blood pressure, and ACE2 deficiency contributing to hypertension.
+Experimental hypertension studies have measured ACE2 in either the heart or kidney and/or plasma, and have reported that deletion or inhibition of ACE2 leads to hypertension, whilst enhancing ACE2 protects against the development of hypertension, hence increasing ACE2 may be a therapeutic option for the management of high blood pressure in man.
+There have been relatively few studies of ACE2, either at the gene or the circulating level in patients with hypertension.
+Plasma ACE2 activity is low in healthy subjects, but elevated in patients with cardiovascular risk factors or cardiovascular disease.
+Genetic studies have investigated ACE2 gene polymorphisms with either hypertension or blood pressure, and have produced largely inconsistent findings.
+This review discusses the evidence regarding ACE2 in experimental hypertension models and the association between circulating ACE2 activity and ACE2 polymorphisms with blood pressure and arterial hypertension in man.
+Thanks to high-throughput sequencing technologies, genome sequencing has become a common component in nearly all aspects of viral research; thus, we are experiencing an explosion in both the number of available genome sequences and the number of institutions producing such data.
+However, there are currently no common standards used to convey the quality, and therefore utility, of these various genome sequences.
+Here, we propose five “standard” categories that encompass all stages of viral genome finishing, and we define them using simple criteria that are agnostic to the technology used for sequencing.
+We also provide genome finishing recommendations for various downstream applications, keeping in mind the cost-benefit trade-offs associated with different levels of finishing.
+Our goal is to define a common vocabulary that will allow comparison of genome quality across different research groups, sequencing platforms, and assembly techniques.
+Protein α-helical coiled coil structures that elicit antibody responses, which block critical functions of medically important microorganisms, represent a means for vaccine development.
+By using bioinformatics algorithms, a total of 50 antigens with α-helical coiled coil motifs orthologous to Plasmodium falciparum were identified in the P. vivax genome.
+The peptides identified in silico were chemically synthesized; circular dichroism studies indicated partial or high α-helical content.
+Antigenicity was evaluated using human sera samples from malaria-endemic areas of Colombia and Papua New Guinea.
+ELISA assays indicated strong reactivity of serum samples from individuals residing in malaria-endemic regions and sera of immunized mice, with the α-helical coiled coil structures.
+In addition, ex vivo production of IFN-γ by murine mononuclear cells confirmed the immunogenicity of these structures and the presence of T-cell epitopes in the peptide sequences.
+Moreover, sera of mice immunized with four of the eight antigens recognized native proteins on blood-stage P. vivax parasites, and antigenic cross-reactivity with three of the peptides was observed when reacted with both the P. falciparum orthologous fragments and whole parasites.
+Results here point to the α-helical coiled coil peptides as possible P. vivax malaria vaccine candidates as were observed for P. falciparum.
+Fragments selected here warrant further study in humans and non-human primate models to assess their protective efficacy as single components or assembled as hybrid linear epitopes.
+Influenza-like illness (ILI) surveillance is important to identify circulating and emerging/reemerging strains and unusual epidemiological trends.
+The present study aimed to give an accurate picture of the 2012–2013 ILI outbreak in Corsica by combining data from several surveillance systems: general practice, emergency general practice, hospital emergency units, intensive care units, and nursing homes.
+Sequence analysis of the genetic changes in the hemagglutinin gene of influenza viruses (A(H1N1)pdm2009, A(H3N2) and B) was performed.
+The trends in ILI/influenza consultation rates and the relative illness ratios (RIRs) of having an ILI consultation were estimated by age group for the different surveillance systems analyzed.
+Of the 182 ILI patients enrolled by general practitioners, 57.7% tested positive for influenza viruses.
+In accordance with virological data, the RIRs of having an ILI consultation were highest among the young (<15 years old) and decreased with age.
+This study is noteworthy in that it is the first extensive description of the 2012–2013 ILI outbreak in Corsica as monitored through several surveillance systems.
+To improve ILI surveillance in Corsica, a consortium that links together the complementary regional surveillance ILI systems described here is being implemented.
+OBJECTIVE: To describe an innovative approach for developing and implementing an in-service curriculum in China for staff of the newly established health emergency response offices (HEROs), and that is generalisable to other settings.
+METHODS: The multi-method training needs assessment included reviews of the competency domains needed to implement the International Health Regulations (2005) as well as China’s policies and emergency regulations.
+The review, iterative interviews and workshops with experts in government, academia, the military, and with HERO staff were reviewed critically by an expert technical advisory panel.
+Of the 18 competency domains identified as essential for HERO staff, nine were developed into priority in-service training modules to be conducted over 2.5 weeks.
+Experts from academia and experienced practitioners prepared and delivered each module through lectures followed by interactive problem-solving exercises and desktop simulations to help trainees apply, experiment with, and consolidate newly acquired knowledge and skills.
+CONCLUSION: This study adds to the emerging literature on China’s enduring efforts to strengthen its emergency response capabilities since the outbreak of SARS in 2003.
+The multi-method approach to curriculum development in partnership with senior policy-makers, researchers, and experienced practitioners can be applied in other settings to ensure training is responsive and customized to local needs, resources and priorities.
+Ongoing curriculum development should reflect international standards and be coupled with the development of appropriate performance support systems at the workplace for motivating staff to apply their newly acquired knowledge and skills effectively and creatively.
+Inappropriate platelet aggregation creates a cardiovascular risk that is largely managed with thienopyridines and aspirin.
+Although effective, these drugs carry risks of increased bleeding and drug ‘resistance’, underpinning a drive for new antiplatelet agents.
+To discover such drugs, one strategy is to identify a suitable druggable target and then find small molecules that modulate it.
+A good and unexploited target is the platelet collagen receptor, GPVI, which promotes thrombus formation.
+To identify inhibitors of GPVI that are safe and bioavailable, we docked a FDA-approved drug library into the GPVI collagen-binding site in silico.
+We now report that losartan and cinanserin inhibit GPVI-mediated platelet activation in a selective, competitive and dose-dependent manner.
+This mechanism of action likely underpins the cardioprotective effects of losartan that could not be ascribed to its antihypertensive effects.
+We have, therefore, identified small molecule inhibitors of GPVI-mediated platelet activation, and also demonstrated the utility of structure-based repurposing.
+The knowledge that HIV-1 changes the host homeostatic equilibrium, which may favor the patient resistance to some co-pathogens, prompted us to investigate whether HIV-1 infection could influence A(H1N1)pdm09 life cycle in vitro.
+We show here that exposure of A(H1N1)pdm09-infected epithelial cells to HIV-1 viral particles or its gp120 enhanced by 25% the IFITM3 content, resulting in a decrease in influenza replication.
+Consequently, the arrival of influenza ribonucleoproteins (RNPs) to nucleus of macrophages was inhibited, as evaluated by different approaches.
+Reduction of influenza RNPs entry into the nucleus tolled A(H1N1)pdm09 life cycle in macrophages earlier than usual, limiting influenza's ability to induce TNF-α.
+As judged by analysis of the influenza hemagglutin (HA) gene from in vitro experiments and from samples of HIV-1/A(H1N1)pdm09 co-infected individuals, the HIV-1-induced reduction of influenza replication resulted in delayed viral evolution.
+Our results may provide insights on the mechanisms that may have attenuated the clinical course of Influenza in HIV-1/A(H1N1)pdm09 co-infected patients during the recent influenza form 2009/2010.
+The carcinoembryonic antigen (CEA) gene family belongs to the immunoglobulin (Ig) superfamily and codes for a vast number of glycoproteins that differ greatly both in amino acid composition and function.
+The CEA family is divided into two groups, the carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) and the pregnancy-specific glycoproteins.
+The CEA family members are implicated in pleiotropic (patho)physiological functions including cell–cell adhesion, pregnancy, immunity, neovascularization, regulation of insulin homeostasis, and carcinogenesis.
+In general, the CEA-encoded proteins are composed of an extracellular region with Ig variable and constant-like domains and a cytoplasmic region containing signaling motifs.
+Of particular interest, the well-studied human and mouse CEA genes are arranged in clusters in a single chromosome.
+Taking into account this characteristic, we made an effort to reconstruct the evolutionary history of the CEA gene family.
+The domain organization of the retrieved protein sequences was analyzed, and, subsequently, comprehensive phylogenetic analyses of the entire length CEA homologous proteins were performed.
+The relative positioning of these residues on the modeled tertiary structure of novel CEA protein domains revealed that they are, also, spatially conserved.
+Furthermore, the chromosomal arrangement of CEA genes was examined, and it was found that the CEA genes are preserved in terms of position, transcriptional orientation, and number in all species under investigation.
+Recently, we showed that the structurally similar flavonoids baicalein and biochanin A inhibit highly pathogenic avian H5N1 influenza A virus replication by different mechanisms in A549 lung cells.
+Here, we investigated the effects of both compounds on H5N1-induced reactive oxygen species (ROS) formation and the role of ROS formation during H5N1 replication.
+FINDINGS: Baicalein and biochanin A enhanced H5N1-induced ROS formation in A549 cells and primary human monocyte-derived macrophages.
+Suppression of ROS formation induced by baicalein and biochanin A using the antioxidant N-acetyl-L-cysteine strongly increased the anti-H5N1 activity of both compounds in A549 cells but not in macrophages.
+CONCLUSIONS: These findings emphasise that flavonoids induce complex pharmacological actions some of which may interfere with H5N1 replication while others may support H5N1 replication.
+A more detailed understanding of these actions and the underlying structure-activity relationships is needed to design agents with optimised anti-H5N1 activity.
+Irrespective of aetiology, infectious respiratory diseases of sheep and goats contribute to 5.6 percent of the total diseases of small ruminants.
+These infectious respiratory disorders are divided into two groups: the diseases of upper respiratory tract, namely, nasal myiasis and enzootic nasal tumors, and diseases of lower respiratory tract, namely, peste des petits ruminants (PPR), parainfluenza, Pasteurellosis, Ovine progressive pneumonia, mycoplasmosis, caprine arthritis encephalitis virus, caseous lymphadenitis, verminous pneumonia, and many others.
+Early, rapid, and specific diagnosis of such diseases holds great importance to reduce the losses.
+The advanced enzyme-linked immunosorbent assays (ELISAs) for the detection of antigen as well as antibodies directly from the samples and molecular diagnostic assays along with microsatellites comprehensively assist in diagnosis as well as treatment and epidemiological studies.
+The present review discusses the advancements made in the diagnosis of common infectious respiratory diseases of sheep and goats.
+It would update the knowledge and help in adapting and implementing appropriate, timely, and confirmatory diagnostic procedures.
+Moreover, it would assist in designing appropriate prevention protocols and devising suitable control strategies to overcome respiratory diseases and alleviate the economic losses.
+PURPOSE: Myeloid differentiation factor 88 (Myd88), a ubiquitous Toll-like receptor adaptor molecule, has been reported to play important roles in B cell responses to infections and vaccination.
+The present study evaluated the effects of genetic adjuvanting with Myd88 on the immune responses to a plasmid DNA rabies vaccine.
+MATERIALS AND METHODS: Plasmids encoding rabies glycoprotein alone (pIRES-Rgp) or a fragment of Myd88 gene in addition (pIRES-Rgp-Myd) were constructed and administered intramuscularly or intrademally in Swiss albino mice (on days 0, 7, and 21).
+Rabies virus neutralizing antibody (RVNA) titres were estimated in the mice sera on days 14 and 28 by rapid fluorescent focus inhibition test.
+The protective efficacy of the constructs was evaluated by an intracerebral challenge with challenge virus standard virus on day 35.
+RESULTS: Co-expression of Myd88 increased RVNA responses to pIRES-Rgp by 3- and 2-folds, following intramuscular and intradermal immunization, respectively.
+pIRES-Rgp protected 80% of the mice following intramuscular and intradermal immunizations, while pIRES-Rgp-Myd afforded 100% protection following similar administrations.
+CONCLUSION: Genetic adjuvanting with Myd88 enhanced the RVNA responses and protective efficacy of a plasmid DNA rabies vaccine.
+This strategy might be useful for rabies vaccination of canines in the field, and needs further evaluation.
+BACKGROUND: Data from prospectively planned cohort studies on risk of major clinical outcomes and prognostic factors for patients with influenza A(H1N1)pdm09 virus are limited.
+In 2009, in order to assess outcomes and evaluate risk factors for progression of illness, two cohort studies were initiated: FLU 002 in outpatients and FLU 003 in hospitalized patients.
+METHODS AND FINDINGS: Between October 2009 and December 2012, adults with influenza-like illness (ILI) were enrolled; outpatients were followed for 14 days and inpatients for 60 days.
+Disease progression was defined as hospitalization and/or death for outpatients, and hospitalization for >28 days, transfer to intensive care unit (ICU) if enrolled from general ward, and/or death for inpatients.
+590 FLU 002 and 392 FLU 003 patients with influenza A (H1N1)pdm09 were enrolled from 81 sites in 17 countries at 2 days (IQR 1–3) and 6 days (IQR 4–10) following ILI onset, respectively.
+Disease progression was experienced by 29 (1 death) outpatients (5.1%; 95% CI: 3.4–7.2%) and 80 inpatients [death (32), hospitalization >28 days (43) or ICU transfer (20)] (21.6%; 95% CI: 17.5–26.2%).
+Disease progression (death) for hospitalized patients was 53.1% (26.6%) and 12.8% (3.8%), respectively, for those enrolled in the ICU and general ward.
+In pooled analyses for both studies, predictors of disease progression were age, longer duration of symptoms at enrollment and immunosuppression.
+CONCLUSIONS: Patients with influenza A(H1N1)pdm09, particularly when requiring hospital admission, are at high risk for disease progression, especially if they are older, immunodeficient, or admitted late in infection.
+These data reinforce the need for international trials of novel treatment strategies for influenza infection and serve as a reminder of the need to monitor the severity of seasonal and pandemic influenza epidemics globally.
+Hepatitis C virus (HCV) replication is dependent on the formation of specialized membrane structures; however, the host factor requirements for the formation of these HCV complexes remain unclear.
+Herein, we demonstrate that inhibition of stearoyl-CoA desaturase 1 (SCD-1) halts the biosynthesis of unsaturated fatty acids, such as oleic acid, and negatively modulates HCV replication.
+Mechanistically, we demonstrate that SCD-1 inhibition disrupts the integrity of membranous HCV replication complexes and renders HCV RNA susceptible to nuclease-mediated degradation.
+The FAT-1 protein is an n-3 fatty acid desaturase, which can recognize a range of 18- and 20-carbon n-6 substrates and transform n-6 polyunsaturated fatty acids (PUFAs) into n-3 PUFAs while n-3 PUFAs have beneficial effect on human health.
+Fat1 gene is the coding sequence from Caenorhabditis elegans which might play an important role on lipometabolism.
+To reveal the function of fat1 gene in bovine fetal fibroblast cells and gain the best cell nuclear donor for transgenic bovines, the codon of fat1 sequence was optimized based on the codon usage frequency preference of bovine muscle protein, and directionally cloned into the eukaryotic expression vector pEF-GFP.
+After identifying by restrictive enzyme digests with AatII/XbaI and sequencing, the fusion plasmid pEF-GFP-fat1 was identified successfully.
+The results showed that a 1,234 bp transcription was amplified by reverse transcription PCR and the positive transgenic fat1 cell line was successfully established.
+Then the expression level of fat1 gene in positive cells was detected using quantitative PCR, and the catalysis efficiency was detected by gas chromatography.
+The results demonstrated that the catalysis efficiency of fat1 was significantly high, which can improve the total PUFAs rich in EPA, DHA and DPA.
+Construction and expression of pEF-GFP-fat1 vector should be helpful for further understanding the mechanism of regulation of fat1 in vitro.
+Investigating gene expression of immune cells of whole blood or peripheral blood mononuclear cells (PBMC) under polyinosinic:polycytidylic acid (poly I:C) stimulation is valuable for understanding the immune response of organism to RNA viruses.
+In the study, using two different analysis programs, geNorm and NormFinder, we systematically evaluated the gene expression stability of six candidate reference genes (GAPDH, ACTB, B2M, RPL4, TBP, and PPIA) in samples of whole blood and PBMC with or without poly I:C stimulation.
+Generally, the six candidate genes performed a similar trend of expression stability in the samples of whole blood and PBMC, but more stably expressed in whole blood than in PBMC.
+geNorm ranked B2M and PPIA as the best combination for gene expression normalization, while according to NormFinder, TBP was ranked as the most stable reference gene, followed by B2M and PPIA.
+Comprehensively considering the results from the two programs, we recommended using the geometric mean of the three genes, TBP, PPIA and B2M, to normalize the gene expression of whole blood and PBMC with poly I:C stimulation.
+Our study is the first detailed survey of the gene expression stability in whole blood and PBMC with or without poly I:C stimulation and should be helpful for investigating the molecular mechanism involved in porcine whole blood and PBMC in response to poly I:C stimulation.
+Following last year's computational vaccinology workshop in Shanghai, China, the third ISV Pre-conference Computational Vaccinology Workshop (ICoVax 2013) was held in Barcelona, Spain.
+ICoVax 2013 provided an international platform for the attendees to showcase their research and discuss problems and solutions in the development and application of computational vaccinology and vaccine informatics tools.
+The first of the three full-length papers presented at ICoVax discussed the discovery of viral "camouflage" through cross-conservation of T-cell epitopes using a tool called JanusMatrix.
+This important paper reports that viruses may camouflage their presence in the human body by incorporating sequences in their proteins that are highly cross-conserved at the T-cell receptor surface with human genome proteins, a discovery that has wide ranging implications for the development of vaccines against viruses that use the camouflage method.
+The other papers described a database for storing experimentally verified data on DNA vaccines and compared therapeutic targets of western drugs to Chinese herbal medicines for cardiovascular diseases.
+The short poster presentations covered various uses of informatics tools for processing the DNA and microRNA of pathogens to improve vaccine coverage, efficacy and development.
+A live (on-line) demonstration of the vaccine design toolkit, iVax, presented by Frances Terry of EpiVax, illustrated how computational vaccinology could be used in the design of next generation vaccines.
+BACKGROUND: The capacity to conduct zoonotic pathogen surveillance in wildlife is critical for the recognition and identification of emerging health threats.
+The PREDICT project, a component of United States Agency for International Development’s Emerging Pandemic Threats program, has introduced capacity building efforts to increase zoonotic pathogen surveillance in wildlife in global ‘hot spot’ regions where zoonotic disease emergence is likely to occur.
+Understanding priorities, challenges, and opportunities from the perspectives of the stakeholders is a key component of any successful capacity building program.
+METHODS: A survey was administered to wildlife officials and to PREDICT-implementing in-country project scientists in 16 participating countries in order to identify similarities and differences in perspectives between the groups regarding capacity needs for zoonotic pathogen surveillance in wildlife.
+areas of high contact between wildlife and humans with the potential risk for disease transmission), such as hunting and markets, as important for ongoing targeting of wildlife surveillance.
+Similarly, findings regarding challenges across stakeholder groups showed some agreement in that a lack of sustainable funding across regions was the greatest challenge for conducting wildlife surveillance for zoonotic pathogens (wildlife officials: 96% and project scientists: 81%).
+However, the opportunity for improving zoonotic pathogen surveillance capacity identified most frequently by wildlife officials as important was increasing communication or coordination among agencies, sectors, or regions (100% of wildlife officials), whereas the most frequent opportunities identified as important by project scientists were increasing human capacity, increasing laboratory capacity, and the growing interest or awareness regarding wildlife disease or surveillance programs (all identified by 69% of project scientists).
+CONCLUSIONS: A One Health approach to capacity building applied at local and global scales will have the greatest impact on improving zoonotic pathogen surveillance in wildlife.
+This approach will involve increasing communication and cooperation across ministries and sectors so that experts and stakeholders work together to identify and mitigate surveillance gaps.
+Over time, this transdisciplinary approach to capacity building will help overcome existing challenges and promote efficient targeting of high risk interfaces for zoonotic pathogen transmission.
+The increased number of outbreaks of H5 and H7 LPAI and HPAI viruses in poultry has major public and animal health implications.
+The continuous rapid evolution of these subtypes and the emergence of new variants influence the ability to undertake effective surveillance.
+Retroviral pseudotypes bearing influenza haemagglutinin (HA) and neuraminidase (NA) envelope glycoproteins represent a flexible platform for sensitive, readily standardized influenza serological assays.
+We describe a multiplex assay for the study of neutralizing antibodies that are directed against both influenza H5 and H7 HA.
+This assay permits the measurement of neutralizing antibody responses against two antigenically distinct HAs in the same serum/plasma sample thus increasing the amount and quality of serological data that can be acquired from valuable sera.
+Sera obtained from chickens vaccinated with a monovalent H5N2 vaccine, chickens vaccinated with a bivalent H7N1/H5N9 vaccine, or turkeys naturally infected with an H7N3 virus were evaluated in this assay and the results correlated strongly with data obtained by HI assay.
+We show that pseudotypes are highly stable under basic cold-chain storage conditions and following multiple rounds of freeze-thaw.
+We propose that this robust assay may have practical utility for in-field serosurveillance and vaccine studies in resource-limited regions worldwide.
+Where formal address networks do not exist, tracking spatial patterns of clinical disease is difficult.
+Methods included geocoding residence by head of compound, participatory mapping and recording the self-reported nearest landmark.
+Geocoding was able to locate 72·9% [95% confidence interval (CI) 67·7–77·6] of individuals to within 250 m of the true compound location.
+The participatory mapping exercise was able to correctly locate 82·0% of compounds (95% CI 78·9–84·8) to a 2 × 2·5 km area with a 500 m buffer.
+The self-reported nearest landmark was able to locate 78·1% (95% CI 73·8–82·1) of compounds to the correct catchment area.
+These strategies tested provide options for quickly obtaining spatial information on individuals presenting at health facilities.
+Airway epithelial cells are the first line of defense against viral infections and are instrumental in coordinating the inflammatory response.
+In this study, we demonstrate the synergistic stimulation of CXCL10 mRNA and protein, a key chemokine responsible for the early immune response to viral infection, following treatment of airway epithelial cells with IFN γ and influenza virus.
+The synergism also occurred when the cells were treated with IFN γ and a viral replication mimicker (dsRNA) both in vitro and in vivo.
+Despite the requirement of type I interferon (IFNAR) signaling in dsRNA-induced CXCL10, the synergism was independent of the IFNAR pathway since it wasn’t affected by the addition of a neutralizing IFNAR antibody or the complete lack of IFNAR expression.
+Furthermore, the same synergistic effect was also observed when a CXCL10 promoter reporter was examined.
+Although the responsive promoter region contains both ISRE and NFκB sites, western blot analysis indicated that the combined treatment of IFN γ and dsRNA significantly augmented NFκB but not STAT1 activation as compared to the single treatment.
+Therefore, we conclude that IFN γ and dsRNA act in concert to potentiate CXCL10 expression in airway epithelial cells via an NFκB-dependent but IFNAR-STAT independent pathway and it is at least partly regulated at the transcriptional level.
+Type I IFN production is one of the hallmarks of host innate immune responses upon virus infection.
+Whilst most respiratory viruses carry IFN antagonists, reports on human metapneumovirus (HMPV) have been conflicting.
+Using deep sequencing, we have demonstrated that HMPV particles accumulate excessive amounts of defective interfering RNA (DIs) rapidly upon in vitro passage, and that these are associated with IFN induction.
+Importantly, the DIs were edited extensively; up to 70 % of the original A and T residues had mutated to G or C, respectively.
+Such high editing rates of viral RNA have not, to our knowledge, been reported before.
+Bioinformatics and PCR assays indicated that adenosine deaminase acting on RNA (ADAR) was the most likely editing enzyme.
+HMPV thus has an unusually high propensity to generate DIs, which are edited at an unprecedented high frequency.
+The conflicting published data on HMPV IFN induction and antagonism are probably explained by DIs in virus stocks.
+The interaction of HMPV DIs with the RNA-editing machinery and IFN responses warrants further investigation.
+Oncolytic viruses are genetically engineered viruses that are designed to kill cancer cells while doing minimal damage to normal healthy tissue.
+After being injected into a tumor, they infect cancer cells, multiply inside them, and when a cancer cell is killed they move on to spread and infect other cancer cells.
+Chondroitinase ABC (Chase-ABC) is a bacterial enzyme that can remove a major glioma ECM component, chondroitin sulfate glycosoamino glycans from proteoglycans without any deleterious effects in vivo.
+It has been shown that Chase-ABC treatment is able to promote the spread of the viruses, increasing the efficacy of the viral treatment.
+In this paper we develop a mathematical model to investigate the effect of the Chase-ABC on the treatment of glioma by oncolytic viruses (OV).
+We then use the model to test various treatment options in the heterogeneous microenvironment of the brain.
+The model predicts that separate injections of OV, one into the center of the tumor and another outside the tumor will result in better outcome than if the total injection is outside the tumor.
+In particular, the injection of the ECM-degrading enzyme (Chase-ABC) on the periphery of the main tumor core need to be administered in an optimal strategy in order to infect and eradicate the infiltrating glioma cells outside the tumor core in addition to proliferative cells in the bulk of tumor core.
+The model also predicts that the size of tumor satellites and distance between the primary tumor and multifocal/satellite lesions may be an important factor for the efficacy of the viral therapy with Chase treatment.
+BACKGROUND: Little is known about the development of cross-reactive antibodies following natural exposure to pathogens.
+METHODS: To study the possibility of the presence of cross-reactive antibodies to influenza viruses which underwent a major antigenic drift between the years 1999 and 2007 sera from samples of 80 children and 400 adults were selected at random from the Israeli national serum bank.
+The sera was obtained in 2002 and in 2007, two time points that followed a major drift in the infectious H3N2 influenza virus strain (A/Panama/2007/99 to A/Wisconsin/67/2005).
+RESULTS: In the summer of 2002, 13% of the children had Hemagglutination Inhibition (HI) antibody titers of at least 40 and these antibodies recognized both A/Panama/2007/99 and A/Wisconsin/67/2005, where the latter strain only began to circulate in Israel in 2006.
+In 2007, 29% of the children had HI antibody titers of at least 40 directed against both A/Wisconsin/67/2005 and A/Panama/2007/99, even though they had never been exposed to the latter virus.
+Anti-A/Panama/2007/99 antibodies were detected in 58% and 68% of the 2002 and 2007 adult samples, respectively, while 8% and 39% had antibodies against A/Wisconsin/67/2005, respectively.
+CONCLUSIONS: The presence of naturally occurring cross-reactive influenza virus antibodies in a significant percentage of children has important implications for the development of a universal influenza vaccine.
+The purpose of this pilot study is to determine whether protein profiling in NTD-mothers differ from normal controls using SELDI-TOF-MS. ProteinChip Biomarker System was used to evaluate 82 maternal serum samples, 78 urine samples and 76 amniotic fluid samples.
+The validity of classification tree was then challenged with a blind test set including another 20 NTD-mothers and 18 controls in serum samples, and another 19 NTD-mothers and 17 controls in urine samples, and another 20 NTD-mothers and 17 controls in amniotic fluid samples.
+Eight proteins detected in serum samples were up-regulated and four proteins were down-regulated in the NTD group.
+Four proteins detected in urine samples were up-regulated and one protein was down-regulated in the NTD group.
+Six proteins detected in amniotic fluid samples were up-regulated and one protein was down-regulated in the NTD group.
+The classification tree for serum samples separated NTDs from healthy individuals, achieving a sensitivity of 91% and a specificity of 97% in the training set, and achieving a sensitivity of 90% and a specificity of 97% and a positive predictive value of 95% in the test set.
+The classification tree for urine samples separated NTDs from controls, achieving a sensitivity of 95% and a specificity of 94% in the training set, and achieving a sensitivity of 89% and a specificity of 82% and a positive predictive value of 85% in the test set.
+The classification tree for amniotic fluid samples separated NTDs from controls, achieving a sensitivity of 93% and a specificity of 89% in the training set, and achieving a sensitivity of 90% and a specificity of 88% and a positive predictive value of 90% in the test set.
+However, the mechanisms underlying the actions of GLN remain unclear, and may depend upon the route of GLN administration and the model of acute lung injury (ALI) used.
+The aim of this study was to investigate whether short-term GLN supplementation had an ameliorative effect on the inflammation induced by direct acid and lipopolysaccharide (LPS) challenge in mice.
+METHODS: Female BALB/c mice were divided into two groups, a control group and a GLN group (4.17% GLN supplementation).
+After a 10-day feeding period, ALI was induced by intratracheal administration of hydrochloric acid (pH 1.0; 2 mL/kg of body weight [BW]) and LPS (5 mg/kg BW).
+In this early phase of ALI, serum, lungs, and bronchoalveolar lavage fluid (BALF) from the mice were collected for further analysis.
+RESULTS: The results of this study showed that ALI-challenged mice had a significant increase in myeloperoxidase activity and expression of interleukin (IL)-1β, IL-6, and tumor necrosis factor-α in the lung compared with unchallenged mice.
+Compared with the control group, GLN pretreatment in ALI-challenged mice reduced the levels of receptor for advanced glycation end-products (RAGE) and IL-1β production in BALF, with a corresponding decrease in their mRNA expression.
+The GLN group also had markedly lower in mRNA expression of cyclooxygenase-2 and NADPH oxidase-1.
+CONCLUSIONS: These results suggest that the benefit of dietary GLN may be partly contributed to an inhibitory effect on RAGE expression and pro-inflammatory cytokines production at an early stage in direct acid and LPS-induced ALI in mice.
+BACKGROUND: Chikungunya virus (CHIKV) is a re-emerging arbovirus associated with febrile illness often accompanied by rash and arthralgia that may persist for several years.
+Outbreaks are associated with high morbidity and create a public health challenge for countries affected.
+Recent outbreaks have occurred in both Europe and the Americas, suggesting CHIKV may continue to spread.
+Despite the sustained threat of the virus, there is no approved vaccine or antiviral therapy against CHIKV.
+Therefore, it is critical to develop a vaccine that is both well tolerated and highly protective.
+METHODOLOGY/PRINCIPAL FINDINGS: In this study, we describe the construction and characterization of a modified Vaccinia virus Ankara (MVA) virus expressing CHIKV E3 and E2 proteins (MVA-CHIK) that protected several mouse models from challenge with CHIKV.
+In particular, BALB/c mice were completely protected against viremia upon challenge with CHIKV after two doses of MVA-CHIK.
+While high anti-virus antibodies were elicited, low or undetectable levels of neutralizing antibodies were produced in both mouse models.
+However, passive transfer of MVA-CHIK immune serum to naïve mice did not protect against mortality, suggesting that antibodies may not be the main effectors of protection afforded by MVA-CHIK.
+Furthermore, depletion of CD4(+), but not CD8(+) T-cells from vaccinated mice resulted in 100% mortality, implicating the indispensable role of CD4(+) T-cells in the protection afforded by MVA-CHIK.
+CONCLUSIONS/SIGNIFICANCE: The results presented herein demonstrate the potential of MVA to effectively express CHIKV E3-E2 proteins and generate protective immune responses.
+Our findings challenge the assumption that only neutralizing antibodies are effective in providing protection against CHIKV, and provides a framework for the development of novel, more effective vaccine strategies to combat CHIKV.
+The vaccine efficacy (VE) of 1 or 2 doses of AS03-adjuvanted influenza A(H1N1) vaccine relative to that of 2 doses of nonadjuvanted influenza A(H1N1) vaccine in children 6 months to <10 years of age in a multinational study conducted during 2010–2011.
+A total of 6145 children were randomly assigned at a ratio of 1:1:1 to receive 2 injections 21 days apart of A/California/7/2009(H1N1)-AS03 vaccine at dose 1 and saline placebo at dose 2, 2 doses 21 days apart of A/California/7/2009(H1N1)-AS03 vaccine (the Ad2 group), or 2 doses 21 days apart of nonadjuvanted A/California/7/2009(H1N1) vaccine (the NAd2 group).
+Nose and throat samples obtained during influenza-like illnesses were tested for A/California/7/2009(H1N1), using reverse-transcriptase polymerase chain reaction.
+There were 23 cases of confirmed 2009 pandemic influenza A(H1N1) (A[H1N1]pdm09) infection for the primary relative VE analysis.
+The VE in the Ad2 group relative to that in the NAd2 group was 76.8% (95% confidence interval, 18.5%–93.4%).
+The benefit of the AS03 adjuvant was demonstrated in terms of the greater immunogenicity observed in the Ad2 group, compared with the NAd2 group.
+The 4–8-fold antigen-sparing adjuvanted pandemic influenza vaccine demonstrated superior and clinically important prevention of A(H1N1)pdm09 infection, compared with nonadjuvanted vaccine, with no observed increase in medically attended or serious adverse events.
+Antibody levels in bulk tank milk (BTM) against bovine respiratory syncytial virus (BRSV) are used to classify BRSV status of herds.
+The aim of this study was to investigate how these levels correspond with the time at which the herds were infected.
+Bulk tank milk, individual milk and serum samples from cows and young stock were investigated using an indirect ELISA.
+Screenings of BTM from 89 dairy herds during two winter seasons revealed a prevalence of positive herds from 82 per cent to 85 per cent.
+Eleven herds showed a marked increase in antibody levels between two screenings, indicating new infection.
+However, two of these herds had been free from BRSV for the last five to seven years.
+Two newly infected herds were monitored for four years and did not appear to get reinfected.
+Surprisingly, the BTM antibody levels in these herds remained high throughout the study period, but fluctuated significantly.
+This shows that the levels of antibodies in BTM can remain high for several years, even in herds where reinfection does not occur.
+BTM serology is a useful tool in the monitoring of infectious diseases in dairy herds, but has limitations as a diagnostic tool for BRSV infections.
+Scorpine, a small cationic peptide from the venom of Pandinus imperator, which has been shown to have anti-bacterial and anti-plasmodial activities, has potential important applications in the pharmaceutical industries.
+Here, we first report the expression and purification of recombinant scorpine in Escherichia coli, using small ubiquitin-related modifier (SUMO) fusion partner.
+The fusion protein was expressed in soluble form in E. coli, and expression was verified by SDS-PAGE and western blotting analysis.
+After the SUMO-scorpine fusion protein was cleaved by the SUMO protease, the cleaved sample was reapplied to a Ni(2+)–NTA column.
+Tricine/SDS-PAGE gel results indicated that Scorpine had been purified successfully to more than 95% purity.
+The recombinantly expressed Scorpine showed anti-bacterial activity against two standard bacteria including Staphylococcus aureus ATCC 29213 and Acinetobacter baumannii ATCC 19606, and clinically isolated bacteria including S. aureus S, S. aureus R, A. baumannii S, and A. baumannii R. It also produced 100% reduction in Plasmodium falciparum parasitemia in vitro.
+Thus, the expression strategy presented in this study allowed convenient high yield and easy purification of recombinant Scorpine for pharmaceutical applications in the future.
+While there has been a major shift away from d4T use in resource-limited countries, a large number of patients have previously received (or continue to receive) d4T, and many have developed peripheral neuropathy.
+The identification of genetic predictors of increased risk might suggest novel therapeutic targets for such patients.
+In AIDS Clinical Trials Group protocol 384, antiretroviral-naïve patients were randomized to d4T/didanosine (ddI)- or zidovudine/lamivudine-containing regimens.
+Data from d4T/ddI recipients were analyzed for genome-wide associations (approximately 1 million genetic loci) with new onset distal sensory peripheral neuropathy.
+Analyses involved 254 patients (49 % White, 34 % Black, 17 % Hispanic), comprising 90 peripheral neuropathy cases (32 grade 1, 35 grade 2, 23 grade 3) and 164 controls.
+After correcting for multiple comparisons, no polymorphism was consistently associated with neuropathy among all patients, among White, Black, and Hispanic patients analyzed separately, both in genome-wide analyses (threshold, P < 5.0 × 10(−8)) and focused on 46 neuropathy-associated genes (threshold, P < 3.5 × 10(−5)).
+In the latter analyses, the lowest P values were in KIF1A among Whites (rs10199388, P = 8.4 × 10(−4)), in LITAF among Blacks (rs13333308, P = 6.0 × 10(−6)), and in NEFL among Hispanics (rs17763685, P = 5.6 × 10(−6)).
+Susceptibility to d4T/ddI-associated neuropathy is not explained by a single genetic variant with a marked effect.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s13365-014-0235-9) contains supplementary material, which is available to authorized users.
+Porcine reproductive and respiratory syndrome (PRRS) is a leading disease in pig industry worldwide and can result in serious economic losses each year.
+The PRRS epidemic situation in China has been very complicated since the unprecedented large-scale highly pathogenic PRRS (HP-PRRS) outbreaks in 2006.
+And now the HP-PRRS virus (HP-PRRSV) and classical North American type PRRSV strains have coexisted in China.
+Rapid differential detection of the two strains of PRRSV is very important for effective PRRS control.
+The real-time RT-PCR for simultaneous detection and differentiation of HP-PRRSV and PRRSV by using both SYBR Green and TaqMan probes was developed and validated.
+Both assays can be used for rapid detection and strain-specific identification of HP-PRRSV and PRRSV.
+However, the TaqMan probe method had the highest detection rate whereas the conventional RT-PCR was the lowest.
+The real-time RT-PCR developed based on SYBR Green and TaqMan probe could be used for simultaneous detection and differentiation of HP-PRRSV and PRRSV in China, which will benefit much the PRRS control and research.
+Internal ribosome entry sites (IRES) are utilized by a subset of cellular and viral mRNAs to initiate translation during cellular stress and virus infection when canonical cap-dependent translation is compromised.
+The intergenic region (IGR) IRES of the Dicistroviridae uses a streamlined mechanism in which it can directly recruit the ribosome in the absence of initiation factors and initiates translation using a non-AUG codon.
+A subset of IGR IRESs including that from the honey bee viruses can also direct translation of an overlapping +1 frame gene.
+In this study, we systematically examined cellular conditions that lead to IGR IRES-mediated 0 and +1 frame translation in Drosophila S2 cells.
+Towards this, a novel bicistronic reporter that exploits the 2A “stop-go” peptide was developed to allow the detection of IRES-mediated translation in vivo.
+Both 0 and +1 frame translation by the IGR IRES are stimulated under a number of cellular stresses and in S2 cells infected by cricket paralysis virus, demonstrating a switch from cap-dependent to IRES-dependent translation.
+The regulation of the IGR IRES mechanism ensures that both 0 frame viral structural proteins and +1 frame ORFx protein are optimally expressed during virus infection.
+Glycyrrhizic acid (GA), a major compound separated from Radix Glycyrrhizae, has been shwon to exert various biochemical effects, including neuroprotective effects.
+In the present study, we investigated the protective effects of GA against 1-methyl-4-phenylpyridinium (MPP(+))-induced damage to differentiated PC12 (DPC12) cells.
+Compared with the MPP(+)-treated cells, GA markedly improved cell viability, restored mitochondrial dysfunction, suppressed the overexpression of cleaved poly(ADP-ribose) polymerase (PARP), and suppressed the overproduction of lactate dehydrogenase (LDH) and intracellular Ca(2+) overload.
+The protective effects of GA on cell survival were further confirmed in primary cortical neurons.
+GA markedly increased the expression of phosphorylated extracellular signal-regulated kinase (p-ERK), as well as its migration from the cytoplasm to nucleus.
+However, pre-treatment with GA had no effects on the expression of phosphorylated AKT (p-AKT) and total AKT (t-AKT).
+These results indicate that the GA-mediated neuroprotective effects are associated with its modulation of multiple anti-apoptotic and pro-apoptotic factors, particularly the ERK signaling pathway.
+This study provides evidence supporting the use of GA as a potential therapeutic agent for the treatment of neurodegenerative diseases and neuronal injury.
+Thyroid transcription factor-1 (TTF-1, also known as NKX2-1) is a tissue-specific transcription factor in lung epithelial cells.
+Although TTF-1 inhibits the epithelial-to-mesenchymal transition induced by transforming growth factor-β (TGF-β) in lung adenocarcinoma cells, the mechanism through which TTF-1 inhibits the functions of TGF-β is unknown.
+Here we show that TTF-1 disrupts the nuclear Smad3-Smad4 complex without affecting the nuclear localization of phospho-Smad3.
+Genome-wide analysis by chromatin immunoprecipitation followed by sequencing revealed that TTF-1 colocalizes with Smad3 on chromatin and alters Smad3-binding patterns throughout the genome, while TTF-1 generally inhibits Smad4 binding to chromatin.
+Moreover, Smad3 binds to chromatin together with TTF-1, but not with Smad4, at some Smad3-binding regions when TGF-β signaling is absent, and knockdown of Smad4 expression does not attenuate Smad3 binding in these regions.
+Thus, TTF-1 may compete with Smad4 for interaction with Smad3, and in the presence of TTF-1, Smad3 regulates the transcription of certain genes independently of Smad4.
+BACKGROUND: During the last century, WHO led public health interventions that resulted in spectacular achievements such as the worldwide eradication of smallpox and the elimination of malaria from the Western world.
+However, besides major successes achieved worldwide in infectious diseases control, most elimination/control programs remain frustrating in many tropical countries where specific biological and socio-economical features prevented implementation of disease control over broad spatial and temporal scales.
+There is consequently an urgent need to develop affordable and sustainable disease control strategies that can target the core of infectious diseases transmission in highly endemic areas.
+DISCUSSION: Meanwhile, although most pathogens appear so difficult to eradicate, it is surprising to realize that human activities are major drivers of the current high rate of extinction among upper organisms through alteration of their ecology and evolution, i.e., their “niche”.
+During the last decades, the accumulation of ecological and evolutionary studies focused on infectious diseases has shown that the niche of a pathogen holds more dimensions than just the immune system targeted by vaccination and treatment.
+Indeed, it is situated at various intra- and inter- host levels involved on very different spatial and temporal scales.
+After developing a precise definition of the niche of a pathogen, we detail how major advances in the field of ecology and evolutionary biology of infectious diseases can enlighten the planning and implementation of infectious diseases control in tropical countries with challenging economic constraints.
+SUMMARY: We develop how the approach could translate into applied cases, explore its expected benefits and constraints, and we conclude on the necessity of such approach for pathogen control in low-income countries.
+Necrotizing enterocolitis (NEC) is among the most common and devastating diseases in neonates and, despite the significant advances in neonatal clinical and basic science investigations, its etiology is largely understood, specific treatment strategies are lacking, and morbidity and mortality remain high.
+Pharmacologic inhibition of toll-like receptor signaling, the use of novel nutritional strategies, and microflora modulation may represent novel promising approaches to the prevention and treatment of NEC.
+This review, starting from the recent acquisitions in the pathogenic mechanisms of NEC, focuses on current and possible therapeutic perspectives.
+The common marmoset (Callithrix jacchus) is increasingly being utilised as a nonhuman primate model for human disease, ranging from autoimmune to infectious disease.
+In order to fully exploit these models, meaningful comparison to the human host response is necessary.
+Commercially available reagents, primarily targeted to human cells, were utilised to assess the phenotype and activation status of key immune cell types and cytokines in naive and infected animals.
+Generally, the phenotype of cells was comparable between humans and marmosets, with approximately 63% of all lymphocytes in the blood of marmosets being T cells, 25% B-cells, and 12% NK cells.
+The percentage of neutrophils in marmoset blood were more similar to human values than mouse values.
+Comparison of the activation status of cells following experimental systemic or inhalational infection exhibited different trends in different tissues, most obvious in cell types active in the innate immune response.
+This work significantly enhances the ability to understand the immune response in these animals and fortifies their use as models of infectious disease.
+BACKGROUND: Despite the fact that traditional Chinese medicine (TCM) has been developed and used to treat acute and urgent illness for many thousands of years.
+TCM has been widely perceived in western societies that TCM may only be effective to treat chronic diseases.
+The aim of this article is to provide some scientific evidence regarding the application of TCM in emergency medicine and its future potential.
+METHODS: Multiple databases (PubMed, ProQuest, Academic Search Elite and Science Direct) were searched using the terms: Traditional Chinese Medicine/ Chinese Medicine, Emergency Medicine, China.
+In addition, three leading TCM Journals in China were searched via Oriprobe Information Services for relevant articles (published from 1990—2012).
+Particular attention was paid to those articles that are related to TCM treatments or combined medicine in dealing with intensive and critical care.
+The clinical practice of TCM is guided by the TCM theoretical framework – a methodology founded thousands of years ago.
+As the methodologies between TCM and Biomedicine are significantly different, it provides an opportunity to combine two medicines, in order to achieve clinical efficacy.
+Nowadays, combined medicine has become a common clinical model particular in TCM hospitals in China.
+CONCLUSIONS: It is evident that TCM can provide some assistance in emergency although to combine them in practice is still its infant form and is mainly at TCM hospitals in China.
+The future effort could be put into TCM research, both in laboratories and clinics, with high quality designs, so that TCM could be better understood and then applied in emergency medicine.
+OBJECTIVES: The emergence of the pandemic influenza A(H1N1)pdm09 virus in 2009 saw a significant increase in the therapeutic and prophylactic use of neuraminidase inhibitors (NAIs) to mitigate the impact of this highly transmissible virus.
+Prior to the pandemic, many countries stockpiled NAIs and developed pandemic plans for the use of antiviral drugs, based on either treatment of high-risk individuals and/or prophylaxis of contacts.
+However, to date there has been a lack of in vivo models to test the efficacy of treatment or prophylaxis with NAIs, for influenza-infected individuals or exposed contacts, in a household setting.
+METHODS: A ferret model of household contact was developed to study the efficacy of different prophylaxis regimens in preventing infection in contact ferrets exposed to influenza A(H1N1)pdm09-infected index ferrets.
+RESULTS: Among the different prophylactic regimens, contact ferrets receiving oseltamivir prophylaxis twice daily showed better outcomes than those receiving oseltamivir once daily.
+Benefits included a significant delay in the time to secondary infection, lower weight loss and higher activity levels.
+The treatment of index ferrets at 36 h post-infection did not influence either secondary infection rates or clinical symptoms in exposed contact ferrets.
+Neither prophylaxis nor treatment prevented infection or reduced the duration of viral shedding, although clinical symptoms did improve in infected animals receiving prophylaxis.
+CONCLUSIONS: Different oseltamivir prophylaxis regimens did not prevent infections, but consistently resulted in a reduction in symptoms in infected ferrets.
+Peste des petits ruminants (PPR) is an acute, febrile, viral disease of small ruminants that has a significant economic impact.
+For many viral diseases, vaccination with virus-like particles (VLPs) has shown considerable promise as a prophylactic approach; however, the processes of assembly and release of peste des petits ruminants virus (PPRV) VLPs are not well characterized, and their immunogenicity in the host is unknown.
+In this study, VLPs of PPRV were generated in a baculovirus system through simultaneous expression of PPRV matrix (M) protein and hemaglutin in (H) or fusion (F) protein.
+Subcutaneous injection of these VLPs (PPRV-H, PPRV-F) into mice and goats elicited PPRV-specific IgG production, increased the levels of virus neutralizing antibodies, and promoted lymphocyte proliferation.
+Without adjuvants, the immune response induced by the PPRV-H VLPs was comparable to that obtained using equivalent amounts of PPRV vaccine.
+Thus, our results demonstrated that VLPs containing PPRV M protein and H or F protein are potential “differentiating infected from vaccinated animals” (DIVA) vaccine candidates for the surveillance and eradication of PPR.
+BACKGROUND: Host genetic factors are thought to modulated the severity of disease caused by infection with the 2009 H1N1 pandemic influenza virus (H1N1pdm09).
+The human CCR5 gene encodes a cytokine receptor important for cell-mediated immune response against H1N1pdm09.
+A 32-bp polymorphic deletion in the coding sequence of CCR5, the so-called CCR5Δ32 allele, segregates in populations of European ancestry with a frequency of 8-15%.
+A high proportion of CCR5Δ32 heterozygotes was reported in a sample of white Canadian critically-ill H1N1pdm09 infected subjects, suggesting an association with disease severity.
+METHODS: We recruited 29 H1N1pdm09 infected subjects from Southern Europe (mostly Italians) with a wide clinical spectrum of disease symptoms; the sample included 7 subjects who developed acute respiratory distress syndrome requiring extracorporeal membrane oxygenation.
+RESULTS: The CCR5Δ32 allele was found in one single subject, who developed a very mild form and was not hospitalized.
+CONCLUSIONS: The CCR5Δ32 allele was not found to be associated with the risk of H1N1pdm09 infection or with a severe disease course.
+HIV-1 uses a number of means to manipulate the immune system, to avoid recognition and to highjack signaling pathways.
+Using biochemical and biophysical approaches, we demonstrate that the trans-membrane domain (TMD) of the HIV-1 envelope (ENV) directly interacts with TLR2 TMD within the membrane milieu.
+This interaction attenuates TNFα, IL-6 and MCP-1 secretion in macrophages, induced by natural ligands of TLR2 both in in vitro and in vivo models.
+Furthermore, mutagenesis demonstrated the importance of a conserved GxxxG motif in driving this interaction within the membrane milieu.
+The administration of the ENV TMD in vivo to lipotechoic acid (LTA)/Galactosamine-mediated septic mice resulted in a significant decrease in mortality and in tissue damage, due to the weakening of systemic macrophage activation.
+Our findings suggest that the TMD of ENV is involved in modulation of the innate immune response during HIV infection.
+Furthermore, due to the high functional homology of viral ENV proteins this function may be a general character of viral-induced immune modulation.
+In addition, the burden of asthma is more significant in the elderly than in their younger counterparts, particularly with regard to mortality, hospitalization, medical costs or health-related quality of life.
+Therefore, it is an imperative task to recognize our current challenges and to set future directions.
+This project aims to review the current literature and identify unmet needs in the fields of research and practice for asthma in the elderly.
+This will enable us to find new research directions, propose new therapeutic strategies, and ultimately improve outcomes for elderly people with asthma.
+There are data to suggest that asthma in older adults is phenotypically different from young patients, with potential impact on the diagnosis, assessment and management in this population.
+The diagnosis of AIE in older populations relies on the same clinical findings and diagnostic tests used in younger populations, but the interpretation of the clinical data is more difficult.
+The challenge today is to encourage new research in AIE but to use the existing knowledge we have to make the diagnosis of AIE, educate the patient, develop a therapeutic approach to control the disease, and ultimately provide a better quality of life to our elderly patients.
+Disease or pathogen risk prioritisations aid understanding of infectious agent impact within surveillance or mitigation and biosecurity work, but take significant development.
+We present a weighted risk analysis describing infectious pathogen impact for human health (human pathogens) and well-being (domestic animal pathogens) using an objective, evidence-based, repeatable approach; the H-index.
+Differences between host types (humans/animals/zoonotic) in pathogen H-indices were explored as a One Health impact indicator.
+Finally, the acceptability of the H-index proxy for animal pathogen impact was examined by comparison with other measures.
+57 pathogens appeared solely in the top 100 highest H-indices (1) human or (2) animal pathogens list, and 43 occurred in both.
+Of human pathogens, 66 were zoonotic and 67 were emerging, compared to 67 and 57 for animals.
+There were statistically significant differences between H-indices for host types (humans, animal, zoonotic), and there was limited evidence that H-indices are a reasonable proxy for animal pathogen impact.
+This work addresses measures outlined by the European Commission to strengthen climate change resilience and biosecurity for infectious diseases.
+The results include a quantitative evaluation of infectious pathogen impact, and suggest greater impacts of human-only compared to zoonotic pathogens or scientific under-representation of zoonoses.
+The outputs separate high and low impact pathogens, and should be combined with other risk assessment methods relying on expert opinion or qualitative data for priority setting, or could be used to prioritise diseases for which formal risk assessments are not possible because of data gaps.
+BACKGROUND: In prolonged hemorrhagic shock, reductions in intestinal mucosal blood perfusion lead to mucosal barrier damage and systemic inflammation.
+Gastrointestinal failure in critically ill patients has a poor prognosis, so early assessment of mucosal barrier injury in shock patients is clinically relevant.
+OBJECTIVE: The aim of this study was to assess if serum diamine oxidase levels can reflect intestinal mucosal injury subsequent to prolonged hemorrhagic shock.
+METHODS: Thirty New Zealand white rabbits were divided into three groups: a control group, a medium blood pressure (BP) group (exsanguinated to a shock BP of 50 to 41 mm Hg), and a low BP group (exsanguinated to a shock blood pressure of 40 to 31 mm Hg), in which the shock BP was sustained for 180 min prior to fluid resuscitation.
+RESULTS: The severity of hemorrhagic shock in the low BP group was significantly greater than that of the medium BP group according to the post-resuscitation BP, serum tumor necrosis factor (TNF)-α, and arterial lactate.
+Intestinal damage was significantly more severe in the low BP group according to Chiu’s scoring, claudin-1, intercellular adhesion molecule (ICAM)-1, and myeloperoxidase expression.
+Serum diamine oxidase was significantly increased in the low BP group compared to the medium BP and control groups and was negatively correlated with shock BP.
+CONCLUSION: Serum diamine oxidase can be used as a serological marker in evaluating intestinal injury and shows promise as an indicator of hemorrhagic shock severity.
+Maternally-derived antibodies (MDAs) can decrease the transmission of pathogens between individuals by reducing shedding from infected animals and/or susceptibility of naïve animals.
+Only a limited number of studies, however, have been carried out to quantify the level of protection conferred by PI in terms of transmission.
+In the present study, an original modeling framework was designed to estimate parameters governing the transmission of infectious agents in the presence and absence of PI.
+This epidemiological model accounts for the distribution of PI duration and two different forces of infection depending on the serological status of animals after colostrum intake.
+The impact of PI on hepatitis E virus transmission in piglets was investigated using longitudinal serological data from six pig farms.
+A strong impact of PI was highlighted, the efficiency of transmission being on average 13 times lower in piglets with maternally-derived antibodies than in fully susceptible animals (range: 5–21).
+Median infection-free survival ages, based on herd-specific estimates, ranged between 8.7 and 13.8 weeks in all but one herd.
+Indeed, this herd exhibited a different profile with a relatively low prevalence of infected pigs (50% at slaughter age) despite the similar proportions of passively immune individuals after colostrum intake.
+These results suggest that the age at HEV infection is not strictly dependent upon the proportion of piglets with PI but is also linked to farm-specific husbandry (mingling of piglets after weaning) and hygiene practices.
+The original methodology developed here, using population-based longitudinal serological data, was able to demonstrate the relative impact of MDAs on the transmission of infectious agents.
+Compartmentalization in a prebiotic setting is an important aspect of early cell formation and is crucial for the development of an artificial protocell system that effectively couples genotype and phenotype.
+Aqueous two-phase systems (ATPSs) and complex coacervates are phase separation phenomena that lead to the selective partitioning of biomolecules and have recently been proposed as membrane-free protocell models.
+We show in this study through fluorescence recovery after photobleaching (FRAP) microscopy that despite the ability of such systems to effectively concentrate RNA, there is a high rate of RNA exchange between phases in dextran/polyethylene glycol ATPS and ATP/poly-L-lysine coacervate droplets.
+In contrast to fatty acid vesicles, these systems would not allow effective segregation and consequent evolution of RNA, thus rendering these systems ineffective as model protocells.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11084-014-9355-8) contains supplementary material, which is available to authorized users.
+Aim: During the last decade it became obvious that viruses belonging to Mimiviridae and Marseilleviridae families (order Megavirales), may be potential causative agents of pneumonia.
+Thus, we have performed a review of the association of Mimiviridae, Marseilleviridae, and virophages with pneumonia, particularly healthcare-associated pneumonia, and other infections of the respiratory tract.
+Results and discussion: According to the analysis of the published articles, viruses belonging to Mimiviridae family can be potential agents of both community-acquired and healthcare-associated pneumonia.
+In particular, these viruses may be associated with poor outcome in patients of intensive care units.
+The discrepancies between the results obtained by serological and genomic methods could be explained by the high polymorphism of nucleotide sequences of Mimiviridae family representatives.
+Further investigations on the Mimiviridae pathogenicity and on the determination of Mimiviridae-caused pneumonia risk groups are required.
+However, the pathogenicity of the viruses belonging to Marseilleviridae family and virophages is unclear up to now.
+BACKGROUND: Kawasaki disease (KD) is a systemic vasculitis with unknown etiology mainly affecting children in Asian countries.
+Dendritic cell-specific intercellular adhesion molecule-3 grabbing non-integrin (DC-SIGN, CD209) in humans was showed to trigger an anti-inflammatory cascade and associated with KD susceptibility.
+This study was conducted to investigate the association between genetic polymorphisms of CD209 and the risk KD.
+Nine tagging SNPs (rs8112310, rs4804800, rs11465421, rs1544766, rs4804801, rs2287886, rs735239, rs735240, rs4804804) were selected for TaqMan allelic discrimination assay.
+Clinical phenotypes, coronary artery lesions (CAL) and intravenous immunoglobulin (IVIG) treatment outcomes were collected for analysis.
+RESULTS: Significant associations were found between CD209 polymorphisms (rs4804800, rs2287886, rs735240) and the risk of KD.
+Haplotype analysis for CD209 polymorphisms showed that A/A/G haplotype (P = 0.0002, OR = 1.61) and G/A/G haplotype (P = 0.0365, OR = 1.52) had higher risk of KD as compared with G/G/A haplotype in rs2287886/rs735239/rs735240 pairwise allele analysis.
+There were no significant association in KD with regards to CAL formation and IVIG treatment responses.
+CONCLUSION: CD209 polymorphisms were responsible for the susceptibility of KD, but not CAL formation and IVIG treatment responsiveness.
+Several host factors including cell-mediated immune cells, such as IL-1, IL-6 and IL-10 have been documented for P. vivax-induced thrombocytopaenia.
+However, study on correlation of cytokines and thrombocytopaenia in P. vivax, particularly in patients with severe signs and symptoms has not been reported from Pakistan.
+METHODS: A case control study to correlate TNF, IL-6 and IL-10 in healthy controls and thrombocytopaenic P. vivax-infected patients (both uncomplicated and complicated cases) from southern Pakistan was carried out during January 2009 to December 2011.
+One Hundred and eighty two patients presenting with microscopy-confirmed asexual P. vivax mono-infection and 100 healthy controls were enrolled in the study at Aga Khan University Hospital, Karachi.
+RESULTS: Out of 182 cases, mild thrombocytopaenia (platelet count 100,000-150,000 mm(3)) was observed in ten (5.5%), moderate (50,000-100,000 mm(3)) in 93 (51.1%), and profound thrombocytopaenia (<50,000 mm(3)) was detected in 79 (43.4%) patients.
+IL-6 and IL-10 levels were found approximately three-fold higher in the mild cases compared to healthy controls.
+Two-fold increase in TNF and IL-10 (p < 0.0001) was observed in profound thrombocytopaenic when compared with moderate cases, while IL-6 was not found to be significantly elevated.
+Findings from this study give first insight from Pakistan on the role of cytokines in P.vivax-associated thrombocytopaenia.
+However, further studies are required to understand the relevance of cytokines in manifestations of thrombocytopaenia in P. vivax malaria.
+The present study focuses on the neuroprotective effect of glycyrrhizic acid (GA, a major compound separated from Glycyrrhiza Radix, which is a crude Chinese traditional drug) against glutamate-induced cytotoxicity in differentiated PC12 (DPC12) cells.
+The results showed that GA treatment improved cell viability and ameliorated abnormal glutamate-induced alterations in mitochondria in DPC12 cells.
+GA reversed glutamate-suppressed B-cell lymphoma 2 levels, inhibited glutamate-enhanced expressions of Bax and cleaved caspase 3, and reduced cytochrome C (Cyto C) release.
+Exposure to glutamate strongly inhibited phosphorylation of AKT (protein kinase B) and extracellular signal-regulated kinases (ERKs); however, GA pretreatment enhanced activation of ERKs but not AKT.
+The presence of PD98059 (a mitogen-activated protein/extracellular signal-regulated kinase kinase [MEK] inhibitor) but not LY294002 (a phosphoinositide 3-kinase [PI3K] inhibitor) diminished the potency of GA for improving viability of glutamate-exposed DPC12 cells.
+These results indicated that ERKs and mitochondria-related pathways are essential for the neuroprotective effect of GA against glutamate-induced toxicity in DPC12 cells.
+The present study provides experimental evidence supporting GA as a potential therapeutic agent for use in the treatment of neurodegenerative diseases.
+[Image: see text] The Dengue virus (DENV) NS2A protein, essential for viral replication, is a poorly characterized membrane protein.
+NS2A displays both protein/protein and membrane/protein interactions, yet neither its functions in the viral cycle nor its active regions are known with certainty.
+To highlight the different membrane-active regions of NS2A, we characterized the effects of peptides derived from a peptide library encompassing this protein’s full length on different membranes by measuring their membrane leakage induction and modulation of lipid phase behavior.
+Following this initial screening, one region, peptide dens25, had interesting effects on membranes; therefore, we sought to thoroughly characterize this region’s interaction with membranes.
+We show that dens25 strongly interacts with membranes that contain a large proportion of lipid molecules with a formal negative charge, and that this effect has a major electrostatic contribution.
+Considering its membrane modulating capabilities, this region might be involved in membrane rearrangements and thus be important for the viral cycle.
+BACKGROUND: FTY720 (fingolimod) is the first oral drug approved by the Food and Drug Administration for treatment of patients with the relapsing-remitting form of the human demyelinating disease multiple sclerosis.
+Evidence suggests that the therapeutic benefit of FTY720 occurs by preventing the egress of lymphocytes from lymph nodes thereby inhibiting the infiltration of disease-causing lymphocytes into the central nervous system (CNS).
+We hypothesized that FTY720 treatment would affect lymphocyte migration to the CNS and influence disease severity in a mouse model of viral-induced neurologic disease.
+Infected animals were treated with increasing doses (1, 3 and 10 mg/kg) of FTY720 and morbidity and mortality recorded.
+Infiltration of inflammatory virus-specific T cells (tetramer staining) into the CNS of FTY720-treated mice was determined using flow cytometry.
+The effects of FTY720 treatment on virus-specific T cell proliferation, cytokine production and cytolytic activity were also determined.
+The severity of neuroinflammation and demyelination in FTY720-treated mice was examined by flow cytometry and histopathologically, respectively, in the spinal cords of the mice.
+RESULTS: Administration of FTY720 to JHMV-infected mice resulted in increased clinical disease severity and mortality.
+These results correlated with impaired ability to control viral replication (P < 0.05) within the CNS at days 7 and 14 post-infection, which was associated with diminished accumulation of virus-specific CD4+ and CD8+ T cells (P < 0.05) into the CNS.
+Reduced neuroinflammation in FTY720-treated mice correlated with increased retention of T lymphocytes within draining cervical lymph nodes (P < 0.05).
+Treatment with FTY720 did not affect virus-specific T cell proliferation, expression of IFN-γ, TNF-α or cytolytic activity.
+CONCLUSION: These findings indicate that FTY720 mutes effective anti-viral immune responses through impacting migration and accumulation of virus-specific T cells within the CNS during acute viral-induced encephalomyelitis.
+FTY720 treatment reduces the severity of neuroinflammatory-mediated demyelination by restricting the access of disease-causing lymphocytes into the CNS but is not associated with viral recrudescence in this model.
+In nature, vector-borne flaviviruses are persistently cycled between either the tick or mosquito vector and small mammals such as rodents, skunks, and swine.
+Increasing and substantial evidence of viral persistence in humans, which includes the isolation of RNA by RT-PCR and infectious virus by culture, continues to be reported.
+Viral persistence can also be established in vitro in various human, animal, arachnid and insect cell lines in culture.
+Although some research has focused on the potential roles of defective virus particles, evasion of the immune response through the manipulation of autophagy and/or apoptosis, the precise mechanism of flavivirus persistence is still not well understood.
+We propose additional research for further understanding of how viral persistence is established in different systems.
+Avenues for additional studies include determining if the multifunctional flavivirus protein NS5 has a role in viral persistence, the development of relevant animal models of viral persistence as well as investigating the host responses that allow vector borne flavivirus replication without detrimental effects on infected cells.
+Such studies might shed more light on the viral-host relationships, and could be used to unravel the mechanisms for establishment of persistence.
+Despite the fact that bats carry and shed highly pathogenic viruses including Ebola, Nipah and SARS, they rarely display clinical symptoms of infection.
+Host factors influencing viral replication are poorly understood in bats and are likely to include both pre- and post-transcriptional regulatory mechanisms.
+MicroRNAs are a major mechanism of post-transcriptional gene regulation, however very little is known about them in bats.
+RESULTS: This study describes 399 microRNAs identified by deep sequencing of small RNA isolated from tissues of the Black flying fox, Pteropus alecto, a confirmed natural reservoir of the human pathogens Hendra virus and Australian bat lyssavirus.
+Of the microRNAs identified, more than 100 are unique amongst vertebrates, including a subset containing mutations in critical seed regions.
+Clusters of rapidly-evolving microRNAs were identified, as well as microRNAs predicted to target genes involved in antiviral immunity, the DNA damage response, apoptosis and autophagy.
+Closer inspection of the predicted targets for several highly supported novel miRNA candidates suggests putative roles in host-virus interaction.
+CONCLUSIONS: MicroRNAs are likely to play major roles in regulating virus-host interaction in bats, via dampening of inflammatory responses (limiting the effects of immunopathology), and directly limiting the extent of viral replication, either through restricting the availability of essential factors or by controlling apoptosis.
+Characterisation of the bat microRNA repertoire is an essential step towards understanding transcriptional regulation during viral infection, and will assist in the identification of mechanisms that enable bats to act as natural virus reservoirs.
+This in turn will facilitate the development of antiviral strategies for use in humans and other species.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2164-15-682) contains supplementary material, which is available to authorized users.
+The Mojave Desert of North America has become fire‐prone in recent decades due to invasive annual grasses that fuel wildfires following years of high rainfall.
+Perennial species are poorly adapted to fire in this system, and post‐fire shifts in species composition have been substantial but variable across community types.
+To generalize across a range of conditions, we investigated whether simple life‐history traits could predict how species responded to fire.
+Further, we classified species into plant functional types (PFTs) based on combinations of life‐history traits and evaluated whether these groups exhibited a consistent fire‐response.
+Six life‐history traits varied significantly between burned and unburned areas in short (up to 4 years) or long‐term (up to 52 years) post‐fire datasets, including growth form, lifespan, seed size, seed dispersal, height, and leaf longevity.
+Forbs and grasses consistently increased in abundance after fire, while cacti were reduced and woody species exhibited a variable response.
+Species in Group 1 increased in abundance after fire and were characterized by short lifespans, small, wind‐dispersed seeds, low height, and deciduous leaves.
+Species in Group 2 were reduced by fire and distinguished from Group 1 by longer lifespans and evergreen leaves.
+Group 3 species, which also decreased after fire, were characterized by long lifespans, large non‐wind dispersed seeds, and taller heights.
+Our results show that PFTs based on life‐history traits can reliably predict the responses of most species to fire in the Mojave Desert.
+Dominant, long‐lived species of this region possess a combination of traits limiting their ability to recover, presenting a clear example of how a novel disturbance regime may shift selective environmental pressures to favor alternative life‐history strategies.
+BACKGROUND: Despite the importance of an effective health system response to various disasters, relevant research is still in its infancy, especially in middle- and low-income countries.
+OBJECTIVE: This paper provides an overview of the status of disaster health management in China, with its aim to promote the effectiveness of the health response for reducing disaster-related mortality and morbidity.
+DESIGN: A scoping review method was used to address the recent progress of and challenges to disaster health management in China.
+Major health electronic databases were searched to identify English and Chinese literature that were relevant to the research aims.
+RESULTS: The review found that since 2003 considerable progress has been achieved in the health disaster response system in China.
+However, there remain challenges that hinder effective health disaster responses, including low standards of disaster-resistant infrastructure safety, the lack of specific disaster plans, poor emergency coordination between hospitals, lack of portable diagnostic equipment and underdeveloped triage skills, surge capacity, and psychological interventions.
+Additional challenges include the fragmentation of the emergency health service system, a lack of specific legislation for emergencies, disparities in the distribution of funding, and inadequate cost-effective considerations for disaster rescue.
+CONCLUSIONS: One solution identified to address these challenges appears to be through corresponding policy strategies at multiple levels (e.g.
+OBJECTIVES: To discover an antigen-specific autoimmune response associated with both emphysema and osteoporosis among smokers.
+METHODS: Replicate nonbiased discovery assays indicated that autoimmunity to glucose regulated protein 78 (GRP78), an endoplasmic reticulum chaperone and cell surface signaling receptor, is present in many smokers.
+Subject assessments included spirometry, chest CT scans, dual x-ray absorptiometry, and immunoblots for anti-GRP78 IgG.
+Anti-GRP78 autoantibodies were isolated from patient plasma by affinity chromatography, leukocyte functions assessed by flow cytometry, and soluble metabolites and mediators measured by immunoassays.
+MEASUREMENTS AND MAIN RESULTS: Circulating anti-GRP78 IgG autoantibodies were detected in plasma specimens from 86 (32%) of the 265 smoking subjects.
+Anti-GRP78 autoantibodies were singularly prevalent among subjects with radiographic emphysema (OR 3.1, 95%CI 1.7–5.7, p = 0.003).
+Anti-GRP78 autoantibodies were also associated with osteoporosis (OR 4.7, 95%CI 1.7–13.3, p = 0.002), and increased circulating bone metabolites (p = 0.006).
+Among emphysematous subjects, GRP78 protein was an autoantigen of CD4 T-cells, stimulating lymphocyte proliferation (p = 0.0002) and IFN-gamma production (p = 0.03).
+Patient-derived anti-GRP78 autoantibodies had avidities for osteoclasts and macrophages, and increased macrophage NFkB phosphorylation (p = 0.005) and productions of IL-8, CCL-2, and MMP9 (p = 0.005, 0.007, 0.03, respectively).
+CONCLUSIONS: Humoral and cellular GRP78 autoimmune responses in smokers have numerous biologically-relevant pro-inflammatory and other deleterious actions, and are associated with emphysema and osteoporosis.
+These findings may have relevance for the pathogenesis of smoking-associated diseases, and development of biomarker immunoassays and/or novel treatments for these disorders.
+BACKGROUND: Noack’s leaf-nosed bat, Hipposideros ruber, is a cryptic species within the Hipposideros caffer species complex.
+Despite a widespread distribution in Africa and being host to potentially zoonotic viruses, the genetic structure and ecology of H. ruber is poorly known.
+Here we describe the development of 11 novel polymorphic microsatellite loci to facilitate the investigation of genetic structure.
+FINDINGS: We selected 20 microsatellite sequences identified from high throughput sequence reads and PCR amplified these for 38 individuals, yielding 11 consistently amplifying and scorable loci.
+The number of alleles per locus ranged from two to 12, and observed heterozygosities from 0.00 to 0.865.
+No evidence of linkage disequilibrium was observed, and nine of the markers showed no departure from Hardy-Weinberg equilibrium.
+We demonstrate successful amplification in two closely related species and two divergent lineages of the H. caffer species complex.
+CONCLUSIONS: These new markers will provide a valuable tool to investigate genetic structure in the poorly understood Hipposideros caffer species complex.
+We report on an approach to rapidly screen thousands of Salmonella Enteritidis proteins with the goal of identifying novel immunodominant proteins.
+The large repetitive protein (SEN4030) that plays a role as a putative adhesin in initial cell surface interaction and is highly specific to Salmonella is considered to be the most suitable protein for a diagnostic approach.
+The results further demonstrate that the strategy applied herein is convenient for specifically identifying immunogenic proteins of pathogenic microorganisms.
+Consequently, it enables a sound assessment of promising candidates for diagnostic applications and vaccine development.
+Moreover, the elucidation of immunogenic proteins may assist in unveiling unknown virulence-associated factors, thus furthering the understanding of the underlying pathogenicity of Salmonella in general, and of S. Enteritidis, one of the most frequently detected serovars of this pathogen, in particular.
+We report on the development of an on-chip RPA (recombinase polymerase amplification) with simultaneous multiplex isothermal amplification and detection on a solid surface.
+The isothermal RPA was applied to amplify specific target sequences from the pathogens Neisseria gonorrhoeae, Salmonella enterica and methicillin-resistant Staphylococcus aureus (MRSA) using genomic DNA.
+The amplicon is labeled during on-chip RPA by reverse oligonucleotide primers coupled to a fluorophore.
+Both amplification and spatially resolved signal generation take place on immobilized forward primers bount to expoxy-silanized glass surfaces in a pump-driven hybridization chamber.
+The combination of microarray technology and sensitive isothermal nucleic acid amplification at 38 °C allows for a multiparameter analysis on a rather small area.
+A successful enzymatic reaction is completed in <20 min and results in detection limits of 10 colony-forming units for methicillin-resistant Staphylococcus aureus and Salmonella enterica and 100 colony-forming units for Neisseria gonorrhoeae.
+The results show this method to be useful with respect to point-of-care testing and to enable simplified and miniaturized nucleic acid-based diagnostics.
+[Figure: see text] ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00604-014-1198-5) contains supplementary material, which is available to authorized users.
+Pulmonary hypertension (PH) is a progressive lung disease characterized by elevated pressure in the lung vasculature, resulting in right-sided heart failure and premature death.
+The pathogenesis of PH is complex and multifactorial, involving a dysregulated autonomic nervous system and immune response.
+Inflammatory mechanisms have been linked to the development and progression of PH; however, these are usually restricted to systemic and/or local lung tissue.
+Inflammation within the CNS, often referred to as neuroinflammation involves activation of the microglia, the innate immune cells that are found specifically in the brain and spinal cord.
+Microglial activation results in the release of several cytokines and chemokines that trigger neuroinflammation, and has been implicated in the pathogenesis of several disease conditions such as Alzheimer’s, Parkinson’s, hypertension, atherosclerosis, and metabolic disorders.
+In this review, we introduce the concept of neuroinflammation in the context of PH, and discuss possible strategies that could be developed for PH therapy based on this concept.
+Porcine sapelovirus (PSV), a species of the genus Sapelovirus within the family Picornaviridae, is associated with diarrhea, pneumonia, severe neurological disorders, and reproductive failure in pigs.
+To analyze the structural features of PSV genomes, the full-length nucleotide sequences of three Korean PSV strains were determined and analyzed using bioinformatic techniques in comparison with other known PSV strains.
+The Korean PSV genomes ranged from 7,542 to 7,566 nucleotides excluding the 3′ poly(A) tail, and showed the typical picornavirus genome organization; 5′untranslated region (UTR)-L-VP4-VP2-VP3-VP1-2A-2B-2C-3A-3B-3C-3D-3′UTR.
+Three distinct cis-active RNA elements, the internal ribosome entry site (IRES) in the 5′UTR, a cis-replication element (CRE) in the 2C coding region and 3′UTR were identified and their structures were predicted.
+The availability of these first complete genome sequences for PSV strains will facilitate future investigations of the molecular pathogenesis and evolutionary characteristics of PSV.
+INTRODUCTION: Allergic reaction to dust mites is a relatively common condition among children, triggering cutaneous and respiratory responses that have a great impact on the health of this population.
+Anaphylactic hypersensitivity is characterized by an exacerbated response involving the production of regulatory cytokines responsible for stimulating the production of IgE antibodies.
+OBJECTIVE: To investigate an association of variants in cytokine genes (IL1A (−889), IL1B (−511, +3962), IL1R (1970), IL1RA (11100), IL4RA (+1902), IL12 (−1188), IFNG (+874), TGFB1 (codon 10, codon 25), TNFA (−308, −238), IL2 (−330, +166), IL4 (−1098, −590, −33), IL6 (−174, nt565), and IL10 (−1082, −819, −592)) between patients sensitive to dust mites and a control group.
+METHODS: A total of 254 patients were grouped as atopic and non-atopic according to sensitivity as evaluated by the Prick Test and to cytokine genotyping by the polymerase chain reaction-sequence specific primers (PCR-SSP) method using the Cytokine Genotyping Kit.
+Other associations were observed in the pro-inflammatory cytokines IL1A (−889) (T/T, C, and T) and IL2 (−330) (G/T and T/T) and the anti-inflammatory cytokines IL4RA (+1902) (A and G), IL4 (−590) (T/C, T/T, C, and T), and IL10 (−592) (A/A, C/A, A, and C).
+CONCLUSION: Our results suggest a possible association between single nucleotide polymorphisms (SNPs) in cytokine genes and hypersensitivity to dust mites.
+Screening for thousands of viruses and other pathogenic microorganisms, including bacteria, fungi, and parasites, in human tumor tissues will provide a better understanding of the contributory role of the microbiome in the predisposition for, causes of, and therapeutic responses to the associated cancer.
+Metagenomic assays designed to perform these tasks will have to include rapid and economical processing of large numbers of samples, supported by straightforward data analysis pipeline and flexible sample preparation options for multiple input tissue types from individual patients, mammals, or environmental samples.
+To meet these requirements, the PathoChip platform was developed by targeting viral, prokaryotic, and eukaryotic genomes with multiple DNA probes in a microarray format that can be combined with a variety of upstream sample preparation protocols and downstream data analysis.
+PathoChip screening of DNA plus RNA from formalin-fixed, paraffin-embedded tumor tissues demonstrated the utility of this platform, and the detection of oncogenic viruses was validated using independent PCR and deep sequencing methods.
+These studies demonstrate the use of the PathoChip technology combined with PCR and deep sequencing as a valuable strategy for detecting the presence of pathogens in human cancers and other diseases.
+Advances in cancer therapy have focused attention on the quality of life of cancer survivors.
+Since infertility is a major concern following chemotherapy, it is important to characterize the drug-specific damage to the reproductive system to help find appropriate protective strategies.
+This study investigates the damage on neonatal mouse ovary maintained in vitro for 6 days, and exposed for 24 h (on Day 2) to clinically relevant doses of Docetaxel (DOC; low: 0.1 µM, mid: 1 µM, high: 10 µM).
+At the end of culture, morphological analyses and follicle counts showed that DOC negatively impacts on early growing follicles, decreasing primary follicle number and severely affecting health at the transitional and primary stages.
+Poor follicle health was mainly due to effects on granulosa cells, indicating that the effects of DOC on oocytes were likely to be secondary to granulosa cell damage.
+Immunostaining and western blotting showed that DOC induces activation of intrinsic, type II apoptosis in ovarian somatic cells; increasing the levels of cleaved caspase 3, cleaved caspase 8, Bax and cleaved poly(ADP-ribose) polymerase, while also inducing movement of cytochrome C from mitochondria into the cytosol.
+These results demonstrated that DOC induces a gonadotoxic effect on the mouse ovary through induction of somatic cell apoptosis, with no evidence of direct effects on the oocyte, and that the damaging effect is not mitigated by T3.
+Anxiety and mood disorders are common in the general population in countries around the world.
+This article provides a review of the recent literature on anxiety and depressive disorders with a focus on linkages with several important viral diseases.
+Although the majority of studies have been conducted in developed countries such as the United States and Great Britain, some studies have been carried out in less developed nations where only a small percentage of persons with mental illness receive treatment for their condition.
+The studies summarized in this review indicate that there are important linkages between anxiety and depression and viral diseases such as influenza A (H1N1) and other influenza viruses, varicella-zoster virus, herpes simplex virus, human immunodeficiency virus/acquired immune deficiency syndrome, and hepatitis C. Additional studies are needed to further clarify the mechanisms for interactions between mental health and communicable diseases, in order to assist patients and further prevention and control efforts.
+BACKGROUND: Frequent hand-washing is standard advice for avoidance of respiratory tract infections, but the evidence for a preventive effect in a general community setting is sparse.
+We therefore set out to quantify, in a population-based adult general population cohort, the possible protection against acute respiratory tract infections (ARIs) conferred by a person’s self-perceived hand-washing frequency.
+METHODS: During the pandemic influenza season from September 2009 through May 2010, a cohort of 4365 adult residents of Stockholm County, Sweden, reported respiratory illnesses in real-time.
+A questionnaire about typical contact and hand-washing behaviour was administered at the end of the period (response rate 70%).
+RESULTS: There was no significant decrease in ARI rates among adults with increased daily hand-washing frequency: Compared to 2–4 times/day, 5–9 times was associated with an adjusted ARI rate ratio (RR) of 1.08 (95% confidence interval [CI] 0.87-1.33), 10–19 times with RR = 1.22 (CI 0.97-1.53), and ≥20 times with RR = 1.03 (CI 0.81-1.32).
+A similar lack of effect was seen for influenza-like illness, and in all investigated subgroups.
+CONCLUSIONS: Our results suggest that increases in what adult laymen perceive as being adequate hand-washing may not significantly reduce the risk of ARIs.
+This might have implications for the design of public health campaigns in the face of threatening outbreaks of respiratory infections.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2334-14-509) contains supplementary material, which is available to authorized users.
+BACKGROUND: Isatis indigotica, the source of the traditional Chinese medicine Radix isatidis (Ban-Lan-Gen), is an extremely important economical crop in China.
+To facilitate biological, biochemical and molecular research on the medicinal chemicals in I. indigotica, here we report the first I. indigotica transcriptome generated by RNA sequencing (RNA-seq).
+RESULTS: RNA-seq library was created using RNA extracted from a mixed sample including leaf and root.
+A total of 33,238 unigenes were assembled from more than 28 million of high quality short reads.
+The quality of the assembly was experimentally examined by cDNA sequencing of seven randomly selected unigenes.
+Based on blast search 28,184 unigenes had a hit in at least one of the protein and nucleotide databases used in this study, and 8 unigenes were found to be associated with biosynthesis of indole and its derivatives.
+Furthermore, Clusters of Orthologous Group and Swiss-Port annotation were assigned for 7,707 and 18,679 unigenes, respectively.
+Our results will facilitate studies on the functions of genes involved in the indole alkaloid biosynthesis pathway and on metabolism of nitrogen and indole alkaloids in I. indigotica and its related species.
+It was found that antibodies (Abs) against myelin basic protein (MBP) are the major components of the antibody response in multiple sclerosis (MS) patients.
+We have recently shown that IgGs from sera of MS patients are active in the hydrolysis of MBP.
+However, in literature there are no available data concerning possible MBP-hydrolyzing Abs in cerebrospinal fluid (CSF) of MS patients.
+We have shown that the average content of IgGs in their sera is about 195-fold higher than that in their CSF.
+Here we have compared, for the first time, the average content of lambda- and kappa-IgGs as well as IgGs of four different subclasses (IgG1-IgG4) in CSF and sera of MS patients.
+The average relative content of lambda-IgGs and kappa –IgGs in the case of CSFs (8.0 and 92.0%) and sera (12.3 and 87.7%) are comparable, while IgG1, IgG2, IgG3, and IgG4: CSF - 40.4, 49.0, 8.2, and 2.5% of total IgGs, respectively and the sera - 53.6, 36.0, 5.6, and 4.8%, decreased in different order.
+Electrophoretically and immunologically homogeneous IgGs were obtained by sequential affinity chromatography of the CSF proteins on protein G-Sepharose and FPLC gel filtration.
+We present first evidence showing that IgGs from CSF efficiently hydrolyze MBP and that their average specific catalytic activity is unpredictably ∼54-fold higher than that of Abs from sera of the same MS patients.
+We suggest that anti-MBP abzymes of CSF may promote important neuropathologic mechanisms in this chronic inflammatory disorder and in MS pathogenesis development.
+We aimed to determine whether serum procalcitonin (PCT) levels can effectively and safely reduce antibiotic exposure in patients experiencing exacerbations of asthma.
+METHODS: In this randomized controlled trial, a total of 216 patients requiring hospitalization for severe acute exacerbations of asthma were screened for eligibility to participate and 169 completed the 12-month follow-up visit.
+In the control group, patients received antibiotics according to the attending physician’s discretion; in the PCT group, patients received antibiotics according to an algorithm based on serum PCT levels.
+The primary end point was antibiotic exposure; secondary end points were clinical recovery, length of hospital stay, clinical and laboratory parameters, spirometry, number of asthma exacerbations, emergency room visits, hospitalizations and need for corticosteroid use due to asthma.
+RESULTS: PCT guidance reduced antibiotic prescription (48.9% versus 87.8%, respectively; P < 0.001) and antibiotic exposure (relative risk, 0.56; 95% confidence interval, 0.44 to 0.70; P < 0.001) compared to standard therapy.
+There were no significant differences in clinical recovery, length of hospital stay or clinical, laboratory and spirometry outcomes in both groups.
+Number of asthma exacerbations, emergency room visits, hospitalizations and need for corticosteroid use due to asthma were similar during the 12-month follow-up period.
+CONCLUSION: A PCT-guided strategy allows antibiotic exposure to be reduced in patients with severe acute exacerbation of asthma without apparent harm.
+BACKGROUND: Large RNA molecules are often composed of multiple functional domains whose spatial arrangement strongly influences their function.
+Pre-mRNA splicing, for instance, relies on the spatial proximity of the splice junctions that can be separated by very long introns.
+Albeit a crude measure, the distribution of spatial distances in thermodynamic equilibrium harbors useful information on the shape of the molecule that in turn can give insights into the interplay of its functional domains.
+We show here that the equilibrium distribution of graph-distances between a fixed pair of nucleotides can be computed in polynomial time by means of dynamic programming.
+While a naïve implementation would yield recursions with a very high time complexity of O(n(6)D(5)) for sequence length n and D distinct distance values, it is possible to reduce this to O(n(4)) for practical applications in which predominantly small distances are of of interest.
+They are also theoretically favorable for several real-life applications, in particular since these primarily concern long-range interactions in very large RNA molecules.
+Although a crude approximation of reality, our initial results indicate that the graph-distance can be related to the smFRET data.
+Forecasting the dynamics of influenza outbreaks could be useful for decision-making regarding the allocation of public health resources.
+Reliable forecasts could also aid in the selection and implementation of interventions to reduce morbidity and mortality due to influenza illness.
+This paper reviews methods for influenza forecasting proposed during previous influenza outbreaks and those evaluated in hindsight.
+We discuss the various approaches, in addition to the variability in measures of accuracy and precision of predicted measures.
+PubMed and Google Scholar searches for articles on influenza forecasting retrieved sixteen studies that matched the study criteria.
+We focused on studies that aimed at forecasting influenza outbreaks at the local, regional, national, or global level.
+The selected studies spanned a wide range of regions including USA, Sweden, Hong Kong, Japan, Singapore, United Kingdom, Canada, France, and Cuba.
+Due to differences in measures used to assess accuracy, a single estimate of predictive error for each of the measures was difficult to obtain.
+However, collectively, the results suggest that these diverse approaches to influenza forecasting are capable of capturing specific outbreak measures with some degree of accuracy given reliable data and correct disease assumptions.
+Nonetheless, several of these approaches need to be evaluated and their performance quantified in real-time predictions.
+We aimed to characterize and compare the clinical presentations and disease severity of different RV type circulating in South Africa.
+METHOD: We performed two analyses of RV-positive specimens identified through surveillance in South Africa across all age groups.
+First, RV-positive specimens identified through severe acute respiratory illness (SARI) surveillance in four provinces was randomly selected from 2009 to 2010 for molecular characterization.
+Second, RV-positive specimens identified through SARI, influenza-like illness (ILI) and control surveillance at hospitals and outpatient clinics in during 2012–2013 were used to determine the association of RV type with severe disease.
+RESULTS: Among the 599 sequenced specimens from 2009 to 2010 and 2012 to 2013, RV-A (285, 48%) and RV-C (247, 41%) were more commonly identified than RV-B (67, 11%), with no seasonality and a high genetic diversity.
+A higher prevalence of RV infection was identified in cases with SARI [515/962 (26%); aRRR = 1·6; 95% CI 1·21; 2·2] and ILI [356/962 (28%); aRRR = 1·9; 95% CI 1·37; 2·6] compared with asymptomatic controls (91/962, 22%).
+There was no difference in disease severity between the different type when comparing SARI, ILI and controls.
+CONCLUSION: All three type of RV were identified in South Africa, although RV-A and RV-C were more common than RV-B.
+RV was associated with symptomatic respiratory illness; however, there was no association between RV type and disease severity.
+Early detection of fibrosis progression is of major relevance for the diagnosis and management of patients with liver disease.
+This study was designed to find non-invasive biomarkers for fibrosis in a clinical context where this process occurs rapidly, HCV-positive patients who underwent liver transplantation (LT).
+We analyzed 93 LT patients with HCV recurrence, 41 non-LT patients with liver disease showing a fibrosis stage F≥1 and 9 patients without HCV recurrence who received antiviral treatment before LT, as control group.
+Serum samples were fractionated by ion exchange chromatography and their proteomic profile was analyzed by SELDI-TOF-MS.
+Characterization of the peptide of interest was performed by ion chromatography and electrophoresis, followed by tandem mass spectrometry identification.
+Marked differences were observed between the serum proteome profile of LT patients with early fibrosis recurrence and non-recurrent LT patients.
+A robust peak intensity located at 5905 m/z was the distinguishing feature of non-recurrent LT patients.
+Similar results were found when comparing samples of healthy subjects with those of non-LT fibrotic patients, indicating that our findings were not related to either LT or HCV infection.
+Using tandem mass-spectrometry, we identified the protein peak as a C-terminal fragment of the fibrinogen α chain.
+Cell culture experiments demonstrated that TGF-β reduces α-fibrinogen mRNA expression and 5905 m/z peak intensity in HepG2 cells, suggesting that TGF-β activity regulates the circulating levels of this protein fragment.
+In conclusion, we identified a 5.9 kDa C-terminal fragment of the fibrinogen α chain as an early serum biomarker of fibrogenic processes in patients with liver disease.
+Nerve growth factor (NGF) is overexpressed in patients with inflammatory lung diseases, including virus infections.
+Airway surface liquid (ASL), which is regulated by epithelial cell ion transport, is essential for normal lung function.
+No information is available regarding the effect of NGF on ion transport of airway epithelium.
+To investigate whether NGF can affect ion transport, human primary air‐interface cultured epithelial cells were placed in Ussing chambers to obtain transepithelial voltage (−7.1 ± 3.4 mV), short‐circuit current (I(sc), 5.9 ± 1.0 μA), and transepithelial resistance (750 Ω·cm(2)), and to measure responses to ion transport inhibitors.
+Apically applied NGF (1 ng/mL) reduced I(sc) by 5.3% in 5 min; basolaterally applied NGF had no effect.
+K‐252a (10 nmol/L, apical) did not itself affect Na(+) transport, but it attenuated the NGF‐induced reduction in Na(+) transport, indicating the participation of the trkA receptor in the NGF‐induced reduction in Na(+) transport.
+PD‐98059 (30 μmol/L, apical and basolateral) did not itself affect Na(+) transport, but attenuated the NGF‐induced reduction in Na(+) transport, indicating that trkA activated the Erk 1/2 signaling cascade.
+These results indicate that NGF inhibits Na(+) transport through a trkA‐Erk 1/2‐activated signaling pathway linked to ENaC phosphorylation.
+BACKGROUND: Respiratory syncytial virus (RSV) infects the lung epithelium where it stimulates the production of numerous host cytokines that are associated with disease burden and acute lung injury.
+Characterizing the host cytokine response to RSV infection, the regulation of host cytokines and the impact of neutralizing an RSV-inducible cytokine during infection were undertaken in this study.
+METHODS: A549, primary human small airway epithelial (SAE) cells and wild-type, TIR-domain-containing adapter-inducing interferon-β (Trif) and mitochondrial antiviral-signaling protein (Mavs) knockout (KO) mice were infected with RSV and cytokine responses were investigated by ELISA, multiplex analysis and qPCR.
+Neutralizing anti-leukemia inhibitory factor (LIF) IgG or control IgG was administered to a group of wild-type animals prior to RSV infection.
+RESULTS AND DISCUSSION: RSV-infected A549 and SAE cells release a network of cytokines, including newly identified RSV-inducible cytokines LIF, migration inhibitory factor (MIF), stem cell factor (SCF), CCL27, CXCL12 and stem cell growth factor beta (SCGF-β).
+To identify the regulation of RSV inducible cytokines, Mavs and Trif deficient animals were infected with RSV.
+In vivo induction of airway IL-1β, IL-4, IL-5, IL-6, IL-12(p40), IFN-γ, CCL2, CCL5, CCL3, CXCL1, IP-10/CXCL10, IL-22, MIG/CXCL9 and MIF were dependent on Mavs expression in mice.
+Loss of Trif expression in mice altered the RSV induction of IL-1β, IL-5, CXCL12, MIF, LIF, CXCL12 and IFN-γ.
+Silencing of retinoic acid–inducible gene-1 (RIG-I) expression in A549 cells had a greater impact on RSV-inducible cytokines than melanoma differentiation-associated protein 5 (MDA5) and laboratory of genetics and physiology 2 (LGP2), and Trif expression.
+To evaluate the role of LIF in the airways during RSV infection, animals were treated with neutralizing anti-LIF IgG, which enhanced RSV pathology observed with increased airspace protein content, apoptosis and airway hyperresponsiveness compared to control IgG treatment.
+CONCLUSIONS: RSV infection in the epithelium induces a network of immune factors to counter infection, primarily in a RIG-I dependent manner.
+Expression of LIF protects the lung from lung injury and enhanced pathology during RSV infection.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12865-014-0041-4) contains supplementary material, which is available to authorized users.
+Influenza is a perennial problem affecting millions of people annually with the everpresent threat of devastating pandemics.
+Active prophylaxis by vaccination against influenza virus is currently the main countermeasure supplemented with antivirals.
+However, disadvantages of this strategy include the impact of antigenic drift, necessitating constant updating of vaccine strain composition, and emerging antiviral drug resistance.
+The development of other options for influenza prophylaxis, particularly with broad acting agents able to provide protection in the period between the onset of a pandemic and the development of a strain specific vaccine, is of great interest.
+Exploitation of broad-spectrum mediators could provide barricade protection in the early critical phase of influenza virus outbreaks.
+Passive immunity has the potential to provide immediate antiviral effects, inhibiting virus replication, reducing virus shedding, and thereby protecting vulnerable populations in the event of an impending influenza pandemic.
+Here, we review passive broad-spectrum influenza prophylaxis options with a focus on harnessing natural host defenses, including interferons and antibodies.
+Infectious diseases can constitute public health emergencies of international concern when a pathogen arises, acquires new characteristics, or is deliberately released, leading to the potential for loss of human lives as well as societal disruption.
+A wide range of risk drivers are now known to lead to and/or exacerbate the emergence and spread of infectious disease, including global trade and travel, the overuse of antibiotics, intensive agriculture, climate change, high population densities, and inadequate infrastructures, such as water treatment facilities.
+The varying temporal and geographic frequency with which infectious disease events occur adds yet another layer of complexity to the issue.
+Mitigating the emergence and spread of infectious disease necessitates mapping and prioritising the interdependencies between public health and other sectors.
+Conversely, during an international public health emergency, significant disruption occurs not only to healthcare systems but also to a potentially wide range of sectors, including trade, tourism, energy, civil protection, transport, agriculture, and so on.
+At the same time, dealing with a disease outbreak may require a range of critical sectors for support.
+There is a need to move beyond narrow models of risk to better account for the interdependencies between health and other sectors so as to be able to better mitigate and respond to the risks posed by emerging infectious disease.
+How cells shape and remodel organelles in response to cellular signals is a poorly understood process.
+Using Xenopus laevis egg extract, we found that increases in cytosolic calcium lead to the activation of an endogenous ribonuclease, XendoU.
+A fraction of XendoU localizes to the endoplasmic reticulum (ER) and is required for nuclear envelope assembly and ER network formation in a catalysis-dependent manner.
+Using a purified vesicle fusion assay, we show that XendoU functions on the surface of ER membranes to promote RNA cleavage and ribonucleoprotein (RNP) removal.
+Additionally, RNA removal from the surface of vesicles by RNase treatment leads to increased ER network formation.
+Using human tissue culture cells, we found that hEndoU localizes to the ER, where it promotes the formation of ER tubules in a catalysis-dependent manner.
+Together, these results demonstrate that calcium-activated removal of RNA from membranes by XendoU promotes and refines ER remodeling and the formation of tubular ER.
+An infectious disease that is transmitted from animals to humans, sometimes by a vector, is called zoonosis.
+The focus of this review article is on the most common emerging and re-emerging bacterial zoonotic diseases.
+The role of “One Health” approach, public health education, and some measures that can be taken to prevent zoonotic bacterial infections are discussed.
+Key points: A zoonotic bacterial disease is a disease that can be very commonly transmitted between animals and humans.
+Global climate changes, overuse of antimicrobials in medicine, more intensified farm settings, and closer interactions with animals facilitate emergence or re-emergence of bacterial zoonotic infections.
+The global “One Health” approach, which requires interdisciplinary collaborations and communications in all aspects of health care for humans, animals, and the environment, will support public health in general.
+New strategies for continuous dissemination of multidisciplinary research findings related to zoonotic bacterial diseases are hence needed.
+The blood–brain barrier (BBB) is composed of capillary endothelial cells, pericytes, and perivascular astrocytes, which regulate central nervous system homeostasis.
+Sonic hedgehog (SHH) released from astrocytes plays an important role in the maintenance of BBB integrity.
+BBB disruption and microglial activation are common pathological features of various neurologic diseases such as multiple sclerosis, Parkinson’s disease, amyotrophic lateral sclerosis, and Alzheimer’s disease.
+Here we show that IL-1β abolishes the protective effect of astrocytes on BBB integrity by suppressing astrocytic SHH production.
+Astrocyte conditioned media, SHH, or SHH signal agonist strengthened BBB integrity by upregulating tight junction proteins, whereas SHH signal inhibitor abrogated these effects.
+Moreover, IL-1β increased astrocytic production of pro-inflammatory chemokines such as CCL2, CCL20, and CXCL2, which induce immune cell migration and exacerbate BBB disruption and neuroinflammation.
+Our findings suggest that astrocytic SHH is a potential therapeutic target that could be used to restore disrupted BBB in patients with neurologic diseases.
+The IFITM3 polymorphism rs12252-C, which encodes an IFITM3 isoform (Δ21 IFITM3) lacking 21 amino acids at the amino terminus, has been controversially associated with poor clinical outcomes in patients with H1N1 influenza A virus (IAV) infections.
+In vitro studies have shown that Δ21 IFITM3 loses its ability to restrict H1N1 IAV.
+Subsequent research has also revealed that tyrosine 20 is the key determinant for IFITM3 endocytic trafficking, which is essential for the efficient anti-viral activity of IFITM3.
+In contrast to previous studies, we demonstrated that both Δ21 IFITM3 and an IFITM3 variant (Y20A IFITM3), in which tyrosine 20 is substituted with alanine, strongly restricted entry mediated by IAV H1, H3, H5, and H7 proteins.
+Δ21 IFITM3 also efficiently suppressed replication of H1N1 and, to a lesser extent, H3N2 IAV.
+Δ21 IFITM3 and Y20A IFITM3 had broader subcellular distributions than full-length IFITM3 but an abundant amount of both IFITM3 variants still localized to late endosomes and lysosomes.
+Our data indicate that tyrosine 20 partially regulates the subcellular localization of IFITM3 but is not functionally essential for IFITM3-mediated IAV restriction.
+They also suggested that mechanisms, other than viral entry restriction, might contribute to variations in clinical outcomes of H1N1 influenza associated with rs12252-C.
+BACKGROUND: Nasal potential difference (NPD) and intestinal current measurement (ICM) are functional CFTR tests that are used as adjunctive diagnostic tools for cystic fibrosis (CF).
+A diagnostic comparison between NPD and ICM and the impact of smoking on both CFTR tests has not been done.
+METHODS: The sweat chloride test, NPD, and ICM were performed in 18 patients with CF (sweat chloride >60 mmol/l), including 6 pancreatic sufficient (PS) patients, and 13 healthy controls, including 8 smokers.
+The NPD CFTR response to Cl-free and isoproterenol perfusion (Δ0Cl(-) + Iso) was compared to the ICM CFTR response to forskolin/IBMX, carbachol, and histamine (ΔI(sc, forskolin/IBMX+ carbachol+histamine)).
+RESULTS: The mean NPD CFTR response and ICM CFTR response between patients with CF and healthy controls was significantly different (p <0.001), but not between patients with CF who were PS and those who were pancreatic insufficient (PI).
+In contrast to NPD, there was no overlap of the ICM response between patients with CF and controls.
+CONCLUSIONS: ICM is superior to NPD in distinguishing between patients with CF who have a sweat chloride > 60 mmol/l and healthy controls, including smokers.
+Neither NPD nor ICM differentiated between patients with CF who were PS from those who were PI.
+Smoking has a negative impact on CFTR function in healthy controls measured by NPD and challenges the diagnostic interpretation of NPD, but not ICM.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2466-14-156) contains supplementary material, which is available to authorized users.
+BACKGROUND: In 2007, a novel bunyavirus was found in Henan Province, China and named fever, thrombocytopenia and leukocytopenia syndrome virus (FTLSV); since then, FTLSV has been found in ticks and animals in many Chinese provinces.
+Human-to-human transmission has been documented, indicating that FTLSV should be considered a potential public health threat.
+Determining the historical spread of FTLSV could help curtail its spread and prevent future movement of this virus.
+METHOD/PRINCIPAL FINDINGS: To examine the pattern of FTLSV evolution and the origin of outbreak strains, as well to examine the rate of evolution, the genome of 12 FTLSV strains were sequenced and a phylogenetic and Bayesian phylogeographic analysis of all available FTLSV sequences in China were performed.
+Analysis based on the FTLSV L segment suggests that the virus likely originated somewhere in Huaiyangshan circa 1790 (95% highest probability density interval: 1756–1817) and began spreading around 1806 (95% highest probability density interval: 1773–1834).
+Analysis also indicates that when FTLSV arrived in Jiangsu province from Huaiyangshan, Jiangsu Province became another source for the spread of the disease.
+Bayesian factor test analysis identified three major transmission routes: Huaiyangshan to Jiangsu, Jiangsu to Liaoning, and Jiangsu to Shandong.
+The speed of FTLSV movement has increased in recent decades, likely facilitated by modern human activity and ecosystem changes.
+In addition, evidence of RNA segment reassortment was found in FTLSV; purifying selection appears to have been the dominant force in the evolution of this virus.
+CONCLUSION: Results presented in the manuscript suggest that the Huaiyangshan area is likely be the origin of FTLSV in China and identified probable viral migration routes.
+These results provide new insights into the origin and spread of FTLSV in China, and provide a foundation for future virological surveillance and control.
+BACKGROUND: There are no reports of proteomic analyses of inflamed islets in type 1 diabetes.
+PROCEDURES: Proteins expressed in the islets of enterovirus-associated fulminant type 1 diabetes (FT1DM) with extensive insulitis were identified by laser-capture microdissection mass spectrometry using formalin-fixed paraffin-embedded pancreatic tissues.
+RESULTS: Thirty-eight proteins were identified solely in FT1DM islets, most of which have not been previously linked to type 1 diabetes.
+Five protein-protein interacting clusters were identified, and the cellular localization of selected proteins was validated immunohistochemically.
+Migratory activity-related proteins, including plastin-2 (LCP1), moesin (MSN), lamin-B1 (LMNB1), Ras GTPase-activating-like protein (IQGAP1) and others, were identified in CD8(+) T cells and CD68(+) macrophages infiltrated to inflamed FT1DM islets.
+Proteins involved in successive signaling in innate/adaptive immunity were identified, including SAM domain and HD domain-containing protein 1 (SAMHD1), Ras GTPase-activating-like protein (IQGAP1), proteasome activator complex subunit 1 (PSME1), HLA class I histocompatibility antigen (HLA-C), and signal transducer and activator of transcription 1-alpha/beta (STAT1).
+Angiogenic (thymidine phosphorylase (TYMP)) and anti-angiogenic (tryptophan-tRNA ligase (WARS)) factors were identified in migrating CD8(+) T cells and CD68(+) macrophages.
+Proteins related to virus replication and cell proliferation, including probable ATP-dependent RNA helicase DEAD box helicase 5 (DDX5) and heterogeneous nuclear ribonucleoprotein H (HNRNPH1), were identified.
+The anti-apoptotic protein T-complex protein 1 subunit epsilon (CCT5), the anti-oxidative enzyme 6-phosphogluconate dehydrogenase (PDG), and the anti-viral and anti-apoptotic proteins serpin B6 (SERPINB6) and heat shock 70 kDa protein1-like (HSPA1L), were identified in FT1DM-affected islet cells.
+CONCLUSION: The identified FT1DM-characterizing proteins include those involved in aggressive beta cell destruction through massive immune cell migration and proteins involved in angiogenesis and islet vasculature bleeding, cell repair, and anti-inflammatory processes.
+Adaptive management (AM), long-used in natural resource management, is a structured decision-making approach to solving dynamic problems that accounts for the value of resolving uncertainty via real-time evaluation of alternative models.
+We propose an AM approach to design and evaluate intervention strategies in epidemiology, using real-time surveillance to resolve model uncertainty as management proceeds, with foot-and-mouth disease (FMD) culling and measles vaccination as case studies.
+We use simulations of alternative intervention strategies under competing models to quantify the effect of model uncertainty on decision making, in terms of the value of information, and quantify the benefit of adaptive versus static intervention strategies.
+Culling decisions during the 2001 UK FMD outbreak were contentious due to uncertainty about the spatial scale of transmission.
+The expected benefit of resolving this uncertainty prior to a new outbreak on a UK-like landscape would be £45–£60 million relative to the strategy that minimizes livestock losses averaged over alternate transmission models.
+AM during the outbreak would be expected to recover up to £20.1 million of this expected benefit.
+AM would also recommend a more conservative initial approach (culling of infected premises and dangerous contact farms) than would a fixed strategy (which would additionally require culling of contiguous premises).
+For optimal targeting of measles vaccination, based on an outbreak in Malawi in 2010, AM allows better distribution of resources across the affected region; its utility depends on uncertainty about both the at-risk population and logistical capacity.
+When daily vaccination rates are highly constrained, the optimal initial strategy is to conduct a small, quick campaign; a reduction in expected burden of approximately 10,000 cases could result if campaign targets can be updated on the basis of the true susceptible population.
+Formal incorporation of a policy to update future management actions in response to information gained in the course of an outbreak can change the optimal initial response and result in significant cost savings.
+AM provides a framework for using multiple models to facilitate public-health decision making and an objective basis for updating management actions in response to improved scientific understanding.
+Key challenges include mounting dissemination of multiple resistances to antibiotics, the easy transmission and the growing mortality rates of hospital-acquired bacterial diseases.
+In many cases the specific interaction of an antigen and a corresponding antibody is pivotal.
+Additionally, these proteins might be aptly used for the generation of vaccines to improve current treatment options.
+Hence, a cDNA-based expression library was constructed and screened via microarrays to detect novel antigens of Klebsiella pneumoniae, a prominent agent of nosocomial infections well-known for its extensive antibiotics resistance, especially by extended-spectrum beta-lactamases (ESBL).
+Subsequently, each protein was expressed in full-length and its immunodominant character examined by ELISA and microarray analyses.
+After specificity analysis, homology survey and 3d structural modelling, one epitope sequence GAVVALSTTFA of KPN_00363, an ion channel protein, was identified harboring specificity for K. pneumoniae.
+The approach adopted herein has been successfully utilized to discover novel antigens of Campylobacter jejuni and Salmonella enterica antigens before.
+By identifying several novel antigens and their linear epitope sites, we have paved the way for crucial future research and applications including the design of point-of-care devices, vaccine development and serological screenings for a highly relevant nosocomial pathogen.
+Classical Swine Fever (CSF) is a highly infectious fatal pig disease, resulting in huge economic loss to the swine industry.
+Integrins are membrane-bound signal mediators, expressed on a variety of cell surfaces and are known as receptors or co-receptors for many viruses.
+Here, through quantitive PCR, immunofluorescence (IFC) and immunocytohistochemistry (ICC), we revealed that ST (swine testicles epithelial) cells have a prominent advantage in CSFV proliferation as compared to EC (swine umbilical vein endothelial cell), IEC (swine intestinal epithelial cell) and PK (porcine kidney epithelial) cells.
+Meanwhile, ST cells had remarkably more integrin β3 expression as compared to EC, IEC and PK cells, which was positively correlated with CSFV infection and proliferation.
+Integrin β3 was up-regulated post CSFV infection in all the four cell lines, while the CSFV proliferation rate was decreased in integrin β3 function-blocked cells.
+ShRNA1755 dramatically decreased integrin β3, with a deficiency of 96% at the mRNA level and 80% at the protein level.
+CSFV proliferation was dramatically reduced in integrin β3 constantly-defected cells (ICDC), with the deficiencies of 92.6%, 99% and 81.7% at 24 h, 48 h and 72 h post CSFV infection, respectively.
+These results demonstrate that integrin β3 is required in CSFV infection and proliferation, which provide a new insight into the mechanism of CSFV infection.
+Brazil holds approximately 1/3 of population living infected with AIDS (acquired immunodeficiency syndrome) in Central and South Americas, and it was also the first developing country to implement a large-scale control and intervention program against AIDS epidemic.
+In this scenario, we investigate the temporal evolution and current status of the AIDS epidemic in Brazil.
+Specifically, we analyze records of annual absolute frequency of cases for more than 5000 cities for the first 33 years of the infection in Brazil.
+These findings yield a general quantitative description of the AIDS infection dynamics in Brazil since the beginning.
+They also provide clues about the effectiveness of treatment and control programs against the infection, that has had a different impact depending on the number of inhabitants of cities.
+In this framework, our results give insights into the overall dynamics of AIDS epidemic, which may contribute to select empirically accurate models.
+They not only specialize in the production of ribosomal subunits but also play roles in many fundamental cellular activities.
+Concerning ribosome biosynthesis, particular stages of this process, i.e., ribosomal DNA transcription, primary RNA transcript processing, and ribosome assembly proceed in precisely defined nucleolar subdomains.
+Although eukaryotic nucleoli are conservative in respect of their main function, clear morphological differences between these structures can be noticed between individual kingdoms.
+In most cases, a plant nucleolus shows well-ordered structure in which four main ultrastructural components can be distinguished: fibrillar centers, dense fibrillar component, granular component, and nucleolar vacuoles.
+Nucleolonema, although it is not always an unequivocally distinguished nucleolar domain, has often been described as a well-grounded morphological element, especially of plant nucleoli.
+The ratios and morphology of particular subcompartments of a nucleolus can change depending on its metabolic activity which in turn is correlated with the physiological state of a cell, cell type, cell cycle phase, as well as with environmental influence.
+Precise attribution of functions to particular nucleolar subregions in the process of ribosome biosynthesis is now possible using various approaches.
+The presented description of plant nucleolar morphology summarizes previous knowledge regarding the function of nucleoli as well as of their particular subdomains not only in the course of ribosome biosynthesis.
+BACKGROUND: Live poultry traders (LPTs) have greater risk to avian influenza due to occupational exposure to poultry.
+METHODS: Using multi-stage cluster sampling, 306 LPTs were interviewed in Guangzhou by a standardized questionnaire between mid-May to June, 2013.
+Hierarchical logistic regression models were used to identify factors associated with preventive practices and attitudes towards various control measures implemented in live poultry markets against H7N9.
+RESULTS: Only 46.1% of the respondents recognized risks associated with contacts with bird secretions or droppings, and only 22.9% perceived personally "likely/very likely" to contract H7N9 infection.
+Around 60% of the respondents complied with hand-washing and wearing gloves, and only 20% reported wearing face masks.
+Being younger, involving in slaughtering poultry, having longer working hours, less access to H7N9-related information and poorer knowledge, and perceiving lower personal susceptibility to H7N9 infection were negatively associated with preventive practices.
+Comparing with previous studies conducted when human cases of H5N1 avian influenza infection was first identified in Guangdong, LPTs' perceived susceptibility to novel influenza viruses increased significantly but acceptance for central slaughtering of poultry remained low.
+CONCLUSIONS: Information on avian influenza provided through multiple communication tools may be necessary to promote knowledge among poultry traders.
+Familiarity with risk may have led to the lower perceived vulnerability to avian influenza and less protective actions among the LPTs particularly for those involving more risky exposure to live poultry.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-014-0554-8) contains supplementary material, which is available to authorized users.
+Frequently, patients with hepatitis C virus (HCV) chronic infection have high levels of serum anti-thyroperoxidase and/or anti-thyroglobulin autoantibodies, ultrasonographic signs of chronic autoimmune thyroiditis, and subclinical hypothyroidism, in female gender versus healthy controls, or hepatitis B virus infected patients.
+In patients with “HCV-associated mixed cryoglobulinemia” (MC + HCV), a higher prevalence of thyroid autoimmune disorders was shown not only compared to controls, but also versus HCV patients without cryoglobulinemia.
+Patients with MC + HCV or HCV chronic infection show a higher prevalence of papillary thyroid cancer than controls, in particular in patients with autoimmune thyroiditis.
+Patients with HCV chronic infection, or with MC + HCV, in presence of autoimmune thyroiditis, show higher serum levels of T-helper (Th)1 (C-X-C motif) ligand 10 (CXCL10) chemokine, but normal levels of Th2 (C-C motif) ligand 2 chemokine, than patients without thyroiditis.
+HCV thyroid infection could act by upregulating CXCL10 gene expression and secretion in thyrocytes recruiting Th1 lymphocytes that secrete interferon-γ and tumor necrosis factor-α.
+These cytokines might induce a further CXCL10 secretion by thyrocytes, thus perpetuating the immune cascade, which may lead to the appearance of autoimmune thyroid disorders in genetically predisposed subjects.
+A careful monitoring of thyroid function, particularly where nodules occur, is recommended in HCV patients.
+Innate immunity is key to the fight against the daily onslaught from viruses that our bodies are subjected to.
+Essential to this response are the interferons (IFNs) that prime our cells to block viral pathogens.
+Recent evidence suggests that the Type III (λ) IFNs are intimately associated with the immune response to hepatitis C virus (HCV) infection.
+Genome-wide association studies have identified polymorphisms within the IFN-λ gene locus that correlate with response to IFNα-based antiviral therapy and with spontaneous clearance of HCV infection.
+Restricted expression of the IFN-λ receptor, and the ability of IFN-λ to induce IFN-stimulated genes in HCV-infected cells, suggest potential roles for IFN-λ in HCV therapy even in this era of directly acting antivirals.
+This review summarizes our current understanding of the IFN-λ family and the role of λ IFNs in the natural history of HCV infection.
+The rodent arenavirus glycoprotein complex encodes a stable signal peptide (SSP) that is an essential structural component of mature virions.
+The SSP, GP1, and GP2 subunits of the trimeric glycoprotein complex noncovalently interact to stud the surface of virions and initiate arenavirus infectivity.
+Nascent glycoprotein production undergoes two proteolytic cleavage events: first within the endoplasmic reticulum (ER) to cleave SSP from the remaining precursor GP1/2 (glycoprotein complex [GPC]) glycoprotein and second within the Golgi stacks by the cellular SKI-1/S1P for GP1/2 processing to yield GP1 and GP2 subunits.
+Here, we defined functions of the 58-amino-acid lymphocytic choriomeningitis virus (LCMV) SSP in regard to glycoprotein complex processing and maturation.
+Using molecular biology techniques, confocal microscopy, and flow cytometry, we detected SSP at the plasma membrane of transfected cells.
+Further, we identified a sorting signal (FLLL) near the carboxyl terminus of SSP that is required for glycoprotein maturation and trafficking.
+In the absence of SSP, the glycoprotein accumulated within the ER and was unable to undergo processing by SKI-1/S1P.
+Mutation of this highly conserved FLLL motif showed impaired glycoprotein processing and secretory pathway trafficking, as well as defective surface expression and pH-dependent membrane fusion.
+Immunoprecipitation of SSP confirmed an interaction between the signal peptide and the GP2 subunit; however, mutations within this FLLL motif disrupted the association of the GP1 subunit with the remaining glycoprotein complex.
+Cat impoundments were increasing at the municipal San Jose animal shelter in 2009, despite long-term successful low cost sterilization programs and attempts to lower the euthanasia rate of treatable-rehabilitatable impounds beginning in 2008.
+San Jose Animal Care and Services implemented a new strategy designed to control overall feral cat reproduction by altering and returning feral cats entering the shelter system, rather than euthanizing the cats.
+The purpose of this case study was to determine how the program affected the shelter cat intakes over time.
+In just over four years, 10,080 individual healthy adult feral cats, out of 11,423 impounded at the shelter during this time frame, were altered and returned to their site of capture.
+Included in the 11,423 cats were 862 cats impounded from one to four additional times for a total of 958 (9.5%) recaptures of the previously altered 10,080 cats.
+The remaining 385 healthy feral cats were euthanized at the shelter from March 2010 to June 2014.
+Four years into the program, researchers observed cat and kitten impounds decreased 29.1%; euthanasia decreased from over 70% of intakes in 2009, to 23% in 2014.
+Euthanasia in the shelter for Upper Respiratory Disease decreased 99%; dead cat pick up off the streets declined 20%.
+BACKGROUND: Extensive variations in human surfactant protein D (SP-D) levels in circulation as measured by ELISA exist in the published literature.
+In order to determine the source of these variations, factors influencing the measurement by ELISA were explored.
+MATERIALS AND METHODS: Peripheral blood from healthy individuals was collected into various vacutainers during the same blood draw.
+The type of anticoagulant used and dilution factor had very little effect, except for in plasma collected in EDTA vacutainers.
+The extent of variation in published values seemed to be due to the ELISA configuration employed, and, in agreement with this, we found that by switching the detection antibody, there was a 50% decrease in the extrapolated SP-D value of serum and plasma samples.
+CONCLUSIONS: The ELISA configuration employed to measure circulating levels of SP-D has a significant effect on the extrapolated values.
+In both configurations tested, the use of EDTA as a coagulant resulted in inconsistent values, and we, therefore, suggest the avoidance of this anticoagulant when assaying for SP-D by ELISA.
+While the demonstrated effects of several factors on measurement of SP-D may not account for all the disparities amongst the previous studies, they stress that variations in methodologies for measuring the same protein can result in very inconsistent results.
+Ovine rinderpest or goat plague is an economically important and contagious viral disease of sheep and goats, caused by the Peste des petits ruminants virus (PPRV).
+The host innate immune system discriminates between pathogen associated molecular patterns and self antigens through surveillance receptors known as Toll like receptors (TLR).
+We investigated the role of TLR and cytokines in differential susceptibility of goat breeds and water buffalo to PPRV.
+We examined the replication of PPRV in peripheral blood mononuclear cells (PBMC) of Indian domestic goats and water buffalo and demonstrated that the levels of TLR3 and TLR7 and downstream signalling molecules correlation with susceptibility vs resistance.
+Naturally susceptible goat breeds, Barbari and Tellichery, had dampened innate immune responses to PPRV and increased viral loads with lower basal expression levels of TLR 3/7.
+Upon stimulation of PBMC with synthetic TLR3 and TLR7 agonists or PPRV, the levels of proinflammatory cytokines were found to be significantly higher while immunosuppressive interleukin (IL) 10 levels were lower in PPRV resistant Kanni and Salem Black breeds and water buffalo at transcriptional level, correlating with reduced viralloads in infected PBMC.
+Water buffalo produced higher levels of interferon (IFN) α in comparison with goats at transcriptional and translational levels.
+Pre-treatment of Vero cells with human IFNα resulted in reduction of PPRV replication, confirming the role of IFNα in limiting PPRV replication.
+Treatment with IRS66, a TLR7 antagonist, resulted in the reduction of IFNα levels, with increased PPRV replication confirming the role of TLR7.
+Single nucleotide polymorphism analysis of TLR7 of these goat breeds did not show any marked nucleotide differences that might account for susceptibility vs resistance to PPRV.
+Analyzing other host genetic factors might provide further insights on susceptibility to PPRV and genetic polymorphisms in the host.
+In the recent years, it has been demonstrated that the biological activity of mesenchymal stem cells (MSCs) is mediated through the release of paracrine factors.
+Many of these factors are released into exosomes, which are small membranous vesicles that participate in cell–cell communication.
+Exosomes from MSCs are thought to have similar functions to MSCs such as repairing and regeneration of damaged tissue, but little is known about the immunomodulatory effect of these vesicles.
+Based on an extensive bibliography where the immunomodulatory capacity of MSCs has been demonstrated, here we hypothesized that released exosomes from MSCs may have an immunomodulatory role on the differentiation, activation and function of different lymphocyte subsets.
+According to this hypothesis, in vitro experiments were performed to characterize the immunomodulatory effect of human adipose MSCs derived exosomes (exo-hASCs) on in vitro stimulated T cells.
+The phenotypic characterization of cytotoxic and helper T cells (activation and differentiation markers) together with functional assays (proliferation and IFN-γ production) demonstrated that exo-hASCs exerted an inhibitory effect in the differentiation and activation of T cells as well as a reduced T cell proliferation and IFN-γ release on in vitro stimulated cells.
+In summary, here we demonstrate that MSCs-derived exosomes are a cell-derived product that could be considered as a therapeutic agent for the treatment of inflammation-related diseases.
+The 2005 International Health Regulations (IHR) came into force for all Member States of the World Health Organization (WHO) in June 2007 and the deadline for achieving compliance was June 2012.
+The purpose of the IHR is to prevent, protect against, control – and provide a public health response to – international spread of disease.
+The territory of the United Kingdom of Great Britain and Northern Ireland and that of several other Member States, such as China, Denmark, France, the Netherlands and the United States of America, include overseas territories, which cover a total population of approximately 15 million people.
+Member States have a responsibility to ensure that all parts of their territory comply with the IHR.
+Since WHO has not provided specific guidance on compliance in the special circumstances of the overseas territories of Member States, compliance by these territories is an issue for self-assessment by Member States themselves.
+To date, no reports have been published on the assessment of IHR compliance in countries with overseas territories.
+We describe a gap analysis done in the United Kingdom to assess IHR compliance of its overseas territories.
+The findings and conclusions are broadly applicable to other countries with overseas territories which may have yet to assess their compliance with the IHR.
+Such assessments are needed to ensure compliance across all parts of a Member States’ territory and to increase global health security.
+There is an emerging paradigm that the human microbiome is central to many aspects of health and may have a role in preventing enteric infection.
+Therefore, as the microbiota is highly variable within individuals, we sought to determine if a component of the microbiota could regulate susceptibility to infection.
+In studies utilizing a murine model, we demonstrated that colonization of the gut with the commensal Clostridia-related bacteria known as segmented filamentous bacteria (SFB) is protective during E. histolytica infection.
+SFB colonization in this model was associated with elevated cecal levels of interleukin 17A (IL-17A), dendritic cells, and neutrophils.
+Bone marrow-derived dendritic cells (BMDCs) from SFB-colonized mice had higher levels of IL-23 production in response to stimulation with trophozoites.
+Adoptive transfer of BMDCs from an SFB(+) to an SFB(−) mouse was sufficient to provide protection against E. histolytica.
+This work demonstrates that intestinal colonization with a specific commensal bacterium can provide protection during amebiasis in a murine model.
+Most importantly, this work demonstrates that the microbiome can mediate protection against an enteric infection via extraintestinal effects on bone marrow-derived dendritic cells.
+BACKGROUND: Respiratory syncytial virus (RSV) infection is the second most important cause of death in the first year of life, and early RSV infections are associated with the development of asthma.
+OBJECTIVE: To investigate whether IgG purified from bovine milk (bIgG) can modulate immune responses against human RSV.
+bIgG or hRSV was coated to plates to assess dose-dependent binding of bIgG to human Fcγ receptors (FcγR) or bIgG-mediated binding of myeloid cells to hRSV respectively.
+S. Epidermidis and RSV were used to test bIgG-mediated binding and internalisation of pathogens by myeloid cells.
+Finally, the ability of bIgG to neutralise infection of HEp2 cells by hRSV was evaluated.
+bIgG bound to FcγRII on neutrophils, monocytes and macrophages, but not to FcγRI and FcγRIII, and could bind simultaneously to hRSV and human FcγRII on neutrophils.
+CONCLUSIONS: The data presented here show that bIgG binds to hRSV and other human respiratory pathogens and induces effector functions through binding to human FcγRII on phagocytes.
+Transcription of hepatitis B virus (HBV) from the covalently closed circular DNA (cccDNA) template is essential for its replication.
+Although cellular transcription factors, such as CREB, which mediate HBV transcription, have been well described, transcriptional coactivators that facilitate this process are incompletely understood.
+In this study we showed that CREB-regulated transcriptional coactivator 1 (CRTC1) is required for HBV transcription and replication.
+The steady-state levels of CRTC1 protein were elevated in HBV-positive hepatoma cells and liver tissues.
+Ectopic expression of CRTC1 or its homolog CRTC2 or CRTC3 in hepatoma cells stimulated the activity of the preS2/S promoter of HBV, whereas overexpression of a dominant inactive form of CRTC1 inhibited HBV transcription.
+CRTC1 interacts with CREB and they are mutually required for the recruitment to the preS2/S promoter on cccDNA and for the activation of HBV transcription.
+Accumulation of pregenomic RNA (pgRNA) and cccDNA was observed when CRTC1 or its homologs were overexpressed, whereas the levels of pgRNA, cccDNA and secreted HBsAg were diminished when CRTC1 was compromised.
+In addition, HBV transactivator protein HBx stabilized CRTC1 and promoted its activity on HBV transcription.
+Our work reveals an essential role of CRTC1 coactivator in facilitating and supporting HBV transcription and replication.
+Its RNA-binding cap comprises the eukaryotic orthologs Rrp4 and Csl4, and an archaea-specific subunit annotated as DnaG.
+Archaeal DnaG contains N- and C-terminal domains (NTD and CTD) of unknown function flanking a TOPRIM domain.
+We found that the NT and TOPRIM domains have comparable, high conservation in all archaea, while the CTD conservation correlates with the presence of exosome.
+We show that the NTD is a novel RNA-binding domain with poly(rA)-preference cooperating with the TOPRIM domain in binding of RNA.
+Consistently, a fusion protein containing full-length Csl4 and NTD of DnaG led to enhanced degradation of A-rich RNA by the exosome.
+We also found that DnaG strongly binds native and in vitro transcribed rRNA and enables its polynucleotidylation by the exosome.
+Furthermore, rRNA-derived transcripts with heteropolymeric tails were degraded faster by the exosome than their non-tailed variants.
+Based on our data, we propose that archaeal DnaG is an RNA-binding protein, which, in the context of the exosome, is involved in targeting of stable RNA for degradation.
+Identification of the full complement of genes and other functional elements in any virus is crucial to fully understand its molecular biology and guide the development of effective control strategies.
+RNA viruses have compact multifunctional genomes that frequently contain overlapping genes and non-coding functional elements embedded within protein-coding sequences.
+Overlapping features often escape detection because it can be difficult to disentangle the multiple roles of the constituent nucleotides via mutational analyses, while high-throughput experimental techniques are often unable to distinguish functional elements from incidental features.
+However, RNA viruses evolve very rapidly so that, even within a single species, substitutions rapidly accumulate at neutral or near-neutral sites providing great potential for comparative genomics to distinguish the signature of purifying selection.
+Here we analyze alignments of protein-coding virus sequences to identify regions where there is a statistically significant reduction in the degree of variability at synonymous sites, a characteristic signature of overlapping functional elements.
+Having previously tested this technique by experimental verification of discoveries in selected viruses, we now analyze sequence alignments for ∼700 RNA virus species to identify hundreds of such regions, many of which have not been previously described.
+Recently bats have been associated with the emergence of diseases, both as reservoirs for several new viral diseases in humans and other animals and, in the northern Americas, as hosts for a devastating fungal disease that threatens to drive several bat species to regional extinction.
+However, despite these catastrophic events little Information is available on bat defences or how they interact with their pathogens.
+Even less is known about the response of bats to infection during torpor or long-term hibernation.
+Using tissue samples collected at the termination of an experiment to explore the pathogenesis of White Nose Syndrome in Little Brown Bats, we determined if hibernating bats infected with the fungus Pseudogymnoascus destructans could respond to infection by activating genes responsible for innate immune and stress responses.
+Lesions due to fungal infection and, in some cases, secondary bacterial infections, were restricted to the skin.
+We therefore examined lungs for response at an epithelial surface not linked to the primary site of infection.
+We found that bats responded to infection with a significant increase in lungs of transcripts for Cathelicidin (an anti-microbial peptide) as well as the immune modulators tumor necrosis factor alpha and interleukins 10 and 23.
+In conclusion, hibernating bats can respond to experimental P. destructans infection by activating expression of innate immune response genes.
+INTRODUCTION: Inherited variability in host immune responses influences susceptibility and outcome of Influenza A virus (IAV) infection, but these factors remain largely unknown.
+Components of the innate immune response may be crucial in the first days of the infection.
+The collectins surfactant protein (SP)-A1, -A2, and -D and mannose-binding lectin (MBL) neutralize IAV infectivity, although only SP-A2 can establish an efficient neutralization of poorly glycosylated pandemic IAV strains.
+METHODS: We studied the role of polymorphic variants at the genes of MBL (MBL2), SP-A1 (SFTPA1), SP-A2 (SFTPA2), and SP-D (SFTPD) in 93 patients with H1N1 pandemic 2009 (H1N1pdm) infection.
+RESULTS: Multivariate analysis showed that two frequent SFTPA2 missense alleles (rs1965708-C and rs1059046-A) and the SFTPA2 haplotype 1A(0) were associated with a need for mechanical ventilation, acute respiratory failure, and acute respiratory distress syndrome.
+Kaplan-Meier analysis and Cox regression also showed that diplotypes not containing the 1A(1) haplotype were associated with a significantly shorter time to ICU admission in hospitalized patients.
+In addition, rs1965708-C (P = 0.0007), rs1059046-A (P = 0.0007), and haplotype 1A(0) (P = 0.0004) were associated, in a dose-dependent fashion, with lower PaO(2)/FiO(2) ratio, whereas haplotype 1A(1) was associated with a higher PaO(2)/FiO(2) ratio (P = 0.001).
+CONCLUSIONS: Our data suggest an effect of genetic variants of SFTPA2 on the severity of H1N1pdm infection and could pave the way for a potential treatment with haplotype-specific (1A(1)) SP-A2 for future IAV pandemics.
+The central nervous system (CNS), once viewed as an immune-privileged site protected by the blood–brain barrier (BBB), is now known to be a dynamic immunological environment through which immune cells migrate to prevent and respond to events such as localized infection.
+During these responses, endogenous glial cells, including astrocytes and microglia, become highly reactive and may secrete inflammatory mediators that regulate BBB permeability and recruit additional circulating immune cells.
+Here, we discuss the various roles played by astrocytes, microglia, and infiltrating immune cells during host immunity to non-tumor antigens in the CNS, focusing first on bacterial and viral infections, and then turning to responses directed against self-antigens in the setting of CNS autoimmunity.
+BACKGROUND: In many applications, a family of nucleotide or protein sequences classified into several subfamilies has to be modeled.
+Profile Hidden Markov Models (pHMMs) are widely used for this task, modeling each subfamily separately by one pHMM.
+However, a major drawback of this approach is the difficulty of dealing with subfamilies composed of very few sequences.
+One of the most crucial bioinformatical tasks affected by the problem of small-size subfamilies is the subtyping of human immunodeficiency virus type 1 (HIV-1) sequences, i.e., HIV-1 subtypes for which only a small number of sequences is known.
+RESULTS: To deal with small samples for particular subfamilies of HIV-1, we introduce a novel model-based information sharing protocol.
+It estimates the emission probabilities of the pHMM modeling a particular subfamily not only based on the nucleotide frequencies of the respective subfamily but also incorporating the nucleotide frequencies of all available subfamilies.
+To this end, the underlying probabilistic model mimics the pattern of commonality and variation between the subtypes with regards to the biological characteristics of HI viruses.
+In order to implement the proposed protocol, we make use of an existing HMM architecture and its associated inference engine.
+CONCLUSIONS: We apply the modified algorithm to classify HIV-1 sequence data in the form of partial HIV-1 sequences and semi-artificial recombinants.
+Thereby, we demonstrate that the performance of pHMMs can be significantly improved by the proposed technique.
+Oct4 is a key component of the pluripotency regulatory network, and its reciprocal interaction with Cdx2 has been shown to be a determinant of either the self-renewal of embryonic stem cells (ESCs) or their differentiation into trophoblast.
+Oct4 of maternal origin is postulated to play critical role in defining totipotency and inducing pluripotency during embryonic development.
+However, the genetic elimination of maternal Oct4 using a Cre-lox approach in mouse revealed that the establishment of totipotency in maternal Oct4–depleted embryos was not affected, and that these embryos could complete full-term development without any obvious defect.
+These results indicate that Oct4 is not essential for the initiation of pluripotency, in contrast to its critical role in maintaining pluripotency.
+This conclusion is further supported by the formation of Oct4-GFP– and Nanog- expressing inner cell masses (ICMs) in embryos with complete inactivation of both maternal and zygotic Oct4 expression and the reprogramming of fibroblasts into fully pluripotent cells by Oct4-deficient oocytes.
+The viral protein U (Vpu) encoded by HIV-1 has been shown to assist in the detachment of virion particles from infected cells.
+Vpu forms cation-specific ion channels in host cells, and has been proposed as a potential drug target.
+An understanding of the mechanism of ion transport through Vpu is desirable, but remains limited because of the unavailability of an experimental structure of the channel.
+Using a structure of the pentameric form of Vpu – modeled and validated based on available experimental data – umbrella sampling molecular dynamics simulations (cumulative simulation time of more than 0.4 µs) were employed to elucidate the energetics and the molecular mechanism of ion transport in Vpu.
+Free energy profiles corresponding to the permeation of Na(+) and K(+) were found to be similar to each other indicating lack of ion selection, consistent with previous experimental studies.
+The Ser23 residue is shown to enhance ion transport via two mechanisms: creating a weak binding site, and increasing the effective hydrophilic length of the channel, both of which have previously been hypothesized in experiments.
+A two-dimensional free energy landscape has been computed to model multiple ion permeation, based on which a mechanism for ion conduction is proposed.
+It is shown that only one ion can pass through the channel at a time.
+This, along with a stretch of hydrophobic residues in the transmembrane domain of Vpu, explains the slow kinetics of ion conduction.
+The results are consistent with previous conductance studies that showed Vpu to be a weakly conducting ion channel.
+Repeat-associated disorders caused by expansions of short sequences have been classified as coding and noncoding and are thought to be caused by protein gain-of-function and RNA gain-of-function mechanisms, respectively.
+The boundary between such classifications has recently been blurred by the discovery of repeat-associated non-AUG (RAN) translation reported in spinocerebellar ataxia type 8, myotonic dystrophy type 1, fragile X tremor/ataxia syndrome and C9ORF72 amyotrophic lateral sclerosis and frontotemporal dementia.
+This noncanonical translation requires no AUG start codon and can initiate in multiple frames of CAG, CGG and GGGGCC repeats of the sense and antisense strands of disease-relevant transcripts.
+RNA structures formed by the repeats have been suggested as possible triggers; however, the precise mechanism of the translation initiation remains elusive.
+Templates containing expansions of microsatellites have also been shown to challenge translation elongation, as frameshifting has been recognized across CAG repeats in spinocerebellar ataxia type 3 and Huntington's disease.
+Determining the critical requirements for RAN translation and frameshifting is essential to decipher the mechanisms that govern these processes.
+In this review, we present current knowledge regarding RAN translation and frameshifting and discuss the proposed mechanisms of translational challenges imposed by simple repeat expansions.
+The thiazolidinedione class peroxisome proliferator-activated receptor gamma (PPARγ) agonists are restricted in clinical use as antidiabetic agents because of side effects such as edema, weight gain, and heart failure.
+The single and selective agonism of PPARγ is the main cause of these side effects.
+Multitargeted PPARα/γ/δ pan agonist development is the hot topic in the antidiabetic drug research field.
+In order to identify PPARα/γ/δ pan agonists, a compound database was established by core hopping of rosiglitazone, which was then docked into a PPARα/γ/δ active site to screen out a number of candidate compounds with a higher docking score and better interaction with the active site.
+Molecular dynamics simulation of the representative Cpd#1 showed more favorable binding conformation for PPARs receptor than the original ligand.
+BACKGROUND: The Syrian hamster (golden hamster, Mesocricetus auratus) is gaining importance as a new experimental animal model for multiple pathogens, including emerging zoonotic diseases such as Ebola.
+Nevertheless there are currently no publicly available transcriptome reference sequences or genome for this species.
+RESULTS: A cDNA library derived from mRNA and snRNA isolated and pooled from the brains, lungs, spleens, kidneys, livers, and hearts of three adult female Syrian hamsters was sequenced.
+This combined contig/singleton dataset, designated as the Syrian hamster transcriptome, represents a total of 60,117,204 nucleotides.
+Our Mesocricetus auratus Syrian hamster transcriptome mapped to 11,648 mouse transcripts representing 9,562 distinct genes, and mapped to a similar number of transcripts and genes in the rat.
+Canonical pathways involved in a broad spectrum of fundamental biological processes were significantly represented in the library.
+The Syrian hamster transcriptome was aligned to the current release of the Chinese hamster ovary (CHO) cell transcriptome and genome to improve the genomic annotation of this species.
+Finally, our Syrian hamster transcriptome was aligned against 14 other rodents, primate and laurasiatheria species to gain insights about the genetic relatedness and placement of this species.
+CONCLUSIONS: This Syrian hamster transcriptome dataset significantly improves our knowledge of the Syrian hamster's transcriptome, especially towards its future use in infectious disease research.
+Moreover, this library is an important resource for the wider scientific community to help improve genome annotation of the Syrian hamster and other closely related species.
+Furthermore, these data provide the basis for development of expression microarrays that can be used in functional genomics studies.
+Marine photosynthetic microorganisms are the basis of marine food webs and are responsible for nearly 50% of the global primary production.
+Emiliania huxleyi forms massive oceanic blooms that are routinely terminated by large double-stranded DNA coccolithoviruses.
+The cellular mechanisms that govern the replication cycle of these giant viruses are largely unknown.
+We used diverse techniques, including fluorescence microscopy, transmission electron microscopy, cryoelectron tomography, immunolabeling and biochemical methodologies to investigate the role of autophagy in host–virus interactions.
+Hallmarks of autophagy are induced during the lytic phase of E. huxleyi viral infection, concomitant with up-regulation of autophagy-related genes (ATG genes).
+Pretreatment of the infected cells with an autophagy inhibitor causes a major reduction in the production of extracellular viral particles, without reducing viral DNA replication within the cell.
+The host-encoded Atg8 protein was detected within purified virions, demonstrating the pivotal role of the autophagy-like process in viral assembly and egress.
+We show that autophagy, which is classically considered as a defense mechanism, is essential for viral propagation and for facilitating a high burst size.
+This cellular mechanism may have a major impact on the fate of the viral-infected blooms, and therefore on the cycling of nutrients within the marine ecosystem.
+Human bocavirus (HBoV) was identified as the second human parvovirus with pathogenic potential in 2005 in respiratory samples from children suffering from viral respiratory infections of unknown etiology.
+Since its first description, a large number of clinical studies have been performed that address the clinical significance of HBoV detection and the molecular biology of the virus.
+This review summarizes the most important steps taken in HBoV research to date and addresses open questions that need to be answered in the future to provide a better understanding of the role of a virus that is difficult to grow in cell culture and is suspected to be a pathogen, although it has not yet fulfilled Koch’s postulates.
+The 3′ untranslated region (3′UTR) of human astroviruses (HAstV) consists of two hairpin structures (helix I and II) joined by a linker harboring a conserved PTB/hnRNP1 binding site.
+The identification and characterization of cellular proteins that interact with the 3′UTR of HAstV-8 virus will help to uncover cellular requirements for viral functions.
+To this end, mobility shift assays and UV cross-linking were performed with uninfected and HAstV-8-infected cell extracts and HAstV-8 3′UTR probes.
+Complex CII formation was compromised with cold homologous RNA, and seven proteins of 35, 40, 45, 50, 52, 57/60 and 75 kDa were cross-linked to the 3′UTR.
+Supermobility shift assays indicated that PTB/hnRNP1 is part of this complex, and 3′UTR-crosslinked PTB/hnRNP1 was immunoprecipitated from HAstV-8 infected cell-membrane extracts.
+Also, immunofluorescence analyses revealed that PTB/hnRNP1 is distributed in the nucleus and cytoplasm of uninfected cells, but it is mainly localized perinuclearly in the cytoplasm of HAstV-8 infected cells.
+Furthermore, the minimal 3′UTR sequences recognized by recombinant PTB are those conforming helix I, and an intact PTB/hnRNP1-binding site.
+Finally, small interfering RNA-mediated PTB/hnRNP1 silencing reduced synthesis viral genome and virus yield in CaCo2 cells, suggesting that PTB/hnRNP1 is required for HAstV replication.
+In conclusion, PTB/hnRNP1 binds to the 3′UTR HAstV-8 and is required or participates in viral replication.
+Viruses readily mutate and gain the ability to infect novel hosts, but few data are available regarding the number of possible host range-expanding mutations allowing infection of any given novel host, and the fitness consequences of these mutations on original and novel hosts.
+To gain insight into the process of host range expansion, we isolated and sequenced 69 independent mutants of the dsRNA bacteriophage Φ6 able to infect the novel host, Pseudomonas pseudoalcaligenes.
+In total, we found at least 17 unique suites of mutations among these 69 mutants.
+We assayed fitness for 13 of 17 mutant genotypes on P. pseudoalcaligenes and the standard laboratory host, P. phaseolicola.
+Furthermore, 12 of the 13 assayed mutants showed reduced fitness on P. phaseolicola compared to wildtype Φ6, confirming the prevalence of antagonistic pleiotropy during host range expansion.
+Further experiments revealed that the mechanistic basis of these fitness differences was likely variation in host attachment ability.
+In addition, using computational protein modeling, we show that host-range expanding mutations occurred in hotspots on the surface of the phage's host attachment protein opposite a putative hydrophobic anchoring domain.
+BACKGROUND: In the current information age, the use of data has become essential for decision making in public health at the local, national, and global level.
+Despite a global commitment to the use and sharing of public health data, this can be challenging in reality.
+No systematic framework or global operational guidelines have been created for data sharing in public health.
+Barriers at different levels have limited data sharing but have only been anecdotally discussed or in the context of specific case studies.
+Incomplete systematic evidence on the scope and variety of these barriers has limited opportunities to maximize the value and use of public health data for science and policy.
+METHODS: We conducted a systematic literature review of potential barriers to public health data sharing.
+Documents that described barriers to sharing of routinely collected public health data were eligible for inclusion and reviewed independently by a team of experts.
+RESULTS: Twenty potential barriers were identified and classified in six categories: technical, motivational, economic, political, legal and ethical.
+The first three categories are deeply rooted in well-known challenges of health information systems for which structural solutions have yet to be found; the last three have solutions that lie in an international dialogue aimed at generating consensus on policies and instruments for data sharing.
+CONCLUSIONS: The simultaneous effect of multiple interacting barriers ranging from technical to intangible issues has greatly complicated advances in public health data sharing.
+A systematic framework of barriers to data sharing in public health will be essential to accelerate the use of valuable information for the global good.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2458-14-1144) contains supplementary material, which is available to authorized users.
+BACKGROUND: The extracellular domains of cytokine receptors are released during inflammation, but little is known about the shedding of Toll-like receptors (TLR) and whether they can be used as diagnostic biomarkers.
+METHODS: The release of sTLR2 and sTLR4 was studied in in-vitro stimulations, as well as in-vivo during experimental human endotoxemia (n = 11, 2 ng/kg LPS), and in plasma of 394 patients with infections (infectious mononucleosis, measles, respiratory tract infections, bacterial sepsis and candidemia) or non-infectious inflammation (Crohn’s disease, gout, rheumatoid arthritis, autoinflammatory syndromes and pancreatitis).
+Using C-statistics, the value of sTLR2 and sTLR4 levels for discrimination between infections and non-infectious inflammatory diseases, as well as between viral and bacterial infections was analyzed.
+RESULTS: In-vitro, peripheral blood mononuclear cells released sTLR2 and sTLR4 by exposure to microbial ligands.
+During experimental human endotoxemia, plasma concentrations peaked after 2 hours (sTLR4) and 4 hours (sTLR2).
+sTLR4 did not correlate with cytokines, but sTLR2 correlated positively with TNFα (r(s) = 0.80, P < 0.05), IL-6 (r(s) = 0.65, P < 0.05), and IL-1Ra (r(s) = 0.57, P = 0.06), and negatively with IL-10 (r(s) = -0.58, P = 0.06), respectively.
+sTLR4 had a similar area under the ROC curve [AUC] for differentiating infectious and non-infectious inflammation compared to CRP: 0.72 (95% CI 0.66-0.79) versus 0.74 (95% CI 0.69-0.80) [P = 0.80], while sTLR2 had a lower AUC: 0.60 (95% CI 0.54-0.66) [P = 0.0004].
+CRP differentiated bacterial infections better from viral infections than sTLR2 and sTLR4: AUC 0.94 (95% CI 0.90-0.96) versus 0.58 (95% CI 0.51-0.64) and 0.75 (95% CI 0.70-0.80), respectively [P < 0.0001 for both].
+CONCLUSIONS: sTLRs are released into the circulation, and suggest the possibility to use sTLRs as diagnostic tool in inflammatory conditions.
+BACKGROUND: This systematic literature review aimed to summarize evidence for the added value of drug sales data analysis for the surveillance of infectious diseases.
+METHODS: A search for relevant publications was conducted in Pubmed, Embase, Scopus, Cochrane Library, African Index Medicus and Lilacs databases.
+Retrieved studies were evaluated in terms of objectives, diseases studied, data sources, methodologies and performance for real-time surveillance.
+Most studies compared drug sales data to reference surveillance data using correlation measurements or indicators of outbreak detection performance (sensitivity, specificity, timeliness of the detection).
+Nineteen studies retrospectively compared drug sales data to reference clinical data, and significant correlations were observed in 17 of them.
+Four studies found that over-the-counter drug sales preceded clinical data in terms of incidence increase.
+Five studies developed and evaluated statistical algorithms for selecting drug groups to monitor specific diseases.
+CONCLUSIONS: Drug sales data analyses appear to be a useful tool for surveillance of gastrointestinal and respiratory disease, and OTC drugs have the potential for early outbreak detection.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-014-0604-2) contains supplementary material, which is available to authorized users.
+BACKGROUND: Tuberculosis (TB) during pregnancy may lead to severe consequences affecting both mother and child.
+Prenatal care could be a very good opportunity for TB care, especially for women who have limited access to health services.
+The aim of this review was to gather and evaluate studies on TB care for pregnant women.
+METHODS: We used a combination of the terms “tuberculosis” and “pregnancy”, limited to human, to search for published articles.
+RESULTS: Thirty five studies were selected for review and their data showed that diagnosis was often delayed because TB symptoms during pregnancy were not typical.
+TB prophylaxis and anti-TB therapy appeared to be safe and effective for pregnant women and their babies when suitable follow up and early initiation were present, but the compliance rate to TB prophylaxis is still low due to lack of follow up and referral services.
+TB care practices in the reviewed studies were in line in principle with the WHO International Standards for Tuberculosis Care (ISTC).
+CONCLUSIONS: Integration of TB care within prenatal care would improve TB diagnosis and treatment for pregnant women.
+To improve the quality of TB care, it is necessary to develop national level guidelines based on the ISTC with detailed guidelines for pregnant women.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-014-0617-x) contains supplementary material, which is available to authorized users.
+RATIONALE: The family of natriuretic peptides (NPs), including atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP), and C-type natriuretic peptide (CNP), exert important and diverse actions for cardiovascular and renal homeostasis.
+The autocrine and paracrine functions of the NPs are primarily mediated through the cellular membrane bound guanylyl cyclase-linked receptors GC-A (NPR-A) and GC-B (NPR-B).
+As the ligands and receptors each contain disulfide bonds, a regulatory role for the cell surface protein disulfide isomerase (PDI) was investigated.
+OBJECTIVE: We utilized complementary in vitro and in vivo models to determine the potential role of PDI in regulating the ability of the NPs to generate its second messenger, cyclic guanosine monophosphate.
+METHODS AND RESULTS: Inhibition of PDI attenuated the ability of ANP, BNP and CNP to generate cGMP in human mesangial cells (HMCs), human umbilical vein endothelial cells (HUVECs), and human aortic smooth muscle cells (HASMCs), each of which were shown to express PDI.
+In LLC-PK1 cells, where PDI expression was undetectable by immunoblotting, PDI inhibition had a minimal effect on cGMP generation.
+Surface Plasmon Resonance demonstrated modest and differential binding of the natriuretic peptides with immobilized PDI in a cell free system.
+However, PDI was shown to co-localize on the surface of cells with GC-A and GC-B by co-immunoprecpitation and immunohistochemistry.
+CONCLUSION: These data demonstrate for the first time that cell surface PDI expression and function regulate the capacity of natriuretic peptides to generate cGMP through interaction with their receptors.
+INTRODUCTION: The production of antimicrobial peptides by airway epithelial cells is an important component of the innate immune response to pulmonary infection and inflammation.
+Hepcidin is mostly produced by hepatocytes, but is also expressed by other cells, such as airway epithelial cells.
+We therefore sought to investigate the role of airway epithelial cell-derived hepcidin in sepsis-induced acute lung injury.
+METHODS: Acute lung injury was induced by polymicrobial sepsis via cecal ligation and puncture (CLP) surgery.
+Adenovirus-mediated short hairpin RNA specific for the mouse hepcidin gene hepc1 and control adenovirus were intratracheally injected into mice.
+The levels of hepcidin-related iron export protein ferroportin were measured, and the iron content and function of alveolar macrophages were evaluated.
+The knockdown of airway epithelial cell-derived hepcidin aggravated the polymicrobial sepsis-induced lung injury and pulmonary bacterial infection and increased mortality (53.33% in Ad-shHepc1-treated mice versus 12.5% in Ad-shNeg-treated mice, P <0.05).
+The knockdown of hepcidin in airway epithelial cells also led to reduced ferroportin degradation and a low intracellular iron content in alveolar macrophages.
+Moreover, alveolar macrophages form the airway epithelial cell-derived hepcidin knockdown mice showed impaired phagocytic ability than those from the control mice.
+The severe lung injury in the airway epithelial cell-derived hepcidin knockdown mice is at least partially related to the altered intracellular iron level and function of alveolar macrophages.
+However, few studies have so far reviewed analyses of autopsy findings in patients with AE-IPF.
+METHODS: We retrospectively reviewed 52 consecutive patients with AE-IPF who underwent autopsies at five university hospitals and one municipal hospital between 1999 and 2013.
+The following variables were abstracted from the medical records: demographic and clinical data, autopsy findings and complications during the clinical course until death.
+RESULTS: The median age at autopsy was 71 years (range 47–86 years), and the subjects included 38 (73.1%) males.
+The underling fibrotic lesion was classified as having the usual interstitial pneumonia (UIP) pattern in all cases.
+Furthermore, 41 (78.8%) patients had diffuse alveolar damage (DAD), 15 (28.8%) exhibited pulmonary hemorrhage, nine (17.3%) developed pulmonary thromboembolism and six (11.5%) were diagnosed with lung carcinoma.
+In addition, six (11.5%) patients developed pneumothorax prior to death and 26 (53.1%) developed diabetes that required insulin treatment after the administration of high-dose corticosteroid therapy.
+In addition, 15 (28.8%) patients presented with bronchopneumonia during their clinical course and/or until death, including fungal (seven, 13.5%), cytomegalovirus (six, 11.5%) and bacterial (five, 9.6%) infections.
+CONCLUSIONS: The pathological findings in patients with AE-IPF represent not only DAD, but also a variety of pathological conditions.
+Therefore, making a diagnosis of AE-IPF is often difficult, and the use of cautious diagnostic approaches is required for appropriate treatment.
+INTRODUCTION: Since 2008, severe cases of emerging human adenovirus type 55 (HAdV-55) in immunocompetent adults have been reported sporadically in China.
+The clinical features and outcomes of the most critically ill patients with severe acute respiratory distress syndrome (ARDS) caused by HAdV-55 requiring invasive mechanical ventilation (IMV) and/or extracorporeal membrane oxygenation (ECMO) are lacking.
+METHODS: We conducted a prospective, single-center observational study of pneumonia with ARDS in immunocompetent adults admitted to our respiratory ICU.
+We prospectively collected and analyzed clinical, laboratory, radiological characteristics, sequential tests of viral load in respiratory tract and blood, treatments and outcomes.
+RESULTS: The results for a total of five consecutive patients with severe ARDS with confirmed HAdV-55 infection were included.
+Mean durations from onset to a single-lobe consolidation shown on chest X-rays (CXRs) and, from the first positive CXR to bilateral multilobar lung infiltrates, were 2 days and 4.8 days, respectively.
+The viral load was higher than 1 × 10(8) copies in three patients and was 1 × 10(4) in one patient.
+The mean duration for noninvasive positive pressure ventilation (NPPV) failure and IMV failure were 30.8 hours and 6.2 days, respectively.
+Persistent high fever, dyspnea and rapid progression to respiratory failure within 2 weeks, together with bilateral consolidations and infiltrates, are the most frequent clinical manifestations of HAdV-55-induced severe ARDS.
+The NPPV and IMV failure rates were very high, but ECMO may still be the respiratory support therapy of choice.
+Understanding infection dynamics of respiratory diseases requires the identification and quantification of behavioural, social and environmental factors that permit the transmission of these infections between humans.
+Little empirical information is available about contact patterns within real-world social networks, let alone on differences in these contact networks between populations that differ considerably on a socio-cultural level.
+Here we compared contact network data that were collected in the Netherlands and Thailand using a similar online respondent-driven method.
+By asking participants to recruit contact persons we studied network links relevant for the transmission of respiratory infections.
+We studied correlations between recruiter and recruited contacts to investigate mixing patterns in the observed social network components.
+In both countries, mixing patterns were assortative by demographic variables and random by total numbers of contacts.
+However, in Thailand participants reported overall more contacts which resulted in higher effective contact rates.
+Our findings provide new insights on numbers of contacts and mixing patterns in two different populations.
+These data could be used to improve parameterisation of mathematical models used to design control strategies.
+Although the spread of infections through populations depends on more factors, found similarities suggest that spread may be similar in the Netherlands and Thailand.
+Considering the high morbidity of hepatitis B in China, many epidemiological studies based on classic medical statistical analysis have been started but lack spatial information.
+However, spatial information such as the spatial distribution, autocorrelation and risk factors of the disease is of great help in studying patients with hepatitis B.
+This study examined 2851 cases of hepatitis B that were hospitalized in Shenzhen in 2010 and studied the spatial distribution, risk factors and spatial access to health services using spatial interpolation, Pearson correlation analysis and the improved two-step floating catchment area method.
+The results showed that the spatial distribution of hepatitis B, along with risk factors as well as spatial access to the regional medical resources, was uneven and mainly concentrated in the south and southwest of Shenzhen in 2010.
+In addition, the distribution characteristics of hepatitis B revealed a positive correlation between four types of service establishments and risk factors for the disease.
+The Pearson correlation coefficients are 0.566, 0.515, 0.626, 0.538 corresponding to bath centres, beauty salons, massage parlours and pedicure parlours (p < 0.05).
+Additionally, the allocation of medical resources for hepatitis B is adequate, as most patients could be treated at nearby hospitals.
+BACKGROUND: Clinical differentiation of influenza from dengue and other febrile illnesses (OFI) is difficult, and available rapid diagnostic tests have limited sensitivity.
+METHODS: We conducted a retrospective study to compare clinical and laboratory findings between (i) influenza and dengue and (ii) influenza and OFI.
+RESULTS: Of 849 enrolled patients, the mean time between illness onset and hospital presentation was 1.7, 3.7, and 3 days for influenza, dengue, and OFI, respectively.
+Among pediatric patients (≤18 years) (445 influenza, 24 dengue, and 130 OFI), we identified absence of rashes, no leukopenia, and no marked thrombocytopenia (platelet counts <100 × 10(9) cells/L) as predictors to distinguish influenza from dengue, whereas rhinorrhea, malaise, sore throat, and mild thrombocytopenia (platelet counts 100-149 × 10(9)/L) were predictors that differentiated influenza from OFI.
+Among adults (>18 years) (81 influenza, 124 dengue, and 45 OFI), no leukopenia and no marked thrombocytopenia distinguished influenza from dengue, while rhinorrhea and malaise differentiated influenza from OFI.
+A diagnostic algorithm developed to distinguish influenza from dengue using rash, leukopenia, and marked thrombocytopenia showed >90% sensitivity to identify influenza in pediatric patients.
+CONCLUSIONS: This study identified simple clinical and laboratory parameters that can assist clinicians to distinguish influenza from dengue and OFI.
+These findings may help clinicians diagnose influenza and facilitate appropriate management of affected patients, particularly in resource-poor settings.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-014-0623-z) contains supplementary material, which is available to authorized users.
+BACKGROUND: Infectious disease surveillance is a process the product of which reflects both actual disease trends and public awareness of the disease.
+Decisions made by patients, health care providers, and public health professionals about seeking and providing health care and about reporting cases to health authorities are all influenced by the information environment, which changes constantly.
+Biases are therefore imbedded in surveillance systems; these biases need to be characterized to provide better situational awareness for decision-making purposes.
+Our goal is to develop a statistical framework to characterize influenza surveillance systems, particularly their correlation with the information environment.
+METHODS: We identified Hong Kong influenza surveillance data systems covering healthcare providers, laboratories, daycare centers and residential care homes for the elderly.
+A Bayesian hierarchical statistical model was developed to examine the statistical relationships between the influenza surveillance data and the information environment represented by alerts from HealthMap and web queries from Google.
+Different models were fitted for non-pandemic and pandemic periods and model goodness-of-fit was assessed using common model selection procedures.
+RESULTS: Some surveillance systems — especially ad hoc systems developed in response to the pandemic flu outbreak — are more correlated with the information environment than others.
+General practitioner (percentage of influenza-like-illness related patient visits among all patient visits) and laboratory (percentage of specimen tested positive) seem to proportionally reflect the actual disease trends and are less representative of the information environment.
+Surveillance systems using influenza-specific code for reporting tend to reflect biases of both healthcare seekers and providers.
+CONCLUSIONS: This study shows certain influenza surveillance systems are less correlated with the information environment than others, and therefore, might represent more reliable indicators of disease activity in future outbreaks.
+Although the patterns identified in this study might change in future outbreaks, the potential susceptibility of surveillance data is likely to persist in the future, and should be considered when interpreting surveillance data.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2458-14-850) contains supplementary material, which is available to authorized users.
+Since the tumorigenesis process is not completely understood and it is known that some viruses can induce carcinogenesis, it is highly important to identify novel oncoviruses and extensively study underlying oncogenic mechanisms.
+Here, we investigated a case of diffuse histiocytic sarcoma in a 22 year old slow loris (Nycticebus coucang), using a broad spectrum virus discovery technique.
+A novel parvovirus was discovered and the phylogenetic analysis performed on its fully sequenced genome demonstrated that it represents the first member of a novel genus.
+The possible causative correlation between this virus and the malignancy was further investigated and 20 serum and 61 organ samples from 25 animals (N. coucang and N. pygmaeus) were screened for the novel virus but only samples collected from the originally infected animal were positive.
+The virus was present in all tested organs (intestine, liver, spleen, kidneys, and lungs) and in all banked serum samples collected up to 8 years before death.
+All attempts to identify a latent viral form (integrated or episomal) were unsuccessful and the increase of variation in the viral sequences during the years was consistent with absence of latency.
+Since it is well known that parvoviruses are dependent on cell division to successfully replicate, we hypothesized that the virus could have benefitted from the constantly dividing cancer cells and may not have been the cause of the histiocytic sarcoma.
+It is also possible to conjecture that the virus had a role in delaying the tumor progression and this report might bring new exciting opportunities in recognizing viruses to be used in cancer virotherapy.
+Several studies investigated associations of IFN-γ rs2430561 T/A, IL28B rs12979860 C/T and ERα rs2077647 T/C gene polymorphisms with outcomes of hepatitis B virus (HBV) infection, but the results were controversial.
+Literature was searched in online database and a systematic review was conducted based on the search results.
+A total of 24 studies were included and dichotomous data were presented as odds ratio (OR) with a 95% confidence interval (CI).
+The rs2430561 T allele was associated with reduced persistent HBV infection risk (T vs. A: OR, 0.690; 95% CI, [0.490, 0.971]), while the rs2077647 T allele significantly increased the risk of persistent HBV infection (T vs. C: OR, 1.678; 95% CI, [1.212, 2.323]).
+Rs 2077647 CC might play a role in protecting individuals against HBV persistence (TT vs. CC: OR, 4.109; 95% CI, [2.609, 6.473]).
+Furthermore, carriers of the rs2430561 TT genotype were more likely to clear HBV spontaneously compared with those of the AA genotype (TT vs. AA: OR, 0.555; 95% CI, [0.359, 0.856]).
+However, for rs2077647 TT vs. TC+CC, significantly increased risks were observed in the Asian and hospital-based population, but not in the overall analysis.
+IFN-γ rs2430561 T/A and ERα rs2077647 T/C genetic polymorphisms were associated with outcomes of HBV infection, but no association was found between IL28B rs12979860 C/T and HBV infection.
+A nested PCR assay was used to determine the viral RNA and proviral DNA status of naturally infected cats.
+Selected samples that were FeLV-positive by PCR were subjected to sequencing, phylogenetic analysis, and motifs search.
+Of the 39 samples that were positive for FeLV p27 antigen, 87.2% (34/39) were confirmed positive with nested PCR.
+Malaysian FeLV isolates are found to be highly similar with a homology of 91% to 100%.
+Phylogenetic analysis revealed that Malaysian FeLV isolates divided into two clusters, with a majority (86.2%) sharing similarity with FeLV-K01803 and fewer isolates (13.8%) with FeLV-GM1 strain.
+Different enhancer motifs including NF-GMa, Krox-20/WT1I-del2, BAF1, AP-2, TBP, TFIIF-beta, TRF, and TFIID are found to occur either in single, duplicate, triplicate, or sets of 5 in different positions within the U3-LTR-gag region.
+The present result confirms the occurrence of FeLV viral RNA and provirus DNA in naturally infected cats.
+Malaysian FeLV isolates are highly similar, and a majority of them are closely related to a UK isolate.
+It has been reported that miRNAs are involved in host-virus interaction, but evidence that cellular miRNAs promote virus replication has been limited.
+Here, we found that miR-23a promoted the replication of human herpes simplex virus type 1 (HSV-1) in HeLa cells, as demonstrated by a plaque-formation assay and quantitative real-time PCR.
+Furthermore, interferon regulatory factor 1 (IRF1), an innate antiviral molecule, is targeted by miR-23a to facilitate viral replication.
+Notably, IRF1 contributes to innate antiviral immunity by binding to IRF-response elements to regulate the expression of interferon-stimulated genes (ISGs) and apoptosis, revealing a complex interaction between miR-23a and HSV-1.
+MiR-23a thus contributes to HSV-1 replication through the regulation of the IRF1-mediated antiviral signal pathway, which suggests that miR-23a may represent a promising target for antiviral treatments.
+However, current identification tools are far from being satisfactory for both reliable diagnosis and epidemiological investigations.
+A rapid, simple, and highly efficient molecular based method for identification of agents of black grain eumycetoma is introduced, aiming to improve diagnostic in endemic areas.
+The tests were based on ITS sequences and developed for Falciformispora senegalensis, F. tompkinsii, Madurella fahalii, M. mycetomatis, M. pseudomycetomatis, M. tropicana, Medicopsis romeroi, and Trematosphaeria grisea.
+With the isothermal RCA assay, 62 isolates were successfully identified with 100% specificity and no cross reactivity or false results.
+Despite safe and efficacious vaccines against peste des petits ruminants virus (PPRV), this virus has emerged as the cause of a highly contagious disease with serious economic consequences for small ruminant agriculture across Asia, the Middle East, and Africa.
+We used complete and partial genome sequences of all 4 lineages of the virus to investigate evolutionary and epidemiologic dynamics of PPRV.
+A Bayesian phylogenetic analysis of all PPRV lineages mapped the time to most recent common ancestor and initial divergence of PPRV to a lineage III isolate at the beginning of 20th century.
+A phylogeographic approach estimated the probability for root location of an ancestral PPRV and individual lineages as being Nigeria for PPRV, Senegal for lineage I, Nigeria/Ghana for lineage II, Sudan for lineage III, and India for lineage IV.
+Substitution rates are critical parameters for understanding virus evolution because restrictions in genetic variation can lead to lower adaptability and pathogenicity.
+Generation of energy in mitochondria is subjected to physiological regulation at many levels, and its malfunction may result in mitochondrial diseases.
+Mitochondrial dysfunction is associated with different environmental influences or certain genetic conditions, and can be artificially induced by inhibitors acting at different steps of the mitochondrial electron transport chain (ETC).
+We found that a short-term (5 h) inhibition of ETC complex III with myxothiazol results in the phosphorylation of translation initiation factor eIF2α and upregulation of mRNA for the activating transcription factor 4 (ATF4) and several ATF4-regulated genes.
+The changes are characteristic for the adaptive integrated stress response (ISR), which is known to be triggered by unfolded proteins, nutrient and metabolic deficiency, and mitochondrial dysfunctions.
+However, after a prolonged incubation with myxothiazol (13–17 h), levels of ATF4 mRNA and ATF4-regulated transcripts were found substantially suppressed.
+The suppression was dependent on the p53 response, which is triggered by the impairment of the complex III-dependent de novo biosynthesis of pyrimidines by mitochondrial dihydroorotate dehydrogenase.
+The initial adaptive induction of ATF4/ISR acted to promote viability of cells by attenuating apoptosis.
+In contrast, the induction of p53 upon a sustained inhibition of ETC complex III produced a pro-apoptotic effect, which was additionally stimulated by the p53-mediated abrogation of the pro-survival activities of the ISR.
+Interestingly, a sustained inhibition of ETC complex I by piericidine did not induce the p53 response and stably maintained the pro-survival activation of ATF4/ISR.
+We conclude that a downregulation of mitochondrial ETC generally induces adaptive pro-survival responses, which are specifically abrogated by the suicidal p53 response triggered by the genetic risks of the pyrimidine nucleotide deficiency.
+In order to search for potent steroidal aromatase inhibitors (SAIs) with lower side effects and overcome cellular resistance, comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were performed on a series of SAIs to build 3D QSAR models.
+The reliable and predictive CoMFA and CoMSIA models were obtained with statistical results (CoMFA: q(2) = 0.636, r(2)(ncv) = 0.988, r(2)(pred) = 0.658; CoMSIA: q(2) = 0.843, r(2)(ncv) = 0.989, r(2)(pred) = 0.601).
+This 3D QSAR approach provides significant insights that can be used to develop novel and potent SAIs.
+In addition, Genetic algorithm with linear assignment of hypermolecular alignment of database (GALAHAD) was used to derive 3D pharmacophore models.
+The selected pharmacophore model contains two acceptor atoms and four hydrophobic centers, which was used as a 3D query for virtual screening against NCI2000 database.
+Six hit compounds were obtained and their biological activities were further predicted by the CoMFA and CoMSIA models, which are expected to design potent and novel SAIs.
+BACKGROUND: Plasmodium vivax causes almost half of all malaria cases in Asia and is recognised as a significant cause of morbidity.
+METHODS: To define the epidemiology of mortality attributable to vivax malaria in southern Papua, Indonesia, a retrospective clinical records-based audit was conducted of all deaths in patients with vivax malaria at a tertiary referral hospital.
+RESULTS: Between January 2004 and September 2009, hospital surveillance identified 3,495 inpatients with P. vivax monoinfection and 65 (1.9%) patients who subsequently died.
+Charts for 54 of these 65 patients could be reviewed, 40 (74%) of whom had pure P. vivax infections on cross-checking.
+Using pre-defined conservative criteria, vivax malaria was the primary cause of death in 6 cases, a major contributor in 17 cases and a minor contributor in a further 13 cases.
+Malnutrition, sepsis with respiratory and gastrointestinal manifestations, and chronic diseases were the commonest attributed causes of death for patients in the latter two categories.
+There were an estimated 293,763 cases of pure P. vivax infection in the community during the study period giving an overall minimum case fatality of 0.12 per 1,000 infections.
+CONCLUSIONS: Although uncommonly directly fatal, vivax malaria is an important indirect cause of death in southern Papua in patients with malnutrition, sepsis syndrome and chronic diseases, including HIV infection.
+Acute respiratory distress syndrome (ARDS) is defined as an acute-onset, progressive, hypoxic condition with radiographic bilateral lung infiltration, which develops after several diseases or injuries, and is not derived from hydrostatic pulmonary edema.
+In 2012, in an effort to increase diagnostic specificity, a revised definition of ARDS was published in JAMA.
+Discriminating between ARDS and other similar diseases is critically important; however, only a few biomarkers are currently available for diagnostic purposes.
+Furthermore, predicting the severity, response to therapy, or outcome of the illness is also important for developing treatment strategies for each patient.
+In parallel with progress in understanding the pathophysiology of ARDS, various humoral factors induced by inflammation and molecules derived from activated cells or injured tissues have been shown as potential biomarkers that may be applied in clinical practice.
+In this review, the current understanding of the basic pathophysiology of ARDS and associated candidate biomarkers will be discussed.
+Natural compounds are becoming popular for the treatment of illnesses and health promotion, but the mechanisms of action and safety profiles are often unknown.
+Xyloketal B (XKB) is a novel marine compound isolated from the mangrove fungus Xylaria sp., with potent antioxidative, neuroprotective, and cardioprotective effects.
+This study aimed to investigate the potential molecular targets of XKB using bioinformatic approaches and to examine the effect of XKB on the expression and activity of rat cytochrome P450 3a (Cyp3a) subfamily members using midazolam as a model probe.
+DDI-CPI, a server that can predict drug–drug interactions via the chemical–protein interactome, was employed to predict the targets of XKB, and the Database for Annotation, Visualization and Integrated Discovery (DAVID) was used to analyze the pathways of the predicted targets of XKB.
+The activity and expression of rat hepatic Cyp3a were examined after the rats were treated with XKB at 7 and 14 mg/kg for 8 consecutive days.
+Rat plasma concentrations of midazolam and its metabolite 1′-OH-midazolam were determined using a validated high-performance liquid chromatographic method.
+Bioinformatic analysis showed that there were over 324 functional proteins and 61 related signaling pathways that were potentially regulated by XKB.
+A molecular docking study showed that XKB bound to the active site of human cytochrome P450 3A4 and rat Cyp3a2 homology model via the formation of hydrogen bonds.
+The in vivo study showed that oral administration of XKB at 14 mg/kg to rats for 8 days significantly increased the area under the plasma concentration-time curve (AUC) of midazolam, with a concomitant decrease in the plasma clearance and AUC ratio of 1′-OH-midazolam over midazolam.
+Further, oral administration of 14 mg/kg XKB for 8 days markedly reduced the activity and expression of hepatic Cyp3a in rats.
+Taken together, the results show that XKB could regulate networks of molecular proteins and related signaling pathways and that XKB downregulated hepatic Cyp3a in rats.
+XKB might cause drug interactions through modulation of the activity and expression of Cyp3a members.
+More studies are warranted to confirm the mechanisms of action of XKB and to investigate the underlying mechanism for the regulating effect of XKB on Cyp3a subfamily members.
+BACKGROUND: Sepsis causes neutrophil sequestration in the lung which leads to acute lung injury (ALI).
+Radix Ginseng (RG), a traditional herb used as herbal remedy in eastern Asia for thousands of years, which has been traditionally used in China to improve blood circulation and ameliorate pathological hemostasis.
+This study investigated whether Ginsenoside Rb1, the main components of RG, can attenuate ALI induced by LPS.
+METHODS: In vivo, 30 male Wistar rats were divided into three groups (n = 10 each groups) on the basis of the reagent used, which were subjected to LPS injection with or without Ginsenoside Rb1 (5 mg/kg) treatments to induce ALI model.
+Lung injury was assessed by pulmonary histology, lung wet-weight to dry-weight (W/D) ratio, the number of myeloperoxidase (MPO) positive cells, immunohistochemical analysis of intercellular adhesion molecule-1 (ICAM-1), gene expression of ICAM-1, ultrastructure changes of pulmonary microvasculature, concentration of inflammatory markers and in plasma.
+In vitro, pulmonary microvascular endothelial cells (PMVECs) were stimulated with LPS in the presence and absence of Ginsenoside Rb1 (50 mM), nuclear factor-κB (NF-κB) p65 was measured by immunocytochemistry staining and western blotting.
+RESULTS: Infusion of LPS induced lung injury, in vivo, as demonstrated by pulmonary edema with infiltration of neutrophils and hemorrhage, the increase in lung W/D ratio, the number of MPO positive cells, the level of inflammatory markers such as TNF-α, MCP-1 and IL-8, enhanced expression of ICAM-1 and ICAM-1 gene.
+Moreover, resulted in the changes of intercellular junctions in the endothelial cells of pulmonary microvasculature.
+In vitro, the significant increased release of NF-κB p65 and its subsequent translocation into the nucleus in PMVECs were observed.
+In contrast, Ginsenoside Rb1 treatment significantly ameliorated the LPS-induced lung injury, as judged by the marked improvement in all these indices.
+CONCLUSIONS: These results indicate that Ginsenoside Rb1 attenuated LPS-induced lung injury through an inhibition of the inflammatory signaling pathway, besides the direct inhibitory effect on proinflammatory molecules.
+Within the last decade new technologies have been developed and implemented which employ light, often in the presence of a photosensitizer, to inactivate pathogens that reside in human blood products for the purpose of transfusion.
+These pathogen reduction technologies attempt to find the proper balance between pathogen kill and cell quality.
+Each system utilizes various chemistries that not only impact which pathogens they can inactivate and how, but also how the treatments affect the plasma and cellular proteins and to what degree.
+This paper aims to present the various chemical mechanisms for pathogen reduction in transfusion medicine that are currently practiced or in development.
+The advancement of high throughput omic technologies during the past few years has made it possible to perform many complex assays in a much shorter time than the traditional approaches.
+The rapid accumulation and wide availability of omic data generated by these technologies offer great opportunities to unravel disease mechanisms, but also presents significant challenges to extract knowledge from such massive data and to evaluate the findings.
+To address these challenges, a number of pathway and network based approaches have been introduced.
+This review article evaluates these methods and discusses their application in cancer biomarker discovery using hepatocellular carcinoma (HCC) as an example.
+Cyclic adenosine monophosphate (cAMP) is a crucial intracellular second messenger molecule that converts extracellular molecules to intracellular signal transduction pathways generating cell- and stimulus-specific effects.
+Importantly, specific phosphodiesterase (PDE) subtypes control the amplitude and duration of cAMP-induced physiological processes and are therefore a prominent pharmacological target currently used in a variety of fields.
+Here we tested the extracts from traditional Chinese medicine, Forsythia suspense seeds, which have been used for more than 2000 years to relieve respiratory symptoms.
+Using structural-functional analysis we found its major lignin, Forsynthin, acted as an immunosuppressant by inhibiting PDE4 in inflammatory and immune cell.
+Moreover, several novel, selective small molecule derivatives of Forsythin were tested in vitro and in murine models of viral and bacterial pneumonia, sepsis and cytokine-driven systemic inflammation.
+Thus, pharmacological targeting of PDE4 may be a promising strategy for immune-related disorders characterized by amplified host inflammatory response.
+Collectively, viruses have the greatest genetic diversity on Earth, occupy extremely varied niches and are likely able to infect all living organisms.
+Viral infections are an important issue for human health and cause considerable economic losses when agriculturally important crops or husbandry animals are infected.
+The advent of metagenomics has provided a precious tool to study viruses by sampling them in natural environments and identifying the genomic composition of a sample.
+However, reaching a clear recognition and taxonomic assignment of the identified viruses has been hampered by the computational difficulty of these problems.
+In this perspective paper we examine the trends in current research for the identification of viral sequences in a metagenomic sample, pinpoint the intrinsic computational difficulties for the identification of novel viral sequences within metagenomic samples, and suggest possible avenues to overcome them.
+Our current recognition of the renin-angiotensin system is more convoluted than originally thought due to the discovery of multiple novel enzymes, peptides, and receptors inherent to this interactive biochemical cascade.
+Over the last decade angiotensin converting enzyme 2 (ACE2) has emerged as a key player in the pathophysiology of hypertension and cardiovascular and renal disease due to its pivotal role in metabolizing vasoconstrictive/hypertrophic/proliferative angiotensin II into favorable angiotensin-(1-7).
+This review addresses a considerable advancement in research on the role of tissue ACE2 in development and progression of hypertension and cardiorenal injury.
+We also summarize the results from recent clinical and experimental studies suggesting that serum or urine soluble ACE2 may serve as a novel biomarker or independent risk factor relevant for diagnosis and prognosis of cardiorenal disease.
+The potential for therapeutic application of splice-switching oligonucleotides (SSOs) to modulate pre-mRNA splicing is increasingly evident in a number of diseases.
+However, the primary drawback of this approach is poor cell and in vivo oligonucleotide uptake efficacy.
+Biological activities can be significantly enhanced through the use of synthetically conjugated cationic cell penetrating peptides (CPPs).
+Studies to date have focused on the delivery of a single SSO conjugated to a CPP, but here we describe the conjugation of two phosphorodiamidate morpholino oligonucleotide (PMO) SSOs to a single CPP for simultaneous delivery and pre-mRNA targeting of two separate genes, exon 23 of the Dmd gene and exon 5 of the Acvr2b gene, in a mouse model of Duchenne muscular dystrophy.
+Conjugations of PMOs to a single CPP were carried out through an amide bond in one case and through a triazole linkage (‘click chemistry’) in the other.
+The most active bi-specific CPP–PMOs demonstrated comparable exon skipping levels for both pre-mRNA targets when compared to individual CPP–PMO conjugates both in cell culture and in vivo in the mdx mouse model.
+Thus, two SSOs with different target sequences conjugated to a single CPP are biologically effective and potentially suitable for future therapeutic exploitation.
+The replication enzyme of RNA viruses must preferentially recognize their RNAs in an environment that contains an abundance of cellular RNAs.
+The factors responsible for specific RNA recognition are not well understood, in part because viral RNA synthesis takes place within enzyme complexes associated with modified cellular membrane compartments.
+Recombinant RNA-dependent RNA polymerases (RdRps) from the human norovirus and the murine norovirus (MNV) were found to preferentially recognize RNA segments that contain the promoter and a short template sequence for subgenomic RNA synthesis.
+Both the promoter and template sequence contribute to stable RdRp binding, accurate initiation of the subgenomic RNAs and efficient RNA synthesis.
+Using a method that combines RNA crosslinking and mass spectrometry, residues near the template channel of the MNV RdRp were found to contact the hairpin RNA motif.
+Mutations in the hairpin contact site in the MNV RdRp reduced MNV replication and virus production in cells.
+This work demonstrates that the specific recognition of the norovirus subgenomic promoter is through binding by the viral RdRp.
+BACKGROUND: Zoonotic infections, which transmit from animals to humans, form the majority of new human pathogens.
+Following zoonotic transmission, the pathogen may already have, or may acquire, the ability to transmit from human to human.
+With infections such as Lassa fever (LF), an often fatal, rodent-borne, hemorrhagic fever common in areas of West Africa, rodent-to-rodent, rodent-to-human, human-to-human and even human-to-rodent transmission patterns are possible.
+METHODOLOGY/PRINCIPAL FINDINGS: Here, we make use of an innovative modeling approach to analyze data from published outbreaks and the number of LF hospitalized patients to Kenema Government Hospital in Sierra Leone to estimate the likely contribution of human-to-human transmission.
+The analyses show that almost [Image: see text] of the cases at KGH are secondary cases arising from human-to-human transmission.
+However, we found much of this transmission is associated with a disproportionally large impact of a few individuals (‘super-spreaders’), as we found only [Image: see text] of human cases result in an effective reproduction number (i.e.
+the average number of secondary cases per infectious case) [Image: see text], with a maximum value up to [Image: see text].
+CONCLUSIONS/SIGNIFICANCE: This work explains the discrepancy between the sizes of reported LF outbreaks and a clinical perception that human-to-human transmission is low.
+Future assessment of risks of LF and infection control guidelines should take into account the potentially large impact of super-spreaders in human-to-human transmission.
+Our work highlights several neglected topics in LF research, the occurrence and nature of super-spreading events and aspects of social behavior in transmission and detection.
+BACKGROUND: Cryptococcal meningitis (CM) is a severe AIDS-defining illness with 90-day case mortality as high as 70% in sub-Saharan Africa, despite treatment.
+The mainstays of induction therapy are amphotericin B and flucytosine, but these are often poorly available where the disease burden is highest.
+Adjunctive treatments, such as dexamethasone, have had dramatic effects on mortality in other neurologic infections, but are untested in CM.
+Given the high death rates in patients receiving current optimal treatment, and the lack of new agents on the horizon, adjuvant treatments, which offer the potential to reduce mortality in CM, should be tested.
+The principal research question posed by this study is as follows: does adding dexamethasone to standard antifungal therapy for CM reduce mortality?
+METHOD: A double-blind placebo-controlled trial with parallel arms in which patients are randomised to receive either dexamethasone or placebo, in addition to local standard of care.
+The study recruits patients in both Asia and Africa to ensure the relevance of its results to the populations in which the disease burden is highest.
+The 10-week mortality risk in the control group is expected to be between 30% and 50%, depending on location, and the target hazard ratio of 0.7 corresponds to absolute risk reductions in mortality from 30% to 22%, or from 50% to 38%.
+Assuming an overall 10-week mortality of at least 30% in our study population, recruitment of 824 patients will be sufficient to observe the expected number of deaths.
+Allowing for some loss to follow-up, the total sample size for this study is 880 patients.
+To generate robust evidence across both continents, we aim to recruit roughly similar numbers of patients from each continent.
+Ethical approval has been obtained from Oxford University’s Tropical Research Ethics Committee (OxTREC), and as locally mandated at each site.
+BACKGROUND: Hepatitis B is endemic in the Indigenous communities of the Northern Territory of Australia and significantly contributes to liver-related morbidity and mortality.
+It is recognised that low health literacy levels, different worldviews and English as a second language all contribute to the difficulties health workers often have in explaining biomedical health concepts, relevant to hepatitis B infection, to patients.
+The aim of this research project was to explore the knowledge, perceptions and experiences of remote dwelling Indigenous adults and their health care providers relating to hepatitis B infection with a view to using this as the evidence base to develop a culturally appropriate educational tool.
+METHODS: The impetus for this project came from health clinic staff at a remote community in Arnhem Land in the Northern Territory, in partnership with a visiting specialist liver clinic from the Royal Darwin Hospital.
+Participants were clinic patients with hepatitis B (n = 12), community members (n = 9) and key informants (n = 13); 25 were Indigenous individuals.
+Semi-structured interviews were undertaken to explore: current understanding of hepatitis B, desire for knowledge, and perspectives on how people could acquire the information needed.
+RESULTS: Low levels of biomedical knowledge about Hepatitis B, negative perceptions of Hepatitis B, communication (particularly language) and culture were the major themes that emerged from the data.
+Accurate concepts grounded in Indigenous culture such as “only your blood can tell the story” were present but accompanied by a feeling of disempowerment due to perceived lack of “medical” understanding, and informed partnerships between caregiver and patient.
+Culturally appropriate discussions in a patient’s first language using visual aids were identified as vital to improving communication.
+CONCLUSIONS: Having an educational tool in Indigenous patient’s first language is crucial in developing treatment partnerships for Indigenous patients with hepatitis B.
+Using a culturally appropriate worldview as the foundation for development should help to reduce disempowerment and improve health literacy.
+Glycyrrhiza glabra, commonly known as licorice, is a popular herbal supplement used for the treatment of chronic inflammatory conditions and as sweetener in the food industry.
+This species contains a myriad of phytochemicals including the major saponin glycoside glycyrrhizin (G) of Glycyrrhetinic acid (GA) aglycone.
+In this study, 2D-ROESY NMR technique was successfully applied for distinguishing 18α and 18β glycyrrhetinic acid (GA).
+ROESY spectra acquired from G. glabra, Glycyrrhiza uralensis and Glycyrrhiza inflata crude extracts revealed the presence of G in its β-form.
+Anti-inflammatory activity of four Glycyrrhiza species, G, glabra, G. uralensis, G. inflata, and G. echinata roots was assessed against COX-1 inhibition revealing that phenolics rather than glycyrrhizin are biologically active in this assay.
+G. inflata exhibits a strong cytotoxic effect against PC3 and HT29 cells lines, whereas other species are inactive.
+This study presents an effective NMR method for G isomer assignment in licorice extracts that does not require any preliminary chromatography or any other purification step.
+Live poultry markets are a source of human infection with avian influenza A (H7N9) virus.
+On February 21, 2014, a poultry farmer infected with H7N9 virus was identified in Jilin, China, and H7N9 and H9N2 viruses were isolated from the patient's farm.
+Reassortment between these subtype viruses generated five genotypes, one of which caused the human infection.
+The date of H7N9 virus introduction to the farm is estimated to be between August 21, 2013 (95% confidence interval [CI] June 6, 2013-October 6, 2013) and September 25, 2013 (95% CI May 28, 2013-January 4, 2014), suggesting that the most likely source of virus introduction was the first batch of poultry purchased in August 2013.
+The reassortment event that led to the human virus may have occurred between January 2, 2014 (95% CI November 8, 2013-February 12, 2014) and February 12, 2014 (95% CI January 19, 2014-February 18, 2014).
+Our findings demonstrate that poultry farms could be a source of reassortment between H7N9 virus and H9N2 virus as well as human infection, which emphasizes the importance to public health of active avian influenza surveillance at poultry farms.
+Measuring adverse events is necessary for quality improvement, but current detection methods are inaccurate, untimely and expensive.
+The advent of electronic health records and the development of automated methods for encoding and classifying electronic narrative data, such as natural language processing, offer an opportunity to identify potentially better methods.
+The objective of this study is to determine the accuracy of using automated methods for detecting three highly prevalent adverse events: a) hospital-acquired pneumonia, b) catheter-associated bloodstream infections, and c) in-hospital falls.
+METHODS/DESIGN: This validation study will be conducted at two large Canadian academic health centres: the McGill University Health Centre (MUHC) and The Ottawa Hospital (TOH).
+The study population consists of all medical, surgical and intensive care unit patients admitted to these centres between 2008 and 2014.
+An automated detection algorithm will be developed and validated for each of the three adverse events using electronic data extracted from multiple clinical databases.
+A random sample of MUHC patients will be used to develop the automated detection algorithms (cohort 1, development set).
+The accuracy of these algorithms will be assessed using chart review as the reference standard.
+Then, receiver operating characteristic curves will be used to identify optimal cut points for each of the data sources.
+Multivariate logistic regression and the areas under curve (AUC) will be used to identify the optimal combination of data sources that maximize the accuracy of adverse event detection.
+The most accurate algorithms will then be validated on a second random sample of MUHC patients (cohort 1, validation set), and accuracy will be measured using chart review as the reference standard.
+The most accurate algorithms validated at the MUHC will then be applied to TOH data (cohort 2), and their accuracy will be assessed using a reference standard assessment of the medical chart.
+DISCUSSION: There is a need for more accurate, timely and efficient measures of adverse events in acute care hospitals.
+This is a critical requirement for evaluating the effectiveness of preventive interventions and for tracking progress in patient safety through time.
+Animal production and health (APH) is an important sector in the world economy, representing a large proportion of the budget of all member states in the European Union and in other continents.
+APH is a highly competitive sector with a strong emphasis on innovation and, albeit with country to country variations, on scientific research.
+Proteomics (the study of all proteins present in a given tissue or fluid – i.e.
+Nevertheless, for a variety of reasons and in contrast to disciplines such as plant sciences or human biomedicine, such potential is only now being tapped.
+To counter such limited usage, 6 years ago we created a consortium dedicated to the applications of Proteomics to APH, specifically in the form of a Cooperation in Science and Technology (COST) Action, termed FA1002 – Proteomics in Farm Animals: www.cost-faproteomics.org.
+In 4 years, the consortium quickly enlarged to a total of 31 countries in Europe, as well as Israel, Argentina, Australia and New Zealand.
+First, we aim to provide clear examples on the applications and benefits of the use of proteomics in all aspects related to APH.
+Second, we provide insights and possibilities on the new trends and objectives for APH proteomics applications and technologies for the years to come.
+Finally, we provide an overview and balance of the major activities and accomplishments of the COST Action on Farm Animal Proteomics.
+These include activities such as the organization of seminars, workshops and major scientific conferences, organization of summer schools, financing Short-Term Scientific Missions (STSMs) and the generation of scientific literature.
+Overall, the Action has attained all of the proposed objectives and has made considerable difference by putting proteomics on the global map for animal and veterinary researchers in general and by contributing significantly to reduce the East–West and North–South gaps existing in the European farm animal research.
+Future activities of significance in the field of scientific research, involving members of the action, as well as others, will likely be established in the future.
+Carefully calibrated transmission models have the potential to guide public health officials on the nature and scale of the interventions required to control epidemics.
+In the context of the ongoing Ebola virus disease (EVD) epidemic in Liberia, Drake and colleagues, in this issue of PLOS Biology, employed an elegant modeling approach to capture the distributions of the number of secondary cases that arise in the community and health care settings in the context of changing population behaviors and increasing hospital capacity.
+Their findings underscore the role of increasing the rate of safe burials and the fractions of infectious individuals who seek hospitalization together with hospital capacity to achieve epidemic control.
+However, further modeling efforts of EVD transmission and control in West Africa should utilize the spatial-temporal patterns of spread in the region by incorporating spatial heterogeneity in the transmission process.
+Detailed datasets are urgently needed to characterize temporal changes in population behaviors, contact networks at different spatial scales, population mobility patterns, adherence to infection control measures in hospital settings, and hospitalization and reporting rates.
+BACKGROUND: A total of 453 laboratory-confirmed cases infected with avian influenza A (H7N9) virus (including 175 deaths) have been reported till October 2,2014, of which 30.68% (139/453) of the cases were identified from Zhejiang Province.
+We describe the largest reported cluster of virologically confirmed H7N9 cases, comprised by a fatal Index case and two mild secondary cases.
+Three confirmed cases, their close contacts, and relevant environments samples were tested by real-time reverse transcriptase-polymerase chain reaction (RT-PCR), viral culture, and sequencing.
+RESULTS: The Index case, a 49-year-old farmer with type II diabetes, who lived with his daughter (Case 2, aged 24) and wife (Case 3, aged 43) and his son-in-law (H7N9 negative).
+Onset of illness in Index case occurred in January 13, 2014 and subsequently, he died of multi-organ failure on January 20.
+Case 2 presented with mild symptoms on January 20 following frequent unprotected bed-side care of the Index case between January 14 to 19, and exposed to live bird market on January 17.
+Case 3 became unwell on January 23 after providing bedside care to the Index case on January 17 to 18, and following the contact with Case 2 during January 21 to 22 at the funeral of the Index case.
+The two secondary cases were discharged on February 2 and 5 separately after early treatment with antiviral medication.
+Four virus strains were isolated and genome analyses showed 99.6 ~100% genetic homology, with two amino mutations (V192I in NS and V280A in NP).
+Twenty-five close contacts remained well and were negative for H7N9 infection by RT-PCR and HI assay.
+CONCLUSIONS: In the present study, the Index case was infected from a live bird market while the two secondary cases were infected by the Index case during unprotected exposure.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-014-0698-6) contains supplementary material, which is available to authorized users.
+We are currently faced with a global infectious disease crisis which has been anticipated for decades.
+While many promising biotherapeutics are being tested, the search for a small molecule has yet to deliver an approved drug or therapeutic for the Ebola or similar filoviruses that cause haemorrhagic fever.
+Two recent high throughput screens published in 2013 did however identify several hits that progressed to animal studies that are FDA approved drugs used for other indications.
+The current computational analysis uses these molecules from two different structural classes to construct a common features pharmacophore.
+This ligand-based pharmacophore implicates a possible common target or mechanism that could be further explored.
+A recent structure based design project yielded nine co-crystal structures of pyrrolidinone inhibitors bound to the viral protein 35 (VP35).
+When receptor-ligand pharmacophores based on the analogs of these molecules and the protein structures were constructed, the molecular features partially overlapped with the common features of solely ligand-based pharmacophore models based on FDA approved drugs.
+These previously identified FDA approved drugs with activity against Ebola were therefore docked into this protein.
+We propose that these drugs identified to date as inhibitors of the Ebola virus may be targeting VP35.
+These computational models may provide preliminary insights into the molecular features that are responsible for their activity against Ebola virus in vitro and in vivo and we propose that this hypothesis could be readily tested.
+BACKGROUND: Theory suggests that individual behavioral responses impact the spread of flu-like illnesses, but this has been difficult to empirically characterize.
+Social distancing is an important component of behavioral response, though analyses have been limited by a lack of behavioral data.
+Our objective is to use media data to characterize social distancing behavior in order to empirically inform explanatory and predictive epidemiological models.
+METHODS: We use data on variation in home television viewing as a proxy for variation in time spent in the home and, by extension, contact.
+This behavioral proxy is imperfect but appealing since information on a rich and representative sample is collected using consistent techniques across time and most major cities.
+We study the April-May 2009 outbreak of A/H1N1 in Central Mexico and examine the dynamic behavioral response in aggregate and contrast the observed patterns of various demographic subgroups.
+We develop and calibrate a dynamic behavioral model of disease transmission informed by the proxy data on daily variation in contact rates and compare it to a standard (non-adaptive) model and a fixed effects model that crudely captures behavior.
+RESULTS: We find that after a demonstrable initial behavioral response (consistent with social distancing) at the onset of the outbreak, there was attenuation in the response before the conclusion of the public health intervention.
+We also find that the dynamic behavioral and fixed effects transmission models better account for variation in new confirmed cases, generate more stable estimates of the baseline rate of transmission over time and predict the number of new cases over a short horizon with substantially less error.
+CONCLUSIONS: Results suggest that A/H1N1 had an innate transmission potential greater than previously thought but this was masked by behavioral responses.
+Observed differences in behavioral response across demographic groups indicate a potential benefit from targeting social distancing outreach efforts.
+In the prevaccination era, HBV infections were endemic due to frequent mother to child transmission in large regions of the world.
+Recommended treatment of chronic hepatitis B with interferon-α and/or nucleos(t)ide analogues does not lead to satisfactory results.
+Induction of HBV-specific T cells by therapeutic vaccination or immunomodulation may be an innovative strategy to overcome virus persistence.
+Vaccination with commercially available HBV vaccines in patients with or without therapeutic reduction of viral load did not result in effective immune control of HBV infection, suggesting that combination of antiviral treatment with new formulations of therapeutic vaccines is needed.
+The woodchuck (Marmota monax) and its HBV-like woodchuck hepatitis virus are a useful preclinical animal model for developing new therapeutic approaches in chronic hepadnaviral infections.
+Several innovative approaches combining antiviral treatments using nucleos(t)ide analogues, with prime-boost vaccination using DNA vaccines, new hepadnaviral antigens or recombinant adenoviral vectors were tested in the woodchuck model.
+In addition, we present potential innovations in immunostimulatory strategies by blocking the interaction of the inhibitory programmed death receptor 1 with its ligand in this animal model.
+BACKGROUND: For disease surveillance, manual data collection using paper-based questionnaires can be time consuming and prone to errors.
+We introduced smartphone data collection to replace paper-based data collection for an influenza sentinel surveillance system in four hospitals in Kenya.
+We compared the quality, cost and timeliness of data collection between the smartphone data collection system and the paper-based system.
+METHODS: Since 2006, the Kenya Ministry of Health (MoH) with technical support from the Kenya Medical Research Institute/Centers for Disease Control and Prevention (KEMRI/CDC) conducted hospital-based sentinel surveillance for influenza in Kenya.
+In May 2011, the MOH replaced paper-based collection with an electronic data collection system using Field Adapted Survey Toolkit (FAST) on HTC Touch Pro2 smartphones at four sentinel sites.
+We compared 880 paper-based questionnaires dated Jan 2010-Jun 2011 and 880 smartphone questionnaires dated May 2011-Jun 2012 from the four surveillance sites.
+For each site, we compared the quality, cost and timeliness of each data collection system.
+RESULTS: Incomplete records were more likely seen in data collected using pen-and-paper compared to data collected using smartphones (adjusted incidence rate ratio (aIRR) 7, 95% CI: 4.4-10.3).
+Errors and inconsistent answers were also more likely to be seen in data collected using pen-and-paper compared to data collected using smartphones (aIRR: 25, 95% CI: 12.5-51.8).
+Smartphone data was uploaded into the database in a median time of 7 days while paper-based data took a median of 21 days to be entered (p < 0.01).
+It cost USD 1,501 (9.4%) more to establish the smartphone data collection system ($17,500) than the pen-and-paper system (USD $15,999).
+During two years, however, the smartphone data collection system was $3,801 (7%) less expensive to operate ($50,200) when compared to pen-and-paper system ($54,001).
+CONCLUSIONS: Compared to paper-based data collection, an electronic data collection system produced fewer incomplete data, fewer errors and inconsistent responses and delivered data faster.
+Although start-up costs were higher, the overall costs of establishing and running the electronic data collection system were lower compared to paper-based data collection system.
+Electronic data collection using smartphones has potential to improve timeliness, data integrity and reduce costs.
+In recent years, the within-host viral dynamics of dengue infections have been increasingly characterized, and the relationship between aspects of these dynamics and the manifestation of severe disease has been increasingly probed.
+Despite this progress, there are few mathematical models of within-host dengue dynamics, and the ones that exist focus primarily on the general role of immune cells in the clearance of infected cells, while neglecting other components of the immune response in limiting viraemia.
+Here, by considering a suite of mathematical within-host dengue models of increasing complexity, we aim to isolate the critical components of the innate and the adaptive immune response that suffice in the reproduction of several well-characterized features of primary and secondary dengue infections.
+By building up from a simple target cell limited model, we show that only the innate immune response is needed to recover the characteristic features of a primary symptomatic dengue infection, while a higher rate of viral infectivity (indicative of antibody-dependent enhancement) and infected cell clearance by T cells are further needed to recover the characteristic features of a secondary dengue infection.
+We show that these minimal models can reproduce the increased risk of disease associated with secondary heterologous infections that arises as a result of a cytokine storm, and, further, that they are consistent with virological indicators that predict the onset of severe disease, such as the magnitude of peak viraemia, time to peak viral load, and viral clearance rate.
+Finally, we show that the effectiveness of these virological indicators to predict the onset of severe disease depends on the contribution of T cells in fuelling the cytokine storm.
+Eukaryotic translation is a complex process composed of three main steps: initiation, elongation, and termination.
+During infections by RNA- and DNA-viruses, the eukaryotic translation machinery is used to assure optimal viral protein synthesis.
+Human immunodeficiency virus type I (HIV-1) uses several non-canonical pathways to translate its own proteins, such as leaky scanning, frameshifting, shunt, and cap-independent mechanisms.
+Moreover, HIV-1 modulates the host translation machinery by targeting key translation factors and overcomes different cellular obstacles that affect protein translation.
+In this review, we describe how HIV-1 proteins target several components of the eukaryotic translation machinery, which consequently improves viral translation and replication.
+The accumulation of multidisciplinary knowledge and the investment of massive funding have enabled the development of vaccines against many infectious diseases as well as other diseases including malignant tumors.
+The paradigm of clinical vaccine evaluation and licensure has also been modernized based on scientific improvements and historical experience.
+Continuous efforts are focused on increasing the efficacy and reducing the risks related to vaccine use.
+Thus, physicians and others involved in the clinical development of vaccines should have sufficient understanding of the recent developmental trends in vaccination and the diseases of interest.
+This study investigated the diarrhoea seasonality and its potential drivers as well as potential opportunities for future diarrhoea control and prevention in China.
+Data on weekly infectious diarrhoea cases in 31 provinces of China from 2005 to 2012, and data on demographic and geographic characteristics, as well as climatic factors, were complied.
+A cosinor function combined with a Poisson regression was used to calculate the three seasonal parameters of diarrhoea in different provinces.
+Diarrhoea in children <5 years was more likely to peak in fall-winter seasons, while diarrhoea in persons > = 5 years peaked in summer.
+Latitude was significantly associated with spatial pattern of diarrhoea seasonality, with peak and trough times occurring earlier at high latitudes (northern areas), and later at low latitudes (southern areas).
+The annual amplitudes of diarrhoea in persons > = 5 years increased with latitude (r = 0.62, P<0.001).
+Latitude 27.8° N and 38.65° N were the latitudinal thresholds for diarrhoea seasonality in China.
+We used area under receiver operator characteristic curves (AUC) to quantify our ability to predict therapeutic resistance in individual patients where AUC=1.0 denotes perfect prediction and AUC=0.5 denotes a coin flip, using data from 4,601 patients with newly diagnosed AML given induction therapy with 3+7 or more intense standard regimens in MRC/NCRI, HOVON, SWOG, and MD Anderson Cancer Center studies.
+Age, performance status, white blood cell count, secondary disease, cytogenetic risk, and FLT3-ITD/NPM1 mutation status were each independently associated with failure to achieve complete remission despite no early death (“primary refractoriness”).
+However, the AUC of a bootstrap-corrected multivariable model predicting this outcome was only 0.78, indicating only fair predictive ability.
+Prediction of resistance, defined as primary refractoriness or short relapse-free survival (RFS), was even more difficult.
+Our ability to forecast resistance based on routinely available pre-treatment covariates provides a rationale for continued randomization between standard and new therapies and supports further examination of genetic and post-treatment data to optimize resistance prediction in AML.
+This phase 2/3, randomized, placebo-controlled, observer-blinded study assessed the immunogenicity, reactogenicity, and safety of an inactivated, split-virion H5N1 influenza vaccine (A/Indonesia/5/2005) in children aged 6 months through 17 years.
+Children received 2 influenza vaccine doses 21 days apart, each containing 1.9 µg of hemagglutinin and AS03(B) adjuvant (5.93 mg of α-tocopherol).
+The randomization ratio was 8:3 for vaccine to placebo, with equal allocation between 3 age strata (6–35 months, 3–8 years, and 9–17 years).
+Immunogenicity against the vaccine strain was assessed 21 days after the first and second vaccine doses for all vaccinees, at day 182 for half, and at day 385 for the remaining half.
+Within each age stratum, the lower limit of the 98.3% confidence interval for the day 42 seroprotection rate was ≥70%, thus fulfilling the US and European licensure criteria.
+AS03(B)-adjuvanted H5N1 influenza vaccine was immunogenic and showed an acceptable safety profile in all age groups studied.
+A series of nine substituted 2-hydroxy-N-[1-oxo-1-(phenylamino)alkan-2-yl]benzamides was assessed as prospective bactericidal agents against three clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) and S. aureus ATCC 29213 as the reference and quality control strain.
+The minimum bactericidal concentration was determined by subculturing aliquots from MIC determination onto substance-free agar plates.
+The bactericidal kinetics of compounds 5-chloro-2-hydroxy-N-[(2S)-3-methyl-1-oxo-1-{[4-(trifluoromethyl)phenyl]amino}butan-2-yl]benzamide (1f), N-{(2S)-1-[(4-bromophenyl)amino]-3-methyl-1-oxobutan-2-yl}-4-chloro-2-hydroxybenzamide (1g), and 4-chloro-N-{(2S)-1-[(3,4-dichlorophenyl)amino]-3-methyl-1-oxobutan-2-yl}-2-hydroxybenzamide (1h) was established by time-kill assay with a final concentration of the compound equal to 1x, 2x, and 4x MIC; aliquots were removed at 0, 4, 6, 8, and 24 h time points.
+The most potent bactericidal agent was compound 1f exhibiting remarkable rapid concentration-dependent bactericidal effect even at 2x MIC at 4, 6, and 8 h (with a reduction in bacterial count ranging from 3.08 to 3.75 log(10) CFU/mL) and at 4x MIC at 4, 6, 8, and 24 h (5.30 log(10) CFU/mL reduction in bacterial count) after incubation against MRSA 63718.
+INTRODUCTION: The extracellular signals regulating mammary epithelial cell growth are of relevance to understanding the pathophysiology of mammary epithelia, yet they remain poorly characterized.
+In this study, we applied an unbiased approach to understanding the functional role of signalling molecules in several models of normal physiological growth and translated these results to the biological understanding of breast cancer subtypes.
+METHODS: We developed and utilized a cytogenetically normal clonal line of hTERT immortalized human mammary epithelial cells in a fibroblast-enhanced co-culture assay to conduct a genome-wide small interfering RNA (siRNA) screen for evaluation of the functional effect of silencing each gene.
+In rigorous postscreen validation processes, including quantitative RT-PCR, to ensure on-target silencing, deconvolution of pooled siRNAs and independent confirmation of effects with lentiviral short-hairpin RNA constructs, we identified a subset of genes required for mammary epithelial cell growth.
+Using three-dimensional Matrigel growth and differentiation assays and primary human mammary epithelial cell colony assays, we confirmed that these growth effects were not limited to the 184-hTERT cell line.
+We utilized the METABRIC dataset of 1,998 breast cancer patients to evaluate both the differential expression of these genes across breast cancer subtypes and their prognostic significance.
+RESULTS: We identified 47 genes that are critically important for fibroblast-enhanced mammary epithelial cell growth.
+This group was enriched for several axonal guidance molecules and G protein–coupled receptors, as well as for the endothelin receptor PROCR.
+The majority of genes (43 of 47) identified in two dimensions were also required for three-dimensional growth, with HSD17B2, SNN and PROCR showing greater than tenfold reductions in acinar formation.
+Several genes, including PROCR and the neuronal pathfinding molecules EFNA4 and NTN1, were also required for proper differentiation and polarization in three-dimensional cultures.
+The 47 genes identified showed a significant nonrandom enrichment for differential expression among 10 molecular subtypes of breast cancer sampled from 1,998 patients.
+CONCLUSION: Diverse transmembrane signals are required for mammary epithelial cell growth in two-dimensional and three-dimensional conditions.
+Strikingly, we define novel roles for axonal pathfinding receptors and ligands and the endothelin receptor in both growth and differentiation.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13058-014-0510-y) contains supplementary material, which is available to authorized users.
+METHODS: A multicenter, randomized, blinded phase 1 clinical trial evaluated safety and antibody responses after point-of-use mixing of influenza A/Indonesia/05/2005 (H5N1) vaccine with MF59 adjuvant.
+Field-site pharmacies mixed 3.75, 7.5, or 15 mcg of antigen with or without MF59 adjuvant just prior to intramuscular administration on days 0 and 21 of healthy adults aged 18–49 years.
+After vaccination, titers of hemagglutination inhibition antibody ≥1:40 were achieved in 80% of subjects receiving 3.75 mcg + MF59 vs only 14% receiving 15 mcg without adjuvant (P < .0001).
+Peak hemagglutination inhibition antibody geometric mean titers for vaccine + MF59 were ∼65 regardless of antigen dose, and neutralizing titers were 2- to 3-fold higher.
+CONCLUSIONS: Point-of-use mixing of H5N1 antigen and MF59 adjuvant achieved target antibody titers in a high percentage of subjects and was safe.
+BACKGROUND: The national stockpile for influenza pandemic preparedness includes vaccines against an array of strains and adjuvants that could be utilized to induce immunologic priming as a pandemic wave emerges.
+We assessed the feasibility of a strategy that allows the flexibility of postmanufacture mixture of vaccine and adjuvant at the point of care.
+METHODS: We conducted a randomized, double-blind, multicenter trial among healthy adults aged 18–49 years who received 2 doses of inactivated influenza A/Indonesia/05/2005 (H5N1 clade 2.2.3) virus vaccine containing either 3.75, 7.5, or 15 µg of hemagglutinin (HA) with or without AS03 adjuvant, administered 21 days apart.
+Sera were tested for hemagglutination inhibition (HAI) and microneutralization (MN) antibody levels against the homologous strain and 4 heterologous avian strains.
+RESULTS: Vaccine containing ASO3 adjuvant was associated with significantly more local reactions compared with nonadjuvanted vaccine, but these were short-lived and resolved spontaneously.
+Although the immune response to nonadjuvanted vaccine was poor, 2 doses of AS03-adjuvanted vaccine containing as little as 3.75 µg of HA elicited robust immune responses resulting in seroprotective titers (≥1:40) to the homologous strain in ≥86% of subjects by HAI and in 95% of subjects by MN.
+CONCLUSIONS: AS03 adjuvant formulated with inactivated vaccine at the administration site significantly enhanced the immune responses to H5N1 vaccine and has the potential to markedly improve vaccine responses and accelerate delivery during an influenza pandemic.
+Nelfinavir (NFV) is an HIV-1 aspartyl protease inhibitor that has numerous effects on human cells, which impart attractive antitumor properties.
+NFV has also been shown to have in vitro inhibitory activity against human herpesviruses (HHVs).
+Given the apparent absence of an aspartyl protease encoded by HHVs, we investigated the mechanism of action of NFV herpes simplex virus type 1 (HSV-1) in cultured cells.
+Selection of HSV-1 resistance to NFV was not achieved despite multiple passages under drug pressure.
+Normal numbers of viral particles appeared to be produced in NFV-treated cells by electron microscopy but remain within the cytoplasm more often than controls.
+NFV did not inhibit the activity of the HSV-1 serine protease nor could its antiviral activity be attributed to inhibition of Akt phosphorylation.
+NFV was found to decrease glycosylation of viral glycoproteins B and C and resulted in aberrant subcellular localization, consistent with induction of endoplasmic reticulum stress and the unfolded protein response by NFV.
+These results demonstrate that NFV causes alterations in HSV-1 glycoprotein maturation and egress and likely acts on one or more host cell functions that are important for HHV replication.
+In a previous study from our group PBMC from patients with favourable rs12979860 genotype showed higher levels of IFNAR-1 mRNA.
+Recently, a dinucleotide polymorphism, ss469415590 (TT or ΔG), has been discovered in the region upstream IFNL3 gene, which is in high linkage disequilibrium with rs12979860.
+ss469415590[ΔG] is a frameshift variant that creates a novel gene, designed IFNL4, encoding the interferon-lambda 4 protein (IFNL4).
+The aim of the present study was to extend the analysis of IFNAR-1 mRNA levels to the ss469415590 variants.
+Our results highlight that the difference of IFNAR-1 mRNA levels between favourable and unfavourable genotype combinations, at both rs12979860 and ss469415590 loci, is stronger than that observed for single polymorphisms at each locus.
+These findings suggest may represent the biological basis for the observed association between IFNL3 CC and IFNL4 TT/TT genotypes and favourable outcome of either natural HCV infection (clearance vs chronic evolution) or IFN-based therapy.
+Identification of epitopes which invokes strong humoral responses is an essential issue in the field of immunology.
+Various computational methods that have been developed based on the antigen structures and the mimotopes these years narrow the search for experimental validation.
+Though new methods of the two kinds have been proposed in these years, they cannot maintain a high degree of satisfaction in various circumstances.
+In this paper, we proposed a new conformational B-cell epitope prediction method based on antigen preprocessing and mimotopes analysis.
+The method classifies the antigen surface residues into “epitopes” and “nonepitopes” by six epitope propensity scales, removing the “nonepitopes” and using the preprocessed antigen for epitope prediction based on mimotope sequences.
+The proposed method gives out the mean F score of 0.42 on the testing dataset.
+When compared with other publicly available servers by using the testing dataset, the new method yields better performance.
+RNA-protein complexes are essential in mediating important fundamental cellular processes, such as transport and localization.
+In particular, ncRNA-protein interactions play an important role in post-transcriptional gene regulation like mRNA localization, mRNA stabilization, poly-adenylation, splicing and translation.
+Here, we present the RPI-Pred (RNA-protein interaction predictor), a new support-vector machine-based method, to predict protein-RNA interaction pairs, based on both the sequences and structures.
+The results show that RPI-Pred can correctly predict RNA-protein interaction pairs with ∼94% prediction accuracy when using sequence and experimentally determined protein and RNA structures, and with ∼83% when using sequences and predicted protein and RNA structures.
+Further, our proposed method RPI-Pred was superior to other existing ones by predicting more experimentally validated ncRNA-protein interaction pairs from different organisms.
+Motivated by the improved performance of RPI-Pred, we further applied our method for reliable construction of ncRNA-protein interaction networks.
+Infectious complications, particularly in the respiratory tract of critically ill patients, are related to increased mortality.
+Severe infection is part of a multiple system illness and female patients with severe sepsis have a worse prognosis compared to males.
+Kallistatin is a protective hormokine released during monocyte activation and low levels in the setting of septic shock can predict adverse outcomes.
+Presepsin is another biomarker that was recently evaluated and is elevated in patients with severe sepsis patients at risk of dying.
+The Centers for Disease Control and Prevention has introduced new definitions for identifying patients at risk of ventilator-associated complications (VACs), but several other conditions, such as pulmonary edema and acute respiratory distress syndrome, may cause VACs, and not all patients with VACs may have ventilator-associated pneumonia.
+New studies have suggested strategies to identify patients at risk for resistant pathogen infection and therapies that optimize efficacy, without the overuse of broad-spectrum therapy in patients with healthcare-associated pneumonia.
+Innovative strategies using optimized dosing of antimicrobials, maximizing the pharmacokinetic and pharmacodynamic properties of drugs in critically ill patients, and newer routes of drug delivery are being explored to combat drug-resistant pathogens.
+We summarize the major clinical studies on respiratory infections in critically ill patients published in 2013.
+In recent years, novel circular ssDNA genomes have recently been detected in a variety of fecal and environmental samples using deep sequencing approaches.
+In this study the identification of genomes of novel circoviruses and cycloviruses in feces of insectivorous bats is reported.
+Pan-reactive primers were used targeting the conserved rep region of circoviruses and cycloviruses to screen DNA bat fecal samples.
+Using this approach, partial rep sequences were detected which formed five phylogenetic groups distributed among the Circovirus and the recently proposed Cyclovirus genera of the Circoviridae.
+Further analysis using inverse PCR and Sanger sequencing led to the characterization of four new putative members of the family Circoviridae with genome size ranging from 1,608 to 1,790 nt, two inversely arranged ORFs, and canonical nonamer sequences atop a stem loop.
+Avian influenza A (H5N1) viruses cause severe disease in humans(1,2), but the basis for their virulence remains unclear.
+In vitro and animal studies indicate that high and disseminated viral replication is important for disease pathogenesis(3,4,5).
+To assess the relevance of these findings for human disease, we performed virological and immunological studies in 18 individuals with H5N1 and 8 individuals infected with human influenza virus subtypes.
+Influenza H5N1 infection in humans is characterized by high pharyngeal virus loads and frequent detection of viral RNA in rectum and blood.
+Viral RNA in blood was present only in fatal H5N1 cases and was associated with higher pharyngeal viral loads.
+We observed low peripheral blood T-lymphocyte counts and high chemokine and cytokine levels in H5N1-infected individuals, particularly in those who died, and these correlated with pharyngeal viral loads.
+Genetic characterization of H5N1 viruses revealed mutations in the viral polymerase complex associated with mammalian adaptation and virulence.
+Our observations indicate that high viral load, and the resulting intense inflammatory responses, are central to influenza H5N1 pathogenesis.
+The focus of clinical management should be on preventing this intense cytokine response, by early diagnosis and effective antiviral treatment.
+SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nm1477) contains supplementary material, which is available to authorized users.
+Polydatin and resveratrol, as major active components in Polygonum cuspidatum, have anti-inflammatory, antioxidant and antitumor functions.
+However, the effect and mechanism of polydatin and resveratrol on enterovirus 71 (EV71) have not been reported.
+In this study, resveratrol revealed strong antiviral activity on EV71, while polydatin had weak effect.
+Resveratrol could effectively inhibit the synthesis of EV71/VP1 and the phosphorylation of IKKα, IKKβ, IKKγ, IKBα, NF-κB p50 and NF-κB p65, respectively.
+Meanwhile, the remarkably increased secretion of IL-6 and TNF-α in EV71-infected rhabdosarcoma (RD) cells could be blocked by resveratrol.
+These results demonstrated that resveratrol inhibited EV71 replication and cytokine secretion in EV71-infected RD cells through blocking IKKs/NF-κB signaling pathway.
+This study examined links among unrealistic optimism, sex, and risk perception of type 2 diabetes onset in college students.
+The results showed significant differences between students who perceived that they were at risk for type 2 diabetes onset and those who thought their peers were the ones at risk.
+A higher prevalence of participants thought their peers were the ones at risk for type 2 diabetes.
+Women were more likely than men to report a higher risk perception, indicating that their peers were at lower risk for diabetes onset.
+However, genome size in RNA viruses is likely limited by a high mutation rate, resulting in the evolution of various mechanisms to increase complexity while minimising genome expansion.
+Here we conduct a large-scale analysis of the genome sequences of 99 animal rhabdoviruses, including 45 genomes which we determined de novo, to identify patterns of genome expansion and the evolution of genome complexity.
+All but seven of the rhabdoviruses clustered into 17 well-supported monophyletic groups, of which eight corresponded to established genera, seven were assigned as new genera, and two were taxonomically ambiguous.
+We show that the acquisition and loss of new genes appears to have been a central theme of rhabdovirus evolution, and has been associated with the appearance of alternative, overlapping and consecutive ORFs within the major structural protein genes, and the insertion and loss of additional ORFs in each gene junction in a clade-specific manner.
+Changes in the lengths of gene junctions accounted for as much as 48.5% of the variation in genome size from the smallest to the largest genome, and the frequency with which new ORFs were observed increased in the 3’ to 5’ direction along the genome.
+We also identify several new families of accessory genes encoded in these regions, and show that non-canonical expression strategies involving TURBS-like termination-reinitiation, ribosomal frame-shifts and leaky ribosomal scanning appear to be common.
+We conclude that rhabdoviruses have an unusual capacity for genomic plasticity that may be linked to their discontinuous transcription strategy from the negative-sense single-stranded RNA genome, and propose a model that accounts for the regular occurrence of genome expansion and contraction throughout the evolution of the Rhabdoviridae.
+The recent outbreak of the human Zaire ebolavirus (EBOV) epidemic is spiraling out of control in West Africa.
+The EBOV is classified as a biosafety level 4 pathogen and is considered a category A agent of bioterrorism by Centers for Disease Control and Prevention, with no approved therapies and vaccines available for its treatment apart from supportive care.
+Although several promising therapeutic agents and vaccines against EBOV are undergoing the Phase I human trial, the current epidemic might be outpacing the speed at which drugs and vaccines can be produced.
+Like all viruses, the EBOV largely relies on host cell factors and physiological processes for its entry, replication, and egress.
+We have reviewed currently available therapeutic agents that have been shown to be effective in suppressing the proliferation of the EBOV in cell cultures or animal studies.
+Most of the therapeutic agents in this review are directed against non-mutable targets of the host, which is independent of viral mutation.
+These medications are approved by the Food and Drug Administration (FDA) for the treatment of other diseases.
+They may also have a complementary role to those therapeutic agents under development that are directed against the mutable targets of the EBOV.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/2049-9957-3-43) contains supplementary material, which is available to authorized users.
+To evaluate the effects of storage conditions on total protein (TP) and globulin fractions in fresh frozen bovine plasma units prepared and stored for transfusion, TP and globulin fractions were evaluated in fresh plasma and at 1 month and 6 and 12 months after blood collection in plasma stored at −20°C.
+This study suggests that total gamma globulin concentration in bovine frozen plasma is stable for 12 months at −20°C.
+Total protein, ALB, and beta-2 fraction have significantly different concentrations (g/dL) when compared to prestorage.
+This study has shown IgG protein fraction stability in bovine fresh frozen plasma collected for transfusion; therefore, bovine fresh frozen plasma seems to be suitable for the treatment of hypogammaglobulinemia (failure of passive transfer) in calves when stored for 12 months at −20°C.
+We recently showed that VLPs protect mice from lethal EBOV infection when given before or after viral infection.
+To elucidate pathways through which VLPs confer post-exposure protection, we investigated the role of type I interferon (IFN) signaling.
+We found that VLPs lead to accelerated induction of IFN stimulated genes (ISGs) in liver and spleen of wild type mice, but not in Ifnar(-/-) mice.
+Accordingly, EBOV infected Ifnar(-/-) mice, unlike wild type mice succumbed to death even after VLP treatment.
+The ISGs induced in wild type mice included anti-viral proteins and negative feedback factors known to restrict viral replication and excessive inflammatory responses.
+Importantly, proinflammatory cytokine/chemokine expression was much higher in WT mice without VLPs than mice treated with VLPs.
+In EBOV infected Ifnar(-/-) mice, however, uninhibited viral replication and elevated proinflammatory factor expression ensued, irrespective of VLP treatment, supporting the view that type I IFN signaling helps to limit viral replication and attenuate inflammatory responses.
+Further analyses showed that VLP protection requires the transcription factor, IRF8 known to amplify type I IFN signaling in dendritic cells and macrophages, the probable sites of initial EBOV infection.
+Together, this study indicates that VLPs afford post-exposure protection by promoting expeditious initiation of type I IFN signaling in the host.
+To generate the most diverse phylogenetic dataset for the flaviviruses to date, we determined the genomic sequences and phylogenetic relationships of 14 flaviviruses, of which 10 are primarily associated with Culex spp.
+We analyze these data, in conjunction with a comprehensive collection of flavivirus genomes, to characterize flavivirus evolutionary and biogeographic history in unprecedented detail and breadth.
+Based on the presumed introduction of yellow fever virus into the Americas via the transatlantic slave trade, we extrapolated a timescale for a relevant subset of flaviviruses whose evolutionary history, shows that different Culex-spp.
+associated flaviviruses have been introduced from the Old World to the New World on at least five separate occasions, with 2 different sets of factors likely to have contributed to the dispersal of the different viruses.
+We also discuss the significance of programmed ribosomal frameshifting in a central region of the polyprotein open reading frame in some mosquito-associated flaviviruses.
+Emergence of infectious diseases like influenza pandemic (H1N1) 2009 has become great concern, which posed new challenges to the health authorities worldwide.
+To control these diseases various studies have been developed in the field of mathematical modelling, which is useful tool for understanding the epidemiological dynamics and their dependence on social mixing patterns.
+We have used Bayesian approach to quantify the disease outbreak through key epidemiological parameter basic reproduction number (R (0)), using effective contacts, defined as sum of the product of incidence cases and probability of generation time distribution.
+We have estimated R (0) from daily case incidence data for pandemic influenza A/H1N1 2009 in India, for the initial phase.
+The estimated R (0) with 95% credible interval is consistent with several other studies on the same strain.
+Basic reproduction number R (0) provides the useful information to the public health system to do some effort in controlling the disease by using mitigation strategies like vaccination, quarantine, and so forth.
+B cells are essential for antiviral immune defence because they produce neutralizing antibodies, present antigen and maintain the lymphoid architecture.
+Here we show that intrinsic signalling of CEACAM1 is essential for generating efficient B-cell responses.
+Although CEACAM1 exerts limited influence on the proliferation of B cells, expression of CEACAM1 induces survival of proliferating B cells via the BTK/Syk/NF-κB-axis.
+The absence of this signalling cascade in naive Ceacam1(−/−) mice limits the survival of B cells.
+During systemic infection with cytopathic vesicular stomatitis virus, Ceacam1(−/−) mice can barely induce neutralizing antibody responses and die early after infection.
+We find, therefore, that CEACAM1 is a crucial regulator of B-cell survival, influencing B-cell numbers and protective antiviral antibody responses.
+Recent studies in mouse models have revealed an indispensable role for the innate immune system in defense against influenza virus.
+Recognition of the virus by innate immune receptors in a multitude of cell types activates intricate signaling networks, functioning to restrict viral replication.
+Downstream effector mechanisms include activation of innate immune cells and, induction and regulation of adaptive immunity.
+However, uncontrolled innate responses are associated with exaggerated disease, especially in pandemic influenza virus infection.
+Despite advances in the understanding of innate response to influenza in the mouse model, there is a large knowledge gap in humans, particularly in immunocompromised groups such as infants and the elderly.
+We propose here, the need for further studies in humans to decipher the role of innate immunity to influenza virus, particularly at the site of infection.
+These studies will complement the existing work in mice and facilitate the quest to design improved vaccines and therapeutic strategies against influenza.
+The tick is a well-known vector for arthropod-borne pathogens, such as tick-borne encephalitis, Lyme disease, Japanese spotted fever and severe fever with thrombocytopenia syndrome.
+It is therefore important to know the tick population and distribution in our environment and wild animals in order to prevent tick-borne diseases.
+Here, we report the results of tick surveillance from May to September 2011 at 14 geographical points and in 5 wild boars in Kyoto City, Kyoto prefecture, Japan.
+We collected 3,198 ticks comprising 5 tick species, Haemaphysalis (H.) longicornis, H. flava, H. kitaokai, Amblyomma testudinarium and Dermacentor taiwanensis.
+The ticks collected in the city were reported as potential vectors of pathogens, such as rickettsiosis.
+The sequences of PCR-amplified DNA fragments were determined and showed similarities to spotted fever group rickettsiae.
+Although their pathogenicity for animals including humans is still unclear, it is important to stay alert and pay attention to tick-borne diseases in order to ensure the safety of the citizens of the city as well as that of visitors.
+INTRODUCTION: Corticosteroids are used empirically in influenza A (H1N1) treatment despite lack of clear evidence for effective treatment.
+METHODS: Systematic review and meta-analysis were used to estimate the efficacy of corticosteroids for the prevention of mortality in H1N1 infection.
+Databases searched included MEDLINE, EMBASE, PubMed, Cochrane Central Register of Controlled Clinical Trials and so on, and bibliographies of retrieved articles, from April 2009 to October 2014.
+We included both cohort studies and case-control studies reported in English or Chinese that compared treatment effects between corticosteroids and non-corticosteroids therapy in inpatients with H1N1 virus infection.
+Cohort studies employed mortality as outcome, and case-control studies employed deaths as cases and survivors as controls; both were assessed in this meta-analysis.
+Both cohort studies (nine studies, n = 1,405) and case-control studies (14 studies, n = 4,700) showed a similar trend toward increased mortality (cohort studies relative risk was 1.85 with 95% confidence interval (CI) 1.46 to 2.33; case-control studies odds ratio was 4.22 with 95% CI 3.10 to 5.76).
+The results from both subgroup analyses and sensitive analyses were consistent with each other, showing that steroid treatment is associated with mortality.
+However, considering the fact that corticosteroids were tend to be used in sickest case-patients and heterogeneity was observed between studies, we cannot make a solid conclusion.
+CONCLUSIONS: Available evidence did not support the use of corticosteroids as standard care for patients with severe influenza.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13054-015-0764-5) contains supplementary material, which is available to authorized users.
+They encode an NS6 protease that cleaves a viral polyprotein at specific sites to produce mature viral proteins.
+In an earlier study we obtained crystals of murine norovirus (MNV) NS6 protease in which crystal contacts were mediated by specific insertion of the C-terminus of one protein (which contains residues P5-P1 of the NS6-7 cleavage junction) into the peptide binding site of an adjacent molecule, forming an adventitious protease-product complex.
+We sought to reproduce this crystal form to investigate protease–substrate complexes by extending the C-terminus of NS6 construct to include residues on the C-terminal (P′) side of the cleavage junction.
+We report the crystallization and crystal structure determination of inactive mutants of murine norovirus NS6 protease with C-terminal extensions of one, two and four residues from the N-terminus of the adjacent NS7 protein (NS6 1′, NS6 2′, NS6 4′).
+We also determined the structure of a chimeric extended NS6 protease in which the P4-P4′ sequence of the NS6-7 cleavage site was replaced with the corresponding sequence from the NS2-3 cleavage junction (NS6 4′ 2|3).The constructs NS6 1′ and NS6 2′ yielded crystals that diffracted anisotropically.
+We found that, although the uncorrected data could be phased by molecular replacement, refinement of the structures stalled unless the data were ellipsoidally truncated and corrected with anisotropic B-factors.
+These corrections significantly improved phasing by molecular replacement and subsequent refinement.The refined structures of all four extended NS6 proteases are very similar in structure to the mature MNV NS6—and in one case reveal additional details of a surface loop.
+Although the packing arrangement observed showed some similarities to those observed in the adventitious protease-product crystals reported previously, in no case were specific protease–substrate interactions observed.
+INTRODUCTION: We report a case of an adult patient with human immunodeficiency virus (HIV), acute respiratory distress syndrome (ARDS) and ventilator associated pneumonia (VAP) caused by multidrug resistant (MDR) bacteria that was successfully managed with veno-venous extracorporeal membrane oxygenation (ECMO).
+CASE REPORT: A 25 year old male with no significant past medical history had been admitted to a local hospital due to dyspnea and fever.
+The patient was transported for 300 km by road on ECMO to a tertiary medical center.
+Patient was successfully treated with antiretroviral therapy (ART), anti-infective agents and 58 days of veno-venous ECMO support, with complete resolution of the respiratory symptoms.
+CONCLUSION: HIV infected patients with ARDS and MDR bacterial VAP whose HIV replication is controlled by ART could be successfully managed with ECMO.
+The increased emphasis in MSF on research led to the creation of an ethics review board (ERB) in 2001.
+The ERB has encouraged innovation in the review of proposals and the interaction between the ERB and the organization.
+This has led to some of the advances in ethics governance described in this paper.
+Some of the innovations implemented by the ERB, such as review exemption or approval of generic protocols, may run counter to many standard operating procedures.
+We argue that much standard practice in research ethics review ought to be open to challenge and revision.
+Continued interaction between MSF researchers and independent ERB members has allowed for progressive innovations based on a trustful and respectful partnership between the ERB and the researchers.
+Second, the impact of research needs to be defined more precisely as a first step towards being meaningfully assessed, including changes of impact over time.
+Finally, the dialogue between the MSF ERB and the ethics committees in the study countries should be enhanced.
+SUMMARY: We hope that the innovations in research ethics governance described may be relevant for other organisations carrying out research in fragile contexts and for ethics committees reviewing such research.
+Human Enterovirus 71 (EV71) commonly causes Hand, Foot and Mouth Disease in young children, and occasional occurrences of neurological complications can be fatal.
+In this study, a high-throughput cell-based screening on the serine/threonine kinase siRNA library was performed to identify potential antiviral agents against EV71 replication.
+Among the hits, Misshapen/NIKs-related kinase (MINK) was selected for detailed analysis due to its strong inhibitory profile and novelty.
+In the investigation of the stage at which MINK is involved in EV71 replication, virus RNA transfection in MINK siRNA-treated cells continued to cause virus inhibition despite bypassing the normal entry pathway, suggesting its involvement at the post-entry stage.
+We have also shown that viral RNA and protein expression level was significantly reduced upon MINK silencing, suggesting its involvement in viral protein synthesis which feeds into viral RNA replication process.
+Through proteomic analysis and infection inhibition assay, we found that the activation of MINK was triggered by early replication events, instead of the binding and entry of the virus.
+Proteomic analysis on the activation profile of p38 Mitogen-activated Protein Kinase (MAPK) indicated that the phosphorylation of p38 MAPK was stimulated by EV71 infection upon MINK activation.
+Luciferase reporter assay further revealed that the translation efficiency of the EV71 internal ribosomal entry site (IRES) was reduced after blocking the MINK/p38 MAPK pathway.
+Further investigation on the effect of MINK silencing on heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) localisation demonstrated that cytoplasmic relocalisation of hnRNP A1 upon EV71 infection may be facilitated via the MINK/p38 MAPK pathway which then positively regulates the translation of viral RNA transcripts.
+These novel findings hence suggest that MINK plays a functional role in the IRES-mediated translation of EV71 viral RNA and may provide a potential target for the development of specific antiviral strategies against EV71 infection.
+BACKGROUND: Influenza H7N9 has become an endemic pathogen in China where circulating virus is found extensively in wild birds and domestic poultry.
+Two epidemic waves of Human H7N9 infections have taken place in Eastern and South Central China during the years of 2013 and 2014.
+In this study, we report on the first four human cases of influenza H7N9 in Shantou, Guangdong province, which occurred during the second H7N9 wave, and the subsequent analysis of the viral isolates.
+Later, phylogenetic analyses of influenza H7N9 viruses were performed to establish the evolutionary context of the disease in humans.
+RESULTS: The sequences of the isolates from Shantou have closer evolutionary proximity to the predominant Eastern H7N9 cluster (similar to A/Shanghai/1/2013 (H7N9)) than to the Southern H7N9 cluster (similar to A/Guangdong/1/2013 (H7N9)).
+CONCLUSIONS: Two distinct phylogenetic groups of influenza H7N9 circulate currently in China and cause infections in humans as a consequence of cross-species spillover from the avian disease.
+The Eastern cluster, which includes the four isolates from Shantou, presents a wide geographic distribution and overlaps with the more restricted area of circulation of the Southern cluster.
+Continued monitoring of the avian disease is of critical importance to better understand and predict the epidemiological behaviour of the human cases.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-015-0829-8) contains supplementary material, which is available to authorized users.
+BACKGROUND: Focus on “social determinants of health” provides a welcome alternative to the bio-medical illness paradigm.
+However, the tendency to concentrate on the influence of “risk factors” related to living and working conditions of individuals, rather than to more broadly examine dynamics of the social processes that affect population health, has triggered critical reaction not only from the Global North but especially from voices the Global South where there is a long history of addressing questions of health equity.
+In this article, we elaborate on how focusing instead on the language of “social determination of health” has prompted us to attempt to apply a more equity-sensitive approaches to research and related policy and praxis.
+DISCUSSION: In this debate, we briefly explore the epistemological and historical roots of epidemiological approaches to health and health equity that have emerged in Latin America to consider its relevance to global discourse.
+In this region marked by pronounced inequity, context-sensitive concepts such as “collective health” and “critical epidemiology” have been prominent, albeit with limited acknowledgement by the Global North.
+We illustrate our attempts to apply a social determination approach (and the “4 S” elements of bio-Security, Sovereignty, Solidarity and Sustainability) in five projects within our research collaboration linking researchers and knowledge users in Ecuador and Canada, in diverse settings (health of healthcare workers; food systems; antibiotic resistance; vector borne disease [dengue]; and social circus with street youth).
+CONCLUSIONS: We argue that the language of social determinants lends itself to research that is more reductionist and beckons the development of different skills than would be applied when adopting the language of social determination.
+We conclude that this language leads to more direct analysis of the systemic factors that drive, promote and reinforce disparities, while at the same time directly considering the emancipatory forces capable of countering negative health impacts.
+It follows that “reverse innovation” must not only recognize practical solutions being developed in low and middle income countries, but must also build on the strengths of the theoretical-methodological reasoning that has emerged in the South.
+Acute respiratory tract infections (ARTIs) are associated with significant morbidity and mortality worldwide, especially in children under the age of 5 years.
+Almost 2 million children die from ARTIs each year, and most of them are from developing countries.
+The prevalence and correlation of pathogens in ARTIs are poorly understood, but are critical for improving case prevention, treatment, and management.
+In this study, we investigated the prevalence and correlation of infectious agents in children with ARTIs.
+A total of 39,756 children with one or more symptoms, including fever, cough, sore throat, tonsillitis, pharyngitis, herpangina, pneumonia, and bronchiolitis, were enrolled in the study.
+All patients were hospitalized in Wuhan Children’s Hospital between October 1, 2010 and September 30, 2012, and were evaluated for infectious agents.
+Pathogens, including Mycoplasma pneumoniae, influenza A virus, influenza B virus, adenoviruses, respiratory syncytial virus, parainfluenza virus, Legionella pneumophila, Chlamydophila pneumoniae, and Coxiella burnetii, were screened simultaneously in patient blood samples using anti-pathogen IgM tests.
+Our results showed that one or more pathogens were identified in 10,206 patients, and that Mycoplasma pneumoniae, adenoviruses, and influenza B virus were the leading infectious agents.
+Mixed-infections of pathogens were detected in 2,391 cases, with Mycoplasma pneumoniae as the most frequent pathogen.
+Regression analysis revealed a linear correlation between the proportion of mixed infections and the incidence of multi-pathogen infections.
+While many HLA class I molecules interact directly with the peptide loading complex (PLC) for conventional loading of peptides certain class I molecules are able to present peptides in a way that circumvents the PLC components.
+We investigated micropolymorphisms at position 156 of HLA-A(*)24 allotypes and their effects on PLC dependence for assembly and peptide binding specificities.
+HLA-A(*)24:06(156Trp) and HLA-A(*)24:13(156Leu) showed high levels of cell surface expression while HLA-A(*)24:02(156Gln) was expressed at low levels in tapasin deficient cells.
+Immunoprecipitation experiments demonstrated all the HLA-A(*)24/156 variants to associate at similar levels with tapasin when present.
+Structurally, HLA-A(*)24:02 contains the residue triad Met97/His114/Gln156 and a Trp156 or Leu156 polymorphism provides tapasin independence by stabilizing these triad residues, thus generating an energetically stable and a more peptide receptive environment.
+Micropolymorphisms at position 156 can influence the generic peptide loading pathway for HLA-A(*)24 by altering their tapasin dependence for peptide selection.
+The trade-off for this tapasin independence could be the presentation of unusual ligands by these alleles, imposing significant risk following hematopoietic stem cell transplantation (HSCT).
+Priority setting research has focused on the macro (national) and micro (bedside) level, leaving the meso (institutional, hospital) level relatively neglected.
+This is surprising given the key role that hospitals play in the delivery of healthcare services and the large proportion of health systems resources that they absorb.
+To explore the factors that impact upon priority setting at the hospital level, we conducted a thematic review of empirical studies.
+A systematic search of PubMed, EBSCOHOST, Econlit databases and Google scholar was supplemented by a search of key websites and a manual search of relevant papers’ reference lists.
+We applied a policy analysis framework to examine and synthesize the findings of the selected papers.
+Findings suggest that priority setting practice in hospitals was influenced by (1) contextual factors such as decision space, resource availability, financing arrangements, availability and use of information, organizational culture and leadership, (2) priority setting processes that depend on the type of priority setting activity, (3) content factors such as priority setting criteria and (4) actors, their interests and power relations.
+We observe that there is need for studies to examine these issues and the interplay between them in greater depth and propose a conceptual framework that might be useful in examining priority setting practices in hospitals.
+Palivizumab, a humanized monoclonal antibody, is the only product approved to prevent serious RSV infection, but its high cost is prohibitive in low-income countries.
+Here, we aimed to identify an effective, safe, and affordable antiviral agent for pre-exposure prophylaxis (PrEP) of RSV infection in children at high risk.
+We found that maleic anhydride (ML)-modified human serum albumin (HSA), designated ML-HSA, exhibited potent antiviral activity against RSV and that the percentages of the modified lysines and arginies in ML- are correlated with such anti-RSV activity.
+ML-HSA inhibited RSV entry and replication by interacting with viral G protein and blocking RSV attachment to the target cells, while ML-HAS neither bound to F protein, nor inhibited F protein-mediated membrane fusion.
+Intranasal administration of ML-HSA before RSV infection resulted in significant decrease of the viral titers in the lungs of mice.
+ML-HSA shows promise for further development into an effective, safe, affordable, and easy-to-use intranasal regimen for pre-exposure prophylaxis of RSV infection in children at high risk in both low- and high-income countries.
+BACKGROUND: Hepatocellular carcinoma (HCC) is on the rise and the sixth most common cancer worldwide.
+To combat HCC effectively research is directed towards its early detection and the development of targeted therapies.
+Given the fact that epidermal growth factor (EGF) is an important mitogen for hepatocytes we searched for disease regulated proteins to improve an understanding of the molecular pathogenesis of EGF induced HCC.
+Disease regulated proteins were studied by 2DE MALDI-TOF/TOF and a transcriptomic approach, by immunohistochemistry and advanced bioinformatics.
+RESULTS: Mapping of EGF induced liver cancer in a transgenic mouse model identified n = 96 (p < 0.05) significantly regulated proteins of which n = 54 were tumour-specific.
+To unravel molecular circuits linked to aberrant EGFR signalling diverse computational approaches were employed and this defined n = 7 key nodes using n = 82 disease regulated proteins for network construction.
+STRING analysis revealed protein-protein interactions of > 70% disease regulated proteins with individual proteins being validated by immunohistochemistry.
+The disease regulated network proteins were mapped to distinct pathways and bioinformatics provided novel insight into molecular circuits associated with significant changes in either glycolysis and gluconeogenesis, argine and proline metabolism, protein processing in endoplasmic reticulum, Hif- and MAPK signalling, lipoprotein metabolism, platelet activation and hemostatic control as a result of aberrant EGF signalling.
+The biological significance of the findings was corroborated with gene expression data derived from tumour tissues to evntually define a rationale by which tumours embark on intriguing changes in metabolism that is of utility for an understanding of tumour growth.
+Moreover, among the EGF tumour specific proteins n = 11 were likewise uniquely expressed in human HCC and for n = 49 proteins regulation in human HCC was confirmed using the publically available Human Protein Atlas depository, therefore demonstrating clinical significance.
+CONCLUSION: Novel insight into the molecular pathogenesis of EGF induced liver cancer was obtained and among the 37 newly identified proteins several are likely candidates for the development of molecularly targeted therapies and include the nucleoside diphosphate kinase A, bifunctional ATP-dependent dihydroyacetone kinase and phosphatidylethanolamine-binding protein1, the latter being an inhibitor of the Raf-1 kinase.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-015-1312-z) contains supplementary material, which is available to authorized users.
+Influenza infection during pregnancy is associated with adverse fetal outcomes such as preterm birth and small for gestational age (SGA).
+We conducted a retrospective cohort study of live births within Kaiser Permanente (KP) Georgia and Mid-Atlantic States (n = 3327) during the period of 2009 influenza A (H1N1) virus circulation.
+Primary outcomes were third-trimester preterm birth (27–36 weeks), birth weight, low birth weight (LBW, <2500 g), and SGA.
+Among H1N1-vaccinated mothers (n = 1125), there were 86 (7.6%) preterm, 68 (6.4%) LBW, and 99 (9.3%) SGA births, and the mean birth weight was 3308.5 g (95% confidence interval [CI], 3276.6–3340.4).
+Among unvaccinated mothers (n = 1581), there were 191 (12.1%) preterm, 132 (8.8%) LBW, and 123 (8.2%) SGA births, and the mean birth weight was 3245.3 g (95% CI, 3216.5–3274.2).
+Infants of H1N1-vaccinated mothers had 37% lower odds of being born preterm than infants of unvaccinated mothers (adjusted odds ratio, 0.63 [95% CI, .47–.84]).
+The mean birth weight difference between infants of H1N1-vaccinated mothers and infants of unvaccinated mothers was 45.1 g (95% CI, 1.8–88.3).
+Pregnant women who received H1N1 influenza vaccine were less likely to give birth preterm, and gave birth to heavier infants.
+The findings support US vaccine policy choices to prioritize pregnant women during the 2009 influenza A (H1N1) pandemic.
+Activation of the NLRP3 inflammasome and subsequent maturation of IL-1β have been implicated in acute lung injury (ALI), resulting in inflammation and fibrosis.
+We investigated the role of vimentin, a type III intermediate filament, in this process using three well-characterized murine models of ALI known to require NLRP3 inflammasome activation.
+We demonstrate that central pathophysiologic events in ALI (inflammation, IL-1β levels, endothelial and alveolar epithelial barrier permeability, remodelling and fibrosis) are attenuated in the lungs of Vim(−/−) mice challenged with LPS, bleomycin and asbestos.
+Bone marrow chimeric mice lacking vimentin have reduced IL-1β levels and attenuated lung injury and fibrosis following bleomycin exposure.
+Furthermore, decreased active caspase-1 and IL-1β levels are observed in vitro in Vim(−/−) and vimentin-knockdown macrophages.
+This study provides insights into lung inflammation and fibrosis and suggests that vimentin may be a key regulator of the NLRP3 inflammasome.
+SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/ncomms7574) contains supplementary material, which is available to authorized users.
+The purpose of the report is to provide a standardized method, developed as a part of a multicenter study of vertically transmitted HIV, for assessing chest radiographic results.
+Eight hundred and five infants and children were studied at five centers; 3057 chest radiographs were scored.
+Inter-rater agreement was moderate to high for most findings, with the best correlation reported for the presence of bronchovascular markings and/or reticular densities addressed as a composite question (kappa = 0.71).
+The presence of nodular densities (kappa = 0.56) and parenchymal consolidation (kappa = 0.57) had moderate agreement.
+The current tool, developed for use in the pediatric population, is applicable to any study involving the assessment of pediatric chest radiographs for a large population, whether at one or many centers.
+The impact of porcine epidemic diarrhea virus (PEDv) infection on the US pork industry has mainly been attributed to the mortality that it causes in suckling piglets, and, consequently, much effort has been invested in the quantification of its effect in sow farms.
+However, no information on the performance of surviving pigs that were exposed to the PEDv as piglets is available.
+Here, a retrospective cohort study to evaluate the impact of porcine epidemic diarrhea virus (PEDv) infection on growing pigs’ performance, as indicated by mortality, average daily gain (ADG), average daily feed intake (ADFI), and feed conversion ratio (FCR) was performed using production records from weaned pigs in nursery and wean-to-finish sites from sow farms that became PEDv-infected between May 2013 and June 2014.
+Production records from the first batch of growing pigs weaned in infected flows after the PEDv outbreak (“infected batches”) were compared with those from pigs weaned within the previous 14 to 120 days (“control batches”).
+Performance records from infected and control batches, paired by flow, were compared using non-parametric paired tests.
+Mortality, ADG and FCR were significantly different in PEDv-positive (infected) compared with PEDv-negative (control) batches, with a mean increase of mortality and FCR of 11% and 0.5, respectively, and a decrease of ADG of 0.16 lb/day.
+Our results demonstrate a poorer performance of growing pigs weaned after a PEDv outbreak compared with those weaned within the previous 14-120 days, suggesting that in addition to the mortality induced by PEDv in suckling pigs, the disease also impairs the performance of surviving pig.
+These findings help to quantify the impact of PEDv infection in the US and, ultimately, contribute to efforts to quantify the cost-effectiveness of disease prevention and control measures.
+The objective of this work was to screen human suspension cell lines for the capacity to support viral replication.
+As the first step, it was investigated whether poliovirus can replicate in such cell lines.
+Sabin poliovirus type 1 was serially passaged on five human cell lines, HL60, K562, KG1, THP-1, and U937.
+Sabin type 1 was capable of efficiently replicating in three cell lines (K562, KG1, and U937), yielding high viral titers after replication.
+Expression of CD155, the poliovirus receptor, did not explain susceptibility to replication, since all cell lines expressed CD155.
+Furthermore, we showed that passaged virus replicated more efficiently than parental virus in KG1 cells, yielding higher virus titers in the supernatant early after infection.
+Infection of cell lines at an MOI of 0.01 resulted in high viral titers in the supernatant at day 4.
+Infection of K562 with passaged Sabin type 1 in a bioreactor system yielded high viral titers in the supernatant.
+Altogether, these data suggest that K562, KG1, and U937 cell lines are useful for propagation of poliovirus.
+We previously discovered one particular HLA-A*02:01 mutant that enhanced peptide-specific cytotoxic T lymphocyte (CTL) recognition in vitro compared to wild-type HLA-A*02:01.
+This mutant contains a single amino acid substitution from histidine to leucine at position 74 (H74L) that is located in the peptide-binding groove.
+To investigate the effect of the H74L mutation on the in vivo CTL priming, we took advantage of the technology of the HLA class I single-chain trimer (SCT) in which three components involving a peptide, β2 microglobulin and the HLA class I heavy chain are joined together via flexible linkers.
+We generated recombinant adenovirus expressing SCT comprised influenza A matrix protein (FMP)-derived peptide, β2 microglobulin and the H74L heavy chain.
+HLA-A*02:01 transgenic mice were immunized with the adenovirus, and the induction of peptide-specific CTLs and antitumor immunity was investigated.
+It was clearly shown that the H74L mutation enabled the HLA-A*02:01 SCT molecule to dramatically enhance both in vivo priming of FMP-specific CTLs and protection against a lethal challenge of tumor cells expressing FMP.
+These data present the first evidence that a simple point mutation in the HLA class I heavy chain of SCT is beneficial for improving CTL-based immunotherapy and prophylaxis to control tumors.
+BACKGROUND: The current Ebola Virus Disease (EVD) epidemic has ravaged the social fabric of three West African countries and affected people worldwide.
+We report key themes from an agenda-setting, multi-disciplinary roundtable convened to examine experiences and implications for health systems in Ghana, a nation without cases but where risk for spread is high and the economic, social and political impact of the impending threat is already felt.
+DISCUSSION: Participants’ personal stories and the broader debates to define fundamental issues and opportunities for preparedness focused on three inter-related themes.
+First, the dangers of the fear response itself were highlighted as a threat to the integrity and continuity of quality care.
+Second, healthcare workers’ fears were compounded by a demonstrable lack of societal and personal protections for infection prevention and control in communities and healthcare facilities, as evidenced by an ongoing cholera epidemic affecting over 20,000 patients in the capital Accra alone since June 2014.
+Third, a lack of coherent messaging and direction from leadership seems to have limited coordination and reinforced a level of mistrust in the government’s ability and commitment to mobilize an adequate response.
+Initial recommendations include urgent investment in the needed supplies and infrastructure for basic, routine infection control in communities and healthcare facilities, provision of assurances with securities for frontline healthcare workers, establishment of a multi-sector, “all-hazards” outbreak surveillance system, and engaging directly with key community groups to co-produce contextually relevant educational messages that will help decrease stigma, fear, and the demoralizing perception that the disease defies remedy or control.
+SUMMARY: The EVD epidemic provides an unprecedented opportunity for West African countries not yet affected by EVD cases to make progress on tackling long-standing health systems weaknesses.
+This roundtable discussion emphasized the urgent need to strengthen capacity for infection control, occupational health and safety, and leadership coordination.
+Significant commitment is needed to raise standards of hygiene in communities and health facilities, build mechanisms for collaboration across sectors, and engage community stakeholders in creating the needed solutions.
+Although HAD is now rare due to HAART, the milder forms of HAND persist in HIV-infected patients.
+HIV-induced systemic and localized inflammation is considered to be one of the mechanisms of HAND.
+However, the changes of cytokines involved in cognition impairment in plasma have not been shown, and their relationships between CSF and plasma require to be addressed.
+We compared cytokine levels in paired CSF and plasma samples from HIV-infected individuals with or without neurocognitive impairment.
+In comparing the expression levels of cytokines in plasma and CSF, IFN-α2, IL-8, IP-10, and MCP-1 were significantly higher in CSF.
+Eotaxin was significantly higher in plasma, whereas G-CSF showed no difference between plasma and CSF.
+G-CSF (P = 0.0079), IL-8 (P = 0.0223), IP-10 (P = 0.0109), and MCP-1 (P = 0.0497) in CSF showed significant difference between HIV-CI and HIV-NC group, which may indicate their relationship to HIV associated neurocognitive impairment.
+In addition, G-CSF (P = 0.0191) and IP-10 (P = 0.0377) in plasma were significantly higher in HIV-CI than HIV-NC.
+The consistent changes of G-CSF and IP-10 in paired plasma and CSF samples might enhance their potential for predicting HAND.
+Human papilloma virus-like particles (HPV VLP) serve as the basis of the current licensed vaccines for HPV.
+We have previously shown that encapsidation of DNA expressing the model antigen M/M2 from respiratory syncytial virus (RSV) in HPV pseudovirions (PsV) is immunogenic when delivered intravaginally.
+Because the HPV capsids confer tropism for basal epithelium, they represent attractive carriers for vaccination targeted to the skin using microneedles.
+In this study we asked: 1) whether HPV16 VLP administered by microneedles could induce protective immune responses to HPV16 and 2) whether HPV16 PsV-encapsidated plasmids delivered by microneedles could elicit immune responses to both HPV and the antigen delivered by the transgene.
+Mice immunized with HPV16 VLP coated microneedles generated robust neutralizing antibody responses and were protected from HPV16 challenge.
+Microneedle arrays coated with HPV16-M/M2 or HPV16-F protein (genes of RSV) were then tested and dose-dependent HPV and F-specific antibody responses were detected post-immunization, and M/M2-specific T-cell responses were detected post RSV challenge, respectively.
+HPV16 PsV-F immunized mice were fully protected from challenge with HPV16 PsV and had reduced RSV viral load in lung and nose upon intranasal RSV challenge.
+In summary, HPV16 PsV-encapsidated DNA delivered by microneedles induced neutralizing antibody responses against HPV and primed for antibody and T-cell responses to RSV antigens encoded by the encapsidated plasmids.
+Although the immunogenicity of the DNA component was just above the dose response threshold, the HPV-specific immunity was robust.
+Taken together, these data suggest microneedle delivery of lyophilized HPV PsV could provide a practical, thermostable combined vaccine approach that could be developed for clinical evaluation.
+Bacterial and viral infections are often clinically indistinguishable, leading to inappropriate patient management and antibiotic misuse.
+Bacterial-induced host proteins such as procalcitonin, C-reactive protein (CRP), and Interleukin-6, are routinely used to support diagnosis of infection.
+However, their performance is negatively affected by inter-patient variability, including time from symptom onset, clinical syndrome, and pathogens.
+Our aim was to identify novel viral-induced host proteins that can complement bacterial-induced proteins to increase diagnostic accuracy.
+The resulting 600 candidates were then quantitatively screened for diagnostic potential using blood samples from 1002 prospectively recruited patients with suspected acute infectious disease and controls with no apparent infection.
+For each patient, three independent physicians assigned a diagnosis based on comprehensive clinical and laboratory investigation including PCR for 21 pathogens yielding 319 bacterial, 334 viral, 112 control and 98 indeterminate diagnoses; 139 patients were excluded based on predetermined criteria.
+The best performing host-protein was TNF-related apoptosis-inducing ligand (TRAIL) (area under the curve [AUC] of 0.89; 95% confidence interval [CI], 0.86 to 0.91), which was consistently up-regulated in viral infected patients.
+We further developed a multi-protein signature using logistic-regression on half of the patients and validated it on the remaining half.
+The signature with the highest precision included both viral- and bacterial-induced proteins: TRAIL, Interferon gamma-induced protein-10, and CRP (AUC of 0.94; 95% CI, 0.92 to 0.96).
+The signature was superior to any of the individual proteins (P<0.001), as well as routinely used clinical parameters and their combinations (P<0.001).
+It remained robust across different physiological systems, times from symptom onset, and pathogens (AUCs 0.87-1.0).
+The accurate differential diagnosis provided by this novel combination of viral- and bacterial-induced proteins has the potential to improve management of patients with acute infections and reduce antibiotic misuse.
+The rapid technological developments following the Human Genome Project have made possible the availability of personalized genomes.
+As the focus now shifts from characterizing genomes to making personalized disease associations, in combination with the availability of other omics technologies, the next big push will be not only to obtain a personalized genome, but to quantitatively follow other omics.
+This will include transcriptomes, proteomes, metabolomes, antibodyomes, and new emerging technologies, enabling the profiling of thousands of molecular components in individuals.
+Furthermore, omics profiling performed longitudinally can probe the temporal patterns associated with both molecular changes and associated physiological health and disease states.
+Such data necessitates the development of computational methodology to not only handle and descriptively assess such data, but also construct quantitative biological models.
+Here we describe the availability of personal genomes and developing omics technologies that can be brought together for personalized implementations and how these novel integrated approaches may effectively provide a precise personalized medicine that focuses on not only characterization and treatment but ultimately the prevention of disease.
+Mathematical epidemiology, one of the oldest and richest areas in mathematical biology, has significantly enhanced our understanding of how pathogens emerge, evolve, and spread.
+Classical epidemiological models, the standard for predicting and managing the spread of infectious disease, assume that contacts between susceptible and infectious individuals depend on their relative frequency in the population.
+There is, however, an emerging a class of models that addresses the feedbacks between infectious disease dynamics and the behavioral decisions driving host contact.
+Referred to as “economic epidemiology” or “epidemiological economics,” the approach explores the determinants of decisions about the number and type of contacts made by individuals, using insights and methods from economics.
+We show how the approach has the potential both to improve predictions of the course of infectious disease, and to support development of novel approaches to infectious disease management.
+The renal response to persistent leptospiral colonization, as measured by urinary protein biosignatures, has not been systematically studied.
+Urinary exosomes--bioactive membrane-bound nanovesicles--contain cell-state specific cargo that additively reflect formation all along the nephron.
+We hypothesized that Leptospira-infection will alter the content of urine exosomes, and further, that these Leptospira-induced alterations will hold clues to unravel novel pathways related to bacterial-host interactions.
+METHODOLOGY/PRINCIPAL FINDINGS: Exosome protein content from 24 hour urine samples of Leptospira-infected rats was compared with that of uninfected rats using SDS-PAGE and liquid chromatography/tandem mass spectrometry (LC-MS/MS).
+Statistical models were used to identify significantly dysregulated proteins in Leptospira-infected and uninfected rat urine exosomes.
+In all, 842 proteins were identified by LC-MS/MS proteomics of total rat urine and 204 proteins associated specifically with exosomes.
+Alanyl (membrane) aminopeptidase, also known as CD13 topped this list with the highest score, a finding we validated by Western immunoblotting.
+CONCLUSIONS: We identified exosome-associated renal tubule-specific responses to Leptospira infection in a rat chronic colonization model.
+Quantitative differences in infected male and female rat urine exosome proteins vs. uninfected controls suggest that urine exosome analysis identifies important differences in kidney function that may be of clinical and pathological significance.
+With the advent of antiretroviral therapy that can control virus replication below the detection levels of conventional assays, a new clinical landscape of AIDS emerged, in which non-AIDS complications prevail over AIDS-defining conditions.
+These comorbidities are diverse and affect multiple organs, thus resulting in cardiovascular, kidney, neurocognitive and liver disease, osteopenia/osteoporosis, and cancers.
+A common feature of these conditions is that they are generally associated with accelerated aging.
+The mechanism behind these comorbidities is chronic excessive inflammation induced by HIV infection, which persists under antiretroviral therapy.
+Progressive simian immunodeficiency virus (SIV) infection of nonhuman primates (NHPs) closely reproduces these comorbidities and offers a simplified system in which most of the traditional human risk factors for comorbidities (i.e., smoking, hyperlipidemia) are absent.
+Additionally, experimental conditions can be properly controlled during a shorter course of disease for SIV infection.
+As such, NHPs can be employed to characterize new paradigms of AIDS pathogenesis and to test the efficacy of interventions aimed at alleviating non-AIDS-related comorbidities.
+BACKGROUND: Early diagnosis and appropriate antibiotic treatment can significantly reduce mortality of nosocomial bacterial meningitis.
+However, it is a challenge for clinicians to make an accurate and rapid diagnosis of bacterial meningitis.
+This study aimed at determining whether combined biomarkers can provide a useful tool for the diagnosis of bacterial meningitis.
+Cerebrospinal fluid (CSF) levels of decoy receptor 3 (DcR3) and soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) were detected by enzyme-linked immunosorbent assay (ELISA).
+RESULTS: The patients with bacterial meningitis had significantly elevated levels of the above mentioned biomarkers.
+The discriminative performance of the bioscore was better than that of each biomarker, with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.842 (95% confidence intervals (CI) 0.770–0.914; p< 0.001).
+CONCLUSIONS: Combined measurement of CSF DcR3 and sTREM-1 concentrations improved the prediction of nosocomial bacterial meningitis.
+The combined strategy is of interest and the validation of that improvement needs further studies.
+TP53 gene is known as the “guardian of the genome” as it plays a vital role in regulating cell cycle, cell proliferation, DNA damage repair, initiation of programmed cell death and suppressing tumor growth.
+Non uniform usage of synonymous codons for a specific amino acid during translation of protein known as codon usage bias (CUB) is a unique property of the genome and shows species specific deviation.
+Analysis of codon usage bias with compositional dynamics of coding sequences has contributed to the better understanding of the molecular mechanism and the evolution of a particular gene.
+In this study, the complete nucleotide coding sequences of TP53 gene from eight different mammalian species were used for CUB analysis.
+Our results showed that the codon usage patterns in TP53 gene across different mammalian species has been influenced by GC bias particularly GC(3) and a moderate bias exists in the codon usage of TP53 gene.
+Moreover, we observed that nature has highly favored the most over represented codon CTG for leucine amino acid but selected against the ATA codon for isoleucine in TP53 gene across all mammalian species during the course of evolution.
+HIV-1 utilises −1 programmed ribosomal frameshifting to translate structural and enzymatic domains in a defined proportion required for replication.
+A slippery sequence, U UUU UUA, and a stem-loop are well-defined RNA features modulating −1 frameshifting in HIV-1.
+The GGG glycine codon immediately following the slippery sequence (the ‘intercodon’) contributes structurally to the start of the stem-loop but has no defined role in current models of the frameshift mechanism, as slippage is inferred to occur before the intercodon has reached the ribosomal decoding site.
+When the natural intercodon was replaced with a stop codon two different decoding molecules—eRF1 protein or a cognate suppressor tRNA—were able to access and decode the intercodon prior to −1 frameshifting.
+This implies significant slippage occurs when the intercodon is in the (perhaps distorted) ribosomal A site.
+We accommodate the influence of the intercodon in a model of frame maintenance versus frameshifting in HIV-1.
+Cells of specialized secretory organs expand their secretory pathways to accommodate the increased protein load necessary for their function.
+The endoplasmic reticulum (ER), the Golgi apparatus and the secretory vesicles, expand not only the membrane components but also the protein machinery required for increased protein production and transport.
+Increased protein load causes an ER stress response akin to the Unfolded Protein Response (UPR).
+Recent work has implicated several bZip transcription factors in the regulation of protein components of the early secretory pathway necessary to alleviate this stress.
+These include components of the three canonical branches of the UPR-ATF4, XBP1, and ATF6, as well as the five members of the Creb3 family of transcription factors.We review findings from both invertebrate and vertebrate model systems suggesting that all of these proteins increase secretory capacity in response to increased protein load.
+Finally, we propose that the Creb3 family of factors may have a dual role in secretory cell differentiation by also regulating the pathways necessary for cell cycle exit during terminal differentiation.
+ELECTRONIC SUPPLEMENTARY MATERIAL: Supplementary material is available for this article at 10.1007/s11515-014-1338-7 and is accessible for authorized users.
+A C-terminal cleaved product of Dicer protein was detected in the presence of MG132 during VV infection.
+Thus, it is possible that Dicer protein is cleaved by a viral protease followed by proteasome degradation of the cleaved product.
+Indeed, reduction of Dicer protein was detected when Dicer was co-expressed with I7 protease but not with an I7 protease mutant protein lack of the protease activity.
+Mutation of the potential I7 cleavage site in the C-terminus of Dicer protein resisted its degradation during VV infection.
+Furthermore, Dicer protein was reduced dramatically by recombinant VV vI7Li after the induction of I7 protease.
+If VV could facilitate the degradation of Dicer protein, the process of miRNA should be affected by VV infection.
+Reduction of miR122 would result in the suppression of HCV sub-genomic RNA replication, and, in turn, the amount of viral proteins.
+As expected, significant reduction of HCVNS5A protein was detected after VV infection and I7 protease expression.
+Therefore, our results suggest that VV could cleave Dicer protein through I7 protease to facilitate Dicer degradation, and in turn, suppress the processing of miRNAs.
+Exogenous expression of Dicer protein suppresses VV replication slightly while knockdown of Dicer protein does not affect VV replication significantly.
+HCV exploits complex molecular mechanisms, which result in a high degree of intrahost genetic heterogeneity.
+This high degree of variability represents a challenge for the accurate establishment of genetic relatedness between cases and complicates the identification of sources of infection.
+Tracking HCV infections is crucial for the elucidation of routes of transmission in a variety of settings.
+Accounting for virulence is also important for HCV AMS and both viral and host factors contribute to the disease outcome.
+Therefore, HCV AMS requires the incorporation of host factors as an integral component of the algorithms used to monitor disease occurrence.
+Importantly, implementation of comprehensive global databases and data mining are also needed for the proper study of the mechanisms responsible for HCV transmission.
+Here, we review molecular aspects associated with HCV transmission, as well as the most recent technological advances used for virus and host characterization.
+Additionally, the cornerstone discoveries that have defined the pathway for viral characterization are presented and the importance of implementing advanced HCV molecular surveillance is highlighted.
+It has been demonstrated that MEK1, one of the two MEK isoforms in Raf-MEK-ERK1/2 pathway, is essential for successful EV71 propagation.
+However, the distinct function of ERK1 and ERK2 isoforms, the downstream kinases of MEKs, remains unclear in EV71 replication.
+Silencing specific ERK did not significantly impact on the EV71-caused biphasic activation of the other ERK isoform, suggesting the EV71-induced activations of ERK1 and ERK2 were non-discriminative and independent to one another.
+Knockdown of either ERK1 or ERK2 markedly impaired progeny EV71 propagation (both by more than 90%), progeny viral RNA amplification (either by about 30% to 40%) and protein synthesis (both by around 70%), indicating both ERK1 and ERK2 were critical and not interchangeable to EV71 propagation.
+Moreover, suppression of EV71 replication by inhibiting both early and late phases of ERK1/2 activation showed no significant difference from that of only blocking the late phase, supporting the late phase activation was more importantly responsible for EV71 life cycle.
+Taken together, this study for the first time identified both ERK1 and ERK2 were required for EV71 efficient replication and further verified the important role of MEK1-ERK1/2 in EV71 replication.
+BACKGROUND: Porcine transmissible gastroenteritis virus (TGEV) is the major etiological agent of viral enteritis and severe diarrhea in suckling piglets.
+In China, TGEV has caused great economic losses, but its role in epidemic diarrhea is unclear.
+This study aims to reveal the etiological role of TGEV in piglet diarrhea via molecular characterization and phylogenetic analysis.
+RESULTS: A TGEV-HX strain was isolated from China, and its complete genome was amplified, cloned, and sequenced.
+Sequence analysis indicated that it was conserved in the 5′ and 3′-non-translated regions, and there were no insertions or deletions in nonstructural genes, such as ORF1a, ORF1b, ORF3a, ORF3b, and ORF7, as well as in genes encoding structural proteins, such as the envelope (E), membrane (M), and nucleoprotein (N) proteins.
+Furthermore, the phylogenetic analysis indicated that the TGEV-HX strain was more similar to the TGEV Purdue cluster than to the Miller cluster.
+The detailed analysis of the genetic variation of TGEVs in China provides essential information for further understanding the evolution of TGEVs.
+We hypothesised that exposure of peripheral monocytes (PBMCs) to syncytin-1 would impair responses to H1N1pdm09 influenza.
+PBMCs from non-pregnant women (n=10) were exposed to H1N1pdm09 in the presence and absence of syncytin-1 and compared to responses of PBMCs from pregnant women (n=12).
+PBMCs were characterised using flow cytometry, release of interferon (IFN)-α, IFN-λ, IFN-γ, IL-10, IL-2, IL-6 and IL-1β were measured by cytometric bead array or ELISA.
+Exposure of PBMCs to H1N1pdm09 resulted in the release of IFN-α, (14,787 pg/mL, 95% CI 7311-22,264 pg/mL) IFN-λ (1486 pg/mL, 95% CI 756-2216 pg/mL) and IFN-γ (852 pg/mL, 95% CI 193-1511 pg/mL) after 48 hours.
+Furthermore, in the presence of syncytin-1, PBMCs demonstrated marked reductions in IFN-α and IFN-λ, while enhanced release of IL-10 as well as IL-6 and IL-1β.
+CONCLUSIONS: Our data indicates that a placental derived protein, syncytin-1 may be responsible for the heightened vulnerability of pregnant women to influenza.
+Type I interferon (IFN) activation and its subsequent effects are important in the response to viral infections.
+Here we show that human astroviruses (HAstVs), which are important agents of acute gastroenteritis in children, induce a mild and delayed IFN response upon infecting CaCo-2 cells.
+Although IFN-β mRNA is detected within infected cells and supernatant from infected cells show antiviral activity against the replication of other well-known IFN-sensitive viruses, these responses occur at late stages of infection once genome replication has taken place.
+On the other hand, HAstV replication can be partially reduced by the addition of exogenous IFN, and inhibition of IFN activation by BX795 enhances viral replication, indicating that HAstVs are IFN-sensitive viruses.
+Finally, different levels of IFN response were observed in cells infected with different HAstV mutants with changes in the hypervariable region of nsP1a/4, suggesting that nsP1a/4 genotype may potentially have clinical implications due to its correlation with the viral replication phenotype and the antiviral responses induced within infected cells.
+An early and accurate diagnosis of dengue can support clinical management, surveillance and disease control and is central to achieving the World Health Organisation target of a 50% reduction in dengue case mortality by 2020.
+METHODS: 5729 children with fever of <72hrs duration were enrolled into this multicenter prospective study in southern Vietnam between 2010-2012.
+Using statistical methods, a novel Early Dengue Classifier (EDC) was developed that used patient age, white blood cell count and platelet count to discriminate dengue cases from non-dengue cases.
+RESULTS: The EDC had a sensitivity of 74.8% (95%CI: 73.0-76.8%) and specificity of 76.3% (95%CI: 75.2-77.6%) for the diagnosis of dengue.
+As an adjunctive test alongside NS1 rapid testing, sensitivity of the composite test was 91.6% (95%CI: 90.4-92.9%).
+CONCLUSIONS: We demonstrate that the early diagnosis of dengue can be enhanced beyond the current standard of care using a simple evidence-based algorithm.
+This research focused on the modification of the functional groups of oseltamivir as neuraminidase inhibitor against influenza A virus subtype H1N1.
+Interactions of three of the best ligands were evaluated in the hydrated state using molecular dynamics simulation at two different temperatures.
+The docking result showed that AD3BF2D ligand (N-[(1S,6R)-5-amino-5-{[(2R,3S,4S)-3,4-dihydroxy-4-(hydroxymethyl) tetrahydrofuran-2-yl]oxy}-4-formylcyclohex-3-en-1-yl]acetamide-3-(1-ethylpropoxy)-1-cyclohexene-1-carboxylate) had better binding energy values than standard oseltamivir.
+AD3BF2D had several interactions, including hydrogen bonds, with the residues in the catalytic site of neuraminidase as identified by molecular dynamics simulation.
+The results showed that AD3BF2D ligand can be used as a good candidate for neuraminidase inhibitor to cope with influenza A virus subtype H1N1.
+Taiep rat has a failure in myelination and remyelination processes leading to a state of hypomyelination throughout its life.
+Chemokines, which are known to play a role in inflammation, are also involved in the remyelination process.
+We aimed to demonstrate that remyelination-stimulating factors are altered in the brainstem of 1- and 6-month-old taiep rats.
+We used a Rat RT(2) Profiler PCR Array to assess mRNA expression of 84 genes coding for cytokines, chemokines, and their receptors.
+We also evaluated protein levels of CCL2, CCR1, CCR2, CCL5, CCR5, CCR8, CXCL1, CXCR2, CXCR4, FGF2, and VEGFA by ELISA.
+In contrast, some mRNA levels of beta and alpha chemokines were upregulated in 1-month-old rats, but CXCR4 was downregulated at their 6 months of age.
+ELISA results showed that CXCL1, CCL2, CCR2, CCR5, CCR8, and CXCR4 protein levels were decreased in brainstem at the age of 6 months.
+These results suggest the presence of a chronic neuroinflammation process with deficiency of remyelination-stimulating factors (CXCL1, CXCR2, and CXCR4), which might account for the demyelination in the taiep rat.
+F4/AS01 consists of F4 recombinant fusion protein (containing clade B Gag/p24, Pol/RT, Nef and Gag/p17) formulated in AS01 Adjuvant System, and was shown to induce F4-specific polyfunctional CD4(+) T-cell responses in humans.
+While replication-incompetent recombinant HIV-1/SIV antigen-expressing human adenoviral vectors can elicit high-frequency antigen-specific CD8(+) T-cell responses, their use is hampered by widespread pre-existing immunity to human serotypes.
+We evaluated the immunogenicity of AdC7-GRN (‘A’), a recombinant chimpanzee adenovirus type 7 vector expressing clade B Gag, RT and Nef, and F4/AS01 (‘P’), when delivered intramuscularly in homologous (PP or AA) and heterologous (AAPP or PPAA) prime-boost regimens, in macaques and mice.
+Vaccine-induced HIV-1-antigen-specific T cells in peripheral blood (macaques), liver, spleen, and intestinal and genital mucosa (mice) were characterized by intracellular cytokine staining.
+In macaques, only the heterologous prime-boost regimens induced polyfunctional, persistent and balanced CD4(+) and CD8(+) T-cell responses specific to each HIV-1 vaccine antigen.
+In mice, antigen-specific CD4(+) and CD8(+) T-cell responses were detected in the mucosal and systemic anatomical compartments assessed.
+When administered in heterologous prime-boost regimens, AdC7-GRN and F4/AS01 candidate vaccines acted complementarily in inducing potent and persistent peripheral blood HIV-1-specific CD4(+) and CD8(+) T-cell responses and antibodies in macaques.
+This suggests that prime-boost regimens combining adjuvanted protein and low-seroprevalent chimpanzee adenoviral vectors represent an attractive vaccination strategy for clinical evaluation.
+The IfitmDel animals exhibit a steady and significantly enhanced weight gain relative to wild-type controls beginning about three months of age and under normal feeding conditions.
+The increased weight corresponds with elevated fat mass, and in tolerance tests they are hyporesponsive to insulin but respond normally to glucose.
+Both young (4 mo) and older (12 mo) IfitmDel mice have enhanced levels of serum leptin suggesting a defect in leptin/leptin receptor signaling.
+Analysis of the gene expression profiles in the hypothalamus of IfitmDel animals, compared to WT, demonstrated an altered ratio of Pomc and Npy neuropeptide expression, which likely impairs the satiation response of the IfitmDel animal leading to an increased eating behavior.
+Anatomical analysis of the hypothalamus using immunohistochemistry revealed that microglia exhibit an abnormal morphology in IfitmDel animals and respond abnormally to Poly:IC challenge.
+These abnormalities extend the phenotype of the IfitmDel mouse beyond abnormal responses to viral challenge to include a metabolic phenotype and weight gain.
+Further, this novel phenotype for the IfitmDel mouse could be related to abnormal neuropeptide production, inflammatory status and microglia status in the hypothalamus.
+To date, not many studies have been reported on the identification of suitable reference genes in buffaloes.
+The present study was undertaken to determine the panel of suitable reference genes in heat-stressed buffalo mammary epithelial cells (MECs).
+Briefly, MEC culture from buffalo mammary gland was exposed to 42 °C for one hour and subsequently allowed to recover at 37 °C for different time intervals (from 30 m to 48 h).
+Three different algorithms, geNorm, NormFinder, and BestKeeper softwares, were used to evaluate the stability of 16 potential reference genes from different functional classes.
+Our data identified RPL4, EEF1A1, and RPS23 genes to be the most appropriate reference genes that could be utilized for normalization of qPCR data in heat-stressed buffalo MECs.
+Human rhinoviruses (HRVs) are responsible for more than half of all cases of the common cold and cost billions of USD annually in medical visits and missed school and work.
+An assessment was made of the antiviral activities and mechanisms of action of paeonol (PA) and 1,2,3,4,6-penta-O-galloyl-β-D-glucopyranose (PGG) from Paeonia lactiflora root toward HRV-2 and HRV-4 in MRC5 cells using a tetrazolium method and real-time quantitative reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay.
+Based on 50% inhibitory concentration values, PGG was 13.4 and 18.0 times more active toward HRV-2 (17.89 μM) and HRV-4 (17.33 μM) in MRC5 cells, respectively, than ribavirin.
+The 100 μg/mL PA and 20 μg/mL PGG did not interact with the HRV-4 particles.
+These constituents inhibited HRV-4 infection only when they were added during the virus inoculation (0 h), the adsorption period of HRVs, but not after 1 h or later.
+Moreover, the RNA replication levels of HRVs were remarkably reduced in the MRC5 cultures treated with these constituents.
+These findings suggest that PGG and PA may block or reduce the entry of the viruses into the cells to protect the cells from the virus destruction and abate virus replication, which may play an important role in interfering with expressions of rhinovirus receptors (intercellular adhesion molecule-1 and low-density lipoprotein receptor), inflammatory cytokines (interleukin (IL)-6, IL-8, tumor necrosis factor, interferon beta, and IL-1β), and Toll-like receptor, which resulted in diminishing symptoms induced by HRV.
+Global efforts to reduce the level of synthetic drugs justify further studies on P. lactiflora root-derived materials as potential anti-HRV products or lead molecules for the prevention or treatment of HRV.
+Alveolar epithelial type II (AEII) cells are a key structure and defender in the lung but also are the targets in many lung diseases, including acute respiratory distress syndrome, ventilator-induced lung injury, and pulmonary fibrosis.
+We sought to establish an optimized method for high yielding and long maintenance of characteristics of primary human AEII cells to facilitate the investigation of the mechanisms of lung diseases at the cellular and molecular levels.
+The AEII cells were isolated and identified by the expression of pro-surfactant protein (SP)C, epithelial sodium channel (αENaC) and cytokeratin (CK)-8, the lamellar bodies specific for AEII cells, and confirmed by the histology using electron microscopy.
+The phenotype of AEII cells was characterized by the expression of surfactant proteins (SP-A, SP-B, SP-C, SP-D), CK-8, KL-6, αENaC, and aquaporin (AQP)-3, which was maintained over 20 days.
+The biological activity of the primary human AEII cells producing SP-C, cytokines, and intercellular adhesion molecule-1 was vigorous in response to stimulation with tumor necrosis factor-α.
+We have modified previous methods and optimized a method for isolation of high purity and long maintenance of the human AEII cell phenotype in primary culture.
+This method provides an important tool for studies aiming at elucidating the molecular mechanisms of lung diseases exclusively in AEII cells.
+Dilated cardiomyopathy is a disease of left ventricular dysfunction accompanied by impairment of the β(1)-adrenergic receptor (β(1)-AR) signal cascade.
+The disturbed β(1)-AR function may be based on an elevated sympathetic tone observed in patients with heart failure.
+Prolonged adrenergic stimulation may induce metabolic and electrophysiological disturbances in the myocardium, resulting in tachyarrhythmia that leads to the development of heart failure in human and sudden death.
+Hence, β(1)-AR is considered as a promising drug target but attempts to develop effective and specific drug against this tempting pharmaceutical target is slowed down due to the lack of 3D structure of Homo sapiens β(1)-AR (hsβADR1).
+This study encompasses elucidation of 3D structural and physicochemical properties of hsβADR1 via threading-based homology modeling.
+Furthermore, the docking performance of several docking programs including Surflex-Dock, FRED, and GOLD were validated by re-docking and cross-docking experiments.
+This study provides clear understanding of hsβADR1 structure and its binding mechanism, thus help in providing the remedial solutions of cardiovascular, effective treatment of asthma and other diseases caused by malfunctioning of the target protein.
+Talaromyces marneffei (Basionym: Penicillium marneffei) is a significant opportunistic fungal pathogen in patients infected with human immunodeficiency virus in Southeast Asia.
+Melanins are pigment biopolymers which act as a non-specific protectant against various stressors and which play an important role during virulence in fungi.
+The synthesis of the two most commonly found melanins in fungi, the eumelanin DOPA-melanin and the allomelanin DHN-melanin, requires the action of laccase enzymes.
+The T. marneffei genome encodes a number of laccases and this study describes the characterization of one of these, pbrB, during growth and development.
+A strain carrying a PbrB-GFP fusion shows that pbrB is expressed at high levels during asexual development (conidiation) but not in cells growing vegetatively.
+The pbrB gene is required for the synthesis of DHN-melanin in conidia and when deleted results in brown pigmented conidia, in contrast to the green conidia of the wild type.
+We established two Madin-Darby canine kidney (MDCK) cell lines stably expressing human airway transmembrane protease: transmembrane protease, serine 2 (TMPRSS2) and mosaic serine protease large form (MSPL) which support multicycle growth of two H5 highly pathogenic avian influenza viruses (HPAIV) recombinant vaccines (Re-5 and Re-6) and an H9 avian influenza virus (AIV) recombinant vaccine (Re-9) in the absence of trypsin.
+Data showed that the cell lines stably expressed TMPRSS2 and MSPL after 20 serial passages.
+Both MDCK-TMPRSS2 and MDCK-MSPL could proteolytically cleave the HA of Re-5, Re-6, and Re-9 and supported high-titer growth of the vaccine without exogenous trypsin.
+Re-5, Re-6, and Re-9 efficiently infected and replicated within MDCK-TMPRSS2 and MDCK-MSPL cells and viral titer were comparable to the virus grown in MDCK cells with TPCK-trypsin.
+Thus, our results indicate a potential application for these cell lines in cell-based influenza vaccine production and may serve as a useful tool for HA proteolytic cleavage-related studies.
+BACKGROUND: The performance of recommended control measures is necessary for quick and uniform infectious disease outbreak control.
+To assess whether these procedures are performed, a valid set of quality indicators (QIs) is required.
+The goal of this study was to select a set of key recommendations that can be systematically translated into QIs to measure the quality of infectious disease outbreak response from the perspective of disaster emergency responders and infectious disease control professionals.
+METHODS: Applying the Rand modified Delphi procedure, the following steps were taken to systematically select a set of key recommendations: extraction of recommendations from relevant literature; appraisal of the recommendations in terms of relevance through questionnaires to experts; expert meeting to discuss recommendations; prioritization of recommendations through a second questionnaire; and final expert meeting to approve the selected set.
+Infectious disease physicians and nurses, policymakers and communication experts participated in the expert group (n = 48).
+RESULTS: In total, 54 national and international publications were systematically searched for recommendations, yielding over 200 recommendations.
+The key recommendations were categorized into 10 domains describing the whole response pathway from outbreak recognition to aftercare.
+CONCLUSION: This study provides a set of key recommendations that represents ‘good quality of response to an infectious disease outbreak’.
+Organizations and professionals involved in outbreak control can use these QIs to monitor the quality of response to infectious disease outbreaks and to assess in which domains improvement is needed.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-015-0896-x) contains supplementary material, which is available to authorized users.
+BACKGROUND: A novel, swine-origin influenza A (H1N1) virus was detected worldwide in April 2009, and the World Health Organization (WHO) declared a global pandemic that June.
+We describe the rapid production and clinical evaluation of a DNA vaccine encoding the hemagglutinin protein of the 2009 pandemic A/California/04/2009(H1N1) influenza virus, accomplished nearly two months faster than production of A/California/07/2009(H1N1) licensed monovalent inactivated vaccine (MIV).
+METHODS: 20 subjects received three H1 DNA vaccinations (4 mg intramuscularly with Biojector) at 4-week intervals.
+Antibody responses were assessed by ELISA, HAI and neutralization assays, and T cell responses by ELISpot and flow cytometry.
+As evaluated by HAI, 6/20 developed positive responses at 4 weeks after third DNA injection and 13/18 at 4 weeks after MIV boost.
+The antibody responses were significantly amplified by the MIV boost, however, the boost did not increased T cell responses induced by DNA vaccine.
+CONCLUSIONS: H1 DNA vaccine was produced quickly, was well-tolerated, and had modest immunogenicity as a single agent.
+Other HA DNA prime-MIV boost regimens utilizing one DNA prime vaccination and longer boost intervals have shown significant immunogenicity.
+Rapid and large-scale production of HA DNA vaccines has the potential to contribute to an efficient response against future influenza pandemics.
+Infectious bursal disease virus (IBDV), a member of the Birnaviridae family, is a major avian pathogen responsible for an immunosuppressive disease affecting juvenile chickens.
+The largest one harbors two partially overlapping open reading frames encoding a non-structural polypeptide, known as VP5, and a large polyprotein, respectively.
+Updated topological prediction algorithm servers fail to identify a transmembrane domain within the VP5 sequence.
+However, the VP5 polycationic C-terminal region, harboring three closely spaced patches formed by two or three consecutive basic amino acid residues (lysine or arginine), might account for its PM tropism.
+We have found that mutations, either C-terminal VP5 deletions or replacement of basic amino acids by alanine residues, that reduce the electropositive charge of the VP5 C-terminus abolish PM targeting.
+Lipid overlay assays performed with an affinity-purified Flag-tagged VP5 (FVP5) protein version show that this polypeptide binds several phosphoinositides (PIP), exhibiting a clear preference for monophosphate species.
+Experiments performed with FVP5 mutant proteins lacking the polycationic domain demonstrate that this region is essential for PIP binding.
+Data gathered with IBDV mutants expressing C-terminal deleted VP5 polypeptides generated by reverse genetics demonstrate that the VP5-PIP binding domain is required both for its PM targeting in infected cells, and for efficient virus dissemination.
+Data presented here lead us to hypothesize that IBDV might use a non-lytic VP5-dependent cell-to-cell spreading mechanism.
+Herpes simplex virus-1 (HSV-1) infection causes severe conditions, with serious complications, including corneal blindness from uncontrolled ocular infections.
+In this study, we performed a detailed analysis of autophagy in multiple HSV-1-targeted cell types, and under various infection conditions that recapitulate a productive infection model.
+We found that autophagy was slightly inhibited in one cell type, while in other cell types autophagy maintained its basal levels mostly unchanged during productive infection.
+This study refines the concept of HSV-1-mediated autophagy regulation to imply either inhibition, or prevention of activation, of the innate immune pathway.
+BACKGROUND: Viral and bacterial infections are the most common causes of chronic obstructive pulmonary disease (COPD) exacerbations.
+Whether serum inflammatory markers can differentiate bacterial from virus infection in patients with COPD exacerbation requiring emergency department (ED) visits remains controversial.
+METHODS: Viral culture and polymerase chain reaction (PCR) were used to identify the viruses in the oropharynx of patients with COPD exacerbations.
+The peripheral blood white blood cell (WBC) counts, serum C-reactive protein (CRP), procalcitonin (PCT), and clinical symptoms were compared among patients with different types of infections.
+A total of 30 (41.7%) patients had positive bacterial cultures, with the most commonly found bacteria being Haemophilus influenzae and Haemophilus parainfluenzae.
+The WBC, CRP, and PCT levels of the bacteria-positive and bacteria-negative groups were not statistically different.
+Multivariate analysis showed that patients with increased sputum volumes during the COPD exacerbations had higher risks of recurrent exacerbations in the 1-year period following the first exacerbation.
+CONCLUSION: WBC, CRP, or PCT could not differentiate between bacterial and viral infections in patients with COPD exacerbation requiring ED visits.
+INTRODUCTION: This study was designed as an external validation of the recently proposed Predicting Death for Severe ARDS on V-V ECMO (PRESERVE) score, The respiratory extracorporeal membrane oxygenation survival prediction (RESP) score and a scoring system developed for externally retrieved patients on extracorporeal membrane oxygenation (ECMO) at our institution.
+All scores are proposed for the estimation of survival probability after ECMO treatment for severe adult respiratory distress syndrome.
+METHODS: Data from 51 patients (2008 to 2013) were analyzed in this retrospective single-center study.
+A calculation of an adapted PRESERVE score, the RESP score as well as the score developed for externally retrieved ECMO patients was performed.
+RESULTS: Seventy one percent of patients received veno-venous (v-v) and 29% venous-arterial (v-a) ECMO support during the study period.
+Overall survival at 6 months was 55%, with a 61% survival rate for v-v cannulated patients and a 40% survival rate for v-a cannulated patients.
+The PRESERVE score discriminated survivors and non-survivors with an area under the curve of 0.67 (95% CI 0.52 to 0.82, P = 0.03).
+Analyzing survival prediction according to cannulation modus, the PRESERVE score and the RESP score significantly predicted survival for patients on v-v ECMO with an area under the curve of 0.75 (95% CI 0.57 to 0.92, P = 0.01) and 0.81 (95% CI 0.67 to 0.95, P = 0.035), respectively, while the scoring system developed for externally retrieved ECMO patients failed to predict survival in our study population.
+CONCLUSION: Our single-center validation confirms that the proposed PRESERVE and RESP score predict survival for patients treated with v-v ECMO for severe adult respiratory distress syndrome.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13054-015-0875-z) contains supplementary material, which is available to authorized users.
+BACKGROUND: The benign character formerly attributed to Plasmodium vivax infection has been dismantled by the increasing number of reports of severe disease associated with infection with this parasite, prompting the need for more thorough and comprehensive characterization of the spectrum of resulting clinical complications.
+This study, conducted simultaneously in Brazil and India, constitutes, to our knowledge, the first multisite study focused on clinical characterization of P. vivax severe disease.
+METHODS: Patients admitted with P. vivax mono-infection at reference centers in Manaus (Amazon - Brazil) and Bikaner (Rajasthan - India), where P. vivax predominates, were submitted to standard thorough clinical and laboratory evaluations in order to characterize clinical manifestations and identify concurrent co-morbidities.
+RESULTS: In total, 778 patients (88.0% above 12 years old) were hospitalized at clinical discretion with PCR-confirmed P. vivax mono-infection (316 in Manaus and 462 in Bikaner), of which 197 (25.3%) presented at least one severity criterion as defined by the World Health Organization (2010).
+Noteworthy, pregnancy status was associated as a risk factor for severe disease (OR = 2.03; 95% CI = 1.2-3.4; P = 0.007).
+The overall case fatality rate was 0.3/1,000 cases in Manaus and 6.1/1,000 cases in Bikaner, with all deaths occurring among patients fulfilling at least one severity criterion.
+Within this subgroup, case fatality rates increased respectively to 7.5% in Manaus and 4.4% in Bikaner.
+CONCLUSION: P. vivax-associated severity is not negligible, and although lethality observed for complicated cases was similar, the overall fatality rate was about 20-fold higher in India compared to Brazil, highlighting the variability observed in different settings.
+Our observations highlight that pregnant women and patients with co-morbidities need special attention when infected by this parasite due to higher risk of complications.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12916-015-0302-y) contains supplementary material, which is available to authorized users.
+PURPOSE: Malignant melanoma’s (MM) incidence is rising faster than that of any other cancer in the US and the overall survival at 5 years is less than 10%.
+B cell associated protein 31 (BAP31) is overexpressed in most MMs and might be a promising target for immunotherapy of this disease.
+EXPERIMENTAL DESIGN: Firstly, we investigated the expression profiles of human BAP31 (hBAP31) and mouse BAP31 (mBAP31) in human and mouse normal tissues, respectively.
+The expression level of hBAP31 in human MMs and mBAP31 in B16 melanoma cells was also analyzed.
+Then we constructed novel mBAP31 DNA vaccines and tested there ability to stimulate mBAP31-specific immune responses and antitumor immunity in B16 melanoma-bearing mice.
+RESULTS: For the first time, we found that protein expression of hBAP31 were dramatically upregulated in human MMs when compared with human normal tissues.
+Predominant protein expression of mBAP31 was found in mouse B16 melanoma cells but not in mouse important organs.
+When mice were immunized with mBAP31 DNA vaccines, strong cellular response to mBAP31 was observed in the vaccinated mice.
+CTLs isolated from immunized mice could effectively kill mBAP31-positive target mouse B16 melanoma tumor cells in vitro and vaccination with mBAP31 DNA vaccines had potent anti-tumor activity in therapeutic model using B16 melanoma cells.
+CONCLUSIONS: These are the first data supporting a vaccine targeting BAP31 that is capable of inducing effective immunity against BAP31-expressing MMs and will be applicable to human MMs and hBAP31 DNA vaccine warrants investigation in human clinical trials.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13046-015-0153-6) contains supplementary material, which is available to authorized users.
+Surface protein hemagglutinin (HA) mediates the binding of influenza virus to host cell receptors containing sialic acid, facilitating the entry of the virus into host cells.
+Therefore, the HA protein is regarded as a suitable target for the development of influenza virus detection devices.
+In this study, we isolated single-stranded DNA (ssDNA) aptamers binding to the HA1 subunit of subtype H1 (H1-HA1), but not to the HA1 subunit of subtype H5 (H5-HA1), using a counter-systematic evolution of ligands by exponential enrichment (counter-SELEX) procedure.
+Enzyme-linked immunosorbent assay and surface plasmon resonance studies showed that the selected aptamers bind tightly to H1-HA1 with dissociation constants in the nanomolar range.
+Western blot analysis demonstrated that the aptamers were binding to H1-HA1 in a concentration-dependent manner, yet were not binding to H5-HA1.
+Further biophysical analysis showed that the G-rich sequences formed a G-quadruplex structure, which is a distinctive structure compared to the starting ssDNA library.
+Using flow cytometry analysis, we found that the aptamers did not bind to the receptor-binding site of H1-HA1.
+These results indicate that the selected aptamers that distinguish H1-HA1 from H5-HA1 can be developed as unique probes for the detection of the H1 subtype of influenza virus.
+OBJECTIVE: The relation between various infections and adult asthma exacerbations was investigated in clinical practice.
+METHODS: The study subjects included 50 adult inpatients due to asthma exacerbations and 20 stable outpatients for comparison.
+The numbers of patients with viral, bacterial, or both infections were 16, 9, and 9, respectively.
+Compared to pathogen-free patients, the patients with pathogens were older and non-atopic and had later onset of disease, lower FeNO levels, lower IgE titers, and a higher incidence of comorbid sinusitis, COPD, or pneumonia.
+Compared to stable outpatients, asthma exacerbation inpatients had a higher incidence of smoking and comorbid sinusitis, COPD, or pneumonia.
+Viruses were detected in 50% of stable outpatients, but a higher incidence of rhinovirus, respiratory syncytial virus, and metapneumovirus infections was observed in asthma exacerbation inpatients.
+CONCLUSION: Viral or bacterial infections were observed in 70% of inpatients with an asthma exacerbation in clinical practice.
+Swine influenza virus and Streptococcus suis are two important contributors to the porcine respiratory disease complex, and both have significant economic impacts.
+Clinically, influenza virus and Streptococcus suis co-infections in pigs are very common, which often contribute to severe pneumonia and can increase the mortality.
+In the present study, co-infection experiments were performed using swine H1N1 influenza virus and Streptococcus suis serotype 2 (SS2).
+The H1N1-SS2 co-infected pigs exhibited more severe clinical symptoms, serious pathological changes, and robust apoptosis of lungs at 6 days post-infection compared with separate H1N1 and SS2 infections.
+A comprehensive gene expression profiling using a microarray approach was performed to investigate the global host responses of swine lungs against the swine H1N1 infection, SS2 infection, co-infection, and phosphate-buffered saline control.
+Results showed 457, 411, and 844 differentially expressed genes in the H1N1, SS2, and H1N1-SS2 groups, respectively, compared with the control.
+Noticeably, genes associated with the immune, inflammatory, and apoptosis responses were highly overexpressed in the co-infected group.
+Pathway analysis indicated that the cytokine–cytokine receptor interactions, MAPK, toll-like receptor, complement and coagulation cascades, antigen processing and presentation, and apoptosis pathway were significantly regulated in the co-infected group.
+However, the genes related to these were less regulated in the separate H1N1 and SS2 infection groups.
+This observation suggested that a certain level of synergy was induced by H1N1 and SS2 co-infection with significantly stronger inflammatory and apoptosis responses, which may lead to more serious respiratory disease syndrome and pulmonary pathological lesion.
+Here, we investigated four members of the fibroblast growth factor receptor (FGFR) family; FGFR1 to 4, and examined their expression patterns in human lung epithelial cells A549 with influenza A virus infection.
+We identified a functional role of FGFR1 in influenza A/Puerto Rico/8/1934 (PR8) and A/Anhui/01/2005 (H5N1) virus replication.
+Our results showed that FGFR1 silencing by siRNA interference promoted influenza A/PR8 and H5N1 virus replication in A549 cells, while lentivirus-mediated exogenous FGFR1 expression significantly suppressed influenza A virus replication; however, FGFR4 did not have the same effects.
+Moreover, FGFR1 phosphorylation levels were downregulated in A549 cells by influenza A virus infection, while the repression of FGFR1 kinase using PD173074, a potent and selective FGFR1 inhibitor, could enhance virus replication.
+Furthermore, we found that FGFR1 inhibits influenza virus internalization, but not binding, during viral entry.
+These results suggested that FGFR1 specifically antagonizes influenza A virus replication, probably by blocking viral entry.
+Mosquito-borne flaviviruses can persistently infect the mosquito central nervous system without causing dramatic pathology or influencing the mosquito behavior and lifespan.
+The mechanism by which the mosquito nervous system resists flaviviral infection is still largely unknown.
+Here we report that an Aedes aegypti homologue of the neural factor Hikaru genki (AaHig) efficiently restricts flavivirus infection of the central nervous system.
+AaHig was predominantly expressed in the mosquito nervous system and localized to the plasma membrane of neural cells.
+Functional blockade of AaHig enhanced Dengue virus (DENV) and Japanese encephalitis virus (JEV), but not Sindbis virus (SINV), replication in mosquito heads and consequently caused neural apoptosis and a dramatic reduction in the mosquito lifespan.
+Furthermore, the membrane-localized AaHig directly interfaced with a highly conserved motif in the surface envelope proteins of DENV and JEV, and consequently interrupted endocytic viral entry into mosquito cells.
+Interestingly, Culex pipien pallens Hig also demonstrated a prominent anti-flavivirus activity, suggesting a functionally conserved function for Hig.
+Our results demonstrate that an evolutionarily conserved antiviral mechanism prevents lethal flaviviral infection of the central nervous system in mosquitoes, and thus may facilitate flaviviral transmission in nature.
+There has been a dramatic increase in the number of insect-specific flaviviruses (ISFs) discovered in the last decade.
+Historically, these viruses have generated limited interest due to their inability to infect vertebrate cells.
+This viewpoint has changed in recent years because some ISFs have been shown to enhance or suppress the replication of medically important flaviviruses in co-infected mosquito cells.
+Additionally, comparative studies between ISFs and medically important flaviviruses can provide a unique perspective as to why some flaviviruses possess the ability to infect and cause devastating disease in humans while others do not.
+ISFs have been isolated exclusively from mosquitoes in nature but the detection of ISF-like sequences in sandflies and chironomids indicates that they may also infect other dipterans.
+The first group currently consists of approximately 12 viruses and includes cell fusing agent virus, Kamiti River virus and Culex flavivirus.
+The second group, which is apparently not monophyletic, currently consists of nine viruses and includes Chaoyang virus, Nounané virus and Lammi virus.
+This article provides a review of the discovery, host range, mode of transmission, superinfection exclusion ability and genomic organization of ISFs.
+This article also attempts to clarify the ISF nomenclature because some of these viruses have been assigned more than one name due to their simultaneous discoveries by independent research groups.
+BACKGROUND: Sepsis is now the leading cause of death in the non-cardiovascular intensive care unit (ICU).
+Recent research suggests that sepsis is likely to be due to an interaction between genetic and environmental factors.
+Genetic mutations of toll-like receptor 4 (TLR4) and cluster of differentiation 14 (CD14) genes are involved in the immune and (or) inflammatory response.
+This study was designed to evaluate whether the TLR4 and cluster CD14 gene polymorphisms are associated with susceptibility to sepsis.
+METHODS: The single nucleotide polymorphisms (SNPs) of TLR4 (rs10759932, rs11536889, rs7873784, rs12377632, rs1927907, rs1153879) and CD14 (rs2569190 and rs2563298) in patients with sepsis and control subjects in the Guangxi Province were analyzed by using the polymerase chain reaction-single base extension (PCR-SBE) and DNA sequencing methods.
+RESULTS: The rs11536889 polymorphism in TLR4 and rs2563298 polymorphism in CD14 were significantly associated with the risk of sepsis when compared to the control group.
+The frequencies of rs11536889 and rs2563298 polymorphisms in the group with sepsis were higher than that in the control group (OR = 1.430, 95% CI, 1.032-1.981, P<0.05; OR = 2.454, 95% CI, 1.458-4.130, P<0.05, respectively).
+Followed up haplotype analysis suggested that there were two haplotypes in which increased risk factors for sepsis were indicated.
+CONCLUSIONS: The rs11536889 polymorphism in TLR4 and rs2563298 polymorphism in CD14, and two haplotypes were associated with increased susceptibility to sepsis.
+The use of vaccination against the influenza virus remains the most effective method of mitigating the significant morbidity and mortality caused by this virus.
+Antibodies elicited by currently licensed influenza vaccines are predominantly hemagglutination-inhibition (HI)-competent antibodies that target the globular head of hemagglutinin (HA) thus inhibiting influenza virus entry into target cells.
+However, recent academia or pharma-led R&D toward the production of a “universal vaccine” has centered on the elicitation of antibodies directed against the stalk of the influenza HA that has been shown to confer broad protection across a range of different subtypes (H1–H16).
+The accurate and sensitive measurement of antibody responses elicited by these “next-generation” influenza vaccines is, however, hampered by the lack of sensitivity of the traditional influenza serological assays HI, single radial hemolysis, and microneutralization.
+Assays utilizing pseudotypes, chimeric viruses bearing influenza glycoproteins, have been shown to be highly efficient for the measurement of homosubtypic and heterosubtypic broadly neutralizing antibodies, making them ideal serological tools for the study of cross-protective responses against multiple influenza subtypes with pandemic potential.
+In this review, we will analyze and compare literature involving the production of influenza pseudotypes with particular emphasis on their use in serum antibody neutralization assays.
+This will enable us to establish the parameters required for optimization and propose a consensus protocol to be employed for the further deployment of these assays in influenza vaccine immunogenicity studies.
+We describe the production and characterization of human monoclonal antibodies (mAb) specific for the major hepatitis B virus (HBV) S protein.
+The mAbs, two IgG1κ and one IgG1λ, were secreted by B-cell clones obtained from peripheral blood mononuclear cells (PBMC) of one person convalescent from acute hepatitis B and one vaccinated individual.
+The former recognized a denaturation-insensitive epitope within the p24 protein whereas the latter recognized a denaturation-sensitive, conformational epitope located within the HBsAg common “a” determinant.
+This mAb, denominated ADRI-2F3, displayed a very high protective titer of over 43,000 IU/mg mAb and showed an extremely potent neutralizing activity in the in vitro model of HBV infection using primary hepatocytes from Tupaia belangeri as target.
+Recombinant variable heavy and light domain sequences derived from mAb ADRI-2F3 were cloned into eukaryotic expression vectors and showed identical fine specificity and 1 log(10) higher titer than the original IgG1λ.
+It is envisaged that such mAb will be able to efficiently prevent HBV reinfection after liver transplantation for end-stage chronic HBV infection or infection after needle-stick exposure, providing an unlimited source of valuable protective anti-HBs antibody.
+Porcine reproductive and respiratory syndrome virus (PRRSV) is a major threat to the swine industry and food security worldwide.
+The primary function of this protein is to encapsidate the viral RNA genome, and it is also thought to participate in the modulation of host cell biology and recruitment of cellular factors to facilitate virus infection.
+In order to the better understand these latter roles the cellular interactome of PRRSV N protein was defined using label free quantitative proteomics.
+This identified several cellular factors that could interact with the N protein including poly [ADP-ribose] polymerase 1 (PARP-1), a cellular protein, which can add adenosine diphosphate ribose to a protein.
+Use of the PARP-1 small molecule inhibitor, 3-AB, in PRRSV infected cells demonstrated that PARP-1 was required and acted as an enhancer factor for virus biology.
+Serial growth of PRRSV in different concentrations of 3-AB did not yield viruses that were able to grow with wild type kinetics, suggesting that by targeting a cellular protein crucial for virus biology, resistant phenotypes did not emerge.
+This study provides further evidence that cellular proteins, which are critical for virus biology, can also be targeted to ablate virus growth and provide a high barrier for the emergence of drug resistance.
+BACKGROUND: Swine influenza virus (SIV) is the cause of an acute respiratory disease that affects swine worldwide.
+After the emergence of pandemic H1N1 in 2009 (H1N1pdm09), few studies reported the presence of influenza virus in Brazilian herds.
+OBJECTIVES: The objective of this study was to evaluate the serological profile for influenza virus in farrow-to-finish pig farms in Minas Gerais state, Brazil.
+METHODS: Thirty farms with no SIV vaccination history were selected from the four larger pig production areas in Minas Gerais state (Zona da Mata, Triângulo Mineiro/Alto Paranaíba, South/Southwest and the Belo Horizonte metropolitan area).
+At each farm, blood samples were randomly collected from 20 animals in each production cycle category: breeding animals (sows and gilts), farrowing crate (2–3 weeks), nursery (4–7 weeks), grower pigs (8–14 weeks), and finishing pigs (15–16 weeks), with 100 samples per farm and a total of 3000 animals in this study.
+The samples were tested for hemagglutination inhibition activity against H1N1 pandemic strain (A/swine/Brazil/11/2009) and H3N2 SIV (A/swine/Iowa/8548-2/98) reference strain.
+RESULTS: The percentages of seropositive animals for H1N1pdm09 and H3N2 were 26·23% and 1·57%, respectively, and the percentages of seropositive herds for both viruses were 96·6% and 13·2%, respectively.
+CONCLUSIONS: The serological profiles differed for both viruses and among the studied areas, suggesting a high variety of virus circulation around the state, as well as the presence of seronegative animals susceptible to influenza infection and, consequently, new respiratory disease outbreaks.
+It is well established that trans-placental transmission of classical swine fever virus (CSFV) during mid-gestation can lead to persistently infected offspring.
+The aim of the present study was to evaluate the ability of CSFV to induce viral persistence upon early postnatal infection.
+Two litters of 10 piglets each were infected intranasally on the day of birth with low and moderate virulence CSFV isolates, respectively.
+During six weeks after postnatal infection, most of the piglets remained clinically healthy, despite persistent high virus titres in the serum.
+Four weeks after infection, PBMCs from the persistently infected seronegative piglets were unresponsive to both, specific CSFV and non-specific PHA stimulation in terms of IFN-γ-producing cells.
+These results suggested the development of a state of immunosuppression in these postnatally persistently infected pigs.
+Nevertheless, despite the addition of the anti-IL-10 antibody in the PBMC culture from persistently infected piglets, the response of the IFN-γ producing cells was not restored.
+Therefore, other factors than IL-10 may be involved in the general suppression of the T-cell responses upon CSFV and mitogen activation.
+Interestingly, bone marrow immature granulocytes were increased and targeted by the virus in persistently infected piglets.
+Taken together, we provided the first data demonstrating the feasibility of CSFV in generating a postnatal persistent disease, which has not been shown for other members of the Pestivirus genus yet.
+Since serological methods are routinely used in CSFV surveillance, persistently infected pigs might go unnoticed.
+In addition to the epidemiological and economic significance of persistent CSFV infection, this model could be useful for understanding the mechanisms of viral persistence.
+This paper establishes reference ranges for hematologic and plasma biochemistry values in wild Black flying-foxes (Pteropus alecto) captured in South East Queensland, Australia.
+Four hundred and forty-seven animals were sampled over 12 months and significant differences were found between age, sex, reproductive and body condition cohorts in the sample population.
+Mean values for each cohort fell within the determined normal adult reference range, with the exception of elevated levels of alkaline phosphatase in juvenile animals.
+Hematologic and biochemistry parameters of injured animals showed little or no deviation from the normal reference values for minor injuries, while two animals with more severe injury or abscessation showed leucocytosis, anaemia, thrombocytosis, hyperglobulinemia and hypoalbuminemia.
+BACKGROUND: Understanding viral etiology and age-specific incidence of acute respiratory infections in infants can help identify risk groups and inform vaccine delivery, but community-based data is lacking from tropical settings.
+METHODS: One thousand four hundred and seventy-eight infants in urban Ho Chi Minh City and 981 infants in a semi-rural district in southern Vietnam were enrolled at birth and followed to 1 year of age.
+Acute respiratory infection (ARI) episodes were identified through clinic-based illness surveillance, hospital admissions and self-reports.
+Nasopharyngeal swabs were collected from infants with respiratory symptoms and tested for 14 respiratory pathogens using multiplex reverse transcription-polymerase chain reaction.
+RESULTS: Estimated incidence of ARI was 542 and 2691 per 1000 infant-years, and hospitalization rates for ARI were 81 and 138 per 1000 infant-years, in urban and semi-rural cohorts, respectively, from clinic- and hospital-based surveillance.
+However self-reported ARI episodes were just 1.5-fold higher in the semi-rural versus urban cohort, indicating that part of the urban–rural difference was explained by under-ascertainment in the urban cohort.
+Incidence was higher in infants ≥6 months of age than <6 months, but this was pathogen-specific.
+One or more viruses were detected in 53% (urban) and 64% (semi-rural) of samples from outpatients with ARI and in 78% and 66% of samples from hospitalized ARI patients, respectively.
+The most frequently detected viruses were rhinovirus, respiratory syncytial virus, influenza virus A and bocavirus.
+ARI-associated hospitalizations were associated with longer stays and more frequent ICU admission than other infections.
+CONCLUSIONS: ARI is a significant cause of morbidity in Vietnamese infants and influenza virus A is an under-appreciated cause of vaccine-preventable disease and hospitalizations in this tropical setting.
+There is a prevailing view, however, that the general public is resistant to communications on pandemic influenza and that behavioural responses to the 2009/10 H1N1 pandemic were not sufficient.
+Using qualitative methods, this paper investigates how members of the general public respond to pandemic influenza and the hygiene, social isolation and other measures proposed by public health.
+Going beyond the commonly deployed notion that the general public is resistant to public health communications, this paper examines how health individualism, gender and real world constraints enable and limit individual action.
+METHODS: In-depth interviews (n = 57) and focus groups (ten focus groups; 59 individuals) were conducted with community samples in Melbourne, Sydney and Glasgow.
+Participants were selected according to maximum variation sampling using purposive criteria, including: 1) pregnancy in 2009/2010; 2) chronic illness; 3) aged 70 years and over; 4) no disclosed health problems.
+RESULTS: Respondents did not express resistance to public health communications, but gave insight into how they interpreted and implemented guidance.
+The uptake of hygiene, social isolation and vaccine strategies was constrained by seeing oneself ‘at risk’ but not ‘a risk’ to others.
+Other challenges pertained to over-reliance on perceived remoteness from risk, expectation of recovery from infection and practical constraints on the uptake of vaccination.
+CONCLUSIONS: Overall, respondents were engaged with public health advice regarding pandemic influenza, indicating that the idea of public resistance has limited explanatory power.
+Individualistic approaches to pandemic risk inhibit acting for the benefit of others and may deepen divisions in the community according to health status.
+Public communications on pandemics are mediated by gender norms that may overburden women and limit the action of men.
+Social research on the public response to pandemics needs to focus on the social structures and real world settings and relationships that shape the action of individuals.
+A diverse subset of pattern recognition receptors (PRRs) detects pathogen-associated nucleic acids to initiate crucial innate immune responses in host organisms.
+Reflecting their importance for host defense, pathogens encode various countermeasures to evade or inhibit these immune effectors.
+PRRs directly engaged by pathogen inhibitors often evolve under recurrent bouts of positive selection that have been described as molecular ‘arms races.’ Cyclic GMP-AMP synthase (cGAS) was recently identified as a key PRR.
+Upon binding cytoplasmic double-stranded DNA (dsDNA) from various viruses, cGAS generates the small nucleotide secondary messenger cGAMP to signal activation of innate defenses.
+Here we report an evolutionary history of cGAS with recurrent positive selection in the primate lineage.
+Recent studies indicate a high degree of structural similarity between cGAS and 2’-5’-oligoadenylate synthase 1 (OAS1), a PRR that detects double-stranded RNA (dsRNA), despite low sequence identity between the respective genes.
+We present comprehensive comparative evolutionary analysis of cGAS and OAS1 primate sequences and observe positive selection at nucleic acid binding interfaces and distributed throughout both genes.
+Our data revealed homologous regions with strong signatures of positive selection, suggesting common mechanisms employed by unknown pathogen encoded inhibitors and similar modes of evasion from antagonism.
+Our analysis of cGAS diversification also identified alternately spliced forms missing multiple sites under positive selection.
+Further analysis of selection on the OAS family in primates, which comprises OAS1, OAS2, OAS3 and OASL, suggests a hypothesis where gene duplications and domain fusion events result in paralogs that provide another means of escaping pathogen inhibitors.
+Together our comparative evolutionary analysis of cGAS and OAS provides new insights into distinct mechanisms by which key molecular sentinels of the innate immune system have adapted to circumvent viral-encoded inhibitors.
+Understanding how a pathogen colonizes and adapts to a new host environment is a primary aim in studying emerging infectious diseases.
+Adaptive mutations arise among the thousands of variants generated during RNA virus infection, and identifying these variants will shed light onto how changes in tropism and species jumps can occur.
+Using deep sequencing and bioinformatics, we identified a multi-step adaptive process to adaptation involving residues in the receptor footprints that correlated with receptor availability and with increase in virus fitness in an environment-specific manner.
+We show that adaptation occurs by selection of a dominant mutation followed by group selection of minority variants that together, confer the fitness increase observed in the population, rather than selection of a single dominant genotype.
+The contact system, also named as plasma kallikrein-kinin system, consists of three serine proteinases: coagulation factors XII (FXII) and XI (FXI), and plasma prekallikrein (PK), and the nonenzymatic cofactor high molecular weight kininogen (HK).
+The components of this system and their interactions have been elucidated from in vitro experiments, which indicates that this system is prothrombotic by activating intrinsic pathway, and proinflammatory by producing bioactive peptide bradykinin.
+Although the activation of the contact system have been implicated in various types of human disease, in only a few instances is its role clearly defined.
+In the last 10 years, our understanding of the contact system, particularly its biology and (patho)physiology has greatly increased through investigations using gene-modified animal models.
+In this review we will describe a revitalized view of the contact system as a critical (patho)physiologic mediator of coagulation and inflammation.
+Ribosomal RNA (rRNA) gene (rDNA) transcription by RNA Polymerase I (Pol I) drives cell growth and underlies nucleolar structure and function, indirectly coordinating many fundamental cellular processes.
+The importance of keeping rDNA transcription under tight control is reflected by the fact that deranged Pol I transcription is a feature of cancer and other human disorders.
+In this review, we discuss multiple aspects of rDNA function including the relationship between Pol I transcription and proliferative capacity, the role of Pol I transcription in mediating nucleolar structure and integrity, and rDNA/nucleolar interactions with the genome and their influence on heterochromatin and global genome stability.
+Furthermore, we discuss how perturbations in the structure of the rDNA loci might contribute to human disease, in some cases independent of effects on ribosome biogenesis.
+BACKGROUND: Infectious bursal disease (IBD) is a highly contagious and acute viral disease, which has caused high mortality rates in birds and considerable economic losses in different parts of the world for more than two decades and it still represents a considerable threat to poultry.
+The current study was designed to rigorously measure the reliability of a phylogenetic marker included into segment B.
+This marker can facilitate molecular epidemiology studies, incorporating this segment of the viral genome, to better explain the links between emergence, spreading and maintenance of the very virulent IBD virus (vvIBDV) strains worldwide.
+METHODOLOGY/PRINCIPAL FINDINGS: Sequences of the segment B gene from IBDV strains isolated from diverse geographic locations were obtained from the GenBank Database; Cuban sequences were obtained in the current work.
+A phylogenetic marker named B-marker was assessed by different phylogenetic principles such as saturation of substitution, phylogenetic noise and high consistency.
+This last parameter is based on the ability of B-marker to reconstruct the same topology as the complete segment B of the viral genome.
+From the results obtained from B-marker, demographic history for both main lineages of IBDV regarding segment B was performed by Bayesian skyline plot analysis.
+Phylogenetic analysis for both segments of IBDV genome was also performed, revealing the presence of a natural reassortant strain with segment A from vvIBDV strains and segment B from non-vvIBDV strains within Cuban IBDV population.
+CONCLUSIONS/SIGNIFICANCE: This study contributes to a better understanding of the emergence of vvIBDV strains, describing molecular epidemiology of IBDV using the state-of-the-art methodology concerning phylogenetic reconstruction.
+This study also revealed the presence of a novel natural reassorted strain as possible manifest of change in the genetic structure and stability of the vvIBDV strains.
+Therefore, it highlights the need to obtain information about both genome segments of IBDV for molecular epidemiology studies.
+Drak2(-/-) mice are resistant to autoimmunity in mouse models of type 1 diabetes and multiple sclerosis.
+Resistance to these diseases occurs, in part, because Drak2 is required for the survival of autoreactive T cells that induce disease.
+However, the molecular mechanisms by which Drak2 affects T cell survival and autoimmunity are not known.
+A recent report demonstrated that Drak2 negatively regulated transforming growth factor-β (TGF-β) signaling in tumor cell lines.
+Thus, increased TGF-β signaling in the absence of Drak2 may contribute to the resistance to autoimmunity in Drak2(-/-) mice.
+Therefore, we examined if Drak2 functioned as a negative regulator of TGF-β signaling in T cells, and whether the enhanced susceptibility to death of Drak2(-/-) T cells was due to augmented TGF-β signaling.
+Using several in vitro assays to test TGF-β signaling and T cell function, we found that activation of Smad2 and Smad3, which are downstream of the TGF-β receptor, was similar between wildtype and Drak2(-/-) T cells.
+Furthermore, TGF-β-mediated effects on naïve T cell proliferation, activated CD8(+) T cell survival, and regulatory T cell induction was similar between wildtype and Drak2(-/-) T cells.
+Finally, the increased susceptibility to death in the absence of Drak2 was not due to enhanced TGF-β signaling.
+Together, these data suggest that Drak2 does not function as a negative regulator of TGF-β signaling in primary T cells stimulated in vitro.
+It is important to investigate and discern potential molecular mechanisms by which Drak2 functions in order to better understand the etiology of autoimmune diseases, as well as to validate the use of Drak2 as a target for therapeutic treatment of these diseases.
+Small exogenous noncoding RNAs (ncRNAs) such as siRNA and shRNA are the active silencing agents, intended to target and cleave complementary mRNAs in a specific way.
+They are widely and successfully employed in functional studies, and several ongoing and already completed siRNA-based clinical trials suggest encouraging results in the regulation of overexpressed genes in disease.
+siRNAs share many aspects of their biogenesis and function with miRNAs, small ncRNA molecules transcribed from endogenous genes which are able to repress the expression of target mRNAs by either inhibiting their translation or promoting their degradation.
+Although siRNA and artificial miRNA molecules can significantly reduce the expression of overexpressed target genes, cancer and other diseases can also be triggered or sustained by upregulated miRNAs.
+Thus, in the past recent years, molecular tools for miRNA silencing, such as antagomiRs and miRNA sponges, have been developed.
+These molecules have shown their efficacy in the derepression of genes downregulated by overexpressed miRNAs.
+In particular, while a single antagomiR is able to inhibit a single complementary miRNA, an artificial sponge construct usually contains one or more binding sites for one or more miRNAs and functions by competing with the natural targets of these miRNAs.
+In this chapter we review the most successful methods for the computational design of siRNAs, antagomiRs, and miRNA sponges and describe the most popular tools that implement them.
+BACKGROUND: The growth potential of the tumor-like Echinococcus multilocularis metacestode (causing alveolar echinococcosis, AE) is directly linked to the nature/function of the periparasitic host immune-mediated processes.
+We previously showed that Fibrinogen-like-protein 2 (FGL2), a novel CD4(+)CD25(+) Treg effector molecule, was over-expressed in the liver of mice experimentally infected with E. multilocularis.
+However, little is known about its contribution to the control of this chronic helminth infection.
+METHODS/FINDINGS: Key parameters for infection outcome in E. multilocularis-infected fgl2(-/-) (AE-fgl2(-/-)) and wild type (AE-WT) mice at 1 and 4 month(s) post-infection were (i) parasite load (i. e. wet weight of parasitic metacestode tissue), and (ii) parasite cell proliferation as assessed by determining E. multilocularis 14-3-3 gene expression levels.
+Spleen cells cultured with ConA for 48h or with E. multilocularis Vesicle Fluid (VF) for 96h were analyzed ex-vivo and in-vitro.
+In addition, spleen cells from non-infected WT mice were cultured with rFGL2/anti-FGL2 or rIL-17A/anti-IL-17A for further functional studies.
+For Treg-immune-suppression-assays, purified CD4(+)CD25(+) Treg suspensions were incubated with CD4(+) effector T cells in the presence of ConA and irradiated spleen cells as APCs.
+Flow cytometry and qRT-PCR were used to assess Treg, Th17-, Th1-, Th2-type immune responses and maturation of dendritic cells.
+We showed that AE-fgl2(-/-) mice exhibited (as compared to AE-WT-animals) (a) a significantly lower parasite load with reduced proliferation activity, (b) an increased T cell proliferative response to ConA, (c) reduced Treg numbers and function, and (d) a persistent capacity of Th1 polarization and DC maturation.
+CONCLUSIONS: FGL2 appears as one of the key players in immune regulatory processes favoring metacestode survival by promoting Treg cell activity and IL-17A production that contributes to FGL2-regulation.
+Prospectively, targeting FGL2 could be an option to develop an immunotherapy against AE and other chronic parasitic diseases.
+The detection of West Nile virus (WNV) nucleic acid in a blood donation from Vienna, Austria, as well as in Culex pipiens pupae and egg rafts, sampled close to the donor’s residence, is reported.
+Complete genomic sequences of the human- and mosquito-derived viruses were established, genetically compared and phylogenetically analyzed.
+The viruses were not identical, but closely related to each other and to recent Czech and Italian isolates, indicating co-circulation of related WNV strains within a confined geographic area.
+The detection of WNV in a blood donation originating from an area with low WNV prevalence in humans (only three serologically diagnosed cases between 2008 and 2014) is surprising and emphasizes the importance of WNV nucleic acid testing of blood donations even in such areas, along with active mosquito surveillance programs.
+Avian influenza (AI) is an infectious disease caused by avian influenza viruses (AIVs) which belong to the influenza virus A group.
+AI causes tremendous economic losses in poultry industry and pose great threatens to human health.
+In this study, a protein microarray using nucleoprotein (NP) of H5N1 AIV expressed in insect cells was developed to detect antibodies against AIV NP protein.
+The protein microarray was used to test Newcastle disease virus (NDV), infectious bursal disease virus (IBDV), AIV positive and negative sera.
+The results indicated that the protein microarray could hybridize specifically with antibodies against AIV with strong signals and without cross-hybridization.
+Moreover, 76 field serum samples were detected by microarray, enzyme-linked immunosorbent assay (ELISA) and hemagglutination inhibition test (HI).
+The positive rate was 92.1% (70/76), 93.4% (71/76) and 89.4% (68/76) by protein microarray, ELISA and HI test, respectively.
+Compared with ELISA, the microarray showed 100% (20/20) agreement ratio in chicken and 98.2% (55/56) in ornamental bird.
+In conclusion, this method provides an alternative serological diagnosis for influenza antibody screening and will provide a basis for the development of protein microarrays that can be used to respectively detect antibodies of different AIV subtypes and other pathogens.
+Macrophage-derived chemokine, C-C motif chemokine 22 (MDC/CCL22), is one of the inflammatory chemokines that controls the movement of monocytes, monocyte-derived dendritic cells, and natural killer cells.
+Serum and skin MDC/CCL22 levels are elevated in atopic dermatitis, which suggests that the chemokines produced from keratinocytes are responsible for attracting inflammatory lymphocytes to the skin.
+A major signaling pathway in the interferon-γ (IFN-γ)-stimulated inflammation response involves the signal transducers and activators of transcription 1 (STAT1).
+In the present study, we investigated the anti-inflammatory effect of dieckol and its possible action mechanisms in the category of skin inflammation including atopic dermatitis.
+The high burden of respiratory syncytial virus (RSV)-associated morbidity and mortality makes vaccine development a priority.
+As part of an efficacy trial of pandemic influenza vaccines (NCT01051661), RSV epidemiology in healthy children aged 6 months to <10 years at first vaccination with influenza-like illness (ILI) was evaluated in Australia, Brazil, Colombia, Costa Rica, Mexico, the Philippines, Singapore, and Thailand between February 2010 and August 2011.
+Active surveillance for ILI was conducted for approximately 1 year, with nasal and throat swabs analyzed by polymerase chain reaction.
+A total of 6266 children were included, of whom 2421 experienced 3717 ILI episodes with a respiratory sample available.
+RSV was detected for 359 ILI episodes, a prevalence of 9.7% (95% confidence interval: 8.7–10.7).
+The highest prevalence was in children aged 12–23 or 24–35 months in all countries except the Philippines, where it was in children aged 6–11 months.
+Eighty-eight ILI episodes resulted in hospitalization, of which 8 were associated with RSV (prevalence 9.1% [4.0–17.1]; incidence 0.2 [0.1–0.3] per 100 PY).
+The incidence of RSV-associated ILI resulting in medical attendance was 6.0 (5.4–6.7) per 100 PY.
+Active surveillance demonstrated the considerable burden of RSV-associated illness that would not be identified through hospital-based surveillance, with a substantial part of the burden occurring in older infants and children.
+The seasonality of influenza virus infections in temperate climates and the role of environmental conditions like temperature and humidity in the transmission of influenza virus through the air are not well understood.
+Using ferrets housed at four different environmental conditions, we evaluated the respiratory droplet transmission of two influenza viruses (a seasonal H3N2 virus and an H3N2 variant virus, the etiologic virus of a swine to human summertime infection) and concurrently characterized the aerosol shedding profiles of infected animals.
+Comparisons were made among the different temperature and humidity conditions and between the two viruses to determine if the H3N2 variant virus exhibited enhanced capabilities that may have contributed to the infections occurring in the summer.
+We report here that although increased levels of H3N2 variant virus were found in ferret nasal wash and exhaled aerosol samples compared to the seasonal H3N2 virus, enhanced respiratory droplet transmission was not observed under any of the environmental settings.
+However, overall environmental conditions were shown to modulate the frequency of influenza virus transmission through the air.
+Transmission occurred most frequently at 23°C/30%RH, while the levels of infectious virus in aerosols exhaled by infected ferrets agree with these results.
+Improving our understanding of how environmental conditions affect influenza virus infectivity and transmission may reveal ways to better protect the public against influenza virus infections.
+Infectious diseases are one of the leading causes of morbidity and mortality around the world; thus, forecasting their impact is crucial for planning an effective response strategy.
+According to the Centers for Disease Control and Prevention (CDC), seasonal influenza affects 5% to 20% of the U.S. population and causes major economic impacts resulting from hospitalization and absenteeism.
+Understanding influenza dynamics and forecasting its impact is fundamental for developing prevention and mitigation strategies.
+We combine modern data assimilation methods with Wikipedia access logs and CDC influenza-like illness (ILI) reports to create a weekly forecast for seasonal influenza.
+The methods are applied to the 2013-2014 influenza season but are sufficiently general to forecast any disease outbreak, given incidence or case count data.
+We adjust the initialization and parametrization of a disease model and show that this allows us to determine systematic model bias.
+In addition, we provide a way to determine where the model diverges from observation and evaluate forecast accuracy.
+Wikipedia article access logs are shown to be highly correlated with historical ILI records and allow for accurate prediction of ILI data several weeks before it becomes available.
+The results show that prior to the peak of the flu season, our forecasting method produced 50% and 95% credible intervals for the 2013-2014 ILI observations that contained the actual observations for most weeks in the forecast.
+However, since our model does not account for re-infection or multiple strains of influenza, the tail of the epidemic is not predicted well after the peak of flu season has passed.
+Reticuloendotheliosis virus (REV), a member of the Gammaretrovirus genus in the Retroviridae family, causes an immunosuppressive, oncogenic and runting-stunting syndrome in multiple avian hosts.
+To better understand the host interactions at the transcriptional level, microarray data analysis was performed in chicken embryo fibroblast cells at 1, 3, 5, and 7 days after infection with REV.
+This study identified 1,785 differentially expressed genes that were classified into several functional groups including signal transduction, immune response, biological adhesion and endocytosis.
+Significant differences were mainly observed in the expression of genes involved in the immune response, especially during the later post-infection time points.
+These results revealed that differentially expressed genes IL6, STAT1, MyD88, TLRs, NF-κB, IRF-7, and ISGs play important roles in the pathogenicity of REV infection.
+Our study is the first to use microarray analysis to investigate REV, and these findings provide insights into the underlying mechanisms of the host antiviral response and the molecular basis of viral pathogenesis.
+This is partly due to the absence of a highly sensitive assay to measure individual species of arenavirus replicative RNAs.
+To overcome this obstacle, we designed a quantitative reverse transcription (RT)-PCR assay for selective quantitation of each of the lymphocytic choriomeningitis virus (LCMV) genomic or antigenomic RNAs.
+During the course of assay design, we identified a nonspecific priming phenomenon whereby, in the absence of an RT primer, cDNAs complementary to each of the LCMV replicative RNA species are generated during RT.
+We successfully circumvented this nonspecific priming event through the use of biotinylated primers in the RT reaction, which permitted affinity purification of primer-specific cDNAs using streptavidin-coated magnetic beads.
+As proof of principle, we used the assay to map the dynamics of LCMV replication at acute and persistent time points and to determine the quantities of genomic and antigenomic RNAs that are incorporated into LCMV particles.
+This assay can be adapted to measure total S or L segment-derived viral RNAs and therefore represents a highly sensitive diagnostic platform to screen for LCMV infection in rodent and human tissue samples and can also be used to quantify virus-cell attachment.
+Dickkopf-1 (DKK1), a secretory inhibitor of canonical Wnt signaling, plays a critical role in certain bone loss diseases.
+Studies have shown that serum levels of DKK1 are significantly higher in rheumatoid arthritis (RA) patients and are correlated with the severity of the disease, which indicates the possibility that bone erosion in RA may be inhibited by neutralizing the biological activity of DKK1.
+In this study, we selected a panel of twelve peptides using the software DNASTAR 7.1 and screened high affinity and immunogenicity epitopes in vitro and in vivo assays.
+Furthermore, we optimized four B cell epitopes to design a novel DKK1 multiepitope DNA vaccine and evaluated its bone protective effects in collagen-induced arthritis (CIA), a mouse model of RA.
+In addition, intramuscular immunization of BALB/c mice with this vaccine was also highly expressed and sufficient to induce the production of long-term IgG, which neutralized natural DKK1 in vivo.
+Importantly, this vaccine significantly attenuated bone erosion in CIA mice compared with positive control mice.
+These results provide evidence for the development of a DNA vaccine targeted against DKK1 to attenuate bone erosion.
+INTRODUCTION: Human infection with avian influenza A (H7N9) virus was first reported on March, 2013 in the Yangtze River Delta region of China.
+The majority of human cases were detected in mainland China; other regions out of mainland China reported imported human cases, including Hong Kong SAR, Taiwan (the Republic of China) and Malaysia, due to human transportation.
+Here, we report the first human case of H7N9 infection imported into Guizhou Province during the Spring Festival travel season in January 2014.
+CASE PRESENTATION: In early January 2014, a 38-year-old healthy Chinese man, a migrant worker returning from previously H7N9-affected Zhejiang Province, was identified as the first human case of infection with avian influenza A(H7N9) virus in Guizhou Province.
+He developed fever in Zhejiang at the beginning of January 2014, and returned to Guizhou for the Chinese New Year the next day.
+He went to seek medical care, but deteriorated rapidly and died on day 8 after his illness onset.
+The influenza virus A/Guizhou/01502/2014 isolated from the patient had 99% identity with viruses circulating in the Yangtze River Delta region.
+Selected amino acids substitutions, well-known to be associated with mammalian adaptation, viral replication and drug resistance were similar to other H7N9 viruses circulating in humans.
+CONCLUSIONS: Epidemiology investigation and laboratory results confirmed it was the first imported case of H7N9 infection in Guizhou Province.
+This finding further indicated that more human H7N9 cases may be detected in other regions due to frequent travel both domestically and internationally.
+The use of immunomodulatory agents such as statins to target host inflammatory responses in influenza virus infection has been suggested as an adjunct treatment, especially during pandemics, when antiviral quantities are limited or vaccine production can be delayed.
+We used population-based, influenza hospitalization surveillance data, propensity score-matched analysis, and Cox regression to determine whether there was an association between mortality (within 30 days of a positive influenza test) and statin treatment among hospitalized cohorts from 2 influenza seasons (October 1, 2007 to April 30, 2008 and September 1, 2009 to April 31, 2010).
+Hazard ratios for death within the 30-day follow-up period were 0.41 (95% confidence interval [CI], .25–.68) for a matched sample from the 2007–2008 season and 0.77 (95% CI, .43–1.36) for a matched sample from the 2009 pandemic.
+The analysis suggests a protective effect against death from influenza among patients hospitalized in 2007–2008 but not during the pandemic.
+This analysis does not support using statins as an adjunct treatment for preventing death among persons hospitalized for influenza.
+Arenaviruses are one of the largest families of human hemorrhagic fever viruses and are known to infect both mammals and snakes.
+For segmented RNA viruses like these, novel genotypes can be generated through mutation, recombination, and reassortment.
+Although it is believed that an ancient recombination event led to the emergence of a new lineage of mammalian arenaviruses, neither recombination nor reassortment has been definitively documented in natural arenavirus infections.
+Here, we used metagenomic sequencing to survey the viral diversity present in captive arenavirus-infected snakes.
+From 48 infected animals, we determined the complete or near complete sequence of 210 genome segments that grouped into 23 L and 11 S genotypes.
+The majority of snakes were multiply infected, with up to 4 distinct S and 11 distinct L segment genotypes in individual animals.
+This S/L imbalance was typical: in all cases intrahost L segment genotypes outnumbered S genotypes, and a particular S segment genotype dominated in individual animals and at a population level.
+We corroborated sequencing results by qRT-PCR and virus isolation, and isolates replicated as ensembles in culture.
+Numerous instances of recombination and reassortment were detected, including recombinant segments with unusual organizations featuring 2 intergenic regions and superfluous content, which were capable of stable replication and transmission despite their atypical structures.
+Overall, this represents intrahost diversity of an extent and form that goes well beyond what has been observed for arenaviruses or for viruses in general.
+This diversity can be plausibly attributed to the captive intermingling of sub-clinically infected wild-caught snakes.
+Thus, beyond providing a unique opportunity to study arenavirus evolution and adaptation, these findings allow the investigation of unintended anthropogenic impacts on viral ecology, diversity, and disease potential.
+A rapid, cost-effective diagnostic test for the detection of acute HIV-1 infection is highly desired.
+Isothermal amplification techniques, such as reverse-transcription loop-mediated isothermal amplification (RT-LAMP), exhibit characteristics that are ideal for the development of a rapid nucleic acid amplification test (NAAT) because they are quick, easy to perform and do not require complex, dedicated equipment and laboratory space.
+In this study, we assessed the ability of the HIV-1 RT-LAMP assay to detect acute HIV infection as compared to a representative rapid antibody test and several FDA-approved laboratory-based assays.
+The HIV-1 RT-LAMP assay detected seroconverting individuals one to three weeks earlier than a rapid HIV antibody test and up to two weeks earlier than a lab-based antigen/antibody (Ag/Ab) combo enzyme immunoassay (EIA).
+RT-LAMP was not as sensitive as a lab-based qualitative RNA assay, which could be attributed to the significantly smaller nucleic acid input volume.
+To our knowledge, this is the first demonstration of detecting acute HIV infection using the RT-LAMP assay.
+The availability of a rapid NAAT, such as the HIV-1 RT-LAMP assay, at the point of care (POC) or in laboratories that do not have access to large platform NAAT could increase the percentage of individuals who receive an acute HIV infection status or confirmation of their HIV status, while immediately linking them to counseling and medical care.
+In addition, early knowledge of HIV status could lead to reduced high-risk behavior at a time when individuals are at a higher risk for transmitting the virus.
+On oceanic islands, the ecology of IAV could be affected by the relative diversity, abundance and density of seabirds and ducks.
+Seabirds are the most abundant and widespread avifauna in the Western Indian Ocean and, in this region, oceanic islands represent major breeding sites for a large diversity of potential IAV host species.
+Based on serological assays, we assessed the host range of IAV and the virus subtype diversity in terns of the islands of the Western Indian Ocean.
+We further investigated the spatial variation in virus transmission patterns between islands and identified the origin of circulating viruses using a molecular approach.
+Our findings indicate that terns represent a major host for IAV on oceanic islands, not only for seabird-related virus subtypes such as H16, but also for those commonly isolated in wild and domestic ducks (H3, H6, H9, H12 subtypes).
+We also identified strong species-associated variation in virus exposure that may be associated to differences in the ecology and behaviour of terns.
+We discuss the role of tern migrations in the spread of viruses to and between oceanic islands, in particular for the H2 and H9 IAV subtypes.
+Francisella tularensis is classified as a Tier 1 select agent by the CDC due to its low infectious dose and the possibility that the organism can be used as a bioweapon.
+The low dose of infection suggests that Francisella is unusually efficient at evading host defenses.
+Although ~50 cfu are necessary to cause human respiratory infection, the early interactions of virulent Francisella with the lung environment are not well understood.
+To provide additional insights into these interactions during early Francisella infection of mice, we performed TEM analysis on mouse lungs infected with F. tularensis strains Schu S4, LVS and the O-antigen mutant Schu S4 waaY::TrgTn.
+For all three strains, the majority of the bacteria that we could detect were observed within alveolar type II epithelial cells at 16 hours post infection.
+Although there were no detectable differences in the amount of bacteria within an infected cell between the three strains, there was a significant increase in the amount of cellular debris observed in the air spaces of the lungs in the Schu S4 waaY::TrgTn mutant compared to either the Schu S4 or LVS strain.
+We also studied the interactions of Francisella strains with human AT-II cells in vitro by characterizing the ability of these three strains to invade and replicate within these cells.
+Gentamicin assay and confocal microscopy both confirmed that F. tularensis Schu S4 replicated robustly within these cells while F. tularensis LVS displayed significantly lower levels of growth over 24 hours, although the strain was able to enter these cells at about the same level as Schu S4 (1 organism per cell), as determined by confocal imaging.
+The Schu S4 waaY::TrgTn mutant that we have previously described as attenuated for growth in macrophages and mouse virulence displayed interesting properties as well.
+This mutant induced significant airway inflammation (cell debris) and had an attenuated growth phenotype in the human AT-II cells.
+These data extend our understanding of early Francisella infection by demonstrating that Francisella enter significant numbers of AT-II cells within the lung and that the capsule and LPS of wild type Schu S4 helps prevent murine lung damage during infection.
+Furthermore, our data identified that human AT-II cells allow growth of Schu S4, but these same cells supported poor growth of the attenuated LVS strain in vitro.
+Collectively, these data further our understanding of the role of AT-II cells in Francisella infections.
+A mainstream procedure to analyze the wealth of genomic data available nowadays is the detection of homologous regions shared across genomes, followed by the extraction of biological information from the patterns of conservation and variation observed in such regions.
+Although of pivotal importance, comparative genomic procedures that rely on homology inference are obviously not applicable if no homologous regions are detectable.
+This fact excludes a considerable portion of “genomic dark matter” with no significant similarity — and, consequently, no inferred homology to any other known sequence — from several downstream comparative genomic methods.
+In this review we compile several sequence metrics that do not rely on homology inference and can be used to compare nucleotide sequences and extract biologically meaningful information from them.
+These metrics comprise several compositional parameters calculated from sequence data alone, such as GC content, dinucleotide odds ratio, and several codon bias metrics.
+They also share other interesting properties, such as pervasiveness (patterns persist on smaller scales) and phylogenetic signal.
+We also cite examples where these homology-independent metrics have been successfully applied to support several bioinformatics challenges, such as taxonomic classification of biological sequences without homology inference.
+They where also used to detect higher-order patterns of interactions in biological systems, ranging from detecting coevolutionary trends between the genomes of viruses and their hosts to characterization of gene pools of entire microbial communities.
+We argue that, if correctly understood and applied, homology-independent metrics can add important layers of biological information in comparative genomic studies without prior homology inference.
+INTRODUCTION: Diffuse alveolar damage (DAD) is the pathological hallmark of acute respiratory distress syndrome (ARDS), however, the presence of DAD in the clinical criteria of ARDS patients by Berlin definition is little known.
+This study is designed to investigate the role of DAD in ARDS patients who underwent open lung biopsy.
+METHODS: We retrospectively reviewed all ARDS patients who met the Berlin definition and underwent open lung biopsy from January 1999 to January 2014 in a referred medical center.
+DAD is characterized by hyaline membrane formation, lung edema, inflammation, hemorrhage and alveolar epithelial cell injury.
+Clinical data including baseline characteristics, severity of ARDS, clinical and pathological diagnoses, and survival outcomes were analyzed.
+RESULTS: A total of 1838 patients with ARDS were identified and open lung biopsies were performed on 101 patients (5.5 %) during the study period.
+Of these 101 patients, the severity of ARDS on diagnosis was mild of 16.8 %, moderate of 56.5 % and severe of 26.7 %.
+The hospital mortality rate was not significant difference between the three groups (64.7 % vs 61.4 % vs 55.6 %, p = 0.81).
+Of the 101 clinical ARDS patients with open lung biopsies, 56.4 % (57/101) patients had DAD according to biopsy results.
+The proportion of DAD were 76.5 % (13/17) in mild, 56.1 % (32/57) in moderate and 44.4 % (12/27) in severe ARDS and there is no significant difference between the three groups (p = 0.113).
+Pathological findings of DAD patients had a higher hospital mortality rate than non-DAD patients (71.9 % vs 45.5 %, p = 0.007).
+Pathological findings of DAD (odds ratio: 3.554, 95 % CI, 1.385–9.12; p = 0.008) and Sequential Organ Failure Assessment score on the biopsy day (odds ratio: 1.424, 95 % CI, 1.187–1.707; p<0.001) were significantly and independently associated with hospital mortality.
+The baseline demographics and clinical characteristics were not significantly different between DAD and non-DAD patients.
+CONCLUSIONS: The correlation of pathological findings of DAD and ARDS diagnosed by Berlin definition is modest.
+A pathological finding of DAD in ARDS patients is associated with hospital mortality and there are no clinical characteristics that could identify DAD patients before open lung biopsy.
+BACKGROUND: The current standard care therapy for hepatitis C virus (HCV) infection consists of two regimes, namely interferon-based and interferon-free treatments.
+The treatment through the combination of ribavirin and pegylated interferon is expensive, only mildly effective, and is associated with severe side effects.
+In 2011, two direct-acting antiviral (DAA) drugs, boceprevir and telaprevir, were licensed that have shown enhanced sustained virologic response (SVR) in phase III clinical trial, however, these interferon-free treatments are more sensitive to HCV genotype 1 infection.
+The variable nature of HCV, and the limited number of inhibitors developed thus aim in expanding the repertoire of available drug targets, resulting in targeting the virus assembly therapeutically.
+AIM: We conducted this study to predict the 3D structure of the p7 protein from the HCV genotypes 3 and 4.
+Approximately 63 amino acid residues encoded in HCV render this channel sensitive to inhibitors, making p7 a promising target for novel therapies.
+HCV p7 protein forms a small membrane known as viroporin, and is essential for effective self-assembly of large channels that conduct cation assembly and discharge infectious virion particles.
+METHOD: In this study, we screened drugs and flavonoids known to disrupt translation and production of HCV proteins, targeted against the active site of p7 residues of HCV genotype 3 (GT3) (isolatek3a) and HCV genotype 4a (GT4) (isolateED43).
+RESULTS: The drug NB-DNJ formed the highest number of hydrogen bond interactions with both modeled p7 proteins with high interaction energy, followed by BIT225.
+A flavonoid screen demonstrated that Epigallocatechin gallate (EGCG), nobiletin, and quercetin, have more binding modes in GT3 than in GT4.
+Thus, the predicted p7 protein molecule of HCV from GT3 and GT4 provides a general avenue to target structure-based antiviral compounds.
+CONCLUSIONS: We hypothesize that the inhibitors of viral p7 identified in this screen may be a new class of potent agents, but further confirmation in vitro and in vivo is essential.
+This structure-guided drug design for both GT3 and GT4 can lead to the identification of drug-like natural compounds, confirming p7 as a new target in the rapidly increasing era of HCV.
+CD4(+) T follicular helper cells (T(FH)) in germinal centers are required for maturation of B-cells.
+While the role of T(FH)-cells has been studied in blood and lymph nodes of HIV-1 infected individuals, its role in the mucosal tissues has not been investigated.
+We show that the gut and female reproductive tract (FRT) of humanized DRAG mice have a high level of human lymphocytes and a high frequency of T(FH) (CXCR5(+)PD-1(++)) and precursor-T(FH) (CXCR5(+)PD-1(+)) cells.
+The majority of T(FH)-cells expressed CCR5 and CXCR3 and are the most permissive to HIV-1 infection.
+A single low-dose intravaginal HIV-1 challenge of humanized DRAG mice results in 100% infectivity with accumulation of T(FH)-cells mainly in the Peyer’s patches and FRT.
+The novel finding of T(FH)-cells in the FRT may contribute to the high susceptibility of DRAG mice to HIV-1 infection.
+This mouse model thus provides new opportunities to study T(FH)-cells and to evaluate HIV-1 vaccines.
+Ebola virus disease (EVD) outbreaks have occurred during the past 5 decades, but none has affected European countries like the 2014 epidemic in West Africa.
+We used an online questionnaire to investigate risk perceptions in Germany during this epidemic peak.
+Our questionnaire covered risk perceptions, knowledge about transmission routes, media use, reactions to the outbreak, attitudes toward measures to prevent the spread of EVD and vaccination against EVD, and willingness to volunteer for aid missions.
+Of 974 participants, 29% indicated that they worried about EVD, 4% correctly stated virus transmission routes, and 75% incorrectly rated airborne transmission and transmission by asymptomatic patients as possible.
+Many indicated that if a patient were flown to Germany for treatment in a nearby hospital, they would adapt preventive behavior.
+Although most participants were not worried about EVD at the current stage of the epidemic, misperceptions regarding transmission were common and could trigger inappropriate behavior changes.
+In a previous study, we demonstrated that oral immunization using Autographa californica baculovirus driving the expression of the Gal-lectin LC3 fragment (AcNPV-LC3) of Entamoeba histolytica conferred protection against ALA development in hamsters.
+In this study, we determined the ability of AcNPV-LC3 to protect against ALA by the intramuscular route as well as the liver immune response associated with protection.
+Results showed that 55% of hamsters IM immunized with AcNPV-LC3 showed sterile protection against ALA, whereas other 20% showed reduction in the size and extent of abscesses, resulting in some protection in 75% of animals compared to the sham control group.
+Levels of protection showed a linear correlation with the development and intensity of specific antiamoeba cellular and humoral responses, evaluated in serum and spleen of hamsters, respectively.
+Evaluation of the Th1/Th2 cytokine patterns expressed in the liver of hamsters showed that sterile protection was associated with the production of high levels of IFNγ and IL-4.
+These results suggest that the baculovirus system is equally efficient by the intramuscular as well as the oral routes for ALA protection and that the Gal-lectin LC3 fragment is a highly protective antigen against hepatic amoebiasis through the local induction of IFNγ and IL-4.
+Danhong injection (DHI) is a widely used Chinese Materia Medica standardized product for the clinical treatment of ischemic encephalopathy and coronary heart disease.
+The bindings of eight natural components in DHI between bovine serum albumin (BSA) were studied by fluorescence spectroscopy technology and molecular docking.
+According to the results, the quenching process of salvianolic acid B and hydroxysafflor yellow A was a static quenching procedure through the analysis of quenching data by the Stern-Volmer equation, the modified Stern-Volmer equation, and the modified Scatchard equation.
+Meanwhile, syringin (Syr) enhanced the fluorescence of BSA, and the data were analyzed using the Lineweaver-Burk equation.
+Molecular docking suggested that all of these natural components bind to serum albumin at the site I location.
+Further competitive experiments of SaB confirmed the result of molecular docking studies duo to the displacement of warfarin by SaB.
+Base on these studies, we selected SaB as a research target because it presented the strongest binding ability to BSA and investigated the influence of the multi-components coexisting in DHI on the interaction between the components of the SaB-BSA binding system.
+The participation of these natural components in DHI affected the interaction between the components of the SaB-BSA system.
+Therefore, when DHI is used in mammals, SaB is released from serum albumin more quickly than it is used alone.
+This work would provide a new experiment basis for revealing the scientific principle of compatibility for Traditional Chinese Medicine.
+Pegylated interferon-α and ribavirin (PEG-IFN/RBV) is widely used to treat chronic hepatitis C virus infection with notorious adverse reactions since the broad expression of IFN-α receptors on all nucleated cells.
+Accordingly, a Type III IFN with restricted receptors distribution is much safer as an alternative for HCV therapy.
+In addition, single nucleotide polymorphisms (SNPs) near the human IFN-λ3 gene, IL-28B, correlate strongly with the ability to achieve a sustained virological response (SVR) to therapy with pegylated IFN-α plus ribavirin in patients infected with chronic hepatitis C. Furthermore, we also discuss the most recent findings: IFN-λ4 predicts treatment outcomes of HCV infection.
+In consideration of the apparent limitations of current HCV therapy, especially high failure rate and universal side effects, prediction of treatment outcomes prior to the initiation of treatment and developing new alternative drugs are two important goals in HCV research.
+BACKGROUND: The complexity of providing medical care in a high-tech environment with a highly specialized, limited labour force makes hospitals more crisis-prone than other industries.
+An effective defence against crises is only possible if the organizational resilience and the capacity to handle crises become part of the hospitals’ organizational culture.
+To become more resilient to crises, a raised awareness—especially in the area of human resource (HR)—is necessary.
+The aim of this paper is to contribute to the process robustness against crises through the identification and evaluation of relevant HR crises and their causations in hospitals.
+METHODS: Qualitative and quantitative methods were combined to identify and evaluate crises in hospitals in the HR sector.
+A structured workshop with experts was conducted to identify HR crises and their descriptions, as well as causes and consequences for patients and hospitals.
+To evaluate the findings, an online survey was carried out to rate the occurrence (past, future) and dangerousness of each crisis.
+RESULTS: Six HR crises were identified in this study: staff shortages, acute loss of personnel following a pandemic, damage to reputation, insufficient communication during restructuring, bullying, and misuse of drugs.
+The highest occurrence probability in the future was seen in staff shortages, followed by acute loss of personnel following a pandemic.
+Staff shortages, damage to reputation, and acute loss of personnel following a pandemic were seen as the most dangerous crises.
+CONCLUSIONS: The study concludes that coping with HR crises in hospitals is existential for hospitals and requires increased awareness.
+The six HR crises identified occurred regularly in German hospitals in the past, and their occurrence probability for the future was rated as high.
+The well described conventional antigen-processing pathway is accountable for most peptides that end up in MHC class I molecules at the cell surface.
+However, there are multiple roads that lead to Rome, illustrated by the increasing number of alternative processing pathways that have been reported during last years.
+Interestingly, TAP-deficient individuals do not succumb to viral infections, suggesting that CD8 T cell immunity is sufficiently supported by alternative TAP-independent processing pathways.
+To date, a diversity of viral and endogenous TAP-independent peptides have been identified in the grooves of different MHC class I alleles.
+Some of these peptides are not displayed by normal TAP-positive cells and we therefore called them TEIPP, for “T-cell epitopes associated with impaired peptide processing.” TEIPPs are hidden self-antigens, are derived from normal housekeeping proteins, and are processed via unconventional processing pathways.
+Per definition, TEIPPs are presented via TAP-independent pathways, but recent data suggest that part of this repertoire still depend on proteasome and metalloprotease activity.
+An exception is the C-terminal peptide of the endoplasmic reticulum (ER)-membrane-spanning ceramide synthase Trh4 that is surprisingly liberated by the signal peptide peptidase (SPP), the proteolytic enzyme involved in cleaving leader sequences.
+Its family members, like the Alzheimer’s related presenilins, might contribute as well, according to our preliminary data.
+Finally, alternative peptide routing is an emerging field and includes processes like the unfolded protein response, the ER-associated degradation, and autophagy-associated vesicular pathways.
+These data convince us that there is a world to be discovered in the field of unconventional antigen processing.
+Seasonal influenza virus infections cause hundreds of thousands of deaths annually while viral mutation raises the threat of a novel pandemic strain.
+Thus, targeting the host response directly has been proposed as a novel therapeutic strategy with the added potential benefit of not eliciting viral resistance.
+Severe influenza virus infections are complicated by respiratory failure due to the development of lung microvascular leak and acute lung injury.
+Here we demonstrate that the Tie2-agonist tetrameric peptide Vasculotide improves survival in murine models of severe influenza, even if administered as late as 72 hours after infection; the benefit was observed using three strains of the virus and two strains of mice.
+The effect required Tie2, was independent of viral replication and did not impair lung neutrophil recruitment.
+Administration of the drug decreased lung edema, arterial hypoxemia and lung endothelial apoptosis; importantly, Vasculotide is inexpensive to produce, is chemically stable and is unrelated to any Tie2 ligands.
+Highly pathogenic influenza virus infections generally coincide with early, high levels of inflammatory cytokines that some studies have suggested may be regulated in a strain-dependent manner.
+However, a comprehensive characterization of the complex dynamics of the inflammatory response induced by virulent influenza strains is lacking.
+Here, we applied gene co-expression and nonlinear regression analysis to time-course, microarray data developed from influenza-infected mouse lung to create mathematical models of the host inflammatory response.
+We found that the dynamics of inflammation-associated gene expression are regulated by an ultrasensitive-like mechanism in which low levels of virus induce minimal gene expression but expression is strongly induced once a threshold virus titer is exceeded.
+Cytokine assays confirmed that the production of several key inflammatory cytokines, such as interleukin 6 and monocyte chemotactic protein 1, exhibit ultrasensitive behavior.
+A systematic exploration of the pathways regulating the inflammatory-associated gene response suggests that the molecular origins of this ultrasensitive response mechanism lie within the branch of the Toll-like receptor pathway that regulates STAT1 phosphorylation.
+This study provides the first evidence of an ultrasensitive mechanism regulating influenza virus-induced inflammation in whole lungs and provides insight into how different virus strains can induce distinct temporal inflammation response profiles.
+The approach developed here should facilitate the construction of gene regulatory models of other infectious diseases.
+Adenoviral vectors are now being explored as vaccine carriers to prevent infectious diseases in humans and animals.
+There are two strategies aimed at the expression of a vaccine antigen by adenoviral vectors.
+The first includes an insertion of the foreign gene expression cassette into the E1 region.
+To extend this methodology, we have searched for new sites at the human adenovirus serotype 5 major capsid protein hexon for a vaccine antigen insertion.
+To this end, we utilized sites in the hexon hypervariable region (HVR) 7, 8 and 9 to display a 15-mer peptide containing the main neutralizing epitope of porcine reproductive and respiratory syndrome virus.
+However, we could not rescue the viruses with the insertions of the peptide into HVR 8 and 9, consistent with the viruses being unable to tolerate insertions at these sites.
+In contrast, the virus with the insertion of the peptide in HVR 7 was viable - growing well in cell culture and the inserted peptide was exposed on the virion surface.
+BACKGROUND: Hematophagy arose independently multiple times during metazoan evolution, with several lineages of vampire animals particularly diversified in invertebrates.
+However, the biochemistry of hematophagy has been studied in a few species of direct medical interest and is still underdeveloped in most invertebrates, as in general is the study of venom toxins.
+In cone snails, leeches, arthropods and snakes, the strong target specificity of venom toxins uniquely aligns them to industrial and academic pursuits (pharmacological applications, pest control etc.)
+and provides a biochemical tool for studying biological activities including cell signalling and immunological response.
+are carnivorous and include active predators, scavengers, grazers on sessile invertebrates and hematophagous parasites; most of them use venoms to efficiently feed.
+It has been hypothesized that trophic innovations were the main drivers of rapid radiation of Neogastropoda in the late Cretaceous.
+We present here the first molecular characterization of the alimentary secretion of a non-conoidean neogastropod, Colubraria reticulata.
+Colubrariids successfully feed on the blood of fishes, throughout the secretion into the host of a complex mixture of anaesthetics and anticoagulants.
+We used a NGS RNA-Seq approach, integrated with differential expression analyses and custom searches for putative secreted feeding-related proteins, to describe in detail the salivary and mid-oesophageal transcriptomes of this Mediterranean vampire snail, with functional and evolutionary insights on major families of bioactive molecules.
+RESULTS: A remarkably low level of overlap was observed between the gene expression in the two target tissues, which also contained a high percentage of putatively secreted proteins when compared to the whole body.
+CONCLUSIONS: Colubraria feeding physiology seems to involve inhibitors of both primary and secondary haemostasis, anaesthetics, a vasoconstrictive enzyme to reduce feeding time and tissue-degrading proteins such as Porins and Astacins.
+The complexity of Colubraria venomous cocktail and the divergence from the arsenal of the few neogastropods studied to date (mostly conoideans) suggest that biochemical diversification of neogastropods might be largely underestimated and worth of extensive investigation.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-015-1648-4) contains supplementary material, which is available to authorized users.
+The host tolerance mechanisms to avian influenza virus (H5N1) infection that limit tissue injury remain unknown.
+Emerging evidence indicates that cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP-dependent Cl(−) channel, modulates airway inflammation.
+Janus tyrosine kinase (JAK) 3, a JAK family member that plays a central role in inflammatory responses, prominently contributes to the dysregulated innate immune response upon H5N1 attachment; therefore, this study aims to elucidate whether JAK3 activation induced by H5N1 hemagglutinin (HA) inhibits cAMP-dependent CFTR channels.
+We performed short-circuit current, immunohistochemistry and molecular analyses of the airway epithelium in Jak3(+/+) and Jak3(+/−) mice.
+We demonstrate that H5N1 HA attachment inhibits cAMP-dependent CFTR Cl(−) channels via JAK3-mediated adenylyl cyclase (AC) suppression, which reduces cAMP production.
+Our findings provide novel insight into the pathogenesis of acute lung injury via the inhibition of cAMP-dependent CFTR channels, indicating that the administration of cAMP-elevating agents and targeting JAK3 may activate host tolerance to infection for the management of influenza virus–induced fatal pneumonia.
+A simple and versatile colorimetric biosensor has been developed for sensitive and specific detection of a wide range of biomolecules, such as oligonucleotides and aptamer-recognized targets.
+Combining the signal transducer and catalyzed hairpin assembly (CHA)-based signal amplification, the target DNA binds with the hairpin DNA to form a new nucleic acid sequence and creates a toehold in the transducer for initiating the recycle amplification reaction of CHA.
+In the presence of hemin, the G-rich DNA forms G-quadruplex/hemin complex and mimic horseradish peroxidase activity, which catalyzes a colorimetric reaction.
+Under optimal conditions, the calibration curve of synthetic target DNA has good linearity from 50 pM to 200 nM with a detection limit of 32 pM.
+This strategy has been successfully applied to detect S. pneumoniae as low as 156 CFU mL(−1), and shows a good specificity against closely related streptococci and major pathogenic bacteria.
+In addition, the developed method enables successful visual analysis of S. pneumoniae in clinical samples by the naked eye.
+BACKGROUND: Previous investigations have presumed a potential therapeutic effect of statin therapy in patients with acute respiratory distress syndrome (ARDS).
+Statins are expected to attenuate inflammation in the lungs of patients with ARDS due to their anti-inflammatory effects.
+This study aimed to investigate whether pretreatment and continuous therapy with statins in patients with sepsis-associated ARDS are associated with 28-day survival according to disease severity (mild, moderate, or severe).
+METHODS: Patients with sepsis-associated ARDS from the surgical intensive care were enrolled in this prospective observational investigation.
+ARDS was classified into three groups (mild, moderate, and severe); 28-day mortality was recorded as the primary outcome variable and organ failure was recorded as secondary outcome variable.
+Sequential Organ Failure Assessment scores and the requirements for organ support were evaluated throughout the observational period to assess organ failure.
+The distribution of the ARDS subgroups was 13 %, 59 %, and 28 % for mild, moderate, and severe disease, respectively.
+Statin therapy improved 28-day survival exclusively in the patients with severe ARDS compared with patients without statin therapy (88.5 % and 62.5 %, respectively; P = 0.0193).
+To exclude the effects of several confounders, we performed multivariate Cox regression analysis, which showed that statin therapy remained a significant covariate for mortality (hazard ratio, 5.46; 95 % CI, 1.38–21.70; P = 0.0156).
+Moreover, after carrying a propensity score-matching in the severe ARDS cohort, Kaplan-Meier survival analysis confirmed the improved 28-day survival among patients with statin therapy (P = 0.0205).
+Patients with severe ARDS who received statin therapy had significantly more vasopressor-free days compared with those without statin therapy (13 ± 7 and 9 ± 7, respectively; P = 0.0034), and they also required less extracorporeal membrane oxygenation (ECMO) therapy and had more ECMO-free days (18 ± 9 and 15 ± 9, respectively; P = 0.0873).
+CONCLUSIONS: This investigation suggests a beneficial effect of continuous statin therapy in patients with severe sepsis-associated ARDS and a history of prior statin therapy.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12916-015-0368-6) contains supplementary material, which is available to authorized users.
+BACKGROUND: Bacteria and respiratory viruses are implicated in the pathogenesis of acute otitis media (AOM); however, data from low–middle income countries are sparse.
+We investigated the etiology of AOM in HIV-infected (HIV+), HIV-uninfected (HIV−) and HIV-exposed clinically asymptomatic for HIV-infection (HEU) South African children.
+METHODS: Children ≥3 months to <5 years of age with AOM were enrolled between May 2009 and April 2010 (NCT01031082).
+Middle ear fluid samples were cultured for bacteria; antibacterial susceptibility was done and serotyping undertaken for Streptococcus pneumoniae and Haemophilus influenzae.
+RESULTS: Of 260 AOM episodes (HIV+:15; HIV−:182; HEU:63), bacteria were found in 54.6%, including Haemophilus influenzae (30.8%), 98.8% of which were nontypeable, and Streptococcus pneumoniae (20.4%), Staphylococcus aureus (15.8%), Moraxella catarrhalis (5.0%) and Streptococcus pyogenes (1.5%).
+Human rhinovirus was most frequently detected (37.7%), followed by adenovirus (14.2%) and human bocavirus (11.5%) overall and irrespective of HIV status.
+Respiratory viruses were identified concurrently with S. pneumoniae, H. influenzae, M. catarrhalis (76.9–78.8%) and Staphylococcus aureus (63.4%) cultured from middle ear fluid, as well as in 72.0% of episodes negative for any bacteria.
+CONCLUSION: The study suggests that respiratory viruses and pathogenic bacteria play an important role in the development of AOM in children.
+Vaccines targeting both nontypeable Haemophilus influenzae and S. pneumoniae may have a broad impact on AOM in South Africa.
+T-cell-mediated immunotherapy of hematological malignancies requires selection of targeted tumor-associated antigens and T-cell epitopes contained in these tumor proteins.
+Epidermal growth factor receptor pathway substrate 8 (EPS8), whose function is pivotal for tumor proliferation, progression and metastasis, has been found to be overexpressed in most human tumor types, while its expression in normal tissue is low.
+The aim of the present study was to identify human leukemia antigen (HLA)-A*0201-restricted epitopes of EPS8 by using a reverse immunology approach.
+To achieve this, computer algorithms were used to predict HLA-A*0201 molecular binding, proteasome cleavage patterns as well as translocation of transporters associated with antigen processing.
+The functional avidity of peptide-specific cytotoxic T lymphocytes (CTLs) induced from peripheral blood mononuclear cells of healthy volunteers were evaluated by using an enzyme-linked immunosorbent spot assay and a cytotoxicity assay.
+Four peptides, designated as P455, P92, P276 and P360, had high affinity and stability of binding towards the HLA-A*0201 molecule, and specific CTLs induced by them significantly responded to the corresponding peptides and secreted IFN-γ.
+At the same time, the CTLs were able to specifically lyse EPS8-expressing cell lines in an HLA-A*0201-restricted manner.
+The present study demon-strated that P455, P92, P276 and P360 were CTL epitopes of EPS8, and were able to be used for epitope-defined adoptive T-cell transfer and multi-epitope-based vaccine design.
+Dietary fats and sodium are both palatable and are hypothesized to synergistically contribute to ingestive behavior and thereby obesity.
+Contrary to this hypothesis, C57BL/6J mice fed a 45% high fat diet exhibited weight gain that was inhibited by increased dietary sodium content.
+This suppressive effect of dietary sodium upon weight gain was mediated specifically through a reduction in digestive efficiency, with no effects on food intake behavior, physical activity, or resting metabolism.
+Replacement of circulating angiotensin II levels reversed the effects of high dietary sodium to suppress digestive efficiency.
+While the AT(1) receptor antagonist losartan had no effect in mice fed low sodium, the AT(2) receptor antagonist PD-123,319 suppressed digestive efficiency.
+Correspondingly, genetic deletion of the AT(2) receptor in FVB/NCrl mice resulted in suppressed digestive efficiency even on a standard chow diet.
+Together these data underscore the importance of digestive efficiency in the pathogenesis of obesity, and implicate dietary sodium, the renin-angiotensin system, and the AT(2) receptor in the control of digestive efficiency regardless of mouse strain or macronutrient composition of the diet.
+These findings highlight the need for greater understanding of nutrient absorption control physiology, and prompt more uniform assessment of digestive efficiency in animal studies of energy balance.
+BACKGROUND: Over 2.5 billion people are exposed to the risk of contracting dengue fever (DF).
+Real-time reverse transcription polymerase amplification assays (RT-PCR) are the standard method for molecular detection of the dengue virus (DENV).
+Real-time RT-PCR analysis is not suitable for on-site screening since mobile devices are large, expensive, and complex.
+METHODOLOGY/PRINCIPAL FINDINGS: Using two quantitative RNA molecular standards, the analytical sensitivity of a RT-RPA targeting the 3´non-translated region of DENV1-4 was found to range from 14 (DENV4) to 241 (DENV1-3) RNA molecules detected.
+The RT-RPA assay was tested in a mobile laboratory combining magnetic-bead based total nucleic acid extraction and a portable detection device in Kedougou (Senegal) and in Bangkok (Thailand).
+In Kedougou, the RT-RPA was operated at an ambient temperature of 38°C with auxiliary electricity tapped from a motor vehicle and yielded a clinical sensitivity and specificity of 98% (n=31) and 100% (n=23), respectively.
+While in the field trial in Bangkok, the clinical sensitivity and specificity were 72% (n=90) and 100%(n=41), respectively.
+CONCLUSIONS/SIGNIFICANCE: During the first 5 days of infection, the developed DENV1-4 RT-RPA assays constitute a suitable accurate and rapid assay for DENV diagnosis.
+Moreover, the use of a portable fluorescence-reading device broadens its application potential to the point-of-care for outbreak investigations.
+Transgenic mice (Tg) overexpressing human apolipoprotein D (H-apoD) in the brain are resistant to neurodegeneration.
+Despite the use of a neuron-specific promoter to generate the Tg mice, they expressed significant levels of H-apoD in both plasma and liver and they slowly develop hepatic steatosis and insulin resistance.
+We show here that hepatic PPARγ expression in Tg mice is increased by 2-fold compared to wild type (WT) mice.
+Consequently, PPARγ target genes Plin2 and Cide A/C are overexpressed, leading to increased lipid droplets formation.
+Expression of the fatty acid transporter CD36, another PPARgamma target, is also increased in Tg mice associated with elevated fatty acid uptake as measured in primary hepatocytes.
+Elevated expression of AMPK in the liver of Tg leads to phosphorylation of acetyl CoA carboxylase, indicating a decreased activity of the enzyme.
+Fatty acid synthase expression is also induced but the hepatic lipogenesis measured in vivo is not significantly different between WT and Tg mice.
+In addition, expression of carnitine palmitoyl transferase 1, the rate-limiting enzyme of beta-oxidation, is slightly upregulated.
+Finally, we show that overexpressing H-apoD in HepG2 cells in presence of arachidonic acid (AA), the main apoD ligand, increases the transcriptional activity of PPARγ.
+Supporting the role of apoD in AA transport, we observed enrichment in hepatic AA and a decrease in plasmatic AA concentration.
+Taken together, our results demonstrate that the hepatic steatosis observed in apoD Tg mice is a consequence of increased PPARγ transcriptional activity by AA leading to increased fatty acid uptake by the liver.
+The role of Bone Tissue Engineering in the field of Regenerative Medicine has been the topic of substantial research over the past two decades.
+However, improvements in surgical techniques to reconstruct bone have been limited by the paucity of autologous materials available and donor site morbidity.
+Recent advances in the development of biomaterials have provided attractive alternatives to bone grafting expanding the surgical options for restoring the form and function of injured bone.
+Specifically, novel bioactive (second generation) biomaterials have been developed that are characterised by controlled action and reaction to the host tissue environment, whilst exhibiting controlled chemical breakdown and resorption with an ultimate replacement by regenerating tissue.
+Future generations of biomaterials (third generation) are designed to be not only osteoconductive but also osteoinductive, i.e.
+to stimulate regeneration of host tissues by combining tissue engineering and in situ tissue regeneration methods with a focus on novel applications.
+At present, tissue engineered constructs that may find future use as bone grafts for complex skeletal defects, whether from post-traumatic, degenerative, neoplastic or congenital/developmental “origin” require osseous reconstruction to ensure structural and functional integrity.
+Engineering functional bone using combinations of cells, scaffolds and bioactive factors is a promising strategy and a particular feature for future development in the area of hybrid materials which are able to exhibit suitable biomimetic and mechanical properties.
+This review will discuss the state of the art in this field and what we can expect from future generations of bone regeneration concepts.
+This retrospective study provides an overview on spontaneous diseases occurring in 38 captive wild felids submitted for necropsy by German zoological gardens between 2004 and 2013.
+Species included 18 tigers, 8 leopards, 7 lions, 3 cheetahs and 2 cougars with an age ranging from 0.5 to 22 years.
+Renal lesions, predominantly tubular alterations (intra-tubular concrements, tubular degeneration, necrosis, intra-tubular cellular debris, proteinaceous casts, dilated tubuli) followed by interstitial (lympho-plasmacytic inflammation, fibrosis, metastatic-suppurative inflammation, eosinophilic inflammation) and glomerular lesions (glomerulonephritis, glomerulosclerosis, amyloidosis) were detected in 33 out of 38 animals (87%).
+Tumors were found in 19 of 38 felids (50%) with 12 animals showing more than one neoplasm.
+Neoplasms originated from endocrine (11), genital (8), lympho-hematopoietic (5) and alimentary organs (4) as well as the mesothelium (3).
+Most common neoplasms comprised uterine/ovarian leiomyomas (5/2), thyroid adenomas/adenocarcinoma (5/1), pleural mesotheliomas (3), hemangiosarcomas (2) and glossal papillomas (2).
+One tiger exhibited degenerative white matter changes consistent with an entity termed large felid leukoencephalomyelopathy.
+Various hyperplastic, degenerative and inflammatory changes with minor clinical significance were found in several organs.
+Summarized, renal lesions followed by neoplastic changes as well as inflammatory changes in lung and gastrointestinal tract represent the most frequent findings in captive wild felids living in German zoological gardens.
+There is growing evidence that factors encoded by cytoplasmic replicating viruses functionally interact with components of the nucleocytoplasmic transport apparatus.
+They do so either to access the cell nucleus, thus affecting genes expression, or to interfere with nuclear transport functionality, hindering host immune response.
+Recent studies revealed that the hepatitis C virus (HCV) makes no exception, interacting with the host cell nuclear transport machinery at two different levels.
+On the one hand, small amounts of both core and NS5A localize within the host cell nucleus during productive infection, modulating gene expression and signaling functions to promote persistent infection.
+On the other hand, HCV infection causes a profound redistribution of certain nucleoproteins to the close proximity of endoplasmic reticulum membrane-derived viral replication factories, where viral RNA amplification occurs.
+These nucleoporins are believed to form nuclear pore complex-like structures, as suggested by their ability to recruit nuclear localization sequence-bearing proteins.
+Thus, both processes are linked to virus-induced persistence and pathogenesis, representing possible targets for the development of novel anti-HCV therapeutics.
+It is an emerging orthopoxvirus zoonosis in the tropical rain forest of Africa and is endemic in the Congo-basin and sporadic in West Africa; it remains a tropical neglected disease of persons in impoverished rural areas.
+Interaction of the human population with wildlife increases human infection with MPX virus (MPXV), and infection from human to human is possible.
+Smallpox vaccination provides good cross-protection against MPX; however, the vaccination campaign ended in Africa in 1980, meaning that a large proportion of the population is currently unprotected against MPXV infection.
+Disease control hinges on deterring zoonotic exposure to the virus and, barring that, interrupting person-to-person spread.
+However, there are no FDA-approved therapies against MPX, and current vaccines are limited due to safety concerns.
+For this reason, new studies on pathogenesis, prophylaxis and therapeutics are still of great interest, not only for the scientific community but also for the governments concerned that MPXV could be used as a bioterror agent.
+In the present study, a new vaccination strategy approach based on three recombinant bovine herpesvirus 4 (BoHV-4) vectors, each expressing different MPXV glycoproteins, A29L, M1R and B6R were investigated in terms of protection from a lethal MPXV challenge in STAT1 knockout mice.
+BoHV-4-A-CMV-A29LgD(106)ΔTK, BoHV-4-A-EF1α-M1RgD(106)ΔTK and BoHV-4-A-EF1α-B6RgD(106)ΔTK were successfully constructed by recombineering, and their capacity to express their transgene was demonstrated.
+A small challenge study was performed, and all three recombinant BoHV-4 appeared safe (no weight-loss or obvious adverse events) following intraperitoneal administration.
+Further, BoHV-4-A-EF1α-M1RgD(106)ΔTK alone or in combination with BoHV-4-A-CMV-A29LgD(106)ΔTK and BoHV-4-A-EF1α-B6RgD(106)ΔTK, was shown to be able to protect, 100% alone and 80% in combination, STAT1((-/-)) mice against mortality and morbidity.
+This work demonstrated the efficacy of BoHV-4 based vectors and the use of BoHV-4 as a vaccine-vector platform.
+Newly emerging influenza A viruses (IAV) pose a major threat to human health by causing seasonal epidemics and/or pandemics, the latter often facilitated by the lack of pre-existing immunity in the general population.
+Early recognition of candidate pandemic influenza viruses (CPIV) is of crucial importance for restricting virus transmission and developing appropriate therapeutic and prophylactic strategies including effective vaccines.
+Often, the pandemic potential of newly emerging IAV is only fully recognized once the virus starts to spread efficiently causing serious disease in humans.
+Here, we used a novel phylogenetic algorithm based on the informational spectrum method (ISM) to identify potential CPIV by predicting mutations in the viral hemagglutinin (HA) gene that are likely to (differentially) affect critical interactions between the HA protein and target cells from bird and human origin, respectively.
+Predictions were subsequently validated by generating pseudotyped retrovirus particles and genetically engineered IAV containing these mutations and characterizing potential effects on virus entry and replication in cells expressing human and avian IAV receptors, respectively.
+Our data suggest that the ISM-based algorithm is suitable to identify CPIV among IAV strains that are circulating in animal hosts and thus may be a new tool for assessing pandemic risks associated with specific strains.
+Human noroviruses (HuNoV) are a significant cause of acute gastroenteritis in the developed world, and yet our understanding of the molecular pathways involved in norovirus replication and pathogenesis has been limited by the inability to efficiently culture these viruses in the laboratory.
+Using the murine norovirus (MNV) model, we have recently identified a network of host factors that interact with the 5′ and 3′ extremities of the norovirus RNA genome.
+In addition to a number of well-known cellular RNA binding proteins, the molecular chaperone Hsp90 was identified as a component of the ribonucleoprotein complex.
+Here, we show that the inhibition of Hsp90 activity negatively impacts norovirus replication in cell culture.
+Small-molecule-mediated inhibition of Hsp90 activity using 17-DMAG (17-dimethylaminoethylamino-17-demethoxygeldanamycin) revealed that Hsp90 plays a pleiotropic role in the norovirus life cycle but that the stability of the viral capsid protein is integrally linked to Hsp90 activity.
+Furthermore, we demonstrate that both the MNV-1 and the HuNoV capsid proteins require Hsp90 activity for their stability and that targeting Hsp90 in vivo can significantly reduce virus replication.
+In summary, we demonstrate that targeting cellular proteostasis can inhibit norovirus replication, identifying a potential novel therapeutic target for the treatment of norovirus infections.
+RNA viruses, including noroviruses, rely heavily on host cell proteins and pathways for all aspects of their life cycle.
+Here, we identify one such protein, the molecular chaperone Hsp90, as an important factor required during the norovirus life cycle.
+We demonstrate that both murine and human noroviruses require the activity of Hsp90 for the stability of their capsid proteins.
+Furthermore, we demonstrate that targeting Hsp90 activity in vivo using small molecule inhibitors also reduces infectious virus production.
+Given the considerable interest in the development of Hsp90 inhibitors for use in cancer therapeutics, we identify here a new target that could be explored for the development of antiviral strategies to control norovirus outbreaks and treat chronic norovirus infection in immunosuppressed patients.
+BACKGROUND: Most studies about septic shock report a crude mortality rate that neither distinguishes between early and late deaths nor addresses the direct causes of death.
+All consecutive patients diagnosed for septic shock within the first 48 h of intensive care unit (ICU) admission were included.
+Early and late deaths were defined as occurring within or after 3 days following ICU admission, respectively.
+A multinomial logistic regression analysis using the status alive as the reference category was performed to identify the prognostic factors associated with early and late deaths.
+RESULTS: Five hundred forty-three patients were included, with a mean age of 66 ± 15 years and a high proportion (67 %) of comorbidities.
+Deaths occurred early for 78 (32 %) and later on for 166 (68 %) patients in the ICU (n = 124) or in the hospital (n = 42).
+Early deaths were mainly attributable to intractable multiple organ failure related to the primary infection (82 %) and to mesenteric ischemia (6.4 %).
+In-ICU late deaths were directly related to end-of-life decisions in 29 % of patients and otherwise mostly related to ICU-acquired complications, including nosocomial infections (20.4 %) and mesenteric ischemia (16.6 %).
+Independent determinants of early death were age, malignancy, diabetes mellitus, no pathogen identification, and initial severity.
+Among 3-day survivors, independent risk factors for late death were age, cirrhosis, no pathogen identification, and previous corticosteroid treatment.
+Pulmonary alveolar proteinosis (PAP) is a severe autoimmune disease caused by autoantibodies that neutralize GM-CSF resulting in impaired function of alveolar macrophages.
+In this study, we characterize 21 GM-CSF autoantibodies from PAP patients and find that somatic mutations critically determine their specificity for the self-antigen.
+Individual antibodies only partially neutralize GM-CSF activity using an in vitro bioassay, depending on the experimental conditions, while, when injected in mice together with human GM-CSF, they lead to the accumulation of a large pool of circulating GM-CSF that remains partially bioavailable.
+In contrast, a combination of three non-cross-competing antibodies completely neutralizes GM-CSF activity in vitro by sequestering the cytokine in high-molecular-weight complexes, and in vivo promotes the rapid degradation of GM-CSF-containing immune complexes in an Fc-dependent manner.
+Taken together, these findings provide a plausible explanation for the severe phenotype of PAP patients and for the safety of treatments based on single anti-GM-CSF monoclonal antibodies.
+By the use of a modified ionizer device we describe effective prevention of airborne transmitted influenza A (strain Panama 99) virus infection between animals and inactivation of virus (>97%).
+Moreover, the device effectively captured airborne transmitted calicivirus, rotavirus and influenza virus, with recovery rates up to 21% after 40 min in a 19 m(3) room.
+The ionizer generates negative ions, rendering airborne particles/aerosol droplets negatively charged and electrostatically attracts them to a positively charged collector plate.
+The device enables unique possibilities for rapid and simple removal of virus from air and offers possibilities to simultaneously identify and prevent airborne transmission of viruses.
+Twelve months after the LDLT, she developed acute hepatitis (alanine aminotransferase 584 IU/L) and was diagnosed with disseminated varicella-zoster virus (VZV) infection with high level of serum VZV-DNA (1.5 × 10(5) copies/mL) and generalized vesicular rash.
+She had received the VZV vaccination when she was 5-years-old and had not been exposed to chicken pox before the LDLT, and her serum was positive for VZV immunoglobulin G at the time of the LDLT.
+Although she underwent treatment with intravenous acyclovir, intravenous immunoglobulin, and withdrawal of immunosuppressants, her symptoms worsened and were accompanied by disseminated intravascular coagulation, pneumonia, and encephalitis.
+Five weeks later, her clinical findings improved, although her VZV-DNA levels remained high (8.5 × 10(3)copies/mL).
+Oral acyclovir was added for 2 weeks, and she was eventually discharged from our hospital on day 86 after admission; she has not experienced a recurrence.
+In conclusion, although disseminated VZV infection with multiple organ failure after pediatric LDLT is a life-threatening disease, it can be cured via an early diagnosis and intensive treatment.
+Each population of RNA virus is composed of a collection of different, yet related genomes often referred to as mutant spectra or quasispecies.
+Virologists using deep sequencing technologies face major obstacles when studying virus population dynamics, both experimentally and in natural settings due to the relatively high error rates of these technologies and the lack of high performance pipelines.
+In order to overcome these hurdles we developed a computational pipeline, termed ViVan (Viral Variance Analysis).
+ViVan is a complete pipeline facilitating the identification, characterization and comparison of sequence variance in deep sequenced virus populations.
+Results: Applying ViVan on deep sequenced data obtained from samples that were previously characterized by more classical approaches, we uncovered novel and potentially crucial aspects of virus populations.
+With our experimental work, we illustrate how ViVan can be used for studies ranging from the more practical, detection of resistant mutations and effects of antiviral treatments, to the more theoretical temporal characterization of the population in evolutionary studies.
+Availability and implementation: Freely available on the web at http://www.vivanbioinfo.org Contact: nshomron@post.tau.ac.il Supplementary information: Supplementary data are available at Bioinformatics online.
+Recently published studies have demonstrated that in some rare cases pathogens can confer protection from autoimmunity.
+Trypanosoma brucei parasites are tsetse fly transmitted extracellular protozoans causing sleeping sickness disease in humans and Nagana in livestock in sub-Saharan endemic areas.
+In the past, we demonstrated that trypanosome infections impair B cell homeostasis and abolish vaccine-induced protection against unrelated antigens.
+Hence, here we hypothesized that trypanosome infection can affect the onset of CIA by specifically dampening specific B-cell responses and type II collagen antibody titers in DBA/1 prone mice.
+We observed a substantial delay in the onset of collagen-induced arthritis in T. brucei-infected DBA/1 mice that correlates with a drastic decrease of type II collagen titers of the different IgG isotypes in the serum.
+Treatment of infected mice with Berenil, a trypanocidal drug, restored the development of CIA-associated clinical symptoms.
+Interestingly, these data were confirmed by the challenge of immunized DBA/1 prone mice with T. brucei-infected tsetse flies.
+Together, these results demonstrate that T. brucei infection is impairing the maintenance of the antigen specific plasma B cell pool driving the development of CIA in DBA/1 prone mice.
+Helicobacter pylori causes cellular vacuolation in host cells, a cytotoxic event attributed to vacuolating cytotoxin (VacA) and the presence of permeant weak bases such as ammonia.
+We report here the role of γ-glutamyl transpeptidase (GGT), a constitutively expressed secretory enzyme of H. pylori, in potentiating VacA-dependent vacuolation formation in H. pylori-infected AGS and primary gastric cells.
+The enhancement is brought about by GGT hydrolysing glutamine present in the extracellular medium, thereby releasing ammonia which accentuates the VacA-induced vacuolation.
+The events of vacuolation in H. pylori wild type (WT)- and Δggt-infected AGS cells were first captured and visualized by real-time phase-contrast microscopy where WT was observed to induce more vacuoles than Δggt.
+By using semi-quantitative neutral red uptake assay, we next showed that Δggt induced significantly less vacuolation in AGS and primary gastric epithelial cells as compared to the parental strain (P<0.05) indicating that GGT potentiates the vacuolating effect of VacA.
+Notably, vacuolation induced by WT was significantly reduced in the absence of GGT substrate, glutamine (P<0.05) or in the presence of a competitive GGT inhibitor, serine-borate complex.
+Furthermore, the vacuolating ability of Δggt was markedly restored when co-incubated with purified recombinant GGT (rGGT), although rGGT itself did not induce vacuolation independently.
+Similarly, the addition of exogenous ammonium chloride as a source of ammonia also rescued the ability of Δggt to induce vacuolation.
+Additionally, we also show that monoclonal antibodies against GGT effectively inhibited GGT activity and successfully suppressed H. pylori-induced vacuolation.
+Collectively, our results clearly demonstrate that generation of ammonia by GGT through glutamine hydrolysis is responsible for enhancing VacA-dependent vacuolation.
+Our findings provide a new perspective on GGT as an important virulence factor and a promising target in the management of H. pylori-associated gastric diseases.
+The filoviruses, which include the marburg- and ebolaviruses, have caused multiple outbreaks among humans this decade.
+Antibodies against the filovirus surface glycoprotein (GP) have been shown to provide life-saving therapy in nonhuman primates, but such antibodies are generally virus-specific.
+Here we present ten mAbs elicited by immunization of mice using recombinant mucin-deleted GPs from different Marburg virus (MARV) strains.
+Surprisingly, two of the mAbs raised against MARV GP also cross-react with the mucin-deleted GP cores of all tested ebolaviruses (Ebola, Sudan, Bundibugyo, Reston), but these epitopes are masked differently by the mucin-like domains themselves.
+The most efficacious mAbs in this panel were found to recognize a novel “wing” feature on the GP2 subunit that is unique to Marburg and does not exist in Ebola.
+Two of these anti-wing antibodies confer 90 and 100% protection, respectively, one hour post-exposure in mice challenged with MARV.
+INTRODUCTION: The purpose of this study was to investigate whether common variants across the nuclear factor erythroid 2-like 2 (NFE2L2) gene contribute to the development of the acute respiratory distress syndrome (ARDS) in patients with severe sepsis.
+NFE2L2 is involved in the response to oxidative stress, and it has been shown to be associated with the development of ARDS in trauma patients.
+METHODS: We performed a case–control study of 321 patients fulfilling international criteria for severe sepsis and ARDS who were admitted to a Spanish network of post-surgical and critical care units, as well as 871 population-based controls.
+Six tagging single-nucleotide polymorphisms (SNPs) of NFE2L2 were genotyped, and, after further imputation of additional 34 SNPs, association testing with ARDS susceptibility was conducted using logistic regression analysis.
+RESULTS: After multiple testing adjustments, our analysis revealed 10 non-coding SNPs in tight linkage disequilibrium (0.75 ≤ r(2) ≤ 1) that were associated with ARDS susceptibility as a single association signal.
+One of those SNPs (rs672961) was previously associated with trauma-induced ARDS and modified the promoter activity of the NFE2L2 gene, showing an odds ratio of 1.93 per T allele (95 % confidence interval, 1.17–3.18; p = 0.0089).
+CONCLUSIONS: Our findings support the involvement of NFE2L2 gene variants in ARDS susceptibility and reinforce further exploration of the role of oxidant stress response as a risk factor for ARDS in critically ill patients.
+ADP-ribosylation is a post-translational modification where single units (mono-ADP-ribosylation) or polymeric chains (poly-ADP-ribosylation) of ADP-ribose are conjugated to proteins by ADP-ribosyltransferases.
+This post-translational modification and the ADP-ribosyltransferases (also known as PARPs) responsible for its synthesis have been found to play a role in nearly all major cellular processes, including DNA repair, transcription, translation, cell signaling, and cell death.
+Furthermore, dysregulation of ADP-ribosylation has been linked to diseases including cancers, diabetes, neurodegenerative disorders, and heart failure, leading to the development of therapeutic PARP inhibitors, many of which are currently in clinical trials.
+The study of this therapeutically important modification has recently been bolstered by the application of mass spectrometry-based proteomics, arguably the most powerful tool for the unbiased analysis of protein modifications.
+Unfortunately, progress has been hampered by the inherent challenges that stem from the physicochemical properties of ADP-ribose, which as a post-translational modification is highly charged, heterogeneous (linear or branched polymers, as well as monomers), labile, and found on a wide range of amino acid acceptors.
+In this Perspective, we discuss the progress that has been made in addressing these challenges, including the recent breakthroughs in proteomics techniques to identify ADP-ribosylation sites, and future developments to provide a proteome-wide view of the many cellular processes regulated by ADP-ribosylation.
+[Image: see text] The high mutation rate of the human immunodeficiency virus type 1 (HIV-1) virus is a major problem since it evades the function of antibodies and chemical inhibitors.
+Here, we demonstrate a viral detection strategy based on synthetic biology principles to detect a specific viral function rather than a particular viral protein.
+The resistance caused by mutations can be circumvented since the mutations that cause the loss of function also incapacitate the virus.
+Many pathogens encode proteases that are essential for their replication and that have a defined substrate specificity.
+A genetically encoded sensor composed of a fused membrane anchor, viral protease target site, and an orthogonal transcriptional activator was engineered into a human cell line.
+The HIV-1 protease released the transcriptional activator from the membrane, thereby inducing transcription of the selected genes.
+The device was still strongly activated by clinically relevant protease mutants that are resistant to protease inhibitors.
+In the future, a similar principle could be applied to detect also other pathogens and functions.
+Anthrax is a highly lethal infectious disease caused by the bacterium Bacillus anthracis, and the associated shock is closely related to the lethal toxin (LeTx) produced by the bacterium.
+The central role played by the 63 kDa protective antigen (PA63) region of LeTx in the pathophysiology of anthrax makes it an excellent therapeutic target.
+In the present study, a human/murine chimeric IgG mAb, hmPA6, was developed by inserting murine antibody variable regions into human constant regions using antibody engineering technology.
+At a dose of 0.3 mg/kg, it could protect all tested rats from a lethal dose of LeTx.
+Even administration of 0.6 mg/kg hmPA6 48 h before LeTx challenge protected all tested rats.
+The results indicate that hmPA6 is a potential candidate for clinical application in anthrax treatment.
+We looked at a software system (a) used in shelters across the United States to determine if it can be used to track URI frequency and risk factors in a population.
+This showed that data currently collected were not useful for tracking URI frequency and risk factors.
+However, potential exists to increase the practicality and usefulness of this shelter software system to monitor URI and other diseases.
+ABSTRACT: Objective—Feline upper respiratory infection (URI) is a common, multi-factorial infectious disease syndrome endemic to many animal shelters.
+Although a significant cause of morbidity and mortality in shelter cats, URI is seldom formally monitored in shelter cat populations.
+We looked at an integrated case management software system (a) for animal care organizations, widely used in shelters across the United States.
+Shelter staff routinely enter information regarding individual animals and disease status, but do not commonly use the software system to track frequency of disease.
+The purpose of this study was to determine if the software system (a) can be used to track URI frequency and selected risk factors in a population, and to evaluate the quality and completeness of the data as currently collected in a shelter.
+Procedures—Reports from the software system (a) containing data regarding daily inventory, daily intake, animal identification, location, age, vaccination status, URI diagnosis and URI duration were evaluated.
+The reports were compared to data collected manually by an observer (Ann Therese Kommedal) to assess discrepancies, completeness, timeliness, availability and accuracy.
+Results—Comparisons between the software system (a) reports and manually collected reports showed that 93% of inventory reports were complete and of these 99% were accurate.
+Two-hundred and twenty-three cats were assigned a positive or negative URI diagnosis by the observer.
+The predictive value of the URI status in the software system (a) was below 60% both for positive and negative URI diagnosis.
+Conclusions and Clinical Relevance—data currently collected and entered into the software systems in the study shelter, was not useful for tracking URI frequency and risk factors, due to issues with both data quality and capture.
+However, the potential exists to increase the practicality and usefulness of this shelter software system to monitor URI and other diseases.
+Relevant data points, i.e., health status at intake and outcome, vaccination date and status, as well as age, should be made mandatory to facilitate more useful data collection and reporting.
+In 2010 the population of South Africa was 50 million and the HIV prevalence was 11%.
+Hospitalized severe acute respiratory illness (SARI) incidence was calculated, stratified by HIV status, for four age groups using data from population-based surveillance in one site situated in Gauteng Province for 2009–2011.
+These rates were adjusted for each of the remaining 8 provinces based on their prevalence of risk factors for pneumonia and healthcare-seeking behavior.
+We estimated non-hospitalized influenza-associated SARI from healthcare utilization surveys at two sites and used the percent of SARI cases positive for influenza from sentinel surveillance to derive the influenza-associated SARI rate.
+We applied rates of hospitalized and non-hospitalized influenza-associated SARI to census data to calculate the national number of cases.
+The percent of SARI cases that tested positive for influenza ranged from 7–17% depending on age group, year, province and HIV status.
+In 2010, there were an estimated 21,555 total severe influenza cases in HIV-uninfected individuals and 13,876 in HIV-infected individuals.
+In 2011, there were an estimated 29,892 total severe influenza cases in HIV-uninfected individuals and 17,289 in HIV-infected individuals.
+The incidence of influenza-associated SARI was highest in children <5 years and was higher in HIV-infected than HIV-uninfected persons in all age groups.
+Influenza virus was associated with a substantial amount of severe disease, especially in young children and HIV-infected populations in South Africa.
+Interleukin (IL)-8 is a potent neutrophil chemotactic factor and a crucial mediator in neutrophil-dependent inflammation.
+Various cell types produce IL-8, either in response to external stimuli such as cytokines or bacterial infection, or after malignant transformation.
+In this paper we demonstrate that the RNA interference technique can be used to efficiently down-regulate IL-8 protein expression in airway epithelial cells.
+We used a helper-dependent adenoviral vector to express a small hairpin (sh)RNA targeting human IL-8 in cultured airway epithelial cells (IB3-1, Cftr(−/−); C38, Cftr-corrected) stimulated with TNF-α, IL-1β or heat-inactivated Burkholderia cenocepacia.
+The shRNA targeting IL-8 had no effect on the activation of NF-κB, or on the protein levels of IκB or IL-6, suggesting that this anti-IL-8 strategy was highly specific, and therefore may offer potential for the treatment of inflammatory diseases.
+SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/sj.cr.7290275) contains supplementary material, which is available to authorized users.
+Viral metagenomics has recently revealed the ubiquitous and diverse nature of single-stranded DNA (ssDNA) viruses that encode a conserved replication initiator protein (Rep) in the marine environment.
+Although eukaryotic circular Rep-encoding ssDNA (CRESS-DNA) viruses were originally thought to only infect plants and vertebrates, recent studies have identified these viruses in a number of invertebrates.
+To further explore CRESS-DNA viruses in the marine environment, this study surveyed CRESS-DNA viruses in various marine invertebrate species.
+A total of 27 novel CRESS-DNA genomes, with Reps that share less than 60.1% identity with previously reported viruses, were recovered from 21 invertebrate species, mainly crustaceans.
+Phylogenetic analysis based on the Rep revealed a novel clade of CRESS-DNA viruses that included approximately one third of the marine invertebrate associated viruses identified here and whose members may represent a novel family.
+Investigation of putative capsid proteins (Cap) encoded within the eukaryotic CRESS-DNA viral genomes from this study and those in GenBank demonstrated conserved patterns of predicted intrinsically disordered regions (IDRs), which can be used to complement similarity-based searches to identify divergent structural proteins within novel genomes.
+Overall, this study expands our knowledge of CRESS-DNA viruses associated with invertebrates and explores a new tool to evaluate divergent structural proteins encoded by these viruses.
+Human populations worldwide are increasingly confronted with infectious diseases and antimicrobial resistance spreading faster and appearing more frequently.
+Knowledge regarding their occurrence and worldwide transmission is important to control outbreaks and prevent epidemics.
+Here, we performed shotgun sequencing of toilet waste from 18 international airplanes arriving in Copenhagen, Denmark, from nine cities in three world regions.
+An average of 18.6 Gb (14.8 to 25.7 Gb) of raw Illumina paired end sequence data was generated, cleaned, trimmed and mapped against reference sequence databases for bacteria and antimicrobial resistance genes.
+An average of 106,839 (0.06%) reads were assigned to resistance genes with genes encoding resistance to tetracycline, macrolide and beta-lactam resistance genes as the most abundant in all samples.
+We found significantly higher abundance and diversity of genes encoding antimicrobial resistance, including critical important resistance (e.g.
+Presence of Salmonella enterica and norovirus were also detected in higher amounts from South Asia, whereas Clostridium difficile was most abundant in samples from North America.
+Our study provides a first step towards a potential novel strategy for global surveillance enabling simultaneous detection of multiple human health threatening genetic elements, infectious agents and resistance genes.
+Nogo-B, a member of the reticulon 4 protein family, plays a critical role in tissue repair and acute inflammation.
+Here, we assessed the function of Nogo-B during tissue injury in a lipopolysaccharide (LPS)-induced ALI mouse model.
+Over-expression of pulmonary Nogo-B using an adenovirus vector carrying the Nogo-B-RFP-3flag gene (Ad-Nogo-B) significantly prolonged the survival of mice challenged with a lethal dose of LPS.
+The Ad-Nogo-B-treated mice also had less severe lung injury, less alveolar protein exudation, and a higher number of macrophages but less neutrophil infiltration compared with Ad-RFP-treated mice.
+Interestingly, microarray analysis showed that the Ad-Nogo-B-treated mice had different gene expression profiles compared with the controls and the prominent expression of genes related to wound healing and the humoral immune response after LPS induction.
+Of the 49 differently expressed genes, we found that the expression of PTX3 was significantly up-regulated following Nogo-B over-expression as observed in lung tissues and RAW264.7 cells.
+In conclusion, Nogo-B plays a protective role against LPS-induced ALI, and this effect might be exerted through the modulation of alveolar macrophage recruitment and PTX3 production.
+In this study, we demonstrated a novel mechanism by which EGCG reverses the neutrophil elastase-induced migration of A549 cells.
+We found that neutrophil elastase directly triggered human adenocarcinoma A549 cell migration and that EGCG suppressed the elevation of tumor cell migration induced by neutrophil elastase.
+We observed that EGCG directly binds to neutrophil elastase and inhibits its enzymatic activity based on the CDOCKER algorithm, MD stimulation by GROMACS, SPR assay and elastase enzymatic activity assay.
+We further demonstrated that the expression of α1-antitrypsin was up-regulated after EGCG treatment in neutrophil elastase-treated A549 cells.
+We preliminarily discovered that the EGCG-mediated induction of α1-antitrypsin expression might be correlated with the regulatory effect of EGCG on the PI3K/Akt pathway.
+The mechanism underlying this effect may include two processes: EGCG directly binds to neutrophil elastase and inhibits its enzymatic activity; EGCG enhances the expression of α1-antitrypsin by regulating the PI3K/AKT pathway.
+BACKGROUND: Since 2010, a variant Porcine epidemic diarrhea virus (PEDV), which causes an acute, highly contagious, and devastating viral enteric disease with a high mortality rate in suckling pigs, broke out in China and spread rapidly to neighboring countries, even to the North America.
+However, there were no reports of mild pathogenicity of a variant porcine epidemic diarrhea virus in China.
+FINDINGS: In 2013, a PEDV-positive sample from a sow with very mild clinical sign was used to inoculate in Vero cells to isolate the virus.
+The phylogenetic trees based upon either the complete genome or S gene showed that the FL2013 strain belongs to the genogroup G2b.
+The S gene of FL2013 has a 7-aa deletion (FEKVHVQ) in the C-terminus comparison with the other G2 PEDV sequences.
+Further comparative pathology study indicated that the FL2013 strain had reduced virulence to newborn piglets.
+CONCLUSIONS: A novel variant PEDV strain FL2013 with reduced virulence, as determined by the pathological study, was identified from east China.
+This strain is closely related to the genogroup- 2 PEDV strains prevalent in the U.S. and China currently, but had a short deletion at the 3′- end of the spike gene.
+In ecology, the grouping of species into functional groups has played a valuable role in simplifying ecological complexity.
+In epidemiology, further clarifications of epidemiological functions are needed: while host roles may be defined, they are often used loosely, partly because of a lack of clarity on the relationships between a host’s function and its epidemiological role.
+Bridge hosts provide a link through which pathogens can be transmitted from maintenance host populations or communities to receptive populations that people want to protect (i.e., target hosts).
+A bridge host should (1) be competent for the pathogen or able to mechanically transmit it; and (2) come into direct contact or share habitat with both maintenance and target populations.
+We illustrate this framework using the example of the transmission of Avian Influenza Viruses across wild bird/poultry interfaces in Africa and discuss a range of other examples that demonstrate the usefulness of our definition for other multi-host systems.
+Bridge hosts can be particularly important for understanding and managing infectious disease dynamics in multi-host systems at wildlife/domestic/human interfaces, including emerging infections.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13567-015-0217-9) contains supplementary material, which is available to authorized users.
+Apolipoprotein L9b (Apol9b) is an interferon-stimulated gene (ISG) that has antiviral activity and is weakly expressed in primary mouse neurons as compared to other cell types.
+Here, we show that both Apol9 isoforms (Apol9b and Apol9a) inhibit replication of Theiler’s murine encephalomyelitis virus (TMEV) but not replication of vesicular stomatitis virus (VSV), Murid herpesvirus-4 (MuHV-4), or infection by a lentiviral vector.
+Apol9 genes are strongly expressed in mouse liver and, to a lesser extent, in pancreas, adipose tissue and intestine.
+In contrast to genuine apolipoproteins that are involved in lipid transport, ApoL9 has an intracytoplasmic localization and does not seem to be secreted.
+The cytoplasmic localization of ApoL9 is in line with the observation that ApoL9 inhibits the replication step of TMEV infection.
+In contrast to human ApoL6, ApoL9 did not sensitize cells to apoptosis, in spite of the presence of a conserved putative BH3 domain, required for antiviral activity.
+ApoL9a and b isoforms interact with cellular prohibitin 1 (Phb1) and prohibitin 2 (Phb2) and this interaction might contribute to ApoL9 antiviral activity.
+The antiviral activity of prohibitins against TMEV contrasts with the pro-viral activity of prohibitins observed for VSV and reported previously for Dengue 2 (DENV-2), Chikungunya (CHIKV) and influenza H5N1 viruses.
+ApoL9 is thus an example of ISG displaying a narrow antiviral range, which likely acts in complex with prohibitins to restrict TMEV replication.
+BACKGROUND: The 2014/15 influenza season in Canada was characterized by an early epidemic due to vaccine-mismatched influenza A(H3N2) viruses, disproportionately affecting elderly individuals ≥65-years-old.
+We assessed vaccine effectiveness (VE) against A(H3N2) hospitalization among elderly individuals during the peak weeks of the 2014/15 epidemic in Quebec, Canada.
+METHODS: Nasal specimens and clinical/epidemiological data were collected within 7 days of illness onset from elderly patients admitted with respiratory symptoms to one of four participating hospitals between November 30, 2014 and January 13, 2015.
+RESULTS: There were 314 participants including 186 cases (62% vaccinated) and 128 controls (59% vaccinated) included in primary VE analysis.
+Median age was 81.5 years, two-thirds were admitted from the community and 91% had underlying comorbidity.
+Crude VE against A(H3N2) hospitalization was -17% (95%CI: -86% to 26%), decreasing to -23% (95%CI: -99 to 23%) with adjustment for age and comorbidity, and to -39% (95%CI: -142 to 20%) with additional adjustment for specimen collection interval, calendar time, type of residence and hospital.
+In sensitivity analyses, VE estimates were improved toward the null with restriction to participants admitted from the community (-2%; 95%CI: -105 to 49%) or with specimen collection ≤4 days since illness onset (- 8%; 95%CI: -104 to 43%) but further from the null with restriction to participants with comorbidity (-51%; 95%CI: -169 to 15%).
+CONCLUSION: The 2014/15 mismatched influenza vaccine provided elderly patients with no cross-protection against hospitalization with the A(H3N2) epidemic strain, reinforcing the need for adjunct protective measures among high-risk individuals and improved vaccine options.
+Human immunodeficiency virus (HIV)-specific CD8(+) T cells play a critical role in containing HIV replication and delaying disease progression.
+Symptoms of T cell exhaustion range from expression of inhibitory receptors and selective loss of cytokine production capacity through reduced proliferative potential, impaired differentiation into effector cells and increased susceptibility to apoptosis.
+While effective combination antiretroviral therapy (cART) durably reduces HIV viremia to undetectable levels, this alone does not restore the full pluripotency of HIV-specific CD8(+) T cells.
+In a number of studies, a subset of peptide epitope variants categorized as heteroclitic, restimulated more potent cellular immune responses in vitro than did the native, immunizing peptides themselves.
+This property of heteroclitic peptides has been exploited in experimental cancer and chronic viral infection models to promote clearance of transformed cells and persistent viruses.
+In this review, we consider the possibility that heteroclitic peptides could improve the efficacy of therapeutic vaccines as part of HIV immunotherapy or eradication strategies.
+We review literature on heteroclitic peptides and illustrate their potential to beneficially modulate the nature of HIV-specific T cell responses toward those found in the small minority of HIV-infected, aviremic cART-naïve persons termed elite controllers or long-term non-progressors.
+Our review suggests that the efficacy of HIV vaccines could be improved by identification, testing, and incorporation of heteroclitic variants of native HIV peptide epitopes.
+However, this involvement has not been well-studied in the paradigm of macrophage polarization, which typically has been categorized by the dichotomy of classical (M1) and alternative (M2) statuses.
+Recent studies have revealed the complexity of macrophage polarization in response to various cellular mediators and exogenous stimuli by adopting a multipolar view to revisit the differential process of macrophages, especially those re-polarized during viral infections.
+Here, through examination of viral infections targeting macrophages/monocytic cells, we focus on the direct involvement of macrophage polarization during viral infections.
+Type I and type III interferons (IFNs) are critical in regulation of viral pathogenesis and host antiviral infection; thus, we propose to incorporate IFN-mediated antiviral states into the framework of macrophage polarization.
+This view is supported by the multifunctional properties of type I IFNs, which potentially elicit and regulate both M1- and M2-polarization in addition to inducing the antiviral state, and by the discoveries of viral mechanisms to adapt and modulate macrophage polarization.
+Indeed, several recent studies have demonstrated effective prevention of viral diseases through manipulation of macrophage immune statuses.
+BACKGROUND: Cell-culture-derived (CC) influenza vaccine production methods could provide benefits over classical embryonated-egg technology, including a higher production capacity and the faster creation of a supply that meets demand.
+METHODS: A CC-inactivated split-virus influenza A/Indonesia/5/2005(H5N1) vaccine derived from the EB66 cell line (hereafter, “CC-H5N1”) was investigated in a phase 1 randomized, blinded study.
+Healthy adults (n = 521) received 2 vaccine doses (days 0 and 21) of either investigational CC-H5N1 vaccine (1.9 µg or 3.75 µg of hemagglutinin antigen [HA] with the AS03 adjuvant system or 15 µg of plain HA), embryonated-egg-derived vaccines (3.75 µg of HA with AS03 or 15 µg of plain HA), or placebo.
+Assessment of the adjuvant effect and immunogenicity was performed using Center for Biologics Evaluation and Research acceptability criteria 21 days after dose 2.
+RESULTS: AS03-adjuvanted CC-H5N1 elicited a homologous hemagglutination inhibition antibody response that satisfied immunogenicity criteria 21 days after dose 2 and persisted at month 12.
+The immunogenicity and safety of the CC-H5N1 formulation containing 3.75 µg of HA and AS03 appeared to be similar to those for the licensed egg-derived AS03-adjuvanted control vaccine.
+CONCLUSIONS: The feasibility of the EB66 cell line to produce an immunogenic influenza vaccine with acceptable safety profile was demonstrated.
+This CC-H5N1 might contribute to the rapid access of vaccine in the event of an influenza A(H5N1) pandemic.
+We hypothesized that heliox ventilation allows for a reduction in minute volume ventilation and inspiratory pressures needed for adequate gas exchange in an animal model of an acute lung injury.
+METHODS: After intratracheal instillation of lipopolysaccharide (10 mg/kg), adult rats were randomized to ventilation with either a gas mixture of helium/oxygen (50:50%) or oxygen/air (50:50%).
+They were mechanically ventilated according to the ARDSnet recommendations with tidal volumes of 6 ml/kg and monitored with a pneumotachometer.
+Bronchoalveolar lavage fluid was analyzed for markers of lung injury, and embedded lung sections were histologically scored for lung injury.
+RESULTS: Heliox limited the increase in driving pressures needed to achieve preset tidal volumes, with a concomitant decrease in loss of compliance.
+Heliox did neither allow for reduced minute volume ventilation in this model nor improve gas exchange.
+CONCLUSIONS: Heliox modestly improved respiratory mechanics but did not improve lung injury in this rat model of acute respiratory distress syndrome.
+The activation of astrocytes and microglia is often associated with diseases of the central nervous system (CNS).
+Understanding how activation alters the transcriptome of these cells may offer valuable insight regarding how activation of these cells mediate neurological damage.
+Furthermore, identifying common and unique pathways of gene expression during activation may provide new insight into the distinct roles these cells have in the CNS during infection and inflammation.
+Since recent studies indicate that TLR7 recognizes not only viral RNA but also microRNAs that are released by damaged neurons and elevated during neurological diseases, we first examined the response of glial cells to TLR7 stimulation using microarray analysis.
+Microglia were found to generate a much stronger response to TLR7 activation than astrocytes, both in the number of genes induced as well as fold induction.
+Although the primary pathways induced by both cell types were directly linked to immune responses, microglia also induced pathways associated with cellular proliferation, while astrocytes did not.
+Targeted analysis of a subset of the upregulated genes identified unique mRNA, including Ifi202b which was only upregulated by microglia and was found to be induced during both retroviral and bunyavirus infections in the CNS.
+In addition, other genes including Birc3 and Gpr84 as well as two expressed sequences AW112010 and BC023105 were found to be induced in both microglia and astrocytes and were upregulated in the CNS following virus infection.
+Thus, expression of these genes may a useful measurement of glial activation during insult or injury to the CNS.
+However, only a selection of their products have been demonstrated to be responsible for the inhibition of rhabdovirus replication in cultured cells; and only a few have been shown to play a role in mediating the antiviral response in vivo using gene knockout mouse models.
+IFNs inhibit rhabdovirus replication at different stages via the induction of a variety of ISGs.
+This review will discuss how individual ISG products confer resistance to rhabdoviruses by blocking viral entry, degrading single stranded viral RNA, inhibiting viral translation or preventing release of virions from the cell.
+BACKGROUND: The Gene Ontology project is a collaborative effort to provide descriptions of gene products in a consistent and computable language, and in a species-independent manner.
+The Gene Ontology is designed to be applicable to all organisms but up to now has been largely under-utilized for prokaryotes and viruses, in part because of a lack of appropriate ontology terms.
+METHODS: To address this issue, we have developed a set of Gene Ontology classes that are applicable to microbes and their hosts, improving both coverage and quality in this area of the Gene Ontology.
+Describing microbial and viral gene products brings with it the additional challenge of capturing both the host and the microbe.
+Recognising this, we have worked closely with annotation groups to test and optimize the GO classes, and we describe here a set of annotation guidelines that allow the controlled description of two interacting organisms.
+CONCLUSIONS: Building on the microbial resources already in existence such as ViralZone, UniProtKB keywords and MeGO, this project provides an integrated ontology to describe interactions between microbial species and their hosts, with mappings to the external resources above.
+Housing this information within the freely-accessible Gene Ontology project allows the classes and annotation structure to be utilized by a large community of biologists and users.
+BACKGROUND: Surgical site infection (SSI) remains a significant problem in the postoperative period that can negatively affect clinical outcomes.
+Microbiology findings are typically similar to other nosocomial infections, with differences dependent on microbiology selection due to antibiotic pressure or the resident flora.
+We therefore aimed to assess the incidence, epidemiology and microbiology of SSI and its association with outcomes in patients with severe peritonitis in the intensive care unit (ICU).
+METHODS: We prospectively studied 305 consecutive patients admitted to our surgical ICU from 2010 to 2014 with a diagnosis of secondary or tertiary peritonitis.
+We collected the following data: SSI diagnosis, demographics, Acute Physiology and Chronic Health Evaluation (APACHE) II score, Simplified Acute Physiology Score (SAPS) II score, type of surgery, microbiology, antibiotic treatment and outcomes.
+RESULTS: We identified 269 episodes of SSI in 162 patients (53.1 %) aged 64.4 ± 14.3 years, of which 200 episodes occurred in men (64.6 %).
+The mean APACHE II and SAPS II scores were 19.7 ± 7.8 and 36.5 ± 16.1 respectively.
+The mean ICU and hospital stays were 19.8 ± 24.8 and 21.7 ± 30 days respectively.
+(n = 52, 19.3 %), Escherichia coli (n = 55, 20.4 %) and Candida spp.
+(n = 46, 17.1 %) were the most frequently isolated microorganisms, but gram-positive cocci (n = 80, 29.7 %) were also frequent.
+Microorganisms isolated from SSIs were associated with a higher incidence of antibiotic resistance (64.9 %) in ICU patients, but not with higher in-hospital mortality.
+However, patients who suffered from SSI had longer ICU admissions (odds ratio = 1.024, 95 % confidence interval 1.010–1.039, P = 0.001).
+CONCLUSIONS: The incidence of SSI in secondary or tertiary peritonitis requiring ICU admission is very high.
+Physicians may consider antibiotic-resistant pathogens, gram-positive cocci and fungi when choosing empiric antibiotic treatment for SSI, although more studies are needed to confirm our results due to the inherent limitations of the microbiological sampling with swabs performed in our research.
+The presence of SSI may be associated with prolonged ICU stays, but without any influence on overall mortality.
+For the past 25 years, phage display technology has been an invaluable tool for studies of protein–protein interactions.
+However, the inherent biological, biochemical, and biophysical properties of filamentous bacteriophage, as well as the ease of its genetic manipulation, also make it an attractive platform outside the traditional phage display canon.
+This review will focus on the unique properties of the filamentous bacteriophage and highlight its diverse applications in current research.
+Despite their ubiquity in the biosphere, metagenomics work is just beginning to explore the ecology of filamentous and non-filamentous phage, and their role in the evolution of bacterial populations.
+Thus, the filamentous phage represents a robust, inexpensive, and versatile microorganism whose bioengineering applications continue to expand in new directions, although its limitations in some spheres impose obstacles to its widespread adoption and use.
+However, the knowledge about the specificity of teleost Tlr factors for distinct pathogens is limited so far.
+We measured baseline expression profiles of 18 tlr genes and associated signaling factors in four immune-relevant tissues of rainbow trout Oncorhynchus mykiss.
+In contrast, only the fish-specific tlr22a2 and the downstream factor irak1 featured clearly increased transcript levels, while the mRNA concentrations of many other tlr genes decreased.
+Flow cytometry quantified cell trafficking after infection indicating a dramatic influx of myeloid cells into the peritoneum and a belated low level immigration of lymphoid cells.
+T and B lymphocytes were differentiated with RT-qPCR revealing that B lymphocytes emigrated from and T lymphocytes immigrated into head kidney.
+In conclusion, no specific TLR can be singled out as a dominant receptor for A. salmonicida.
+The recruitment of cellular factors of innate immunity rather than induced expression of pathogen receptors is hence of key importance for mounting a first immune defense against invading A. salmonicida.
+Autophagy is a conserved catabolic process of the cell, which plays an important role in regulating plethora of infections.
+Here, we found that HSV-2 does not allow induction of an autophagic response to infection, but maintains basal autophagy levels mostly unchanged during productive infection.
+Thus, we investigated the importance of basal autophagy for HSV-2 infection, using pharmacological autophagy suppression or cells genetically deficient in an autophagy-essential gene (ATG5).
+Interference with basal autophagy flux in cells significantly reduced viral replication and diminished the infection.
+These results indicate that basal autophagy plays an indispensable role required for a productive infection.
+Importantly, this study draws a sharp distinction between induced and basal autophagy, where the former acts as a viral clearance mechanism abrogating infection, while the latter supports infection.
+Influenza poses a significant health threat to children, and schools may play a critical role in community outbreaks.
+Mathematical outbreak models require assumptions about contact rates and patterns among students, but the level of temporal granularity required to produce reliable results is unclear.
+We collected objective contact data from students aged 5–14 at an elementary school and middle school in the state of Utah, USA, and paired those data with a novel, data-based model of influenza transmission in schools.
+We compared simulated outbreaks over the full resolution dynamic network with simulations on networks with averaged representations of contact timing and duration.
+For both schools, averaging the timing of contacts over one or two school days caused average outbreak sizes to increase by 1–8%.
+Averaging both contact timing and pairwise contact durations caused average outbreak sizes to increase by 10% at the middle school and 72% at the elementary school.
+Averaging contact durations separately across within-class and between-class contacts reduced the increase for the elementary school to 5%.
+Thus, the effect of ignoring details about contact timing and duration in school contact networks on outbreak size modelling can vary across different schools.
+From 1992 onwards, outbreaks of a previously unknown illness have been reported in Asian seabass (Lates calcarifer) kept in maricultures in Southeast Asia.
+By using a next-generation virus discovery technique, VIDISCA-454, sequences of an unknown virus were detected in serum of diseased fish.
+The near complete genome sequence of the virus was determined, which shows a unique genome organization, and low levels of identity to known members of the Iridoviridae.
+Based on homology of a series of putatively encoded proteins, the virus is a novel member of the Megalocytivirus genus of the Iridoviridae family.
+The virus was isolated and propagated in cell culture, where it caused a cytopathogenic effect in infected Asian seabass kidney and brain cells.
+In vitro cultured virus induced scale drop syndrome in Asian seabass in vivo and the virus could be reisolated from these infected fish.
+These findings show that the virus is the causative agent for the scale drop syndrome, as each of Koch’s postulates is fulfilled.
+Vaccines prepared from BEI- and formalin inactivated virus, as well as from E. coli produced major capsid protein provide efficacious protection against scale drop disease.
+The leishmaniases are a complex of vector-borne diseases caused by protozoan parasites of the genus Leishmania.
+Here, we describe the safety testing of LEISHDNAVAX in naive mice and rats, complemented by the demonstration of tolerability in Leishmania-infected mice.
+Although vector DNA was cleared from most other tissues within 60 days after the last injection, it persisted in skin at the site of injection and in draining lymph nodes.
+Taken together, our results substantiate a favorable safety profile of LEISHDNAVAX in both naive and infected animals and thus, support the initiation of clinical trials for both preventive and therapeutic applications of the vaccine.
+Children born preterm often exhibit reduced lung function and increased severity of response to respiratory viruses, suggesting that premature birth has compromised proper development of the respiratory epithelium and innate immune defenses.
+Increasing evidence suggests that premature birth promotes aberrant lung development likely due to the neonatal oxygen transition occurring before pulmonary development has matured.
+Given that preterm infants are born at a point of time where their immune system is also still developing, early life oxygen exposure may also be disrupting proper development of innate immunity.
+Here, we review current literature in hopes of stimulating research that enhances understanding of how the oxygen environment at birth influences lung development and host defense.
+This knowledge may help identify those children at risk for disease and ideally culminate in the development of novel therapies that improve their health.
+Dengue genome encodes a two component protease complex (NS2B-NS3pro) essential for the viral maturation/infectivity, thus representing a key drug target.
+Previously, due to its “complete insolubility”, the isolated NS3pro could not be experimentally studied and it remains elusive what structure it adopts without NS2B and why NS2B is indispensable.
+Here as facilitated by our previous discovery, the isolated NS3pro has been surprisingly deciphered by NMR to be the first intrinsically-disordered chymotrypsin-like fold, which exists in a loosely-packed state with non-native long-range interactions as revealed by paramagnetic relaxation enhancement (PRE).
+The disordered NS3pro appears to be needed for binding a human host factor to trigger the membrane remodeling.
+Moreover, we have in vitro refolded the NS3pro in complex with either NS2B (48–100) or the full-length NS2B (1–130) anchored into the LMPC micelle, and the two complexes have similar activities but different dynamics.
+We also performed molecular dynamics (MD) simulations and the results revealed that NS2B shows the highest structural fluctuations in the complex, thus providing the dynamic basis for the observation on its conformational exchange between open and closed states.
+Remarkably, the NS2B cofactor plays a central role in maintaining the correlated motion network required for the catalysis as we previously decoded for the SARS 3CL protease.
+Indeed, a truncated NS2B (48–100;Δ77–84) with the flexible loop deleted is able to trap the NS2B-NS3pro complex in a highly dynamic and catalytically-impotent state.
+Taken together, our study implies potential strategies to perturb the NS2B-NS3pro interface for design of inhibitors for treating dengue infection.
+BACKGROUND: Human infections with avian influenza viruses (AIVs) have frequently raised global concerns of emerging, interspecies-transmissible viruses with pandemic potential.
+Waterfowl, the predominant reservoir of influenza viruses in nature, harbor precursors of different genetic lineages that have contributed to novel pandemic influenza viruses in the past.
+METHODS: Two duck influenza H5N2 viruses, DV518 and DV413, isolated through virological surveillance at a live-poultry market in Taiwan, showed phylogenetic relatedness but exhibited different replication capabilities in mammalian Madin-Darby Canine Kidney (MDCK) cells.
+This study characterizes the replication properties of the two duck H5N2 viruses and the determinants involved.
+RESULTS: The DV518 virus replicated more efficiently than DV413 in both MDCK and chicken DF1 cells.
+Interestingly, the infection of MDCK cells by DV518 formed heterogeneous plaques with great differences in size [large (L) and small (S)], and the two viral strains (p518-L and p518-S) obtained from plaque purification exhibited distinguishable replication kinetics in MDCK cells.
+Nonetheless, both plaque-purified DV518 strains still maintained their growth advantages over the plaque-purified p413 strain.
+Moreover, three amino acid substitutions in PA (P224S), PB2 (E72D), and M1 (A128T) were identified in intra-duck variations (p518-L vs p518-S), whereas other changes in HA (N170D), NA (I56T), and NP (Y289H) were present in inter-duck variations (DV518 vs DV413).
+Both p518-L and p518-S strains had the N170D substitution in HA, which might be related to their greater binding to MDCK cells.
+Additionally, polymerase activity assays on 293T cells demonstrated the role of vRNP in modulating the replication capability of the duck p518-L viruses in mammalian cells.
+In view of recent human infections by low pathogenic AIVs, this study suggests possible determinants involved in the stepwise selection of virus variants from the duck influenza virus population which may facilitate inter-species transmission.
+Central nervous system (CNS) dysfunction caused by neurovirulent influenza viruses is a dreaded complication of infection, and may play a role in some neurodegenerative conditions, such as Parkinson-like diseases and encephalitis lethargica.
+Although CNS infection by highly pathogenic H5N1 virus has been demonstrated, it is unknown whether H5N1 infects neural progenitor cells, nor whether such infection plays a role in the neuroinflammation and neurodegeneration.
+To pursue this question, we infected human neural progenitor cells (hNPCs) differentiated from human embryonic stem cells in vitro with H5N1 virus, and studied the resulting cytopathology, cytokine expression, and genes involved in the differentiation.
+Human embryonic stem cells (BG01) were maintained and differentiated into the neural progenitors, and then infected by H5N1 virus (A/Chicken/Thailand/CUK2/04) at a multiplicity of infection of 1.
+Then cells were characterized by immunofluorescence and electron microscopy, supernatants quantified for virus titers, and sampled cells studied for candidate genes.The hNPCs were susceptible to H5N1 virus infection as determined by morphological observation and immunofluorescence.
+The infection was characterized by a significant up-regulation of TNF-α gene expression, while expressions of IFN-α2, IFN-β1, IFN-γ and IL-6 remained unchanged compared to mock-infected controls.
+Moreover, H5N1 infection did not appear to alter expression of neuronal and astrocytic markers of hNPCs, such as β-III tubulin and GFAP, respectively.
+The results indicate that hNPCs support H5N1 virus infection and may play a role in the neuroinflammation during acute viral encephalitis.
+BACKGROUND: Variant influenza A(H3N2) viruses (H3N2v) have transmitted recently from pigs to humans in the United States.
+METHODS: Healthy adults received 2 doses of subvirion H3N2v vaccine (15 µg of hemagglutinin/dose) 21 days apart in this open-label trial.
+Serum hemagglutination inhibition (HAI) and neutralizing (Neut) antibody (Ab) titers were measured before and 8 and 21 days after each dose.
+A total of 40% of subjects had an HAI Ab titer of ≥40 before vaccination.
+Eight-seven percent (95% confidence interval [CI], 79%–93%) and 73% (95% CI, 63%–81%) of subjects 18–64 years old (98 subjects) and ≥65 years old (90 subjects), respectively, had an HAI titer of ≥40 21 days after dose 1 (P = .01); 51% (95% CI, 41%–61%) and 52% (95% CI, 41%–62%) of younger and older subjects, respectively, developed ≥4-fold rises in titer (P = not significant).
+CONCLUSIONS: In most healthy adults, one 15-µg dose of vaccine elicited levels of HAI Abs associated with protection.
+Studies in children and elderly individuals are indicated to define the immunization needs of these groups.
+Schistosoma japonicum, a zoonotic parasite with a wide range of mammalian hosts, is one of the major pathogens of this disease.
+Although numerous studies on schistosomiasis japonica have been performed using laboratory animal models, systematic comparative analysis of whole-genome expression profiles in parasites from different laboratory animals and nature mammalian hosts is lacking to date.
+METHODOLOGY/PRINCIPAL FINDINGS: Adult schistosomes were obtained from laboratory animals BALB/c mice, C57BL/6 mice, New Zealand white rabbits and the natural host, water buffaloes.
+The gene expression profiles of schistosomes from these animals were obtained and compared by genome-wide oligonucleotide microarray analysis.
+The results revealed that the gene expression profiles of schistosomes from different laboratory animals and buffaloes were highly consistent (r>0.98) genome-wide.
+Meanwhile, a total of 450 genes were identified to be differentially expressed in schistosomes which can be clustered into six groups.
+Pathway analysis revealed that these genes were mainly involved in multiple signal transduction pathways, amino acid, energy, nucleotide and lipid metabolism.
+We also identified a group of 1,540 abundantly and stably expressed gene products in adult worms, including a panel of 179 Schistosoma- or Platyhelminthes-specific genes that may be essential for parasitism and may be regarded as novel potential anti-parasite intervention targets for future research.
+CONCLUSIONS/SIGNIFICANCE: This study provides a comprehensive database of gene expression profiles of schistosomes derived from different laboratory animals and water buffaloes.
+An expanded number of genes potentially affecting the development of schistosomes in different animals were identified.
+These findings lay the foundation for schistosomiasis research in different laboratory animals and natural hosts at the transcriptional level and provide a valuable resource for screening anti-schistosomal intervention targets.
+Enfuvirtide (T20), is the first HIV fusion inhibitor approved for treatment of HIV/AIDS patients who fail to respond to the current antiretroviral drugs.
+However, its clinical application is limited because of short half-life, drug resistance and cross-reactivity with the preexisting antibodies in HIV-infected patients.
+Using an artificial peptide strategy, we designed a peptide with non-native protein sequence, AP3, which exhibited potent antiviral activity against a broad spectrum of HIV-1 strains, including those resistant to T20, and had remarkably longer in vivo half-life than T20.
+While the preexisting antibodies in HIV-infected patients significantly suppressed T20’s antiviral activity, these antibodies neither recognized AP3, nor attenuated its anti-HIV-1 activity.
+The two residues, Met and Thr, at the N-terminus of AP3 form a hook-like structure to stabilize interaction between AP3 and NHR helices.
+Therefore, AP3 has potential for further development as a new HIV fusion inhibitor with improved antiviral efficacy, resistance profile and pharmacological properties over enfuvirtide.
+Meanwhile, this study highlighted the advantages of artificially designed peptides, and confirmed that this strategy could be used in developing artificial peptide-based viral fusion inhibitors against HIV and other enveloped viruses.
+BACKGROUND: The majority of cases with severe pulmonary alveolar proteinosis (PAP) are caused by auto-antibodies against GM-CSF.
+Goal of this study was to determine the prevalence of GATA2 deficiency in children and adults with PAP and hematologic disorders.
+METHODS: Of 21 patients with GM-CSF-autoantibody negative PAP, 13 had no other organ involvement and 8 had some form of hematologic disorder.
+RESULTS: Age at start of PAP ranged from 0.3 to 64 years, 4 patients were children.
+In half of the subjects GATA2-sequence variations were found, two of which were considered disease causing.
+Those two patients had the typical phenotype of GATA2 deficiency, one of whom additionally showed a previously undescribed feature – a cholesterol pneumonia.
+Hematologic disorders included chronic myeloic leukemia, juvenile myelo-monocytic leukemia, lymphoblastic leukemia, sideroblastic anemia and two cases of myelodysplastic syndrome (MDS).
+A 4 year old child with MDS and DiGeorge Syndrome Type 2 was rescued with repetitive whole lung lavages and her PAP was cured with heterologous stem cell transplant.
+CONCLUSIONS: In children and adults with severe GM-CSF negative PAP a close cooperation between pneumologists and hemato-oncologists is needed to diagnose the underlying diseases, some of which are caused by mutations of transcription factor GATA2.
+BACKGROUND: International development assistance for health (DAH) quadrupled between 1990 and 2012, from US$ 5.6 billion to US$ 28.1 billion.
+This generates an increasing need for transparent and replicable tools that could be used to set investment priorities, monitor the distribution of funding in real time, and evaluate the impact of those investments.
+Fundamentally, PLANET is based on crowdsourcing approach to obtaining information relevant to deployment of large–scale programs.
+Information is contributed in real time by a diverse group of participants involved in the program delivery.
+FINDINGS: PLANET relies on real–time information from three levels of participants in large–scale programs: funders, managers and recipients.
+At each level, information is solicited to assess five key risks that are most relevant to each level of operations.
+The risks at the level of funders involve systematic neglect of certain areas, focus on donor’s interests over that of program recipients, ineffective co–ordination between donors, questionable mechanisms of delivery and excessive loss of funding to “middle men”.
+At the level of managers, the risks are corruption, lack of capacity and/or competence, lack of information and /or communication, undue avoidance of governmental structures / preference to non–governmental organizations and exclusion of local expertise.
+At the level of primary recipients, the risks are corruption, parallel operations / “verticalization”, misalignment with local priorities and lack of community involvement, issues with ethics, equity and/or acceptability, and low likelihood of sustainability beyond the end of the program’s implementation.
+INTERPRETATION: PLANET is intended as an additional tool available to policy–makers to prioritize, monitor and evaluate large–scale development programs.
+In this, it should complement tools such as LiST (for health care/interventions), EQUIST (for health care/interventions) and CHNRI (for health research), which also rely on information from local experts and on local context to set priorities in a transparent, user–friendly, replicable, quantifiable and specific, algorithmic–like manner.
+A viral metagenomic approach was used to identify the eukaryotic viruses in fecal samples from 29 Thai children with clinical diagnosis of HFMD collected during the 2012 outbreak.
+These children had previously tested negative by PCR for enterovirus 71 and coxsackievirus A16 and A6.
+Deep sequencing revealed nine virus families: Picornaviridae, Astroviridae, Parvoviridae, Caliciviridae, Paramyxoviridae, Adenoviridae, Reoviridae, Picobirnaviridae, and Polyomaviridae.
+The highest number of viral sequences belonged to human rhinovirus C, astrovirus-MLB2, and coxsackievirus A21.
+Our study provides an overview of virus community and highlights a broad diversity of viruses found in feces from children with HFMD.
+Particle size determines the distance across which pathogens can be transported, as well as the site of deposition and the survivability of the pathogen.
+Despite the importance of this information, the size distribution of particles bearing viruses emitted by infectious animals remains unknown.
+In this study we characterized the concentration and size distribution of inhalable particles that transport influenza A virus (IAV), porcine reproductive and respiratory syndrome virus (PRRSV), and porcine epidemic diarrhea virus (PEDV) generated by acutely infected pigs and assessed virus viability for each particle size range.
+Aerosols from experimentally infected pigs were sampled for 24 days using an Andersen cascade impactor able to separate particles by size (ranging from 0.4 to 10 micrometer (μm) in diameter).
+Air samples collected for the first 9, 20 and the last 3 days of the study were analyzed for IAV, PRRSV and PEDV, respectively, using quantitative reverse transcription polymerase chain reaction (RT-PCR) and quantified as geometric mean copies/m(3) within each size range.
+IAV was detected in all particle size ranges in quantities ranging from 5.5x10(2) (in particles ranging from 1.1 to 2.1μm) to 4.3x10(5) RNA copies/m(3) in the largest particles (9.0–10.0μm).
+PRRSV was detected in all size ranges except particles between 0.7 and 2.1μm in quantities ranging from 6x10(2) (0.4–0.7μm) to 5.1x10(4) RNA copies/m(3) (9.0–10.0μm).
+PEDV, an enteric virus, was detected in all particle sizes and in higher quantities than IAV and PRRSV (p < 0.0001) ranging from 1.3x10(6) (0.4–0.7μm) to 3.5x10(8) RNA copies/m(3) (9.0–10.0μm).
+Infectious status was demonstrated for the 3 viruses, and in the case of IAV and PRRSV, viruses were isolated from particles larger than 2.1μm.
+In summary, our results indicated that airborne PEDV, IAV and PRRSV can be found in a wide range of particle sizes.
+INTRODUCTION: Japanese encephalitis (JE) is a major cause of high morbidity and mortality in several states across India.
+However, in 2014, a sharp rise was observed in the number of cases of JE in north-eastern Assam state, and 51% of the total cases of JE in India were reported from the Assam in the same year.
+In this regard, a study was conducted to evaluate the knowledge and attitudes of healthcare workers in Darrang, a district of Assam highly affected by JE.
+METHODS: A cross sectional study was conducted for 2 months among HCWs in the major district hospital of Darrang, Assam.
+RESULTS: The knowledge of HCWs regarding JE was poor with a mean knowledge score of 11.02±2.39 (out of 17), while their attitudes were positive with a mean attitudes score of 43.16± 2.47 (ranging from 13 to 52).
+Cut-off score for good knowledge and positive attitudes toward JE was set as ≥12 and >40 respectively.
+Older participants (40–49 years) and experienced workers (>10 years) were significantly associated with good knowledge as compared to their referent group (p<0.05), while knowledge of nurses and other orderlies were significantly lower than physicians (p<0.01).
+Similar factors were associated with the positive attitudes of the participants with the exception of experience.
+Future research is required to design, implement and evaluate interventions to improve the knowledge of JE among HCWs.
+Herein, we describe a case series of 12 patients presenting with refractory shock secondary to endocrine emergencies who were rescued by ECMO support.
+The diagnostic distribution was as follows: pheochromocytoma crisis (n = 4), thyroid storm (n = 5), and diabetic ketoacidosis (n = 3).
+The initial presentation of pheochromocytoma crisis was indistinguishable from acute myocardial infarction (AMI) and frequently accompanied by paroxysmal hypertension and limb ischemia.
+Thyroid storm was characterized by hyperbilirubinemia and severe gastrointestinal bleeding, whereas neurological symptoms were common in diabetic ketoacidosis.
+The clinical outcomes of patients with endocrine emergencies were compared with those of 80 cases with AMI who received ECMO because of cardiogenic shock.
+The cardiac function and the general conditions showed a significantly faster recovery in patients with endocrine emergencies than in those with AMI.
+The screening of endocrine diseases should be considered during the resuscitation of patients with refractory circulatory shock.
+BACKGROUND: Influenza and pneumonia combined are the leading causes of death due to infectious diseases in the United States.
+METHODS: Through the Emerging Infections Program, we identified adults ≥ 18 years, who were hospitalized with laboratory-confirmed influenza during October 2005 through April 2008, and had a chest radiograph (CXR) performed.
+Pneumonia was defined as the presence of a CXR infiltrate and either an ICD-9-CM code or discharge summary diagnosis of pneumonia.
+In multivariable analysis, factors associated with pneumonia included: age ≥ 75 years, adjusted odds ratio (AOR) 1.27 (95 % confidence interval 1.10–1.46), white race AOR 1.24 (1.03–1.49), nursing home residence AOR 1.37 (1.14–1.66), chronic lung disease AOR 1.37 (1.18–1.59), immunosuppression AOR 1.45 (1.19–1.78), and asthma AOR 0.76 (0.62–0.92).
+Patients with pneumonia were significantly more likely to require intensive care unit (ICU) admission (27 % vs. 10 %), mechanical ventilation (18 % vs. 5 %), and to die (9 % vs. 2 %).
+CONCLUSIONS: Pneumonia was present in nearly one-third of adults hospitalized with influenza and was associated with ICU admission and death.
+Among patients hospitalized with influenza, older patients and those with certain underlying conditions are more likely to have pneumonia.
+Pneumonia is common among adults hospitalized with influenza and should be evaluated and treated promptly.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-015-1004-y) contains supplementary material, which is available to authorized users.
+BACKGROUND: The Marburg virus (MARV) has a negative-sense single-stranded RNA genome, belongs to the family Filoviridae, and is responsible for several outbreaks of highly fatal hemorrhagic fever.
+Codon usage patterns of viruses reflect a series of evolutionary changes that enable viruses to shape their survival rates and fitness toward the external environment and, most importantly, their hosts.
+To understand the evolution of MARV at the codon level, we report a comprehensive analysis of synonymous codon usage patterns in MARV genomes.
+Multiple codon analysis approaches and statistical methods were performed to determine overall codon usage patterns, biases in codon usage, and influence of various factors, including mutation pressure, natural selection, and its two hosts, Homo sapiens and Rousettus aegyptiacus.
+RESULTS: Nucleotide composition and relative synonymous codon usage (RSCU) analysis revealed that MARV shows mutation bias and prefers U- and A-ended codons to code amino acids.
+Effective number of codons analysis indicated that overall codon usage among MARV genomes is slightly biased.
+The Parity Rule 2 plot analysis showed that GC and AU nucleotides were not used proportionally which accounts for the presence of natural selection.
+This indicates that MARV have evolved codon usage patterns that are specific to both of its hosts.
+Moreover, selection pressure from R. aegyptiacus on the MARV RSCU patterns was found to be dominant compared with that from H. sapiens.
+Overall, mutation pressure was found to be the most important and dominant force that shapes codon usage patterns in MARV.
+CONCLUSIONS: To our knowledge, this is the first detailed codon usage analysis of MARV and extends our understanding of the mechanisms that contribute to codon usage and evolution of MARV.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12862-015-0456-4) contains supplementary material, which is available to authorized users.
+BACKGROUND: Many RNA viruses arise from animal reservoirs, namely bats, rodents and insectivores but mechanisms of virus maintenance and transmission still need to be addressed.
+The bicolored white-toothed shrew (Crocidura leucodon) has recently been identified as reservoir of the neurotropic Borna disease virus 1 (BoDV-1).
+PRINCIPAL FINDINGS: Six out of eleven wild living bicoloured white-toothed shrews were trapped and revealed to be naturally infected with BoDV-1.
+All shrews were monitored in captivity in a long-term study over a time period up to 600 days that differed between the individual shrews.
+Interestingly, all six animals showed an asymptomatic course of infection despite virus shedding via various routes indicating a highly adapted host-pathogen interaction.
+Infectious virus and viral RNA were demonstrated in saliva, urine, skin swabs, lacrimal fluid and faeces, both during the first 8 weeks of the investigation period and for long time shedding after more than 250 days in captivity.
+CONCLUSIONS: The various ways of shedding ensure successful virus maintenance in the reservoir population but also transmission to accidental hosts such as horses and sheep.
+Naturally BoDV-1-infected living shrews serve as excellent tool to unravel host and pathogen factors responsible for persistent viral co-existence in reservoir species while maintaining their physiological integrity despite high viral load in many organ systems.
+The family Potyviridae encompasses ∼30% of plant viruses and is responsible for significant economic losses worldwide.
+Recently, a small overlapping coding sequence, termed pipo, was found to be conserved in the genomes of all potyvirids.
+PIPO is expressed as part of a frameshift protein, P3N-PIPO, which is essential for virus cell-to-cell movement.
+Here, we demonstrate that transcriptional slippage, specific to the viral RNA polymerase, results in a population of transcripts with an additional “A” inserted within a highly conserved GAAAAAA sequence, thus enabling expression of P3N-PIPO.
+The slippage efficiency is ∼2% in Turnip mosaic virus and slippage is inhibited by mutations in the GAAAAAA sequence.
+While utilization of transcriptional slippage is well known in negative-sense RNA viruses such as Ebola, mumps and measles, to our knowledge this is the first report of its widespread utilization for gene expression in positive-sense RNA viruses.
+The pore-forming toxin pneumolysin is a key virulence factor of S. pneumoniae, which can be sensed by the NLRP3 inflammasome.
+Among the over 90 serotypes, serotype 1 pneumococci (particularly MLST306) have emerged across the globe as a major cause of invasive disease.
+We therefore examined pneumococcal infection in human cells and a human lung organ culture system mimicking infection of the lower respiratory tract.
+We demonstrate that different pneumococcal serotypes differentially activate inflammasome-dependent IL-1β production in human lung tissue and cells.
+Whereas serotype 2, 3, 6B, 9N pneumococci expressing fully haemolytic pneumolysins activate NLRP3 inflammasome-dependent responses, serotype 1 and 8 strains expressing non-haemolytic toxins are poor activators of IL-1β production.
+Accordingly, purified haemolytic pneumolysin but not serotype 1-associated non-haemolytic toxin activates strong IL-1β production in human lungs.
+Our data suggest that the evasion of inflammasome-dependent innate immune responses by serotype 1 pneumococci might contribute to their ability to cause invasive diseases in humans.
+Periparturient cows have been found to reveal immunosuppression, frequently associated with increased susceptibility to uterine and mammary infections.
+To improve understanding of the causes and molecular regulatory mechanisms accounting for this phenomenon around calving, we examined the effect of an antigen challenge on gene expression modulation on cows prior to (BC) or after calving (AC) using whole transcriptome sequencing (RNAseq).
+The transcriptome analysis of the cows’ blood identified a substantially higher number of loci affected in BC cows (2,235) in response to vaccination compared to AC cows (208) and revealed a divergent transcriptional profile specific for each group.
+In BC cows, a variety of loci involved in immune defense and cellular signaling processes were transcriptionally activated, whereas protein biosynthesis and posttranslational processes were tremendously impaired in response to vaccination.
+Furthermore, energy metabolism in the blood cells of BC cows was shifted from oxidative phosphorylation to the glycolytic system.
+In AC cows, the number and variety of regulated pathways involved in immunomodulation and maintenance of immnunocompetence are considerably lower after vaccination, and upregulation of arginine degradation was suggested as an immunosuppressive mechanism.
+Elevated transcript levels of erythrocyte-specific genes involved in gas exchange processes were a specific transcriptional signature in AC cows pointing to hematopoiesis activation.
+The divergent and substantially lower magnitude of transcriptional modulation in response to vaccination in AC cows provides evidence for a suppressed immune capacity of early lactating cows on the molecular level and demonstrates that an efficient immune response of cows is related to their physiological and metabolic status.
+Due to the enormous capacity of Staphylococcus aureus to acquire antibiotic resistance, it becomes imperative to develop vaccines for decreasing the risk of its life-threatening infections.
+However, it has not been used as a vaccine candidate since it is a thymus-independent antigen.
+In this study, we synthesized a multiple antigenic peptide, named MAP27, which comprised four copies of a peptide that mimics the epitope of PGN.
+After immunization with MAP27 five times and boosting with heat-inactivated bacterium one time, anti-MAP27 serum bound directly to S. aureus or PGN.
+Immunization with MAP27 decreased the bacterial burden in organs of BALB/c mice and significantly prolonged their survival time after S. aureus lethal-challenge.
+The percentage of IFN-γ(+)CD3(+) T cells and IL-17(+)CD4(+) T cells in spleen, as well as the levels of IFN-γ, IL-17A/F and CCL3 in spleen and lung, significantly increased in the MAP27-immunized mice after infection.
+Moreover, in vitro incubation of heat-inactivated S. aureus with splenocytes isolated from MAP27-immunized mice stimulated the production of IFN-γ and IL-17A/F.
+Our findings demonstrated that MAP27, as a thymus-dependent antigen, is efficient at eliciting T cell-mediated responses to protect mice from S. aureus infection.
+We sought to describe the epidemiologic, clinical, treatment, and prognostic aspects of the disease in adult patients who required admission to an intensive care unit (ICU).
+We performed a retrospective analysis of a cohort of 36 adults admitted to a total of 64 ICUs throughout France for complications of measles from January 1, 2009, to December 31, 2011.
+All cases of measles were confirmed by serologic testing and/or reverse transcription polymerase chain reaction.
+The cohort consisted of 21 male and 15 female patients, with a median age of 29.2 years (25th–75th interquartile range [IQR], 27.2–34.2 yr) and a median Simplified Acute Physiology Score (SAPS II) of 13 (IQR, 9–18).
+Among the 26 patients whose measles vaccination status was documented, none had received 2 injections.
+Underlying comorbid conditions included chronic respiratory disease in 9 patients, immunosuppression in 7 patients, and obesity in 3 patients, while measles affected 5 pregnant women.
+Respiratory complications induced by measles infection led to ICU admission in 32 cases, and measles-related neurologic complications led to ICU admission in 2 cases.
+Bacterial superinfection of measles-related airway infection was suspected in 28 patients and was documented in 8.
+Four cases of community-acquired pneumonia, 6 cases of ventilator-associated pneumonia, 1 case of tracheobronchitis, and 2 cases of sinusitis were microbiologically substantiated.
+On follow-up, 1 patient had severe chronic respiratory failure related to lung fibrosis, and 2 patients had mild lower limb paraparesis along with bladder dysfunction, both of which were ascribable to measles-induced encephalitis and myelitis.
+Among the 5 pregnant patients, the course of measles infection was uneventful, albeit 1 patient underwent emergent cesarean delivery because of fetal growth restriction.
+Measles is a disease with protean and potentially deceptive clinical manifestations, especially in the immunocompromised patient.
+Measles-associated pneumonitis and its complications, and less commonly postinfectious encephalomyelitis, are the main source of morbidity and mortality.
+In contrast with the usually benign course of the disease in immunocompetent patients, measles occurring in immunocompromised patients gives rise to lethal complications including ARDS, with or without bacterial superinfection.
+Other patients potentially at high risk for severe measles are young adults and pregnant women.
+Human calcitonin (hCT) is a typical amyloidogenic peptide, its aggregation is associated with medullary carcinoma of the thyroid (MTC), and also limits its clinical application.
+Magnolia officinalis is a traditional Chinese herbal medicine; its two major polyphenol components, magnolol (Mag) and honokiol (Hon), have displayed multiple functions.
+However, the anti-amyloidogenic property of a biphenyl backbone containing polyphenols such as Mag and Hon has not been reported.
+We found that Mag and Hon both inhibited the amyloid formation of hCT, whereas Mag showed a stronger inhibitory effect; moreover, they both dose-dependently disassembled preformed hCT aggregates.
+Further immuno-dot blot and dynamic light scattering studies suggested Mag and Hon suppressed the aggregation of hCT both at the oligomerization and the fibrillation stages, while MTT-based and dye-leakage assays demonstrated that Mag and Hon effectively reduced cytotoxicity caused by hCT aggregates.
+Together, our study suggested a potential anti-amyloidogenic property of these two compounds and their structure related derivatives.
+Avian influenza viruses of the H5N1 subtype pose a serious global health threat due to the high mortality (>60%) associated with the disease caused by these viruses and the lack of protective antibodies to these viruses in the general population.
+The factors that enable avian H5N1 influenza viruses to replicate in humans are not completely understood.
+Here we use a high-throughput screening approach to identify novel mutations in the polymerase genes of an avian H5N1 virus that confer efficient polymerase activity in mammalian cells.
+Several of the identified mutations (which have previously been found in natural isolates) increase viral replication in mammalian cells and virulence in infected mice compared with the wild-type virus.
+The identification of amino-acid mutations in avian H5N1 influenza virus polymerase complexes that confer increased replication and virulence in mammals is important for the identification of circulating H5N1 viruses with an increased potential to infect humans.
+SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/ncomms8491) contains supplementary material, which is available to authorized users.
+While international Arctic collaboration on health has enhanced partnerships and advanced the health of inhabitants, significant challenges lie ahead.
+One Health is an approach that considers the connections between the environment, plant, animal and human health.
+Understanding this is increasingly critical in assessing the impact of global climate change on the health of Arctic inhabitants.
+Health risks include changes in the distribution of infectious disease, expansion of zoonotic diseases and vectors, changing migration patterns, impacts on food security and changes in water availability and quality, among others.
+A regional network of diverse stakeholder and transdisciplinary specialists from circumpolar nations and Indigenous groups can advance the understanding of complex climate-driven health risks and provide community-based strategies for early identification, prevention and adaption of health risks in human, animals and environment.
+We propose a regional One Health approach for assessing interactions at the Arctic human–animal–environment interface to enhance the understanding of, and response to, the complexities of climate change on the health of the Arctic inhabitants.
+BACKGROUND: Addition of high-dose cytarabine (HDCA) to the conventional cyclophosphamide/total-body irradiation (CY/TBI) regimen significantly improved prognosis after cord blood transplantation (CBT) for adult acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS).
+The efficacy of HDCA in bone marrow or peripheral blood stem cell transplantation (BMT/PBSCT), however, has not yet been elucidated.
+FINDINGS: We conducted a cohort study to compare the prognosis of HDCA/CY/TBI (N = 435) and CY/TBI (N = 1667) in BMT/PBSCT for AML/MDS using a Japanese transplant registry database.
+Unrelated donors comprised 54.6 %, and 63.9 % of donors were human leukocyte antigen (HLA)-matched.
+Overall survival (OS) was not improved in the HDCA/CY/TBI group (adjusted hazard ratio (HR), 1.14; p = 0.13).
+Neutrophil engraftment was inferior (HR, 0.80; p < 0.01), and the incidence of hemorrhagic cystitis and thrombotic microangiopathy increased in HDCA/CY/TBI (HR, 1.47 and 1.60; p = 0.06 and 0.04, respectively), leading to significantly higher non-relapse mortality (NRM; HR, 1.48; p < 0.01).
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13045-015-0201-x) contains supplementary material, which is available to authorized users.
+Studies administering plasma protein isolates (PPIs) to experimentally challenged animals have reported improvements in growth, food intake, and overall condition when compared with animals fed control diets, due in part to improvements in gut barrier function, normalization of cytokine signals, and support of enteric immune function.
+These and early clinical studies suggest that nutritional therapy with PPIs may similarly assist in restoring homeostasis to gut barrier function in humans experiencing mild or more acute enteropathic symptomatology such as irritable bowel syndrome and inflammatory bowel disease.
+This meta-analysis evaluated the ability of PPIs to promote weight gain and food intake in weanling animals, primarily piglets, after oral challenge with various enteric pathogens or bacterial toxins.
+MEDLINE, EMBASE, and PubMed were searched from 1980 through August 2012 for specified terms and keywords.
+Twenty-nine articles retrieved through this process were evaluated; 11 studies including 13 experiments were selected for inclusion in the analysis.
+The meta-analysis included descriptive analyses and methods for combining P values for the primary endpoint, average daily growth (ADG) at week 1, and secondary endpoints including ADG, average daily feed intake (ADFI), and gain to feed ratio (G:F) at weeks 1 and 2 and at the end of study.
+Primary and secondary endpoint analyses of growth (ADG, ADFI, and G:F) were significant (P < 0.01).
+The proinflammatory cytokines interleukin (IL) 1β, IL-6, and tumor necrosis factor α were significantly lower in animals fed dietary PPIs.
+Additional research in patients experiencing symptoms of enteropathy will further characterize the benefits of PPIs in clinical populations.
+DNA vaccination has been developed in the last two decades in human and animal species as a promising alternative to conventional vaccination.
+It consists in the injection, in the muscle, for example, of plasmid DNA encoding the vaccinating polypeptide.
+Electroporation which forces the entrance of the plasmid DNA in cells at the injection point has been described as a powerful and promising strategy to enhance DNA vaccine efficacy.
+Due to the fact that the vaccine is composed of DNA, close attention on the fate of the plasmid DNA upon vaccination has to be taken into account, especially at the injection point.
+To perform such studies, the muscle injection point has to be precisely recovered and collected several weeks after injection.
+A technique has been developed to localize precisely and collect efficiently the muscle injection points in growing piglets 6 weeks after DNA vaccination accompanied or not by electroporation.
+Electroporation did not significantly increase the level of remaining plasmids compared to nonelectroporated piglets, and, in all the cases, the levels were below the limit recommended by the FDA to research integration events of plasmid DNA into the host DNA.
+Rolling circle amplification (RCA) generates single-stranded DNAs or RNA, and the diverse applications of this isothermal technique range from the sensitive detection of nucleic acids to analysis of single nucleotide polymorphisms.
+Microwave chemistry is widely applied to increase reaction rate as well as product yield and purity.
+The objectives of the present research were to apply microwave heating to RCA and indicate factors that contribute to the microwave selective heating effect.
+The microwave reaction temperature was strictly controlled using a microwave applicator optimized for enzymatic-scale reactions.
+Here, we showed that microwave-assisted RCA reactions catalyzed by either of the four thermostable DNA polymerases were accelerated over 4-folds compared with conventional RCA.
+We concluded that microwave heating accelerated isothermal RCA of DNA because of the differential heating mechanisms of microwaves on the temperatures of reaction components, although the overall reaction temperatures were the same.
+The primary step for efficient control of viral diseases is the development of simple, rapid, and sensitive virus detection.
+Reverse transcription loop-mediated isothermal amplification (RT-LAMP) has been used to detect viral RNA molecules because of its simplicity and high sensitivity for a number of viruses.
+RT-LAMP for the detection of Potato virus X (PVX) was developed and compared with conventional reverse transcription polymerase chain reaction (RT-PCR) to demonstrate its advantages over RT-PCR.
+RT-LAMP reactions were conducted with or without a set of loop primers since one out of six primers showed PVX specificity.
+Based on real-time monitoring, RT-LAMP detected PVX around 30 min, compared to 120 min for RT-PCR.
+By adding a fluorescent reagent during the reaction, the extra step of visualization by gel electrophoresis was not necessary.
+RT-LAMP was conducted using simple inexpensive instruments and a regular incubator to evaluate whether RNA could be amplified at a constant temperature instead of using an expensive thermal cycler.
+This study shows the potential of RT-LAMP for the diagnosis of viral diseases and PVX epidemiology because of its simplicity and rapidness compared to RT-PCR.
+In plants, CRY acts as a blue light receptor to entrain circadian rhythms, and mediates a variety of light responses, such as the regulation of flowering and seedling growth.
+The superfamily consists of 7 major subfamilies: CPD class I and CPD class II photolyases, (6–4) photolyases, CRY-DASH, plant PHR2, plant CRY and animal CRY.
+Although the whole superfamily evolved primarily under strong purifying selection (average ω = 0.0168), some subfamilies did experience strong episodic positive selection during their evolution.
+Photolyases were lost in higher animals that suggests natural selection apparently became weaker in the late stage of evolutionary history.
+The evolutionary time estimates suggested that plant and animal CRYs evolved in the Neoproterozoic Era (~1000–541 Mya), which might be a result of adaptation to the major climate and global light regime changes occurred in that period of the Earth’s geological history.
+The ongoing Ebola virus (EBOV) disease (EVD) epidemic in Western Africa is the largest EVD outbreak recorded to date and requires the rapid development and deployment of antiviral measures.
+The viral glycoprotein (GP) facilitates host cell entry and, jointly with cellular interaction partners, constitutes a potential target for antiviral intervention.
+However, it is unknown whether the GPs of the currently and previously circulating EBOVs use the same mechanisms for cellular entry and are thus susceptible to inhibition by the same antivirals and cellular defenses.
+Here, we show that the GPs of the EBOVs circulating in 1976 and 2014 transduce the same spectrum of target cells, use the same cellular factors for host cell entry, and are comparably susceptible to blockade by antiviral interferon-induced transmembrane proteins and neutralizing antibody KZ52.
+Thus, the viruses responsible for the ongoing EVD epidemic should be fully susceptible to established antiviral strategies targeting GP and cellular entry factors.
+Previously, recombinant vesicular stomatitis virus (rVSV) pseudotypes expressing Ebolavirus glycoproteins (GPs) in place of the VSV G protein demonstrated protection of nonhuman primates from lethal homologous Ebolavirus challenge.
+Here we describe rVSV vectors containing a full complement of VSV genes and expressing the Ebola virus (EBOV) GP from an additional transcription unit.
+These rVSV vectors contain the same combination of attenuating mutations used previously in the clinical development pathway of an rVSV/human immunodeficiency virus type 1 vaccine.
+One of these rVSV vectors (N4CT1-EBOVGP1), which expresses membrane-anchored EBOV GP from the first position in the genome (GP1), elicited a balanced cellular and humoral GP-specific immune response in mice.
+Guinea pigs immunized with a single dose of this vector were protected from any signs of disease following lethal EBOV challenge, while control animals died in 7–9 days.
+These results demonstrate that highly attenuated rVSV vectors expressing EBOV GP may provide safer alternatives to current EBOV vaccines.
+The ability of the infectious bronchitis H120 (a Massachusetts strain) and CR88 (a 793B strain) live attenuated vaccine viruses to protect from two Middle East infectious bronchitis virus isolates, IS/885/00-like (IS/885) and IS/1494/06-like (IS/1494) in broiler chicks was investigated.
+Day-old chicks were separated into three groups, (I) vaccinated with H120 at day-old followed by CR88 at 14 days-old, (II) vaccinated with H120 and CR88 simultaneously at day-old and again with CR88 at 14 days-old, (III) control unvaccinated.
+Protection was evaluated based on the clinical signs, tracheal and kidney gross lesions and tracheal ciliostasis.
+Results showed that administering combined live H120 and CR88 vaccines simultaneously at day-old followed by CR88 vaccine at 14 days-old gave more than 80 per cent tracheal ciliary protection from both of the Middle East isolates.
+In addition, this programme conferred 100 per cent protection from clinical signs and tracheal or kidney lesions.
+The other vaccination programme, H120 at day-old followed by CR88 at 14 days-old, the tracheal ciliary protection conferred were 60 per cent and 80 per cent from IS/885/00-like and IS/1494/06-like, respectively.
+Viral fulminant hepatitis (FH) is a severe disease with high mortality resulting from excessive inflammation in the infected liver.
+Clinical interventions have been inefficient due to the lack of knowledge for inflammatory pathogenesis in the virus-infected liver.
+We show that wild-type mice infected with murine hepatitis virus strain-3 (MHV-3), a model for viral FH, manifest with severe disease and high mortality in association with a significant elevation in IL-1β expression in the serum and liver.
+Whereas, the viral infection in IL-1β receptor-I deficient (IL-1R1 (-/-)) or IL-1R antagonist (IL-1Ra) treated mice, show reductions in virus replication, disease progress and mortality.
+IL-1R1 deficiency appears to debilitate the virus-induced fibrinogen-like protein-2 (FGL2) production in macrophages and CD45(+)Gr-1(high) neutrophil infiltration in the liver.
+The quick release of reactive oxygen species (ROS) by the infected macrophages suggests a plausible viral initiation of NLRP3 inflammasome activation.
+Further experiments show that mice deficient of p47 (phox), a nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunit that controls acute ROS production, present with reductions in NLRP3 inflammasome activation and subsequent IL-1β secretion during viral infection, which appears to be responsible for acquiring resilience to viral FH.
+Moreover, viral infected animals in deficiencies of NLRP3 and Caspase-1, two essential components of the inflammasome complex, also have reduced IL-1β induction along with ameliorated hepatitis.
+Our results demonstrate that the ROS/NLRP3/IL-1β axis institutes an essential signaling pathway, which is over activated and directly causes the severe liver disease during viral infection, which sheds light on development of efficient treatments for human viral FH and other severe inflammatory diseases.
+BACKGROUND: The novel influenza A(H7N9) virus has caused 2013 spring and 2013–2014 winter waves of human infections since its first emergence in China in March 2013.
+METHODS: We conducted population-based surveys in southern China to examine human exposure to live poultry, and population psychological response and behavioral changes in the two waves.
+In Guangzhou, an urban area of Guangdong province, we collected data using telephone surveys with random digit dialing in May-June 2013 and again in December 2013 to January 2014.
+In Zijin county, a rural area of the same province, we used door-to-door surveys under a stratified sampling design in July 2013 and again in December 2013 to January 2014.
+FINDINGS: Around half of the urban respondents (53.8%) reported having visited LPMs in the previous year in the first survey, around double that reported in the second survey (27.7%).
+In the rural surveys, around half of the participants reported raising backyard poultry in the past year in the first survey, increasing to 83.2% participants in the second survey.
+One third of urban subjects supported the permanent closure of LPMs in the first and second surveys, and factors associated with support for closure included female sex, higher level of worry towards H7N9, and worry induced by a hypothetical influenza-like illness.
+CONCLUSIONS: Our study indicated high human exposure to live poultry and low support for permanent closure of markets in both urban and rural residents regardless of increased worry during the epidemic.
+Interferon stimulated genes (ISGs) target viruses at various stages of their infectious life cycles, including at the earliest stage of viral entry.
+Here we identify ArfGAP with dual pleckstrin homology (PH) domains 2 (ADAP2) as a gene upregulated by type I IFN treatment in a STAT1-dependent manner.
+ADAP2 functions as a GTPase-activating protein (GAP) for Arf6 and binds to phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P(3)) and PI(3,4)P(2).
+We show that overexpression of ADAP2 suppresses dengue virus (DENV) and vesicular stomatitis virus (VSV) infection in an Arf6 GAP activity-dependent manner, while exerting no effect on coxsackievirus B (CVB) or Sendai virus (SeV) replication.
+We further show that ADAP2 expression induces macropinocytosis and that ADAP2 strongly associates with actin-enriched membrane ruffles and with Rab8a- and LAMP1-, but not EEA1- or Rab7-, positive vesicles.
+Utilizing two techniques—light-sensitive neutral red (NR)-containing DENV and fluorescence assays for virus internalization—we show that ADAP2 primarily restricts DENV infection at the stage of virion entry and/or intracellular trafficking and that incoming DENV and VSV particles associate with ADAP2 during their entry.
+Taken together, this study identifies ADAP2 as an ISG that exerts antiviral effects against RNA viruses by altering Arf6-mediated trafficking to disrupt viral entry.
+Emerging and re-emerging infections such as SARS (2003) and pandemic H1N1 (2009) have caused concern for public health researchers and policy makers due to the increased burden of these diseases on health care systems.
+This concern has prompted the use of mathematical models to evaluate strategies to control disease spread, making these models invaluable tools to identify optimal intervention strategies.
+Estimation of this quantity is crucial for effective control responses in the early phase of an epidemic.
+In our previous study, an approach for estimating the basic reproduction number in real time was developed.
+This approach uses case notification data and the structure of potential transmission contacts to accurately estimate R(0) from the limited amount of information available at the early stage of an outbreak.
+Based on this approach, we extend the existing methodology; the most recent method features intra- and inter-age groups contact heterogeneity.
+Given the number of newly reported cases at the early stage of the outbreak, with parsimony assumptions on removal distribution and infectivity profile of the diseases, experiments to estimate real time R(0) under different levels of intra- and inter-group contact heterogeneity using two age groups are presented.
+We show that the new method converges more quickly to the actual value of R(0) than the previous one, in particular when there is high-level intra-group and inter-group contact heterogeneity.
+With the age specific contact patterns, number of newly reported cases, removal distribution, and information about the natural history of the 2009 pandemic influenza in Hong Kong, we also use the extended model to estimate R(0) and age-specific R(0).
+AIMS/HYPOTHESIS: We investigated whether heterogeneous nuclear ribonucleoprotein F (hnRNP F) stimulates renal ACE-2 expression and prevents TGF-β1 signalling, TGF-β1 inhibition of Ace-2 gene expression and induction of tubulo-fibrosis in an Akita mouse model of type 1 diabetes.
+METHODS: Adult male Akita transgenic (Tg) mice overexpressing specifically hnRNP F in their renal proximal tubular cells (RPTCs) were studied.
+Immortalised rat RPTCs stably transfected with plasmid containing either rat Hnrnpf cDNA or rat Ace-2 gene promoter were also studied.
+RESULTS: Overexpression of hnRNP F attenuated systemic hypertension, glomerular filtration rate, albumin/creatinine ratio, urinary angiotensinogen (AGT) and angiotensin (Ang) II levels, renal fibrosis and profibrotic gene (Agt, Tgf-β1, TGF-β receptor II [Tgf-βrII]) expression, stimulated anti-profibrotic gene (Ace-2 and Ang 1–7 receptor [MasR]) expression, and normalised urinary Ang 1–7 level in Akita Hnrnpf-Tg mice as compared with Akita mice.
+In vitro, hnRNP F overexpression stimulated Ace-2 gene promoter activity, mRNA and protein expression, and attenuated Agt, Tgf-β1 and Tgf-βrII gene expression.
+CONCLUSIONS/INTERPRETATION: These data demonstrate that hnRNP F stimulates Ace-2 gene transcription, prevents TGF-β1 inhibition of Ace-2 gene transcription and induction of kidney injury in diabetes.
+HnRNP F may be a potential target for treating hypertension and renal fibrosis in diabetes.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00125-015-3700-y) contains peer-reviewed but unedited supplementary material, which is available to authorised users.
+However, the extent to which critically ill children identified by consensus criteria reflect physician diagnosis of severe sepsis, which underlies external validity for pediatric sepsis research, is not known.
+We sought to determine the agreement between physician diagnosis and consensus criteria to identify pediatric patients with severe sepsis across a network of international pediatric intensive care units (PICUs).
+METHODS: We conducted a point prevalence study involving 128 PICUs in 26 countries across 6 continents.
+Over the course of 5 study days, 6925 PICU patients <18 years of age were screened, and 706 with severe sepsis defined either by physician diagnosis or on the basis of 2005 International Pediatric Sepsis Consensus Conference consensus criteria were enrolled.
+The primary endpoint was agreement of pediatric severe sepsis between physician diagnosis and consensus criteria as measured using Cohen’s κ.
+Secondary endpoints included characteristics and clinical outcomes for patients identified using physician diagnosis versus consensus criteria.
+The inter-rater agreement (κ ± SE) between physician diagnosis and consensus criteria was 0.57 ± 0.02.
+Of the 438 patients with a physician’s diagnosis of severe sepsis, only 69 % (301 of 438) would have been eligible to participate in a clinical trial of pediatric severe sepsis that enrolled patients based on consensus criteria.
+Patients with physician-diagnosed severe sepsis who did not meet consensus criteria were younger and had lower severity of illness and lower PICU mortality than those meeting consensus criteria or both definitions.
+After controlling for age, severity of illness, number of comorbid conditions, and treatment in developed versus resource-limited regions, patients identified with severe sepsis by physician diagnosis alone or by consensus criteria alone did not have PICU mortality significantly different from that of patients identified by both physician diagnosis and consensus criteria.
+CONCLUSIONS: Physician diagnosis of pediatric severe sepsis achieved only moderate agreement with consensus criteria, with physicians diagnosing severe sepsis more broadly.
+Consequently, the results of a research study based on consensus criteria may have limited generalizability to nearly one-third of PICU patients diagnosed with severe sepsis.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13054-015-1055-x) contains supplementary material, which is available to authorized users.
+BACKGROUND: Chikungunya virus (CHIKV) is an arthritogenic alphavirus (family Togaviridae), transmitted by Aedes species mosquitoes.
+CHIKV re-emerged in 2004 with multiple outbreaks worldwide and recently reached the Americas where it has infected over a million individuals in a rapidly expanding epidemic.
+While alphavirus replication is well understood in general, the specific function (s) of non-structural protein nsP3 remain elusive.
+CHIKV nsP3 modulates the mammalian stress response by preventing stress granule formation through sequestration of G3BP.
+In mosquitoes, nsP3 is a determinant of vector specificity, but its functional interaction with mosquito proteins is unclear.
+METHODS: In this research we studied the domains required for localization of CHIKV nsP3 in insect cells and demonstrated its molecular interaction with Rasputin (Rin), the mosquito homologue of G3BP.
+RESULTS: In insect cells, nsP3 localized as cytoplasmic granules, which was dependent on the central domain and the C-terminal variable region but independent of the N-terminal macrodomain.
+albopictus Rin displayed a diffuse, cytoplasmic localization, but was effectively sequestered into nsP3-granules upon nsP3 co-expression.
+Site-directed mutagenesis showed that the Rin-nsP3 interaction involved the NTF2-like domain of Rin and two conserved TFGD repeats in the C-terminal variable domain of nsP3.
+Although in vitro silencing of Rin did not impact nsP3 localization or CHIKV replication in cell culture, Rin depletion in vivo significantly decreased the CHIKV infection rate and transmissibility in Ae.albopictus.
+CONCLUSIONS: We identified the nsP3 hypervariable C-terminal domain as a critical factor for granular localization and sequestration of mosquito Rin.
+Our study offers novel insight into a conserved virus-mosquito interaction at the molecular level, and reveals a strong proviral role for G3BP homologue Rin in live mosquitoes, making the nsP3-Rin interaction a putative target to interfere with the CHIKV transmission cycle.
+To survey the prevalence of tick-borne known and putative pathogens, we tested 982 individual adult and nymphal I. pacificus ticks collected throughout California between 2007 and 2009 using a broad-range PCR and electrospray ionization mass spectrometry (PCR/ESI-MS) assay designed to detect a wide range of tick-borne microorganisms.
+Overall, 1.4% of the ticks were found to be infected with Borrelia burgdorferi, 2.0% were infected with Borrelia miyamotoi and 0.3% were infected with Anaplasma phagocytophilum.
+About 1.2% of the ticks were co-infected with more than one pathogen or putative pathogen.
+In addition, we identified a novel Anaplasmataceae species that we characterized by sequencing of its 16S rRNA, groEL, gltA, and rpoB genes.
+Sequence analysis indicated that this organism is phylogenetically distinct from known Anaplasma species with its closest genetic near neighbors coming from Asia.
+The prevalence of this novel Anaplasmataceae species was as high as 21% at one site, and it was detected in 4.9% of ticks tested statewide.
+Based upon this genetic characterization we propose that this organism be called ‘Candidatus Cryptoplasma californiense’.
+Knowledge of this novel microbe will provide awareness for the community about the breadth of the I. pacificus microbiome, the concept that this bacterium could be more widely spread; and an opportunity to explore whether this bacterium also contributes to human or animal disease burden.
+Discovering new binding function via a combinatorial library in small protein scaffolds requires balance between appropriate mutations to introduce favorable intermolecular interactions while maintaining intramolecular integrity.
+Sitewise constraints exist in a non-spatial gradient from diverse to conserved in evolved antibody repertoires; yet non-antibody scaffolds generally do not implement this strategy in combinatorial libraries.
+Despite the fact that biased amino acid distributions, typically elevated in tyrosine, serine, and glycine, have gained wider use in synthetic scaffolds, these distributions are still predominantly applied uniformly to diversified sites.
+While select sites in fibronectin domains and DARPins have shown benefit from sitewise designs, they have not been deeply evaluated.
+Inspired by this disparity between diversity distributions in natural libraries and synthetic scaffold libraries, we hypothesized that binders resulting from discovery and evolution would exhibit a non-spatial, sitewise gradient of amino acid diversity.
+To identify sitewise diversities consistent with efficient evolution in the context of a hydrophilic fibronectin domain, >10(5) binders to six targets were evolved and sequenced.
+Evolutionarily favorable amino acid distributions at 25 sites reveal Shannon entropies (range: 0.3–3.9; median: 2.1; standard deviation: 1.1) supporting the diversity gradient hypothesis.
+Implementation of sitewise constrained diversity enables direct selection of nanomolar affinity binders validating an efficient strategy to balance inter- and intra-molecular interaction demands at each site.
+Objective: To categorize and describe the public health informatics (PHI) and global health informatics (GHI) literature between 2012 and 2014.
+Methods: We conducted a semi-systematic review of articles published between January 2012 and September 2014 where information and communications technologies (ICT) was a primary subject of the study or a main component of the study methodology.
+Additional inclusion and exclusion criteria were used to filter PHI and GHI articles from the larger biomedical informatics domain.
+Articles were identified using MEDLINE as well as personal bibliographies from members of the American Medical Informatics Association PHI and GHI working groups.
+While systems in PHI continue to support surveillance activities, we identified a shift towards support for prevention, environmental health, and public health care services.
+Furthermore, articles from the U.S. reveal a shift towards PHI applications at state and local levels.
+The development of adequate infrastructure to support ICT remains a challenge, although we identified a small but growing set of articles that measure the impact of ICT on clinical outcomes.
+Discussion: There is evidence of growth with respect to both implementation of information systems within the public health enterprise as well as a widening of scope within each informatics discipline.
+Yet the articles also illuminate the need for more primary research studies on what works and what does not as both searches yielded small numbers of primary, empirical articles.
+Conclusion: While the body of knowledge around PHI and GHI continues to mature, additional studies of higher quality are needed to generate the robust evidence base needed to support continued investment in ICT by governmental health agencies.
+BACKGROUND: Respiratory syncytial virus (RSV) is globally ubiquitous, and infection during the first six months of life is a major risk for severe disease and hospital admission; consequently RSV is the most important viral cause of respiratory morbidity and mortality in young children.
+Development of vaccines for young infants is complicated by the presence of maternal antibodies and immunological immaturity, but vaccines targeted at older children avoid these problems.
+Vaccine development for young infants has been unsuccessful, but this is not the case for older children (> 6m).
+METHODS AND FINDINGS: We have used a deterministic age structured model capturing the key epidemiological characteristics of RSV and performed a statistical maximum-likelihood fit to age-specific hospitalization data from a developing country setting.
+To explore the effects of vaccination under different mixing assumptions, we included two versions of contact matrices: one from a social contact diary study, and the second a synthesised construction based on demographic data.
+Our results show that immunisation of young children (5–10m) is likely to be a highly effective method of protection of infants (<6m) against hospitalisation.
+A full sensitivity and uncertainty analysis using Latin Hypercube Sampling of the parameter space shows that our results are robust to model structure and model parameters.
+CONCLUSIONS: This result suggests that vaccinating older infants and children against RSV can have a major public health benefit.
+Porcine reproductive and respiratory syndrome virus (PRRSV) negatively modulates host immune responses, resulting in persistent infection and immunosuppression.
+However, the target antigens for Tregs proliferation in PRRSV infection have not been fully understood.
+In this study, we demonstrated that the highly pathogenic PRRSV (HP-PRRSV) induced more CD4(+)CD25(+)Foxp3(+) Tregs than classical PRRSV (C-PRRSV) strain.
+Of the recombinant GP5, M and N proteins of HP-PRRSV expressed in baculovirus expression systems, only N protein induced Tregs proliferation.
+The Tregs assays showed that three amino-acid regions, 15–21, 42–48 and 88–94, in N protein played an important role in induction of Tregs proliferation with synthetic peptides covering the whole length of N protein.
+By using reverse genetic methods, it was firstly found that the 15N and 46R residues in PRRSV N protein were critical for induction of Tregs proliferation.
+The phenotype of induced Tregs closely resembled that of transforming-growth-factor-β-secreting T helper 3 Tregs in swine.
+These data should be useful for understanding the mechanism of immunity to PRRSV and development of infection control strategies in the future.
+Building on a series of ground breaking reviews that first defined and drew attention to emerging infectious diseases (EID), the ‘convergence model’ was proposed to explain the multifactorial causality of disease emergence.
+The model broadly hypothesizes disease emergence is driven by the co-incidence of genetic, physical environmental, ecological, and social factors.
+We developed and tested a model of the emergence of highly pathogenic avian influenza (HPAI) H5N1 based on suspected convergence factors that are mainly associated with land-use change.
+Building on previous geospatial statistical studies that identified natural and human risk factors associated with urbanization, we added new factors to test whether causal mechanisms and pathogenic landscapes could be more specifically identified.
+Our findings suggest that urbanization spatially combines risk factors to produce particular types of peri-urban landscapes with significantly higher HPAI H5N1 emergence risk.
+The work highlights that peri-urban areas of Viet Nam have higher levels of chicken densities, duck and geese flock size diversities, and fraction of land under rice or aquaculture than rural and urban areas.
+We also found that land-use diversity, a surrogate measure for potential mixing of host populations and other factors that likely influence viral transmission, significantly improves the model’s predictability.
+Similarly, landscapes where intensive and extensive forms of poultry production overlap were found at greater risk.
+These results support the convergence hypothesis in general and demonstrate the potential to improve EID prevention and control by combing geospatial monitoring of these factors along with pathogen surveillance programs.
+Biological systems use complex ‘information processing cores’ composed of molecular networks to coordinate their external environment and internal states.
+An example of this is the acquired, or adaptive, immune system (AIS), which is composed of both humoral and cell-mediated components.
+Here we report the step-by-step construction of a prototype mimic of the AIS which we call Adaptive Immune Response Simulator (AIRS).
+DNA and enzymes are used as simple artificial analogues of the components of the AIS to create a system which responds to specific molecular stimuli in vitro.
+We show that this network of reactions can function in a manner which is superficially similar to the most basic responses of the vertebrate acquired immune system, including reaction sequences that mimic both humoral and cellular responses.
+As such, AIRS provides guidelines for the design and engineering of artificial reaction networks and molecular devices.
+Human immunodeficiency virus (HIV) types 1 and 2 (HIV-1 and HIV-2) are the etiologic agents of AIDS.
+Blocking HIV mucosal transmission and local spread in the female lower genital tract is important in preventing infection and ultimately eliminating the pandemic.
+Thus, a number of different types of microbicides are under investigation, however, the lack of their solubility and bioavailability, and toxicity has been major hurdles.
+Herein, we report the development of multifunctional chitosan-lipid nanocomplexes that can effectively deliver plasmids encoding siRNA(s) as microbicides without adverse effects and provide significant protection against HIV in both in vitro and in vivo models.
+Chitosan or chitosan-lipid (chlipid) was complexed with a cocktail of plasmids encoding HIV-1-specific siRNAs (psiRNAs) and evaluated for their efficacy in HEK-293 cells, PBMCs derived from nonhuman primates, 3-dimensional human vaginal ectocervical tissue (3D-VEC) model and also in non-human primate model.
+Moreover, prophylactic administration of the chlipid to deliver a psiRNA cocktail intravaginally with a cream formulation in a non-human primate model showed substantial reduction of SHIV (simian/human immunodeficiency virus SF162) viral titers.
+Taken together, these studies demonstrate the potential of chlipid-siRNA nanocomplexes as a potential genetic microbicide against HIV infections.
+OBJECTIVES: The current study aims to establish the use of rolling circle amplification (RCA) based on internal transcribed spacer ribosomal DNA (ITS rDNA) as a powerful, simple, and rapid procedure for distinguishing closely related organisms, and specifically to identify Trichophyton species, which cause human and animal disorders.
+MATERIALS AND METHODS: A total of sixty-one isolates belonging to three species of Trichophyton were identified to the species level based on microscopic and macroscopic examinations and their ITS rDNA regions were sequenced.
+Three specific circular oligonucleotide probes targeting the ITS1 and ITS2 regions were designed to differentiate Trichophyton rubrum, T. mentagrophytes, and T. tonsurans.
+RESULTS: Of the 61 putative Trichophyton clinical isolates, 52 were identified to the species level.
+interdigitale (31 isolates), followed by T. rubrum (11 isolates), T. tonsurans (9 isolates), and T. violaceum (1 isolates); moreover, 9 isolates were identified as non-Trichophyton species.
+The RCA method correctly identified four Trichophyton species and was 100% specific for each species.
+Neither cross-reaction between the examined species of Trichophyton nor false positive or false negative results were observed.
+CONCLUSIONS: Species identification of Trichophyton is crucially important for epidemiological and phylogenetic purposes and for genotype delineation.
+RCA based on ITS polymorphisms can be used to generate identification barcodes and as an alternative to DNA sequencing; it is a very fast, specific, and economical tool for species identification.
+In the present narrative review, we analyzed the relationship between seronegative celiac disease (SNCD) and immunoglobulin deficiencies.
+Immunohistochemistry/immunofluorescence tissue transglutaminase (tTG)-targeted mucosal immunoglobulin A (IgA) immune complexes in the intestinal mucosa of SNCD patients may be useful.
+In our experience, tTG-mRNA was similarly increased in seropositive celiac disease (CD) and suspected SNCD, and strongly correlated with the IELs count.
+This increase is found even in the IELs’ range of 15–25/100 enterocytes, suggesting that there may be a “grey zone” of gluten-related disorders.
+An immune deregulation (severely lacking B-cell differentiation) underlies the association of SNCD with immunoglobulin deficiencies.
+Therefore, CD may be linked to autoimmune disorders and immune deficits (common variable immunodeficiency (CVID)/IgA selective deficiency).
+CVID is a heterogeneous group of antibodies dysfunction, whose association with CD is demonstrated only by the response to a gluten-free diet (GFD).
+Selective IgM deficiency (sIgMD) is rare (<300 cases) and associated to CD in 5% of cases.
+This evidence, supporting a link between SNCD and immunoglobulin deficiencies, suggests that we should take a closer look at this association.
+Sequencing DNA or RNA directly from the environment often results in many sequencing reads that have no homologs in the database.
+These are referred to as “unknowns," and reflect the vast unexplored microbial sequence space of our biosphere, also known as “biological dark matter."
+There is a pressure on researchers to publish and move on, and the unknown sequences are often left for what they are, and conclusions drawn based on reads with annotated homologs.
+This can cause abundant and widespread genomes to be overlooked, such as the recently discovered human gut bacteriophage crAssphage.
+The unknowns may be enriched for bacteriophage sequences, the most abundant and genetically diverse component of the biosphere and of sequence space.
+However, it remains an open question, what is the actual size of biological sequence space?
+The de novo assembly of shotgun metagenomes is the most powerful tool to address this question.
+The rate-limiting enzyme in the mevalonic acid (MVA) pathway which can lead to triterpenoid saponin glycyrrhizic acid (GA) is 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR).
+In order to reveal the effect of copy number variation in the HMGR gene on the MVA pathway, the HMGR gene from Glycyrrhiza uralensis Fisch.
+Six recombinant P. pastoris strains containing different copy numbers of the GuHMGR gene were obtained and the content of ergosterol was analyzed by HPLC.
+The results showed that all the recombinant P. pastoris strains contained more ergosterol than the negative control and the strains with 8 and 44 copies contained significantly more ergosterol than the other strains.
+This study provides a rationale for increasing the content of GA through over-expressing the GuHMGR gene in cultivars of G. uralensis.
+The knowledge of the spatial distribution feline immunodeficiency virus and feline leukemia virus infections, which are untreatable, can inform on their risk factors and high-risk areas to enhance control.
+However, when spatial analysis involves aggregated spatial data, results may be influenced by the spatial scale of aggregation, an effect known as the modifiable areal unit problem (MAUP).
+In this study, area level risk factors for both infections in 28,914 cats tested with ELISA were investigated by multivariable spatial Poisson regression models along with MAUP effect on spatial clustering and cluster detection (for postal codes, counties, and states) by Moran's I test and spatial scan test, respectively.
+The study results indicate that the significance and magnitude of the association of risk factors with both infections varied with aggregation scale.
+Further more, Moran's I test only identified spatial clustering at postal code and county levels of aggregation.
+Similarly, the spatial scan test indicated that the number, size, and location of clusters varied over aggregation scales.
+In conclusion, the association between infection and area was influenced by the choice of spatial scale and indicates the importance of study design and data analysis with respect to specific research questions.
+Luckily, in recent years, computational experiments based on artificial society appeared, providing a new approach to study the propagation of EVD and analyze the corresponding interventions.
+Therefore, the rationality of artificial society is the key to the accuracy and reliability of experiment results.
+Firstly, artificial Beijing is reconstructed based on geodemographics and machine learning is involved to optimize individuals' behaviors.
+Meanwhile, Ebola course model and propagation model are built, according to the parameters in West Africa.
+Subsequently, propagation mechanism of EVD is analyzed, epidemic scenario is predicted, and corresponding interventions are presented.
+Finally, by simulating the emergency responses of Chinese government, the conclusion is finally drawn that Ebola is impossible to outbreak in large scale in the city of Beijing.
+To the best of our knowledge, there is no previous report about an association of Toxocara infection with suicide attempts.
+Therefore, we sought to determine whether Toxocara exposure is associated with suicide attempts in psychiatric patients.
+Sera of patients were analyzed for the presence of anti-Toxocara IgG antibodies by using a commercially available enzyme immunoassay.
+One of the 156 (0.6%) suicide attempters and 1 (0.8%) of the 126 controls were positive for anti-Toxocara IgG antibodies (OR = 0.80; 95% CI: 0.04–13.02; P = 1.00).
+Toxocara seropositivity was significantly higher (P = 0.01) in male patients with consumption of raw dried goat meat than male patients without this consumption.
+Results suggest that Toxocara exposure is not associated with suicide attempts in psychiatric outpatients in Durango City, Mexico.
+Too few patients were seropositive to assess further associations of Toxocara exposure with sociodemographic, clinical, and behavioral characteristics of the psychiatric patients.
+Rickettsia felis has been reported to be a cause of fever in sub-Saharan Africa, but this association has been poorly evaluated in Gabon.
+We assessed the prevalence of this bacterium among children <15 years of age in 4 areas of Gabon; the locations were in urban, semiurban, and rural areas.
+DNA samples from 410 febrile children and 60 afebrile children were analyzed by quantitative PCR.
+Overall, the prevalence of R. felis among febrile and afebrile children was 10.2% (42/410 children) and 3.3% (2/60 children), respectively.
+Prevalence differed among febrile children living in areas that are urban (Franceville, 1.3% [1/77]), semiurban (Koulamoutou, 2.1% [3/141]), and rural (Lastourville, 11.2% [15/134]; Fougamou, 39.7% [23/58]).
+Furthermore, in a rural area (Fougamou), R. felis was significantly more prevalent in febrile (39.7% [23/58]) than afebrile children (5.0% [1/20]).
+Additional studies are needed to better understand the pathogenic role of R. felis in this part of the world.
+Seasonal influenza viruses are typically restricted to the human upper respiratory tract whereas influenza viruses with greater pathogenic potential often also target extra-pulmonary organs.
+Infants, pregnant women, and breastfeeding mothers are highly susceptible to severe respiratory disease following influenza virus infection but the mechanisms of disease severity in the mother-infant dyad are poorly understood.
+Here we investigated 2009 H1N1 influenza virus infection and transmission in breastfeeding mothers and infants utilizing our developed infant-mother ferret influenza model.
+Transmission of the virus from infants to mother ferrets led to infection in the lungs and mother mortality.
+Live virus was also found in mammary gland tissue and expressed milk of the mothers which eventually led to milk cessation.
+To understand the molecular mechanisms of mammary gland infection, we performed global transcript analysis which showed downregulation of milk production genes such as Prolactin and increased breast involution pathways indicated by a STAT5 to STAT3 signaling shift.
+Genes associated with cancer development were also significantly increased including JUN, FOS and M2 macrophage markers.
+Immune responses within the mammary gland were characterized by decreased lymphocyte-associated genes CD3e, IL2Ra, CD4 with IL1β upregulation.
+Direct inoculation of H1N1 into the mammary gland led to infant respiratory infection and infant mortality suggesting the influenza virus was able to replicate in mammary tissue and transmission is possible through breastfeeding.
+Together, we have shown that the host-pathogen interactions of influenza virus infection in the mother-infant dyad initiate immunological and oncogenic signaling cascades within the mammary gland.
+These findings suggest the mammary gland may have a greater role in infection and immunity than previously thought.
+Overexpression of RNF166 rather than its homologous proteins RNF114, RNF125, and RNF138, enhanced Sendai virus (SeV)-induced activation of the IFN-β promoter.
+Knockdown of endogenous RNF166, but not other RNFs, inhibited the IFN-β production induced by SeV and encephalomyocarditis virus.
+SeV-induced ubiquitination of TRAF3 and TRAF6 was suppressed when endogenous RNF166 rather than RNF114/138 was knocked down.
+These findings suggest that RNF166 positively regulates RNA virus-triggered IFN-β production by enhancing the ubiquitination of TRAF3 and TRAF6.
+An outbreak in China in April 2013 of human illnesses due to avian influenza A(H7N9) virus provided reason for US public health officials to revisit existing national pandemic response plans.
+We built a spreadsheet model to examine the potential demand for invasive mechanical ventilation (excluding “rescue therapy” ventilation).
+We considered scenarios of either 20% or 30% gross influenza clinical attack rate (CAR), with a “low severity” scenario with case fatality rates (CFR) of 0.05%–0.1%, or a “high severity” scenario (CFR: 0.25%–0.5%).
+We used rates-of-influenza-related illness to calculate the numbers of potential clinical cases, hospitalizations, admissions to intensive care units, and need for mechanical ventilation.
+We assumed 10 days ventilator use per ventilated patient, 13% of total ventilator demand will occur at peak, and a 33.7% weighted average mortality risk while on a ventilator.
+At peak, for a 20% CAR, low severity scenario, an additional 7000 to 11 000 ventilators will be needed, averting a pandemic total of 35 000 to 55 000 deaths.
+A 30% CAR, high severity scenario, will need approximately 35 000 to 60 500 additional ventilators, averting a pandemic total 178 000 to 308 000 deaths.
+Estimates of deaths averted may not be realized because successful ventilation also depends on sufficient numbers of suitably trained staff, needed supplies (eg, drugs, reliable oxygen sources, suction apparatus, circuits, and monitoring equipment) and timely ability to match access to ventilators with critically ill cases.
+There is a clear challenge to plan and prepare to meet demands for mechanical ventilators for a future severe pandemic.
+BACKGROUND: Straw-coloured fruit bats (Eidolon helvum) migrate over vast distances across the African continent, probably following seasonal bursts of resource availability.
+This causes enormous fluctuations in population size, which in turn may influence the bats’ impact on local ecosystems.
+We studied the movement ecology of this central-place forager with state-of-the-art GPS/acceleration loggers and concurrently monitored the seasonal fluctuation of the colony in Accra, Ghana.
+Habitat use on the landscape scale was assessed with remote sensing data as well as ground-truthing of foraging areas.
+PRINCIPAL FINDINGS: During the wet season population low (~ 4000 individuals), bats foraged locally (3.5–36.7 km) in urban areas with low tree cover.
+Foraging distances almost tripled (24.1–87.9 km) during the dry season population peak (~ 150,000 individuals), but this was not compensated for by reduced resting periods.
+Dry season foraging areas were random with regard to urban footprint and tree cover, and food consisted almost exclusively of nectar and pollen of native trees.
+CONCLUSIONS AND SIGNIFICANCE: Our study suggests that straw-coloured fruit bats disperse seeds in the range of hundreds of meters up to dozens of kilometres, and pollinate trees for up to 88 km.
+Straw-coloured fruit bats forage over much larger distances compared to most other Old World fruit bats, thus providing vital ecosystem services across extensive landscapes.
+We recommend increased efforts aimed at maintaining E. helvum populations throughout Africa since their keystone role in various ecosystems is likely to increase due to the escalating loss of other seed dispersers as well as continued urbanization and habitat fragmentation.
+OBJECTIVES: The objective of this study was to evaluate the effectiveness of a nonsurgical treatment regimen in the long-term control of necrotic areas of the jaws and pain in such patients.
+METHODS: A total of 96 patients suffering from the disease were included in this study.
+All patients received nonsurgical treatment regimen for 10 days, and repeated every 3 months for 2 years.
+The size of the osteonecrotic lesions was measured and the pain level was self-assessed with a visual analog scale.
+RESULTS: The patients showed a statistically significant (F = 16.1; p < .01; r(2) = .95) gradual decrease in the size of exposed bone areas during the nonsurgical therapy (from 12.5 to 8.8 mm).
+CONCLUSIONS: This conservative nonsurgical treatment regimen seems to provide successful treatment in reduction of the sizes of exposed bone areas in the majority of patients.
+OBJECTIVES: The population health approach is increasingly recognized for its role in health system reform; however, its broad scope and definition have been criticized for being a barrier to clear communication.
+This qualitative study examined the way senior healthcare leaders in Canada conceptualize and operationalize the population health approach in planning and decision-making.
+FINDINGS: Core elements of the population health approach included focusing on health and wellness rather than illness, taking a population rather than individual orientation, understanding needs and solutions through community outreach, addressing health disparities/health in vulnerable groups, addressing the social determinants of health and inter-sectoral action and partnerships.
+CONCLUSION: The population health approach is increasingly recognized for its role in reducing healthcare demand and contributing to health system sustainability.
+This study demonstrated the growing need to clarify terminology among multiform partners to establish a foundation for future healthcare integration and inter-sectoral action.
+BACKGROUND: Uropathogenic Escherichia coli (UPEC) is one of the most common bacteria that can cause urinary tract infections (UTIs).
+Therefore, it is necessary to develop an efficient and safe vaccine that is able to induce mucosal and systemic immune responses.
+The use of lactic acid bacteria as a delivery system is a promising method to induce the immune system.
+OBJECTIVES: The aim of this study was to establish Lactobacillus reuteri harboring the E. coli PapG antigen on its surface.
+MATERIALS AND METHODS: In this study, the gene encoding PapG was fused to the AcmA gene (which encodes an anchor protein in Lactobacillus) and cloned into the pEX A vector.
+The PapG.AcmA fusion gene was digested with BamHI and NdeI and sub-cloned into the pET21a expression vector at the digestion sites.
+Subsequently, the recombinant plasmids (pET21a-PapG.AcmA and pET21a-PapG) were transformed into the E. coli Origami strain using the calcium chloride method and the fusion protein was expressed under 1 mM IPTG induction.
+The expression of the fusion protein was confirmed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and western blotting.
+Purification of the PapG and PapG.AcmA proteins was carried out using a Ni-NTA column, and surface adsorption was estimated on Lactobacillus.
+Finally, surface localization of the fusion protein was verified by an enzyme-linked immunosorbent assay (ELISA).
+The expression of PapG and PapG.AcmA proteins in the E. coli Origami strain was indicated as protein bands in SDS-PAGE and confirmed by western blotting.
+CONCLUSIONS: In conclusion, we developed a method to express the PapG.AcmA protein on the surface of Lactobacillus.
+This is the first report on the successful application of lactic acid bacteria displaying the PapG.AcmA fusion protein.
+It will be interesting to determine the immune responses against the PapG protein in near future using this surface display strategy.
+Human illness from influenza A(H7N9) was identified in March 2013, and candidate vaccine viruses were soon developed.
+To understand factors that may impact influenza vaccination programs, we developed a model to evaluate hospitalizations and deaths averted considering various scenarios.
+We utilized a model incorporating epidemic curves with clinical attack rates of 20% or 30% in a single wave of illness, case hospitalization ratios of 0.5% or 4.2%, and case fatality ratios of 0.08% or 0.53%.
+The start date of vaccination campaigns most influenced impact; 141 000–2 200 000 hospitalizations and 11 000–281 000 deaths were averted when campaigns started before a pandemic, and <100–1 300 000 hospitalizations and 0–165 000 deaths were averted for programs beginning the same time as or after the introduction of the pandemic virus.
+The rate of vaccine administration and vaccine effectiveness did not influence campaign impact as much as timing of the start of campaign.
+Our findings suggest that efforts to improve the timeliness of vaccine production will provide the greatest impacts for future pandemic vaccination programs.
+Stimulation of the antiviral response depends on the sensing of viral pathogen-associated molecular patterns (PAMPs) by specialized cellular proteins.
+During infection with RNA viruses, 5′-di- or -triphosphates accompanying specific single or double-stranded RNA motifs trigger signaling of intracellular RIG-I-like receptors (RLRs) and initiate the antiviral response.
+Although these molecular signatures are present during the replication of many viruses, it is unknown whether they are sufficient for strong activation of RLRs during infection.
+Immunostimulatory defective viral genomes (iDVGs) from Sendai virus (SeV) are among the most potent natural viral triggers of antiviral immunity.
+Here we describe an RNA motif (DVG(70-114)) that is essential for the potent immunostimulatory activity of 5′-triphosphate-containing SeV iDVGs.
+DVG(70-114) enhances viral sensing by the host cell independently of the long stretches of complementary RNA flanking the iDVGs, and it retains its stimulatory potential when transferred to otherwise inert viral RNA.
+In vitro analysis showed that DVG(70-114) augments the binding of RIG-I to viral RNA and promotes enhanced RIG-I polymerization, thereby facilitating the onset of the antiviral response.
+Together, our results define a new natural viral PAMP enhancer motif that promotes viral recognition by RLRs and confers potent immunostimulatory activity to viral RNA.
+Acute lung injury (ALI) is characterized by pulmonary endothelial and epithelial cell damage, and loss of the alveolar–capillary barrier.
+We have previously shown that P2X7 receptor (P2X7R), a cell death receptor, is specifically expressed in alveolar epithelial type I cells (AEC I).
+In this study, we hypothesized that P2X7R-mediated purinergic signaling and its interaction with Wnt/β-catenin signaling contributes to AEC I death.
+We examined the effect of P2X7R agonist 2′-3′-O-(4-benzoylbenzoyl)-ATP (BzATP) and Wnt agonist Wnt3a on AEC I death in vitro and in vivo.
+We also assessed the therapeutic potential of Wnt3a in a clinically relevant ALI model of intratracheal lipopolysaccharide (LPS) exposure in ventilated mice.
+We found that the activation of P2X7R by BzATP caused the death of AEC I by suppressing Wnt/β-catenin signaling through stimulating glycogen synthase kinase-3β (GSK-3β) and proteasome.
+On the other hand, the activation of Wnt/β-catenin signaling by Wnt3a, GSK-3β inhibitor, or proteasome inhibitor blocked the P2X7R-mediated cell death.
+More importantly, Wnt3a attenuated the AEC I damage caused by intratracheal instillation of BzATP in rats or LPS in ventilated mice.
+Our results suggest that Wnt3a overrides the effect of P2X7R on the Wnt/β-catenin signaling to prevent the AEC I death and restrict the severity of ALI.
+[Image: see text] The prolonged and localized delivery of nitric oxide (NO), a potent antithrombotic and antimicrobial agent, has many potential biomedical applications.
+In this work, the origin of the long-term storage stability and sustained NO release mechanism of S-nitroso-N-acetyl-d-penicillamine (SNAP)-doped CarboSil 20 80A polymer, a biomedical thermoplastic silicone-polycarbonate-urethane, is explored.
+Long-term (22 days) localized NO release is achieved by utilizing a cross-linked silicone rubber as topcoats, which can greatly reduce the amount of SNAP, NAP, and NAP disulfide leaching from the SNAP-doped CarboSil films, as measured by LC–MS.
+Raman spectroscopy and powder X-ray diffraction characterization of SNAP-doped CarboSil films demonstrate that a polymer–crystal composite is formed during the solvent evaporation process when SNAP exceeds its solubility in CarboSil (ca.
+Further, when exceeding this solubility threshold, SNAP exists in an orthorhombic crystal form within the bulk of the polymer.
+The proposed mechanism of sustained NO release in SNAP-doped CarboSil is that the solubilized SNAP in the polymer matrix decomposes and releases NO, primarily in the water-rich regions near the polymer/solution interface, and the dissolved SNAP in the bulk polymeric phase becomes unsaturated, resulting in the dissolution of crystalline SNAP within the bulk of the polymer.
+This is a very slow process that ultimately leads to NO release at the physiological flux levels for >3 weeks.
+The increased stability of SNAP within CarboSil is attributed to the intermolecular hydrogen bonds between the SNAP molecules that crystallize.
+This crystallization also plays a key role in maintaining RSNO stability within the CarboSil polymer for >8 months at 37 °C (88.5% remains).
+Further, intravascular catheters fabricated with this new material are demonstrated to significantly decrease the formation of Staphylococcus aureus biofilm (a leading cause of nosocomial bloodstream infections) (in vitro) over a 7 day period, with 5 log units reduction of viable cell count on catheter surfaces.
+It is also shown that the NO release catheters can greatly reduce thrombus formation on the catheter surfaces during 7 h implantation in rabbit veins, when compared to the control catheters fabricated without SNAP.
+These results suggest that the SNAP-doped CarboSil system is a very attractive new composite material for creating long-term NO release medical devices with increased stability and biocompatibility.
+Next-generation sequencing technologies have been used to sequence the fecal DNA samples of the patient, the within sample diversity analysis, enterotyping, functional gene and metagenomic species analysis have been carried on both the patients and healthy controls.
+The influence of associated treatment in H7N9 infected patients is dramatic and was firstly revealed in species level due to deep sequencing technology.
+We found that most of the MetaGenomic Species (MGS) enriched in the control samples were Roseburia inulinivorans DSM 16841, butyrate producing bacterium SS3/4 and most of MGS enriched in the H7N9 patients were Clostridium sp.
+It was concluded that H7N9 viral infection and antibiotic administration have a significant effect on the microbiota community with decreased diversity and overgrowth of the bacteria such as Escherichia coli and Enterococcus faecium.
+Treatment including antivirals, probiotics and antibiotics helps to improve the microbiota diversity and the abundance of beneficial bacteria in the gut.
+Since their discovery in 1999, over 120 proteins have been described to be localized to these structures (in 154 publications).
+Most of these components are RNA binding proteins (RBPs) or are involved in RNA metabolism and translation.
+SGs have been linked to several pathologies including inflammatory diseases, cancer, viral infection, and neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD).
+In ALS and FTD, the majority of cases have no known etiology and exposure to external stress is frequently proposed as a contributor to either disease initiation or the rate of disease progression.
+Of note, both ALS and FTD are characterized by pathological inclusions, where some well-known SG markers localize with the ALS related proteins TDP-43 and FUS.
+We propose that TDP-43 and FUS serve as an interface between genetic susceptibility and environmental stress exposure in disease pathogenesis.
+Here, we will discuss the role of TDP-43 and FUS in SG dynamics and how disease-linked mutations affect this process.
+BACKGROUND: The mechanisms by which varicella zoster virus (VZV) reactivation causes postherpetic neuralgia (PHN), a debilitating chronic pain condition, have not been fully elucidated.
+Based on previous studies identifying a causative role for anti-cytokine autoantibodies in patients with opportunistic infections, we explored this possibility in PHN.
+METHODS: Sera from herpes zoster (HZ) patients without and with PHN (N = 115 and 83, respectively) were examined for the presence of autoantibodies against multiple cytokines, and other known autoantigens.
+In addition, a cohort of patients with complex regional pain syndrome or neuropathic pain was tested for autoantibodies against selected cytokines.
+Antibody levels against VZV, Epstein Barr virus, and herpes simplex virus-2 were also measured in the HZ and PHN patients.
+Patient sera with high levels of anti-cytokine autoantibodies were functionally tested for in vitro neutralizing activity.
+RESULTS: Six PHN subjects demonstrated markedly elevated levels of single, autoantibodies against interferon-α, interferon-γ, GM-CSF, or interleukin-6.
+In contrast, the HZ and the pain control group showed low or no autoantibodies, respectively, against these four cytokines.
+Further analysis revealed that one PHN patient with high levels of anti-interleukin-6 autoantibodies had a markedly depressed antibody level to VZV, potentially reflecting poor T cell immunity against VZV.
+In vitro functional testing revealed that three of the five anti-cytokine autoantibody positive PHN subjects had neutralizing autoantibodies against interferon-α, GM-CSF or interleukin-6.
+CONCLUSIONS: These results suggest the possibility that sporadic anti-cytokine autoantibodies in some subjects may cause an autoimmune immunodeficiency syndrome leading to uncontrolled VZV reactivation, nerve damage and subsequent PHN.
+They can cause cutaneous, nasopharyngeal, and disseminated infection, leading to granulomatous amebic encephalitis (GAE) in immunocompromised individuals.
+Acanthamoeba GAE is almost always fatal because of difficulty and delay in diagnosis and lack of optimal antimicrobial therapy.
+Here, we report the description of an unusual strain isolated from skin and brain of a GAE patient.
+The amoebae displayed large trophozoites and star‐shaped cysts, characteristics for acanthamoebas belonging to morphology Group 1.
+However, its unique morphology and growth characteristics differentiated this new strain from other Group 1 species.
+DNA sequence analysis, secondary structure prediction, and phylogenetic analysis of the 18S rRNA gene confirmed that this new strain belonged to Group 1, but that it was distinct from the other sequence types within that group.
+To our knowledge, this is the first report of a Group 1 Acanthamoeba that is indisputably pathogenic in humans.
+In order to estimate ongoing transmission in the affected countries, we estimated the weekly average number of secondary cases caused by one individual infected with Ebola throughout the infectious period for each affected West African country using a stochastic hidden Markov model fitted to case data from the World Health Organization.
+If the average number of infections caused by one Ebola infection is less than 1.0, the epidemic is subcritical and cannot sustain itself.
+The epidemics in Liberia and Sierra Leone have approached subcriticality at some point during the epidemic; the epidemic in Guinea is ongoing with no evidence that it is subcritical.
+Response efforts to control the epidemic should continue in order to eliminate Ebola cases in West Africa.
+Different immune-based assays have been reported for the detection and quantification of Ebola virus (EBOV) proteins.
+In particular, several monoclonal antibodies (mAbs) have been described that bind the capsid glycoprotein (GP) of EBOV GP.
+However, the currently available platforms for the design and production of full-length mAbs are cumbersome and costly.
+The use of antibody fragments, rather than full-length antibodies, might represent a cost-effective alternative for the development of diagnostic and possibly even therapeutic alternatives for EBOV.
+METHODS/PRINCIPAL FINDINGS: We report the design and expression of three recombinant anti-GP mAb fragments in Escherichia coli cultures.
+These fragments contained the heavy and light variable portions of the three well-studied anti-GP full-length mAbs 13C6, 13F6, and KZ52, and are consequently named scFv-13C6, scFv-13F6, and Fab-KZ52, respectively.
+All three fragments exhibited specific anti-GP binding activity in ELISA experiments comparable to that of full-length anti-GP antibodies (i.e., the same order of magnitude) and they are easily and economically produced in bacterial cultures.
+CONCLUSION/SIGNIFICANCE: Antibody fragments might represent a useful, effective, and low cost alternative to full-length antibodies in Ebola related capture and diagnostics applications.
+Formalin-inactivated Japanese encephalitis virus (JEV) vaccines are widely available, but the effects of formalin inactivation on the antigenic structure of JEV and the profile of antibodies elicited after vaccination are not well understood.
+We used a panel of monoclonal antibodies (MAbs) to map the antigenic structure of live JEV virus, untreated control virus (UCV), formalin-inactivated commercial vaccine (FICV), and formalin-inactivated virus (FIV).
+The binding activity of T16 MAb against Nakayama-derived FICV and several strains of FIV was significantly lower compared to live virus and UCV.
+T16 MAb, a weakly neutralizing JEV serocomplex antibody, was found to inhibit JEV infection at the post-attachment step.
+The T16 epitope was mapped to amino acids 329, 331, and 389 within domain III (EDIII) of the envelope (E) glycoprotein.
+When we explored the effect of formalin inactivation on the immunogenicity of JEV, we found that Nakayama-derived FICV, FIV, and UCV all exhibited similar immunogenicity in a mouse model, inducing anti-JEV and anti-EDII 101/106/107 epitope-specific antibodies.
+However, the EDIII 329/331/389 epitope-specific IgG antibody and neutralizing antibody titers were significantly lower for FICV-immunized and FIV-immunized mouse serum than for UCV-immunized.
+Formalin inactivation seems to alter the antigenic structure of the E protein, which may reduce the potency of commercially available JEV vaccines.
+Virus inactivation by H(2)O(2), but not by UV or by short-duration and higher temperature formalin treatment, is able to maintain the antigenic structure of the JEV E protein.
+Thus, an alternative inactivation method, such as H(2)O(2), which is able to maintain the integrity of the E protein may be essential to improving the potency of inactivated JEV vaccines.
+BACKGROUND: Nonspecific interstitial pneumonia (NSIP) is characterized by interstitial infiltration of T lymphocytes, and subpopulations of these cells may be associated with the progression of fibrosis.
+Therefore, we performed morphological and quantitative analyses of T lymphocytes in patients with NSIP and evaluated the relationship between T lymphocytes and prognosis.
+METHODS: Immunohistochemistry was used to detect the presence of CD4+ and CD8+ T lymphocytes in 55 biopsies of patients with NSIP to determine the numbers of these T cell subpopulations in lymphoid follicles as well as in perivascular, interstitial, and peribronchial anatomical compartments.
+RESULTS: The mean age of 55 patients was 48.9 ± 10.5 years, and 36 (65 %) of patients were women.
+Perivascular CD4+ lymphocyte infiltration (HR, 0.939; 95 % CI, 0.883–0.999; p = 0.048) was an independent risk factor for survival.
+Perivascular infiltrates of CD4+ T lymphocytes correlated with survival time (r = 0.270, p = 0.046).
+Patients with improved forced vital capacity survived longer and had higher numbers of CD4+ T lymphocytes that infiltrated perivascular tissue.
+The densities of CD4+ and CD8+ T lymphocytes infiltrating other tissues were not significantly associated with survival time.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12890-015-0122-z) contains supplementary material, which is available to authorized users.
+Avian metapneumovirus (aMPV) and human metapneumovirus (hMPV) are members of the genus Metapneumovirus in the subfamily Pneumovirinae.
+Metapneumovirus fusion (F) protein mediates the fusion of host cells with the virus membrane for infection.
+Here, we demonstrated that three subtypes of aMPV (aMPV/A, aMPV/B, and aMPV/C) F proteins promoted cell-cell fusion in the absence of trypsin.
+Mutagenesis of the amino acids at position 100 and/or 101, located at a putative cleavage region in aMPV F proteins, revealed that the trypsin-mediated fusogenicity of aMPV F proteins is regulated by the residues at positions 100 and 101.
+Moreover, we demonstrated that aMPV/A and aMPV/B F proteins mediated cell-cell fusion independent of low pH, whereas the aMPV/C F protein did not.
+Mutagenesis of the residue at position 294 in the aMPV/A, aMPV/B, and aMPV/C F proteins showed that 294G played a critical role in F protein-mediated fusion under low pH conditions.
+These findings on aMPV F protein-induced cell-cell fusion provide new insights into the molecular mechanisms underlying membrane fusion and pathogenesis of aMPV.
+Viruses modulate cellular processes and metabolism in diverse ways, but these are almost universally studied in the infected cell itself.
+Here, we study spatial organization of DNA synthesis during multiround transmission of herpes simplex virus (HSV) using pulse-labeling with ethynyl nucleotides and cycloaddition of azide fluorophores.
+Consistent with the current understanding of the single-step growth cycle, HSV suppresses host DNA synthesis and promotes viral DNA synthesis in spatially segregated compartments within the cell.
+In striking contrast, during progressive rounds of infection initiated at a single cell, we observe that infection induces a clear and pronounced stimulation of cellular DNA replication in remote uninfected cells.
+This induced DNA synthesis was observed in hundreds of uninfected cells at the extended border, outside the perimeter of the progressing infection.
+Moreover, using pulse-chase analysis, we show that this activation is maintained, resulting in a propagating wave of host DNA synthesis continually in advance of infection.
+As the virus reaches and infects these activated cells, host DNA synthesis is then shut off and replaced with virus DNA synthesis.
+Using nonpropagating viruses or conditioned medium, we demonstrate a paracrine effector of uninfected cell DNA synthesis in remote cells continually in advance of infection.
+These findings have significant implications, likely with broad applicability, for our understanding of the ways in which virus infection manipulates cell processes not only in the infected cell itself but also now in remote uninfected cells, as well as of mechanisms governing host DNA synthesis.
+IMPORTANCE We show that during infection initiated by a single particle with progressive cell-cell virus transmission (i.e., the normal situation), HSV induces host DNA synthesis in uninfected cells, mediated by a virus-induced paracrine effector.
+The field has had no conception that this process occurs, and the work changes our interpretation of virus-host interaction during advancing infection and has implications for understanding controls of host DNA synthesis.
+Our findings demonstrate the utility of chemical biology techniques in analysis of infection processes, reveal distinct processes when infection is examined in multiround transmission versus single-step growth curves, and reveal a hitherto-unknown process in virus infection, likely relevant for other viruses (and other infectious agents) and for remote signaling of other processes, including transcription and protein synthesis.
+BACKGROUND: A novel reassortant avian-origin influenza A (H7N9) virus was found to infect three Chinese residents, the first H7N9 infection in humans in Asia.
+Chest computed tomography (CT) for acute respiratory distress syndrome (ARDS) diagnosis is not only expensive but also exposes patients to radiation and might cause patients to be at risk of infection during transportation; in addition, chest radiography cannot be used to monitor the lung repeatedly in real time.
+Therefore, the routine use of bedside lung ultrasonography for critically ill patients with ARDS is especially valuable.
+OBJECTIVES: The aim of this study was to evaluate the application of ultrasound for lung examination in patients with ARDS.
+METHODS: Eleven patients infected with H7N9 avian influenza who developed ARDS were diagnosed by lung ultrasonography.
+RESULTS: Six patients who had severe ARDS showed a diffuse comet tail sign or a consolidation score ≥ 7 and a lung ultrasound score ≥ 20 points.
+A diffuse comet tail sign or a consolidation score ≤ 6 and a lung ultrasound score < 25 were observed in four patients.
+One patient showed a diffuse comet tail sign or consolidation area in four lung areas, with an ultrasound score of 14.
+Among all 11 patients studied, 6 patients had thoracic puncture and drainage of pleural effusion and 2 patients had pneumothorax puncture drainage.
+CONCLUSIONS: Lung ultrasound could be useful for monitoring ARDS caused by the influenza virus A H7N9 strain in clinical applications.
+TAR DNA-binding protein 43 (TDP-43) is normally a nuclear RNA-binding protein that exhibits a range of functions including regulation of alternative splicing, RNA trafficking, and RNA stability.
+However, in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP), TDP-43 is abnormally phosphorylated, ubiquitinated, and cleaved, and is mislocalized to the cytoplasm where it forms distinctive aggregates.
+We previously developed a mouse model expressing human TDP-43 with a mutation in its nuclear localization signal (ΔNLS-hTDP-43) so that the protein preferentially localizes to the cytoplasm.
+These mice did not exhibit a significant number of cytoplasmic aggregates, but did display dramatic changes in gene expression as measured by microarray, suggesting that cytoplasmic TDP-43 may be associated with a toxic gain-of-function.
+Here, we analyze new RNA-sequencing data from the ΔNLS-hTDP-43 mouse model, together with published RNA-sequencing data obtained previously from TDP-43 antisense oligonucleotide (ASO) knockdown mice to investigate further the dysregulation of gene expression in the ΔNLS model.
+This analysis reveals that the transcriptomic effects of the overexpression of the ΔNLS-hTDP-43 transgene are likely due to a gain of cytoplasmic function.
+Moreover, cytoplasmic TDP-43 expression alters transcripts that regulate chromatin assembly, the nucleolus, lysosomal function, and histone 3’ untranslated region (UTR) processing.
+These transcriptomic alterations correlate with observed histologic abnormalities in heterochromatin structure and nuclear size in transgenic mouse and human brains.
+Understanding immune responses elicited by vaccines, together with immune responses required for protection, is fundamental to designing effective vaccines and immunisation programs.
+This study examines the effects of the route of administration of a live attenuated vaccine on its interactions with, and stimulation of, the murine immune system as well as its ability to increase survival and provide protection from colonisation by a virulent challenge strain.
+We assess the effect of administration method using the murine model for typhoid, where animals are infected with S. Typhimurium.
+Mice were vaccinated either intravenously or orally with the same live attenuated S. Typhimurium strain and data were collected on vaccine strain growth, shedding and stimulation of antibodies and cytokines.
+Following vaccination, mice were challenged with a virulent strain of S. Typhimurium and the protection conferred by the different vaccination routes was measured in terms of challenge suppression and animal survival.
+The main difference in immune stimulation found in this study was the development of a secretory IgA response in orally-vaccinated mice, which was absent in IV vaccinated mice.
+While both strains showed similar protection in terms of challenge suppression in systemic organs (spleen and liver) as well as survival, they differed in terms of challenge suppression of virulent pathogens in gut-associated organs.
+This difference in gut colonisation presents important questions around the ability of vaccines to prevent shedding and transmission.
+These findings demonstrate that while protection conferred by two vaccines can appear to be the same, the mechanisms controlling the protection can differ and have important implications for infection dynamics within a population.
+The introduction of multivalent vaccines has coincided with a dramatic decrease in the number of pneumococcal-related deaths.
+In spite of this, at a global level, pneumococcal infection remains an important cause of death among children under 5 years of age and in adults 65 years of age or older.
+In order to properly manage patients and control the spread of infection, a rapid and highly sensitive diagnostic method is needed for routine implementation, especially in resource-limited regions where pneumococcal disease is most prevalent.
+METHODS: Using the gene encoding leader peptidase A as a molecular diagnostics target, a real-time RPA assay was designed and optimised for the detection of S. pneumoniae in whole blood.
+The performance of the assay was compared to real-time PCR in terms of its analytical limit of detection and specificity.
+The potential clinical utility of the assay was investigated using a small number of clinical samples.
+RESULTS: The RPA assay has a limit of detection equivalent to PCR (4.0 and 5.1 genome equivalents per reaction, respectively) and was capable of detecting the equivalent of <1 colony forming unit of S. pneumoniae when spiked into human whole blood.
+The RPA assay was 100 % inclusive (38/38 laboratory reference strains and 19/19 invasive clinical isolates) and 100 % exclusive; differentiating strains of S. pneumoniae species from other viridans group streptococci, including S. pseudopneumoniae.
+When applied to the analysis of a small number (n = 11) of clinical samples (blood culture positive for S. pneumoniae), the RPA assay was demonstrated to be both rapid and sensitive.
+CONCLUSIONS: The RPA assay developed in this work is shown to be as sensitive and as specific as PCR.
+In terms of reaction kinetics, the RPA assay is shown to exceed those of the PCR, with the RPA running to completion in 20 minutes and capable generating a positive signal in as little as 6 minutes.
+It is responsible for the malfunction of various organs, leading to disease particularly in the lungs, liver and kidneys.
+In the present study, the effect of cadmium chloride (CdCl(2)) on cell viability, and the expression levels of interleukin (IL)-1α and IL-10 cytokines at various concentrations and incubation durations were assessed in MRC-9 human normal lung and A549 human lung cancer cells to elucidate the mechanism of cadmium toxicity.
+The expression levels of the cytokines were measured by cytokine specific enzyme-linked immunosorbent assay kits.
+The viability assay results revealed higher sensitivity of the A549 lung cancer cells to CdCl(2) compared with the normal MRC-9 lung cells.
+In the normal MRC-9 lung cells, higher expression levels of the cytokines were observed at the lowest CdCl(2) concentration at a shorter exposure time compared with the lung cancer cells.
+Higher levels of the cytokines were observed in the A549 lung cancer cells at all other times and concentrations compared with the MRC-9 cells, indicating higher levels of inflammation.
+The cytokine levels were reduced at higher CdCl(2) concentrations and longer exposure durations, demonstrating the toxic effect of cadmium.
+The results indicated that CdCl(2) affected the expression levels of the cytokines and led to cytotoxicity in human lung cells, and suggested that compounds which reduce inflammation may prevent cadmium toxicity.
+High-mobility-group-box chromosomal protein 1 (HMGB1) is a ubiquitous and abundant nuclear protein in eukaryotic cells.
+HMGB1, when released extracellularly, is a potent innate signal, which initiates host defense mechanisms or tissue regeneration.
+The HMGB1 A box exhibits an antagonistic, anti-inflammatory effect, and is a potential therapeutic target, however, the large-scale expression and purification of the HMGB1 A box with high efficiency remains to be reported.
+In the present study, a SUMO-fusion expression system was used to express and purify high levels of functional HMGB1 A box to meet the requirements of therapeutic protein production.
+Since the re-emergence of Ebola in West Africa in 2014, comprehensive and stringent interventions have been implemented to decelerate the spread of the disease.
+In this paper, we develop an epidemiological model that includes various controlling measures to systematically evaluate their effects on the disease transmission dynamics.
+By fitting the model to reported cumulative cases and deaths in Guinea, Sierra Leone and Liberia until March 22, 2015, we estimate the basic reproduction number in these countries as 1.2552, 1.6093 and 1.7994, respectively.
+Model analysis shows that there exists a threshold of the effectiveness of isolation, below which increasing the fraction of latent individuals diagnosed prior to symptoms onset or shortening the duration between symptoms onset and isolation may lead to more Ebola infection.
+The response to reported cumulative infected cases and deaths may have a different effect on the epidemic spread in different countries.
+Among all the interventions, we find that shortening the duration between death and burial and improving the effectiveness of isolation are two effective interventions for controlling the outbreak of Ebola virus infection.
+In Saccharomyces cerevisiae, 11 out of 42 tRNA species contain 5-methoxycarbonylmethyl-2-thiouridine (mcm(5)s(2)U), 5-methoxycarbonylmethyluridine (mcm(5)U), 5-carbamoylmethyluridine (ncm(5)U) or 5-carbamoylmethyl-2′-O-methyluridine (ncm(5)Um) nucleosides in the anticodon at the wobble position (U(34)).
+Earlier we showed that mutants unable to form the side chain at position 5 (ncm(5) or mcm(5)) or lacking sulphur at position 2 (s(2)) of U(34) result in pleiotropic phenotypes, which are all suppressed by overexpression of hypomodified tRNAs.
+This observation suggests that the observed phenotypes are due to inefficient reading of cognate codons or an increased frameshifting.
+The latter may be caused by a ternary complex (aminoacyl-tRNA*eEF1A*GTP) with a modification deficient tRNA inefficiently being accepted to the ribosomal A-site and thereby allowing an increased peptidyl-tRNA slippage and thus a frameshift error.
+In this study, we have investigated the role of wobble uridine modifications in reading frame maintenance, using either the Renilla/Firefly luciferase bicistronic reporter system or a modified Ty1 frameshifting site in a HIS4A::lacZ reporter system.
+We here show that the presence of mcm(5) and s(2) side groups at wobble uridines are important for reading frame maintenance and thus the aforementioned mutant phenotypes might partly be due to frameshift errors.
+Fat embolism syndrome (FES) is primarily a lung parenchymal disorder resulting from interstitial and alveolar inflammation triggered by the lipid metabolites in blood circulation.
+The 'low-dose' corticosteroid is supposed to have a prophylactic effect on the incidence of the FES and arterial hypoxemia by reducing this inflammatory response.
+It is expected that inhaled corticosteroids (ciclesonide aerosol) may prevent the development of hypoxemia or fat embolism syndrome in high-risk patients by reducing this inflammatory response.
+Sixty cases of polytrauma patients presenting within eight hours of injury were randomly allocated into one of the two groups.
+In Group 1 (n(1)=30) ciclesonide, 640 mcg, was given with a metered dose inhaler and repeated once again after 24 hours, whereas Group 2 (n(2)=30) was taken as control and observed for 72 hours for any episode of hypoxia.
+The outcome was assessed using Schonfeld’s criteria for the eventual outcome of subclinical or clinical FES.
+Out of 30 patients in each group, six patients developed subclinical FES, whereas three from ciclesonide prophylaxis group and eight from controls developed clinical FES.
+There is no statistical significance found between the eventual outcomes of subclinical or clinical FES between the ciclesonide prophylaxis and control group.
+Although there was a trend seen in the possible preventive efficacy of inhalational steroid in the present study, it did not reach the statistically significant level.
+The prophylactic role of inhalational steroid in post-traumatic subclinical and clinical FES is statistically insignificant in the present study.
+Influenza is one of the most common infections threatening public health worldwide and is caused by the influenza virus.
+Rapid emergence of drug resistance has led to an urgent need to develop new anti-influenza inhibitors.
+In this study we established a 293T cell line that constitutively synthesizes a virus-based negative strand RNA, which expresses Gaussia luciferase upon influenza A virus infection.
+Using this cell line, an assay was developed and optimized to search for inhibitors of influenza virus replication.
+Biochemical studies and statistical analyses presented herein demonstrate the sensitivity and reproducibility of the assay in a high-throughput format (Z′ factor value>0.8).
+Taken together, this work provides a simple, convenient, and reliable HTS assay to identify compounds with anti-influenza activity.
+The Democratic Republic of the Congo has experienced the most outbreaks of Ebola virus disease since the virus' discovery in 1976.
+This article provides for the first time a description and a line list for all outbreaks in this country, comprising 996 cases.
+Compared to patients over 15 years old, the odds of dying were significantly lower in patients aged 5 to 15 and higher in children under five (with 100% mortality in those under 2 years old).
+The odds of dying increased by 11% per day that a patient was not hospitalised.
+Outbreaks with an initially high reproduction number, R (>3), were rapidly brought under control, whilst outbreaks with a lower initial R caused longer and generally larger outbreaks.
+These findings can inform the choice of target age groups for interventions and highlight the importance of both reducing the delay between symptom onset and hospitalisation and rapid national and international response.
+BACKGROUND: The HIV-1 subtype B epidemic amongst men who have sex with men (MSM) is resurgent in many countries despite the widespread use of effective combination antiretroviral therapy (cART).
+In this combined mathematical and phylogenetic study of observational data, we aimed to find out the extent to which the resurgent epidemic is the result of newly introduced strains or of growth of already circulating strains.
+METHODS AND FINDINGS: As of November 2011, the ATHENA observational HIV cohort of all patients in care in the Netherlands since 1996 included HIV-1 subtype B polymerase sequences from 5,852 patients.
+Patients who were diagnosed between 1981 and 1995 were included in the cohort if they were still alive in 1996.
+The ten most similar sequences to each ATHENA sequence were selected from the Los Alamos HIV Sequence Database, and a phylogenetic tree was created of a total of 8,320 sequences.
+Large transmission clusters that included ≥10 ATHENA sequences were selected, with a local support value ≥ 0.9 and median pairwise patristic distance below the fifth percentile of distances in the whole tree.
+We identified 106 large transmission clusters, including 3,061 (52%) ATHENA and 652 Los Alamos sequences.
+Half of the HIV sequences from MSM registered in the cohort in the Netherlands (2,128 of 4,288) were included in 91 large MSM-majority clusters.
+Strikingly, at least 54 (59%) of these 91 MSM-majority clusters were already circulating before 1996, when cART was introduced, and have persisted to the present.
+Overall, 1,226 (35%) of the 3,460 diagnoses among MSM since 1996 were found in these 54 long-standing clusters.
+The reproduction numbers of all large MSM-majority clusters were around the epidemic threshold value of one over the whole study period.
+A tendency towards higher numbers was visible in recent years, especially in the more recently introduced clusters.
+The mean age of MSM at diagnosis increased by 0.45 years/year within clusters, but new clusters appeared with lower mean age.
+Major strengths of this study are the high proportion of HIV-positive MSM with a sequence in this study and the combined application of phylogenetic and modeling approaches.
+Main limitations are the assumption that the sampled population is representative of the overall HIV-positive population and the assumption that the diagnosis interval distribution is similar between clusters.
+CONCLUSIONS: The resurgent HIV epidemic amongst MSM in the Netherlands is driven by several large, persistent, self-sustaining, and, in many cases, growing sub-epidemics shifting towards new generations of MSM.
+Many of the sub-epidemics have been present since the early epidemic, to which new sub-epidemics are being added.
+Polymorphisms near the interferon lambda 3 (IFNL3) gene strongly predict clearance of hepatitis C virus (HCV) infection.
+We analyzed a variant (rs4803217 G/T) located within the IFNL3 mRNA 3′ untranslated region (UTR); the G allele (protective allele) is associated with elevated therapeutic HCV clearance.
+We show that the IFNL3 3′ UTR represses mRNA translation and the rs4803217 allele modulates the extent of translational regulation.
+The rs4803217 G allele mRNA forms well-defined 3′ UTR structure while the T allele mRNA is more dynamic.
+The observed differences between alleles are among the largest possible RNA structural alterations that can be induced by a single nucleotide change and transform the UTR from a single well-defined conformation to one with multiple dynamic interconverting structures.
+These data illustrate that non-coding genetic variants can have significant functional effects by impacting RNA structure.
+Replication of the poliovirus genome is localized to cytoplasmic replication factories that are fashioned out of a mixture of viral proteins, scavenged cellular components, and new components that are synthesized within the cell due to viral manipulation/up-regulation of protein and phospholipid synthesis.
+These membranous replication factories are quite complex, and include markers from multiple cytoplasmic cellular organelles.
+This review focuses on the role of electron microscopy in advancing our understanding of poliovirus RNA replication factories.
+Structural data from the literature provide the basis for interpreting a wide range of biochemical studies that have been published on virus-induced lipid biosynthesis.
+In combination, structural and biochemical experiments elucidate the dramatic membrane remodeling that is a hallmark of poliovirus infection.
+Early electron microscopy studies of morphological changes following viral infection are re-considered in light of more recent data on viral manipulation of lipid and protein biosynthesis.
+These data suggest the existence of distinct subcellular vesicle populations, each of which serves specialized roles in poliovirus replication processes.
+Studies have highlighted the essential nature of a group of small, highly hydrophobic, membrane embedded, channel-forming proteins in the life cycles of a growing number of RNA viruses.
+These viroporins mediate the flow of ions and a range of solutes across cellular membranes and are necessary for manipulating a myriad of host processes.
+Recent discoveries have identified proteins encoded by the small DNA tumor viruses that display a number of viroporin like properties.
+This review article summarizes the recent developments in our understanding of these novel viroporins; describes their roles in the virus life cycles and in pathogenesis and speculates on their potential as targets for anti-viral therapeutic intervention.
+Puumala virus (PUUV) is the agent of nephropathia epidemica (NE), a mild form of hemorrhagic fever with renal syndrome (HFRS) in Europe.
+NE incidence presents a high spatial variation throughout France, while the geographical distribution of the wild reservoir of PUUV, the bank vole, is rather continuous.
+A missing piece of the puzzle is the current distribution and the genetic variation of PUUV in France, which has been overlooked until now and remains poorly understood.
+During a population survey, from 2008 to 2011, bank voles were trapped in eight different forests of France located in areas known to be endemic for NE or in area from where no NE case has been reported until now.
+Bank voles were tested for immunoglobulin (Ig)G ELISA serology and two seropositive animals for each of three different areas (Ardennes, Jura and Orleans) were then subjected to laboratory analyses in order to sequence the whole S, M and L segments of PUUV.
+Phylogenetic analyses revealed that French PUUV isolates globally belong to the central European (CE) lineage although isolates from Ardennes are clearly distinct from those in Jura and Orleans, suggesting a different evolutionary history and origin of PUUV introduction in France.
+Sequence analyses revealed specific amino acid signatures along the N protein, including in PUUV from the Orleans region from where NE in humans has never been reported.
+The Sabin I poliovirus live, attenuated vaccine strain encodes for four amino acid changes (i.e., D53N, Y73H, K250E, and T362I) in the RNA-dependent RNA polymerase (RdRp).
+We have previously shown that the T362I substitution leads to a lower fidelity RdRp, and viruses encoding this variant are attenuated in a mouse model of poliovirus.
+Given these results, it was surprising that the nucleotide incorporation rate and nucleobase fidelity of the Sabin I RdRp is similar to that of wild-type enzyme, although the Sabin I RdRp is less selective against nucleotides with modified sugar groups.
+We suggest that the other Sabin amino acid changes (i.e., D53N, Y73H, K250E) help to re-establish nucleotide incorporation rates and nucleotide discrimination near wild-type levels, which may be a requirement for the propagation of the virus and its efficacy as a vaccine strain.
+These results also suggest that the nucleobase fidelity of the Sabin I RdRp likely does not contribute to viral attenuation.
+Hepatitis C virus (HCV) is a positive-stranded RNA virus that infects approximately 130–170 million people worldwide.
+In 2005, the first HCV infection system in cell culture was established using clone JFH-1, which was isolated from a Japanese patient with fulminant HCV infection.
+JFH-1 replicates efficiently in hepatoma cells and infectious virion particles are released into the culture supernatant.
+The development of cell culture-derived HCV (HCVcc) systems has allowed us to understand how hosts respond to HCV infection and how HCV evades host responses.
+Although the mechanisms underlying the different outcomes of HCV infection are not fully understood, innate immune responses seem to have a critical impact on the outcome of HCV infection, as demonstrated by the prognostic value of IFN-λ gene polymorphisms among patients with chronic HCV infection.
+Herein, we review recent research on interferon response in HCV infection, particularly studies using HCVcc infection systems.
+Previous studies, using short sessions (<12 h), failed to find any effects on respiratory system compliance.
+In the present analysis, the effects of prolonged PP sessions (24 h) were retrospectively studied with regard to safety data, oxygenation and respiratory system compliance.
+PP under VV-ECMO was considered when the patient presented at least one unsuccessful ECMO weaning attempt after day 7 or refractory hypoxemia combined or not with persistent high plateau pressure.
+PP was not performed in patients under vasopressor treatment and in cases of recent open chest cardiac surgery.
+PP, inhaled nitric oxide, recruitment maneuvers), 44 patients received VV-ECMO during the study period for refractory acute respiratory distress syndrome.
+Among the latter, 17 patients underwent PP during VV-ECMO for a total of 27 sessions.
+After 24 h in prone position, PaO(2)/FiO(2) ratio significantly increased from 111 (84–128) to 173 (120–203) mmHg (p < 0.0001) while respiratory system compliance increased from 18 (12–36) to 32 (15–36) ml/cmH(2)O (p < 0.0001).
+Twenty-four hours after the return to supine position, tidal volume was increased from 3.0 (2.2–4.0) to 3.7 (2.8–5.0) ml/kg (p < 0.005).
+PaO(2)/FiO(2) ratio increased by over 20 % in 14/14 sessions for late sessions (≥7 days) and in 7/13 sessions for early sessions (<7 days) (p = 0.01).
+Quantitative CT scan revealed a high percentage of non-aerated or poorly-aerated lung parenchyma [52 % (41–62)] in all patients.
+Hemodynamics did not vary and side effects were rare (one membrane thrombosis and one drop in ECMO blood flow).
+CONCLUSION: When used in combination with VV-ECMO, 24 h of prone positioning improves both oxygenation and respiratory system compliance.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13613-015-0078-4) contains supplementary material, which is available to authorized users.
+Epidemiological studies suggest that, following infection with influenza virus, there is a short period during which a host experiences a lower susceptibility to infection with other influenza viruses.
+Ferrets were first infected then challenged 1–14 days later with pairs of influenza A(H1N1)pdm09, influenza A(H3N2), and influenza B viruses circulating in 2009 and 2010.
+Viral interference was observed when the interval between initiation of primary infection and subsequent challenge was <1 week.
+Ongoing shedding from the primary virus infection was associated with viral interference after the secondary challenge.
+The interval between infections and the sequential combination of viruses were important determinants of viral interference.
+The influenza viruses in this study appear to have an ordered hierarchy according to their ability to block or delay infection, which may contribute to the dominance of different viruses often seen in an influenza season.
+BACKGROUND: The possible transmission of influenza A virus between dogs and humans is important, as in Mexico City there are approximately 1·2 million dogs.
+We present the first evidence of influenza A virus infection in household dogs in Mexico.
+OBJECTIVES: The objective of this study was to identify the presence of antibodies against influenza A virus in dogs and their owners, as well as the presence of RNA of influenza A virus in nasal exudates of dogs and, thereby, assess the possible transmission of the virus between humans and dogs.
+METHODS: Serum samples from household dogs and their owners were analyzed to detect the presence of antibodies against three subtypes of human influenza virus (H1N1pdm09, H1N1, and H3N2), as well as subtype H3N8 of equine influenza.
+The relationship between the seropositivity of dogs and various factors (age, sex, constantly at home, and seropositivity of owners) was statistically analyzed.
+RESULTS: Seroprevalence for human influenza in dogs was 0·9% (1 of 113), and it was 4% (5 of 113) for equine influenza.
+In humans, seroprevalence was 22% for subtype H1N1pdm09, 20% for subtype H1N1, and 11% for subtype H3N2.
+No significant association (P > 0·05) was found between seropositivity and any of the assessed factors.
+It can be assumed that dogs are currently becoming infected with different subtypes of influenza viruses.
+BACKGROUND: H3N2 influenza viruses circulating in humans and European pigs originate from the pandemic A/Hong Kong/68 virus.
+Because of slower antigenic drift in swine, the antigenic divergence between swine and human viruses has been increasing.
+It remains unknown to what extent this results in a reduced cross‐protection between recent human and swine H3N2 influenza viruses.
+OBJECTIVES: We examined whether prior infection of pigs with an old [A/Victoria/3/75 (A/Vic/75)] or a more recent [A/Wisconsin/67/05 (A/Wis/05)] human H3N2 virus protected against a European swine H3N2 virus [sw/Gent/172/08 (sw/Gent/08)].
+Genetic and antigenic relationships between sw/Gent/08 and a selection of human H3N2 viruses were also assessed.
+RESULTS: After challenge with sw/Gent/08, all challenge controls had high virus titers in the entire respiratory tract at 3 days post‐challenge and nasal virus excretion for 5–6 days.
+Pigs previously inoculated with A/Wis/05 showed similar virus titers in the respiratory tract as challenge controls, but the mean duration of nasal shedding was 1·3 days shorter.
+Unlike sw/Gent/08‐ and A/Vic/75‐inoculated pigs, A/Wis/05‐inoculated pigs lacked cross‐reactive neutralizing antibodies against sw/Gent/08 before challenge, but they showed a more rapid antibody response to sw/Gent/08 than challenge controls after challenge.
+CONCLUSIONS: Infection immunity to a recent human H3N2 virus confers minimal cross‐protection against a European swine H3N2 virus.
+We discuss our findings with regard to the recent zoonotic infections of humans in the United States with a swine‐origin H3N2 variant virus.
+METHODS: We analyzed influenza virological data compiled by the World Health Organization from June 2009–August 2010.
+We calculated weekly proportions of A(H1N1)pdm09‐positive specimens out of all A(H1N1)pdm09‐positive specimens detected during the study period for each country.
+We compared parameters of pandemic activity (e.g., peak A[H1N1]pdm09 weekly proportion [peak activity], number of weeks between the 5th and 95th percentiles of A(H1N1)pdm09 cumulative weekly proportion [duration of activity]) between countries in temperate and tropical–subtropical regions.
+We quantified the proportion of A(H1N1)pdm09 out of all influenza A specimens by country and correlated it with countries' central latitudes.
+The median proportion of cases identified during the peak week was higher in temperate (0·12) than in tropical–subtropical (0·09) regions (P < 0·01).
+The median duration of activity was longer in tropical–subtropical (27 weeks) than in temperate countries (20 weeks) (P < 0·01).
+There was a positive correlation between country central latitude and proportion of A(H1N1)pdm09 out of all influenza A specimens (r: 0·76; P < 0·01).
+CONCLUSIONS: The transmission of A(H1N1)pdm09 exhibited similarities with seasonal influenza transmission in that activity varied between temperate and tropical–subtropical countries and by time of year.
+Our findings suggest the potential utility of accounting for these factors during future pandemic planning.
+The panzootic of H5N1 influenza in birds has raised concerns that the virus will mutate to spread more readily in people, leading to a human pandemic.
+Mathematical models have been used to interpret past pandemics and outbreaks, and to thus model possible future pandemic scenarios and interventions.
+We review historical influenza outbreak and transmission data, and discuss the way in which modellers have used such sources to inform model structure and assumptions.
+We suggest that urban attack rates in the 1918–1919 pandemic were constrained by prior immunity, that R (0) for influenza is higher than often assumed, and that control of any future pandemic could be difficult in the absence of significant prior immunity.
+In future, modelling assumptions, parameter estimates and conclusions should be tested against as many relevant data sets as possible.
+To this end, we encourage researchers to access FluWeb, an on‐line influenza database of historical pandemics and outbreaks.
+However, there are no methods available to detect DNA and RNA viruses in the same reaction system in preclinical level.
+In this study, we aimed to develop a duplex ultrasensitive nanoparticle DNA probe-based PCR assay (duplex UNDP-PCR) that was able to simultaneously detect DNA and RNA viruses in the same reaction system.
+PCV2 DNA and TGEV RNA were simultaneously released from the serum sample by boiling with lysis buffer, then magnetic beads and gold nanoparticles coated with single and/or duplex specific probes for TGEV and PCV2 were added to form a sandwich-like complex with nucleic acids released from viruses.
+After magnetic separation, DNA barcodes specific for PCV2 and TGEV were eluted using DTT and characterized by specific PCR assay for specific DNA barcodes subsequently.
+The duplex UNDP-PCR showed similar sensitivity as that of single UNDP-PCR and was able to detect 20 copies each of PCV2 and TGEV in the serum, showing approximately 250-fold more sensitivity than conventional duplex PCR/RT-PCR assays.
+The positive detection rate of single MMPs- and duplex MMPs-based duplex UNDP-PCR was identical, with 29.6% for PCV2, 9.3% for TGEV and 3.7% for PCV2 and TGEV mixed infection.
+This duplex UNDP-PCR assay could detect TGEV (RNA virus) and PCV2 (DNA virus) from large-scale serum samples simultaneously without the need for DNA/RNA extraction, purification and reverse transcription of RNA, and showed a significantly increased positive detection rate for PCV2 (29%) and TGEV (11.7%) preclinical infection than conventional duplex PCR/RT-PCR.
+Therefore, the established duplex UNDP-PCR is a rapid and economical detection method, exhibiting high sensitivity, specificity and reproducibility.
+OBJECTIVE: A large-scale public health emergency, such as a severe influenza pandemic, can generate large numbers of critically ill patients in a short time.
+We modeled the number of mechanical ventilators that could be used in addition to the number of hospital-based ventilators currently in use.
+METHODS: We identified key components of the health care system needed to deliver ventilation therapy, quantified the maximum number of additional ventilators that each key component could support at various capacity levels (ie, conventional, contingency, and crisis), and determined the constraining key component at each capacity level.
+RESULTS: Our study results showed that US hospitals could absorb between 26,200 and 56,300 additional ventilators at the peak of a national influenza pandemic outbreak with robust pre-pandemic planning.
+CONCLUSIONS: The current US health care system may have limited capacity to use additional mechanical ventilators during a large-scale public health emergency.
+Emergency planners need to understand their health care systems’ capability to absorb additional resources and expand care.
+This methodology could be adapted by emergency planners to determine stockpiling goals for critical resources or to identify alternatives to manage overwhelming critical care need.
+Mosquito-borne flaviviruses are important pathogens for humans, and the detection of two or more flaviviruses cocirculating in the same geographic area has often been reported.
+Mosquito-borne flaviviruses are primarily transmitted through Aedes and Culex mosquitoes; these viruses establish a life-long or persistent infection without apparent pathological effects.
+Viral interference is a phenomenon whereby one virus inhibits the replication of other viruses, and this condition is frequently associated with persistent infections.
+Viral interference and persistent infection are determined by several factors, such as defective interfering particles, competition for cellular factors required for translation/replication, and the host antiviral response.
+The interaction between two flaviviruses typically results in viral interference, indicating that these viruses share common features during the replicative cycle in the vector.
+The vision of legendary criminologist Cesare Lombroso to use scientific theories of individual causes of crime as a basis for screening and prevention programmes targeting individuals at risk for future criminal behaviour has resurfaced, following advances in genetics, neuroscience and psychiatric epidemiology.
+This article analyses this idea and maps its ethical implications from a public health ethical standpoint.
+Twenty-seven variants of the new Lombrosian vision of forensic screening and prevention are distinguished, and some scientific and technical limitations are noted.
+Some lures, biases and structural factors, making the application of the Lombrosian idea likely in spite of weak evidence are pointed out and noted as a specific type of ethical aspect.
+Many classic and complex ethical challenges for health screening programmes are shown to apply to the identified variants and the choice between them, albeit with peculiar and often provoking variations.
+These variations are shown to actualize an underlying theoretical conundrum in need of further study, pertaining to the relationship between public health ethics and the ethics and values of criminal law policy.
+Somatostatin receptor 2 (SSTR2) is a negative regulator of cell proliferation in human breast cancer.
+Since there is little information about SSTR2 in canine mammary gland tumor (MGT), we clarified its distribution and expression level in normal mammary gland, benign MGT and malignant MGT.
+SSTR2 expression determined by immunohistochemical staining was observed in the cytoplasm of luminal epithelial cells.
+The intensity was negatively correlated with malignancy: normal tissues and some of the benign tumors had the highest levels, while the malignant tumors had little or no SSTR2 expression.
+As for the Western blotting, SSTR2 protein level in benign tumors was significantly lower than the normal mammary gland.
+On the other hand, SSTR2 protein levels in two of three malignant tumors were higher than the other groups.
+Interferon lambda 4 (IFN-λ4) is a novel type-III interferon that can be generated only in individuals carrying a ΔG frame-shift allele of an exonic genetic variant (rs368234815-ΔG/TT).
+The rs368234815-ΔG allele is strongly associated with decreased clearance of hepatitis C virus (HCV) infection.
+Here, we further explored the biological function of IFN-λ4 expressed in human hepatic cells—a hepatoma cell line HepG2 and fresh primary human hepatocytes (PHHs).
+We performed live confocal imaging, cell death and proliferation assays, mRNA expression profiling, protein detection, and antibody blocking assays using transient and inducible stable in vitro systems.
+Not only did we observe significant intracellular retention of IFN-λ4 but also detected secreted IFN-λ4 in the culture media of expressing cells.
+Secreted IFN-λ4 induced strong activation of the interferon-stimulated genes (ISGs) in IFN-λ4-expressing and surrounding cells in transwell assays.
+Specifically, in PHHs, secreted IFN-λ4 induced expression of the CXCL10 transcript and a corresponding pro-inflammatory chemokine, IP-10.
+All IFN-λ4-induced phenotypes—activation of ISGs, decreased proliferation, and increased cell death—could be inhibited by an anti-IFN-λ4-specific antibody.
+Our study offers new insights into biology of IFN-λ4 and its possible role in HCV clearance.
+Ebola virus outbreaks, such as the 2014 Makona epidemic in West Africa, are episodic and deadly.
+Our findings suggest interferon gamma, an FDA-approved drug, may serve as a novel and effective prophylactic or treatment option.
+Using mouse-adapted Ebola virus, we found that murine interferon gamma administered 24 hours before or after infection robustly protects lethally-challenged mice and reduces morbidity and serum viral titers.
+Furthermore, we demonstrated that interferon gamma profoundly inhibits Ebola virus infection of macrophages, an early cellular target of infection.
+As early as six hours following in vitro infection, Ebola virus RNA levels in interferon gamma-treated macrophages were lower than in infected, untreated cells.
+Addition of the protein synthesis inhibitor, cycloheximide, to interferon gamma-treated macrophages did not further reduce viral RNA levels, suggesting that interferon gamma blocks life cycle events that require protein synthesis such as virus replication.
+These studies provide new potential avenues for antiviral targeting as these genes that have not previously appreciated to inhibit negative strand RNA viruses and specifically Ebola virus infection.
+As treatment of interferon gamma robustly protects mice from lethal Ebola virus infection, we propose that interferon gamma should be further evaluated for its efficacy as a prophylactic and/or therapeutic strategy against filoviruses.
+Traditional modes of investigating influenza nosocomial transmission have entailed a combination of confirmatory molecular diagnostic testing and epidemiological investigation.
+Common hospital-acquired infections like influenza require a discerning ability to distinguish between viral isolates to accurately identify patient transmission chains.
+We assessed whether influenza hemagglutinin sequence phylogenies can be used to enrich epidemiological data when investigating the extent of nosocomial transmission over a four-month period within a paediatric Hospital in Cape Town South Africa.
+Possible transmission chains/channels were initially determined through basic patient admission data combined with Maximum likelihood and time-scaled Bayesian phylogenetic analyses.
+These analyses suggested that most instances of potential hospital-acquired infections resulted from multiple introductions of Influenza A into the hospital, which included instances where virus hemagglutinin sequences were identical between different patients.
+Furthermore, a general inability to establish epidemiological transmission linkage of patients/viral isolates implied that identified isolates could have originated from asymptomatic hospital patients, visitors or hospital staff.
+In contrast, a traditional epidemiological investigation that used no viral phylogenetic analyses, based on patient co-admission into specific wards during a particular time-frame, suggested that multiple hospital acquired infection instances may have stemmed from a limited number of identifiable index viral isolates/patients.
+This traditional epidemiological analysis by itself could incorrectly suggest linkage between unrelated cases, underestimate the number of unique infections and may overlook the possible diffuse nature of hospital transmission, which was suggested by sequencing data to be caused by multiple unique introductions of influenza A isolates into individual hospital wards.
+We have demonstrated a functional role for viral sequence data in nosocomial transmission investigation through its ability to enrich traditional, non-molecular observational epidemiological investigation by teasing out possible transmission pathways and working toward more accurately enumerating the number of possible transmission events.
+C. leptum deficiency exacerbates asthma; however, the impact of early-life C. leptum exposure on cesarean-delivered mice remains unclear.
+This study is to determine the effects of early-life C. leptum exposure on asthma development in infant mice.
+METHODS: We exposed infant mice to C. leptum (fed-CL) and then induced asthma using the allergen ovalbumin (OVA).
+RESULTS: Fed-CL increased regulatory T (Treg) cells in cesarean-delivered mice compared with vaginally delivered mice.
+Compared with OVA-exposed mice, mice exposed to C. leptum + OVA did not develop the typical asthma phenotype, which includes airway hyper-responsiveness, cell infiltration, and T helper cell subset (Th1, Th2, Th9, Th17) inflammation.
+Early-life C. leptum exposure induced an immunosuppressive environment in the lung concurrent with increased Treg cells, resulting in the inhibition of Th1, Th2, Th9, and Th17 cell responses.
+CONCLUSION: These findings demonstrate a mechanism whereby C. leptum exposure modulates adaptive immunity and leads to failure to develop asthma upon OVA sensitization later in life.
+However, the US and Canada have experienced outbreaks of EV-D68 infections between August and December 2014.
+This study aimed to investigate the molecular epidemiology and clinical characteristics of EV-D68 in Chongqing, Southwestern China.
+From January 2012 to November 2014, 1876 nasopharyngeal aspirate specimens (NPAs) were collected from hospitalized children with RTIs.
+Phylogenetic analysis showed that all 13 strains detected in the 2014 Chongqing had high homology with the main strains of the 2014 US outbreak.
+In conclusion, our results found that a history of recurrent wheezing may be a risk factor for the detection of EV-D68 and viral-induced asthma exacerbation may be a clinical feature of EV-D68 infection.
+BACKGROUND: The current vaccines for porcine reproductive and respiratory syndrome virus (PRRSV) have failed to provide broad protection against infection by various strains of PRRSV.
+Porcine Interleukin-4 (pIL-4) plays an important role in the regulation of the immune response and has been used previously as an immunological adjuvant.
+The objective of this study was to construct a recombinant PRRSV expressing pIL-4 and to evaluate the immune response of the recombinant virus in piglets.
+METHODS: The pIL-4 gene was inserted in the PRRSV (CH-1R strain) infectious clone by overlap PCR.
+The stability of the recombinant virus was assessed by DNA sequencing and IFA after 15 passages in vitro.
+Recombinant virus was injected into pigs and efficacy of immune protection was evaluated in comparison with the parental virus.
+RESULTS: The recombinant virus (CH-1R/pIL-4) was successfully rescued and shown to have similar growth kinetics as the parental virus.
+Pigs vaccinated with CH-1R/pIL-4 produced a similar humoral response to the response elicited by parental virus, but IL-4 level in the supernatant of PBMCs from pigs vaccinated with CH-1R/pIL-4 was significantly higher than the parent virus at 28 days post-immunization (DPI).
+Flow cytometric (FCM) analysis showed that the percentage of CD4(+)CD8(+) double positive T (DPT) cells in the CH-1R/pIL-4 vaccinated group was significantly higher than the parental virus at 3 and 7 Days Post-Challenge (DPC), and the IL-4 level in the blood significantly increased at 7 DPC.
+However, the viral load and histopathology did not show significant difference between the two groups.
+CONCLUSIONS: A recombinant PRRSV expressing porcine IL-4 was rescued and it remained genetically stable in vitro.
+The recombinant virus induced higher DPT ratios and IL-4 levels in the blood after HP-PRRSV challenge compared to the parental virus in piglets.
+BACKGROUND: Mouse B78 cells and Chinese hamster ovary (CHO) cells are important to the study of HSV-1 entry because both are resistant to infection at the level of viral entry.
+When provided with a gD-receptor such as nectin-1, these cells support HSV-1 entry by an endocytosis pathway.
+Treating some viruses bound to cells with the fusogen polyethylene glycol (PEG) mediates viral fusion with the cell surface but is insufficient to rescue viral entry.
+It is unclear whether PEG-mediated fusion of HSV with the plasma membrane of B78 or CHO cells results in successful entry and infection.
+FINDINGS: Treating HSV-1 bound to B78 or CHO cells with PEG allowed viral entry as measured by virus-induced beta-galactosidase activity.
+Based on the mechanism of PEG action, we propose that entry likely proceeds by direct fusion of HSV particles with the plasma membrane.
+Under the conditions tested, PEG-mediated infection of CHO cells progressed to the level of HSV late gene expression, while B78 cells supported HSV DNA replication.
+We tested whether proteolysis or acidification of cell-bound virions could trigger HSV fusion with the plasma membrane.
+Under the conditions tested, mildly acidic pH of 5–6 or the protease trypsin were not capable of triggering HSV-1 fusion as compared to PEG-treated cell-bound virions.
+CONCLUSIONS: B78 cells and CHO cells, which typically endocytose HSV prior to viral penetration, are capable of supporting HSV-1 entry via direct penetration.
+HSV capsids delivered directly to the cytosol at the periphery of these cells complete the entry process.
+B78 and CHO cells may be utilized to screen for factors that trigger entry as a consequence of fusion of virions with the cell surface, and PEG treatment can provide a necessary control.
+BACKGROUND: Transmission of respiratory pathogens in a population depends on the contact network patterns of individuals.
+To accurately understand and explain epidemic behaviour information on contact networks is required, but only limited empirical data is available.
+Online respondent-driven detection can provide relevant epidemiological data on numbers of contact persons and dynamics of contacts between pairs of individuals.
+We aimed to analyse contact networks with respect to sociodemographic and geographical characteristics, vaccine-induced immunity and self-reported symptoms.
+METHODS: In 2014, volunteers from two large participatory surveillance panels in the Netherlands and Belgium were invited for a survey.
+Participants were asked to record numbers of contacts at different locations and self-reported influenza-like-illness symptoms, and to invite 4 individuals they had met face to face in the preceding 2 weeks.
+RESULTS: In total 1560 individuals completed the survey who reported in total 30591 contact persons; 488 recruiter-recruit pairs were analysed.
+Recruitment was assortative by age, education, household size, influenza vaccination status and sentiments, indicating that participants tended to recruit contact persons similar to themselves.
+We also found assortative recruitment by symptoms, reaffirming our objective of sampling contact persons whom a participant may infect or by whom a participant may get infected in case of an outbreak.
+CONCLUSIONS: Although complex mechanisms influence online peer recruitment, the observed statistical relationships reflected the observed contact network patterns in the general population relevant for the transmission of respiratory pathogens.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-015-1250-z) contains supplementary material, which is available to authorized users.
+Viral infection triggers a series of signaling cascades, which converge to activate the transcription factors nuclear factor-κB (NF-κB) and interferon regulatory factor 3 (IRF3), thereby inducing the transcription of type I interferons (IFNs).
+Although not fully characterized, these innate antiviral responses are fine-tuned by dynamic ubiquitination and deubiquitination processes.
+In this study, we report ubiquitin-specific protease (USP) 15 is involved in regulation of the retinoic acid-inducible gene I (RIG-I)-dependent type I IFN induction pathway.
+Interestingly, USP15 specifically removed lysine 63-linked polyubiquitin chains from RIG-I among the essential components in RIG-I-like receptor-dependent pathway.
+In addition, we demonstrated that in contrast to USP15 de-ubiquitinating (DUB) activity, USP15-mediated inhibition of IFN signaling was not abolished by mutations eliminating the catalytic activity, indicating that a fraction of USP15-mediated IFN antagonism was independent of the DUB activity.
+Catalytically inactive USP15 mutants, as did the wild-type protein, disrupted virus-induced interaction of RIG-I and IFN-β promoter stimulator 1.
+Taken together, our data demonstrate that USP15 acts as a negative regulator of RIG-I signaling via DUB-dependent and independent mechanisms.
+We report the results of a fact-finding study on general handwashing attitude and practice in the Republic of Korea by analyzing habits and awareness among adults and students (grades 4 to 12) based on the 2006 to 2014 National Handwashing Surveys and observational surveys.
+METHODS: The awareness survey was performed by telephone interviews with adults and students in 16 municipalities and provinces sampled by quota for region, sex and age.
+The observational survey was performed in subway, railway, and other public restrooms in seven municipalities selected through systematic sampling.
+RESULTS: Adults and students washed their hands with soap/sanitizer an average of 6.6 and 5.2 times daily, respectively, in 2014, an increase and decrease compared to 2006 (4.8) and 2013 (6.8).
+Their average daily handwashing frequency in 2014, 9.8 and 8.3, was higher than in 2006 (7.6), but lower than in 2013 (10.3).The percentage of participants handwashing with soap after using the restroom (29.5%) has been increasing since 2009, but remain slower than in other countries (42% to 49%).
+The percentages of participants handwashing with water in 2014, 2013, and 2011 were 57.5%, 72.6%, and 71.4%, respectively.
+CONCLUSIONS: Handwashing with soap is an important national public health issue, and national projects promoting it should be given high priority.
+Research support is necessary to provide scientific evidence of the importance of handwashing with soap and to develop and implement evidence-based policies.
+Normalization of data, by choosing the appropriate reference genes (RGs), is fundamental for obtaining reliable results in reverse transcription-quantitative PCR (RT-qPCR).
+In this study, we assessed Actinidia deliciosa leaves inoculated with two doses of Pseudomonas syringae pv.
+actinidiae during a period of 13 days for the expression profile of nine candidate RGs.
+Their expression stability was calculated using four algorithms: geNorm, NormFinder, BestKeeper and the deltaCt method.
+Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and protein phosphatase 2A (PP2A) were the most stable genes, while β-tubulin and 7s-globulin were the less stable.
+Expression analysis of three target genes, chosen for RGs validation, encoding the reactive oxygen species scavenging enzymes ascorbate peroxidase (APX), superoxide dismutase (SOD) and catalase (CAT) indicated that a combination of stable RGs, such as GAPDH and PP2A, can lead to an accurate quantification of the expression levels of such target genes.
+The APX level varied during the experiment time course and according to the inoculum doses, whereas both SOD and CAT resulted down-regulated during the first four days, and up-regulated afterwards, irrespective of inoculum dose.
+These results can be useful for better elucidating the molecular interaction in the A. deliciosa/P.
+Like other herpesviruses, multiple processes required for KSHV lytic replication, including viral transcription, viral DNA synthesis and capsid assembly occur in virus-induced intranuclear structures, termed replication and transcription compartments (RTCs).
+Here we utilised a novel methodology, combining subcellular fractionation and quantitative proteomics, to identify cellular proteins which are recruited to KSHV-induced RTCs and thus play a key role in KSHV lytic replication.
+We show that several isoforms of the HSP70 chaperone family, Hsc70 and iHsp70, are redistributed from the cytoplasm into the nucleus coinciding with the initial formation of KSHV-induced RTCs.
+We demonstrate that nuclear chaperone foci are dynamic, initially forming adjacent to newly formed KSHV RTCs, however during later time points the chaperones move within KSHV RTCs and completely co-localise with actively replicating viral DNA.
+The functional significance of Hsp70 isoforms recruitment into KSHV RTCs was also examined using the specific Hsp70 isoform small molecule inhibitor, VER-155008.
+Intriguingly, results highlight an essential role of Hsp70 isoforms in the KSHV replication cycle independent of protein stability and maturation.
+Notably, inhibition of Hsp70 isoforms precluded KSHV RTC formation and RNA polymerase II (RNAPII) relocalisation to the viral genome leading to the abolishment of global KSHV transcription and subsequent viral protein synthesis and DNA replication.
+These new findings have revealed novel mechanisms that regulate KSHV lytic replication and highlight the potential of HSP70 inhibitors as novel antiviral agents.
+Angiotensin-converting enzyme 2 (ACE2) gene therapy aimed at counteracting pancreatic ACE2 depletion improves glucose regulation in two diabetic mouse models: db/db mice and angiotensin II-infused mice.
+A disintegrin and metalloproteinase 17 (ADAM17) can cause shedding of ACE2 from the cell membrane.
+The aim of our studies was to determine whether ADAM17 depletes ACE2 levels in pancreatic islets and β-cells.
+Within a wide range of ACE2 expression levels, including the level observed in mouse pancreatic islets, overexpression of ADAM17 increases shed ACE2 and decreases cellular ACE2 levels.
+We provide a mathematical description of shed and cellular ACE2 activities as a function of the ADAM17 activity.
+The effect of ADAM17 on the cellular ACE2 content was relatively modest with an absolute control strength value less than 0.25 and approaching 0 at low ADAM17 activities.
+Although we found that ADAM17 and ACE2 are both expressed in pancreatic islets, the β-cell is not the major cell type expressing ACE2 in islets.
+During diabetes progression in 8-, 12-, and 15-week-old db/db mice, ACE2 mRNA and ACE2 activity levels in pancreatic islets were not decreased over time nor significantly decreased compared with nondiabetic db/m mice.
+We conclude that whereas ADAM17 has the ability to shed ACE2, ADAM17 does not deplete ACE2 from pancreatic islets in diabetic db/db mice.
+In the last decade millions of cases have been reported around the world from Africa to Asia to the Americas.
+The alphavirus nsP2 protein is multifunctional and is considered to be pivotal to viral replication, as the nsP2 protease activity is critical for proteolytic processing of the viral polyprotein during replication.
+Classically the alphavirus nsP2 protease is thought to be papain-like with the enzyme reaction proceeding through a cysteine/histidine catalytic dyad.
+We performed structure-function studies on the chikungunya nsP2 protease and show that the enzyme is not papain-like.
+Characterization of the catalytic dyad cysteine residue enabled us to identify a nearby serine that is catalytically interchangeable with the dyad cysteine residue.
+The enzyme retains activity upon alanine replacement of either residue but a replacement of both cysteine and serine residues results in no detectable activity.
+Protein dynamics appears to allow the use of either the cysteine or the serine residue in catalysis.
+This switchable dyad residue has not been previously reported for alphavirus nsP2 proteases and would have a major impact on the nsP2 protease as an anti-viral target.
+While the magnitude of tissue neutrophil accumulation in innate immune responses is profoundly greater in males than females, fundamental aspects of the molecular mechanisms underlying these sex differences remain largely unknown.
+METHODS: We investigated sex differences in neutrophil stimulation and recruitment in ischemia/reperfusion (I/R; mesenteric or renal) or carrageenan pleurisy in rats or mice, as well as skin injury in human volunteers.
+The induction of potent chemoattractive mediators (chemokines) and neutrophil adhesion molecules were measured by real-time PCR, flow cytometry, and protein assays.
+RESULTS: Mesenteric I/R in age-matched Wistar rats resulted in substantially more neutrophil accumulation and tissue injury at 2 h reperfusion in males than females.
+Using intravital microscopy, we show that the immediate (<30 min) neutrophil response to I/R is similar in males and females but that prolonged neutrophil recruitment occurs in males at sites local and distal to inflammatory insult partly due to an increase in circulating neutrophil populations with elevated surface expression of adhesion molecules.
+Sex differences in neutrophil kinetics were correlated with sustained induction of chemokine Cxcl5 in the tissue, circulation, and bone marrow of males but not females.
+Furthermore, blockade of Cxcl5 in males prior to ischemia resulted in neutrophil responses that were similar in magnitude to those in females.
+Conversely, administration of Cxcl5 to males in the absence of I/R was sufficient to increase levels of systemic neutrophils.
+Cxcl5 treatment of bone marrow neutrophils in vitro caused substantial induction of neutrophil-mobilizing cytokine granulocyte colony-stimulating factor (GCSF) and expression of β2 integrin that accounts for sexual dimorphism in circulating neutrophil populations in I/R.
+Moreover, male Cxcl5-stimulated bone marrow neutrophils had an increased capacity to adhere to β2 integrin ligand ICAM-1, implicating a greater sensitivity of male leukocytes to Cxcl5-mediated activation.
+Differential induction of Cxcl5 (human CXCL6) between the sexes was also evident in murine renal I/R, rat pleurisy, and human skin blisters and correlated with the magnitude of neutrophil accumulation in tissues.
+CONCLUSIONS: Our study reveals that sex-specific induction of chemokine Cxcl5/CXCL6 contributes to sexual dimorphism in neutrophil recruitment in diverse acute inflammatory responses partly due to increased stimulation and trafficking of bone marrow neutrophils in males.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13293-015-0047-5) contains supplementary material, which is available to authorized users.
+In particular, the endoplasmic reticulum (ER) resident chaperones play key roles in synthesizing and processing viral proteins.
+Influx of a large amount of foreign proteins exhausts the folding capacity in ER and triggers the unfolded protein response (UPR).
+A fully-executed UPR comprises signaling pathways that induce ER folding chaperones, increase protein degradation, block new protein synthesis and may eventually activate apoptosis, presenting both opportunities and threats to the virus.
+Here, we define a role of the MHV-68M1 gene in differential modulation of UPR pathways to enhance ER chaperone production.
+The M1 protein accumulates in ER during infection and this localization is indispensable for its function, suggesting M1 acts from the ER.
+We found that M1 protein selectively induces the chaperon-producing pathways (IRE1, ATF6) while, interestingly, sparing the translation-blocking arm (PERK).
+We identified, for the first time, a viral factor capable of selectively intervening the initiation of ER stress signaling to induce chaperon production.
+This finding provides a unique opportunity of using viral protein as a tool to define the activation mechanisms of individual UPR pathways.
+To prevent and control infectious diseases, it is important to understand the interaction between cattle tissue and pathogenic bacteria.
+In this study, we established an in vitro infection model of an immortalized bovine colon-derived epithelial cell line by transducing the cells with lentiviral vectors containing genes encoding cell cycle regulators cyclin D1, mutant cyclin dependent kinase 4 (CDK4), and human telomerase reverse transcriptase (TERT).
+The established cell line showed continuous cell proliferation, expression of epithelial markers, and an intact karyotype, indicating that the cells maintained their original nature as colon-derived epithelium.
+Furthermore, we exposed the established cell line to two strains of Salmonella enterica and EHEC.
+Interestingly, S. Typhimurium showed higher affinity for the established cell line and invaded the cytoplasm than S. Enteritidis.
+Quantitative RT-PCR revealed that gene expression of Toll-like receptor 1 (TLR1), TLR 2 and TLR 3, whereas TLR 4, 5 and 6 were not detectable in established cells.
+Our established immortalized colon-derived epithelial cell should be a useful tool for studies evaluating the molecular mechanisms underlying bacterial infection.
+The pathogenesis of rhegmatogenous retinal detachment (RRD) remains incompletely understood, with no clinically effective treatment for potentially severe complications such as photoreceptor cell death and proliferative vitreoretinopathy.
+Here we investigate the protein profile of the vitreous following experimental retinal detachment using a comparative proteomic based approach.
+Retinal detachment was created in the right eyes of six New Zealand red pigmented rabbits.
+The vitreous samples were evaluated with two-dimensional polyacrylamide gel electrophoresis and the differentially expressed proteins were identified with tandem mass spectrometry.
+Ten protein spots were found to be at least twofold differentially expressed when comparing the vitreous samples of the sham and retinal detachment surgery groups.
+Protein spots that were upregulated in the vitreous following retinal detachment were identified as albumin fragments, and those downregulated were found to be peroxiredoxin 2, collagen-Iα1 fragment, and α-1-antiproteinase F. Conclusions.
+Proteomic investigation of the rabbit vitreous has identified a set of proteins that help further our understanding of the pathogenesis of rhegmatogenous retinal detachment and its complications.
+Although the roles of dendritic cells (DCs) in adaptive defense have been defined well, the contribution of DCs to T cell-independent innate defense and subsequent neuroimmunopathology in immune-privileged CNS upon infection with neurotropic viruses has not been completely defined.
+Notably, DC roles in regulating innate CD11b(+)Ly-6C(hi) monocyte functions during neuroinflammation have not yet been addressed.
+Using selective ablation of CD11c(hi)PDCA-1(int/lo) DCs without alteration in CD11c(int)PDCA-1(hi) plasmacytoid DC number, we found that CD11c(hi) DCs are essential to control neuroinflammation caused by infection with neurotropic Japanese encephalitis virus, through early and increased infiltration of CD11b(+)Ly-6C(hi) monocytes and higher expression of CC chemokines.
+More interestingly, selective CD11c(hi) DC ablation provided altered differentiation and function of infiltrated CD11b(+)Ly-6C(hi) monocytes in the CNS through Flt3-L and GM-CSF, which was closely associated with severely enhanced neuroinflammation.
+Furthermore, CD11b(+)Ly-6C(hi) monocytes generated in CD11c(hi) DC-ablated environment had a deleterious rather than protective role during neuroinflammation, and were more quickly recruited into inflamed CNS, depending on CCR2, thereby exacerbating neuroinflammation via enhanced supply of virus from the periphery.
+Therefore, our data demonstrate that CD11c(hi) DCs provide a critical and unexpected role to preserve the immune-privileged CNS in lethal neuroinflammation via regulating the differentiation, function, and trafficking of CD11b(+)Ly-6C(hi) monocytes.
+Influenza virus (IFV) infection is a common cause of severe viral pneumonia associated with acute respiratory distress syndrome (ARDS), which is difficult to control with general immunosuppressive therapy including corticosteroids due to the unfavorable effect on viral replication.
+Studies have suggested that the excessive activation of the innate immunity by IFV is responsible for severe pathologies.
+In this study, we focused on CARD9, a signaling adaptor known to regulate innate immune activation through multiple innate sensor proteins, and investigated its role in anti-IFV defense and lung pathogenesis in a mouse model recapitulating severe influenza pneumonia with ARDS.
+We found that influenza pneumonia was dramatically attenuated in Card9-deficient mice, which showed improved mortality with reduced inflammatory cytokines and chemokines in the infected lungs.
+However, viral clearance, type-I interferon production, and the development of anti-viral B and T cell immunity were not compromised by CARD9 deficiency.
+Syk or CARD9-deficient DCs but not macrophages showed impaired cytokine but not type-I interferon production in response to IFV in vitro, indicating a possible role for the Syk-CARD9 pathway in DCs in excessive inflammation of IFV-infected lungs.
+Therefore, inhibition of this pathway is an ideal therapeutic target for severe influenza pneumonia without affecting viral clearance.
+Mucosal vaccination is an effective strategy for generating antigen-specific immune responses against mucosal infections of foot-and-mouth disease virus (FMDV).
+In this study, Lactobacillus plantarum strains NC8 and WCFS1 were used as oral delivery vehicles containing a pSIP411-VP1 recombinant plasmid to initiate mucosal and systemic immune responses in guinea pigs.
+Animals immunized with NC8-pSIP411-VP1 and WCFS1-pSIP411-VP1 developed high levels of antigen-specific serum IgG, IgA, IgM, mucosal secretory IgA (sIgA) and neutralizing antibodies, and revealed stronger cell-mediated immune responses and enhanced protection against FMDV challenge compared with control groups.
+Various reports have indicated that a number of viruses could infect neutrophils, but the multiplication of viruses in neutrophils was abortive.
+Based on our previous finding that avian influenza viral RNA and proteins were present in the nucleus of infected human neutrophils in vivo, we investigated the possibility of 2009 A (H1N1) influenza viral synthesis in infected neutrophils and possible release of infectious progeny from host cells.
+In this study we found that human neutrophils in vitro without detectable level of sialic acid expression could be infected by this virus strain.
+We also show that the infected neutrophils can not only synthesize 2009 A (H1N1) viral mRNA and proteins, but also produce infectious progeny.
+These findings suggest that infectious progeny of 2009 A (H1N1) influenza virus could be replicated in and released from human neutrophils with possible clinical implications.
+Avian gastrointestinal (GI) tracts are highly populated with a diverse array of microorganisms that share a symbiotic relationship with their hosts and contribute to the overall health and disease state of the intestinal tract.
+The microbiome of the young chick is easily prone to alteration in its composition by both exogenous and endogenous factors, especially during the early posthatch period.
+The genetic background of the host and exposure to pathogens can impact the diversity of the microbial profile that consequently contributes to the disease progression in the host.
+The objective of this study was to profile the composition and structure of the gut microbiota in young chickens from two genetically distinct highly inbred lines.
+Furthermore, the effect of the Salmonella Enteritidis infection on altering the composition makeup of the chicken microbiome was evaluated through the 16S rRNA gene sequencing analysis.
+One-day-old layer chicks were challenged with S. Enteritidis and the host cecal microbiota profile as well as the degree of susceptibility to Salmonella infection was examined at 2 and 7 days post infection.
+Our result indicated that host genotype had a limited effect on resistance to S. Enteritidis infection.
+Alpha diversity, beta diversity, and overall microbiota composition were analyzed for four factors: host genotype, age, treatment, and postinfection time points.
+S. Enteritidis infection in young chicks was found to significantly reduce the overall diversity of the microbiota population with expansion of Enterobacteriaceae family.
+These changes indicated that Salmonella colonization in the GI tract of the chickens has a direct effect on altering the natural development of the GI microbiota.
+The impact of S. Enteritidis infection on microbial communities was also more substantial in the late stage of infection.
+Significant inverse correlation between Enterobacteriaceae and Lachnospiraceae family in both non-infected and infected groups, suggested possible antagonistic interaction between members of these two taxa, which could potentially influences the overall microbial population in the gut.
+Our results also revealed that genetic difference between two lines had minimal effect on the establishment of microbiota population.
+Overall, this study provided preliminary insights into the contributing role of S. Enteritidis in influencing the overall makeup of chicken’s gut microbiota.
+The Vietnam Initiative for Zoonotic Infections (VIZIONS) includes community-based ‘high-risk sentinel cohort’ (HRSC) studies investigating individuals at risk of zoonotic infection due to occupational or residential exposure to animals.
+A total of 852 HRSC members were recruited between March 2013 and August 2014 from three provinces (Ha Noi, Dak Lak, and Dong Thap).
+The most numerous group (72.8%) corresponded to individuals living on farms, followed by slaughterers (16.3%) and animal health workers (8.5%).
+Nasal/pharyngeal and rectal swabs were collected from HRSC members at recruitment and after notifying illness.
+Exposure to exotic animals (including wild pigs, porcupine, monkey, civet, bamboo rat and bat) was highest for the Dak Lak cohort (53.7%), followed by Ha Noi (13.7%) and Dong Thap (4.0%).
+A total of 26.8% of individuals reported consumption of raw blood over the previous year; 33.6% slaughterers reported no use of protective equipment at work.
+Over 686 person-years of observation, 213 episodes of suspect infectious disease were notified, equivalent of 0.35 reports per person-year.
+There was noticeable time and space clustering of disease episodes suggesting that the VIZIONS set up is also suitable for the formal epidemiological investigation of disease outbreaks.
+The spatial characteristics of these cases revealed that H5N1 infections mainly occurred in the South, Middle, and Northwest of China, while the occurrence of H7N9 was concentrated in coastal areas of East and South of China.
+Aside from spatial-temporal characteristics, the most adaptive meteorological conditions for the occurrence of human infections by these two viral subtypes were different.
+We found that H7N9 infections correlate with climate factors, especially temperature (TEM) and relative humidity (RHU), while H5N1 infections correlate with TEM and atmospheric pressure (PRS).
+Hence, we propose a risky window (TEM 4–14 °C and RHU 65–95%) for H7N9 infection and (TEM 2–22 °C and PRS 980-1025 kPa) for H5N1 infection.
+Our results represent the first step in determining the effects of climate factors on two different virus infections in China and provide warning guidelines for the future when provinces fall into the risky windows.
+These findings revealed integrated predictive meteorological factors rooted in statistic data that enable the establishment of preventive actions and precautionary measures against future outbreaks.
+The question of whether influenza is transmitted to a significant degree by aerosols remains controversial, in part, because little is known about the quantity and size of potentially infectious airborne particles produced by people with influenza.
+In this study, the size and amount of aerosol particles produced by nine subjects during coughing were measured while they had influenza and after they had recovered, using a laser aerosol particle spectrometer with a size range of 0.35 to 10 μm.
+Individuals with influenza produce a significantly greater volume of aerosol when ill compared with afterward (p = 0.0143).
+When the patients had influenza, their average cough aerosol volume was 38.3 picoliters (pL) of particles per cough (SD 43.7); after patients recovered, the average volume was 26.4 pL per cough (SD 45.6).
+The number of particles produced per cough was also higher when subjects had influenza (average 75,400 particles/cough, SD 97,300) compared with afterward (average 52,200, SD 98,600), although the difference did not reach statistical significance (p = 0.1042).
+The average number of particles expelled per cough varied widely from patient to patient, ranging from 900 to 302,200 particles/cough while subjects had influenza and 1100 to 308,600 particles/cough after recovery.
+When the subjects had influenza, an average of 63% of each subject's cough aerosol particle volume in the detection range was in the respirable size fraction (SD 22%), indicating that these particles could reach the alveolar region of the lungs if inhaled by another person.
+This enhancement in aerosol generation during illness may play an important role in influenza transmission and suggests that a better understanding of this phenomenon is needed to predict the production and dissemination of influenza-laden aerosols by people infected with this virus.
+Go to the publisher's online edition of Journal of Occupational and Environmental Hygiene for the following free supplemental resources: a PDF file of demographic information, influenza test results, and volume and peak flow rate during each cough and a PDF file containing number and size of aerosol particles produced.]
+We aimed to test the hypothesis that gene silencing of tumor necrosis factor alpha converting enzyme (TACE) may attenuate lesion inflammation and positive vascular remodeling and enhance plaque stability in a rabbit model of atherosclerosis.
+Lentivirus-mediated TACE shRNA was injected into the abdominal aortic plaques of rabbits which effectively down-regulated TACE expression and activities from week 8 to week 16.
+TACE gene silencing reduced remodeling index and plaque burden, and diminished the content of macrophages and lipids while increased that of smooth muscle cells and collagen in the aortic plaques.
+In addition, TACE gene silencing attenuated the local expression of P65, iNOS, ICAM-1, VEGF and Flt-1 and activities of MMP9 and MMP2 while increased the local expression of TGF-β1 together with reduced number of neovessels in the aorta.
+TACE shRNA treatment resulted in down-regulated expression of TACE in macrophages and blunted ERK-P38 phosphorylation and tube formation of co-cultured mouse vascular smooth muscle cells or human umbilical vein endothelial cells.
+The mechanisms may involve attenuated local inflammation, neovascularization and MMP activation, as well as enhanced collagen production probably via down-regulated ERK-NF-κB and up-regulated TGF-β1 signaling pathways.
+Bacterial enteric infections resulting in diarrhea, dysentery, or enteric fever constitute a huge public health problem, with more than a billion episodes of disease annually in developing and developed countries.
+In this study, the deadly agent of hemorrhagic diarrhea and hemolytic uremic syndrome, Escherichia coli O157:H7 was investigated with extensive computational approaches aimed at identifying novel and broad-spectrum antibiotic targets.
+A systematic in silico workflow consisting of comparative genomics, metabolic pathways analysis, and additional drug prioritizing parameters was used to identify novel drug targets that were essential for the pathogen’s survival but absent in its human host.
+Comparative genomic analysis of Kyoto Encyclopedia of Genes and Genomes annotated metabolic pathways identified 350 putative target proteins in E. coli O157:H7 which showed no similarity to human proteins.
+Further bio-informatic approaches including prediction of subcellular localization, calculation of molecular weight, and web-based investigation of 3D structural characteristics greatly aided in filtering the potential drug targets from 350 to 120.
+Ultimately, 44 non-homologous essential proteins of E. coli O157:H7 were prioritized and proved to have the eligibility to become novel broad-spectrum antibiotic targets and DNA polymerase III alpha (dnaE) was the top-ranked among these targets.
+Moreover, druggability of each of the identified drug targets was evaluated by the DrugBank database.
+In addition, 3D structure of the dnaE was modeled and explored further for in silico docking with ligands having potential druggability.
+Finally, we confirmed that the compounds N-coeleneterazine and N-(1,4-dihydro-5H-tetrazol-5-ylidene)-9-oxo-9H-xanthene-2-sulfon-amide were the most suitable ligands of dnaE and hence proposed as the potential inhibitors of this target protein.
+The results of this study could facilitate the discovery and release of new and effective drugs against E. coli O157:H7 and other deadly human bacterial pathogens.
+BACKGROUND: Idiopathic pulmonary fibrosis acute exacerbation (IPF-AE) constitutes IPF’s most devastating event, representing the unexpected superimposition of diffuse alveolar damage of unknown etiology.
+We hypothesized that previous immunosuppression and the administration of high-dose steroids adversely affect IPF-AE outcome.
+METHODS: We studied all consecutive patients hospitalized in our department for IPF deterioration from 2007 to June 2013.
+Our protocol consisted of immediate cessation of immunosuppression (if any), best supportive care, broad-spectrum antimicrobials and thorough evaluation to detect reversible causes of deterioration.
+As unique events 50 % survived; 3 out of 12 (25 %) in the group previously treated with immunosuppression whereas nine out of 12 (75 %) in the group not receiving immunosuppression (p = 0.041).
+As unique patients 35.3 % survived; 3 out of 6 (50 %) in the never treated group whereas three out of 11 (27.3 %) in the group receiving immunosuppression (p = 0.685).
+Survival was greater in the never treated group compared to the immunosuppressed patients (p = 0.022).
+Avoiding steroids in IPF patients may favor the natural history of the disease even at the moment of its most devastating event.
+A faithful phylogeny and an objective taxonomy for prokaryotes should agree with each other and ultimately follow the genome data.
+With the number of sequenced genomes reaching tens of thousands, both tree inference and detailed comparison with taxonomy are great challenges.
+We now provide one solution in the latest Release 3.0 of the alignment-free and whole-genome-based web server CVTree3.
+The server resides in a cluster of 64 cores and is equipped with an interactive, collapsible, and expandable tree display.
+It is capable of comparing the tree branching order with prokaryotic classification at all taxonomic ranks from domains down to species and strains.
+In addition, it reports a summary of monophyletic and non-monophyletic taxa at all ranks as well as produces print-quality subtree figures.
+After giving an overview of retrospective verification of the CVTree approach, the power of the new server is described for the mega-classification of prokaryotes and determination of taxonomic placement of some newly-sequenced genomes.
+A few discrepancies between CVTree and 16S rRNA analyses are also summarized with regard to possible taxonomic revisions.
+Up-regulation of TGF-β in serum/peritoneal fluid and increased levels of pluripotent transcription factor OCT4 in endometriotic tissues are frequently observed in patients with endometriosis.
+However, the mechanisms underlying how TGF-β/TGF-β receptor and OCT4 affect endometriotic cell migration still remain largely unknown.
+Therefore, endometriotic tissue with high cell migratory capacity were collected from patients with adenomyotic myometrium (n = 23) and chocolate cyst (n = 24); and endometrial tissue with low cell migratory capacity in normal endometrium or hyperplastic endometrium (n = 8) were collected as the controls.
+We found the mRNA levels of TGF-β receptor I (TGF-β RI) and OCT4 were significantly higher in the high-migratory ectopic endometriotic tissues than those of the low-migratory normal or hyperplastic endometrium.
+Positive correlations between TGF-β RI and OCT4, and either TGF-β RI or OCT4 with migration-related genes (SNAIL, SLUG and TWIST) regarding the mRNA levels were observed in human endometriotic tissues.
+TGF-βI dose-dependently increased the gene and protein levels of OCT4, SNAIL and N-Cadherin (N-CAD) and silencing of endogenous OCT4 significantly suppressed the TGF-βI-induced expressions of N-CAD and SNAIL in primary human endometriotic stromal cells and human endometrial carcinoma cell lines RL95-2 and HEC1A.
+Furthermore, TGF-βI significantly increased the migration ability of endometriotic cells and silencing of OCT4 dramatically suppressed the TGF-βI-induced cell migration activity evidenced by wound-closure assay, transwell assay, and confocal image of F-actin cellular distribution.
+In conclusion, the present findings demonstrate that the niche TGF-β plays a critical role in initiating expressions of pluripotent transcription factor OCT4 which may contribute to the ectopic endometrial growth by stimulating endometrial cell migration.
+These findings would be useful for developing therapeutic strategies targeting TGF-β-OCT4 signaling to prevent endometriosis in the future.
+Arginase I (Arg I) and inducible nitric oxide synthase (iNOS) are important in regulating immune functions through their metabolites.
+Previous studies have revealed that the expression of Arg I is increased and the expression of iNOS is reduced in the serum and peripheral blood mononuclear cells of human immunodeficiency virus (HIV)-infected patients.
+As one of the most important immune organs and HIV replication sites, whether similar changes are present in the lymph nodes following HIV infection remains to be elucidated.
+To investigate this, the present study collected lymph node and blood specimens from 52 HIV-infected patients to measure the expression levels of Arg I and iNOS by immunohistochemistry and fluoresence-based flow cytometry.
+Compared with control subjects without HIV infection, the patients with HIV had significantly higher expression levels of Arg I in the lymph nodes and higher frequencies of Arg I(+) CD4(+) T cells and CD8(+) T cells in the blood and lymph nodes, and these results were contrary the those of iNOS in the corresponding compartments.
+The expression levels of Arg I in the lymph nodes and blood were negatively associated with peripheral CD4(+) T cell count and positively associated with viral load.
+However, the expression levels of iNOS in the lymph nodes and blood were positively associated with peripheral CD4(+) T cell count and negatively associated with viral load.
+These results showed that alterations in the expression levels of Arg I and iNOS in the peripheral T cells and peripheral nodes of HIV infected patients are associated with disease progression in these patients.
+These results indicate a potential to therapeutic strategy for delaying disease progression through regulating and manipulating the expression levels of Arg I and iNOS in patients infected with HIV.
+Surgical correction of congenital cardiac malformations or aortocoronary bypass surgery in many cases implies the use of cardiopulmonary-bypass (CPB).
+However, a possible negative impact of CPB on internal organs such as brain, kidney, lung and liver cannot be neglected.
+In general, CPB initiates a systemic inflammatory response (SIRS) which is presumably caused by contact of blood components with the surface of CPB tubing.
+Moreover, during CPB the heart typically undergoes a period of cold ischemia, and the other peripheral organs a global low flow hypoperfusion.
+As a result, a plethora of pro-inflammatory mediators and cytokines is released activating different biochemical pathways, which finally may result in the occurrence of microthrombosis, microemboli, in depletion of coagulation factors and haemorrhagic diathesis besides typical ischemia-reperfusion injuries.
+In our review we will focus on possible pharmacological interventions in patients to decrease negative effects of CPB and to improve post-operative outcome with regard to heart and other organs like brain, kidney, or lung.
+Demyelination in the central nervous system induced by neurovirulent strains of Mouse Hepatitis Virus (MHV) is mediated by the viral spike glycoprotein, but it is not clear whether the mechanism of this disease pathology involves direct viral infection of oligodendrocytes.
+Detailed studies of glial cell tropism of MHV are presented, demonstrating that direct MHV infection of oligodendrocytes differs between demyelinating (RSA59) and non-demyelinating (RSMHV2) viral strains both in vitro and in vivo.
+Our results indicate that direct injury of mature oligodendrocytes is an important mechanism of virus-induced demyelination.
+In vivo, RSA59 infection was identified in spinal cord gray and white matter, but infected oligodendrocytes were restricted to white matter.
+In contrast, RSMHV2 infection was restricted to gray matter neurons and was not localized to oligodendrocytes.
+In vitro, RSA59 can infect both oligodendrocyte precursors and differentiated oligodendrocytes, whereas RSMHV2 can infect oligodendrocyte precursors but not differentiated oligodendrocytes.
+Viral spreading through axonal means to white matter and release of the demyelinating strain MHV at the nerve end is critical for oligodendrocytes infection and subsequent demyelination.
+Understanding the mechanisms by which known viruses effect demyelination in this animal model has important therapeutic implications in the treatment of human demyelinating disease.
+It has been documented that the epidemiological characteristics of human infections with H7N9 differ significantly between H5N1.
+We use boosted regression tree (BRT) models to explore the association of agro-ecological, environmental and meteorological variables with the occurrence of human cases of H7N9 and H5N1, and map the probabilities of occurrence of human cases.
+Live poultry markets, density of human, coverage of built-up land, relative humidity and precipitation were significant predictors for both.
+In addition, density of poultry, coverage of shrub and temperature played important roles for human H7N9 infection, whereas human H5N1 infection was associated with coverage of forest and water body.
+Based on the risks and distribution of ecological characteristics which may facilitate the circulation of the two viruses, we found Yangtze River Delta and Pearl River Delta, along with a few spots on the southeast coastline, to be the high risk areas for H7N9 and H5N1.
+Surveillance of the two viruses needs to be enhanced in these high risk areas to reduce the risk of future epidemics of avian influenza in China.
+As obligate intracellular parasites, viruses need to hijack their cellular hosts and reprogram their machineries in order to replicate their genomes and produce new virions.
+For the direct visualization of the different steps of a viral life cycle (attachment, entry, replication, assembly and egress) electron microscopy (EM) methods are extremely helpful.
+While conventional EM has given important information about virus-host cell interactions, the development of three-dimensional EM (3D-EM) approaches provides unprecedented insights into how viruses remodel the intracellular architecture of the host cell.
+Here we will provide a description of the main approaches and examples of innovative applications.
+Human rhinoviruses (HRVs) and enteroviruses (HEVs) belong to the Enterovirus genus and are the most frequent cause of infection worldwide, but data on their molecular epidemiology in Africa are scarce.
+To understand HRV and HEV molecular epidemiology in this setting, we enrolled febrile pediatric patients participating in a large prospective cohort assessing the causes of fever in Tanzanian children.
+Viruses from positive samples were sequenced and phylogenetic analyses were then applied to highlight the HRV and HEV types as well as recombinant or divergent strains.
+Although some types were predominant, many distinct types were co-circulating, including a vaccinal poliovirus, HEV-A71 and HEV-D68.
+This is the first prospective study focused on HRV and HEV molecular epidemiology in sub-Saharan Africa.
+This systematic and thorough large screening with careful clinical data management confirms the wide genomic diversity of these viruses, brings new insights about their evolution and provides data about associated symptoms.
+Enterovirus 71 (EV71) is a group of viruses that belongs to the Picornaviridae family, which also includes viruses such as polioviruses.
+EV71, together with coxsackieviruses, is widely known for its association with Hand Foot Mouth Disease (HFMD), which generally affects children age five and below.
+Besides HFMD, EV71 can also trigger more severe and life-threatening neurological conditions such as encephalitis.
+Considering the lack of a vaccine and antiviral drug against EV71, together with the increasing spread of these viruses, the development of such drugs and vaccines becomes the top priority in protecting our younger generations.
+This article, hence, reviews some of the recent progress in the formulations of anti-therapeutics and vaccine generation for EV71, covering (i) inactivated vaccines; (ii) baculovirus-expressed vaccines against EV71; (iii) human intravenous immunoglobulin (IVIg) treatment; and (iv) the use of monoclonal antibody therapy as a prevention and treatment for EV71 infections.
+Bacterial pathogens can exploit metabolic pathways to facilitate their successful infection cycles, but little is known about roles of d‐galactosamine (GalN)/N‐acetyl‐d‐galactosamine (GalNAc) catabolism pathway in bacterial pathogenesis.
+Here, we report the genomic reconstruction of GalN/GalNAc utilization pathway in Streptococci and the diversified aga regulons.
+The electrophoretic mobility shift assays experiment demonstrated that AgaR2 (AgaR1) binds the predicted palindromes, and the combined in vivo data from reverse transcription quantitative polymerase chain reaction and RNA‐seq suggested that AgaR2 (not AgaR1) can effectively repress the transcription of the target genes.
+Removal of agaR2 (not agaR1) from Streptococcus suis 05ZYH33 augments significantly the abilities of both adherence to Hep‐2 cells and anti‐phagocytosis against RAW264.7 macrophage.
+As anticipated, the dysfunction in AgaR2‐mediated regulation of S. suis impairs its pathogenicity in experimental models of both mice and piglets.
+Our finding discovered two novel regulators specific for GalN/GalNAc catabolism and assigned them distinct roles into bacterial infections.
+To the best of our knowledge, it might represent a first paradigm that links the GalN/GalNAc catabolism pathway to bacterial pathogenesis.
+BACKGROUND: A variety of different sampling devices are currently available to acquire air samples for the study of the microbiome of the air.
+Here, we evaluate the use of a novel device, which has no technical complexity and is easily deployable.
+RESULTS: An air-cleaning device powered by electrokinetic propulsion has been adapted to provide a universal method for collecting samples of the aerobiome.
+A device and electrode assembly have been re-designed from air-cleaning technology to provide an average air flow of 120 lpm.
+Capture efficiency was determined by comparison with a 0.4 μm polycarbonate reference filter, using fluorescent latex particles in a controlled environment chamber.
+Performance was compared with the same reference filter method in field studies in three different environments.
+For 23 common fungal species by quantitative polymerase chain reaction (qPCR), there was 100 % sensitivity and apparent specificity of 87 %, with the reference filter taken as “gold standard.” Further, bacterial analysis of 16S RNA by amplicon sequencing showed equivalent community structure captured by the electrokinetic device and the reference filter.
+Unlike other current air sampling methods, capture of particles is determined by charge and so is not controlled by particle mass.
+We analyzed particle sizes captured from air, without regard to specific analyte by atomic force microscopy: particles at least as low as 100 nM could be captured from ambient air.
+CONCLUSIONS: This work introduces a very simple plug-and-play device that can sample air at a high-volume flow rate with no moving parts and collect particles down to the sub-micron range.
+The performance of the device is substantially equivalent to capture by pumping through a filter for microbiome analysis by quantitative PCR and amplicon sequencing.
+In spite of this high medical relevance, neither a vaccine nor antiviral therapy is currently available.
+DENV elicits a strong interferon (IFN) response in infected cells, but at the same time actively counteracts IFN production and signaling.
+Although the kinetics of activation of this innate antiviral defense and the timing of viral counteraction critically determine the magnitude of infection and thus disease, quantitative and kinetic analyses are lacking and it remains poorly understood how DENV spreads in IFN-competent cell systems.
+To dissect the dynamics of replication versus antiviral defense at the single cell level, we generated a fully viable reporter DENV and host cells with authentic reporters for IFN-stimulated antiviral genes.
+We find that IFN controls DENV infection in a kinetically determined manner that at the single cell level is highly heterogeneous and stochastic.
+Even at high-dose, IFN does not fully protect all cells in the culture and, therefore, viral spread occurs even in the face of antiviral protection of naïve cells by IFN.
+By contrast, a vaccine candidate DENV mutant, which lacks 2’-O-methylation of viral RNA is profoundly attenuated in IFN-competent cells.
+Through mathematical modeling of time-resolved data and validation experiments we show that the primary determinant for attenuation is the accelerated kinetics of IFN production.
+This rapid induction triggered by mutant DENV precedes establishment of IFN-resistance in infected cells, thus causing a massive reduction of virus production rate.
+In conclusion, these results show that attenuation of the 2’-O-methylation DENV mutant is primarily determined by kinetics of autocrine IFN action on infected cells.
+The aim of the study was to understand more about pre-travel preparations and itineraries of business and occupational travelers.
+METHODS: De-identified data from 18 Global TravEpiNet clinics from January 2009 to December 2012 were analyzed.
+Business travelers were more likely to be men, had short times to departure and shorter trip durations, and commonly refused influenza, meningococcal, and hepatitis B vaccines.
+Most business travelers indicated that employers suggested the pre-travel health consultation, whereas non-occupational travelers sought consultations because of travel health concerns.
+Such consultations, even if scheduled immediately before travel, can identify vaccination gaps and increase coverage.
+BACKGROUND: Microbial aetiology of intensive care unit (ICU)-acquired pneumonia (ICUAP) determines antibiotic treatment and outcomes.
+METHOD: Patients with ICUAP confirmed microbiologically were prospectively compared according to identification of 1 (monomicrobial) or more (polymicrobial) potentially-pathogenic microorganisms.
+RESULTS: Among 441 consecutive patients with ICUAP, 256 (58 %) had microbiologic confirmation, and 41 (16 %) of them polymicrobial pneumonia.
+Compared with monomicrobial, patients with polymicrobial pneumonia had less frequently chronic heart disease (6, 15 % vs. 71, 33 %, p = 0.019), and more frequently pleural effusion (18, 50 %, vs. 54, 25 %, p = 0.008), without any other significant difference.
+Appropriate empiric antimicrobial treatment was similarly frequent in the monomicrobial (185, 86 %) and the polymicrobial group (39, 95 %), as were the initial response to the empiric treatment, length of stay and mortality.
+When empiric treatment is frequently appropriate, polymicrobial aetiology does not influence the outcome of ICUAP.
+The ability to disinfect and reuse disposable N95 filtering facepiece respirators (FFRs) may be needed during a pandemic of an infectious respiratory disease such as influenza.
+However, UV radiation degrades polymers, which presents the possibility that UVGI exposure could degrade the ability of a disposable respirator to protect the worker.
+To study this, we exposed both sides of material coupons and respirator straps from four models of N95 FFRs to UVGI doses from 120–950 J/cm(2).
+We then tested the particle penetration, flow resistance, and bursting strengths of the individual respirator coupon layers, and the breaking strength of the respirator straps.
+We found that UVGI exposure led to a small increase in particle penetration (up to 1.25%) and had little effect on the flow resistance.
+At the higher UVGI doses, the strength of the layers of respirator material was substantially reduced (in some cases, by >90%).
+The changes in the strengths of the respirator materials varied considerably among the different models of respirators.
+UVGI had less of an effect on the respirator straps; a dose of 2360 J/cm(2) reduced the breaking strength of the straps by 20–51%.
+Our results suggest that UVGI could be used to effectively disinfect disposable respirators for reuse, but the maximum number of disinfection cycles will be limited by the respirator model and the UVGI dose required to inactivate the pathogen.
+The L(o) phase of cellular membranes can be isolated from disordered lipids (L(d) phase) after treatment with 1 % Triton X-100 at 4 °C in which the L(o) phase forms the detergent-resistant membrane (DRM) fraction.
+The lipid composition of DRM derived from Madin-Darby canine kidney (MDCK) cells, McArdle cells and porcine sperm is compared with that of the whole cell.
+Remarkably, the unsaturation and chain length degree of aliphatic chains attached to phospholipids is virtually the same between DRM and whole cells.
+Sulfatides (sphingolipids from MDCK cells) were enriched in the DRM while a seminolipid (an alkylacylglycerolipid from sperm) was depleted from the DRM.
+Treatment with <5 mM methyl-ß-cyclodextrin (MBCD) caused cholesterol removal from the DRM without affecting the composition and amount of the phospholipid while higher levels disrupted the DRM.
+The substantial amount of (poly)unsaturated phospholipids in DRMs as well as a low stoichiometric amount of cholesterol suggest that lipid rafts in biological membranes are more fluid and dynamic than previously anticipated.
+Using negative staining, ultrastructural features of DRM were monitored and in all three cell types the DRMs appeared as multi-lamellar vesicular structures with a similar morphology.
+The detergent resistance is a result of protein–cholesterol and sphingolipid interactions allowing a relatively passive attraction of phospholipids to maintain the L(o) phase.
+For this special issue, the relevance of our findings is discussed in a sperm physiological context.
+BACKGROUND: Influenza B virus infection is generally considered to be mild and is rarely associated pulmonary cardiovascular involvement in adults.
+CASE PRESENTATION: A 43-year-old previously healthy Taiwanese male came to our emergency department due to high fever, chills, general malaise and myalgia for about 4 days.
+Emergent intubation was performed and he was transferred to the intensive care unit where oseltamivir (Tamiflu, Roche) 75 mg orally twice daily was given immediately.
+However, a markedly elevated cardiac enzyme level (Troponin I level was up to 71.01 ng/ml), a positive cardiac magnetic resonance imaging findings and no coronary artery stenosis led to the diagnosis of acute myocarditis.
+His condition gradually improved and he was successfully weaned from the ventilator on day 22.
+Early detection, early administration of antiviral agents, appropriate antibiotics and best supportive care, is still the gold standard for patients such as the one reported.
+δ-Crystallin is the major structural protein in avian eye lenses and is homologous to the urea cycle enzyme argininosuccinate lyase.
+Lys-315 is the only residue which is arranged symmetrically at the diagonal subunit interfaces to interact with each other.
+This study found that wild-type protein had both dimers and monomers present in 2–4 M urea whilst only monomers of the K315A mutant were observed under the same conditions, as judged by sedimentation velocity analysis.
+Molecular dynamics simulations showed that the dissociation of primary dimers is prior to the diagonal dimers in wild-type protein.
+These results suggest the critical role of Lys-315 in stabilization of the diagonal dimer structure.
+Guanidinium hydrochloride (GdmCl) denatured wild-type or K315A mutant protein did not fold into functional protein.
+However, the urea dissociated monomers of K315A mutant protein in GdmCl were reversible folding through a multiple steps mechanism as measured by tryptophan and ANS fluorescence.
+Refolding of the intermediates resulted in a conformation with greater amounts of hydrophobic regions exposed which was prone to the formation of protein aggregates.
+These results highlight that the conformational status of the monomers is critical for determining whether reversible oligomerization or aggregate formation occurs.
+To assess relationships between xanthine oxidase (XOD) and nephropathogenic infectious bronchitis virus (NIBV) infection, 240 growing layers (35 days old) were randomly divided into two groups (infected and control) of 120 chickens each.
+Each chicken in the control and infected group was intranasally inoculated with 0.2 mL sterile physiological saline and virus, respectively, after which serum antioxidant parameters and renal XOD mRNA expression in growing layers were evaluated at 8, 15 and 22 days post-inoculation (dpi).
+The results showed that serum glutathione peroxidase and superoxide dismutase activities in the infected group were significantly lower than in the control group at 8 and 15 dpi (p < 0.01), while serum malondialdehyde concentrations were significantly higher (p < 0.01).
+The serum uric acid was significantly higher than that of the control group at 15 dpi (p < 0.01).
+In addition, the kidney mRNA transcript level and serum activity of XOD in the infected group was significantly higher than that of the control group at 8, 15 and 22 dpi (p < 0.05).
+The results indicated that NIBV infection could cause the increases of renal XOD gene transcription and serum XOD activity, leading to hyperuricemia and reduction of antioxidants in the body.
+Monoclonal anti-enrofloxacin antibody was prepared for a direct competitive enzyme-linked immunosorbent assay (ELISA) and purification system using monoclonal antibody (mAb) coupled magnetic nanoparticles (MNPs).
+The IC(50) values of the developed mAb for enrofloxacin (ENR), ciprofloxacin, difloxacin, sarafloxacin, pefloxacin, and norfloxacin were 5.0, 8.3, 9.7, 21.7, 36.0, and 63.7 ng/mL, respectively.
+To validate the developed ELISA in the food matrix, known amounts of ENR were spiked in meat and egg samples at 10, 20 and 30 ng/mL.
+Recoveries for ENR ranged from 72.9 to 113.16% with a coefficient of variation (CV) of 2.42 to 10.11%.
+The applicability of the mAb-MNP system was verified by testing the recoveries for ENR residue in three different matrices.
+Recoveries for ENR ranged from 75.16 to 86.36%, while the CV ranged from 5.08 to 11.53%.
+Overall, ENR-specific monoclonal antibody was prepared and developed for use in competitive to ELISAs for the detection of ENR in animal meat samples.
+Furthermore, we suggest that a purification system for ENR using mAb-coupled MNPs could be useful for determination of ENR residue in food.
+Acute respiratory distress syndrome and multi-organ dysfunction are major complications in patients with severe influenza infection.
+This may be explained by the recent studies which highlighted the role of the pulmonary endothelium as the center of innate immune cells recruitment and excessive pro-inflammatory cytokines production.
+In this report, we examined the potential immunomodulatory effects of two indirubin derivatives, indirubin-3′-(2,3-dihydroxypropyl)-oximether (E804) and indirubin-3′-oxime (E231), on IAV (H9N2) infected-human pulmonary microvascular endothelial cells (HPMECs).
+Infection of H9N2 on HPMECs induced a high level of chemokines and cytokines production including IP-10, RANTES, IL-6, IFN-β and IFN-γ1.
+H9N2 infection rapidly triggered the activation of innate immunity through phosphorylation of signaling molecules including mitogen-activated protein kinases (MAPKs) and signal transducer and activator of transcription (STAT) proteins.
+Using specific inhibitors or small-interfering RNA, we confirmed that indirubin derivatives can suppress H9N2-induced cytokines production through MAPKs and STAT3 signaling pathways.
+These results underscore the immunomodulatory effects of indirubin derivatives on pulmonary endothelium and its therapeutic potential on IAV-infection.
+Given the side effects of vaccination against infectious laryngotracheitis (ILT), novel strategies for ILT control and therapy are urgently needed.
+The modulation of host-virus interactions is a promising strategy to combat the virus; however, the interactions between the host and avian ILT herpesvirus (ILTV) are unclear.
+Using genome-wide transcriptome studies in combination with a bioinformatic analysis, we identified proto-oncogene tyrosine-protein kinase Src (Src) to be an important modulator of ILTV infection.
+Functional studies revealed that Src prolongs the survival of host cells by increasing the threshold of virus-induced cell death.
+Therefore, Src is essential for viral replication in vitro and in ovo but is not required for ILTV-induced cell death.
+Furthermore, our results identify a positive-feedback loop between Src and the tyrosine kinase focal adhesion kinase (FAK), which is necessary for the phosphorylation of either Src or FAK and is required for Src to modulate ILTV infection.
+To the best of our knowledge, we are the first to identify a key host regulator controlling host-ILTV interactions.
+We believe that our findings have revealed a new potential therapeutic target for ILT control and therapy.
+IMPORTANCE Despite the extensive administration of live attenuated vaccines starting from the mid-20th century and the administration of recombinant vaccines in recent years, infectious laryngotracheitis (ILT) outbreaks due to avian ILT herpesvirus (ILTV) occur worldwide annually.
+Targeting of host-virus interactions is considered to be a promising strategy for controlling ILTV infections.
+The results from our study advance our understanding of host-ILTV interactions on a molecular level and provide experimental evidence that it is possible to control ILT via the manipulation of host-virus interactions.
+The National Center for Biotechnology Information (NCBI) provides a large suite of online resources for biological information and data, including the GenBank(®) nucleic acid sequence database and the PubMed database of citations and abstracts for published life science journals.
+Augmenting many of the web applications are custom implementations of the BLAST program optimized to search specialized datasets.
+The foot and mouth disease virus (FMDV) is sensitive to acids and can be inactivated by exposure to low pH conditions.
+Spraying animals at risk of infection with suspensions of acid-forming microorganisms has been identified as a potential strategy for preventing FMD.
+Kombucha is one of the most strongly acid-forming symbiotic probiotics and could thus be an effective agent with which to implement this strategy.
+Chinese herbal kombucha can be prepared by fermenting Chinese herbal extracts with a kombucha culture.
+Previous studies demonstrated that Chinese herbal kombucha prepared in this way efficiently inhibits FMDV replication in vitro.
+To assess the inhibitory effects of Chinese herbal kombucha against FMDV in vitro, swine challenged by intramuscular injection with 1000 SID(50) of swine FMDV serotype O strain O/China/99 after treatment with Chinese herbal kombucha were partially protected against infection, as demonstrated by a lack of clinical symptoms and qRT-PCR analysis.
+In a large scale field trial, spraying cattle in an FMD outbreak zone with kombucha protected against infection.
+Duchenne and Becker muscular dystrophy severity depends upon the nature and location of the DMD gene lesion and generally correlates with the dystrophin open reading frame.
+However, there are striking exceptions where an in-frame genomic deletion leads to severe pathology or protein-truncating mutations (nonsense or frame-shifting indels) manifest as mild disease.
+Exceptions to the dystrophin reading frame rule are usually resolved after molecular diagnosis on muscle RNA.
+We report a moderate/severe Becker muscular dystrophy patient with an in-frame genomic deletion of DMD exon 5.
+This mutation has been reported by others as resulting in Duchenne or Intermediate muscular dystrophy, and the loss of this in-frame exon in one patient led to multiple splicing events, including omission of exon 6, that disrupts the open reading frame and is consistent with a severe phenotype.
+The patient described has a deletion of dystrophin exon 5 that does not compromise recognition of exon 6, and although the deletion does not disrupt the reading frame, his clinical presentation is more severe than would be expected for classical Becker muscular dystrophy.
+We suggest that the dystrophin isoform lacking the actin-binding sequence encoded by exon 5 is compromised, reflected by the phenotype resulting from induction of this dystrophin isoform in mouse muscle in vivo.
+Hence, exon skipping to address DMD-causing mutations within DMD exon 5 may not yield an isoform that confers marked clinical benefit.
+Additional studies will be required to determine whether multi-exon skipping strategies could yield more functional dystrophin isoforms, since some BMD patients with larger in-frame deletions in this region have been reported with mild phenotypes.
+OBJECTIVE: To assess the feasibility and validity of unsupervised participant-collected nasal swabs to detect respiratory pathogens in a low-income, urban minority population.
+METHODS: This project was conducted as part of an ongoing community-based surveillance study in New York City to identify viral etiologies of acute respiratory infection.
+In January 2014, following sample collection by trained research assistants, participants with acute respiratory infection from 30 households subsequently collected and returned a self-collected/parent-collected nasal swab via mail.
+Self/parental swabs corresponding with positive reverse transcription polymerase chain reaction primary research samples were analyzed.
+RESULTS: Nearly all (96.8%, n=30/31) households agreed to participate; 100% reported returning the sample and 29 were received (median time: 8 days).
+Sensitivity of self-swabs for any respiratory pathogen was 83.3% and 87.5% for influenza, and specificity for both was 100%.
+There was no relationship between level of education and concordance of results between positive research samples and their matching participant swab.
+CONCLUSION: In this pilot study, self-swabbing was feasible and valid in a low-income, urban minority population.
+We have made a surprising observation that peptides derived from various hepatitis C virus (HCV) antigens contain extensive regions of homology with multiple adenovirus proteins, and conclusively demonstrate that adenovirus vector can induce robust, heterologous cellular and humoral immune responses against multiple HCV antigens.
+Intriguingly, the induction of this cross-reactive immunity leads to significant reduction of viral loads in a recombinant vaccinia-HCV virus infected mouse model, supporting their role in antiviral immunity against HCV.
+Healthy human subjects with Ad-specific pre-existing immunity demonstrated cross-reactive cellular and humoral immune responses against multiple HCV antigens.
+These findings reveal the potential of a previously uncharacterized property of natural human adenovirus infection to dictate, modulate and/or alter the course of HCV infection upon exposure.
+This intrinsic property of adenovirus vectors to cross-prime HCV immunity can also be exploited to develop a prophylactic and/or therapeutic vaccine against HCV.
+Senecavirus A (SV-A), formerly, Seneca Valley virus (SVV), has been detected in swine with vesicular lesions and is thought to be associated with swine idiopathic vesicular disease (SIVD), a vesicular disease syndrome that lacks a defined causative agent.
+The clinical presentation of SIVD resembles that of other more contagious and economically devastating vesicular diseases, such as foot-and-mouth disease (FMD), swine vesicular disease (SVD), and vesicular stomatitis (VS), that typically require immediate rule out diagnostics to lift restrictions on animal quarantine, movement, and trade.
+This study presents the development of a sensitive, SYBR Green RT-qPCR assay suitable for detection of SV-A in diagnostic swine specimens.
+After testing 50 pigs with clinical signs consistent with vesicular disease, 44 (88%) were found to be positive for SV-A by RT-qPCR as compared to none from a negative cohort of 35 animals without vesicular disease, indicating that the assay is able to successfully detect the virus in an endemic population.
+SV-A RNA was also detectable at a low level in sera from a subset of pigs that presented with (18%) or without (6%) vesicular signs.
+In 2015, there has been an increase in the occurrence of SV-A in the US, and over 200 specimens submitted to our laboratory for vesicular investigation have tested positive for the virus using this method.
+SV-A RNA was detectable in all common types of vesicular specimens including swabs and tissue from hoof lesions, oral and snout epithelium, oral swabs, scabs, and internal organ tissues such as liver and lymph node.
+Genome sequencing analysis from recent virus isolates was performed to confirm target amplicon specificity and was aligned to previous isolates.
+β-keto esters are used as precursors for the synthesis of β-amino acids, which are building blocks for some classes of pharmaceuticals.
+Here we describe the comparison of screening procedures for hydrolases to be used for the hydrolysis of β-keto esters, the first step in the preparation of β-amino acids.
+Two of the tested high throughput screening (HTS) assays depend on coupled enzymatic reactions which detect the alcohol released during ester hydrolysis by luminescence or absorption.
+The third assay detects the pH shift due to acid formation using an indicator dye.
+To choose the most efficient approach for screening, we assessed these assays with different statistical methods—namely, the classical Z’-factor, standardized mean difference (SSMD), the Kolmogorov-Smirnov-test, and t-statistics.
+This revealed that all three assays are suitable for HTS, the pH assay performing best.
+Finally, we successfully employed the pH assay to identify a very fast hydrolase in an enzyme-substrate screening.
+OBJECTIVE: It has proved that muscle paralysis was more protective for injured lung in severe acute respiratory distress syndrome (ARDS), but the precise mechanism is not clear.
+The purpose of this study was to test the hypothesis that abdominal muscle activity during mechanically ventilation increases lung injury in severe ARDS.
+After lung injury, Beagles were randomly assigned into spontaneous breathing group (BIPAP(SB)) and abdominal muscle paralysis group (BIPAP(AP)).
+All groups were ventilated with BIPAP model for 8h, and the high pressure titrated to reached a tidal volume of 6ml/kg, the low pressure was set at 10 cmH(2)O, with I:E ratio 1:1, and respiratory rate adjusted to a PaCO(2) of 35–60 mmHg.
+The levels of Interleukin (IL)-6, IL-8 in lung tissue and plasma were measured by qRT-PCR and ELISA respectively.
+RESULTS: For the comparable ventilator setting, as compared with BIPAP(SB) group, the BIPAP(AP) group presented higher EELV (427±47 vs. 366±38 ml) and oxygenation index (293±36 vs. 226±31 mmHg), lower levels of IL-6(216.6±48.0 vs. 297.5±71.2 pg/ml) and IL-8(246.8±78.2 vs. 357.5±69.3 pg/ml) in plasma, and lower express levels of IL-6 mRNA (15.0±3.8 vs. 21.2±3.7) and IL-8 mRNA (18.9±6.8 vs. 29.5±7.9) in lung tissues.
+In addition, less lung histopathology injury were revealed in the BIPAP(AP) group (22.5±2.0 vs. 25.2±2.1).
+CONCLUSION: Abdominal muscle activity during mechanically ventilation is one of the injurious factors in severe ARDS, so abdominal muscle paralysis might be an effective strategy to minimize ventilator-induce lung injury.
+Ferroptosis is a form of regulated non-apoptotic cell death that has been implicated in several disease contexts.
+A better understanding of the ferroptotic death mechanism could lead to the development of new therapeutics for degenerative diseases, and a better understanding of how to induce ferroptosis in specific tumor contexts.
+We determined that loss of CARS, the cysteinyl-tRNA synthetase, suppresses ferroptosis induced by erastin, which inhibits the cystine–glutamate antiporter known as system x(c)(−).
+Knockdown of CARS inhibited erastin-induced death by preventing the induction of lipid reactive oxygen species, without altering iron homeostasis.
+Knockdown of CARS led to the accumulation of cystathionine, a metabolite on the transsulfuration pathway, and upregulated genes associated with serine biosynthesis and transsulfuration.
+In addition, inhibition of the transsulfuration pathway resensitized cells to erastin, even after CARS knockdown.
+These studies demonstrate a new mechanism of resistance to ferroptosis and may lead to strategies for inducing and suppressing ferroptosis in diverse contexts.
+EBV is a key risk factor for many malignancy diseases such as nasopharyngeal carcinoma (NPC) and Burkitt lymphoma (BL).
+EBV integration has been reported, but its scale and impact to cancer development is remains unclear.
+C666-1 (NPC cell line) and Raji (BL cell line) are commonly studied EBV-positive cancer cells.
+A rare few EBV integration sites in Raji were found in previous research by traditional methods.
+To deeply survey EBV integration, we sequenced C666-1 and Raji whole genomes by the next generation sequencing (NGS) technology and a total of 909 breakpoints were detected in the two cell lines.
+Moreover, we observed that the number of integration sites was positive correlated with the total amount of chromosome structural variations (SVs) and copy number structural variations (CNVs), and most breakpoints located inside or nearby genome structural variations regions.
+It suggested that host genome instability provided an opportunity for EBV integration on one hand and the integration aggravated host genome instability on the other hand.
+Then, we respectively assembled the C666-1 and Raji EBV strains which would be useful resources for EBV-relative studies.
+Thus, we report the most comprehensive characterization of EBV integration in NPC cell and BL cell, and EBV shows the wide range and random integration to increase the tumorigenesis.
+The NGS provides an incomparable level of resolution on EBV integration and a convenient approach to obtain viral strain compared to any research technology before.
+Plants synthesize and accumulate large amount of specialized (or secondary) metabolites also known as natural products, which provide a rich source for modern pharmacy.
+Recent development of molecular biology, genomics and functional genomics as well as high-throughput analytical chemical technologies has greatly promoted the research on medicinal plants.
+In this article, we review recent advances in the elucidation of biosynthesis of specialized metabolites in medicinal plants, including phenylpropanoids, terpenoids and alkaloids.
+These natural products may share a common upstream pathway to form a limited numbers of common precursors, but are characteristic in distinct modifications leading to highly variable structures.
+Although this review is focused on traditional Chinese medicine, other plants with a great medicinal interest or potential are also discussed.
+Understanding of their biosynthesis processes is critical for producing these highly value molecules at large scale and low cost in microbes and will benefit to not only human health but also plant resource conservation.
+The ubiquitous presence of cell-surface sialic acid (SIA) has complicated efforts to identify specific transmembrane glycoproteins that function as bone fide entry receptors for influenza A virus (IAV) infection.
+The C-type lectin receptors (CLRs) DC-SIGN (CD209) and L-SIGN (CD209L) enhance IAV infection however it is not known if they act as attachment factors, passing virions to other unknown receptors for virus entry, or as authentic entry receptors for CLR-mediated virus uptake and infection.
+Sialic acid-deficient Lec2 Chinese Hamster Ovary (CHO) cell lines were resistant to IAV infection whereas expression of DC-SIGN/L-SIGN restored susceptibility of Lec2 cells to pH- and dynamin-dependent infection.
+Moreover, Lec2 cells expressing endocytosis-defective DC-SIGN/L-SIGN retained capacity to bind IAV but showed reduced susceptibility to infection.
+These studies confirm that DC-SIGN and L-SIGN are authentic endocytic receptors for IAV entry and infection.
+Virus evolves rapidly to escape vaccine-induced immunity, posing a desperate demand for efficient vaccine development biotechnologies.
+Here we present an express vaccine development strategy based on CRISPR/Cas9 and Cre/Lox system against re-emerging Pseudorabies virus, which caused the recent devastating swine pseudorabies outbreak in China.
+By CRISPR/Cas9 system, the virulent genes of the newly isolated strain were simultaneously substituted by marker genes, which were subsequently excised using Cre/Lox system for vaccine safety concern.
+Finally, vaccination and challenge experiments proved this vaccine candidate’s protective efficacy in pigs and the promise to control current pseudorabies outbreak.
+This is, to our knowledge, the first successful vaccine development based on gene edit technologies, demonstrating these technologies leap from laboratory to industry.
+Human infections with avian influenza H7N9 or H10N8 viruses have been reported in China, raising concerns that they might cause human epidemics and pandemics.
+Here we show that besides the commonly recognized viral polymerase subunit PB2 residue 627 K, other residues including 87E, 292 V, 340 K, 588 V, 648 V, and 676 M in PB2 also play critical roles in mammalian adaptation of the H10N8 virus.
+The avian-origin H10N8, H7N9, and H9N2 viruses harboring PB2-588 V exhibited higher polymerase activity, more efficient replication in mammalian and avian cells, and higher virulence in mice when compared to viruses with PB2-588 A.
+Analyses of available PB2 sequences showed that the proportion of avian H9N2 or human H7N9 influenza isolates bearing PB2-588 V has increased significantly since 2013.
+Taken together, our results suggest that the substitution PB2-A588V may be a new strategy for an avian influenza virus to adapt mammalian hosts.
+Rhinoviruses (RVs) and respiratory enteroviruses (EVs) are leading causes of upper respiratory tract infections and among the most frequent infectious agents in humans worldwide.
+Both are classified in the Enterovirus genus within the Picornaviridae family and they have been assigned to seven distinct species, RV-A, B, C and EV-A, B, C, D. As viral infections of public health significance, they represent an important financial burden on health systems worldwide.
+However, the lack of efficient antiviral treatment or vaccines against these highly prevalent pathogens prevents an effective management of RV-related diseases.
+Current advances in molecular diagnostic techniques have revealed the presence of RV in the lower respiratory tract and its role in lower airway diseases is increasingly reported.
+In addition to an established etiological role in the common cold, these viruses demonstrate an unexpected capacity to spread to other body sites under certain conditions.
+Some of these viruses have received particular attention recently, such as EV-D68 that caused a large outbreak of respiratory illness in 2014, respiratory EVs from species C, or viruses within the newly-discovered RV-C species.
+This review provides an update of the latest findings on clinical and fundamental aspects of RV and respiratory EV, including a summary of basic knowledge of their biology.
+Since its emergence in the 1990s, White Spot Disease (WSD) has had major economic and societal impact in the crustacean aquaculture sector.
+The disease is caused by the White Spot Syndrome Virus (WSSV), a large dsDNA virus and the only member of the Nimaviridae family.
+Susceptibility to WSSV in a wide range of crustacean hosts makes it a major risk factor in the translocation of live animals and in commodity products.
+Understanding the molecular basis of disease processes has contributed significantly to the treatment of many human and animal pathogens, and with a similar aim considerable efforts have been directed towards understanding host–pathogen molecular interactions for WSD.
+Work on the molecular mechanisms of pathogenesis in aquatic crustaceans has been restricted by a lack of sequenced and annotated genomes for host species.
+Nevertheless, some of the key host–pathogen interactions have been established: between viral envelope proteins and host cell receptors at initiation of infection, involvement of various immune system pathways in response to WSSV, and the roles of various host and virus miRNAs in mitigation or progression of disease.
+Despite these advances, many fundamental knowledge gaps remain; for example, the roles of the majority of WSSV proteins are still unknown.
+In this review we assess current knowledge of how WSSV infects and replicates in its host, and critique strategies for WSD treatment.
+Human papilloma virus (HPV) is the primary etiological agent responsible for cervical cancer in women.
+Currently available commercial vaccines are designed by targeting mainly HPV16 and HPV18 viral strains as these are the most common strains associated with cervical cancer.
+Because of the high level of antigenic specificity of HPV capsid antigens, the currently available vaccines are not suitable to provide cross-protection from all other high-risk HPV strains.
+Due to increasing reports of cervical cancer cases from other HPV high-risk strains other than HPV16 and 18, it is crucial to design vaccine that generate reasonable CD8+ T-cell responses for possibly all the high-risk strains.
+With this aim, we have developed a computational workflow to identify conserved cross-clade CD8+ T-cell HPV vaccine candidates by considering E1, E2, E6 and E7 proteins from all the high-risk HPV strains.
+We have identified a set of 14 immunogenic conserved peptide fragments that are supposed to provide protection against infection from any of the high-risk HPV strains across globe.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s13205-015-0352-z) contains supplementary material, which is available to authorized users.
+BACKGROUND: Mosquitoes of the Culex pipiens complex are cosmopolitan, and important vectors of neglected tropical diseases, such as arbovirosis and lymphatic filariasis.
+Mosquitoes of this taxa lack of morphological differences between females, but have frank behavioral and physiological differences and have different trophic preferences that influence their vectorial status.
+Hybridization may change the vectorial capacity of these mosquitoes, increasing vector efficiency and medical importance of resulting hybrids.
+from 35 distinct populations were investigated by the study of mtDNA, symbiotic bacterium Wolbachia pipientis, nuclear DNA and flanking region of microsatellite CQ11 polymorphism using PCR with diagnostic primers, RFLP analysis and sequencing.
+RESULTS: Six different mitochondrial haplotypes were revealed by sequencing of the cytochrome oxidase subunit I (COI) gene and three different Wolbachia (wPip) groups were identified.
+A strong association was observed between COI haplotypes/groups, wPip groups and taxa; haplogroup A and infection with wPipII appear to be typical for Cx.
+pipiens form pipiens, haplotype D and infection with wPipIV for form molestus, while haplogroup E, characteristic of Cx.
+Phylogenetic analysis of COI sequences yielded a tree topology that supported the RFLP analysis with significant bootstrap values for haplotype D and haplogroup E. CONCLUSIONS: Molecular identification provides the first evidence of the presence of hybrids between Cx.
+pipiens as a result of hybridization events in coastal regions of Southern Europe and Mediterranean region.
+Together with observed hybrids between pipiens and molestus forms, these findings point to the presence of hybrids in these areas, with consequent higher potential for disease transmission.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13071-016-1333-8) contains supplementary material, which is available to authorized users.
+Although they are primitive vertebrates, zebrafish (Danio rerio) and medaka (Oryzias latipes) have surpassed other animals as the most used model organisms based on their many advantages.
+Studies on gene expression patterns, regulatory cis-elements identification, and gene functions can be facilitated by using zebrafish embryos via a number of techniques, including transgenesis, in vivo transient assay, overexpression by injection of mRNAs, knockdown by injection of morpholino oligonucleotides, knockout and gene editing by CRISPR/Cas9 system and mutagenesis.
+In addition, transgenic lines of model fish harboring a tissue-specific reporter have become a powerful tool for the study of biological sciences, since it is possible to visualize the dynamic expression of a specific gene in the transparent embryos.
+In particular, some transgenic fish lines and mutants display defective phenotypes similar to those of human diseases.
+Therefore, a wide variety of fish model not only sheds light on the molecular mechanisms underlying disease pathogenesis in vivo but also provides a living platform for high-throughput screening of drug candidates.
+Interestingly, transgenic model fish lines can also be applied as biosensors to detect environmental pollutants, and even as pet fish to display beautiful fluorescent colors.
+Therefore, transgenic model fish possess a broad spectrum of applications in modern biomedical research, as exampled in the following review.
+BACKGROUND: Co-infection of different influenza A viruses is known to occur but how viruses interact within co-infection remains unknown.
+An outbreak in a college campus during the 2009 pandemic involved two subtypes of influenza A: persons infected with pandemic A/H1N1; persons infected with seasonal A/H3N2 viruses; and persons infected with both at the same time (co-infection).
+METHODS: We extend a statistical inference method designed for outbreaks caused by one virus to that caused by two viruses.
+The method uses knowledge of which subtype each case is infected with (and whether they were co-infected), contact information and symptom onset date of each case in the influenza outbreak.
+We then apply it to construct the most likely transmission tree during the outbreak in the college campus.
+RESULTS: Analysis of the constructed transmission tree shows that the simultaneous presence of the two influenza viruses increases the infectivity and the transmissibility of A/H1N1 virus but whether it changes the infectivity of A/H3N2 is unclear.
+The estimation also shows that co-transmission of both subtypes from co-infection is low and therefore co-infection cannot be sustained on its own.
+CONCLUSIONS: This study suggests that influenza A viruses within co-infected patients can interact in some ways rather than transmit independently, and this can enhance the spread of influenza A virus infection.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-016-1373-x) contains supplementary material, which is available to authorized users.
+In preliminary ELISA studies where released-active forms (RAF) of antibodies (Abs) to interferon-gamma (IFNg) were added to the antigen-antibody system, a statistically significant difference in absorbance signals obtained in their presence in comparison to placebo was observed.
+A piezoelectric immunosensor assay was developed to support these data and investigate the effects of RAF Abs to IFNg on the specific interaction between Abs to IFNg and IFNg.
+The experimental conditions were designed and optimal electrode coating, detection circumstances and suitable chaotropic agents for electrode regeneration were selected.
+The difference between the analytical signals of RAF Ab samples and those of the placebo was up to 50.8%, whereas the difference between non-specific controls and the placebo was within 5%–6%.
+Thus, the piezoelectric immunosensor as well as ELISA has the potential to be used for detecting the effects of RAF Abs to IFNg on the antigen-antibody interaction, which might be the result of RAF’s ability to modify the affinity of IFNg to specific/related Abs.
+However, the importance of airborne transmission in the spread of influenza is unclear, in part because of a lack of information about the infectivity of the airborne virus.
+The purpose of this study was to determine the amount of viable influenza A virus that was expelled by patients in aerosol particles while coughing.
+Sixty-four symptomatic adult volunteer outpatients were asked to cough 6 times into a cough aerosol collection system.
+Seventeen of these participants tested positive for influenza A virus by viral plaque assay (VPA) with confirmation by viral replication assay (VRA).
+Viable influenza A virus was detected in the cough aerosol particles from 7 of these 17 test subjects (41%).
+Viable influenza A virus was found in the smallest particle size fraction (0.3 μm to 8 μm), with a mean of 142 plaque-forming units (SD 215) expelled during the 6 coughs in particles of this size.
+These results suggest that a significant proportion of patients with influenza A release small airborne particles containing viable virus into the environment.
+Although the amounts of influenza A detected in cough aerosol particles during our experiments were relatively low, larger quantities could be expelled by influenza patients during a pandemic when illnesses would be more severe.
+Our findings support the idea that airborne infectious particles could play an important role in the spread of influenza.
+OBJECTIVE: Saffold virus (SAFV), a picornavirus, is occasionally detected in children with acute flaccid paralysis, meningitis, and cerebellitis; however, the neuropathogenicity of SAFV remains undetermined.
+METHODS: The virulence of two clinical isolates of SAFV type 3 (SAFV-3) obtained from a patient with aseptic meningitis (AM strain) and acute upper respiratory inflammation (UR strain) was analyzed in neonatal and young mice utilizing virological, pathological, and immunological methods.
+Both clinical isolates were infective, exhibited neurotropism, and were mildly neurovirulent in neonatal ddY mice.
+Both strains pathologically infected neural progenitor cells and glial cells, but not large neurons, with the UR strain also infecting epithelial cells.
+UR infection resulted in longer inflammation in the brain and spinal cord because of demyelination, while the AM strain showed more infectivity in the cerebellum in neonatal ddY mice.
+Additionally, young BALB/c mice seroconverted following mucosal inoculation with the UR, but not the AM, strain.
+CONCLUSIONS: Both SAFV-3 isolates had neurotropism and mild neurovirulence but showed different cell tropisms in both neonatal and young mouse models.
+Knowledge on domain swapping in vitro is increasing, but domain swapping may not occur regularly in vivo, and its information in cells is limited.
+Herein, we show that domain-swapped oligomers of a thermostable c-type cytochrome, Hydrogenobacter thermophilus cyt c(552), are formed in E. coli which expresses cyt c(552).
+The region containing the N-terminal α-helix and heme was domain-swapped between protomers in the dimer formed in E. coli.
+The amount of cyt c(552) oligomers increased in E. coli as the cyt c(552) concentration was increased, whereas that of high-order oligomers decreased in the order of decrease in protein stability, indicating that domain swapping decreases in cells when the protein stability decreases.
+Apo cyt c(552) was detected in the cyt c(552) oligomer formed in E. coli, but not in that of the A5F/M11V/Y32F/Y41E/I76V mutant.
+The cyt c(552) oligomer containing its apo protein may form at the periplasm, since the apo protein detected by mass measurements did not contain the signal peptide.
+These results show that domain-swapped cyt c(552) oligomers were formed in E. coli, owing to the stability of the transient oligomer containing the apo protein before heme attachment.
+This is an indication that exceedingly stable proteins may have disadvantages forming domain-swapped oligomers in cells.
+Epstein-Barr virus (EBV) is classified as a member in the order herpesvirales, family herpesviridae, subfamily gammaherpesvirinae and the genus lymphocytovirus.
+The virus is an exclusively human pathogen and thus also termed as human herpesvirus 4 (HHV4).
+It was the first oncogenic virus recognized and has been incriminated in the causation of tumors of both lymphatic and epithelial nature.
+It was reported in some previous studies that 95% of the population worldwide are serologically positive to the virus.
+Clinically, EBV primary infection is almost silent, persisting as a life-long asymptomatic latent infection in B cells although it may be responsible for a transient clinical syndrome called infectious mononucleosis.
+Following reactivation of the virus from latency due to immunocompromised status, EBV was found to be associated with several tumors.
+EBV linked to oncogenesis as detected in lymphoid tumors such as Burkitt's lymphoma (BL), Hodgkin's disease (HD), post-transplant lymphoproliferative disorders (PTLD) and T-cell lymphomas (e.g.
+It is also linked to epithelial tumors such as nasopharyngeal carcinoma (NPC), gastric carcinomas and oral hairy leukoplakia (OHL).
+In vitro, EBV many studies have demonstrated its ability to transform B cells into lymphoblastoid cell lines (LCLs).
+Despite these malignancies showing different clinical and epidemiological patterns when studied, genetic studies have suggested that these EBV- associated transformations were characterized generally by low level of virus gene expression with only the latent virus proteins (LVPs) upregulated in both tumors and LCLs.
+We also discuss how EBV latent genes may lead to oncogenesis in the different clinical malignancies
+Since mitigation reduces both peak prevalence and the number of people who fall ill, the answer might appear to be yes.
+But mitigation also prolongs epidemics and therefore the time susceptible people engage in activities to avoid infection.
+Whether private mitigation yields net social benefits depends on the social weight given to the costs of illness and illness avoidance, now and into the future.
+We show that, for a large class of infectious diseases, private risk mitigation is socially beneficial.
+However, in cases where society discounts the future at either very low or very high rates relative to private individuals, or where it places a low weight on the private cost of illness, the social cost of illness under proportionate mixing (doing nothing) may be lower than the social cost of illness under preferential mixing (avoiding infectious individuals).
+That is, under some circumstances, society would prefer shorter, more intense epidemics without avoidance costs over longer, less intense epidemics with avoidance costs.
+A sobering (although not surprising) implication of this is that poorer societies should be expected to promote less private disease-risk mitigation than richer societies.
+BACKGROUND: Joint hypermobility syndrome describes a disorder in which musculoskeletal pain occurs in a generalized joint hypermobility substrate.
+The clinical picture comprises variable manifestations which involve mainly but not exclusively the musculoskeletal system, and evolve over the person’s lifetime.
+CASE PRESENTATION: Describing the case of a 20-year-old female with generalized arthro-myalgias, persistent fatigue and troublesome visceral pain, we illustrate how a frequently ignored clinical sign such as joint hypermobility can be the keystone to clarify different simultaneous symptoms.
+All of the patient’s physical complaints had been investigated separately during her previous medical examinations, and several tests repeatedly gave negative results.
+The patient received different diagnoses that describe only part of her problems, such as irritable bowel syndrome for visceral pain, fibromyalgia for arthralgias or depression for fatigue.
+These approaches gave rise to pharmacological or physical treatments which did not improve her quality of life in any way and in some instances worsened the situation.
+Pronounced joint hypermobility which led the patient to flex her joints excessively, causing subluxations in several districts, was the only sign overlooked.
+CONCLUSION: Exploring the patient’s articular features in her clinical context led us to diagnose joint hypermobility syndrome, a complex and often ignored condition.
+The case highlights the utility of a multidisciplinary approach and coordinated interventions to define and manage this clinical entity.
+There is an increasing demand for non-antibiotics solutions to control infectious disease in intensive pig production.
+Here, one such alternative, namely pig antibodies purified from slaughterhouse blood was investigated in order to elucidate its potential usability to control post-weaning diarrhoea (PWD), which is one of the top indications for antibiotics usage in the pig production.
+A very cost-efficient and rapid one-step expanded bed adsorption (EBA) chromatography procedure was used to purify pig immunoglobulin G from slaughterhouse pig plasma (more than 100 litres), resulting in >85% pure pig IgG (ppIgG).
+The ppIgG thus comprised natural pig immunoglobulins and was subsequently shown to contain activity towards four pig-relevant bacterial strains (three different types of Escherichia coli and one type of Salmonella enterica) but not towards a fish pathogen (Yersinia ruckeri), and was demonstrated to inhibit the binding of the four pig relevant bacteria to a pig intestinal cell line (IPEC-J2).
+Finally it was demonstrated in an in vivo weaning piglet model for intestinal colonization with an E. coli F4+ challenge strain that ppIgG given in the feed significantly reduced shedding of the challenge strain, reduced the proportion of the bacterial family Enterobacteriaceae, increased the proportion of families Enterococcoceae and Streptococcaceae and generally increased ileal microbiota diversity.
+Conclusively, our data support the idea that natural IgG directly purified from pig plasma and given as a feed supplement can be used in modern swine production as an efficient and cost-effective means for reducing both occurrence of PWD and antibiotics usage and with a potential for the prevention and treatment of other intestinal infectious diseases even if the causative agent might not be known.
+We compared laboratory developed real-time PCR assays for detection of Mycoplasma hominis and for detection and differentiation of Ureaplasma urealyticum and parvum to culture using genitourinary specimens submitted for M. hominis and Ureaplasma culture.
+283 genitourinary specimens received in the clinical bacteriology laboratory for M. hominis and Ureaplasma species culture were evaluated.
+Nucleic acids were extracted using the Total Nucleic Acid Kit on the MagNA Pure 2.0.
+5 μL of the extracts were combined with 15 μL of each of the two master mixes.
+M. hominis PCR detected 38/42 M. hominis culture-positive specimens, as well as 2 that were culture negative (sensitivity, 90.5%; specificity, 99.2%).
+Ureaplasma PCR detected 139/144 Ureaplasma culture-positive specimens, as well as 9 that were culture negative (sensitivity, 96.5%; specificity, 93.6%).
+Of the specimens that tested positive for Ureaplasma species, U. urealyticum alone was detected in 33, U. parvum alone in 109, and both in 6.
+The described PCR assays are rapid alternatives to culture for detection of M. hominis and Ureaplasma species, and, unlike culture, the Ureaplasma assay easily distinguishes U. urealyticum from parvum.
+Glossina pallidipes salivary gland hypertrophy virus (GpSGHV; family Hytrosaviridae) is a dsDNA virus exclusively pathogenic to tsetse flies (Diptera; Glossinidae).
+The 190 kb GpSGHV genome contains 160 open reading frames and encodes more than 60 confirmed proteins.
+The asymptomatic GpSGHV infection in flies can convert to symptomatic infection that is characterized by overt salivary gland hypertrophy (SGH).
+Although the occurrence of SGH is an exception rather than the rule, G. pallidipes is thought to be the most susceptible to expression of overt SGH symptoms compared to other Glossina species that are largely asymptomatic.
+Although Glossina salivary glands (SGs) play an essential role in GpSGHV transmission, the functions of the salivary components during the virus infection are poorly understood.
+In this study, we used mass spectrometry to study SG proteomes of G. pallidipes and G. m. morsitans, two Glossina model species that exhibit differential GpSGHV pathologies (high and low incidence of SGH, respectively).
+A total of 540 host proteins were identified, of which 23 and 9 proteins were significantly up- and down-regulated, respectively, in G. pallidipes compared to G. m. morsitans.
+Whereas 58 GpSGHV proteins were detected in G. pallidipes F(1) progenies, only 5 viral proteins were detected in G. m. morsitans.
+Unlike in G. pallidipes, qPCR assay did not show any significant increase in virus titers in G. m. morsitans F(1) progenies, confirming that G. m. morsitans is less susceptible to GpSGHV infection and replication compared to G. pallidipes.
+Based on our results, we speculate that in the case of G. pallidipes, GpSGHV employs a repertoire of host intracellular signaling pathways for successful infection.
+BACKGROUND: Equine influenza (EI) is a highly contagious disease caused by viruses of the H3N8 subtype.
+Many rapid antigen detection (RAD) tests for diagnosing human influenza are available, but their ability to diagnose EI has not been systematically evaluated.
+OBJECTIVES: The aim of this study was to compare the performance of 22 RAD tests in the diagnosis of EI.
+METHODS: The 22 RAD tests were performed on fivefold serial dilutions of EI virus to determine their detection limits.
+The four most sensitive RAD tests (ImmunoAce Flu, BD Flu examan, Quick chaser Flu A, B and ESPLINE Influenza A&B‐N) were further evaluated using nasopharyngeal samples collected from experimentally infected and naturally infected horses.
+Even the four RAD tests showing the best sensitivity were 125‐fold less sensitive than the molecular techniques.
+The duration of virus detection in the experimentally infected horses was shorter using the RAD tests than using the molecular techniques.
+The RAD tests detected between 27% and 73% of real‐time RT‐PCR‐positive samples from naturally infected horses.
+CONCLUSIONS: The study demonstrated the importance of choosing the right RAD tests as only three of 22 were fit for diagnosing EI.
+It was also indicated that even RAD tests with the highest sensitivity serve only as an adjunct to molecular tests because of the potential for false‐negative results.
+Neisseria gonorrhoeae is one of the most prevalent sexually transmitted diseases worldwide with more than 100 million new infections per year.
+A lack of intense research over the last decades and increasing resistances to the recommended antibiotics call for a better understanding of gonococcal infection, fast diagnostics and therapeutic measures against N. gonorrhoeae.
+Therefore, the aim of this work was to identify novel immunogenic proteins as a first step to advance those unresolved problems.
+For the identification of immunogenic proteins, pHORF oligopeptide phage display libraries of the entire N. gonorrhoeae genome were constructed.
+Corresponding full-length proteins of the identified oligopeptides were expressed and their immunogenic character was verified by ELISA.
+We used annual rates of age- and cause-specific deaths to estimate pandemic-related mortality in excess of background levels in 39 countries in Europe, the Asia-Pacific region, and the Americas.
+We modeled the relationship between excess mortality and development indicators to extrapolate the global burden of the pandemic.
+The pandemic-associated excess respiratory mortality rate was 1.9/10 000 population (95% confidence interval [CI], 1.2–2.6 cases/10 000 population) on average during 1957–1959.
+Excess mortality rates varied 70-fold across countries; Europe and Latin America experienced the lowest and highest rates, respectively.
+Increases in the mortality rate relative to baseline were greatest in school-aged children and young adults, with no evidence that elderly population was spared from excess mortality.
+Overall, we attribute 1.1 million excess deaths (95% CI, .7 million–1.5 million excess deaths) globally to the 1957–1959 pandemic.
+The global mortality rate of the 1957–1959 influenza pandemic was moderate relative to that of the 1918 pandemic but was approximately 10-fold greater than that of the 2009 pandemic.
+The impact of the pandemic on mortality was delayed in several countries, pointing to a window of opportunity for vaccination in a future pandemic.
+Purpose: In order to improve the immunogenicity of whole tumor cell lysate for tumor vaccine, we have designed a series of CpG ODNs to study their transport and to evaluate their anti-tumor activity in B16 melanoma mouse models.
+Methods: In this study, we investigated whether C-class CpG ODN (CpG ODN-685) could facilitate tumor cell lysate to induce vigorous anti-tumor activity against tumors in mice both prophylactically and therapeutically.
+Results: It was found that the combination of tumor cell lysate and CpG ODN-685 could inhibit the growth of B16 melanoma and prolong the survival of tumor-bearing mice.
+Moreover CpG ODN-685 with the addition of tumor cell lysate can also cause the generation of tumor specific immune memory by inducing specific cytotoxic T lymphocytes and helper T lymphocytes in mice.
+Conclusion: The results suggest that CpG ODN-685 could be developed as an efficient adjuvant for tumor vaccines against melanoma.
+PURPOSE: Cytomegalovirus (CMV) reactivation occurs frequently in patients with the acute respiratory distress syndrome (ARDS) and has been associated with increased mortality.
+We aimed to estimate the attributable effect of CMV reactivation on mortality in immunocompetent ARDS patients.
+METHODS: We prospectively studied immunocompetent ARDS patients who tested seropositive for CMV and remained mechanically ventilated beyond day 4 in two tertiary intensive care units in the Netherlands from 2011 to 2013.
+Competing risks Cox regression was used with CMV reactivation status as a time-dependent exposure variable.
+Subsequently, in sensitivity analyses we adjusted for the evolution of disease severity until onset of reactivation using marginal structural modeling.
+RESULTS: Of 399 ARDS patients, 271 (68 %) were CMV seropositive and reactivation occurred in 74 (27 %) of them.
+After adjustment for confounding and competing risks, CMV reactivation was associated with overall increased ICU mortality (adjusted subdistribution hazard ratio (SHR) 2.74, 95 % CI 1.51–4.97), which resulted from the joint action of trends toward an increased mortality rate (direct effect; cause specific hazard ratio (HR) 1.58, 95 % CI 0.86–2.90) and a reduced successful weaning rate (indirect effect; cause specific HR 0.83, 95 % CI 0.58–1.18).
+The population-attributable fraction of ICU mortality was 23 % (95 % CI 6–41) by day 30 (risk difference 4.4, 95 % CI 1.1–7.9).
+CONCLUSION: CMV reactivation is independently associated with increased case fatality in immunocompetent ARDS patients who are CMV seropositive.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00134-015-4071-z) contains supplementary material, which is available to authorized users.
+RL, a traditional remedy for Rheumatoid arthritis (RA), comprises two edible herbs, Rosae Multiflorae Fructus and Lonicerae Japonicae Flos.
+We have reported that RL could inhibit the production of inflammatory mediators in immune cells.
+Here we investigated the effects and the mechanism of action of RL in collagen-induced arthritis (CIA) rats.
+In conclusion, RL at nontoxic doses inhibited TLR4 signaling and potently improved clinical conditions of CIA rats.
+These findings provide further pharmacological justifications for the traditional use of RL in RA management.
+During the latest outbreak of Ebola virus disease in West Africa, monoclonal antibody therapy (e.g., ZMapp) was utilized to treat patients.
+However, due to the antigenic differences among the five ebolavirus species, the current therapeutic monoclonal antibodies are only effective against viruses of the species Zaire ebolavirus.
+Although this particular species has indeed caused the majority of human infections in Central and, recently, West Africa, other ebolavirus species (e.g., Sudan ebolavirus and Bundibugyo ebolavirus) have also repeatedly caused outbreaks in Central Africa and thus should not be neglected in the development of countermeasures against ebolaviruses.
+Here we report the generation of an ebolavirus glycoprotein-specific monoclonal antibody that effectively inhibits cellular entry of representative isolates of all known ebolavirus species in vitro and show its protective efficacy in mouse models of ebolavirus infections.
+This novel neutralizing monoclonal antibody targets a highly conserved internal fusion loop in the glycoprotein molecule and prevents membrane fusion of the viral envelope with cellular membranes.
+The discovery of this highly cross-neutralizing antibody provides a promising option for broad-acting ebolavirus antibody therapy and will accelerate the design of improved vaccines that can selectively elicit cross-neutralizing antibodies against multiple species of ebolaviruses.
+We investigated whether diminazene aceturate (DIZE), an angiotensin-converting enzyme 2 (ACE2) activator, prevented lipopolysaccharide (LPS)-induced inflammatory response by activating the protective axis and whether the effect was mediated by inhibiting the mitogen-activated protein kinase (MAPK) and the nuclear factor-κB (NF-κB) pathways.
+METHODS: Cell counting kit-8 (CCK-8) assay and real-time PCR were used to determine the optimum concentration and incubation time of DIZE.
+ARPE-19 cells and primary cultured human retinal pigment epithelia (hRPE) were incubated with or without 10 μg/mL DIZE for 6 h before stimulated with 5 μg/mL LPS for 24 h. The mRNA expression of inflammatory cytokines, AT1R, and AT2R was analyzed.
+Phosphorylation of p38 MAPK, extracellular signal-regulated kinase (ERK)1/2, c-Jun N-terminal kinase (JNK) and phosphorylated transcription inhibition factor-κB-α (p-IκB-α) were measured.
+A small interfering RNA (siRNA) targeted to ACE2 and a selective Ang-(1-7) antagonist A779 was used to confirm the role of ACE2 and the involvement of ACE2/Ang-(1-7)/Mas axis.
+RESULTS: DIZE remarkably increased the expression of ACE2 and inhibited the expression of IL-6, IL-8, and MCP-1 at both mRNA and protein levels in both RPE cell lines stimulated with LPS.
+Inhibitors of p38, ERK1/2, JNK, and NF-κB significantly decreased LPS-induced overproduction of IL-6, IL-8, and MCP-1.
+Furthermore, DIZE downregulated the phosphorylation of p38MAPK, ERK1/2, JNK, and the activation of NF-κB upon stimulation with LPS.
+Downregulating ACE2 and pre-treatment with A779 abrogated the effects of DIZE on production of cytokines, the expression of Ang II, Ang-(1-7), AT1R, phosphorylation of MAPKs and activation of NF-κB.
+BACKGROUND: Since the novel H7N9 avian influenza outbreak occurred in China in 2013, neuraminidase inhibitors (NAIs) such as oseltamivir and peramivir have been used as first-line drugs to treat the influenza virus infection.
+METHODS: A retrospective study of 82 H7N9 confirmed patients was conducted by reviewing medical charts at the First Affiliated Hospital of ZheJiang University in China from April 1, 2013 to Feb 28, 2014.
+The patients’ clinical information was collected systematically, and we compared the virology and clinical data between oseltamivir monotherapy group (43 patients) and oseltamivir-peramivir combination group (39 patients).
+RESULTS: The median duration from NAIs administration to H7N9 virus-negative in oseltamivir monotherapy group and oseltamivir-peramivir combination group was 6.50 and 7.00 days (p >0.05), respectively.
+The median decline of Day 2 to Day 0 (initiation of NAIs therapy) viral load was 0.00 and 0.69 log10 copies/μl (p >0.05) respectively in the monotherapy vs. combination therapy groups.
+The incidence of new Acute Respiratory Distress Syndrome during NAI administration was 63.89 and 77.78 % (p >0.05); while the mortality rates were 25.58 and 43.59 % (p >0.05) in the oseltamivir group vs. oseltamivir-peramivir group.
+CONCLUSIONS: Our results suggest that in adults with H7N9 virus infection, the use of oseltamivir-peramivir combination therapy was not superior to oseltamivir monotherapy.
+Hepatitis C virus (HCV) is a positive-strand RNA virus of the Flaviviridae family and a major cause of liver disease worldwide.
+HCV replicates in the cytoplasm, and the synthesis of viral proteins induces extensive rearrangements of host cell membranes producing structures, collectively termed the membranous web (MW).
+The MW contains the sites of viral replication and assembly, and we have identified distinct membrane fractions derived from HCV-infected cells that contain replication and assembly complexes enriched for viral RNA and infectious virus, respectively.
+The complex membrane structure of the MW is thought to protect the viral genome limiting its interactions with cytoplasmic pattern recognition receptors (PRRs) and thereby preventing activation of cellular innate immune responses.
+Here we show that PRRs, including RIG-I and MDA5, and ribosomes are excluded from viral replication and assembly centers within the MW.
+Furthermore, we present evidence that components of the nuclear transport machinery regulate access of proteins to MW compartments.
+We show that the restricted assess of RIG-I to the MW can be overcome by the addition of a nuclear localization signal sequence, and that expression of a NLS-RIG-I construct leads to increased immune activation and the inhibition of viral replication.
+Previous studies have described the pleiotropic role of type I IFNs on innate and adaptive immune cells during viral infection.
+Here, we demonstrate that natural killer (NK) cells from mice lacking the type I IFN-α receptor (Ifnar(−/−)) or STAT1 (which signals downstream of IFNAR) are defective in expansion and memory cell formation after mouse cytomegalovirus (MCMV) infection.
+Despite comparable proliferation, Ifnar(−/−) NK cells showed diminished protection against MCMV infection and exhibited more apoptosis compared with wild-type NK cells.
+Furthermore, we show that Ifnar(−/−) NK cells express increased levels of NK group 2 member D (NKG2D) ligands during viral infection and are susceptible to NK cell–mediated fratricide in a perforin- and NKG2D-dependent manner.
+Adoptive transfer of Ifnar(−/−) NK cells into NK cell–deficient mice reverses the defect in survival and expansion.
+Our study reveals a novel type I IFN–dependent mechanism by which NK cells evade mechanisms of cell death after viral infection.
+The repair of organs and tissues has stepped into a prospective era of regenerative medicine.
+Owing to the complicated three dimensional structures and above 40 types of pulmonary cells, the regeneration of lung tissues becomes a great challenge.
+Compelling evidence has showed that distinct populations of intrapulmonary and extrapulmonary stem/progenitor cells can regenerate epithelia as well as endothelia in various parts of the respiratory tract.
+Recently, the discovery of human lung stem cells and their relevant studies has opened the door of hope again, which might put us on the path to repair our injured body parts, lungs on demand.
+Herein, we emphasized the role of endogenous and exogenous stem/progenitor cells in lungs as well as artificial tissue repair for the injured lungs, which constitute a marvelous toolbox for the treatment of acute lung injury.
+BACKGROUND: Lower respiratory tract infection (LRTI) is a major contributor to respiratory failure requiring intubation and mechanical ventilation.
+We sought to understand the dynamics of respiratory tract microbiota following intubation and the relationship between microbial community structure and infection.
+RESULTS: We enrolled a cohort of 15 subjects with respiratory failure requiring intubation and mechanical ventilation from the medical intensive care unit at an academic medical center.
+Oropharyngeal (OP) and deep endotracheal (ET) secretions were sampled within 24 h of intubation and every 48–72 h thereafter.
+Bacterial community profiling was carried out by purifying DNA, PCR amplification of 16S ribosomal RNA (rRNA) gene sequences, deep sequencing, and bioinformatic community analysis.
+We compared enrolled subjects to a cohort of healthy subjects who had lower respiratory tract sampling by bronchoscopy.
+In contrast to the diverse upper respiratory tract and lower respiratory tract microbiota found in healthy controls, critically ill subjects had lower initial diversity at both sites.
+In several subjects, the bacterial community was dominated by a single taxon over multiple time points.
+The clinical diagnosis of LRTI ascertained by chart review correlated with low community diversity and dominance of a single taxon.
+In several cases, dominant taxa included bacteria not detected by culture, including Ureaplasma parvum and Enterococcus faecalis.
+CONCLUSIONS: Longitudinal analysis of respiratory tract microbiota in critically ill patients provides insight into the pathogenesis and diagnosis of LRTI.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40168-016-0151-8) contains supplementary material, which is available to authorized users.
+However the rate of occult bacteremia in infants with RSV infection is not well established.
+The aim was to determine the actual rate and predictive factors of bacteremia in children admitted to hospital due to confirmed RSV acute respiratory illness (ARI), using both conventional culture and molecular techniques.
+METHODS: A prospective multicenter study (GENDRES-network) was conducted between 2011–2013 in children under the age of two admitted to hospital because of an ARI.
+Among those RSV-positive, bacterial presence in blood was assessed using PCR for Meningococcus, Streptococcus pneumoniae, Haemophilus influenzae, Streptococcus pyogenes, Klebsiella pneumoniae, Pseudomonas aeruginosa, Escherichia coli, and Staphylococcus aureus, in addition to conventional cultures.
+In 10.6% patients, bacterial presence was detected: H. influenzae (n = 4) and S. pneumoniae (n = 2).
+In those patients with bacteremia, there was a previous suspicion of bacterial superinfection and had received empirical antibiotic treatment 6 out of 7 (85.7%) patients.
+There were significant differences in terms of severity between children with positive bacterial PCR and those with negative results: PICU admission (100% vs. 50%, P-value = 0.015); respiratory support necessity (100% vs. 18.6%, P-value < 0.001); Wood-Downes score (mean = 8.7 vs. 4.8 points, P-value < 0.001); GENVIP scale (mean = 17 vs. 10.1, P-value < 0.001); and length of hospitalization (mean = 12.1 vs. 7.5 days, P-value = 0.007).
+CONCLUSION: Bacteremia is not frequent in infants hospitalized with RSV respiratory infection, however, it should be considered in the most severe cases.
+Ebola virus (EBOV) makes extensive and intricate use of host factors in the cellular endosomal/lysosomal pathway to release its genome into the cytoplasm and initiate infection.
+Following viral internalization into endosomes, host cysteine proteases cleave the EBOV fusion glycoprotein (GP) to unmask the binding site for its intracellular receptor, the cholesterol transporter Niemann-Pick C1 (NPC1).
+Despite these and other recent discoveries, late events in EBOV entry following GP-NPC1 binding and culminating in GP-catalyzed fusion between viral and cellular lipid bilayers remain enigmatic.
+A mechanistic understanding of EBOV membrane fusion has been hampered by the failure of previous efforts to reconstitute fusion in vitro or at the cell surface.
+This report describes an assay to monitor initial steps directly in EBOV membrane fusion—triggering of GP and virus-cell lipid mixing—by single virions in live cells.
+Fusogenic triggering of GP occurs predominantly in Rab7-positive (Rab7(+)) endosomes, absolutely requires interaction between proteolytically primed GP and NPC1, and is blocked by key GP-specific neutralizing antibodies with therapeutic potential.
+Unexpectedly, cysteine protease inhibitors do not inhibit lipid mixing by virions bearing precleaved GP, even though they completely block cytoplasmic entry by these viruses, as shown previously.
+These results point to distinct cellular requirements for different steps in EBOV membrane fusion and suggest a model in which host cysteine proteases are dispensable for GP fusion triggering after NPC1 binding but are required for the formation of fusion pores that permit genome delivery.
+BACKGROUND: Rodents are natural reservoirs of hantaviruses, which cause two disease types: hemorrhagic fever with renal syndrome in Eurasia and hantavirus pulmonary syndrome in North America.
+However, the diversity and number of hantaviruses are likely underestimated in China, and hantavirus species that cause disease in many regions, including Yunnan province, are unknown.
+RESULTS: In August 2012, we collected tissue samples from 189 captured animals, including 15 species belonging to 10 genera, 5 families, and 4 orders in Fugong county, Yunnan province, China.
+Seven species were positive for hantavirus: Eothenomys eleusis (42/94), Apodemus peninsulae (3/25), Niviventer eha (3/27), Cryptotis montivaga (2/8), Anourosorex squamipes (1/1), Sorex araneus (1/1), and Mustela sibirica (1/2).
+We characterized one full-length genomic sequence of the virus (named fugong virus, FUGV) from a small oriental vole (Eothenomys eleusis).
+The full-length sequences of the small, medium, and large segments of FUGV were 1813, 3630, and 6531 nt, respectively.
+FUGV was most closely related to hantavirus LX309, a previously reported species detected in the red-backed vole in Luxi county, Yunnan province, China.
+However, the amino acid sequences of nucleocapsid (N), glycoprotein (G), and large protein (L) were highly divergent from those of Hantavirus LX309, with amino acid differences of 11.2, 15.3, and 12.7 %, respectively.
+In phylogenetic trees, FUGV clustered in the lineage corresponding to hantaviruses carried by rodents in the subfamily Arvicolinae.
+CONCLUSIONS: High prevalence of hantavirus infection in small mammals was found in Fugong county, Yunnan province, China.
+BACKGROUND: Selenium (Se) is required for the synthesis of proteins (selenoproteins) with essential biological functions.
+Selenoproteins have a crucial role in the maintenance of cellular redox homeostasis in nearly all tissues, and are also involved in thyroid hormone metabolism, inflammation and immunity.
+Several immune processes rely on Se status and can be compromised if this element is present below the required level.
+Previous work has supported the notion that when Se is delivered at levels above those deemed to be the minimal required but below toxic concentrations it can have a boosting effect on the organism’s immune response.
+Based on this concept Se-enriched supplements may represent a valuable resource for functional feeds in animal farming, including aquaculture.
+RESULTS: In this study we tested the effects of Se supplemented as Sel-Plex during an immune challenge induced by polyinosinic:polycytidylic acid (poly(I:C)), a pathogen-associated molecular pattern (PAMP) that mimics viral infection.
+Trout were fed two diets enriched with 1 or 4 mg Se Kg(−1) of feed (dry weight) by Sel-Plex addition and a commercial formulation as control.
+The whole trout transcriptomic response was investigated by microarray and gene ontology analysis, the latter carried out to highlight the biological processes that were influenced by Sel-Plex supplementation in the head kidney (HK) and liver, the main immune and metabolic organs in fish.
+Overall, Sel-Plex enrichement up to 4 mg Se Kg(−1) induced an important response in the trout HK, eliciting an up-regulation of several genes involved in pathways connected with hematopoiesis and immunity.
+In contrast, a more constrained response was seen in the liver, with lipid metabolism being the main pathway altered by Se supplementation.
+Upon stimulation with poly(I:C), supplementation of 4 mg Se Kg(−1) increased the expression of principal mediators of the antiviral defences, especially IFN-γ, and down-stream molecules involved in the cell-mediated immune response.
+CONCLUSIONS: Supplementation of diets with 4 mg Se Kg(−1) using Sel-Plex remarkably improved the fish response to viral PAMP stimulation.
+Sel-Plex, being a highly bioavailable supplement of organic Se, might represent a suitable option for supplementation of fish feeds, to achieve the final aim of improving fish fitness and resistance against immune challenges.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-016-2418-7) contains supplementary material, which is available to authorized users.
+The classical axis of renin-angiotensin system (RAS), angiotensin (Ang)-converting enzyme (ACE)/Ang II/AT1, contributes to the development of non-alcoholic fatty liver disease (NAFLD).
+However, the role of bypass axis of RAS (Angiotensin-converting enzyme 2 (ACE2)/Ang-(1–7)/Mas) in hepatic steatosis is still unclear.
+Here we showed that deletion of ACE2 aggravates liver steatosis, which is correlated with the increased expression of hepatic lipogenic genes and the decreased expression of fatty acid oxidation-related genes in the liver of ACE2 knockout (ACE2(−/y)) mice.
+On the contrary, overexpression of ACE2 improved fatty liver in db/db mice, and the mRNA levels of fatty acid oxidation-related genes were up-regulated.
+In vitro, Ang-(1–7)/ACE2 ameliorated hepatic steatosis, oxidative stress and inflammation in free fatty acid (FFA)-induced HepG2 cells, and what’s more, Akt inhibitors reduced ACE2-mediated lipid metabolism.
+These results indicated that Ang-(1–7)/ACE2/Mas axis may reduce liver lipid accumulation partly by regulating lipid-metabolizing genes through ATP/P2 receptor/CaM signaling pathway.
+Our findings support the potential role of ACE2/Ang-(1–7)/Mas axis in prevention and treatment of hepatic lipid metabolism.
+T helper (Th) 17 cells and CD4(+) CD25(+) regulatory T (Treg) cells are supposed to be critically involved in regulating autoimmune and inflammatory diseases.
+The aim of this study was to investigate the Th17/Treg pattern in rats with gunpowder smog-induced acute lung injury.
+Wistar rats were equally randomized to three groups: normal control group, ALI 6 h group (smoke inhalation for 6 h) and ALI 24 h group (smoke inhalation for 24 h).
+We observed changes in cell counting in bronchoalveolar lavage fluid (BALF), alveolar-capillary membrane permeability and lung tissue pathology.
+Moreover, rats in ALI 6 h and ALI 24 h group showed increased expression of Th17 cell and related cytokines (IL-17 A, IL-6, TGF-β and IL-23).
+Additionally, Th1 cell decreased while Th2 cell increased at 6 h and 24 h after smoke inhalation.
+In conclusion, Th17/Treg imbalance exists in rats with smoke inhalation-induced acute lung injury, suggesting its potential role in the pathogenesis of this disease.
+Genomic tools, including phylogenetic trees derived from sequence data, are increasingly used to understand outbreaks of infectious diseases.
+Particularly in bacteria that cause chronic infections, this inference is affected by variable infectious periods and infectivity over time.
+It is known that non-exponential infectious periods can have substantial effects on pathogens’ transmission dynamics.
+Here we ask how this non-Markovian nature of an outbreak process affects the branching trees describing that process, with particular focus on tree shapes.
+We find that memory (non-Markovian-ness) in the process can have a pronounced effect on the shapes of the outbreak’s branching pattern.
+However, memory also has a pronounced effect on the sizes of the trees, even when the duration of the simulation is fixed.
+When the sizes of the trees are constrained to a constant value, memory in our processes has little direct effect on tree shapes, but can bias inference of the birth rate from trees.
+We compare simulated branching trees to phylogenetic trees from an outbreak of tuberculosis in Canada, and discuss the relevance of memory to this dataset.
+BACKGROUND: Thrombocytopaenia is the most frequent malaria-associated haematologic alteration observed with all five Plasmodium parasites causing disease in humans.
+Although not included in the World Health Organization criteria for severe Plasmodium falciparum malaria, severe thrombocytopaenia has been increasingly mentioned as an indicator of P. vivax malaria severity.
+CASE: Here, it is described a case of imported P. vivax malaria in a 37-year old man from Pakistan who presented with severe thrombocytopaenia (5 × 10(9)/L).
+He was admitted to the intensive care unit and initially treated with a 1-day course of intravenous quinine followed by oral chloroquine and primaquine.
+The patient’s platelet count increased as early as 4 hours after treatment inception and the clinical course was favourable and uneventful.
+DISCUSSION: This case report, along with a review of published cases focusing on the relationship between thrombocytopaenia and severe P. vivax malaria, suggests that the prognostic role of severe thrombocytopaenia is ambiguous in absence of severe haemorraghic complications and its use as diagnostic criterion of malaria severity may lead to overestimation of severe P. vivax malaria cases.
+CONCLUSION: Due to the lack of high quality studies it is at present unclear if severe thrombocytopaenia in the setting of P. vivax malaria should be considered indicative of severe malaria.
+The robustness of immune responses to an antigen could be dictated by the route of vaccine inoculation.
+Traditional smallpox vaccines, essentially vaccinia virus strains, that were used in the eradication of smallpox were administered by percutaneous inoculation (skin scarification).
+The modified vaccinia virus Ankara is licensed as a smallpox vaccine in Europe and Canada and currently undergoing clinical development in the United States.
+MVA is also being investigated as a vector for the delivery of heterologous genes for prophylactic or therapeutic immunization.
+Since MVA is replication-deficient, MVA and MVA-vectored vaccines are often inoculated through the intramuscular, intradermal or subcutaneous routes.
+Vaccine inoculation via the intramuscular, intradermal or subcutaneous routes requires the use of injection needles, and an estimated 10 to 20% of the population of the United States has needle phobia.
+Following an observation in our laboratory that a replication-deficient recombinant vaccinia virus derived from the New York City Board of Health strain elicited protective immune responses in a mouse model upon inoculation by tail scarification, we investigated whether MVA and MVA recombinants can elicit protective responses following percutaneous administration in mouse models.
+Our data suggest that MVA administered by percutaneous inoculation, elicited vaccinia-specific antibody responses, and protected mice from lethal vaccinia virus challenge, at levels comparable to or better than subcutaneous or intramuscular inoculation.
+High titers of specific neutralizing antibodies were elicited in mice inoculated with a recombinant MVA expressing the herpes simplex type 2 glycoprotein D after scarification.
+Similarly, a recombinant MVA expressing the hemagglutinin of attenuated influenza virus rgA/Viet Nam/1203/2004 (H5N1) elicited protective immune responses when administered at low doses by scarification.
+Taken together, our data suggest that MVA and MVA-vectored vaccines inoculated by scarification can elicit protective immune responses that are comparable to subcutaneous vaccination, and may allow for antigen sparing when vaccine supply is limited.
+Stimulator of interferon genes (STING) is known be involved in control of DNA viruses but has an unexplored role in control of RNA viruses.
+During infection with DNA viruses STING is activated downstream of cGAMP synthase (cGAS) to induce type I interferon.
+Here we identify a STING-dependent, cGAS-independent pathway important for full interferon production and antiviral control of enveloped RNA viruses, including influenza A virus (IAV).
+Interestingly, FP antagonizes interferon production induced by membrane fusion or IAV but not by cGAMP or DNA.
+Similar to the enveloped RNA viruses, membrane fusion stimulates interferon production in a STING-dependent but cGAS-independent manner.
+Abolishment of this pathway led to reduced interferon production and impaired control of enveloped RNA viruses.
+ABSTRACT: Recently, our group has developed a therapeutic hypertensive vaccine against angiotensin (Ang) II type 1 receptor (AT1R) named ATRQβ-001.
+To explore its potential effectiveness on streptozotocin-induced diabetic nephropathy, male Sprague Dawley rats were randomly divided into two groups: a control and a diabetic model.
+After 1 week, the diabetic rats were divided into four subgroups (each with 15 rats) for 14-week treatments with saline, olmesartan, ATRQβ-001, and Qβ virus-like particle (VLP), respectively.
+In addition to lower blood pressure, ATRQβ-001 vaccination ameliorated biochemical parameter changes of renal dysfunction, mesangial expansion, and fibrosis through inhibiting oxidative stress, macrophage infiltration, and proinflammatory factor expression.
+Furthermore, ATRQβ-001 vaccination suppressed renal Ang II-AT1R activation and abrogated the downregulation of angiotensin-converting enzyme 2-Ang (1–7), similar to olmesartan treatment, while no obvious feedback activation of circulating or local renin-angiotensin system (RAS) was only observed in vaccine group.
+In rat mesangial cells, the anti-ATR-001 antibody inhibited high glucose-induced transforming growth factor-β1 (TGF)-β1/Smad3 signal pathway.
+In conclusion, the ATRQβ-001 vaccine ameliorated streptozotocin-induced diabetic renal injury via modulating two RAS axes and inhibiting TGF-β1/Smad3 signal pathway, providing a novel, safe, and promising method to treat diabetic nephropathy.
+KEY MESSAGES: Overactivation of RAS plays a crucial role in the development of the DN.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00109-015-1343-6) contains supplementary material, which is available to authorized users.
+This experiment was conducted to evaluate whether pretreatment with fenofibrate could mitigate acute lung injury (ALI) in a mice model of intestinal ischemia/reperfusion (I/R).
+Male C57BL/6 mice were randomly assigned into three groups (n = 6): sham, intestinal I/R + vehicle, and intestinal I/R + fenofibrate.
+Fenofibrate (100 mg/kg) or equal volume of vehicle was injected intraperitoneally 60 minutes before the ischemia.
+At the end of experiment, measurement of pathohistological score, inflammatory mediators and other markers were performed.
+In addition, a 24-hour survival experiment was conducted in intestinal I/R mice treated with fenofibrate or vehicle.
+Consistently, renal creatine levels and hepatic ALT levels were significantly decreased in the fenofibrate group.
+Collectively, our data indicated that pretreatment with fenofibrate prior to ischemia attenuated intestinal I/R injury and ALI.
+Nucleoprotein (NP) is the most abundant type of RNA-binding viral protein in influenza A virus–infected cells and is necessary for viral RNA transcription and replication.
+The surface of the groove, covered with numerous conserved residues between the head and body domains of influenza A NP, plays a crucial role in RNA binding.
+To explore the mechanism by which NP binds RNA, we performed a series of site-directed mutagenesis in the RNA-binding groove, followed by surface plasmon resonance (SPR), to characterize the interactions between RNA and NP.
+By interrupting the stacking interaction between Y148 and an RNA base, we identified an influenza virus NP inhibitor, (E, E)-1,7-bis(4-hydroxy-3-methoxyphenyl) -1,6-heptadiene-3,5-dione; this inhibitor reduced the NP’s RNA-binding affinity and hindered viral replication.
+Our findings will be useful for the development of new drugs that disrupt the interaction between RNA and viral NP in the influenza virus.
+Two groups with three wild boars each were used: Group A (animals 1 to 3) served as the control, and Group B (animals 4 to 6) was postnatally persistently infected with the Cat01 strain of CSFV (primary virus).
+The animals, six weeks old and clinically healthy, were inoculated with the virulent strain Margarita (secondary virus).
+For exclusive detection of the Margarita strain, a specific qRT-PCR assay was designed, which proved not to have cross-reactivity with the Cat01 strain.
+The wild boars persistently infected with CSFV were protected from superinfection by the virulent CSFV Margarita strain, as evidenced by the absence of clinical signs and the absence of Margarita RNA detection in serum, swabs and tissue samples.
+Additionally, in PBMCs, a well-known target for CSFV viral replication, only the primary infecting virus RNA (Cat01 strain) could be detected, even after the isolation in ST cells, demonstrating SIE at the tissue level in vivo.
+Furthermore, the data analysis of the Margarita qRT-PCR, by means of calculated ΔCt values, supported that PBMCs from persistently infected animals were substantially protected from superinfection after in vitro inoculation with the Margarita virus strain, while this virus was able to infect naive PBMCs efficiently.
+In parallel, IFN-α values were undetectable in the sera from animals in Group B after inoculation with the CSFV Margarita strain.
+Furthermore, these animals were unable to elicit adaptive humoral (no E2-specific or neutralising antibodies) or cellular immune responses (in terms of IFN-γ-producing cells) after inoculation with the second virus.
+Finally, a sequence analysis could not detect CSFV Margarita RNA in the samples tested from Group B.
+Our results suggested that the SIE phenomenon might be involved in the evolution and phylogeny of the virus, as well as in CSFV control by vaccination.
+To the best of our knowledge, this study was one of the first showing efficient suppression of superinfection in animals, especially in the absence of IFN-α, which might be associated with the lack of innate immune mechanisms.
+BACKGROUND: Monoallelic mutations of the Surfactant Protein C gene (SFTPC) are associated with Interstitial Lung Disease in children.
+CASE PRESENTATION: We describe three patients carrying the same I73T SPC mutation with very different phenotypes, clinical course (ranging from mild respiratory symptoms to death for respiratory failure) and outcome.
+CONCLUSIONS: The disease mechanisms associated with SP-C mutations suggest that the combination of individual genetic background and environmental factors contribute largely to the wide variability of clinical expression.
+Infants, children and adults with ILD of unknown etiology should be investigated for SP-C genetic abnormalities.
+These prophylactics have been used for centuries but still to this day only three main design strategies exist: (1) live attenuated virus (LAV) vaccines, (2) killed or inactivated virus vaccines, (3) and subunit vaccines of the three, the most efficacious vaccines remain LAVs.
+LAVs replicate in relevant tissues, elicit strong cellular and humoral responses, and often confer lifelong immunity.
+While this vaccine strategy has produced the majority of successful vaccines in use today, there are also important safety concerns to consider with this approach.
+Blind passage of viruses in various cell types results in the accumulation of multiple attenuating mutations leaving the molecular mechanisms of attenuation unknown.
+Also, due to the high error rate of RNA viruses and selective pressures of the host environment, these LAVs, derived from such viruses, can potentially revert back to wild-type virulence.
+This not only puts the vaccinee at risk, but if shed can put those that are unvaccinated at risk as well.
+While these vaccines have been successful there still remains a need for a rational design strategy by which to create additional LAVs.
+Increased fidelity decreases the viral mutational frequency thereby reducing the genetic variation the virus needs in order to evade the host imposed bottlenecks to infection.
+While polymerase mutants exist which decrease viral mutation frequency the mutations are not in conserved regions of the polymerase, which doesn’t lend itself toward using a common mutant approach toward developing a universal vaccine strategy for all RNA viruses.
+We have identified a conserved lysine residue in the active site of the PV RdRp that acts as a general acid during nucleotide incorporation.
+Mutation from a lysine to an arginine results in a high fidelity polymerase that replicates slowly thus creating an attenuated virus that is genetically stable and less likely to revert to a wild-type phenotype.
+This chapter provides detailed methods in which to identify the conserved lysine residue and evaluating fidelity and attenuation in cell culture (in vitro) and in the PV transgenic murine model (in vivo).
+Haemophilus parasuis is a Gram-negative bacterium that colonizes the upper respiratory tract of swine and is capable of causing a systemic infection, resulting in high morbidity and mortality.
+H. parasuis isolates display a wide range of virulence and virulence factors are largely unknown.
+Commercial bacterins are often used to vaccinate swine against H. parasuis, though strain variability and lack of cross-reactivity can make this an ineffective means of protection.
+Outer membrane vesicles (OMV) are spherical structures naturally released from the membrane of bacteria and OMV are often enriched in toxins, signaling molecules and other bacterial components.
+Examination of OMV structures has led to identification of virulence factors in a number of bacteria and they have been successfully used as subunit vaccines.
+We have isolated OMV from both virulent and avirulent strains of H. parasuis, have examined their protein content and assessed their ability to induce an immune response in the host.
+Vaccination with purified OMV derived from the virulent H. parasuis Nagasaki strain provided protection against challenge with a lethal dose of the bacteria.
+A wide array of wildlife species, including many animals, are used in traditional medicines across many medicinal systems, including in Traditional Chinese Medicine (TCM).
+Due to over-exploitation and habitat loss, the populations of many animals commonly used in TCM have declined and are unable to meet market demand.
+A number of measures have been taken to try to reduce the impact that this large and growing market for TCM may have on wild animal species.
+Consumer preferences and behavior are known to play an important role in the consumption and protection of wild animals used in traditional medicine, and thus are likely to be an important factor in the success of many of these mechanisms—particularly given the significant percentage of TCMs that are over-the-counter products (access to which is not mediated by practitioners).
+In this study we conducted questionnaires and designed stated preference experiments embodying different simulation scenarios using a random sample of the population in Beijing to elicit individuals’ knowledge, perceptions and preferences toward wild or farmed animal materials and their substitutes used in traditional Chinese medicine.
+We found that respondents had a stated preference for wild materials over farm-raised and other alternatives because they believe that the effectiveness of wild-sourced materials is more credible than that of other sources.
+However, we also found that, although respondents used TCM products, they had a poor understanding of the function or composition of either traditional Chinese medicines or proprietary Chinese medicines (PCM), and paid little attention to the composition of products when making purchasing decisions.
+Furthermore, awareness of the need for species protection, or “conservation consciousness” was found to play an important role in willingness to accept substitutions for wild animal materials, while traditional animal medicinal materials (TAMs) derived from well-known endangered species, such as bear bile and tiger bone, show relatively higher substitutability.
+These results suggest that there is still hope for conservation measures which seek to promote a transition to farmed animal, plant and synthetic ingredients and provide clear directions for future social marketing, education and engagement efforts.
+α-defensins are abundant antimicrobial peptides with broad, potent antibacterial, antifungal, and antiviral activities in vitro.
+Although their contribution to host defense against bacteria in vivo has been demonstrated, comparable studies of their antiviral activity in vivo are lacking.
+Using a mouse model deficient in activated α-defensins in the small intestine, we show that Paneth cell α-defensins protect mice from oral infection by a pathogenic virus, mouse adenovirus 1 (MAdV-1).
+Survival differences between mouse genotypes are lost upon parenteral MAdV-1 infection, strongly implicating a role for intestinal defenses in attenuating pathogenesis.
+Although differences in α-defensin expression impact the composition of the ileal commensal bacterial population, depletion studies using broad-spectrum antibiotics revealed no effect of the microbiota on α-defensin-dependent viral pathogenesis.
+Moreover, despite the sensitivity of MAdV-1 infection to α-defensin neutralization in cell culture, we observed no barrier effect due to Paneth cell α-defensin activation on the kinetics and magnitude of MAdV-1 dissemination to the brain.
+This effect was specific to oral viral infection, because antibody responses to parenteral or mucosal ovalbumin exposure were not affected by α-defensin deficiency.
+Thus, α-defensins play an important role as adjuvants in antiviral immunity in vivo that is distinct from their direct antiviral activity observed in cell culture.
+Several studies have shown a reduced efficacy of influenza vaccines in the elderly compared to young adults.
+In this study, we evaluated the immunogenicity and protective efficacy of a commercially available inactivated influenza vaccine (Fluzone(®)) in young adult and aged mice.
+C57/BL6 mice were administered a single or double immunization of Fluzone(®) with or without CpG and challenged intranasally with H1N1 A/California/09 virus.
+A double immunization of Fluzone(®) adjuvanted with CpG elicited the highest level of protection in young adult mice which was associated with increases in influenza specific IgG, elevated HAI titres, reduced viral titres and lung inflammation.
+In contrast, the vaccine schedule which provided fully protective immunity in young adult mice conferred limited protection in aged mice.
+Antigen presenting cells from aged mice were found to be less responsive to in vitro stimulation by Fluzone and CpG which may partially explain this result.
+Our data are supportive of studies that have shown limited effectiveness of influenza vaccines in the elderly and provide important information relevant to the design of more immunogenic vaccines in this age group.
+It is well known that there is no threshold for spreading models on scale-free networks; this suggests that spread can occur on such networks, regardless of how low the contact rate may be.
+In this paper, I consider six models with different contact and propagation mechanisms, which include models studied so far, but are apt to be confused.
+Influenza virus infection has a significant impact on public health, since it is a major cause of morbidity and mortality.
+It is not well-known whether influenza virus infection affects cell death and human immunodeficiency virus (HIV)-1 replication in HIV-1-infected patients.
+Using a lymphoma cell line, Jurkat, we examined the in vitro effects of pandemic influenza A (H1N1) virus (pH1N1) infection on cell death and HIV-1 RNA production in infected cells.
+We found that pH1N1 infection increased apoptotic cell death through Fas and Bax-mediated pathways in HIV-1-infected Jurkat cells.
+Infection with pH1N1 virus could promote HIV-1 RNA production by activating host transcription factors including nuclear factor kappa-light-chain-enhancer of activated B cells (NF-ĸB), nuclear factor of activated T-cells (NFAT) and activator protein 1 (AP-1) through mitogen-activated protein kinases (MAPK) pathways and T-cell antigen receptor (TCR)-related pathways.
+The replication of HIV-1 latent infection could be reactivated by pH1N1 infection through TCR and apoptotic pathways.
+These data indicate that HIV-1 replication can be activated by pH1N1 virus in HIV-1-infected cells resulting in induction of cell death through apoptotic pathways.
+Herpesviruses are highly prevalent viruses associated with numerous pathologies both in animal and human populations.
+Until now, most of the strategies used to prevent or to cure these infections have been unsuccessful because these viruses have developed numerous immune evasion mechanisms.
+In particular, while the genome of numerous herpesviruses has been sequenced, the exact composition of virions remains unknown for most of them.
+Mass spectrometry has recently emerged as a central method and has permitted fundamental discoveries in virology.
+Here, we review mass spectrometry-based approaches that have recently allowed a better understanding of the composition of the herpesvirus virion.
+In particular, we describe strategies commonly used for proper sample preparation and fractionation to allow protein localization inside the particle but also to avoid contamination by nonstructural proteins.
+A collection of other important data regarding post-translational modifications or the relative abundance of structural proteins is also described.
+This review also discusses the poorly studied importance of host proteins in herpesvirus structural proteins and the necessity to develop a quantitative workflow to better understand the dynamics of the structural proteome.
+In the future, we hope that this collaborative effort will assist in the development of new strategies to fight these infections.
+Virus discovery from high throughput sequencing data often follows a bottom-up approach where taxonomic annotation takes place prior to association to disease.
+Albeit effective in some cases, the approach fails to detect novel pathogens and remote variants not present in reference databases.
+We have developed a species independent pipeline that utilises sequence clustering for the identification of nucleotide sequences that co-occur across multiple sequencing data instances.
+We applied the workflow to 686 sequencing libraries from 252 cancer samples of different cancer and tissue types, 32 non-template controls, and 24 test samples.
+Recurrent sequences were statistically associated to biological, methodological or technical features with the aim to identify novel pathogens or plausible contaminants that may associate to a particular kit or method.
+We provide examples of identified inhabitants of the healthy tissue flora as well as experimental contaminants.
+Unmapped sequences that co-occur with high statistical significance potentially represent the unknown sequence space where novel pathogens can be identified.
+Fatal Ebola virus infection is characterized by a systemic inflammatory response similar to septic shock.
+Ebola glycoprotein (GP) is involved in this process through activating dendritic cells (DCs) and macrophages.
+Here, we showed that LSECtin (also known as CLEC4G) plays an important role in GP-mediated inflammatory responses in human DCs.
+Anti-LSECtin mAb engagement induced TNF-α and IL-6 production in DCs, whereas silencing of LSECtin abrogated this effect.
+Intriguingly, as a pathogen-derived ligand, Ebola GP could trigger TNF-α and IL-6 release by DCs through LSECtin.
+Mechanistic investigations revealed that LSECtin initiated signaling via association with a 12-kDa DNAX-activating protein (DAP12) and induced Syk activation.
+Therefore, our results demonstrate that LSECtin is required for the GP-induced inflammatory response, providing new insights into the EBOV-mediated inflammatory response.
+Carbonic anhydrase IX (CAIX) is a tumor-associated antigen and marker of hypoxia that is overexpressed on > 90% of clear-cell type renal cell carcinoma (RCC) but not on neighboring normal kidney tissue.
+Here, we report on the construction of two chimeric antigen receptors (CARs) that utilize a carbonic anhydrase (CA) domain mapped, human single chain antibody (scFv G36) as a targeting moiety but differ in their capacity to provide costimulatory signaling for optimal T cell proliferation and tumor cell killing.
+CAR-transduced T cells (CART cells) expressing second-generation G36-CD28-TCRζ exhibited more potent in vitro antitumor effects on CAIX(+) RCC cells than first-generation G36-CD8-TCRζ including cytotoxicity, cytokine secretion, proliferation, and clonal expansion.
+Adoptive G36-CD28-TCRζ CART cell therapy combined with high-dose interleukin (IL)-2 injection also lead to superior regression of established RCC in nude mice with evidence of tumor cell apoptosis and tissue necrosis.
+These results suggest that the fully human G36-CD28-TCRζ CARs should provide substantial improvements over first-generation mouse anti-CAIX CARs in clinical use through reduced human anti-mouse antibody responses against the targeting scFv and administration of lower doses of T cells during CART cell therapy of CAIX(+) RCC.
+BACKGROUND: The emergency department (ED) increasingly acts as a gateway to the evaluation and treatment of acute illnesses.
+Consequently, it has also become a key testing ground for systems that monitor and identify outbreaks of disease.
+The technology was tested in an ED as an approach to monitoring diseases that cause fever, such as seasonal flu and some pandemics.
+METHODS: Temporal artery thermometers that log temperature measurements were placed in a Boston ED and used for initial triage vital signs.
+Time-stamped measurements were collected from the thermometers to investigate the performance a real-time system would offer.
+The data were summarized in terms of rates of fever (temperatures ≥100.4 °F [≥38.0 °C]) and were qualitatively compared with regional disease surveillance programs in Massachusetts.
+RESULTS: From September 2009 through August 2011, 71,865 body temperatures were collected and included in our analysis, 2073 (2.6 %) of which were fevers.
+The period of study included the autumn–winter wave of the 2009–2010 H1N1 (swine flu) pandemic, during which the weekly incidence of fever reached a maximum of 5.6 %, as well as the 2010–2011 seasonal flu outbreak, during which the maximum weekly incidence of fever was 6.6 %.
+The periods of peak fever rates corresponded with the periods of regionally elevated flu activity.
+CONCLUSIONS: Temperature measurements were monitored at triage in the ED over a period of 2 years.
+The resulting data showed promise as a potential surveillance tool for febrile disease that could complement current disease surveillance systems.
+Because temperature can easily be measured by non-experts, it might also be suitable for monitoring febrile disease activity in schools, workplaces, and transportation hubs, where many traditional syndromic indicators are impractical.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12873-016-0080-7) contains supplementary material, which is available to authorized users.
+BACKGROUND: After the 2009 influenza A (H1N1) pandemic, we conducted hospital-based severe acute respiratory infection (SARI) surveillance in one central Chinese city to assess disease burden attributable to influenza among adults and adolescents.
+METHODS: We defined an adult SARI case as a hospitalized patient aged ≥ 15 years with temperature ≥38.0°C and at least one of the following: cough, sore throat, tachypnea, difficulty breathing, abnormal breath sounds on auscultation, sputum production, hemoptysis, chest pain, or chest radiograph consistent with pneumonia.
+For each enrolled SARI case-patient, we completed a standardized case report form, and collected a nasopharyngeal swab within 24 hours of admission.
+We analyzed data from adult SARI cases in four hospitals in Jingzhou, China from April 2010 to April 2012.
+Nearly all were prescribed antibiotics during their hospitalization, less than 1% were prescribed oseltamivir, and 28% were prescribed corticosteroids.
+Influenza-positive patients had a longer duration from illness onset to hospitalization and a shorter duration from hospital admission to discharge or death compared to influenza negative SARI patients.
+CONCLUSIONS: There is substantial burden of influenza-associated SARI hospitalizations in Jingzhou, China, especially among older adults.
+More effective promotion of annual seasonal influenza vaccination and timely oseltamivir treatment among high risk groups may improve influenza prevention and control in China.
+Here, we report a unique recombinant HAdV strain (CBJ113) isolated from a HAdV-positive child with SARI.
+A phylogenetic analysis of the complete genome indicated that the CBJ113 strain shares a common origin with HAdV-C2, HAdV-C6, HAdV-C1, HAdV-C5, and HAdV-C57 and formed a novel subclade on the same branch as other HAdV-C subtypes.
+BootScan and single nucleotide polymorphism analyses showed that the CBJ113 genome has an intra-subtype recombinant structure and comprises gene regions mainly originating from two circulating viral strains: HAdV-1 and HAdV-2.
+The parental penton base, pVI, and DBP genes of the recombinant strain clustered with the HAdV-1 prototype strain, and the E1B, hexon, fiber, and 100 K genes of the recombinant clustered within the HAdV-2 subtype, meanwhile the E4orf1 and DNA polymerase genes of the recombinant shared the greatest similarity with those of HAdV-5 and HAdV-6, respectively.
+All of these findings provide insight into our understanding of the dynamics of the complexity of the HAdV-C epidemic.
+The journal has since expanded the field, and its influence, with the number of downloaded papers rising 17-fold, to over 4 million.
+Its ground-breaking papers, leading authors -including a Nobel Prize winner- and an impact factor of 2.25 place it among the top global health journals in the world.
+To mark the ten years since the journal’s founding, we, members of the current editorial board, undertook a review of the journal’s progress over the last decade.
+Through the application of an inductive thematic analysis, we systematically identified themes of research published in the journal from 2005 to 2014.
+We identify key areas the journal has promoted and consider these in the context of an existing framework, identify current gaps in global health research and highlight areas we, as a journal, would like to see strengthened.
+BACKGROUND: There is evidence to support a role for angiotensin (Ang) 1–7 in reducing the activity of inflammatory signaling molecules such as MAPK, PKC and SRC.
+Enhanced angiotensin converting enzyme 2 (ACE2) expression has been observed in patients with inflammatory bowel disease (IBD) suggesting a role in its pathogenesis, prompting this study.
+METHODS: The colonic expression/activity profile of ACE2, Ang 1–7, MAS1-receptor (MAS1-R), MAPK family and Akt were determined by western blot and immunofluorescence.
+The effect of either exogenous administration of Ang 1–7 or pharmacological inhibition of its function (by A779 treatment) was determined using the mouse dextran sulfate sodium model.
+CONCLUSION: Our results indicate important anti-inflammatory actions of Ang 1–7 in the pathogenesis of IBD, which may provide a future therapeutic strategy to control the disease progression.
+Andalusia (Southern Spain) is considered one of the main routes of introduction of bluetongue virus (BTV) into Europe, evidenced by a devastating epidemic caused by BTV-1 in 2007.
+Understanding the pattern and the drivers of BTV-1 spread in Andalusia is critical for effective detection and control of future epidemics.
+A long-standing metric for quantifying the behaviour of infectious diseases is the case-reproduction ratio (R(t)), defined as the average number of secondary cases arising from a single infected case at time t (for t>0).
+Here we apply a method using epidemic trees to estimate the between-herd case reproduction ratio directly from epidemic data allowing the spatial and temporal variability in transmission to be described.
+We then relate this variability to predictors describing the hosts, vectors and the environment to better understand why the epidemic spread more quickly in some regions or periods.
+The R(t) value for the BTV-1 epidemic in Andalusia peaked in July at 4.6, at the start of the epidemic, then decreased to 2.2 by August, dropped below 1 by September (0.8), and by October it had decreased to 0.02.
+BTV spread was the consequence of both local transmission within established disease foci and BTV expansion to distant new areas (i.e.
+new foci), which resulted in a high variability in BTV transmission, not only among different areas, but particularly through time, which suggests that general control measures applied at broad spatial scales are unlikely to be effective.
+This high variability through time was probably due to the impact of temperature on BTV transmission, as evidenced by a reduction in the value of R(t) by 0.0041 for every unit increase (day) in the extrinsic incubation period (EIP), which is itself directly dependent on temperature.
+Moreover, within the range of values at which BTV-1 transmission occurred in Andalusia (20.6°C to 29.5°C) there was a positive correlation between temperature and R(t) values, although the relationship was not linear, probably as a result of the complex relationship between temperature and the different parameters affecting BTV transmission.
+R(t) values for BTV-1 in Andalusia fell below the threshold of 1 when temperatures dropped below 21°C, a much higher threshold than that reported in other BTV outbreaks, such as the BTV-8 epidemic in Northern Europe.
+This divergence may be explained by differences in the adaptation to temperature of the main vectors of the BTV-1 epidemic in Andalusia (Culicoides imicola) compared those of the BTV-8 epidemic in Northern Europe (Culicoides obsoletus).
+Importantly, we found that BTV transmission (R(t) value) increased significantly in areas with higher densities of sheep.
+Our analysis also established that control of BTV-1 in Andalusia was complicated by the simultaneous establishment of several distant foci at the start of the epidemic, which may have been caused by several independent introductions of infected vectors from the North of Africa.
+We discuss the implications of these findings for BTV surveillance and control in this region of Europe.
+WT1(126) (RMFPNAPYL) is a human leukocyte antigen-A2 (HLA-A2)-restricted peptide derived from Wilms tumor protein 1 (WT1), which is widely expressed in a broad spectrum of leukemias, lymphomas and solid tumors.
+A novel T-cell-receptor (TCR)-like single-chain variable fragment (scFv) antibody specific for the T-cell epitope consisting of the WT1/HLA-A2 complex was isolated from a human scFv phage library.
+This scFv was affinity-matured by mutagenesis combined with yeast display and structurally analyzed using a homology model.
+This monovalent scFv showed a 100-fold affinity improvement (dissociation constant (K(D))=3 nm) and exquisite specificity towards its targeted epitope or HLA-A2(+)/WT1(+) tumor cells.
+Bivalent scFv-huIgG1-Fc fusion protein demonstrated an even higher avidity (K(D)=2 pm) binding to the T-cell epitope and to tumor targets and was capable of mediating antibody-dependent cell-mediated cytotoxicity or tumor lysis by chimeric antigen receptor-expressing human T- or NK-92-MI-transfected cells.
+This antibody demonstrated specific and potent cytotoxicity in vivo towards WT1-positive leukemia xenograft that was HLA-A2 restricted.
+By combining phage and yeast displays and scFv-Fc fusion platforms, a strategy for developing high-affinity TCR-like antibodies could be rapidly explored for potential clinical development.
+SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/leu.2015.125) contains supplementary material, which is available to authorized users.
+Knowledge of the distribution and diversity of RNA viruses is still limited in spite of their possible environmental and epidemiological impacts because RNA virus-specific metagenomic methods have not yet been developed.
+We herein constructed an effective metagenomic method for RNA viruses by targeting long double-stranded (ds)RNA in cellular organisms, which is a hallmark of infection, or the replication of dsRNA and single-stranded (ss)RNA viruses, except for retroviruses.
+This novel dsRNA targeting metagenomic method is characterized by an extremely high recovery rate of viral RNA sequences, the retrieval of terminal sequences, and uniform read coverage, which has not previously been reported in other metagenomic methods targeting RNA viruses.
+This method revealed a previously unidentified viral RNA diversity of more than 20 complete RNA viral genomes including dsRNA and ssRNA viruses associated with an environmental diatom colony.
+Our approach will be a powerful tool for cataloging RNA viruses associated with organisms of interest.
+Bluetongue virus (BTV), a complex double-stranded segmented RNA virus, has been found to initiate cellular autophagy for its own benefit.
+Here, with a view to understanding the underlying mechanisms, we first systematically dissected the exact signaling network in BTV-induced autophagy.
+We found that the activity of mTOR, a crucial pivot, was inhibited by BTV1 infection, subsequently leading to downstream p70S6K suppression and autophagy initiation.
+We then explored the upstream regulators of mTOR and analyzed their activities via a series of assays.
+However, the BTV1-induced inhibition of PI3K/Akt was found to be partially responsible for mTOR inactivation and subsequent autophagy initiation.
+Furthermore, we found unexpectedly that AMPK seemed to play a more important role in BTV1-induced autophagy.
+Elevated [Ca(2+)](cyto)-mediated activation of CaMKKβ exactly managed the activation of AMPK, which then positively regulated autophagy through suppressing mTOR.
+We must emphasize that TSC2 is a fatal mediator between upstream Akt or AMPK and downstream mTOR through its phosphorylation.
+Taken together, our data suggested that the BTV1-induced inhibition of the Akt-TSC2-mTOR pathway and the upregulation of the AMPK-TSC2-mTOR pathway both contributed to autophagy initiation and further favored virus replication.
+Following viral internalization into endosomes, GP is cleaved by host cysteine proteases to expose a receptor-binding site (RBS) that is otherwise hidden from immune surveillance.
+Here, we present the crystal structure of proteolytically cleaved Ebola virus GP to a resolution of 3.3 Å.
+We use this structure in conjunction with functional analysis of a large panel of pseudotyped viruses bearing mutant GP proteins to map the Ebola virus GP endosomal RBS at molecular resolution.
+Our studies indicate that binding of GP to its endosomal receptor Niemann-Pick C1 occurs in two distinct stages: the initial electrostatic interactions are followed by specific interactions with a hydrophobic trough that is exposed on the endosomally cleaved GP(1) subunit.
+Finally, we demonstrate that monoclonal antibodies targeting the filovirus RBS neutralize all known filovirus GPs, making this conserved pocket a promising target for the development of panfilovirus therapeutics.
+Severe fever with thrombocytopenia syndrome virus (SFTSV) was a novel tick-borne bunyavirus that caused hemorrhagic fever with a high fatality rate in East Asia.
+In this study we analyzed the complete genome sequences of 122 SFTSV strains to determine the phylogeny, evolution and reassortment of the virus.
+We revealed that the evolutionary rate of three genome segments were different, with highest in the S segment and lowest in the L segment.
+The SFTSV strains were phylogenetically classified into 5 lineages (A, B, C, D and E) with each genome segment.
+SFTSV strains from China were classified in all 5 lineages, strains from South Korea were classified into 3 lineages (A, D, and E), and all strains from Japan were classified in only linage E. Using the average evolutionary rate of the three genome segments, we found that the extant SFTSV originated 20–87 years ago in the Dabie Mountain area in central China.
+Selection pressure analysis suggested that SFTSV was under purifying selection according to the four genes (RNA-dependent RNA polymerase, glycoprotein, nucleocapsid protein, non-structural protein), and two sites (37, 1033) of glycoproteins were identified as being under strong positive selection.
+We concluded that SFTSV originated in central China and spread to other places recently and the virus was under purifying selection with high frequency of reassortment.
+BACKGROUND: There is an increasing number of meta-analyses including data from non-randomized studies for therapeutic evaluation.
+We aimed to systematically assess the methods used in meta-analyses including non-randomized studies evaluating therapeutic interventions.
+METHODS: For this methodological review, we searched MEDLINE via PubMed, from January 1, 2013 to December 31, 2013 for meta-analyses including at least one non-randomized study evaluating therapeutic interventions.
+Two reviewers independently assessed the general characteristics and key methodological components of the systematic review process and meta-analysis methods.
+RESULTS: One hundred eighty eight meta-analyses were selected: 119 included both randomized controlled trials (RCTs) and non-randomized studies of interventions (NRSI) and 69 only NRSI.
+An assessment of methodological quality or risk of bias was reported in 135 meta-analyses (72 %) but this assessment considered the risk of confounding bias in only 33 meta-analyses (18 %).
+In 131 (70 %), whether crude or adjusted estimates of treatment effect for NRSI were combined was unclear or not reported.
+Heterogeneity across studies was assessed in 182 meta-analyses (97 %) and further explored in 157 (84 %).
+CONCLUSIONS: Some key methodological components of the systematic review process—search for grey literature, description of the type of NRSI included, assessment of risk of confounding bias and reporting of whether crude or adjusted estimates were combined—are not adequately carried out or reported in meta-analyses including NRSI.
+A CopyControl origin of replication was introduced into the viral genome to facilitate its genetic manipulation in Escherichia coli and to ensure the preparation of large amounts of high quality reBmBac DNA as well as high quality recombinant baculoviruses.
+The ORF1629, cathepsin and chitinase genes were partially deleted or rendered defective to improve the efficiency of recombinant baculovirus generation and the expression of foreign genes.
+The system was validated by the successful expression of luciferase reporter gene and porcine interferon γ.
+This system can be used to produce batches of recombinant baculoviruses and target proteins rapidly and efficiently in silkworms.
+BACKGROUND: Tuberculosis (TB) is difficult to diagnose in children using molecular tests, because children have difficulty providing respiratory samples.
+Stool could replace sputum for diagnostic TB testing if adequate sample processing techniques were available.
+METHODS: We developed a rapid method to process large volumes of stool for downstream testing by the Xpert MTB/RIF (Xpert) TB-detection assay.
+The method was tested and optimized on stool samples spiked with known numbers of M. tuberculosis colony forming units (CFU), and stools from M. tuberculosis-infected cynomolgus macaques (Macaca fascicularis).
+Performance was scored on number of positive Xpert tests, the cycle thresholds (Cts) of the Xpert sample-processing control (SPC), and the Cts of the M. tuberculosis-specific rpoB probes.
+The method was then validated on 20 confirmed TB cases and 20 controls in Durban, South Africa.
+As much as one gram of spiked stool could be tested without showing increased PCR inhibition.
+In analytical spiking experiments using human stool, 1g samples provided the best sensitivity compared to smaller amounts of sample.
+However, in Macaques with TB, 0.6g stool samples performed better than either 0.2g or 1.2g samples.
+Testing the stool of pediatric TB suspects and controls suggested an assay sensitivity of 85% (95% CI 0.6–0.9) and 84% (95% CI 0.6–0.96) for 0.6g and 1.2g stool samples, respectively, and a specificity of 100% (95% CI 0.77–1) and 94% (95% CI 0.7–0.99), respectively.
+CONCLUSION: This novel approach may permit simple and rapid detection of TB using pediatric stool samples.
+Persistently-infected rodents harbor high levels of defective interfering (DI) particles, which are thought to be important for establishing persistence and mitigating virus-induced cytopathic effect.
+We show that neither the PPXY late domain encoded within the lymphocytic choriomeningitis virus (LCMV) matrix protein nor a functional endosomal sorting complex transport (ESCRT) pathway is absolutely required for the generation of standard infectious virus particles.
+Additionally, the terminal tyrosine in the PPXY motif is reversibly phosphorylated and our findings indicate that this posttranslational modification may regulate DI particle formation.
+Thus we have uncovered a new role for the PPXY late domain and a possible mechanism for its regulation.
+We analyzed underlying drivers of 116 IDTEs detected in Europe during 2008–2013 by epidemic intelligence at the European Centre of Disease Prevention and Control.
+Seventeen drivers were identified and categorized into 3 groups: globalization and environment, sociodemographic, and public health systems.
+The driver category globalization and environment contributed to 61% of individual IDTEs, and the top 5 individual drivers of all IDTEs were travel and tourism, food and water quality, natural environment, global trade, and climate.
+Hierarchical cluster analysis of all drivers identified travel and tourism as a distinctly separate driver.
+Monitoring and modeling such disease drivers can help anticipate future IDTEs and strengthen control measures.
+More important, intervening directly on these underlying drivers can diminish the likelihood of the occurrence of an IDTE and reduce the associated human and economic costs.
+Epithelial sodium channels (ENaC) are localized at the apical membrane of the epithelium, and are responsible for salt and fluid reabsorption.
+Loss-of-function ENaC mutations lead to low blood pressure due to salt-wasting, while gain-of-function mutations cause impaired sodium excretion and subsequent hypertension as well as hypokalemia.
+ENaC activity is regulated by intracellular and extracellular signals, including hormones, neurotransmitters, protein kinases, and small compounds.
+Cyclic nucleotides are broadly involved in stimulating protein kinase A and protein kinase G signaling pathways, and, surprisingly, also appear to have a role in regulating ENaC.
+Increasing evidence suggests that the cGMP analog, CPT-cGMP, activates αβγ-ENaC activity reversibly through an extracellular pathway in a dose-dependent manner.
+Furthermore, the parachlorophenylthio moiety and ribose 2'-hydroxy group of CPT-cGMP are essential for facilitating the opening of ENaC channels by this compound.
+Serving as an extracellular ligand, CPT-cGMP eliminates sodium self-inhibition, which is a novel mechanism for stimulating salt reabsorption in parallel to the traditional NO/cGMP/PKG signal pathway.
+In conclusion, ENaC may be a druggable target for CPT-cGMP, leading to treatments for kidney malfunctions in salt reabsorption.
+During virus entry, the surface glycoprotein of Ebola virus (EBOV) undergoes a complex set of transformations within the endosomal network.
+Tools to study EBOV entry have been limited to static immunofluorescence or biochemical and functional analysis.
+reported a novel, live-cell-imaging method that tracks this transformational journey of EBOV in real time [J. S. Spence, T. B. Krause, E. Mittler, R. K. Jangra, and K. Chandran, mBio 7(1):e01857-15, 2016, http://dx.doi.org/10.1128/mBio.01857-15].
+The assay validates known mechanisms of EBOV entry and sheds light on some novel intricacies.
+Direct evidence supports the hypothesis that fusion is a rare event that starts in maturing early endosomes, is completed in late endosomes, and occurs entirely in Niemann-Pick C1 (NPC1)-positive (NPC1(+)) compartments.
+The study demonstrated that lipid mixing and productive fusion are temporally decoupled, with different energetic barriers and a protease-dependent step between the two events.
+Analysis of the mechanism of action of an important class of EBOV neutralizing antibodies, such as KZ52 and ZMapp, provides direct evidence that these antibodies act by inhibiting the membrane fusion.
+The receptor(s) for porcine sapelovirus (PSV), which causes diarrhea, pneumonia, polioencephalomyelitis, and reproductive disorders in pigs, remains largely unknown.
+Given the precedent for other picornaviruses which use terminal sialic acids (SAs) as receptors, we examined the role of SAs in PSV binding and infection.
+Using a variety of approaches, including treating cells with a carbohydrate-destroying chemical (NaIO(4)), mono- or oligosaccharides (N-acetylneuraminic acid, galactose, and 6′-sialyllactose), linkage-specific sialidases (neuraminidase and sialidase S), lectins (Maakia amurensis lectin and Sambucus nigra lectin), proteases (trypsin and chymotrypsin), and glucosylceramide synthase inhibitors (dl-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol and phospholipase C), we demonstrated that PSV could recognize α2,3-linked SA on glycolipids as a receptor.
+On the other hand, PSVs had no binding affinity for synthetic histo-blood group antigens (HBGAs), suggesting that PSVs could not use HBGAs as receptors.
+Depletion of cell surface glycolipids followed by reconstitution studies indicated that GD1a ganglioside, but not other gangliosides, could restore PSV binding and infection, further confirming α2,3-linked SA on GD1a as a PSV receptor.
+Our results could provide significant information on the understanding of the life cycle of sapelovirus and other picornaviruses.
+For the broader community in the area of pathogens and pathogenesis, these findings and insights could contribute to the development of affordable, useful, and efficient drugs for anti-sapelovirus therapy.
+IMPORTANCE The porcine sapelovirus (PSV) is known to cause enteritis, pneumonia, polioencephalomyelitis, and reproductive disorders in pigs.
+Using a variety of approaches, we showed that α2,3-linked terminal sialic acid (SA) on the cell surface GD1a ganglioside could be used for PSV binding and infection as a receptor.
+On the other hand, histo-blood group antigens also present in the cell surface carbohydrates could not be utilized as PSV receptors for binding and infection.
+These findings should contribute to the understanding of the sapelovirus life cycle and to the development of affordable, useful and efficient drugs for anti-sapelovirus therapy.
+Low-fidelity RNA-dependent RNA polymerases for many RNA virus mutators have been shown to confer attenuated phenotypes, presumably due to increased mutation rates.
+Additionally, for many RNA viruses, replication to high titers results in the production of defective interfering particles (DIs) that also attenuate infection.
+We show that a Sindbis virus mutator replicating at a high multiplicity of infection manifests an earlier and greater accumulation of DIs than its wild-type counterpart.
+Importantly, the ability of the mutator virus to overproduce DIs could be linked to an increased recombination frequency.
+These data confirm that RNA-dependent RNA polymerase fidelity and recombination are inversely correlated for this mutator.
+Our findings suggest that defective interference resulting from higher recombination rates may be more detrimental to RNA virus mutators than the increase in mutational burden.
+IMPORTANCE Replication, adaptation, and evolution of RNA viruses rely in large part on their low-fidelity RNA-dependent RNA polymerase.
+Viruses artificially modified in their polymerases to decrease fidelity (mutator viruses) are attenuated in vivo, demonstrating the important role of fidelity in viral fitness.
+However, attenuation was attributed solely to the modification of the viral mutation rate and the accumulation of detrimental point mutations.
+In this work, we described an additional phenotype of mutator viruses: an increased recombination rate leading to defective interfering particle (DI) overproduction.
+Because DIs are known for their inhibitory effect on viral replication, our work suggests that fidelity variants may be attenuated in vivo via several mechanisms.
+This has important implications in the development of fidelity variants as live attenuated vaccine strains.
+The main drawbacks in their development and use have been reliance on an unpredictable method of attenuation and the potential for evolutionary reversion to high virulence.
+Methods of genetic engineering now provide many safer alternatives to live vaccines, so if live vaccines are to compete with these alternatives in the future, they must either have superior immunogenicity or they must be able to overcome these former disadvantages.
+Several live vaccine designs that were historically inaccessible are now feasible because of advances in genome synthesis.
+Some of those methods are addressed here, with an emphasis on whether they enable predictable levels of attenuation and whether they are stable against evolutionary reversion.
+These new designs overcome many of the former drawbacks and position live vaccines to be competitive with alternatives.
+Not only do new methods appear to retard evolutionary reversion enough to prevent vaccine-derived epidemics, but it may even be possible to permanently attenuate live vaccines that are transmissible but cannot evolve to higher virulence under prolonged adaptation.
+Entry by fusion with the endosomal membrane requires the fusion loop (FL, residues 507–560) of the EBOV surface glycoprotein to undergo a pH-dependent conformational change.
+To find the pH trigger for this reaction we mutated multiple conserved histidines and charged and uncharged hydrophilic residues in the FL and measured their activity by liposome fusion and cell entry of virus-like particles.
+The FL location in the membrane was assessed by NMR using soluble and lipid-bound paramagnetic relaxation agents.
+While we could not identify a single residue to be alone responsible for pH triggering, we propose that a distributed pH effect over multiple residues induces the conformational change that enhances membrane insertion and triggers the fusion activity of the EBOV FL.
+BACKGROUND: Immunocompromised patients are at high risk for morbidity and mortality due to respiratory syncytial virus (RSV) infection.
+Data regarding the clinical presentation and outcomes of RSV in the outpatient pediatric immunocompromised population are limited.
+METHODS: We performed a retrospective cohort study of children with hematologic malignancy or hematopoietic or solid organ transplant with laboratory‐confirmed RSV infection diagnosed as outpatients at an academic medical center between 2008 and 2013.
+RESULTS: Of 54 patients with RSV detected while outpatients, 15 (28%) were hospitalized, 7 (13%) received ribavirin, and one (2%) received intravenous immunoglobulin.
+One (2%) patient was critically ill, but there were no deaths due to RSV infection.
+CONCLUSIONS: Most immunocompromised children with RSV detected while outpatients did not require hospitalization or receive antiviral treatment.
+To examine coxsackievirus pathogenesis, we orally inoculated mice with the coxsackievirus B3 (CVB3) Nancy strain.
+Using HeLa cell plaque assays with agar overlays, we noticed that some fecal viruses generated plaques >100 times as large as inoculum viruses.
+We identified a single amino acid change, N63Y, in the VP3 capsid protein that was sufficient to confer the large-plaque phenotype.
+Wild-type CVB3 and N63Y mutant CVB3 had similar plaque sizes when agarose was used in the overlay instead of agar.
+We determined that sulfated glycans in agar inhibited plaque formation by wild-type CVB3 but not by N63Y mutant CVB3.
+Furthermore, N63Y mutant CVB3 bound heparin, a sulfated glycan, less efficiently than wild-type CVB3 did.
+While N63Y mutant CVB3 had a growth defect in cultured cells and reduced attachment, it had enhanced replication and pathogenesis in mice.
+Infection with N63Y mutant CVB3 induced more severe hepatic damage than infection with wild-type CVB3, likely because N63Y mutant CVB3 disseminates more efficiently to the liver.
+Our data reinforce the idea that culture-adapted laboratory virus strains can have reduced fitness in vivo.
+N63Y mutant CVB3 may be useful as a platform to understand viral adaptation and pathogenesis in animal studies.
+Recent research has suggested significant negative effects of the Global Financial Crisis (GFC) on mental health and wellbeing.
+In this article, the authors suggest that the developmental period of late adolescence may be at particular risk of economic downturns.
+Harmonizing 4 longitudinal cohorts of Australian youth (N = 38,017), we estimate the impact of the GFC on 1 general and 11 domain specific measures of wellbeing at age 19 and 22.
+Significant differences in wellbeing in most life domains were found, suggesting that wellbeing is susceptible to economic shocks.
+Given that the GFC in Australia was relatively mild, the finding of clear negative effects across 2 ages is of international concern.
+AIM: To investigate the antiviral effects of vectors expressing specific short hairpin RNAs (shRNAs) against Hantaan virus (HTNV) infection in vitro and in vivo.
+METHODS: Based on the effects of 4 shRNAs targeting different regions of HTNV genomic RNA on viral replication, the most effective RNA interference fragments of the S and M genes were constructed in pSilencer-3.0-H1 vectors, and designated pSilencer-S and pSilencer-M, respectively.
+The antiviral effect of pSilencer-S/M against HTNV was evaluated in both HTNV-infected Vero-E6 cells and mice.
+RESULTS: In HTNV-infected Vero-E6 cells, pSilencer-S and pSilencer-M targeted the viral nucleocapsid proteins and envelope glycoproteins, respectively, as revealed in the immunofluorescence assay.
+Transfection with pSilencer-S or pSilencer-M (1, 2, 4 μg) markedly inhibited the viral antigen expression in dose- and time-dependent manners.
+Transfection with either plasmid (2 μg) significantly decreased HTNV-RNA level at 3 day postinfectin (dpi) and the progeny virus titer at 5 dpi.
+In mice infected with lethal doses of HTNV, intraperitoneal injection of pSilencer-S or pSilencer-M (30 μg) considerably increased the survival rates and mean time to death, and significantly reduced the mean virus yields and viral RNA level, and alleviated virus-induced pathological lesions in lungs, brains and kidneys.
+Our results provide a basis for development of shRNA as therapeutics for HTNV infections in humans.
+The chick chorioallantoic membrane (CAM) is a widely used model for the study of angiogenesis, tumour growth, as well as drug efficacy.
+In spite of this, little is known about the developmental alteration from its appearance to the time of hatching.
+Expression levels of selected angiogenesis-related molecules were estimated by RT-PCR and cell dynamics assessed by proliferation and apoptosis assays.
+Absolute CAM volume increased from a low of 0.47 ± 0.11 cm(3) at embryonic day 8 (E8) to a high of 2.05 ± 0.27 cm(3) at E18, and then decreased to 1.6 ± 0.47 cm(3) at E20.
+Between E8-13 (phase I), the CAM grew fastest; moderately in phase II (E13-18) but was regressing in phase III (E18-20).
+The chorion, the mesenchyme and the allantoic layers grew fastest in phase I, but moderately in phase II.
+Both the chorion and the allantois grew by intrinsic cell proliferation as well as recruitment of cells from the mesenchyme.
+Cell proliferation was prominent in the allantois and chorion early during development, declined after E17 and apoptosis started mainly in the chorion from E14.
+VEGFR2 expression peaked at E11 and declined steadily towards E20, VEGF peaked at E13 and E20 while HIF 1α had a peak at E11 and E20.
+BACKGROUND: cRel, a subunit of NF-κB, is implicated in the inflammatory response observed in autoimmune disease.
+Hence, knocked-out mice for cRel had a significantly higher mortality, providing new and important functions of cRel in the physiopathology of septic shock.
+Whether genetic variants in the human REL gene are associated with severity of septic shock is unknown.
+METHODS: We genotyped a population of 1040 ICU patients with septic shock and 855 ICU controls for two known polymorphisms of REL; REL rs842647 and REL rs13031237.
+RESULTS: The distribution of REL variant alleles was not significantly different between patients and controls.
+Among the septic shock group, REL rs13031237*T minor allele was not associated with worse outcome.
+In contrast, REL rs842647*G minor allele was significantly associated with more multi-organ failure and early death [OR 1.4; 95 % CI (1.02–1.8)].
+CONCLUSION: In a large ICU population, we report a significant clinical association between a variation in the human REL gene and severity and mortality of septic shock, suggesting for the first time a new insight into the role of cRel in response to infection in humans.
+The small GTPase Rab5 has been well defined to control the vesicle-mediated plasma membrane protein transport to the endosomal compartment.
+However, its function in the internalization of vascular endothelial (VE)-cadherin, an important component of adherens junctions, and as a result regulating the endothelial cell polarity and barrier function remain unknown.
+Here, we demonstrated that lipopolysaccharide (LPS) simulation markedly enhanced the activation and expression of Rab5 in human pulmonary microvascular endothelial cells (HPMECs), which is accompanied by VE-cadherin internalization.
+In parallel, LPS challenge also induced abnormal cell polarity and dysfunction of the endothelial barrier in HPMECs.
+LPS stimulation promoted the translocation of VE-cadherin from the plasma membrane to intracellular compartments, and intracellularly expressed VE-cadherin was extensively colocalized with Rab5.
+Small interfering RNA (siRNA)-mediated depletion of Rab5a expression attenuated the disruption of LPS-induced internalization of VE-cadherin and the disorder of cell polarity.
+Furthermore, knockdown of Rab5 inhibited the vascular endothelial hyperpermeability and protected endothelial barrier function from LPS injury, both in vitro and in vivo.
+These results suggest that Rab5 is a critical mediator of LPS-induced endothelial barrier dysfunction, which is likely mediated through regulating VE-cadherin internalization.
+These findings provide evidence, implicating that Rab5a is a potential therapeutic target for preventing endothelial barrier disruption and vascular inflammation.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00018-015-1973-4) contains supplementary material, which is available to authorized users.
+Recent successes with monoclonal antibody cocktails ZMapp(TM) and MIL77 against Ebola virus (EBOV) infections have reignited interest in antibody-based therapeutics.
+Since the production process for monoclonal antibodies can be prolonged and costly, alternative treatments should be investigated.
+We produced purified equine antisera from horses hyperimmunized with EBOV virus-like particles, and tested the post-exposure efficacy of the antisera in a mouse model of infection.
+BALB/c mice were given up to 2 mg of purified equine antisera per animal, at 30 minutes, 1 or 2 days post-infection (dpi), in which all animals survived.
+To decrease the possibility of serum sickness, the equine antisera was digested with pepsin to generate F(ab′)(2) fragments, with in vitro neutralizing activity comparable to whole immunoglobulin.
+Full protection was achieved with when treatment was initiated at 1 dpi, but the suboptimal protection observed with the 30 minute and 2 dpi groups demonstrate that in addition to virus neutralization, other Fc-dependent antibody mechanisms may also contribute to survival.
+Guinea pigs given 20 mg of antisera or F(ab′)(2) at or starting at 1 or 2 dpi were also fully protected from EBOV infection.
+Accumulating evidence indicates that angiotensin-converting enzyme 2 (ACE2) plays a critical role in cardiovascular homeostasis, and its altered expression is associated with major cardiac and vascular disorders.
+The aim of this study was to evaluate the regulation of vascular function and assess the vascular redox balance in ACE2-deficient (ACE2(-/y)) animals.
+Evaluation of endothelium-dependent and -independent relaxation revealed an impairment of in vitro and in vivo vascular function in ACE2(-/y) mice.
+Drastic reduction in eNOS expression at both protein and mRNA levels, and a decrease in (•)NO concentrations were observed in aortas of ACE2(-/y) mice in comparison to controls.
+Consistently, these mice presented a lower plasma and urine nitrite concentration, confirming reduced (•)NO availability in ACE2-deficient animals.
+Lipid peroxidation was significantly increased and superoxide dismutase activity was decreased in aorta homogenates of ACE2(-/y) mice, indicating impaired antioxidant capacity.
+Taken together, our data indicate, that ACE2 regulates vascular function by modulating nitric oxide release and oxidative stress.
+In conclusion, we elucidate mechanisms by which ACE2 is involved in the maintenance of vascular homeostasis.
+Furthermore, these findings provide insights into the role of the renin-angiotensin system in both vascular and systemic redox balance.
+Physical entanglement, and particularly knots arise spontaneously in equilibrated polymers that are sufficiently long and densely packed.
+Biopolymers are no exceptions: knots have long been known to occur in proteins as well as in encapsidated viral DNA.
+The rapidly growing number of RNA structures has recently made it possible to investigate the incidence of physical knots in this type of biomolecule, too.
+In this Point of View Article we discuss the absence of knots in currently available RNAs and consider the reasons why knots in RNA have not yet been found, despite the expectation that they should exist in Nature.
+We conclude by singling out a number of RNA sequences that, based on the properties of their predicted secondary structures, are good candidates for knotted RNAs.
+Detection of small particles, including viruses and particulate matter (PM), has been attracting much attention in light of increasing need for environmental monitoring.
+Owing to their high versatility, a nanomechanical sensor is one of the most promising sensors which can be adapted to various monitoring systems.
+In this study, we present an optimization strategy to efficiently detect small particles with nanomechanical sensors.
+Adsorption of particles on the receptor layer of nanomechanical sensors and the resultant signal are analyzed using finite element analysis (FEA).
+We investigate the effect of structural parameters (e.g., adsorption position and embedded depth of a particle and thickness of the receptor layer) and elastic properties of the receptor layer (e.g., Young's modulus and Poisson's ratio) on the sensitivity.
+It is found that a membrane-type surface stress sensors (MSS) has the potential for robust detection of small particles.
+Bovine respiratory disease (BRD) is the leading cause of morbidity and mortality in feedlot cattle, caused by multiple pathogens that become more virulent in response to stress.
+As clinical signs often go undetected and various preventive strategies failed, identification of genes affecting BRD is essential for selection for resistance.
+Selective DNA pooling (SDP) was applied in a genome wide association study (GWAS) to map BRD QTLs in Israeli Holstein male calves.
+Kosher scoring of lung adhesions was used to allocate 122 and 62 animals to High (Glatt Kosher) and Low (Non-Kosher) resistant groups, respectively.
+Moving average of -logP was used to map QTLs and Log drop was used to define their boundaries (QTLRs).
+The QTLRs contain polymorphic functional and expression candidate genes to affect kosher status, with putative immunological and wound healing activities.
+Kosher phenotyping was shown to be a reliable means to map QTLs affecting BRD morbidity.
+The current parenteral mode of vaccination stimulates systemic immunity well, but it does not induce sufficient mucosal immunity.
+Retinoic acid (RA) plays an important role in the induction of cells that imprint gut-homing molecules.
+We demonstrated that elevated numbers of gut-homing CD8(+) T cells (which express α4β7 and CCR9 molecules) were presented in porcine inguinal lymph nodes and were recruited to the small intestine by RA.
+Intestinal mucosal immunity (IgA titre) and systemic immunity (serum IgG titre) were enhanced by RA.
+Therefore, we hypothesized that RA could induce DCs to form an immature mucosal phenotype and could recruit them to the small intestinal submucosa.
+Porcine T-cells expressed β7 integrin and CCR9 receptors and migrated to CCL25 by a mechanism that was dependent of activation by RA-pretreated DCs, rather than direct activation by RA.
+Together, our results provide powerful evidence that RA can assist whole inactivated TGEV (WI-TGEV) via subcutaneous (s.c.) immunization to generate intestinal immunity, and offer new vaccination strategies against TGEV.
+BACKGROUND: Pulmonary infections caused by Pneumocystis jirovecii in immunocompromised host can be associated with cysts, pneumatoceles and air leaks that can progress to pneumomediastinum and pneumothoraxes.
+In such cases, it can be challenging to maintain adequate gas exchange by conventional mechanical ventilation and at the same time prevent further ventilator-induced lung injury.
+We report a young HIV positive male with poorly compliant lungs and pneumomediastinum secondary to severe Pneumocystis infection, rescued with veno-venous extra corporeal membrane oxygenation (V-V ECMO).
+CASE PRESENTATION: A 26 year old male with no significant past medical history was admitted with fever, cough and shortness of breath.
+However, his respiratory function progressively deteriorated due to increasing pulmonary infiltrates and development of pneumomediastinum, eventually requiring endotracheal intubation and invasive ventilation.
+Despite attempts at optimizing gas exchange by ventilatory maneuvers, patients’ pulmonary parameters worsened necessitating rescue ECMO therapy.
+The introduction of V-V ECMO facilitated the use of ultra-protective lung ventilation and prevented progression of pneumomediastinum, maintaining optimal gas exchange.
+Further diagnostic workup revealed Pneumocystis jirovecii as the causative organism for pneumonia and serology confirmed Human Immunodeficiency Virus infection.
+Patient was successfully treated with appropriate antimicrobials and de-cannulated after six days of ECMO support.
+CONCLUSION: ECMO was an effective salvage therapy in HIV positive patient with an otherwise fatal respiratory failure due to Pneumocystis pneumonia and air leak syndrome.
+BACKGROUND: Japanese encephalitis (JE), a leading cause of viral encephalitis, is characterized by extensive neuroinflammation following infection with neurotropic JE virus (JEV).
+Although the regulatory role of IDO in viral replication has been postulated, the in vivo role of IDO activity has not been fully addressed in neurotropic virus-caused encephalitis.
+METHODS: Mice in which IDO activity was inhibited by genetic ablation or using a specific inhibitor were examined for mortality and clinical signs after infection.
+IDO expression, viral burden, JEV-specific T-cell, and type I/II interferon (IFN-I/II) innate responses were also analyzed.
+RESULTS: Elevated expression of IDO activity in myeloid and neuron cells of the lymphoid and CNS tissues was closely associated with clinical signs of JE.
+Furthermore, inhibition of IDO activity enhanced resistance to JE, reduced the viral burden in lymphoid and CNS tissues, and resulted in early and increased CNS infiltration by Ly-6C(hi) monocytes, NK, CD4(+), and CD8(+) T-cells.
+JE amelioration in IDO-ablated mice was also associated with enhanced NK and JEV-specific T-cell responses.
+More interestingly, IDO ablation induced rapid enhancement of type I IFN (IFN-I) innate responses in CD11c(+) dendritic cells (DCs), including conventional and plasmacytoid DCs, following JEV infection.
+This enhanced IFN-I innate response in IDO-ablated CD11c(+) DCs was coupled with strong induction of PRRs (RIG-I, MDA5), transcription factors (IRF7, STAT1), and antiviral ISG genes (Mx1, Mx2, ISG49, ISG54, ISG56).
+IDO ablation also enhanced the IFN-I innate response in neuron cells, which may delay the spread of virus in the CNS.
+Finally, we identified that IDO ablation in myeloid cells derived from hematopoietic stem cells (HSCs) dominantly contributed to JE amelioration and that HSC-derived leukocytes played a key role in the enhanced IFN-I innate responses in the IDO-ablated environment.
+CONCLUSIONS: Inhibition of IDO activity ameliorated JE via enhancement of antiviral IFN-I/II innate and adaptive T-cell responses and increased CNS infiltration of peripheral leukocytes.
+Therefore, our data provide valuable insight into the use of IDO inhibition by specific inhibitors as a promising tool for therapeutic and prophylactic strategies against viral encephalitis caused by neurotropic viruses.
+Cleavage of influenza virus hemagglutinin (HA) by host cell proteases is necessary for viral activation and infectivity.
+In humans and mice, members of the type II transmembrane protease family (TTSP), e.g., TMPRSS2, TMPRSS4, and TMPRSS11d (HAT), have been shown to cleave influenza virus HA for viral activation and infectivity in vitro.
+Recently, we reported that inactivation of a single HA-activating protease gene, Tmprss2, in knockout mice inhibits the spread of H1N1 influenza viruses.
+However, after infection of Tmprss2 knockout mice with an H3N2 influenza virus, only a slight increase in survival was observed, and mice still lost body weight.
+Both TMPRSS2 and TMPRSS4 are expressed in the same cell types of the mouse lung.
+Deletion of Tmprss4 alone in knockout mice does not protect them from body weight loss and death upon infection with H3N2 influenza virus.
+In contrast, Tmprss2(−/−) Tmprss4(−/−) double-knockout mice showed a remarkably reduced virus spread and lung pathology, in addition to reduced body weight loss and mortality.
+Thus, our results identified TMPRSS4 as a second host cell protease that, in addition to TMPRSS2, is able to activate the HA of H3N2 influenza virus in vivo.
+Due to high variability of the virus genome, resistance to available antiviral drugs is frequently observed, and new targets for treatment of influenza are needed.
+Host cell factors essential for processing of the virus hemagglutinin represent very suitable drug targets because the virus is dependent on these host factors for replication.
+We reported previously that Tmprss2-deficient mice are protected against H1N1 virus infections, but only marginal protection against H3N2 virus infections was observed.
+Here we show that deletion of two host protease genes, Tmprss2 and Tmprss4, strongly reduced viral spread as well as lung pathology and resulted in increased survival after H3N2 virus infection.
+Thus, TMPRSS4 represents another host cell factor that is involved in cleavage activation of H3N2 influenza viruses in vivo.
+Pigs are believed to be one of the important sources of emerging human and swine influenza viruses (SwIV).
+Influenza virus conserved peptides have the potential to elicit cross-protective immune response, but without the help of potent adjuvant and delivery system they are poorly immunogenic.
+Biodegradable polylactic-co-glycolic acid (PLGA) nanoparticle (PLGA-NP) based vaccine delivery system enhances cross-presentation of antigens by the professional antigen presenting cells.
+In this study, Norovirus P particle containing SwIV M2e (extracellular domain of the matrix protein 2) chimera and highly conserved two each of H1N1 peptides of pandemic 2009 and classical human influenza viruses were entrapped in PLGA-NPs.
+Influenza antibody-free pigs were vaccinated with PLGA-NPs peptides cocktail vaccine twice with or without an adjuvant, Mycobacterium vaccae whole cell lysate, intranasally as mist.
+Vaccinated pigs were challenged with a virulent heterologous zoonotic SwIV H1N1, and one week later euthanized and the lung samples were analyzed for the specific immune response and viral load.
+Clinically, pigs vaccinated with PLGA-NP peptides vaccine had no fever and flu symptoms, and the replicating challenged SwIV was undetectable in the bronchoalveolar lavage fluid.
+Immunologically, PLGA-NP peptides vaccination (without adjuvant) significantly increased the frequency of antigen-specific IFNγ secreting CD4 and CD8 T cells response in the lung lymphocytes, despite not boosting the antibody response both at pre- and post-challenge.
+In summary, our data indicated that nanoparticle-mediated delivery of conserved H1N1 influenza peptides induced the virus specific T cell response in the lungs and reduced the challenged heterologous virus load in the airways of pigs.
+The genome of influenza A virus (IAV) comprises eight RNA segments (vRNA) which are transcribed and replicated by the heterotrimeric IAV RNA-dependent RNA-polymerase (RdRp).
+RdRp consists of three subunits (PA, PB1 and PB2) and binds both the highly conserved 3′- and 5′-ends of the vRNA segment.
+The IAV RdRp is an important antiviral target, but its structural mechanism has remained largely elusive to date.
+By applying a polyprotein strategy, we produced RdRp complexes and define a minimal human IAV RdRp core complex.
+We show that PA-PB1 forms a stable heterodimeric submodule that can strongly interact with 5′-vRNA.
+Moreover, we demonstrate that PA-PB1 forms a stable and stoichiometric complex with host nuclear import factor RanBP5 that can be modelled using SAXS and we show that the PA-PB1-RanPB5 complex is no longer capable of 5′-vRNA binding.
+Our results provide further evidence for a step-wise assembly of IAV structural components, regulated by nuclear transport mechanisms and host factor binding.
+OBJECTIVES: Actively recruit and intensively follow pregnant women receiving a dose of acellular pertussis vaccine for 4 weeks after vaccination.
+PARTICIPANTS: Women in their 28th–38th week of pregnancy, recruited from primary care and antenatal clinics at the time of Tdap administration.
+MAIN OUTCOMES MEASURES: Outcomes were injection site reactions, systemic symptoms and serious adverse events (SAEs).
+Any swelling was reported by 7.6%, induration by 12.0% (collected from 1 site only, n=326), and erythema by 5.8% of participants.
+Fever was reported by 17 (2.1%) participants, 14 of these occurred within 24 h. Headache, dizziness, nausea, myalgia or arthralgia was reported by <4% of participants, respectively, and fatigue by 8.4%.
+During the study period, there were 115 adverse events in 113 participants, most of which were minor.
+At the end of the reporting period, 31 events were classified as serious (eg, obstetric bleeding, hypertension, infection, tachycardia, preterm labour, exacerbation of pre-existing condition and pre-eclampsia).
+CONCLUSIONS: Vaccination with Tdap in pregnant women was well tolerated with no SAE likely to be caused by the vaccine.
+West Nile virus (WNV) is a positive sense, single-stranded RNA virus that can cause illness in humans when transmitted via mosquito vectors.
+Unfortunately, no antivirals or vaccines are currently available, and therefore efficient and safe antivirals are urgently needed.
+We developed a high throughput screen to discover small molecule probes that inhibit virus infection of Vero E6 cells.
+A primary screen of a 13,001 compound library at a 10 μM final concentration was conducted using the 384-well format.
+Twenty-six compounds showed a dose response in the HT screen and were further evaluated in a time of addition assay and in a titer reduction assay.
+The hit rate from the primary screen was 0.185% (24 compounds out of 13,001 compounds) and from the secondary screens was 0.053% (7 out of 13,001 compounds) respectively.
+The Ebola outbreak of 2013–15 infected more than 28 000 people and claimed more lives than all previous filovirus outbreaks combined.
+Governmental agencies, clinical teams, and the world scientific community pulled together in a multifaceted response ranging from prevention and disease control, to evaluating vaccines and therapeutics in human trials.
+As this epidemic is finally coming to a close, refocusing on long-term prevention strategies becomes paramount.
+Given the very real threat of future filovirus outbreaks, and the inherent uncertainty of the next outbreak virus and geographic location, it is prudent to consider the extent and implications of known natural diversity in advancing vaccines and therapeutic approaches.
+To facilitate such consideration, we have updated and enhanced the content of the filovirus portion of Los Alamos Hemorrhagic Fever Viruses Database.
+We have integrated and performed baseline analysis of all family Filoviridae sequences deposited into GenBank, with associated immune response data, and metadata, and we have added new computational tools with web-interfaces to assist users with analysis.
+Here, we (i) describe the main features of updated database, (ii) provide integrated views and some basic analyses summarizing evolutionary patterns as they relate to geo-temporal data captured in the database and (iii) highlight the most conserved regions in the proteome that may be useful for a T cell vaccine strategy.
+In this study, surgically isolated ileal segments in newborn calves (n = 5) were used to establish in vivo MAP infection adjacent to an uninfected control intestinal compartment.
+RNA-Seq was used to profile the whole transcriptome (mRNAs) and the microRNAome (miRNAs) of ileal tissues collected at one-month post-infection.
+The most related function of the differentially expressed mRNAs between infected and uninfected tissues was “proliferation of endothelial cells”, indicating that MAP infection may lead to the over-proliferation of endothelial cells.
+The pre-mRNA of two genes related to macrophage maturation (monocyte to macrophage differentiation-associated) and lysosome function (adenosine deaminase) showed differential alternative splicing events, suggesting that specific changes in the pre-mRNA splicing sites may be a mechanism by which MAP escapes host immune responses.
+The integrated analysis of microRNAome and transcriptome revealed that these miRNAs might regulate host responses to MAP infection, such as “proliferation of endothelial cells” (bta-miR-196 b), “bacteria recognition” (bta-miR-146 b), and “regulation of the inflammatory response” (bta-miR-146 b).
+Differences in the pathogenicity of genetically closely related H5N1 highly pathogenic avian influenza viruses (HPAIVs) were evaluated in White Leghorn chickens.
+These viruses varied in the clinical symptoms they induced, including lethality, virus shedding, and replication in host tissues.
+A comparison of the host responses in the lung, brain, and spleen suggested that the differences in viral replication efficiency were related to the host cytokine response at the early phase of infection, especially variations in the proinflammatory cytokine IL-6.
+Based on these findings, we inoculated the virus that showed the mildest pathogenicity among the five tested, A/pigeon/Thailand/VSMU-7-NPT/2004, into four breeds of Thai indigenous chicken, Phadu-Hung-Dang (PHD), Chee, Dang, and Luang-Hung-Khao (LHK), to explore effects of genetic background on host response.
+Among these breeds, Chee, Dang, and LHK showed significantly longer survival times than White Leghorns.
+Virus shedding from dead Thai indigenous chickens was significantly lower than that from White Leghorns.
+Although polymorphisms were observed in the Mx and MHC class I genes, there was no significant association between the polymorphisms in these loci and resistance to HPAIV.
+In this study, we describe a web-based resource, developed for assisting the scientific community in designing an effective therapeutics against the Ebola virus.
+Firstly, we predicted and identified experimentally validated epitopes in each of the antigens/proteins of the five known ebolaviruses.
+Thirdly, conserved peptides across all the five ebolaviruses (four human pathogenic species) with no identical sequence in the human proteome, based on 1000 Genomes project, were identified.
+Finally, we identified peptide or epitope-based vaccine candidates that could activate both the B- and T-cell arms of the immune system.
+In addition, we also identified efficacious siRNAs against the mRNA transcriptome (absent in human transcriptome) of all the five ebolaviruses.
+It was observed that three species can potentially be targeted by a single siRNA (19mer) and 75 siRNAs can potentially target at least two species.
+A web server, EbolaVCR, has been developed that incorporates all the above information and useful computational tools (http://crdd.osdd.net/oscadd/ebola/).
+Porcine reproductive and respiratory syndrome virus (PRRSV) is known to cause reproductive disorders, such as abortion, in pregnant sows as well as immunosuppressive respiratory complications, leading to severe respiratory tract infections in young pigs.
+In this study, an in-depth analysis of the miRNomes in mock- and virus-infected pig lungs was carried out.
+We found that highly expressed ssc-miR-30d-R_1 was decreased in infected lungs, and reduced levels were significantly correlated with infection by PRRSV.
+Moreover, ssc-miR-30d-R_1 was shown to target Toll-like receptor 4 (TLR4) and to suppress the production of immune cytokines through inhibition of the TLR4/MyD88/NF-κB pathway.
+Our current study reveals the miRNomes of PRRSV-infected pig lungs and indicates that ssc-miR-30d-R_1 is potential therapeutic agent for controlling PRRSV infection.
+Enteroviruses such as poliovirus (PV) and coxsackievirus B3 (CVB3) have evolved several parallel strategies to regulate cellular gene expression and stress responses to ensure efficient expression of the viral genome.
+Enteroviruses utilize their encoded proteinases to take over the cellular translation apparatus and direct ribosomes to viral mRNAs.
+In addition, viral proteinases are used to control and repress the two main types of cytoplasmic RNA granules, stress granules (SGs) and processing bodies (P-bodies, PBs), which are stress-responsive dynamic structures involved in repression of gene expression.
+This review discusses these processes and the current understanding of the underlying mechanisms with respect to enterovirus infections.
+In addition, the review discusses accumulating data suggesting linkage exists between RNA granule formation and innate immune sensing and activation.
+Chains can be formed via different linkages, which determines the type of signal they convey.
+Most tools for monitoring DUB specificity target binding pockets on opposing sides of the active site; however, some DUBs contain additional pockets.
+We report the development of active site-directed probes and fluorogenic substrates, based on non-hydrolyzable diubiquitin, that are equipped with a C-terminal warhead or a fluorogenic activity reporter moiety.
+We demonstrate that various DUBs in lysates display differential reactivity toward differently linked diubiquitin probes, as exemplified by the proteasome-associated DUB USP14.
+Despite considerable advances in the research and treatment, the precise relationship between inflammation and cardiovascular (CV) disease remains incompletely understood.
+Therefore, understanding the immunoinflammatory processes underlying the initiation, progression, and exacerbation of many cardiovascular diseases is of prime importance.
+Recent studies suggest that altered ionic balance, and production of noxious gaseous mediators link to immune and inflammatory responses with altered ion channel expression and function.
+Among plausible candidates for this are transient receptor potential (TRP) channels that function as polymodal sensors and scaffolding proteins involved in many physiological and pathological processes.
+In this review, we will first focus on the relevance of TRP channel to both exogenous and endogenous factors related to innate immune response and transcription factors related to sustained inflammatory status.
+The emerging role of inflammasome to regulate innate immunity and its possible connection to TRP channels will also be discussed.
+Secondly, we will discuss about the linkage of TRP channels to inflammatory CV diseases, from a viewpoint of inflammation in a general sense which is not restricted to the innate immunity.
+These knowledge may serve to provide new insights into the pathogenesis of various inflammatory CV diseases and their novel therapeutic strategies.
+BACKGROUND: It has been observed that, historically, strains of pandemic influenza led to succeeding seasonal waves, albeit with decidedly different patterns.
+Recent studies suggest that the 2009 A(H1N1)pdm09 pandemic has had an impact on the circulation patterns of seasonal influenza strains in the post-pandemic years.
+In this work we aim to investigate this issue and also to compare the relative transmissibility of these waves of differing strains using Taiwan influenza surveillance data before, during and after the pandemic.
+METHODS: We make use of the Taiwan Center for Disease Control and Prevention influenza surveillance data on laboratory-confirmed subtyping of samples and a mathematical model to determine the waves of circulating (and co-circulating) H1, H3 and B virus strains in Taiwan during 2008–2014; or namely, short before, during and after the 2009 pandemic.
+We further pinpoint the turning points and relative transmissibility of each wave, in order to ascertain whether any temporal pattern exists.
+RESULTS/FINDINGS: For two consecutive years following the 2009 pandemic, A(H1N1)pdm09 circulated in Taiwan (as in most of Northern Hemisphere), sometimes co-circulating with AH3.
+From the evolution point of view, A(H1N1)pdm09 and AH3 were able to sustain their circulation patterns to the end of 2010.
+In fact, A(H1N1)pdm09 virus circulated in six separate waves in Taiwan between summer of 2009 and spring of 2014.
+Since 2009, a wave of A(H1N1)pmd09 occurred every fall/winter influenza season during our study period except 2011–2012 season, when mainly influenza strain B circulated.
+Moreover, when AH3 or A(H1N1)pdm09 exhibit high incidence, reported cases of subtype B decreases and vice versa.
+Further modeling analysis indicated that during the study period, Taiwan nearly experienced at least one wave of influenza epidemic of some strain every summer except in 2012.
+DISCUSSION: Estimates of R for seasonal influenza are consistent with that of temperate and tropical-subtropical regions, while estimate of R for A(H1N1)pdm09 is comparatively less than countries in Europe and North America, but similar to that of tropical-subtropical regions.
+This offers indication of regional differences in transmissibility of influenza virus that exists only for pandemic influenza.
+Currently, studies are underway to assess the use of probiotics to improve rotavirus vaccine protection.
+infantis CECT 7210 is able to hinder rotavirus replication both in vitro and in vivo.
+The present study takes a systematic approach in order to identify the molecule directly involved in rotavirus inhibition.
+Supernatant protease digestions revealed both the proteinaceous nature of the active substance and the fact that the molecule responsible for inhibiting rotavirus replication is released to the supernatant.
+Following purification by cationic exchange chromatography, active fractions were obtained and the functional compound was identified as an 11-amino acid peptide (MHQPHQPLPPT, named 11-mer peptide) with a molecular mass of 1.282 KDa.
+The functionality of 11-mer was verified using the synthesized peptide in Wa, Ito, and VA70 rotavirus infections of both HT-29 and MA-104 cell lines.
+An outbreak of influenza H1N1 in 2009, representing the first influenza pandemic of the 21st century, was transmitted to over a million individuals and claimed 18,449 lives.
+The current status in many countries is to prepare influenza vaccine using cell-based or egg-based killed vaccine.
+To overcome these limitations, many researchers have tried various approaches to develop alternative production platforms.
+One of the alternative approach, we reported the efficacy of influenza HA vaccination using a baculoviral DNA vaccine (AcHERV-HA).
+However, the immune response elicited by the AcHERV-HA vaccine, which only targets the HA antigen, was lower than that of the commercial killed vaccine.
+To overcome the limitations of this previous vaccine, we constructed a human endogenous retrovirus (HERV) envelope-coated, baculovirus-based, virus-like-particle (VLP)–forming DNA vaccine (termed AcHERV-VLP) against pandemic influenza A/California/04/2009 (pH1N1).
+As a result, AcHERV-VLP immunization produced a greater humoral immune response and exhibited neutralizing activity with an intrasubgroup H1 strain (PR8), elicited neutralizing antibody production, a high level of interferon-γ secretion in splenocytes, and diminished virus shedding in the lung after challenge with a lethal dose of influenza virus.
+In conclusion, VLP-forming baculovirus DNA vaccine could be a potential vaccine candidate capable of efficiently delivering DNA to the vaccinee and VLP forming DNA eliciting stronger immunogenicity than egg-based killed vaccines.
+It is important to elucidate the potential genetic variations that contribute to virus infection susceptibilities.
+In order to identify genetic mutations that might increase host susceptibility to infection, we performed exon sequencing and validated the SNPS by Sanger sequencing on 18 H7N9 patients.
+The genomic DNA was captured with the Agilent SureSelect Human All Exon kit, sequenced on the Illumina Hiseq 2000, and the resulting data processed and annotated with Genome analysis Tool.
+Through exon sequencing and Sanger sequencing, we identified 21 genes that were highly associated with H7N9 influenza infection.
+Protein-protein interaction analysis showed that direct interactions among genetic products were significantly higher than expected (p = 0.004), and DAVID analysis confirmed the defense-related functions of these genes.
+Gene mutation profiles of survived and non-survived patients were similar, suggesting some of genes identified in this study may be associated with H7N9 influenza susceptibility.
+Host specific genetic determinants of disease severity identified by this approach may provide new targets for the treatment of H7N9 influenza.
+The genome sequence of Catopsilia pomona nucleopolyhedrovirus (CapoNPV) was determined by the Roche 454 sequencing system.
+There were 130 hypothetical open reading frames (ORFs) potentially encoding proteins of more than 50 amino acids and covering 92% of the genome.
+Among all the hypothetical ORFs, 37 baculovirus core genes, 23 lepidopteran baculovirus conserved genes and 10 genes conserved in Group I alphabaculoviruses were identified.
+Phylogenic analysis showed that CapoNPV was in a distinct branch of clade “a” in Group I alphabaculoviruses.
+Gene parity plot analysis and overall similarity of ORFs indicated that CapoNPV is more closely related to the Group I alphabaculoviruses than to other baculoviruses.
+Interesting, CapoNPV lacks the genes encoding the fibroblast growth factor (fgf) and ac30, which are conserved in most lepidopteran and Group I baculoviruses, respectively.
+Sequence analysis of the F-like protein of CapoNPV showed that some amino acids were inserted into the fusion peptide region and the pre-transmembrane region of the protein.
+All these unique features imply that CapoNPV represents a member of a new baculovirus species.
+Bombyx mori nucleopolyhedrovirus (BmNPV) is one of the primary pathogens causing severe economic losses in sericulture.
+Here, the recurrent parent P50 (susceptible strain) and the near-isogenic line BC9 (resistance strain) were used in a comparative transcriptome study examining the response to infection with BmNPV.
+A total of 14,300 unigenes were obtained from two different resistant strains; of these, 869 differentially expressed genes (DEGs) were identified after comparing the four transcriptomes.
+Many DEGs associated with protein metabolism, cytoskeleton, and apoptosis may be involved in the host response to BmNPV infection.
+Specifically, after removing genetic background and individual immune stress response genes, 22 genes were found to be potentially involved in repressing BmNPV infection.
+Our study provided an overview of the molecular mechanism of silkworm resistance to BmNPV infection and laid a foundation for controlling BmNPV in the future.
+This paper presents the results of investigations whose aim was to describe the influence of the pressure difference level on the ability of contaminants migration between neighbouring rooms in dynamic conditions associated with door swing.
+The analysis was based on airflow visualization made with cold smoke, which simulated the heavy contaminants.
+The test room was pressurized to a specific level and then the door was opened to observe the trail of the smoke plume in the plane of the door.
+This study focuses on the visualization of smoke plume discharge and an uncertainty analysis is not applicable.
+Unlike other studies which focus on the analysis of pressure difference, the present study looks at the contaminants which are heavier than air and on “pumping out” the contaminants by means of door swing.
+Setting the proper level of pressure difference between the contaminated room and the neighbouring rooms can prove instrumental in ensuring protection against toxic contaminants migration.
+This study helped to establish the threshold of pressure difference necessary to reduce migration of heavy contaminants to neighbouring rooms.
+Endogenous bornavirus-like L (EBLL) elements are inheritable sequences derived from ancient bornavirus L genes that encode a viral RNA-dependent RNA polymerase (RdRp) in many eukaryotic genomes.
+Here, we demonstrate that bats of the genus Eptesicus have preserved for more than 11.8 million years an EBLL element named eEBLL-1, which has an intact open reading frame of 1,718 codons.
+The eEBLL-1 coding sequence revealed that functional motifs essential for mononegaviral RdRp activity are well conserved in the EBLL-1 genes.
+To the best of our knowledge, this study is the first report showing that the eukaryotic genome has gained a riboviral polymerase gene from an ancient virus that has the potential to encode a functional RdRp.
+Antibiotic resistance (AR) is an epidemic of increasing magnitude requiring rapid identification and profiling for appropriate and timely therapeutic measures and containment strategies.
+In this context, ciprofloxacin is part of the first-line of countermeasures against numerous high consequence bacteria.
+Significant resistance can occur via single nucleotide polymorphisms (SNP) and deletions within ciprofloxacin targeted genes.
+Ideally, use of ciprofloxacin would be prefaced with AR determination to avoid overuse or misuse of the antibiotic.
+Here, we describe the development and evaluation of a panel of 44 single-stranded molecular inversion probes (MIPs) coupled to next-generation sequencing (NGS) for the detection of genetic variants known to confer ciprofloxacin resistance in Bacillus anthracis, Yersinia pestis, and Francisella tularensis.
+Sequencing results demonstrate MIPs capture and amplify targeted regions of interest at significant levels of coverage.
+Depending on the genetic variant, limits of detection (LOD) for high-throughput pooled sequencing ranged from approximately 300–1800 input genome copies.
+In addition, we show that MIPs can be used as an enrichment step with high resolution melt (HRM) real-time PCR which is a sensitive assay with a rapid time-to-answer.
+Overall, this technology is a multiplexable upfront enrichment applicable with multiple downstream molecular assays for the detection of targeted genetic regions.
+Ebola virus infections cause a deadly hemorrhagic disease for which no vaccines or therapeutics has received regulatory approval.
+Here we show isolation of three (Q206, Q314 and Q411) neutralizing monoclonal antibodies (mAbs) against the surface glycoprotein (GP) of Ebola virus identified in West Africa in 2014 through sequential immunization of Chinese rhesus macaques and antigen-specific single B cell sorting.
+These mAbs demonstrated potent neutralizing activities against both pseudo and live Ebola virus independent of complement.
+Biochemical, single particle EM, and mutagenesis analysis suggested Q206 and Q411 recognized novel epitopes in the head while Q314 targeted the glycan cap in the GP1 subunit.
+Treatment with these mAbs provided partial but significant protection against disease in a mouse model of Ebola virus infection.
+These novel mAbs could serve as promising candidates for prophylactic and therapeutic interventions against Ebola virus infection.
+BACKGROUND: The widespread sharing of biologicaConcluding Comments: Teaching Responsible Datal and biomedical data is recognised as a key element in facilitating translation of scientific discoveries into novel clinical applications and services.
+At the same time, twenty-first century states are increasingly concerned that this data could also be used for purposes of bioterrorism.
+There is thus a tension between the desire to promote the sharing of data, as encapsulated by the Open Data movement, and the desire to prevent this data from ‘falling into the wrong hands’ as represented by ‘dual use’ policies.
+Both frameworks posit a moral duty for life sciences researchers with respect to how they should make their data available.
+However, Open data and dual use concerns are rarely discussed in concert and their implementation can present scientists with potentially conflicting ethical requirements.
+DISCUSSION: Both dual use and Open data policies frame scientific data and data dissemination in particular, though different, ways.
+Both approaches are limited by a focus on abstract conceptions of data and data sharing.
+As an alternative, this paper proposes that an ethics of responsible management of scientific data should be based on a more nuanced understanding of the everyday data practices of life scientists.
+Responsibility for these ‘micromovements’ of data must consider the needs and duties of scientists as individuals and as collectively-organised groups.
+SUMMARY: Researchers in the life sciences are faced with conflicting ethical responsibilities to share data as widely as possible, but prevent it being used for bioterrorist purposes.
+In order to reconcile the responsibilities posed by the Open Data and dual use frameworks, approaches should focus more on the everyday practices of laboratory scientists and less on abstract conceptions of data.
+The devastation caused by the Ebola virus disease (EVD) outbreak in West Africa has brought to the fore a number of important ethical debates about how best to respond to a health crisis.
+These debates include issues related to prevention and containment, management of the health care workforce, clinical care, and research design, all of which are situated within the overarching moral problem of severe transnational disadvantage, which has very real and specific impacts upon the ability of citizens of EVD-affected countries to respond to a disease outbreak.
+Ethical issues related to prevention and containment include the appropriateness and scope of quarantine and isolation within and outside affected countries.
+The possibility of infection in health care workers impelled consideration of whether there is an obligation to provide health services where personal protection equipment is inadequate, alongside the issue of whether the health care workforce should have special access to experimental treatment and care interventions under development.
+In clinical care, ethical issues include the standards of care owed to people who comply with quarantine and isolation restrictions.
+Ethical issues in research include appropriate study design related to experimental vaccines and treatment interventions, and the sharing of data and biospecimens between research groups.
+BACKGROUND: Live poultry markets (LPMs) pose a threat to public health by promoting the amplification and dissemination of avian influenza viruses (AIVs) and by providing the ideal setting for zoonotic influenza transmission.
+OBJECTIVE: This review assessed the impact of different interventions implemented in LPMs to control the emergence of zoonotic influenza.
+METHODS: Publications were identified through a systematic literature search in the PubMed, MEDLINE and Web of Science databases.
+Eligible studies assessed the impact of different interventions, such as temporary market closure or a ban on holding poultry overnight, in reducing i) AIV-detection rates in birds and the market environment or ii) influenza incidence in humans.
+Unpublished literature, reviews, editorials, cross-sectional studies, theoretical models and publications in languages other than English were excluded.
+For the comparative analysis of findings across studies, standardized outcome measures were computed as i) the relative risk reduction (RRR) of AIV-detection in LPMs and ii) incidence rate ratios (IRRs) of H7N9-incidence in humans.
+Collectively, the data suggest that AIV-circulation can be significantly reduced in the LPM-environment and among market-birds through (i) temporary LPM closure, (ii) periodic rest days (iii) market depopulation overnight and (iv) improved hygiene and disinfection.
+Overall, the findings indicate that the length of stay of poultry in the market is a critical control point to interrupt the AIV-replication cycle within LPMs.
+In addition, temporary LPM closure was associated with a significant reduction of the incidence of zoonotic influenza.
+In addition, some of the included studies were of ecologic nature or lacked an inferential framework, which might have lead to cosiderable confounding and bias.
+CONCLUSIONS: The evidence collected in this review endorses permanent LPM-closure as a long-term objective to reduce the zoonotic risk of avian influenza, although its economic and socio-political implications favour less drastic interventions, e.g.
+In addition to the primary role of the capsid protein (CP) in encapsidating the RNA progeny, experimental evidence on positive sense single-stranded RNA viruses suggests that the CP also regulates RNA synthesis.
+Here, we demonstrate that replication of Satellite tobacco mosaic virus (STMV) is controlled by the cooperative interaction between STMV CP and the helper virus (HV) Tobacco mosaic virus (TMV) replicase.
+We identified that the STMV CP-HV replicase interaction requires a positively charged residue at the third position (3R) in the N-terminal 13 amino acid (aa) motif.
+An STMV CP variant having an arginine to alanine substitution at position 3 in the N-terminal 13aa motif abolished replicase-CP binding.
+The N-terminal 13aa motif of the CP bearing alanine substitutions for positively charged residues located at positions 5, 7, 10 and 11 are defective in packaging full-length STMV, but can package a truncated STMV RNA lacking the 3′ terminal 150 nt region.
+These findings provide insights into the mechanism underlying the regulation of STMV replication and packaging.
+The study of antibodies has been a focal point in modern biology and medicine since the early 1900s.
+The first antibody therapy, murine-derived murononab OKT3 for acute organ rejection, was approved by the US Food and Drug Administration (FDA) in 1986, more than a decade after César Milstein and Georges Köhler developed methods for the isolation of mouse monoclonal antibodies from hybridoma cells in 1975.
+As a result of the scientific, technological, and clinical breakthroughs in the 1980s and 1990s, the pace of therapeutic antibody discovery and development accelerated.
+Antibodies are becoming a major drug modality with more than two dozen therapeutic antibodies in the clinic and hundreds more in development.
+Antibody therapeutics provides fertile ground for protein scientists to fulfill the dream of personalized medicine through basic scientific discovery and technological innovation.
+Influenza virus contains three integral membrane proteins: haemagglutinin, neuraminidase, and matrix protein (M1 and M2).
+Among them, M2 protein functions as an ion channel, important for virus uncoating in endosomes of virus-infected cells and essential for virus replication.
+In an effort to explore potential new functions of M2 in the virus life cycle, we used yeast two-hybrid system to search for M2-associated cellular proteins.
+Here, we report that both BM2 (M2 of influenza B virus) and A/M2 (M2 of influenza A virus) interacted with Hsp40 in vitro and in vivo.
+Hsp40 has been reported to be a regulator of PKR signaling pathway by interacting with p58(IPK) that is a cellular inhibitor of PKR.
+We therefore attempted to understand the relationship among M2, Hsp40 and p58(IPK) by further experimentation.
+The results demonstrated that both A/M2 and BM2 are able to bind to p58(IPK)in vitro and in vivo and enhance PKR autophosphorylation probably via forming a stable complex with Hsp40 and P58(IPK), and consequently induce cell death.
+These results suggest that influenza virus M2 protein is involved in p58(IPK) mediated PKR regulation during influenza virus infection, therefore affecting infected-cell life cycle and virus replication.
+Beta-arrestin-2 has been reported to be an important protein involved in D(2) dopamine receptor desensitization, which is essential to Parkinson’s disease.
+Moreover, the potential value of pharmacological inactivation of G protein-coupled receptor kinase or arrestin in the treatment of patients with Parkinson’s disease has recently been shown.
+We studied the interaction between D(2) dopamine receptor and beta-arrestin-2 and the pharmacological regulation of chemical compounds on such interaction using capillary zone electrophoresis.
+The results from screening more than 40 compounds revealed three compounds that remarkably inhibit the beta-arrestin-2/D(2) dopamine receptor interaction among them.
+These compounds are promising therapies for Parkinson’s disease, and the method used in this study has great potential for application in large-scale drug screening and evaluation.
+Dendritic-cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN; CD209) has an important role in mediating adherence of Mycobacteria species, including M. tuberculosis and M. bovis BCG to human dendritic cells and macrophages, in which these bacteria can survive intracellularly.
+DC-SIGN is a C-type lectin, and interactions with mycobacterial cells are believed to occur via mannosylated structures on the mycobacterial surface.
+Here we identify, by affinity chromatography and mass-spectrometry, four novel ligands of M. bovis BCG that bind to DC-SIGN.
+The novel ligands are chaperone protein DnaK, 60 kDa chaperonin-1 (Cpn60.1), glyceraldehyde-3 phosphate dehydrogenase (GAPDH) and lipoprotein lprG.
+Of these ligands, lprG appears to bind DC-SIGN via typical proteinglycan interactions, but DnaK and Cpn60.1 binding do not show evidence of carbohydrate-dependent interactions.
+LprG was also identified as a ligand for DC-SIGNR (L-SIGN; CD299) and the M. tuberculosis orthologue of lprG has been found previously to interact with human toll-like receptor 2.
+Collectively, these findings offer new targets for combating mycobacterial adhesion and within-host survival, and reinforce the role of DCSIGN as an important host ligand in mycobacterial infection.
+The enzyme can also locate on the cell surface and bind to plasminogen, via which contributing to the mucosal surface localization of the bacterial pathogens and assisting the invasion into the host cells.
+The functions of the eukaryotic enzymes on the cell surface expression (including T cells, B cells, neutrophils, monocytoes, neuronal cells and epithelial cells) are not known.
+Streptococcus suis serotype 2 (S. suis 2, SS2) is an important zoonotic pathogen which has recently caused two large-scale outbreaks in southern China with severe streptococcal toxic shock syndrome (STSS) never seen before in human sufferers.
+We recently identified the SS2 enolase as an important protective antigen which could protect mice from fatal S.suis 2 infection.
+In this study, a 2.4-angstrom structure of the SS2 enolase is solved, revealing an octameric arrangement in the crystal.
+We further demonstrated that the enzyme exists exclusively as an octamer in solution via a sedimentation assay.
+These results indicate that the octamer is the biological unit of SS2 enolase at least in vitro and most likely in vivo as well.
+This is, to our knowledge, the first comprehensive characterization of the SS2 enolase octamer both structurally and biophysically, and the second octamer enolase structure in addition to that of Streptococcus pneumoniae.
+BACKGROUND: Some plants had been used in the treatment of cancer and one of these has attracted scientific interest, the Euphorbia tirucalli (E. tirucalli), used in the treatment of asthma, ulcers, warts has active components with activities scientifically proven as antimutagenic, anti-inflammatory and anticancer.
+METHODS: We evaluate the influence of the antitumoral fraction of the E. tirucalli latex in the larynx squamous cell carcinoma (Hep-2), on the morphology, cell proliferation and gene expression.
+The Hep-2 cells were cultivated in complete medium (MEM 10 %) and treated with E. tirucalli latex for 1, 3, 5 and 7 days.
+After statistically analyzing the proliferation of the tested cells, the cells were cultivated again for RNA extraction and the Rapid Subtractive Hybridization (RaSH) technique was used to identify genes with altered expression.
+The genes found using the RaSH technique were analyzed by Gene Ontology (GO) using Ingenuity Systems.
+RESULTS: The five genes found to have differential expression were validated by real-time quantitative PCR.
+Though treatment with E. tirucalli latex did not change the cell morphology in comparison to control samples, but the cell growth was significantly decreased.
+The RaSH showed change in the expression of some genes, including ANXA1, TCEA1, NGFRAP1, ITPR1 and CD55, which are associated with inflammatory response, transcriptional regulation, apoptosis, calcium ion transport regulation and complement system, respectively.
+The E. tirucalli latex treatment down-regulated ITPR1 and up-regulated ANXA1 and CD55 genes, and was validated by real-time quantitative PCR.
+CONCLUSIONS: The data indicate the involvement of E. tirucalli latex in the altered expression of genes involved in tumorigenic processes, which could potentially be applied as a therapeutic indicator of larynx cancer.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12906-016-1115-z) contains supplementary material, which is available to authorized users.
+However, relatively little is known about whether resveratrol modulates the ion channels in cortical neurons.
+The large-conductance calcium-activated potassium channels (BK(Ca)) and voltage-gated sodium channels were expressed in cortical neurons and play important roles in regulation of neuronal excitability.
+The present study aimed to determine the effects of resveratrol on BK(Ca) currents and voltage-gated sodium currents in cortical neurons.
+RESULTS: Resveratrol concentration-dependently increased the current amplitude and the opening activity of BK(Ca) channels, but suppressed the amplitude of voltage-gated sodium currents.
+Similar to the BK(Ca) channel opener NS1619, resveratrol decreased the firing rate of action potentials.
+In addition, the enhancing effects of BK(Ca) channel blockers tetraethylammonium (TEA) and paxilline on action potential firing were sensitive to resveratrol.
+Our results indicated that the attenuation of action potential firing rate by resveratrol might be mediated through opening the BK(Ca) channels and closing the voltage-gated sodium channels.
+CONCLUSIONS: As BK(Ca) channels and sodium channels are critical molecular determinants for seizure generation, our findings suggest that regulation of these two channels in cortical neurons probably makes a considerable contribution to the antiseizure activity of resveratrol.
+Respiratory Syncytial Virus (RSV) is responsible for considerable morbidity and mortality worldwide and is the most important respiratory viral pathogen in infants.
+Extensive sequence variability within and between RSV group A and B viruses and the ability of multiple clades and sub-clades of RSV to co-circulate are likely mechanisms contributing to the evasion of herd immunity.
+Surveillance and large-scale whole-genome sequencing of RSV is currently limited but would help identify its evolutionary dynamics and sites of selective immune evasion.
+In this study, we performed complete-genome next-generation sequencing of 92 RSV isolates from infants in central Tennessee during the 2012–2014 RSV seasons.
+Analyses of specific RSV genes revealed high rates of positive selection in the attachment (G) gene.
+We identified RSV-A viruses in circulation with and without a recently reported 72-nucleotide G gene sequence duplication.
+Furthermore, we show evidence of convergent evolution of G gene sequence duplication and fixation over time, which suggests a potential fitness advantage of RSV with the G sequence duplication.
+The porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most important swine pathogens and often serves as an entry door for other viral or bacterial pathogens, of which Streptococcus suis is one of the most common.
+Since antigen presenting cells play a major role in the initiation of the immune response, the in vitro transcriptional response of bone marrow-derived dendritic cells (BMDCs) and monocytes in the context of PRRSV and S. suis co-infection was investigated.
+BMDCs were found to be more permissive than monocytes to PRRSV infection; S. suis phagocytosis by PRRSV-infected BMDCs was found to be impaired, whereas no effect was found on bacterial intracellular survival.
+Transcription profile analysis, with a major focus on inflammatory genes, following S. suis infection, with and without pre-infection with PRRSV, was then performed.
+While PRRSV pre-infection had little effect on monocytes response to S. suis infection, a significant expression of several pro-inflammatory molecules was observed in BMDCs pre-infected with PRRSV after a subsequent infection with S. suis.
+While an additive effect could be observed for CCL4, CCL14, CCL20, and IL-15, a distinct synergistic up-regulatory effect was observed for IL-6, CCL5 and TNF-α after co-infection.
+This increased pro-inflammatory response by DCs could participate in the exacerbation of the disease observed during PRRSV and S. suis co-infection.
+BACKGROUND: Herpes B virus (BV) is a zoonotic disease caused by double-stranded enveloped DNA virus with cercopithecidae as its natural host.
+The mortality rate of infected people could be up to 70% with fatal encephalitis and encephalomyelitis.
+Among the various proteins encoded by monkey B virus, gD, a conserved structural protein, harbors important application value for serological diagnosis of frequent variations of the monkey B virus.
+OBJECTIVES: This study aimed to expressed the gD protein of BV in Escherichia coli by a recombinant vector, and prepare specific monoclonal antibodies against gD of BV to pave the way for effective and quick diagnosis reagent research.
+MATERIALS AND METHODS: The gD gene of BV was optimized by OptimWiz to improve codon usage bias and synthesis, and the recombinant plasmid, pET32a/gD, was constructed and expressed in E. coli Rosetta (DE3).
+The expressed fusion protein, His-gD, was purified and the BALB/c mice were immunized by this protein.
+Spleen cells from the immunized mice and SP2/0 myeloma cells were fused together, and the monoclonal cell strains were obtained by indirect enzyme-linked immunosorbent assay (ELISA) screening, followed by preparation of monoclonal antibody ascetic fluid.
+Five monoclonal antibodies (mAbs) against BV were obtained and named as 4E3, 3F8, 3E7, 1H3 and 4B6, and with ascetic fluid titers of 2 × 10(6), 2 × 10(5), 2 × 10(5), 2 × 10(3) and 2 × 10(2), respectively.
+The 1H3 and 4E3 belonged to the IgG2b subclass, while 3E7, 3F8 and 4B6 belonged to the IgG1 subclass.
+CONCLUSIONS: The cell lines obtained in this work secreted potent, stable and specific anti-BV mAbs, which were suitable for the development of herpes B virus diagnosis reagents.
+Crimean Congo hemorrhagic fever virus (CCHFV) is a highly virulent tick-borne pathogen that causes hemorrhagic fever in humans.
+In order to assess the presence of CCHFV in a wide range of bat species over a wide geographic range, we analyzed 1,135 sera from 16 different bat species collected in Congo, Gabon, Ghana, Germany, and Panama.
+Using a CCHFV glycoprotein-based indirect immunofluorescence test (IIFT), we identified reactive antibodies in 10.0% (114/1,135) of tested bats, pertaining to 12/16 tested species.
+Depending on the species, 3.6%–42.9% of cave-dwelling bats and 0.6%–7.1% of foliage-living bats were seropositive (two-tailed t-test, p = 0.0447 cave versus foliage).
+11/30 IIFT-reactive sera from 10 different African bat species had neutralizing activity in a virus-like particle assay.
+Widespread infection of cave-dwelling bats may indicate a role for bats in the life cycle and geographic dispersal of CCHFV.
+Since the precise mechanism of the innate immune response induced by ALV-J is unknown, we investigated the antiviral innate immune responses induced by ALV-J in chicks and chickens that had developed tumors.
+Spleen levels of interleukin-6 (IL-6), IL-10, IL-1β, and interferon-β (IFN-β) were not significantly different between the infected chick groups and the control groups from 1 day post hatch to 7 days post hatch.
+However, IL-6, IL-1β, and IFN-β protein levels in the three clinical samples with hemangiomas were dramatically increased compared to the healthy samples.
+We also found a more than 20-fold up-regulation of ISG12-1 mRNA at 1 day post infection (d.p.i.)
+However, there were no statistical differences in ISG12-1 and ZC3HAV1 mRNA expression levels in the tumorigenesis phase.
+and dramatically increased the mRNA levels of melanoma differentiation-associated gene 5 (MDA5) in the tumorigenesis phase.
+Moreover, the protein levels of interferon regulatory factor 1 (IRF-1) and signal transducer and activator of transcription 1 (STAT1) were decreased in chickens with tumors.
+These results suggest that ALV-J was primarily recognized by chicken TLR7 and MDA5 at early and late in vivo infection stages, respectively.
+ALV-J strain SCAU-HN06 did not induce any significant antiviral innate immune response in 1 week old chicks.
+However, interferon-stimulated genes were not induced normally during the late phase of ALV-J infection due to a reduction of IRF1 and STAT1 expression.
+Emerging and re-emerging infectious diseases caused by RNA viruses pose a critical public health threat.
+Next generation sequencing (NGS) is a powerful technology to define genomic sequences of the viruses.
+Of particular interest is the use of whole genome sequencing (WGS) to perform phylogeographic analysis, that allows the detection and tracking of the emergence of viral infections.
+Hantaviruses, Bunyaviridae, cause hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS) in humans.
+A novel multiplex PCR-based NGS was developed to gather whole genome sequences of Hantaan virus (HTNV) from HFRS patients and rodent hosts in endemic areas.
+The obtained genomes were described for the spatial and temporal links between cases and their sources.
+Phylogenetic analyses demonstrated geographic clustering of HTNV strains from clinical specimens with the HTNV strains circulating in rodents, suggesting the most likely site and time of infection.
+The multiplex PCR-based NGS is useful and robust to acquire viral genomic sequences and may provide important ways to define the phylogeographical association and molecular evolution of hantaviruses.
+Middle East respiratory syndrome coronavirus is a recently emerged pathogen associated with severe human disease.
+Because of logistic difficulties in working with dromedaries in containment, a more manageable animal model would be desirable.
+We report shedding and transmission of this virus in experimentally infected alpacas (n = 3) or those infected by contact (n = 3).
+Infectious virus was detected in all infected animals and in 2 of 3 in-contact animals.
+Experimentally infected animals were protected against reinfection, and those infected by contact were partially protected.
+Necropsy specimens from immunologically naive animals (n = 3) obtained on day 5 postinfection showed virus in the upper respiratory tract.
+These data demonstrate efficient virus replication and animal-to-animal transmission and indicate that alpacas might be useful surrogates for camels in laboratory studies.
+During 2004–2009, the Centers for Disease Control and Prevention (CDC) partnered with 39 national governments to strengthen global influenza surveillance.
+Using World Health Organization data and program evaluation indicators collected by CDC in 2013, we retrospectively evaluated progress made 4–9 years after the start of influenza surveillance capacity strengthening in the countries.
+Our results showed substantial increases in laboratory and sentinel surveillance capacities, which are essential for knowing which influenza strains circulate globally, detecting emergence of novel influenza, identifying viruses for vaccine selection, and determining the epidemiology of respiratory illness.
+Twenty-eight of 35 countries responding to a 2013 questionnaire indicated that they have leveraged routine influenza surveillance platforms to detect other pathogens.
+Furthermore, 34 countries reported an increased ability to use data in decision making; data-driven decisions are critical for improving local prevention and control of influenza around the world.
+A 73-year-old man was confirmed to have an influenza A (H7N9) virus infection, and the causative agent A/Beijing/02/2014(H7N9) virus was isolated.
+Genetic and phylogenetic analyses revealed that the virus belonged to a novel genotype, which probably emerged and further reassorted with other H9 or H7 viruses in poultry before transmitting to humans.
+Taken together, our findings indicated that this novel genotype of the human H7N9 virus did not evolve directly from the first Beijing isolate A/Beijing/01/2013(H7N9), suggesting that the H7N9 virus has not obtained the ability for human-to-human transmissibility and the virus only evolves in poultry and then infects human by direct contact.
+Hence, the major measures to prevent human H7N9 virus infection are still to control and standardize the live poultry trade.
+Early antiviral treatment with combination therapies, including mechanical ventilation, nutrition support and symptomatic treatment, are effective for H7N9 infection.
+While local infection often remains asymptomatic, severe or even fatal diseases occur when streptococci become invasive and spread to different sites in the infected host.
+We have established porcine respiratory air-liquid interface cultures (ALI) from the porcine lung to analyze the interaction of streptococci with their primary target cells.
+As representative of the streptococcal family we chose Streptococcus suis (S. suis) that is not only a major swine respiratory pathogen but can also infect humans.
+By comparing a S. suis wt strain with a suilysin-deficient mutant, we demonstrate that suilysin contributes to (i) adherence to airway cells (ii) loss of ciliated cells (iii) apoptosis, and (iv) invasion.
+A striking result of our analysis was the high efficiency of S. suis-induced apoptosis and invasion upon infection under ALI conditions.
+We hypothesize that soluble effectors such as suilysin are present at higher concentrations in cells kept at ALI conditions and thus more effective.
+These results should be relevant also for infection of the respiratory tract by other respiratory pathogens.
+Although many studies have detected it throughout the world, its molecular epidemiology has not been characterized in northwest China.
+To understand its prevalence, 203 fecal samples were collected from different regions of Gansu Province and tested with reverse transcription-polymerase chain reaction.
+In this study, we tested these samples for PKV, porcine epidemic diarrhea virus (PEDV), and sapovirus and analyzed the amplified 2C gene fragments of PKV.
+Of the 74 piglets samples among the 203 fecal samples, 65 (87.8%) were positive for PKV.
+PKV infection was often accompanied by PEDV, but the relationship between the two viruses must be confirmed.
+A phylogenetic analysis indicated that the PKV strains isolated from the same regions clustered on the same branches.
+This investigation shows that PKV infections are highly prevalent in pigs in northwest China, especially in piglets with symptoms of diarrhea.
+Commonly used tests based on wild-type viruses, such as immunostaining, cannot meet the demands for rapid detection of viral replication, high-throughput screening for antivirals, as well as for tracking viral proteins or virus transport in real time.
+Notably, the development of replicating-competent reporter-expressing viruses (RCREVs) has provided an excellent option to detect directly viral replication without the use of secondary labeling, which represents a significant advance in virology.
+This article reviews the applications of RCREVs in diagnostic and molecular virology, including rapid neutralization tests, high-throughput screening systems, identification of viral receptors and virus-host interactions, dynamics of viral infections in vitro and in vivo, vaccination approaches and others.
+However, there remain various challenges associated with RCREVs, including pathogenicity alterations due to the insertion of a reporter gene, instability or loss of the reporter gene expression, or attenuation of reporter signals in vivo.
+Despite all these limitations, RCREVs have become powerful tools for both basic and applied virology with the development of new technologies for generating RCREVs, the inventions of novel reporters and the better understanding of regulation of viral replication.
+Melanoma is one of the most aggressive forms of cancer, usually resistant to standard chemotherapeutics.
+Despite a huge number of clinical trials, any success to find a chemotherapeutic agent that can effectively destroy melanoma is yet to be achieved.
+Para-phenylenediamine (p-PD) in the hair dyes is reported to purely serve as an external dyeing agent.
+Very little is known about whether p-PD has any effect on the melanin producing cells.
+We have demonstrated p-PD mediated apoptotic death of both human and mouse melanoma cells in vitro.
+Mouse melanoma tumour growth was also arrested by the apoptotic activity of intraperitoneal administration of p-PD with almost no side effects.
+This apoptosis is shown to occur primarily via loss of mitochondrial membrane potential (MMP), generation of reactive oxygen species (ROS), and caspase 8 activation.
+Thus, our experimental observation suggests that p-PD can be a potential less expensive candidate to be developed as a chemotherapeutic agent for melanoma.
+BACKGROUND: Noninvasive ventilation (NIV) is a cornerstone for the treatment of acute respiratory failure of various etiologies.
+Using NIV is discussed in mild-to-moderate acute respiratory distress syndrome (ARDS) patients (PaO(2)/FiO(2) > 150).
+The primary outcome of this prospective observational study was to evaluate the feasibility, safety and contribution in diagnosis and/or modification of the ongoing treatment of fiberoptic bronchoscopy (FOB) in patients with ARDS treated with NIV.
+METHODS: ARDS patients treated with NIV and who require FOB as the diagnostic or therapeutic procedure were included the study.
+Pressure support or inspiratory positive airway pressure (IPAP), external positive end expiratory pressure (PEEP) or expiratory positive airway pressure (EPAP) levels were titrated to achieve an expiratory tidal volume of 8 to 10 ml/kg according to ideal body weight, SpO(2) > 90 % and respiratory rate below 25/min.
+RESULTS: Twenty eight subjects (mean age 63.3 ± 15.9 years, 15 men, 13 women, PaO(2)/FiO(2) rate 145 ± 50.1 at admission) were included the study.
+Overall the procedure was well tolerated with only 5 (17.9 %) patients showing minor complications.
+10.7, 32.1 and 39.3 % of the patients required invasive mechanical ventilation after 8 h, 24 h and 48 h, respectively.
+Appropriate treatment was decided according to the results of the bronchoscopic sampling in 20 (71.4 %) patients.
+CONCLUSION: FOB under NIV could be considered as a feasible tool for diagnosis and guide for treatment of patients with ARDS treated via NIV in intensive care units.
+Furthermore, further controlled studies involving a larger series of homogeneous ARDS patients undergoing FOB under NIV are needed to confirm these preliminary findings.
+Inflammation may be maladaptive to the control of viral infection when it impairs interferon (IFN) responses, enhancing viral replication and spread.
+Dysregulated immunity as a result of inappropriate innate inflammatory responses is a hallmark of chronic viral infections such as, hepatitis B virus and hepatitis C virus (HCV).
+Previous studies from our laboratory have shown that expression of an IFN-stimulated gene (ISG), ubiquitin-like protease (USP)18 is upregulated in chronic HCV infection, leading to impaired hepatocyte responses to IFN-α.
+We examined the ability of inflammatory stimuli, including tumor necrosis factor alpha (TNF-α), lipopolysaccharide (LPS), interleukin-6 (IL-6) and IL-10 to upregulate hepatocyte USP18 expression and blunt the IFN-α response.
+Human hepatoma cells and primary murine hepatocytes were treated with TNF-α/LPS/IL-6/IL-10 and USP18, phosphorylated (p)-STAT1 and myxovirus (influenza virus) resistance 1 (Mx1) expression was determined.
+Treatment of Huh7.5 cells and primary murine hepatocytes with LPS and TNF-α, but not IL-6 or IL-10, led to upregulated USP18 expression and induced an IFN-α refractory state, which was reversed by USP18 knockdown.
+Hepatic ischemia/reperfusion injury led to an induction of USP18 expression in liver tissue and promotion of lymphocytic choriomeningitis replication.
+These data demonstrate that certain inflammatory stimuli (TNF-α and LPS) but not others (IL-6 and IL-10) target USP18 expression and thus inhibit IFN signaling.
+These findings represent a new paradigm for how inflammation alters hepatic innate immune responses, with USP18 representing a potential target for intervention in various inflammatory states.
+IMPORTANCE Inflammation may prevent the control of viral infection when it impairs the innate immune response, enhancing viral replication and spread.
+Blunted immunity as a result of inappropriate innate inflammatory responses is a common characteristic of chronic viral infections.
+Previous studies have shown that expression of certain interferon-stimulated genes is upregulated in chronic HCV infection, leading to impaired hepatocyte responses.
+In this study, we show that multiple inflammatory stimuli can modulate interferon stimulated gene expression and thus inhibit hepatocyte interferon signaling via USP18 induction.
+These findings represent a new paradigm for how inflammation alters hepatic innate immune responses, with the induction of USP18 representing a potential target for intervention in various inflammatory states.
+Angiotensin-converting enzyme 2 (ACE2) degrades angiotensin (Ang) II to Ang-(1–7), and protects against diabetic renal injury.
+Soluble ACE2 fragments are shed from the proximal tubule, and appear at high levels in the urine with diabetes.
+High glucose-induced shedding of ACE2 from proximal tubular cells is mediated by the enzyme “a disintegrin and metalloproteinase-17″ (ADAM17).
+Mouse proximal tubular cells were cultured and ACE2 shedding into the media was assessed by enzyme activity assay and immunoblot analysis.
+Incubation of proximal tubular cells with increasing concentrations of D-glucose stimulated ACE2 shedding, which peaked at 16 mM, while L-glucose (osmotic control) had no effect on shedding.
+In cells maintained in 7.8 mM D-glucose, ACE2 shedding was significantly inhibited by the pan-protein kinase C (PKC) competitive inhibitor sotrastaurin, but not by an inhibitor of ADAM17.
+Incubation of cells with the PKC-α and -β1-specific inhibitor Go6976, the PKC β1 and β2-specific inhibitor ruboxistaurin, inhibitors of matrix metalloproteinases-2,-8, and -9, or an inhibitor of ADAM10 (GI250423X) had no effect on basal ACE2 shedding.
+By contrast, the PKC-δ inhibitor rottlerin significantly inhibited both constitutive and high glucose-induced ACE2 shedding.
+Transfection of cells with siRNA directed against PKC-δ reduced ACE2 shedding by 20%, while knockdown of PKC-ε was without effect.
+These results indicate that constitutive shedding of ACE2 from proximal tubular cells is mediated by PKC-δ, which is also linked to high glucose-induced shedding.
+Targeting PKC-δ may preserve membrane-bound ACE2 in proximal tubule in disease states and diminish Ang II-stimulated adverse signaling.
+Single-nucleotide polymorphisms (SNPs) represent the most widespread type of genetic variation (approximately 90%) in the human genome, and the demand to overcome such variation has received more attention now than ever before.
+The capacity to rapidly assess SNPs that correlate with disease predisposition, drug efficacy and drug toxicity is a key step for the development of personalized medicine.
+In this work, a rapid one-step SNP detection method, real-time loop-mediated isothermal amplification (RT-LAMP), was first applied for CYP2C19 polymorphisms testing.
+The optimized method was established with specifically designed primers for target amplification by real-time detection in approximately 30 min under isothermal conditions.
+RT-LAMP amplified few copies of template to produce significant amounts of product and quantitatively detected human DNA with compatible specificity and sensitivity.
+The success in the establishment of this RT-LAMP protocol for CYP2C19 polymorphism testing is significant for the extension of this technique for the detection of other SNPs, which will further facilitate the development of personalized medicine.
+Remarkable progress has been made in image recognition, primarily due to the availability of large-scale annotated datasets and deep convolutional neural networks (CNNs).
+However, obtaining datasets as comprehensively annotated as ImageNet in the medical imaging domain remains a challenge.
+There are currently three major techniques that successfully employ CNNs to medical image classification: training the CNN from scratch, using off-the-shelf pre-trained CNN features, and conducting unsupervised CNN pre-training with supervised fine-tuning.
+Another effective method is transfer learning, i.e., fine-tuning CNN models pre-trained from natural image dataset to medical image tasks.
+In this paper, we exploit three important, but previously understudied factors of employing deep convolutional neural networks to computer-aided detection problems.
+The studied models contain 5 thousand to 160 million parameters, and vary in numbers of layers.
+Finally, we examine when and why transfer learning from pre-trained ImageNet (via fine-tuning) can be useful.
+We study two specific computer-aided detection (CADe) problems, namely thoraco-abdominal lymph node (LN) detection and interstitial lung disease (ILD) classification.
+We achieve the state-of-the-art performance on the mediastinal LN detection, and report the first five-fold cross-validation classification results on predicting axial CT slices with ILD categories.
+Our extensive empirical evaluation, CNN model analysis and valuable insights can be extended to the design of high performance CAD systems for other medical imaging tasks.
+Influenza virus mutants that encode C-terminally truncated NS1 proteins (NS1-truncated mutants) are attractive candidates for avian live attenuated influenza vaccine (LAIV) development because they are both attenuated and immunogenic in chickens.
+We previously showed that a high protective efficacy of NS1-truncated LAIV in chickens corresponds with induction of high levels of type I interferon (IFN) responses in chicken embryonic fibroblast cells.
+In this study, we investigated the relationship between induction of IFN and IFN-stimulated gene responses in vivo and the immunogenicity and protective efficacy of NS1-truncated LAIV.
+Our data demonstrates that accelerated antibody induction and protective efficacy of NS1-truncated LAIV correlates well with upregulation of IFN-stimulated genes.
+Further, through oral administration of recombinant chicken IFN alpha in drinking water, we provide direct evidence that type I IFN can promote rapid induction of adaptive immune responses and protective efficacy of influenza vaccine in chickens.
+The estimation of disease prevalence in online search engine data (e.g., Google Flu Trends (GFT)) has received a considerable amount of scholarly and public attention in recent years.
+While the utility of search engine data for disease surveillance has been demonstrated, the scientific community still seeks ways to identify and reduce biases that are embedded in search engine data.
+The primary goal of this study is to explore new ways of improving the accuracy of disease prevalence estimations by combining traditional disease data with search engine data.
+A novel method, Biased Sentinel Hospital-based Area Disease Estimation (B-SHADE), is introduced to reduce search engine data bias from a geographical perspective.
+To monitor search trends on Hand, Foot and Mouth Disease (HFMD) in Guangdong Province, China, we tested our approach by selecting 11 keywords from the Baidu index platform, a Chinese big data analyst similar to GFT.
+After decomposing the composite index at the city level, we found that only 10 cities presented a correlation of close to 0.8 or higher.
+These cities were found to be more stable with respect to search volume, and they were selected as sample cities in order to estimate the search volume of the entire province.
+After fitting the revised search volume with historical cases, the mean absolute error was 11.19% lower than it was when the original search volume and historical cases were combined.
+To our knowledge, this is the first study to reduce search engine data bias levels through the use of rigorous spatial sampling strategies.
+Dengue viruses (DENVs) and their vectors are widely distributed throughout the tropical and subtropical regions of the world.
+An autochthonous case of DENV was reported in Tokyo, Japan, in 2014, for the first time in 70 years.
+A comprehensive database of DENV sequences containing both serotype and genotype data and epidemiological data is crucial to trace DENV outbreak isolates and promptly respond to outbreaks.
+We constructed a DENV database containing the serotype, genotype, year and country/region of collection by collecting all publically available DENV sequence information from the National Center for Biotechnology Information (NCBI) and assigning genotype information.
+We also implemented the web service Dengue Genographic Viewer (DGV), which shows the geographical distribution of each DENV genotype in a user-specified time span.
+DGV also assigns the serotype and genotype to a user-specified sequence by performing a homology search against the curated DENV database, and shows its homologous sequences with the geographical position and year of collection.
+DGV also shows the distribution of DENV-infected entrants to Japan by plotting epidemiological data from the Infectious Agents Surveillance Report (IASR), Japan.
+This overview of the DENV genotype distribution may aid in planning for the control of DENV infections.
+Mixed results were reported on the associations between HFMD incidence and meteorological factors or school holidays, while limited studies focused on their association on transmissibility.
+We aimed to measure the transmissibility of HFMD and to examine its potential driving factors in Hong Kong.
+A likelihood-based procedure was used to estimate time-dependent effective reproduction number (R(t)) based on weekly number of HFMD-associated hospitalizations from 2010 to 2014.
+The associations of between-year effects, depletion of susceptibles, absolute humidity and school holidays with R(t) were examined using linear regression.
+R(t) usually started increasing between early spring and summer and peaked in April to May at around 1.1–1.2, followed by a slight rebound in autumn.
+Depletion of susceptibles and between-years effects explained most of the variances (19 and 13% respectively) in R(t).
+We found a negative association between depletion of susceptibles and R(t) (coefficients ranged from −0.14 to −0.03 for different years), but the estimated effects of absolute humidity and school holidays were insignificant.
+Overall, HFMD transmission was moderate in Hong Kong and was mainly associated with depletion of susceptibles.
+BACKGROUND: Porcine reproductive and respiratory syndrome virus (PRRSV) induces one of most important devastating disease of swine worldwide, and the current methods poorly control it.
+Previous studies have indicated that the nonstructural protein 11 (nsp11) of PRRSV may be an important protein for the immune escape of PRRSV.
+RESULTS: Here, we firstly explored the effect of over-expression of nsp11 on PRRSV infection and found that over-expression of nsp11 enhanced the PRRSV titers while the small interfering RNA (siRNAs) specifically targeting nsp11 could reduce the PRRSV titers in MARC-145 cells.
+CONCLUSION: In conclusion, PRRSV nsp11 promotes PRRSV infection in MARC-145 cells and siRNAs targeting nsp11 may be a potential therapeutic strategy to control PRRSV in future.
+Acute inflammation is a form of innate immune defence and represents one of the primary responses to injury, infection and irritation, largely mediated by granulocyte effector cells such as neutrophils and eosinophils.
+Failure to remove an inflammatory stimulus (often resulting in failed resolution of inflammation) can lead to chronic inflammation resulting in tissue injury caused by high numbers of infiltrating activated granulocytes.
+Under normal physiological conditions, apoptosis (programmed cell death) precedes phagocytic recognition and clearance of these cells by, for example, macrophages, dendritic and epithelial cells (a process known as efferocytosis).
+Inflammation contributes to immune defence within the respiratory mucosa (responsible for gas exchange) because lung epithelia are continuously exposed to a multiplicity of airborne pathogens, allergens and foreign particles.
+Failure to resolve inflammation within the respiratory mucosa is a major contributor of numerous lung diseases.
+This review will summarise the major mechanisms regulating lung inflammation, including key cellular interplays such as apoptotic cell clearance by alveolar macrophages and macrophage/neutrophil/epithelial cell interactions.
+The different acute and chronic inflammatory disease states caused by dysregulated/impaired resolution of lung inflammation will be discussed.
+Furthermore, the resolution of lung inflammation during neutrophil/eosinophil-dominant lung injury or enhanced resolution driven via pharmacological manipulation will also be considered.
+Testing for the presence of genetically modified material in seed samples is of critical importance for all stakeholders in the agricultural industry, including growers, seed manufacturers, and regulatory bodies.
+While rapid antibody-based testing for the transgenic protein has fulfilled this need in the past, the introduction of new variants of a given transgene demands new diagnostic regimen that allows distinguishing different traits at the nucleic acid level.
+Although such molecular tests can be performed by PCR in the laboratory, their requirement for expensive equipment and sophisticated operation have prevented its uptake in point-of-use applications.
+A recently developed isothermal DNA amplification technique, recombinase polymerase amplification (RPA), combines simple sample preparation and amplification work-flow procedures with the use of minimal detection equipment in real time.
+Here, we report the development of a highly sensitive and specific RPA-based detection system for Genuity Roundup Ready 2 Yield (RR2Y) material in soybean (Glycine max) seed samples and present the results of studies applying the method in both laboratory and field-type settings.
+In this study we determined that two inbred lines of chicken differing in their genetic background , Lines 0 and C-B12, were respectively relatively resistant and susceptible to infection with the low pathogenicity influenza virus A/Turkey/England/647/77 as defined by substantial differences in viral shedding trajectories.
+Resistant birds, although infected, were unable to transmit virus to contact birds, as ultimately only the presence of a sustained cloacal shedding (and not oropharyngeal shedding) was critical for transmission.
+Restriction of within-bird transmission of virus occurred in the resistant line, with intra-nares or cloacal infection resulting in only local shedding and failing to transmit fully through the gastro-intestinal-pulmonary tract.
+Resistance to infection was independent of adaptive immune responses, including the expansion of specific IFNγ secreting cells or production of influenza-specific antibody.
+Genetic resistance to a novel H9N2 virus was less robust, though significant differences between host genotypes were still clearly evident.
+The existence of host-genetic determination of the outcome of influenza infection offers tools for the further dissection of this regulation and also for understanding the mechanisms of influenza transmission within and between birds.
+We evaluated the acceptability of an additional ad hoc influenza vaccination among the health care professionals following seasons with significant antigenic drift.
+Self-administered, anonymous surveys were performed by hard copy questionnaires in public hospitals, and by an on-line platform available to all healthcare professionals, from April 1st to May 31st, 2015.
+A total of 1290 healthcare professionals completed the questionnaires, including doctors, nurses, and allied health professionals working in both the public and private systems.
+Only 31.8% of participating respondents expressed an intention to receive the additional vaccine, despite that the majority of them agreed or strongly agreed that it would bring benefit to the community (88.9%), save lives (86.7%), reduce medical expenses (76.3%), satisfy public expectation (82.8%), and increase awareness of vaccination (86.1%).
+However, a significant proportion expressed concern that the vaccine could disturb the normal immunization schedule (45.5%); felt uncertain what to do in the next vaccination round (66.0%); perceived that the summer peak might not occur (48.2%); and believed that the summer peak might not be of the same virus (83.5%).
+Furthermore, 27.8% of all respondents expected that the additional vaccination could weaken the efficacy of previous vaccinations; 51.3% was concerned about side effects; and 61.3% estimated that there would be a low uptake rate.
+If the supply of vaccine was limited, higher priority groups were considered to include the elderly aged ≥65 years with chronic medical conditions (89.2%), the elderly living in residential care homes (87.4%), and long-stay residents of institutions for the disabled (80.7%).
+The strongest factors associated with accepting the additional vaccine included immunization with influenza vaccines in the past 3 years, higher perceived risk of contracting influenza, and higher perceived severity of the disease impact.
+This could have a negative impact on such additional vaccination campaigns since healthcare professionals are a key driver for vaccine acceptance.
+The discordance in perceived risk and acceptance of vaccination regarding self versus public deserves further evaluation.
+BACKGROUND: Tuberculosis is one of the leading causes of death from infectious diseases worldwide, mainly after the human immunodeficiency virus (HIV) epidemics.
+Patient with HIV-related illness are more likely to present with severe TB due to immunosuppression.
+The goal of this study was to analyze factors associated with long-term mortality in critically ill patient with HIV-related disease coinfected with TB.
+METHODS: We conducted a retrospective study in an infectious disease reference center in Brazil that included all patient with HIV-related illness admitted to the ICU with laboratory-confirmed tuberculosis from March 2007 until June 2012.
+The main causes of admission were respiratory failure (41 %), severe sepsis/septic shock (32 %) and coma/torpor (14 %).
+The median time between HIV diagnosis and ICU admission was 5 (1–60) months, and 41 % of patients received their HIV infection diagnosis ≤ 30 days before admission.
+The clinical presentation was pulmonary tuberculosis in 22 patients (50 %) and disseminated TB in 20 patients (45.5 %).
+Neurological dysfunction was more prevalent among nonsurvivors (43 % vs. 14 %, p = 0.04).
+The nadir CD4 cell count lower than 50 cells/mm(3) was independently associated with Six-month mortality (hazard ratio 4.58 [1.64–12.74], p < 0.01), while HIV diagnosis less than three months after positive serology was protective (hazard ratio 0.27, CI 95 % [0.10–0.72], p = 0.01).
+CONCLUSION: The Six-month mortality of HIV critically ill patients with TB coinfection is high and strongly associated with the nadir CD4 cell count less than 50 cels/mm(3).
+Background: During the last two decades, protein aggregation at all organismal levels, from viruses to humans, has emerged from a neglected area of protein science to become a central issue in biology and biomedicine.
+This article constitutes a risk-based review aimed at supporting an etiologic scenario of selected, sporadic, protein-associated, i.e., conformational, neurodegenerative disorders (NDDs), and their vascular- and metabolic-associated ailments.
+Methods: A rationale is adopted, to incorporate selected clinical data and results from animal-model research, complementing epidemiologic evidences reported in two prior articles.
+Findings: Theory is formulated assuming an underlying conformational transmission mechanism, mediated either by horizontal transfer of mammalian genes coding for specific aggregation-prone proteins, or by xeno-templating between bacterial and host proteins.
+Conclusion: Implications for cohort alignment and experimental animal research are discussed and research lines proposed.
+One of the main strategies to control the spread of infectious animal diseases is the implementation of movement restrictions.
+This paper shows a loss in efficiency of the movement restriction policy (MRP) when behavioral responses of farmers are taken into account.
+Incorporating the strategic behavior of farmers in an epidemiologic model reveals that the MRP can trigger premature animal sales by farms at high risk of becoming infected that significantly reduce the efficacy of the policy.
+The results are validated in a parameterized network via Monte Carlo simulations and measures to mitigate the loss of efficiency of the MRP are discussed.
+Financial aid to farmers can be justified by public health concerns, not only for equity.
+This paper contributes to developing an interdisciplinary analytical framework regarding the expansion of infectious diseases combining economic and epidemiologic dimensions.
+This study was planned to test for the association of TNF-α − 308 and IFN-γ + 874 gene polymorphisms with susceptibility and severity of SLE in Egyptian cases.
+SUBJECTS AND METHODS: This is a case controlled study including 125 Egyptian cases with SLE in addition to 112 healthy unrelated individuals from the same locality.
+For all participants, TNF-α − 308 G > A and IFN-γ + 874 A > T genetic polymorphisms were characterized using the PCR technique.
+RESULTS: Cases with SLE showed a significantly higher TNF-α − 308 A allele carriage rate (AA + GA genotypes) compared to controls (26.4% vs. 12.5%, p = 0.009, OR = 2.51, 95% CI = 1.26–4.99).
+These cases showed also a significantly higher carriage rate for the IFN-γ + 874 T allele (AT + TT genotypes) compared to controls (47.2% vs. 32.1%, p = 0.02, OR = 1.89, 95% CI = 1.11–3.21).
+Comparing age, gender, and disease severity presented by nephritis class, activity and chronicity indices in cases carrying the TNF-α − 308 A allele and in cases carrying IFN-γ + 874 T allele versus others showed no significant difference (p > 0.05).
+CONCLUSIONS: TNF-α − 308 A and IFN-γ + 874 T allele carriage are associated with susceptibility but not severity of SLE in Egyptian subjects.
+We have recently described sustained clinical recovery associated with dampened neuroinflammation and remyelination following transplantation of neural precursor cells (NPCs) derived from human embryonic stem cells (hESCs) in a viral model of the human demyelinating disease multiple sclerosis.
+The hNPCs used in that study were derived by a novel direct differentiation method (direct differentiation, DD-NPCs) that resulted in a unique gene expression pattern when compared to hNPCs derived by conventional methods.
+Since the therapeutic potential of human NPCs may differ greatly depending on the method of derivation and culture, we wanted to determine whether NPCs differentiated using conventional methods would be similarly effective in improving clinical outcome under neuroinflammatory demyelinating conditions.
+For the current study, we utilized hNPCs differentiated from a human induced pluripotent cell line via an embryoid body intermediate stage (EB-NPCs).
+Intraspinal transplantation of EB-NPCs into mice infected with the neurotropic JHM strain of mouse hepatitis virus (JHMV) resulted in decreased accumulation of CD4+ T cells in the central nervous system that was concomitant with reduced demyelination at the site of injection.
+Dampened neuroinflammation and remyelination was correlated with a transient increase in CD4+FOXP3+ regulatory T cells (Tregs) concentrated within the peripheral lymphatics.
+However, compared to our earlier study, pathological improvements were modest and did not result in significant clinical recovery.
+We conclude that the genetic signature of NPCs is critical to their effectiveness in this model of viral-induced neurologic disease.
+These comparisons will be useful for understanding what factors are critical for the sustained clinical improvement.
+Primary ciliary dyskinesia (PCD) is a genetically heterogeneous, rare lung disease resulting in chronic oto‐sino‐pulmonary disease in both children and adults.
+Many physicians incorrectly diagnose PCD or eliminate PCD from their differential diagnosis due to inexperience with diagnostic testing methods.
+This review article outlines consensus recommendations from PCD physicians in North America who have been engaged in a PCD centered research consortium for the last 10 years.
+These recommendations have been adopted by the governing board of the PCD Foundation to provide guidance for PCD clinical centers for diagnostic testing, monitoring, and appropriate short and long‐term therapeutics in PCD patients.
+Vesicular stomatitis virus (VSV) is highly immunogenic and able to stimulate both innate and adaptive immune responses.
+However, its ability to induce adverse effects has held back the use of VSV as a potential vaccine vector.
+In this study we developed VSV-ΔP, a safe yet potent replication-defective recombinant VSV in which the phosphoprotein (P) gene was deleted.
+VSV-ΔP replicated only in supporting cells expressing P (BHK-P cells) and at levels more than 2 logs lower than VSV.
+In vivo studies indicated that the moderate replication of VSV-ΔP in vitro was associated with the attenuation of this virus in the mouse model, whereas mice intracranially injected with VSV succumbed to neurotoxicity.
+Furthermore, we constructed VSV and VSV-ΔP expressing a variety of antigens including hemagglutinin-neuraminidase (HN) from Newcastle disease virus (NDV), hemagglutinin (HA) from either a 2009 H1N1 pandemic influenza virus (pdm/09) or the avian H7N9.
+VSV and VSV-ΔP incorporated the foreign antigens on their surface resulting in induction of robust neutralizing antibody, serum IgG, and hemagglutination inhibition (HAI) titers against their corresponding viruses.
+These results indicated that VSV with P gene deletion was attenuated in vitro and in vivo, and possibly expressed the foreign antigen on its surface.
+Therefore, the P gene-deletion strategy may offer a potentially useful and safer approach for attenuating negative-sense RNA viruses which use phosphoprotein as a cofactor for viral replication.
+Necrotizing enterocolitis (NEC) is a devastating condition of premature infants that results from the gut microbiome invading immature intestinal tissues.
+This results in a life-threatening disease that is frequently treated with the surgical removal of diseased and dead tissues.
+Epidermal growth factor (EGF), typically found in bodily fluids, such as amniotic fluid, salvia and mother’s breast milk, is an intestinotrophic growth factor and may reduce the onset of NEC in premature infants.
+We have produced human EGF in soybean seeds to levels biologically relevant and demonstrated its comparable activity to commercially available EGF.
+Transgenic soybean seeds expressing a seed-specific codon optimized gene encoding of the human EGF protein with an added ER signal tag at the N’ terminal were produced.
+Seven independent lines were grown to homozygous and found to accumulate a range of 6.7 +/- 3.1 to 129.0 +/- 36.7 μg EGF/g of dry soybean seed.
+Proteomic and immunoblot analysis indicates that the inserted EGF is the same as the human EGF protein.
+Phosphorylation and immunohistochemical assays on the EGF receptor in HeLa cells indicate the EGF protein produced in soybean seed is bioactive and comparable to commercially available human EGF.
+This work demonstrates the feasibility of using soybean seeds as a biofactory to produce therapeutic agents in a soymilk delivery platform.
+In order for a virus to persist, there must be a balance between viral replication and immune clearance.
+It is commonly believed that adaptive immunity drives clearance of viral infections and, thus, dysfunction or viral evasion of adaptive immunity is required for a virus to persist.
+Type I interferons (IFNs) play pleiotropic roles in the antiviral response, including through innate control of viral replication.
+Murine norovirus (MNoV) replicates in dendritic cells (DCs) and type I IFN signaling in DCs is important for early control of MNoV replication.
+We show here that the non-persistent MNoV strain CW3 persists systemically when CD11c positive DCs are unable to respond to type I IFN.
+Persistence in this setting is associated with increased early viral titers, maintenance of DC numbers, increased expression of DC activation markers and an increase in CD8 T cell and antibody responses.
+Furthermore, CD8 T cell function is maintained during the persistent phase of infection and adaptive immune cells from persistently infected mice are functional when transferred to Rag1 (-/-) recipients.
+Finally, increased early replication and persistence are also observed in mixed bone marrow chimeras where only half of the CD11c positive DCs are unable to respond to type I IFN.
+These findings demonstrate that increased early viral replication due to a cell-intrinsic innate immune deficiency is sufficient for persistence and a functional adaptive immune response is not sufficient for viral clearance.
+The bacterium Tropheryma whipplei, which causes Whipple disease in humans, is commonly detected in the feces of persons in Africa.
+We investigated the role of T. whipplei in febrile patients from 2 rural villages in Senegal.
+During June 2010–March 2012, we collected whole-blood finger-prick samples from 786 febrile and 385 healthy villagers.
+T. whipplei was detected in blood specimens from 36 (4.6%) of the 786 febrile patients and in 1 (0.25%) of the 385 apparently healthy persons.
+The availability of over 800 sequenced chloroplast genomes from a variety of land plants has enhanced our understanding of chloroplast biology, intracellular gene transfer, conservation, diversity, and the genetic basis by which chloroplast transgenes can be engineered to enhance plant agronomic traits or to produce high-value agricultural or biomedical products.
+In this review, we discuss the impact of chloroplast genome sequences on understanding the origins of economically important cultivated species and changes that have taken place during domestication.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13059-016-1004-2) contains supplementary material, which is available to authorized users.
+BACKGROUND: During pandemics, health authorities may be uncertain about the spread and severity of the disease and the effectiveness and safety of available interventions.
+This was the case during the swine flu (H1N1) pandemic of 2009–2010, and governments were forced to make decisions despite these uncertainties.
+While many countries chose to implement wide scale vaccination programmes, few accomplished their vaccination goals.
+Many research studies aiming to explore barriers and facilitators to vaccine uptake have been conducted in the aftermath of the pandemic, including several qualitative studies.
+To explore public attitudes to the swine flu vaccine in different countries through a review of qualitative primary studies.
+Study quality was appraised using an adaptation of the Critical Appraisal Skills Programme (CASP) quality assessment tool.
+RESULTS: The review indicates that the public had varying opinions about disease risk and prevalence and had concerns about vaccine safety.
+Most primary study authors concluded that participants were uninformed, and that more information about the disease and the vaccine would have led to an increase in vaccine uptake.
+We suggest instead that people’s questions and concerns were legitimate given the uncertainties of the situation at the time and the fact that the authorities did not have the necessary information to convince the public.
+Our quality assessment of the included studies points to a lack of reflexivity and a lack of information about study context.
+We suggest that these study weaknesses are tied to primary study authors’ lack of acknowledgement of the uncertainties surrounding the disease and the vaccine.
+CONCLUSION: While primary study authors suggest that authorities could increase vaccine uptake through increased information, we suggest instead that health authorities should be more transparent in their information and decision-making processes in future pandemic situations.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12913-016-1466-7) contains supplementary material, which is available to authorized users.
+PURPOSE: The aim of this study was to evaluate the individual change of International prostate Symptom Score (IPSS) and Overactive Bladder Symptom Score (OABSS) in each patient by temperature conditions.
+MATERIALS AND METHODS: The severity of lower urinary tract symptoms (LUTS) was explored using the IPSS and OABSS questionnaires that were completed by 2.486 subjects (923 males and 1.563 females) aged 60 years and older.
+Korea Meteorological Administration data was used to determine daily average temperature and daily temperature difference on the interview dates at each site.
+RESULTS: The mean IPSS and mean age for males was 13.45±8.24 and 75.03±6.20 years, respectively.
+Age was a significantly risk factor for IPSS, OABSS, and QoL (P<0.001, <0.001, and 0.005, respectively).
+After multiple regression analysis, daily average temperatures did not show a statistically significant change in IPSS and OABSS.
+CONCLUSIONS: While LUTS could be worsened in low temperatures generally, IPSS and OABSS were not affected by daily average temperature conditions.
+The objective of this study was to obtain insight into the adverse health effects of airborne particulate matter (PM) collected from live bird markets and to determine whether biological material in PM accounts for immune-related inflammatory response.
+Mice were exposed to a single or repeated dose of PM, after which the expression of toll-like receptors (TLRs), cytokines, and chemokines in the lungs of infected mice were examined by enzyme-linked immunosorbent assay and histopathological analysis.
+Results after single and repeated PM stimulation with [Formula: see text] indicated that TLR2 and TLR4 played a dominant role in the inflammatory responses of the lung.
+Further analysis demonstrated that the expression levels of IL-1β, TNF-α, IFN-γ, IL-8, IP-10, and MCP-1 increased significantly, which could eventually contribute to lung injury.
+Moreover, biological components in PM were critical in mediating immune-related inflammatory responses and should therefore not be overlooked.
+Cancer stem cells, also known as cancer initiating cells (CICs), are considered to be responsible for tumor growth and chemoresistance.
+Different hypotheses have been proposed to explain the origin of CICs, including mutations in adult stem/progenitor cells or the acquisition of stem-like characteristics in differentiated cells; however, studies have yielded conflicting identification for CICs and have little information for the origin to generate CICs.
+Part of the difficulty in identifying CICs may stem from the fact that the CICs studied have been largely derived from cancer cell lines or well-developed tumors.
+In previous studies, we have reported the enrichment of mouse pulmonary stem/progenitor cells (mPSCs) by using serum-free primary selection culture followed by FACS isolation using the coxsackievirus/adenovirus receptor (CAR) as the positive selection marker.
+Here, we demonstrated that overexpression of the pluripotent transcription factor Oct-4 is sufficient to induce CAR(+)/mPSCs transformation, which we name CAR(+)/mPSCs(Oct-4_hi).
+These transformed cells possess cancer initiating and chemoresistance potential, as well as exhibiting remarkable expression of certain proangiogenic factors, including angiopoietins (ANGs) and VEGF, and enhanced angiogenic potential.
+Moreover, CAR(+)/mPSCs(Oct-4_hi) actively participated in tumor blood vessel formation and triggered a novel angiogenic mechanism, the angiopoietins/Tie2 signaling pathway.
+These study provide critical evidence supporting the possible origin to generate CICs, and help elucidate the pathways responsible for CICs-mediated blood vessel formation.
+The genus Phlebovirus of the family Bunyaviridae contains a number of emerging virus species which pose a threat to both human and animal health.
+Most prominent members include Rift Valley fever virus (RVFV), sandfly fever Naples virus (SFNV), sandfly fever Sicilian virus (SFSV), Toscana virus (TOSV), Punta Toro virus (PTV), and the two new members severe fever with thrombocytopenia syndrome virus (SFTSV) and Heartland virus (HRTV).
+The nonstructural protein NSs is well established as the main phleboviral virulence factor in the mammalian host.
+Recent progress in the elucidation of the molecular functions of a growing list of NSs proteins highlights the astonishing variety of strategies employed by phleboviruses to evade the IFN system.
+Viral protein U (Vpu) encoded by human immunodeficiency virus type 1 (HIV-1) is a short integral membrane protein which is known to self-assemble within the lipid membrane and associate with host factors during the HIV-1 infectivity cycle.
+In this study, full-length Vpu (M group) from clone NL4-3 was over-expressed in human cells and purified in an oligomeric state.
+Various single and double mutations were constructed on its phosphorylation sites to mimic different degrees of phosphorylation.
+Size exclusion chromatography of wild-type Vpu and mutants indicated that the smallest assembly unit of Vpu was a dimer and over time Vpu formed higher oligomers.
+The rate of oligomerization increased when (i) the degree of phosphorylation at serines 52 and 56 was decreased and (ii) when the ionic strength was increased indicating that the cytoplasmic domain of Vpu affects oligomerization.
+Coarse-grained molecular dynamic simulations with models of wild-type and mutant Vpu in a hydrated lipid bilayer supported the experimental data in demonstrating that, in addition to a previously known role in downregulation of host factors, the phosphorylation sites of Vpu also modulate oligomerization.
+Small glutamine-rich tetratricopeptide repeat-containing protein α (SGTA) has been implicated as a co-chaperone and regulator of androgen and growth hormone receptor (AR, GHR) signalling.
+We investigated the functional consequences of partial and full Sgta ablation in vivo using Cre-lox Sgta-null mice.
+Body size was significantly and proportionately smaller in male and female Sgta(−/−) (vs WT, Sgta(+/−) P < 0.001) from d19.
+Vital and sex organs had normal relative weight, morphology and histology, although certain androgen-sensitive measures such as penis and preputial size, and testis descent, were greater in Sgta(−/−).
+Expression of AR and its targets remained largely unchanged, although AR localisation was genotype- and tissue-dependent.
+In conclusion, this thorough investigation of SGTA-null mutation reports a mild phenotype of reduced body size.
+The model’s full potential likely will be realised by genetic crosses with other models to interrogate the role of SGTA in the many diseases in which it has been implicated.
+CMV reactivates in approximately one-third of latently infected non-immune-suppressed hosts during critical illness; however, its role as a pathogen in these patients remains unclear.
+CMV reactivation has been linked to bacterial sepsis and likely results from inflammation, transient immune compromise, and viral epigenetic changes.
+While CMV may improve immune response to some bacterial infections, other data suggest that CMV induces exaggerated responses to severe infections that may be harmful to latently infected hosts.
+These results also suggest that previous infection history may explain significant differences seen between human septic responses and murine models of sepsis.
+While critically ill human hosts clearly have worse outcomes associated with CMV reactivation, determining causality remains an area of investigation, with randomized control trials currently being performed.
+Although β-amyloid (Aβ) may be the primary driver of Alzheimer’s disease (AD) pathology, accumulation of pathological tau correlates with dementia in AD patients.
+Thus, the prevention/inhibition of AD may require vaccine/s targeting Aβ and tau simultaneously or sequentially.
+Since high antibody titers are required for AD vaccine efficacy, we have decided to generate vaccines, targeting Aβ (AV-1959R), Tau (AV-1980R) or Aβ/tau (AV-1953R) B cell epitopes, based on immunogenic MultiTEP platform and evaluate the immunogenicity of these vaccines formulated with Advax(CpG), delta inulin, Alhydrogel(®), Montanide-ISA51, Montanide-ISA720, MPLA-SM pharmaceutical grade adjuvants.
+Formulation of AV-1959R in Advax(CpG) induced the highest cellular and humoral immune responses in mice.
+The dual-epitope vaccine, AV-1953R, or the combination of AV-1959R and AV-1980R vaccines formulated with Advax(CpG) induced robust antibody responses against various forms of both, Aβ and tau pathological molecules.
+While anti-Aβ antibody titers after AV-1953R immunization were similar to that in mice vaccinated with AV-1959R or AV-1959R/AV-1980R combination, anti-tau titers were significantly lower after AV-1953R injection when compared to the AV-1980R or AV-1959R/AV-1980R.
+In sum, AV-1959R and AV-1980R formulated with Advax(CpG) adjuvant were identified as promising immunogenic vaccines for ongoing pre-clinical assessment and future human clinical trials.
+Our recent studies have found that one subset of hematopoietic cells can be induced to dedifferentiate into multipotent stem cells by means of a proliferating fibroblast releasable factor, M-CSF.
+Understanding the importance of stem cells on skin wound healing, here we evaluate the biological significance of M-CSF on skin wound healing.
+In an in vivo mouse skin excisional wound model, we found that SSEA-positive stem cells were present in wounded but not normal skin.
+After isolating skin cells from either normal or wounded skin by collagenase digestion, and analyzing the SSEA-1 positive cells by flow cytometry, we found a significant increase in the number of SSEA-1 positive cells in wounded skin.
+Topical application of M-CSF in skin wounds accelerated healing remarkably, while application of M-CSF-neutralizing antibody slowed wound healing.
+Furthermore, injection of EGFP-labeled hematopoietic cell-derived stem cells generated from M-CSF treated splenocytes resulted in EGFP-labeled cells being enriched in the skin wound site and further differentiated into functional organ-specific cells.
+Together, these data demonstrated that M-CSF makes a significant contribution to the healing process by inducing hematopoietic cell dedifferentiation into stem cells.
+IFIT proteins are interferon-inducible, innate immune effector molecules that are thought to confer antiviral defence through disruption of protein-protein interactions in the host translation initiation machinery.
+However, recently it was discovered that IFITs could directly recognize viral RNA bearing a 5′-triphosphate group (PPP-RNA), which is a molecular signature that distinguishes it from host RNA.
+Here, we report crystal structures of human IFIT5, its complex with PPP-RNAs, and an N-terminal fragment of IFIT1.
+The structures reveal a new helical domain that houses a positively charged cavity designed to specifically engage only single stranded PPP-RNA, thus distinguishing it from the canonical cytosolic sensor of double stranded viral PPP-RNA, RIG-I.
+Mutational analysis, proteolysis and gel-shift assays reveal that PPP-RNA is bound in a non-sequence specific manner and requires approximately a 3-nucleotide 5′-overhang.
+Abrogation of PPP-RNA binding in IFIT1 and IFIT5 were found to cause a defect in the anti-viral response by HEK cells.
+These results demonstrate the mechanism by which IFIT proteins selectively recognize viral RNA and lend insight into their downstream effector function.
+Avian influenza viruses A(H5N1) have caused a large number of typically severe human infections since the first human case was reported in 1997.
+However, there is a lack of comprehensive epidemiological analysis of global human cases of H5N1 from 1997-2015.
+Moreover, few studies have examined in detail the changing epidemiology of human H5N1 cases in Egypt, especially given the most recent outbreaks since November 2014 which have the highest number of cases ever reported globally over a similar period.
+Data on individual cases were collated from different sources using a systematic approach to describe the global epidemiology of 907 human H5N1 cases between May 1997 and April 2015.
+The number of affected countries rose between 2003 and 2008, with expansion from East and Southeast Asia, then to West Asia and Africa.
+Most cases (67.2%) occurred from December to March, and the overall case fatality risk was 53.5% (483/903) which varied across geographical regions.
+Although the incidence in Egypt has increased dramatically since November 2014, compared to the cases beforehand there were no significant differences in the fatality risk , history of exposure to poultry, history of human case contact, and time from onset to hospitalization in the recent cases.
+Like all other positive-strand RNA viruses, enteroviruses generate new organelles (replication organelles [ROs]) with a unique protein and lipid composition on which they multiply their viral genome.
+Suitable tools for live-cell imaging of enterovirus ROs are currently unavailable, as recombinant enteroviruses that carry genes that encode RO-anchored viral proteins tagged with fluorescent reporters have not been reported thus far.
+To overcome this limitation, we used a split green fluorescent protein (split-GFP) system, comprising a large fragment [strands 1 to 10; GFP(S1-10)] and a small fragment [strand 11; GFP(S11)] of only 16 residues.
+The GFP(S11) (GFP with S11 fragment) fragment was inserted into the 3A protein of the enterovirus coxsackievirus B3 (CVB3), while the large fragment was supplied by transient or stable expression in cells.
+The introduction of GFP(S11) did not affect the known functions of 3A when expressed in isolation.
+Using correlative light electron microscopy (CLEM), we showed that GFP fluorescence was detected at ROs, whose morphologies are essentially identical to those previously observed for wild-type CVB3, indicating that GFP(S11)-tagged 3A proteins assemble with GFP(S1-10) to form GFP for illumination of bona fide ROs.
+Through live-cell imaging of infected cells expressing an mCherry-tagged Golgi marker, we monitored RO development and revealed the dynamics of Golgi disassembly in real time.
+Having demonstrated the suitability of this virus for imaging ROs, we constructed a CVB3 encoding GFP(S1-10) and GFP(S11)-tagged 3A to bypass the need to express GFP(S1-10) prior to infection.
+These tools will have multiple applications in future studies on the origin, location, and function of enterovirus ROs.
+IMPORTANCE Enteroviruses induce the formation of membranous structures (replication organelles [ROs]) with a unique protein and lipid composition specialized for genome replication.
+Electron microscopy has revealed the morphology of enterovirus ROs, and immunofluorescence studies have been conducted to investigate their origin and formation.
+Yet, immunofluorescence analysis of fixed cells results in a rather static view of RO formation, and the results may be compromised by immunolabeling artifacts.
+While live-cell imaging of ROs would be preferred, enteroviruses encoding a membrane-anchored viral protein fused to a large fluorescent reporter have thus far not been described.
+Here, we tackled this constraint by introducing a small tag from a split-GFP system into an RO-resident enterovirus protein.
+This new tool bridges a methodological gap by circumventing the need for immunolabeling fixed cells and allows the study of the dynamics and formation of enterovirus ROs in living cells.
+Spinal cord injury results in a life-disrupting series of deleterious interconnected mechanisms encompassed by the primary and secondary injury.
+These events are mediated by the upregulation of genes with roles in inflammation, transcription, and signaling proteins.
+In particular, cytokines and growth factors are signaling proteins that have important roles in the pathophysiology of SCI.
+The balance between the proinflammatory and anti-inflammatory effects of these molecules plays a critical role in the progression and outcome of the lesion.
+The excessive inflammatory Th1 and Th17 phenotypes observed after SCI tilt the scale towards a proinflammatory environment, which exacerbates the deleterious mechanisms present after the injury.
+These mechanisms include the disruption of the spinal cord blood barrier, edema and ion imbalance, in particular intracellular calcium and sodium concentrations, glutamate excitotoxicity, free radicals, and the inflammatory response contributing to the neurodegenerative process which is characterized by demyelination and apoptosis of neuronal tissue.
+Andes virus (ANDV) is associated with a lethal vascular leak syndrome in humans termed hantavirus pulmonary syndrome (HPS).
+The mechanism for the massive vascular leakage associated with HPS is poorly understood; however, dysregulation of components of the immune response is often suggested as a possible cause.
+Alveolar macrophages are found in the alveoli of the lung and represent the first line of defense to many airborne pathogens.
+To determine whether alveolar macrophages play a role in HPS pathogenesis, alveolar macrophages were depleted in an adult rodent model of HPS that closely resembles human HPS.
+Syrian hamsters were treated, intratracheally, with clodronate-encapsulated liposomes or control liposomes and were then challenged with ANDV.
+Treatment with clodronate-encapsulated liposomes resulted in significant reduction in alveolar macrophages, but depletion did not prevent pathogenesis or prolong disease.
+Depletion also did not significantly reduce the amount of virus in the lung of ANDV-infected hamsters but altered neutrophil recruitment, MIP-1α and MIP-2 chemokine expression, and vascular endothelial growth factor (VEGF) levels in hamster bronchoalveolar lavage (BAL) fluid early after intranasal challenge.
+These data demonstrate that alveolar macrophages may play a limited protective role early after exposure to aerosolized ANDV but do not directly contribute to hantavirus disease pathogenesis in the hamster model of HPS.
+IMPORTANCE Hantaviruses continue to cause disease worldwide for which there are no FDA-licensed vaccines, effective postexposure prophylactics, or therapeutics.
+Much of this can be attributed to a poor understanding of the mechanism of hantavirus disease pathogenesis.
+Hantavirus disease has long been considered an immune-mediated disease; however, by directly manipulating the Syrian hamster model, we continue to eliminate individual immune cell types.
+As the most numerous immune cells present in the respiratory tract, alveolar macrophages are poised to defend against hantavirus infection, but those antiviral responses may also contribute to hantavirus disease.
+Here, we demonstrate that, like in our prior T and B cell studies, alveolar macrophages neither prevent hantavirus infection nor cause hantavirus disease.
+While these studies reflect pathogenesis in the hamster model, they should help us rule out specific cell types and prompt us to consider other potential mechanisms of disease in an effort to improve the outcome of human HPS.
+Influenza A and B viruses show clear differences in their host specificity and pandemic potential.
+Recent studies have revealed that the host protease TMPRSS2 plays an essential role for proteolytic activation of H1, H3, and H7 subtype strains of influenza A virus (IAV) in vivo.
+IAV possessing a monobasic cleavage site in the haemagglutinin (HA) protein replicates poorly in TMPRSS2 knockout mice owing to insufficient HA cleavage.
+In the present study, human isolates of influenza B virus (IBV) strains and a mouse-adapted IBV strain were analysed.
+The data showed that IBV successfully underwent HA cleavage in TMPRSS2 knockout mice, and that the mouse-adapted strain was fully pathogenic to these mice.
+The present data demonstrate a clear difference between IAV and IBV in their molecular mechanisms for spreading in vivo.
+BACKGROUND: In dogs with canine monocytic ehrlichiosis (CME), respiratory signs are uncommon and clinical and radiographic signs of interstitial pneumonia are poorly described.
+However, in human monocytic ehrlichiosis, respiratory signs are common and signs of interstitial pneumonia are well known.
+Pulmonary hypertension (PH) is classified based on the underlying disease and its treatment is aimed at reducing the clinical signs and, if possible, addressing the primary disease process.
+PH is often irreversible, but can be reversible if it is secondary to a treatable underlying etiology.
+CME is currently not generally recognized as one of the possible diseases leading to interstitial pneumonia and secondary PH in dogs.
+CASE PRESENTATION: A seven-year-old, male intact, mixed breed dog was presented with 2 weeks history of lethargy and dyspnea.
+Thoracic radiography showed moderate right-sided cardiomegaly with dilation of the main pulmonary artery and a mild diffuse interstitial lung pattern with peribronchial cuffing.
+On arterial blood gas analysis, severe hypoxemia was found and complete blood count revealed moderate regenerative anemia and severe thrombocytopenia.
+Treatment with oxygen supplementation, a typed packed red blood cell transfusion and medical therapy with doxycycline, pimobendan and sildenafil was initiated and the dog improved clinically.
+Approximately 2 weeks later, there was complete resolution of all clinical signs and marked improvement of the PH.
+CONCLUSION: This report illustrates that CME might be associated with significant pulmonary disease and should be considered as a possible differential diagnosis in dogs presenting with dyspnea and secondary pulmonary hypertension, especially in dogs that have been in endemic areas.
+This is important because CME is a treatable disease and its secondary lung and cardiac manifestations may be completely reversible.
+Carbapenem-resistant Acinetobacter (CRA) is becoming a serious concern with increasing patient morbidity, mortality, and lengths of hospital stay.
+Polymerase chain reaction (PCR) has been extensively used for the rapid identification of most pathogens.
+In this study, we have developed two multiplex real-time PCR assays to detect and differentiate A. baumannii and non-A.
+We demonstrate the potential utility of these assays for the direct detection of bla(NDM)-, bla(OXA-23-like)-, bla(OXA-40-like)-, bla(OXA-51-like)-, and bla(OXA-58-like)-positive CRA in clinical specimens.
+Primers were specifically designed, and two multiplex real-time PCR assays were developed: multiplex real-time PCR assay1 for the detection of Acinetobacter baumannii 16S–23S rRNA internal transcribed spacer sequence, the Acinetobacter recA gene, and class-B-metalloenzyme-encoding gene bla(NDM); and multiplex real-time PCR assay2 to detect class-D-oxacillinase-encoding genes (bla(OXA-23-like), bla(OXA-40-like), bla(OXA-51-like),and bla(OXA-58-like)).
+Known amounts of CRA cells were added to sputum and fecal specimens and used to test the multiplex real-time PCR assays.
+The results for target and nontarget amplification showed that the multiplex real-time PCR assays were specific, the limit of detection for each target was 10 copies per 20 μL reaction volume, the assays were linear over six log dilutions of the target genes (r(2) > 0.99), and the Ct values of the coefficients of variation for intra- and interassay reproducibility were less than 5%.
+The multiplex real-time PCR assays showed 100% concordance with conventional PCR when tested against 400 CRA isolates and their sensitivity for the target DNA in sputum and fecal specimens was 10(2) CFU/mL.
+Therefore, these novel multiplex real-time PCR assays allow the sensitive and specific characterization and differentiation of bla(NDM)-, bla(OXA-23-like)-, bla(OXA-40-like)-, bla(OXA-51-like)-, and bla(OXA-58-like)-positive CRA, making them potential tools for the direct detection of CRA in clinical specimens and the surveillance of nosocomial infections.
+Foamy viruses (FV) belong to the genus Spumavirus, which forms a distinct lineage in the Retroviridae family.
+Although the infection in natural hosts and zoonotic transmission to humans is asymptomatic, FVs can replicate well in human cells making it an attractive gene therapy vector candidate.
+Here we present cryo-electron microscopy and (cryo-)electron tomography ultrastructural data on purified prototype FV (PFV) and PFV infected cells.
+Mature PFV particles have a distinct morphology with a capsid of constant dimension as well as a less ordered shell of density between the capsid and the membrane likely formed by the Gag N-terminal domain and the cytoplasmic part of the Env leader peptide gp18(LP).
+In situ 3D reconstruction by subtomogram averaging of wild type Env and of a Env gp48(TM)- gp80(SU) cleavage site mutant showed a similar spike architecture as well as stabilization of the hexagonal lattice by clear connections between lower densities of neighboring trimers.
+Cryo-EM was employed to obtain a 9 Å resolution map of the glycoprotein in its pre-fusion state, which revealed extensive trimer interactions by the receptor binding subunit gp80(SU) at the top of the spike and three central helices derived from the fusion protein subunit gp48(TM).
+The lower part of Env, presumably composed of interlaced parts of gp48(TM), gp80(SU) and gp18(LP) anchors the spike at the membrane.
+We propose that the gp48(TM) density continues into three central transmembrane helices, which interact with three outer transmembrane helices derived from gp18(LP).
+Our ultrastructural data and 9 Å resolution glycoprotein structure provide important new insights into the molecular architecture of PFV and its distinct evolutionary relationship with other members of the Retroviridae.
+BACKGROUND: Our aim was to investigate the influence of FTS on human cellular and humoral immunity using a randomized controlled clinical study in esophageal cancer patients.
+METHODS: Between October 2013 and December 2014, 276 patients with esophageal cancer in our department were enrolled in the study.
+The markers of inflammatory and immune function were measured before operation as well as on the 1st, 3rd, and 7th postoperative days (POD), including serum level of interleukin-6 (IL-6), C-reactive protein (CRP), serum globulin, immunoglobulin G (IgG), immunoglobulin M (IgM), immunoglobulin A (IgA) and lymphocyte subpopulations (CD3 lymphocytes, CD4 lymphocytes, CD8 lymphocytes and the CD4/CD8 ratio) in the patients between the two groups.
+RESULTS: In all, 260 patients completed the study: 128 in the FTS group and 132 in the conventional group.
+We found implementation of FTS pathway decreases postoperative length of stay and hospital charges (P < 0.05).
+In addition, inflammatory reactions, based on IL-6 and CRP levels, were less intense following FTS pathway compared to conventional pathway on POD1 and POD3 (P < 0.05).
+On POD1 and POD3, the levels of IgG, IgA, CD3 lymphocytes, CD4 lymphocytes and the CD4/CD8 ratio in FTS group were significantly higher than those in control group (All P < 0.05).
+However, there were no differences in the level of IgM and CD8 lymphocytes between the two groups.
+CONCLUSIONS: FTS improves postoperative clinical recovery and effectively inhibited release of inflammatory factors via the immune system after esophagectomy for esophageal cancer.
+The nucleoprotein (NP) of Ebola virus (EBOV) and Marburg virus (MARV) is an essential component of the viral ribonucleoprotein complex and significantly impacts replication and transcription of the viral RNA genome.
+Although NP is regarded as a promising antiviral druggable target, no chemical ligands have been reported to interact with EBOV NP or MARV NP.
+We identified two compounds from a traditional Chinese medicine Gancao (licorice root) that can bind both NPs by combining affinity mass spectrometry and metabolomics approaches.
+These two ligands, 18β-glycyrrhetinic acid and licochalcone A, were verified by defined compound mixture screens and further characterized with individual ligand binding assays.
+Accompanying biophysical analyses demonstrate that binding of 18β-glycyrrhetinic acid to EBOV NP significantly reduces protein thermal stability, induces formation of large NP oligomers, and disrupts the critical association of viral ssRNA with NP complexes whereas the compound showed no such activity on MARV NP.
+Our study has revealed the substantial potential of new analytical techniques in ligand discovery from natural herb resources.
+In addition, identification of a chemical ligand that influences the oligomeric state and RNA-binding function of EBOV NP sheds new light on antiviral drug development.
+Background Virus‐inducible reporter genes have been used as the basis of virus detection and quantitation assays for a number of viruses.
+In this report, we describe the extension of this strategy to influenza B virus, the generation of stable cell lines with influenza A and B virus‐inducible reporter genes, and the use of these cells in various clinically relevant viral assays.
+Each of the cell lines described herein constitutively express an RNA transcript that contains a reporter gene coding region flanked by viral 5′‐ and 3′‐untranslated regions (UTR) and therefore mimics an influenza virus genomic segment.
+Upon infection of the cells with influenza virus the virus‐inducible reporter gene segment (VIRGS) is replicated and transcribed by the viral polymerase complex resulting in reporter gene expression.
+Findings Reporter gene induction occurs after infection with a number of laboratory strains and clinical isolates of influenza virus including several H5N1 strains.
+Conclusions These cell lines provide the basis of simple, rapid, and objective assays that involve virus quantitation such as determination of viral titer, assessment of antiviral susceptibility, and determination of antibody neutralization titer.
+Methyl bromide (CH3Br) is a colorless and odorless volatile gas, used as an insecticide, fire extinguisher, fumigant, and refrigerant.
+Although forbidden since 1987 for domestic use, it is still used in industry, for example, to fumigate agricultural fields which are for importation in the United States.
+Here is the case of a 74-year-old man who was accidentally exposed to methyl bromide after using an old fire extinguisher.
+Even though he finally survived, he developed a severe multiple organ failure and spent 2 months in intensive care unit.
+We present in this report all the difficulties we had to diagnose this unusual poisoning.
+Multiple sclerosis (MS) is an inflammatory disease in which myelin in the spinal cord is damaged.
+C-C chemokine receptor type 5 (CCR5) is implicated in immune cell migration and cytokine release in central nervous system (CNS).
+We investigated whether CCR5 plays a role in MS progression using a murine model, experimental autoimmune encephalomyelitis (EAE), in CCR5 deficient (CCR5(−/−)) mice.
+CCR5(−/−) and CCR5(+/+) (wild-type) mice were immunized with myelin oligodendrocyte glycoprotein 35-55 (MOG(35-55)) followed by pertussis toxin, after which EAE paralysis was scored for 28 days.
+We found that clinical scoring and EAE neuropathology were lower in CCR5(−/−) mice than CCR5(+/+) mice.
+Immune cells (CD3(+), CD4(+), CD8(+), B cell, NK cell and macrophages) infiltration and astrocytes/microglial activation were attenuated in CCR5(−/−) mice.
+Moreover, levels of IL-1β, TNF-α, IFN-γ and MCP-1 cytokine levels were decreased in CCR5(−/−) mice spinal cord.
+Myelin basic protein (MBP) and CNPase were increased while NG2 and O4 were decreased in CCR5(−/−) mice, indicating that demyelination was suppressed by CCR5 gene deletion.
+These findings suggest that CCR5 is likely participating in demyelination in the spinal cord the MS development, and that it could serve as an effective therapeutic target for the treatment of MS.
+The mucus-dwelling parasite Ostertagia ostertagi is one of the most important gastrointestinal nematodes in cattle.
+Our group has previously demonstrated the protective capacity of a vaccine against this parasite based on a native activation-associated secreted protein ASP1 (nASP) in combination with the saponin adjuvant QuilA.
+The aim of the current study was to analyse the effect of both antigen and adjuvant on the cellular and humoral vaccine-induced immune responses by comparing the native ASP to a recombinant version expressed in Pichia pastoris (pASP) and replacing QuilA by Al(OH)(3).
+Immunization of cattle with the protective nASP+QuilA vaccine was associated with antigen-induced proliferation of natural killer (NK) cells combined with IFN-γ secretion and the induction of a mixed IgG1/IgG2 antibody response.
+ASP-specific activation and proliferation of NK cells was also observed in mice following the same vaccination regime.
+Replacing QuilA by Al(OH)(3) or nASP by pASP significantly decreased the capacity of the vaccines to trigger both NK cell activation and antibody responses and failed to induce protection against a challenge infection.
+Reduction of the structurally anchoring disulphide bonds of the nASP completely abolished its ability to induce NK cell activation and antibody responses, highlighting the importance of protein conformation for the immunostimulatory activity.
+(2012) Molecular and phylogenetic analysis of matrix gene of avian influenza viruses isolated from wild birds and live bird markets in the USA.
+Background Wild birds are the natural hosts for influenza A viruses (IAVs) and provide a niche for the maintenance of this virus.
+Objectives This study was undertaken to analyze nucleotide sequences of the matrix (M) gene of AIVs isolated from wild birds and live bird markets (LBMs) to index the changes occurring in this gene.
+Methods M‐gene of 229 avian influenza virus (AIV) isolates obtained from wild birds and LBMs was amplified and sequenced.
+thus obtained were analyzed to identify changes that may be associated with resistance to adamantanes.
+Phylogenetic analysis of all sequences was performed using clustalw, and evolutionary distances were calculated by maximum composite likelihood method using mega (ver.
+Results Twenty‐seven different viral subtypes were represented with H3N8 being the most dominant subtype in wild birds and H7N2 being the predominant subtype among isolates from LBMs.
+Phylogenetic analysis of the M‐gene showed a high degree of nucleotide sequence identity with US isolates of AIVs but not with those of Asian or European lineages.
+While none of the isolates from wild birds had any antiviral resistance–associated mutations, 17 LBM isolates carried polymorphisms known to cause reduced susceptibility to antiviral drugs (adamantanes).
+Conclusions These results indicate independent evolution of M‐gene in the absence of any antiviral drugs leading to mutations causing resistance indicating the need for continued active surveillance of AIVs.
+Background The emergence of zoonotic viruses in domestic animals is a significant public health concern.
+Canine influenza virus (CIV) H3N2 is a virus that can infect companion animals and is, therefore, a potential public health concern.
+Objective This study investigated the inter‐ and intraspecies transmission of CIV among dogs, cats, and ferrets, under laboratory conditions, to determine whether transmission of the virus was possible between as well as within these domestic animal species.
+Method The transmission routes for inter‐ and intraspecies transmission were airborne and direct contact, respectively.
+Transmission was conducted through intranasal infection of dogs followed by exposure to either cats or ferrets and by comingling infected and naïve animals of the same species.
+Results The interspecies transmission of CIV H3N2 via airborne was only observed from dogs to cats and not from dogs to ferrets.
+However, direct intranasal infection of either cats or ferrets with CIV could induce influenza‐like clinical signs, viral shedding, and serological responses.
+Additionally, naïve cats and ferrets could be infected by CIV via direct contact with infected animals of the same species.
+Conclusion Cats appear to be another susceptible host of CIV H3N2, whereas ferrets are not likely natural hosts.
+The molecular‐based mechanism of interspecies and intraspecies transmission of CIV H3N2 should be further studied.
+Background Chloroquine is an inexpensive and widely available 9‐aminoquinolone used in the management of malaria.
+Recently, in vitro assays suggest that chloroquine may have utility in the treatment of several viral infections including influenza.
+Objectives We sought to test whether chloroquine is effective against influenza in vivo in relevant animal models.
+Methods The effectiveness of chloroquine at preventing or ameliorating influenza following viral challenge was assessed in established mouse and ferret disease models.
+Results Although active against influenza viruses in vitro, chloroquine did not prevent the weight loss associated with influenza virus infection in mice after challenge with viruses expressing an H1 or H3 hemagglutinin protein.
+Similarly, clinical signs and viral replication in the nose of ferrets were not altered by treatment.
+Conclusions Although in vitro results were promising, chloroquine was not effective as preventive therapy in vivo in standard mouse and ferret models of influenza virus infection.
+Background Recent studies have revealed the existence of genetic diversity in swine influenza viruses (SIVs) in the world.
+In Thailand, there has been a little information on the molecular characteristics of the SIVs since the first isolation of viruses of H1N1 and H3N2 subtypes in the late 1970s.
+Our previous study demonstrated that Thai H1N1 SIVs possessed the classical swine H1 and avian‐like swine N1 genes (Takemae et al., Proceedings of the Options for the Control of Influenza VI.2007;350–353).
+Objectives In the present study, we genetically characterized 12 SIVs including those of H1N1, H1N2 and H3N2 subtypes isolated between 2000 and 2005.
+Methods We determined the entire nucleotide sequences of the eight gene segments of those isolates.
+The existence of two distinct sublineages within classical swine H1 and NS, avian‐like swine PA and M and human H3 and N2 genes of the Thai SIVs suggested that introduction of viruses of classical swine, avian‐like swine and human origins occurred twice respectively into the Thai pig population.
+In particular, three polymerase (PB1, PB2 and PA) and matrix genes of avian‐like swine origin were retained in all the Thai SIVs examined.
+Conclusions These observations may suggest that genes of avian‐like swine lineages have some advantages to be maintained in pigs as seen in the SIVs established through multiple introductions in other regions.
+Background The threat posed by swine influenza viruses with potential to transmit from pig populations to other hosts, including humans, requires the development of new experimental systems to study different aspects of influenza infection.
+Ex vivo organ culture (EVOC) systems have been successfully used in the study of both human and animal respiratory pathogens.
+Objectives We aimed to develop an air interface EVOC using pig tracheas in the study of influenza infection demonstrating that tracheal explants can be effectively maintained in organ culture and support productive influenza infection.
+Histological characteristics were analysed with different staining protocols and co‐ordinated ciliary movement on the epithelial surface was evaluated through a bead clearance assay.
+Influenza infection of epithelial cells was confirmed by immunohistochemistry and viral replication was quantified by plaque assays and real‐time RT‐PCR.
+Results Histological analysis and bead clearance assay showed that the tissue architecture of the explants was maintained for up to 7 days, while ciliary movement exhibited a gradual decrease after 4 days.
+Challenge with swine H1N1 influenza virus showed that the EVOC tracheal system shows histological changes consistent with in vivo influenza infection and supported productive viral replication over multiple cycles of infection.
+Conclusion The air interface EVOC system using pig trachea described here constitutes a useful biological tool with a wide range of applications in the study of influenza infection.
+Background Annual influenza vaccination is recommended for all Australian health care workers (HCWs) including those working in primary health care.
+There is limited published data on coverage, workplace provision, attitudes and personal barriers to influenza vaccination amongst primary health care staff.
+The aim of this study was to contribute to the limited literature base in this important area by investigating these issues in the primary health care setting in New South Wales (NSW), Australia.
+Methods A postal survey was sent to general practitioners (GPs) and practice nurses (PNs) from inner city, semi‐urban and rural areas of NSW, Australia.
+There were 139 responses in total (response rate 36%) from 79 GPs (response rate 30%) and 60 PNs (response rate 46%).
+Results Reported influenza vaccination coverage in both 2007 and 2008 was greater than 70%, with GPs reporting higher coverage than PNs in both years.
+The main barriers identified were lack of awareness of vaccination recommendations for general practice staff and concern about adverse effects from the vaccine.
+Conclusions Rates of influenza vaccination coverage reported in this study were higher than in previous studies of hospital and institutional HCWs, though it is possible that the study design may have contributed to these higher results.
+Nevertheless, these findings highlight that more needs to be done to understand barriers to vaccination in this group, to inform the development of appropriate strategies to increase vaccination coverage in primary health care staff, with a special focus on PNs.
+Background The new influenza virus A/H1N1 (2009), identified in mid‐2009, rapidly spread over the world.
+Methods We reviewed all studies presenting estimates of the serial interval or generation time and the reproduction number of the A/H1N1 (2009) virus infection.
+Results Thirteen studies documented the serial interval from household or close‐contact studies, with overall mean 3 days (95% CI: 2·4, 3·6); taking into account tertiary transmission reduced this estimate to 2·6 days.
+Accounting for under‐reporting in the early period of the pandemic and limiting variation because of the choice of the generation time interval, the reproduction number was between 1·2 and 2·3 with median 1·5.
+Discussion The serial interval of A/H1N1 (2009) flu was typically short, with mean value similar to the seasonal flu.
+Compared with past influenza pandemics, the median reproduction number was similar (1968) or slightly smaller (1889, 1918, 1957).
+Mammalian host response to pathogenic infections is controlled by a complex regulatory network connecting regulatory proteins such as transcription factors and signaling proteins to target genes.
+An important challenge in infectious disease research is to understand molecular similarities and differences in mammalian host response to diverse sets of pathogens.
+Recently, systems biology studies have produced rich collections of omic profiles measuring host response to infectious agents such as influenza viruses at multiple levels.
+To gain a comprehensive understanding of the regulatory network driving host response to multiple infectious agents, we integrated host transcriptomes and proteomes using a network-based approach.
+Our approach combines expression-based regulatory network inference, structured-sparsity based regression, and network information flow to infer putative physical regulatory programs for expression modules.
+We applied our approach to identify regulatory networks, modules and subnetworks that drive host response to multiple influenza infections.
+The inferred regulatory network and modules are significantly enriched for known pathways of immune response and implicate apoptosis, splicing, and interferon signaling processes in the differential response of viral infections of different pathogenicities.
+We used the learned network to prioritize regulators and study virus and time-point specific networks.
+RNAi-based knockdown of predicted regulators had significant impact on viral replication and include several previously unknown regulators.
+Taken together, our integrated analysis identified novel module level patterns that capture strain and pathogenicity-specific patterns of expression and helped identify important regulators of host response to influenza infection.
+Canine parvovirus (CPV) reproduces by co-opting the resources of host cells, inevitably causing cytotoxic effects to the host cells.
+Feline kidney F81 cells are sensitive to CPV infection and show disparate growing statuses at different time points post-infection.
+This study analysed the response of F81 cells to CPV infection at successive infection time points by iTRAQ-based quantitative proteomics.
+Differentially expressed proteins (DEPs) during 60 h of infection and at selected time points post-infection were identified by an analysis of variance test and a two-tailed unpaired t test, respectively.
+DEPs with similar quantitative changes were clustered by hierarchical clustering and analysed by gene ontology enrichment, revealing that 12 h and 60 h post-infection were the optimal times to analyse the autonomous parvovirus replication and apoptosis processes, respectively.
+Using the Metacore(TM) database, 29 DEPs were enriched in a network involved in p53 regulation.
+Besides, a significantly enriched pathway suggests that the CPV-induced cytopathic effect was probably due to the deficiency of functional CFTR caused by CPV infection.
+This study uncovered the systemic changes in key cellular factors involved in CPV infection and help to understand the molecular mechanisms of the anti-cancer activity of CPV and the cytopathic effects induced by CPV infection.
+Antibodies against spike proteins of influenza are used as a tool for characterization of viruses and therapeutic approaches.
+To circumvent these difficulties, three peptides were derived from complementarity determining regions of an antibody heavy chain against influenza A spike glycoprotein.
+One of them, termed PeB, with the highest affinity prevented binding to and infection of target cells in the micromolar region without any cytotoxic effect.
+PeB bound also to other medical relevant influenza strains, such as human-pathogenic A/California/7/2009 H1N1, and avian-pathogenic A/Mute Swan/Rostock/R901/2006 H7N1.
+Strategies to improve the affinity and to adapt specificity are discussed and exemplified by a double amino acid substituted peptide, obtained by substitutional analysis.
+The peptides and their derivatives are of great potential for drug development as well as biosensing.
+Listeria monocytogenes is an environmental saprophyte and facultative intracellular bacterial pathogen with a well-defined life-cycle that involves escape from a phagosome, rapid cytosolic growth, and ActA-dependent cell-to-cell spread, all of which are dependent on the master transcriptional regulator PrfA.
+The environmental cues that lead to temporal and spatial control of L. monocytogenes virulence gene expression are poorly understood.
+In this study, we took advantage of the robust up-regulation of ActA that occurs intracellularly and expressed Cre recombinase from the actA promoter and 5’ untranslated region in a strain in which loxP sites flanked essential genes, so that activation of actA led to bacterial death.
+Upon screening for transposon mutants that survived intracellularly, six genes were identified as necessary for ActA expression.
+Strikingly, most of the genes, including gshF, spxA1, yjbH, and ohrA, are predicted to play important roles in bacterial redox regulation.
+The mutants identified in the genetic selection fell into three broad categories: (1) those that failed to reach the cytosolic compartment; (2) mutants that entered the cytosol, but failed to activate the master virulence regulator PrfA; and (3) mutants that entered the cytosol and activated transcription of actA, but failed to synthesize it.
+The identification of mutants defective in vacuolar escape suggests that up-regulation of ActA occurs in the host cytosol and not the vacuole.
+Moreover, these results provide evidence for two non-redundant cytosolic cues; the first results in allosteric activation of PrfA via increased glutathione levels and transcriptional activation of actA while the second results in translational activation of actA and requires yjbH.
+Although the precise host cues have not yet been identified, we suggest that intracellular redox stress occurs as a consequence of both host and pathogen remodeling their metabolism upon infection.
+These were the fundamental questions driving a workshop to examine the future of predictive surveillance for viruses that might jump from animals to infect humans.
+Virologists, ecologists and computational biologists from academia, federal government and non-governmental organizations discussed opportunities as well as obstacles to the prediction of species jumps using genetic and ecological data from viruses and their hosts, vectors and reservoirs.
+This workshop marked an important first step towards envisioning both scientific and organizational frameworks for this future capability.
+Canine parvoviruses as well as seasonal H3N2 and pandemic H1N1 influenza viruses are discussed as exemplars that suggest what to look for in anticipating species jumps.
+To answer the question of where to look, prospects for discovering emerging viruses among wildlife, bats, rodents, arthropod vectors and occupationally exposed humans are discussed.
+Finally, opportunities and obstacles are identified and accompanied by suggestions for how to look for species jumps.
+Taken together, these findings constitute the beginnings of a conceptual framework for achieving a virus surveillance capability that could predict future species jumps.
+The Ebola virus disease (EVD) epidemic in West Africa in 2013–2015 spread heterogeneously across the three hardest-hit countries Guinea, Liberia and Sierra Leone and the estimation of national transmission of EVD provides little information about local dynamics.
+To investigate district-level transmissibility of EVD, we applied a statistical modelling approach to estimate the basic reproduction number (R(0)) for each affected district and each country using weekly incident case numbers.
+We estimated growth rates during the early exponential phase of the outbreak using exponential regression of the case counts on the first eight weeks since onset.
+To take into account the heterogeneity between and within countries, we fitted a mixed effects model and calculated R(0) based on the predicted individual growth rates and the reported serial interval distribution.
+At district level, R(0) ranged from 0.36 (Dubréka) to 1.72 (Beyla) in Guinea, from 0.53 (Maryland) to 3.37 (Margibi) in Liberia and from 1.14 (Koinadugu) to 2.73 (Western Rural) in Sierra Leone.
+At national level, we estimated an R(0) of 0.97 (95% CI 0.77–1.18) for Guinea, 1.26 (95% CI 0.98–1.55) for Liberia and 1.66 (95% CI 1.32–2.00) for Sierra Leone.
+Socio-demographic variables related to urbanisation such as high population density and high wealth index were found positively associated with R(0) suggesting that the consequences of fast urban growth in West Africa may have contributed to the increased spread of EVD.
+BACKGROUND: The first government funded and sustainable dialysis unit was established in Ethiopia at Saint Paul’s Hospital Millennium Medical College (SPHMMC).
+This has led to the development of a unique cohort of patients about which very little is known.
+This study was conducted to describe the clinical profile and outcome of adult Acute Kidney Injury (AKI) patients treated with intermittent haemodialysis at the dialysis center of SPHMMC.
+METHODS: A retrospective review of clinical records of cases of AKI who required haemodialysis support during the time period from August 1, 2013 to February 1, 2015 was conducted.
+Overall, the patients were generally younger with a mean age of 36.7 years and thus with few premorbid conditions.
+The most common causes of AKI were hypovolemia (22.5 %), acute glomerulonephritis (AGN) (21.9 %) and pregnancy related causes (18.5 %).
+CONCLUSION: Infections, AGN, obstetric causes and nephrotoxins were the primary causes of dialysis requiring AKI.
+Most of these causes can be prevented with simple interventions such as health education on oral rehydration, quality prenatal and emergency obstetric care, appropriate management of infections and taking appropriate precautions when prescribing potentially nephrotoxic medications.
+Heat-labile enterotoxins (LT) of enterotoxigenic Escherichia coli (ETEC) are structurally and functionally related to cholera toxin (CT).
+LT-I toxins are plasmid-encoded and flanked by IS elements, while LT-II toxins of type II ETEC are chromosomally encoded with flanking genes that appear phage related.
+Here, I determined the complete genomic sequence of the locus for the LT-IIa type strain SA53, and show that the LT-IIa genes are encoded by a 51 239 bp lambdoid prophage integrated at the rac locus, the site of a defective prophage in E. coli K12 strains.
+Of 50 LT-IIa and LT-IIc, 46 prophages also encode one member of two novel two-gene ADP-ribosyltransferase toxin families that are both related to pertussis toxin, which I named eplBA or ealAB, respectively.
+The eplBA and ealAB genes are syntenic with the Shiga toxin loci in their lambdoid prophages of the enteric pathogen enterohemorrhagic E. coli.
+These novel AB(5) toxins show pertussis-toxin-like activity on tissue culture cells, and like pertussis toxin bind to sialic acid containing glycoprotein ligands.
+Type II ETEC are the first mucosal pathogens known to simultaneously produce two ADP-ribosylating toxins predicted to act on and modulate activity of both stimulatory and inhibitory alpha subunits of host cell heterotrimeric G-proteins.
+Avian influenza viruses sporadically cross the species barrier to mammals, including humans, in which they may cause epidemic disease.
+Recently such an epidemic occurred due to the emergence of avian influenza virus of the subtype H10N7 (Seal/H10N7) in harbor seals (Phoca vitulina).
+This epidemic caused high mortality in seals along the north-west coast of Europe and represented a potential risk for human health.
+To characterize the spectrum of lesions and to identify the target cells and viral distribution, findings in 16 harbor seals spontaneously infected with Seal/H10N7 are described.
+The seals had respiratory tract inflammation extending from the nasal cavity to bronchi associated with intralesional virus antigen in respiratory epithelial cells.
+The fatal outcome of the viral infection in seals was most likely caused by secondary bacterial infections.
+To investigate the pathogenic potential of H10N7 infection for humans, we inoculated the seal virus intratracheally into six ferrets and performed pathological and virological analyses at 3 and 7 days post inoculation.
+These experimentally inoculated ferrets displayed mild clinical signs, virus excretion from the pharynx and respiratory tract inflammation extending from bronchi to alveoli that was associated with virus antigen expression exclusively in the respiratory epithelium.
+In conclusion, Seal/H10N7 infection in naturally infected harbor seals and experimentally infected ferrets shows that respiratory epithelial cells are the permissive cells for viral replication.
+Fatal outcome in seals was caused by secondary bacterial pneumonia similar to that in fatal human cases during influenza pandemics.
+This outbreak of LPAI from wild birds to seals demonstrates the risk of such occasions for mammals and thus humans.
+We screened a siRNA library targeting human tyrosine kinases in Huh-7 cells and identified c-terminal Src kinase (Csk) as one of the kinases involved in dengue virus replication.
+Knock-down of Csk expression by siRNAs or inhibition of Csk by an inhibitor reduced dengue virus RNA levels but did not affect viral entry.
+Dengue infection was drastically reduced in cells lacking the three ubiquitous src family kinases, Src, Fyn and Yes.
+Csk knock-down in these cells failed to block dengue virus replication suggesting that the effect of Csk is via regulation of Src family kinases.
+Csk was found to be hyper-phosphorylated during dengue infection and inhibition of protein kinase A led to a block in Csk phosphorylation and dengue virus replication.
+Overexpression studies suggest an important role for the kinase and SH3 domains in this process.
+Our results identified a novel role for Csk as a host tyrosine kinase involved in dengue virus replication and provide further insights into the role of host factors in dengue replication.
+BACKGROUND: A wide variety of probiotic products has been introduced into the market in the past decade.
+Research trends and activity on probiotics help understand how these products were evolved and their potential future role in medicine.
+The objective of this study was to assess the research activity on probiotics in pediatrics using bibliometric indicators and network visualization.
+METHODS: Original and review articles on probiotics in pediatrics published worldwide were retrieved from SciVerse, Scopus (1994–2014) and analyzed.
+Research activity on probiotics in pediatrics showed approximately 90- fold increase during the study period.
+Approximately 22 % of published articles originated from USA and has the greatest share, however, Finland ranked first when data were stratified by population or income.
+The most productive institution in this field was Turku University in Finland with 82 (2.91 %) articles.
+The total number of citations for the retreived documents documents was 70991, and the average citation per article was 25.20.
+CONCLUSIONS: Interest in probiotic research and its potential benefits in pediatric ailments is relatively recent but significantly increasing.
+Bibliometric analysis can be used as an indicator of the importance and growth of probiotic use in pediatrics.
+There is growing scientific and public recognition that human actions, directly and indirectly, have profoundly changed the Earth system, in a still accelerating process, increasingly called the “Anthropocene”.
+Planetary transformation, including of the atmosphere, climate, ecosystems and biodiversity, has enormous implications for human health, many of which are deeply disturbing, especially in low-income settings.
+A few health consequences of the Anthropocene have been partially recognized, including within environmental epidemiology, but their long-term consequences remain poorly understood and greatly under-rated.
+For example Syria could be a “sentinel” population, giving a glimpse to a much wider dystopian future.
+Health-Earth is a research network, co-founded in 2014, which seeks, with other groups, to catalyse a powerful curative response by the wider health community.
+This paper builds on a symposium presented by Health-Earth members at the 2015 conference of the International Society for Environmental Epidemiology.
+It reviews and synthesizes parts of the large literature relevant to the interaction between the changing Earth system and human health.
+It concludes that this topic should be prominent within future environmental epidemiology and public health.
+Created by our species, these challenges may be soluble, but solutions require far more understanding and resources than are currently being made available.
+Analysis of codon usage data has both practical and theoretical applications in understanding the basics of molecular biology.
+Differences in codon usage patterns among genes reflect variations in local base compositional biases and the intensity of natural selection.
+Recently, there have been several reports related to codon usage in fungi, but little is known about codon usage bias in Epichloë endophytes.
+The present study aimed to assess codon usage patterns and biases in 4870 sequences from Epichloë festucae, which may be helpful in revealing the constraint factors such as mutation or selection pressure and improving the bioreactor on the cloning, expression, and characterization of some special genes.
+The GC content with 56.41% is higher than the AT content (43.59%) in E. festucae.
+The results of neutrality and effective number of codons plot analyses showed that both mutational bias and natural selection play roles in shaping codon usage in this species.
+We found that gene length is strongly correlated with codon usage and may contribute to the codon usage patterns observed in genes.
+E. festucae exhibits codon usage bias based on the relative synonymous codon usage (RSCU) values of 61 sense codons, with 25 codons showing an RSCU larger than 1.
+To determine the effectiveness of immunization strategies used in therapeutic antibody or vaccine development, it is critical to assess the quality of immunization-induced polyclonal antibody responses.
+Here, we developed a workflow that uses sensitive methods to quantitatively and qualitatively assess immune responses against foreign antigens with regard to antibody binding affinity and epitope diversity.
+The application of such detailed assessments throughout an immunization campaign can significantly reduce the resources required to generate highly specific antibodies.
+Our workflow consists of the following two steps: 1) the use of surface plasmon resonance to quantify antigen-specific antibodies and evaluate their apparent binding affinities, and 2) the recovery of serum IgGs using an automated small scale purification system, followed by the determination of their epitope diversity using hydrogen deuterium exchange coupled with mass spectrometry.
+We showed that these methods were sensitive enough to detect antigen-specific IgGs in the nanogram/μl range and that they provided information for differentiating the antibody responses of the various immunized animals that could not be obtained by conventional methods.
+We also showed that this workflow can guide the selection of an animal that produces high affinity antibodies with a desired epitope coverage profile, resulting in the generation of potential therapeutic monoclonal antibody clones with desirable functional profiles.
+We postulate that this workflow will be an important tool in the development of effective vaccines to combat the highly sophisticated evasion mechanisms of pathogens.
+As of 20 May 2016 there have been 28,646 cases and 11,323 deaths resulting from the West African Ebola virus disease (EVD) outbreak reported to the World Health Organization.
+EVD presentation is nonspecific and characterized initially by onset of fatigue, myalgias, arthralgias, headache, and fever; this is followed several days later by anorexia, nausea, vomiting, diarrhea, and abdominal pain.
+Anorexia and gastrointestinal losses lead to dehydration, electrolyte abnormalities, and metabolic acidosis, and, in some patients, acute kidney injury.
+Hypoxia and ventilation failure occurs most often with severe illness and may be exacerbated by substantial fluid requirements for intravascular volume repletion and some degree of systemic capillary leak.
+Although minor bleeding manifestations are common, hypovolemic and septic shock complicated by multisystem organ dysfunction appear the most frequent causes of death.
+Males and females have been equally affected, with children (0–14 years of age) accounting for 19 %, young adults (15–44 years) 58 %, and older adults (≥45 years) 23 % of reported cases.
+While the current case fatality proportion in West Africa is approximately 40 %, it has varied substantially over time (highest near the outbreak onset) according to available resources (40–90 % mortality in West Africa compared to under 20 % in Western Europe and the USA), by age (near universal among neonates and high among older adults), and by Ebola viral load at admission.
+While there is no Ebola virus-specific therapy proven to be effective in clinical trials, mortality has been dramatically lower among EVD patients managed with supportive intensive care in highly resourced settings, allowing for the avoidance of hypovolemia, correction of electrolyte and metabolic abnormalities, and the provision of oxygen, ventilation, vasopressors, and dialysis when indicated.
+This experience emphasizes that, in addition to evaluating specific medical treatments, improving the global capacity to provide supportive critical care to patients with EVD may be the greatest opportunity to improve patient outcomes.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13054-016-1325-2) contains supplementary material, which is available to authorized users.
+Influenza virus remains a threat because of its ability to evade vaccine-induced immune responses due to antigenic drift.
+Here, we describe the isolation, evolution, and structure of a broad-spectrum human monoclonal antibody (mAb), MEDI8852, effectively reacting with all influenza A hemagglutinin (HA) subtypes.
+MEDI8852 uses the heavy-chain VH6-1 gene and has higher potency and breadth when compared to other anti-stem antibodies.
+MEDI8852 is effective in mice and ferrets with a therapeutic window superior to that of oseltamivir.
+Crystallographic analysis of Fab alone or in complex with H5 or H7 HA proteins reveals that MEDI8852 binds through a coordinated movement of CDRs to a highly conserved epitope encompassing a hydrophobic groove in the fusion domain and a large portion of the fusion peptide, distinguishing it from other structurally characterized cross-reactive antibodies.
+The unprecedented breadth and potency of neutralization by MEDI8852 support its development as immunotherapy for influenza virus-infected humans.
+Influenza viruses (IVs) circulate seasonally and are a common cause of respiratory infections in pediatric and adult patients.
+Since accurate treatment strategies are still missing, research refocuses attention to lung pathology and cellular crosstalk to develop new therapeutic options.
+Alveolar epithelial cells (AECs) play an important role in orchestrating the pulmonary antiviral host response.
+After IV infection they release a cascade of immune mediators, one of which is granulocyte and macrophage colony-stimulating factor (GM-CSF).
+In the lung, GM-CSF drives immune functions of alveolar macrophages and dendritic cells (DCs) and also improves epithelial repair processes through direct interaction with AECs.
+During IV infection, AEC-derived GM-CSF shows a lung-protective effect that is also present after local GM-CSF application.
+This mini-review provides an overview on GM-CSF-modulated immune responses to IV pneumonia and its therapeutic potential in severe IV pneumonia.
+There is great interest in the development of Ab-inducing subunit vaccines targeting infections, including HIV, malaria, and Ebola.
+We previously reported that adenovirus vectored vaccines are potent in priming Ab responses, but uncertainty remains regarding the optimal approach for induction of humoral immune responses.
+In this study, using OVA as a model Ag, we assessed the magnitude of the primary and anamnestic Ag–specific IgG responses of mice to four clinically relevant vaccine formulations: replication-deficient adenovirus; modified vaccinia Ankara (a poxvirus); protein with alum; and protein in the squalene oil-in-water adjuvant Addavax.
+We then used flow cytometric assays capable of measuring total and Ag-specific germinal center (GC) B cell and follicular Th cell responses to compare the induction of these responses by the different formulations.
+We report that adenovirus vectored vaccines induce Ag insert–specific GC B cell and Ab responses of a magnitude comparable to those induced by a potent protein/squalene oil-in-water formulation whereas—despite a robust overall GC response—the insert-specific GC B cell and Ab responses induced by modified vaccinia Ankara were extremely weak.
+Ag-specific follicular Th cell responses to adenovirus vectored vaccines exceeded those induced by other platforms at day 7 after immunization.
+We found little evidence that innate immune activation by adenovirus may act as an adjuvant in such a manner that the humoral response to a recombinant protein may be enhanced by coadministering with an adenovirus lacking a transgene of interest.
+Overall, these studies provide further support for the use of replication-deficient adenoviruses to induce humoral responses.
+In addition, IAV have been implicated in occasional pandemics with inordinate health and economic consequences.
+Studying IAV, in vitro or in vivo, requires the use of laborious secondary methodologies to identify virus-infected cells.
+To circumvent this requirement, replication-competent IAV expressing an easily traceable reporter protein can be used.
+Here we discuss the development and applications of recombinant replication-competent IAV harboring diverse fluorescent or bioluminescent reporter genes in different locations of the viral genome.
+These viruses have been employed for in vitro and in vivo studies, such as the screening of neutralizing antibodies or antiviral compounds, the identification of host factors involved in viral replication, cell tropism, the development of vaccines, or the assessment of viral infection dynamics.
+In summary, reporter-expressing, replicating-competent IAV represent a powerful tool for the study of IAV both in vitro and in vivo.
+Bunyaviruses are enveloped viruses with a tripartite RNA genome that can pose a serious threat to animal and human health.
+Members of the Phlebovirus genus of the family Bunyaviridae are transmitted by mosquitos and ticks to humans and include highly pathogenic agents like Rift Valley fever virus (RVFV) and severe fever with thrombocytopenia syndrome virus (SFTSV) as well as viruses that do not cause disease in humans, like Uukuniemi virus (UUKV).
+Phleboviruses and other bunyaviruses use their envelope proteins, Gn and Gc, for entry into target cells and for assembly of progeny particles in infected cells.
+Thus, binding of Gn and Gc to cell surface factors promotes viral attachment and uptake into cells and exposure to endosomal low pH induces Gc-driven fusion of the viral and the vesicle membranes.
+Moreover, Gn and Gc facilitate virion incorporation of the viral genome via their intracellular domains and Gn and Gc interactions allow the formation of a highly ordered glycoprotein lattice on the virion surface.
+Studies conducted in the last decade provided important insights into the configuration of phlebovirus Gn and Gc proteins in the viral membrane, the cellular factors used by phleboviruses for entry and the mechanisms employed by phlebovirus Gc proteins for membrane fusion.
+Here, we will review our knowledge on the glycoprotein biogenesis and the role of Gn and Gc proteins in the phlebovirus replication cycle.
+The chicken upper respiratory tract is the portal of entry for respiratory pathogens, such as avian influenza virus (AIV).
+The presence of microorganisms is sensed by pathogen recognition receptors (such as Toll-like receptors (TLRs)) of the innate immune defenses.
+Innate responses are essential for subsequent induction of potent adaptive immune responses, but little information is available about innate antiviral responses of the chicken trachea.
+To confirm the antiviral responses of stimulated TOC, chicken macrophages were treated with supernatants from stimulated TOC, prior to infection with AIV.
+The results demonstrated that TLR ligands induced the expression of pro-inflammatory cytokines, type I interferons and interferon stimulated genes in the chicken trachea.
+In conclusion, TLR ligands induce functional antiviral responses in the chicken trachea, which may act against some pathogens, such as AIV.
+CF is caused by mutations of the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) which is an anion selective transmembrane ion channel that mainly regulates chloride transport, expressed in the epithelia of various organs.
+Recently, we have demonstrated CFTR expression in the brain, the spinal cord and the sympathetic ganglia.
+This study aims to investigate the expression and distribution of CFTR in the ganglia of the human gastrointestinal tract.
+Fresh tissue and formalin-fixed paraffin-embedded normal gastrointestinal tract samples were collected from eleven surgical patients and five autopsy cases.
+Immunohistochemistry, in situ hybridization, laser-assisted microdissection and nested reverse transcriptase polymerase chain reaction were performed.
+Expression of CFTR protein and mRNA was detected in neurons of the ganglia of all segments of the human gastrointestinal tract examined, including the stomach, duodenum, jejunum, ileum, cecum, appendix, colon and rectum.
+The extensive expression of CFTR in the enteric ganglia suggests that CFTR may play a role in the physiology of the innervation of the gastro-intestinal tract.
+The presence of dysfunctional CFTRs in enteric ganglia could, to a certain extent, explain the gastrointestinal symptoms frequently experienced by CF patients.
+Crystallins are found widely in animal lenses and have important functions due to their refractive properties.
+In the coleoid cephalopods, a lens with a graded refractive index provides good vision and is required for survival.
+Cephalopod S-crystallin is thought to have evolved from glutathione S-transferase (GST) with various homologs differentially expressed in the lens.
+However, there is no direct structural information that helps to delineate the mechanisms by which S-crystallin could have evolved.
+The 2.35-Å crystal structure of a S-crystallin mutant from Octopus vulgaris reveals an active-site architecture that is different from that of GST.
+We’ve also identified four historical mutations that are able to produce a “GST-like” S-crystallin that has regained activity.
+Protein stability studies suggest that S-crystallin is stabilized by glutathione binding to prevent its aggregation; this contrasts with GST-σ, which do not possess this protection.
+We suggest that a tradeoff between enzyme activity and the stability of the lens protein might have been one of the major driving force behind lens evolution.
+Owing to the reports of microcephaly as a consistent outcome in the fetuses of pregnant women infected with ZIKV in Brazil, Zika virus (ZIKV)—microcephaly etiomechanistic relationship has recently been implicated.
+Researchers, however, are still struggling to establish an embryological basis for this interesting causal handcuff.
+The rationale is based on: (1) sequence homology between ZIKV genome and the response element of an early neural tube developmental marker “retinoic acid” in human DNA and (2) comprehensive similarities between the details of brain defects in ZIKV-microcephaly and retinoic acid embryopathy.
+Retinoic acid is considered as the earliest factor for regulating anteroposterior axis of neural tube and positioning of structures in developing brain through retinoic acid response elements (RARE) consensus sequence (5′–AGGTCA–3′) in promoter regions of retinoic acid-dependent genes.
+We screened genomic sequences of already reported virulent ZIKV strains (including those linked to microcephaly) and other viruses available in National Institute of Health genetic sequence database (GenBank) for the RARE consensus repeats and obtained results strongly bolstering our hypothesis that ZIKV strains associated with microcephaly may act through precipitation of dysregulation in retinoic acid-dependent genes by introducing extra stretches of RARE consensus sequence repeats in the genome of developing brain cells.
+Additional support to our hypothesis comes from our findings that screening of other viruses for RARE consensus sequence repeats is positive only for those known to display neurotropism and cause fetal brain defects (for which maternal-fetal transmission during developing stage may be required).
+The numbers of RARE sequence repeats appeared to match with the virulence of screened positive viruses.
+Although, bioinformatic evidence and embryological features are in favor of our hypothesis, additional studies including animal models are warranted to validate our proposition.
+Such studies are likely to unfold ZIKV-microcephaly association and may help in devising methods to combat it.
+Previously, we demonstrated that pyroptosis in alveolar macrophages (AMs) plays an essential role in lipopolysaccharide (LPS)-induced acute lung injury.
+Here, we show that the absence of interferon regulatory factor 1 (IRF-1) in genetic knock-out mice strongly abrogates pyroptosis in AMs and alleviates the LPS-induced lung injury and systemic inflammation.
+Our study demonstrates that IRF-1 contributes to caspase-1 activation and apoptosis-associated speck-like protein containing a caspase activation and recruitment domain pyroptosome formation in AMs and leads to downstream inflammatory cytokine release, including that of IL-1β, IL-18, and HMGB1.
+The nuclear translocation of IRF-1 is linked to the presence of toll-like receptor 4 (TLR4).
+Our findings suggest that pyroptosis and the downstream inflammatory response in AMs induced by LPS is a process that is dependent on TLR4-mediated up-regulation of IRF-1.
+The impact of metabolic engineering on nontarget pathways and outcomes of metabolic engineering from different genomes are poorly understood questions.
+Therefore, squalene biosynthesis genes FARNESYL DIPHOSPHATE SYNTHASE (FPS) and SQUALENE SYNTHASE (SQS) were engineered via the Nicotiana tabacum chloroplast (C), nuclear (N) or both (CN) genomes to promote squalene biosynthesis.
+SQS levels were ~4300‐fold higher in C and CN lines than in N, but all accumulated ~150‐fold higher squalene due to substrate or storage limitations.
+Abnormal leaf and flower phenotypes, including lower pollen production and reduced fertility, were observed regardless of the compartment or level of transgene expression.
+Substantial changes in metabolomes of all lines were observed: levels of 65–120 unrelated metabolites, including the toxic alkaloid nicotine, changed by as much as 32‐fold.
+Profound effects of transgenesis on nontarget gene expression included changes in the abundance of 19 076 transcripts by up to 2000‐fold in CN; 7784 transcripts by up to 1400‐fold in N; and 5224 transcripts by as much as 2200‐fold in C. Transporter‐related transcripts were induced, and cell cycle‐associated transcripts were disproportionally repressed in all three lines.
+The mechanism underlying these large changes likely involves metabolite‐mediated anterograde and/or retrograde signalling irrespective of the level of transgene expression or end product, due to imbalance of metabolic pools, offering new insight into both anticipated and unanticipated consequences of metabolic engineering.
+Invasive Aspergillosis (IA) is an opportunistic infection caused by Aspergillus, a ubiquitously present airborne pathogenic mold.
+Here, we evaluated whether 14 single-nucleotide polymorphisms within NFκB1, NFκB2, RelA, RelB, Rel, and IRF4 genes influence the risk of IA in a population of 834 high-risk patients (157 IA and 677 non-IA) recruited through a collaborative effort involving the aspBIOmics consortium and four European clinical institutions.
+No significant overall associations between selected SNPs and the risk of IA were found in this large cohort.
+Although a hematopoietic stem cell transplantation (HSCT)-stratified analysis revealed that carriers of the IRF4(rs12203592T/T) genotype had a six-fold increased risk of developing the infection when compared with those carrying the C allele (OR(REC) = 6.24, 95%CI 1.25–31.2, P = 0.026), the association of this variant with IA risk did not reach significance at experiment-wide significant threshold.
+In addition, we found an association of the IRF4(AATC) and IRF4(GGTC) haplotypes (not including the IRF4(rs12203592T) risk allele) with a decreased risk of IA but the magnitude of the association was similar to the one observed in the single-SNP analysis, which indicated that the haplotypic effect on IA risk was likely due to the IRF4(rs12203592) SNP.
+Finally, no evidence of significant interactions among the genetic markers tested and the risk of IA was found.
+These results suggest that the SNPs on the studied genes do not have a clinically relevant impact on the risk of developing IA.
+Current hemagglutinin (HA)-based seasonal influenza vaccines induce vaccine strain-specific neutralizing antibodies that usually fail to provide protection against mismatched circulating viruses.
+Inclusion in the vaccine of highly conserved internal proteins such as the nucleoprotein (NP) and the matrix protein 1 (M1) was shown previously to increase vaccine efficacy by eliciting cross-reactive T-cells.
+In this study, we demonstrated that administration of novel self-amplifying mRNA (SAM(®)) vectors expressing influenza NP (SAM(NP)), M1 (SAM(M1)), and NP and M1 (SAM(M1-NP)) delivered with lipid nanoparticles (LNP) induced robust polyfunctional CD4 T helper 1 cells, while NP-containing SAM also induced cytotoxic CD8 T cells.
+Robust expansions of central memory (T(CM)) and effector memory (T(EM)) CD4 and CD8 T cells were also measured.
+An enhanced recruitment of NP-specific cytotoxic CD8 T cells was observed in the lungs of SAM(NP)-immunized mice after influenza infection that paralleled with reduced lung viral titers and pathology, and increased survival after homologous and heterosubtypic influenza challenge.
+Finally, we demonstrated for the first time that the co-administration of RNA (SAM(M1-NP)) and protein (monovalent inactivated influenza vaccine (MIIV)) was feasible, induced simultaneously NP-, M1- and HA-specific T cells and HA-specific neutralizing antibodies, and enhanced MIIV efficacy against a heterologous challenge.
+In conclusion, systemic administration of SAM vectors expressing conserved internal influenza antigens induced protective immune responses in mice, supporting the SAM(®) platform as another promising strategy for the development of broad-spectrum universal influenza vaccines.
+Previous empirical studies on fitness landscapes were confined to either the neighborhood around the wild type sequence, involving mostly single and double mutants, or a combinatorially complete subgraph involving only two amino acids at each site.
+In reality, the dimensionality of protein sequence space is higher (20(L)) and there may be higher-order interactions among more than two sites.
+Here we experimentally characterized the fitness landscape of four sites in protein GB1, containing 20(4) = 160,000 variants.
+We found that while reciprocal sign epistasis blocked many direct paths of adaptation, such evolutionary traps could be circumvented by indirect paths through genotype space involving gain and subsequent loss of mutations.
+These indirect paths alleviate the constraint on adaptive protein evolution, suggesting that the heretofore neglected dimensions of sequence space may change our views on how proteins evolve.
+Unlike schools in the US, human contacts within Chinese colleges are extremely clustered, partly due to the highly organized lifestyle of Chinese college students.
+Simulations of influenza spreading across real contact networks are in good accordance with real influenza records; however, epidemic simulations across idealized scale-free or small-world networks show considerable overestimation of disease prevalence, thus challenging the widely-applied idealized human contact models in epidemiology.
+Furthermore, the special contact pattern within Chinese colleges results in disease spreading patterns distinct from those of the US schools.
+Remarkably, class cancelation, though simple, shows a mitigating power equal to quarantine/vaccination applied on ~25% of college students, which quantitatively explains its success in Chinese colleges during the SARS period.
+Our findings greatly facilitate reliable prediction of epidemic prevalence, and thus should help establishing effective strategies for respiratory infectious diseases control.
+The present study demonstrated the use of the Linear Quantitative Profiling Method (LQPM) to evaluate the quality of Alkaloids of Sophora flavescens (ASF) based on chromatographic fingerprints in an accurate, economical and fast way.
+Both linear qualitative and quantitative similarities were calculated in order to monitor the consistency of the samples.
+The results indicate that the linear qualitative similarity (LQLS) is not sufficiently discriminating due to the predominant presence of three alkaloid compounds (matrine, sophoridine and oxymatrine) in the test samples; however, the linear quantitative similarity (LQTS) was shown to be able to obviously identify the samples based on the difference in the quantitative content of all the chemical components.
+In addition, the fingerprint analysis was also supported by the quantitative analysis of three marker compounds.
+The LQTS was found to be highly correlated to the contents of the marker compounds, indicating that quantitative analysis of the marker compounds may be substituted with the LQPM based on the chromatographic fingerprints for the purpose of quantifying all chemicals of a complex sample system.
+Furthermore, once reference fingerprint (RFP) developed from a standard preparation in an immediate detection way and the composition similarities calculated out, LQPM could employ the classical mathematical model to effectively quantify the multiple components of ASF samples without any chemical standard.
+The proteasome is a central regulatory hub for intracellular signaling by degrading numerous signaling mediators.
+Immunoproteasomes are specialized types of proteasomes involved in shaping adaptive immune responses, but their role in innate immune signaling is still elusive.
+Here, we analyzed immunoproteasome function for polarization of alveolar macrophages, highly specialized tissue macrophages of the alveolar lung surface.
+Classical activation (M1 polarization) of primary alveolar macrophages by LPS/IFNγ transcriptionally induced all three immunoproteasome subunits, low molecular mass protein 2 (LMP2), LMP7 and multicatalytic endopeptidase complex-like 1, which was accompanied by increased immunoproteasome activity in M1 cells.
+Deficiency of LMP7 had no effect on the LPS/IFNγ-triggered M1 profile indicating that immunoproteasome function is dispensable for classical alveolar macrophage activation.
+In contrast, IL-4 triggered alternative (M2) activation of primary alveolar macrophages was accompanied by a transcriptionally independent amplified expression of LMP2 and LMP7 and an increase in immunoproteasome activity.
+Alveolar macrophages from LMP7 knockout mice disclosed a distorted M2 profile upon IL-4 stimulation as characterized by increased M2 marker gene expression and CCL17 cytokine release.
+Comparative transcriptome analysis revealed enrichment of IL-4-responsive genes and of genes involved in cellular response to defense, wounding and inflammation in LMP7-deficient alveolar macrophages indicating a distinct M2 inflammation resolving phenotype.
+Moreover, augmented M2 polarization was accompanied by amplified AKT/STAT6 activation and increased RNA and protein expression of the M2 master transcription factor interferon regulatory factor 4 in LMP7(−/−) alveolar macrophages.
+IL-13 stimulation of LMP7-deficient macrophages induced a similar M2-skewed profile indicative for augmented signaling via the IL-4 receptor α (IL4Rα).
+IL4Rα expression was generally elevated only on protein but not RNA level in LMP7(−/−) alveolar macrophages.
+Importantly, specific catalytic inhibition with an LMP7-specific proteasome inhibitor confirmed augmented IL-4-mediated M2 polarization of alveolar macrophages.
+Our results thus suggest a novel role of immunoproteasome function for regulating alternative activation of macrophages by limiting IL4Rα expression and signaling.
+However, it is also well established that LC3 can localize on various membranous structures other than autophagosomes.
+We recently demonstrated that the LC3 conjugation system (ATG7, ATG3, and ATG12–ATG5-ATG16L1) is required to target LC3 and IFNG (interferon, gamma)-inducible GTPases to the parasitophorus vacuole membrane (PVM) of a protist parasite Toxoplasma gondii and consequently for IFNG to control T. gondii infection.
+Here we show that not only LC3, but also its homologs (GABARAP, GABARAPL1, and GABARAPL2) localize on the PVM of T. gondii in a conjugation-dependent manner.
+Knockout/knockdown of all LC3 homologs led to a significant reduction in targeting of the IFNG-inducible GTPases to the PVM of T. gondii and the IFNG-mediated control of T. gondii infection.
+Furthermore, when we relocated the ATG12–ATG5-ATG16L1 complex, which specifies the conjugation site of LC3 homologs, to alternative target membranes, the IFNG-inducible GTPases were targeted to the new target membranes rather than the PVM of T. gondii.
+These data suggest that the localization of LC3 homologs onto a membrane by the LC3 conjugation system is necessary and sufficient for targeting of the IFNG-inducible GTPases to the membrane, implying Targeting by AutophaGy proteins (TAG).
+Our data further suggest that the conjugation of ubiquitin-like LC3 homologs to the phospholipids of membranes may change the destiny of the membranes beyond degradation through lysosomal fusion, as the conjugation of ubiquitin to proteins changes the destiny of the proteins beyond proteasomal degradation.
+The role of CMV in the development of lymphoma is not clear, though both CMV and HHV-8 have been reported in tissues adjacent to the tumour in Burkitt lymphoma patients.
+Here we present a patient with asymptomatic HIV infection, that contracted a primary cytomegalovirus (CMV) infection and human herpes virus 8 (HHV-8) infection.
+Three weeks before onset of symptoms the patient had unprotected sex which could be possible source of his CMV and also HHV-8 infection He deteriorated rapidly and died with a generalized anaplastic large cell lymphoma (ALCL).
+METHODS: A Caucasian homosexual male with asymptomatic human immunodeficiency virus (HIV) infection contracted a primary cytomegalovirus (CMV) infection and human herpes virus 8 (HHV-8) infection.
+Immunohistochemistry was performed on lymphoid tissues, a liver biopsy, a bone marrow aspirate and the spleen during the illness and at autopsy.
+Serology and PCR for HIV, CMV, EBV, HHV-1–3 and 6–8 was performed on blood drawn during the course of disease.
+Biopsies taken 2 weeks before death showed a small focus of ALCL in one lymph node of the neck.
+Autopsy demonstrated a massive infiltration of ALCL in lymph nodes, liver, spleen and bone marrow.
+Blood samples confirmed primary CMV- infection, a HHV-8 infection together with reactivation of Epstein- Barr-virus (EBV).
+Quantitative PCR blood analysis for EBV, CMV and HHV-8 could be valuable in diagnosis and treatment of this type of very rapidly developing lymphoma.
+It is also a reminder of the importance of prevention and prophylaxis of several infections by having protected sex.
+Drug induced exfoliative dermatitis (ED) are a group of rare and severe drug hypersensitivity reactions (DHR) involving skin and usually occurring from days to several weeks after drug exposure.
+Erythema multiforme (EM), Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are the main clinical presentations of drug induced ED.
+Here we provide a systematic review on frequency, risk factors, pathogenesis, clinical features and management of patients with drug induced ED.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12948-016-0045-0) contains supplementary material, which is available to authorized users.
+It has been well characterized that the neonatal Fc receptor (FcRn) transports maternal IgG to a fetus or newborn and protects IgG from degradation.
+We previously reported that FcRn is expressed in a model of normal porcine intestinal epithelial cells (IPEC-J2).
+Transmissible gastroenteritis is an acute enteric disease of swine that is caused by transmissible gastroenteritis virus (TGEV).
+Furthermore, treatment of TGEV-infected IPEC-J2 cells with the NF-κB-specific inhibitor BAY 11-7082 resulted in down-regulation of pFcRn expression.
+Transient transfection of pFcRn promoter luciferase report plasmids with overexpression of NF-κB p65 transcription factor enhanced the activation of the luciferase report plasmids.
+We identified four NF-κB transcription factor binding sites in the promoter region of this gene using luciferase reporter system, chromatin immunoprecipitation, electromobility shift assay, and supershift analysis.
+Together, the data provide the first evidence that TGEV infection up-regulates pFcRn expression via activation of NF-κB signaling.
+Microfluidic components and systems for rapid (<60 min), low-cost, convenient, field-deployable sequence-specific nucleic acid-based amplification tests (NAATs) are described.
+A microfluidic point-of-care (POC) diagnostics test to quantify HIV viral load from blood samples serves as a representative and instructive example to discuss the technical issues and capabilities of “lab on a chip” NAAT devices.
+A modified chip with conduits hosting a diffusion-mode amplification process provides a simple visual indicator to readily quantify sample NA template.
+In addition, a companion microfluidic device for extracting plasma from whole blood without a centrifuge, generating cell-free plasma for chip-based molecular diagnostics, is described.
+Extensions to a myriad of related applications including, for example, food testing, cancer screening, and insect genotyping are briefly surveyed.
+BACKGROUND: There are currently no vaccines or antivirals available for dengue virus infection, which can cause dengue hemorrhagic fever and death.
+A better understanding of the host pathogen interaction is required to develop effective therapies to treat DENV.
+In particular, very little is known about how cellular RNA binding proteins interact with viral RNAs.
+RNAs within cells are not naked; rather they are coated with proteins that affect localization, stability, translation and (for viruses) replication.
+METHODOLOGY/PRINCIPAL FINDINGS: Seventy-nine novel RNA binding proteins for dengue virus (DENV) were identified by cross-linking proteins to dengue viral RNA during a live infection in human cells.
+These cellular proteins were specific and distinct from those previously identified for poliovirus, suggesting a specialized role for these factors in DENV amplification.
+Knockdown of these proteins demonstrated their function as viral host factors, with evidence for some factors acting early, while others late in infection.
+Their requirement by DENV for efficient amplification is likely specific, since protein knockdown did not impair the cell fitness for viral amplification of an unrelated virus.
+The protein abundances of these host factors were not significantly altered during DENV infection, suggesting their interaction with DENV RNA was due to specific recruitment mechanisms.
+However, at the global proteome level, DENV altered the abundances of proteins in particular classes, including transporter proteins, which were down regulated, and proteins in the ubiquitin proteasome pathway, which were up regulated.
+CONCLUSIONS/SIGNIFICANCE: The method for identification of host factors described here is robust and broadly applicable to all RNA viruses, providing an avenue to determine the conserved or distinct mechanisms through which diverse viruses manage the viral RNA within cells.
+This study significantly increases the number of cellular factors known to interact with DENV and reveals how DENV modulates and usurps cellular proteins for efficient amplification.
+Murine norovirus-1 (MNV-1) is known to subvert host cell division inducing an accumulation of cells in the G(0)/G(1) phase, creating conditions where viral replication is favored.
+This study identified that NS5 (VPg), is capable of inducing cell cycle arrest in the absence of viral replication or other viral proteins in an analogous manner to MNV-1 infection.
+NS5 expression induced an accumulation of cells in the G(0)/G(1) phase in an asynchronous population by inhibiting progression at the G(1)/S restriction point.
+Furthermore, NS5 expression resulted in a down-regulation of cyclin A expression in asynchronous cells and inhibited cyclin A expression in cells progressing from G(1) to S phase.
+Amino acid substitutions of NS5(Y26A) and NS5(F123A) that inhibit the ability for NS5 to attach to RNA and recruit host eukaryotic translation initiation factors, respectively, retained the ability to induce an accumulation of cells in the G(0)/G(1) phase as identified for wild-type NS5.
+To the best of our knowledge, this is the first report of a VPg protein manipulating the host cell cycle.
+Gain-of-function (GOF) research involves experimentation that aims or is expected to (and/or, perhaps, actually does) increase the transmissibility and/or virulence of pathogens.
+Such research, when conducted by responsible scientists, usually aims to improve understanding of disease causing agents, their interaction with human hosts, and/or their potential to cause pandemics.
+The ultimate objective of such research is to better inform public health and preparedness efforts and/or development of medical countermeasures.
+Despite these important potential benefits, GOF research (GOFR) can pose risks regarding biosecurity and biosafety.
+In 2014 the administration of US President Barack Obama called for a “pause” on funding (and relevant research with existing US Government funding) of GOF experiments involving influenza, SARS, and MERS viruses in particular.
+With announcement of this pause, the US Government launched a “deliberative process” regarding risks and benefits of GOFR to inform future funding decisions—and the US National Science Advisory Board for Biosecurity (NSABB) was tasked with making recommendations to the US Government on this matter.
+The aim should be that any GOFR pursued (and/or funded) should be as far as possible towards the former end of the spectrum.
+Renin angiotensin system (RAS) is a key hormonal system which regulates the cardiovascular function and is implicated in several autoimmune diseases.
+With the discovery of the angiotensin-converting enzyme 2 (ACE2), a protective axis of RAS namely ACE2/Ang-(1–7)/Mas that counteracts the deleterious ACE/AngII/AT1R axis has been established.
+We investigated the hypothesis that enhancing the activity of the protective axis of RAS by subretinal delivery of an AAV8 (Y733F)-ACE2 vector would protect against the ocular inflammation in experimental autoimmune uveitis (EAU) mice through regulating the local immune responses.
+Our studies demonstrated that increased ACE2 expression exerts protective effects on inflammation in EAU mouse by modulating ocular immune responses, including the differentiation of Th1/Th17 cells and the polarization of M1/M2 macrophages; whereas the systemic immune responses appeared not affected.
+These effects were mediated by activating the Ang-(1–7)/Mas and inhibiting the MAPK, NF-κB and STAT3 signaling pathways.
+This proof-of-concept study suggests that activation of ocular ACE2/Ang-(1–7)/Mas axis with AAV gene transfer modulates local immune responses and may be a promising, long-lasting therapeutic strategy for refractory and recurrent uveitis, as well as other inflammatory eye diseases.
+Objective: The outbreak of the Ebola epidemic in West Africa in 2014 exerted enormous global public reaction via the Internet and social media.
+This study aimed to investigate and evaluate the public reaction to Ebola in China and identify the primitive correlation between possible influence factors caused by the outbreak of Ebola in West Africa and Chinese public attention via Internet surveillance.
+Methods: Baidu Index (BDI) and Sina Micro Index (SMI) were collected from their official websites, and the disease-related data were recorded from the websites of the World Health Organization (WHO), U.S. Centers for Disease Control and Prevention (CDC), and U.S. National Ministries of Health.
+The average BDI of Internet users in different regions were calculated to identify the public reaction to the Ebola outbreak.
+Spearman’s rank correlation was used to check the relationship of epidemic trends with BDI and SMI.
+Additionally, spatio-temporal analysis and autocorrelation analysis were performed to detect the clustered areas with the high attention to the topic of “Ebola”.
+Results: The BDI and the SMI for “Ebola” showed a similar fluctuating trend with a correlation coefficient = 0.9 (p < 0.05).
+The most likely cluster identified by spatiotemporal cluster analysis was in the northeast regions of China with the relative risk (RR) of 2.26 (p ≤ 0.01) from 30 July to 14 August in 2014.
+Qualitative analysis indicated that negative news could lead to a continuous increase of the public’s attention until the appearance of a positive news report.
+Conclusions: Confronted with the risk of cross-border transmission of the infectious disease, online surveillance might be used as an innovative approach to perform public communication and health education through examining the public’s reaction and attitude.
+The 2014 outbreak of Ebola virus (EBOV) in Western Africa highlighted the need for anti-EBOV therapeutics.
+Clomiphene is a U.S. Food and Drug Administration (FDA)-approved drug that blocks EBOV entry and infection in cells and significantly protects EBOV-challenged mice.
+The pharmacokinetic properties of the two isomers vary, but both accumulate in the eye and male reproductive tract, tissues in which EBOV can persist.
+Here we compared the ability of clomiphene and its isomers to inhibit EBOV using viral-like particle (VLP) entry and transcription/replication-competent VLP (trVLP) assays.
+Clomiphene and its isomers inhibited the entry and infection of VLPs and trVLPs with similar potencies.
+This was demonstrated with VLPs bearing the glycoproteins from three filoviruses (EBOV Mayinga, EBOV Makona, and Marburg virus) and in two cell lines (293T/17 and Vero E6).
+Visual problems have been noted in EBOV survivors, and viral RNA has been isolated from semen up to nine months post-infection.
+Since the clomiphene isomers accumulate in these affected tissues, clomiphene or one of its isomers warrants consideration as an anti-EBOV agent, for example, to potentially help ameliorate symptoms in EBOV survivors.
+During chikungunya virus (CHIKV) infection however, excessive production of MCP-1 has been linked to disease pathogenesis.
+High MCP-1 serum levels are detected during the viremic phase of CHIKV infection and correlate with the virus titre.
+In vitro CHIKV infection was also shown to stimulate MCP-1 production in whole blood; yet the role and the mechanism of MCP-1 production upon infection of human peripheral blood mononuclear cells remain unknown.
+Importantly however, we found that communication with other leukocytes is crucial to yield MCP-1 by monocytes upon CHIKV infection.
+Indeed, blocking interferon-α/β receptor or the JAK1/JAK2 signalling downstream of the receptor abolished CHIKV-mediated MCP-1 production.
+Additionally, we show that despite the apparent correlation between IFN type I, CHIKV replication and MCP-1, modulating the levels of the chemokine did not influence CHIKV infection.
+In summary, our data disclose the complexity of MCP-1 regulation upon CHIKV infection and point to a crucial role of IFNβ in the chemokine secretion.
+We propose that balance between these soluble factors is imperative for an appropriate host response to CHIKV infection.
+Although vaccines and antibiotics could kill or inhibit microbes, many infectious diseases remain difficult to treat because of acquired resistance and adverse side effects.
+Nano-carriers-based technology has made significant progress for a long time and is introducing a new paradigm in drug delivery.
+However, it still has some challenges like lack of specificity toward targeting the infectious site.
+Nano-carriers utilized targeting ligands on their surface called ‘active target’ provide the promising way to solve the problems like accelerating drug delivery to infectious areas and preventing toxicity or side-effects.
+In this mini review, we demonstrate the recent studies using the active targeted strategy to kill or inhibit microbes.
+We evaluated the impact of serum uric acid (SUA) on mortality in patients with chronic dialysis.
+A total of 4132 adult patients on dialysis were enrolled prospectively between August 2008 and September 2014.
+Among them, we included 1738 patients who maintained dialysis for at least 3 months and had available SUA in the database.
+We categorized the time averaged-SUA (TA-SUA) into 5 groups: <5.5, 5.5–6.4, 6.5–7.4, 7.5–8.4, and ≥8.5 mg/dL.
+Cox regression analysis was used to calculate the hazard ratio (HR) of all-cause mortality according to SUA group.
+Patients with lower TA-SUA level tended to have lower body mass index (BMI), phosphorus, serum albumin level, higher proportion of diabetes mellitus (DM), and higher proportion of malnourishment on the subjective global assessment (SGA).
+Patients with the highest SUA had a similar risk to the middle 3 TA-SUA groups, but the lowest TA-SUA group had a significantly elevated HR for mortality.
+The lowest TA-SUA group was significantly associated with increased all-cause mortality (adjusted HR, 1.720; 95% confidence interval, 1.007–2.937; P = 0.047) even after adjusting for demographic, comorbid, nutritional covariables, and medication use that could affect SUA levels.
+This association was prominent in patients with well nourishment on the SGA, a preserved serum albumin level, a higher BMI, and concomitant DM although these parameters had no significant interaction in the TA-SUA-mortality relationship except DM.
+In conclusion, a lower TA-SUA level <5.5 mg/dL predicted all-cause mortality in patients with chronic dialysis.
+The aim of the study was to comprehensively examine the efficacy and safety of noninvasive ventilation used at the pulmonary infection control (PIC) window for acute respiratory failure (ARF) in patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD).
+Seven electronic databases and relevant resources were searched to identify randomized controlled trials (RCTs) comparing patients using noninvasive ventilation at PIC window with those continuing receiving invasive ventilation.
+Retrieved citations were screened, risk of bias was assessed, and data were extracted by 2 independent review authors.
+Quality of evidence was rated by using Grading of Recommendations, Assessment, Development and Evaluation approach.
+Compared with continuous invasive ventilation, noninvasive ventilation used at PIC window significantly reduced mortality, ventilator-associated pneumonia, weaning failures, reintubations, duration of invasive ventilation, total duration of mechanical ventilation, length of stay (LOS) in intensive care unit, and LOS in hospital as well as hospital costs.
+Of these, mortality significantly decreased (risk ratio = 0.27, 95% confidence interval: 0.17–0.42, P < 0.001) without significant heterogeneity (I(2) = 0%, P = 0.99).
+Quality of evidence regarding the 9 outcomes across the included studies was rated from moderate to low.
+Use of noninvasive ventilation at PIC window showed beneficial effects across identified trials for ARF in AECOPD patients.
+Considering the absence of high quality of available evidence and the uncertainty of long-term effect of this intervention, a weak recommendation for clinical practice was generated, and further well-designed and adequately powered RCTs are required to validate this conclusion.
+This cross-sectional study evaluated the air and objects in patient-occupied rooms in pediatric wards for the presence of common respiratory viruses and Mycoplasma pneumoniae.
+Air samplers were placed at a short (60–80 cm) and long (320 cm) distance from the head of the beds of 58 pediatric patients, who were subsequently confirmed to be infected with enterovirus (n = 17), respiratory syncytial virus (RSV) (n = 13), influenza A virus (n = 13), adenovirus (n = 9), or M pneumoniae (n = 6).
+Swab samples were collected from the surfaces of 5 different types of objects in the patients’ rooms.
+All air and swab samples were analyzed via real-time quantitative polymerase chain reaction assay for the presence of the above pathogens.
+All pathogens except enterovirus were detected in the air, on the objects, or in both locations in the patients’ rooms.
+The detection rates of influenza A virus, adenovirus, and M pneumoniae for the long distance air sampling were 15%, 67%, and 17%, respectively.
+Both adenovirus and M pneumoniae were detected at very high rates, with high concentrations, on all sampled objects.
+The respiratory pathogens RSV, influenza A virus, adenovirus, and M pneumoniae were detected in the air and/or on the objects in the pediatric ward rooms.
+Malignant brain tumors continue to represent a devastating diagnosis with no real chance for cure.
+Despite an increasing list of potential salvage therapies, standard-of-care for these patients has not changed in over a decade.
+Immunotherapy has been seen as an exciting option, with the potential to offer specific and long lasting tumor clearance.
+The “gold standard” in immunotherapy has been the development of a tumor-specific CD8 T cell response to potentiate tumor clearance and immunological memory.
+While many advances have been made in the field of immunotherapy, few therapies have seen true success.
+Many of the same principles used to develop immunotherapy in tumors of the peripheral organs have been applied to brain tumor immunotherapy.
+The immune-specialized nature of the brain should call into question whether this approach is appropriate.
+Perhaps a CD8 T cell response is not sufficient for an organ as immunologically unique as the brain.
+Examination of previously elucidated principles of the brain’s immune-specialized status and known immunological preferences should generate discussion and experimentation to address the failure of current therapies.
+Angiotensin converting enzyme (ACE) 2 is a negative regulator of the renin angiotensin system (RAS) through its role to degrade angiotensin II.
+In rats with subtotal nephrectomy (STNx), adverse cardiac remodelling occurs despite elevated cardiac ACE2 activity.
+We hypothesised that diminazene aceturate (DIZE), which has been described as having an off-target effect to activate ACE2, would have beneficial cardiac effects in STNx rats.
+STNx led to hypertension, diastolic dysfunction, left ventricular hypertrophy, cardiac fibrosis, and increased cardiac ACE, ACE2, Ang II and Ang 1–7 levels.
+In STNx, two-weeks of subcutaneous DIZE (15mg/kg/d) had no effect on blood pressure but improved diastolic dysfunction and cardiac fibrosis, reduced ADAM17 mRNA and shifted the cardiac RAS balance to a cardioprotective profile with reduced ACE and Ang II.
+There was no change in cardiac ACE2 activity or in cardiac Ang 1–7 levels with DIZE.
+In conclusion, our results suggest that DIZE exerts a protective effect on the heart under the pathological condition of kidney injury.
+This effect was not due to improved kidney function, a fall in blood pressure or a reduction in LVH but was associated with a reduction in cardiac ACE and cardiac Ang II levels.
+As in vitro studies showed no direct effect of DIZE on ACE2 or ACE activity, the precise mechanism of action of DIZE remains to be determined.
+A virus’ mutational robustness is described in terms of the strength and distribution of the mutational fitness effects, or MFE.
+The distribution of MFE is central to many questions in evolutionary theory and is a key parameter in models of molecular evolution.
+Here we define the mutational fitness effects in influenza A virus by generating 128 viruses, each with a single nucleotide mutation.
+In contrast to mutational scanning approaches, this strategy allowed us to unambiguously assign fitness values to individual mutations.
+The presence of each desired mutation and the absence of additional mutations were verified by next generation sequencing of each stock.
+A mutation was considered lethal only after we failed to rescue virus in three independent transfections.
+We measured the fitness of each viable mutant relative to the wild type by quantitative RT-PCR following direct competition on A549 cells.
+We found that 31.6% of the mutations in the genome-wide dataset were lethal and that the lethal fraction did not differ appreciably between the HA- and NA-encoding segments and the rest of the genome.
+Of the viable mutants, the fitness mean and standard deviation were 0.80 and 0.22 in the genome-wide dataset and best modeled as a beta distribution.
+The fitness impact of mutation was marginally lower in the segments coding for HA and NA (0.88 ± 0.16) than in the other 6 segments (0.78 ± 0.24), and their respective beta distributions had slightly different shape parameters.
+The results for influenza A virus are remarkably similar to our own analysis of CirSeq-derived fitness values from poliovirus and previously published data from other small, single stranded DNA and RNA viruses.
+These data suggest that genome size, and not nucleic acid type or mode of replication, is the main determinant of viral mutational fitness effects.
+Understanding of the mechanisms underlying each event is necessary for the intervention of virus infection in human healthcare and agriculture.
+Here we report the visualization of Singapore grouper iridovirus (SGIV) assembly in the medaka haploid embryonic stem (ES) cell line HX1.
+SGIV is a highly infectious DNA virus that causes a massive loss in marine aquaculture.
+Ectopic expression of VP88GFP, a fusion between green fluorescent protein and the envelope protein VP088, did not compromise the ES cell properties and susceptibility to SGIV infection.
+Although VP88GFP disperses evenly in the cytoplasm of non-infected cells, it undergoes aggregation and redistribution in SGIV-infected cells.
+Real-time visualization revealed multiple key stages of VP88GFP redistribution and the dynamics of viral assembly site (VAS).
+Specifically, VP88GFP entry into and condensation in the VAS occurred within a 6-h duration, a similar duration was observed also for the release of VP88GFP-containing SGIV out of the cell.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s13238-016-0292-3) contains supplementary material, which is available to authorized users.
+INTRODUCTION: Polymorphisms in the type III interferon IFN‐λ3 and the killer cell immunoglobulin‐like receptor (KIR) genes controlling the activity of natural killer (NK) cells can predict spontaneous resolution of acute hepatitis C virus (HCV) infection.
+METHODS: We monitored the plasma levels of type III IFNs in relation to the phenotype and the function of NK cells in a cohort of people who inject drugs (PWID) during acute HCV infection with different outcomes.
+RESULTS: Early acute HCV was associated with high variability in type III IFNs plasma levels and the favorable IFN‐λ3 CC genotype was associated with higher viral loads.
+Reduced expression of Natural Killer Group Protein 2A (NKG2A) was associated with lower IFN‐λ3 plasma levels and the CC genotype.
+IFN‐γ production by NK cells was higher in individuals with the CC genotype during acute infection but this did not prevent viral persistence.
+IFN‐λ3 plasma levels did not correlate with function of NK cells and IFN‐λ3 prestimulation did not affect NK cell activation and function.
+CONCLUSIONS: These results suggest that IFN‐λ3 polymorphism indirectly influences NK cell phenotype and function during acute HCV but other factors may act in concert to determine the outcome of the infection.
+Autophagy is a catabolic process regulated by the orchestrated action of the autophagy-related (ATG) proteins.
+Using an unbiased siRNA screen approach, we explored the extent of these unconventional functions of ATG proteins.
+We determined the effects of the depletion of each ATG proteome component on the replication of six different viruses.
+Our screen reveals that up to 36% of the ATG proteins significantly alter the replication of at least one virus in an unconventional fashion.
+Detailed analysis of two candidates revealed an undocumented role for ATG13 and FIP200 in picornavirus replication that is independent of their function in autophagy as part of the ULK complex.
+The high numbers of unveiled ATG gene-specific and pathogen-specific functions of the ATG proteins calls for caution in the interpretation of data, which rely solely on the depletion of a single ATG protein to specifically ablate autophagy.
+Senescent cells accumulate in tissues with age, undergo widespread changes in gene expression, and typically demonstrate altered, pro-inflammatory profiles.
+Astrocyte senescence has been implicated in neurodegenerative disease, and to better understand senescence-associated changes in astrocytes, we investigated changes in their transcriptome using RNA sequencing.
+Brain-expressed genes, including those involved in neuronal development and differentiation, were downregulated in senescent astrocytes.
+Remarkably, several genes indicative of astrocytic responses to injury were also downregulated, including glial fibrillary acidic protein and genes involved in the processing and presentation of antigens by major histocompatibility complex class II proteins, while pro-inflammatory genes were upregulated.
+Overall, our findings suggest that senescence-related changes in the function of astrocytes may impact the pathogenesis of age-related brain disorders.
+INTRODUCTION: The aim of this review was to record systematically and assess the published literature relating to the occupational risk of influenza A (H1N1) infection among healthcare personnel during the 2009 pandemic.
+It was applied to the electronic databases EMBASE, MEDLINE, PsycINFO, PubMed, CINAHL and Google Scholar.
+A meta-analysis was carried out to compute pooled effect estimates for influenza A (H1N1) infection.
+RESULTS: A total of 26 studies were included in the review, 15 studies met the criteria for the meta-analysis.
+After a sensitivity analysis the pooled analysis showed a significantly increased odds for influenza A (H1N1) infection for healthcare personnel compared to controls/comparisons (OR = 2.08, 95% CI = 1.73 to 2.51).
+CONCLUSIONS: This review corroborates the assumption that healthcare personnel were particularly at risk of influenza A (H1N1) infection during the 2009 pandemic.
+Healthcare facilities should intensify their focus on strategies to prevent infections among healthcare personnel, especially during the first period of pandemics.
+N-myc oncogene amplification is associated but not present in all cases of high-risk neuroblastoma (NB).
+Since oncogene expression could often modulate sensitivity to oncolytic viruses, we wanted to examine if N-myc expression status would determine virotherapy efficacy to high-risk NB.
+We showed that induction of exogenous N-myc in a non-N-myc-amplified cell line background (TET-21N) increased susceptibility to oncolytic vesicular stomatitis virus (mutant VSVΔM51) and alleviated the type I IFN-induced antiviral state.
+Cells with basal N-myc, on the other hand, were less susceptible to virus-induced oncolysis and established a robust IFN-mediated antiviral state.
+The same effects were also observed in NB cell lines with and without N-myc amplification.
+Microarray analysis showed that N-myc overexpression in TET-21N cells downregulated IFN-stimulated genes (ISGs) with known antiviral functions.
+Furthermore, virus infection caused significant changes in global gene expression in TET-21N cells overexpressing N-myc.
+Therefore, the present study showed that augmented susceptibility to VSVΔM51 by N-myc at least involves downregulation of ISGs with antiviral functions and alleviation of the IFN-stimulated antiviral state.
+Our studies suggest the potential utility of N-myc amplification/overexpression as a predictive biomarker of virotherapy response for high-risk NB using IFN-sensitive oncolytic viruses.
+Wild populations of the model organism Drosophila melanogaster experience highly heterogeneous environments over broad geographical ranges as well as over seasonal and annual timescales.
+Diapause is a primary adaptation to environmental heterogeneity, and in D. melanogaster the propensity to enter diapause varies predictably with latitude and season.
+Here we performed global transcriptomic profiling of naturally occurring variation in diapause expression elicited by short day photoperiod and moderately low temperature in two tissue types associated with neuroendocrine and endocrine signaling, heads, and ovaries.
+We show that diapause in D. melanogaster is an actively regulated phenotype at the transcriptional level, suggesting that diapause is not a simple physiological or reproductive quiescence.
+Differentially expressed genes and pathways are highly distinct in heads and ovaries, demonstrating that the diapause response is not uniform throughout the soma and suggesting that it may be comprised of functional modules associated with specific tissues.
+Genes downregulated in heads of diapausing flies are significantly enriched for clinally varying single nucleotide polymorphism (SNPs) and seasonally oscillating SNPs, consistent with the hypothesis that diapause is a driving phenotype of climatic adaptation.
+We also show that chromosome location-based coregulation of gene expression is present in the transcriptional regulation of diapause.
+Taken together, these results demonstrate that diapause is a complex phenotype actively regulated in multiple tissues, and support the hypothesis that natural variation in diapause propensity underlies adaptation to spatially and temporally varying selective pressures.
+BACKGROUND: Felid herpesvirus 1 (FHV-1) causes upper respiratory tract diseases in cats worldwide, including nasal and ocular discharge, conjunctivitis and oral ulceration.
+Genetic determinants of virulence are likely to contribute to differences in the in vivo phenotype of FHV-1 isolates, but to date there have been limited studies investigating FHV-1 genetic diversity.
+This study used next generation sequencing to compare the genomes of contemporary Australian clinical isolates of FHV-1, vaccine isolates and historical clinical isolates, including isolates that predated the introduction of live attenuated vaccines into Australia.
+Analysis of the genome sequences aimed to assess the level of genetic diversity, identify potential genetic markers that could influence the in vivo phenotype of the isolates and examine the sequences for evidence of recombination.
+RESULTS: The full genome sequences of 26 isolates of FHV-1 were determined, including two vaccine isolates and 24 clinical isolates that were collected over a period of approximately 40 years.
+Analysis of the genome sequences revealed a remarkably low level of diversity (0.0–0.01 %) between the isolates.
+No potential genetic determinants of virulence were identified, but unique single nucleotide polymorphisms (SNPs) in the UL28 and UL44 genes were detected in the vaccine isolates that were not present in the clinical isolates.
+No evidence of FHV-1 recombination was detected using multiple methods of recombination detection, even though many of the isolates originated from cats housed in a shelter environment where high infective pressures were likely to exist.
+Evidence of displacement of dominant FHV-1 isolates with other (genetically distinct) FHV-1 isolates over time was observed amongst the isolates obtained from the shelter-housed animals.
+The lack of recombination detected in the FHV-1 genomes suggests that the risk of attenuated vaccines recombining to generate virulent field viruses is lower than has been suggested for some other herpesviruses.
+The SNPs detected only in the vaccine isolates offer the potential to develop PCR-based methods of differentiating vaccine and clinical isolates of FHV-1 in order to facilitate future epidemiological studies.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-016-3050-2) contains supplementary material, which is available to authorized users.
+Revealing the evolutionary processes that allow novel pathogens to adapt to new hosts, also the potential barriers to host adaptation, is central to understanding the drivers of disease emergence.
+In particular, it is unclear how the genetics and ecology of pathogens interact to shape the likelihood of successful cross-species transmission.
+To better understand the determinants of host adaptation and emergence, we modelled key aspects of pathogen evolutionary dynamics at both intra- and inter-host scales, using parameter values similar to those observed in influenza virus.
+We considered the possibility of acquiring the necessary host adaptive mutations both before (‘off-the-shelf’ emergence) and after (‘tailor-made’ emergence) a virus is transmitted from a donor to a new recipient species.
+Under both scenarios, population bottlenecks at inter-host transmission act as a major barrier to host adaptation, greatly limiting the number of adaptive mutations that are able to cross the species barrier.
+In addition, virus emergence is hindered if the fitness valley between the donor and recipient hosts is either too steep or too shallow.
+Overall, our results reveal where in evolutionary parameter space a virus could adapt to and become transmissible in a new species.
+When controlling an emerging outbreak of an infectious disease, it is essential to know the key epidemiological parameters, such as the basic reproduction number R(0) and the control effort required to prevent a large outbreak.
+These parameters are estimated from the observed incidence of new cases and information about the infectious contact structures of the population in which the disease spreads.
+However, the relevant infectious contact structures for new, emerging infections are often unknown or hard to obtain.
+Here, we show that, for many common true underlying heterogeneous contact structures, the simplification to neglect such structures and instead assume that all contacts are made homogeneously in the whole population results in conservative estimates for R(0) and the required control effort.
+This means that robust control policies can be planned during the early stages of an outbreak, using such conservative estimates of the required control effort.
+A phylogeny has been calculated by maximum likelihood comparisons of the concatenated consensus protein sequences of 29 tobamoviruses shown to be non-recombinant.
+The viruses form eight lineages that are congruent with the taxonomy of the hosts from which each was first isolated and, with the exception of three of the twenty-nine species, all fall into three clusters that have either asterid or rosid or caryophyllid hosts (i.e.
+A modified Mantel permutation test showed that the patristic distances of virus and host phylogenies are significantly correlated, especially when the three anomalously placed viruses are removed.
+The simplest explanation of this congruence of the virus and host phylogenies is that most tobamovirus lineages have co-diverged with their primary plant hosts for more than 110 million years, and only the brassica-infecting lineage originated from a major host switch from asterids to rosids.
+Their co-divergence seems to have been ‘fuzzy’ rather than ‘strict’, permitting viruses to switch hosts within major host clades.
+Our conclusions support those of a coalesence analysis of tobamovirus sequences, that used proxy node dating, but not a similar analysis of nucleotide sequences from dated samples, which concluded that the tobamoviruses originated only 100 thousand years ago.
+Emerging diseases may spread rapidly through dense and large urban contact networks, especially they are transmitted by the airborne route, before new vaccines can be made available.
+Airborne diseases may spread rapidly as people visit different indoor environments and are in frequent contact with others.
+We constructed a simple indoor contact model for an ideal city with 7 million people and 3 million indoor spaces, and estimated the probability and duration of contact between any two individuals during one day.
+To do this, we used data from actual censuses, social behavior surveys, building surveys, and ventilation measurements in Hong Kong to define eight population groups and seven indoor location groups.
+Our indoor contact model was integrated with an existing epidemiological Susceptible, Exposed, Infectious, and Recovered (SEIR) model to estimate disease spread and with the Wells-Riley equation to calculate local infection risks, resulting in an integrated indoor transmission network model.
+This model was used to estimate the probability of an infected individual infecting others in the city and to study the disease transmission dynamics.
+We predicted the infection probability of each sub-population under different ventilation systems in each location type in the case of a hypothetical airborne disease outbreak, which is assumed to have the same natural history and infectiousness as smallpox.
+We compared the effectiveness of controlling ventilation in each location type with other intervention strategies.
+We conclude that increasing building ventilation rates using methods such as natural ventilation in classrooms, offices, and homes is a relatively effective strategy for airborne diseases in a large city.
+Theiler´s murine encephalomyelitis virus (TMEV)-infection is a widely used animal model for studying demyelinating disorders, including multiple sclerosis (MS).
+The immunosuppressive cytokine Interleukin (IL)-10 counteracts hyperactive immune responses and critically controls immune homeostasis in infectious and autoimmune disorders.
+In order to investigate the effect of signaling via Interleukin-10 receptor (IL-10R) in infectious neurological diseases, TMEV-infected SJL mice were treated with IL-10R blocking antibody (Ab) in the acute and chronic phase of the disease.
+The findings demonstrate that (i) Ab-mediated IL-10 neutralization leads to progressive colitis with a reduction in Foxp3(+) regulatory T cells and increased numbers of CD8(+)CD44(+) memory T cells as well as activated CD4(+)CD69(+) and CD8(+)CD69(+) T cells in uninfected mice.
+Virus-triggered effects were associated with an enhanced activation of CD4(+) T helper cells and CD8(+) cytotoxic T lymphocytes and augmented cytokine expression.
+By contrast, (iii) IL-10R neutralization during chronic TMEV-infection was not associated with enhanced peripheral immunopathology but an increased CD3(+) T cell influx in the spinal cord.
+IL-10R neutralization causes a breakdown in peripheral immune tolerance in genetically predisposed mice, which leads to immune-mediated colitis, resembling inflammatory bowel disease.
+Hyperactive immune state following IL-10R blockade is enhanced by central nervous system-restricted viral infection in a disease phase-dependent manner.
+The ubiquitin-like protein ISG15 and its conjugation to proteins (ISGylation) are strongly induced by type I interferon.
+Influenza B virus encodes non-structural protein 1 (NS1B) that binds human ISG15 and provides an appropriate model for determining how ISGylation affects virus replication in human cells.
+Here using a recombinant virus encoding a NS1B protein defective in ISG15 binding, we show that NS1B counteracts ISGylation-mediated antiviral activity by binding and sequestering ISGylated viral proteins, primarily ISGylated viral nucleoprotein (NP), in infected cells.
+ISGylated NP that is not sequestered by mutant NS1B acts as a dominant-negative inhibitor of oligomerization of the more abundant unconjugated NP.
+Consequently formation of viral ribonucleoproteins that catalyse viral RNA synthesis is inhibited, causing decreased viral protein synthesis and virus replication.
+We verify that ISGylated NP is largely responsible for inhibition of viral RNA synthesis by generating recombinant viruses that lack known ISGylation sites in NP.
+Interferons (IFNs) exert their anti-viral effects by inducing the expression of hundreds of IFN-stimulated genes (ISGs).
+The activity of known ISGs is insufficient to account for the antiretroviral effects of IFN, suggesting that ISGs with antiretroviral activity are yet to be described.
+We constructed an arrayed library of ISGs from rhesus macaques and tested the ability of hundreds of individual macaque and human ISGs to inhibit early and late replication steps for 11 members of the retroviridae from various host species.
+These screens uncovered numerous ISGs with antiretroviral activity at both the early and late stages of virus replication.
+Detailed analyses of two antiretroviral ISGs indicate that indoleamine 2,3-dioxygenase 1 (IDO1) can inhibit retroviral replication by metabolite depletion while tripartite motif-56 (TRIM56) accentuates ISG induction by IFNα and inhibits the expression of late HIV-1 genes.
+Understanding the natural evolution and structural changes involved in broadly neutralizing antibody (bnAb) development holds great promise for improving the design of prophylactic influenza vaccines.
+Here we report an haemagglutinin (HA) stem-directed bnAb, 3I14, isolated from human memory B cells, that utilizes a heavy chain encoded by the IGHV3-30 germline gene.
+MAb 3I14 binds and neutralizes groups 1 and 2 influenza A viruses and protects mice from lethal challenge.
+Analysis of VH and VL germline back-mutants reveals binding to H3 and H1 but not H5, which supports the critical role of somatic hypermutation in broadening the bnAb response.
+Moreover, a single VLD94N mutation improves the affinity of 3I14 to H5 by nearly 10-fold.
+These data provide evidence that memory B cell evolution can expand the HA subtype specificity.
+Our results further suggest that establishing an optimized memory B cell pool should be an aim of ‘universal' influenza vaccine strategies.
+Respiratory syncytial virus (RSV) causes severe acute lower respiratory tract disease leading to numerous hospitalizations and deaths among the infant and elderly populations worldwide.
+Natural RSV infection stimulates the Th1 immune response and activates the production of neutralizing antibodies, while earlier vaccine trials that used UV-inactivated RSV exacerbated the disease due to the activation of the allergic Th2 response.
+With a focus on Th1 immunity, we developed a DNA vaccine containing the native RSV fusion (RSV F) protein and studied its immune response in BALB/c mice.
+Also, sera from RSV F immunized and RSV infected mice reduced the RSV infection by 50% and 80%, respectively.
+Our data evidently showed that the RSV F DNA vaccine activated the Th1 biased immune response and led to the production of neutralizing antibodies, which is the desired immune response required for protection from RSV infections.
+OBJECTIVES: Alarm over the reported high failure rates for metal-on-metal (MoM) hip implants as well as their potential for locally aggressive Adverse Reactions to Metal Debris (ARMDs) has prompted government agencies, internationally, to recommend the monitoring of patients with MoM hip implants.
+We report a systematic review and meta-analysis of the performance of metal ion testing for ARMDs.
+METHODS: We searched MEDLINE and EMBASE to identify articles from which it was possible to reconstruct a 2 × 2 table.
+RESULTS: Our literature search returned 575 unique articles; only six met inclusion criteria defined a priori.
+The discriminative capacity of ion tests was homogeneous across studies but that there was substantial cut-point heterogeneity.
+Our best estimate of the “true” area under curve (AUC) for metal ion testing is 0.615, with a 95% credible interval of 0.480 to 0.735, thus we can state that the probability that metal ion testing is actually clinically useful with an AUC ≥ 0.75 is 1.7%.
+CONCLUSION: Metal ion levels are not useful as a screening test for identifying high risk patients because ion testing will either lead to a large burden of false positive patients, or otherwise marginally modify the pre-test probability.
+With the availability of more accurate non-invasive tests, we did not find any evidence for using blood ion levels to diagnose symptomatic patients.
+Cite this article: M. Pahuta, J. M. Smolders, J. L. van Susante, J. Peck, P. R. Kim, P. E. Beaule.
+Blood metal ion levels are not a useful test for adverse reactions to metal debris: a systematic review and meta-analysis.
+In order to investigate the mechanisms of persistent foot-and-mouth disease virus (FMDV) infection in cattle, transcriptome alterations associated with the FMDV carrier state were characterized using a bovine whole-transcriptome microarray.
+Eighteen cattle (8 vaccinated with a recombinant FMDV A vaccine, 10 non-vaccinated) were challenged with FMDV A(24) Cruzeiro, and the gene expression profiles of nasopharyngeal tissues collected between 21 and 35 days after challenge were compared between 11 persistently infected carriers and 7 non-carriers.
+Carriers and non-carriers were further compared to 2 naïve animals that had been neither vaccinated nor challenged.
+At a controlled false-discovery rate of 10% and a minimum difference in expression of 50%, 648 genes were differentially expressed between FMDV carriers and non-carriers, and most (467) had higher expression in carriers.
+Among these, genes associated with cellular proliferation and the immune response–such as chemokines, cytokines and genes regulating T and B cells–were significantly overrepresented.
+Differential gene expression was significantly correlated between non-vaccinated and vaccinated animals (biological correlation +0.97), indicating a similar transcriptome profile across these groups.
+Genes related to prostaglandin E(2) production and the induction of regulatory T cells were overexpressed in carriers.
+In contrast, tissues from non-carrier animals expressed higher levels of complement regulators and pro-apoptotic genes that could promote virus clearance.
+Based on these findings, we propose a working hypothesis for FMDV persistence in nasopharyngeal tissues of cattle, in which the virus may be maintained by an impairment of apoptosis and the local suppression of cell-mediated antiviral immunity by inducible regulatory T cells.
+Host shutoff is a common strategy used by viruses to repress cellular mRNA translation and concomitantly allow the efficient translation of viral mRNAs.
+Here we use RNA-sequencing and ribosome profiling to explore the mechanisms that are being utilized by the Influenza A virus (IAV) to induce host shutoff.
+We show that viral transcripts are not preferentially translated and instead the decline in cellular protein synthesis is mediated by viral takeover on the mRNA pool.
+Our measurements also uncover strong variability in the levels of cellular transcripts reduction, revealing that short transcripts are less affected by IAV.
+Interestingly, these mRNAs that are refractory to IAV infection are enriched in cell maintenance processes such as oxidative phosphorylation.
+Our results advance our understanding of IAV-induced shutoff, and suggest a mechanism that facilitates the translation of genes with important housekeeping functions.
+BACKGROUND: This study aimed to investigate the possible serum protein changes after endotoxin administration in healthy and choline-treated calves using proteomics.
+These results are expected to contribute to the understanding of the pathophysiological mechanisms of endotoxemia and the beneficial effect of choline administration in this clinical situation.
+METHODS: Healthy-calves (n = 20) were divided into 4 groups: Control, Choline treated (C), Lipopolysaccharide administered (LPS), and LPS + C. Control calves received 0.9 % NaCl injection.
+Endotoxin (LPS) was injected (2 μg/kg/iv) to the calves in LPS and LPS + C groups.
+RESULTS: After LPS administration, 14 proteins increased, and 13 proteins decreased within 48 h as compared to controls.
+In the LPS group, there were significant increases in serum levels of ragulator complex protein (189-fold) and galectin-3-binding protein (10-fold), but transcription factor MafF and corticosteroid binding globulin were down regulated (≥ 5 fold).
+As compared with the LPS group, in LPS + C group, fibrinogen gamma-B-chain and antithrombin were up-regulated, while hemopexin and histone H4 were down-regulated.
+CONCLUSIONS: LPS administration produces changes in serum proteins associated with lipid metabolism, immune and inflammatory response, protein binding/transport, cell adhesion, venous thrombosis, cardiac contractility and blood coagulation.
+The administration of choline is associated with changes in proteins which can be related with its beneficial effect in this clinical situation.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12917-016-0837-y) contains supplementary material, which is available to authorized users.
+The APETALA2 (AP2) genes represent the AP2 group within a large group of DNA-binding proteins called AP2/EREBP.
+The AP2 gene is functional and necessary for flower development, stem cell maintenance, and seed development, whereas the other members of AP2 group redundantly affect flowering time.
+Spermatophyte AP2 group genes can be classified into AP2 and TOE types, six clades, and we found that the AP2 group homologs in gymnosperms belong to the AP2 type, whereas TOE types are absent, which indicates the AP2 type gene are more ancient and TOE type was split out of AP2 type and losing the major function.
+In Brassicaceae, the expansion of AP2 and TOE type lead to the gene number of AP2 group were up to six.
+Purifying selection appears to have been the primary driving force of spermatophyte AP2 group evolution, although positive selection occurred in the AP2 clade.
+The transition from exon to intron of AtAP2 in Arabidopsis mutant leads to the loss of gene function and the same situation was found in AtTOE2.
+Combining this evolutionary analysis and published research, the results suggest that typical AP2 group genes may first appear in gymnosperms and diverged in angiosperms, following expansion of group members and functional differentiation.
+In angiosperms, AP2 genes (AP2 clade) inherited key functions from ancestors and other genes of AP2 group lost most function but just remained flowering time controlling in gene formation.
+In this study, the phylogenies of AP2 group genes in spermatophytes was analyzed, which supported the evidence for the research of gene functional evolution of AP2 group.
+The outcome of Mycobacterium tuberculosis infection and the immunological response to the bacillus Calmette-Guerin (BCG) vaccine are highly variable in humans.
+Deciphering the relative importance of host genetics, environment, and vaccine preparation for the efficacy of BCG has proven difficult in natural populations.
+We developed a model system that captures the breadth of immunological responses observed in outbred individual mice, which can be used to understand the contribution of host genetics to vaccine efficacy.
+This system employs a panel of highly diverse inbred mouse strains, consisting of the founders and recombinant progeny of the “Collaborative Cross” project.
+Unlike natural populations, the structure of this panel allows the serial evaluation of genetically identical individuals and the quantification of genotype-specific effects of interventions such as vaccination.
+When analyzed in the aggregate, our panel resembled natural populations in several important respects: the animals displayed a broad range of susceptibility to M. tuberculosis, differed in their immunological responses to infection, and were not durably protected by BCG vaccination.
+However, when analyzed at the genotype level, we found that these phenotypic differences were heritable.
+The efficacy of BCG was genetically separable from susceptibility to M. tuberculosis, and the lack of efficacy in the aggregate analysis was driven by nonresponsive lines that mounted a qualitatively distinct response to infection.
+These observations support an important role for host genetic diversity in determining BCG efficacy and provide a new resource to rationally develop more broadly efficacious vaccines.
+The TNF-α biological inhibitors have significantly improved the clinical outcomes of many autoimmune diseases, in particular rheumatoid arthritis.
+However, the practical uses are limited due to high costs and the risk of anti-drug antibody responses.
+Attempts to develop anti-TNF-α vaccines have generated encouraging data in animal models, however, data from clinical trials have not met expectations.
+In present study, we designed a TNF-α epitope-scaffold immunogen DTNF7 using the transmembrane domain of diphtheria toxin, named DTT as a scaffold.
+Molecular dynamics simulation shows that the grafted TNF-α epitope is entirely surface-exposed and presented in a native-like conformation while the rigid helical structure of DTT is minimally perturbed, thereby rendering the immunogen highly stable.
+Immunization of mice with alum formulated DTNF7 induced humoral responses against native TNF-α, and the antibody titer was sustained for more than 6 months, which supports a role of the universal CD4 T cell epitopes of DTT in breaking self-immune tolerance.
+In a mouse model of rheumatoid arthritis, DTNF7-alum vaccination markedly delayed the onset of collagen-induced arthritis, and reduced incidence as well as clinical score.
+DTT is presumed safe as an epitope carrier because a catalytic inactive mutant of diphtheria toxin, CRM197 has good clinical safety records as an active vaccine component.
+Taken all together, we show that DTT-based epitope vaccine is a promising strategy for prevention and treatment of autoimmune diseases.
+Sporadic human infections with the highly pathogenic avian influenza (HPAI) A (H5N6) virus have been reported in different provinces in China since April 2014.
+From June 2015 to January 2016, routine live poultry market (LPM) surveillance was conducted in Shenzhen, Guangdong Province.
+The H5N6 virus-positive rate increased markedly beginning in December 2015, and viruses were detected in LPMs in all districts of the city.
+Coincidently, two human cases with histories of poultry exposure developed symptoms and were diagnosed as H5N6-positive in Shenzhen during late December 2015 and early January 2016.
+In contrast to previously reported H5N6 viruses, viruses with six internal genes derived from the H9N2 or H7N9 viruses were detected in the present study.
+The increased H5N6 virus-positive rate in the LPMs and the subsequent human infections demonstrated that sustained LPM surveillance for avian influenza viruses provides an early warning for human infections.
+Interventions, such as LPM closures, should be immediately implemented to reduce the risk of human infection with the H5N6 virus when the virus is widely detected during LPM surveillance.
+The genus Sapovirus, in the family Caliciviridae, includes enteric viruses of humans and domestic animals.
+Information on sapovirus infection of wildlife is limited and is currently lacking for any free-ranging wildlife species in Africa.
+By screening a large number of predominantly fecal samples (n = 631) obtained from five carnivore species in the Serengeti ecosystem, East Africa, sapovirus RNA was detected in the spotted hyena (Crocuta crocuta, family Hyaenidae), African lion (Panthera leo, family Felidae), and bat-eared fox (Otocyon megalotis, family Canidae), but not in golden or silver-backed jackals (Canis aureus and C. mesomelas, respectively, family Canidae).
+A phylogenetic analysis based on partial RNA-dependent RNA polymerase (RdRp) gene sequences placed the sapovirus strains from African carnivores in a monophyletic group.
+Within this monophyletic group, sapovirus strains from spotted hyenas formed one independent sub-group, and those from bat-eared fox and African lion a second sub-group.
+The percentage nucleotide similarity between sapoviruses from African carnivores and those from other species was low (< 70.4%).
+Long-term monitoring of sapovirus in a population of individually known spotted hyenas from 2001 to 2012 revealed: i) a relatively high overall infection prevalence (34.8%); ii) the circulation of several genetically diverse variants; iii) large fluctuations in infection prevalence across years, indicative of outbreaks; iv) no significant difference in the likelihood of infection between animals in different age categories.
+The likelihood of sapovirus infection decreased with increasing hyena group size, suggesting an encounter reduction effect, but was independent of socially mediated ano-genital contact, or the extent of the area over which an individual roamed.
+BACKGROUND: Taiwan has been considered free from canine parvovirus type 2c (CPV-2c) based on the last report of canine parvovirus type 2 (CPV-2) surveillance.
+However, since January 2015, the first report of CPV-2c in a puppy has occurred in Taiwan.
+In the present study, we characterized the previously unidentified CPV-2c variant and investigated the distribution of CPV-2 variants in Taiwan.
+METHODS: During January 2014 to April 2016, fecal or rectal swab samples from 99 dogs with suspected CPV-2 infection in Taiwan were collected.
+Eighty-eight were identified as being either CPV-2a, −2b or -2c variants positive by real-time PCR and sequence analysis.
+RESULTS: Sequence analysis of the 88 isolates confirmed CPV-2c as the dominant variant (54.6 %), followed by CPV-2b (26.1 %) and CPV-2a (19.3 %).
+Phylogenetic analysis demonstrated that the recent CPV-2c variants are similar to the Chinese CPV-2c strain but can be considered as novel Asian CPV-2c isolates.
+CONCLUSION: The present study provides evidence for the existence of a novel CPV-2c variant in Taiwan.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12985-016-0620-5) contains supplementary material, which is available to authorized users.
+BACKGROUND: Antimicrobial resistance is a global public health challenge and carbapenem resistance, in particular, is considered an urgent global health threat.
+This study was carried out to give a bibliometric overview of literature on carbapenem resistance.
+In specific, number of publications, top productive countries and institutes, highly cited articles, citation analysis, co-authorships, international collaboration, top active authors, and journals publishing articles on carbapenem resistance were analyzed and discussed.
+Quantitative and qualitative analysis of retrieved data were presented using appropriate bibliometric indicators and visualization maps.
+Approximately 9 % of retrieved articles on carbapenem resistance were published in Antimicrobial Agents and Chemotherapy journal.
+The United States of America (USA) contributed most with 437 (16.70 %) articles followed by China with 257 (9.82 %) articles.
+Asian countries have lesser international collaboration compared with other countries in the top ten list.
+Five of top ten productive institutes were Europeans (France, the UK, Greece, Italy, and Switzerland) and two were Asians (China and South Korea).
+Four of the top ten cited articles were published in Antimicrobial Agents and Chemotherapy journal and two were published in The Lancet Infectious Diseases.
+CONCLUSION: There was a dramatic increase in number of publications on carbapenem resistance in the past few years.
+These publications were produced from different world regions including Asia, Europe, Middle East, and Latin America.
+Molecular biology and epidemiology dominated the theme of the top ten cited articles on carbapenem resistance.
+This bibliometric study will hopefully help health policy makers in planning future research and allocating funds pertaining to carbapenem resistance.
+As the predominant aetiological agent of the common cold, human rhinovirus (HRV) is the leading cause of human infectious disease.
+Early studies showed that a monovalent formalin-inactivated HRV vaccine can be protective, and virus-neutralizing antibodies (nAb) correlated with protection.
+Here, we test the hypothesis that increasing virus input titres in polyvalent inactivated HRV vaccine may result in broad nAb responses.
+We show that serum nAb against many rhinovirus types can be induced by polyvalent, inactivated HRVs plus alhydrogel (alum) adjuvant.
+Using formulations up to 25-valent in mice and 50-valent in rhesus macaques, HRV vaccine immunogenicity was related to sufficient quantity of input antigens, and valency was not a major factor for potency or breadth of the response.
+Thus, we have generated a vaccine capable of inducing nAb responses to numerous and diverse HRV types.
+Enhancing the knowledge of host factors that are required for efficient influenza A virus (IAV) replication is essential to address questions related to pathogenicity and to identify targets for antiviral drug development.
+Here we focused on the interplay between IAV and DExD-box RNA helicases (DDX), which play a key role in cellular RNA metabolism by remodeling RNA-RNA or RNA-protein complexes.
+We performed a targeted RNAi screen on 35 human DDX proteins to identify those involved in IAV life cycle.
+In DDX19-depleted cells the accumulation of viral RNAs and proteins was delayed, and the production of infectious IAV particles was strongly reduced.
+We show that DDX19 associates with intronless, unspliced and spliced IAV mRNAs and promotes their nuclear export.
+In addition, we demonstrate an RNA-independent association between DDX19 and the viral polymerase, that is modulated by the ATPase activity of DDX19.
+Our results provide a model in which DDX19 is recruited to viral mRNAs in the nucleus of infected cells to enhance their nuclear export.
+Information gained from this virus-host interaction improves the understanding of both the IAV replication cycle and the cellular function of DDX19.
+Pneumonia refers to lung inflammation caused by different pathogens or other factors, and is a common pediatric disease occurring in infants and young children.
+It is closely related to the anatomical and physiological characteristics of infants and young children and is more frequent during winter and spring, or sudden changes in temperature.
+Pneumonia is a serious disease that poses a threat to children's health and its morbidity and mortality rank first, accounting for 24.5–65.2% of pediatric inpatients.
+Due to juvenile age, severe illness and rapid changes, children often suffer acute heart failure, respiratory failure and even toxic encephalopathy at the same time.
+The concurrence in different stages of the process of emergency treatment tends to relapse, which directly places the lives of these children at risk.
+In the process of nursing children with severe pneumonia, intensive care was provided, including condition assessment and diagnosis, close observation of disease, keeping the airway unblocked, rational oxygen therapy, prevention and treatment of respiratory and circulatory failure, support of vital organs, complications, and health education.
+In summary, positive and effective nursing can promote the rehabilitation of children patients, which can be reinforced with adequate communication with the parents and/or caretakers.
+Although it is well established that VZV is transmitted via the respiratory route, the host-pathogen interactions during acute VZV infection in the lungs remain poorly understood due to limited access to clinical samples.
+To address these gaps in our knowledge, we leveraged a nonhuman primate model of VZV infection where rhesus macaques are intrabronchially challenged with the closely related Simian Varicella Virus (SVV).
+Acute infection is characterized by immune infiltration of the lung airways, a significant up-regulation of genes involved in antiviral-immunity, and a down-regulation of genes involved in lung development.
+This is followed by a decrease in viral loads and increased expression of genes associated with cell cycle and tissue repair.
+These data provide the first characterization of the host response required to control varicella virus replication in the lung and provide insight into mechanisms by which VZV infection can cause lung injury in an immune competent host.
+There is a great need for development of rational ways of detecting and quantifying antibodies, both for humans and animals.
+Traditionally, serology using synthetic antigens covers linear epitopes using up to 30 amino acid peptides.
+Methods: We here report that peptides of 100 amino acids or longer (“megapeptides”), designed and synthesized for optimal serological performance, can successfully be used as detection antigens in a suspension multiplex immunoassay (SMIA).
+A combination of rational sequencing and bioinformatic routines for definition of diagnostically-relevant antigens can, thus, rapidly yield efficient serological diagnostic tools for an emerging infectious pathogen.
+These long peptides were tested as antigens for the presence of antibodies in human serum to the filo-, herpes-, and polyoma virus families in a multiplex microarray system.
+Conclusion: Long synthetic peptides can be useful as serological diagnostic antigens, serving as biomarkers, in suspension microarrays.
+The interferon (IFN) induced anti-viral response is amongst the earliest and most potent of the innate responses to fight viral infection.
+The induction of the Janus kinase/signal transducer and activation of transcription (JAK/STAT) signalling pathway by IFNs leads to the upregulation of hundreds of interferon stimulated genes (ISGs) for which, many have the ability to rapidly kill viruses within infected cells.
+During the long course of evolution, viruses have evolved an extraordinary range of strategies to counteract the host immune responses in particular by targeting the JAK/STAT signalling pathway.
+Understanding how the IFN system is inhibited has provided critical insights into viral virulence and pathogenesis.
+Moreover, identification of factors encoded by viruses that modulate the JAK/STAT pathway has opened up opportunities to create new anti-viral drugs and rationally attenuated new generation vaccines, particularly for RNA viruses, by reverse genetics.
+Recent reports suggest that human neutrophil elastase (HNE) plays a key role in the inflammatory response that is characteristic of ALI, which indicates that the development of HNE inhibitors could be an efficient treatment strategy.
+In the current study, an enzyme-based screening assay was used to identify effective HNE inhibitors from a number of traditional Chinese medicines (TCMs).
+Among them, a water extract of Ilex kaushue (IKWE) effectively inhibited HNE activity (IC(50), 11.37 ± 1.59 μg/mL).
+Compound 6 (identified as 3,5-dicaffeoylquinic acid; 3,5-DCQA) exerted the most potent and selective inhibitory effect on HNE activity (IC(50), 1.86 ± 0.06 μM).
+In a cell-based assay, 3,5-DCQA not only directly reduced superoxide generation and elastase activity but also attenuated the Src family kinase (SRKs)/Vav signaling pathway in N-formyl-L-Met-L-Leu-L-Phe (fMLF)-stimulated human neutrophils.
+In an animal disease model, both 3,5-DCQA and standardized IKWE protected against lipopolysaccharide-induced ALI in mice, which provides support for their potential as candidates in the development of new therapeutic agents for neutrophilic inflammatory diseases.
+The family Picornaviridae contains clinically important pathogens that infect humans and animals, and increasing numbers of rodent picornaviruses have recently been associated with zoonoses.
+We collected 574 pharyngeal and anal swab specimens from 287 rodents of 10 different species from eight representative regions of China from October 2013 to July 2015.
+Seven representative sequences identified from six rodent species were amplified as full genomes and classified into four lineages.
+Three lineage 1 viruses belonged to a novel genus of picornaviruses and was more closely related to Hepatovirus than to others genera of picornaviruses based on aa homology.
+Lineage 2, lineage 3, and lineage 4 viruses belonged to the genera Rosavirus, Hunnivirus, and Enterovirus, respectively, representing new species.
+According to both phylogenetic and identity analyses, Lineage 2 viruses had a close relationship with rosavirus 2 which was recovered from the feces of a child in Gambia and Lineage 3 viruses had a close relationship with domestic animal Hunnivirus.
+Lineage 4 viruses provide the first evidence of these enteroviruses and their evolution in rodent hosts in China.
+The objective of this study was to determine the role of XB130 in lipopolysaccharide (LPS)-induced septic responses and acute lung injury.
+There was a significant weight loss in KO mice at Day 2 and significantly higher disease scores during the 7 days of observation.
+The levels of tumor necrosis factor-alpha, monocyte chemoattractant protein-1, interleukin-6 and interleukin-10 in the serum were significantly higher in KO mice at Day 2.
+In KO mice there were a significantly higher lung injury score, higher wet/dry lung weight ratio, more apoptotic cells and less proliferative cells in the lung.
+There was significantly increased number of p-GSK-3β positive cells in KO mice, which were mainly neutrophils and macrophages.
+XB130 deficiency delayed the recovery from systemic septic responses, and the presence of XB130 in the alveolar epithelial cells may provide protective mechanisms by reducing cell death and promoting cell proliferation, and reducing pulmonary permeability.
+Detection of the infection is mostly done using RT-RCR or ELISA, which are not suitable for point-of-care diagnosis.
+METHODOLOGY/PRINCIPAL FINDINGS: In this study, a reverse transcription recombinase polymerase amplification (RT-RPA) assay for the detection of the CHIKV was developed.
+CHIKV RT-RPA assay detected down to 80 genome copies/reaction in a maximum of 15 minutes.
+No cross-reactivity was detected to other alphaviruses and arboviruses except O'nyong'nyong virus, which could be differentiated by a modified RPA primer pair.
+CONCLUSIONS/SIGNIFICANCE: The developed RT-RPA assay represents a promising method for the molecular detection of CHIKV at point of need.
+OBJECTIVES: The purpose of this study was to obtain a natural antibiotic from Phenol-rich compounds; for the dressing and the treatment of chronic wounds.
+METHODS: The Phenol-rich compound sweet gel was prepared by blending four natural herbal extracts, Acacia catechu (L.F.), Momia (Shilajit), Castanea sativa, and Ephedra sinica stapf, with combination of a sweet gel medium, including honey, maple saps, Phoenix dactylifera L. (date), pomegranate extract and Azadirachta indica gum as a stabilizer.
+The zones of inhibition in agar culture were measured for each individual component and for the compound, and the results were compared with those of the control group which had been treated with cloxacillin.
+RESULTS: The antibiotic effect of the Phenol-rich compound sweet gel was statistically shown to be more significant than that of cloxacillin against Pseudomonas aeruginosa (P < 0.05).
+CONCLUSION: Our novel approach to fighting the antibiotic resistance of Pseudomonas proved to be successful.
+The Phenol-rich compound sweet gel was found to be suitable for use as an alternative medicine and bioactive dressing material, for the treatment of patients with various types of wounds, including burns, venous leg ulcers, ulcers of various etiologies, leg ulcers on the feet of diabetic, unhealed graft sampling sites, abscesses, boils, surgical wounds, necrotic process, post-operative and neonatal wound infection, and should be considered as an alternative to the usual methods of cure.
+We have previously shown that IFIT1 is primarily responsible for the antiviral action of interferon (IFN) alpha/beta against parainfluenza virus type 5 (PIV5), selectively inhibiting the translation of PIV5 mRNAs.
+Here we report that while PIV2, PIV5, and mumps virus (MuV) are sensitive to IFIT1, nonrubulavirus members of the paramyxoviridae such as PIV3, Sendai virus (SeV), and canine distemper virus (CDV) are resistant.
+The IFIT1 sensitivity of PIV5 was not rescued by coinfection with an IFIT1-resistant virus (PIV3), demonstrating that PIV3 does not specifically inhibit the antiviral activity of IFIT1 and that the inhibition of PIV5 mRNAs is regulated by cis-acting elements.
+We developed an in vitro translation system using purified human IFIT1 to further investigate the mechanism of action of IFIT1.
+While the translations of PIV2, PIV5, and MuV mRNAs were directly inhibited by IFIT1, the translations of PIV3, SeV, and CDV mRNAs were not.
+Using purified human mRNA-capping enzymes, we show biochemically that efficient inhibition by IFIT1 is dependent upon a 5′ guanosine nucleoside cap (which need not be N7 methylated) and that this sensitivity is partly abrogated by 2′O methylation of the cap 1 ribose.
+Intriguingly, PIV5 M mRNA, in contrast to NP mRNA, remained sensitive to inhibition by IFIT1 following in vitro 2′O methylation, suggesting that other structural features of mRNAs may influence their sensitivity to IFIT1.
+Thus, surprisingly, the viral polymerases (which have 2′-O-methyltransferase activity) of rubulaviruses do not protect these viruses from inhibition by IFIT1.
+IMPORTANCE Paramyxoviruses cause a wide variety of diseases, and yet most of their genes encode structural proteins and proteins involved in their replication cycle.
+Thus, the amount of genetic information that determines the type of disease that paramyxoviruses cause is relatively small.
+One factor that will influence disease outcomes is how they interact with innate host cell defenses, including the interferon (IFN) system.
+Here we show that different paramyxoviruses interact in distinct ways with cells in a preexisting IFN-induced antiviral state.
+Strikingly, all the rubulaviruses tested were sensitive to the antiviral action of ISG56/IFIT1, while all the other paramyxoviruses tested were resistant.
+We developed novel in vitro biochemical assays to investigate the mechanism of action of IFIT1, demonstrating that the mRNAs of rubulaviruses can be directly inhibited by IFIT1 and that this is at least partially because their mRNAs are not correctly methylated.
+The aim of this study was to identify indicators for whether children at an early stage of M pneumoniae infection develop mild or severe pneumonia.
+CASE SUMMARY: Herein, we retrospectively reviewed 2 pediatric cases caused by macrolide-resistant M pneumoniae, but with markedly different severity of pneumonia.
+First, we compared the clinical courses of the patients, then isolated the pathogens and tested their response to macrolides, then finally, carried out whole genome sequencing of these isolates.
+Despite the difference in clinical presentation of the infection, both isolates exhibited a high level of resistance to macrolide antibiotics.
+Analysis of clinical data showed that the erythrocyte sedimentation rate in blood samples of the patients in the early stages of disease varied greatly.
+Genome sequence analysis revealed single nucleotide polymorphisms mainly focused on adhesin P1, which is involved in the pathogenicity of M pneumoniae.
+CONCLUSION: The differences of erythrocyte sedimentation rate in the early stage of M pneumoniae pneumonia and mutations in P1 protein may help us to distinguish between severe or mild disease after infection with macrolide-resistant M pneumoniae.
+These findings could lead to the development of screening assays that will allow us to distinguish severe or mild M pneumoniae pneumonia early.
+Despite improvements in the management of community-acquired pneumonia (CAP), morbidity and mortality are still high, especially in patients with more severe disease.
+However, two aspects seem to contribute to a worse outcome: an uncontrolled inflammatory reaction and an inadequate immune response.
+Adjuvant treatments, such as corticosteroids and intravenous immunoglobulins, have been proposed to counterbalance these effects.
+The use of corticosteroids in patients with severe CAP and a strong inflammatory reaction can reduce the time to clinical stability, the risk of treatment failure, and the risk of progression to acute respiratory distress syndrome.
+The administration of intravenous immunoglobulins seems to reinforce the immune response to the infection in particular in patients with inadequate levels of antibodies and when an enriched IgM preparation has been used; however, more studies are needed to determinate their impact on outcome and to define the population that will receive more benefit.
+BACKGROUND: Guangzhou reported its first laboratory-confirmed case of influenza A (H7N9) on January 10, 2014.
+A total of 25 cases were reported from the first wave of the epidemic until April 8, 2014.
+The objective of the current work was to describe the clinical and epidemiological characteristics of A (H7N9) patients in Guangzhou and explore possible reasons for the high fatality rate.
+METHODS: Clinical and epidemiological information regarding A (H7N9) cases in Guangzhou was collected through review of medical records and field research.
+Fifteen patients (60.0 %) developed moderate to severe acute respiratory distress syndrome (ARDS), and 14 (56 %) died of the ARDS or multiorgan failure.
+Patients with longer delay between onset of illness and initiation of oseltamivir treatment were more likely to develop ARDS.
+Elevated C-creative protein, aspartate aminotransferase, creatine kinase, and lymphocytopenia predicted a higher risk of developing ARDS.
+A central challenge in pharmaceutical research is to investigate genetic variation in response to drugs.
+The Collaborative Cross (CC) mouse reference population is a promising model for pharmacogenomic studies because of its large amount of genetic variation, genetic reproducibility, and dense recombination sites.
+While the CC lines are phenotypically diverse, their genetic diversity in drug disposition processes, such as detoxification reactions, is still largely uncharacterized.
+Here we systematically measured RNA-sequencing expression profiles from livers of 29 CC lines under baseline conditions.
+We then leveraged a reference collection of metabolic biotransformation pathways to map potential relations between drugs and their underlying expression quantitative trait loci (eQTLs).
+By applying this approach on proximal eQTLs, including eQTLs acting on the overall expression of genes and on the expression of particular transcript isoforms, we were able to construct the organization of hepatic eQTL-drug connectivity across the CC population.
+The analysis revealed a substantial impact of genetic variation acting on drug biotransformation, allowed mapping of potential joint genetic effects in the context of individual drugs, and demonstrated crosstalk between drug metabolism and lipid metabolism.
+Our findings provide a resource for investigating drug disposition in the CC strains, and offer a new paradigm for integrating biotransformation reactions to corresponding variations in DNA sequences.
+The expression of PTEN controlled by p53 regulates autoimmune arthritis through modulating the balance between Th17 and Treg.
+We hypothesized that PTEN regulated by p53 might reduce CIA severity and inflammatory response via inhibiting STAT3 activation.
+Our results revealed that PTEN could ameliorate experimental autoimmune arthritis by reducing STAT3 activity and Th17 differentiation.
+In addition, PTEN overexpression decreased the activation of T cells and modulated reciprocal differentiation of Th17 and Treg cells.
+These data suggest that induction of STAT3-modulatory activity of PTEN may be a therapeutic target for rheumatoid arthritis therapy.
+Small-molecule fragments binding to biomacromolecules can be starting points for the development of drugs, but are often difficult to detect due to low affinities.
+Here we present a strategy that identifies protein-binding fragments through their potential to induce the target-guided formation of covalently bound, irreversible enzyme inhibitors.
+A protein-binding nucleophile reacts reversibly with a bis-electrophilic warhead, thereby positioning the second electrophile in close proximity of the active site of a viral protease, resulting in the covalent de-activation of the enzyme.
+The concept is implemented for Coxsackie virus B3 3C protease, a pharmacological target against enteroviral infections.
+Using an aldehyde-epoxide as bis-electrophile, active fragment combinations are validated through measuring the protein inactivation rate and by detecting covalent protein modification in mass spectrometry.
+OBJECTIVE: In this study, we aimed to describe the processes of both the donning and the doffing of personal protective equipment for Ebola and evaluate contamination during the doffing process.
+METHODS: We recruited study participants among physicians and nurses of the emergency department of Samsung Medical Center in Seoul, Korea.
+Participants were asked to carry out doffing and donning procedures with a helper after a 50-minute brief training and demonstration based on the 2014 Centers for Disease Control and Prevention protocol.
+Two separate cameras with high-density capability were set up, and the donning and doffing processes were video-taped.
+A trained examiner inspected all video recordings and coded for intervals, errors, and contaminations defined as the outside of the equipment touching the clinician’s body surface.
+For the donning process, the average interval until the end was 234.2 seconds (standard deviation [SD], 65.7), and the most frequent errors occurred when putting on the outer gloves (27.5%), respirator (20.6%), and hood (20.6%).
+For the doffing process, the average interval until the end was 183.7 seconds (SD, 38.4), and the most frequent errors occurred during disinfecting the feet (37.9%), discarding the scrubs (17.2%), and putting on gloves (13.7%), respectively.
+The most vulnerable processes were removing respirators (79.2%), removing the shoe covers (65.5%), and removal of the hood (41.3%).
+CONCLUSION: A significant number of contaminations occur during the doffing process of personal protective equipment.
+On 1 February 2016, the World Health Organization (WHO) declared that clusters of microcephaly cases and other neurological disorders occurring in Zika virus (ZIKV)-affected areas constituted a public health emergency of international concern.
+Increased surveillance of the virus, including the requirement for laboratory confirmation of infection, was recommended.
+The WHO Regional Office for the Western Pacific therefore initiated a rapid survey among national-level public health laboratories in 19 countries and areas to determine regional capacity for ZIKV detection.
+The survey indicated that 16/19 (84%) countries had capacity for molecular detection of ZIKV while others facilitated testing through referral.
+These results suggest that robust laboratory capacity is in place to support ZIKV surveillance in the Western Pacific Region.
+Rift Valley fever virus (RVFV), a member of the genus Phlebovirus within the family Bunyaviridae, causes periodic outbreaks in livestocks and humans in countries of the African continent and Middle East.
+RVFV NSs protein, a nonstructural protein, is a major virulence factor that exhibits several important biological properties.
+These include suppression of general transcription, inhibition of IFN-β promoter induction and degradation of double-stranded RNA-dependent protein kinase R. Although each of these biological functions of NSs are considered important for countering the antiviral response in the host, the individual contributions of these functions towards RVFV virulence remains unclear.
+Each carried mutations in NSs that specifically targeted its general transcription inhibition function without affecting its ability to degrade PKR and inhibit IFN-β promoter induction, through its interaction with Sin3-associated protein 30, a part of the repressor complex at the IFN-β promoter.
+Using these mutant viruses, we have dissected the transcription inhibition function of NSs and examined its importance in RVFV virulence.
+Both NSs mutant viruses exhibited a differentially impaired ability to inhibit host transcription when compared with MP-12.
+It has been reported that NSs suppresses general transcription by interfering with the formation of the transcription factor IIH complex, through the degradation of the p62 subunit and sequestration of the p44 subunit.
+Our study results lead us to suggest that the ability of NSs to induce p62 degradation is the major contributor to its general transcription inhibition property, whereas its interaction with p44 may not play a significant role in this function.
+Importantly, RVFV MP-12-NSs mutant viruses with an impaired general transcription inhibition function showed a reduced cytotoxicity in cell culture and attenuated virulence in young mice, compared with its parental virus MP-12, highlighting the contribution of NSs-mediated general transcription inhibition towards RVFV virulence.
+In eukaryotes, the degradation of cellular mRNAs is accomplished by Xrn1 and the cytoplasmic exosome.
+Because viral RNAs often lack canonical caps or poly-A tails, they can also be vulnerable to degradation by these host exonucleases.
+Yeast lack sophisticated mechanisms of innate and adaptive immunity, but do use RNA degradation as an antiviral defense mechanism.
+We find a highly refined, species-specific relationship between Xrn1p and the “L-A” totiviruses of different Saccharomyces yeast species.
+We show that the gene XRN1 has evolved rapidly under positive natural selection in Saccharomyces yeast, resulting in high levels of Xrn1p protein sequence divergence from one yeast species to the next.
+We also show that these sequence differences translate to differential interactions with the L-A virus, where Xrn1p from S. cerevisiae is most efficient at controlling the L-A virus that chronically infects S. cerevisiae, and Xrn1p from S. kudriavzevii is most efficient at controlling the L-A-like virus that we have discovered within S. kudriavzevii.
+All Xrn1p orthologs are equivalent in their interaction with another virus-like parasite, the Ty1 retrotransposon.
+Thus, Xrn1p appears to co-evolve with totiviruses to maintain its potent antiviral activity and limit viral propagation in Saccharomyces yeasts.
+We demonstrate that Xrn1p physically interacts with the Gag protein encoded by the L-A virus, suggesting a host-virus interaction that is more complicated than just Xrn1p-mediated nucleolytic digestion of viral RNAs.
+The unprecedented outbreak of Ebola in West Africa resulted in over 28,000 cases and 11,000 deaths, underlining the need for a better understanding of the biology of this highly pathogenic virus to develop specific counter strategies.
+Two filoviruses, the Ebola and Marburg viruses, result in a severe and often fatal infection in humans.
+The molecular basis of this striking difference in the response to filovirus infections is not well understood.
+We report a systematic overview of differentially expressed genes, activity motifs and pathways in human and bat cells infected with the Ebola and Marburg viruses, and we demonstrate that the replication of filoviruses is more rapid in human cells than in bat cells.
+We also found that the most strongly regulated genes upon filovirus infection are chemokine ligands and transcription factors.
+We observed a strong induction of the JAK/STAT pathway, of several genes encoding inhibitors of MAP kinases (DUSP genes) and of PPP1R15A, which is involved in ER stress-induced cell death.
+We used comparative transcriptomics to provide a data resource that can be used to identify cellular responses that might allow bats to survive filovirus infections.
+AIM: To investigate autophagy-related genes, particularly ATG12, in apoptosis and cell cycle in hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) and non-HBV-HCC cell lines.
+METHODS: The expression of autophagy-related genes in HBV-associated hepatocellular carcinoma and non-HBV-HCC cell lines and human liver tissues was examined by quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR) and western blotting.
+The silencing of target genes was used to examine the function of various genes in apoptosis and cell cycle progression.
+RESULTS: The expression of autophagy related genes ATG5, ATG12, ATG9A and ATG4B expression was analyzed in HepG2.2.15 cells and compared with HepG2 and THLE cells.
+We found that ATG5 and ATG12 mRNA expression was significantly increased in HepG2.2.15 cells compared to HepG2 cells (P < 0.005).
+Moreover, ATG5-ATG12 protein levels were increased in tumor liver tissues compared to adjacent non-tumor tissues mainly from HCC patients with HBV infection.
+The percentage of apoptotic cells increased by 11.4% in ATG12-silenced HepG2.2.15 cells (P < 0.005) but did not change in ATG12-silenced HepG2 cells under starvation with Earle’s balanced salt solution.
+However, the combination blockade of Notch signaling and ATG12 decreased the apoptotic rate of HepG2.2.15 cells from 55.6% to 50.4% (P < 0.05).
+The Ebola virus in West Africa has infected almost 30,000 and killed over 11,000 people.
+Recent models of Ebola Virus Disease (EVD) have often made assumptions about how the disease spreads, such as uniform transmissibility and homogeneous mixing within a population.
+In this paper, we test whether these assumptions are necessarily correct, and offer simple solutions that may improve disease model accuracy.
+First, we use data and models of West African migration to show that EVD does not homogeneously mix, but spreads in a predictable manner.
+Next, we estimate the initial growth rate of EVD within country administrative divisions and find that it significantly decreases with population density.
+Finally, we test whether EVD strains have uniform transmissibility through a novel statistical test, and find that certain strains appear more often than expected by chance.
+Computer-aided detection systems aim at the automatic detection of diseases using different medical imaging modalities.
+In this paper, a novel approach to detecting normality/pathology in digital chest radiographs is proposed.
+The problem tackled is complicated since it is not focused on particular diseases but anything that differs from what is considered as normality.
+First, the areas of interest of the chest are found using template matching on the images.
+After that, LBP histograms are applied in a classifier algorithm, which produces the final normality/pathology decision.
+Our experimental results show the feasibility of the proposal, with success rates above 87% in the best cases.
+Moreover, our technique is able to locate the possible areas of pathology in nonnormal radiographs.
+The objective was to investigate porcine epidemic diarrhea (PED) outbreak that occurred in 2014 in Japan and its effects on herd-level productivity using a data recording system (PigINFO).
+The study herds were selected from farrow-to-finish herds (n=99) that entered in the PigINFO system between July 2013 and March 2015.
+From 1 April to 30 June 2014 (PED epidemic), any herds with clinical signs of PED and feces positive for porcine epidemic diarrhea virus (PEDV) on polymerase chain reaction analysis and/or immunohistochemical staining were defined as PED-positive (n=38).
+They were further classified into those with long PED periods (L-PED-positive; n=28) and those with short PED periods (S-PED-positive; n=10).
+Herd-level production data, including preweaning mortality (%; PRWM), postweaning mortality (%; POWM), pigs weaned per litter (PWL), pigs born alive per litter, litters per mated female per year and pigs marketed per sow (MP), were calculated every 3 months during study period.
+During the PED epidemic, L-PED-positive herds had significantly higher PRWM and POWM than PED-negative herds, and L-PED-positive and S-PED-positive herds had significantly lower PWL.
+The rapid control of an outbreak is important for reducing the financial losses arising from PED infections.
+BACKGROUND: Human rhinoviruses (HRV) cause a wide spectrum of disease, ranging from a mild influenza‐like illness (ILI) to severe respiratory infection.
+OBJECTIVES: To identify the species and genotypes of HRV from clinical samples collected in Sydney, Australia, from 2006 to 2009.
+METHODS: Combined nose and throat swabs or nasopharyngeal aspirates collected from individuals with ILI were tested for HRV using real‐time reverse‐transcriptase polymerase chain reaction (RT‐PCR).
+Phylogenetic analysis of 5′UTR and VP4/VP2 on HRV‐positive samples was concordant in the grouping of HRV A and B species but not HRV C species.
+Eighty per cent (16/20) of sequences that grouped as HRV C in the VP4/VP2 tree clustered as HRV A, alongside some previously described C strains as subspecies C/A.
+Discordant branching was seen within HRV A group: two sequences clustering as A in the VP4/VP2 tree branched within the C/A subspecies in the 5′UTR tree, and one sequence showed identity to different HRV A strains in the two genes.
+The prevalence of HRV C and C/A species was greater in paediatric compared to adult patients (47.9% vs 25.5%, P = .032).
+CONCLUSION: Human rhinoviruses are a common cause of respiratory infections, and HRV C is present in the Southern Hemisphere.
+Novel avian H7N9 virus emerged in China in 2013 resulting in a case fatality rate of around 39% and continues to pose zoonotic and pandemic risk.
+Amino acid substitutions in PB2 protein were shown to influence the pathogenicity and transmissibility of H7N9 following experimental infection of ferrets and mice.
+In this study, we evaluated the role of amino acid substitution PB2-627K or compensatory changes at PB2-591K and PB2-701N, on the tropism and replication competence of H7N9 viruses for human and swine respiratory tracts using ex vivo organ explant cultures.
+Recombinant viruses of A/Shanghai/2/2013 (rgH7N9) and its mutants with PB2-K627E, PB2-K627E + Q591K and PB2-K627E + D701N were generated by plasmid-based reverse genetics.
+PB2-E627K was essential for efficient replication of rgH7N9 in ex vivo cultures of human and swine respiratory tracts.
+Mutant rgPB2-K627E + D701N replicated better than rgPB2-K627E in human lung but not as well as rgH7N9 virus.
+The rgPB2-K627E mutant failed to replicate in human type I-like pneumocytes (ATI) and peripheral blood monocyte-derived macrophages (PMϕ) at 37 °C while the compensatory mutant rgPB2-K627E + Q591K and rgPB2-K627E + D701N had partly restored replication competence in PMϕ.
+Our results demonstrate that PB2-E627K was important for efficient replication of influenza H7N9 in both human and swine respiratory tracts.
+Virus pseudotyping is a useful and safe technique for studying entry of emerging strains of influenza virus.
+However, few studies have compared different reassortant combinations in pseudoparticle systems, or compared entry kinetics of native viruses and their pseudotyped analogs.
+Here, vesicular stomatitis virus (VSV)-based pseudovirions displaying distinct influenza virus envelope proteins were tested for fusion activity.
+We produced VSV pseudotypes containing the prototypical X-31 (H3) HA, either alone or with strain-matched or mismatched N2 NAs.
+We performed single-particle fusion assays using total internal reflection fluorescence microscopy to compare hemifusion kinetics among these pairings.
+Pseudoparticles harboring mismatched HA-NA pairings fuse at significantly slower rates than native virus, and NA-lacking pseudoparticles exhibiting the slowest fusion rates.
+Relative viral membrane HA density of matching pseudoparticles was higher than in mismatching or NA-lacking pseudoparticles.
+An equivalent trend of HA expression level on cell membranes of HA/NA co-transfected cells was observed and intracellular trafficking of HA was affected by NA co-expression.
+Overall, we show that specific influenza HA-NA combinations can profoundly affect the critical role played by HA during entry, which may factor into viral fitness and the emergence of new pandemic influenza viruses.
+Specifically, caspase-11–dependent cell death contributes to pathology and decreases in survival time in sepsis models.
+Priming of the host cell, through TLR4 and interferon receptors, induces caspase-11 expression, and cytosolic LPS directly stimulates caspase-11 activation, promoting the release of proinflammatory cytokines through pyroptosis and caspase-1 activation.
+We found a complement-related peptidase, carboxypeptidase B1 (Cpb1), to be required for caspase-11 gene expression and subsequent caspase-11–dependent cell death.
+Cpb1 modifies a cleavage product of C3, which binds to and activates C3aR, and then modulates innate immune signaling.
+We find the Cpb1–C3–C3aR pathway induces caspase-11 expression through amplification of MAPK activity downstream of TLR4 and Ifnar activation, and mediates severity of LPS-induced sepsis (endotoxemia) and disease outcome in mice.
+We show C3aR is required for up-regulation of caspase-11 orthologues, caspase-4 and -5, in primary human macrophages during inflammation and that c3aR1 and caspase-5 transcripts are highly expressed in patients with severe sepsis; thus, suggesting that these pathways are important in human sepsis.
+Our results highlight a novel role for complement and the Cpb1–C3–C3aR pathway in proinflammatory signaling, caspase-11 cell death, and sepsis severity.
+It is transmitted by mosquitoes, and the main strategy for epidemic prevention and control is insecticide fumigation.
+People’s day-to-day movement about the city is believed to be an important factor in the epidemiological dynamics.
+We use a simple model to examine the fundamental roles of broad demographic and spatial structures in epidemic initiation, growth and control.
+We show that the key factors are local dilution, characterised by the vector–host ratio, and spatial connectivity, characterised by the extent of habitually variable movement patterns.
+Epidemic risk in the population is driven by the demographic groups that frequent the areas with the highest vector–host ratio, even if they only spend some of their time there.
+Synchronisation of epidemic trajectories in different demographic groups is governed by the vector–host ratios to which they are exposed and the strength of connectivity.
+Strategies for epidemic prevention and management may be made more effective if they take into account the fluctuating landscape of transmission intensity associated with spatial heterogeneity in the vector–host ratio and people’s day-to-day movement patterns.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11538-016-0209-6) contains supplementary material, which is available to authorized users.
+The advent and application of high-throughput molecular techniques for analyzing microbial communities in the indoor environment have led to illuminating findings and are beginning to change the way we think about human health in relation to the built environment.
+Here I review recent studies on the microbiology of the built environment, organize their findings into 12 major thematic categories, and comment on how these studies have or have not advanced knowledge in each area beyond what we already knew from over 100 years of applying culture-based methods to building samples.
+I propose that while we have added tremendous complexity to the rich existing knowledge base, the practical implications of this added complexity remain somewhat elusive.
+It remains to be seen how this new knowledge base will change how we design, build, and operate buildings.
+Much more research is needed to better understand the complexity with which indoor microbiomes may affect human health in both positive and negative ways.
+Climate change is anticipated to alter the production, use, release, and fate of environmental chemicals, likely leading to increased uncertainty in exposure and human health risk predictions.
+The theme of the 2015 Annual Meeting of the International Society of Exposure Science—Exposures in an Evolving Environment—brought this issue to the fore.
+By directing attention to questions that may affect society in profound ways, exposure scientists have an opportunity to conduct “consequential science”—doing science that matters, using our tools for the greater good and to answer key policy questions, and identifying causes leading to implementation of solutions.
+Understanding the implications of changing exposures on public health may be one of the most consequential areas of study in which exposure scientists could currently be engaged.
+In this paper, we use a series of case studies to identify exposure data gaps and research paths that will enable us to capture the information necessary for understanding climate change-related human exposures and consequent health impacts.
+We hope that paper will focus attention on under-developed areas of exposure science that will likely have broad implications for public health.
+The virus is endemic in over 120 countries, causing over 350 million infections per year.
+Dengue vaccine development is challenging because of the need to induce simultaneous protection against four antigenically distinct DENV serotypes and evidence that, under some conditions, vaccination can enhance disease due to specific immunity to the virus.
+While several live-attenuated tetravalent dengue virus vaccines display partial efficacy, it has been challenging to induce balanced protective immunity to all 4 serotypes.
+Instead of using whole-virus formulations, we are exploring the potentials for a particulate subunit vaccine, based on DENV E-protein displayed on nanoparticles that have been precisely molded using Particle Replication in Non-wetting Template (PRINT) technology.
+The ectodomain of DENV2-E protein was expressed as a secreted recombinant protein (sRecE), purified and adsorbed to poly (lactic-co-glycolic acid) (PLGA) nanoparticles of different sizes and shape.
+We show that PRINT nanoparticle adsorbed sRecE without any adjuvant induces higher IgG titers and a more potent DENV2-specific neutralizing antibody response compared to the soluble sRecE protein alone.
+Antigen trafficking indicate that PRINT nanoparticle display of sRecE prolongs the bio-availability of the antigen in the draining lymph nodes by creating an antigen depot.
+Our results demonstrate that PRINT nanoparticles are a promising platform for delivering subunit vaccines against flaviviruses such as dengue and Zika.
+The emergence in 2009 of Plasmodium falciparum parasites resistant to the primary therapies currently in use (artemisinin-based combination therapy, ACT) in Southeast Asia threatens to set back decades of global progress in malaria control and elimination.
+Progress to date through multiple sets of initiatives and partners to contain or eliminate these parasites has been hampered due to a wide range of organizational, financial, and health systems-level challenges.
+In this commentary, a set of seven specific and concrete actions are proposed to directly address these issues and to accelerate P. falciparum elimination within the Greater Mekong Subregion to avert a wider public health crisis.
+These actions are specifically needed to elevate the situation and response mechanisms to those of a true emergency; to address systems-level challenges with personnel limitations and stock-outs of key commodities; and to restructure the response mechanisms to be well-aligned with the required outcomes.
+Consideration of these issues is especially pressing with planning meetings for renewal of the Regional Artemisinin-resistance Initiative (RAI) framework slated for late 2016 and into 2017, but these suggestions are also relevant for malaria programmes globally.
+Respiratory infectious disease epidemics and pandemics are recurring events that levy a high cost on individuals and society.
+The health-protective behavioral response of the public plays an important role in limiting respiratory infectious disease spread.
+Behaviors can be categorized as pharmaceutical (e.g., vaccination uptake, antiviral use) or non-pharmaceutical (e.g., hand washing, face mask use, avoidance of public transport).
+Due to the limitations of pharmaceutical interventions during respiratory epidemics and pandemics, public health campaigns aimed at limiting disease spread often emphasize both non-pharmaceutical and pharmaceutical behavioral interventions.
+Understanding the determinants of the public’s behavioral response is crucial for devising public health campaigns, providing information to parametrize mathematical models, and ultimately limiting disease spread.
+While other reviews have qualitatively analyzed the body of work on demographic determinants of health-protective behavior, this meta-analysis quantitatively combines the results from 85 publications to determine the global relationship between gender and health-protective behavioral response.
+The results show that women in the general population are about 50% more likely than men to adopt/practice non-pharmaceutical behaviors.
+Conversely, men in the general population are marginally (about 12%) more likely than women to adopt/practice pharmaceutical behaviors.
+It is possible that factors other than pharmaceutical/non-pharmaceutical status not included in this analysis act as moderators of this relationship.
+These results suggest an inherent difference in how men and women respond to epidemic and pandemic respiratory infectious diseases.
+This information can be used to target specific groups when developing non-pharmaceutical public health campaigns and to parameterize epidemic models incorporating demographic information.
+CCHF is a life-threatening disease observed endemically over a wide geographical regions in the world and a little known about pulmonary findings in CCHF patients.
+METHODS: The patients that were admitted and diagnosed with CCHF between April 2010 and September 2015 were examined.
+Patients who underwent thorax CT evaluation based on the clinical findings at the time of admission and/or during the hospital stay were included in the study.
+Patients’ laboratory test results and thorax CT findings for respiratory assessment along with demographic characteristics.
+RESULTS: Forty patients diagnosed with CCHF that underwent thorax CT based on their indications were included in the study.
+Twenty-seven patients (62.5 %) were male with a mean age of 55.22 ± 19.84 years.
+According to these results, the three most common thorax CT findings were parenchymal infiltration [32 patients (80 %)], pleural effusion [31 patients (77.5 %)], and alveolar infiltration [28 patients (70 %)].
+We also would like to emphasize that both direct radiography and thorax CT are highly successful in detecting frequently encountered radiological findings such as pleural effusion, alveolar hemorrhage, and parenchymal infiltration that indicate pulmonary involvement.
+Inflammation is a comprehensive array of physiological response to a foreign organism, including human pathogens, dust particles, and viruses.
+Inflammations are mainly divided into acute and chronic inflammation depending on various inflammatory processes and cellular mechanisms.
+Recent investigations have clarified that inflammation is a major factor for the progression of various chronic diseases/disorders, including diabetes, cancer, cardiovascular diseases, eye disorders, arthritis, obesity, autoimmune diseases, and inflammatory bowel disease.
+Free radical productions from different biological and environmental sources are due to an imbalance of natural antioxidants which further leads to various inflammatory associated diseases.
+In this review article, we have outlined the inflammatory process and its cellular mechanisms involved in the progression of various chronic modern human diseases.
+In addition, we have discussed the role of free radicals-induced tissue damage, antioxidant defence, and molecular mechanisms in chronic inflammatory diseases/disorders.
+The systematic knowledge regarding the role of inflammation and its associated adverse effects can provide a clear understanding in the development of innovative therapeutic targets from natural sources that are intended for suppression of various chronic inflammations associated diseases.
+Interleukin (IL)-17 producing T helper (Th17) cells are major effector cells in the pathogenesis of rheumatoid arthritis (RA).
+The P2X7 receptor (P2X7R) has emerged as a potential site in the regulation of inflammation in RA but little is known of its functional role on the differentiation of Th17 cells.
+This study investigates the in vitro and in vivo effects of P2X7R on Th17 cell differentiation during type II collagen (CII) induced experimental arthritis model.
+In CII-treated dendritic cells (DCs) and DC/CD4(+) T coculture system, pretreatment with pharmacological antagonists of P2X7R (Suramin and A-438079) caused strong inhibition of production of Th17-promoting cytokines (IL-1β, TGF-β1, IL-23p19 and IL-6).
+Exposure to CII induced the elevation of mRNAs encoding retinoic acid receptor-related orphan receptor α and γt, which were abolished by pretreatment with P2X7R antagonists.
+Blockade of P2X7R remarkably inhibited hind paw swelling and ameliorated pathological changes in ankle joint of the collagen-induced arthritis mice.
+Thus, we demonstrated a novel function for P2X7R signaling in regulating CII-induced differentiation of Th17 cells.
+P2X7R signaling facilitates the development of the sophisticated network of DC-derived cytokines that favors a Th17 phenotype.
+Macrophage colony-stimulating factor (CSF1) is an essential growth and differentiation factor for cells of the macrophage lineage.
+To explore the role of CSF1 in steady-state control of monocyte production and differentiation and tissue repair, we previously developed a bioactive protein with a longer half-life in circulation by fusing pig CSF1 with the Fc region of pig IgG1a.
+CSF1-Fc administration to pigs expanded progenitor pools in the marrow and selectively increased monocyte numbers and their expression of the maturation marker CD163.
+There was a rapid increase in the size of the liver, and extensive proliferation of hepatocytes associated with increased macrophage infiltration.
+Despite the large influx of macrophages, there was no evidence of liver injury and no increase in circulating liver enzymes.
+Microarray expression profiling of livers identified increased expression of macrophage markers, i.e., cytokines such as TNF, IL1, and IL6 known to influence hepatocyte proliferation, alongside cell cycle genes.
+The analysis also revealed selective enrichment of genes associated with portal, as opposed to centrilobular regions, as seen in hepatic regeneration.
+Combined with earlier data from the mouse, this study supports the existence of a CSF1-dependent feedback loop, linking macrophages of the liver with bone marrow and blood monocytes, to mediate homeostatic control of the size of the liver.
+The results also provide evidence of safety and efficacy for possible clinical applications of CSF1-Fc.
+Endogenous viruses integrate into host genomes and can recombine with exogenous avian leukosis virus (ALV).
+In this study, we analyzed the interaction of endogenous retrovirus 21 (ev21) with the ALV-J in late-feathering Chinese yellow chicken.
+Two ALV-J strains M180 and K243 were isolated from late-feathering and fast-feathering Chinese yellow chicken flocks, respectively.
+The env gene of the two strains showed 94.2–94.8% nucleotide identity with reference ALV-J strains.
+Compared with the env gene and the LTR of ev21 and M180, the nucleotide identity of LTR was 69.7% and env gene was 58.4%, respectively, especially the amino acid identity of env gene as low as 14.2%.
+Phylogenetic analysis of the nucleotide sequence of the env gene and the 3′LTR showed that M180 was closely related to ALV-J, and was located in a distinct group with ev21 in the phylogenetic tree.
+Using co-immunoprecipitation (co-IP), we next demonstrate that the envelope protein of ev21 does not interact with the M180 envelope protein.
+We further show that the envelope protein of ev21 cannot activate ALV-J LTR promoter activity using luciferase-reporter assays.
+qPCR and western blot analysis revealed that envelope protein of endogenous ev21 can facilitate the expression of PKR at 6h post ALV-J infection (hpi) and facilitate the expression of ISG12 and CH25H at 24 hpi.
+However, the expression of the env gene of M180 strain was not significantly at 6 and 24 hpi.
+We conclude that there is no evidence of recombination between endogenous retrovirus ev21 and ALV-J strain M180 in late-feathering Chinese yellow chicken, and envelope protein of ev21 can affect the expression of host ISGs, but appears not to influence the replication of ALV-J strain M180.
+This is the first report of interaction among the endogenous retrovirus ev21, ALV-J and the late-feathering chicken.
+Sapelovirus A (SV-A), formerly known as porcine sapelovirus as a member of a new genus Sapelovirus, is known to cause enteritis, pneumonia, polioencephalomyelitis and reproductive disorders in pigs.
+We have recently identified α2,3-linked sialic acid on GD1a ganglioside as a functional SV-A receptor rich in the cells of pigs and chickens.
+Here, we demonstrated that a Korean SV-A strain could induce diarrhoea and intestinal pathology in piglets but not in chicks.
+Moreover, this Korean SV-A strain had mild extra-intestinal tropisms appearing as mild, non-suppurative myelitis, encephalitis and pneumonia in piglets, but not in chicks.
+By real-time reverse transcription (RT) PCR, higher viral RNA levels were detected in faecal samples than in sera or extra-intestinal organs from virus-inoculated piglets.
+Immunohistochemistry confirmed that high viral antigens were detected in the epithelial cells of intestines from virus-inoculated piglets but not from chicks.
+This Korean SV-A strain could bind the cultured cell lines originated from various species, but replication occurred only in cells of porcine origin.
+These data indicated that this Korean SV-A strain could replicate and induce pathology in piglets but not in chicks, suggesting that additional porcine-specific factors are required for virus entry and replication.
+In addition, this Korean SV-A strain is enteropathogenic, but could spread to the bloodstream from the gut and disseminate to extra-intestinal organs and tissues.
+These results will contribute to our understanding of SV-A pathogenesis so that efficient anti-sapelovirus drugs and vaccines could be developed in the future.
+Eight manufacturing facilities participating in the National Institutes of Health–sponsored Clinical Islet Transplantation (CIT) Consortium jointly developed and implemented a harmonized process for the manufacture of allogeneic purified human pancreatic islet (PHPI) product evaluated in a phase 3 trial in subjects with type 1 diabetes.
+Manufacturing was controlled by a common master production batch record, standard operating procedures that included acceptance criteria for deceased donor organ pancreata and critical raw materials, PHPI product specifications, certificate of analysis, and test methods.
+This report describes the manufacturing process for 75 PHPI clinical lots and summarizes the results, including lot release.
+The results demonstrate the feasibility of implementing a harmonized process at multiple facilities for the manufacture of a complex cellular product.
+The quality systems and regulatory and operational strategies developed by the CIT Consortium yielded product lots that met the prespecified characteristics of safety, purity, potency, and identity and were successfully transplanted into 48 subjects.
+No adverse events attributable to the product and no cases of primary nonfunction were observed.
+Studying the effects of HIV infection on the host transcriptome has typically focused on protein-coding genes.
+However, recent advances in the field of RNA sequencing revealed that long non-coding RNAs (lncRNAs) add an extensive additional layer to the cell’s molecular network.
+Here, we performed transcriptome profiling throughout a primary HIV infection in vitro to investigate lncRNA expression at the different HIV replication cycle processes (reverse transcription, integration and particle production).
+Subsequently, guilt-by-association, transcription factor and co-expression analysis were performed to infer biological roles for the lncRNAs identified in the HIV-host interplay.
+Many lncRNAs were suggested to play a role in mechanisms relying on proteasomal and ubiquitination pathways, apoptosis, DNA damage responses and cell cycle regulation.
+Through transcription factor binding analysis, we found that lncRNAs display a distinct transcriptional regulation profile as compared to protein coding mRNAs, suggesting that mRNAs and lncRNAs are independently modulated.
+In addition, we identified five differentially expressed lncRNA-mRNA pairs with mRNA involvement in HIV pathogenesis with possible cis regulatory lncRNAs that control nearby mRNA expression and function.
+Altogether, the present study demonstrates that lncRNAs add a new dimension to the HIV-host interplay and should be further investigated as they may represent targets for controlling HIV replication.
+Chronic intermittent hypoxia is used to model the arterial hypoxemia seen in SA, and through this paradigm, the mechanisms that underlie SA-induced hypertension are becoming clear.
+Cyclic hypoxic exposure during sleep chronically stimulates the carotid chemoreflexes, inducing sensory long-term facilitation, and drives sympathetic outflow from the hindbrain.
+The elevated sympathetic tone drives hypertension and renal sympathetic activity to the kidneys resulting in increased plasma renin activity and eventually angiotensin II (Ang II) peripherally.
+This is partially because of adaptations leading to overactivation of the hindbrain regions controlling sympathetic outflow such as the nucleus tractus solitarius (NTS), and rostral ventrolateral medulla (RVLM).
+The sustained sympathetic activity is also due to enhanced synaptic signaling from the forebrain through the paraventricular nucleus (PVN).
+During the waking hours, when the chemoreceptors are not exposed to hypoxia, the forebrain circumventricular organs (CVOs) are stimulated by peripherally circulating Ang II from the elevated plasma renin activity.
+The CVOs and median preoptic nucleus chronically activate the PVN due to the Ang II signaling.
+All together, this leads to elevated nocturnal mean arterial pressure (MAP) as a response to hypoxemia, as well as inappropriately elevated diurnal MAP in response to maladaptations.
+Exosomes are emerging as important mediators of cell-matrix interactions by means of specific adhesion proteins.
+Changes in the tissue-specific exosomal protein expression may underlie pathological conditions whereby extracellular matrix turnover and homeostasis is disrupted.
+Ocular hypertension due to extracellular matrix accumulation in the trabecular meshwork is a hallmark of glucocorticoid-induced glaucoma.
+In the trabecular meshwork, exosomal fibronectin mediates cell matrix interactions at cellular structures called “invadosomes”.
+Trabecular meshwork cells use invadosomes to turn over their surrounding matrix and maintain passageways for flow of aqueous humor.
+In this study, we observed that human trabecular meshwork explants treated with dexamethasone released exosomes with significantly reduced amounts of fibronectin bound per exosome.
+Further, we found that exosome-fibronectin binding is heparan sulfate-dependent, consistent with our observation that trabecular meshwork exosomes are enriched in the heparin/heparan sulfate binding annexins A2 and A6.
+In this way, dexamethasone-treated explants released exosomes with a significant reduction in annexin A2 and A6 per exosome.
+Interestingly, we did not detect exosomal matrix metalloproteinases, but we identified abundant dipeptidyl peptidase 4, a serine protease whose activity was reduced on exosomes isolated from dexamethasone-treated explants.
+Together, our findings demonstrate mechanistically how corticosteroid-induced alterations in exosomal adhesion cargo and properties can account for the pathological matrix accumulation seen in many glaucoma patients.
+Ventilator-associated pneumonia (VAP) is the most frequent intensive care unit (ICU)-acquired infection that is independently associated with mortality.
+Chest X-ray or computed tomography imaging are used for conventional assessment of VAP, but these methods are impractical for real-time measurement in critical patients.
+Therefore, lung ultrasound (LUS) has been increasingly used for the assessment of VAP in the ICU.
+Traditionally, LUS has seemed unsuitable for the detection of lung parenchyma owing to the high acoustic impedance of air; however, the fact that the reflection and reverberation in the detection region of the ultrasound reflect the underlying pathology of lung diseases has led to the increased use of ultrasound imaging as a standard of care supported by evidence-based and expert consensus in the ICU.
+Considering that any type of pneumonia causes air volume changes in the lungs, accumulating evidence has shown that LUS effectively measures the presence of VAP as well as dynamic changes in VAP.
+This review offers evidence for ultrasound as a noninvasive, easily repeatable, and bedside means to assess VAP; in addition, it establishes a protocol for qualitative and quantitative monitoring of VAP.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13054-016-1487-y) contains supplementary material, which is available to authorized users.
+BACKGROUND: The avian influenza virus (AIV) can cross species barriers and expand its host range from birds to mammals, even humans.
+Avian influenza is characterized by pronounced activation of the proinflammatory cytokine cascade, which perpetuates the inflammatory response, leading to persistent systemic inflammatory response syndrome and pulmonary infection in animals and humans.
+METHODS: We hypothesized that mesenchymal stromal cells (MSCs) would have beneficial effects in the treatment of H9N2 AIV-induced acute lung injury in mice.
+Six- to 8-week-old C57BL/6 mice were infected intranasally with 1 × 10(4) MID(50) of A/HONG KONG/2108/2003 [H9N2 (HK)] H9N2 virus to induce acute lung injury.
+Three days after infection, we measured the survival rate, lung weight, arterial blood gas, and cytokines in both bronchoalveolar lavage fluid (BALF) and serum, and assessed pathological changes to the lungs.
+RESULTS: MSC administration significantly palliated H9N2 AIV-induced pulmonary inflammation by reducing chemokines and proinflammatory cytokines levels, as well as reducing inflammatory cell recruit into the lungs.
+Lung histopathology and arterial blood gas analysis were improved in mice with H9N2 AIV-induced lung injury following MSC treatment.
+CONCLUSIONS: MSC treatment significantly reduces H9N2 AIV-induced acute lung injury in mice and is associated with reduced pulmonary inflammation.
+These results indicate a potential role for MSC therapy in the treatment of clinical avian influenza.
+Disease prevention through vaccination is considered to be the greatest contribution to public health over the past century.
+Every year more than 100 million children are vaccinated with the standard World Health Organization (WHO)-recommended vaccines including hepatitis B (HepB).
+HepB is the most serious type of liver infection caused by the hepatitis B virus (HBV), however, it can be prevented by currently available recombinant vaccine, which has an excellent record of safety and effectiveness.
+To date, recombinant vaccines are produced in many systems of bacteria, yeast, insect, and mammalian and plant cells.
+Among these platforms, the use of plant cells has received considerable attention in terms of intrinsic safety, scalability, and appropriate modification of target proteins.
+Research groups worldwide have attempted to develop more efficacious plant-derived vaccines for over 30 diseases, most frequently HepB and influenza.
+More inspiring, approximately 12 plant-made antigens have already been tested in clinical trials, with successful outcomes.
+In this study, the latest information from the last 10 years on plant-derived antigens, especially hepatitis B surface antigen, approaches are reviewed and breakthroughs regarding the weak points are also discussed.
+The influenza A virus (IAV) PB1-F2 protein is a virulence factor contributing to the pathogenesis observed during IAV infections in mammals.
+In this study, using a mouse model, we compared the host response associated with PB1-F2 with an early transcriptomic signature that was previously associated with neutrophils and consecutively fatal IAV infections.
+This allowed us to show that PB1-F2 is partly involved in neutrophil-related mechanisms leading to death.
+Using neutropenic mice, we confirmed that the harmful effect of PB1-F2 is due to an excessive inflammation mediated by an increased neutrophil mobilization.
+PB1-F2 had no impact on the lymphocyte recruitment in the airways at day 8 pi.
+However, functional genomics analysis and flow cytometry in broncho-alveolar lavages at 4 days pi revealed that PB1-F2 induced a NK cells deficiency.
+Thus, our results identify PB1-F2 as an important immune disruptive factor during the IAV infection.
+To establish experimental approaches that may complement the current vaccine strain selection process, we selected antigenic variants from human H1N1 and H3N2 influenza virus libraries possessing random mutations in the globular head of the haemagglutinin protein (which includes the antigenic sites) by incubating them with human and/or ferret convalescent sera to human H1N1 and H3N2 viruses.
+We also selected antigenic escape variants from human viruses treated with convalescent sera and from mice that had been previously immunized against human influenza viruses.
+Our pilot studies with past influenza viruses identified escape mutants that were antigenically similar to variants that emerged in nature, establishing the feasibility of our approach.
+Our studies with contemporary human influenza viruses identified escape mutants before they caused an epidemic in 2014–2015.
+This approach may aid in the prediction of potential antigenic escape variants and the selection of future vaccine candidates before they become widespread in nature.
+SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nmicrobiol.2016.58) contains supplementary material, which is available to authorized users.
+BACKGROUND: The term triaditis designates the concurrent presence of idiopathic inflammatory bowel disease (IBD), cholangitis, and pancreatitis in cats.
+HYPOTHESIS/OBJECTIVES: The histopathology of concurrent, but often subclinical, inflammatory processes in the small intestine, liver, and pancreas of cats is poorly described.
+We aimed to investigate the frequency of enteritis, cholangitis, pancreatitis, or some combination of these in symptomatic and asymptomatic cats, compare clinicopathological features, and correlate histopathological with laboratory findings.
+Physical examination, laboratory variables (CBC, serum biochemistry profile, serum thyroxine concentration, serum feline trypsin‐like immunoreactivity [fTLI], feline lipase immunoreactivity [fPLI, as measured by Spec fPL (®)], urinalysis, and fecal analysis), imaging, and histopathological examinations were conducted.
+In total, 20 cats had histopathologic lesions of IBD (13/47, 27.7%), cholangitis (6/47, 12.8%), or pancreatitis (1/47, 2.1%) alone, or inflammation involving >1 organ (27/47, 57.4%).
+More specifically, 16/47 cats (34.0%) had concurrent lesions of IBD and cholangitis, 3/47 (6.4%) of IBD and pancreatitis, and 8/47 cats (17%) of triaditis.
+A mild, positive correlation was detected between the severity (score) of IBD lesions and the number of comorbidities (rho = +0.367, P = .022).
+CONCLUSIONS AND CLINICAL IMPORTANCE: Histopathological evidence of IBD or IBD with comorbidities was detected in both symptomatic and asymptomatic cats.
+Moreover, proteins often have multiple functions, with overlapping sequences that present challenges to accurate annotation of the exact functions of individual residues by conservation-based methods.
+Using the influenza A virus PB1 protein as an example, we developed a method to systematically identify and annotate functional residues.
+We used saturation mutagenesis and high-throughput sequencing to measure the replication capacity of single nucleotide mutations across the entire PB1 protein.
+After predicting protein stability upon mutations, we identified functional PB1 residues that are essential for viral replication.
+To further annotate the functional residues important to the canonical or noncanonical functions of viral RNA-dependent RNA polymerase (vRdRp), we performed a homologous-structure analysis with 16 different vRdRp structures.
+Moreover, we identified a cluster of noncanonical functional residues located in the loop region of the PB1 β-ribbon.
+We further demonstrated that these residues were important for PB1 protein nuclear import through the interaction with Ran-binding protein 5.
+In summary, we developed a systematic and sensitive method to identify and annotate functional residues that are not restrained by sequence conservation.
+Importantly, this method is generally applicable to other proteins about which homologous-structure information is available.
+Lumpy skin disease (LSD) leads to significant economic losses due to hide damage, reduction of milk production, mastitis, infertility and mortalities (10 %).
+Laboratory diagnostics including virus isolation, sequencing and real-time polymerase chain reaction (PCR) are performed at well-equipped laboratories.
+In this study, a portable, simple, and rapid recombinase polymerase amplification (RPA) assay for the detection of LSDV-genome for the use on farms was developed.
+RESULTS: The LSDV RPA assay was performed at 42 °C and detected down to 179 DNA copies/reaction in a maximum of 15 min.
+Unspecific amplification was observed with neither LSDV-negative samples (n = 12) nor nucleic acid preparations from orf virus, bovine papular stomatitis virus, cowpoxvirus, Peste des petits ruminants and Blue tongue virus (serotypes 1, 6 and 8).
+The clinical sensitivity of the LSDV RPA assay matched 100 % (n = 22) to real-time PCR results.
+CONCLUSION: The LSDV RPA assay is a rapid and sensitive test that could be implemented in field or at quarantine stations for the identification of LSDV infected case.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12917-016-0875-5) contains supplementary material, which is available to authorized users.
+Some studies have demonstrated an association between CMV disease and increased mortality rates, prolonged intensive care unit and hospital length of stay, prolonged mechanical ventilation, and nosocomial infections.
+However, there is a considerable controversy whether such association represents a causal relationship between CMV disease and unfavorable outcomes or just a marker of the severity of the critical illness.
+Detection of CMV using polymerase chain reaction and CMV antigenemia is the standard diagnostic approach.
+Treatment of CMV in critical care is challenging due to diagnostic challenge and drug toxicity, and building predictive model for CMV disease in critical care setting would be promising to identify patients at risk and starting prophylactic therapy.
+Our objective was to broadly review the current literature on the prevalence and incidence, clinical manifestations, potential limitations of different diagnostic modalities, prognosis, and therapeutic options of CMV disease in critically ill patients.
+Host genetic variability is an important determinant of the risk of developing TB in humans.
+Although the association between MBL2 polymorphisms and TB has been studied in various populations, the results are controversial.
+In this study four functional single-nucleotide polymorphisms (SNPs, H/L, X/Y, P/Q and A/B) across the MBL2 gene were genotyped by direct DNA sequencing of PCR products in a case-control population of Chinese Han origin, consisting of 1,020 patients with pulmonary TB and 1,020 controls.
+We found that individuals carrying variant allele at A/B (namely BB or AB genotypes) was associated with increased susceptibility to TB (odds ratios [OR] = 1.57, 95% confidence interval [CI] 1.30–1.91, P = 1.3 × 10(−6)).
+Additionally, LYPB haplotype showed a significant association with increased risk of TB (OR = 1.54, 95% CI 1.27–1.87, P = 4.2 × 10(−6); global haplotype association P = 3.5 × 10(−5)).
+Furthermore, individuals bearing low- or medium- MBL expression haplotype pairs had an increased risk of TB (OR = 1.56, 95% CI 1.29–1.90, P = 1.4 × 10(−6)).
+Thus, the reduced expression of functional MBL secondary to having MBL2 variants may partially mediate the increased susceptibility to TB risk.
+Rhizoctonia solani represents an important plant pathogenic Basidiomycota species complex and the host of many different mycoviruses, as indicated by frequent detection of dsRNA elements in natural populations of the fungus.
+To date, eight different mycoviruses have been characterized in Rhizoctonia and some of them have been reported to modulate its virulence.
+DsRNA extracts of the avirulent R. solani isolate DC17 (AG2-2-IV) displayed a diverse pattern, indicating multiple infections with mycoviruses.
+Deep sequencing analysis of the dsRNA extract, converted to cDNA, revealed that this isolate harbors at least 17 different mycovirus species.
+Based on the alignment of the conserved RNA-dependent RNA-polymerase (RdRp) domain, this viral community included putative members of the families Narnaviridae, Endornaviridae, Partitiviridae and Megabirnaviridae as well as of the order Tymovirales.
+Furthermore, viruses, which could not be assigned to any existing family or order, but showed similarities to so far unassigned species like Sclerotinia sclerotiorum RNA virus L, Rhizoctonia solani dsRNA virus 1, Aspergillus foetidus slow virus 2 or Rhizoctonia fumigata virus 1, were identified.
+This is the first report of a fungal isolate infected by 17 different viral species and a valuable study case to explore the diversity of mycoviruses infecting R. solani.
+The present study used microarray analysis to compare gene expression levels between allergic rhinitis patients before and after a series of acupoint herbal plaster applications.
+METHODS: In this experimental pilot study, volunteers experiencing sneezing, runny nose, and congestion for more than 9 months in the year following initial diagnoses were included after diagnostic confirmation by otolaryngologists to exclude patients with sinusitis and nasal polyps.
+Patients with persistent allergic rhinitis each received four acupoint herbal plaster treatments applied using the moxibustion technique.
+Peripheral blood samples were analyzed using an ImmunoCAP Phadiatop test, and patients were classified as phadiatop (Ph)-positive or -negative.
+Microarray results were analyzed for genes that were differentially expressed between (1) Ph-positive and -negative patients treated with herbal plaster; and (2) before and after herbal plaster treatment in the Ph-positive patient group.
+RESULTS: Nineteen Ph-positive and four Ph-negative participants with persistent allergic rhinitis were included in the study.
+RQLQ results indicated that the 19 Ph-positive volunteers experienced improvement in six of seven categories following acupoint herbal plaster treatments, whereas the four Ph-negative participants reported improvement in only two categories.
+Hierarchical clustering and principle component analysis of the gene expression profiles of Ph-positive and –negative participants indicated the groups exhibited distinct physiological responses to acupoint herbal treatment.
+Evaluation of gene networks using MetaCore identified that the “Immune response_IL-13 signaling via JAK-STAT” and the “Inflammation_Interferon signaling” were down- and up-regulated, respectively, among Ph-positive subjects.
+CONCLUSIONS: In this preliminary study, we find that the IL-13 immune response via JAK-STAT signaling and interferon inflammation signaling were down- and upregulated, respectively, in the Ph-positive group.
+Further studies are required to verify these pathways in Ph-positive patients, and to determine the mechanism of such pathway dysregulation.
+BACKGROUND: The lack of a patent source of infection after 24 hours of management of shock considered septic is a common and disturbing scenario.
+We aimed to determine the prevalence and the causes of shock with no diagnosis 24 hours after its onset, and to compare the outcomes of patients with early-confirmed septic shock to those of others.
+METHODS: We conducted a pragmatic, prospective, multicenter observational cohort study in ten intensive care units (ICU) in France.
+We included all consecutive patients admitted to the ICU with suspected septic shock defined by clinical suspicion of infection leading to antibiotic prescription plus acute circulatory failure requiring vasopressor support.
+Among them, 374 (74 %) had early-confirmed septic shock, while the 134 others (26 %) had no source of infection identified nor microbiological documentation retrieved 24 hours after shock onset.
+Among these, 37/134 (28 %) had late-confirmed septic shock diagnosed after 24 hours, 59/134 (44 %) had a condition mimicking septic (septic shock mimicker, mainly related to adverse drug reactions, acute mesenteric ischemia and malignancies) and 38/134 (28 %) had shock of unknown origin by the end of the ICU stay.
+There were no differences between patients with early-confirmed septic shock and the remainder in ICU mortality and the median duration of ICU stay, of tracheal intubation and of vasopressor support.
+The multivariable Cox model showed that the risk of day-60 mortality did not differ between patients with or without early-confirmed septic shock.
+A sensitivity analysis was performed in the subgroup (n = 369/508) of patients meeting the Sepsis-3 definition criteria and displayed consistent results.
+CONCLUSIONS: One quarter of the patients admitted in the ICU with suspected septic shock had no infection identified 24 hours after its onset and almost half of them were eventually diagnosed with a septic shock mimicker.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13054-016-1537-5) contains supplementary material, which is available to authorized users.
+BACKGROUND: Coagulation abnormalities are involved in the pathogenesis of acute exacerbations of idiopathic pulmonary fibrosis (AE-IPF).
+The administration of recombinant human soluble thrombomodulin (rhTM), which has both anti-inflammatory and anticoagulant activities, improves outcomes and respiratory function in patients with acute respiratory distress syndrome.
+Therefore, we conducted a prospective clinical study to examine the effects of rhTM on respiratory function, coagulation markers, and outcomes for patients with AE-IPF.
+METHODS: After registration of the protocol, the patients with AE-IPF who satisfied the study inclusion criteria were treated daily with 380 U/kg of rhTM for 7 days and steroid pulse therapy.
+The primary study outcome was the improvement of PaO(2)/FiO(2) ratio a week after treatment initiation.
+Secondary outcomes were change in D-dimer level over time and 28-day survival rate in patients without intubation.
+Study data were compared with historical untreated comparison group, including 13 patients with AE-IPF who were treated without rhTM before the registration.
+RESULTS: The mean PaO(2)/FiO(2) ratio for the rhTM treatment group (n = 10) on day 8 significantly improved compared with that on day one (two-way analysis of variance, p = 0.01).
+The mean D-dimer level tended to decrease in the rhTM group on day 8, but the change was not significant.
+The 28-day survival rate was 50 % higher in the rhTM group than in the historical untreated comparison group, but the difference was not significant.
+A post hoc analysis showed that overall survival time was significantly longer in the treated group compared with that of the historical untreated comparison group (p = 0.04, log-rank test).
+CONCLUSION: rhTM plus steroid pulse therapy improves respiratory functions in patients with AE-IPF and is expected to improve overall patient survival without using other combination therapies.
+TRIAL REGISTRATION: The study was registered with University Hospital Medical Information Network Clinical Trial Registry (UMIN-CTR) in October 2012 (UMIN000009082).
+Staphylococcus aureus is a major pathogen in humans and causes serious problems due to antibiotic resistance.
+We investigated the antimicrobial effect of glycyrrhetinic acid (GRA) and its derivatives against 50 clinical S. aureus strains, including 18 methicillin-resistant strains.
+The minimum inhibitory concentrations (MICs) of GRA, dipotassium glycyrrhizate, disodium succinoyl glycyrrhetinate (GR-SU), stearyl glycyrrhetinate and glycyrrhetinyl stearate were evaluated against various S. aureus strains.
+Additionally, we investigated the bactericidal effects of GRA and GR-SU against two specific S. aureus strains.
+DNA microarray analysis was also performed to clarify the mechanism underlying the antibacterial activity of GR-SU.
+At a higher concentration (above 2x MIC), GRA and GR-SU showed bactericidal activity, whereas at a concentration of 1x MIC, they showed a bacteriostatic effect.
+The expression of a large number of genes (including transporters) and metabolic factors (carbohydrates and amino acids) was altered by the addition of GR-SU, suggesting that the inhibition of these metabolic processes may influence the degree of the requirement for carbohydrates or amino acids.
+In fact, the requirement for carbohydrates or amino acids was increased in the presence of either GRA or GR-SU.
+This activity may be partly due to the inhibition of several pathways involved in carbohydrate and amino acid metabolism.
+Viral replicase recruitment and long-range RNA interactions are essential for RNA virus replication, yet the mechanism of their interplay remains elusive.
+Here, we revealed a highly conserved, conformation-tunable cis-acting element named 5′-UAR-flanking stem (UFS) in the flavivirus genomic 5′ terminus.
+We demonstrated that the UFS was critical for efficient NS5 recruitment and viral RNA synthesis in different flaviviruses.
+Moreover, the UFS unwound in response to genome cyclization, leading to the decreased affinity of NS5 for the viral 5′ end.
+Thus, we propose that the UFS is switched by genome cyclization to regulate dynamic RdRp binding for vRNA replication.
+This study demonstrates that the UFS enables communication between flavivirus genome cyclization and RdRp recruitment, highlighting the presence of switch-like mechanisms among RNA viruses.
+Ehrlichia chaffeensis is an obligatory intracellular bacterium that causes a potentially fatal emerging zoonosis, human monocytic ehrlichiosis.
+E. chaffeensis has a limited capacity for biosynthesis and metabolism and thus depends mostly on host-synthesized nutrients for growth.
+Although the host cell cytoplasm is rich with these nutrients, as E. chaffeensis is confined within the early endosome-like membrane-bound compartment, only host nutrients that enter the compartment can be used by this bacterium.
+We found that ehrlichial replication depended on autophagy induction involving class III phosphatidylinositol 3-kinase (PtdIns3K) activity, BECN1 (Beclin 1), and ATG5 (autophagy-related 5).
+Ehrlichia acquired host cell preincorporated amino acids in a class III PtdIns3K-dependent manner and ehrlichial growth was enhanced by treatment with rapamycin, an autophagy inducer.
+RAB5A/B/C siRNA knockdown, or overexpression of a RAB5-specific GTPase-activating protein or dominant-negative RAB5A inhibited ehrlichial infection, indicating the critical role of GTP-bound RAB5 during infection.
+Both native and ectopically expressed ehrlichial type IV secretion effector protein, Etf-1, bound RAB5 and the autophagy-initiating class III PtdIns3K complex, PIK3C3/VPS34, and BECN1, and homed to ehrlichial inclusions.
+Ectopically expressed Etf-1 activated class III PtdIns3K as in E. chaffeensis infection and induced autophagosome formation, cleared an aggregation-prone mutant huntingtin protein in a class III PtdIns3K-dependent manner, and enhanced ehrlichial proliferation.
+These data support the notion that E. chaffeensis secretes Etf-1 to induce autophagy to repurpose the host cytoplasm and capture nutrients for its growth through RAB5 and class III PtdIns3K, while avoiding autolysosomal killing.
+Mesenchymal stem cells have been widely studied to promote local bone regeneration of osteonecrosis of the femoral head (ONFH).
+Previous studies observed that dimethyloxaloylglycine (DMOG) enhanced the angiogenic and osteogenic activity of mesenchymal stem cells by activating the expression of hypoxia inducible factor-1α (HIF-1α), thereby improving the bone repair capacity of mesenchymal stem cells.
+In the present study, it was investigated whether DMOG could increase the bone repair capacity of adipose-derived stem cells (ASCs) in the treatment of ONFH.
+Western blot analysis was performed to detect HIF-1α protein expression in ASCs treated with different concentrations of DMOG.
+The results showed DMOG enhanced HIF-1α expression in ASCs in a dose-dependent manner at least for 7 days.
+Furthermore, DMOG-treated ASCs were transplanted into the necrotic area of a rabbit model of ONFH to treat the disease.
+Four weeks later, micro-computed tomography (CT) quantitative analysis showed that 58.8±7.4% of the necrotic area was regenerated in the DMOG-treated ASCs transplantation group, 45.5±3.4% in normal ASCs transplantation group, 25.2±2.8% in only core decompression group and 10.6±2.6% in the untreated group.
+Histological analysis showed that transplantation of DMOG-treated ASCs clearly improved the bone regeneration of the necrotic area compared with the other three groups.
+Micro-CT and immunohistochemical analysis demonstrated the revasculation of the necrotic area were also increased significantly in the DMOG-treated ASC group compared with the control groups.
+Thus, it is hypothesized that DMOG could increase the bone repair capacity of ASCs through enhancing HIF-1α expression in the treatment of ONFH.
+Although IFNλ1, IFNλ2, and IFNλ3 act antiviral, genetic association studies have shown that expression of the recently discovered IFNL4 is detrimental to hepatitis C virus (HCV) infection through a yet unknown mechanism.
+We performed a molecular and biochemical characterization of IFNλ4 to determine its role and regulation of expression.
+We found that IFNλ4 exhibits similar antiviral activity to IFNλ3 without negatively affecting antiviral IFN activity or cell survival.
+We show that humans deploy several mechanisms to limit expression of functional IFNλ4 through noncoding splice variants and nonfunctional protein isoforms.
+Furthermore, protein-coding IFNL4 mRNA are not loaded onto polyribosomes and lack a strong polyadenylation signal, resulting in poor translation efficiency.
+This study provides mechanistic evidence that humans suppress IFNλ4 expression, suggesting that immune function is dependent on other IFNL family members.
+BACKGROUND: Multiplex polymerase chain reaction (mPCR) enables recovery of viruses from airways of patients with community-acquired pneumonia (CAP), although their clinical impact remains uncertain.
+METHODS: Among consecutive adult patients who had undergone a mPCR within 72 hours following their admission to one intensive care unit (ICU), we retrospectively included those with a final diagnosis of CAP.
+A composite criterion of complicated course (hospital death or mechanical ventilation > 7 days) was used.
+A subgroup analysis compared patients with bacterial and viral-bacterial CAP matched on the bacterial pathogens.
+RESULTS: Among 174 patients (132 men [76 %], age 63 [53–75] years, SAPSII 38 [27;55], median PSI score 106 [78;130]), bacterial, viral, mixed and no etiology groups gathered 46 (26 %), 53 (31 %), 45 (26 %) and 30 (17 %) patients, respectively.
+Virus-infected patients displayed a high creatine kinase serum level, a low platelet count, and a trend toward more frequent alveolar-interstitial infiltrates.
+A complicated course was more frequent in the mixed group (31/45, 69 %), as compared to bacterial (18/46, 39 %), viral (15/53, 28 %) and no etiology (12/30, 40 %) groups (p < 0.01).
+In multivariate analysis, the mixed (viral-bacterial) infection was independently associated with complicated course (reference: bacterial pneumonia; OR, 3.58; CI 95 %, 1.16–11; p = 0.03).
+CONCLUSIONS: Viral-bacterial coinfection during severe CAP in adults is associated with an impaired presentation and a complicated course.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13054-016-1517-9) contains supplementary material, which is available to authorized users.
+The recent spread of Zika virus (ZIKV) and its association with increased rates of Guillain Barre and other neurological disorders as well as congenital defects that include microcephaly has created an urgent need to develop animal models to examine the pathogenesis of the disease and explore the efficacy of potential therapeutics and vaccines.
+In this study we establish and characterize a new model of peripheral ZIKV infection using immunocompetent neonatal C57BL/6 mice and compare its clinical progression, virus distribution, immune response, and neuropathology with that of C57BL/6-IFNAR KO mice.
+We show that while ZIKV infected IFNAR KO mice develop bilateral hind limb paralysis and die 5–6 days post-infection (dpi), immunocompetent B6 WT mice develop signs of neurological disease including unsteady gait, kinetic tremors, severe ataxia and seizures by 13 dpi that subside gradually over 2 weeks.
+Immunohistochemistry show viral antigen predominantly in cerebellum at the peak of the disease in both models.
+However, whereas IFNAR KO mice showed infiltration by neutrophils and macrophages and higher expression of IL-1, IL-6 and Cox2, B6 WT mice show a cellular infiltration in the CNS composed predominantly of T cells, particularly CD8+ T cells, and increased mRNA expression levels of IFNg, GzmB and Prf1 at peak of disease.
+Lastly, the CNS of B6 WT mice shows evidence of neurodegeneration predominantly in the cerebellum that are less prominent in mice lacking the IFN response possibly due to the difference in cellular infiltrates and rapid progression of the disease in that model.
+The development of the B6 WT model of ZIKV infection will provide insight into the immunopathology of the virus and facilitate assessments of possible therapeutics and vaccines.
+Neverthless, it may result in severe complications, especially in particular age groups and clinical conditions.
+Down Syndrome represents a risk factor for developing complications, because of the frequent comorbidities and their immunodeficiency.
+CASE PRESENTATION: A 2-year-old white Caucasian female affected by Down Syndrome was referred to our hospital for cardiac arrest in course of varicella disease.
+After cardiopulmonary resuscitation and stabilization, her clinical conditions didn’t improve and she developed a massive pulmonary hemorrage, which led her to exitus.
+CONCLUSIONS: Mortality due to varicella infection is rare, but it is more common in subjects with immune deficit or chronic pathologies, and in particular age-groups.
+The importance of the vaccine for preventable infectious diseases is stressed in this paper, in which we present a case of death in an unvaccinated cardiopathic child with Down Syndrome affected by varicella.
+We investigated the ability of monoclonal B cells to restore primary and secondary T-cell dependent antibody responses in adoptive immune-deficient hosts.
+Priming induced B cell activation and expansion, AID expression, antibody production and the generation of IgM(+)IgG(-) and IgM(-)IgG(+) antigen-experienced B-cell subsets that persisted in the lymphopenic environment by cell division.
+Upon secondary transfer and recall the IgM(-)IgG(+) cells responded by the production of antigen-specific IgG while the IgM(+) memory cells secreted mainly IgM and little IgG, but generated new B cells expressing germinal center markers.
+The recall responses were more efficient if the antigenic boost was delayed suggesting that a period of adaptation is necessary before the transferred cells are able to respond.
+Overall these findings indicate that reconstitution of a functional and complete memory pool requires transfer of all different antigen-experienced B cell subsets.
+We also found that the size of the memory B cell pool did not rely on the number of the responding naïve B cells, suggesting autonomous homeostatic controls for naïve and memory B cells.
+By reconstituting a stable memory B cell pool in immune-deficient hosts using a monoclonal high-affinity B cell population we demonstrate the potential value of B cell adoptive immunotherapy.
+Studies have suggested that excessive activation of the host immune system including macrophages is responsible for the severe pathologies mediated by IFV infection.
+Here, we focused on the X11 protein family member Mint3/Apba3, known to promote ATP production via glycolysis by activating hypoxia inducible factor-1 (HIF-1) in macrophages, and examined its roles in lung pathogenesis and anti-viral defence upon IFV infection.
+Mint3-deficient mice exhibited improved influenza pneumonia with reduced inflammatory cytokines/chemokine levels and neutrophil infiltration in the IFV-infected lungs without alteration in viral burden, type-I interferon production, or acquired immunity.
+In macrophages, Mint3 depletion attenuated NF-κB signalling and the resultant cytokine/chemokine production in response to IFV infection by increasing IκBα and activating the cellular energy sensor AMPK, respectively.
+Thus, Mint3 might represent one of the likely therapeutic targets for the treatment of severe influenza pneumonia without affecting host anti-viral defence through suppressing macrophage cytokine/chemokine production.
+BACKGROUND: Hyperactivity of the classical axis of the renin-angiotensin system (RAS), mediated by angiotensin II (Ang II) activation of the angiotensin II type 1 receptor (AT1R), is implicated in the pathogenesis of Alzheimer’s disease (AD).
+Angiotensin-converting enzyme-2 (ACE-2) degrades Ang II to angiotensin 1–7 (Ang (1-7)) and counter-regulates the classical axis of RAS.
+We have investigated the expression and distribution of ACE-2 in post-mortem human brain tissue in relation to AD pathology and classical RAS axis activity.
+METHODS: We measured ACE-2 activity by fluorogenic peptide substrate assay in mid-frontal cortex (Brodmann area 9) in a cohort of AD (n = 90) and age-matched non-demented controls (n = 59) for which we have previous data on ACE-1 activity, amyloid β (Aβ) level and tau pathology, as well as known ACE1 (rs1799752) indel polymorphism, apolipoprotein E (APOE) genotype, and cerebral amyloid angiopathy severity scores.
+RESULTS: ACE-2 activity was significantly reduced in AD compared with age-matched controls (P < 0.0001) and correlated inversely with levels of Aβ (r = −0.267, P < 0.001) and phosphorylated tau (p-tau) pathology (r = −0.327, P < 0.01).
+ACE-2 was reduced in individuals possessing an APOE ε4 allele (P < 0.05) and was associated with ACE1 indel polymorphism (P < 0.05), with lower ACE-2 activity in individuals homozygous for the ACE1 insertion AD risk allele.
+ACE-2 activity correlated inversely with ACE-1 activity (r = −0.453, P < 0.0001), and the ratio of ACE-1 to ACE-2 was significantly elevated in AD (P < 0.0001).
+Finally, we show that the ratio of Ang II to Ang (1–7) (a proxy measure of ACE-2 activity indicating conversion of Ang II to Ang (1–7)) is reduced in AD.
+CONCLUSIONS: Together, our findings indicate that ACE-2 activity is reduced in AD and is an important regulator of the central classical ACE-1/Ang II/AT1R axis of RAS, and also that dysregulation of this pathway likely plays a significant role in the pathogenesis of AD.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13195-016-0217-7) contains supplementary material, which is available to authorized users.
+BACKGROUND: Emergence of insecticide resistance in malaria vectors is a real threat to future goals of elimination and control of malaria.
+Therefore, the objective of this study was to assess research trend on insecticide resistance of Anopheles mosquito.
+In specific, number of publications, countries, institutions, and authors’ research profile, citation analysis, international collaborations, and impact of journals publishing documents on insecticide resistance will be presented.
+RESULTS: A total of 616 documents, mainly as original research articles (n = 569; 92.37%) were retrieved.
+Poisson log-linear regression analysis indicated that there was a 6.00% increase in the number of publications for each extra article on pyrethroid resistance.
+The United Kingdom (UK) ranked first in number of publications followed by the United States of America (USA) and France.
+The journal that published most on this topic was Malaria Journal (n = 101; 16.4%).
+Four of the top active authors were from South Africa and two were from the UK.
+CONCLUSION: Publications on insecticide resistance in malaria vector has gained momentum in the past decade.
+International collaborations enhanced the knowledge about the situation of vector resistance in countries with endemic malaria.
+Molecular biology of insecticide resistance is the key issue in understanding and overcoming this emerging problems.
+A plethora of new development goals and funding institutions have greatly increased the demand for internationally comparable health estimates in recent years, and have brought important new players into the field of health estimate production.
+This paper draws on country case studies and personal experience to support our opinion that the production and use of estimates are deeply embedded in specific social, economic, political and ideational contexts, which differ at different levels of the global health architecture.
+Broadly, most global health estimates tend to be made far from the local contexts in which the data upon which they are based are collected, and where the results of estimation processes must ultimately be used if they are to make a difference to the health of individuals.
+Internationally standardised indicators are necessary, but they are no substitute for data that meet local needs, and that fit with local ideas of what is credible and useful.
+In other words, data that are both technically and socially robust for those who make key decisions about health.
+We suggest that greater engagement of local actors (and local data) in the formulation, communication and interpretation of health estimates would increase the likelihood that these data will be used by those most able to translate them into health gains for the longer term.
+Besides strengthening national information systems, this requires ongoing interaction, building trust and establishing a communicative infrastructure.
+BACKGROUND: The interferon-gamma release assay (IGRA) is more specific than the tuberculin skin test to discriminate between tuberculosis (TB) and nontuberculous mycobacterial (NTM) diseases.
+Here we performed a retrospective study to evaluate the performance of the T-SPOT.TB in patients with NTM diseases.
+METHODS: Between March, 2013 and Nov, 2015, a total of 58 patients with NTM diseases had a T-SPOT.TB performed were enrolled, 30 patients had definite NTM diseases, 28 had probable diseases.
+The indirect proportion method with Löwenstein–Jensen (L-J) medium was used for first-line drug susceptibility test.
+Data were expressed as mean ± standard deviation (continuous variables) and as numbers and percentages (categorical variables).
+RESULTS: The average age was 51.8 ± 16.1 years (range 10 to 77 years), 58.6% (34/58) were male.
+34 (58.6%) isolates were Mycobacterium intracellulare, ten (17.2%) were Mycobacterium chelonae and seven (12.1%) were Mycobacterium fortuitum.
+Fifty-two (89.7%) patients were NTM lung disease, five (8.6%) were pleural disease, and one (1.7%) lymphadenitis.
+The total positivity of T-SPOT.TB was 53.4% (31/58) among the whole group (probable and definite).
+For probable cases, the T-SPOT.TB assay was positive in 53.5% (15/28); for definite cases, 16 (53.3%) of 30 definite cases were positive.
+CONCLUSIONS: In the study, we showed that a significant portion of NTM diseases were T-SPOT.TB positive in China.
+Although T-SPOT.TB is useful diagnostic method for differentiating TB from NTM diseases, in China, the IGRA assay show limited value in the discrimination.
+In addition, further research is needed to investigate the association between TB infection and treatment for NTM patients.
+H5N1 highly pathogenic avian influenza (H5N1 HPAI) virus causes elevated mortality compared with seasonal influenza viruses like H1N1 pandemic influenza (H1N1 pdm) virus.
+We identified a mechanism associated with the severe symptoms seen with H5N1 HPAI virus infection.
+H5N1 HPAI virus infection induced a decrease of dendritic cell number in the splenic extrafollicular T-cell zone and impaired formation of the outer layers of B-cell follicles, resulting in insufficient levels of antibody production after infection.
+However, in animals vaccinated with a live recombinant vaccinia virus expressing the H5 hemagglutinin, infection with H5N1 HPAI virus induced parafollicular dendritic cell accumulation and efficient antibody production.
+These results indicate that a recombinant vaccinia encoding H5 hemagglutinin gene does not impair dendritic cell recruitment and can be a useful vaccine candidate.
+Bacterial genomes and proteins are detected in brains from humans, nonhuman primates, rodents and other species in the absence of neurological disease.
+We investigated the composition and abundance of microbiota in frozen and fixed autopsied brain samples from patients with multiple sclerosis (MS) and age- and sex-matched nonMS patients as controls, using neuropathological, molecular and bioinformatics tools.
+16s rRNA sequencing revealed Proteobacteria to be the dominant phylum with restricted diversity in cerebral white matter (WM) from MS compared to nonMS patients.
+RNAseq analyses showed a predominance of Proteobacteria in progressive MS patients’ WM, associated with increased inflammatory gene expression, relative to a broader range of bacterial phyla in relapsing-remitting MS patients’ WM.
+Although bacterial peptidoglycan (PGN) and RNA polymerase beta subunit immunoreactivities were observed in all patients, PGN immunodetection was correlated with demyelination and neuroinflammation in MS brains.
+Principal component analysis revealed that demyelination, PGN and inflammatory gene expression accounted for 86% of the observed variance.
+Thus, inflammatory demyelination is linked to an organ-specific dysbiosis in MS that could contribute to underlying disease mechanisms.
+SM934 is an artemisinin analogue with immunosuppressive properties and potent therapeutic activity against lupus-like diseases in autoimmune mice.
+In this report, the therapeutic efficacy and underlying mechanisms of SM934 on rheumatoid arthritis (RA) was investigated using collagen-induced arthritis (CIA) in DBA/1J mice.
+We demonstrated that SM934 treatment alleviate the severity of arthritis in CIA mice with established manifestations.
+The therapeutic benefits were associated with ameliorated joint swelling and reduced extent of bone erosion and destruction.
+Further, administration of SM934 diminished the development of T follicular helper (Tfh) cells and Th17 cells and suppressed the production of pathogenic antibodies, without altering the proportion of germinal center B cells.
+Ex vivo, SM934 treatment inhibited the bovine type II collagen (CII) induced proliferation and inflammatory cytokines secretion of CII -reactive T cells.
+In vitro, SM934 impeded the polarization of naïve CD4(+) T cells into Tfh cells and the expression of its transcript factor Bcl-6.
+Moreover, SM934 decreased the IL-21-producing CD4(+) T cells and dampened the IL-21 downstream signaling through STAT3.
+These finding offered the convincing evidence that artemisinin derivative might attenuate RA by simultaneously interfering with the generation of Tfh cells and Th17 cells as well as the subsequent antibody-mediated immune responses.
+In light of the recent outbreak of Ebola virus (EBOV) disease in West Africa, there have been renewed efforts to search for effective antiviral countermeasures.
+A range of compounds currently available with broad antimicrobial activity have been tested for activity against EBOV.
+The compounds were selected on a rational basis because their mechanisms of action suggested that they had the potential to disrupt EBOV entry, replication or exit from cells or because they had displayed some antiviral activity against EBOV in previous tests.
+Nine compounds caused no reduction in viral replication despite cells remaining healthy, so they were excluded from further analysis (zidovudine; didanosine; stavudine; abacavir sulphate; entecavir; JB1a; Aimspro; celgosivir; and castanospermine).
+A second screen of the remaining compounds and the feasibility of appropriateness for in vivo testing removed six further compounds (ouabain; omeprazole; esomeprazole; Gleevec; D-LANA-14; and Tasigna).
+The three most promising compounds (17-DMAG; BGB324; and NCK-8) were further screened for in vivo activity in the guinea pig model of EBOV disease.
+Two of the compounds, BGB324 and NCK-8, showed some effect against lethal infection in vivo at the concentrations tested, which warrants further investigation.
+Further, these data add to the body of knowledge on the antiviral activities of multiple compounds against EBOV and indicate that the scientific community should invest more effort into the development of novel and specific antiviral compounds to treat Ebola virus disease.
+Viruses interact intimately with the host cell at nearly every stage of replication, and the cell model that is chosen to study virus infection is critically important.
+Although primary cells reflect the phenotype of healthy cells in vivo better than cell lines, their limited lifespan makes experimental manipulation challenging.
+However, many tumor-derived and artificially immortalized cell lines have defects in induction of interferon-stimulated genes and other antiviral defenses.
+These defects can affect virus replication, especially when cells are infected at lower, more physiologically relevant, multiplicities of infection.
+Understanding the selective pressures and mechanisms underlying the loss of innate signaling pathways is helpful to choose immortalized cell lines without impaired antiviral defense.
+We describe the trials and tribulations we encountered while searching for an immortalized cell line with intact innate signaling, and how directed immortalization of primary cells avoids many of the pitfalls of spontaneous immortalization.
+Molecular epidemiology has become an indispensable tool in the diagnosis of diseases and in tracing the infection routes of pathogens.
+Due to advances in conventional sequencing and the development of high throughput technologies, the field of sequence determination is in the process of being revolutionized.
+Platforms for sharing sequence information and providing standardized tools for phylogenetic analyses are becoming increasingly important.
+The database (DB) of the European Union (EU) and World Organisation for Animal Health (OIE) Reference Laboratory for classical swine fever offers one of the world’s largest semi-public virus-specific sequence collections combined with a module for phylogenetic analysis.
+The classical swine fever (CSF) DB (CSF-DB) became a valuable tool for supporting diagnosis and epidemiological investigations of this highly contagious disease in pigs with high socio-economic impacts worldwide.
+The DB has been re-designed and now allows for the storage and analysis of traditionally used, well established genomic regions and of larger genomic regions including complete viral genomes.
+We present an application example for the analysis of highly similar viral sequences obtained in an endemic disease situation and introduce the new geographic “CSF Maps” tool.
+The concept of this standardized and easy-to-use DB with an integrated genetic typing module is suited to serve as a blueprint for similar platforms for other human or animal viruses.
+Human mobility continues to increase in terms of volumes and reach, producing growing global connectivity.
+This connectivity hampers efforts to eliminate infectious diseases such as malaria through reintroductions of pathogens, and thus accounting for it becomes important in designing global, continental, regional, and national strategies.
+Recent works have shown that census-derived migration data provides a good proxy for internal connectivity, in terms of relative strengths of movement between administrative units, across temporal scales.
+To support global malaria eradication strategy efforts, here we describe the construction of an open access archive of estimated internal migration flows in endemic countries built through pooling of census microdata.
+These connectivity datasets, described here along with the approaches and methods used to create and validate them, are available both through the WorldPop website and the WorldPop Dataverse Repository.
+RNAi pathway is an antiviral defence mechanism employed by insects that result in degradation of viral RNA thereby curbing infection.
+Several viruses including flaviviruses encode viral suppressors of RNAi (VSRs) to counteract the antiviral RNAi pathway.
+The present study was undertaken to evaluate chikungunya virus (CHIKV) proteins for RNAi suppressor activity.
+We systematically analyzed all nine CHIKV proteins for RNAi suppressor activity using Sf21 RNAi sensor cell line based assay.
+We further validated the findings in natural hosts, namely in Aedes and in mammalian cell lines and further through EMSA and Agrobacterium infiltration in GFP silenced transgenic tobacco plants.
+RNA binding motifs in these domains were identified and their participation in RNAi suppression evaluated using site directed mutagenesis.
+Sequence alignment of these motifs across all species of known alphaviruses revealed conservation of these motifs emphasizing on a similar role of action in other species of alphaviruses as well.
+Further validation of RNAi suppressor activity of these proteins awaits establishment of specific virus infection models.
+In order to better understand national and international research output on Campylobacter, we conducted this bibliometric overview of publications on Campylobacter.
+This study can be used to assess extent of interaction and response of researchers, food regulators, and health policy makers to global burden of campylobacateriosis.
+METHODS: Scopus database was used to retrieve publications with the following keywords (Campylobacter/campylobacteriosis, C. jejuni, C. coli).
+Bibliometric indicators such as annual growth of publications, country contribution, international collaboration, and citation analysis were presented.
+The quality of retrieved data was indirectly assessed by Hirsch index and impact factor of journals.
+RESULTS: A total of 5522 documents were retrieved with median (Q1–Q3) citations of 9 (2–23) and h-index of 113.
+The core leading journals were Applied and Environmental Microbiology journal and Journal of Food Protection with 246 (4.46%) publications for each.
+The USA (1309; 23.6%) was the most productive country while Danmarks Tekniske Universitet (150; 2.7%) was the most productive institution.
+France had the lowest percentage (33.5%) of articles with international collaboration while Netherlands (57.7%) had the highest percentage of articles with international collaboration.
+Approximately half (50.1%) of retrieved articles were published in journals under the subject area of “immunology/microbiology”.
+Main themes in highly cited articles were molecular biology/genetics and public health burden of campylobacteriosis.
+There were 728 (13.1%) articles on campylobacter-related drug resistance, and the top cited articles focused mainly on increasing resistance to quinolones and fluoroquinolones.
+International collaboration is highly required particularly in implementing new diagnostic screening technologies to minimize global health burden of Campylobacter and ensure food safety.
+CONTEXT: Hand, foot and mouth disease (HFMD) is a widespread pediatric disease caused primarily by human enterovirus 71 (EV-A71) and Coxsackievirus A16 (CV-A16).
+DATA SOURCES: PubMed, Web of Science and Google Scholar were searched up to December 2014.
+STUDY SELECTION: Two reviewers independently assessed studies for epidemiologic and serologic information about prevalence and incidence of HFMD against predetermined inclusion/exclusion criteria.
+RESULTS: HFMD is found to be seasonal in temperate Asia with a summer peak and in subtropical Asia with spring and fall peaks, but not in tropical Asia; evidence of a climatic role was identified for temperate Japan.
+Risk factors for HFMD include hygiene, age, gender and social contacts, but most studies were underpowered to adjust rigorously for confounding variables.
+Both community-level and school-level transmission have been implicated, but their relative importance for HFMD is inconclusive.
+Epidemiologic indices are poorly understood: No supporting quantitative evidence was found for the incubation period of EV-A71; the symptomatic rate of EV-A71/Coxsackievirus A16 infection was from 10% to 71% in 4 studies; while the basic reproduction number was between 1.1 and 5.5 in 3 studies.
+CONCLUSIONS: Knowledge on HFMD remains insufficient to guide interventions such as the incorporation of an EV-A71 vaccine in pediatric vaccination schedules.
+BACKGROUND: Major trauma patients (TP) developing imbalanced immune response are at high risk for infectious post-injury complications including pneumonia.
+Neutrophils play a central role in the host defense against bacteria and thereby pathogenesis of infections.
+While there are numerous studies about neutrophil function after trauma, data about their biology in patients who suffer from pneumonia following trauma are sparse.
+Here, we studied the effect of serum isolated from patients who do and do not develop infection (inf.)
+METHODS: Sera samples from eighteen TP with an injury severity score above 16 were obtained.
+Samples were obtained at admission to emergency department (ED), a day prior pneumonia diagnosis (1 d prior inf) or at the day of diagnosis (1 d prior inf).
+Migratory capacity of neutrophils towards TP’s serum, their CD11b and CD62L membrane receptor expression and oxidative burst activity after stimulation with TP’s serum were determined and compared between groups.
+RESULTS: Migratory capacity of neutrophils was significantly increased after trauma and persisted during the study period.
+groups showed significantly decreased migratory capacity, increased CD11b and significantly decreased CD62L expression in the no inf.
+CONCLUSIONS: This data indicate that patients at risk for pneumonia development have differentially and early activated neutrophils following trauma compared to patients who are not at risk for post-injury complication.
+Studies about the differential biology of neutrophils and their immediately after trauma modified activity depending on the post-injury clinical course are warranted, and may deliver predictive or even therapeutic strategies to control inflammation.
+As a result of rapid economic growth over the previous three decades, China has become the second largest economy worldwide since 2010.
+However, as a developing country with the largest population, this rapid economic growth primarily based on excessive consumption and waste of resources.
+Thus, China has been facing particularly severe ecological and environmental problems in speeding up industrialization and urbanization.
+Therefore, it is critical to investigate potential threats in the context of the human-animal-environment interface to protect human and animal health.
+The “One Health” concept recognizes that human health is connected to animal and environmental health.
+This review primarily discusses specific health problems in China, particularly zoonoses, and explains the origin and development of the One Health approach, as well as the importance of a holistic approach in China.
+The interferon α (IFN-α) has been often used as a sensitizing agent for the treatment of various malignancies such as hepatocellular carcinoma, malignant melanoma, and renal cell cancer by promoting the apoptosis of thesetumor cell types.
+In this study, HeLa cells were used as a testing model for the treatment of IFN-α on cervical cancer.
+The results indicate that IFN-α markedly inhibits the proliferation and induces the apoptosis of HeLa cells.
+The activation of caspase 3, the up-regulation of both Bim and cleaved poly (ADP-ribose) polymerase (PARP) 1, the down-regulation of Bcl-xL, as well as the release of cytochrome c from mitochondria were significantly induced upon IFN-α treatment, indicating that the intrinsic apoptotic pathway could be activated by IFN-α treatment.
+In addition, caspase 4—which is involved in the endoplasmic reticulum (ER) stress-induced apoptosis—was activated in response to IFN-α treatment.
+Knocking down caspase 4 by small interfering RNA (siRNA) markedly reduced the IFN-α-mediated cell apoptosis.
+However, no significant changes in the expressions of caspases 8 and 10 were observed upon IFN-α treatment, indicating that the apoptosis caused by IFN-α might be independent of the extrinsic apoptotic pathway.
+These findings suggest that IFN-α may possess anti-cervical cancer capacity by activating cell apoptosis via the intrinsic mitochondrial pathway and caspase-4-related ER stress-induced pathway.
+Ethyl pyruvate (EP) is a simple derivative of pyruvic acid, which is an important endogenous metabolite that can scavenge reactive oxygen species (ROS).
+Treatment with EP is able to ameliorate systemic inflammation and multiple organ dysfunctions in multiple animal models, such as acute pancreatitis, alcoholic liver injury, acute respiratory distress syndrome (ARDS), acute viral myocarditis, acute kidney injury and sepsis.
+Recent studies have demonstrated that prolonged treatment with EP can ameliorate experimental ulcerative colitis and slow multiple tumor growth.
+It has become evident that EP has pharmacological anti-inflammatory effect to inhibit multiple early inflammatory cytokines and the late inflammatory cytokine HMGB1 release, and the anti-tumor activity is likely associated with its anti-inflammatory effect.
+EP has been tested in human volunteers and in a clinical trial of patients undergoing cardiac surgery in USA and shown to be safe at clinical relevant doses, even though EP fails to improve outcome of the heart surgery, EP is still a promising agent to treat patients with multiple inflammatory organ injuries and the other clinical trials are on the way.
+This review focuses on how EP is able to ameliorate multiple organ injuries and summarize recently published EP investigations.
+Antigenic drift of seasonal influenza viruses and the occasional introduction of influenza viruses of novel subtypes into the human population complicate the timely production of effective vaccines that antigenically match the virus strains that cause epidemic or pandemic outbreaks.
+The development of game-changing vaccines that induce broadly protective immunity against a wide variety of influenza viruses is an unmet need, in which recombinant viral vectors may provide.
+Use of viral vectors allows the delivery of any influenza virus antigen, or derivative thereof, to the immune system, resulting in the optimal induction of virus-specific B- and T-cell responses against this antigen of choice.
+This systematic review discusses results obtained with vectored influenza virus vaccines and advantages and disadvantages of the currently available viral vectors.
+We compared the clinical and epidemiologic characteristics for the first three waves of virus circulation.
+METHODS: The first wave was defined as reported cases with onset dates between March 31-September 30, 2013, the second wave was defined as October 1, 2013-September 30, 2014 and the third wave was defined as October 1, 2014-September 30, 2015.
+We used simple descriptive statistics to compare characteristics of the three distinct waves of virus circulation.
+RESULTS: In mainland China, 134 cases, 306 cases and 219 cases were detected and reported in first three waves, respectively.
+The median age of cases was statistically significantly older in the first wave (61 years vs. 56 years, 56 years, p < 0.001) compared to the following two waves.
+There was no statistically significant difference between case fatality proportions (33, 42 and 45%, respectively, p = 0.08).
+There were no significant statistical differences for time from illness onset to first seeking healthcare, hospitalization, lab confirmation, initiation antiviral treatment and death between the three waves.
+A similar percentage of cases in all waves reported exposure to poultry or live poultry markets (87%, 88%, 90%, respectively).
+There was no statistically significant difference in the occurrence of severe disease between the each of the first three waves of virus circulation.
+Twenty-one clusters were reported during these three waves (4, 11 and 6 clusters, respectively), of which, 14 were considered to be possible human-to-human transmission.
+CONCLUSION: Though our case investigation for the first three waves found few differences between the epidemiologic and clinical characteristics, there is continued international concern about the pandemic potential of this virus.
+Since the virus continues to circulate, causes more severe disease, has the ability to mutate and become transmissible from human-to-human, and there is limited natural protection from infection in communities, it is critical that surveillance systems in China and elsewhere are alert to the influenza H7N9 virus.
+BACKGROUND: Organ regeneration in mammals is hypothesized to require a functional pool of stem or progenitor cells, but the role of these cells in lung regeneration is unknown.
+METHODS: Based on the fact that postnatal regeneration of alveolar tissue has been attributed to alveolar epithelial cells, we established a hemorrhagic shock and Lipopolysaccharide (LPS) lung injury model.
+RESULTS: The results showed that alveolar epithelium type 2 cells (AEC2s) are damage resistant during acute lung injury, they might be the main cells involved in lung injury and repair.
+Then we observed the relationship between the expression of HGF, c-Met following ALI in rat lung and proliferation of AEC2s.
+The proliferation of AEC2s was inhibited when isolated primary AEC2s were co-cultured with c-Met inhibitor SU11274.
+Furthermore, the numbers of AEC2s was significantly decreased when ALI rats were administrated with SU11274 in vivo.
+It provided further evidence that the HGF/c-Met signaling plays a vital role in ALI-induced AEC2s proliferation.
+CONCLUSIONS: AEC2s are damage resistant during acute lung injury and the HGF/c-Met signaling pathway is of vital importance in the proliferation of AEC2s after ALI.
+Ischemia is a state of oxygen deprivation in tissues, whereas reperfusion is restoration of blood flow in ischemic tissues.
+Myocardial damage of tissue during reperfusion after ischemic insult is known as myocardial ischemia–reperfusion (I/R) injury.
+It induces damage to cardiac muscle via increasing expression of oxygen, sodium and calcium ions which are responsible in the activation of proteases and cell death.
+Heart renin angiotensin system (RAS) plays an important role in the myocardial ischemia and reperfusion injury.
+Here-in we reviewed how myocardial I/R injury sets in by up-regulation of angiotensin II that leads to increased infarct size, which can be reduced by the use of ACE inhibitors, ACE2 activators and angiotensin II antagonist.
+Interferon-α (IFN-α) and IFN-λ are structurally distinct cytokines that bind to different receptors, but induce expression of similar sets of genes through Janus kinase (JAK)-signal transducers and activators of transcription (STAT) pathways.
+Here, using the CRISPR/Cas9 system, we examine the role of STAT1 and STAT2 in the inhibition of hepatitis C virus (HCV) replication by IFN-α and IFN-λ.
+Treatment with IFN-α increases expression of IFN-stimulated genes (ISGs) such as double-stranded RNA-activated protein kinase (PKR) and decreases viral RNA and protein levels in HCV-infected Huh-7.5 human hepatoma cells.
+These responses are only partially attenuated by knockout of STAT1 but are abolished by knockout of STAT2.
+In contrast, the inhibition of HCV replication by IFN-λ is abolished by knockout of STAT1 or STAT2.
+Microarray analysis reveals that IFN-α but not IFN-λ can induce expression of the majority of ISGs in STAT1 knockout cells.
+These findings suggest that IFN-α can inhibit HCV replication through a STAT2-dependent but STAT1-independent pathway, whereas IFN-λ induces ISG expression and inhibits HCV replication exclusively through a STAT1- and STAT2-dependent pathway.
+Almost 700 cases of human infection with avian influenza A/H7N9 have been reported since 2013.
+We evaluated an inactivated H7N9 vaccine in an observer-blind study in healthy adults aged 18–64 years.
+Participants (420) were randomized to receive 1 of 4 AS03-adjuvanted vaccines (low or medium dose of hemagglutinin with AS03(A) or AS03(B)), one nonadjuvanted vaccine, or placebo.
+The coprimary immunogenicity objective determined whether adjuvanted vaccines elicited an immune response against the vaccine-homologous virus, 21 days after the second vaccine dose per US and European licensure criteria in the per-protocol cohort (n = 389).
+In groups receiving adjuvanted formulations, seroconversion rates were ≥85.7%, seroprotection rates ≥91.1%, and geometric mean titers ≥92.9% versus 23.2%, 28.6%, and 17.2 for the nonadjuvanted vaccine.
+Injection site pain occurred more frequently with adjuvanted vaccines (in ≤98.3% of vaccinees) than with the nonadjuvanted vaccine (40.7%) or placebo (20.0%).
+Two doses of AS03-adjuvanted H7N9 vaccine were well tolerated and induced a robust antibody response at antigen-sparing doses in healthy adults.
+In 2014–2016, Guinea, Sierra Leone and Liberia in West Africa experienced the largest and longest Ebola epidemic since the discovery of the virus in 1976.
+To monitor the epidemic as it spread within and between districts, we develop an analysis method that exploits the full spatiotemporal resolution of the data by combining a local model for time-varying effective reproduction numbers with a gravity-type model for spatial dispersion of the infection.
+We test this method in simulations and apply it to the weekly incidences of confirmed and probable cases per district up to June 2015, as reported by the World Health Organization.
+Our results indicate that, of the newly infected cases, only a small percentage, between 4% and 10%, migrates to another district, and a minority of these migrants, between 0% and 23%, leave their country.
+The epidemics in the three countries are found to be similar in estimated effective reproduction numbers, and in the probability of importing infection into a district.
+The countries might have played different roles in cross-border transmissions, although a sensitivity analysis suggests that this could also be related to underreporting.
+The spatiotemporal analysis method can exploit available longitudinal incidence data at different geographical locations to monitor local epidemics, determine the extent of spatial spread, reveal the contribution of local and imported cases, and identify sources of introductions in uninfected areas.
+With good quality data on incidence, this data-driven method can help to effectively control emerging infections.
+Comparison of amino acid sequence similarity is the fundamental concept behind the protein phylogenetic tree formation.
+By virtue of this method, we can explain the evolutionary relationships, but further explanations are not possible unless sequences are studied through the chemical nature of individual amino acids.
+Here we develop a new methodology to characterize the protein sequences on the basis of the chemical nature of the amino acids.
+We design various algorithms for studying the variation of chemical group transitions and various chemical group combinations as patterns in the protein sequences.
+The amino acid sequence of conventional myosin II head domain of 14 family members are taken to illustrate this new approach.
+We find two blocks of maximum length 6 aa as ‘FPKATD’ and ‘Y/FTNEKL’ without repeating the same chemical nature and one block of maximum length 20 aa with the repetition of chemical nature which are common among all 14 members.
+Based on our analysis we find a common block of length 8 aa both in myosin II and KIF1A.
+This motif is located in the neck linker region which could be responsible for the generation of mechanical force, enabling us to find the unique blocks which remain chemically conserved across the family.
+We also validate our methodology with different protein families such as MYOI, Myosin light chain kinase (MLCK) and Rho-associated protein kinase (ROCK), Na(+)/K(+)-ATPase and Ca(2+)-ATPase.
+Altogether, our studies provide a new methodology for investigating the conserved amino acids’ pattern in different proteins.
+Porcine epidemic diarrhea virus (PEDV) is the main causative agent of porcine diarrhea, which has resulted in devastating damage to swine industry and become a perplexed global problem.
+PEDV infection causes lesions and clinical symptoms, and infected pigs often succumb to severe dehydration.
+If there is not a timely and effective method to control its infection, PEDV will spread rapidly across the whole swine farm.
+Therefore, preclinical identification of PEDV is of great significance for preventing the outbreak and spread of this disease.
+In this study, a functionalized nanoparticles-based PCR method (UNDP-PCR) specific for PEDV was developed through systematic optimization of functionalized magnetic beads and gold nanoparticles which were further used to specifically enrich viral RNA from the lysate of PEDV stool samples, forming a MMPs-RNA-AuNPs complex.
+Then, oligonucleotides specific for PEDV coated on AuNPs were eluted from the complex and were further amplified and characterized by PCR.
+The detection limitation of the established UNDP-PCR method for PEDV was 25 copies in per gram PEDV stool samples, which is 400-fold more sensitive than conventional RT-PCR for stool samples.
+The UNDP-PCR for PEDV exhibited reliable reproducibility and high specificity, no cross-reaction was observed with other porcine viruses.
+In 153 preclinical fecal samples, the positive detection rate of UNDP-PCR specific for PEDV (30.72%) was much higher than that of conventional RT-PCR (5.88%) and SYBR Green real-time RT-PCR.
+In a word, this study provided a RNA extraction and transcription free, rapid and economical method for preclinical PEDV infection, which showed higher sensitivity, specificity and reproducibility, and exhibited application potency for evaluating viral loads of preclinical samples.
+The threat of an influenza A virus pandemic stems from continual virus spillovers from reservoir species, a tiny fraction of which spark sustained transmission in humans.
+To date, no pandemic emergence of a new influenza strain has been preceded by detection of a closely related precursor in an animal or human.
+Nonetheless, influenza surveillance efforts are expanding, prompting a need for tools to assess the pandemic risk posed by a detected virus.
+The goal would be to use genetic sequence and/or biological assays of viral traits to identify those non-human influenza viruses with the greatest risk of evolving into pandemic threats, and/or to understand drivers of such evolution, to prioritize pandemic prevention or response measures.
+We describe such efforts, identify progress and ongoing challenges, and discuss three specific traits of influenza viruses (hemagglutinin receptor binding specificity, hemagglutinin pH of activation, and polymerase complex efficiency) that contribute to pandemic risk.
+The H1 subtype of influenza A viruses (IAVs) has been circulating in swine since the 1918 human influenza pandemic.
+Over time, and aided by further introductions from nonswine hosts, swine H1 viruses have diversified into three genetic lineages.
+Due to limited global data, these H1 lineages were named based on colloquial context, leading to a proliferation of inconsistent regional naming conventions.
+In this study, we propose rigorous phylogenetic criteria to establish a globally consistent nomenclature of swine H1 virus hemagglutinin (HA) evolution.
+These criteria applied to a data set of 7,070 H1 HA sequences led to 28 distinct clades as the basis for the nomenclature.
+We developed and implemented a web-accessible annotation tool that can assign these biologically informative categories to new sequence data.
+The annotation tool assigned the combined data set of 7,070 H1 sequences to the correct clade more than 99% of the time.
+Our analyses indicated that 87% of the swine H1 viruses from 2010 to the present had HAs that belonged to 7 contemporary cocirculating clades.
+Our nomenclature and web-accessible classification tool provide an accurate method for researchers, diagnosticians, and health officials to assign clade designations to HA sequences.
+The tool can be updated readily to track evolving nomenclature as new clades emerge, ensuring continued relevance.
+A common global nomenclature facilitates comparisons of IAVs infecting humans and pigs, within and between regions, and can provide insight into the diversity of swine H1 influenza virus and its impact on vaccine strain selection, diagnostic reagents, and test performance, thereby simplifying communication of such data.
+IMPORTANCE A fundamental goal in the biological sciences is the definition of groups of organisms based on evolutionary history and the naming of those groups.
+For influenza A viruses (IAVs) in swine, understanding the hemagglutinin (HA) genetic lineage of a circulating strain aids in vaccine antigen selection and allows for inferences about vaccine efficacy.
+Previous reporting of H1 virus HA in swine relied on colloquial names, frequently with incriminating and stigmatizing geographic toponyms, making comparisons between studies challenging.
+To overcome this, we developed an adaptable nomenclature using measurable criteria for historical and contemporary evolutionary patterns of H1 global swine IAVs.
+This classification system will aid agricultural production and pandemic preparedness through the identification of important changes in swine IAVs and provides terminology enabling discussion of swine IAVs in a common context among animal and human health initiatives.
+Background: Although Mycoplasma pneumoniae (MP) is a common cause of community-acquired pneumonia (CAP) in children, the currently used diagnostic methods are not optimal.
+Methods: Label-free quantitative proteomics and liquid chromatography-mass/mass spectrometry were used to analyze the fold change of protein expression in plasma of children with MP pneumonia (MPP), infectious disease control (IDC), and healthy control (HC) groups.
+Selected proteins that can distinguish MPP from HC and IDC were further validated by enzyme-linked immunosorbent assay (ELISA).
+Results: After multivariate analyses, 27 potential plasma biomarkers were identified to be expressed differently among child MPP, HC, and IDC groups.
+SERPINA3, APOC1, and CFLAR levels were significantly different among the three groups and the ratios were consistent with the trends of proteomics results.
+A comparison of MPP patients and HC showed APOC1 had the largest area under the curve (AUC) of 0.853, with 77.6% sensitivity and 81.1% specificity.
+When APOC1 levels were compared between MPP and IDC patients, it also showed a relatively high AUC of 0.882, with 77.6% sensitivity and 85.3% specificity.
+Conclusion: APOC1 is a potential biomarker for the rapid and noninvasive diagnosis of MPP in children.
+The present finding may offer new insights into the pathogenesis and biomarker selection of MPP in children.
+Avian leucosis virus subgroup J (ALV-J) can cause lifelong infection and can escape from the host immune defenses in chickens.
+Since macrophages act as the important defense line against invading pathogens in host innate immunity, we investigated the function and innate immune responses of chicken primary monocyte-derived macrophages (MDM) after ALV-J infection in this study.
+Our results indicated that ALV-J was stably maintained in MDM cells but that the viral growth rate was significantly lower than that in DF-1 cells.
+We also found that ALV-J infection significantly increased nitric oxide (NO) production, but had no effect on MDM phagocytic capacity.
+Interestingly, infection with ALV-J rapidly promoted the expression levels of Myxovirus resistance 1 (Mx) (3 h, 6 h), ISG12 (6 h), and interleukin-1β (IL-1β) (3 h, 12 h) at an early infection stage, whereas it sharply decreased the expression of Mx (24 h, 36 h), ISG12 (36 h), and made little change on IL-1β (24 h, 36 h) production at a late infection stage in MDM cells.
+Moreover, the protein levels of interferon-β (IFN-β) and interleukin-6 (IL-6) had sharply increased in infected MDM cells from 3 to 36 h post infection (hpi) of ALV-J.
+And, the protein level of interleukin-10 (IL-10) was dramatically decreased at 36 hpi in MDM cells infected with ALV-J.
+These results demonstrate that ALV-J can induce host innate immune responses and we hypothesize that macrophages play an important role in host innate immune attack and ALV-J immune escape.
+Existing interferon-signaling/receptor-deficient mouse models may not be suitable for evaluating treatment effects of recombinant interferons.
+METHODS: We developed a novel mouse model for ZIKV infection by immunosuppressing BALB/c mice with dexamethasone.
+RESULTS: Dexamethasone-immunosuppressed male mice (6–8 weeks) developed disseminated infection as evidenced by the detection of ZIKV-NS1 protein expression and high viral loads in multiple organs.
+They had ≥ 10% weight loss and high clinical scores soon after dexamethasone withdrawal (10 dpi), which warranted euthanasia at 12 dpi.
+Viral loads in blood and most tissues at 5 dpi were significantly higher than those at 12 dpi (P < 0.05).
+Histological examination revealed prominent inflammatory infiltrates in multiple organs, and CD45 + and CD8 + inflammatory cells were seen in the testis.
+CONCLUSIONS: Besides virus dissemination, inflammation of various tissues, especially orchitis, may be potential complications of ZIKV infection with significant implications on disease transmission and male fertility.
+Interferon treatment should be considered in patients at high risks for ZIKV-associated complications when the potential benefits outweigh the side effects of treatment.
+Several technologies have been developed to isolate human antibodies against different target antigens as a source of potential therapeutics, including hybridoma technology, phage and yeast display systems.
+For conventional antibodies, this involves either random pairing of VH and variable light (VL) domains in combinatorial display libraries or isolation of cognate pairs of VH and VL domains from human B cells or from transgenic mice carrying human immunoglobulin loci followed by single-cell sorting, single-cell RT-PCR, and bulk cloning of isolated natural VH–VL pairs.
+Here, we present an automatable novel, high-throughput technology for rapid direct cloning and production of fully human HCAbs from sorted population of transgenic mouse plasma cells carrying a human HCAb locus.
+Utility of the technique is demonstrated by isolation of diverse sets of sequence unique, soluble, high-affinity influenza A strain X-31 hemagglutinin-specific HCAbs.
+Minus-one ribosomal frameshifting is a translational recoding mechanism widely utilized by many RNA viruses to generate accurate ratios of structural and catalytic proteins.
+An RNA pseudoknot structure located in the overlapping region of the gag and pro genes of Simian Retrovirus type 1 (SRV-1) stimulates frameshifting.
+However, the experimental characterization of SRV-1 pseudoknot (un)folding dynamics and the effect of the base triple formation is lacking.
+Here, we report the results of our single-molecule nanomanipulation using optical tweezers and theoretical simulation by steered molecular dynamics.
+Our results directly reveal that the energetic coupling between loop 2 and stem 1 via minor-groove base triple formation enhances the mechanical stability.
+The terminal base pair in stem 1 (directly in contact with a translating ribosome at the slippery site) also affects the mechanical stability of the pseudoknot.
+The −1 frameshifting efficiency is positively correlated with the cooperative one-step unfolding force and inversely correlated with the one-step mechanical unfolding rate at zero force.
+A significantly improved correlation was observed between −1 frameshifting efficiency and unfolding rate at forces of 15–35 pN, consistent with the fact that the ribosome is a force-generating molecular motor with helicase activity.
+Avian influenza virus (AIV) can infect birds and mammals, including humans, and are thus a serious threat to public health.
+In this study, we generated a recombinant lactobacillus expressing the NP-M1-DCpep of H9N2 avian influenza virus and evaluated the activation effect of NC8-pSIP409-NP-M1-DCpep on dendritic cells (DCs) in a mouse model.
+The specific mucosal antibody responses and B and T cell responses in lymphoid tissues were also characterized.
+Importantly, we confirmed that specific CD8 T cells presented in vitro and antigen-specific cytotoxicity (activated the expression of CD107a) and in vivo antigen-specific cytotoxicity after vaccination.
+The adoptive transfer of NC8-pSIP409-NP-M1-DCpep-primed CD8(+) T cells into NOD-SCID mice resulted in effective protection against mouse-adapted AIV infection.
+In addition, we observed protection in immunized mice challenged with mouse-adapted H9N2 AIV and H1N1 influenza virus, as evidenced by reductions in the lung virus titers, improvements in lung pathology, and weight loss and complete survival.
+BACKGROUND: Infectious diseases such as SARS and H1N1 can significantly impact people’s lives and cause severe social and economic damages.
+Recent outbreaks have stressed the urgency of effective research on the dynamics of infectious disease spread.
+However, it is difficult to predict when and where outbreaks may emerge and how infectious diseases spread because many factors affect their transmission, and some of them may be unknown.
+METHODS: One feasible means to promptly detect an outbreak and track the progress of disease spread is to implement surveillance systems in regional or national health and medical centres.
+The accumulated surveillance data, including temporal, spatial, clinical, and demographic information can provide valuable information that can be exploited to better understand and model the dynamics of infectious disease spread.
+The aim of this work is to develop and empirically evaluate a stochastic model that allows the investigation of transmission patterns of infectious diseases in heterogeneous populations.
+RESULTS: We test the proposed model on simulation data and apply it to the surveillance data from the 2009 H1N1 pandemic in Hong Kong.
+In the simulation experiment, our model achieves high accuracy in parameter estimation (less than 10.0 % mean absolute percentage error).
+In terms of the forward prediction of case incidence, the mean absolute percentage errors are 17.3 % for the simulation experiment and 20.0 % for the experiment on the real surveillance data.
+CONCLUSION: We propose a stochastic model to study the dynamics of infectious disease spread in heterogeneous populations from temporal-spatial surveillance data.
+The proposed model is evaluated using both simulated data and the real data from the 2009 H1N1 epidemic in Hong Kong and achieves acceptable prediction accuracy.
+We believe that our model can provide valuable insights for public health authorities to predict the effect of disease spread and analyse its underlying factors and to guide new control efforts.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40249-016-0199-5) contains supplementary material, which is available to authorized users.
+The interferon (IFN)-λ family of type III cytokines includes the closely related interleukin (IL)-28A (IFN-λ2), IL-28B (IFN-λ3), and IL-29 (IFN-λ1).
+They signal through the Janus kinases (JAK)-signal transducers and activators of transcription pathway and promote an antiviral state by the induction of expression of several interferon-stimulated genes (ISGs).
+Contrary to type I IFNs, the effect of IFN-λ cytokines is largely limited to epithelial cells due to the restricted pattern of expression of their specific receptor.
+Several genome-wide association studies have established a strong correlation between polymorphism in the region of IL-28B gene (encoding for IFN-λ3) and both spontaneous and therapeutic IFN-mediated clearance of hepatitis C virus (HCV) infection, but the mechanism(s) underlying this enhanced viral clearance are not fully understood.
+IFN-λ3 directly inhibits HCV replication, and in vitro studies suggest that polymorphism in the IFN-λ3 and its recently identified overlapping IFN-λ4 govern the pattern of ISGs induced upon HCV infection of hepatocytes.
+IFN-λ can also be produced by dendritic cells, and apart from its antiviral action on hepatocytes, it can regulate the inflammatory response of monocytes/macrophages, thus acting at the interface between innate and adaptive immunity.
+Here, we review the current state of knowledge about the role of IFN-λ cytokines in mediating and regulating the immune response during acute and chronic HCV infections.
+In this study, we conducted a comprehensive toxicogenomic analysis of lung responses in mice exposed to six individual TiO(2)NPs exhibiting different sizes (8, 20 and 300nm), crystalline structure (anatase, rutile or anatase/rutile) and surface modifications (hydrophobic or hydrophilic) to investigate whether the mechanisms leading to TiO(2)NP-induced lung inflammation are property specific.
+A detailed histopathological analysis was conducted to investigate the long-term disease implications of acute exposure to TiO(2)NPs.
+C57BL/6 mice were exposed to 18, 54, 162 or 486 µg of TiO(2)NPs/mouse via single intratracheal instillation.
+Bronchoalveolar lavage fluid (BALF) and lung tissue were sampled on 1, 28 and 90 days post-exposure.
+Although all TiO(2)NPs induced lung inflammation as measured by the neutrophil influx in BALF, rutile-type TiO(2)NPs induced higher inflammation with the hydrophilic rutile TiO(2)NP showing the maximum increase.
+Histopathological analysis of lung sections on Day 90 post-exposure showed increased collagen staining and fibrosis-like changes following exposure to the rutile TiO(2)NPs at the highest dose tested.
+The results suggest that the severity of lung inflammation is property specific; however, the underlying mechanisms (genes and pathways perturbed) leading to inflammation were the same for all particle types.
+While the particle size clearly influenced the overall acute lung responses, a combination of small size, crystalline structure and hydrophilic surface contributed to the long-term pathological effects observed at the highest dose (486 µg/mouse).
+Although the dose at which the pathological changes were observed is considered physiologically high, the study highlights the disease potential of certain TiO(2)NPs of specific properties.
+Correct identification of medicinal plant ingredients is essential for their safe use and for the regulation of herbal drug supply chain.
+This novel molecular biology technique enables timely and accurate testing, especially in settings where infrastructures to support polymerase chain reaction facilities are lacking.
+Studies that used this method have altered our view on the extent and complexity of herbal medicine identification.
+In this review, we give an introduction into LAMP analysis, covers the basic principles and important aspects in the development of LAMP analysis method.
+Then we presented a critical review of the application of LAMP-based methods in detecting and identifying raw medicinal plant materials and their processed products.
+We also provide a practical standard operating procedure (SOP) for the utilization of the LAMP protocol in herbal authentication, and consider the prospects of LAMP technology in the future developments of herbal medicine identification and the challenges associated with its application.
+West Nile virus (WNV) is prevalent in Africa, Europe, the Middle East, West Asia, and North America, and causes epidemic encephalitis.
+To date, no effective therapy for WNV infection has been developed; therefore, there is urgent need to find an efficient method to prevent WNV disease.
+In this study, we prepared and evaluated the protective efficacy of immune serum IgG and pepsin-digested F(ab′)(2) fragments from horses immunized with the WNV virus-like particles (VLP) expressing the WNV M and E proteins.
+Immune equine F(ab′)(2) fragments and immune horse sera efficiently neutralized WNV infection in tissue culture.
+The passive transfer of equine immune antibodies significantly accelerated the virus clearance in the spleens and brains of WNV infected mice, and reduced mortality.
+Thus, equine immunoglobulin or equine neutralizing F(ab′)(2) passive immunotherapy is a potential strategy for the prophylactic or therapeutic treatment of patients infected with WNV.
+BACKGROUND: To investigate the anti-inflammatory effects of specific small interfering RNA targeting NF-κB on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in rats.
+METHOD: Acute lung injury was induced in Sprague-Dawley rats by intraperitoneal injection with LPS (5 mg/kg), followed by immediate intratracheal instillation of siRNA targeting NF-κB p65 (40 μg/ml).
+Animals in each group were sacrificed at 1 h or 8 h after the instillation.
+Expressions of NF-κB in lung cells and TNF-α in bronchoalveolar lavage fluid (BALF) were determined by western blot analysis and enzyme-linked immunosorbent assay (ELISA) respectively.
+RESULTS: LPS administration reduced the rectal temperature and white blood cell counts at 1 h, increased lung wet/dry weight ratios, caused evident lung histopathological injury, and increased the detectable transcript and cytokine levels of TNF-α in lung tissue in BALF.
+siRNA targeting of NF-κB p65 effectively abrogated the expression of NF-κB p65 in lung cells and, aside from rectal temperatures, ameliorated all changes induced by LPS.
+CONCLUSIONS: NF-κB knockdown exerts anti-inflammatory effects on LPS-induced ALI especially in the initial phase, which may be due in part to reduced levels of the proinflammatory cytokine TNF-α.
+NF-κB siRNA’s rapidity and effectiveness to abrogate ALI development may provide an effective therapeutic method with future clinical applications.
+Research shows that worker subjective well-being influences physiological functioning—an early signal of poor health outcomes.
+While several theoretical perspectives provide insights on this relationship, the literature lacks an integrative framework explaining the relationship.
+We develop a conceptual model explaining the link between subjective well-being and physiological functioning in the context of work.
+Integrating positive psychology and occupational stress perspectives, our model explains the relationship between subjective well-being and physiological functioning as a result of the direct influence of subjective well-being on physiological functioning and of their common relationships with work stress and personal resources, both of which are influenced by job conditions.
+Heme oxygenase-1 (HO-1) is known for its cytoprotective effect against oxidative stress and inflammation, suggesting its immune regulatory role in allergic lung inflammation.
+HO-1 has been implicated in affecting DC maturation; however, its role in DC-mediated T-cell differentiation is unclear.
+In this study, we demonstrated that HO-1-expressing bone marrow-derived dendritic cells (BM-DCs) displayed tolerogenic phenotypes, including their resistance to lipopolysaccharide (LPS)-induced maturation, high level expression of IL-10, and low T-cell stimulatory activity.
+In addition, HO-1-expressing DCs were able to induce antigen-specific Foxp3(+) regulatory T cells (Treg) differentiation in vitro and in vivo.
+Also, HO-1-expressing DCs modulated the severity of lung inflammatory responses in two murine models of airway inflammation.
+This study provided evidence supporting the role of HO-1-expressing DCs in tolerance induction and as a potential therapeutic target for allergic asthma as well as other inflammatory diseases.
+Influenza is active during the winter and spring in the city of Beijing, which has a typical temperate climate with four clear distinct seasons.
+The clinical and laboratory surveillance data for influenza have been used to construct critical indicators for influenza activities in the community, and previous studies have reported varying degrees of association between laboratory-confirmed influenza specimens and outpatient consultation rates of influenza-like illness in subtropical cities.
+However, few studies have reported on this issue for cities in temperate regions, especially in developing countries.
+Furthermore, the mechanism behind age-specific seasonal epidemics remains unresolved, although it has been widely discussed.
+We utilized a wavelet analysis method to monitor the coherence of weekly percentage of laboratory-confirmed influenza specimens with the weekly outpatient consultation rates of influenza-like illness in Beijing, China.
+We first examined the seasonal pattern of laboratory-confirmed cases of influenza A (subtyped into seasonal A(H1N1) and A(H3N2) and pandemic virus A(H1N1) pdm09) and influenza B separately within the period from 2008–2015; then, we detected the coherence of clinical and laboratory surveillance data in this district, specially examining weekly time series of age-specific epidemics of influenza-like illnesses in the whole study period for three age categories (age 0–5, 5–15 and 25–60).
+We found that influenza A and B were both active in winter but were not always seasonally synchronous in Beijing.
+Our findings suggested that peaks of influenza-like illness in individuals aged 0–5 and 5–15 years consistently appeared ahead of those of adults, implying the possibility that schoolchildren may lead epidemic fluctuations.
+Inflammatory lung diseases like asthma bronchiale, chronic obstructive pulmonary disease and allergic airway inflammation are widespread public diseases that constitute an enormous burden to the health systems.
+Mainly classified as inflammatory diseases, the treatment focuses on strategies interfering with local inflammatory responses by the immune system.
+Inflammatory lung diseases predispose patients to severe lung failures like alveolar oedema, respiratory distress syndrome and acute lung injury.
+These life-threatening syndromes are caused by increased permeability of the alveolar and airway epithelium and exudate formation.
+This review emphasises the role of the tight junction of the airway epithelium as the predominating structure conferring epithelial tightness and preventing exudate formation and the impact of inflammatory perturbations on their function.
+Protein synthesis can be segmented into distinct phases comprising mRNA translation initiation, elongation, and termination.
+Translation initiation is a highly regulated and rate-limiting step of protein synthesis that requires more than 12 eukaryotic initiation factors (eIFs).
+Extensive evidence shows that the transcriptome and corresponding proteome do not invariably correlate with each other in a variety of contexts.
+In particular, translation of mRNAs specific to angiogenesis, tumor development, and apoptosis is altered during physiological and pathophysiological stress conditions.
+In cancer cells, the expression and functions of eIFs are hampered, resulting in the inhibition of global translation and enhancement of translation of subsets of mRNAs by alternative mechanisms.
+A precise understanding of mechanisms involving eukaryotic initiation factors leading to differential protein expression can help us to design better strategies to diagnose and treat cancer.
+The high spatial and temporal resolution of translation control can have an immediate effect on the microenvironment of the cell in comparison with changes in transcription.
+The dysregulation of mRNA translation mechanisms is increasingly being exploited as a target to treat cancer.
+In this review, we will focus on this context by describing both canonical and noncanonical roles of eIFs, which alter mRNA translation.
+Feline herpesvirus 1 (FHV-1), an enveloped dsDNA virus, is one of the major pathogens of feline upper respiratory tract disease (URTD) and ocular disease.
+Currently, polymerase chain reaction (PCR) remains the gold standard diagnostic tool for FHV-1 infection but is relatively expensive, requires well-equipped laboratories and is not suitable for field tests.
+Recombinase polymerase amplification (RPA), an isothermal gene amplification technology, has been explored for the molecular diagnosis of infectious diseases.
+The RPA reaction was performed successfully at 39°C and the results were obtained within 20 min.
+Using different copy numbers of recombinant plasmid DNA that contains the TK gene as template, we showed the detection limit of exo-RPA was 10(2) copies DNA/reaction, the same as that of real time PCR.
+The exo-RPA assay did not cross-detect feline panleukopenia virus, feline calicivirus, bovine herpesvirus-1, pseudorabies virus or chlamydia psittaci, a panel of pathogens important in feline URTD or other viruses in Alphaherpesvirinae, demonstrating high specificity.
+The assay was validated by testing 120 nasal and ocular conjunctival swabs of cats, and the results were compared with those obtained with real-time PCR.
+Compared with real time PCR, the exo-RPA assay uses less-complex equipment that is portable and the reaction is completed much faster.
+Additionally, commercial RPA reagents in vacuum-sealed pouches can tolerate temperatures up to room temperature for days without loss of activity, suitable for shipment and storage for field tests.
+Taken together, the exo-RPA assay is a simple, fast and cost-effective alternative to real time PCR, suitable for use in less advanced laboratories and for field detection of FHV-1 infection.
+Routine childhood vaccination against measles, mumps and rubella has virtually abolished virus-related morbidity and mortality.
+Notwithstanding this, we describe here devastating neurological complications associated with the detection of live-attenuated mumps virus Jeryl Lynn (MuV(JL5)) in the brain of a child who had undergone successful allogeneic transplantation for severe combined immunodeficiency (SCID).
+This is the first confirmed report of MuV(JL5) associated with chronic encephalitis and highlights the need to exclude immunodeficient individuals from immunisation with live-attenuated vaccines.
+Sequence comparison of the vaccine batch to the MuV(JL5) isolated from brain identified biased hypermutation, particularly in the matrix gene, similar to those found in measles from cases of SSPE.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00401-016-1629-y) contains supplementary material, which is available to authorized users.
+Three-dimensional Gaussian functions have been shown useful in representing electron microscopy (EM) density maps for studying macromolecular structure and dynamics.
+Methods that require setting a desired number of Gaussian functions or a maximum number of iterations may result in suboptimal representations of the structure.
+An alternative is to set a desired error of approximation of the given EM map and then optimize the number of Gaussian functions to achieve this approximation error.
+In this article, we review different applications of such an approach that uses spherical Gaussian functions of fixed standard deviation, referred to as pseudoatoms.
+Some of these applications use EM-map normal mode analysis (NMA) with elastic network model (ENM) (applications such as predicting conformational changes of macromolecular complexes or exploring actual conformational changes by normal-mode-based analysis of experimental data) while some other do not use NMA (denoising of EM density maps).
+In applications based on NMA and ENM, the advantage of using pseudoatoms in EM-map coarse-grain models is that the ENM springs are easily assigned among neighboring grains thanks to their spherical shape and uniformed size.
+EM-map denoising based on the map coarse-graining was so far only shown using pseudoatoms as grains.
+BACKGROUND: Dengue and malaria are two common, mosquito-borne infections, which may lead to mortality if not managed properly.
+Concurrent infections of dengue and malaria are rare due to the different habitats of its vectors and activities of different carrier mosquitoes.
+Since then, several concurrent infections have been reported between the dengue virus (DENV) and the malaria protozoans, Plasmodium falciparum and Plasmodium vivax.
+Symptoms of each infection may be masked by a simultaneous second infection, resulting in late treatment and severe complications.
+Plasmodium knowlesi is also a common cause of malaria in Malaysia with one of the highest rates of mortality.
+This report is one of the earliest in literature of concomitant infection between DENV and P. knowlesi in which a delay in diagnosis had placed a patient in a life-threatening situation.
+CASE PRESENTATION: A 59-year old man staying near the Belum-Temengor rainforest at the Malaysia–Thailand border was admitted with fever for 6 days, with respiratory distress.
+Treating the dengue had so distracted the clinicians that a blood film for the malaria parasite was not done.
+Despite aggressive supportive treatment in the intensive care unit (ICU), the patient had unresolved acidosis as well as multi-organ failure involving respiratory, renal, liver, and haematological systems.
+It was due to the presentation of shivering in the ICU, that a blood film was done on the second day that revealed the presence of P. knowlesi with a parasite count of 520,000/μL.
+The patient was subsequently treated with artesunate-doxycycline and made a good recovery after nine days in ICU.
+CONCLUSIONS: This case contributes to the body of literature on co-infection between DENV and P. knowlesi and highlights the clinical consequences, which can be severe.
+Awareness should be raised among health-care workers on the possibility of dengue-malaria co-infection in this region.
+Further research is required to determine the real incidence and risk of co-infection in order to improve the management of acute febrile illness.
+Recent experimental and computational improvements have led to a dramatic increase in the number of viral genome sequences identified primarily from metagenomic samples.
+As a result of the expanding catalog of metagenomic viral sequences, there exists a need for a comprehensive computational platform integrating all these sequences with associated metadata and analytical tools.
+Here we present IMG/VR (https://img.jgi.doe.gov/vr/), the largest publicly available database of 3908 isolate reference DNA viruses with 264 413 computationally identified viral contigs from >6000 ecologically diverse metagenomic samples.
+Microbial hosts are predicted for 20 000 viral sequences, revealing nine microbial phyla previously unreported to be infected by viruses.
+Viral sequences can be queried using a variety of associated metadata, including habitat type and geographic location of the samples, or taxonomic classification according to hallmark viral genes.
+IMG/VR has a user-friendly interface that allows users to interrogate all integrated data and interact by comparing with external sequences, thus serving as an essential resource in the viral genomics community.
+The Eukaryotic Pathogen Genomics Database Resource (EuPathDB, http://eupathdb.org) is a collection of databases covering 170+ eukaryotic pathogens (protists & fungi), along with relevant free-living and non-pathogenic species, and select pathogen hosts.
+To facilitate the discovery of meaningful biological relationships, the databases couple preconfigured searches with visualization and analysis tools for comprehensive data mining via intuitive graphical interfaces and APIs.
+All data are analyzed with the same workflows, including creation of gene orthology profiles, so data are easily compared across data sets, data types and organisms.
+New tools include GO, metabolic pathway and word enrichment analyses plus an online workspace for analysis of personal, non-public, large-scale data.
+Expanded data content is mostly genomic and functional genomic data while new data types include protein microarray, metabolic pathways, compounds, quantitative proteomics, copy number variation, and polysomal transcriptomics.
+New features include consistent categorization of searches, data sets and genome browser tracks; redesigned gene pages; effective integration of alternative transcripts; and a EuPathDB Galaxy instance for private analyses of a user's data.
+Forthcoming upgrades include user workspaces for private integration of data with existing EuPathDB data and improved integration and presentation of host–pathogen interactions.
+Loop-mediated isothermal amplification (LAMP), an attractive DNA amplification method, was developed as a valuable tool for the rapid detection of Toxoplasma gondii.
+In this study, species-specific LAMP primers were designed by targeting the AF146527 sequence, which was a conserved sequence of 200- to 300-fold repetitive 529 bp fragment of T.gondii.
+LAMP reaction system was optimized so that it could detect the minimal DNA sample such as a single tachyzoite or 10 copies of recombinant plasmid.
+Subsequently, a total of 200 human blood samples were directly investigated by two diagnostic methods, LAMP and conventional PCR.
+Fourteen of 200 (7%) samples were positive for Toxoplasma by LAMP (the primers developed in this study), whereas only 5 of 200 (2.5%) were proved positive by conventional PCR.
+The procedure of the LAMP assay was very simple, as the reaction would be carried out in a single tube under isothermal conditions at 64°C and the result would be read out with 1 h (as early as 35 min with loop primers).
+Thus, this method has the advantages of rapid amplification, simple operation, and easy detection and would be useful for rapid and reliable clinical diagnosis of acute toxoplasmosis, especially in developing countries.
+Monodominant patches of forest dominated by Gilbertiodendron dewevrei are commonly found in central African tropical forests, alongside forests with high species diversity.
+Although these forests are generally found sparsely distributed along rivers, their occurrence is not thought to be (clearly) driven by edaphic conditions but rather by trait combinations of G. dewevrei that aid in achieving monodominance.
+Functional community structure between these monodominant and mixed forests has, however, not yet been compared.
+We investigate the functional community structure of 10 one‐hectare plots of monodominant and mixed forests in a central region of the Congo basin, in DR Congo.
+Thirteen leaf and wood traits are measured, covering 95% (basal area weighted) of all species present in the plots, including leaf nutrient contents, leaf isotopic compositions, specific leaf area, wood density, and vessel anatomy.
+The trait‐based assessment of G. dewevrei shows an ensemble of traits related to water use and transport that could be favorable for its location near forest rivers.
+Moreover, indications have been found for N and P limitations in the monodominant forest, possibly related to ectomycorrhizal associations formed with G. dewevrei.
+Reduced leaf N and P contents are found at the community level for the monodominant forest and for different nondominant groups, as compared to those in the mixed forest.
+In summary, this work shows that environmental filtering does prevail in the monodominant G. dewevrei forest, leading to lower functional diversity in this forest type, with the dominant species showing beneficial traits related to its common riverine locations and with reduced soil N and P availability found in this environment, both coregulating the tree community assembly.
+Hepatitis C virus (HCV) infection induces intracellular membrane rearrangements, thus forming a membranous web (MW) in which HCV replication and assembly occur.
+The HCV-induced MW is primarily composed of double membrane vesicles (DMVs) transfused by multi-membrane vesicles.
+However, no clear evidence has been found linking autophagy to the formation of these DMVs.
+In this study, we evaluated the role of the autophagy elongation complex (ATG5-12/16L1) in HCV replication and MW formation.
+Using a dominant negative form of ATG12 and an siRNA approach, we demonstrated that the ATG5-12 conjugate, but not LC3-II formation, is crucial for efficient viral replication.
+Furthermore, purification of HCV MW revealed the presence of ATG5-12 and ATG16L1 along with HCV nonstructural proteins.
+Interestingly, LC3 was not recruited along with the elongation complex to the site of viral replication.
+Finally, inhibition of the elongation complex, but not LC3, greatly impaired the formation of the wild-type MW phenotype.
+To our knowledge, this study provides the first evidence of the involvement of autophagy proteins in the formation of wild-type MWs.
+CFTR is a transmembrane protein that reaches the cell surface via the conventional Golgi mediated secretion pathway.
+Interestingly, ER-to-Golgi blockade or ER stress induces alternative GRASP-mediated, Golgi-bypassing unconventional trafficking of wild-type CFTR and the disease-causing ΔF508-CFTR, which has folding and trafficking defects.
+Here, we show that Sec16A, the key regulator of conventional ER-to-Golgi transport, plays a critical role in the ER exit of protein cargos during unconventional secretion.
+In an initial gene silencing screen, Sec16A knockdown abolished the unconventional secretion of wild-type and ΔF508-CFTR induced by ER-to-Golgi blockade, whereas the knockdown of other COPII-related components did not.
+Notably, during unconventional secretion, Sec16A was redistributed to cell periphery and associated with GRASP55 in mammalian cells.
+Molecular and morphological analyses revealed that IRE1α-mediated signaling is an upstream regulator of Sec16A during ER-to-Golgi blockade or ER stress associated unconventional secretion.
+These findings highlight a novel function of Sec16A as an essential mediator of ER stress-associated unconventional secretion.
+Viruses are obligatory intracellular pathogens and completely depend on their hosts for survival and reproduction.
+The strategies adopted by viruses to exploit host cell processes and to evade host immune systems during infections may differ largely with the type of the viral genetic material.
+An improved understanding of these viral infection mechanisms is only possible through a better understanding of the pathogen–host interactions (PHIs) that enable viruses to enter into the host cells and manipulate the cellular mechanisms to their own advantage.
+Experimentally‐verified protein–protein interaction (PPI) data of pathogen–host systems only became available at large scale within the last decade.
+In this study, we comparatively analyzed the current PHI networks belonging to DNA and RNA viruses and their human host, to get insights into the infection strategies used by these viral groups.
+We investigated the functional properties of human proteins in the PHI networks, to observe and compare the attack strategies of DNA and RNA viruses.
+We observed that DNA viruses are able to attack both human cellular and metabolic processes simultaneously during infections.
+On the other hand, RNA viruses preferentially interact with human proteins functioning in specific cellular processes as well as in intracellular transport and localization within the cell.
+Observing virus‐targeted human proteins, we propose heterogeneous nuclear ribonucleoproteins and transporter proteins as potential antiviral therapeutic targets.
+The observed common and specific infection mechanisms in terms of viral strategies to attack human proteins may provide crucial information for further design of broad and specific next‐generation antiviral therapeutics.
+Panax ginseng Meyer, belonging to the genus Panax of the family Araliaceae, is known for its human immune system-related effects, such as immune-boosting effects.
+Ginseng polysaccharides (GPs) are the responsible ingredient of ginseng in immunomodulation, and are classified as acidic and neutral GPs.
+Although GPs participate in various immune reactions including the stimulation of immune cells and production of cytokines, the precise function of GPs together with its potential receptor(s) and their signal transduction pathways have remained largely unknown.
+Among many different biological functions in vivo, animal lectins especially play important roles in the immune system by recognizing carbohydrates that are found exclusively on pathogens or that are inaccessible on host cells.
+This review summarizes the immunological activities of GPs and the diverse roles of animal lectins in the immune system, suggesting the possibility of animal lectins as the potential receptor candidates of GPs and giving insights into the development of GPs as therapeutic biomaterials for many immunological diseases.
+Our sensing platform relies on graphene oxide (GO) nanosheets conjugated with antibodies to provide quantitative binding sites for analyte proteins.
+When analyte proteins and standard fluorescein-labelled proteins are competing for the binding sites, the assay exhibits quantitative fluorescence quenching by GO for the fluorescein-labelled proteins as determined by the analyte protein concentration.
+Because of this mechanism, measured fluorescence intensity from unquenched fluorescein-labelled protein was shown to increase with an increasing analyte protein concentration.
+As an alternative to the conventional enzyme-linked immunosorbent assay (ELISA), our method does not require an enzyme-linked second antibody for protein recognition and the enzyme for optical signal measurement.
+Thus, it is beneficial with its low cost and fewer systematic errors caused by the series of antigen-antibody recognition steps in ELISA.
+Immune globulin G (IgG) was introduced as a model protein to test our method and our results showed that the limit of detection for IgG was 4.67 pmol mL(−1) in the buffer solution.
+This sensing mechanism could be developed into a promising biosensor for the detection of proteins, which would broaden the spectrum of GO applications in both analytical biochemistry and clinical diagnosis.
+Secondary infection with a heterologous dengue virus (DENV) serotype increases the risk of severe dengue, through a process termed antibody-dependent enhancement (ADE).
+During ADE, DENV is opsonized with non- or sub-neutralizing antibody levels that augment entry into monocytes and dendritic cells through Fc-gamma receptors (FcγRs).
+We previously reported that co-ligation of leukocyte immunoglobulin-like receptor-B1 (LILRB1) by antibody-opsonized DENV led to recruitment of SH2 domain-containing phosphatase-1 (SHP-1) to dephosphorylate spleen tyrosine kinase (Syk) and reduce interferon stimulated gene induction.
+Here, we show that LILRB1 also signals through SHP-1 to attenuate the otherwise rapid acidification for lysosomal enzyme activation following FcγR-mediated uptake of DENV.
+Reduced or slower trafficking of antibody-opsonized DENV to lytic phagolysosomal compartments, demonstrates how co-ligation of LILRB1 also permits DENV to overcome a cell-autonomous immune response, enhancing intracellular survival of DENV.
+Our findings provide insights on how antiviral drugs that modify phagosome acidification should be used for viruses such as DENV.
+The detection and quantification of enteric RNA viruses is based on isolation of viral RNA from the sample followed by quantitative reverse transcription polymerase chain reaction (RT-qPCR).
+To control the whole process of analysis and in order to guarantee the validity and reliability of results, process control viruses (PCV) are used.
+The present article describes the process of preparation and use of such PCV– MS2 phage-like particles (MS2 PLP) – in RT-qPCR detection and quantification of enteric RNA viruses.
+The MS2 PLP were derived from bacteriophage MS2 carrying a unique and specific de novo-constructed RNA target sequence originating from the DNA of two extinct species.
+The amount of prepared MS2 particles was quantified using four independent methods – UV spectrophotometry, fluorimetry, transmission electron microscopy and a specifically developed duplex RT-qPCR.
+To evaluate the usefulness of MS2 PLP in routine diagnostics different matrices known to harbor enteric RNA viruses (swab samples, liver tissue, serum, feces, and vegetables) were artificially contaminated with specific amounts of MS2 PLP.
+The prepared particles fulfill all requirements for PCV – they are very stable, non-infectious, and are genetically distinct from the target RNA viruses.
+The use of MS2 PLP as a PCV in detection and quantification of enteric RNA viruses was evaluated in different types of matrices.
+α-fetoprotein (AFP) is an early serum growth factor in foetal embryonic development and hepatic oncogenesis.
+A growing number of investigations of AFP as a tumour-specific biomarker have concluded that AFP is an important target for cancer treatment.
+AFP also plays an immunomodulatory role in the treatment of several autoimmune diseases, such as rheumatoid arthritis, multiple sclerosis, myasthenia gravis and thyroiditis.
+In an effort to support biochemical screening and drug design and discovery, we attempted to express and purify human AFP in a Bac-to-Bac system.
+Two key factors affecting the expression of recombinant human AFP (R-AFP), namely the infectious baculovirus inoculum volume and the culturing time post-infection, were optimized to maximize the yield.
+We achieved a high yield of approximately 1.5 mg/l of harvested medium with a 72–96 h incubation period after infection and an inoculum volume ratio of 1:100.
+We also assessed the role of R-AFP in the proliferation of the human liver cancer cell line Bel 7402, and the results indicated that R-AFP promoted the growth of hepatoma cells.
+We concluded that this method can produce high yields of R-AFP, which can be used for studies related to AFP.
+Stochastic transmission dynamic models are especially useful for studying the early emergence of novel pathogens given the importance of chance events when the number of infectious individuals is small.
+However, methods for parameter estimation and prediction for these types of stochastic models remain limited.
+In this manuscript, we describe a calibration and prediction framework for stochastic compartmental transmission models of epidemics.
+The proposed method, Multiple Shooting for Stochastic systems (MSS), applies a linear noise approximation to describe the size of the fluctuations, and uses each new surveillance observation to update the belief about the true epidemic state.
+Using simulated outbreaks of a novel viral pathogen, we evaluate the accuracy of MSS for real-time parameter estimation and prediction during epidemics.
+We assume that weekly counts for the number of new diagnosed cases are available and serve as an imperfect proxy of incidence.
+mean duration of infectiousness, R(0), and R(eff)) and can provide an accurate estimate of the unobserved number of infectious individuals during the course of an epidemic.
+MSS also allows for accurate prediction of the number and timing of future hospitalizations and the overall attack rate.
+We compare the performance of MSS to three state-of-the-art benchmark methods: 1) a likelihood approximation with an assumption of independent Poisson observations; 2) a particle filtering method; and 3) an ensemble Kalman filter method.
+We find that MSS significantly outperforms each of these three benchmark methods in the majority of epidemic scenarios tested.
+In summary, MSS is a promising method that may improve on current approaches for calibration and prediction using stochastic models of epidemics.
+We have previously reported that the absence of sphingosine kinase 1 (SK1) affects both dengue virus (DENV) infection and innate immune responses in vitro.
+Here we aimed to define SK1-dependancy of DENV-induced disease and the associated innate responses in vivo.
+The lack of a reliable mouse model with a fully competent interferon response for DENV infection is a challenge, and here we use an experimental model of DENV infection in the brain of immunocompetent mice.
+Intracranial injection of DENV-2 into C57BL/6 mice induced body weight loss and neurological symptoms which was associated with a high level of DENV RNA in the brain.
+Body weight loss and DENV RNA level tended to be greater in SK1(-/-) compared with wildtype (WT) mice.
+Brain infection with DENV-2 is associated with the induction of interferon-β (IFN-β) and IFN-stimulated gene (ISG) expression including viperin, Ifi27l2a, IRF7, and CXCL10 without any significant differences between WT and SK1(-/-) mice.
+The SK2 and sphingosine-1-phosphate (S1P) levels in the brain were unchanged by DENV infection or the lack of SK1.
+Histological analysis demonstrated the presence of a cellular infiltrate in DENV-infected brain with a significant increase in mRNA for CD8 but not CD4 suggesting this infiltrate is likely CD8(+) but not CD4(+) T-lymphocytes.
+Overall, DENV-infection in the brain induces IFN and T-cell responses but does not influence the SK/S1P axis.
+In contrast to our observations in vitro, SK1 has no major influence on these responses following DENV-infection in the mouse brain.
+The 2013–2016 West Africa Ebola virus disease pandemic was the largest, longest, deadliest, and most geographically expansive outbreak in the 40-year interval since Ebola was first identified.
+Fear-related behaviors are defined as “individual or collective behaviors and actions initiated in response to fear reactions that are triggered by a perceived threat or actual exposure to a potentially traumatizing event.
+FRBs modify the future risk of harm.” This review examines how fear-related behaviors were implicated in (1) accelerating the spread of Ebola, (2) impeding the utilization of life-saving Ebola treatment, (3) curtailing the availability of medical services for treatable conditions, (4) increasing the risks for new-onset psychological distress and psychiatric disorders, and (5) amplifying the downstream cascades of social problems.
+Particularly notable are behaviors such as treating Ebola patients in home or private clinic settings, the “laying of hands” on Ebola-infected individuals to perform faith-based healing, observing hands-on funeral and burial customs, foregoing available life-saving treatment, and stigmatizing Ebola survivors and health professionals.
+Future directions include modeling the onset, operation, and perpetuation of fear-related behaviors and devising strategies to redirect behavioral responses to mass threats in a manner that reduces risks and promotes resilience.
+Viral sewage metagenomics is a novel field of study used for surveillance, epidemiological studies, and evaluation of waste water treatment efficiency.
+In raw sewage human waste is mixed with household, industrial and drainage water, and virus particles are, therefore, only found in low concentrations.
+Additionally, viruses harbor a large diversity of both surface and genome structures, which makes universal viral genomic extraction difficult.
+Current studies have tackled these challenges in many different ways employing a wide range of viral concentration and extraction procedures.
+However, there is limited knowledge of the efficacy and inherent biases associated with these methods in respect to viral sewage metagenomics, hampering the development of this field.
+By the use of next generation sequencing this study aimed to evaluate the efficiency of four commonly applied viral concentrations techniques (precipitation with polyethylene glycol, organic flocculation with skim milk, monolithic adsorption filtration and glass wool filtration) and extraction methods (Nucleospin RNA XS, QIAamp Viral RNA Mini Kit, NucliSENS(®) miniMAG(®), or PowerViral(®) Environmental RNA/DNA Isolation Kit) to determine the viriome in a sewage sample.
+The viral richness was largest in samples extracted with QIAamp Viral RNA Mini Kit or PowerViral(®) Environmental RNA/DNA Isolation Kit.
+Highest viral specificity were found in samples concentrated by precipitation with polyethylene glycol or extracted with Nucleospin RNA XS.
+These results contribute to the understanding of method associated biases, within the field of viral sewage metagenomics, making evaluation of the current literature easier and helping with the design of future studies.
+Specialized pro-resolving mediators (SPMs) are enzymatically derived from essential fatty acids and have important roles in orchestrating the resolution of tissue inflammation — that is, catabasis.
+Host responses to tissue infection elicit acute inflammation in an attempt to control invading pathogens.
+SPMs are lipid mediators that are part of a larger family of pro-resolving molecules, which includes proteins and gases, that together restrain inflammation and resolve the infection.
+These immunoresolvents are distinct from immunosuppressive molecules as they not only dampen inflammation but also promote host defence.
+Here, we focus primarily on SPMs and their roles in lung infection and inflammation to illustrate the potent actions these mediators play in restoring tissue homeostasis after an infection.
+SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nri.2015.4) contains supplementary material, which is available to authorized users.
+Alternative processing of human bocavirus (HBoV) P5 promoter-transcribed RNA is critical for generating the structural and nonstructural protein-encoding mRNA transcripts.
+The regulatory mechanism by which HBoV RNA transcripts are polyadenylated at proximal [(pA)p] or distal [(pA)d] polyadenylation sites is still unclear.
+We constructed a recombinant HBoV infectious clone to study the alternative polyadenylation regulation of HBoV.
+Surprisingly, in addition to the reported distal polyadenylation site, (pA)d, a novel distal polyadenylation site, (pA)d2, which is located in the right-end hairpin (REH), was identified during infectious clone transfection or recombinant virus infection.
+(pA)d2 does not contain typical hexanucleotide polyadenylation signal, upstream elements (USE), or downstream elements (DSE) according to sequence analysis.
+Further study showed that HBoV nonstructural protein NS1, REH, and cis elements of (pA)d were necessary and sufficient for efficient polyadenylation at (pA)d2.
+The distance and sequences between (pA)d and (pA)d2 also played a key role in the regulation of polyadenylation at (pA)d2.
+Finally, we demonstrated that efficient polyadenylation at (pA)d2 resulted in increased HBoV capsid mRNA transcripts and protein translation.
+Thus, our study revealed that all the bocaviruses have distal poly(A) signals on the right-end palindromic terminus, and alternative polyadenylation at the HBoV 3′ end regulates its capsid expression.
+IMPORTANCE The distal polyadenylation site, (pA)d, of HBoV is located about 400 nucleotides (nt) from the right-end palindromic terminus, which is different from those of bovine parvovirus (BPV) and canine minute virus (MVC) in the same genus whose distal polyadenylation is located in the right-end stem-loop structure.
+A novel polyadenylation site, (pA)d2, was identified in the right-end hairpin of HBoV during infectious clone transfection or recombinant virus infection.
+Sequence analysis showed that (pA)d2 does not contain typical polyadenylation signals, and the last 42 nt form a stem-loop structure which is almost identical to that of MVC.
+Further study showed that NS1, REH, and cis elements of (pA)d are required for efficient polyadenylation at (pA)d2.
+Our study demonstrates alternative polyadenylation at the 3′ end of HBoV and suggests an additional mechanism by which capsid expression is regulated.
+Dysregulated Toll-like receptor (TLR)-4 activation is involved in acute systemic sepsis, chronic inflammatory diseases, such as atherosclerosis and diabetes, and in viral infections, such as influenza infection.
+Here we tested the activity of the small-molecule synthetic TLR4 antagonist, FP7, in vitro on human monocytes and monocyte-derived dendritic cells (DCs) and in vivo during influenza virus infection of mice.
+Our results indicate that FP7 antagonized the secretion of proinflammatory cytokines (IL-6, IL-8, and MIP-1β) by monocytes and DCs (IC(50) < 1 μM) and prevented DC maturation upon TLR4 activation by ultrapure lipopolysaccharide (LPS).
+TLR4 stimulation of human DCs resulted in increased glycolytic activity that was also antagonized by FP7.
+FP7 protected mice from influenza virus-induced lethality and reduced both proinflammatory cytokine gene expression in the lungs and acute lung injury (ALI).
+Therefore, FP7 can antagonize TLR4 activation in vitro and protect mice from severe influenza infection, most likely by reducing TLR4-dependent cytokine storm mediated by damage-associated molecular patterns (DAMPs) like HMGB1.
+However, the current OIT strategy is limited in terms of the long-term efficacy and safety.
+We have previously demonstrated that kakkonto, a traditional Japanese herbal medicine, suppresses the occurrence of allergic symptoms in a murine model of ovalbumin (OVA)-induced FA, which is attributed to the induction of the Foxp3(+) CD4(+) regulatory T cells.
+In this study, we established an OIT model using the FA mice with already established allergic symptoms and determined whether kakkonto could improve the efficacy of OIT.
+The OIT method consisted of initially administrating a very small amount of OVA and slowly increasing the amount.
+OIT significantly downregulated Th2 immune response-related gene expression in the FA mouse colon, and decreased the level of mouse mast cell protease-1, a marker of mast cell degranulation in the FA mouse plasma.
+Moreover, the concomitant use of kakkonto significantly enhanced the effectiveness of OIT on the allergic symptoms, and the combination therapy further suppressed the Th2 immune responses and the mast cell degranulation.
+In addition, OIT significantly increased the population of Foxp3(+) CD4(+) regulatory T cells in the FA mouse colon, and this population was further increased by OIT in combination with kakkonto.
+Furthermore, the combined therapy with kakkonto reduced the expression of RA-degrading enzyme CYP26B1 mRNA in the FA mouse colon.
+These findings indicated that the combination of OIT with kakkonto represents a promising approach for FA treatment.
+A survey was conducted into respiratory infectious diseases of poultry on a chicken breeder farm run by the Ethiopian Institute of Agricultural Research (EIAR), located in Debre Zeit, Ethiopia.
+Oropharyngeal swabs were collected from 117 randomly selected birds, and blood was taken from a subset of 73 of these birds.
+For the first time in Ethiopia, we report the detection of variant infectious bronchitis virus (793B genotype), avian metapneumovirus subtype B and Mycoplasma synoviae in poultry.
+Mycoplasma gallisepticum was also found to be present; however, infectious laryngotracheitis virus was not detected by PCR.
+Newcastle disease virus (NDV) was not detected by PCR, but variable levels of anti-NDV HI antibody titres shows possible exposure to virulent strains or poor vaccine take, or both.
+For the burgeoning-intensive industry in Ethiopia, this study highlights several circulating infectious respiratory pathogens that can impact on poultry welfare and productivity.
+Despite the acknowledgement of 2 common components of resilience, that is, adversity and positive adaptation, no consensus operational definition has been agreed.
+Resilience operationalisations have been reviewed in a cross-sectional context; however, a review of longitudinal methods of operationalising resilience has not been conducted.
+The present study conducts a systematic review across Scopus and Web of Science capturing studies of ageing that posited operational definitions of resilience in longitudinal studies of ageing.
+Non-acute events, for example, cancer, were the most common form of adversity identified and psychological components, for example, the absence of depression, the most common forms of positive adaptation.
+Of the included studies, 4 used psychometrically driven methods, that is, repeated administration of established resilience metrics, 9 used definition-driven methods, that is, a priori establishment of resilience components and criteria, and 23 used data-driven methods, that is, techniques that identify resilient individuals using latent variable models.
+Acknowledging the strengths and limitations of each operationalisation is integral to the appropriate application of these methods to life course and longitudinal resilience research.
+By analyzing the structures of SERMs and their incidental biological activity (cholesterol accumulation), we hypothesized that this incidental biological activity induced by SERMs could be a plausible mechanism as to their inhibitory effects on Ebola infection.
+Herein, we demonstrated that the same dosages of SERMs which induced cholesterol accumulation also inhibited Ebola infection.
+SERMs reduced the cellular sphingosine and subsequently caused endolysosomal calcium accumulation, which in turn led to blocking the Ebola entry.
+Our study clarified the specific anti-Ebola mechanism of SERMs, even the cationic amphiphilic drugs (CADs), this mechanism led to the endolysosomal calcium as a critical target for development of anti-Ebola drugs.
+Ongoing evolution of viral pathogens is a significant issue in diagnostic virology employing TaqMan qPCR/RT-qPCR.
+One option for compensating for such deficiency is to integrate a second identically labelled probe in the assay.
+In the present study, we evaluate a TaqMan protocol using two identically labelled hydrolysis probes (simple, LNA (locked-nucleic-acid)) and MGB (minor-groove-binder) modified probes and combinations thereof in a single assay.
+Our results based on a synthetic amplicon suggest that the second probe does not compromise the TaqMan qPCR/RT-qPCR parameters, which repeatedly and reproducibly remained comparable to those of the corresponding single-probe assays, irrespective of the relative probe orientation, whether opposite or tandem, and probe modifications or combinations thereof.
+The utility of the dual-probe approach was demonstrated on practical examples by using field specimens.
+We hope that the present study might serve as a theoretical basis for the development or improvement of TaqMan qPCR/RT-qPCR assays for the detection of highly variable nucleic acid templates.
+Since it emerged in Brazil in May 2015, the mosquito-borne Zika virus (ZIKV) has raised global concern due to its association with a significant rise in the number of infants born with microcephaly and neurological disorders such as Guillain-Barré syndrome.
+We developed prototype subunit and adenoviral-based Zika vaccines encoding the extracellular portion of the ZIKV envelope gene (E) fused to the T4 fibritin foldon trimerization domain (Efl).
+The immunogenicity of these two vaccines, named Ad5.ZIKV-Efl and ZIKV-rEfl, was tested in C57BL/6 mice.
+Prime/boost immunization regimen was associated with induction of a ZIKV-specific antibody response, which provided neutralizing immunity.
+Pups born to mice immunized with Ad5.ZIKV-Efl were all protected against lethal challenge infection without weight loss or neurological signs, while pups born to dams immunized with MNA-ZIKV-rEfl were partially protected (50%).
+This study illustrates the preliminary efficacy of the E ZIKV antigen vaccination in controlling ZIKV infectivity, providing a promising candidate vaccine and antigen format for the prevention of Zika virus disease.
+Spiroplasma eriocheiris is a novel pathogen found in recent years, causing the tremor disease (TD) of Chinese mitten crab Eriocheir sinensis.
+Like Spiroplasma mirum, S. eriocheiris infects the newborn mouse (adult mice are not infected) and can cause cataract.
+In this study, the Adhesin-like Protein (ALP) of S. eriocheiris was detected on its outer membrane by using immune electron microscopy, and was found to be involved in the bacterium's infection of mouse embryo fibroblasts (3T6-Swiss albino).
+The interactions between recombinant partial fibulin7 (FBLN7; including two epidermal growth factor [EGF] domains) and ALP were confirmed by Far-western blotting and colocalization.
+We synthetized the domains of FBLN7 [EGF domain: amino acids 136–172 and complement control protein (CCP) domain: 81–134 amino acids], and demonstrated that only EGF domain of FBLN7 can interact with ALP.
+Because the EGF domain has high degree of similarity to EGF, it can activate the downstream EGFR signaling pathway, in key site amino acids.
+The EGFR pathway in 3T6 cells was restrained after rALP stimulation resulting from competitive binding of ALP to EGF.
+The unborn mouse, newborn mouse, and the adult mouse with cataract have a small amount of expressed FBLN7; however, none was detected in the brain and very little expression was seen in the eye of normal adult mice.
+In short, ALP as a S. eriocheiris surface protein, is critical for infection and further supports the role of ALP in S. eriocheiris infection by competitive effection of the EGF/EGFR axis of the target cells.
+BACKGROUND: The survival predictors and optimal mechanical ventilator settings in patients with severe acute respiratory distress syndrome (ARDS) undergoing extracorporeal membrane oxygenation (ECMO) are uncertain.
+This study was designed to investigate the influences of clinical variables and mechanical ventilation settings on the outcomes for severe ARDS patients receiving ECMO.
+METHODS: We reviewed severe ARDS patients who received ECMO due to refractory hypoxemia from May 2006 to October 2015.
+Serial mechanical ventilator settings before and after ECMO and factors associated with survival were analyzed.
+After ECMO initiation, tidal volume, peak inspiratory pressure and dynamic driving pressure were decreased, while positive end-expiratory pressure levels were relative maintained.
+After ECMO initiation, nonsurvivors had significantly higher dynamic driving pressure until day 7 than survivors.
+CONCLUSIONS: For severe ARDS patients receiving ECMO, immunocompromised status, APACHE II score and the duration of ARDS before ECMO initiation were significantly associated with ICU survival.
+Higher dynamic driving pressure during first 3 days of ECMO support was also independently associated with increased ICU mortality.
+BACKGROUND: Chikungunya virus (CHIKV), a reemerging pathogen causes a self limited illness characterized by fever, headache, myalgia and arthralgia.
+The present study investigated the possible occurrence of molecular mimicry between CHIKV E1 glycoprotein and host human components.
+METHODOLOGY: Bioinformatic tools were used to identify peptides of CHIKV E1 exhibiting similarity to host components.
+Two peptides (A&B) were identified using several bioinformatic tools, synthesised and used to validate the results obtained in silico.
+An ELISA was designed to assess the immunoreactivity of serum samples from CHIKV patients to these peptides.
+Further, experiments were conducted in a C57BL/6J experimental mouse model to investigate if peptide A and peptide B were indeed capable of inducing pathology.
+FINDINGS: The serum samples showed reactivity of varying degrees, indicating that these peptides are indeed being recognized by the host immune system during CHIKV infection.
+Further, these peptides when injected into C57BL/6J mice were able to induce significant inflammation in the muscles of C57BL/6J mice, similar to that observed in animals that were injected with CHIKV alone.
+Additionally, animals that were primed initially with CHIKV followed by a subsequent injection of the CHIKV peptides exhibited enhanced inflammatory pathology in the skeletal muscles as compared to animals that were injected with peptides or virus alone.
+Collectively these observations validate the hypothesis that molecular mimicry between CHIKV E1 protein and host proteins does contribute to pathology in CHIKV infection.
+Human dendritic cell‐specific intercellular adhesion molecule‐1 grabbing nonintegrin, DC‐SIGN, and the sinusoidal endothelial cell receptor DC‐SIGNR or L‐SIGN, are closely related sugar‐binding receptors.
+DC‐SIGN acts both as a pathogen‐binding endocytic receptor and as a cell adhesion molecule, while DC‐SIGNR has only the pathogen‐binding function.
+In addition to differences in the sugar‐binding properties of the carbohydrate‐recognition domains in the two receptors, there are sequence differences in the adjacent neck domains, which are coiled‐coil tetramerization domains comprised largely of 23‐amino acid repeat units.
+A series of model polypeptides consisting of uniform repeat units have been characterized by gel filtration, differential scanning calorimetry and circular dichroism.
+The results demonstrate that two features characterize repeat units which form more stable tetramers: a leucine reside in the first position of the heptad pattern of hydrophobic residues that pack on the inside of the coiled coil and an arginine residue on the surface of the coiled coil that forms a salt bridge with a glutamic acid residue in the same polypeptide chain.
+In DC‐SIGNR from all primates, very stable repeat units predominate, so the carbohydrate‐recognition domains must be held relatively closely together.
+The presence of residues that disrupt tetramer formation in repeat units near the carbohydrate‐recognition domains of DC‐SIGN would allow these domains to splay further apart.
+Thus, the neck domains of DC‐SIGN and DC‐SIGNR can contribute to the different functions of these receptors by presenting the sugar‐binding sites in different contexts.
+Both node height and topological differences may occur, depending on the interaction between within-host evolutionary dynamics and between-host transmission patterns.
+To investigate these interactions, we added a within-host evolutionary model in epidemiological simulations and examined if the resulting phylogeny could recover different types of contact networks.
+To further improve realism, we also introduced patient-specific differences in infectivity across disease stages, and on the epidemic level we considered incomplete sampling and the age of the epidemic.
+Second, we implemented an inference method based on approximate Bayesian computation (ABC) to discriminate among three well-studied network models and jointly estimate both network parameters and key epidemiological quantities such as the infection rate.
+Our ABC framework used both topological and distance-based tree statistics for comparison between simulated and observed trees.
+Overall, our simulations showed that a virus time-scaled phylogeny (genealogy) may be substantially different from the between-host transmission tree.
+This has important implications for the interpretation of what a phylogeny reveals about the underlying epidemic contact network.
+In particular, we found that while the within-host evolutionary process obscures the transmission tree, the diversification process and infectivity dynamics also add discriminatory power to differentiate between different types of contact networks.
+We also found that the possibility to differentiate contact networks depends on how far an epidemic has progressed, where distance-based tree statistics have more power early in an epidemic.
+Finally, we applied our ABC inference on two different outbreaks from the Swedish HIV-1 epidemic.
+Endoribonucleases participate in almost every step of eukaryotic RNA metabolism, acting either as degradative or biosynthetic enzymes.
+We previously identified the founding member of the Eukaryotic EndoU ribonuclease family, whose components display unique biochemical features and are flexibly involved in important biological processes, such as ribosome biogenesis, tumorigenesis and viral replication.
+Here we report the discovery of the CG3303 gene product, which we named DendoU, as a novel family member in Drosophila.
+Pan-neuronal silencing of dendoU resulted in fly immature phenotypes, highly reduced lifespan and dramatic motor performance defects.
+At the molecular level, we unveiled that DendoU is a positive regulator of the neurodegeneration-associated protein dTDP-43, whose downregulation recapitulates the ensemble of dendoU-dependent phenotypes.
+This interdisciplinary work, which comprehends in silico, in vitro and in vivo studies, unveils a relevant role for DendoU in Drosophila nervous system physio-pathology and highlights that DendoU-mediated neurotoxicity is, at least in part, contributed by dTDP-43 loss-of-function.
+2H enzymes are found in all kingdoms of life, sharing little sequence identity despite the conserved overall fold and active site.
+Here, we studied the structure of the 2H family member LigT from Escherichia coli both in the apo form and complexed with different active-site ligands, including ATP, 2′-AMP, 3′-AMP, phosphate, and NADP(+).
+Comparisons to the well-characterized vertebrate myelin enzyme 2′,3′-cyclic nucleotide 3′-phosphodiesterase (CNPase) highlight specific features of the catalytic cycle and substrate recognition in both enzymes.
+The role played by the helix α7, unique to CNPases within the 2H family, is apparently taken over by Arg130 in the bacterial enzyme.
+Other residues and loops lining the active site groove are likely to be important for RNA substrate binding.
+We visualized conformational changes related to ligand binding, as well as the position of the nucleophilic water molecule.
+We also present a low-resolution model of E. coli LigT bound to tRNA in solution, and provide a model for RNA binding by LigT, involving flexible loops lining the active site cavity.
+Taken together, our results both aid in understanding the common features of 2H family enzymes and help highlight the distinct features in the 2H family members, which must result in different reaction mechanisms.
+Unique aspects in different 2H family members can be observed in ligand recognition and binding, and in the coordination of the nucleophilic water molecule and the reactive phosphate moiety.
+Canine parvovirus type 2 (CPV-2) is the main etiological agent of viral enteritis in dogs.
+Actually in literature, CPV-2 has been reported with clinical signs that vary from the classical disease, and immunochromatography test and PCR technique have been introduced to veterinary hospitals to confirm CPV-2 diagnosis and other infections.
+In this study, we evaluated the sensitivity and specificity of veterinary clinical diagnosis, immunochromatography test and PCR technique.
+Our data indicate that variations in the clinical signs of CPV-2 complicate the gathering of an appropriate diagnosis; and immunochromatography test and PCR technique do not have adequate sensitivity to diagnose positive cases.
+PURPOSE: To describe the incidence, clinical courses, and risk factors for mortality of lower respiratory tract diseases (LRDs) caused by common respiratory viruses (CRVs) in stem cell transplantation (SCT) recipients.
+MATERIALS AND METHODS: We retrospectively reviewed the medical records of 1038 patients who received SCT between January 2007 and August 2011 at a single center in Korea.
+The human parainfluenza virus (HPIV) was the most common causative pathogen of CRV-LRDs at 100 days [cumulative incidence estimate, 23.5%; 95% confidence interval (CI), 3.3–43.7] and 1 year (cumulative incidence estimate, 69.2%; 95% CI, 45.9–92.5) following SCT.
+The 30-day overall mortality rates due to influenza-LRDs, respiratory syncytial virus-LRDs, HPIV-LRDs, and human rhinovirus-LRDs were 35.7, 25.8, 31.6, and 42.8%, respectively.
+High-dose steroid usage (p=0.025), a severe state of immunodeficiency (p=0.033), and lymphopenia (p=0.006) were significantly associated with death within 30 days following CRV-LRD diagnosis in a univariate analysis.
+Multivariate logistic regression analysis revealed that high-dose steroid usage [odds ratio (OR), 4.05; 95% CI, 1.12–14.61; p=0.033] and lymphopenia (OR, 6.57; 95% CI, 1.80–24.03; p=0.004) were independent risk factors for mortality within 30 days of CRV-LRDs.
+Therefore, the implement of an active diagnostic approaches for CRV infections is required for SCT recipients with respiratory symptoms, especially those receiving high-dose steroids or with lymphopenia.
+Since May 2006, a highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) has emerged and prevailed in mainland China, affecting over 2 million pigs.
+Commercial PRRSV killed and modified live vaccines cannot provide complete protection against HP-PRRSV due to genetic variation.
+In our previous studies, two formulations of DNA vaccines (pcDNA3.1-PoIFN-λ1-SynORF5 and BPEI/PLGA-SynORF5) based on the HP-PRRSV were constructed and shown to induce enhanced humoral and cellular immune responses in mice.
+The objective of this study was to evaluate the immune response induced by these novel formulations in piglets.
+PcDNA3.1-PoIFN-λ1-SynORF5 and BPEI/PLGA-SynORF5 vaccines induced significantly enhanced GP5-specific antibody and PRRSV-specific neutralizing antibody in pigs compared with the pcDNA3.1-SynORF5 parental construct.
+Though IFN-γ levels and lymphocyte proliferation responses induced by the two DNA vaccine formulations were comparable to that induced by the pcDNA3.1-SynORF5 construct, each of the novel formulations provided efficient protection against challenge with HP-PRRSV.
+Non-severe clinical signs and rectal temperatures were observed in pigs immunized with BPEI/PLGA-SynORF5 compared with other groups.
+Tuberculosis (TB) remains a serious health problem worldwide, and an urgent need exists to improve or replace the available vaccine, Mycobacterium bovis bacillus Calmette-Guérin (BCG).
+Our previous study showed that the naked DNA encoding the triple-antigen fusion TFP846 (Rv3615c-Mtb10.4-Rv2660c) induced robust T cellular immune responses accompanying four inoculations against mycobacteria infection.
+However, a number of compliance issues exist in some areas lacking the appropriate medical infrastructure with multiple administrations.
+In this study, a novel vesicular stomatitis virus expressing TFP846 (VSV-846) was developed and the immune responses elicited by VSV-846 were evaluated.
+We observed that intranasal delivery of VSV-846 induced a potent antigen-specific T cell response following a single dose and VSV-846 efficiently controlled bacterial growth to levels ~10-fold lower than that observed in the mock group 6 weeks post-infection in BCG-infected mice.
+Importantly, mice immunized with VSV-846 provided long-term protection against mycobacteria infection compared with those receiving p846 or BCG immunization.
+Increased memory T cells were also observed in the spleens of VSV-846-vaccinated mice, which could be a potential mechanism associated with long-term protective immune response.
+These findings supported the use of VSV as an antigen delivery vector with the potential for TB vaccine development.
+Conventional photocatalysts are primarily stimulated using ultraviolet (UV) light to elicit reactive oxygen species and have wide applications in environmental and energy fields, including self-cleaning surfaces and sterilization.
+Because UV illumination is hazardous to humans, visible light-responsive photocatalysts (VLRPs) were discovered and are now applied to increase photocatalysis.
+However, fundamental questions regarding the ability of VLRPs to trigger DNA mutations and the mutation types it elicits remain elusive.
+Here, through plasmid transformation and β-galactosidase α-complementation analyses, we observed that visible light-responsive platinum-containing titania (TiO(2)) nanoparticle (NP)-mediated photocatalysis considerably reduces the number of Escherichia coli transformants.
+DNA sequencing results demonstrated that the DNA damage comprises three mutation types, namely nucleotide insertion, deletion and substitution; this is the first study to report the types of mutations occurring after photocatalysis by TiO(2)-VLRPs.
+Our results may facilitate the development and appropriate use of new-generation TiO(2) NPs for biomedical applications.
+Myocarditis can present in many different forms and can be overlooked by more life-threatening conditions.
+At times it may mimic conditions such as acute myocardial infarction and although it may have features highly suggestive of myocarditis, other etiologies need to be excluded.
+Thus, due to its clinical presentation, lab findings, and electrocardiogram analysis, it often can be confused with other conditions, making it a diagnostic dilemma of uncertainty.
+Here we report a case of a 52-year-old gentleman who presented with a clinical picture of acute myocardial ischemia versus dissection, which overlooked a rather less threatening etiology of myopericarditis.
+BACKGROUND: Utilization of extracorporeal membrane oxygenation (ECMO) has increased worldwide, but its use remains restricted to severely ill patients, and few referral centers are properly structured to offer this support.
+In this study, we report a single-center experience and a systematic review of the available published data on complications and mortality associated with ECMO transportation.
+METHODS: We reported single-center data regarding complications and mortality associated with the transportation of patients on ECMO support.
+Additionally, we searched multiple databases for case series, observational studies, and randomized controlled trials regarding mortality of patients transferred on ECMO support.
+RESULTS: A total of 38 manuscripts, including our series, were included in the final analysis, totaling 1481 patients transported on ECMO support.
+The pooled survival rates for adult and pediatric patients were 62% (95% CI 57–68) and 68% (95% CI 60–75), respectively.
+CONCLUSION: Using the available pooled data, we found that patient transfer to a referral institution while on ECMO support seems to be safe and adds no significant risk of mortality to ECMO patients.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13613-016-0232-7) contains supplementary material, which is available to authorized users.
+Influenza virus infections represent a serious public health and economic problem, which are most effectively prevented through vaccination.
+However, influenza viruses undergo continual antigenic variation, which requires either the annual reformulation of seasonal influenza vaccines or the rapid generation of vaccines against potential pandemic virus strains.
+The segmented nature of influenza virus allows for the reassortment between two or more viruses within a co-infected cell, and this characteristic has also been harnessed in the laboratory to generate reassortant viruses for their use as either inactivated or live-attenuated influenza vaccines.
+With the implementation of plasmid-based reverse genetics techniques, it is now possible to engineer recombinant influenza viruses entirely from full-length complementary DNA copies of the viral genome by transfection of susceptible cells.
+These reverse genetics systems have provided investigators with novel and powerful approaches to answer important questions about the biology of influenza viruses, including the function of viral proteins, their interaction with cellular host factors and the mechanisms of influenza virus transmission and pathogenesis.
+In addition, reverse genetics techniques have allowed the generation of recombinant influenza viruses, providing a powerful technology to develop both inactivated and live-attenuated influenza vaccines.
+In this review, we will summarize the current knowledge of state-of-the-art, plasmid-based, influenza reverse genetics approaches and their implementation to provide rapid, convenient, safe and more effective influenza inactivated or live-attenuated vaccines.
+Understanding the dynamics of pathogen spread within urban areas is critical for the effective prevention and containment of communicable diseases.
+At these relatively small geographic scales, short-distance interactions and tightly knit sub-networks dominate the dynamics of pathogen transmission; yet, the effective boundaries of these micro-scale groups are generally not known and often ignored.
+Using clinical test results from hospital admitted patients we analyze the spatio-temporal distribution of Influenza Like Illness (ILI) in the city of Jerusalem over a period of three winter seasons.
+We demonstrate that this urban area is not a single, perfectly mixed ecology, but is in fact comprised of a set of more basic, relatively independent pathogen transmission units, which we term here Local Transmission Zones, LTZs.
+By identifying these LTZs, and using the dynamic pathogen-content information contained within them, we are able to differentiate between disease-causes at the individual patient level often with near-perfect predictive accuracy.
+The bactericidal activity of conventional titanium dioxide (TiO(2)) photocatalyst is effective only on irradiation by ultraviolet light, which restricts the applications of TiO(2) for use in living environments.
+Recently, carbon-containing TiO(2) nanoparticles [TiO(2)(C) NP] were found to be a visible-light-responsive photocatalyst (VLRP), which displayed significantly enhanced antibacterial properties under visible light illumination.
+Bacteria-killing experiments indicated that a significantly higher proportion (40%–60%) of all tested Bacillus species, including B. subtilis, B. cereus, B. thuringiensis, and B. anthracis, were considerably eliminated by TiO(2)(C) NPs.
+Toxin inactivation analysis further suggested that the TiO(2)(C) NPs efficiently detoxify approximately 90% of tested anthrax lethal toxin, a major virulence factor of anthrax.
+Notably, macrophage clearance experiments further suggested that, even under suboptimal conditions without considerable bacterial killing, the TiO(2)(C) NP-mediated photocatalysis still exhibited antibacterial properties through the reduction of bacterial resistance against macrophage killing.
+Our results collectively suggested that TiO(2)(C) NP is a conceptually feasible anti-anthrax material, and the relevant technologies described herein may be useful in the development of new strategies against anthrax.
+The human interferon (IFN) response is a key innate immune mechanism to fight virus infection.
+Among the three classes of IFNs, type III IFNs, also called IFN lambdas (IFNLs), are an essential component of the innate immune response to hepatitis C virus (HCV).
+In particular, human polymorphisms in IFNL gene loci correlate with hepatitis C disease progression and with treatment response.
+To date, the underlying mechanisms remain mostly elusive; however it seems clear that viral infection of the liver induces IFNL responses.
+As IFNL receptors show a more restricted tissue expression than receptors for other classes of IFNs, IFNL treatment has reduced side effects compared to the classical type I IFN treatment.
+In HCV therapy, however, IFNL will likely not play an important role as highly effective direct acting antivirals (DAA) exist.
+Here, we will review our current knowledge on IFNL gene expression, protein properties, signaling, ISG induction, and its implications on HCV infection and treatment.
+Finally, we will discuss the lessons learnt from the HCV and IFNL field for virus infections beyond hepatitis C.
+Toll-like receptors in alveolar macrophages (AMΦ) recognize the molecular constituents of pathogens and activate the host’s innate immune responses.
+Numerous studies have documented the importance of TLR-TLR cross talk, but few studies have specifically addressed the relationship between TLR4 and TLR3.
+We explored a novel mechanism of TLR3 up-regulation that is induced by LPS-TLR4 signaling in a dose- and time-dependent manner in AMΦ from C57BL/6 mice, while the LPS-induced TLR3 expression was significantly reduced in TLR4(−/−) and Myd88(−/−) mice and following pretreatment with a NF-κB inhibitor.
+The enhanced TLR3 up-regulation in AMΦ augmented the expression of cytokines and chemokines in response to sequential challenges with LPS and Poly I:C, a TLR3 ligand, which was physiologically associated with amplified AMΦ-induced PMN migration into lung alveoli.
+Our study demonstrates that the synergistic effect between TLR4 and TLR3 in macrophages is an important determinant in acute lung injury and, more importantly, that TLR3 up-regulation is dependent on TLR4-MyD88-NF-κB signaling.
+These results raise the possibility that bacterial infections can induce sensitivity to viral infections, which may have important implications for the therapeutic manipulation of the innate immune system.
+The study reports the development of a polymerase cross-linking spiral reaction (PCLSR) for the detection of African swine fever virus (ASFV) DNA in blood collected from infected pigs and wild boars.
+Two outer-spiral primers comprising of 3′ sequences complementary to ASFV p72 gene sequence and 5′end sequences complementary to exogenous gene of black widow alpha-latrotoxin as well as additional ASFV specific cross-linking primer.
+The method is specific exclusively to ASFV DNA without cross-reactions with cDNA of classical swine fever virus (CSFV), porcine reproductive respiratory syndrome (PRRSV) or porcine epidemic diarrhea virus (PEDV).
+The sensitivity of this technique reached 7.2 × 10(2) copies per μl(−1) of plasmid containing p72 gene.
+The results of PCLSR were visualized using SYBR Green I dye, gel electrophoresis while the reaction progress was traced using real-time PCR system that resulted in registration of fluorescent curves and melting peaks at 85.3 °C.
+The developed PCLSR was examined using blood or tissue samples collected from selected 17 ASF cases from infected wild boars and 3 outbreaks in pigs.
+Further tests have been also conducted using 55 tissue samples from 23 outbreaks and 22 cases.
+These results showed that PCLSR might be further used for preliminary and cost-effective detection and surveillance of ASFV.
+Dengue virus (DENV) is a member of the genus Flavivirus and can cause severe febrile illness.
+Here, we show that FLJ11286, which we refer to as IRAV, is induced by DENV in an interferon-dependent manner, displays antiviral activity against DENV, and localizes to the DENV replication complex.
+IRAV is an RNA binding protein and localizes to cytoplasmic processing bodies (P bodies) in uninfected cells, where it interacts with the MOV10 RISC complex RNA helicase, suggesting a role for IRAV in the processing of viral RNA.
+After DENV infection, IRAV, along with MOV10 and Xrn1, localizes to the DENV replication complex and associates with DENV proteins.
+These data serve to characterize an interferon-stimulated gene with antiviral activity against DENV, as well as to propose a mechanism of activity involving the processing of viral RNA.
+IMPORTANCE Dengue virus, a member of the family Flaviviridae, can result in a life-threatening illness and has a significant impact on global health.
+Dengue virus has been shown to be particularly sensitive to the effects of type I interferon; however, little is known about the mechanisms by which interferon-stimulated genes function to inhibit viral replication.
+A better understanding of the interferon-mediated antiviral response to dengue virus may aid in the development of novel therapeutics.
+Here, we examine the influence of the interferon-stimulated gene IRAV (FLJ11286) on dengue virus replication.
+We show that IRAV associates with P bodies in uninfected cells and with the dengue virus replication complex after infection.
+Our results provide insight into a newly identified antiviral gene, as well as broadening our understanding of the innate immune response to dengue virus infection.
+BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is performed as an acceptable life-saving bridging procedure in patients with severe acute respiratory distress syndrome (ARDS).To patients with avian influenza A (H7N9)-associated ARDS, ECMO could be adopted as a feasible therapeutic solution.
+We present our successful experience with ECMO utilized in a respiratory failure patient with H7N9 infection.
+CASE PRESENTATION: A 44 years-old female with H7N9-induced ARDS was admitted to intensive care unit (ICU) and was treated with veno-venous ECMO for six days, antiviral therapy, prolonged corticosteroid infusion and other therapies.
+She suffered significant hemorrhage requiring transfusion of platelets and multidrug-resistant Acinetobacter Baumannii infection during ECMO support.
+Fortunately, she was alive at last and completly recovered after 38 days of ICU stay.
+Mechanical circulatory support was the only chance for our patient with H7N9-associated ARDS to survive until respiratory function recovery.
+Early detection and rapid response are essential to these serious ECMO-associated complications such as hemorrhage, thrombosis and infection.
+Acute respiratory distress syndrome (ARDS) is a potentially devastating form of acute lung injury, which involves neutrophilic inflammation and pulmonary cell death.
+Carnosine (β-alanyl-L-histidine) is a small di-peptide with numerous activities, including antioxidant effects, metal chelation, proton buffering capacity and the inhibition of protein carbonylation and glycoxidation.
+We have examined the preventive effects of carnosine on tissue injury, oedema and inflammation in a murine model for ARDS.
+Oral administration of carnosine suppressed lipopolysaccharide (LPS)-induced vascular permeability, tissue injury and inflammation in the lung.
+In vivo imaging analysis revealed that LPS administration increased the level of ROS and that this increase was inhibited by carnosine administration.
+Carnosine also suppressed LPS-induced neutrophilic inflammation (evaluated by activation of myeloperoxidase in the lung and increased extracellular DNA in bronchoalveolar lavage fluid).
+These results suggest that the oral administration of carnosine suppresses LPS-induced lung injury via carnosine’s ROS-reducing activity.
+The aim of this study was molecular identification of Cryptosporidium species and assessment of their prevalence in different breeds of sheep and goat reared in Poland.
+In addition, the relationship between animal age, breed type, and the frequency of Cryptosporidium infections was determined.
+Fecal samples from 234 lambs and 105 goat kids aged up to 9 weeks, representing 24 breeds and their cross-breeds were collected from 71 small ruminant farms across Poland.
+The identification of Cryptosporidium species was performed at the 18 SSU ribosomal RNA (rRNA) and COWP loci followed by subtyping of C. parvum and C. hominis strains at GP60 gene locus.
+The presence of Cryptosporidium DNA at the 18 SSU rRNA locus was detected in 45/234 (19.2%) lamb feces samples and in 39/105 (37.1%) taken from goats.
+The following Cryptosporidium species: C. xiaoi, C. bovis, C. ubiquitum, C. parvum, and C. hominis were detected in small ruminants.
+Subsequent GP60 subtyping revealed the presence of C. parvum IIaA17G1R1 subtype in sheep and IIdA23G1 subtype in goats.
+There were no significant differences found in frequency of infections between the age groups (<3 and 3–9 weeks) of lambs (P = 0.14, α > 0.05) or goat kids (P = 0.06, α > 0.05).
+In addition, there was no correlation observed between the frequency in occurrence of particular parasite species and breed type in relation to native sheep breeds (F = 0.11; P = 0.990 > 0.05).
+The results of this study improve our knowledge on the breed-related occurrence of Cryptosporidium infections in the population of small ruminants reared in Poland.
+BACKGROUND: Ethiopia has the second largest human population in Africa and the largest livestock population on the continent.
+About 80% of Ethiopians are dependent on agriculture and have direct contact with livestock or other domestic animals.
+As the first step of the country's engagement in the Global Health Security Agenda, a zoonotic disease prioritization workshop was held to identify significant zoonotic diseases of mutual concern for animal and human health agencies.
+METHODS: A semi-quantitative tool developed by the US CDC was used for prioritization of zoonotic diseases.
+Workshop participants representing human, animal, and environmental health ministries were selected as core decision-making participants.
+Over 300 articles describing the zoonotic diseases considered at the workshop were reviewed for disease specific information on prevalence, morbidity, mortality, and DALYs for Ethiopia or the East Africa region.
+Committee members individually ranked the importance of each criterion to generate a final group weight for each criterion.
+Criteria selected in order of importance were: 1)severity of disease in humans, 2)proportion of human disease attributed to animal exposure, 3)burden of animal disease, 4)availability of interventions, and 5)existing inter-sectoral collaboration.
+Based on the results from the decision tree analysis and subsequent discussion, participants identified the following five priority zoonotic diseases: rabies, anthrax, brucellosis, leptospirosis, and echinococcosis.
+DISCUSSION: Multi-sectoral collaborations strengthen disease surveillance system development in humans and animals, enhance laboratory capacity, and support implementation of prevention and control strategies.
+Enhancement of public health and veterinary laboratories, joint outbreak and surveillance activities, and intersectoral linkages created to tackle the prioritized zoonotic diseases will undoubtedly prepare the country to effectively address newly emerging zoonotic diseases.
+BACKGROUND: Injury to the kidney epithelial barrier is a characteristic feature of acute kidney injury (AKI).
+Serum surfactant protein-D (SP-D), a known biomarker of damaged alveolar epithelium, is also secreted by renal tubular epithelial cells.
+Therefore, the aim of this study was to examine the possible association of SP-D with AKI susceptibility and prognosis.
+SP-D polymorphisms Thr11Met and Thr160Ala, AKI patient serum SP-D levels at days 1, 3 and 7 and urine KIM-1 levels in both AKI patients and controls were examined.
+The obtained results were correlated with the AKI stage, duration of renal replacement therapy (RRT) and prognosis.
+SP-D 11Thr/Thr genotype was more frequent in AKI patients than in controls (p < 0.01).
+Furthermore, AKI patients with SP-D 11Thr/Thr genotype had significantly higher serum SP-D levels (p < 0.05) compared to other genotypes.
+Serum SP-D levels corrected to the progression of AKI with a peak at day 3.
+Furthermore, the SP-D 11Thr/Thr genotype frequency and baseline serum SP-D level were higher in patients who subsequently died.
+Baseline serum SP-D levels positively correlated with the urine KIM-1 levels, AKI stage and RRT duration.
+CONCLUSION: In our study, elevated serum SP-D was associated with worse AKI clinical outcomes and patients with SP-D 11Thr/Thr genotype were more susceptible to AKI.
+Collectively, these findings suggest that SP-D may be useful as a biomarker of AKI susceptibility and prognosis.
+Pseudoviruses are useful virological tools because of their safety and versatility; however the low titer of these viruses substantially limits their wider applications.
+We developed a highly efficient pseudovirus production system capable of yielding 100 times more rabies pseudovirus than the traditional method.
+Employing the high-titer pseudoviruses, we have developed robust in vitro and in vivo neutralization assays for the evaluation of rabies vaccine, which traditionally relies on live-virus based assays.
+Compared with current rapid fluorescent focus inhibition test (RFFIT), our in vitro pseudovirus-based neutralization assay (PBNA) is much less labor-intensive while demonstrating better reproducibility.
+Moreover, the in vivo PBNA assay was also found to be superior to the live virus based assay.
+Following intravenous administration, the pseudovirus effectively infected the mice, with dynamic viral distributions being sequentially observed in spleen, liver and brain.
+Furthermore, data from in vivo PBNA showed great agreement with those generated from the live virus model but with the experimental time significantly reduced from 2 weeks to 3 days.
+Taken together, the effective pseudovirus production system facilitated the development of novel PBNA assays which could replace live virus-based traditional assays due to its safety, rapidity, reproducibility and high throughput capacity.
+As a predominant cause of human hand, foot, and mouth disease, enterovirus 71 (EV71) infection may lead to serious diseases and result in severe consequences that threaten public health and cause widespread panic.
+Although the systematic identification of physical interactions between viral proteins and host proteins provides initial information for the recognition of the cellular mechanism involved in viral infection and the development of new therapies, EV71-host protein interactions have not been explored.
+Here, we identified interactions between EV71 proteins and host cellular proteins and confirmed the functional relationships of EV71-interacting proteins (EIPs) with virus proliferation and infection by integrating a human protein interaction network and by functional annotation.
+We also predicted ATP6V0C as a broad-spectrum essential host factor and validated its essentiality for EV71 infection in vitro.
+EIPs and their interacting proteins were more likely to be targets of anti-inflammatory and neurological drugs, indicating their potential to serve as host-oriented antiviral targets.
+These findings provide the first systematic identification of EV71-host protein interactions, an analysis of EIP protein characteristics and a demonstration of their value in developing host-oriented antiviral therapies.
+Our objective was to identify cohort retention strategies and implementation approaches used in studies with high retention rates.
+METHODS: Longitudinal studies with ≥200 participants, ≥80% retention rates over ≥1 year of follow-up were queried from an Institutional Review Board database at a large research-intensive U.S. university; additional studies were identified through networking.
+Through in-depth semi-structured interviews, participants provided retention strategies based on themes identified from previous literature reviews.
+RESULTS: The most commonly used retention strategies were: study reminders, study visit characteristics, emphasizing study benefits, and contact/scheduling strategies.
+CONCLUSIONS: These studies included specialized and persistent teams and utilized tailored strategies specific to their cohort and individual participants.
+Studies’ written protocols and published manuscripts often did not reflect the varied strategies employed and adapted through the duration of study.
+Appropriate retention strategy use requires cultural sensitivity and more research is needed to identify how strategy use varies globally.
+The cross-species transmission of viruses from one host species to another is responsible for the majority of emerging infections.
+However, it is unclear whether some virus families have a greater propensity to jump host species than others.
+If related viruses have an evolutionary history of co-divergence with their hosts there should be evidence of topological similarities between the virus and host phylogenetic trees, whereas host jumping generates incongruent tree topologies.
+By analyzing co-phylogenetic processes in 19 virus families and their eukaryotic hosts we provide a quantitative and comparative estimate of the relative frequency of virus-host co-divergence versus cross-species transmission among virus families.
+Notably, our analysis reveals that cross-species transmission is a near universal feature of the viruses analyzed here, with virus-host co-divergence occurring less frequently and always on a subset of viruses.
+Despite the overall high topological incongruence among virus and host phylogenies, the Hepadnaviridae, Polyomaviridae, Poxviridae, Papillomaviridae and Adenoviridae, all of which possess double-stranded DNA genomes, exhibited more frequent co-divergence than the other virus families studied here.
+At the other extreme, the virus and host trees for all the RNA viruses studied here, particularly the Rhabdoviridae and the Picornaviridae, displayed high levels of topological incongruence, indicative of frequent host switching.
+Overall, we show that cross-species transmission plays a major role in virus evolution, with all the virus families studied here having the potential to jump host species, and that increased sampling will likely reveal more instances of host jumping.
+The recent growth in publicly available sequence data has introduced new opportunities for studying microbial evolution and spread.
+Because the pace of sequence accumulation tends to exceed the pace of experimental studies of protein function and the roles of individual amino acids, statistical tools to identify meaningful patterns in protein diversity are essential.
+Large sequence alignments from fast-evolving micro-organisms are particularly challenging to dissect using standard tools from phylogenetics and multivariate statistics because biologically relevant functional signals are easily masked by neutral variation and noise.
+To meet this need, a novel computational method is introduced that is easily executed in parallel using a cluster environment and can handle thousands of sequences with minimal subjective input from the user.
+The usefulness of this kind of machine learning is demonstrated by applying it to nearly 5000 haemagglutinin sequences of influenza A/H3N2.Antigenic and 3D structural mapping of the results show that the method can recover the major jumps in antigenic phenotype that occurred between 1968 and 2013 and identify specific amino acids associated with these changes.
+The method is expected to provide a useful tool to uncover patterns of protein evolution.
+BACKGROUND: In a new influenza pandemic, travel data such as arrival times of cases seeded by the originating country can be regarded as a combination of the epidemic size and the mobility networks of infections connecting the originating country with other regions.
+It can be a complete and timely source for estimating the basic reproduction number (R (0)), a key indicator of disease transmissibility.
+METHOD: In this study, we developed a likelihood-based method using arrival times of infected cases in different countries to estimate R (0) for influenza pandemics.
+We further applied the method to the outbreak of the influenza pandemic A/H1N1 in Mexico.
+RESULTS: In the numerical application, the estimated R (0) was equal to 1.69 with a 95% confidence interval (1.65, 1.73).
+For the simulation results, the estimations were robust to the decline of travel rate and other parameter assumptions.
+CONCLUSIONS: Our approach as well as the estimate is potential to assist officials in planning control and prevention measures.
+Improved coordination to streamline or even centralize surveillance of imported cases among countries will thus be beneficial to public health.
+INTRODUCTION: Mathematical models and field data suggest that human mobility is an important driver for Dengue virus transmission.
+Nonetheless little is known on this matter due the lack of instruments for precise mobility quantification and study design difficulties.
+MATERIALS AND METHODS: We carried out a cohort-nested, case-control study with 126 individuals (42 cases, 42 intradomestic controls and 42 population controls) with the goal of describing human mobility patterns of recently Dengue virus-infected subjects, and comparing them with those of non-infected subjects living in an urban endemic locality.
+Mobility was quantified using a GPS-data logger registering waypoints at 60-second intervals for a minimum of 15 natural days.
+RESULTS: Although absolute displacement was highly biased towards the intradomestic and peridomestic areas, occasional displacements exceeding a 100-Km radius from the center of the studied locality were recorded for all three study groups and individual displacements were recorded traveling across six states from central Mexico.
+Additionally, cases had a larger number of visits out of the municipality´s administrative limits when compared to intradomestic controls (cases: 10.4 versus intradomestic controls: 2.9, p = 0.0282).
+We were able to identify extradomestic places within and out of the locality that were independently visited by apparently non-related infected subjects, consistent with houses, working and leisure places.
+CONCLUSIONS: Results of this study show that human mobility in a small urban setting exceeded that considered by local health authority’s administrative limits, and was different between recently infected and non-infected subjects living in the same household.
+These observations provide important insights about the role that human mobility may have in Dengue virus transmission and persistence across endemic geographic areas that need to be taken into account when planning preventive and control measures.
+Finally, these results are a valuable reference when setting the parameters for future mathematical modeling studies.
+The recent emergence of A(H7N9) avian influenza poses a significant challenge to public health in China and around the world; however, understanding of the transmission dynamics and progression of influenza A(H7N9) infection in domestic poultry, as well as spillover transmission to humans, remains limited.
+Here, we develop a mathematical model–Bayesian inference system which combines a simple epidemic model and data assimilation method, and use it in conjunction with data on observed human influenza A(H7N9) cases from 19 February 2013 to 19 September 2015 to estimate key epidemiological parameters and to forecast infection in both poultry and humans.
+Our findings indicate a high outbreak attack rate of 33% among poultry but a low rate of chicken-to-human spillover transmission.
+In addition, we generated accurate forecasts of the peak timing and magnitude of human influenza A(H7N9) cases.
+This work demonstrates that transmission dynamics within an avian reservoir can be estimated and that real-time forecast of spillover avian influenza in humans is possible.
+Within the last two decades, the incidence of invasive fungal infections has been significantly increased.
+They are characterized by high mortality rates and are often caused by Candida albicans and Aspergillus fumigatus.
+The increasing number of infections underlines the necessity for additional anti-fungal therapies, which require extended knowledge of gene regulations during fungal infection.
+By analyzing their regulation and impact on target genes, novel therapeutic and diagnostic approaches may be developed.
+By applying next-generation sequencing of small RNAs, we quantify microRNA expression in monocyte-derived dendritic cells after 6 and 12 h of infection with C. albicans and A. fumigatus as well as treatment with lipopolysaccharides (LPS).
+We identified 26 microRNAs that are differentially regulated after infection by the fungi or LPS.
+Three and five of them are specific for fungal infections after 6 and 12 h, respectively.
+We further validated interactions of miR-132-5p and miR-212-5p with immunological relevant target genes, such as FKBP1B, KLF4, and SPN, on both RNA and protein level.
+Our results indicate that these microRNAs fine-tune the expression of immune-related target genes during fungal infection.
+A comparison with known microRNAs revealed possible relations with the miR-378 family and miR-1260a/b for two of them, while the third one features a unique sequence with no resemblance to known microRNAs.
+In summary, this study analyzes the effect of known microRNAs in dendritic cells during fungal infections and proposes novel microRNAs that could be experimentally verified.
+A number scales have been developed to measure conspiracist ideation, but little attention has been paid to the factorial validity of these scales.
+We reassessed the psychometric properties of four widely-used scales, namely the Belief in Conspiracy Theories Inventory (BCTI), the Conspiracy Mentality Questionnaire (CMQ), the Generic Conspiracist Beliefs Scale (GCBS), and the One-Item Conspiracy Measure (OICM).
+Eight-hundred-and-three U.S. adults completed all measures, along with measures of endorsement of 9/11 and anti-vaccination conspiracy theories.
+Through both exploratory and confirmatory factor analysis, we found that only the BCTI had acceptable factorial validity.
+We failed to confirm the factor structures of the CMQ and the GBCS, suggesting these measures had poor factorial validity.
+Indices of convergent validity were acceptable for the BCTI, but weaker for the other measures.
+Based on these findings, we provide suggestions for the future refinement in the measurement of conspiracist ideation.
+Many of these arboviruses, such as West Nile, dengue, and Zika viruses, infect humans by way of a bite from an infected mosquito.
+This infectious inoculum is insect cell-derived giving the virus particles distinct qualities not present in secondary infectious virus particles produced by infected vertebrate host cells.
+The insect cell-derived particles differ in the glycosylation of virus structural proteins and the lipid content of the envelope, as well as their induction of cytokines.
+Thus, in order to accurately mimic the inoculum delivered by arthropods, arboviruses should be derived from arthropod cells.
+Previous studies have packaged replicon genome in mammalian cells to produce replicon particles, which undergo only one round of infection, but no studies exist packaging replicon particles in mosquito cells.
+Here we optimized the packaging of West Nile virus replicon genome in mosquito cells and produced replicon particles at high concentration, allowing us to mimic mosquito cell-derived viral inoculum.
+Both replicon particles infected skin at the inoculation site and the draining lymph node by 3 hours post-inoculation.
+The mammalian cell-derived replicon particles spread from the site of inoculation to the spleen and contralateral lymph nodes significantly more than the particles derived from mosquito cells.
+This in vivo difference in spread of West Nile replicons in the inoculum demonstrates the importance of using arthropod cell-derived particles to model early events in arboviral infection and highlights the value of these novel arthropod cell-derived replicon particles for studying the earliest virus-host interactions for arboviruses.
+Emergence and intercontinental spread of highly pathogenic avian influenza A(H5Nx) virus clade 2.3.4.4 is unprecedented.
+H5N8 and H5N2 viruses have caused major economic losses in the poultry industry in Europe and North America, and lethal human infections with H5N6 virus have occurred in Asia.
+Knowledge of the evolution of receptor-binding specificity of these viruses, which might affect host range, is urgently needed.
+We report that emergence of these viruses is accompanied by a change in receptor-binding specificity.
+In contrast to ancestral clade 2.3.4 H5 proteins, novel clade 2.3.4.4 H5 proteins bind to fucosylated sialosides because of substitutions K222Q and S227R, which are unique for highly pathogenic influenza virus H5 proteins.
+North American clade 2.3.4.4 virus isolates have retained only the K222Q substitution but still bind fucosylated sialosides.
+Altered receptor-binding specificity of virus clade 2.3.4.4 H5 proteins might have contributed to emergence and spread of H5Nx viruses.
+Japanese encephalitis virus (JEV) is the most prevalent cause of viral encephalitis in Asia and the western Pacific.
+Neuronal death caused by JEV infection and inflammation induced cytotoxicity leads to progression and deterioration of Japanese encephalitis (JE).
+Mixed-lineage kinase domain-like protein (MLKL) mediated necroptosis is a newly discovered pathway of programmed cell death and participates in many inflammatory diseases.
+In this study, we demonstrated for the first time that necroptosis was involved in the neuronal loss during JE via immune-electron microscopy and immunochemistry.
+The expression of MLKL in neurons was upregulated in presence of JEV infection in vitro and in vivo.
+Deletion of MLKL alleviated the progression of JE and decreased the level of inflammatory cytokines in mice model.
+Taken together, this study provides evidence for the participation of necroptosis in the pathogenesis of JEV infection.
+The unprecedented impact and modeling efforts associated with the 2014–2015 Ebola epidemic in West Africa provides a unique opportunity to document the performances and caveats of forecasting approaches used in near-real time for generating evidence and to guide policy.
+A number of international academic groups have developed and parameterized mathematical models of disease spread to forecast the trajectory of the outbreak.
+These modeling efforts often relied on limited epidemiological data to derive key transmission and severity parameters, which are needed to calibrate mechanistic models.
+Here, we provide a perspective on some of the challenges and lessons drawn from these efforts, focusing on (1) data availability and accuracy of early forecasts; (2) the ability of different models to capture the profile of early growth dynamics in local outbreaks and the importance of reactive behavior changes and case clustering; (3) challenges in forecasting the long-term epidemic impact very early in the outbreak; and (4) ways to move forward.
+We conclude that rapid availability of aggregated population-level data and detailed information on a subset of transmission chains is crucial to characterize transmission patterns, while ensemble-forecasting approaches could limit the uncertainty of any individual model.
+We believe that coordinated forecasting efforts, combined with rapid dissemination of disease predictions and underlying epidemiological data in shared online platforms, will be critical in optimizing the response to current and future infectious disease emergencies.
+Malnutrition affects millions of children in developing countries, compromising immunity and contributing to increased rates of death from infectious diseases.
+Rotavirus is a major etiological agent of childhood diarrhea in developing countries, where malnutrition is prevalent.
+However, the interactions between the two and their combined effects on immune and intestinal functions are poorly understood.
+In this study, we used neonatal gnotobiotic (Gn) pigs transplanted with the fecal microbiota of a healthy 2-month-old infant (HIFM) and fed protein-deficient or -sufficient bovine milk diets.
+Protein deficiency induced hypoproteinemia, hypoalbuminemia, hypoglycemia, stunting, and generalized edema in Gn pigs, as observed in protein-malnourished children.
+Irrespective of the diet, human rotavirus (HRV) infection early, at HIFM posttransplantation day 3 (PTD3), resulted in adverse health effects and higher mortality rates (45 to 75%) than later HRV infection (PTD10).
+Protein malnutrition exacerbated HRV infection and affected the morphology and function of the small intestinal epithelial barrier.
+In pigs infected with HRV at PTD10, there was a uniform decrease in the function and/or frequencies of natural killer cells, plasmacytoid dendritic cells, and CD103(+) and apoptotic mononuclear cells and altered gene expression profiles of intestinal epithelial cells (chromogranin A, mucin 2, proliferating cell nuclear antigen, SRY-Box 9, and villin).
+Thus, we have established the first HIFM-transplanted neonatal pig model that recapitulates major aspects of protein malnutrition in children and can be used to evaluate physiologically relevant interventions.
+Our findings provide an explanation of why nutrient-rich diets alone may lack efficacy in malnourished children.
+IMPORTANCE Malnutrition and rotavirus infection, prevalent in developing countries, individually and in combination, affect the health of millions of children, compromising their immunity and increasing the rates of death from infectious diseases.
+However, the interactions between the two and their combined effects on immune and intestinal functions are poorly understood.
+We have established the first human infant microbiota-transplanted neonatal pig model of childhood malnutrition that reproduced the impaired immune, intestinal, and other physiological functions seen in malnourished children.
+Our findings provide an explanation of why adequate nutrition alone may lack efficacy in malnourished children.
+Bats belong to the order Chiroptera that represents the second largest order of mammals with more than 1200 species and an almost global distribution.
+Environmental changes and deforestation have severely influenced many ecosystems, intensifying the contact between wildlife and humans.
+In recent years, bats have been found to harbor a number of different viruses with zoonotic potential, as well as a great diversity of astroviruses, for which the question of zoonotic potential remains unanswered to date.
+Human astroviruses have been identified as the causative agent for diarrhea in children and immunocompromised patients.
+However, a great genetic diversity has recently been discovered among animal and human astroviruses that might indicate the potential of these viruses to cross species barriers.
+Furthermore, our knowledge about the tissue tropism of astroviruses has been expanded to some neurotropic strains that have recently been shown to be responsible for encephalitis in humans and livestock.
+This review gives an overview on what is known about astroviruses in bats, humans and livestock, especially bovines and pigs.
+Future research activities are suggested to unravel astrovirus infection dynamics in bat populations to further assess the zoonotic potential of these viruses.
+Given the rapid rate of global spread and consequently healthcare costs related to influenza, surveillance plays an important role in monitoring the emerging pandemics in China.
+Our study use the surveillance data collected from 16 sentinel hospitals across Zhejiang Province during March 2011 through June 2015, including the demographic information and respiratory specimens from influenza-like illness (ILI) patients and severe acute respiratory illness (SARI) patients.
+As analysis results, most SARI and ILI patients were in the age group of 0–4 years old (62.38% of ILI and 71.54% of SARI).
+The respiratory specimens have statistically significantly higher positive rate for influenza among ILI patients than that among SARI patients (p < 0.001).
+The comparison between ILI patients and SARI patients shows no statistically significantly difference in detecting influenza virus type and influenza A virus subtype.
+The SARI and ILI patients were found to be positively correlated for overall positive rate (r = 0.63, p < 0.001), the weekly percentage of A(H1N1)pdm09 (r = 0.51, p < 0.001), influenza B virus (r = 0.17, p = 0.013), and A/H3N2 (r = 0.43, p < 0.001) among all the positive numbers.
+Our study demonstrated that the activities of influenza virus, including its subtypes, had a similar temporal pattern between ILI and SARI cases.
+Turnip crinkle virus contains a T-shaped, ribosome-binding, translation enhancer (TSS) in its 3’UTR that serves as a hub for interactions throughout the region.
+The viral RNA-dependent RNA polymerase (RdRp) causes the TSS/surrounding region to undergo a conformational shift postulated to inhibit translation.
+Using optical tweezers (OT) and steered molecular dynamic simulations (SMD), we found that the unusual stability of pseudoknotted element H4a/Ψ(3) required five upstream adenylates, and H4a/Ψ(3) was necessary for cooperative association of two other hairpins (H5/H4b) in Mg(2+).
+SMD recapitulated the TSS unfolding order in the absence of Mg(2+), showed dependence of the resistance to pulling on the 3D orientation and gave structural insights into the measured contour lengths of the TSS structure elements.
+Adenylate mutations eliminated one-site RdRp binding to the 3’UTR, suggesting that RdRp binding to the adenylates disrupts H4a/Ψ(3), leading to loss of H5/H4b interaction and promoting a conformational switch interrupting translation and promoting replication.
+Interleukin 6 (IL-6) is involved in innate and adaptive immune responses to defend against pathogens.
+It also participates in the process of influenza infection by affecting viral clearance and immune cell responses.
+IL-6-deficient mice infected with influenza virus exhibited higher lethality, lost more body weight and had higher fibroblast accumulation and lower extracellular matrix (ECM) turnover in the lung than their wild-type counterparts.
+Deficiency in IL-6 enhanced proliferation, migration and survival of lung fibroblasts, as well as increased virus-induced apoptosis of lung epithelial cells.
+Furthermore, macrophage recruitment to the lung and phagocytic activities of macrophages during influenza infection were reduced in IL-6-deficient mice.
+Collectively, our results indicate that IL-6 is crucial for lung repair after influenza-induced lung injury through reducing fibroblast accumulation, promoting epithelial cell survival, increasing macrophage recruitment to the lung and enhancing phagocytosis of viruses by macrophages.
+Error-free replication and repair of DNA are pivotal to organisms for faithful transmission of their genetic information.
+Post-translational protein modifications by ubiquitin and ubiquitin-like proteins, including SUMO and NEDD8, are critically involved in DNA damage response (DDR) and DNA damage tolerance (DDT).
+The expression of interferon-stimulated gene 15 (ISG15), the first identified ubiquitin-like protein, has recently been shown to be induced under various DNA damage conditions, such as exposure to UV, camptothecin, and doxorubicin.
+Here we overview the recent findings on the role of ISG15 and its conjugation to target proteins (e.g., p53, ΔNp63α, and PCNA) in the control of cellular responses to genotoxic stress, such as the inhibition of cell growth and tumorigenesis.
+BACKGROUND: Human adenovirus 7 (HAdV-7) was responsible for a significant number of fatalities during the 2011 community outbreak in Taiwan.
+Adenovirus pneumonia was associated with pleural effusion in a number of patients from the 2011 outbreak suggesting that similar to bacterial pneumonia, patients diagnosed with adenovirus pneumonia who have pleural effusion are more severely and systemically infected, and may have a more protracted disease course.
+METHODS: This retrospective case series study included patients diagnosed with severe lower respiratory tract infections at the National Cheng Kung University Hospital in southern Taiwan between December 2010 and October 2011.
+The main inclusion criteria were 1) presence of multifocal patchy infiltrates, lobar consolidation or reticular interstitial opacities in chest X-rays, and 2) presence of adenovirus isolated from respiratory specimens.
+Clinical features and laboratory data were compared in patients with (n = 12) and without (n = 15) parapneumonic effusion.
+RESULTS: Presence of parapneumonic effusion was significantly associated with a longer febrile duration, more complicated clinical management, and a greater risk of extrapulmonary involvement, notably hepatitis.
+Patients without pleural effusion had significantly higher numbers of WBCs, platelets, and absolute segment cell counts (ASCs) compared to patients with pleural effusion (all p < 0.05).
+Patients without pleural effusion had significantly higher counts of CD4+, CD8+, and CD20+ T cells (all p < 0.05) compared to patients with pleural effusion.
+CONCLUSION: Our data indicated that presence of parapneumonic effusion in adenoviral pneumonia was associated with longer febrile duration, more complicated clinical management, a greater risk of hepatitis, and suppression of host cellular immunity.
+The porcine reproductive and respiratory syndrome (PRRS) is a devastating viral disease affecting swine production, health and welfare throughout the world.
+A synergistic action of the innate and the adaptive immune system of the host is essential for mounting a durable protective immunity through vaccination.
+Therefore, the current study aimed to investigate the transcriptome profiles of peripheral blood mononuclear cells (PBMCs) to characterize the innate and the adaptive immune response to PRRS Virus (PRRSV) vaccination in Pietrain pigs.
+The Affymetrix gene chip porcine gene 1.0 ST array was used for the transcriptome profiling of PBMCs collected at immediately before (D0), at one (D1) and 28 days (D28) post PRRSV vaccination with three biological replications.
+With FDR <0.05 and log2 fold change ±1.5 as cutoff criteria, 295 and 115 transcripts were found to be differentially expressed in PBMCs during the stage of innate and adaptive response, respectively.
+The gene ontology terms such as viral life cycle, regulation of lymphocyte activation, cytokine activity and inflammatory response were enriched during the innate immunity; cytolysis, T cell mediated cytotoxicity, immunoglobulin production were enriched during adaptive immunity to PRRSV vaccination.
+Significant enrichment of cytokine-cytokine receptor interaction, signaling by interleukins, signaling by the B cell receptor (BCR), viral mRNA translation, IFN-gamma pathway and AP-1 transcription factor network pathways were indicating the involvement of altered genes in the antiviral defense.
+Network analysis revealed that four network modules were functionally involved with the transcriptional network of innate immunity, and five modules were linked to adaptive immunity in PBMCs.
+The innate immune transcriptional network was found to be regulated by LCK, STAT3, ATP5B, UBB and RSP17.
+While TGFß1, IL7R, RAD21, SP1 and GZMB are likely to be predictive for the adaptive immune transcriptional response to PRRSV vaccine in PBMCs.
+Results of the current immunogenomics study advances our understanding of PRRS in term of host-vaccine interaction, and thereby contribute to design a rationale for disease control strategy.
+BACKGROUND: Despite increased efforts to control and ultimately eradicate human malaria, Plasmodium ovale malaria is for the most part outside the focus of research or public health programmes.
+Importantly, the understanding of P. ovale—nowadays regarded as the two distinct species P. ovale wallikeri and P. ovale curtisi���largely stems from case reports and case series lacking study designs providing high quality evidence.
+Consecutively, there is a lack of systematic evaluation of the clinical presentation, appropriate treatment and relapse characteristics of P. ovale malaria.
+The aim of this systematic review is to provide a systematic appraisal of the current evidence for severe manifestations, relapse characteristics and treatment options for human P. ovale malaria.
+METHODS AND RESULTS: This systematic review was performed according to the PRISMA guidelines and registered in the international prospective register for systematic reviews (PROSPERO 2016:CRD42016039214).
+Of 3454 articles identified by the literature search, 33 articles published between 1922 and 2015 met the inclusion criteria.
+P. ovale was sensitive to all tested drugs within the follow-up periods and on interpretable in vitro assays.
+Since its first description in 1922, only 18 relapsing cases of P. ovale with a total of 28 relapse events were identified in the scientific literature.
+There was however no molecular evidence for a causal relationship between dormant liver stages and subsequent relapses.
+A total of 22 severe cases of P. ovale malaria were published out of which five were fatal.
+CONCLUSIONS: Current knowledge of P. ovale malaria is based on small trials with minor impact, case reports and clinical observations.
+This systematic review highlights that P. ovale is capable of causing severe disease, severe congenital malaria and may even lead to death.
+Evidence for relapses in patients with P. ovale malaria adds up to only a handful of cases.
+Nearly 100 years after P. ovale’s first description by Stephens the evidence for the clinical characteristics, relapse potential and optimal treatments for P. ovale malaria is still scarce.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12936-017-1759-2) contains supplementary material, which is available to authorized users.
+The insulin-like growth factor-1 receptor (IGF-1R) overexpression contributes to the development of a variety of cancers.
+The present study explored the role of IGF-1R in the development and progression of hepatocellular carcinoma (HCC) and the possibility of IGF-1R silencing by lentivirus-mediated RNA interference (RNAi) as a therapeutic target for HCC.
+We showed that IGF-1R mRNA was up-regulated in Huh7 and Hep3B cells and human HCC tissues, and that IGF-1R knockdown by RNAi led to decreased proliferation, apoptosis induction, and decreased migration and invasion of Huh7 and Hep3B cells.
+Further, the in vivo study indicated that IGF-1R knockdown markedly diminished the tumorigenesis and metastasis of Huh7 xenograft.
+Moreover, the intratumoral administration of lentivirus-IGF-1R siRNA led to significant tumor growth inhibition in an established Huh7 xenograft model.
+Mechanistic investigations showed that midkine was found to be the most significantly down-regulated protein in Huh7 cells with IGF-1R knockdown, and ectopic overexpression of midkine significantly rescued inhibition of Huh7 cell proliferation, migration, and invasion caused by IGF-1R suppression.
+Collectively, these data suggest that IGF-1R inhibition by RNAi can significantly suppress HCC growth and invasion at least partially through down-regulating midkine expression, and IGF-1R is a potential target for HCC gene therapy.
+Homo sapiens harbor two distinct, medically significant species of simplexviruses, herpes simplex virus (HSV)-1 and HSV-2, with estimated divergence 6–8 million years ago (MYA).
+Unexpectedly, we found that circulating HSV-2 strains can contain HSV-1 DNA segments in three distinct genes.
+Using over 150 genital swabs from North and South America and Africa, we detected recombinants worldwide.
+Common, widely distributed gene UL39 genotypes are parsimoniously explained by an initial >457 basepair (bp) HSV-1 × HSV-2 crossover followed by back-recombination to HSV-2.
+Blocks of >244 and >539 bp of HSV-1 DNA within genes UL29 and UL30, respectively, have reached near fixation, with a minority of strains retaining sequences we posit as ancestral HSV-2.
+Our data add to previous in vitro and animal work, implying that in vivo cellular co-infection with HSV-1 and HSV-2 yields viable interspecies recombinants in the natural human host.
+The calicivirus Rabbit haemorrhagic disease virus (RHDV) is widely used in Australia as a biocontrol agent to manage wild European rabbit (Oryctolagus cuniculus) populations.
+To overcome this, we developed an experimental platform for the selection and characterisation of novel RHDV strains.
+As RHDV does not replicate in cell culture, variant viruses were selected by serially passaging a highly virulent RHDV field isolate in immunologically naïve laboratory rabbits that were passively immunised 18–24 hours post-challenge with a neutralising monoclonal antibody.
+After seven passages, two amino acid substitutions in the P2 domain of the capsid protein became fixed within the virus population.
+Furthermore, a synonymous substitution within the coding sequence of the viral polymerase appeared and was also maintained in all subsequent passages.
+These findings demonstrate proof-of-concept that RHDV evolution can be experimentally manipulated to select for virus variants with altered phenotypes, in this case partial immune escape.
+Individuals change their behavior during an epidemic in response to whether they and/or those they interact with are healthy or sick.
+This paper proposes a stochastic network disease game model that captures the self-interests of individuals during the spread of a susceptible-infected-susceptible disease.
+We show that there is a critical level of concern, i.e., empathy, by the sick individuals above which disease is eradicated rapidly.
+Furthermore, we find that risk averse behavior by the healthy individuals cannot eradicate the disease without the preemptive measures of the sick individuals.
+Empathy is more effective than risk-aversion because when infectious individuals change behavior, they reduce all of their potential infections, whereas when healthy individuals change behavior, they reduce only a small portion of potential infections.
+This imbalance in the role played by the response of the infected versus the susceptible individuals on disease eradication affords critical policy insights.
+Lysophosphatidic acid (LPA), a naturally occurring bioactive phospholipid, activates G protein-coupled receptors (GPCRs), leading to regulation of diverse cellular events including cell survival and apoptosis.
+Despite extensive studies of the signaling pathways that mediate LPA-regulated cell growth and survival, the mechanisms underlying the apoptotic effect of LPA remain largely unclear.
+Our data demonstrate that LPA induces apoptosis in HeLa cells at pathologic concentrations with a concomitant upregulation of the expression of TNFRSF21 (tumor necrosis factor receptor superfamily member 21), also known as death receptor number 6 (DR6) involved in inflammation.
+Moreover, treatment of cells with LPA receptor (LPAR) antagonist abolished the DR6 upregulation by LPA.
+LPA-induced DR6 expression was also abrogated by pertussis toxin (PTX), an inhibitor of GPCRs, and by inhibitors of PI3K, PKC, MEK, and ERK.
+These results suggest that activation of the MEK/ERK pathway and the transcription factor CREB mediate LPA-induced DR6 expression.
+In conclusion, our results suggest that LPA-induced apoptosis in HeLa cells is mediated by the upregulation of DR6 expression.
+AIM: To estimate the pharyngeal carriage rate of Neisseria meningitidis (N. meningitidis), Streptococcus pneumoniae (S. pneumoniae) and Staphylococcus aureus (S. aureus) among Australian Hajj pilgrims.
+METHODS: In 2014, surveillance was conducted in two phases among Australian Hajj pilgrims: The first phase during Hajj in Mina, and the second phase soon after returning home to Australia.
+Nasopharyngeal or oropharyngeal swabs were taken from participants then tested, firstly by nucleic acid testing, and also by standard culture.
+RESULTS: Of 183 participants recruited in the first phase, 26 (14.2%) tested positive for S. pneumoniae; 4 had received pneumococcal conjugate vaccine (PCV13).
+Of 93 2(nd) phase samples cultured, 17 (18.3%) grew S. aureus, all methicillin sensitive, 2 (2.2%) grew N. meningitidis (on subculture; one serotype B, one negative), and 1 (1%), from an unvaccinated pilgrim, grew S. pneumoniae.
+This indicates the importance of a larger study for improved infection surveillance and possible vaccine evaluation.
+OBJECTIVE: To assess the effects of winter/summer school breaks on occurrences of influenza-like illness (ILI).
+METHODS: We jointly analysed ILI surveillance data with the timing of school breaks in a temperate district in Beijing, China from 2008 to 2015.
+ILI incidence rate ratios (IRRs) of schoolchildren (5–14 and 15–24 years of age) to adults (25–59 and >60 years of age) were used to measure the age shift of ILI incidence before, during and after the 4-week winter/7-week summer breaks.
+Serfling-based Poisson regression model with adjustment for unmeasured confounders was built to further assess the effect of winter school breaks.
+RESULTS: ILI incidences were consistently lower during winter breaks than before winter breaks for all age groups.
+IRRs of younger schoolchildren aged 5–14 to adults were higher during winter school breaks than before breaks, while the opposite was true for the IRRs of older schoolchildren aged 15–24 to adults.
+Schoolchildren-to-adults IRRs during summer breaks were significantly lower than before or after school breaks (p<0.001).
+CONCLUSIONS: Both winter and summer breaks were associated with reductions of ILI incidences among schoolchildren and adults.
+Our study contributes additional evidence on the effects of school breaks on ILI incidence, suggesting school closure could be effective in controlling influenza transmission in developing countries.
+The study of microbe infections has always been a very effective approach to unveil and dissect cellular pathways.
+Although some of the breakthrough discoveries in the field were obtained using yeast, pathogens have been and still are a great tool to discover and characterize new molecular and functional aspects of autophagy.
+Research on pathogens has helped to acquire knowledge about selective types of autophagy and the assembly of the autophagy machinery, i.e the autophagy-related (ATG) proteins, but also about alternative cellular roles of this pathway, such as secretion.
+Finally, microbes have also served to discover and characterize unconventional functions of the ATG proteins, which are uncoupled from their role in autophagy.
+In our recent study, we have taken advantage of viruses as a screening tool to determine the extent of the unconventional functions of the ATG proteome and characterize one of them.
+OBJECTIVE: This study was conducted to assess the correlation between central venous pressure (CVP) and venous blood gas (VBG) analysis parameters, to facilitate management of severe sepsis and septic shock in emergency department.
+MATERIAL AND METHODS: This diagnostic study was conducted from January 2014 until June 2015 in three major educational medical centers, Tehran, Iran.
+For patients selected with diagnosis of septic shock, peripheral blood sample was taken for testing the VBG parameters and the anion gap (AG) was calculated.
+All the mentioned parameters were measured again after infusion of 500 cc of normal saline 0.9% in about 1 h. RESULTS: Totally, 93 patients with septic shock were enrolled, 63 male and 30 female.
+The mean age was 72.53 ± 13.03 and the mean Shock Index (SI) before fluid therapy was 0.79 ± 0.30.
+AG and pH showed significant negative correlations with CVP, While HCO3 showed a significant positive correlation with CVP.
+These relations can be affected by the treatment modalities used in shock management such as fluid therapy, mechanical ventilation and vasopressor treatment.
+CONCLUSION: It is likely that there is a significant statistical correlation between VBG parameters and AG with CVP, but further research is needed before implementation of the results of this study.
+Here we performed epigenome-wide screening and validation to identify mortality-related DNAm signatures in a general population-based cohort with up to 14 years follow-up.
+58 CpGs, mapping to 38 well-known disease-related genes and 14 intergenic regions, are confirmed in a validation panel.
+A mortality risk score based on ten selected CpGs exhibits strong association with all-cause mortality, showing hazard ratios (95% CI) of 2.16 (1.10–4.24), 3.42 (1.81–6.46) and 7.36 (3.69–14.68), respectively, for participants with scores of 1, 2–5 and 5+ compared with a score of 0.
+These associations are confirmed in an independent cohort and are independent from the ‘epigenetic clock'.
+Considering the fatal human victims and economic loss caused by influenza virus infection every year, methodologies for rapid and on-site detection of influenza viruses are urgently needed.
+LAMP is the most commonly used nucleic acid isothermal amplification technology suitable for on-site use.
+However, for multiplex LAMP, differentiation of the amplicons derived from multiple targets is still challengeable currently.
+Here we developed a multiplex RT-LAMP assay for simultaneous amplification of three prominent subtypes of influenza viruses (A/H5, A/H7 and 2009A/H1).
+The amplicons were further identified by cascade invasive reaction and nanoparticle hybridization in separate target-specific detection tubes (referred to as mRT-LAMP-IRNH).
+The analytic sensitivities of the assay are 10 copies of RNA for all the three HA subtypes, and the specificity reached 100%.
+Clinical specimen analysis showed this assay had a combined sensitivity and specificity of 98.1% and 100%, respectively.
+Overall, the mRT-LAMP-IRNH assay can be used as a cost-saving method that utilizes a simple instrument to detect A/H5, A/H7, and 2009A/H1 influenza viruses, especially in resource-limited settings.
+Biliary atresia (BA) is a neonatal obstructive cholangiopathy which progresses to end stage liver disease, often requiring transplantation.
+The murine model of BA, employing rhesus rotavirus (RRV), parallels human disease and has been used to elucidate mechanistic aspects of a virus induced biliary cholangiopathy.
+We previously reported that RRV VP4 gene plays an integral role in activating the immune system and induction of BA.
+Utilizing rotavirus binding and blocking assays, this study elucidated how RRV VP4 protein governs cholangiocyte susceptibility to infection both in vitro and in vivo in the murine model of BA.
+We identified the amino acid sequence on VP4 and its cholangiocyte binding protein, finding that the sequence is specific to those rotavirus strains which cause an obstructive cholangiopathy.
+Pretreatment of murine and human cholangiocytes with this VP4 derived peptide (TRTRVSRLY), significantly reduced RRV’s ability to bind and infect the cells.
+However, the peptide did not block cholangiocyte binding of TUCH and Ro1845, strains which do not induce murine BA.
+This virus-cholangiocyte interaction is also seen in vivo in the murine model of BA, where inoculation of mice with TRTRVSRLY peptide significantly reduced symptoms and mortality in RRV-injected mice.
+CONCLUSION: The tri-peptide SRL on RRV VP4 binds to the cholangiocyte membrane protein Hsc70 defining a novel binding site governing VP4 attachment.
+Investigations are underway to determine the cellular response following this interaction to understand how it contributes to the pathogenesis of BA.
+Infection of respiratory mucosa with viral pathogens triggers complex immunologic events in the affected host.
+We sought to characterize this response through proteomic analysis of nasopharyngeal lavage in human subjects experimentally challenged with influenza A/H3N2 or human rhinovirus, and to develop targeted assays measuring peptides involved in this host response allowing classification of acute respiratory virus infection.
+Unbiased proteomic discovery analysis identified 3285 peptides corresponding to 438 unique proteins, and revealed that infection with H3N2 induces significant alterations in protein expression.
+These include proteins involved in acute inflammatory response, innate immune response, and the complement cascade.
+These data provide insights into the nature of the biological response to viral infection of the upper respiratory tract, and the proteins that are dysregulated by viral infection form the basis of signature that accurately classifies the infected state.
+Verification of this signature using targeted mass spectrometry in independent cohorts of subjects challenged with influenza or rhinovirus demonstrates that it performs with high accuracy (0.8623 AUROC, 75% TPR, 97.46% TNR).
+With further development as a clinical diagnostic, this signature may have utility in rapid screening for emerging infections, avoidance of inappropriate antibacterial therapy, and more rapid implementation of appropriate therapeutic and public health strategies.
+Human paramyxoviruses include global causes of lower respiratory disease like the parainfluenza viruses, as well as agents of lethal encephalitis like Nipah virus.
+Paramyxovirus viral fusion proteins (F) insert into the target cell membrane, and form a transient intermediate that pulls the viral and cell membranes together as two heptad-repeat regions refold to form a six-helix bundle structure that can be specifically targeted by fusion-inhibitory peptides.
+Antiviral potency can be improved by sequence modification and lipid conjugation, and by adding linkers between the protein and lipid components.
+We exploit the uniquely broad spectrum antiviral activity of a parainfluenza F-derived peptide sequence that inhibits both parainfluenza and Nipah viruses, to investigate the influence of peptide orientation and intervening linker length on the peptides’ interaction with transitional states of F, solubility, membrane insertion kinetics, and protease sensitivity.
+We assessed the impact of these features on biodistribution and antiviral efficacy in vitro and in vivo.
+The engineering approach based on biophysical parameters resulted in a peptide that is a highly effective inhibitor of both paramyxoviruses and a set of criteria to be used for engineering broad spectrum antivirals for emerging paramyxoviruses.
+BACKGROUND: The nasopharyngeal (NP) microbiota plays an important role in bovine health, comprising a rich and diverse microbial community.
+The nasopharynx is also the niche for potentially pathogenic agents which are associated with bovine respiratory disease (BRD), a serious and costly illness in feedlot cattle.
+We used 14 beef heifers from a closed and disease-free herd to assess the dynamics of the NP microbiota of cattle that are transported to a feedlot.
+Cattle were sampled prior to transport to the feedlot (day 0) and at days 2, 7, and 14.
+RESULTS: The structure of the NP microbiota changed significantly over the course of the study, with the largest shift occurring between day 0 (prior to transport) and day 2 (P < 0.001).
+The genera Pasteurella, Bacillus, and Proteus were enriched at day 0, Streptococcus and Acinetobacter at day 2, Bifidobacterium at day 7, and Mycoplasma at day 14.
+The functional potential of the NP microbiota was assessed using PICRUSt, revealing that replication and repair, as well as translation pathways, were more relatively abundant in day 14 samples.
+Although eight cattle were culture-positive for the BRD-associated bacterium Pasteurella multocida at one or more sampling times, none were culture-positive for Mannheimia haemolytica or Histophilus somni.
+CONCLUSIONS: This study investigated the effect that feedlot placement has on the NP microbiota of beef cattle over a 14-d period.
+Within two days of transport to the feedlot, the NP microbiota changed significantly, increasing in both phylogenetic diversity and richness.
+These results demonstrate that there is an abrupt shift in the NP microbiota of cattle after transportation to a feedlot.
+This may have importance for understanding why cattle are most susceptible to BRD after feedlot placement.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12866-017-0978-6) contains supplementary material, which is available to authorized users.
+BACKGROUND: Zika virus (ZIKV) transmission has been reported in 67 countries/territories in the Oceania region and the Americas since 2015, prompting the World Health Organization (WHO) to declare ZIKV as a Public Health Emergency of International Concern in February 2016, due to its strong association with medical complications such as microcephaly and Guillain–Barré Syndrome (GBS).
+However, a substantial gap in knowledge still exists regarding differing temporal pattern and potential of transmission of ZIKV in different regions of the world.
+RESULTS: Six of these time series datasets resulted in statistically significant model fit of at least one wave of reported cases, namely that of French Polynesia, Colombia, Puerto Rico, Guatemala, Suriname and Saint Martin.
+However, only Colombia and Guatemala exhibited two waves of cases while the others had only one wave.
+Temporal patterns of the second wave in Colombia and the single wave in Suriname are very similar, with the respective turning points separated by merely a week.
+Moreover, the mean estimates of R(0) for Colombia, Guatemala and Suriname, all land-based populations, range between 1.05 and 1.75, while the corresponding mean estimates for R(0) of island populations in French Polynesia, Puerto Rico and Saint Martin are significantly lower with a range of 5.70–6.89.
+We also fit the Richards model to Zika case data from six main archipelagos in French Polynesia, suggesting the outbreak in all six island populations occurred during the same time, albeit with different peak time, with mean R(0) range of 3.09–5.05.
+DISCUSSION: Using the same modeling methodology, in this study we found a significant difference between transmissibility (as quantified by R(0)) in island populations as opposed to land-based countries/territories, possibly suggesting an important role of geographic heterogeneity in the spread of vector-borne diseases and its future course, which requires further monitoring.
+Our result has potential implications for planning respective intervention and control policies targeted for island and land-based populations.
+BACKGROUND: In recent years, global public health security has been threatened by zoonotic disease emergence as exemplified by outbreaks of H5N1 and H1N1 influenza, SARS, and most recently Ebola and Zika.
+Additionally, endemic zoonoses, such as rabies, burden countries year after year, placing demands on limited finances and personnel.
+To survey the baseline status of the emerging and endemic zoonoses programmes of the Latin American and the Caribbean (LAC) countries, the Pan American Health Organization (PAHO) conducted a survey of priority emerging and endemic zoonoses, countries´ prioritization criteria and methodologies, and suggestions to strengthen countries capacities and regional approaches to zoonoses control.
+METHODS: A fillable online questionnaire was sent to the zoonoses programme managers of the Ministries of Health (MOH) and Ministries of Agriculture (MAg) of 33 LAC countries from January to April of 2015.
+The questionnaire comprised 36 single, multiple choice and open-ended questions to inform the objectives of the survey.
+RESULTS: Fifty-four ministries (26 MOH, 25 MAg, and 3 combined responses) in 31 LAC countries responded to the survey.
+Within the ministries, 22 (85%) MOH, 5 (20%) MAg, and 2 (67%) combined entities indicated they had specialized zoonoses units.
+For endemic zoonoses, 32 of 54 ministries responded that they conduct formal prioritization exercises, most of them annually (69%).
+The three priority endemic zoonoses for the MOHs were leptospirosis, rabies, and brucellosis while the three priorities for the MAgs were brucellosis, rabies, and tuberculosis.
+Diagnosis for rabies and leptospirosis were cited as the capacities most in need of development.
+The three priority emerging zoonoses for the MOHs were Ebola viral disease, avian influenza, and Chikungunya while for the MAgs were avian influenza, bovine spongiform encephalopathy and West Nile virus disease.
+Surveillance for avian influenza and Ebola, and diagnosis for BSE were quoted as the capacities most needed.
+For all zoonoses, the majority of respondents (69%) ranked their relationship with the other Ministry as productive or very productive, and 31% minimally productive.
+Many countries requested a formal regional network, better regional communication and collaboration, and integrated surveillance.
+CONCLUSIONS: The survey is the first comprehensive effort to date to inform the status of zoonoses programmes in LAC.
+The information collected here will be used to develop a regional strategy for zoonoses (both endemic and emerging), increase efforts, advocacy, and promote prompt identification and management of EIDs and improvement of endemic programmes.
+Influenza A virus (IAV) membrane proteins hemagglutinin (HA) and neuraminidase (NA) are determinants of virus infectivity, transmissibility, pathogenicity, host specificity, and major antigenicity.
+HA binds to a virus receptor, a sialoglycoprotein or sialoglycolipid, on the host cell and mediates virus attachment to the cell surface.
+The hydrolytic enzyme NA cleaves sialic acid from viral receptors and accelerates the release of progeny virus from host cells.
+In this study, we identified a novel function of HA and NA as machinery for viral motility.
+HAs exchanged binding partner receptors iteratively, generating virus movement on a receptor-coated glass surface instead of a cell surface.
+Virus movement mediated by HA and NA resulted in a three to four-fold increase in virus internalisation by cultured cells.
+We concluded that cooperation of HA and NA moves IAV particles on a cell surface and enhances virus infection of host cells.
+Ebola virus (EBOV) is one of the lethal viruses, causing more than 24 epidemic outbreaks to date.
+Despite having available molecular knowledge of this virus, no definite vaccine or other remedial agents have been developed yet for the management and avoidance of EBOV infections in humans.
+Disclosing this, the present study described an epitope-based peptide vaccine against EBOV, using a combination of B-cell and T-cell epitope predictions, followed by molecular docking and molecular dynamics simulation approach.
+Here, protein sequences of all glycoproteins of EBOV were collected and examined via in silico methods to determine the most immunogenic protein.
+From the identified antigenic protein, the peptide region ranging from 186 to 220 and the sequence HKEGAFFLY from the positions of 154–162 were considered the most potential B-cell and T-cell epitopes, correspondingly.
+Moreover, this peptide (HKEGAFFLY) interacted with HLA-A*32:15 with the highest binding energy and stability, and also a good conservancy of 83.85% with maximum population coverage.
+The results imply that the designed epitopes could manifest vigorous enduring defensive immunity against EBOV.
+Since the development of antibody-production techniques, a number of immunoglobulins have been developed on a large scale using conventional methods.
+Hybridoma technology opened a new horizon in the production of antibodies against target antigens of infectious pathogens, malignant diseases including autoimmune disorders, and numerous potent toxins.
+Therefore, to overcome these difficulties, recent advances in genetic engineering techniques and phage display technique have allowed the production of highly specific recombinant antibodies.
+These engineered antibodies have been constructed in the hunt for novel therapeutic drugs equipped with enhanced immunoprotective abilities, such as engaging immune effector functions, effective development of fusion proteins, efficient tumor and tissue penetration, and high-affinity antibodies directed against conserved targets.
+Advanced antibody engineering techniques have extensive applications in the fields of immunology, biotechnology, diagnostics, and therapeutic medicines.
+Furthermore, recent advances in antibody engineering techniques together with antibody fragments, display technologies, immunomodulation, and broad applications of antibodies are discussed to enhance innovative antibody production in pursuit of a healthier future for humans.
+In particular, how protein folding is genetically regulated has been a long-standing issue for genetics and protein biology.
+While putting the effect of codon optimality on debate, these studies have supplied mounting evidence suggesting a role of mRNA structure in the regulation of protein folding by modulating translational elongation rate.
+In conjunctions with previous theories, this mechanistic model of protein folding guided by mRNA structure shall expand our understandings of genetic information and offer new insights into various biomedical puzzles.
+This study aimed to assess the mortality risks for human infection with high (HPAI) and low (LPAI) pathogenicity avian influenza viruses.
+The HPAI case fatality rate (CFR) was far higher than the LPAI CFR [66.0% (293/444) vs. 68.75% (11/16) vs. 40.4% (265/656) vs. 0.0% (0/18) in the cases with H5N1, H5N6, H7N9, and H9N2 viruses, respectively; p < 0.001].
+Similarly, the CFR of the index cases was greater than the secondary cases with H5N1 [100% (43/43) vs. 43.3% (42/97), p < 0.001].
+Old age [22.5 vs. 17 years for H5N1, p = 0.018; 61 vs. 49 years for H7H9, p < 0.001], concurrent diseases [18.8% (15/80) vs. 8.33% (9/108) for H5N1, p = 0.046; 58.6% (156/266) vs. 34.8% (135/388) for H7H9, p < 0.001], delayed confirmation [13 vs. 6 days for H5N1, p < 0.001; 10 vs. 8 days for H7N9, p = 0.011] in the fatalities and survivors, were risk factors for deaths.
+With regard to the H5N1 clusters, exposure to poultry [67.4% (29/43) vs. 45.2% (19/42), p = 0.039] was the higher risk for the primary than the secondary deaths.
+In conclusion, old age, comorbidities, delayed confirmation, along with poultry exposure are the major risks contributing to fatal outcomes in human HPAI and LPAI infections.
+An exacerbated immune response is one of the main causes of influenza-induced lung damage during infection.
+The molecular mechanisms regulating the fate of the initial immune response to infection, either as a protective response or as detrimental immunopathology, are not well understood.
+The purinergic receptor P2X7 is an ionotropic nucleotide-gated ion channel receptor expressed on immune cells that has been implicated in induction and maintenance of excessive inflammation.
+Here, we analyze the role of this receptor in a mouse model of influenza virus infection using a receptor knockout (KO) mouse strain.
+Our results demonstrate that the absence of the P2X7 receptor results in a better outcome to influenza virus infection characterized by reduced weight loss and increased survival upon experimental influenza challenge compared to wild-type mice.
+Production of proinflammatory cytokines and chemokines such as interleukin-10 (IL-10), gamma interferon (IFN-γ), and CC chemokine ligand 2 (CCL2) was also reduced in the lungs of the infected KO mice.
+Infiltration of neutrophils and depletion of CD11b(+) macrophages, characteristic of severe influenza virus infection in mice, were lower in the KO animals.
+Together, these results demonstrate that activation of the P2X7 receptor is involved in the exacerbated immune response observed during influenza virus infection.
+Renin angiotensin system (RAS) is known to play a key role in several diseases such as diabetes, and renal and cardiovascular pathologies.
+Its blockade has been demonstrated to delay chronic kidney disease progression and cardiovascular damage in diabetic patients.
+In this sense, since local RAS has been described, the aim of this study is to characterize angiotensin converting enzyme (ACE) and ACE2 activities, as well as protein expression, in several tissues of the non-obese diabetic (NOD) mice model.
+After 21 or 40 days of diabetes onset, mouse serums and tissues were analyzed for ACE and ACE2 enzyme activities and protein expression.
+Thus, whereas ACE activity was highly expressed in lungs, ACE2 activity was highly expressed in pancreas among the studied tissues.
+Interestingly, we also observed that diabetes up-regulates ACE mainly in serum, lung, heart, and liver, and ACE2 mainly in serum, liver, and pancreas.
+In conclusion, we found a marked serum and pulmonary alteration in ACE activity of diabetic mice, suggesting a common regulation.
+The increase of ACE2 activity within the circulation in diabetic mice may be ascribed to a compensatory mechanism of RAS.
+Four major nucleosides, adenosine, guanosine, cytidine and uridine, compose RNAs and provide sequence variation, but are limited in contributions to structural variation as well as distinct chemical properties.
+The ability of RNAs to play multiple roles in cellular metabolism is made possible by extensive variation in length, conformational dynamics, and the over 100 post-transcriptional modifications.
+There are several reviews of the biochemical pathways leading to RNA modification, but the physicochemical nature of modified nucleosides and how they facilitate RNA function is of keen interest, particularly with regard to the contributions of modified nucleosides.
+The added chemistry, conformation and dynamics of modified nucleosides occurring at the termini of stems in tRNA’s cloverleaf secondary structure affect the global three-dimensional conformation, produce unique recognition determinants for macromolecules to recognize tRNAs, and affect the accurate and efficient decoding ability of tRNAs.
+This review will discuss the impact of specific chemical moieties on the structure, stability, electrochemical properties, and function of tRNAs.
+BACKGROUND: A number of membrane-anchored proteins are known to be released from cell surface via ectodomain shedding.
+The cleavage and release of membrane proteins has been shown to modulate various cellular processes and disease pathologies.
+Numerous studies revealed that cell membrane molecules of diverse functional groups are subjected to proteolytic cleavage, and the released soluble form of proteins may modulate various signaling processes.
+Therefore, in addition to the secreted protein markers that undergo secretion through the secretory pathway, the shed membrane proteins may comprise an additional resource of noninvasive and accessible biomarkers.
+In this context, identifying the membrane-bound proteins that will be shed has become important in the discovery of clinically noninvasive biomarkers.
+Nevertheless, a data repository for biological and clinical researchers to review the shedding information, which is experimentally validated, for membrane-bound protein shed markers is still lacking.
+RESULTS: In this study, the database SheddomeDB was developed to integrate publicly available data of the shed membrane proteins.
+A comprehensive literature survey was performed to collect the membrane proteins that were verified to be cleaved or released in the supernatant by immunological-based validation experiments.
+From 436 studies on shedding, 401 validated shed membrane proteins were included, among which 199 shed membrane proteins have not been annotated or validated yet by existing cleavage databases.
+SheddomeDB attempted to provide a comprehensive shedding report, including the regulation of shedding machinery and the related function or diseases involved in the shedding events.
+In addition, our published tool ShedP was embedded into SheddomeDB to support researchers for predicting the shedding event on unknown or unrecorded membrane proteins.
+CONCLUSIONS: To the best of our knowledge, SheddomeDB is the first database for the identification of experimentally validated shed membrane proteins and currently may provide the most number of membrane proteins for reviewing the shedding information.
+The database included membrane-bound shed markers associated with numerous cellular processes and diseases, and some of these markers are potential novel markers because they are not annotated or validated yet in other databases.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12859-017-1465-7) contains supplementary material, which is available to authorized users.
+Dielectrophoresis (DEP) is a label-free, accurate, fast, low-cost diagnostic technique that uses the principles of polarization and the motion of bioparticles in applied electric fields.
+This technique has been proven to be beneficial in various fields, including environmental research, polymer research, biosensors, microfluidics, medicine and diagnostics.
+Biomedical science research is one of the major research areas that could potentially benefit from DEP technology for diverse applications.
+Nevertheless, many medical science research investigations have yet to benefit from the possibilities offered by DEP.
+This paper critically reviews the fundamentals, recent progress, current challenges, future directions and potential applications of research investigations in the medical sciences utilizing DEP technique.
+This review will also act as a guide and reference for medical researchers and scientists to explore and utilize the DEP technique in their research fields.
+Here, using mouse squamous cell carcinoma cells, we report a completely new function for the autophagy protein Ambra1 as the first described ‘spatial rheostat’ controlling the Src/FAK pathway.
+Ambra1 regulates the targeting of active phospho-Src away from focal adhesions into autophagic structures that cancer cells use to survive adhesion stress.
+When FAK is present, Ambra1 is recruited to focal adhesions, promoting FAK-regulated cancer cell direction-sensing and invasion.
+However, when Ambra1 cannot bind to FAK, abnormally high levels of phospho-Src and phospho-FAK accumulate at focal adhesions, positively regulating adhesion and invasive migration.
+Spatial control of active Src requires the trafficking proteins Dynactin one and IFITM3, which we identified as Ambra1 binding partners by interaction proteomics.
+We conclude that Ambra1 is a core component of an intracellular trafficking network linked to tight spatial control of active Src and FAK levels, and so crucially regulates their cancer-associated biological outputs.
+Periplasmic c7 type cytochrome A (PpcA) protein is determined in Geobacter sulfurreducens along with its other four homologs (PpcB-E).
+From the crystal structure viewpoint the observation emerges that PpcA protein can bind with Deoxycholate (DXCA), while its other homologs do not.
+But it is yet to be established with certainty the reason behind this from primary protein sequence information.
+This study is primarily based on primary protein sequence analysis through the chemical basis of embedded amino acids.
+Along with this, we have developed a new methodology for the phylogenetic analysis based on chemical group dissimilarities of amino acids.
+This new methodology is applied to the cytochrome c7 family members and pinpoint how a particular sequence is differing with others.
+Secondly, we build a graph theoretic model on using amino acid sequences which is also applied to the cytochrome c7 family members and some unique characteristics and their domains are highlighted.
+Thirdly, we search for unique patterns as subsequences which are common among the group or specific individual member.
+In all the cases, we are able to show some distinct features of PpcA that emerges PpcA as an outstanding protein compared to its other homologs, resulting towards its binding with deoxycholate.
+Similarly, some notable features for the structurally dissimilar protein PpcD compared to the other homologs are also brought out.
+Further, the five members of cytochrome family being homolog proteins, they must have some common significant features which are also enumerated in this study.
+The microbial contamination of central air conditioning system is one of the important factors that affect the indoor air quality.
+Actual measurement and analysis were carried out on microbial contamination in central air conditioning system at a venue in Dalian, China.
+Illumina miseq method was used and three fungal samples of two units were analysed by high throughput sequencing.
+Results showed that the predominant fungus in air conditioning unit A and B were Candida spp.
+Based on the data of Cladosporium in hygrothermal response experiment, this paper used the logistic equation and the Gompertz equation to fit the growth predictive model of Cladosporium genera in different temperature and relative humidity conditions, and the square root model was fitted based on the two environmental factors.
+In addition, the models were carried on the analysis to verify the accuracy and feasibility of the established model equation.
+Zika virus (ZIKV) is a mosquito-borne flavivirus distributed all over Africa, South America and Asia.
+The infection with the virus may cause acute febrile sickness that clinically resembles dengue fever, yet there is no vaccine, no satisfactory treatment, and no means of evaluating the risk of the disease or prognosis in the infected people.
+In the present study, the efficacy of the host's immune response in reducing the risk of infectious diseases was taken into account to carry out immuno-informatics driven epitope screening strategy of vaccine candidates against ZIKV.
+In this study, HLA distribution analysis was done to ensure the coverage of the vast majority of the population.
+Systematic screening of effective dominant immunogens was done with the help of Immune Epitope & ABCPred databases.
+The outcomes suggested that the predicted epitopes may be protective immunogens with highly conserved sequences and bear potential to induce both protective neutralizing antibodies, T & B cell responses.
+A total of 25 CD4+ and 16 CD8+ peptides were screened for T-cell mediated immunity.
+These peptides were further screened as non-toxic, immunogenic and non-mutated residues of envelop viral protein.
+Further, experimental validation of these epitopes is warranted to ensure the potential of B- and T-cells stimulation for their efficient use as vaccine candidates, and as diagnostic agents against ZIKV.
+Finding the partners MAGE-G1 interacting with will surely contribute to the function study of MAGE-G1.
+In this study, using Stable Isotope Labeling by Amino acids in Cell culture-immunoprecipitation quantitative proteomics, we screened the interacting proteins of MAGE-G1 during retinoic acid -induced neuronal differentiation of P19 cells and firstly found that FSCN1 and VIME were potential novel MAGE-G1-interacting proteins.
+Then, the interaction between overexpressed MAGE-G1 and FSCN1 or VIME was validated by GST-pull down assay in bacteria and by co-immunoprecipitation assay in COS7 cells.
+Endogenous co-immunoprecipitation assay further confirmed that MAGE-G1 interacted with FSCN1 or VIME in P19 cells after a 6-day retinoic acid-induced neuronal differentiation.
+Those results provide a functional linkage between MAGE-G1 and FSCN1 or VIME and may facilitate a better understanding of the fundamental aspects of MAGE-G1 during neurogenesis.
+BACKGROUND: Zoonotic avian influenza poses a major risk to China, and other parts of the world.
+H5N1 has remained endemic in China and globally for nearly two decades, and in 2013, a novel zoonotic influenza A subtype H7N9 emerged in China.
+This study aimed to improve upon our current understanding of the spreading mechanisms of H7N9 and H5N1 by generating spatial risk profiles for each of the two virus subtypes across mainland China.
+We produced high performing SDMs (6 of 8 models with AUC > 0.9) for both H5N1 and H7N9.
+In all our SDMs, H7N9 consistently showed higher AUC results compared to H5N1, suggesting H7N9 suitability could be better explained by environmental variables.
+For both subtypes, high risk areas were primarily located in south-eastern China, with H5N1 distributions found to be more diffuse and extending more inland compared to H7N9.
+CONCLUSIONS: We provide projections of our risk models to public health policy makers so that specific high risk areas can be targeted for control measures.
+We recommend comparing H5N1 and H7N9 prevalence rates and survivability in the natural environment to better understand the role of animal and environmental transmission in human infections.
+One of such fungi is Fomitopsis betulina (formerly Piptoporus betulinus), which causes brown rot of birch wood.
+Annual white to brownish fruiting bodies of the species can be found on trees in the northern hemisphere but F. betulina can also be cultured as a mycelium and fruiting body.
+The fungus has a long tradition of being applied in folk medicine as an antimicrobial, anticancer, and anti-inflammatory agent.
+Probably due to the curative properties, pieces of its fruiting body were carried by Ötzi the Iceman.
+Pharmacological studies have provided evidence supporting the antibacterial, anti-parasitic, antiviral, anti-inflammatory, anticancer, neuroprotective, and immunomodulating activities of F. betulina preparations.
+The mushroom is also a reservoir of valuable enzymes and other substances such as cell wall (1→3)-α-d-glucan which can be used for induction of microbial enzymes degrading cariogenic dental biofilm.
+In conclusion, F. betulina can be considered as a promising source for the development of new products for healthcare and other biotechnological uses.
+Degradation of the biologically potent octapeptide angiotensin Ang II-(1-8) is mediated by the activities of several peptidases.
+The conversion of Ang II to the septapeptide Ang-(1-7) is of particular interest as the latter also confers organ protection.
+The conversion is catalyzed by angiotensin-converting enzyme 2 and other enzymes that selectively cleave the peptide bond between the proline and the phenylalanine at the carboxyl terminus of Ang II.
+The contribution of various enzyme activities that collectively lead to the formation of Ang-(1-7) from Ang II, in both normal conditions and in disease states, remains only partially understood.
+This is largely due to the lack of a reliable and sensitive method to detect these converting activities in complex samples, such as blood and tissues.
+Here, we report a fluorometric method to measure carboxypeptidase activities that cleave the proline-phenylalanine dipeptide bond in Ang II.
+The assay detects the release of phenylalanine amino acid in a reaction with the yeast enzyme of phenylalanine ammonia lyase (PAL).
+When used in cell and mouse organs, the assay can robustly measure endogenous Ang II and apelin-13-converting activities involved in the renin-angiotensin and the apelinergic systems, respectively.
+The influenza pandemic is a major threat to human health, and highly aggressive strains such as H1N1, H5N1 and H7N9 have emphasized the need for therapeutic strategies to combat these pathogens.
+Influenza anti-viral agents, especially active small molecular inhibitors play important roles in controlling pandemics while vaccines are developed.
+Currently, only a few drugs, which function as influenza neuraminidase (NA) inhibitors and M2 ion channel protein inhibitors, are approved in clinical.
+However, the acquired resistance against current anti-influenza drugs and the emerging mutations of influenza virus itself remain the major challenging unmet medical needs for influenza treatment.
+This paper reviews the progress of small molecular inhibitors act as antiviral agents, which include hemagglutinin (HA) inhibitors, RNA-dependent RNA polymerase (RdRp) inhibitors, NA inhibitors and M2 ion channel protein inhibitors etc.
+Moreover, we also summarize new, recently reported potential targets and discuss strategies for the development of new anti-influenza virus drugs.
+Myelodysplastic syndrome (MDS) is a heterogeneous group of hematological malignancies with considerably variable prognoses and curable only with hematopoietic cell transplantation (HCT).
+Few studies comparing MDS HCT outcomes between sibling and umbilical cord blood (UCB) donors exist.
+Using the University of Minnesota Blood and Marrow Transplant (BMT) database, we retrospectively analyzed HCT outcomes among 89 MDS patients undergoing either sibling or double UCB HCT in 2000–2013.
+Relapse was increased in those with monosomal karyotype (P=0.04) and with reduced intensity conditioning (P<0.01).
+In summary, our data highlight similar MDS HCT outcomes regardless of donor source and support the use of UCB as an alternative donor when a sibling is unavailable.
+Canonical translation of host mRNAs depends on structural elements such as the 5′ cap structure and/or the 3′ poly(A) tail of the mRNAs.
+Although many viral mRNAs are devoid of one or both of these structures, they can still translate efficiently using non-canonical mechanisms.
+Here, we review the tools utilized by positive-sense single-stranded (+ss) RNA plant viruses to initiate non-canonical translation, focusing on cis-acting sequences present in viral mRNAs.
+We highlight how these elements may interact with host translation factors and speculate on their contribution for achieving translational control.
+We also describe other translation strategies used by plant viruses to optimize the usage of the coding capacity of their very compact genomes, including leaky scanning initiation, ribosomal frameshifting and stop-codon readthrough.
+Finally, future research perspectives on the unusual translational strategies of +ssRNA viruses are discussed, including parallelisms between viral and host mRNAs mechanisms of translation, particularly for host mRNAs which are translated under stress conditions.
+Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by a progressive upper and lower motor neuron degeneration.
+One of the peculiar clinical characteristics of ALS is the wide distribution in age of onset, which is probably caused by different combinations of intrinsic and exogenous factors.
+We investigated whether these modifying factors are converging into common pathogenic pathways leading either to an early or a late disease onset.
+This would imply the identification of phenotypic biomarkers, that can distinguish the two populations of ALS patients, and of relevant pathways to consider in a therapeutic intervention.
+Toward this aim a differential proteomic analysis was performed in peripheral blood mononuclear cells (PBMC) from a group of 16 ALS patients with an age of onset ≤55 years and a group of 16 ALS patients with an age of onset ≥75 years, and matched healthy controls.
+Gene ontology analysis revealed that there was a significant enrichment in annotations associated with protein folding and response to stress.
+We next validated a selected number of proteins belonging to this functional group in 85 patients and 83 age- and sex-matched healthy controls using immunoassays.
+The results of the validation study confirmed that there was a decreased level of peptidyl-prolyl cis-trans isomerase A (also known as cyclophilin A), heat shock protein HSP 90-alpha, 78 kDa glucose-regulated protein (also known as BiP) and protein deglycase DJ-1 in PBMC of ALS patients with an early onset.
+Similar results were obtained in PBMC and spinal cord from two SOD1(G93A) mouse models with an early and late disease onset.
+This study suggests that a different ability to upregulate proteins involved in proteostasis, such as foldase and chaperone proteins, may be at the basis of a different susceptibility to ALS, putting forward the development of therapeutic approaches aiming at boosting the protein quality control system.
+Attempts for a sustainable control of this scourge by vaccination have not yet fully satisfied.
+With an increasing knowledge and methodology in disease resistance, a new world-wide endeavour has been started to support the combat of animal diseases, based on the existence of valuable gene variants with regard to any host-pathogen interaction.
+Several groups have produced a wealth of evidence for natural variability in resistance/susceptibility to PRRS in our commercial breeding lines.
+However, up to now, exploiting existing variation has failed because of the difficulty to detect the carriers of favourable and unfavourable alleles, especially with regard to such complex polygenic traits like resistance to PRRS.
+New hope comes from new genomic tools like next generation sequencing which have become extremely fast and low priced.
+Thus, research is booming world-wide and the jigsaw puzzle is filling up – slowly but steadily.
+On the other hand, knowledge from virological and biomedical basic research has opened the way for an “intervening way”, i.e.
+the modification of identified key genes that occupy key positions in PRRS pathogenesis, like CD163.
+CD163 was identified as the striking receptor in PRRSV entry and its knockout from the genome by gene editing has led to the production of pigs that were completely resistant to PRRSV – a milestone in modern pig breeding.
+However, at this early step, concerns remain about the acceptance of societies for gene edited products and regulation still awaits upgrading to the new technology.
+Further questions arise with regard to upcoming patents from an ethical and legal point of view.
+Eventually, the importance of CD163 for homeostasis, defence and immunity demands for more insight before its complete or partial silencing can be answered.
+Whatever path will be followed, even a partial abolishment of PRRSV replication will lead to a significant improvement of the disastrous herd situation, with a significant impact on welfare, performance, antimicrobial consumption and consumer protection.
+BACKGROUND: Crisis happens daily yet its understanding is often limited, even in the field of psychiatry.
+Indeed, a challenge is to assess the potential for change of patients so as to offer appropriate therapeutic interventions and enhance treatment program efficacy.
+This naturalistic study aimed to identify the socio-demographical characteristics and clinical profiles at admission of patients referred to a specialized Crisis Intervention Center (CIC) and to examine the effectiveness of the intervention.
+METHOD: The sample was composed of 352 adult outpatients recruited among the referrals to the CIC.
+Assessment completed at admission and at discharge examined psychiatric symptoms, defense mechanisms, recovery styles and global functioning.
+RESULTS: Regarding the clinical profiles at intake, patients were middle-aged (M = 38.56, SD = 10.91), with a higher proportion of women (62.22%).
+They were addressed to the CIC because they had attempted to commit suicide or had suicidal ideation or presented depressed mood related to interpersonal difficulties.
+No statistical differences were found between patients dropping out (n = 215) and those attending the crisis intervention (n = 137).
+Crisis intervention demonstrated a beneficial effect (p < 0.01) on almost all variables, with Effect Sizes (ES) ranging from small to large (0.12 < ES < 0.75; median = 0.49).
+However, the Reliable Change Index indicated that most of the issues fall into the undetermined category (range 41.46 to 96.35%; median = 66.20%).
+CONCLUSIONS: This study establishes the profile of patients referred to the CIC and shows that more than half of the patients dropped out from the crisis intervention before completion.
+Thus, the effectiveness of crisis intervention in naturalistic context is not fully determined and should be more rigorously studied in future research.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12888-017-1293-3) contains supplementary material, which is available to authorized users.
+BACKGROUND: Changes in the levels of circulating microRNAs (miRNAs) in the serum of humans and animals have been detected as a result of infection with a variety of viruses.
+However, to date, such a miRNA profiling study has not been conducted for foot-and-mouth disease virus (FMDV) infection.
+METHODS: The relative abundance of 169 miRNAs was measured in bovine serum collected at three different phases of FMDV infection in a proof-of-concept study using miRNA PCR array plates.
+RESULTS: Alterations in specific miRNA levels were detected in serum during acute, persistent, and convalescent phases of FMDV infection.
+Subclinical FMDV persistence produced a circulating miRNA profile distinct from cattle that had cleared infection.
+bta-miR-17-5p was highest expressed during acute infection, whereas bta-miR-31 was the highest during FMDV persistence.
+Cattle that cleared infection resembled the baseline profile, adding support to applying serum miRNA profiling for identification of sub-clinically infected FMDV carriers.
+Significantly regulated miRNAs during acute or persistent infection were associated with cellular proliferation, apoptosis, modulation of the immune response, and lipid metabolism.
+CONCLUSIONS: These findings suggest a role for non-coding regulatory RNAs in FMDV infection of cattle.
+Future studies will delineate the individual contributions of the reported miRNAs to FMDV replication, determine if this miRNA signature is applicable across all FMDV serotypes, and may facilitate development of novel diagnostic applications.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12985-017-0743-3) contains supplementary material, which is available to authorized users.
+The probability of these particles to deposit in the respiratory tract during breathing is essential for their toxic effects.
+Observations have shown that there is a substantial variability in deposition between subjects, not only due to respiratory diseases, but also among individuals with healthy lungs.
+METHOD: In this study we experimentally investigate factors that determine individual differences in the respiratory tract depositions of inhaled particles for healthy subjects at relaxed breathing.
+The study covers particles of diameters 15–5000 nm and includes 67 subjects aged 7–70 years.
+Principal component analyses and multiple regression analyses were used to explore the relationships between subject characteristics and particle deposition.
+Individuals with high deposition of a certain particle size generally had high deposition for all particles <3500 nm.
+The individual variability was explained by two factors: breathing pattern, and lung structural and functional properties.
+The most important predictors were found to be breathing frequency and anatomical airway dead space.
+We also present a linear regression model describing the deposition based on four variables: tidal volume, breathing frequency, anatomical dead space and resistance of the respiratory system (the latter measured with impulse oscillometry).
+CONCLUSIONS: To understand why some individuals are more susceptible to airborne particles we must understand, and take into account, the individual variability in the probability of particles to deposit in the respiratory tract by considering not only breathing patterns but also adequate measures of relevant structural and functional properties.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12989-017-0190-8) contains supplementary material, which is available to authorized users.
+Canine distemper virus (CDV) is the causative agent of canine distemper (CD) that is a highly contagious, lethal, multisystemic viral disease of receptive carnivores.
+Presently, it is unclear whether intragenic recombination can contribute to gene mutations and segment reassortment in the virus.
+In this study, 25 full-length CDV genome sequences were subjected to phylogenetic and recombinational analyses.
+The results of phylogenetic analysis, intragenic recombination, and nucleotide selection pressure indicated that mutation and recombination occurred in the six individual genes segment (H, F, P, N, L, M) of the CDV genome.
+The analysis also revealed pronounced genetic diversity in the CDV genome according to the geographically distinct lineages (genotypes), namely Asia-1, Asia-2, Asia-3, Europe, America-1, and America-2.
+The analysis of selection pressure demonstrated that a majority of the nucleotides in the CDV individual gene were under negative selection.
+Collectively, these data suggested that homologous recombination acts as a key force driving the genetic diversity and evolution of canine distemper virus.
+BACKGROUND: The widespread application of silver nanoparticles (AgNPs) and silver-containing products has raised public safety concerns about their adverse effects on human health and the environment.
+To date, in vitro toxic effects of AgNPs and ionic silver (Ag(+)) on many somatic cell types are well established.
+However, no studies have been conducted hitherto to evaluate their effect on cellular transcriptome in embryonic stem cells (ESCs).
+RESULTS: The present study characterized transcriptomic changes induced by 5.0 µg/ml AgNPs during spontaneous differentiation of mouse ESCs, and compared them to those induced by Ag(+) under identical conditions.
+After 24 h exposure, 101 differentially expressed genes (DEGs) were identified in AgNP-treated cells, whereas 400 genes responded to Ag(+).
+Despite the large differences in the numbers of DEGs, functional annotation and pathway analysis of the regulated genes revealed overall similarities between AgNPs and Ag(+).
+In both cases, most of the functions and pathways impacted fell into two major categories, embryonic development and metabolism.
+Nevertheless, a number of canonical pathways related to cancer were found for Ag(+) but not for AgNPs.
+Conversely, it was noted that several members of the heat shock protein and the metallothionein families were upregulated by AgNPs but not Ag(+), suggesting specific oxidative stress effect of AgNPs in ESCs.
+The effects of AgNPs on oxidative stress and downstream apoptosis were subsequently confirmed by flow cytometry analysis.
+CONCLUSIONS: Taken together, the results presented in the current study demonstrate that both AgNPs and Ag(+) caused transcriptomic changes that could potentially exert an adverse effect on development.
+Although transcriptomic responses to AgNPs and Ag(+) were substantially similar, AgNPs exerted specific effects on ESCs due to their nanosized particulate form.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12951-017-0265-6) contains supplementary material, which is available to authorized users.
+We present the structure of the surface Ebola virus (EBOV) trimeric glycoprotein (GP) spike at 11 Å resolution, in situ within the viral plasma membrane of purified virus particles.
+GP functions in cellular attachment, endosomal entry, and membrane fusion to initiate infection, and is a key therapeutic target.
+Nevertheless, only about half of the GP molecule has yet been solved to atomic resolution, excluding the mucin-like and transmembrane domains, and some of the glycans.
+Fitting of the atomic resolution X-ray data from expressed, truncated deletion constructs within our 11 Å structure of the entire molecule demonstrates the relationship between the GP1-GP2 domains, the mucin-like and transmembrane domains, and the bilaminar lipid envelope.
+We show that the mucin-like domain covers the glycan cap and partially occludes the receptor binding sites prior to proteolytic cleavage.
+Our structure is also consistent with key antibody neutralisation sites on GP being accessible prior to proteolysis.
+Based on the findings of us and others, GP-mediated binding may create an angle of 18 degrees between the planes of viral and endosomal membranes.
+We conducted a questionnaire survey on air travel-associated TB contact investigations in local health offices of Japan from 2012 to 2015, focusing on IGRA positivity.
+Among 651 air travel-associated TB contacts, average positivity was 3.8% (95% confidence interval (CI): 2.5–5.6) with a statistically significant increasing trend with older age (p < 0.0094).
+Positivity among 0–34 year-old contacts was 1.0% (95% CI: 0.12–3.5%), suggesting their risk of TB infection is as small as among Japanese young adults with low risk of TB infection (positivity: 0.85–0.90%).
+Limiting the contact investigation to fewer passengers (within two seats surrounding the index case, rather than two rows) seems reasonable in the case of aircraft with many seats per row.
+The World Health Organization has declared the 2014–2015 Ebola Virus Disease outbreak a Public Health Emergency of International Concern.
+In response to this, preparations were made in various health facilities and entry points across Ghana.
+This study explored health workers perceptions, and attitude about Ghana’s preparedness towards preventing and containing Ebola Virus Disease.
+METHODS: We conducted a qualitative study in five (5) of the ten (10) regions in Ghana.
+Five focus group discussions (N = 44) were conducted among nurses; one in each region.
+In addition, ten (10) health workers (2 in each region) who are members of regional Ebola Virus Disease task force were recruited and interviewed.
+In the Greater Accra, Volta and Western regions that have ports, six (6) port health officials: two in each of these regions were also interviewed.
+Thematic content analysis was used to analyze the transcripts with the aid of NVivo 10 software.
+RESULTS: The results of this study showed that Ghanaian health workers perceived the screening at various ports as important and ongoing but felt that the screenings at in-land ports were being undermined by the use of unapproved routes.
+Training of health workers was also being carried out in all the regions, however, there was a general perception among 33 out of 44 nurses that majority of health workers have not received training on Ebola Virus Disease prevention and management.
+Logistical challenges were also reported as some health facilities did not have adequate Personal Protective Equipment.
+In facilities where equipment was available, they were stored in places which are not easily accessible to health workers at all times of the day.
+Human resource preparation was also perceived to be a challenge as health workers (38/44 of nurses) generally expressed fear and unwillingness to work in Ebola treatment centres in the event of an outbreak in Ghana.
+CONCLUSIONS: Our study concludes that preparatory work for Ebola Virus Disease prevention and containment in Ghana is perceived as inadequate by health workers.
+Ghana needs to strengthen preparation in the area of training of health workers, provision and accessibility of Personal Protective Equipment and incentives for health workers to better position her to contain and manage any Ebola Virus Disease outbreak.
+Previous studies have shown that SIRT7 is required for RNA polymerase I (Pol I) transcription and pre-rRNA processing.
+Here, we took a proteomic approach to identify novel molecular targets and characterize the role of SIRT7 in non-nucleolar processes.
+We show that SIRT7 interacts with numerous proteins involved in transcriptional regulation and RNA metabolism, the majority of interactions requiring ongoing transcription.
+In addition to its role in Pol I transcription, we found that SIRT7 also regulates transcription of snoRNAs and mRNAs.
+Mechanistically, SIRT7 promotes the release of P-TEFb from the inactive 7SK snRNP complex and deacetylates CDK9, a subunit of the elongation factor P-TEFb, which activates transcription by phosphorylating serine 2 within the C-terminal domain (CTD) of Pol II.
+SIRT7 counteracts GCN5-directed acetylation of lysine 48 within the catalytic domain of CDK9, deacetylation promoting CTD phosphorylation and transcription elongation.
+Programmed -1 ribosomal frameshifting (-1PRF) is tightly regulated by messenger RNA (mRNA) sequences and structures in expressing two or more proteins with precise ratios from a single mRNA.
+Using single-molecule fluorescence resonance energy transfer (smFRET) between (Cy5)EF-G and (Cy3)tRNA(Lys), we studied the translational elongation dynamics of -1PRF in the Escherichia coli dnaX gene, which contains three frameshifting signals: a slippery sequence (A AAA AAG), a Shine-Dalgarno (SD) sequence and a downstream hairpin.
+The frameshift promoting signals mostly impair the EF-G-catalyzed translocation step of the two tRNA(Lys) and the slippery codons from the A- and P- sites.
+The upstream SD sequence together with the hairpin promotes dissociation of futile EF-G and thus causes multiple EF-G driven translocation attempts.
+These results indicate that frameshifting takes place during the repetitive ribosomal conformational changes associated with EF-G dissociation upon unsuccessful translocation attempts of the second slippage codon from the A- to the P- sites.
+Bamboo mosaic virus (BaMV), which belongs to the genus Potexvirus in the family Alphaflexiviridae, has a single-stranded positive-sense RNA genome that is approximately 6400 nucleotides (nts) in length.
+Positive-sense RNA viruses can use genomic RNA as a template for translation and replication after entering a suitable host cell.
+Furthermore, such viral RNA is recognized by capsid protein for packaging and by viral movement protein(s) or the movement protein complex for cell-to-cell and systemic movement.
+Hence, viral RNA must contain signals for different functions to complete the viral infection cycle.
+The highly structured 3′ untranslated region (UTR) of the BaMV genomic RNA plays multiple roles in the BaMV infection cycle, including targeting chloroplasts for RNA replication, providing an initiation site for the synthesis of minus-strand RNA, signaling for polyadenylation, and directing viral long-distance movement.
+The nt at the extreme 3′ end and the structure of the 3′-terminus of minus-strand RNA are involved in the initiation of plus-strand genomic RNA synthesis.
+Both these regions have been mapped and reported to interact with the viral-encoded RNA-dependent RNA polymerase.
+Moreover, the sequences upstream of open reading frames (ORFs) 2, 3, and 5 are involved in regulating subgenomic RNA synthesis.
+The cis-acting elements that were identified in BaMV RNA are discussed and compared with those of other potexviruses.
+Cell death plays a crucial role for a myriad of physiological processes, and several human diseases such as cancer are characterized by its deregulation.
+There are many methods available for both quantifying and qualifying the accurate process of cell death which occurs.
+Choosing the right assay tool is essential to generate meaningful data, provide sufficient information for clinical applications, and understand cell death processes.
+In vitro cell death assays are important steps in the search for new therapies against cancer as the ultimate goal remains the elaboration of drugs that interfere with specific cell death mechanisms.
+However, choosing a cell viability or cytotoxicity assay among the many available options is a daunting task.
+Indeed, cell death can be approached by several viewpoints and require a more holistic approach.
+This review provides an overview of cell death assays usually used in vitro for assessing cell death so as to elaborate new potential chemotherapeutics and discusses considerations for using each assay.
+Porcine circovirus type 2 (PCV2) has recently been reported to elicit the unfolded protein response (UPR) via activation of the PERK/eIF2α (RNA-activated protein kinase-like endoplasmic reticulum (ER) kinase/eukaryotic initiation factor 2α) pathway.
+This study attempted to examine which viral protein might be involved in inducing UPR and whether this cellular event would lead to apoptosis of the cells expressing the viral protein.
+By transient expression, we found that both replicase (Rep) and capsid (Cap) proteins of PCV2 could induce ER stress as shown by increased phosphorylation of PERK with subsequent activation of the eIF2α-ATF4 (activating transcription factor 4)-CHOP (CCAAT/enhancer-binding protein homologous protein) axis.
+Cap expression, but not Rep, significantly reduced antiapoptotic B-cell lymphoma-2 (Bcl-2) and increased caspase-3 cleavage, possibly due to increased expression of CHOP.
+Since knockdown of PERK by RNA interference clearly reduced Cap-induced CHOP expression, caspase-3 cleavage, and apoptotic cell death possibly by partially rescuing Bcl-2 expression, we propose that there is connection between Cap-induced UPR and apoptosis via the PERK/eIF2α/ATF4/CHOP/Bcl-2 pathway.
+This study, together with our earlier studies, provides insight into the mechanisms underlying PCV2 pathogenesis.
+Sporadic outbreaks of Ebola virus infection have been documented since the mid-Seventies and viral exposure can lead to lethal haemorrhagic fever with case fatalities as high as 90%.
+There is now a comprehensive body of data from both ongoing and completed clinical trials assessing various vaccine strategies, which were rapidly advanced through clinical trials in response to the 2013–2016 Ebola virus disease (EVD) public health emergency.
+Careful consideration of immunogenicity post vaccination is essential but has been somewhat stifled because of the wide array of immunological assays and outputs that have been used in the numerous clinical trials.
+We discuss here the different aspects of the immune assays currently used in the Phase I clinical trials for Ebola virus vaccines, and draw comparisons across the immune outputs where possible; various trials have examined both cellular and humoral immunity in European and African cohorts.
+Assessment of the safety data, the immunological outputs and the ease of field deployment for the various vaccine modalities will help both the scientific community and policy-makers prioritize and potentially license vaccine candidates.
+If this can be achieved, the next outbreak of Ebola virus, or other emerging pathogen, can be more readily contained and will not have such widespread and devastating consequences.
+This article is part of the themed issue ‘The 2013–2016 West African Ebola epidemic: data, decision-making and disease control’.
+Juniperus rigida (J. rigida) which is endemic to East Asia, has traditionally been used as an ethnomedicinal plant in China.
+This study was undertaken to evaluate the quality of J. rigida samples derived from 11 primary regions in China.
+Ten phenolic compounds were simultaneously quantified using reversed-phase high-performance liquid chromatography (RP-HPLC), and chlorogenic acid, catechin, podophyllotoxin, and amentoflavone were found to be the main compounds in J. rigida needles, with the highest contents detected for catechin and podophyllotoxin.
+J. rigida from Jilin (S9, S10) and Liaoning (S11) exhibited the highest contents of phenolic profiles (total phenolics, total flavonoids and 10 phenolic compounds) and the strongest antioxidant and antibacterial activities, followed by Shaanxi (S2, S3).
+A similarity analysis (SA) demonstrated substantial similarities in fingerprint chromatograms, from which 14 common peaks were selected.
+Chemometrics techniques, including hierarchical cluster analysis (HCA), principal component analysis (PCA), and discriminant analysis (DA), were further applied to facilitate accurate classification and quantification of the J. rigida samples derived from the 11 regions.
+The results supported HPLC data showing that all J. rigida samples exhibit considerable variations in phenolic profiles, and the samples were further clustered into three major groups coincident with their geographical regions of origin.
+In addition, two discriminant functions with a 100% discrimination ratio were constructed to further distinguish and classify samples with unknown membership on the basis of eigenvalues to allow optimal discrimination among the groups.
+Our comprehensive findings on matching phenolic profiles and bioactivities along with data from fingerprint chromatograms with chemometrics provide an effective tool for screening and quality evaluation of J. rigida and related medicinal preparations.
+We employ a novel paradigm to test whether six basic emotions (sadness, fear, disgust, anger, surprise, and happiness; Ekman, 1992) contain both negativity and positivity, as opposed to consisting of a single continuum between negative and positive.
+We examined the perceived negativity and positivity of these emotions in terms of their affective and cognitive components among Korean, Chinese, Canadian, and American students.
+Assessing each emotion at the cognitive and affective levels cross-culturally provides a fairly comprehensive picture of the positivity and negativity of emotions.
+Cross-culturally, Americans and Canadians gave higher valence ratings to the salient valence of each emotion, and lower ratings to the non-salient valence of an emotion, compared to Chinese and Koreans.
+The results suggest that emotions encompass both positivity and negativity, and there were cross-cultural differences in reported emotions.
+This paradigm complements existing emotion theories, building on past research and allowing for more parsimonious explanations of cross-cultural research on emotion.
+BACKGROUND: Real-time reverse transcription polymerase chain reaction (RT-PCR) is routinely used to detect viral infections.
+In Brazil, it is mandatory the use of nucleic acid tests to detect hepatitis C virus (HCV), hepatitis B virus and human immunodeficiency virus in blood banks because of the immunological window.
+The use of an internal control (IC) is necessary to differentiate the true negative results from those consequent from a failure in some step of the nucleic acid test.
+OBJECTIVES: The aim of this study was the construction of virus-modified particles, based on MS2 bacteriophage, to be used as IC for the diagnosis of RNA viruses.
+MS2-like particles were produced through the synthesis of MS2 RNA genome by T7 RNA polymerase.
+In addition, a competitive control for HCV diagnosis was developed by cloning a mutated HCV sequence into the MS2 replicase gene of pET47b(+)-MS2, which produces a non-propagating MS2 particle.
+The utility of MS2-like particles as IC was evaluated in a one-step format multiplex real-time RT-PCR for HCV detection.
+FINDINGS: We demonstrated that both competitive and non-competitive IC could be successfully used to monitor the HCV amplification performance, including the extraction, reverse transcription, amplification and detection steps, without compromising the detection of samples with low target concentrations.
+In conclusion, MS2-like particles generated by this strategy proved to be useful IC for RNA virus diagnosis, with advantage that they are produced by a low cost protocol.
+An attractive feature of this system is that it allows the construction of a multicontrol by the insertion of sequences from more than one pathogen, increasing its applicability for diagnosing different RNA viruses.
+It is increasing studies in patients with pneumonia to reveal that coinfection with viral and bacterial infection can lead to poorer outcomes than no coinfection.
+This study evaluated the role of coinfection identified through bronchoalveolar lavage (BAL) examination on the outcomes of pneumonia-related ARDS.
+METHODS: We performed a prospective observational study at Chang Gung Memorial Hospital from October 2012 to May 2015.
+The indications for BAL were clinically suspected pneumonia-related ARDS and no definite microbial sample identified from tracheal aspirate or sputum.
+A total of 142 (55.7%) patients were identified to have a microbial pathogen through BAL and were classified into three groups: a virus-only group (n = 41 [28.9%]), no virus group (n = 60 [42.2%]), and coinfection group (n = 41 [28.9%]).
+The hospital mortality rates were 53.7% in virus-only identified group, 63.3% in no virus identified group, and 80.5% in coinfection identified group.
+The coinfection group had significantly higher mortality than virus-only group (80.5% vs. 53.7%; P = 0.01).
+CONCLUSION: In patients with pneumonia-related ARDS, the BAL pathogen-positive patients had a trend of higher mortality rate than pathogen-negative patients.
+Coinfection with a virus and another pathogen was associated with increased hospital mortality in pneumonia-related ARDS patients.
+For viruses to utilize environmental vectors (hard surfaces, soil, water) for transmission, physical and chemical stability is a prerequisite.
+There are many factors including pH, salinity, temperature, and turbidity that are known to contribute to the ability of viruses to persist in water.
+Equine herpesvirus type-1 (EHV-1) is a pathogenic alphaherpesvirus associated with domestic horses and wild equids.
+EHV-1 and recombinants of EHV-1 and EHV-9 are able to cause infections in non-equid animal species, particularly in captive settings.
+Many of the captive non-equid mammals are not naturally sympatric with equids and do not share enclosures, however, in many cases water sources may overlap.
+Similarly, in the wild, equids encounter many species at waterholes in times of seasonal drought.
+Therefore, we hypothesized that EHV-1 is stable in water and that water may act as a vector for EHV-1.
+In order to establish the conditions promoting or hindering EHV-1 longevity, infectivity and genomic stability in water; we exposed EHV-1 to varied water environments (pH, salinity, temperature, and turbidity) in controlled experiments over 21 days.
+The presence and infectivity of the virus was confirmed by both qPCR and cell culture experiments.
+Our results show that EHV-1 remains stable and infectious under many conditions in water for up to three weeks.
+Detailed information on the source, spread and evolution of respiratory syncytial virus (RSV) during seasonal community outbreaks remains sparse.
+Molecular analyses of attachment (G) gene sequences from hospitalized cases suggest that multiple genotypes and variants co-circulate during epidemics and that RSV persistence over successive seasons is characterized by replacement and multiple new introductions of variants.
+No studies have defined the patterns of introduction, spread and evolution of RSV at the local community and household level.
+We present a whole genome sequence analysis of 131 RSV group A viruses collected during 6-month household-based RSV infection surveillance in Coastal Kenya, 2010 within an area of 12 km(2).
+Phylogenetic analysis revealed that the RSV A viruses in nine households were closely related to genotype GA2 and fell within a single branch of the global phylogeny.
+For comparison, using only G gene analysis, household-specific variation was found only in one of the nine households.
+Nucleotide changes were observed both intra-host (viruses identified from same individual in follow-up sampling) and inter-host (viruses identified from different household members) and these coupled with sampling dates enabled a partial reconstruction of the within household transmission chains.
+The genomic evolutionary rate for the household dataset was estimated as 2.307 × 10 (−) (3) (95% highest posterior density: 0.935–4.165× 10 (−) (3)) substitutions/site/year.
+We conclude that (i) at the household level, most RSV infections arise from the introduction of a single virus variant followed by accumulation of household specific variation and (ii) analysis of complete virus genomes is crucial to better understand viral transmission in the community.
+A key question arising is whether prevention of RSV introduction or spread within the household by vaccinating key transmitting household members would lead to a reduced onward community-wide transmission.
+Bartonella infections were investigated in seven species of bats from four regions of the Republic of Georgia.
+Of the 236 bats that were captured, 212 (90%) specimens were tested for Bartonella infection.
+Colonies identified as Bartonella were isolated from 105 (49.5%) of 212 bats Phylogenetic analysis based on sequence variation of the gltA gene differentiated 22 unique Bartonella genogroups.
+Genetic distances between these diverse genogroups were at the level of those observed between different Bartonella species described previously.
+Some Bartonella genotypes found in bats clustered with those identified in dogs from Thailand and humans from Poland.
+Broadly Cross clade Neutralizing (BCN) antibodies are recognized as potential therapeutic tools and leads for the design of a vaccine that can protect human beings against various clades of Human Immunodeficiency Virus (HIV).
+In the present study, we screened plasma of 88 HIV-1 infected ART naïve individuals for their neutralization potential using a standard panel of 18 pseudoviruses belonging to different subtypes and different levels of neutralization.
+Four of these samples neutralized even the difficult-to-neutralize tier-3 pseudoviruses with great potency (GMT > 600).
+Analysis of neutralization specificities indicated that four samples had antibodies with multiple epitope binding specificities, viz.
+CD4-binding site (CD4BS), glycans in the V1/V2 and V3 regions and membrane proximal external region (MPER).
+Our findings indicate the strong possibility of identifying highly potent bNAbs with known or novel specificities from HIV-1 subtype C infected individuals from India that can be exploited as therapeutic tools or lead molecules for the identification of potential epitopes for design of a protective HIV-1 vaccine.
+Phosphatidylinositol-3-phosphate 5-kinase (PIKfyve) is a lipid kinase involved in endosome maturation that emerged from a haploid genetic screen as being required for Ebola virus (EBOV) infection.
+Here we analyzed the effects of apilimod, a PIKfyve inhibitor that was reported to be well tolerated in humans in phase 2 clinical trials, for its effects on entry and infection of EBOV and Marburg virus (MARV).
+We first found that apilimod blocks infections by EBOV and MARV in Huh 7, Vero E6 and primary human macrophage cells, with notable potency in the macrophages (IC(50), 10 nM).
+We next observed that similar doses of apilimod block EBOV-glycoprotein-virus like particle (VLP) entry and transcription-replication competent VLP infection, suggesting that the primary mode of action of apilimod is as an entry inhibitor, preventing release of the viral genome into the cytoplasm to initiate replication.
+After providing evidence that the anti-EBOV action of apilimod is via PIKfyve, we showed that it blocks trafficking of EBOV VLPs to endolysosomes containing Niemann-Pick C1 (NPC1), the intracellular receptor for EBOV.
+We did not detect any effects of apilimod on bulk endosome acidification, on the activity of cathepsins B and L, or on cholesterol export from endolysosomes.
+Hence by antagonizing PIKfyve, apilimod appears to block EBOV trafficking to its site of fusion and entry into the cytoplasm.
+Given the drug’s observed anti-filoviral activity, relatively unexplored mechanism of entry inhibition, and reported tolerability in humans, we propose that apilimod be further explored as part of a therapeutic regimen to treat filoviral infections.
+The Communicable Disease Control Medical Network (CDCMN), established in 2003 after the SARS outbreak in Taiwan, has undergone several phases of modification in structure and activation.
+The main organizing principles of the CDCMN are centralized isolation of patients with severe highly infectious diseases and centralization of medical resources, as well as a network of designated regional hospitals like those in other countries.
+It was tested and activated in response to the H1N1 influenza pandemic in 2009-10 and the Ebola outbreak in West Africa in 2014-2016, and it demonstrated high-level functioning and robust capacity.
+In this article, the history, structure, and operation of the CDCMN is introduced globally for the first time, and the advantages and challenges of this system are discussed.
+The Taiwanese experience shows an example of a collaboration between the public health system and the medical system that may help other public health authorities plan management and hospital preparedness for highly infectious diseases.
+Protein modification by ubiquitin and ubiquitin-like modifiers (Ubls) is counteracted by ubiquitin- and Ubl-proteases collectively called DUBs.
+In contrast to other proteases of the ubiquitin-specific protease (USP) family, USP18 shows no reactivity towards ubiquitin but specifically deconjugates the interferon induced Ubl ISG15.
+To identify molecular determinants for this specificity, we solved the crystal structures of mouse USP18 and of mouse USP18 in complex with mouse ISG15.
+USP18 was crystallized in an open and a closed conformation revealing high flexibility of the enzyme.
+Structural data, biochemical and mutational analysis showed that only the C-terminal ubiquitin-like domain of ISG15 is recognized and essential for USP18 activity.
+A critical hydrophobic patch in USP18 interacts with a hydrophobic region unique to ISG15 providing evidence that ISG15 specificity of USP18 is mediated by a small interaction interface.
+Our results may provide the structural basis for the development of new drugs modulating ISGylation.
+Immune responses combat various infectious agents by inducing inflammatory responses, antimicrobial pathways and adaptive immunity.
+Specific lncRNAs are induced to modulate innate and adaptive immune responses which can function through various target interactions like RNA-DNA, RNA-RNA, and RNA-protein interaction and hence affect the immunogenic regulation at various stages of gene expression.
+LncRNA are found to be present in various immune cells like monocytes, macrophages, dendritic cells, neutrophils, T cells and B cells.
+They have been shown to be involved in many biological processes, including the regulation of the expression of genes, the dosage compensation and genomics imprinting, but the knowledge how lncRNAs are regulated and how they alter cell differentiation/function is still obscure.
+Further dysregulation of lncRNA has been seen in many diseases, but as yet very less research has been carried out to understand the role of lncRNAs in regulation during host-pathogens interactions.
+In this review, we summarize the functional developments and mechanism of action of lncRNAs, in immunity and defense of host against pathogens.
+Allotransplantation and xenotransplantation may be associated with the transmission of pathogens from the donor to the recipient.
+Whereas in the case of allotransplantation the transmitted microorganisms and their pathogenic effect are well characterized, the possible influence of porcine microorganisms on humans is mostly unknown.
+Porcine circoviruses (PCVs) are common in pig breeds and they belong to porcine microorganisms that still have not been fully addressed in terms of evaluating the potential risk of xenotransplantation using pig cells, tissues, and organs.
+Although most pigs are subclinically infected, we do not know whether this infection impairs pig transplant functionality, particularly because PCV2 is immunosuppressive.
+In addition, vaccination against PCV2 is able to prevent diseases, but in most cases not transmission of the virus.
+Although there is evidence that PCV2 does not infect—at least immunocompetent—humans, animals should be screened using sensitive methods to ensure virus elimination by selection, Cesarean delivery, vaccination, or embryo transfer.
+While evidence exists to support the effectiveness of neuraminidase inhibitors (NAIs) in reducing mortality when given to hospitalized patients with A(H1N1)pdm09 virus infection, the impact of outpatient treatment on hospitalization has not been clearly established.
+We investigated the impact of outpatient NAI treatment on subsequent hospitalization in patients with A(H1N1)pdm09 virus infection.
+We assembled general community and outpatient data from 9 clinical centers in different countries collected between January 2009 and December 2010.
+We standardized data from each study center to create a pooled dataset and then used mixed-effects logistic regression modeling to determine the effect of NAI treatment on hospitalization.
+We adjusted for NAI treatment propensity and preadmission antibiotic use, including “study center” as a random intercept to account for differences in baseline hospitalization rate between centers.
+Eight hundred seventy-three patients (25.8%) received outpatient or community-based NAI treatment, 928 of 2395 (38.8%) with available data had dyspnea or respiratory distress, and hospitalizations occurred in 1705 (50.5%).
+After adjustment for preadmission antibiotics and NAI treatment propensity, preadmission NAI treatment was associated with decreased odds of hospital admission compared to no NAI treatment (adjusted odds ratio, 0.24; 95% confidence interval, 0.20–0.30).
+In a population with confirmed or suspected A(H1N1)pdm09 and at high risk of hospitalization, outpatient or community-based NAI treatment significantly reduced the likelihood of requiring hospital admission.
+In addition to its well-known role of binding iron, lactoferrin carries many important biological functions, including the promotion of cell proliferation and differentiation, and as an anti-bacterial, anti-viral, and anti-parasitic protein.
+Although considerable attention has been given to the many functions of lactoferrin, its primary nutritional contribution is presumed to be related to its iron-binding characteristics, whereas the role of glycosylation has been neglected.
+Given the critical role of glycan binding in many biological processes, the glycan moieties in lactoferrin are likely to contribute significantly to the biological roles of lactoferrin.
+Despite the high amino acid sequence homology in different lactoferrins (up to 99%), each exhibits a unique glycosylation pattern that may be responsible for heterogeneity of the biological properties of lactoferrins.
+An important task for the production of biotherapeutics and medical foods containing bioactive glycoproteins is the assessment of the contributions of individual glycans to the observed bioactivities.
+This review examines how the study of lactoferrin glycosylation patterns can increase our understanding of lactoferrin functionality.
+With the advent of potent immunosuppressive options, acute rejection episodes have decreased at the expense of increased incidence of opportunistic infections in solid organ recipients.
+In the absence of any preventive therapy, 30–75 % of transplant recipients develop cytomegalovirus (CMV) infection.
+A 54-year-old male patient presented with fever, shortness of breath, and chest pain on the 9th posttransplant week after renal transplantation.
+There were inspiratory crackles at both lung bases, and chest computed tomography (CT) revealed multiple fungal balls throughout the right lung.
+Galactomannan antigen was positive, and voriconazole and other antimicrobials were subsequently added to the treatment.
+At the end of the therapy, on control CT, pneumonic consolidation had disappeared, sputum cultures didn’t show Aspergillus spp., and CMV-DNA reduced to 700 copies/ml.
+The patient showed a favorable clinical response to combined treatment; fever, dyspnea, and pleuritic chest pain disappeared.
+Both CMV disease and aspergillosis may present as pulmonary disease; thus, the characterization of one may not preclude the search for the other and the timely initiation of treatment is of paramount importance for good outcomes.
+Severe cases such as, hyperinfection syndrome (HS) and disseminated strongyloidiasis (DS), can involve pulmonary manifestations.
+METHODS: From January 2004 to December 2014, all patients diagnosed with severe strongyloidiasis at the University of the Ryukyus Hospital or affiliated hospitals in Okinawa, Japan, were included in this retrospective study.
+Severe strongyloidiasis was defined by the presence of any of the following: 1) the identification of S. stercoralis from extra gastrointestinal specimens, 2) sepsis, 3) meningitis, 4) acute respiratory failure, or 5) respiratory tract hemorrhage.
+Of those, fifteen cases had pulmonary manifestations, eight had acute respiratory distress syndrome (ARDS) (53%), seven had enteric bacterial pneumonia (46%) and five had pulmonary hemorrhage (33%).
+Additionally, ileum gas was detected for ten of the sixteen cases in the upper abdomen during assessment with chest X-ray.
+CONCLUSIONS: In summary, our study described HS/DS cases with pulmonary manifestations including, ARDS, bacterial pneumonia and pulmonary hemorrhage.
+Chest X-ray findings in HS/DS cases frequently showed diffuse shadows, and the combination of GGO and interlobular septal thickening in chest CT was common in HS/DS, regardless of accompanying pulmonary manifestations.
+This CT finding suggests alveolar hemorrhage could be used as a potential marker indicating the transition from latent to symptomatic state.
+The success of lentiviral vectors in curing fatal genetic and acquired diseases has opened a new era in human gene therapy.
+However, variability in the efficacy and safety of this therapeutic approach has been reported in human patients.
+Consequently, lentiviral-vector-based gene therapy is limited to incurable human diseases, with little understanding of the underlying causes of adverse effects and poor efficacy.
+To assess the role that host genetic variation has on efficacy of gene therapy, we characterized lentiviral-vector gene therapy within a set of 12 collaborative cross mouse strains.
+Lentiviral vectors carrying the firefly luciferase cDNA under the control of a liver-specific promoter were administered to female mice, with total-body and hepatic luciferase expression periodically monitored through 41 weeks post-vector administration.
+Vector copy number per diploid genome in mouse liver and spleen was determined at the end of this study.
+We identified major strain-specific contributions to overall success of transduction, vector biodistribution, maximum luciferase expression, and the kinetics of luciferase expression throughout the study.
+Our results highlight the importance of genetic variation on gene-therapeutic efficacy; provide new models with which to more rigorously assess gene therapy approaches; and suggest that redesigning preclinical studies of gene-therapy methodologies might be appropriate.
+Although a sizable proportion of deaths by suicide may be preventable, it is well documented that despite major governmental and international investments in research, education and clinical practice suicide rates have not diminished and are even increasing among several at-risk populations.
+Although nonhuman animals do not engage in suicidal behavior amenable to translational studies, we argue that animal model systems are necessary to investigate candidate endophenotypes of suicidal behavior and the neurobiology underlying these endophenotypes.
+Animal models are similarly a critical resource to help delineate treatment targets and pharmacological means to improve our ability to manage the risk of suicide.
+In particular, certain pathophysiological pathways to suicidal behavior, including stress and hypothalamic–pituitary–adrenal axis dysfunction, neurotransmitter system abnormalities, endocrine and neuroimmune changes, aggression, impulsivity and decision-making deficits, as well as the role of critical interactions between genetic and epigenetic factors, development and environmental risk factors can be modeled in laboratory animals.
+We broadly describe human biological findings, as well as protective effects of medications such as lithium, clozapine, and ketamine associated with modifying risk of engaging in suicidal behavior that are readily translatable to animal models.
+Endophenotypes of suicidal behavior, studied in animal models, are further useful for moving observed associations with harmful environmental factors (for example, childhood adversity, mechanical trauma aeroallergens, pathogens, inflammation triggers) from association to causation, and developing preventative strategies.
+Further study in animals will contribute to a more informed, comprehensive, accelerated and ultimately impactful suicide research portfolio.
+Massive all-atom molecular dynamics simulations were conducted across a distributed computing network to study the folding, unfolding, misfolding and conformational plasticity of the high-efficiency frameshifting double mutant of the 26 nt potato leaf roll virus RNA pseudoknot.
+Our robust sampling, which included over 40 starting structures spanning the spectrum from the extended unfolded state to the native fold, yielded nearly 120 μs of cumulative sampling time.
+Conformational microstate transitions on the 1.0 ns to 10.0 μs timescales were observed, with post-equilibration sampling providing detailed representations of the conformational free energy landscape and the complex folding mechanism inherent to the pseudoknot motif.
+Herein, we identify and characterize two alternative native structures, three intermediate states, and numerous misfolded states, the latter of which have not previously been characterized via atomistic simulation techniques.
+While in line with previous thermodynamics-based models of a general RNA folding mechanism, our observations indicate that stem-strand-sequence-separation may serve as an alternative predictor of the order of stem formation during pseudoknot folding.
+Our results contradict a model of frameshifting based on structural rigidity and resistance to mechanical unfolding, and instead strongly support more recent studies in which conformational plasticity is identified as a determining factor in frameshifting efficiency.
+Embryonic growth and development of skeletal muscle is a major determinant of muscle mass, and has a significant effect on meat production in chicken.
+To assess the protein expression profiles during embryonic skeletal muscle development, we performed a proteomics analysis using isobaric tags for relative and absolute quantification (iTRAQ) in leg muscle tissues of female Xinghua chicken at embryonic age (E) 11, E16, and 1-day post hatch (D1).
+We identified 3,240 proteins in chicken embryonic muscle and 491 of them were differentially expressed (fold change ≥ 1.5 or ≤ 0.666 and p < 0.05).
+There were 19 up- and 32 down-regulated proteins in E11 vs. E16 group, 238 up- and 227 down-regulated proteins in E11 vs. D1 group, and 13 up- and 5 down-regulated proteins in E16 vs. D1 group.
+Protein interaction network analyses indicated that these differentially expressed proteins were mainly involved in the pathway of protein synthesis, muscle contraction, and oxidative phosphorylation.
+Integrative analysis of proteome and our previous transcriptome data found 189 differentially expressed proteins that correlated with their mRNA level.
+The interactions between these proteins were also involved in muscle contraction and oxidative phosphorylation pathways.
+The lncRNA-protein interaction network found four proteins DMD, MYL3, TNNI2, and TNNT3 that are all involved in muscle contraction and may be lncRNA regulated.
+These results provide several candidate genes for further investigation into the molecular mechanisms of chicken embryonic muscle development, and enable us to better understanding their regulation networks and biochemical pathways.
+Farnesyltransferase has been regarded as a promising drug target against cancer as it is critical for membrane association of several signal transduction proteins.
+It exhibits stronger potency (IC(50)s: 6.92–8.99 μM) than Sunitinib against all of the tested cancer cell lines.
+Preliminary studies on mechanism reveal that IMB-1406 induces apoptosis in HepG2 cells by arresting the cell cycle at the S phase, altering anti- and pro-apoptotic proteins leading to mitochondrial dysfunction and activation of caspase-3.
+This anti-tumor effect is most probably related to the inhibition of farnesyltransferase as indicated by molecular docking.
+Overall, IMB-1406 is a novel lead compound with potent antitumor activity and deserves further structural modifications.
+Changes in lifestyle and environmental conditions give rise to an increasing prevalence of liver and lung fibrosis, and both have a poor prognosis.
+Promising results have been reported for recombinant angiotensin-converting enzyme 2 (ACE2) protein administration in experimental liver and lung fibrosis.
+However, the full potential of ACE2 may be achieved by localized translation of a membrane-anchored form.
+For this purpose, we advanced the latest RNA technology for liver- and lung-targeted ACE2 translation.
+We demonstrated in vitro that transfection with ACE2 chemically modified messenger RNA (cmRNA) leads to robust translation of fully matured, membrane-anchored ACE2 protein.
+In a second step, we designed eight modified ACE2 cmRNA sequences and identified a lead sequence for in vivo application.
+Finally, formulation of this ACE2 cmRNA in tailor-made lipidoid nanoparticles and in lipid nanoparticles led to liver- and lung-targeted translation of significant amounts of ACE2 protein, respectively.
+In summary, we provide evidence that RNA transcript therapy (RTT) is a promising approach for ACE2-based treatment of liver and lung fibrosis to be tested in fibrotic disease models.
+Oncolytic virotherapy has advanced since the days of its conception but therapeutic efficacy in the clinics does not seem to reach the same level as in animal models.
+One reason is premature oncolytic virus clearance in humans, which is a reasonable assumption considering the immune-stimulating nature of the oncolytic agents.
+However, several studies are beginning to reveal layers of restriction to oncolytic virotherapy that are present before an adaptive neutralizing immune response.
+Some of these barriers are present constitutively halting infection before it even begins, whereas others are raised by minute cues triggered by virus infection.
+Indeed, we and others have noticed that delivering viruses to tumors may not be the biggest obstacle to successful therapy, but instead the physical make-up of the tumor and its capacity to mount antiviral defenses seem to be the most important efficacy determinants.
+In this review, we summarize the constitutive and innate barriers to oncolytic virotherapy and discuss strategies to overcome them.
+This study examined the transcriptome of tracheal epithelial cells from two inbred chicken lines that differ in NDV susceptibility after challenge with a high-titer inoculum of lentogenic NDV.
+The Fayoumi line had a significantly lower NDV load postchallenge than the Leghorn line, demonstrating the Fayoumi line's classification as a relatively NDV-resistant breed.
+Examination of the trachea transcriptome showed a large increase in immune cell infiltration in the trachea in both lines at all times postinfection.
+The pathways conserved across lines and at all three time points postinfection included iCOS-iCOSL signaling in T helper cells, NF-κB signaling, the role of nuclear factor of activated T cells in the regulation of the immune response, calcium-induced T lymphocyte apoptosis, phospholipase C signaling, and CD28 signaling in T helper cells.
+Although shared pathways were seen in the Fayoumi and Leghorn lines, each line showed unique responses as well.
+The downregulation of collagen and the activation of eukaryotic translation initiation factor 2 signaling in the Fayoumis relative to the Leghorns at 2 days postinfection may contribute to the resistance phenotype seen in the Fayoumis.
+This study provides a further understanding of host-pathogen interactions which could improve vaccine efficacy and, in combination with genome-wide association studies, has the potential to advance strategies for breeding chickens with enhanced resistance to NDV.
+To keep interested readers up to speed with this literature, we continue a “Digested Disorder” project and represent a series of reader’s digest type articles objectively representing the research papers and reviews on intrinsically disordered proteins.
+The only 2 criteria for inclusion in this digest are the publication date (a paper should be published within the covered time frame) and topic (a paper should be dedicated to any aspect of protein intrinsic disorder).
+The current digest issue covers papers published during the period of April, May, and June of 2013.
+The papers are grouped hierarchically by topics they cover, and for each of the included paper a short description is given on its major findings.
+BACKGROUND: Studies in murine models suggested that platelet desialylation was an important mechanism of thrombocytopenia during sepsis.
+METHODS: First, we performed a prospective, multicenter, observational study that enrolled septic patients with or without thrombocytopenia to determine the association between platelet desialylation and thrombocytopenia in patients with sepsis, severe sepsis, and septic shock.
+Gender- and age-matched healthy adults were selected as normal controls in analysis of the platelet desialylation levels (study I).
+Next, we conducted an open-label randomized controlled trial (RCT) in which the patients who had severe sepsis with thrombocytopenia (platelet counts ≤50 × 10(9)/L) were randomly assigned to receive antimicrobial therapy alone (control group) or antimicrobial therapy plus oseltamivir (oseltamivir group) in a 1:1 ratio (study II).
+The primary outcomes were platelet desialylation level at study entry, overall platelet response rate within 14 days post-randomization, and all-cause mortality within 28 days post-randomization.
+Secondary outcomes included platelet recovery time, the occurrence of bleeding events, and the amount of platelets transfused within 14 days post-randomization.
+RESULTS: The platelet desialylation levels increased significantly in the 127 septic patients with thrombocytopenia compared to the 134 patients without thrombocytopenia.
+A platelet response was achieved in 45 of the 54 patients in the oseltamivir group (83.3%) compared with 34 of the 52 patients in the control group (65.4%; P = 0.045).
+The median platelet recovery time was 5 days (interquartile range 4–6) in the oseltamivir group compared with 7 days (interquartile range 5–10) in the control group (P = 0.003).
+The amount of platelets transfused decreased significantly in the oseltamivir group compared to the control group (P = 0.044).
+There was no difference in the overall 28-day mortality regardless of whether oseltamivir was used.
+The Sequential Organ Failure Assessment score and platelet recovery time were independent indicators of oseltamivir therapy.
+The addition of oseltamivir could significantly increase the platelet response rate, shorten platelet recovery time, and reduce platelet transfusion.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13045-017-0476-1) contains supplementary material, which is available to authorized users.
+The human cytomegalovirus major immediate early proteins IE1 and IE2 are critical drivers of virus replication and are considered pivotal in determining the balance between productive and latent infection.
+IE1 and IE2 are derived from the same primary transcript by alternative splicing and regulation of their expression likely involves a complex interplay between cellular and viral factors.
+Here we show that knockdown of the host ubiquitin-dependent segregase VCP/p97, results in loss of IE2 expression, subsequent suppression of early and late gene expression and, ultimately, failure in virus replication.
+RNAseq analysis showed increased levels of IE1 splicing, with a corresponding decrease in IE2 splicing following VCP knockdown.
+Global analysis of viral transcription showed the expression of a subset of viral genes is not reduced despite the loss of IE2 expression, including UL112/113.
+Furthermore, Immunofluorescence studies demonstrated that VCP strongly colocalised with the viral replication compartments in the nucleus.
+Finally, we show that NMS-873, a small molecule inhibitor of VCP, is a potent HCMV antiviral with potential as a novel host targeting therapeutic for HCMV infection.
+In this study, we found that H(2)S alleviated gentamicin-induced nephrotoxicity by reducing reactive oxygen species (ROS)-mediated apoptosis in normal rat kidney-52E cells.
+We found that H(2)S decreased the protein levels of Bax, Caspase-3, and Cleaved-caspase-3, but increased the expression of Bcl-2.
+Treatment with H(2)S reduced the levels of malondialdehyde and ROS and increased the activities of superoxide dismutase and glutathione peroxidase.
+H(2)S significantly abolished the phosphorylation of extracellular signal-regulated protein kinase 1/2, c-Jun N-terminal kinase, and p38 in the kidney of CRF rats.
+Furthermore, H(2)S decreased the expression levels of tumor necrosis factor-α, interleukin (IL)-6, IL-10, and monocyte chemoattractant protein-1, as well as the protein levels of p50, p65, and p-p65 in the kidney of CRF rats.
+In conclusion, H(2)S could ameliorate adenine-induced CRF in rats by inhibiting apoptosis and inflammation through ROS/mitogen-activated protein kinase and nuclear factor-kappa B signaling pathways.
+A growing body of literature suggests that most chronic autoimmune diseases are associated with inappropriate inflammation mediated by Toll-like receptor (TLR) 3, TLR7/8, or TLR9.
+Therefore, research into blocking TLR activation to treat these disorders has become a hot topic.
+Here, we report the immunomodulatory properties of a nonstimulatory CpG-containing oligodeoxynucleotide (CpG-ODN), CpG-c41, which had previously only been known as a TLR9 antagonist.
+In this study, we found that both in vitro and in vivo CpG-c41 decreased levels of various proinflammatory factors that were induced by single activation or coactivation of intracellular TLRs, but not membrane-bound TLRs, no matter what downstream signal pathways the TLRs depend on.
+Moreover, CpG-c41 attenuated excessive inflammation in the imiquimod-induced psoriasis-like mouse model of skin inflammation by suppressing immune cell infiltration and release of inflammatory factors.
+We also found evidence that the immunosuppressive effects of CpG-c41 on other intracellular TLRs are mediated by a TLR9-independent mechanism.
+These results suggest that CpG-c41 acts as an upstream of signaling cascades, perhaps on the processes of ligand internalization and transfer.
+Taken together, these results suggest that CpG-c41 disrupts various aspects of intracellular TLR activation and provides a deeper insight into the regulation of innate immunity.
+Specially, establishing whether invasive species operate within the constraint of conservative ecological niches, or if niche shifts occur at all commonly as part of the invasion process, is indispensable to identifying and anticipating potential areas of invasion.
+Ecological niche modeling (ENM) has been used to address such questions, but improvements and debate in study design, model evaluation, and methods are still needed to mature this field.
+We reanalyze data for Gray Squirrels (Sciurus carolinensis), native to North America, but invasive in Europe.
+Our main finding was that, when the analysis extent is established carefully based on analogous sets of environmental conditions, all evidence of niche shifts disappears, suggesting that previous reports of niche shifts for this species are artifacts of methods and interpretation, rather than biological reality.
+Niche conservatism should be tested only within appropriate, similar, environmental spaces that are accessible to both species or populations being compared, thus avoiding model extrapolation related to model transfers.
+Testing for environmental similarity between native and invaded areas is critical to identifying niche shifts during species invasion robustly, but also in applications of ENM to understanding temporal dimensions of niche dynamics.
+Previously developed Asn-Gly-Arg (NGR) peptide-modified multifunctional poly(ethyleneimine)–poly(ethylene glycol) (PEI–PEG)-based nanoparticles (TPIC) have been considered to be promising carriers for the co-delivery of DNA and doxorubicin (DOX).
+As a continued effort, the aim of the present study was to further evaluate the interaction between TPIC and human umbilical vein endothelial cells (HUVEC) to better understand the cellular entry mechanism.
+In the present investigation, experiments relevant to co-localization, endocytosis inhibitors and factors influencing the internalization were performed.
+Without any treatment, there was no co-localization between aminopeptidase N/CD13 (APN/CD13) and caveolin 1 (CAV1).
+However, co-localization between CD13 and CAV1 was observed when cells were incubated with an anti-CD13 antibody or TPIC.
+As compared with antibody treatment, TPIC accelerated the speed and enhanced the degree of co-localization.
+However, this internalization was not dependent on the enzyme activity of CD13 but could be inhibited by methyl-β-eyclodextfin (MβCD), further identifying the involvement of caveolae-mediated endocytosis (CvME).
+Our group recently identified 16 genes whose peripheral blood expression levels are differentially regulated in acute ischemic stroke.
+The purpose of this study was to determine whether the early expression levels of any of these 16 genes are predictive for post-stroke blood brain barrier (BBB) disruption.
+Transcriptional expression levels of candidate genes were measured in peripheral blood sampled from ischemic stroke patients at emergency department admission, and BBB permeability was assessed at 24 hour follow up via perfusion-weighted imaging.
+Early heightened expression levels of AKAP7, a gene encoding a protein kinase A-binding scaffolding molecule, were significantly associated with BBB disruption 24 hours post-hospital admission.
+We then determined that AKAP7 is predominantly expressed by lymphocytes in peripheral blood, and strongly co-expressed with ITGA3, a gene encoding the adhesion molecule integrin alpha 3.
+Subsequent in vitro experiments revealed that heightened expression of AKAP7 and ITGA3 in primary human lymphocytes is associated with a highly adherent phenotype.
+Collectively, our results suggest that AKAP7 expression levels may have clinical utility as a prognostic biomarker for post-stroke BBB complications, and are likely elevated early in patients who later develop post-stroke BBB disruption due to the presence of an invasive lymphocyte population in the peripheral blood.
+This study aimed to investigate the epidemiological, clinical, and virologic characteristics of avian influenza A (H7N9) confirmed cases from two family clusters in Southeast China.
+Epidemiological data of the H7N9 confirmed cases and their close contacts were obtained through interviews and reviews of medical records.
+Of the four patients in these two family clusters, two cases had mild symptoms, one had severe symptoms, and one died.
+Three of the four patients had a history of exposure to live poultry or contaminated environments.
+The complete genome sequences of the H7N9 viruses from the same family cluster were highly homologous, and the four isolated viruses from the two family clusters exhibited the virologic features of the H7N9 virus, in terms of transmissibility, pathogenicity, host adaptation, and antiviral drug resistance.
+In addition, our findings indicated that the A/Fujian/18/2015 viral strain contained an additional hemagglutinin G225D substitution, which preferentially binds α2,6-linked sialic acids.
+The results of this study demonstrate that one family cluster was infected through common exposure to live poultry or contaminated environments, and the other was more likely to be infected through the human-to-human route.
+Although preclinical studies demonstrated that TAMs preferentially express CD163 and CD204, the TAM subsets in oral squamous cell carcinoma (OSCC) remain unknown.
+Forty-six patients with OSCC were analyzed for expression of TAMs in biopsy samples by immunohistochemistry.
+We examined TAM subsets and their production of immune suppressive molecules (IL-10 and PD-L1) in peripheral blood mononuclear cells from three OSCC patients by flow cytometry.
+CD163 was detected around the tumor or connective tissue, while CD204 was detected in/around the tumors.
+Flow cytometric analysis revealed that CD163(+)CD204(+) TAMs strongly produced IL-10 and PD-L1 in comparison with CD163(+)CD204(−) and CD163(−)CD204(+) TAMs.
+Furthermore, the number of activated CD3(+) T cells after co-culture with CD163(+)CD204(+) TAMs was significantly lower than that after co-culture with other TAM subsets.
+In clinical findings, the number of CD163(+)CD204(+) TAMs was negatively correlated with that of CD25(+) cells and 5-year progression-free survival.
+These results suggest that CD163(+)CD204(+) TAMs possibly play a key role in the invasion and metastasis of OSCC by T-cell regulation via IL-10 and PD-L1 production.
+Host genetic variability is an important determinant of the risk of developing TB in humans.
+Although the association between MBL polymorphisms and TB has been studied in various populations, the results are controversial.
+The aim of this study was to investigate mannose-binding lectin (MBL) gene polymorphisms with susceptibility to pulmonary tuberculosis (PTB) in a Lur population of Iran.
+METHODS: In this case-control study, four functional MBL gene polymorphisms (HL, XY, PQ and AB) were genotyped by using PCR Single Strand Conformation Polymorphism (SSCP) technique in a Lur population living in Lorestan Province, consisting of 100 patients with pulmonary tuberculosis (PTB) age and sex matched 100 healthy controls (HCs).
+RESULTS: We found that MBL (HH) genotype polymorphism significantly was associated with increased susceptibility to TB (35% in patients vs. 22% in controls, P = 0.0417, OR = 1.909, %95 CI = 1.020–3.573).
+Additionally, H allele showed a significant association with increased risk of TB (56.5% in patients vs. 46% in controls, P = 0.0357, OR = 1.525, %95 CI = 1.028–2.262).
+Also, the distribution of L allele in patients was significantly lower frequency in TB patients compared to controls (43.5% vs. 54%, P = 0.0357, OR = 0.656, %95 CI = 0.442–0.973).
+However, the allelic and genotypic frequencies of AB, XY and PQ polymorphisms were not significantly different between the patients and the controls.
+CONCLUSIONS: Our findings demonstrated that HH genotype and H allele may increase the susceptibility to pulmonary TB in the Lur population of Iran, although L allele may decrease the susceptibility to pulmonary TB in this population.
+We suggest that it is necessary to further more studies with larger sample size and other ethnic population.
+Glycoprotein B (gB) is the conserved herpesvirus fusion protein, and it is required for the entry of herpesviruses.
+The structure of the postfusion conformation of gB has been solved for several herpesviruses; however, the gB prefusion crystal structure and the details of how the protein refolds from a prefusion to a postfusion form to mediate fusion have not been determined.
+Using structure-based mutagenesis, we previously reported that three mutations (I671A, H681A, and F683A) in the C-terminal arm of the gB ectodomain greatly reduced cell-cell fusion.
+This fusion deficit could be rescued by the addition of a hyperfusogenic mutation, suggesting that the gB triple mutant was not misfolded.
+Using a bacterial artificial chromosome (BAC), we constructed two independent herpes simplex virus 1 mutant strains (gB 3A) carrying the three arm mutations.
+The gB 3A viruses have 200-fold smaller plaques than the wild-type virus and demonstrate remarkably delayed entry into cells.
+We propose that the gB 3A viruses’ entry deficit is due to a loss of interactions between residues in the gB C-terminal arm and the coiled-coil core of gB.
+The results suggest that the triple alanine mutation may destabilize the postfusion gB conformation and/or stabilize the prefusion gB conformation and that exposure to elevated temperatures can overcome the defect in gB 3A viruses.
+BACKGROUND: Glypican-3 (GPC3) is a cell surface-bound proteoglycan which has been identified as a potential biomarker candidate in hepatocellular carcinoma, lung carcinoma, severe pneumonia, and acute respiratory distress syndrome (ARDS).
+The aim of our review is to evaluate whether GPC3 has utility as a disease-specific biomarker, to discuss the potential involvement of GPC3 in cell biology, and to consider the changes of GPC3 gene and protein expression and regulation in hepatocellular carcinoma, lung cancer, severe pneumonia, and ARDS.
+RESULTS: Immunohistochemical studies have suggested that over-expression of GPC3 is associated with a poorer prognosis for hepatocellular carcinoma patients.
+Expression of GPC3 leads to an increased apoptosis response in human lung carcinoma tumor cells, and is considered to be a candidate lung tumor suppressor gene.
+CONCLUSIONS: Glypican-3 could be considered as a clinically useful biomarker in hepatocellular carcinoma, lung carcinoma, and ARDS, but further research is needed to confirm and expand on these findings.
+In this paper, we propose a model where two strains compete with each other at the expense of common susceptible individuals on heterogeneous networks by using pair-wise approximation closed by the probability-generating function (PGF).
+From a special perspective, we first study the dynamical behaviour of an SIR model closed by the PGF, and obtain the basic reproduction number via two methods.
+Then we build a model to study the spreading dynamics of competing viruses and discuss the conditions for the local stability of equilibria, which is different from the condition obtained by using the heterogeneous mean-field approach.
+Finally, we perform numerical simulations on Barabási–Albert networks to complement our theoretical research, and show some dynamical properties of the model with competing viruses.
+This article is part of the themed issue ‘Mathematical methods in medicine: neuroscience, cardiology and pathology’.
+Defective-Interfering RNAs (DI-RNAs) have long been known to play an important role in virus replication and transmission.
+DI-RNAs emerge during virus passaging in both cell-culture and their hosts as a result of non-homologous RNA recombination.
+Using a combination of long- and short-read Next-Generation Sequencing, we have characterized the formation of DI-RNAs during serial passaging of Flock House virus (FHV) in cell-culture over a period of 30 days in order to elucidate the pathways and potential mechanisms of DI-RNA emergence and evolution.
+For short-read RNAseq, we employed ‘ClickSeq’ due to its ability to sensitively and confidently detect RNA recombination events with nucleotide resolution.
+In parallel, we used the Oxford Nanopore Technologies’s (ONT) MinION to resolve full-length defective and wild-type viral genomes.
+Together, these accurately resolve both rare and common RNA recombination events, determine the correlation between recombination events, and quantifies the relative abundance of different DI-RNAs throughout passaging.
+We observe the formation of a diverse pool of defective RNAs at each stage of viral passaging.
+However, many of these ‘intermediate’ species, while present in early stages of passaging, do not accumulate.
+After approximately 9 days of passaging we observe the rapid accumulation of DI-RNAs with a correlated reduction in specific infectivity and with the Nanopore data find that DI-RNAs are characterized by multiple RNA recombination events.
+This suggests that intermediate DI-RNA species are not competitive and that multiple recombination events interact epistatically to confer ‘mature’ DI-RNAs with their selective advantage allowing for their rapid accumulation.
+Alternatively, it is possible that mature DI-RNA species are generated in a single event involving multiple RNA rearrangements.
+These insights have important consequences for our understanding of the mechanisms, determinants and limitations in the emergence and evolution of DI-RNAs.
+INTRODUCTION: Non-invasive ventilation (NIV) is not proven to be effective in treating respiratory failure in severe pneumonia.
+However, some clinicians nevertheless attempt NIV to indirectly deliver adequate oxygenation and avoid unnecessary endotracheal intubation.
+CASE PRESENTATION: In this article, we report the case of a 24-year-old woman at 32 weeks' gestation who presented with hypoxemic respiratory failure requiring mechanical ventilation.
+This is of the utmost importance in avoiding any delay should the patient's condition worsen and require endotracheal intubation.
+Moreover, in pregnant women, the severity of illness may progress quickly due to the immunosuppression inherent in these patients.
+CONCLUSION: Special attention should be given to the choices of invasive ventilation and NIV to manage community acquired pneumonia patients in third trimester.
+Neutrophil gelatinase-associated lipocalin (NGAL) is a 25-kDa protein of the lipocalin superfamily and its presence was initially observed in activated neutrophils.
+It has previously been demonstrated that the expression of NGAL is markedly increased in stimulated epithelia, and is important in the innate immunological response to various pathophysiological conditions, including infection, cancer, inflammation and kidney injury.
+NGAL mRNA and protein expression levels in lung tissue were detected using reverse transcription-quantitative polymerase chain reaction and western blotting, respectively.
+In addition, NGAL protein levels in bronchoalveolar lavage fluid and serum were measured via western blotting.
+The results of the present study suggested that NGAL expression increased under all mechanical ventilation treatments.
+The increase was most prominent in the high peak inflation pressure and high-volume mechanical ventilation groups, where there was the greatest extent of lung injury.
+In addition, NGAL expression increased in a time-dependent manner under high-volume mechanical ventilation, consistent with the degree of lung injury.
+These findings suggested that NGAL may serve as a potential novel biomarker in ventilator-associated lung injury.
+BACKGROUND: Poultry farmers are at high-risk from avian influenza A/H7N9 infection due to sustained occupational exposures to live poultry.
+This study examined factors associated with poultry farmers’ adoption of personal protective behaviours (PPBs) based on Protection Motivation Theory (PMT).
+METHODS: Totally, 297 poultry farmers in three cities of Jiangsu Province, China were interviewed during November 2013-January 2014.
+Data on PMT constructs, perceived trustworthiness of A/H7N9 information from mass media (formal sources), friends and family (informal sources), intention to adopt and actual adoption of PPBs and respondents’ demographics were collected.
+Structural equation modeling (SEM) identified associations between demographic factors and PMT constructs associated with A/H7N9-oriented PPB intention.
+Moderated mediation analysis examined how demographics moderated the effects of information trust on PPB intention via risk perceptions of A/H7N9.
+The SEM found that male respondents perceived lower severity of (β = −0.23), and lower vulnerability to (β = -0.15) A/H7N9 infection; age was positively associated with both perceived personal vulnerability to (β = 0.21) and perceived self-efficacy (β = 0.24) in controlling A/H7N9; education was positively associated with perceived response efficacy (β = 0.40).
+Furthermore, perceived vulnerability (β = 0.16), perceived self-efficacy (β = 0.21) and response efficacy (β = 0.67) were positively associated with intention to adopt PPBs against A/H7N9.
+More trust in informal information (TII) was only significantly associated with greater PPB intention through its positive association with perceived response efficacy.
+Age significantly moderated the associations of TII with perceived Self-efficacy and perceived response efficacy, with younger farmers who had greater TII perceiving lower self-efficacy but higher response efficacy.
+Interventions designed to enhance perceived response efficacy, particularly among lower educated respondents may effectively motivate adoption of PPBs.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12889-017-4364-y) contains supplementary material, which is available to authorized users.
+This study aimed to evaluate the anti-influenza viral activity and possible mechanisms of 12 phenanthrenes from the medicinal plant Bletilla striata (Orchidaceae family).
+Phenanthrenes mixed with the virus were incubated at 37 °C for 1 h and then inoculated into 9-day-old embryonated chicken eggs via the allantoic route to survey the antiviral activity in vivo.
+A (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H–tetrazolium) (MTS)-based assay was performed to evaluate the reduction of cytopathic effect induced by H3N2 on Madin-Darby canine kidney (MDCK) cells.
+The hemagglutination inhibition assay was used to study the blockage of virus receptors by the phenanthrenes, and the neuraminidase (NA) inhibition assay to evaluate the effects of the release of virus.
+The synthesis of influenza viral matrix protein mRNA in response to compound treatment was measured by real-time polymerase chain reaction.
+RESULTS: This study showed that phenanthrenes 1, 2, 3, 4, 6, 9, 10, 11, and 12 significantly inhibited the viruses in vivo, with inhibition rates of 20.7, 79.3, 17.2, 34.5, 34.5, 34.5, 44.8, 75.9, and 34.5%, respectively.
+In MDCK models, the phenanthrenes did not show significant antiviral activity when administered as pretreatment, while phenanthrenes 2, 3, 4, 6, 7 10, and 11 exhibited inhibitory activities as simultaneous treatment with 50% inhibition concentration (IC(50)) ranging from 14.6 ± 2.4 to 43.3 ± 5.3 μM.
+The IC(50) ranged from 18.4 ± 3.1 to 42.3 ± 3.9 μM in the post-treatment assays.
+Compounds 1, 3, 4, 6, 10, and 11 exhibited an inhibitory effect on NA; and compounds 2, 3, 4 6, 7, 10, and 11 resulted in the reduced transcription of virus matrix protein mRNA.
+CONCLUSION: Phenanthrenes from B. striata had strong anti-influenza viral activity in both embryonated eggs and MDCK models, and diphenanthrenes seemed to have stronger inhibition activity compared with monophenanthrenes.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12906-017-1780-6) contains supplementary material, which is available to authorized users.
+A novel avian-origin influenza A (H7N9) virus emerged in China in 2013 and has caused zoonotic disease in over 1123 persons with an overall mortality around 30%.
+Amino acid changes at the residues 591, 627 and 701 of polymerase basic protein 2 (PB2) have been found frequently in the human H7N9 isolates but not in viruses isolated from avian species.
+We have recently identified a cluster of H7N9 viruses in ducks which circulated in China prior to the first recognition of zoonotic disease in 2013.
+We found that the introduction of PB2 mutation with K at 627 but not K at 591 or N at 701 to the duck H7N9 virus led to increased pathogenicity in mice.
+We also found that the induction of pro-inflammatory cytokines including TNF-α, IP-10, MCP-1 and MIP-1α were associated with increased severity of infection.
+We conclude that introduction of the mammalian adaptation mutations into the PB2 gene of duck H7N9 viruses, which are genetically unrelated to the zoonotic H7N9 lineage, can also enhance pathogenicity in mice.
+Bovine paratuberculosis (PTB) is a chronic enteric inflammatory disease of ruminants caused by Mycobacterium avium subsp.
+Spread of PTB is mainly provoked by a long subclinical stage during which MAP is shed into the environment with feces; accordingly, detection of subclinical animals is very important to its control.
+Therefore, the current study was conducted to develop a diagnostic method for analysis of the expression of genes of prognostic potential biomarker candidates in the whole blood of cattle naturally infected with MAP.
+Real-time PCR with nine potential biomarker candidates was developed for the diagnosis of MAP subclinical infection.
+Eight genes (Timp1, Hp, Serpine1, Tfrc, Mmp9, Defb1, Defb10, and S100a8) were up-regulated in MAP-infected cattle (p <0.05).
+Moreover, ROC analysis revealed that eight genes (Timp1, Hp, Serpine1, Tfrc, Mmp9, Defb1, Defb10, and S100a8) showed fair diagnostic performance (AUC≥0.8).
+Four biomarkers (Timp1, S100a8, Defb1, and Defb10) showed the highest diagnostic accuracy in the PCR positive and ELISA negative group (PN group) and three biomarkers (Tfrc, Hp, and Serpine1) showed the highest diagnostic accuracy in the PCR negative and ELISA positive group (NP group).
+Moreover, three biomarkers (S100a8, Hp, and Defb10) were considered the most reliable for the PCR positive and ELISA positive group (PP group).
+Taken together, our data suggest that real-time PCR based on eight biomarkers (Timp1, Hp, Serpine1, Tfrc, Mmp9, Defb1, Defb10, and S100a8) might be useful for diagnosis of JD, including subclinical stage cases.
+We previously described that immunopotentiators, CVCVA5, increased the efficacy of H5 and H9 subtype avian influenza vaccines in chickens, ducks, and geese.
+In this study, we further investigated the effects of the CVCVA5 for improving the efficacy of other univalent or multivalent inactivated vaccines.
+The immune response administrated with half-dose of monovalent vaccine plus CVCVA5 were higher than those of one dose of monovalent vaccine without immunopotentiators as measured by levels of antibodies from serum, tears and bronchoalveolar lavage fluids, and cytokines of IFNγ and IL-4 from serum.
+Vaccines included the univalent vaccine of Newcastle Disease virus (ND), Egg Drop Syndrome virus (EDS), Infectious Bronchitis virus (IB), and Infectious Bursal Disease virus (IBD).
+The CVCVA5 also improved the immune response of both ND and IBD vaccines with less dosage.
+The sterile protective immunity was monitored with one- or a half-dose of adjuvanted ND vaccine or one dose of adjuvanted IBD vaccine, respectively.
+The improved immune efficacy was observed in a half-dose of adjuvanted bivalent vaccines compared to one dose of vaccines without CVCVA5 as measured by the antibody levels, including bivalent vaccine of ND-H9, ND-IB, and ND-IBD.
+A half-dose of adjuvanted commercial vaccine or 75% antigen-sparing adjuvanted vaccine elicited similar antibody levels to those of one dose non-adjuvanted commercial vaccines.
+The CVCVA5 improved the effect of a booster vaccination as measured by the antibody levels against H5 or H9 virus antigens, in which chickens primed with the adjuvanted ND-IB vaccines given a booster with H5–H9 bivalent vaccines without CVCVA5 using 5-day intervals.
+The inflammatory response may contribute to these additional effects by increasing the levels of IFNγ and IL-4 after the injection of the adjuvanted ND-IB vaccines.
+Results indicated that the CVCVA5 improved the serum and mucosal antibody levels, cytokine levels of the chickens given the univalent vaccine, and also improved serum antibody titers in bivalent and tetravalent vaccines.
+Objective: To investigate impacts of triamcinolone acetonide (TRI) on femoral head chondrocytic (FHC) structures when used for lumbosacral plexus block (LPB).
+Methods: A total of 32 6-month-old New Zealand white rabbits were selected (averagely weighing 2.75–3.25 kg) and added TRI into nerve block solution for LPB.
+The rabbit were randomly divided into four groups: group A1: 2.5 ml × 2 times, group A2 2.5 ml × 4 times, group B1 5 ml × 2 times, and group B2 5 ml × 4 times; the time interval among the injection was 5 days, and the structural changes of FHC were the observed using 50/100/200 light microscope; the modified Mankin pathological scoring was also performed for the evaluation.
+Results: There exhibited significant microscopic changes of FHC structures between the rabbits performed LPB and the normal rabbits, among which group B2 exhibited the most serious FHC damages, and the Mankin pathological score in group B2 was much higher than those in the other three groups, and the scores of the experimental group were higher than the control group.
+Conclusions: The addition of TRI in LPB can damage the FHC structures, and large-dose (5 ml/once) and long-course (four times) will result in more serious injuries.
+In pneumonia, specimens are rarely obtained directly from the infection site, the lung, so the pathogen causing infection is determined indirectly from multiple tests on peripheral clinical specimens, which may have imperfect and uncertain sensitivity and specificity, so inference about the cause is complex.
+Analytic approaches have included expert review of case-only results, case–control logistic regression, latent class analysis, and attributable fraction, but each has serious limitations and none naturally integrate multiple test results.
+The Pneumonia Etiology Research for Child Health (PERCH) study required an analytic solution appropriate for a case–control design that could incorporate evidence from multiple specimens from cases and controls and that accounted for measurement error.
+We describe a Bayesian integrated approach we developed that combined and extended elements of attributable fraction and latent class analyses to meet some of these challenges and illustrate the advantage it confers regarding the challenges identified for other methods.
+Human rhinovirus (HRV) is the common virus that causes acute respiratory infection (ARI) and is frequently associated with lower respiratory tract infections (LRTIs).
+We aimed to investigate whether HRV infection induces a specific gene expression pattern in airway epithelial cells.
+RNA was extracted from both supernatants and infected monolayer cells at 6, 12, 24 and 48 hours post infection (hpi) and transcriptional profile was analyzed using Affymetrix GeneChip and the results were subsequently validated using quantitative Real-time PCR method.
+Differential gene expression at 6 hpi (187 genes up-regulated vs. 156 down-regulated) were significantly represented by gene ontologies related to the chemokines and inflammatory molecules indicating characteristic of viral infection.
+The 75 up-regulated genes surpassed the down-regulated genes (35) at 12 hpi and their enriched ontologies fell into discrete functional entities such as regulation of apoptosis, anti-apoptosis, and wound healing.
+At later time points of 24 and 48 hpi, predominated down-regulated genes were enriched for extracellular matrix proteins and airway remodeling events.
+The study suggests the underlying molecular regulatory networks genes which might be involved in pathogenicity of the HRV-B and potential targets for further validations and development of effective treatment.
+Even if European Union (EU) Member States are obliged to implement EU Directives 2000/54/EC on the protection of workers from risks related to exposure to biological agents at work, national biosafety regulations and practices varied from country to country.
+In fact, EU legislation on biological agents and genetically modified microorganisms is often not specific enough to ensure harmonization leading to difficulties in implementation for most laboratories.
+In the same way, biosecurity is a relatively new concept and a few EU Member States are known to have introduced national laboratory biosecurity legislation.
+In France, recent regulations have reinforced biosafety/biosecurity in containment level 3 (CL-3) laboratories but they concern a specific list of pathogens with no correlation in other European Members States.
+The objective of this review was to summarize European biosafety/biosecurity measures concerning CL-3 facilities focusing on French specificities.
+Essential requirements needed to preserve efficient biosafety measures when manipulating risk group 3 biological agents are highlighted.
+In addition, International, European and French standards related to containment laboratory planning, operation or biosafety equipment are described to clarify optimal biosafety and biosecurity requirements.
+The ribosome may slip backward when encountering a frameshift motif on the messenger RNA, which usually contains a pseudoknot structure involving tertiary base pair interactions.
+Due to the lack of detailed molecular explanations, previous studies investigating which features of the pseudoknot are important to stimulate frameshifting have presented diverse conclusions.
+Here we constructed a bimolecular pseudoknot to dissect the interior tertiary base pairs and used single-molecule approaches to assess the structure targeted by ribosomes.
+We found that the first ribosome target stem was resistant to unwinding when the neighboring loop was confined along the stem; such constrained conformation was dependent on the presence of consecutive adenosines in this loop.
+Our results demonstrate that various tertiary base pairs are coordinated inside a highly efficient frameshift-stimulating RNA pseudoknot and suggest a mechanism by which mechanical resistance of the pseudoknot may persistently act on translocating ribosomes.
+BACKGROUND: Interferon inducible transmembrane (IFITM) proteins are effectors of the immune system widely characterized for their role in restricting infection by diverse enveloped and non-enveloped viruses.
+The chicken IFITM (chIFITM) genes are clustered on chromosome 5 and to date four genes have been annotated, namely chIFITM1, chIFITM3, chIFITM5 and chIFITM10.
+However, due to poor assembly of this locus in the Gallus Gallus v4 genome, accurate characterization has so far proven problematic.
+Recently, a new chicken reference genome assembly Gallus Gallus v5 was generated using Sanger, 454, Illumina and PacBio sequencing technologies identifying considerable differences in the chIFITM locus over the previous genome releases.
+METHODS: We re-sequenced the locus using both Illumina MiSeq and PacBio RS II sequencing technologies and we mapped RNA-seq data from the European Nucleotide Archive (ENA) to this finalized chIFITM locus.
+Using SureSelect probes capture probes designed to the finalized chIFITM locus, we sequenced the locus of a different chicken breed, namely a White Leghorn, and a turkey.
+RESULTS: We confirmed the Gallus Gallus v5 consensus except for two insertions of 5 and 1 base pair within the chIFITM3 and B4GALNT4 genes, respectively, and a single base pair deletion within the B4GALNT4 gene.
+The pull down revealed a single amino acid substitution of A63V in the CIL domain of IFITM2 compared to Red Jungle fowl and 13, 13 and 11 differences between IFITM1, 2 and 3 of chickens and turkeys, respectively.
+RNA-seq shows chIFITM2 and chIFITM3 expression in numerous tissue types of different chicken breeds and avian cell lines, while the expression of the putative chIFITM1 is limited to the testis, caecum and ileum tissues.
+CONCLUSIONS: Locus resequencing using these capture probes and RNA-seq based expression analysis will allow the further characterization of genetic diversity within Galliformes.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-017-3801-8) contains supplementary material, which is available to authorized users.
+Core decompression (CD) is regarded as an effective therapy for early-stage SAON, but the prognosis is unsatisfactory due to incomplete bone repair.
+We therefore evaluated the effects of PTH on improving the effects of CD in Early-Stage SAON.
+Distal femoral CD was performed two weeks after osteonecrosis induction or vehicle injection, with ten of the ON-induced rabbits being subjected to six-week PTH[1–34] treatment and the others, including ON-induced and non-induced rabbits, being treated with vehicle.
+Bone repair was enhanced with decreased empty osteocyte lacunae and necrosis foci area, resulting in enhanced peak load and stiffness of the tunnel.
+Additionally, PTH enlarged the mean diameter of vessels in the marrow and increased the number of vessels within the tunnels, as well as elevated the expression of BMP-2, RUNX2, IGF-1, bFGF and VEGF, together with serum OCN and VEGF levels.
+Therefore, PTH[1–34] enhances the efficacy of CD on osteogenesis and neovascularization, thus promoting bone and blood vessels repair in the SAON model.
+Human rhinoviruses are the most common respiratory viruses detected in patients after hematopoietic cell transplantation.
+Although rhinovirus appears to occasionally cause severe lower respiratory tract infection in immunocompromised patients, the clinical significance of rhinovirus detection in the lower respiratory tract remains unknown.
+As comparative cohorts, 273 recipients with lower respiratory tract infection caused by respiratory syncytial virus (N=117), parainfluenza virus (N=120), or influenza (N=36) were analyzed.
+Among 569 subjects with rhinovirus upper respiratory tract infection and 128 subjects with rhinovirus lower respiratory tract infection, probabilities of overall mortality at 90 days were 6% and 41%, respectively (P<0.001).
+The survival rate after lower respiratory tract infection was not affected by the presence of co-pathogens (55% in patients with co-pathogens, 64% in patients without, P=0.34).
+Low monocyte count (P=0.027), oxygen use (P=0.015), and steroid dose greater than 1 mg/kg/day (P=0.003) before diagnosis were significantly associated with mortality among patients with lower respiratory tract infection in multivariable analysis.
+Mortality after rhinovirus lower respiratory tract infection was similar to that after lower respiratory tract infection by respiratory syncytial virus, parainfluenza virus or influenza in an adjusted model.
+In summary, transplant recipients with rhinovirus detection in the lower respiratory tract had high mortality rates comparable to viral pneumonia associated with other well-established respiratory viruses.
+However, in human liver, interferon (IFN)‐stimulated gene expression can mask direct transcriptional responses to infection.
+To better characterize the direct effects of HCV infection in vivo, we analyze the transcriptomes of HCV‐infected patients lacking an activated endogenous IFN system.
+We show that expression changes observed in these patients predominantly reflect immune cell infiltrates rather than cell‐intrinsic pathways.
+We also investigate the transcriptomes of patients with endogenous IFN activation, which paradoxically cannot eradicate viral infection.
+We find that most IFN‐stimulated genes are induced by both recombinant IFN therapy and the endogenous IFN system, but with lower induction levels in the latter, indicating that the innate immune response in chronic hepatitis C is too weak to clear the virus.
+Several microRNA primary transcripts, including that of miR‐122, are significantly down‐regulated in response to IFN treatment, suggesting a new mechanism for IFN‐induced expression fine‐tuning.
+The virome has been increasingly investigated in numerous animal species and in different sites of the body, facilitating the identification and discovery of a variety of viruses.
+In this study we describe the faecal virome of healthy dogs and dogs with acute diarrhoea in Australia, using a shotgun metagenomic approach.
+Viral sequences from a range of different virus families, including both RNA and DNA families, and known pathogens implicated in enteric disease were documented.
+Eight eukaryotic viral families were detected: Astroviridae, Coronaviridae, Reoviridae, Picornaviridae, Caliciviridae, Parvoviridae, Adenoviridae and Papillomaviridae.
+Families Astroviridae, Picornaviridae and Caliciviridae were found only in dogs with acute diarrhoea, with Astroviridae being the most common family identified in this group.
+These studies indicate that metagenomic analyses are useful for the investigation of viral populations in the faeces of dogs.
+In the last decades, molecular research has gained a lot of new information about its causative agent, newcastle disease virus (NDV).
+In poultry industry, certain strains of NDV have been used for preventive vaccination for more than 60 years.
+NDV has also been applied to cancer patients with beneficial effects for about 50 years, but this is less well known.
+The molecular basis for these differential effects of NDV in birds and man have been elucidated in the last decades and are explained in this review.
+The anti-neoplastic and immune-stimulatory properties in non-permissive hosts such as mouse and man have to do with the strong type I interferon responses induced in these foreign species.
+Additionally, NDV has the potential to break various types of tumor resistances and also to affect liver fibrosis.
+A main section is devoted to the benefits of clinical application of NDV and NDV-based vaccines to cancer patients.
+Examples will be provided in which genetically engineered NDV is being used successfully as vector against new emerging viruses.
+BACKGROUND: Alternative splicing of Vascular endothelial growth factor-A mRNA transcripts (commonly referred as VEGF) leads to the generation of functionally differing isoforms, the relative amounts of which have potentially significant physiological outcomes in conditions such as acute respiratory distress syndrome (ARDS).
+We hypothesised that VEGF(165)a and VEGF(165)b isoforms would have differing effects on pulmonary vascular permeability caused by differential activation of intercellular signal transduction pathways.
+METHOD: To test this hypothesis we investigated the physiological effect of VEGF(165)a and VEGF(165)b on Human Pulmonary Microvascular Endothelial Cell (HPMEC) permeability using three different methods: trans-endothelial electrical resistance (TEER), Electric cell-substrate impedance sensing (ECIS) and FITC-BSA passage.
+In addition, potential downstream signalling pathways of the VEGF isoforms were investigated by Western blotting and the use of specific signalling inhibitors.
+RESULTS: VEGF(165)a increased HPMEC permeability using all three methods (paracellular and transcellular) and led to associated VE-cadherin and actin stress fibre changes.
+In contrast, VEGF(165)b decreased paracellular permeability and did not induce changes in VE-cadherin cell distribution.
+Furthermore, VEGF(165)a and VEGF(165)b had differing effects on both the phosphorylation of VEGF receptors and downstream signalling proteins pMEK, p42/44MAPK, p38 MAPK, pAKT and peNOS.
+Interestingly specific inhibition of the pMEK, p38 MAPK, PI3 kinase and eNOS pathways blocked the effects of both VEGF(165)a and VEGF(165)b on paracellular permeability and the effect of VEGF(165)a on proliferation/migration, suggesting that this difference in cellular response is mediated by an as yet unidentified signalling pathway(s).
+CONCLUSION: This study demonstrates that the novel isoform VEGF(165)a and VEGF(165)b induce differing effects on permeability in pulmonary microvascular endothelial cells.
+Enterovirus 71 (EV71) is the major causative agent of hand‐foot‐and‐mouth disease in young children and can cause severe cerebral and pulmonary complications and even fatality.
+This study aimed at elucidating whether and how EV71 infection is regulated by a cellular microRNA, miR‐127‐5p.
+We found that miR‐127‐5p can downregulate the expression of SCARB2, a main receptor of EV71, by targeting two potential sites in its 3′ UTR region and inhibit EV71 infection.
+Notably, transfecting cells with miR‐127‐5p mimics led to a significant decrease in viral replication, while inhibition of endogenous miR‐127‐5p facilitated viral replication.
+Taken together, these results indicated that miR‐127‐5p inhibited EV71 replication by targeting the SCARB2 mRNA.
+Rodents, in particular Mus musculus, have a long and invaluable history as models for human diseases in biomedical research, although their translational value has been challenged in a number of cases.
+We provide some examples in which rodents have been suboptimal as models for human biology and discuss confounders which influence experiments and may explain some of the misleading results.
+Infections of rodents with protozoan parasites are no exception in requiring close consideration upon model choice.
+We focus on the significant differences between inbred, outbred and wild animals, and the importance of factors such as microbiota, which are gaining attention as crucial variables in infection experiments.
+Frequently, mouse or rat models are chosen for convenience, e.g., availability in the institution rather than on an unbiased evaluation of whether they provide the answer to a given question.
+Apart from a general discussion on translational success or failure, we provide examples where infections with single-celled parasites in a chosen lab rodent gave contradictory or misleading results, and when possible discuss the reason for this.
+We present emerging alternatives to traditional rodent models, such as humanized mice and organoid primary cell cultures.
+So-called recombinant inbred strains such as the Collaborative Cross collection are also a potential solution for certain challenges.
+In addition, we emphasize the advantages of using wild rodents for certain immunological, ecological, and/or behavioral questions.
+The experimental challenges (e.g., availability of species-specific reagents) that come with the use of such non-model systems are also discussed.
+Our intention is to foster critical judgment of both traditional and newly available translational rodent models for research on parasitic protozoa that can complement the existing mouse and rat models.
+The importance of spatial clusters, or “hotspots,” in infectious disease epidemiology has been increasingly recognized, and targeting hotspots is often seen as an important component of disease-control strategies.
+Hotspots have been variously described as areas of elevated incidence or prevalence, higher transmission efficiency or risk, or higher probability of disease emergence.
+This ambiguity has led to confusion and may result in mistaken inferences regarding the best way to target interventions.
+We surveyed the literature on epidemiologic hotspots, examining the multitude of ways in which the term is used; and highlight the difference in the geographic scale of hotspots and the properties they are supposed to have.
+In response to the diversity in the term's usage, we advocate the use of more precise terms, such as “burden hotspot,” “transmission hotspot,” and “emergence hotspot,” as well as explicit specification of the spatiotemporal scale of interest.
+Increased precision in terminology is needed to ensure clear and effective policies for disease control.
+The present study was performed to investigate the potential protective effect of myricitrin against hypoxia/reoxygenation (H/R)-induced H9c2 cardiomyocyte injury and its underlying mechanisms.
+Myricitrin pretreatment improved cardiomyocyte viability, inhibited ROS generation, maintained the mitochondrial membrane potential, reduced apoptotic cardiomyocytes, decreased the caspase-3 activity, upregulated antiapoptotic proteins and downregulated proapoptotic proteins during H/R injury.
+Moreover, the potential targets of myricitrin was predicted using Discovery Studio software, and heat shock protein 90 (Hsp90) was identified as the main disease-related target.
+Further mechanistic investigation revealed that 17-AAG, a pharmacologic inhibitor of Hsp90, significantly blocked the myricitrin-induced cardioprotective effect demonstrated by increased apoptosis and ROS generation.
+These results suggested that myricitrin provides protection to H9c2 cardiomyocytes against H/R-induced oxidative stress and apoptosis, most likely via increased expression of Hsp90.
+The evolution of drug-resistant phenotypes has been linked to the parasites’ intrinsic genome instability, with frequent gene and chromosome amplifications causing fitness gains that are directly selected by environmental factors, including the presence of antileishmanial drugs.
+Thus, even though the unique eukaryotic biology of Leishmania and its dependence on parasite-specific virulence factors provide valid opportunities for chemotherapeutical intervention, all strategies that target the parasite in a direct fashion are likely prone to select for resistance.
+Here, we review the current state of antileishmanial chemotherapy and discuss the limitations of ongoing drug discovery efforts.
+We finally propose new strategies that target Leishmania viability indirectly via mechanisms of host–parasite interaction, including parasite-released ectokinases and host epigenetic regulation, which modulate host cell signaling and transcriptional regulation, respectively, to establish permissive conditions for intracellular Leishmania survival.
+Splice-switching antisense oligonucleotides are emerging treatments for neuromuscular diseases, with several splice-switching oligonucleotides (SSOs) currently undergoing clinical trials such as for Duchenne muscular dystrophy (DMD) and spinal muscular atrophy (SMA).
+However, the development of systemically delivered antisense therapeutics has been hampered by poor tissue penetration and cellular uptake, including crossing of the blood–brain barrier (BBB) to reach targets in the central nervous system (CNS).
+For SMA application, we have investigated the ability of various BBB-crossing peptides for CNS delivery of a splice-switching phosphorodiamidate morpholino oligonucleotide (PMO) targeting survival motor neuron 2 (SMN2) exon 7 inclusion.
+We identified a branched derivative of the well-known ApoE (141–150) peptide, which as a PMO conjugate was capable of exon inclusion in the CNS following systemic administration, leading to an increase in the level of full-length SMN2 transcript.
+Treatment of newborn SMA mice with this peptide-PMO (P-PMO) conjugate resulted in a significant increase in the average lifespan and gains in weight, muscle strength, and righting reflexes.
+Systemic treatment of adult SMA mice with this newly identified P-PMO also resulted in small but significant increases in the levels of SMN2 pre-messenger RNA (mRNA) exon inclusion in the CNS and peripheral tissues.
+This work provides proof of principle for the ability to select new peptide paradigms to enhance CNS delivery and activity of a PMO SSO through use of a peptide-based delivery platform for the treatment of SMA potentially extending to other neuromuscular and neurodegenerative diseases.
+Zika virus (ZIKV) is an emerging pathogen causally associated with serious sequelae in fetuses, inducing fetal microcephaly and other neurodevelopment defects.
+ZIKV is primarily transmitted by mosquitoes, but can persist in human semen and sperm, and sexual transmission has been documented.
+Moreover, exposure of type-I interferon knockout mice to ZIKV results in severe damage to the testes, epididymis and sperm.
+Candidate ZIKV vaccines have shown protective efficacy in preclinical studies carried out in animal models, and several vaccines have entered clinical trials.
+Here, we report that administration of a synthetic DNA vaccine encoding ZIKV pre-membrane and envelope (prME) completely protects mice against ZIKV-associated damage to the testes and sperm and prevents viral persistence in the testes following challenge with a contemporary strain of ZIKV.
+These data suggest that DNA vaccination merits further investigation as a potential means to reduce ZIKV persistence in the male reproductive tract.
+It is now well recognised that cardiac events occur relatively commonly in patients with acute community-acquired pneumonia.
+While these events are more frequent in patients with underlying risk factors—such as those with underlying chronic cardiovascular and respiratory comorbidities, the elderly, and in nursing home residents—they also occur in patients with no underlying risks other than severe pneumonia.
+Recent research elucidating the underlying pathogenic mechanisms related to these cardiac events has indicated a probable role for platelet activation, which is possibly exacerbated by pneumolysin in the case of pneumococcal infections.
+This, in turn, has resulted in the identification of possible therapeutic strategies targeting platelet activation, as well as the cardio-toxic activity of pneumolysin.
+In recent years, there has been an increasing appreciation of the importance of secreted and extracellular proteins that traditionally have been considered as intracellular components.
+Vimentin is a highly abundant intermediate filament protein, and its intracellular functions have been investigated in a large number of studies.
+Recently, however, vimentin has been shown to take part in significant processes outside the cell.
+In this study we demonstrate that a vimentin specific antibody, obtained by phage antibody technology, promotes tube formation of endothelial cells in a 2D matrigel assay.
+By binding vimentin, the antibody increases the tube formation by 21% after 5 hours of incubation.
+Addition of the antibody directly to cultured endothelial cells does not influence endothelial cell migration or proliferation.
+The enhanced tube formation can be seen for up to 10 hours where after the effect decreases.
+It is shown that the antibody-binding site is located on the coil 2 domain of vimentin.
+To our knowledge this is the first study that demonstrates an enhanced tube formation by binding vimentin in a 2D matrigel assay under normoxic conditions.
+In mammals, two factors likely to affect the diversity and composition of intestinal bacteria (bacterial microbiome) and eukaryotes (eukaryome) are social status and age.
+In species in which social status determines access to resources, socially dominant animals maintain better immune processes and health status than subordinates.
+As high species diversity is an index of ecosystem health, the intestinal biome of healthier, socially dominant animals should be more diverse than those of subordinates.
+Gradual colonization of the juvenile intestine after birth predicts lower intestinal biome diversity in juveniles than adults.
+We tested these predictions on the effect of: (1) age (juvenile/adult) and (2) social status (low/high) on bacterial microbiome and eukaryome diversity and composition in the spotted hyena (Crocuta crocuta), a highly social, female-dominated carnivore in which social status determines access to resources.
+We comprehensively screened feces from 35 individually known adult females and 7 juveniles in the Serengeti ecosystem for bacteria and eukaryotes, using a set of 48 different amplicons (4 for bacterial 16S, 44 for eukaryote 18S) in a multi-amplicon sequencing approach.
+For all parasite taxa detected in more than six samples, the number of sequence reads significantly predicted the number of eggs or oocysts counted, underscoring the value of an amplicon sequencing approach for quantitative measurements of parasite load.
+In line with our predictions, our results revealed a significantly less diverse microbiome in juveniles than adults and a significantly higher diversity of eukaryotes in high-ranking than low-ranking animals.
+We propose that free-ranging wildlife can provide an intriguing model system to assess the adaptive value of intestinal biome diversity for both bacteria and eukaryotes.
+Massive studies have indicated that long non-coding RNAs (lncRNAs) are critical for the regulation of cellular biological processes by binding with RNA-related proteins.
+Existing network-based methods are typically focused on intrinsic features of lncRNA and protein but ignore the information implicit in the topologies of biological networks associated with lncRNAs.
+Considering the limitations in previous methods, we propose PLPIHS, an effective computational method for Predicting lncRNA-Protein Interactions using HeteSim Scores.
+PLPIHS uses the HeteSim measure to calculate the relatedness score for each lncRNA-protein pair in the heterogeneous network, which consists of lncRNA-lncRNA similarity network, lncRNA-protein association network and protein-protein interaction network.
+The results show that PLPIHS performs significantly better than the existing state-of-the-art approaches and achieves an AUC score of 0.97 in the leave-one-out validation test.
+We also compare the performances of networks with different connectivity density and find that PLPIHS performs well across all the networks.
+Highly-ranked proteins are verified by the biological studies and demonstrate the effectiveness of our method.
+Genetic polymorphisms in IFNL4 have been shown to predict responses to IFN-α-based therapy in hepatitis C virus (HCV)-infected patients.
+The IFNL4-ΔG genotype, which encodes functional IFN-λ4 protein, is associated with a poor treatment response.
+In the present study, we investigated the induction and biological effects of IFN-λ4 in HCV-infected hepatocytes and their association with responsiveness to IFN-α.
+We also studied the effects of direct-acting antiviral (DAA) treatment on IFN-λ4 expression and IFN-α responsiveness.
+HCV infection induced IFN-λ4 expression at mRNA and protein levels in primary human hepatocytes (PHHs).
+In hepatoma cells, IFNL4 gene transfection or recombinant IFN-λ4 protein treatment robustly increased the protein levels of ISG15 and USP18 in an IFNLR1-dependent manner and potently blocked IFN-α signalling.
+DAA treatment of HCV-infected PHHs reduced the expression of IFN-λs, including IFN-λ4, and restored IFN-α responsiveness.
+These results demonstrate that virus-induced IFN-λ4 potently blocks IFN-α signalling by inducing high protein levels of ISG15 and USP18.
+BACKGROUND: Postoperative operative pulmonary complications (PPCs) after hepatic surgery are associated with increased length of hospital stays.
+Other parameters, like time of hepatic ischemia, have neither been clinically studied, though experimental studies show that hepatic ischemia can provide lung injury.
+The objective of this study was to determinate the risk factors of postoperative pulmonary complications (PPCs) after hepatic resection within 7 postoperative days.
+Demographic data, pathological variables, and preoperative, intraoperative, and postoperative variables had been prospectively collected in a data base.
+The dependant variables studied were the occurrence of PPCs, defined before analysis of the data.
+On multivariate analysis, preoperative gamma-glutamyltransferase (GGT) elevation OR =5,12 [1,85-15,69] p = 0,002, liver ischemia duration OR = 1,03 [1,01-1,06] p = 0,01 and the intraoperative use of vasopressor OR = 4,40 [1,58-13,36] p = 0,006 were independently associated with PPCs.
+For every 10 min added in ischemia duration, the OR of the risk of PPCs was estimated to be 1.37 (CI(95%) = [1.08-1.81], p = 0.01).
+CONCLUSION: Three risk factors for PPCs have been identified in a population undergoing liver resection: preoperative GGT elevation, ischemia duration and the intraoperative use of vasopressor.
+PPCs after liver surgery could be related to lung injury induced by liver ischemia reperfusion and not solely by direct infectious process.
+That could explain why factors influencing directly or indirectly liver ischemia were independently associated with PPCs.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12871-017-0372-9) contains supplementary material, which is available to authorized users.
+Presence of ducks, and in particular of free-grazing ducks, has consistently been shown to be one of the most important risk factors for highly pathogenic avian influenza outbreaks which has compromised poultry production in South-East Asia since the early 2000s and continues to threaten public health, farmers’ livelihood and food security.
+Although free-grazing duck production has been practised for decades in South-East Asia, there are few published studies describing this production system, which is suspected to play an important role in the maintenance of avian influenza viruses.
+This study aimed at describing quantitatively the long-distance free-grazing duck production system in South Vietnam, characterising the movement and contact patterns of the duck flocks, and identifying potential associations between farming practices, movement and contact patterns and the circulation of avian influenza viruses.
+We conducted interviews among stakeholders involved in the free-grazing duck production system (duck farmers, transporters and rice paddy owners) in combination with a virological cross-sectional survey in South Vietnam.
+Results show that both direct and indirect contacts between free-grazing duck flocks were frequent and diverse.
+The flocks were transported extensively across district and province boundaries, mainly by boat but also by truck or on foot.
+A third of the investigated flocks had a positive influenza A virology test, indicating current circulation of avian influenza viruses, but none were positive for H5 subtypes.
+The age and size of the flock as well as its location at the time of sampling were associated with the risk of influenza A circulation in the flocks.
+These findings should be considered when developing risk assessment models of influenza virus spread aimed at informing the development of improved biosecurity practices leading to enhanced animal health, sustainable animal production and reliable income for farmers.
+AIM: To study the uptake, barriers and motivators of influenza, pneumococcal, meningococcal and pertussis vaccines among members of public in Arabian Gulf countries.
+The survey variables aimed to investigate the respondents’ awareness about vaccines against influenza, pneumococcal, meningococcal and pertussis infections.
+Collected data concerning the respondents’ socio-demographic characteristics, their perception toward vaccine uptake and the factors that motivate or demotivate them from taking influenza vaccine.
+Their mean age was 27 years, 82% were male and 24% had ≥ 1 chronic diseases.
+The overall uptake of influenza vaccine was 17% (21% among “at risk” people) and ranged from 15% in Saudi Arabia to 24% in Qatar.
+Doctor’s advice (23%) and a perception of having low body immunity (21%) were the main cited reasons for being vaccinated, whereas unawareness about the vaccine (43%) was the main barrier.
+The overall uptake of pneumococcal vaccine in the preceding three years was 22% (25% among “at risk” individuals) and ranged from 0% in Bahrain to 79% in Kuwait.
+The overall uptake of pertussis vaccine was 16% (31% among “vulnerable” people), and ranged from 7% in Saudi Arabia to 75% in Oman.
+The overall uptake of meningococcal vaccine was 20% (29% among the “at risk” people) and ranged from 3% in Oman to 50% in Bahrain.
+CONCLUSION: The vaccination uptake across GCC countries is suboptimal and varies widely across the countries.
+The lay press, as well as government and non-government agencies, play a complementary role of extracting findings of high interest or importance and translating them for general viewing.
+The need for accurate reporting and public advising is paramount when attempting to tackle epidemic outbreaks through behavior change.
+The Crisis and Emergency Risk Communication (CERC) model for media reporting on public health emergencies was established in 2005 and has subsequently been used to analyze media reporting on outbreaks of influenza and measles as well as smoking habits and medication compliance.
+However, no media analysis had yet been performed on the 2013–2016 Ebola Virus Disease (EVD) outbreak.
+This study compared the EVD information relayed by lay press sources with general review articles in the academic literature through a mixed-methods analysis.
+These findings suggest that comprehensive review articles could not serve as a source to clarify and contextualize the uncertainties around the EVD outbreak, perhaps due to adherence to technical accuracy at the expense of clarity within the context of outbreak conditions.
+This finding does not imply inferiority of the academic literature, nor does it draw direct causation between confusion in review articles and public misunderstanding.
+Given the erosion of the barriers siloing academia, combined with the demands of today’s fast-paced media environment, contemporary researchers should realize that no study is outside the public forum and to therefore consider shifting the paradigm to take personal responsibility in the process of accurately translating their scientific words into public policy actions to best serve as a source of clarity.
+The isolation of neutralizing monoclonal antibodies (nmAbs) against the Zika virus (ZIKV) might lead to novel preventative strategies for infections in at-risk individuals, primarily pregnant women.
+Here we describe the characterization of human mAbs from the plasmablasts of an acutely infected patient.
+One of the 18 mAbs had the unusual feature of binding to and neutralizing ZIKV despite not appearing to have been diversified by affinity maturation.
+This mAb neutralized ZIKV (Neut(50) ~ 2 μg/ml) but did not react with any of the four dengue virus serotypes.
+Except for the expected junctional diversity created by the joining of the V-(D)-J genes, there was no deviation from immunoglobulin germline genes.
+This is a rare example of a human mAb with neutralizing activity in the absence of detectable somatic hypermutation.
+Importantly, binding of this mAb to ZIKV was specifically inhibited by human plasma from ZIKV-exposed individuals, suggesting that it may be of value in a diagnostic setting.
+Cholera, Leptospirosis, Giardiasis) remain an important cause of morbidity and mortality, especially in low-income countries.
+Climate and weather factors are known to affect the transmission and distribution of infectious diseases and statistical and mathematical modelling are continuously developing to investigate the impact of weather and climate on water-associated diseases.
+Our objective is to review and summarize statistical and modelling methods used to investigate the effects of weather and climate on infectious diseases associated with water, in order to identify limitations and knowledge gaps in developing of new methods.
+Search terms included concepts related to water-associated diseases, weather and climate, statistical, epidemiological and modelling methods.
+We found 102 full text papers that met our criteria and were included in the analysis.
+The most commonly used methods were grouped in two clusters: process-based models (PBM) and time series and spatial epidemiology (TS-SE).
+In general, PBM methods were employed when the bio-physical mechanism of the pathogen under study was relatively well known (e.g.
+Vibrio cholerae); TS-SE tended to be used when the specific environmental mechanisms were unclear (e.g.
+Important data and methodological challenges emerged, with implications for surveillance and control of water-associated infections.
+biological mechanism, demographic heterogeneity, human behavior), reporting bias, poor data quality, and collinearity in exposures.
+Key areas of future research include: disentangling the complex effects of weather/climate on each exposure-health outcome pathway (e.g.
+Toxoplasma gondii is a worldwide spread protozoan and is able to infect almost all warm-blood animals.
+This work aims to assess the protective efficacy of combined Chinese herbs against T. gondii.
+We screened five herbal medicines that have different pharmacological effects and combined them into a prescription according to the traditional Chinese medicine compatibility principle.
+The drug potential and protective efficacy were evaluated through a mouse model by determining the survival time, the parasite load in blood and tissues, the change of cell proportions in blood and histological detection.
+The results showed that the survival time of mice in the 500 mg Chinese herbs group and sulfadiazine group was significantly longer than that of the PBS control group.
+Also the parasite load in blood and tissues of 500 mg Chinese herbs and sulfadiazine groups was significantly lower than that of PBS group at 7 days post infection (dpi), which was in accordance with the result of histological detection.
+Monocyte and neutrophil of infected mice were remarkably increased while lymphocyte was dramatically decreased compared to that of blank group at 7 dpi.
+The results demonstrated that the 500 mg dosage of our Chinese herbs could slow down the replication of T. gondii and prolong the survival time of mice and could be considered as possible candidate drug against toxoplasmosis.
+Myeloid cell leukemia-1 (Mcl-1) is often overexpressed in human cancer and is an important target for developing antineoplastic drugs.
+In this study, a data set containing 2.3 million lead-like molecules and a data set of all the US Food and Drug Administration (FDA)-approved drugs are virtually screened for potential Mcl-1 ligands using Protein Data Bank (PDB) ID 2MHS.
+The potential Mcl-1 ligands are evaluated and computationally docked on to three conformation ensembles generated by normal mode analysis (NMA), molecular dynamics (MD), and nuclear magnetic resonance (NMR), respectively.
+Remarkably, half of the top 30 potential drugs are used clinically to treat cancer, thus partially validating our virtual screen.
+The partial validation also favors the idea that the other half of the top 30 potential drugs could be used in the treatment of cancer.
+The normal mode-, MD-, and NMR-based conformation greatly expand the conformational sampling used herein for in silico identification of potential Mcl-1 inhibitors.
+Japanese encephalitis (JE) is neuroinflammation characterized by uncontrolled infiltration of peripheral leukocytes into the central nervous system (CNS).
+We previously demonstrated exacerbation of JE following CD11c(hi) dendritic cell (DC) ablation in CD11c-DTR transgenic mice.
+Moreover, CD11c(hi) DC ablation led to abnormal differentiation of CD11b(+)Ly-6C(hi) monocytes and enhanced permeability of the blood-brain barrier (BBB), resulting in promoting the progression of JE.
+Here, we examined changes in lymphoid and myeloid-derived leukocyte subpopulations associated with pro- and anti-inflammation during JE progression.
+The analyses of this study focused on regulatory CD4(+)Foxp3(+) regulatory T cells (Tregs), IL-17(+)CD4(+) Th17 cells, and CD11b(+)Ly-6C(hi) and Ly-6C(lo) monocytes.
+CD11c(hi) DC ablation resulted in the accumulation of IL-17(+)CD4(+) Th17 cells in the CNS, thereby leading to lower ratio of Tregs to Th17 cells.
+This result was corroborated by the higher expression levels of IL-17 and RORγT in CD4(+) T cells from the brains of CD11c(hi) DC-ablated mice.
+In addition, CD11c(hi) DC-ablated mice showed higher frequency and total number of inflammatory CD11b(+)Ly-6C(hi) monocytes, whereas CD11b(+)Ly-6C(lo) monocytes were detected with lower frequency and total number in CD11c(hi) DC-ablated mice.
+Furthermore, CD11c(hi) DC ablation altered the phenotype and function of CD11b(+)Ly-6C(lo) monocytes, resulting in lower levels of activation marker and anti-inflammatory cytokine (IL-10 and TGF-β) expression.
+Collectively, these results indicate that CD11c(hi) DC ablation caused an imbalance in CD4(+) Th17/Treg cells and CD11b(+)Ly-6C(hi)/Ly-6C(lo) monocytes in the lymphoid tissue and CNS during JE progression.
+This imbalanced orchestration of pro- and anti-inflammatory leukocytes following CD11c(hi) DC ablation may contribute to the exacerbation of JE.
+BACKGROUND: Nipah virus infection (NiV) is a bat-borne zoonosis transmitted to humans through consumption of NiV-contaminated raw date palm sap in Bangladesh.
+The objective of this analysis was to measure the cost of an NiV prevention intervention and estimate the cost of scaling it up to districts where spillover had been identified.
+METHODS: We implemented a behavior change communication intervention in two districts, testing different approaches to reduce the risk of NiV transmission using community mobilization, interpersonal communication, posters and TV public service announcements on local television during the 2012–2014 sap harvesting seasons.
+In one district, we implemented a “no raw sap” approach recommending to stop drinking raw date palm sap.
+In another district, we implemented an “only safe sap” approach, recommending to stop drinking raw date palm sap but offering the option of drinking safe sap.
+This is sap covered with a barrier, locally called bana, to interrupt bats’ access during collection.
+We conducted surveys among randomly selected respondents two months after the intervention to measure the proportion of people reached.
+RESULTS: The implementation cost of the “no raw sap” intervention was $30,000 and the “only safe sap” intervention was $55,000.
+To scale up a similar intervention in 30 districts where NiV spillover has occurred, would cost between $2.6 and $3.5 million for one season.
+Placing the posters would cost $96,000 and only broadcasting the public service announcement through local channels in 30 districts would cost $26,000.
+CONCLUSIONS: Broadcasting a TV public service announcement is a potential low cost option to advance NiV prevention.
+It could be supplemented with posters and targeted interpersonal communication, in districts with a high risk of NiV spillover.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13104-017-2549-1) contains supplementary material, which is available to authorized users.
+Chitin-binding lectins form the hevein family in plants, which are defined by the presence of single or multiple structurally conserved GlcNAc (N-acetylglucosamine)-binding domains.
+Although they have been used as probes for chito-oligosaccharides, their detailed specificities remain to be investigated.
+In this study, we analyzed six chitin-binding lectins, DSA, LEL, PWM, STL, UDA, and WGA, by quantitative frontal affinity chromatography.
+Some novel features were evident: WGA showed almost comparable affinity for pyridylaminated chitotriose and chitotetraose, while LEL and UDA showed much weaker affinity, and DSA, PWM, and STL had no substantial affinity for the former.
+UDA showed extensive binding to high-mannose type N-glycans, with affinity increasing with the number of Man residues.
+DSA showed the highest affinity for highly branched N-glycans consisting of type II LacNAc (N-acetyllactosamine).
+The lectins showed substantial binding to immobilized LacNAc as well as chito-oligosaccharides, although the extents to which they bound varied among them.
+The US swine industry has been impaired over the last 25 years by the far-reaching financial losses caused by the porcine reproductive and respiratory syndrome (PRRS).
+Here, we explored the relations between the spatial risk of PRRS outbreaks and its phylodynamic history in the U.S during 1998–2016 using ORF5 sequences collected from swine farms in the Midwest region.
+We used maximum entropy and Bayesian phylodynamic models to generate risk maps for PRRS outbreaks and reconstructed the evolutionary history of three selected phylogenetic clades (A, B and C).
+High-risk areas for PRRS were best-predicted by pig density and climate seasonality and included Minnesota, Iowa and South Dakota.
+Phylodynamic models demonstrated that the geographical spread of the three clades followed a heterogeneous spatial diffusion process.
+However, endemic strains were characterized by a substantially slower population growth and evolutionary rates, as well as smaller spatial dispersal rates when compared to emerging strains.
+We demonstrated the prospects of combining inferences derived from two unique analytical methods to inform decisions related to risk-based interventions of an important pathogen affecting one of the largest food animal industries in the world.
+Hepatitis E virus (HEV) and porcine reproductive and respiratory syndrome virus (PRRSV) and are both globally prevalent in the pig population.
+While HEV does not cause clinical disease in pigs, its zoonotic potential has raised concerns in the food safety sector.
+PRRS has become endemic in the United Kingdom (UK) since its introduction in 1991, and continues to cause considerable economic losses to the swine industry.
+A better understanding of the current prevalence and diversity of PRRSV and HEV in the UK, and their potential association, is needed to assess risks and target control measures appropriately.
+This study used plasma, tonsil, and cecal content samples previously collected from pigs in 14 abattoirs in England and Northern Ireland to study the prevalence of several pathogens including PRRSV and HEV.
+The diversity of PRRSV strains detected in these samples was analyzed by sequencing open reading frame 5 (ORF5), revealing no substantial difference in PRRSV strains from these clinically unaffected pigs relative to those from clinical cases of disease in the UK.
+Despite the potential immuno-modulatory effect of PRRSV infection, previously demonstrated to affect Salmonella and HEV shedding profiles, no significant association was found between positive PRRSV status and positive HEV status.
+The adaptive immune response is necessary for the development of protective immunity against infectious diseases.
+Porcine reproductive and respiratory syndrome virus (PRRSV), a genetically heterogeneous and rapidly evolving RNA virus, is the most burdensome pathogen of swine health and wellbeing worldwide.
+However, the resulting immune memory, induced by virulent or attenuated vaccine viruses, is inconsistently protective against diverse viral strains.
+The immunological mechanisms by which primary and memory protection are generated and used are not well understood.
+Here, we summarize current knowledge regarding cellular and humoral components of the adaptive immune response to PRRSV infection that mediate primary and memory immune protection against viruses.
+COPD is characterized by an ongoing inflammatory process of the airways that leads to obstruction or limitation of airflow.
+In addition, it is considered, at present, a serious public health problem, ranking fourth in mortality worldwide.
+Many cells participate in the pathophysiology of COPD, the most important are neutrophils, macrophages and CD4+ and CD8+ T cells.
+Neutrophil migration to the inflammation area could be mediated largely by cytokines related to CD4+ Th17 lymphocytes, because it has been shown that IL-17A, IL-17F and IL-22 act as inducers for CXCL8, CXCL1, CXCL5, G-CSF, and GM-CSF secretion by epithelial cells of the airways.
+Furthermore, it is believed that CD4+ lymphocytes Th17 may be involved in protection against pathogens for which Th1 and Th2 are not prepared to fight.
+In COPD exacerbations, there is an increased cellularity in the lung region and respiratory tract.
+Therefore, the increase in the number of neutrophils and macrophages in the airways and the increase in proinflammatory cytokines are directly related to the severity of exacerbations and that is the importance of the functions of Th17 profile in this entity.
+BACKGROUND: Syndromic surveillance of severe acute respiratory infections (SARI) is important to assess seriousness of disease as recommended by WHO for influenza.
+In 2015 the Robert Koch Institute (RKI) started to collaborate with a private hospital network to develop a SARI surveillance system using case-based data on ICD-10 codes.
+This first-time description of the system shows its application to the analysis of five influenza seasons.
+METHODS: Since week 40/2015, weekly updated anonymized data on discharged patients overall and on patients with respiratory illness including ICD-10 codes of primary and secondary diagnoses are transferred from the network data center to RKI.
+Our descriptive analysis is based on data of 47 sentinel hospitals collected between weeks 1/2012 to 20/2016.
+We applied three different SARI case definitions (CD) based on ICD-10 codes for discharge diagnoses of respiratory tract infections (J09 - J22): basic CD (BCD), using only primary diagnoses; sensitive CD (SCD), using primary and secondary diagnoses; timely CD (TCD), using only primary diagnoses of patients hospitalized up to one week.
+We compared the CD with regard to severity, age distribution and timeliness and with results from the national primary care sentinel system.
+RESULTS: The 47 sentinel hospitals covered 3.6% of patients discharged from all German hospitals in 2013.
+The SCD comprised 2.2 times patients as the BCD, and 3.6 times as many as the TCD.
+Time course of SARI cases corresponded well to results from primary care surveillance and influenza virus circulation.
+The patients fulfilling the TCD had been completely reported after 3 weeks, which was fastest among the CD.
+The proportion of SARI cases among patients was highest in the youngest age group of below 5-year-olds.
+CONCLUSIONS: In general, available data and the implemented reporting system are appropriate to provide timely and reliable information on SARI in inpatients in Germany.
+The exploratory approach gave valuable insights in data structure and emphasized the advantages of different CD.
+P001 - Sepsis impairs the capillary response within hypoxic capillaries and decreases erythrocyte oxygen-dependent ATP efflux R. M. Bateman, M. D. Sharpe, J. E. Jagger, C. G. Ellis P002 - Lower serum immunoglobulin G2 level does not predispose to severe flu.
+Struck, A. Cariou, N. Deye, B. Guidet, S. Jabert, J. Launay, M. Legrand, M. Léone, M. Resche-Rigon, E. Vicaut, A. Vieillard-Baron, A. Mebazaa P020 - Impact of disease severity assessment on performance of heparin-binding protein for the prediction of septic shock R. Arnold, M. Capan, A. Linder, P. Akesson P021 - Kinetics and prognostic value of presepsin (sCD14) in septic patients.
+P. Van der Geest, M. Mohseni, J. Linssen, R. De Jonge, S. Duran, J. Groeneveld P035 - Challenges in the clinical diagnosis of sepsis R. Miller III, B. K. Lopansri, L. C. McHugh, A. Seldon, J. P. Burke P036 - Does zero heat flux thermometry more accurately identify sepsis on intensive care?
+Bond, A. Molokhia P037 - Advancing quality (AQ) sepsis programme: Improving early identification & treatment of sepsis in North West England.
+C. Mcgrath, E. Nsutebu P038 - Prehospital transport of acute septic patients P. Bank Pedersen, D. Pilsgaard Henriksen, S. Mikkelsen, A. Touborg Lassen P039 - Vasodilatory plant extracts gel as an alternative treatment for fever in critically ill patients R. Tincu, C. Cobilinschi, D. Tomescu, Z. Ghiorghiu, R. Macovei P040 - Host response and outcome of hypothermic sepsis M. A. Wiewel, M. B. Harmon, L. A.
+Dean, A. Molokhia P044 - Culture negative sepsis in the ICU – what is unique to this patient population?
+A retrospective series of 39 patients L. Caneva, A. Casazza, E. Bellazzi, S. Marra, L. Pagani, M. Vetere, R. Vanzino, D. Ciprandi, R. Preda, R. Boschi, L. Carnevale P050 - Methylene blue effectiveness as contributory treatment in patients with septic shock V. Lopez, M. Aguilar Arzapalo, L. Barradas, A. Escalante, J. Gongora, M. Cetina P051 - Coagulation disorders in patients with severe sepsis and DIC evaluated with thromboelastometry.
+B Adamik, D Jakubczyk, A Kübler P052 - Frequency and outcome of early sepsis-associated coagulopathy A. Radford, T. Lee, J.
+Singer, J. Boyd, D. Fineberg, M. Williams, J. Russell P053 - Assessment of coagulopathy in cancer patients with severe sepsis or septic shock.
+Obstacles on the 4 year journey and our strategies to overcome them – experience from an Indian ICU V. Adora, A. Kar, A. Chakraborty, S. Roy, A. Bandyopadhyay, M. Das P060 - Novel molecular techniques to identify central venous catheter (CVC) associated blood stream infections (BSIs) T. Mann Ben Yehudah, G. Ben Yehudah, M. Salim, N. Kumar, L. Arabi, T. Burger, P. Lephart, E. Toth-martin P061 - Zero clabsi” – can we get there?
+Van Vught, M. A. Wiewel, O. L. Cremer, J. Horn, M. J. Bonten, M. J. Schultz, T. Van der Poll, W. J. Wiersinga P071 - Botulism outbreak associated with people who inject drugs (PWIDs) in Scotland.
+Mebazaa P092 - Correlation between percentages of ventilated patients developed vap and use of antimicrobial agents in ICU patients.
+R. Iqbal, Y. Alhamdi, N. Venugopal, S. Abrams, C. Downey, C. H. Toh, I. D. Welters P128 - Validity of the age-adjusted d-dimer cutoff in patients with COPD B. Bombay, J. M. Chauny, R. D. Daoust, J. L. Lessard, M. M. Marquis, J. P. Paquet P129 - A scoping review of strategies for prevention and management of bleeding following paediatric cardiopulmonary bypass surgery K. Siemens, D. Sangaran, B. J.
+B. Belli, S. M. Martni, V. C. Cotticelli, F. Mounajergi, R. Barchetta P197 - An observational prospective study on the onset of augmented renal clearance: the first report S. Morimoto, H. Ishikura P198 - An ultrasound- guided algorithm for the management of oliguria in severe sepsis I. Hussain, N. Salahuddin, A. Nadeem, K. Ghorab, K. Maghrabi P199 - Ultrasound in acute kidney injury (aki).
+De Cagny, A. Riviere, T. Soupison, M. Joris, M. Slama P209 - A worldwide multicentre evaluation of acute kidney injury in septic and non-septic critically ill patients: the intensive care over nations (icon) audit E. Peters, H. Njimi, P. Pickkers, J. L. Vincent P210 - Does enhanced recovery after surgery reduce the incidence of acute kidney injury in those undergoing major gynae-oncological surgery?
+M. Waraich , J. Doyle, T. Samuels, L. Forni P211 - Identification of risk factors for the development of acute kidney injury after lower limb arthroplasty N. Desai, R. Baumber, P. Gunning, A.
+Sell P212 - Incidences and associations of acute kidney injury after major trauma S. Lin, H. Torrence, M. O’Dwyer, C. Kirwan, J. Prowle P213 - Acute kidney injury of major trauma patients T Kim P214 - Trajectory of serum creatinine after major surgery and the diagnosis of acute kidney injury M. E. O’Connor, R. W. Hewson, C. J. Kirwan, R. M. Pearse, J. Prowle P215 - Epidemiology of acute kidney injury after cardiac surgery.
+R. Cho, A. Adams , S. Lunos, S. Ambur, R. Shapiro, M. Prekker P248 - Pulse oximetry in the icu patient: is the perfusion index of any value?
+De Cagny, F. Brazier, D. Titeca, G. Bacari-Risal, J. Maizel, M. Amato, M. Slama P272 - Effect of recruitment maneuver on left ventricular systolic strain P. Mercado, J. Maizel, L. Kontar, D. Titeca, F. Brazier, A. Riviere, M. Joris, T. Soupison, B.
+De Cagny, S. El Dash, M. Slama P273 - Inhaled nitric oxide – is switching supplier cost effective?
+Remmington, A. Fischer, S. Squire, M. Boichat P274 - Epidemiological study of severe acute pancreatitis in Japan, comparison of the etiology and the patient outcomes on 1159 patients.
+H. Honzawa, H. Yasuda, T. Adati, S. Suzaki, M. Horibe, M. Sasaki, M. Sanui P275 - Extracorporeal liver support therapy.
+T. Oshima, S. Graf, C. Heidegger, L. Genton, V. Karsegard, Y. Dupertuis, C. Pichard P285 - Revisiting the refeeding syndrome: results of a systematic review N. Friedli, Z. Stanga, B. Mueller, P. Schuetz P286 - Compliance with the new protocol for parenteral nutrition in our ICU L. Vandersteen, B. Stessel, S. Evers, A.
+Van Assche, L. Jamaer, J. Dubois P287 - Nutrition may be another treatment in the intensive care unit where less is more?
+R. Marinho, H. Castro, J. Moura, J. Valente, P. Martins, P. Casteloes, C. Magalhaes, S. Cabral, M. Santos, B. Oliveira, A. Salgueiro, A. Marinho P288 - Should we provide more protein to critically ill patients?
+A. Patarchi, T. Spina P324 Factors associated with ventilator weaning after targeted temperature management for cardiac arrest patients in japan H. Tanaka, N. Otani, S. Ode, S. Ishimatsu P325 Differential activation of c-fos in paraventricular nuclei of the hypothalamus and thalamus of the rat following myocardial infarction J. Cho, J.
+Moon, C. W. Park, T. G. Ohk, M. C. Shin, M. H. Won P326 Monitoring of cTroponin I in patients with acute ischemic stroke - predictor of inhospital mortality S. Dakova, Z. Ramsheva, K. Ramshev P327 Hyperthermic preconditioning severely accelerates neuronal damage in the gerbil ischemic hippocampal dentate gyrus via decreasing sods expressions J. Cho, J.
+Moon, C. W. Park, T. G. Ohk, M. C. Shin P328 Failure in neuroprotection of remote limb ischemic post conditioning in the hippocampus of a gerbil model of transient cerebral ischemia J. Cho, J.
+Moon, C. W. Park, T. G. Ohk, M. C. Shin P329 Brain death and admission diagnosis in neurologic intensive care unit, a correlation?
+A Marudi, S Baroni, A Gaspari, E Bertellini P330 Brain magnetic resonance imaging findings in patients with septic shock G. Orhun, E. Senturk, P. E. Ozcan, S. Sencer, C. Ulusoy, E. Tuzun, F .
+Esen P331 Benefits of L-carnitine in valproic acid induced encephalopathy R. Tincu, C. Cobilinschi, D. Tomescu, Z. Ghiorghiu, R. Macovei P332Automatic analysis of EEG reactivity in comatose patients M. Van Assen, M. M. Admiraal, M. J.
+A. Meynaar P360 - Central nervous system depressants poisoning and ventilator associated pneumonia: an underrated risk factor in toxicological intensive care unit H. Talaie P361 - Acute barium intoxication treated with hemodiafiltration D. Silva, S. Fernandes, J. Gouveia, J. Santos Silva P362 - Major trauma presenting to the emergency department.
+the spectrum of cycling injuries in Ireland J. Foley, A. Kaskovagheorgescu, D. Evoy, J. Cronin, J. Ryan P363 - Burns from French military operations: a 14-year retrospective observational analysis.
+M. Huck, C. Hoffmann, J. Renner, P. Laitselart, N. Donat, A. Cirodde, J. V. Schaal, Y. Masson, A. Nau, T. Leclerc P364 - A comparison of mortality scores in burns patients on the intensive care unit.
+J. Perry, H. Hines P396 - Identifying poor outcome patient groups in a resource-constrained critical care unit K. M. Wilkinson, C. Tordoff, B. Sloan, M. C. Bellamy P397 - Effects of icu weekend admission and discharge on mortality.
+E. Moreira, F. Verga, M. Barbato, G. Burghi P398 - Organizational factors, outcomes and resource use in 9,946 cancer patients admitted to 70 ICUs M Soares, U. V. Silva, L. C. Azevedo, A. P. Torelly, J. M. Kahn, D. C. Angus, M. F. Knibel, P. E. Brasil, F. A. Bozza, J. I. Salluh P399 - Evaluation of oncological critically ill patients, severity score and outcome compared to not oncological in a particular hospital cti.
+Miles , S. Madden, H. Devine P418 - Mobilization in patients on vasoactive drugs use – a pilot study.
+T. Hall, W. C. Ngu, J. M. Jack, P. Morgan P423 - Measuring urine output in ward patients: is it helpful?
+B. Avard, A. Pavli, X. Gee P424 - The incidence of pressure ulcers in an adult mixed intensive care unit in turkey C .
+P. Ostrowski, A. Omar P439 - Icu patients suffer from circadian rhythm desynchronisation K. Kiss , B. Köves, V. Csernus, Z. Molnár P440 - Noise reduction in the ICU: feasible ?
+Van Assche, L. Jamaer, J. Dubois P441 - Accidental removal of invasive devices in the critical patient into the bed-washing.
+V. Medo, R. Galvez, J. P. Miranda P442 - Deprivation of liberty safeguards (dols): audit of compliance in a of a 16-bed specialist cancer critical care unit.
+P. Molmy, N. Van Grunderbeeck, O. Nigeon, M. Lemyze, D. Thevenin, J. Mallat P446 - Palliative care consultation and intensive care unit admission request: a cohort study J. Ramos, M. Correa, R. T. Carvalho, D. Forte P447 - Nursing and medicine together in postsurgical intensive care unit: situations of prognostic conflict at the end of life.
+A. Fernandez, C. McBride P448 - End of life who may decide E. Koonthalloor, C. Walsh P449 - Correctly diagnosing death A. Webber, M. Ashe, K. Smith, P. Jeanrenaud P450 - Skin procurement performed by intensive care physicians: yes, we can.
+A. Marudi , S. Baroni, F. Ragusa, E. Bertellini P451 - Death analysis in pediatric intensive care patients E. A. Volakli , E. Chochliourou, M. Dimitriadou, A. Violaki, P. Mantzafleri, E. Samkinidou, O. Vrani, A. Arbouti, T. Varsami, M. Sdougka P452 - The potential impact of euthanasia on organ donation: analysis of data from belgium J.
+B. Bilsen P456 - Does the source of admission to critical care affect family satisfaction?
+P. Morelli, M. Degiovanangelo, F. Lemos, V. MArtinez, F. Verga, J. Cabrera, G. Burghi P460 - Guidance of visiting children at an adult intensive care unit (icu) A. Rutten , S. Van Ieperen, S. De Geer, M. Van Vugt, E. Der Kinderen P461 - Visiting policies in Italian pediatric ICUs: an update A. Giannini, G Miccinesi, T Marchesi, E Prandi
+This is one of the few examples in which the diverse products have been synthesized just by changing the applied potential.
+The synthesis of sulfonyl derivatives of p-methylaminophenol were carried out by reaction of the electrogenerated p-methylquinoneimine with sulfinic acids.
+Various types of mono (MSP), bis (BSP) and tris (TSP) sulfonyl p-methyl aminophenols were obtained by changing the electrode potential, in one pot under green conditions.
+The mono sulfonyl-p-(methylamino)phenol derivatives (MSP) were assessed for their in vitro antibacterial activity against the gram positive (Staphylococcus aureus) and gram negative (Escherichia coli) strains.
+It was found that the tested compounds were more active against Staphylococcus aureus than Escherichia coli.
+We also found that the antimicrobial activity of MSP derivatives to vary in the order MSP(4) (R = CH(3)) > MSP(1) (R = p-tolyl) ≈ MSP(2) (R = phenyl) > MSP(3) (R = p-ClC(6)H(4)).
+Moreover, the observed homogeneous rate constants (k (obs)) of the reaction of p-methyl quinoneimine with sulfinic acids were estimated in various pH values, based on the EC and ECEC mechanisms, by comparing the simulated cyclic voltammograms with the experimental ones.
+Ten reference genes were investigated for normalization of gene expression data in the shell gland of laying hens.
+Analyses performed with geNorm revealed that hypoxanthine phosphoribosyltransferase 1 (HPRT1) and hydroxymethylbilane synthase (HMBS) were the two most stable reference genes in response to post-oviposition time alone (POT) or with nicarbazin treatment (POT+N) of laying hens.
+NormFinder analyses showed that the two most stable reference genes in response to POT and POT+N were 18S ribosomal RNA (18S rRNA), ribosomal protein L4 (RPL4) and HMBS, RPL4, respectively.
+BestKeeper analyses showed that 18S rRNA, RPL4 and HPRT1, HMBS were the two most stable reference genes for POT, and POT+N, respectively.
+Of the ten reference genes, all except B2M showed geNorm M <0.5, suggesting that they were stably expressed in the shell gland tissue.
+Consensus from these three programs suggested HPRT1 and HMBS could be used as the two most stable reference genes in the present study.
+Expression analyses of four candidate target genes with the two most and the two least stable genes showed that a combination of stable reference genes leads to more discriminable quantification of expression levels of target genes, while the least stable genes failed to do so.
+Therefore, HMBS and HPRT1 are recommended as the two most stable reference genes for the normalization of gene expression data at different stages of eggshell formation in brown-egg laying hens.
+Available statistical programs for reference gene ranking should include more robust analysis capability to analyse the gene expression data generated from factorial design experiments.
+In western Switzerland, an increase of severe cases of S. pyogenes invasive infections was observed between December 2015 and March 2016.
+Our aim was (i) to investigate these cases by the use of Whole Genome Sequencing (WGS) and (ii) to determine the specific virulome and resistome of each isolate in order to undertake adequate public health measures.
+Eleven Streptococcus pyogenes strains isolated from 11 patients with severe invasive infections between December 13, 2015 and March 12, 2016 were included in our study.
+The presence of virulence and antibiotic resistance genes as well as mutations in transcriptional regulators of virulence and in genes encoding for antibiotic targets were assessed.
+Single Nucleotide Polymorphism (SNP) analysis revealed 14 to 32 SNPs between the strains of the same emm-type group, ruling out the possibility of a clonal outbreak.
+As these reassuring results were obtained in less than 10 days, no specific hospital hygiene and no dedicated public health measures had to be undertaken.
+WGS is a powerful technique to discriminate between closely related strains, excluding an outbreak in less than 10 days.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10096-017-2905-z) contains supplementary material, which is available to authorized users.
+OBJECTIVE: The global resurgence of dengue has been attributed to rapid population growth, urban expansion, increased air travel, globalization, and climate change.
+The interrelationship between climatic, ecological, social, and cultural factors that affect dengue and other arboviruses' transmission is understudied.
+DESIGN: The objective of this systematic review is to examine the interrelationship between climatic, ecological, social, and cultural factors on dengue transmission in Puerto Rico and to draw lessons for Zika response.
+RESULTS: A comprehensive search of peer-reviewed journal articles was performed, producing 562 articles; 26 were selected for this review.
+Findings indicate that human activities and behaviors (urbanization, migration, and consumption) as well as climate have a significant impact on the abundance and the transmission potential of Ae.
+CONCLUSION: Despite the public health burden of dengue limited investments have been made in research and surveillance.
+Future research is needed to develop models that integrate the multivariate effects of climatic, ecological, social, and cultural factors, which for Puerto Rico have mostly been examined independently.
+We investigated the diagnostic and prognostic utility of plasma PENK in comparison with neutrophil gelatinase-associated lipocalin (NGAL) and estimated glomerular filtration rates (eGFR) in septic patients.
+METHODS: A total of 167 septic patients were enrolled: 99 with sepsis, 37 with septic shock, and 31 with suspected sepsis.
+PENK and NGAL concentrations were measured and GFR was estimated by using the isotope dilution mass spectrometry traceable-Modification of Diet in Renal Disease (MDRD) Study and three Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations: CKD-EPI(Cr), CDK-EPI(CysC), and CKD-EPI(Cr-CysC).
+The PENK, NGAL, and eGFR results were compared according to sepsis severity, presence or absence of acute kidney injury (AKI), and clinical outcomes.
+RESULTS: The PENK, NGAL, and eGFR results were significantly associated with sepsis severity and differed significantly between patients with and without AKI only in the sepsis group (all P<0.05).
+PENK was superior to NGAL in predicting AKI (P=0.022) and renal replacement therapy (RRT) (P=0.0085).
+Regardless of the variable GFR category by the different eGFR equations, PENK showed constant and significant associations with all eGFR equations.
+CONCLUSIONS: PENK is a highly sensitive and objective biomarker of AKI and RRT and is useful for prognosis prediction in septic patients.
+With its diagnostic robustness and predictive power for survival, PENK constitutes a promising biomarker in critical care settings including sepsis.
+Tuberculosis (TB), caused by Mycobacterium tuberculosis infection, is a leading cause of mortality and morbidity, causing ∼1.5 million deaths annually.
+CD4(+) T cells and several cytokines, such as the Th1 cytokine IFN-γ, are critical in the control of this infection.
+Conversely, the immunosuppressive cytokine IL-10 has been shown to dampen Th1 cell responses to M. tuberculosis infection impairing bacterial clearance.
+Using IL-10 reporter mice, we show in this article that during the first 14 d of M. tuberculosis infection, the predominant cells expressing IL-10 in the lung were Ly6C(+) monocytes.
+Notably, mice deficient in T cell–derived IL-10, but not mice deficient in monocyte-derived IL-10, showed a significant reduction in lung bacterial loads during chronic M. tuberculosis infection compared with fully IL-10–competent mice, indicating a major role for T cell–derived IL-10 in TB susceptibility.
+IL-10–expressing cells were detected among both CD4(+) and CD8(+) T cells, expressed high levels of CD44 and Tbet, and were able to coproduce IFN-γ and IL-10 upon ex vivo stimulation.
+Furthermore, during M. tuberculosis infection, Il10 expression in CD4(+) T cells was partially regulated by both IL-27 and type I IFN signaling.
+Together, our data reveal that, despite the multiple immune sources of IL-10 during M. tuberculosis infection, activated effector T cells are the major source accounting for IL-10–induced TB susceptibility.
+We studied a child with life-threatening, recurrent respiratory tract infections, caused by viruses including human rhinovirus (HRV), influenza virus, and respiratory syncytial virus (RSV).
+Mutant MDA5 was expressed but did not recognize the synthetic MDA5 agonist/(ds)RNA mimic polyinosinic-polycytidylic acid.
+When overexpressed, mutant MDA5 failed to drive luciferase activity from the IFNB1 promoter or promoters containing ISRE or NF-κB sequence motifs.
+In respiratory epithelial cells or fibroblasts, wild-type but not knockdown of MDA5 restricted HRV infection while increasing IFN-stimulated gene expression and IFN-β/λ.
+Moreover, nasal epithelial cells from the patient, or fibroblasts gene-edited to express mutant MDA5, showed increased replication of HRV but not influenza or RSV.
+Thus, human MDA5 deficiency is a novel inborn error of innate and/or intrinsic immunity that causes impaired (ds)RNA sensing, reduced IFN induction, and susceptibility to the common cold virus.
+Since the emergence of the pandemic H1N1pdm09 virus in Mexico and California, biannual increases in the number of cases have been detected in Mexico.
+As observed in previous seasons, pandemic A/H1N1 09 virus was detected in severe cases during the 2011–2012 winter season and finally, during the 2013–2014 winter season it became the most prevalent influenza virus.
+Molecular and phylogenetic analyses of the whole viral genome are necessary to determine the antigenic and pathogenic characteristics of influenza viruses that cause severe outcomes of the disease.
+In this paper, we analyzed the evolution, antigenic and genetic drift of Mexican isolates from 2009, at the beginning of the pandemic, to 2014.
+We found a clear variation of the virus in Mexico from the 2011–2014 season due to different markers and in accordance with previous reports.
+In this study, we identified 13 novel substitutions with important biological effects, including virulence, T cell epitope presented by MHC and host specificity shift and some others substitutions might have more than one biological function.
+The systematic monitoring of mutations on whole genome of influenza A pH1N1 (2009) virus circulating at INER in Mexico City might provide valuable information to predict the emergence of new pathogenic influenza virus
+The recent Zika viral (ZIKV) epidemic has been associated with severe neurological pathologies such as neonatal microcephaly and Guillain-Barre syndrome but unfortunately no vaccine or medication is effectively available yet.
+Zika NS2B-NS3pro is essential for the proteolysis of the viral polyprotein and thereby viral replication.
+Here, we have characterized the solution conformations and catalytic parameters of both linked and unlinked Zika NS2B-NS3pro complexes and found that the unlinked complex manifested well-dispersed NMR spectra.
+Subsequently with selective isotope-labeling using NMR spectroscopy, we demonstrated that C-terminal residues (R73-K100) of NS2B is highly disordered without any stable tertiary and secondary structures in the Zika NS2B-NS3pro complex in the free state.
+Upon binding to the well-characterized serine protease inhibitor, bovine pancreatic trypsin inhibitor (BPTI), only the extreme C-terminal residues (L86-K100) remain disordered.
+Additionally, we have identified five flavonoids and one natural phenol rich in edible plants including fruits and vegetables, which inhibit Zika NS2B-NS3pro in a non-competitive mode, with Ki ranging from 770 nM for Myricetin to 34.02 μM for Apigenin.
+Molecular docking showed that they all bind to a pocket on the back of the active site and their structure-activity relationship was elucidated.
+Our study provides valuable insights into the solution conformation of Zika NS2B-NS3pro and further deciphers its susceptibility towards allosteric inhibition by natural products.
+As these natural product inhibitors fundamentally differ from the currently-known active site inhibitors in terms of both inhibitory mode and chemical scaffold, our finding might open a new avenue for development of better allosteric inhibitors to fight ZIKV infection.
+Traumatic brain injury (TBI) is set to become the leading cause of neurological disability across all age groups.
+Currently, no reliable biomarkers exist to help diagnose the severity of TBI to identify patients who are at risk of developing secondary injuries.
+Thus, the discovery of reliable biomarkers for the management of TBI would improve clinical interventions.
+Inflammatory markers are particularly suited for biomarker discovery as TBI leads to very early alterations in inflammatory proteins.
+Using the Proseek Multiplex Inflammation assay, we measured in patients that had suffered mild TBI (n = 10) or severe TBI (n = 10) with extra-cranial injury or extracranial injury only (EC) (n = 10), 92 inflammation-associated proteins in serum obtained: <1 hr (within 1-hour), 4–12 hr and 48–72 hr post injury.
+CST5 identified patients with severe TBI from all other cohorts and importantly was able to do so within the first hour of injury.
+We conclude that CST5, AXIN1 and TRAIL are worthy of further study in the context of a pre-hospital or pitch-side test to detect brain injury.
+The pathogenesis of Japanese encephalitis virus (JEV) is complex and unclearly defined, and in particular, the effects of the JEV receptor (JEVR) on diverse susceptible cells are elusive.
+In contrast to previous studies investigating JEVR in rodent or mosquito cells, in this study, we used primate Vero cells instead.
+We noted that few novel proteins co-immunoprecipitated with JEV, and discovered that one of these was heat shock protein 90β (HSP90β), which was probed by mass spectrometry with the highest score of 60.3 after questing the monkey and human protein databases.
+The specific HSP90β-JEV binding was confirmed by western blot analysis under non-reducing conditions, and this was significantly inhibited by an anti-human HSP90β monoclonal antibody in a dose-dependent manner, as shown by immunofluorescence assay and flow cytometry.
+In addition, the results of confocal laser scanning microscopic examination demonstrated that the HSP90β-JEV binding occurred on the Vero cell surface.
+Finally, JEV progeny yields determined by plaque assay were also markedly decreased in siRNA-treated Vero cells, particularly at 24 and 36 h post-infection.
+Thus, our data indicate that HSP90β is a binding receptor for JEV in Vero cells.
+A three-year study examined changes in N95 filtering-facepiece respirator (FFR) fit at six-month intervals and the relationship between fit and changes in weight for 229 subjects.
+During each visit, subjects performed a total of nine fit tests using three samples of the same FFR model.
+Inward leakage and filter penetration were measured for each donned respirator to determine face seal leakage (FSL).
+A total of 195 subjects completed the second visit and 134 subjects completed all seven visits.
+Acceptable fit was defined as 90th percentile FSL ≤ 5% and at least one fit factor ≥ 100.
+An unacceptable fit was observed for 14, 10, 7, 12, 15, and 16% of subjects on Visits 2–7, respectively.
+The predicted risk of an unacceptable fit increased with increasing length of time between fit tests, from 10% at Year 1 to 20% at Year 2 and to 25% at Year 3.
+Twenty-four percent of subjects who lost ≥ 20 lb had an unacceptable fit; these percentages ranged from 7–17% for subjects with lower weight losses or any degree of weight gain.
+Results support the current OSHA requirement for annual fit testing and suggest that respirator users who lose more than 20 lb should be re-tested for respirator fit.
+Background: Influenza viruses are among the major causes of serious human respiratory tract infection worldwide.
+In line with the high disease burden attributable to influenza, these viruses play an important, but often neglected, role in travel medicine.
+Of special interest for travel medicine are risk populations and also circumstances that facilitate influenza virus transmission and spread, like travel by airplane or cruise ship and mass gatherings.
+Methods: We conducted a PUBMED/MEDLINE search for a combination of the MeSH terms Influenza virus, travel, mass gathering, large scale events and cruise ship.
+In addition we gathered guidelines and recommendations from selected countries and regarding influenza prevention and management in travellers.
+By reviewing these search results in the light of published knowledge in the fields of influenza prevention and management, we present best practice advice for the prevention and management of influenza in travel medicine.
+Known host-associated risk factors include extremes of age and being immune-compromised, while the most relevant environmental factors are associated with holiday cruises and mass gatherings.
+Conclusions: Pre-travel advice should address influenza and its prevention for travellers, whenever appropriate on the basis of the epidemiological situation concerned.
+In addition, seasonal influenza vaccination should be considered for any traveller wishing to reduce the risk of incapacitation, particularly cruise ship crew and passengers, as well as those participating in mass gatherings.
+Besides advice concerning preventive measures and vaccination, advice on the use of antivirals may be considered for some travellers.
+Bats are suspected to be a reservoir of several bacterial and viral pathogens relevant to animal and human health, but studies on Escherichia coli in these animals are sparse.
+We investigated the presence of E. coli in tissue samples (liver, lung and intestines) collected from 50 fruit bats of five different species (Eidolon helvum, Epomops franqueti, Hypsignathus monstrosus, Myonycteris torquata, Rousettus aegyptiacus) of two different areas in the Republic of Congo between 2009 and 2010.
+To assess E. coli pathotypes and phylogenetic relationships, we determined the presence of 59 virulence associated genes and multilocus sequence types (STs).
+Isolates were further tested for their susceptibility to several antimicrobial substances by agar disk diffusion test and for the presence of an Extended-Spectrum Beta-Lactamase phenotype.
+The diversity of E. coli strains was very high, with 37 different STs within 40 isolates.
+Although the majority of strains were assigned to phylogenetic group B2 (46.2%), which is linked with the ExPEC pathovar, occurrence of virulence-associated genes in these strains were unexpectedly low.
+Due to this, and as only few of the E. coli isolates showed intermediate resistance to certain antimicrobial substances, we assume a rather naïve E. coli population, lacking contact to humans or domestic animals.
+Future studies featuring in depth comparative whole genome sequence analyses will provide insights into the microevolution of this interesting strain collection.
+Alphaviruses are arthropod-borne viruses that represent a significant threat to public health at a global level.
+While the formation of alphaviral nucleocapsid cores, consisting of cargo nucleic acid and the viral capsid protein, is an essential molecular process of infection, the precise interactions between the two partners are ill-defined.
+A CLIP-seq approach was used to screen for candidate sites of interaction between the viral Capsid protein and genomic RNA of Sindbis virus (SINV), a model alphavirus.
+The data presented in this report indicates that the SINV capsid protein binds to specific viral RNA sequences in the cytoplasm of infected cells, but its interaction with genomic RNA in mature extracellular viral particles is largely non-specific in terms of nucleotide sequence.
+Mutational analyses of the cytoplasmic viral RNA-capsid interaction sites revealed a functional role for capsid binding early in infection.
+Interaction site mutants exhibited decreased viral growth kinetics; however, this defect was not a function of decreased particle production.
+Rather mutation of the cytoplasmic capsid-RNA interaction sites negatively affected the functional capacity of the incoming viral genomic RNAs leading to decreased infectivity.
+Furthermore, cytoplasmic capsid interaction site mutants are attenuated in a murine model of neurotropic alphavirus infection.
+Collectively, the findings of this study indicate that the identified cytoplasmic interactions of the viral capsid protein and genomic RNA, while not essential for particle formation, are necessary for genomic RNA function early during infection.
+This previously unappreciated role of capsid protein during the alphaviral replication cycle also constitutes a novel virulence determinant.
+We assembled and analyzed a database of 330 disease systems in which a pathogen spills over from a reservoir of one or more species.
+Further, 65% of pathogens depended on a community of reservoir hosts, rather than a single species, for persistence.
+The distribution among orders of mammalian species identified as reservoirs did not differ from that expected by chance.
+Among disease systems with high priority pathogens and epidemic potential, we found birds, primates, and bats to be overrepresented.
+We also analyzed the life history traits of mammalian reservoir hosts and compared them to mammals as a whole.
+Reservoir species had faster life history characteristics than mammals overall, exhibiting traits associated with greater reproductive output rather than long-term survival.
+There is a lack of definitive data on the effective management of acute respiratory distress syndrome (ARDS) in infants and children.
+The development and validation of the Berlin definition (BD) for ARDS and the Pediatric Acute Lung Injury Consensus Conference (PALICC) recommendations in children represented a major advance in optimizing research and treatment, mainly due to the introduction of a severe ARDS category.
+Proposed reasons for the lack of consistent results with surfactants in children and infants compared with neonates include different causes, type of lung damage (direct or indirect), timing and mode of administration as well as the type of surfactant used.
+Secretory phospholipase A2 plays an important role in inflammation and possible dysfunction of surfactants in ARDS.
+Bronchoalveolar lavage (BAL) with normal saline and surfactant allows the removal of inhaled material, the recruitment of non-ventilating areas and the maintenance of the surfactant pool size.
+BAL with diluted surfactant allows rapid absorption of the surfactant at the air/liquid interface, which blocks the progression of pathological lung disease and in turn disrupts the inflammatory cycle.
+Importantly, it is now recognized that the type of surfactant, the time of administration and the method of administration could all play an important role in the management of ARDS, and there is evidence that surfactant is effective and well tolerated in children and infants with ARDS.
+Antibody and T-cell immunity to conserved influenza virus antigens can protect animals against infection with diverse influenza strains.
+Although immunity against conserved antigens occurs in humans, whether such responses provide cross-protection in humans and could be harnessed as the basis for universal influenza vaccines is controversial.
+The 2009 pandemic provided an opportunity to investigate whether pre-existing cross-reactive immunity affected susceptibility to infection.
+In 2009, we banked sera and peripheral blood mononuclear cells (PBMC) from blood donors, then monitored them for pandemic influenza infection (pH1N1) by polymerase chain reaction or seroconversion.
+Antibodies to hemagglutinin (HA), neuraminidase (NA), nucleoprotein (NP), matrix 2 (M2), and HA-pseudotypes were measured in sera.
+Pre-existing T-cell reactivity to pH1N1 was substantial (of 153 donors tested, 146 had >100 spot-forming cells/10(6) cells).
+Unexpectedly, donors with symptomatic pH1N1 infection had sharp rises in HA pseudotype-neutralizing antibodies, not only pH1N1 but also against multiple seasonal H1s.
+In addition, an exploratory study of a T-cell marker (response to NP(418-426)) identified probable infection missed by standard criteria.
+Although the number of infections was inadequate for conclusions about mechanisms of protection, this study documents the wide variety of pre-existing, cross-reactive, humoral and cellular immune responses to pandemic influenza virus antigens in humans.
+These responses can be compared with results of other studies and explored in universal influenza vaccine studies.
+The giant triton snail (Charonia tritonis) is one of the few natural predators of the adult Crown-of-Thorns starfish (COTS), a corallivore that has been damaging to many reefs in the Indo-Pacific.
+Charonia species have large salivary glands (SGs) that are suspected to produce either a venom and/or sulphuric acid which can immobilize their prey and neutralize the intrinsic toxic properties of COTS.
+Then, the C. tritonis SG, which itself is made up of an anterior lobe (AL) and posterior lobe (PL), was analyzed using an integrated transcriptomics and proteomics approach, to identify putative toxin- and feeding-related proteins.
+A de novo transcriptome database and in silico protein analysis predicts that ~3800 proteins have features consistent with being secreted.
+A gland-specific proteomics analysis confirmed the presence of numerous SG-AL and SG-PL proteins, including those with similarity to cysteine-rich venom proteins.
+Our analysis of the C. tritonis SG (AL and PL) has provided a deeper insight into the biomolecular toolkit used for predation and feeding by C. tritonis.
+Viruses co-evolve with their hosts, and many viruses have developed mechanisms to suppress or modify the host cell apoptotic response for their own benefit.
+Some viruses have developed the ability to co-opt apoptotic caspase activity to facilitate their own proliferation.
+In these strategies, viral proteins are cleaved by host caspases to create cleavage products with novel activities which facilitate viral replication.
+This represents a novel and interesting class of viral–host interactions, and also represents a new group of non-apoptotic roles for caspases.
+Here we review the evidence for such strategies, and discuss their origins and their implications for our understanding of the relationship between viral pathogenesis and programmed cell death.
+Little is known about the specific contributions of aging to the neuron dysfunction and death in Alzheimer’s disease (AD).
+AD is characterized by the pathological accumulation of abnormal tau (a microtubule-associated protein), and the mislocalization of tau from the axon to the somatodendritic compartment is thought to play an important role in disease pathogenesis.
+The axon initial segment (AIS) is thought to play a role in the selective localization of tau in the axonal compartment.
+Thus, disruption in the AIS barrier may allow tau to diffuse freely back into the somatodendritic compartment and potentially lead to neurotoxicity.
+Here, we analyzed AISs using stereological methods and protein immunoblotting, and the localization of tau was assessed with immunofluorescence optical density measurements and protein immunoblotting.
+None of the outcome measurements assessed, including AIS structure, AIS protein levels, the distribution of tau in neurons of the hippocampus (HP), and total tau or phospho-tau protein levels were different in young, middle-, and old-age Fischer 344 rats.
+The outcome measurements assessed, including AIS structure, AIS protein levels, the distribution of tau in neurons of the HP, and total tau or phospho-tau protein levels were not different in young, middle-, and old-age Fischer 344 rats, with the exception of a small reduction in AIS volume and diameter in the CA2 region of aged animals.
+These data suggest that aging largely has no effect on these properties of the AIS or tau distribution, and thus, may not contribute directly to tau mislocalization.
+To investigate the role of the protein C system, endothelial protein C receptor (EPCR) and thrombomodulin (TM) in the pathogenesis of malaria-associated acute respiratory distress syndrome (ARDS) in relation to hemozoin and proinflammatory cytokines-induced type II pneumocyte injury and -aggravated pulmonary resolution.
+A total of 29 left-over lung specimens that were obtained from patients who died from severe falciparum malaria were examined.
+Histopathological, immunohistochemical and electron microscopic analyses revealed that ARDS coexisted with pulmonary edema and systemic bleeding; the severity was dependent on the level of hemozoin deposition in the lung and internal alveolar hemorrhaging.
+The loss of EPCR and TM was primarily identified in ARDS patients and was related to the level of hemozoin, parasitized red blood cell (PRBC) and white blood cell accumulation in the lung.
+Moreover, an in vitro analysis demonstrated that interleukin-13 and -31 and hemozoin induced pneumocytic cell injury and apoptosis, as assessed by EB/AO staining, electron microscopy and the up-regulation of CARD-9 mRNA (caspase recruitment domain-9 messenger-ribonucleic acid).
+The dysregulation of EPCR and TM in the lung, especially in those with increased levels of hemozoin, may play an important role in the pathogenesis of malaria-associated ARDS through an apoptotic pathway.
+BACKGROUND: The Ebola virus has been responsible for numerous outbreaks since the 1970s, with the most recent outbreak taking place between 2014 and 2016 and causing an international public health emergency.
+Ebola virus disease (EVD) has a high mortality rate and no approved targeted treatment exists to date.
+A number of established drugs are being considered as potential therapeutic agents for the treatment of EVD.
+OBJECTIVE: We aimed to identify potential drug repositioning candidates and to assess the scientific evidence available on their efficacy.
+METHODS: We conducted a systematic literature search in MEDLINE, Embase, and other relevant trial registry platforms for studies published between January 1976 and January 2017.
+We included drug screening, preclinical studies, and clinical studies on repurposed drugs for the treatment of EVD.
+Finally, we selected drugs approved by established regulatory authorities, which have positive in vitro study outcomes and at least one additional animal or clinical trial.
+CONCLUSIONS: Several established drugs may have therapeutic effects on EVD, but the quality and quantity of current scientific evidence is lacking.
+This review highlights the need for well-designed and conducted preclinical and clinical research to establish the efficacy of potential repurposed drugs against EVD.
+Extensive functional studies of the exchange protein directly activated by cAMP (EPAC) family of signaling molecules have demonstrated that EPAC proteins play a fundamental role in several physiological and pathophysiological responses, therefore are attractive drug targets.
+In this report, the development of a cell-based, medium to high throughput screening assay that is capable of monitoring EPAC-mediated activation of cellular Rap1 in an isoform-specific manner is described.
+This assay adapts a conventional ELISA format with immobilized RalGDS-RBD as a bait to selectively capture GTP-bound active Rap1.
+As a result, it fills an urgent need for a cell-based EPAC assay that can be conveniently performed using microtiter plates for the discovery and/or validation of isoform-specific EPAC agonists and antagonists.
+The definition of the immunological response to Zika (ZIKV) infection in humans represents a key issue to identify protective profile useful for vaccine development and for pathogenesis studies.
+No data are available on the cellular immune response in the acute phase of human ZIKV infection, and its role in the protection and/or pathogenesis needs to be clarified.
+We studied and compared the phenotype and functionality of T-cells in patients with acute ZIKV and Dengue viral (DENV) infections.
+ZIKV infection was characterized by a CD4 T cell differentiation toward effector cells and by a lower frequency of IFN-γ producing CD4 T cells.
+Moreover, a substantial expansion of CD3(+)CD4(−)CD8(−) T-cell subset expressing Vδ2 TCR was specifically observed in ZIKV patients.
+Vδ2 T cells presented a terminally differentiated profile, expressed granzyme B and maintained their ability to produce IFN-γ.
+These findings provide new knowledge on the immune response profile during self-limited infection that may help in vaccine efficacy definition, and in identifying possible immuno-pathogenetic mechanisms of severe infection.
+We evaluated the infection and tropism of human and avian H9 influenza virus in the human respiratory tract using ex vivo respiratory organ culture.
+H9 viruses infected the upper and lower respiratory tract and the majority of H9 viruses had a decreased ability to release virus from the bronchus rather than the lung.
+This may be attributed to a weak neuraminidase (NA) cleavage of carbon-6-linked sialic acid (Sia) rather than carbon-3-linked Sia.
+The modified cleavage of N-acetlylneuraminic acid (Neu5Ac) and N-glycolylneuraminic acid (Neu5Gc) by NA in H9 virus replication was observed by reverse genetics, and recombinant H9N2 viruses with amino acids (38KQ) deleted in the NA stalk, and changing the amino acid at position 431 from Proline-to-Lysine.
+Using recombinant H9 viruses previously evaluated in the ferret, we found that viruses which replicated well in the ferret did not replicate to the same extent in the human ex vivo cultures.
+The existing risk assessment models for H9N2 viruses in ferrets may not always have a strong correlation with the replication in the human upper respiratory tract.
+The inclusion of the human ex vivo cultures would further strengthen the future risk-assessment strategies.
+The in vitro anti-proliferative potential of the synthesized compounds 4a-o and 7a-e was examined against HT-29 (colon), ZR-75 (breast) and A549 (lung) human cancer cell lines.
+Compounds 7b, 7d and 7e were the most active congeners against the tested human cancer cell lines with average IC(50) values of 4.77, 3.39 and 2.37 μM, respectively, as compared with the reference isatin-based drug, sunitinib, which exhibited an average IC(50) value of 8.11 μM.
+Compound 7e was selected for further pharmacological evaluation in order to gain insight into its possible mechanism of action.
+It increased caspase 3/7 activity by 2.4- and 1.85-fold between 4 and 8 h of treatment, respectively, at 10 μM and it caused a decrease in the percentage of cells in the G1 phase of the cell cycle with a corresponding increase in the S-phase.
+In addition, compound 7e increased phosphorylated tyrosine (p-Tyr) levels nearly two-fold with an apparent IC(50) value of 3.8 μM.
+While, the in vitro release profile of the 7e-loaded microspheres was characterized by slow and continuous release of compound 7e during 21 days and the release curve was fitted to zero order kinetics.
+Incorporation of 7e into PLGA microspheres improved its in vitro anti-proliferative activity toward the human cancer cell line A549 after 120 h incubation period with an IC(50) value less than 0.8 μM.
+Secreted alpha-toxin and surface-localized clumping factor A (ClfA) are key virulence determinants in Staphylococcus aureus bloodstream infections.
+We previously demonstrated that prophylaxis with a multimechanistic monoclonal antibody (MAb) combination against alpha-toxin (MEDI4893*) and ClfA (11H10) provided greater strain coverage and improved efficacy in an S. aureus lethal bacteremia model.
+Subsequently, 11H10 was found to exhibit reduced affinity and impaired inhibition of fibrinogen binding to ClfA002 expressed by members of a predominant hospital-associated methicillin-resistant S. aureus (MRSA) clone, ST5.
+Consequently, we identified another anti-ClfA MAb (SAR114) from human tonsillar B cells with >100-fold increased affinity for three prominent ClfA variants, including ClfA002, and potent inhibition of bacterial agglutination by 112 diverse clinical isolates.
+We next constructed bispecific Abs (BiSAbs) comprised of 11H10 or SAR114 as IgG scaffolds and grafted anti-alpha-toxin (MEDI4893*) single-chain variable fragment to the amino or carboxy terminus of the anti-ClfA heavy chains.
+Although the BiSAbs exhibited in vitro potencies similar to those of the parental MAbs, only 11H10-BiSAb, but not SAR114-BiSAb, showed protective activity in murine infection models comparable to the respective MAb combination.
+In vivo activity with SAR114-BiSAb was observed in infection models with S. aureus lacking ClfA.
+Our data suggest that high-affinity binding to ClfA sequesters the SAR114-BiSAb to the bacterial surface, thereby reducing both alpha-toxin neutralization and protection in vivo.
+These results indicate that a MAb combination targeting ClfA and alpha-toxin is more promising for future development than the corresponding BiSAb.
+This study describes the identification of one linear B-cell epitope on TMUV NS1 protein with monoclonal antibody (mAb) 3G2 by indirect enzyme-linked immunosorbent assay (ELISA).
+One mAb against NS1 protein was generated from Balb/c mice immunized with recombinant protein NS1.
+A set of 35 partially-overlapping polypeptides covering the entire NS1 protein was expressed with PGEX-6P-1 vector and screened with mAb 3G2.
+To map the epitope accurately, one or two amino acid residues were removed from the carboxy and amino terminal of polypeptide sequentially.
+The minimal determinant of the linear B cell epitope was recognized and identified with mAb 3G2.
+Furthermore, sequence alignment showed that the epitope was highly conserved and specific among TMUV strains and other flavivirus respectively.
+The linear B-cell epitope of TMUV NS1 protein could benefit the development of new vaccines and diagnostic assays.
+Stress Granules (SGs) are dynamic ribonucleoprotein aggregates, which have been observed in cells subjected to environmental stresses, such as oxidative stress and heat shock (HS).
+Although pluripotent stem cells (PSCs) are highly sensitive to oxidative stress, the role of SGs in regulating PSC self-renewal and differentiation has not been fully elucidated.
+Here we found that sodium arsenite (SA) and HS, but not hydrogen peroxide (H(2)O(2)), induce SG formation in human induced (hi) PSCs.
+Particularly, we found that these granules contain the well-known SG proteins (G3BP, TIAR, eIF4E, eIF4A, eIF3B, eIF4G, and PABP), were found in juxtaposition to processing bodies (PBs), and were disassembled after the removal of the stress.
+Moreover, we showed that SA and HS, but not H(2)O(2), promote eIF2α phosphorylation in hiPSCs forming SGs.
+Analysis of pluripotent protein expression showed that HS significantly reduced all tested markers (OCT4, SOX2, NANOG, KLF4, L1TD1, and LIN28A), while SA selectively reduced the expression levels of NANOG and L1TD1.
+Finally, in addition to LIN28A and L1TD1, we identified DPPA5 (pluripotent protein marker) as a novel component of SGs.
+Collectively, these results provide new insights into the molecular cues of hiPSCs responses to environmental insults.
+Novel testing must be brought to the clinic with safety and accuracy, but also in a timely and cost-effective manner, so that patients can benefit and laboratories can offer testing consistent with current guidelines.
+Under the oversight provided by the Clinical Laboratory Improvement Amendments, laboratories have been able to develop and optimize laboratory procedures for use in-house.
+Quality improvement programs, interlaboratory comparisons, and the ability of laboratories to adjust assays as needed to improve results, utilize new sample types, or incorporate new mutations, information, or technologies are positive aspects of Clinical Laboratory Improvement Amendments oversight of laboratory-developed procedures.
+Laboratories have a long history of successful service to patients operating under Clinical Laboratory Improvement Amendments.
+A series of detailed clinical examples illustrating the quality and positive impact of laboratory-developed procedures on patient care is provided.
+These examples also demonstrate how Clinical Laboratory Improvement Amendments oversight ensures accurate, reliable, and reproducible testing in clinical laboratories.
+BACKGROUND: Positive-pressure mechanical ventilation is essential in assisting patients with respiratory failure in the intensive care unit and facilitating oxygenation in the operating room.
+However, it was also recognized as a primary factor leading to hospital-acquired pulmonary dysfunction, in which pulmonary oxidative stress and lung inflammation had been known to play important roles.
+In this study, we aimed to study the efficacy of Cu/Zn SOD, administered intravenously during high tidal volume (HTV) ventilation, to prevent impairment of lung function.
+METHODS: Thirty-eight male Sprague-Dawley rats were divided into 3 groups: 5 h ventilation with (A) low tidal volume (LTV; 8 mL/kg; n = 10), (B) high tidal volume (HTV; 18 mL/kg; n = 14), or (C) HTV and intravenous treatment of Cu/Zn SOD at a dose of 1000 U/kg/h (HTV + SOD; n = 14).
+Lung injury was assessed by histological examination, lung water and protein contents in the bronchoalveolar lavage fluid (BALF).
+Pulmonary oxidative stress was examined by concentrations of methylguanidine (MG) and malondialdehyde (MDA) in BALF, and antioxidative activity by protein expression of glutathione peroxidase-1 (GPx-1) in the lung.
+Severity of lung inflammation was evaluated by white blood cell and differential count in BALF, and protein expression of inducible nitric oxide synthase (iNOS), intercellular adhesion molecule-1 (ICAM-1), tumor necrosis factor-α (TNF-α), matrix metalloproteinase-9 (MMP-9), and mRNA expression of nuclear factor-κB (NF-κB) in the lung.
+We also examined protein expression of surfactant protein (SP)-A and D and we measured hourly changes in serum nitric oxide (NO) level.
+RESULTS: Five hours of LTV ventilation did not induce a major change in lung function, whereas 5 h of HTV ventilation induced apparent combined restrictive and obstructive lung disorder, together with increased pulmonary oxidative stress, decreased anti-oxidative activity and increased lung inflammation (P < 0.05).
+HTV ventilation also decreased SP-A and SP-D expression and suppressed serum NO level during the time course of ventilation.
+Cu/Zn SOD administered intravenously during HTV ventilation effectively reversed associated pulmonary oxidative stress and lung inflammation (P < 0.05); moreover, it preserved SP-A and SP-D expressions in the lung and increased serum nitric oxide (NO) level, enhancing vascular NO bioavailability.
+Intravenous administration of Cu/Zn SOD during HTV ventilation can prevent lung function impairment and lung injury via reducing pulmonary oxidative stress and lung inflammation, preserving pulmonary surfactant expression, and enhancing vascular NO bioavailability.
+Several approaches have been employed in the treatment of gemcitabine-induced hemolytic uremic syndrome with different outcomes.
+One of the most promising agents is eculizumab, which is a monoclonal antibody directed against C5 complement protein.
+CASE PRESENTATION: We reported the case of a 3-year-old white boy with medulloblastoma who underwent high-dose chemotherapy and craniospinal irradiation.
+After five courses he presented a progressive clinical worsening, which resulted in a systemic thrombotic microangiopathy.
+After seven infusions he showed a gradual improvement and finally a complete remission of gemcitabine-induced hemolytic uremic syndrome.
+Classical swine fever virus (CSFV) non-structural protein 3 (NS3) is a multifunctional non-structural protein that plays a major role in viral replication.
+Here, we identified tumour necrosis factor receptor-associated factor 6 (TRAF6) as a novel NS3-interacting protein via yeast two-hybrid analysis, co-immunoprecipitation, and glutathione S-transferase pull-down assays.
+Furthermore, we observed that TRAF6 overexpression significantly inhibited CSFV replication, and TRAF6 knockdown promoted CSFV replication in porcine alveolar macrophages.
+Additionally, TRAF6 was degraded during CSFV infection or NS3 expression exclusively, indicating that CSFV and TRAF6 were mutually antagonistic and that TRAF6 degradation might contribute to persistent CSFV replication.
+Moreover, nuclear factor-kappa B (NF-κB) activity and interferon (IFN)-β and interleukin (IL)-6 expression were increased in TRAF6-overexpressing cells, whereas TRAF6-knockdown cells exhibited decreased NF-κB activity and IFN-β and IL-6 levels.
+Notably, TRAF6 overexpression did not reduce CSFV replication following inhibition of NF-κB activation by p65 knockdown.
+Our findings revealed that TRAF6 inhibits CSFV replication via activation of NF-κB-signalling pathways along with increases in the expression of its targets IFN-β and IL-6.
+This work addresses a novel aspect concerning the regulation of innate antiviral immune response during CSFV infection.
+All immunotherapeutic drugs target relapsing remitting MS (RRMS) and it still remains a medical challenge in MS to develop a treatment for progressive forms.
+The most common injectable disease-modifying therapies in RRMS include β-interferons 1a or 1b and glatiramer acetate.
+However, one of the major challenges of injectable disease-modifying therapies has been poor treatment adherence with approximately 50% of patients discontinuing the therapy within the first year.
+Herein, we go back to the basics to understand the immunopathophysiology of MS to gain insights in the development of new improved drug treatments.
+We present current disease-modifying therapies (interferons, glatiramer acetate, dimethyl fumarate, teriflunomide, fingolimod, mitoxantrone), humanized monoclonal antibodies (natalizumab, ofatumumab, ocrelizumab, alemtuzumab, daclizumab) and emerging immune modulating approaches (stem cells, DNA vaccines, nanoparticles, altered peptide ligands) for the treatment of MS.
+OBJECTIVES: The study assessed the existence and significance of associations between the expression of fifteen renin-angiotensin system component genes and lung adenocarcinoma.
+MATERIALS AND METHODS: NCBI's built-in statistical tool, GEO2R, was used to calculate Student's t-tests for the associations found in a DNA expression study of adenocarcinoma and matched healthy lung tissue samples.
+The raw data was processed with GeneSpring™ and then used to generate figures with and without Sidak's multiple comparison correction.
+Notably, AGTR2, which encodes the AT(2) angiotensin II receptor subtype, was significantly underexpressed in adenocarcinoma tissue (p < 0.01).
+AGTR1, ACE, ENPEP, MME, and PRCP, which encode the AT(1) angiotensin II receptor, angiotensin-converting enzyme, aminopeptidase N, neprilysin, and prolylcarboxypeptidase, respectively, were also underexpressed.
+CONCLUSION: The results suggest an association between the expression of the genes for renin-angiotensin system-related proteins and adenocarcinoma.
+While further research is necessary to conclusively demonstrate a link between the renin-angiotensin system and lung cancers, the results suggest that the renin-angiotensin system plays a role in the pathology of adenocarcinoma.
+A novel service oriented platform has been developed under the framework of the Telerehabilitation Service funded by the Cross Border Cooperation Programme Greece Cyprus 2007 – 2013 to support tele-supervised exercise rehabilitation for patients after hospitalization in intensive care units (ICU).
+It also enables patient group-based vital sign real time monitoring, patients’ clinical record bookkeeping, and individualized and group-based patient online exercise programs.
+The exercise programs intended for the service are based on successful cardiorespiratory rehabilitation programs, individualized and monitored by a multidisciplinary team.
+The eligibility study of former ICU patients to participate in such a service as well as a cost benefit analysis are presented to support the cost effectiveness of the telerehabilitation program in addition to the expected health benefits to a large proportion of former ICU patients.
+We performed integrative analysis of genes associated with type 2 Diabetes Mellitus (T2DM) associated complications by automated text mining with manual curation and also gene expression analysis from Gene Expression Omnibus.
+They were analysed for pathogenic or protective role, trends, interaction with risk factors, Gene Ontology enrichment and tissue wise differential expression.
+Seven genes AGER, TNFRSF11B, CRK, PON1, ADIPOQ, CRP and NOS3 are associated with all 5 complications.
+Several genes are studied in multiple years in all complications with high proportion in cardiovascular (75.8%) and atherosclerosis (51.3%).
+A few genes ACE2, ADCYAP1, HDAC4, NCF1, NFE2L2, OSM, SMAD1, TGFB1, BDNF, SYVN1, TXNIP, CD36, CYP2J2, NLRP3 with details of protective role are catalogued.
+Obesity is clearly a dominant risk factor interacting with the genes of T2DM complications followed by inflammation, diet and stress to variable extents.
+This information emerging from the integrative approach used in this work could benefit further therapeutic approaches.
+Sudan virus (SUDV) outbreaks in Africa are highly lethal; however, the development and testing of novel antivirals and vaccines for this virus has been limited by a lack of suitable animal models.
+Non-human primates (NHP) remain the gold standard for modeling filovirus disease, but they are not conducive to screening large numbers of experimental compounds and should only be used to test the most promising candidates.
+We have recently developed a guinea-pig adapted SUDV virus that is lethal in guinea pigs.
+In our current study, we show that ferrets are susceptible to wild-type SUDV, providing a small animal model to directly study clinical isolates, screen experimental anti-SUDV compounds and potentially study viral transmission.
+BACKGROUND: Diffuse alveolar damage (DAD), which is the histological surrogate for acute respiratory distress syndrome (ARDS), has a multifactorial aetiology.
+The aim of this study is to compare lung immunopathology of viral (influenza A(H1N1)pdm09) to non-viral, extrapulmonary aetiologies in autopsy cases with DAD.
+METHODS: The lung tissue of 44 patients, was divided in the H1N1 group (n = 15) characterized by severe pulmonary injury due to influenza A(H1N1)pdm09 infection; the ARDS group (n = 13), characterized by patients with DAD due to non-pulmonary causes; and the Control group (n = 16), consisting of patients with non-pulmonary causes of death.
+Immunohistochemistry and image analysis were used to quantify, in the parenchyma and small airways, several immune cell markers.
+RESULTS: Both DAD groups had higher expression of neutrophils and macrophages in parenchyma and small airways.
+However, there was a higher expression of CD4+ and CD8+ T lymphocytes, CD83+ dendritic cells, granzyme A+ and natural killer + cell density in the lung parenchyma of the H1N1 group (p < 0.05).
+In the small airways, there was a lower cell density of tryptase + mast cells and dendritic + cells and an increase of IL-17 in both DAD groups (p < 0.05).
+CONCLUSION: DAD due to viral A(H1N1)pdm09 is associated with a cytotoxic inflammatory phenotype, with partially divergent responses in the parenchyma relative to the small airways.
+In non-viral DAD, main immune cell alterations were found at the small airway level, reinforcing the role of the small airways in the pathogenesis of the exudative phase of DAD.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12931-017-0630-x) contains supplementary material, which is available to authorized users.
+New influenza A viruses that emerge frequently elicit composite inflammatory responses to both infection and structural damage of alveolar-capillary barrier cells that hinders regeneration of respiratory function.
+The host factors that relinquish restoration of lung health to enduring lung injury are insufficiently understood.
+Here, we investigated the role of endophilin B2 (B2) in susceptibility to severe influenza infection.
+WT and B2-deficient mice were infected with H1N1 PR8 by intranasal administration and course of influenza pneumonia, inflammatory, and tissue responses were monitored over time.
+Disruption of B2 enhanced recovery from severe influenza infection as indicated by swift body weight recovery and significantly better survival of endophilin B2-deficient mice compared to WT mice.
+Compared to WT mice, the B2-deficient lungs exhibited induction of genes that express surfactant proteins, ABCA3, GM-CSF, podoplanin, and caveolin mRNA after 7 days, temporal induction of CCAAT/enhancer binding protein CEBPα, β, and δ mRNAs 3–14 days after infection, and differences in alveolar extracellular matrix integrity and respiratory mechanics.
+Flow cytometry and gene expression studies demonstrated robust recovery of alveolar macrophages and recruitment of CD4+ lymphocytes in B2-deficient lungs.
+Targeting of endophilin B2 alleviates adverse effects of IAV infection on respiratory and immune cells enabling restoration of alveolar homeostasis.
+Vaccines have shown great success in treating and preventing tumors and infections, while adjuvants are always demanded to ensure potent immune responses.
+Polyethylenimine (PEI), as one of the well-studied cationic polymers, has been used as a transfection reagent for decades.
+However, increasing evidence has shown that PEI-based particles are also capable of acting as adjuvants.
+In this paper, we briefly review the physicochemical properties and the broad applications of PEI in different fields, and elaborate on the intracellular processes of PEI-based vaccines.
+We also highlight some mechanisms proposed for the intrinsic immunoactivation function of PEI, followed by the challenges and future perspectives of the applications of PEI in the vaccines, as well as some strategies to elicit the desirable immune responses.
+A febrile respiratory infectious disease unit (FRIDU) with a negative pressure ventilation system was constructed outside the emergency department (ED) of the Samsung Medical Center in 2015, to screen for patients with contagious diseases requiring isolation.
+We analyzed 1,562 patients who were hospitalized after FRIDU screening between August 2015 and July 2016.
+The level of isolation recommended during their screening at the FRIDU was compared with the level deemed appropriate given their final diagnosis.
+Of the 1,562 patients screened at the FRIDU, 198 (13%) were isolated, 194 (12%) were reverse isolated, and 1,170 (75%) were not isolated.
+While hospitalized, 97 patients (6%) were confirmed to have a contagious disease requiring isolation, such as tuberculosis; 207 patients (13%) were confirmed to be immunocompromised and to require reverse isolation, mainly due to neutropenia; and the remaining 1,258 patients (81%) did not require isolation.
+The sensitivity and negative predictive value of FRIDU screening for diagnosing contagious disease requiring isolation are 76% and 98%, respectively.
+During FRIDU screening, 114 patients were admitted to the resuscitation zone due to clinical instability, and three of these patients died.
+The initial isolation levels resulting from FRIDU screening were moderately well correlated with the isolation levels required by the final diagnosis, demonstrating the utility of pre-hospitalization screening units.
+BACKGROUND: Social networking services (SNSs) contain abundant information about the feelings, thoughts, interests, and patterns of behavior of adolescents that can be obtained by analyzing SNS postings.
+An ontology that expresses the shared concepts and their relationships in a specific field could be used as a semantic framework for social media data analytics.
+OBJECTIVE: The aim of this study was to refine an adolescent depression ontology and terminology as a framework for analyzing social media data and to evaluate description logics between classes and the applicability of this ontology to sentiment analysis.
+The concepts constituting the ontology and terminology were collected from clinical practice guidelines, the literature, and social media postings on adolescent depression.
+An internal structure of the ontology was designed using the entity-attribute-value (EAV) triplet data model, and superclasses of the ontology were aligned with the upper ontology.
+Description logics between classes were evaluated by mapping concepts extracted from the answers to frequently asked questions (FAQs) onto the ontology concepts derived from description logic queries.
+The applicability of the ontology was validated by examining the representability of 1358 sentiment phrases using the ontology EAV model and conducting sentiment analyses of social media data using ontology class concepts.
+RESULTS: We developed an adolescent depression ontology that comprised 443 classes and 60 relationships among the classes; the terminology comprised 1682 synonyms of the 443 classes.
+In the description logics test, no error in relationships between classes was found, and about 89% (55/62) of the concepts cited in the answers to FAQs mapped onto the ontology class.
+Regarding applicability, the EAV triplet models of the ontology class represented about 91.4% of the sentiment phrases included in the sentiment dictionary.
+In the sentiment analyses, “academic stresses” and “suicide” contributed negatively to the sentiment of adolescent depression.
+CONCLUSIONS: The ontology and terminology developed in this study provide a semantic foundation for analyzing social media data on adolescent depression.
+To be useful in social media data analysis, the ontology, especially the terminology, needs to be updated constantly to reflect rapidly changing terms used by adolescents in social media postings.
+In addition, more attributes and value sets reflecting depression-related sentiments should be added to the ontology.
+Cassiae semen (Leguminosae), a well-known traditional Chinese medicine, has been used for a number of centuries in areas of Southeast Asia, including Korea, Japan and China.
+The present review aims to provide updated and comprehensive information, on the botany, phytochemistry and pharmacology of Cassiae semen.
+The available information on Cassiae semen was collected using several different resources, including classic books on Chinese herbal medicine and a number of scientific databases, including the China Academic Journals full-text database, PubMed, SciFinder, the Web of Science and Science Direct.
+To date >70 chemical compounds have been isolated from Cassiae semen, and the major components have been determined to be anthraquinones, naphthopyrones and volatile oil.
+The crude extracts and pure compounds of Cassiae semen have been used as effective agents in preclinical and clinical practice due to their beneficial activities, including antihyperlipidemic, antidiabetic, neuroprotective, hepatoprotective, antibacterial, antioxidant and hypotensive activities.
+With the body of reported data, it has been suggested that Cassiae semen has convincing medicinal potential.
+However, the pharmacological mechanisms of the main bioactive compounds and the association between structure and activity require further investigation.
+The avian origin influenza A virus (IAV) H7N9 has caused a considerable number of human infections associated with high rates of death since its emergence in 2013.
+As a vital component of the host innate immune system, the nucleotide-binding domain leucine-rich repeat containing receptor, pyrin domain containing 3 (NLRP3) inflammasome plays a critical role against H1N1 viral infection.
+However, the function of NLRP3 inflammasome in host immunological responses to the lethal H7N9 virus is still obscure.
+Here, we demonstrated that mice deficient for NLRP3 inflammasome components, including NLRP3, caspase-1, and Apoptosis-associated speck-like protein containing a CARD (ASC), were less susceptible to H7N9 viral challenge than wild type (WT) controls.
+Inflammasome deficiency in these animals led to significantly milder mortality and less pulmonary inflammation compared with WT mice.
+Thus, our study reveals that the NLRP3 inflammasome is deleterious for the host during H7N9 infection in mice, which is due to an overwhelming inflammatory response via caspase-1 activation and associated IL-1 signal.
+Therefore, fine-tuning the activity of NLRP3 inflammasome or IL-1 signaling may be beneficial for the host to control H7N9 associated lethal pathogenesis.
+In-vitro metabolite and drug detection rely on designed materials-based analytical platforms, which are universally used in biomedical research and clinical practice.
+However, metabolic analysis in bio-samples needs tedious sample preparation, due to the sample complexity and low molecular abundance.
+We identified patients with postoperative brain infection through daily monitoring and glucose quantitation in cerebrospinal fluid.
+We measured drug distribution in blood and cerebrospinal fluid systems and validated the function of blood-brain/cerebrospinal fluid-barriers for pharmacokinetics.
+Our work sheds light on the design of materials for advanced metabolic analysis and precision diagnostics.
+The spread of many respiratory infections is determined by contact patterns between infectious and susceptible individuals in the population.
+There are no published data for quantifying social contact patterns relevant to the spread of respiratory infectious diseases in Hong Kong which is a hotspot for emerging infectious diseases due to its high population density and connectivity in the air transportation network.
+We adopted a commonly used diary-based design to conduct a social contact survey in Hong Kong in 2015/16 using both paper and online questionnaires.
+Participants using paper questionnaires reported more contacts and longer contact duration than those using online questionnaires.
+Participants reported 13 person-hours of contact and 8 contacts per day on average, which decreased over age but increased with household size, years of education and income level.
+Prolonged and frequent contacts, and contacts at home, school and work were more likely to involve physical contacts.
+We evaluated the characteristics of social contact patterns relevant to the spread of respiratory infectious diseases in Hong Kong.
+Our findings could help to improve the design of future social contact surveys, parameterize transmission models of respiratory infectious diseases, and inform intervention strategies based on model outputs.
+This study aims to assess the efficacy of HA330 resin-directed hemoadsorption (HA) on endotoxin-induced porcine acute respiratory distress syndrome (ARDS) model.
+METHODS: Twenty-four Chinese domestic pigs were allocated into saline group receiving intravenous infusion of saline (N = 6) and endotoxin group receiving intravenous infusion of LPS (N = 18).
+When ALI model was initially diagnosed, six pigs in the LPS and saline group were killed for BALF and histopathological analysis.
+The remaining 12 pigs in LPS group received 3-h HA (N = 6) or HA-sham (N = 6) treatment, respectively.
+Variables on hemodynamics, blood gases and lung mechanics were recorded at a series of time points.
+HA also partially improved the barrier permeability and reduced lung edema and inflammation/injury induced by LPS infusion.
+Proteomic analysis showed the differentially expressed proteins between HA- and HA-sham-treated groups mostly belonged to the categories of acute inflammation/immune response, and proteolysis.
+CONCLUSIONS: Hemoadsorption improved ARDS possibly by blunting the cytokine storm and by restoring homeostasis of the disordered proteome milieu in the exudative phase.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13613-017-0287-0) contains supplementary material, which is available to authorized users.
+Severe malaria has a poor prognosis with a morbidity rate of 80% in tropical areas.
+The early parasite detection is one of the effective means to prevent severe malaria of which specific treatment strategies are limited.
+Many clinical characteristics and laboratory testings have been used for the early diagnosis and prediction of severe disease.
+MicroRNAs (miRNAs) were demonstrated as useful biomarkers in many diseases such as malignant diseases and cardiovascular diseases.
+Recently it was found that plasma miR-451 and miR-16 were downregulated in malaria infection at parasitic stages or with multi-organ failure involvement.
+MiR-125b, -27a, -23a, -150, 17–92 and -24 are deregulated in malaria patients with multiple organ failures.
+Here, the current findings of miRNAs were reviewed in relation to clinical severity of malaria infection and emphasized that miRNAs are potential biomarkers for severe malaria infection.
+Venezuelan equine encephalitis (VEE) complex alphaviruses are important re-emerging arboviruses that cause life-threatening disease in equids during epizootics as well as spillover human infections.
+We conducted a comprehensive analysis of VEE complex alphaviruses by sequencing the genomes of 94 strains and performing phylogenetic analyses of 130 isolates using complete open reading frames for the nonstructural and structural polyproteins.
+Our analyses confirmed purifying selection as a major mechanism influencing the evolution of these viruses as well as a confounding factor in molecular clock dating of ancestors.
+Times to most recent common ancestors (tMRCAs) could be robustly estimated only for the more recently diverged subtypes; the tMRCA of the ID/IAB/IC/II and IE clades of VEE virus (VEEV) were estimated at ca.
+Evolution of the IE subtype has been characterized by a significant evolutionary shift from the rest of the VEEV complex, with an increase in structural protein substitutions that are unique to this group, possibly reflecting adaptation to its unique enzootic mosquito vector Culex (Melanoconion) taeniopus.
+Our inferred tree topologies suggest that VEEV is maintained primarily in situ, with only occasional spread to neighboring countries, probably reflecting the limited mobility of rodent hosts and mosquito vectors.
+Lethal mutagenesis is a broad-spectrum antiviral strategy that employs mutagenic nucleoside analogs to exploit the high mutation rate and low mutational tolerance of many RNA viruses.
+Studies of mutagen-resistant viruses have identified determinants of replicative fidelity and the importance of mutation rate to viral population dynamics.
+We have previously demonstrated the effective lethal mutagenesis of influenza A virus using three nucleoside analogs as well as the virus’s high genetic barrier to mutagen resistance.
+We find that PB1 T123A has higher replicative fitness than the wild type, PR8, and maintains its level of genome production during 5-fluorouracil (2,4-dihydroxy-5-fluoropyrimidine) treatment.
+Surprisingly, this mutagen-resistant variant also has an increased baseline rate of C-to-U and G-to-A mutations.
+A second drug-selected mutation, PA T97I, interacts epistatically with PB1 T123A to mediate high-level mutagen resistance, predominantly by limiting the inhibitory effect of nucleosides on polymerase activity.
+Consistent with the importance of epistatic interactions in the influenza virus polymerase, our data suggest that nucleoside analog resistance and replication fidelity are strain dependent.
+Two previously identified ribavirin {1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-1H-1,2,4-triazole-3-carboxamide} resistance mutations, PB1 V43I and PB1 D27N, do not confer drug resistance in the PR8 background, and the PR8-PB1 V43I polymerase exhibits a normal baseline mutation rate.
+Our results highlight the genetic complexity of the influenza A virus polymerase and demonstrate that increased replicative capacity is a mechanism by which an RNA virus can counter the negative effects of elevated mutation rates.
+This standing genetic diversity gives them the potential to adapt rapidly, evolve resistance to antiviral therapeutics, and evade immune responses.
+Viral mutants with altered mutation rates or mutational tolerance have provided insights into how genetic diversity arises and how it affects the behavior of RNA viruses.
+To this end, we identified variants within the polymerase complex of influenza virus that are able to tolerate drug-mediated increases in viral mutation rates.
+We find that drug resistance is highly dependent on interactions among mutations in the polymerase complex.
+In contrast to other viruses, influenza virus counters the effect of higher mutation rates primarily by maintaining high levels of genome replication.
+These findings suggest the importance of maintaining large population sizes for viruses with high mutation rates and show that multiple proteins can affect both mutation rate and genome synthesis.
+A scenario tree model was developed to propose efficient bovine viral diarrhea (BVD) control measures.
+The model used field data in eastern Hokkaido where the risk of BVDV infection in cattle has been reduced by an eradication program including mass vaccination, individual tests prior to communal pasture grazing, herd screening tests using bulk milk, and outbreak investigations of newly infected herds.
+In each simulation, the numbers of cattle infected persistently and transiently with BVDV detected by clinical manifestations and diagnosis tests and of missed by all of the diagnosis tests were calculated, and the numbers were used as indicators to be compared for the efficacy of the control measures.
+The model outputs indicated that the adoption of mass vaccination decreased the number of missed BVD cattle, although it did not increase the number of detected BVD cattle.
+Under implementation of mass vaccination, the efficacy of individual tests on selected 20% of the young and adult cattle was equal to that of the herd screening test performed in all the herds.
+When the virus prevalence or the number of sensitive animals becomes low, the efficacy of herd screening test was superior to one of individual tests.
+Considering the model outputs together, the scenario tree model developed in the present study was useful to compare the efficacy of the control measures for BVD.
+Yellow fever virus (YFV) is an arthropod-borne flavivirus, infecting ~200,000 people worldwide annually and causing about 30,000 deaths.
+The live attenuated vaccine strain, YFV-17D, has significantly contributed in controlling the global burden of yellow fever worldwide.
+Type I interferon (IFN-α/β) signaling and type II interferon (IFN-γ) signaling have been shown to be mutually supportive in controlling YFV-17D infection despite distinct mechanisms of action in viral infection.
+Here, we report that while wild-type (WT) and IFN-λ receptor knockout (λR(−/−)) mice were largely resistant to YFV-17D, deficiency in type I IFN signaling resulted in robust infection.
+Although IFN-α/β receptor knockout (α/βR(−/−)) mice survived the infection, mice with combined deficiencies in both type I signaling and type III IFN signaling were hypersusceptible to YFV-17D and succumbed to the infection.
+α/βR(−/−) λR(−/−) mice also exhibited distinct changes in the frequencies of multiple immune cell lineages, impaired T-cell activation, and severe perturbation of the proinflammatory cytokine balance.
+Taken together, our data highlight that type III IFN has critical immunomodulatory and neuroprotective functions that prevent viral neuroinvasion during active YFV-17D replication.
+Type III IFN thus likely represents a safeguard mechanism crucial for controlling YFV-17D infection and contributing to shaping vaccine immunogenicity.
+Modified Vaccinia virus Ankara (MVA) is a promising vaccine vector with an excellent safety profile.
+However, despite extensive pre-clinical and clinical testing, surprisingly little is known about the cellular tropism of MVA, especially in relevant animal species.
+Here, we performed in vitro, ex vivo and in vivo experiments with recombinant MVA expressing green fluorescent protein (rMVA-GFP).
+In both human peripheral blood mononuclear cells and mouse lung explants, rMVA-GFP predominantly infected antigen presenting cells.
+Subsequent in vivo experiments performed in mice, ferrets and non-human primates indicated that preferential targeting of dendritic cells and alveolar macrophages was observed after respiratory administration, although subtle differences were observed between the respective animal species.
+Following intramuscular injection, rMVA-GFP was detected in interdigitating cells between myocytes, but also in myocytes themselves.
+These data are important in advancing our understanding of the basis for the immunogenicity of MVA-based vaccines and aid rational vaccine design and delivery strategies.
+Although targeting radio-resistant cancer cells is important for improving the treatmental efficiency, the signaling pathway- and therapeutic strategy-related to laryngeal carcinoma still require further study.
+Galangin is an active pharmacological ingredient, isolated from propolis and Alpinia officinarum Hance, and has been reported to have anticancer and anti-oxidative properties through regulation of cell cycle, resulting in angiogenesis, apoptosis, invasion and migration without triggering any toxicity in normal cells.
+PI3K/AKT and p38 are important signaling pathways to modulate cancer cell apoptosis and proliferation through caspase-3, NF-κB and mTOR signal pathways.
+Also, flow cytometry, immunohistochemical and western blot analysis indicated that cell apoptosis was induced for galangin administration, promoting caspase-3 expression through regulating PI3K/AKT/NF-κB.
+Additionally, mTOR activation regulated by PI3K/AKT was reduced by galangin, suppressing cancer cell transcription and proliferation.
+Our data also indicated that the tumor volume and weight in nude mice were reduced for galangin use in vivo accompanied by Ki-67 decrease and TUNEL increase in tumor tissues.
+Together, our data indicated that galangin has a potential role in suppressing human laryngeal cancer via inhibiting tumor cell proliferation, activating apoptosis and autophagy, which were regulated by p38 and AKT/NF-κB/mTOR pathways, providing a therapeutic strategy for human laryngeal cancer treatment.
+Severe pulmonary infection or vigorous cyclic deformation of the alveolar epithelial type I (AT I) cells by mechanical ventilation leads to massive extracellular ATP release.
+High levels of extracellular ATP saturate the ATP hydrolysis enzymes CD39 and CD73 resulting in persistent high ATP levels despite the conversion to adenosine.
+Above a certain level, extracellular ATP molecules act as danger-associated molecular patterns (DAMPs) and activate the pro-inflammatory response of the innate immunity through purinergic receptors on the surface of the immune cells.
+This results in lung tissue inflammation, capillary leakage, interstitial and alveolar oedema and lung injury reducing the production of surfactant by the damaged AT II cells and deactivating the surfactant function by the concomitant extravasated serum proteins through capillary leakage followed by a substantial increase in alveolar surface tension and alveolar collapse.
+The resulting inhomogeneous ventilation of the lungs is an important mechanism in the development of ventilation-induced lung injury.
+The high levels of extracellular ATP and the upregulation of ecto-enzymes and soluble enzymes that hydrolyse ATP to adenosine (CD39 and CD73) increase the extracellular adenosine levels that inhibit the innate and adaptive immune responses rendering the host susceptible to infection by invading microorganisms.
+Moreover, high levels of extracellular adenosine increase the expression, the production and the activation of pro-fibrotic proteins (such as TGF-β, α-SMA, etc.)
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11302-017-9564-5) contains supplementary material, which is available to authorized users.
+OBJECTIVES: To critically appraise the efficacy and safety of Kangfuxinye enema combined with mesalamine for the ulcerative colitis (UC) patients and in addition to grade the quality of evidence by using the GRADE (grading of recommendations, assessment, development, and evaluation) approach.
+METHODS: A literature search was performed in the Cochrane Library, MEDLINE, EMBASE, CBM, CNKI, VIP, and WanFang Databases.
+We found significant benefits of Kangfuxinye combined with mesalamine against mesalamine alone in improving response rate as well as reducing the recurrence rate and inflammation rate; meanwhile, the increase of the adverse events rate was not observed.
+Additionally, GRADE results indicated that the quality of evidence regarding the above 6 outcomes was rated from very low to moderate quality.
+CONCLUSIONS: Although Kangfuxinye enema seems effective and safe for treating UC patients in this systematic review, Kangfuxinye enema combined with mesalamine was weakly recommended due to very low to moderate quality of available evidence by the GRADE approach.
+To facilitate the next generation of environmental material for white light emitting diodes, the discovery of natural luminesce is essential.
+In this study, we disclose a rare-earth free and yellow-emission phosphor, Phellodendron, which could be both excited by near ultraviolet light and blue light.
+The emission wavelength, full width at half maximum and CIE coordinates of extracted Phellodendron are 540 nm, 120 nm and (0.41, 0.55), respectively.
+The corresponding luminescent properties of Phellodendron are characterized by PL, PLE, reflection spectra, FITR and decay lifetime.
+Surprising thing is luminous intensity of Phellodendron phosphors excited at 380 nm was stronger than YAG:Ce phosphor by more than 139%.
+In addition, we firstly introduce the yellow phosphor in white LED fabrication by combining blue chip and Y(3)Al(5)O(12):Ce(3+) phosphor, to create warm white.
+Asthmatic patients present more rapid progression of respiratory distress after A(H1N1)pdm09 influenza infection than after seasonal infection.
+Here, we sought to clarify the pathophysiology of early deterioration in asthmatic patients after A(H1N1)pdm09 infection.
+Cytokine levels and virus titres in bronchoalveolar lavage fluid from mice with and without asthma after A(H1N1)pdm09 or seasonal H1N1 infection were examined.
+In asthma/A(H1N1)pdm09 mice, IL-6 and TNF-α levels peaked at 3 days post-infection and were higher than those in all other groups.
+IFN-γ levels in asthma/A(H1N1)pdm09 mice at 3 days post-infection were higher than in all other mice at any time point, whereas at 7 days post-infection, the levels were lowest in asthma/A(H1N1)pdm09 mice.
+Virus titres in asthma/A(H1N1)pdm09 mice were highest at 3 days post-infection, and decreased by 7 days post-infection, although the levels at this time point were still higher than that in any other group.
+Histopathological examination showed more inflammatory cell infiltration and lung tissue destruction in the asthma/A(H1N1)pdm09 group than in any other group.
+The distinct cytokine profiles in A(H1N1)pdm09-infected asthmatic mice indicated excessive inflammation and virus replication within a few days after infection.
+Thus, bronchial asthma could be a more exacerbating factor for pandemic influenza infection than for seasonal influenza infection.
+In addition to mediating regulation of endogenous gene expression, RNA interference (RNAi) in plants and invertebrates plays a crucial role in defense against viruses via virus-specific siRNAs.
+Different studies have demonstrated that the functional diversity of RNAi in animals is linked to the diversification of the Argonaute superfamily, central components of RISCs (RNA induced silencing complexes).
+Yet, by performing phylogenetic analyses and determining the selective evolutionary pressure in the metazoan Argonaute superfamily, we provide evidence for the existence of three conserved Argonaute lineages between basal metazoans and protostomes, namely siRNA-class AGO, miRNA-class AGO and PIWI Argonautes.
+In addition, it shown that the siRNA-class AGO lineage is characterized by high rates of molecular evolution, suggesting a role in the arms race with viruses, while the miRNA-class AGOs display strong sequence conservation.
+Interestingly, we also demonstrate that vertebrates lack siRNA-class AGO proteins and that vertebrate AGOs display low rates of molecular evolution.
+In this way, we provide supportive evidence for the loss of the antiviral siRNA-class AGO group in vertebrates and discuss the consequence hereof on antiviral immunity and the use of RNAi as a loss of function tool in these animals.
+The majority of human emerging infectious diseases (EIDs) are zoonotic, with viruses originating in wild mammals of particular concern (e.g.
+Understanding patterns of viral diversity in wildlife and determinants of successful cross-species transmission, or spillover, are therefore key goals for pandemic surveillance programs(4).
+However, few analytical tools exist to identify which host species likely harbor the next human virus, or which viruses can cross species boundaries(5–7).
+Here we conduct the most comprehensive analysis yet of mammalian host-virus relationships and show that both the total number of viruses that infect a given species, and the proportion likely to be zoonotic are predictable.
+After controlling for research effort, the proportion of zoonotic viruses per species is predicted by phylogenetic relatedness to humans, host taxonomy, and human population within a species range – which may reflect human-wildlife contact.
+We demonstrate for the first time that bats harbor a significantly higher proportion of zoonotic viruses than all other mammalian orders.
+We identify the taxa and geographic regions with the largest estimated number of ‘missing viruses’ and ‘missing zoonoses’ and therefore of highest value for future surveillance.
+We then show that phylogenetic host breadth and other viral traits are significant predictors of zoonotic potential, providing a novel framework to assess if a newly discovered mammalian virus could infect people.
+Most often these rates must be estimated from longitudinal field data, which are costly and time-consuming to conduct.
+Consequently, measures to reduce cost like increased sampling intervals or subsampling of the population are implemented.
+To assess the impact of such measures we implement two different SIS models to simulate disease transmission: A simple closed population model and a realistic dairy herd including population dynamics.
+We use data from the two simulation models and vary the sampling intervals and the size of the population sampled.
+We devise two new methods to determine transmission rate, and compare these to the frequently used Poisson regression method in both epidemic and endemic situations.
+For most tested scenarios these new methods perform similar or better than Poisson regression, especially in the case of long sampling intervals.
+We conclude that transmission rate estimates are easily biased, which is important to take into account when using these rates in simulation models.
+Much of the fear and uncertainty around Zika epidemics stem from potential association between Zika virus (ZIKV) complications on infected pregnant women and risk of their babies being born with microcephaly and other neurological abnormalities.
+Worries of these unknowns necessitate the need for effective and efficient psychosocial programs and medical-legal strategies to alleviate and mitigate ZIKV related burdens.
+In this light, local and global efforts in maintaining fundamental health principles of moral, medical and legal decision-making policies, and interventions to preserve and promote individual and collectiveHuman Rights, autonomy, protection of the most vulnerable, equity, dignity, integrity and beneficence that should not be confused and relegated by compassionate humanitarian assistance and support.
+This paper explores the potential medical and ethical-legal implications of ZIKV epidemics emergency response packages and strategies alongside optimizing reproductive and mental health policies, programs and best practice measures.
+Further long-term cross-borders operational research is required in elucidating Zika-related population-based epidemiology, ethical-medical and societal implications in guiding evidence-based local and global ZIKV maternal-child health complications related approaches and interventions.
+Core programs and interventions including future Zika safe and effective vaccines for global Zika immunization program in most vulnerable and affected countries and worldwide should be prioritized.
+BACKGROUND: The FOLFOX regimen, i.e., folinic acid (FOL), fluorouracil (F) and oxaliplatin (OX), is a drug cocktail that is used to treat gastric and colorectal cancers.
+Despite the concomitant improvements in response rate, duration of response and patient survival, reports of serious toxic pulmonary side effects have progressively emerged.
+CASE PRESENTATION: We describe a patient who was treated with FOLFOX as an adjuvant to a rectosigmoidal resection of a rectosigmoidal carcinoma and who developed respiratory insufficiency requiring mechanical ventilation.
+Computed tomography (CT) imaging and open lung biopsy findings were compatible with interstitial pneumonia (IP).
+We performed a systematic literature search and reviewed all 45 reported cases of FOLFOX-related lung toxicity and/or pulmonary fibrosis for their clinical characteristics and their outcomes related to therapy.
+CONCLUSIONS: We found that for the 45 cases with available data, the median age was 70 years, and the male–female ratio was 3.5: 1.
+In the patients exhibiting only mild respiratory symptoms, discontinuation of the culprit drug (oxaliplatin) resulted in a 100% regression of the symptoms.
+However the prognosis of the respiratory insufficient patient proved to be grim: death occurred in 76.9% of the cases despite conventional treatment with corticosteroids.
+We therefore urge oncologists and critical care specialists not to limit their interventions to the discontinuation of chemotherapy, artificial ventilation, corticosteroids and glutathione replenishment and to consider the gradual introduction of additional immune-modulating agents whenever life-threatening respiratory symptoms in oxaliplatin-treated patients do not subside; all the more so considering the fact that our analysis showed that every patient who survived intubation and mechanical ventilation experienced a full clinical recovery.
+This study compares detection rates, genotype distribution and viral loads of different enteric viral agents in HIV-1 seropositive (n = 200) and HIV-1 seronegative (n = 125) children hospitalized with DD in Rio de Janeiro, Brazil.
+Except for group A rotavirus (RVA), which were detected through enzyme immunoassay, the other enteric viruses (norovirus [NoV], astrovirus [HAstV], adenovirus [HAdV] and bocavirus [HBoV]) were detected through PCR or RT-PCR.
+Infections with NoV (19% vs. 9.6%; p<0.001), HBoV (14% vs. 7.2%; p = 0.042) and HAdV (30.5% vs. 14.4%; p<0.001) were significantly more frequent among HIV-1 seropositive children.
+Similarly, frequency of infection with HAstV was lower among HIV-1 seropositive children (5.5% vs. 12.8%; p = 0.018).
+Among HIV-1 seropositive children 33 (16.5%) had co-infections, including three enteric viruses, such as NoV, HBoV and HAdV (n = 2) and NoV, HAstV and HAdV (n = 2).
+The frequency of infection with more than one virus was 17 (13.6%) in the HIV-1 negative group, triple infection (NoV + HAstV + HBoV) being observed in only one patient.
+The median viral load of HAstV in feces was significantly higher among HIV-1 positive children compared to HIV-1 negative children.
+Concerning children infected with RVA, NoV, HBoV and HAdV, no statistically significant differences were observed in the medians of viral loads in feces, comparing HIV-1 seropositive and HIV-1 seronegative children.
+Similar detection rates were observed for RVA, HAstV and HAdV, whilst NoV and HBoV were significantly more prevalent among children with CD4(+) T lymphocyte count below 200 cells/mm(3).
+Enteric viruses should be considered an important cause of DD in HIV-1 seropositive children, along with pathogens more classically associated with intestinal infections in immunocompromised hosts.
+We report the full-length sequence of two chicken source influenza A (H7N9) viruses found in Guangdong live poultry market (LPM) during the most recent wave of human infections (from October 2016 to the present time).
+These viruses carry insertion of poly-basic amino acids (KGKRTAR/G) at the protease cleavage site of the HA protein, which were previously found in the highly pathogenic (HP) human influenza A (H7N9) [IAV(H7N9)] strains.
+Phylogenetic analysis of these two novel avian influenza viruses (AIVs) suggested that their genomes reassorted between the Yangtze River Delta (YRD) and Pearl River Delta (PRD) clades.
+Collectively, our results suggest that IAV(H7N9) viruses evolve in chickens through antigenic drift to include a signature HP sequence in the HA gene, which highlights challenges in risk assessment and public health management of IAV(H7N9) infections at the human-animal interface.
+H1N1 swine influenza viruses (SIV) are prevalent in pigs globally, and occasionally emerge in humans, which raises concern about their pandemic threats.
+To stimulate hemagglutination (HA) of A/Swine/Guangdong/LM/2004 (H1N1) (SW/GD/04) antibody response, eukaryotic expression plasmid pCI-neo-HA was constructed and used as an immunogen to prepare monoclonal antibodies (mAbs).
+Five mAbs (designed 8C4, 8C6, 9D6, 8A4, and 8B1) against HA protein were obtained and characterized.
+Western blot showed that the 70 kDa HA protein could be detected by all mAbs in MDCK cells infected with SW/GD/04.
+Three mAbs—8C4, 8C6, and 9D6—have hemagglutination inhibition (HI) and neutralization test (NT) activities, and 8C6 induces the highest HI and NT titers.
+The protection efficacy of 8C6 was investigated in BALB/c mice challenged with homologous or heterologous strains of the H1 subtype SIV.
+The results indicate that mAb 8C6 protected the mice from viral infections, especially the homologous strain, which was clearly demonstrated by the body weight changes and reduction of viral load.
+Thus, our findings document for the first time that mAb 8C6 might be of potential therapeutic value for H1 subtype SIV infection.
+The biggest challenge for accurate diagnosis of viral infectious disease is the high genetic variability of involved viruses, which affects amplification efficiency and results in low sensitivity and narrow spectrum.
+Fluorescent signal was generated from the 3′–5′ hydrolysis of HFman probe by HF DNA polymerase before elongation initiation.
+Mismatches between probe/primer and template have less influence on the amplification efficiency of the new method.
+The new qPCR exhibited higher sensitivity and better adaptability to sequence variable templates than the conventional TaqMan probe based-qPCR in quantification of HIV-1 viral load.
+Further comparison with COBAS TaqMan HIV-1 Test (v2.0) showed a good correlation coefficient (R(2) = 0.79) between both methods in quantification of HIV-1 viral load among 21 clinical samples.
+The characteristics of tolerance to variable templates and one probe-one primer system imply that the probe/primer design for the new method will be easier and more flexible than the conventional method for highly heterogeneous viruses.
+Therefore, the HF DNA polymerase-mediated qPCR method is a simple, sensitive and promising approach for the development of diagnostics for viral infectious diseases.
+IFN-λ4, a recent member of this family is expressed only in a subset of the population due to a frameshift-causing DNA polymorphism rs368234815.
+We examined the association of this polymorphism with atopy (aeroallergen sensitization) and asthma in a Polish hospital-based case-control cohort comprising of well-characterized adult asthmatics (n = 326) and healthy controls (n = 111).
+In the combined cohort, we saw no association of the polymorphism with asthma and/or atopy.
+However, the IFN-λ4-generating ΔG allele protected older asthmatic women (>50 yr of age) from atopic sensitization.
+Further, ΔG allele significantly associated with features of less-severe asthma including bronchodilator response and corticosteroid usage in older women in this Polish cohort.
+We tested the association of related IFNL locus polymorphisms (rs12979860 and rs8099917) with atopy, allergic rhinitis and presence/absence of asthma in three population-based cohorts from Europe, but saw no significant association of the polymorphisms with any of the phenotypes in older women.
+The polymorphisms associated marginally with lower occurrence of asthma in men/older men after meta-analysis of data from all cohorts.
+Current studies of human gut microbiome usually do not consider the special functional role of transient microbiota, although some of its members remain in the host for a long time and produce broad spectrum of biologically active substances.
+Getting into the gastrointestinal tract (GIT) with food, water and probiotic preparations, two representatives of Bacilli class, genera Bacillus and Lactobacillus, colonize epithelium blurring the boundaries between resident and transient microbiota.
+Despite their minor proportion in the microbiome composition, these bacteria can significantly affect both the intestinal microbiota and the entire body thanks to a wide range of secreted compounds.
+This review aims to characterize the Bacillus and Lactobacillus in GIT, as well as the functional roles of the components released by these members of microbial intestinal community.
+Complex of their secreted compounds is referred by us as the “bacillary secretome.” The composition of the bacillary secretome, its biological effects in GIT and role in counteraction to infectious diseases and oncological pathologies in human organism is the subject of the review.
+Grouper aquaculture around Asia is impacted by the nervous necrosis virus (NNV) and, in response, host resistance to this infection is being considered as a trait for selection.
+However efficient selection may be confounded if there are different genetic strains of NNV within and between regions and over years.
+nucleotide positions that discriminate among strains) to assess whether published and new NNV RNA2 cds sequences show genetic differentiation over geography, host species and years.
+Interestingly, most of the geographic defining “characteristic attributes” were in codon position three, and not translated into differences for the protein capsid (i.e.
+they were synonymous variations), suggesting that while NNV strains were geographically isolated and had diverged in different regions for RNA sequences, selection had largely conserved the protein sequences among regions.
+The apparent selection constraint on the capsid protein may mitigate the risk that despite geographic subdivision, NNV strain variability will confound genetic selection for host resistance.
+The existence of regional Asian NNV strains may suggest that hatcheries are at risk from NNV not only from imported material but also from endemic reservoirs.
+BACKGROUND: The parasitic disease malaria remains a major global public health concern and no truly effective vaccine exists.
+One approach to the development of a malaria vaccine is to target the asexual blood stage that results in clinical symptoms.
+Multiple studies have demonstrated that antigens are more immunogenic and are better correlated with protection when presented on particulate delivery systems.
+One such particulate delivery system is the self-assembling protein nanoparticle (SAPN) that relies on coiled-coil domains of proteins to form stable nanoparticles.
+In the past we have used de novo designed amino acid domains to drive the formation of the coiled-coil scaffolds which present the antigenic epitopes on the particle surface.
+RESULTS: Here we use naturally occurring domains found in the tex1 protein to form the coiled-coil scaffolding of the nanoparticle.
+Thus, by engineering P27A and a new extended form of the coiled-coil domain P27 onto the N and C terminus of the SAPN protein monomer we have developed a particulate delivery system that effectively displays both antigens on a single particle that uses malaria tex1 sequences to form the nanoparticle scaffold.
+These particles are immunogenic in a murine model and induce immune responses similar to the ones observed in seropositive individuals in malaria endemic regions.
+CONCLUSIONS: We demonstrate that our P27/P27A-SAPNs induce an immune response akin to the one in seropositive individuals in Burkina Faso.
+Since P27 is highly conserved among different Plasmodium species, these novel SAPNs may even provide cross-protection between Plasmodium falciparum and Plasmodium vivax the two major human malaria pathogens.
+As the SAPNs are also easy to manufacture and store they can be delivered to the population in need without complication thus providing a low cost malaria vaccine.
+Although much is known about its bone-restricted gene expression pattern and protein biochemical and topological features, little information is available for BRIL physiological function.
+Two autosomal dominant forms of osteogenesis imperfecta (OI) are caused by distinct, but recurrent mutations in the BRIL gene.
+Yet, the underlying mechanisms by which those mutations lead to OI are still poorly understood.
+A previous report indicated that BRIL knockout (KO) mice had bone deformities, shortened long bones, and reproductive problems.
+Here we generated and systematically analyzed the skeletal phenotype of a new global Bril KO/LacZ knockin mouse model.
+The skeletal phenotype of KO and WT littermates was assessed at embryonic (E13.5 to E18.5) and postnatal (2 days, 3 weeks, 3 months and 8 months) time-points.
+Embryos from E13.5 through to E18.5 showed significant X-Gal staining in all skeletal elements without any apparent patterning anomalies.
+Although bone deformities were never observed at any postnatal ages, minor and transient differences were noted in terms of bone length and static uCT parameters, but not systematically across all ages and genders.
+These changes, however, were not accompanied by significant alteration in bone material properties as assessed by a 3-point bending test.
+In addition, no changes were detected in circulating serum markers of bone turnover (P1NP, CTX-I, and osteocalcin).
+Further, when mice were challenged with a surgically-induced fracture in tibia, bones repaired equally well in the KO mice as compared to WT.
+Finally, we showed that BRIL C-terminus is not a bona fide binding site for calcium.
+In conclusion, our in depth analysis suggest that skeletal patterning, bone mass accrual and remodeling in mice proceeded independent of BRIL.
+Ebola haemorrhagic fever causes deadly disease in humans and non-human primates resulting from infection with the Ebola virus (EBOV) genus of the family Filoviridae.
+However, the mechanisms of EBOV lifecycle in host cells, including viral entry, membrane fusion, RNP formation, GP-tetherin interaction, and VP40-inner leaflet association remain poorly understood.
+This review describes the biological functions of EBOV proteins and their roles in the lifecycle, summarizes the factors related to EBOV proteins or RNA expression throughout the different phases, and reviews advances with regards to the molecular events and mechanisms of the EBOV lifecycle.
+Furthermore, the review outlines the aspects remain unclear that urgently need to be solved in future research.
+Bacterial pneumonia can induce uncontrolled and massive neutrophil recruitment ultimately leading to acute respiratory distress syndrome and epithelium damage.
+In this study, we aimed to evaluate the role of interleukin-22 and its soluble receptor IL-22BP in an acute Pseudomonas aeruginosa pneumonia model in mice.
+Using an antibody-based approach, we demonstrated that IL-22 neutralisation led to increased susceptibility to infection and to lung damage correlated with an increase in neutrophil accumulation in the lungs.
+On the contrary, rIL-22 administration or IL-22BP neutralisation led to a decrease in mouse susceptibility and lung damage associated with a decrease in neutrophil accumulation.
+This study demonstrated that the IL-22/IL-22BP system plays a major role during Pseudomonas aeruginosa pneumonia by moderating neutrophil accumulation in the lungs that ultimately leads to epithelium protection.
+Being a neurodegenerative disorder, Alzheimer's disease (AD) is the one of the most terrible diseases.
+Acetylcholinesterase inhibitors (AChEI) are considered to be one of the effective drugs for the treatment of AD.
+The aim of this study is to find a novel potential AChEI as a drug for the treatment of AD.
+In this study, instead of using the synthetic compounds, we used those extracted from plants to investigate the interaction between floribundiquinone B (FB) and AChE by means of both the experimental approach such as fluorescence spectra, ultraviolet-visible (UV-vis) absorption spectrometry, circular dichroism (CD) and the theoretical approaches such as molecular docking.
+The findings reported here have provided many useful clues and hints for designing more effective and less toxic drugs against Alzheimer's disease.
+BACKGROUND: Individual-based models (IBMs) are useful to simulate events subject to stochasticity and/or heterogeneity, and have become well established to model the potential (re)emergence of pathogens (e.g., pandemic influenza, bioterrorism).
+Individual heterogeneity at the host and pathogen level is increasingly documented to influence transmission of endemic diseases and it is well understood that the final stages of elimination strategies for vaccine-preventable childhood diseases (e.g., polio, measles) are subject to stochasticity.
+We review a decade of IBM publications aiming to obtain insights in their advantages, pitfalls and rationale for use and to make recommendations facilitating knowledge transfer within and across disciplines.
+METHODS: We systematically identified publications in Web of Science and PubMed from 2006-2015 based on title/abstract/keywords screening (and full-text if necessary) to retrieve topics, modeling purposes and general specifications.
+We extracted detailed modeling features from papers on established vaccine-preventable childhood diseases based on full-text screening.
+RESULTS: We identified 698 papers, which applied an IBM for infectious disease transmission, and listed these in a reference database, describing their general characteristics.
+The diversity of disease-topics and overall publication frequency have increased over time (38 to 115 annual publications from 2006 to 2015).
+The inclusion of intervention strategies (8 to 52) and economic consequences (1 to 20) are increasing, to the detriment of purely theoretical explorations.
+We retrieved 24 studies on a vaccine-preventable childhood disease (covering 7 different diseases), with publication frequency increasing from the first such study published in 2008.
+IBMs have been useful to explore heterogeneous between- and within-host interactions, but combined applications are still sparse.
+CONCLUSIONS: IBMs are suited to combine heterogeneous within- and between-host interactions, which offers many opportunities, especially to analyze targeted interventions for endemic infections.
+Using (existing) conventions and reporting protocols would stimulate cross-fertilization between research groups and fields, and ultimately policy making in decades to come.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-017-2699-8) contains supplementary material, which is available to authorized users.
+Viral cell tropism is a key determinant of viral pathogenesis, but the tropism of RV is currently poorly understood.
+We analyzed various human cell lines and determined that RV only establishes an infection efficiently in particular non-immune cell lines.
+To assess the susceptibility of individual cell lines, we generated a pseudotype vesicular stomatitis virus bearing RV envelope proteins (VSV-RV/CE2E1).
+VSV-RV/CE2E1 entered cells in an RV envelope protein-dependent manner, and thus the infection was neutralized completely by an RV-specific antibody.
+The infection was Ca(2+)-dependent and inhibited by endosomal acidification inhibitors, further confirming the dependency on RV envelope proteins for the VSV-RV/CE2E1 infection.
+Human non-immune cell lines were mostly susceptible to VSV-RV/CE2E1, while immune cell lines were much less susceptible than non-immune cell lines.
+Our data therefore suggest that immune cells are generally less susceptible to RV infection than non-immune cells, but the susceptibility of immune cells is enhanced upon stimulation.
+After influenza infection, lineage-negative epithelial progenitors (LNEPs) exhibit a binary response to reconstitute epithelial barriers: activating a Notch-dependent ΔNp63/cytokeratin 5 (Krt5) remodelling program or differentiating into alveolar type II cells (AEC2s).
+Here we show that local lung hypoxia, through hypoxia-inducible factor (HIF1α), drives Notch signalling and Krt5(pos) basal-like cell expansion.
+Single-cell transcriptional profiling of human AEC2s from fibrotic lungs revealed a hypoxic subpopulation with activated Notch, suppressed surfactant protein C (SPC), and transdifferentiation toward a Krt5(pos) basal-like state.
+Activated murine Krt5(pos) LNEPs and diseased human AEC2s upregulate strikingly similar core pathways underlying migration and squamous metaplasia.
+While robust, HIF1α-driven metaplasia is ultimately inferior to AEC2 reconstitution in restoring normal lung function.
+HIF1α deletion or enhanced Wnt/β-catenin activity in Sox2(pos) LNEPs blocks Notch and Krt5 activation, instead promoting rapid AEC2 differentiation and migration and improving the quality of alveolar repair.
+SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/ncb3580) contains supplementary material, which is available to authorized users.
+It has been characterized that the programmed ribosomal −1 frameshifting often occurs at the slippery sequence on the presence of a downstream mRNA pseudoknot.
+In some prokaryotic cases such as the dnaX gene of Escherichia coli, an additional stimulatory signal—an upstream, internal Shine–Dalgarno (SD) sequence—is also necessary to stimulate the efficient −1 frameshifting.
+Here, we propose a model of the pathway of the −1 translational frameshifting during ribosome translation of the dnaX −1 frameshift mRNA.
+(2014) [29]) on the dynamics of the shunt either to long pausing or to normal translation, the tRNA transit and sampling dynamics in the long-paused rotated state, the EF-G sampling dynamics, the mean rotated-state lifetimes, etc., are explained quantitatively.
+In addition, we present some predicted results, which can be easily tested by future optical trapping experiments.
+BACKGROUND: A subanalysis of a randomized clinical trial indicated sepsis survival benefit from interleukin (IL)-1 blockade in patients with features of the macrophage activation-like syndrome (MALS).
+This study aimed to investigate the frequency of MALS and to develop a biomarker of diagnosis and prognosis.
+METHODS: Patients with infections and systemic inflammatory response syndrome were assigned to one test cohort (n = 3417) and a validation cohort (n = 1704).
+MALS was diagnosed for patients scoring positive either for the hemophagocytic syndrome score and/or having both hepatobiliary dysfunction and disseminated intravascular coagulation.
+Logistic regression analysis was used to estimate the predictive value of MALS for 10-day mortality in both cohorts.
+Ferritin, sCD163, IL-6, IL-10, IL-18, interferon gamma (IFN-γ), and tumor necrosis factor alpha (TNF-α) were measured in the blood the first 24 h; ferritin measurements were repeated in 747 patients on day 3.
+RESULTS: The frequency of MALS was 3.7% and 4.3% in the test and the validation cohort, respectively.
+A ferritin level above 4420 ng/ml was accompanied by 66.7% and 66% mortality after 28 days, respectively.
+Ferritin levels above 4420 ng/ml were associated with an increase of IL-6, IL-18, INF-γ, and sCD163 and a decreased IL-10/TNF-α ratio, indicating predominance of pro-inflammatory phenomena.
+Any less than 15% decrease of ferritin on day 3 was associated with more than 90% sensitivity for unfavorable outcome after 10 days.
+This high mortality risk was also validated in an independent Swedish cohort (n = 109).
+Viral entry into the host cell is the first step of virus infection; however, its dynamic process via endocytosis remains largely elusive.
+Here, the force tracing technique and single particle simulation are combined to investigate the invagination of single human enterovirus 71 (HEV71, a positive single‐stranded RNA virus that is associated with hand, foot, and mouth disease) via cell membranes during its host cell entry.
+The experimental results reveal that the HEV71 invaginates in membrane vesicles at a force of 58 ± 16 pN, a duration time of 278 ± 68 ms.
+The simulation further shows that the virus can reach a partially wrapped state very fast, then the upper surface of the virus is covered by the membrane traveling over a long period of time.
+Combining the experiment with the simulation, the mechanism of membrane wrapping of virus is uncovered, which provides new insights into how the cell is operated to initiate the endocytosis of virus.
+Shigellosis, a bacillary dysentery, is closely associated with diarrhoea in human and causes infection of 165 million people worldwide per year.
+Casein-degrading serine protease autotransporter of enterobacteriaceae (SPATE) subfamily protein SigA, an outer membrane protein, exerts both cytopathic and enterotoxic effects especially cytopathic to human epithelial cell type-2 (HEp-2) and is shown to be highly immunogenic.
+In the present study, we have tried to impose the vaccinomics approach for designing a common peptide vaccine candidate against the immunogenic SigA of Shigella spp.
+At first, 44 SigA proteins from different variants of S. flexneri, S. dysenteriae, S. boydii, and S. sonnei were assessed to find the most antigenic protein.
+We retrieved 12 peptides based on the highest score for human leukocyte antigen (HLA) supertypes analysed by NetCTL.
+Initially, these peptides were assessed for the affinity with MHC class I and class II alleles, and four potential core epitopes VTARAGLGY, FHTVTVNTL, HTTWTLTGY, and IELAGTLTL were selected.
+Finally, IELAGTLTL was shown to have the highest population coverage (83.86%) among the whole world population.
+In vivo study of the proposed epitope might contribute to the development of functional and unique widespread vaccine, which might be an operative alleyway to thwart dysentery from the world.
+HBV and its satellite hepatitis D virus (HDV) infect hepatocytes via binding of the preS1 domain of its large envelope protein to sodium taurocholate cotransporting polypeptide (NTCP).
+Here, we developed novel human monoclonal antibodies that block the engagement of preS1 with NTCP and neutralize HBV and HDV with high potency.
+It also acts therapeutically by eliciting antibody-Fc-dependent immunological effector functions that impose durable suppression of viral infection in HBV-infected mice, resulting in reductions in the levels of the small envelope antigen and viral DNA, with no emergence of escape mutants.
+Our results illustrate a novel antibody-Fc-dependent approach for HBV treatment and suggest 2H5-A14 as a novel clinical candidate for HBV prevention and treatment of chronic HBV infection.
+The spread of the 2009 H1N1 influenza pandemic in England was characterized by two major waves of infections: the first one was highly spatially localized (mainly in the London area), while the second one spread homogeneously through the entire country.
+In this study, we perform a Bayesian analysis of five models entailing different hypotheses on the possible determinants of the observed pattern.
+We find a consensus among all models in showing a surprisingly low transmission distance (defined as the geographic distance between the place of residence of the infectors and her/his infectees) during the first wave: about 1.5 km (2.2 km if infections linked to household and school transmission are excluded).
+The best-fitting model entails a change in human activity regarding contacts not related to household and school.
+By using this model we estimate that the transmission distance sharply increased to 5.3 km (10 km when excluding infections linked to household and school transmission) during the second wave.
+Our study reveals a possible explanation for the observed pattern and highlights the need of better understanding human mobility and activity patterns under the pressure posed by a pandemic threat.
+Salivary diagnostics is an emerging field for the encroachment of point of care technology (PoCT).
+The necessity of the development of point-of-care (PoC) technology, the potential of saliva, identification and validation of biomarkers through salivary diagnostic toolboxes, and a broad overview of emerging technologies is discussed in this review.
+Furthermore, novel advanced techniques incorporated in devices for the early detection and diagnosis of several oral and systemic diseases in a non-invasive, easily-monitored, less time consuming, and in a personalised way is explicated.
+The latest technology detection systems and clinical utilities of saliva as a liquid biopsy, electric field-induced release and measurement (EFIRM), biosensors, smartphone technology, microfluidics, paper-based technology, and how their futuristic perspectives can improve salivary diagnostics and reduce hospital stays by replacing it with chairside screening is also highlighted.
+Survival of mosquitoes from dengue virus (DENV) infection is a prerequisite of viral transmission to the host.
+This study aimed to see how mosquito cells can survive the infection during prosperous replication of the virus.
+In C6/36 cells, global protein translation was shut down after infection by DENV type 2 (DENV2).
+However, it returned to a normal level when infected cells were treated with an inhibitor of the protein kinase RNA (PKR)-like ER kinase (PERK) signaling pathway.
+Based on a 7-Methylguanosine 5′-triphosphate (m7GTP) pull-down assay, the eukaryotic translation initiation factor 4F (eIF4F) complex was also identified in DENV2-infected cells.
+When the PERK signal pathway was inhibited, both accumulation of reactive oxygen species and changes in the mitochondrial membrane potential increased.
+This suggested that ER stress response was alleviated through the PERK-mediated shutdown of global proteins in DENV2-infected C6/36 cells.
+In the meantime, the activities of caspases-9 and -3 and the apoptosis-related cell death rate increased in C6/36 cells with PERK inhibition.
+This reflected that the PERK-signaling pathway is involved in determining cell survival, presumably by reducing DENV2-induced ER stress.
+Looking at the PERK downstream target, α-subunit of eukaryotic initiation factor 2 (eIF2α), an increased phosphorylation status was only shown in infected C6/36 cells.
+This indicated that recruitment of ribosome binding to the mRNA 5′-cap structure could have been impaired in cap-dependent translation.
+It turned out that shutdown of cellular protein translation resulted in a pro-survival effect on mosquito cells in response to DENV2 infection.
+As synthesis of viral proteins was not affected by the PERK signal pathway, an alternate mode other than cap-dependent translation may be utilized.
+This finding provides insights into elucidating how the PERK signal pathway modulates dynamic translation of proteins and helps mosquito cells survive continuous replication of the DENV2.
+We evaluated the antitumour effects of dihydroberberine combined with sunitinib (DCS) on the human non‐small cell lung cancer cell lines (NSCLC), A549, NCI‐H460, and NCI‐H1299 in vitro and in vivo.
+DCS showed synergic effects on NCI‐H460 cell proliferation, colony formation and transplantable tumour growth, which suggested dihydroberberine increases the sensitivity of lung carcinoma to sunitinib.
+Further studies indicated that DCS down‐regulated phosphorylation of JNK, p38, and NF‐κB in NCI‐H460 cells and tumours and suppressed the IκB and COX‐2 expression.
+Inhibition of p38 activation by DCS was a likely contributing factor in IL‐1 and COX‐2 down‐regulation.
+Consistent with these results, a genomewide microarray analysis found that DCS induced the expression of cell cycle signal molecules that are known to be affected by JNK and p38.
+The change of cell cycle, in turn, led to down‐regulation of JNK and p38, and further reduced IL‐1 secretion.
+Collectively, these findings highlight potential molecular mechanisms of DCS chemotherapeutic activity and suggest that DCS is an efficacious strategy in NSCLC therapy.
+Respiratory Syncytial Virus (RSV) infects respiratory epithelial cells and deregulates host gene expression by many mechanisms including expression of RSV G protein (RSV G).
+RSV G protein encodes a central conserved region (CCR) containing a CX3C motif that functions as a fractalkine mimic.
+Disruption of the CX3C motif (a.a. 182–186) located in the CCR of the G protein has been shown to affect G protein function in vitro and the severity of RSV disease pathogenesis in vivo.
+We show that infection of polarized Calu3 respiratory cells with recombinant RSV having point mutations in Cys173 and 176 (C173/176S) (rA2-GC12), or Cys186 (C186S) (rA2-GC4) is associated with a decline in the integrity of polarized Calu-3 cultures and decreased virus production.
+This is accompanied with downregulation of miRNAs let-7f and miR-24 and upregulation of interferon lambda (IFNλ), a primary antiviral cytokine for RSV in rA2-GC12/rA2-GC4 infected cells.
+These results suggest that residues in the cysteine noose region of RSV G protein can modulate IFN λ expression accompanied by downregulation of miRNAs, and are important for RSV G protein function and targeting.
+BACKGROUND: Non-cystic fibrosis bronchiectasis is a chronic structural lung condition that courses with recurrent infectious exacerbations that lead to frequent antibiotic treatment making this population more susceptible to acquire pathogens with antibiotic resistance.
+We aimed to investigate risk factors associated with isolation of multidrug-resistant pathogens in bronchiectasis exacerbations.
+METHODS: A prospective observational study was conducted in two tertiary-care hospitals, enrolling patients when first exacerbation appeared.
+RESULTS: Two hundred thirty three exacerbations were included and microorganisms were isolated in 159 episodes.
+Multidrug-resistant pathogens were found in 20.1% episodes: Pseudomonas aeruginosa (48.5%), methicillin-resistant Staphylococcus aureus (18.2%) and Extended spectrum betalactamase + Enterobacteriaceae (6.1%), and they were more frequent in exacerbations requiring hospitalization (24.5% vs. 10.2%, p: 0.016).
+Three independent multidrug-resistant risk factors were found: chronic renal disease (Odds ratio (OR), 7.60, 95% CI 1.92–30.09), hospitalization in the previous year (OR, 3.88 95% CI 1.37–11.02) and prior multidrug-resistant isolation (OR, 5.58, 95% CI 2.02–15.46).
+The proportion of multidrug-resistant in the 233 exacerbations was as follows: 3.9% in patients without risk factors, 12.6% in those with 1 factor and 53.6% if ≥2 risk factors.
+CONCLUSIONS: Hospitalization in the previous year, chronic renal disease, and prior multidrug-resistant isolation are risk factors for identification multidrug-resistant pathogens in exacerbations.
+The flavonoid-rich extract from Paulownia fortunei flowers (EPF) has been reported to prevent obesity and other lipid metabolism disease.
+The objective of this study was to investigate molecular factors involved in the hypoglycemic and hypolipidemic effects of EPF in obese mice fed a high-fat diet (HFD).
+Male h ICR (Institute of Cancer Research) mice were fed a HFD containing or not containing the EPF (50 or 100 mg/kg) for eight weeks.
+EPF reduced body weight gain, lipid accumulation in livers and levels of lipid, glucose and insulin in plasma as well as reduced insulin resistance as compared with the HFD group.
+We observed that EPF administration significantly increased the level of AMP-activated kinase (AMPK) phosphorylation and prevented fat deposits in livers and HepG2 cells, but these effects were blocked by compound C (an AMPK inhibitor).
+The protective effects of EPF were probably associated with the decrease in HMGCR, SREBP-1c and FAS expressions and the increase in CPT1 and phosphor-IRS-1 expressions.
+Our results suggest that EPF might be a potential natural candidate for the treatment and/or prevention of overweight and hepatic and metabolic-related alterations induced by HFD.
+Glycyrrhetinic acid monoglucuronide (GAMG) is a great value-added and has considerable commercial interest due to its strong pharmacological activities and functional low-calorie sweetener.
+However GAMG is quite rare in natural plants, and it must be prepared from glycyrrhizin (GL) by hydrolysing one terminal glucuronic acid.
+β-Glucuronidase is the key enzyme in the biotransformation of GL to GAMG, but its activities need to be enhanced to facilitate the industrial large-scale production of GAMG.
+In this study, we identified that isoliquiritigenin (ISL), as one of chemical compositions from the total flavonoids glycyrrhiza (TFG), can significantly enhance β-glucuronidase activity in vitro.
+Measurements using high-performance liquid chromatography (HPLC) showed that the activity of β-glucuronidase could be increased by 2.66-fold via the addition of ISL to a β-glucuronidase solution that contained GL at a 3:10 molar ratio of ISL to GL.
+ISL was concluded to be an activator because ISL could reduce the K(m) and E(a) of β-glucuronidase reacting with GL.
+This study sheds new light on the mechanism of β-glucuronidase and helps to make industrial production of GAMG through fermentation feasible.
+Following escape into the cytoplasm of host cells, Burkholderia pseudomallei and the related species Burkholderia thailandensis employ the type VI secretion system 5 (T6SS-5) to induce plasma membrane fusion with an adjacent host cell.
+This process leads to the formation of multinucleated giant cells and facilitates bacterial access to an uninfected host cell in a direct manner.
+Despite its importance in virulence, the mechanism of the T6SS-5 and the role of host cell factors in cell-cell fusion remain elusive.
+To date, the T6SS-5 is the only system of bacterial origin known to induce host-cell fusion.
+To gain insight into the nature of T6SS-5-stimulated membrane fusion, we investigated the contribution of cholesterol and proteins exposed on the host cell surface, which were shown to be critically involved in virus-mediated giant cell formation.
+In particular, we analyzed the effect of host cell surface protein and cholesterol depletion on the formation of multinucleated giant cells induced by B. thailandensis.
+Acute protease treatment of RAW264.7 macrophages during infection with B. thailandensis followed by agarose overlay assays revealed a strong reduction in the number of cell-cell fusions compared with EDTA treated cells.
+Similarly, proteolytic treatment of specifically infected donor cells or uninfected recipient cells significantly decreased multinucleated giant cell formation.
+Furthermore, modulating host cell cholesterol content by acute cholesterol depletion from cellular membranes by methyl- β-cyclodextrin treatment or exogenous addition of cholesterol impaired the ability of B. thailandensis to induce cell-cell fusions.
+The requirement of physiological cholesterol levels suggests that the membrane organization or mechanical properties of the lipid bilayer influence the fusion process.
+Altogether, our data suggest that membrane fusion induced by B. pseudomallei and B. thailandensis involves a complex interplay between the T6SS-5 and the host cell.
+Type III interferons (IFNs), also termed lambda IFNs (IFNλs) or interleukins-28/29, constitute a new addition to the IFN family.
+They are induced upon infection and are particularly abundant at barrier surfaces, such as the respiratory and gastrointestinal tracts.
+Although they signal through a unique heterodimeric receptor complex comprising IFNLR1 and IL10RB, they activate a downstream signaling pathway remarkably similar to that of type I IFNs and share many functions with them.
+Here, we review the current literature implicating type III IFNs in the regulation of immunity and homeostasis in the respiratory tract.
+We survey the common and unique characteristics of type III IFNs in terms of expression patterns, cellular targets, and biological activities and discuss their emerging role in first line defenses against respiratory viral infections.
+We further explore their immune modulatory functions and their involvement in the regulation of inflammatory responses during chronic respiratory diseases, such as asthma and chronic obstructive pulmonary disease.
+Type III IFNs are, therefore, arising as front-line guardians of immune defenses in the respiratory tract, fine tuning inflammation, and as potential novel therapeutics for the treatment of diverse respiratory diseases, including influenza virus infection and asthma.
+A novel avian influenza subtype, A/H7N9, emerged in 2013 and represents a public health threat with pandemic potential.
+We have previously shown that DNA vaccine priming increases the magnitude and quality of antibody responses to H5N1 monovalent inactivated boost.
+We now report the safety and immunogenicity of a H7 DNA-H7N9 monovalent inactivated vaccine prime-boost regimen.
+In this Phase 1, open label, randomized clinical trial, we evaluated three H7N9 vaccination regimens in healthy adults, with a prime-boost interval of 16 weeks.
+Group 2 received H7 DNA and H7N9 monovalent inactivated vaccine as a prime and H7N9 monovalent inactivated vaccine as a boost.
+Overall, 30 individuals between 20 to 60 years old enrolled and 28 completed both vaccinations.
+2 weeks post-boost, 50% of Group 1 and 33% of Group 2 achieved a HAI titer ≥1:40 compared with 11% of Group 3.
+Also, at least a fourfold increase in neutralizing antibody responses was seen in 90% of Group 1, 100% of Group 2, and 78% of Group 3 subjects.
+Peak neutralizing antibody geometric mean titers were significantly greater for Group 1 (GMT = 440.61, p < 0.05) and Group 2 (GMT = 331, p = 0.02) when compared with Group 3 (GMT = 86.11).
+A novel H7 DNA vaccine was safe, well-tolerated, and immunogenic when boosted with H7N9 monovalent inactivated vaccine, while priming for higher HAI and neutralizing antibody titers than H7N9 monovalent inactivated vaccine alone.
+A major limitation to current vaccinations and therapies against influenza virus is pathogenic diversity generated by shift and drift.
+A simple, cost-effective passive immunization strategy via in vivo production of cross-protective antibody molecules may augment existing vaccines and antiviral drugs in seasonal and pandemic outbreaks.
+We engineered synthetic plasmid DNA to encode two novel and broadly cross-protective monoclonal antibodies targeting influenza A and B.
+We utilized enhanced in vivo delivery of these plasmid DNA-encoded monoclonal antibody (DMAb) constructs and show that this strategy induces robust levels of functional antibodies directed against influenza A and B viruses in mouse sera.
+Mice receiving a single inoculation with anti-influenza A DMAb survive lethal Group 1 H1 and Group 2 H3 influenza A challenges, while inoculation with anti-influenza B DMAb yields protection against lethal Victoria and Yamagata lineage influenza B morbidity and mortality.
+Furthermore, these two DMAbs can be delivered coordinately resulting in exceptionally broad protection against both influenza A and B.
+DMAbs warrant further investigation as a novel immune therapy platform with distinct advantages for sustained immunoprophylaxis against influenza.
+This self-assembling protein nanoparticle contains five CD8(+) HLA-A03-11 supertypes-restricted epitopes from antigens expressed during Toxoplasma gondii’s lifecycle, the universal CD4(+) T cell epitope PADRE, and flagellin as a scaffold and TLR5 agonist.
+These CD8(+) T cell epitopes were separated by N/KAAA spacers and optimized for proteasomal cleavage.
+Self-assembling protein nanoparticle adjuvanted with TLR4 ligand-emulsion GLA-SE were evaluated for their efficacy in inducing IFN-γ responses and protection of HLA-A*1101 transgenic mice against T. gondii.
+Self-assembling protein nanoparticle-GLA-SE also protected HLA-A*1101 transgenic mice against subsequent challenge with Type II parasites.
+Hence, combining CD8(+) T cell-eliciting peptides and PADRE into a multi-epitope protein that forms a nanoparticle, administered with GLA-SE, leads to efficient presentation by major histocompatibility complex Class I and II molecules.
+Furthermore, these results suggest that activation of TLR4 and TLR5 could be useful for development of vaccines that elicit T cells to prevent toxoplasmosis in humans.
+One of the complications of dengue is dehydration which, if not carefully monitored and treated, may lead to shock, particularly in those with dengue haemorrhagic fever.
+WHO has recommended oral fluid intake of five glasses or more for adults who are suspected to have dengue fever.
+However, there have been no published studies looking at self-care intervention measures to improve oral fluid intake among patients suspected of dengue fever.
+OBJECTIVE: To assess the feasibility and effectiveness of using a fluid chart to improve oral fluid intake in patients with suspected dengue fever in a primary care setting.
+The data was collected over two months at a primary care clinic in a teaching hospital.
+The inclusion criteria were: age > 12 years, patients who were suspected to have dengue fever based on the assessment by the primary healthcare clinician, fever for > three days, and thrombocytopenia (platelets < 150 x 10(9)/L).
+Baseline clinical and laboratory data, 24-hour fluid recall (control group), and fluid chart were collected.
+FINDINGS: Among the 138 participants who were included in the final analysis, there were fewer hospital admissions in the intervention group (n = 7, 10.0%) than the control group (n = 12, 17.6%) (p = 0.192).
+Similarly, fewer patients (n = 9, 12.9%) in the intervention group required intravenous fluid compared to the control group (n = 15, 22.1%), (p = 0.154).
+There was an increase in the amount of daily oral fluid intake in the intervention group (about 3,000 ml) compared to the control group (about 2,500 ml, p = 0.521).
+CONCLUSION: This is a feasible and acceptable study to perform in a primary care setting.
+The fluid chart is a simple, inexpensive tool that may reduce hospitalization and intravenous fluid requirement in suspected dengue patients.
+Hepatitis B virus (HBV) core protein assembles viral pre-genomic (pg) RNA and DNA polymerase into nucleocapsids for reverse transcriptional DNA replication to take place.
+Several chemotypes of small molecules, including heteroaryldihydropyrimidines (HAPs) and sulfamoylbenzamides (SBAs), have been discovered to allosterically modulate core protein structure and consequentially alter the kinetics and pathway of core protein assembly, resulting in formation of irregularly-shaped core protein aggregates or “empty” capsids devoid of pre-genomic RNA and viral DNA polymerase.
+Interestingly, in addition to inhibiting nucleocapsid assembly and subsequent viral genome replication, we have now demonstrated that HAPs and SBAs differentially modulate the biosynthesis of covalently closed circular (ccc) DNA from de novo infection and intracellular amplification pathways by inducing disassembly of nucleocapsids derived from virions as well as double-stranded DNA-containing progeny nucleocapsids in the cytoplasm.
+Specifically, the mistimed cuing of nucleocapsid uncoating prevents cccDNA formation during de novo infection of hepatocytes, while transiently accelerating cccDNA synthesis from cytoplasmic progeny nucleocapsids.
+Our studies indicate that elongation of positive-stranded DNA induces structural changes of nucleocapsids, which confers ability of mature nucleocapsids to bind CpAMs and triggers its disassembly.
+Understanding the molecular mechanism underlying the dual effects of the core protein allosteric modulators on nucleocapsid assembly and disassembly will facilitate the discovery of novel core protein-targeting antiviral agents that can more efficiently suppress cccDNA synthesis and cure chronic hepatitis B.
+Unlike canonical pre-mRNAs, animal replication-dependent histone pre-mRNAs lack introns and are processed at the 3’-end by a mechanism distinct from cleavage and polyadenylation.
+They have a 3’ stem loop and histone downstream element (HDE) that are recognized by stem-loop binding protein (SLBP) and U7 snRNP, respectively.
+The N-terminal domain (NTD) of Lsm11, a component of U7 snRNP, interacts with FLASH NTD and these two proteins recruit the histone cleavage complex containing the CPSF-73 endonuclease for the cleavage reaction.
+Here, we determined crystal structures of FLASH NTD and found that it forms a coiled-coil dimer.
+Using solution light scattering, we characterized the stoichiometry of the FLASH NTD-Lsm11 NTD complex and found that it is a 2:1 heterotrimer, which is supported by observations from analytical ultracentrifugation and crosslinking.
+This study investigates the effects of five decontamination methods on the filter quality (q(f)) of three commercially available electret masks—N95, Gauze and Spunlace nonwoven masks.
+Newly developed evaluation methods, the overall filter quality (q(f,o)) and the q(f) ratio were applied to evaluate the effectiveness of decontamination methods for respirators.
+A scanning mobility particle sizer is utilized to measure the concentration of polydispersed particles with diameter 14.6–594 nm.
+The penetration of particles and pressure drop (Δp) through the mask are used to determine q(f) and q(f,o).
+Experimental results reveal that the most penetrating particle size (MPS) for the pre-decontaminated N95, Gauze and Spunlace masks were 118 nm, 461 nm and 279 nm, respectively, and the respective penetration rates were 2.6%, 23.2% and 70.0%.
+The Δp through the pretreated N95 masks was 9.2 mm H(2)O at the breathing flow rate of heavy-duty workers, exceeding the Δp values obtained through Gauze and Spunlace masks.
+Decontamination increased the sizes of the most penetrating particles, changing the q(f) values of all of the masks: q(f) fell as particle size increased because the penetration increased.
+However, the use of an autoclave reduces the Δp values of both the N95 and the Gauze mask.
+The value of q(f,o) for PM(0.1) exceeded that for PM(0.1–0.6), because particles smaller than 100 nm had lower penetration, resulting in a better q(f) for a given pressure drop.
+The values of q(f,o), particularly for PM(0.1), reveal that for the tested treatments and masks, physical decontamination methods are less destructive to the filter than chemical methods.
+The ongoing epidemic of chronic wasting disease (CWD) within cervid populations indicates the need for novel approaches for disease management.
+A vaccine that either reduces susceptibility to infection or reduces shedding of prions by infected animals, or a combination of both, could be of benefit for disease control.
+The development of such a vaccine is challenged by the unique nature of prion diseases and the requirement for formulation and delivery in an oral format for application in wildlife settings.
+To address the unique nature of prions, our group targets epitopes, termed disease specific epitopes (DSEs), whose exposure for antibody binding depends on disease-associated misfolding of PrP(C) into PrP(Sc).
+Here, a DSE corresponding to the rigid loop (RL) region, which was immunogenic following parenteral vaccination, was translated into an oral vaccine.
+This vaccine consists of a replication-incompetent human adenovirus expressing a truncated rabies glycoprotein G recombinant fusion with the RL epitope (hAd5:tgG-RL).
+Oral immunization of white-tailed deer with hAd5:tgG-RL induced PrP(Sc)-specific systemic and mucosal antibody responses with an encouraging safety profile in terms of no adverse health effects nor prolonged vector shedding.
+By building upon proven strategies of formulation for wildlife vaccines, these efforts generate a particular PrP(Sc)-specific oral vaccine for CWD as well as providing a versatile platform, in terms of carrier protein and biological vector, for generation of other oral, peptide-based CWD vaccines.
+Macroautophagy/autophagy has been shown to mediate the selective lysosomal degradation of pathogenic bacteria and viruses (xenophagy), and to contribute to the activation of innate and adaptative immune responses.
+Autophagy can serve as an antiviral defense mechanism but also as a proviral process during infection.
+Atg8-family proteins play a central role in the autophagy process due to their ability to interact with components of the autophagy machinery as well as selective autophagy receptors and adaptor proteins.
+So far, only one viral protein has been experimentally shown to have a functional LIR motif, leaving open a vast field for investigation.
+Here, we have developed the iLIR@viral database (http://ilir.uk/virus/) as a freely accessible web resource listing all the putative canonical LIR motifs identified in viral proteins.
+Additionally, we used a curated text-mining analysis of the literature to identify novel putative LIR motif-containing proteins (LIRCPs) in viruses.
+We anticipate that iLIR@viral will assist with elucidating the full complement of LIRCPs in viruses.
+We investigated whether pathogens present in mucus acquire resistance to alcohol-based disinfectants, and elucidated the underlying mechanism.
+Both the resistance of influenza A virus and Escherichia coli to alcohol-based disinfectants or ultraviolet irradiation and the diffusion rate of ethanol were determined in artificial mucus or sputum samples obtained from 27 individuals with acute upper respiratory infection.
+Pathogens in mucus (artificial mucus or sputum samples) were not completely inactivated by alcohol-based disinfectants (survival rate >10%), suggesting that the alcohol-based disinfectants were ineffective.
+Additionally, the ethanol diffusion rate decreased with increasing mucus viscosity, which contributed to ethanol resistance.
+Pronase treatment of sputum samples significantly decreased sputum viscosity and increased the disinfectant effect (P < 0.001 for all).
+Thus, mucus viscosity contributes to resistance of pathogens to alcohol-based disinfectants by decreasing the alcohol diffusion rate.
+These findings can provide a basis for developing new strategies, including improved disinfectants, for overcoming HAI.
+Japanese encephalitis virus (JEV), an arthropod-borne flavivirus, is a major cause of acute viral encephalitis in humans.
+No approved drug is available for the specific treatment of JEV infections, and the available vaccines are not effective against all clinical JEV isolates.
+In the study described here, a high-throughput screening of an FDA-approved drug library for inhibitors of JEV was performed.
+Five hit drugs that inhibited JEV infection with a selective index of >10 were identified.
+The antiviral activities of these five hit drugs against other flavivirus, including Zika virus, were also validated.
+As three of the five hit drugs were calcium inhibitors, additional types of calcium inhibitors that confirmed that calcium is essential for JEV infection, most likely during viral replication, were utilized.
+Adaptive mutant analysis uncovered that replacement of Q130, located in transmembrane domain 3 of the nonstructural NS4B protein, which is relatively conserved in flaviviruses, with R or K conferred JEV resistance to manidipine, a voltage-gated Ca(2+) channel (VGCC) inhibitor, without an apparent loss of the viral growth profile.
+Furthermore, manidipine was indicated to protect mice against JEV-induced lethality by decreasing the viral load in the brain, while it abrogated the histopathological changes associated with JEV infection.
+This study provides five antiflavivirus candidates and identifies cytoplasmic calcium to be a novel antiviral target for the treatment of JEV infection.
+IMPORTANCE No approved therapy for the treatment of Japanese encephalitis virus infection is currently available.
+In this study, we screened a library of FDA-approved drugs and identified five hit drugs, especially calcium inhibitors, exerting antiflavivirus activity that blocked viral replication.
+The in vivo efficacy and toxicity of manidipine were investigated with a mouse model of JEV infection, and the viral target was identified by generating an adaptive mutant.
+Na/K-ATPase has been extensively studied for its ion pumping function, but, in the past several decades, has been identified as a scaffolding and signaling protein.
+Initially it was found that cardiotonic steroids (CTS) mediate signal transduction through the Na/K-ATPase and result in the generation of reactive oxygen species (ROS), which are also capable of initiating the signal cascade.
+However, in recent years, this Na/K-ATPase/ROS amplification loop has demonstrated significance in oxidative stress related disease states, including obesity, atherosclerosis, heart failure, uremic cardiomyopathy, and hypertension.
+The discovery of this novel oxidative stress signaling pathway, holds significant therapeutic potential for the aforementioned conditions and others that are rooted in ROS.
+The Y chromosome has long been considered a ‘genetic wasteland’ on a trajectory to completely disappear from the human genome.
+These views have been challenged in recent times with the identification of multiple ubiquitously expressed Y-chromosome genes and the discovery of several unexpected associations between the Y chromosome, immune system and complex polygenic traits.
+The collected evidence suggests that the Y chromosome influences immune and inflammatory responses in men, translating into genetically programmed susceptibility to diseases with a strong immune component.
+Phylogenetic studies reveal that carriers of a common European lineage of the Y chromosome (haplogroup I) possess increased risk of coronary artery disease.
+This occurs amidst upregulation of inflammation and suppression of adaptive immunity in this Y lineage, as well as inferior outcomes in human immunodeficiency virus infection.
+From structural analysis and experimental data, the UTY (Ubiquitously Transcribed Tetratricopeptide Repeat Containing, Y-Linked) gene is emerging as a promising candidate underlying the associations between Y-chromosome variants and the immunity-driven susceptibility to complex disease.
+This review synthesises the recent structural, experimental and clinical insights into the human Y chromosome in the context of men’s susceptibility to disease (with a particular emphasis on cardiovascular disease) and provides an overview of the paradigm shift in the perception of the Y chromosome.
+Feline immunodeficiency virus (FIV) is one of the most common infectious agents affecting cats worldwide .FIV and human immunodeficiency virus (HIV) share many properties: both are lifelong persistent lentiviruses that are similar genetically and morphologically and both viruses propagate in T-lymphocytes, macrophages, and neural cells.
+Experimentally infected cats have measurable immune suppression, which sometimes progresses to an acquired immunodeficiency syndrome.
+A transient initial state of infection is followed by a long latent stage with low virus replication and absence of clinical signs.
+Thus, FIV infection in cats has become an important natural model for studying HIV infection in humans, especially for evaluation of antiviral compounds.
+Of particular importance for chemotherapeutic studies is the close similarity between the reverse transcriptase (RT) of FIV and HIV, which results in high in vitro susceptibility of FIV to many RT-targeted antiviral compounds used in the treatment of HIV-infected patients.
+Thus, the aim of this article is to provide an up-to-date review of studies on antiviral treatment of FIV, focusing on commercially available compounds for human or animal use.
+Effector T cell migration through tissues can enable control of infection or mediate inflammatory damage.
+Nevertheless, the molecular mechanisms that regulate migration of effector T cells within the interstitial space of inflamed lungs are incompletely understood.
+Here, we show T cell migration in a mouse model of acute lung injury with two-photon imaging of intact lung tissue.
+Computational analysis indicates that T cells migrate with an intermittent mode, switching between confined and almost straight migration, guided by lung-associated vasculature.
+By contrast, inhibition of Gα(i) signaling with pertussis toxin affects speed but not the intermittent migration of lung-infiltrating T cells.
+Computational modeling shows that an intermittent migration pattern balances both search area and the duration of contacts between T cells and target cells.
+These data identify that ROCK-dependent intermittent T cell migration regulates tissue-sampling during acute lung injury.
+The recent outbreak of Zika virus (ZIKV) disease caused an enormous number of infections in Central and South America, and the unusual increase in the number of infants born with microcephaly associated with ZIKV infection aroused global concern.
+Here, we developed a reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay using a portable device for the detection of ZIKV.
+The assay specifically detected ZIKV strains of both Asian and African genotypes without cross-reactivity with other arboviruses, including Dengue and Chikungunya viruses.
+The assay detected viral RNA at 14.5 TCID(50)/mL in virus-spiked serum or urine samples within 15 min, although it was slightly less sensitive than reference real time RT-PCR assay.
+We then evaluated the utility of this assay as a molecular diagnostic test using 90 plasma or serum samples and 99 urine samples collected from 120 suspected cases of arbovirus infection in the states of Paraíba and Pernambuco, Brazil in 2016.
+This portable RT-LAMP assay was highly specific for ZIKV, and enable rapid diagnosis of the virus infection.
+Our results provide new insights into ZIKV molecular diagnostics and may improve preparedness for future outbreaks.
+BACKGROUND: The study objective was to investigate and synthesize available evidence relating to the psychological health of Emergency Dispatch Centre (EDC) operatives, and to identify key stressors experienced by EDC operatives.
+METHODS: Eight electronic databases (Embase, PubMed, Medline, CINAHL, PsycInfo, PsycArticles, The Psychology and Behavioural Sciences Collection, and Google Scholar) were searched.
+Studies were included if they were published in English, and explored the psychological health of any EDC operatives, across fire, police, and emergency medical services.
+Studies were excluded if they related solely to other emergency workers, such as police officers or paramedics.
+Methodological quality of included studies was assessed using checklists adapted from the Critical Appraisal Skills Programme.
+Two overarching themes were identified during the narrative synthesis: ‘Organisational and Operational Factors’ and ‘Interactions with Others’.
+Stressors identified included being exposed to traumatic calls, lacking control over high workload, and working in under-resourced and pressured environments.
+Lack of support from management and providing an emotionally demanding service were additional sources of stress.
+Peer support and social support from friends and family were helpful in managing work-related stress.
+DISCUSSION: EDC operatives experience stress as a result of their work, which appears to be related to negative psychological health outcomes.
+Future research should explore the long-term effects of this stress, and the potential for workplace interventions to alleviate the negative impacts on psychological health.
+Bid, BH3-interacting domain death agonist, is a pro-apoptotic BH3-only member of Bcl-2 family, playing an important role in apoptosis.
+In the study, Bid genes from grass carp (Ctenopharyngodon idellus) and rare minnow (Gobiocypris rarus), named CiBid and GrBid, were cloned and analyzed.
+Bid was constitutively expressed in all examined tissues of grass carp, but the expression level varied in different tissues.
+Following grass carp reovirus (GCRV) stimulation in vivo, Bid and apoptosis related genes Caspase-9 and Caspase-3 was up-regulated significantly at the late stage of infection.
+Moreover, we generated a Bid-deficient rare minnow (Bid(-/-)) to investigate the possible role of Bid in GCRV-triggered apoptosis.
+We found that the survival time of Bid(-/-) rare minnow after GCRV infection was extended when compared with wild-type fish, the relative copy number of GCRV in Bid(-/-) rare minnow was lower than that in wild-type fish, and the expression level of Caspase-9 and Caspase-3 in Bid(-/-) rare minnow were significantly lower than that in the wild-type fish.
+Collectively, the current data revealed the important role of Bid during virus-induced apoptosis in teleost fish.
+Our study would provide new insight into understanding the GCRV induced apoptosis and may provide a target gene for virus-resistant breeding in grass carp.
+The actual strategy to improve current therapies in advanced prostate cancer involves targeting genes activated by androgen withdrawal, either to delay or prevent the emergence of the castration-refractory phenotype.
+However, these genes are often implicated in several physiological processes, and long-term inhibition of survival proteins might be accompanied with cytotoxic effects.
+To avoid this problem, an alternative therapeutic strategy relies on the identification and use of compounds that disrupt specific protein-protein interactions involved in androgen withdrawal.
+Specifically, the interaction of the chaperone protein Hsp27 with the initiation factor eIF4E leads to the protection of protein synthesis initiation process and enhances cell survival during cell stress induced by castration or chemotherapy.
+Thus, in this work we aimed at i) identifying the interaction site of the Hsp27/eIF4E complex and ii) interfere with the relevant protein/protein association mechanism involved in castration-resistant progression of prostate cancer.
+By a combination of experimental and modeling techniques, we proved that eIF4E interacts with the C-terminal part of Hsp27, preferentially when Hsp27 is phosphorylated.
+In order to find a potential inhibitor of Hsp27/eIF4E interaction, BRET assays in combination with molecular simulations identified the phenazine derivative 14 as the compound able to efficiently interfere with this protein/protein interaction, thereby inhibiting cell viability and increasing cell death in chemo- and castration-resistant prostate cancer models in vitro and in vivo.
+Mounting data show that substantial critical illness-induced changes in the immune system can be observed in most ICU patients and that not only “hyper-inflammation” but also persistence of an anti-inflammatory phenotype (as in sepsis-associated immunosuppression) is associated with increased morbidity and mortality.
+Despite common perception, changes in functional immunity cannot be adequately assessed by routine inflammatory biomarkers such as C-reactive protein, procalcitonin, or numerical analysis of leukocyte (sub)-counts.
+Cytokines appear also not suited due to their short half-life and pleiotropy, their unexclusive origin from immune cells, and their potential to undergo antagonization by circulating inactivating molecules.
+Thus, beyond leukocyte quantification and use of routine biomarkers, direct assessment of immune cell function seems required to characterize the immune systems’ status.
+This may include determination of, e.g., ex vivo cellular cytokine release, phagocytosis activity, and/or antigen-presenting capacity.
+In this regard, standardized flow-cytometric assessment of the major histocompatibility-II complex human leukocyte antigen (-D related) (HLA-DR) has gained particular interest.
+Monocytic HLA-DR (mHLA-DR) controls the interplay between innate and adaptive immunity and may serve as a “global” biomarker of injury-associated immunosuppression, and its decreased expression is associated with adverse clinical outcomes (e.g., secondary infection risk, mortality).
+Importantly, recent data demonstrate that injury-associated immunosuppression can be reversed—opening up new therapeutic avenues in affected patients.
+Here we discuss the potential scientific and clinical value of assessment of functional immunity with a focus on monocytes/macrophages and review the current state of knowledge and potential perspectives for affected critically ill patients.
+INTRODUCTION: Positron emission tomography (PET) is increasingly applied for infection imaging using [(18)F]FDG as tracer, but uptake is unspecific.
+The present study compares the kinetics of [(18)F]FDG and three other PET tracers with relevance for infection imaging.
+Eleven pigs underwent PET/CT with 60-minute dynamic PET imaging of [(18)F]FDG, [(68)Ga]Ga-citrate, [(11)C]methionine, and/or [(11)C]donepezil, along with blood sampling.
+For infectious lesions, kinetic modelling with one- and two-tissue-compartment models was conducted for each tracer.
+RESULTS: Irreversible uptake was found for [(18)F]FDG and [(68)Ga]Ga-citrate; reversible uptake was found for [(11)C]methionine (two-tissue model) and [(11)C]donepezil (one-tissue model).
+Net uptake rate for [(18)F]FDG and distribution volume for [(11)C]methionine were significantly higher for infectious lesions than for correspondingly noninfected tissue.
+Infection with hepatitis A virus (HAV) causes a highly contagious illness that can lead to serious morbidity and occasional mortality.
+Although the overall incidence of HAV has been declining since the introduction of the HAV vaccine, there have been an increasing number of outbreaks within the United States and elsewhere between 2016 and 2017.
+These outbreaks have had far-reaching consequences, with a large number of patients requiring hospitalization and several deaths.
+Through use of the “Identify-Isolate-Inform” tool as adapted for HAV, emergency physicians can become more familiar with the identification and management of patients presenting to the emergency department (ED) with exposure, infection, or risk of contracting disease.
+While it can be asymptomatic, HAV typically presents with a prodrome of fever, nausea/vomiting, and abdominal pain followed by jaundice.
+Healthcare providers should maintain strict standard precautions for all patients suspected of having HAV infection as well as contact precautions in special cases.
+Hand hygiene with soap and warm water should be emphasized, and affected patients should be counseled to avoid food preparation and close contact with vulnerable populations.
+Additionally, ED providers should offer post-exposure prophylaxis to exposed contacts and encourage vaccination as well as other preventive measures for at-risk individuals.
+Leukemia/lymphoma‐related factor (LRF), a zinc‐finger transcription factor encoded by Zbtb7a, is a protooncogene that regulates differentiation in diverse cell lineages, and in the CNS, its function is relatively unexplored.
+We first examined LRF expression in a murine viral model of spinal cord demyelination with clinically relevant lesion characteristics.
+LRF was rarely expressed in oligodendrocyte progenitors (OP) yet, was detected in nuclei of the majority of oligodendrocytes in healthy adult CNS and during remyelination.
+Plp/CreER (T) :Zbtb7a (fl/fl) mice were then used with cuprizone demyelination to determine the effect of LRF knockdown on oligodendrocyte repopulation and remyelination.
+LRF knockdown earlier within the oligodendrocyte lineage using NG2CreER (T) :Zbtb7a (fl/fl) mice reduced myelination after 6 weeks of cuprizone.
+LRF knockdown from either the Plp/CreER (T) line or the NG2CreER (T) line did not significantly change OP or oligodendrocyte populations.
+In vitro promoter assays demonstrated the potential for LRF to regulate transcription of myelin‐related genes and the notch target Hes5, which has been implicated in control of myelin formation and repair.
+In summary, in the oligodendrocyte lineage, LRF is expressed mainly in oligodendrocytes but is not required for oligodendrocyte repopulation of demyelinated lesions.
+Furthermore, LRF can modulate the extent of remyelination, potentially by contributing to interactions regulating transcription.
+BACKGROUND: The human virome consists of animal‐cell viruses causing transient infections, bacteriophage (phage) predators of bacteria and archaea, endogenous retroviruses and viruses causing persistent and latent infections.
+High‐throughput, inexpensive, sensitive sequencing methods and metagenomics now make it possible to study the contribution dsDNA, ssDNA and RNA virus‐like particles make to the human virome, and in particular the intestinal virome.
+AIM: To review and evaluate the pioneering studies that have attempted to characterise the human virome and generated an increased interest in understanding how the intestinal virome might contribute to maintaining health, and the pathogenesis of chronic diseases.
+METHODS: Relevant virome‐related articles were selected for review following extensive language‐ and date‐unrestricted, electronic searches of the literature.
+It develops soon after birth in parallel with prokaryotic communities of the microbiota, becoming established during the first few years of life.
+By infecting specific populations of bacteria, phages can alter microbiota structure by killing host cells or altering their phenotype, enabling phages to contribute to maintaining intestinal homeostasis or microbial imbalance (dysbiosis), and the development of chronic infectious and autoimmune diseases including HIV infection and Crohn's disease, respectively.
+CONCLUSIONS: Our understanding of the intestinal virome is fragmented and requires standardised methods for virus isolation and sequencing to provide a more complete picture of the virome, which is key to explaining the basis of virome‐disease associations, and how enteric viruses can contribute to disease aetiologies and be rationalised as targets for interventions.
+Appropriate adjuvant selection may be essential to optimize the potency and to tailor the immune response of subunit vaccines.
+To induce protective responses against respiratory syncytial virus (RSV)—a highly prevalent childhood pathogen without a licensed vaccine—we previously engineered a pre-fusion-stabilized trimeric RSV F (pre-F) “DS-Cav1” immunogen, which induced high titer RSV-neutralizing antibodies, in mice and non-human primates, when formulated with adjuvants Poly (I:C) and Poly (IC:LC), respectively.
+To assess the impact of different adjuvants, here we formulated RSV F DS-Cav1 with multiple adjuvants and assessed immune responses.
+Very high RSV-neutralizing antibody responses (19,006 EC(50)) were observed in naïve mice immunized with 2 doses of DS-Cav1 adjuvanted with Sigma adjuvant system (SAS), an oil-in-water adjuvant, plus Carbopol; high responses (3658–7108) were observed with DS-Cav1 adjuvanted with Alum, SAS alone, Adjuplex, Poly (I:C) and Poly (IC:LC); and moderate responses (1251–2129) were observed with DS-Cav1 adjuvanted with the TLR4 agonist MPLA, Alum plus MPLA or AddaVax.
+A balanced IgG1 and IgG2a (Th2/Th1) immune response was elicited in most of the high to very high response groups (all but Alum and Adjuplex).
+We also tested the immune response induced by DS-Cav1 in elderly mice with pre-existing DS-Cav1 immunity; we observed that DS-Cav1 adjuvanted with SAS plus Carbopol boosted the response 2-3-fold, whereas DS-Cav1 adjuvanted with alum boosted the response 5-fold.
+Finally, we tested whether a mixture of ISA 71 VG and Carbopol would enhanced the antibody response in DS-Cav1 immunized calves.
+While pre-F-stabilized bovine RSV F induced very high titers in mice when adjuvanted with SAS plus Carbopol, the addition of Carbopol to ISA 71 VG did not enhance immune responses in calves.
+The vaccine response to pre-F-stabilized RSV F is augmented by adjuvant, but the degree of adjuvant-induced enhancement appears to be both context-dependent and species-specific.
+Interferon‐induced transmembrane protein 3 (IFITM3) is an antiviral transmembrane protein that is thought to serve as the primary factor for inhibiting the replication of a large number of viruses, including West Nile virus, Dengue virus, Ebola virus, and Zika virus.
+Production of this 14.5 kDa, 133‐residue transmembrane protein, especially with essential posttranslational modifications, by recombinant expression is challenging.
+In this report, we document the chemical synthesis of IFTIM3 in multi‐milligram quantities (>15 mg) and the preparation of phosphorylated and fluorescent variants.
+The synthesis was accomplished by using KAHA ligations, which operate under acidic aqueous/organic mixtures that excel at solubilizing even the exceptionally hydrophobic C‐terminal region of IFITM3.
+The synthetic material is readily incorporated into model vesicles and forms the basis for using synthetic, homogenous IFITM3 and its derivatives for further studying its structure and biological mode of action.
+Ten reference genes were investigated for normalisation of candidate target gene expression data in the shell gland and spleen of laying hens challenged with two strains of infectious bronchitis virus (IBV).
+Data were analysed with geNorm, NormFinder and BestKeeper, and a comprehensive ranking (geomean) was calculated.
+In the combined data set of IBV challenged shell gland samples, the comprehensive ranking showed TATA-box binding protein (TBP) and tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta (YWHAZ) as the two most stable, and succinate dehydrogenase complex flavoprotein subunit A (SDHA) and albumin (ALB) as the two least stable reference genes.
+In the spleen, and in the combined data set of the shell gland and spleen, the two most stable and the two least stable reference genes were TBP and YWHAZ, and ribosomal protein L4 (RPL4) and ALB, respectively.
+Validation studies showed that the use of the two most stable reference genes produced accurate and more robust gene expression data.
+The two most and least stable reference genes obtained in the study, were further used for candidate target gene expression data normalisation of the shell gland and spleen under an IBV infection model.
+Autoimmune diseases emerge due to several reasons, of which molecular mimicry i.e., similarity between the host's and pathogen's interacting peptides is an important reason.
+In the present study we have reported a database of only experimentally verified peptide sequences, which exhibit molecular mimicry.
+The database is named as miPepBase (Mimicry Peptide Database) and contains comprehensive information about mimicry proteins and peptides of both host (and model organism) and pathogen.
+It also provides information about physicochemical properties of protein and mimicry peptides, which might be helpful in predicting the nature of protein and optimization of protein expression.
+The miPepBase can be searched using a keyword or, by autoimmune disease(s) or by a combination of host and pathogen taxonomic group or their name.
+To facilitate the search of proteins and/or epitope in miPepBase, which is similar to the user's interest, BLAST search tool is also incorporated.
+MicroRNA-21 (mir-21) induced by angiotensin II (AngII) plays a vital role in the development of pulmonary fibrosis, and the NLRP3 inflammasome is known to be involved in fibrogenesis.
+However, whether there is a link between mir-21 and the NLRP3 inflammasome in pulmonary fibrosis is unknown.
+Angiotensin-converting enzyme 2/angiotensin(1–7) [ACE2/Ang(1–7)] has been shown to attenuate AngII-induced pulmonary fibrosis, but it is not clear whether ACE2/Ang(1–7) protects against pulmonary fibrosis by inhibiting AngII-induced mir-21 expression.
+This study’s aim was to investigate whether mir-21 activates the NLRP3 inflammasome and mediates the different effects of AngII and ACE2/Ang(1–7) on lung fibroblast apoptosis and collagen synthesis.
+In vivo, AngII exacerbated bleomycin (BLM)-induced lung fibrosis in rats, and elevated mir-21 and the NLRP3 inflammasome.
+In vitro, AngII activated the NLRP3 inflammasome by up-regulating mir-21, and ACE2/Ang(1–7) inhibited NLRP3 inflammasome activation by down-regulating AngII-induced mir-21.
+Over-expression of mir-21 activated the NLRP3 inflammasome via the ERK/NF-κB pathway by targeting Spry1, resulting in apoptosis resistance and collagen synthesis in lung fibroblasts.
+These results indicate that mir-21 mediates the inhibitory effect of ACE2/Ang(1–7) on AngII-induced activation of the NLRP3 inflammasome by targeting Spry1 in lung fibroblasts.
+The epigenetic silencing of tumor suppressor genes in myelodysplastic syndromes (MDS) can potentially confer a growth advantage to individual cellular clones.
+Currently, the recommended treatment for patients with high-risk MDS is the methylation agent decitabine (DAC), a drug that can induce the reexpression of silenced tumor suppressor genes.
+We investigated the effects of DAC treatment on the myeloid MDS cell line SKM-1 and investigated the role of FOXO3A, a potentially tumor-suppressive transcription factor, by silencing its expression prior to DAC treatment.
+We found that FOXO3A exists in an inactive, hyperphosphorylated form in SKM-1 cells, but that DAC both induces FOXO3A expression and reactivates the protein by reducing its phosphorylation level.
+Furthermore, we show that this FOXO3A activation is responsible for the DAC-induced differentiation of SKM-1 cells into monocytes, as well as for SKM-1 cell cycle arrest, apoptosis, and autophagy.
+Collectively, these results suggest that FOXO3A reactivation may contribute to the therapeutic effects of DAC in MDS.
+While autophagy has been shown to function in host antiviral defense by eliminating intracellular viruses and regulating adaptive immunity, several viruses have evolved molecular mechanisms to get benefits from it.
+The deltaretrovirus human T-cell leukemia virus type-1 (HTLV-1) has been reported to profit its replication from enhancing autophagosome accumulation.
+Here, we reported that HLA-DMB (generally referred to here as DMB), the beta chain of the non-classical MHC-II protein HLA-DM, had strong expression in HTLV-1-transformed T-cell lines and could be induced in Hela, PMA-differentiated THP1 (PMA-THP1) or primary human monocytes by HTLV-1 infection.
+Immunoblot and real-time PCR assays demonstrated that overexpression of DMB decreased HTLV-1 protein expression while the knockdown of DMB increased HTLV-1 protein expression.
+Immunoblot and confocal microscopy assays indicated that overexpression of DMB decreased HTLV-1 induced autophagosome accumulation while the knockdown of DMB yielded the opposite effects.
+Coimmunoprecipitation and immunoprecipitation experiments suggested DMB interacted with autophagy-related gene (ATG) 7 and increased the acetylation of ATG7.
+Taken together, these results suggested DMB modulated HTLV-1 protein expression through regulation of autophagosome accumulation and our findings suggested a new mechanism by which the host cells defended against HTLV-1 infection.
+The obligate intracellular parasite, Toxoplasma gondii, manipulates the cytoskeleton of its host cells to facilitate infection.
+A significant rearrangement of host cell vimentin around Toxoplasma parasitophorous vacuoles is observed during the course of infection.
+ROP18 (TgROP18) is a serine-threonine kinase secreted by T. gondii rhoptry and a major virulence factor; however, the mechanisms by which this kinase modulates host factors remain poorly understood.
+Different and dynamic patterns of vimentin solubility, phosphorylation, and expression levels were observed in host cells infected with T. gondii strain RH and RH Δrop18 strains, suggesting that TgROP18 contributes to the regulation of these dynamic patterns.
+A significant increase in T. gondii infection rate was observed in vimentin knockout human brain microvessel endothelial cells (HBMEC), while vimentin knockout or knock down in host cells had no impact on parasite proliferation and egress.
+Interestingly, western blotting of different mouse tissues indicated that the lowest vimentin expression level was present in the brain, which may explain the mechanism underlying the nervous system tropism of T. gondii, and the phenomenon of huge cyst burdens developing in the mouse brain during chronic infection.
+High salt intake has been related to the development to chronic kidney disease (CKD) as well as hypertension.
+In its early stages, symptoms of CKD are usually not apparent, especially those that are induced in a “silent” manner in normotensive individuals, thereby providing a need for some kind of urinary biomarker to detect injury at an early stage.
+Because traditional renal biomarkers such as serum creatinine are insensitive, it is difficult to detect kidney injury induced by a high-salt diet, especially in normotensive individuals.
+Recently, several new biomarkers for damage of renal tubular epithelia such as neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (Kim-1) have been identified.
+Previously, we found a novel renal biomarker, urinary vanin-1, in several animal models with renal tubular injury.
+However, there are few studies about early biomarkers of the progression to CKD associated with a high-salt diet.
+This review presents some new insights about these novel biomarkers for CKD in normotensives and hypertensives under a high salt intake.
+Interestingly, our recent reports using spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY) fed a high-salt diet revealed that urinary vanin-1 and NGAL are earlier biomarkers of renal tubular damage in SHR and WKY, whereas urinary Kim-1 is only useful as a biomarker of salt-induced renal injury in SHR.
+Rationale: Cell-free protein microarrays display naturally-folded proteins based on just-in-time in situ synthesis, and have made important contributions to basic and translational research.
+However, the risk of spot-to-spot cross-talk from protein diffusion during expression has limited the feature density of these arrays.
+Methods: In this work, we developed the Multiplexed Nucleic Acid Programmable Protein Array (M-NAPPA), which significantly increases the number of displayed proteins by multiplexing as many as five different gene plasmids within a printed spot.
+Results: Even when proteins of different sizes were displayed within the same feature, they were readily detected using protein-specific antibodies.
+Protein-protein interactions and serological antibody assays using human viral proteome microarrays demonstrated that comparable hits were detected by M-NAPPA and non-multiplexed NAPPA arrays.
+An ultra-high density proteome microarray displaying > 16k proteins on a single microscope slide was produced by combining M-NAPPA with a photolithography-based silicon nano-well platform.
+Finally, four new tuberculosis-related antigens in guinea pigs vaccinated with Bacillus Calmette-Guerin (BCG) were identified with M-NAPPA and validated with ELISA.
+Conclusion: All data demonstrate that multiplexing features on a protein microarray offer a cost-effective fabrication approach and have the potential to facilitate high throughput translational research.
+Mucosal immunization of influenza vaccine is potentially an effective approach for the prevention and control of influenza.
+The objective of the present study was to evaluate the ability of oral immunization with a non-recombinant Lactococcus lactis displaying HA1/L/AcmA recombinant protein, LL-HA1/L/AcmA, to induce mucosal immune responses and to accord protection against influenza virus infection in mice.
+Mice immunized with LL-HA1/L/AcmA developed detectable specific sIgA in faecal extract, small intestine wash, BAL fluid and nasal fluid.
+The results obtained demonstrated that oral immunization of mice with LL-HA1/L/AcmA elicited mucosal immunity in both the gastrointestinal tract and the respiratory tract.
+The protective efficacy of LL-HA1/L/AcmA in immunized mice against a lethal dose challenge with influenza virus was also assessed.
+In conclusion, oral administration of LL-HA1/L/AcmA in mice induced mucosal immunity and most importantly, provided protection against lethal influenza virus challenge.
+These results highlight the potential application of L. lactis as a platform for delivery of influenza virus vaccine.
+OATP1B1 and OATP1B3 mediate hepatic uptake of many drugs (e.g., statins) and can mediate transporter-mediated drug-drug-interactions (DDIs).
+Bortezomib is the first-in-class proteasome inhibitor drug approved by the U. S. Food and Drug Administration for the treatment of multiple myeloma.
+The current study investigated the involvement of the ubiquitin-proteasome system (UPS) in OATP1B1 and OATP1B3 degradation and determined the effects of proteasome inhibitors on OATP1B1- and OATP1B3-mediated transport.
+Co-immunoprecipitation of FLAG-OATP1B1/1B3 and HA-ubiquitin was observed in human embryonic kidney (HEK) 293 cells co-transfected with FLAG-tagged OATP1B1/OATP1B3 and hemagglutinin (HA)-tagged ubiquitin, suggesting that OATP1B1 and OATP1B3 can be ubiquitin-modified.
+Although blocking proteasome activity by bortezomib treatment (50 nM, 7 h) increased the endogenous ubiquitin-conjugated FLAG-OATP1B1 and FLAG-OATP1B3 in HEK293-FLAG-OATP1B1 and–OATP1B3 cells, such treatment did not affect the total protein levels of OATP1B1 and OATP1B3, suggesting that the UPS plays a minor role in degradation of OATP1B1 and OATP1B3 under current constitutive conditions.
+Pretreatment with bortezomib (50–250 nM, 2–7 h) significantly decreased transport of [(3)H]CCK-8, a specific OATP1B3 substrate, in HEK293-OATP1B3 and human sandwich-cultured hepatocytes (SCH).
+However, bortezomib pretreatment had negligible effects on the transport of [(3)H]E(2)17βG and [(3)H]pitavastatin, dual substrates of OATP1B1 and OATP1B3, in HEK293-OATP1B1/1B3 cells and/or human SCH.
+Compared with vehicle control treatment, bortezomib pretreatment significantly decreased the maximal transport velocity (V(max)) of OATP1B3-mediated transport of CCK-8 (92.25 ± 14.2 vs. 133.95 ± 15.5 pmol/mg protein/min) without affecting the affinity constant (K(m)) values.
+Treatment with other proteasome inhibitors MG132, epoxomicin, and carfilzomib also significantly decreased OATP1B3-mediated [(3)H]CCK-8 transport.
+In summary, the current studies for the first time report ubiquitination of OATP1B1 and OATP1B3 and the apparent substrate-dependent inhibitory effect of bortezomib on OATP1B3-mediated transport.
+Exacerbation of macrophage-mediated inflammation contributes to pathogenesis of various inflammatory diseases, but the immunometabolic programs underlying regulation of macrophage activation are unclear.
+Here we show that V-set immunoglobulin-domain-containing 4 (VSIG4), a B7 family-related protein that is expressed by resting macrophages, inhibits macrophage activation in response to lipopolysaccharide.
+Vsig4 (−/−) mice are susceptible to high-fat diet-caused obesity and murine hepatitis virus strain-3 (MHV-3)-induced fulminant hepatitis due to excessive macrophage-dependent inflammation.
+VSIG4 activates the PI3K/Akt–STAT3 pathway, leading to pyruvate dehydrogenase kinase-2 (PDK2) upregulation and subsequent phosphorylation of pyruvate dehydrogenase, which results in reduction in pyruvate/acetyl-CoA conversion, mitochondrial reactive oxygen species secretion, and macrophage inhibition.
+BACKGROUND: Nosocomial infections occurring during extracorporeal membrane oxygenation (ECMO) support have already been reported, but few studied infections directly related to ECMO devices.
+This study aims to evaluate the rate of both colonisations and infections related to ECMO devices at the time of ECMO removal.
+RESULTS: We included all consecutive adult patients treated with venovenous ECMO (VV-ECMO) for at least 48 h during a 34-month study.
+At the time of ECMO removal, blood cultures, swab cultures on insertion cannula site and intravascular cannula extremity cultures were systematically performed.
+Each ECMO device was classified according to the infectious status into three groups: (1) uninfected/uncolonised ECMO device, (2) ECMO device colonisation and (3) ECMO device infection.
+The ECMO device infection rate was 9.7% (10 events), including 7 ECMO device-related bloodstream infections (6.8%).
+No difference was observed between the three groups, regarding days of mechanical ventilation, ICU length of stay, ICU mortality and in-hospital mortality.
+We observed a longer ECMO duration in the ECMO device colonisation group as compared to the uninfected/uncolonised ECMO device group [12 (9–20 days) vs. 5 days (5–16 days), respectively, p < 0.05].
+CONCLUSIONS: At the time of ECMO removal, systematic blood culture and intravascular extremity cannula culture may help to diagnose ECMO device-related infection.
+Further studies are needed to evaluate the benefits of systematic strategies of cannula culture at the time of ECMO removal.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13613-017-0335-9) contains supplementary material, which is available to authorized users.
+Prostate-specific membrane antigen (PSMA) is expressed at high levels on malignant prostate cells and is likely an important therapeutic target for the treatment of prostate carcinoma.
+Current immunotherapy approaches to target PSMA include peptide, cell, vector or DNA-based vaccines as well as passive administration of PSMA-specific monoclonal antibodies (mAb).
+Conventional mAb immunotherapy has numerous logistical and practical limitations, including high production costs and a requirement for frequent dosing due to short mAb serum half-life.
+In this report, we describe a novel strategy of antibody-based immunotherapy against prostate carcinoma that utilizes synthetic DNA plasmids that encode a therapeutic human mAb that target PSMA.
+Electroporation-enhanced intramuscular injection of the DNA-encoded mAb (DMAb) plasmid into mice led to the production of functional and durable levels of the anti-PSMA antibody.
+The anti-PSMA produced in vivo controlled tumor growth and prolonged survival in a mouse model.
+This is likely mediated by antibody-dependent cellular cytotoxicity (ADCC) effect with the aid of NK cells.
+Further study of this novel approach for treatment of human prostate disease and other malignant conditions is warranted.
+BACKGROUND: The human immunodeficiency virus type 1 (HIV-1) structural protein Gag is necessary and sufficient to form viral particles.
+In addition to encoding the amino acid sequence for Gag, the underlying RNA sequence could encode cis-acting elements or nucleotide biases that are necessary for viral replication.
+However, the functional relevance of RNA elements and nucleotide biases that promote or repress HIV-1 replication remain poorly understood.
+RESULTS: To characterize if the RNA sequence in gag controls HIV-1 replication, the matrix (MA) region was codon modified, allowing the RNA sequence to be altered without affecting the protein sequence.
+Codon modification of nucleotides (nt) 22-261 or 22-378 in gag inhibited viral replication by decreasing genomic RNA (gRNA) abundance, gRNA stability, Gag expression, virion production and infectivity.
+Comparing the effect of these point mutations to deletions of the same region revealed that the mutations inhibited infectious virus production while the deletions did not.
+There is a much lower than expected frequency of CpG dinucleotides in HIV-1 and codon modification introduced a substantial increase in CpG abundance.
+To determine if they are necessary for inhibition of HIV-1 replication, codons introducing CpG dinucleotides were mutated back to the wild type codon, which restored efficient Gag expression and infectious virion production.
+To determine if they are sufficient to inhibit viral replication, CpG dinucleotides were inserted into gag in the absence of other changes.
+Increasing the abundance of CpG dinucleotides inhibits multiple steps of the viral life cycle, providing a functional explanation for why CpG dinucleotides are suppressed in HIV-1.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12977-017-0374-1) contains supplementary material, which is available to authorized users.
+Cowpox virus infections in captive cheetahs (Acinonyx jubatus) with high morbidity and mortality have already been reported in the UK and Russia in the 1970s.
+Here, we report a total of five cowpox virus outbreaks in cheetahs in the same safari park in Denmark between 2010 and 2014.
+No other carnivores kept at the same institution nor the keepers taking care of the animals were clinically affected.
+The clinical picture of cowpox was confirmed by extensive laboratory investigations including histopathological and molecular analyses as well as cell culture isolation of a cowpox virus.
+High anti-orthopoxvirus antibody titers were detected in all 9 diseased cheetahs compared to seven contact cheetahs without clinical signs and 13 cheetahs not in direct contact.
+Additionally, whole genome sequencing from one sample of each cluster with subsequent phylogenetic analysis showed that the viruses from different outbreaks have individual sequences but clearly form a clade distinct from other cowpox viruses.
+However, the intra-clade distances are still larger than those usually observed within clades of one event.
+These findings indicate multiple and separate introductions of cowpox virus, probably from wild rodent populations, where the virus keeps circulating naturally and is only sporadically introduced into the cheetahs.
+As a consequence, recommendations are given for medical and physical management of diseased cheetahs, for hygienic measures as well as for pre-shipment isolation before cheetah export from zoo grounds.
+In recent years there has been growing availability of individual-level spatio-temporal disease data, particularly due to the use of modern communicating devices with GPS tracking functionality.
+These detailed data have been proven useful for inferring disease transmission to a more refined level than previously.
+However, there remains a lack of statistically sound frameworks to model the underlying transmission dynamic in a mechanistic manner.
+Such a development is particularly crucial for enabling a general epidemic predictive framework at the individual level.
+In this paper we propose a new statistical framework for mechanistically modelling individual-to-individual disease transmission in a landscape with heterogeneous population density.
+The methodology is subsequently applied to data that describes a regional Ebola outbreak in Western Africa (2014-2015).
+Our results show that the methods are able to obtain estimates of key epidemiological parameters that are broadly consistent with the literature, while revealing a significantly shorter distance of transmission.
+More importantly, in contrast to existing approaches, we are able to perform a more general model prediction that takes into account the susceptible population.
+Finally, our results show that, given reasonable scenarios, the framework can be an effective surrogate for susceptible-explicit individual models which are often computationally challenging.
+Multipartite viruses have genomes segmented in pieces enclosed in different capsids that are independently transmitted.
+Since all segments have to meet in the host for complementation and completion of the viral cycle, multipartite viruses are bound to fight the loss of genomic information.
+While this is an obvious disadvantage of this strategy, no consensus on its actual advantages has been reached.
+In this review we present an exhaustive summary of all multipartite viruses described to date.
+Based on evidence, we discuss possible mechanistic and evolutionary origins of different groups, as well as their mutual relationships.
+We argue that the ubiquitous interactions of viruses with other unrelated viruses and with subviral elements might be regarded as a plausible first step towards multipartitism.
+In agreement with the view of the Virosphere as a deeply entangled network of gene sharing, we contend that the power of multipartitism relies on its dynamical and opportunistic nature, because it enables immediate adaptive responses to environmental changes.
+As such, perhaps the reasons for its success should be shought in multipartitism itself as an adaptive mechanism, to which its evolutionarily short-lived products (that is, the extant ensemble of multipartite viral species) are subordinated.
+We close by discussing how our understanding of multipartitism would improve by using concepts and tools from systems biology.
+OBJECTIVES: Use of point-of-care testing is increasing, however many haematology analysers can only determine granulocyte count without further differentiation into neutrophils, eosinophils and basophils.
+Since the diagnosis of life-threatening neutropenia in cancer patients requires a distinct neutrophil count, this study aimed to determine the comparative performance between the neutrophil and granulocyte count.
+DESIGN AND METHODS: A database of 508 646 venous full blood count results measured on a laboratory reference analyser was mined from a large oncology unit.
+Multinomial logistic regression was used to classify results into neutropenia grades using an equivalent granulocyte count.
+The accuracy for classification into neutropenia grades using the derived equivalent granulocyte count ranges was 96.4%.
+Identification of results with a neutrophil count <1.5×10(9) cells/L using an equivalent granulocyte count of <1.69×10(9) cells/L resulted in sensitivity, specificity, positive and negative predictive values of 98.0%, 99.5%, 97.8% and 99.5%, respectively.
+CONCLUSIONS: These results describe the relationship between granulocyte and neutrophil counts, measured on a laboratory analyser, in a large population of patients with malignancies and receiving anti-cancer therapies.
+However, this relationship must be established using a point of care testing system with a three-part differential count before considering the possibility that a granulocyte count can guide clinical decisions in the absence of a definitive neutrophil count, to reduce the frequency and severity of neutropenic complications in patients receiving cancer treatments.
+BACKGROUND: This study aimed to analyze and explore the relationship between the cytokines IL-4 and IL-10 in relation to gene polymorphism and their respective effects on the susceptibility to virus-induced encephalitis.
+MATERIAL/METHODS: From January 2012 to June 2013, 112 patients with virus-induced encephalitis (the case group and 109 healthy individuals (the control group) were recruited for the purposes of this study.
+The functional variations that IL-4 and IL-10 genes exhibit were detected through the use of a function analysis and selection tool for single-nucleotide polymorphisms (FASTSNP).
+The genotypes of IL-4 were rs2227283 and IL-4 rs2227288, and the genotypes of IL-10 were rs1800871 and IL-10 rs1800872.
+RESULTS: IL-4 rs2227283 and IL-10 rs1800871 have no correlation in with risk of virus-induced encephalitis (both P>0.05) GA and AA genotypes were related to IL-4 rs2227288 and GT, while TT and GT + TT genotypes were related to IL-10 rs1800872.
+However, the duration of fever, white blood cell (WBC) count, C-reactive protein (CRP), neutrophils, and lymphocytes and monocytes of virus-induced encephalitis patients with IL-4 rs2227288 and IL-10 rs1800872 all displayed significant differences (all P<0.05).
+Frequencies of GAGT and CAGT haplotypes were evaluated and deemed to be of statistical significance and subsequently were highlighted as being risk factors in virus-induced encephalitis (all P<0.05).
+CONCLUSIONS: IL-4 rs2227288 and IL-10 rs1800872 may contribute to an increased risk for virus-induced encephalitis.
+Through use of direct sequencing, we showed that genotypes of IL-4 rs2227288 and IL-10 rs1800872 may have particular host susceptibility to virus-induced encephalitis.
+BACKGROUND: Influenza outbreaks can occur among passengers and crews during the Alaska summertime cruise season.
+Ill travellers represent a potential source for introduction of novel or antigenically drifted influenza virus strains to the United States.
+From May to September 2013–2015, the Alaska Division of Public Health, the Centers for Disease Control and Prevention (CDC), and two cruise lines implemented a laboratory-based public health surveillance project to detect influenza and other respiratory viruses among ill crew members and passengers on select cruise ships in Alaska.
+METHODS: Cruise ship medical staff collected 2–3 nasopharyngeal swab specimens per week from passengers and crew members presenting to the ship infirmary with acute respiratory illness (ARI).
+Specimens were tested for respiratory viruses at the Alaska State Virology Laboratory (ASVL); a subset of specimens positive for influenza virus were sent to CDC for further antigenic characterization.
+RESULTS: Of 410 nasopharyngeal specimens, 83% tested positive for at least one respiratory virus; 71% tested positive for influenza A or B virus.
+Antigenic characterization of pilot project specimens identified strains matching predominant circulating seasonal influenza virus strains, which were included in the northern or southern hemisphere influenza vaccines during those years.
+Onset dates of illness relative to date of boarding differed between northbound (occurring later in the voyage) and southbound (occurring within the first days of the voyage) cruises.
+CONCLUSIONS: The high yield of positive results indicated that influenza was common among passengers and crews sampled with ARI.
+This finding reinforces the need to bolster influenza prevention and control activities on cruise ships.
+Laboratory-based influenza surveillance on cruise ships may augment inland influenza surveillance and inform control activities.
+However, these benefits should be weighed against the costs and operational limitations of instituting laboratory-based surveillance programs on ships.
+A country's ability to robustly detect ZIKV introduction and local transmission is important to minimise the risk for a ZIKV outbreak.
+To assess the capacity, quality, operational specifics (guidelines and algorithms), technical and interpretation issues and other possible difficulties that were related to ZIKV diagnostics in European countries, a questionnaire was conducted among national reference laboratories in 30 countries in the European Union/European Economic Area (EU/EEA) in May 2016.
+While the coverage and capacity of ZIKV diagnostics in the EU/EEA national reference laboratories were found to be adequate, the assessment of the quality and needs indicated several crucial points of improvement that will need support at national and EU/EEA level to improve ZIKV preparedness, response and EU/EEA ZIKV surveillance activities.
+The progressive loss of immunological memory during aging correlates with a reduced proliferative capacity and shortened telomeres of T cells.
+The antigenic volume imposed by persistent and latent viruses exposes the immune system to unique challenges that lead to host T-cell exhaustion, characterized by impaired T-cell functions.
+These dysfunctional memory T cells lack telomerase, the protein capable of extending and stabilizing chromosome ends, imposing constraints on telomere dynamics.
+A deleterious consequence of this excessive telomere shortening is the premature induction of replicative senescence of viral-specific CD8+ memory T cells.
+While senescent cells are unable to expand, they can survive for extended periods of time and are more resistant to apoptotic signals.
+This review takes a closer look at T-cell exhaustion in chronic viruses known to cause human disease: Epstein–Barr virus (EBV), Hepatitis B/C/D virus (HBV/HCV/HDV), human herpesvirus 8 (HHV-8), human immunodeficiency virus (HIV), human T-cell leukemia virus type I (HTLV-I), human papillomavirus (HPV), herpes simplex virus-1/2 (HSV-1/2), and Varicella–Zoster virus (VZV).
+The concept that enduring antigen stimulation leads to T-cell exhaustion that favors telomere attrition and a cell fate marked by enhanced T-cell senescence appears to be a common endpoint to chronic viral infections.
+CASE SUMMARY: A 6-year-old female neutered domestic shorthair cat from Cyprus was presented with multiple ulcerated skin nodules.
+Cytology and histopathology of the lesions revealed granulomatous dermatitis with intracytoplasmic organisms, consistent with amastigotes of Leishmania species.
+Blood extraction and PCR detected Leishmania species, Hepatozoon species and ‘Candidatus Mycoplasma haemominutum’ (CMhm) DNA.
+Additionally, the rRNA internal transcribed spacer 1 locus of Leishmania infantum was partially sequenced and phylogeny showed it to cluster with species derived from dogs in Italy and Uzbekistan, and a human in France.
+Clinical signs resolved in the second month of treatment with no deterioration 8 months post-treatment cessation.
+Quantitative PCR and ELISA were used to monitor L infantum blood DNA and antibody levels.
+The cat had high L infantum DNA levels pretreatment that gradually declined during treatment but increased 8 months post-treatment cessation.
+Similarly, ELISA revealed high levels of antibodies pretreatment, which gradually declined during treatment and increased slightly 8 months post-treatment cessation.
+RELEVANCE AND NOVEL INFORMATION: To our knowledge, this is the first clinical report of a cat with leishmaniosis with H felis and CMhm coinfections.
+The high L infantum DNA levels post-treatment cessation might indicate that although the lesions had resolved, prolonged or an alternative treatment could have been considered.
+In today’s global economy and affordable vacation travel, it is increasingly important that visitors to another country and their physician be familiar with emerging infections, infections unique to a specific geographic region, and risks related to the process of travel.
+A recent review addressing common causes of fever in travelers provides important information for the general population Thwaites and Day (N Engl J Med 376:548-560, 2017).
+This review covers critical infectious and management concerns specifically related to travel for patients with PIDD.
+This review will discuss the context of the changing landscape of infections, highlight specific infections of concern, and profile distinct infection phenotypes in patients who are immune compromised.
+The organization of this review will address the environment driving emerging infections and several concerns unique to patients with PIDD.
+The first section addresses general considerations, the second section profiles specific infections organized according to mechanism of transmission, and the third section focuses on unique phenotypes and unique susceptibilities in patients with PIDDs.
+Reference tables provide easily accessible information on a broader range of infections than is described in the text.
+We have examined the possibility to encode an arbitrary pair of protein domains as a dual gene, with the shorter coding sequence completely embedded in the longer one.
+For 500 × 500 domain pairs (X, Y), we computationally designed homologous pairs (X′, Y′) coded this way, using an algorithm that provably maximizes the sequence similarity between (X′, Y′) and (X, Y).
+Three schemes were considered, with X′ and Y′ coded on the same or complementary strands.
+For 16% of the pairs, an overlapping coding exists where the level of homology of X′, Y′ to the natural proteins represents an E-value of 10(−10) or better.
+Thus, for an arbitrary domain pair, it is surprisingly easy to design homologous sequences that can be encoded as a fully-overlapping gene pair.
+The algorithm is general and was used to design 200 triple genes, with three proteins encoded by the same DNA segment.
+The ease of design suggests overlapping genes may have occurred frequently in evolution and could be readily used to compress or constrain artificial genomes.
+BACKGROUND: We compared in a single mixed intensive care unit (ICU) patients with influenza A(H1N1) pdm09 between pandemic and postpandemic periods.
+RESULTS: Seventy-six influenza A(H1N1) pdm09 patients were admitted to the ICU: 16 during the pandemic period and 60 during the postpandemic period.
+Postpandemic patients were significantly older (60 years vs. 43 years, p < 0.001) and less likely to have epilepsy or other neurological diseases compared with pandemic patients (5 [8.3%] vs. 6 [38%], respectively; p = 0.009).
+Postpandemic patients were more likely than pandemic patients to have cardiovascular disease (24 [40%] vs. 1 [6%], respectively; p = 0.015), and they had higher scores on APACHE II (17 [13–22] vs. 14 [10–17], p = 0.002) and SAPS II (40 [31–51] vs. 31 [25–35], p = 0.002) upon admission to the ICU.
+Postpandemic patients had higher maximal SOFA score (9 [5–12] vs. 5 [4–9], respectively; p = 0.03) during their ICU stay.
+Postpandemic patients had more often septic shock (40 [66.7%] vs. 8 [50.0%], p = 0.042), and longer median hospital stays (15.0 vs. 8.0 days, respectively; p = 0.006).
+CONCLUSIONS: Postpandemic ICU-treated A(H1N1) pdm09 influenza patients were older and developed more often septic shock and had longer hospital stays than influenza patients during the 2009 pandemic.
+We investigated the spatiotemporal dynamics of HSV genome transport during the initiation of infection using viruses containing bioorthogonal traceable precursors incorporated into their genomes (HSV(EdC)).
+In vitro assays revealed a structural alteration in the capsid induced upon HSV(EdC) binding to solid supports that allowed coupling to external capture agents and demonstrated that the vast majority of individual virions contained bioorthogonally-tagged genomes.
+Using HSV(EdC) in vivo we reveal novel aspects of the kinetics, localisation, mechanistic entry requirements and morphological transitions of infecting genomes.
+Uncoating and nuclear import was observed within 30 min, with genomes in a defined compaction state (ca.
+Free cytosolic uncoated genomes were infrequent (7–10% of the total uncoated genomes), likely a consequence of subpopulations of cells receiving high particle numbers.
+Uncoated nuclear genomes underwent temporal transitions in condensation state and while ICP4 efficiently associated with condensed foci of initial infecting genomes, this relationship switched away from residual longer lived condensed foci to increasingly decondensed genomes as infection progressed.
+Inhibition of transcription had no effect on nuclear entry but in the absence of transcription, genomes persisted as tightly condensed foci.
+Ongoing transcription, in the absence of protein synthesis, revealed a distinct spatial clustering of genomes, which we have termed genome congregation, not seen with non-transcribing genomes.
+Genomes expanded to more decondensed forms in the absence of DNA replication indicating additional transitional steps.
+During full progression of infection, genomes decondensed further, with a diffuse low intensity signal dissipated within replication compartments, but frequently with tight foci remaining peripherally, representing unreplicated genomes or condensed parental strands of replicated DNA.
+Uncoating and nuclear entry was independent of proteasome function and resistant to inhibitors of nuclear export.
+Together with additional data our results reveal new insight into the spatiotemporal dynamics of HSV genome uncoating, transport and organisation.
+Aphid saliva plays important roles in aphid-host interactions, such as assisting aphid digestion, detoxification, activating or suppressing plant defenses.
+The grain aphid, Sitobion avenae, is one of the most devastating pests of cereals worldwide.
+Of the all obtained unigenes, 15,833(47.86%) and 10,829(32.73%) unigenes showed high similarity to known proteins in Nr and Swiss-Prot databases respectively.
+526 unigenes were predicted to encode secretory proteins, including some digestive and detoxifying enzymes and potential effectors.
+The RT-PCR and RT-qPCR results showed that all of the 15 most highly expressed putative secretory proteins specifically expressed in salivary glands.
+Interestingly, 11 of the 15 most highly expressed putative secretory proteins were still not matched to function-known proteins.
+We also detected the expression of 9 interested putative secretory proteins in aphid different tissues, including some digestive and detoxifying enzymes, effectors and Ca(2+) binding proteins.
+These findings provide a further insight into the identification of potential effectors involving in aphid-cereals interactions.
+In this study, RNA-Seq technology was applied to investigate the transcriptome-wide changes of DF-1 cells upon ARV infection at the middle stage.
+RESULTS: Total RNA of ARV-infected or mock-infected samples at 10 and 18 h post infection (hpi) was extracted to build RNA-Seq datasets.
+Analysis of the sequencing data revealed that the expressions of numerous genes were altered, and a panel of differentially expressed genes were confirmed with RT-qPCR.
+At 10 hpi, 104 genes were down-regulated and 64 were up-regulated, while the expressions of 47 genes were increased and only one was down-regulated, which may play a role in retinoic acid biosynthesis, at 18 hpi in the ARV-infected cells.
+The similar profiles of up-regulated genes between the two groups of infected cells suggest that ARV infection activated a prolonged antiviral response of host cells.
+CONCLUSIONS: Overall, the differential expression profile presented in this study can be used to expand our understanding of the comprehensive interactions between ARV and the host cells, and may be helpful for us to reveal the pathogenic mechanism on the molecular level.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12864-017-4310-5) contains supplementary material, which is available to authorized users.
+Liquid–liquid phase separation (LLPS) is thought to contribute to the establishment of many biomolecular condensates, eukaryotic cell structures that concentrate diverse macromolecules but lack a bounding membrane.
+RNA granules control RNA metabolism and comprise a large class of condensates that are enriched in RNA-binding proteins and RNA molecules.
+Many RNA granule proteins are composed of both modular domains and intrinsically disordered regions (IDRs) having low amino acid sequence complexity.
+Phase separation of these molecules likely plays an important role in the generation and stability of RNA granules.
+To understand how folded domains and IDRs can cooperate to modulate LLPS, we generated a series of engineered proteins.
+These were based on fusions of an IDR derived from the RNA granule protein FUS (fused in sarcoma) to a multivalent poly-Src homology 3 (SH3) domain protein that phase-separates when mixed with a poly-proline–rich-motif (polyPRM) ligand.
+We found that the wild-type IDR promotes LLPS of the polySH3–polyPRM system, decreasing the phase separation threshold concentration by 8-fold.
+Systematic mutation of tyrosine residues in Gly/Ser-Tyr-Gly/Ser motifs of the IDR reduced this effect, depending on the number but not on the position of these substitutions.
+Mutating all tyrosines to non-aromatic residues or phosphorylating the IDR raised the phase separation threshold above that of the unmodified polySH3–polyPRM pair.
+These results show that low-complexity IDRs can modulate LLPS both positively and negatively, depending on the degree of aromaticity and phosphorylation status.
+Our findings provide plausible mechanisms by which these sequences could alter RNA granule properties on evolutionary and cellular timescales.
+CONTEXT: During the Ebola outbreak in West Africa in 2014-2015, close cooperation between the curative sector and the public health sector in the Netherlands was necessary for timely identification, referral, and investigation of patients with suspected Ebola virus disease (EVD).
+OBJECTIVE: In this study, we evaluated experiences in preparedness among stakeholders of both curative and public health sectors to formulate recommendations for optimizing preparedness protocols.
+DESIGN: In focus group sessions and semistructured interviews, experiences of curative and public health stakeholders about the regional and national process of preparedness and response were listed.
+Timeliness recordings of all referred patients with suspected EVD (13) were collected from first date of illness until arrival in the referral academic hospital.
+RESULTS: Ebola preparedness was considered extensive compared with the risk of an actual patient, however necessary.
+More standardization of regional preparation and operational guidelines was requested, as well as nationally standardized contingency criteria, and the National Centre for Infectious Disease Control was expected to coordinate the development of these guidelines.
+For the timeliness of referred patients with suspected EVD, the median delay between first date of illness until triage was 2.0 days (range: 0-10 days), and between triage and arrival in the referral hospital, it was 5.0 hours (range: 2-7.5 hours).
+CONCLUSIONS: Coordination between the public health sector and the curative sector needs improvement to reduce delay in patient management in emerging infectious diseases.
+Standardization of preparedness and response practices, through guidelines for institutional preparedness and blueprints for regional and national coordination, is necessary, as preparedness for emerging infectious diseases needs a multidisciplinary approach overarching both the public health sector and the curative sector.
+In the Netherlands a national platform for preparedness is established, in which both the curative sector and public health sector participate, in order to implement the outcomes of this study.
+Hand, foot and mouth disease (HFMD) is a childhood disease causing large outbreaks frequently in Asia and occasionally in Europe and the US.
+The incubation period of HFMD was typically described as about 3–7 days but empirical evidence is lacking.
+In this study, we estimated the incubation period of HFMD from school outbreaks in Hong Kong, utilizing information on symptom onset and sick absence dates of students diagnosed with HFMD.
+Based on the best-fitted distributions, the estimated median incubation periods were 4.4 (95% CI 3.8–5.1) days, 4.7 (95% CI 4.5–5.1) days and 5.7 (95% CI 4.6–7.0) days for children in kindergartens, primary schools and secondary schools respectively.
+From the fitted distribution, the estimated incubation periods can be longer than 10 days for 8.8% and 23.2% of the HFMD cases in kindergarten and secondary schools respectively.
+Our results show that the incubation period of HFMD for secondary schools students can be longer than the ranges commonly described.
+An extended period of enhanced personal hygiene practice and disinfection of the environment may be needed to control outbreaks.
+OBJECTIVES: The objective of these recommendations is to highlight the importance of infection prevention and control in ultrasound (US), including diagnostic and interventional settings.
+METHODS: Review of available publications and discussion within a multidisciplinary group consistent of radiologists and microbiologists, in consultation with European patient and industry representatives.
+Any equipment in direct patient contact must be cleaned and disinfected prior to first use and after every examination.
+As outlined in presented flowcharts, low level disinfection is sufficient for standard US on intact skin.
+For all other minor and major interventional procedures as well as all endo-cavity US, high level disinfection is mandatory.
+Dedicated transducer covers must be used when transducers are in contact with mucous membranes or body fluids and sterile gel should be used inside and outside covers.
+CONCLUSIONS: Good standards of basic hygiene and thorough decontamination of all US equipment as well as appropriate use of US gel and transducer covers are essential to keep patients safe.
+Significant concerns have been raised owing to the rapid global spread of infection and disease caused by the mosquito-borne Zika virus (ZIKV).
+Recent studies suggest that ZIKV can also be transmitted sexually, further increasing the exposure risk for this virus.
+Associated with this spread is a dramatic increase in cases of microcephaly and additional congenital abnormalities in infants of ZIKV-infected mothers, as well as a rise in the occurrence of Guillain Barre’ syndrome in infected adults.
+In this study, we generate and evaluate the in vivo efficacy of a novel, synthetic, DNA vaccine targeting the pre-membrane+envelope proteins (prME) of ZIKV.
+Following initial in vitro development and evaluation studies of the plasmid construct, mice and non-human primates were immunised with this prME DNA-based immunogen through electroporation-mediated enhanced DNA delivery.
+In mice lacking receptors for interferon (IFN)-α/β (designated IFNAR(−/−)) immunisation with this DNA vaccine induced, following in vivo viral challenge, 100% protection against infection-associated weight loss or death in addition to preventing viral pathology in brain tissue.
+In addition, passive transfer of non-human primate anti-ZIKV immune serum protected IFNAR(−/−) mice against subsequent viral challenge.
+This study in NHP and in a pathogenic mouse model supports the importance of immune responses targeting prME in ZIKV infection and suggests that additional research on this vaccine approach may have relevance for ZIKV control and disease prevention in humans.
+Many viral pathogens are persistently transmitted by insect vectors and cause agricultural or health problems.
+Generally, an insect vector can use autophagy as an intrinsic antiviral defense mechanism against viral infection.
+Whether viruses can evolve to exploit autophagy to promote their transmission by insect vectors is still unknown.
+Here, we show that the autophagic process is triggered by the persistent replication of a plant reovirus, rice gall dwarf virus (RGDV) in cultured leafhopper vector cells and in intact insects, as demonstrated by the appearance of obvious virus-containing double-membrane autophagosomes, conversion of ATG8-I to ATG8-II and increased level of autophagic flux.
+Such virus-containing autophagosomes seem able to mediate nonlytic viral release from cultured cells or facilitate viral spread in the leafhopper intestine.
+Applying the autophagy inhibitor 3-methyladenine or silencing the expression of Atg5 significantly decrease viral spread in vitro and in vivo, whereas applying the autophagy inducer rapamycin or silencing the expression of Torc1 facilitate such viral spread.
+Furthermore, we find that activation of autophagy facilitates efficient viral transmission, whereas inhibiting autophagy blocks viral transmission by its insect vector.
+Together, these results indicate a plant virus can induce the formation of autophagosomes for carrying virions, thus facilitating viral spread and transmission by its insect vector.
+We believe that such a role for virus-induced autophagy is common for vector-borne persistent viruses during their transmission by insect vectors.
+BACKGROUND: The 2014–2016 Ebola crisis in West Africa had approximately eight times as many reported deaths as the sum of all previous Ebola outbreaks.
+The outbreak magnitude and occurrence of multiple Ebola cases in at least seven countries beyond Liberia, Sierra Leone, and Guinea, hinted at the possibility of broad-scale transmission of Ebola.
+MAIN TEXT: Using a modeling tool developed by the US Centers for Disease Control and Prevention during the Ebola outbreak, we estimated the number of Ebola cases that might have occurred had the disease spread beyond the three countries in West Africa to cities in other countries at high risk for disease transmission (based on late 2014 air travel patterns).
+We estimated Ebola cases in three scenarios: a delayed response, a Liberia-like response, and a fast response scenario.
+Based on our estimates of the number of Ebola cases that could have occurred had Ebola spread to other countries beyond the West African foci, we emphasize the need for improved levels of preparedness and response to public health threats, which is the goal of the Global Health Security Agenda.
+Our estimates suggest that Ebola could have potentially spread widely beyond the West Africa foci, had local and international health workers and organizations not committed to a major response effort.
+Our results underscore the importance of rapid detection and initiation of an effective, organized response, and the challenges faced by countries with limited public health systems.
+Actionable lessons for strengthening local public health systems in countries at high risk of disease transmission include increasing health personnel, bolstering primary and critical healthcare facilities, developing public health infrastructure (e.g.
+With stronger local public health systems infectious disease outbreaks would still occur, but their rapid escalation would be considerably less likely, minimizing the impact of public health threats such as Ebola.
+CONCLUSIONS: The Ebola outbreak could have potentially spread to other countries, where limited public health surveillance and response capabilities may have resulted in additional foci.
+Health security requires robust local health systems that can rapidly detect and effectively respond to an infectious disease outbreak.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s40249-017-0373-4) contains supplementary material, which is available to authorized users.
+Mitochondrial function is essential to meet metabolic demand of pancreatic beta cells respond to high nutrient stress.
+Mitophagy is an essential component to normal pancreatic β-cell function and has been associated with β-cell failure in Type 2 diabetes (T2D).
+Our previous studies have indicated that mitochondrial Rho (Miro) GTPase-mediated mitochondrial dysfunction under high nutrient stress leads to NOD-like receptor 3 (NLRP3)-dependent proinflammatory responses and subsequent insulin resistance.
+Here we show firstly that the expression of Miro is reduced in human T2D and mouse db/db islets and in INS-1 cell line exposed to high glucose and palmitate.
+β-cell specific ablation of Miro1 (Miro1f/f: Rip-cre mice, or (IKO) under high nutrient stress promotes the development of hyperglycemia.
+β-cells from IKO mice display an inhibition of mitophagy under oxidative stress and induces mitochondrial dysfunction.
+Dysfunctional mitophagy in IKO mice is represented by damaged islet beta cell mitochondrial and secretory capacity, unbalanced downstream MKK-JNK signalling without affecting the levels of MEK, ERK or p38 activation and subsequently, impaired insulin secretion signaling via inhibition IRS-AKT-Foxo1 pathway, leading to worsening glucose tolerance in these mice.
+Thus, these data suggest that Miro1 may be responsible for mitophagy deficiency and β-cell dysfunction in T2D and that strategies target Miro1 in vivo may provide a therapeutic target to enhance β-cell mitochondrial quality and insulin secretion to ameliorate complications associated with T2D.
+Kaposi’s sarcoma associated herpesvirus (KSHV) regulates the host cellular environment to establish life-long persistent infection by manipulating cellular signaling pathways, with approximately 1- 5% of cells undergoing lytic reactivation during the course of infection.
+Egr-1 (Early Growth Response Factor-1) is one such cellular transcription factor, which gets phosphorylated during the lytic phase of viral life cycle to perpetrate its function.
+This study demonstrates the mechanism of how Egr-1 mediates transcription of the immediate early gene, RTA (Replication and transcription activator), which is the lytic switch gene of KSHV.
+Also, an increase in Egr-1 phosphorylation led to a higher virion production, which was suppressed in the presence of p38 and Raf inhibitors.
+Reporter assays showed that coexpression of Egr-1 and CBP (CREB-binding protein) enhances RTA promoter activity as compared to the expression of either Egr-1 or CBP alone.
+Binding of Egr-1 and CBP at RTA promoter was analyzed by chromatin immunoprecipitation assay (ChIP), which showed an enhanced accumulation during viral reactivation.
+Mutation in Egr-1 binding site of the RTA promoter eliminated Egr-1 response on promoter activation.
+Furthermore, de novo infection of THP-1 (monocytic) and HUVECs (endothelial) cells showed an upregulation of Egr-1 phosphorylation, whereas depletion of Egr-1 reduced the mRNA levels of RTA during primary infection.
+Together, these results demonstrate a cooperative role of Egr-1 and CBP in mediating RTA transcription, which significantly improves our understanding of the involvement of cellular factors controlling RTA transcription in KSHV pathogenesis.
+Recombinant vaccine strain-derived measles virus (MV) is clinically tested both as vaccine platform to protect against other pathogens and as oncolytic virus for tumor treatment.
+To investigate the potential synergism in anti-tumoral efficacy of oncolytic and vaccine properties, we chose Ovalbumin and an ideal tumor antigen, claudin-6, for pre-clinical proof of concept.
+To enhance immunogenicity, both antigens were presented by retroviral virus-like particle produced in situ during MV-infection.
+All recombinant MV revealed normal growths, genetic stability, and proper expression and presentation of both antigens.
+These immune responses significantly inhibited metastasis formation or increased therapeutic efficacy compared to control MV in respective novel in vivo tumor models using syngeneic B16-hCD46/mCLDN6 murine melanoma cells.
+These data indicate the potential of MV to trigger selected tumor antigen-specific immune responses on top of direct tumor lysis for enhanced efficacy.
+BACKGROUND: Over the last decade, capacity for influenza surveillance and research in West Africa has strengthened.
+Data from these surveillance systems showed influenza A(H1N1)pdm09 circulated in West Africa later than in other regions of the continent.
+METHODS: We contacted 11 West African countries to collect information about their influenza surveillance systems (number of sites, type of surveillance, sampling strategy, populations sampled, case definitions used, number of specimens collected and number of specimens positive for influenza viruses) for the time period January 2010 through December 2012.
+RESULTS: Of the 11 countries contacted, 8 responded: Burkina Faso, Cote d’Ivoire, Mali, Mauritania, Niger, Nigeria, Sierra Leone and Togo.
+Countries used standard World Health Organization (WHO) case definitions for influenza-like illness (ILI) and severe acute respiratory illness (SARI) or slight variations thereof.
+Seven countries conducted SARI surveillance and collected 3114 specimens of which 209 (7%) were positive for influenza viruses.
+Among influenza-positive SARI patients, 132 (63%) were influenza A [68 influenza A(H1N1)pdm09, 64 influenza A(H3N2)] and 77 (37%) were influenza B.
+All eight countries conducted ILI surveillance and collected 20,375 specimens, of which 2278 (11%) were positive for influenza viruses.
+Among influenza-positive ILI patients, 1431 (63%) were influenza A [820 influenza A(H1N1)pdm09, 611 influenza A(H3N2)] and 847 (37%) were influenza B.
+A majority of SARI and ILI case-patients who tested positive for influenza (72% SARI and 59% ILI) were children aged 0–4 years, as were a majority of those enrolled in surveillance.
+The seasonality of influenza and the predominant influenza type or subtype varied by country and year.
+CONCLUSIONS: Influenza A(H1N1)pdm09 continued to circulate in West Africa along with influenza A(H3N2) and influenza B during 2010–2012.
+Although ILI surveillance systems produced a robust number of samples during the study period, more could be done to strengthen surveillance among hospitalized SARI case-patients.
+More data on risk groups for severe influenza in West Africa are needed to help shape influenza prevention and clinical management policies and guidelines.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12879-017-2839-1) contains supplementary material, which is available to authorized users.
+OBJECTIVE: For the decision-making process regarding introduction of new vaccines into the National Immunisation Programme (NIP), advance insight into the potential acceptance among the population is relevant.
+We studied the intention of parents to have their child vaccinated against four diseases not currently covered by the NIP in the Netherlands.
+The results on varicella have been published before; this article adds the results on vaccination against rotavirus gastroenteritis, meningococcal B disease, and seasonal influenza.
+RESULTS: We invited a random sample from the national immunisation register of 1500 parents for an internet survey which was completed by 491 parents (33% response).
+The intention to vaccinate was highest for meningococcal B disease (83% positive intention), followed by rotavirus gastroenteritis (38%), and lowest for varicella (28%) and seasonal influenza (15%).
+Prediction analyses were performed to determine which out of seven questionnaire statements was most informative in predicting the intention to vaccinate.
+Main drivers of intention were the perceived importance of vaccination against the particular disease and the perception of whether or not the disease is severe enough to justify vaccination.
+The results of this study can be informative in the decision-making process whether or not to introduce new vaccines into the NIP.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13104-017-3004-z) contains supplementary material, which is available to authorized users.
+Nonspecific interstitial pneumonia (NSIP) is characterised by interstitial infiltration of lymphocytes and varying amounts of interstitial fibrosis.
+In this study, 50 patients with histopathologically confirmed NSIP from Peking Union Medical College Hospital between April 2003 to December 2012 were retrospectively analyzed.
+Using immunohistochemical analyses, CD20+ B cells were counted in the lymphoid follicles, perivascular, interstitial, and peribronchiolar regions of lung tissure.
+The number of follicular CD20+ lymphocytes was higher in the fibrosing than cellular NSIP pattern [255.08 (132.92–449.71) vs. 121.33 (63.54–282.88)/0.1 mm(2), p = 0.017].
+After 1 year of therapy, the follicular CD20+ lymphocytes were significantly higher in patients whose forced vital capacity (FVC) worsened as compared to those who improved (p = 0.014).
+Additionally, follicular CD20+ lymphocytes were negatively correlated with the post-treatment percentage change in FVC (rho = −0.397, p = 0.004).
+These results suggested that pulmonary follicular CD20+ lymphocytes were correlated with the fibrosing pattern of NSIP and predicted less clinical improvement after treatment.
+OBJECTIVE: This study was designed to estimate the prevalence of E. coli which is the main cause of colisepticemia and the potential risk factors associated with the disease.
+A total of 74 calves less than 6 months age were selected for this study.
+RESULT: Out of 74 calves selected for this study, 6 (8.11%) were positive for septicemic E. coli.
+Higher prevalence of 5 (8.93%) was recorded in Holstein Friesian breed than Boran breed 1 (5.56%).
+Higher prevalence of E. coli revealed below age of 30 days (17.39%) than calves aged between 30 and 90 days (8.33%) and above 90 days (0.00%).
+Parity showed a significant difference in prevalence of E. coli (P < 0.05) in which infection increased with number of parity.
+Sex of the animal showed no association with infection of the calves (P > 0.05).
+Diarrheic calves showed higher prevalence (33.3%) than non-diarrheic calves (4.62%) with strong statistical association (P < 0.05).
+The present study showed a high prevalence of septicemic E. coli in the farm and intervention is strongly recommended.
+Patients who survive influenza A (H7N9) virus infection are at risk of physical and psychological complications of lung injury and multi-organ dysfunction.
+However, there were no prospectively individualized assessments of physiological, functional and quality-of-life measures after hospital discharge.
+The current study aims to assess the main determinants of functional disability of these patients during the follow-up.
+Fifty-six influenza A (H7N9) survivors were investigated during the 2-year after discharge from the hospital.
+Results show interstitial change and fibrosis on pulmonary imaging remained 6 months after hospital discharge.
+Both ventilation and diffusion dysfunction improved, but restrictive and obstructive patterns on ventilation function test persisted throughout the follow-up period.
+For patients with acute respiratory distress syndrome lung functions improved faster during the first six months.
+Role-physical and Role-emotional domains in the 36-Item Short-Form Health Survey were worse than those of a sex- and age-matched general population group.
+The quality of life of survivors with ARDS was lower than those with no ARDS.
+Our findings suggest that pulmonary function and imaging findings improved during the first 6 months especially for those with ARDS, however long-term lung disability and psychological impairment in H7N9 survivors persisted at 2 years after discharge from the hospital.
+Human rhinovirus (HRV) remains a leading cause of several human diseases including the common cold.
+Despite considerable research over the last 60 years, development of an effective vaccine to HRV has been viewed by many as unfeasible due, in part, to the antigenic diversity of circulating HRVs in nature.
+Over 150 antigenically distinct types of HRV are currently known which span three species: HRV A, HRV B, and HRV C. Early attempts to develop a rhinovirus vaccine have shown that inactivated HRV is capable of serving as a strong immunogen and inducing neutralizing antibodies.
+Yet, limitations to virus preparation and recovery, continued identification of antigenic variants of HRV, and logistical challenges pertaining to preparing a polyvalent preparation of the magnitude required for true efficacy against circulating rhinoviruses continue to prove a daunting challenge.
+In this review, we describe HRV biology, antigenic diversity, and past and present advances in HRV vaccine design.
+Hepatitis C Virus (HCV) infects 2% of the world’s population and is the leading cause of liver disease and liver transplantation.
+It poses a serious and growing worldwide public health problem that will only be partially addressed with the introduction of new antiviral therapies.
+The introduction of a HCV vaccine has been predicted, using simulation models in a high risk population, to have a significant effect on reducing the incidence of HCV.
+A vaccine with 50 to 80% efficacy targeted to high-risk intravenous drug users could dramatically reduce HCV incidence in this population.
+Virus like particles (VLPs) are composed of viral structural proteins which self-assemble into non-infectious particles that lack genetic material and resemble native viruses.
+Thus, VLPs represent a safe and highly immunogenic vaccine delivery platform able to induce potent adaptive immune responses.
+Currently, many VLP-based vaccines have entered clinical trials, while licensed VLP vaccines for hepatitis B virus (HBV) and human papilloma virus (HPV) have been in use for many years.
+The HCV core, E1 and E2 proteins can self-assemble into immunogenic VLPs while inclusion of HCV antigens into heterogenous (chimeric) VLPs is also a promising approach.
+These VLPs are produced using different expression systems such as bacterial, yeast, mammalian, plant, or insect cells.
+Here, this paper will review HCV VLP-based vaccines and their immunogenicity in animal models as well as the different expression systems used in their production.
+The inflammatory bowel diseases (IBDs), including Crohn’s disease (CD) and ulcerative colitis (UC), are chronic inflammatory conditions of the gastrointestinal tract and involve a complicated reciprocity of environmental, genetic, and immunologic factors.
+Despite substantial advances in the foundational understanding of the immunological pathogenesis of IBD, the detailed mechanism of the pathological progression in IBD remains unknown.
+In addition to Th1/Th2 cells, whose role in IBD has been previously well defined, recent evidence indicates that Th17 cells and Tregs also play a crucial role in the development of IBD.
+Diets which contain excess sugars, salt, and fat may also be important actors in the pathogenesis of IBD, which may be the cause of high IBD incidence in western developed and industrialized countries.
+Up until now, the reason for the variance in prevalence of IBD between developed and developing countries has been unknown.
+This is partly due to the increasing popularity of western diets in developing countries, which makes the data harder to interpret.
+The enterocrinins glucagon-like peptides (GLPs), including GLP-1 and GLP-2, exhibit notable benefits on lipid metabolism, atherosclerosis formation, plasma glucose levels, and maintenance of gastric mucosa integrity.
+In addition to the regulation of nutrient metabolism, the emerging role of GLPs and their degrading enzyme dipeptidyl peptidase-4 (DPP-4) in gastrointestinal diseases has gained increasing attention.
+While 80% of deaths occur within the first 24 hours after trauma, 20% occur later and are mainly due to healthcare-associated infections, including ventilator-associated pneumonia (VAP).
+Preventing underinflation of the tracheal cuff is recommended to reduce microaspiration, which plays a major role in the pathogenesis of VAP.
+Automatic devices facilitate the regulation of tracheal cuff pressure, and their implementation has the potential to reduce VAP.
+The objective of this work is to determine whether continuous regulation of tracheal cuff pressure using a pneumatic device reduces the incidence of VAP compared with intermittent control in severe trauma patients.
+METHODS AND ANALYSIS: This multicentre randomised controlled and open-label trial will include patients suffering from severe trauma who are admitted within the first 24 hours, who require invasive mechanical ventilation to longer than 48 hours.
+Their tracheal cuff pressure will be monitored either once every 8 hours (control group) or continuously using a pneumatic device (intervention group).
+The primary end point is the proportion of patients that develop VAP in the intensive care unit (ICU) at day 28.
+The secondary end points include the proportion of patients that develop VAP in the ICU, early (≤7 days) or late (>7 days) VAP, time until the first VAP diagnosis, the number of ventilator-free days and antibiotic-free days, the length of stay in the ICU, the proportion of patients with ventilator-associated events and that die during their ICU stay.
+ETHICS AND DISSEMINATION: This protocol has been approved by the ethics committee of Poitiers University Hospital, and will be carried out according to the principles of the Declaration of Helsinki and the Good Clinical Practice guidelines.
+The results of this study will be disseminated through presentation at scientific conferences and publication in peer-reviewed journals.
+For most environmental pollutants, including perchloroethylene (PERC), experimental data are lacking, resulting in default assumptions being used to account for variability in toxicokinetics and toxicodynamics.
+OBJECTIVE: We quantitatively examined the relationship between PERC toxicokinetics and toxicodynamics at the population level to test whether individuals with increased oxidative metabolism are be more sensitive to hepatotoxicity following PERC exposure.
+METHODS: Male mice from 45 strains of the Collaborative Cross (CC) were orally administered a single dose of PERC ([Formula: see text]) or vehicle (Alkamuls-EL620) and euthanized at various time points ([Formula: see text] /strain/time).
+Concentration–time profiles were generated for PERC and its primary oxidative metabolite trichloroacetate (TCA) in multiple tissues.
+RESULTS: Significant variability among strains was observed in toxicokinetics of PERC and TCA in every tissue examined.
+Based on area under the curve (AUC), the range of liver TCA levels spanned nearly an order of magnitude ([Formula: see text]-fold).
+Toxicodynamic phenotyping revealed an effect of PERC on bodyweight loss, induction of peroxisome proliferator activated receptor-alpha (PPAR [Formula: see text])-regulated genes, and dysregulation of hepatic lipid homeostasis.
+Clustering was observed among a) liver levels of PERC, TCA, and triglycerides; b) TCA levels in liver and kidney; and c) TCA levels in serum, brain, fat, and lung.
+CONCLUSIONS: Using the CC mouse population model, we have demonstrated a complex and highly variable relationship between PERC and TCA toxicokinetics and toxicodynamics at the population level.
+Mathematical models provide a quantitative framework with which scientists can assess hypotheses on the potential underlying mechanisms that explain patterns in observed data at different spatial and temporal scales, generate estimates of key kinetic parameters, assess the impact of interventions, optimize the impact of control strategies, and generate forecasts.
+We review and illustrate a simple data assimilation framework for calibrating mathematical models based on ordinary differential equation models using time series data describing the temporal progression of case counts relating, for instance, to population growth or infectious disease transmission dynamics.
+In contrast to Bayesian estimation approaches that always raise the question of how to set priors for the parameters, this frequentist approach relies on modeling the error structure in the data.
+We discuss issues related to parameter identifiability, uncertainty quantification and propagation as well as model performance and forecasts along examples based on phenomenological and mechanistic models parameterized using simulated and real datasets.
+Understanding the determinants of polio transmission and its large-scale epidemiology remains a public health priority.
+Despite a 99% reduction in annual wild poliovirus (WPV) cases since 1988, tackling the last 1% has proven difficult.
+We identified key covariates of geographical variation in polio transmission patterns by relating country-specific annual disease incidence to demographic, socio-economic and environmental factors.
+We assessed the relative contributions of these variables to the performance of computer-generated models for predicting polio transmission.
+We also examined the effect of spatial coupling on the polio extinction frequency in islands relative to larger land masses.
+Access to sanitation, population density, forest cover and routine vaccination coverage were the strongest predictors of polio incidence, however their relative effect sizes were inconsistent geographically.
+The effect of climate variables on polio incidence was negligible, indicating that a climate effect is not identifiable at the annual scale, suggesting a role for climate in shaping the transmission seasonality rather than intensity.
+We found polio fadeout frequency to depend on both population size and demography, which should therefore be considered in policies aimed at extinction.
+Recognition of this variation is important for the maintenance of population immunity in a post-polio era.
+Decitabine has been explored as a reduced‐intensity therapy for older or unfit patients with acute myeloid leukemia (AML).
+To better understand the risk of infections during decitabine treatment, we retrospectively examined the culture results from each infection‐related serious adverse event that occurred among 85 AML and myelodysplastic syndromes (MDS) patients treated in a prospective clinical study using 10‐day cycles of decitabine at Washington University School of Medicine.
+Culture results were available for 163 infection‐related complications that occurred in 70 patients: 90 (55.2%) events were culture‐negative, 32 (19.6%) were gram‐positive bacteria, 20 (12.3%) were gram‐negative bacteria, 12 (7.4%) were mixed, 6 (3.7%) were viral, 2 (1.2%) were fungal, and 1 (0.6%) was mycobacterial.
+On average, nearly one third of patients experienced an infection‐related complication with each cycle, and the incidence did not decrease during later cycles.
+In summary, in patients receiving 10‐day decitabine, infectious complications are common and may occur during any cycle of therapy.
+Although febrile events are commonly culture‐negative, gram‐positive infections are the most frequent source of culture‐positive infections, but gram‐negative infections represent a significant risk of mortality in AML and MDS patients treated with decitabine.
+They are able to carry a specific single stranded RNA (ssRNA) sequence of choice inside their capsid, thus protecting it against the effects of ubiquitous nucleases.
+Such particles are able to mimic ssRNA viruses and, thus, may serve as the process control for molecular detection and quantification of such agents in several kinds of matrices, vaccines and vaccine candidates, drug delivery systems, and systems for the display of immunologically active peptides or nanomachines.
+Currently, there are several different in vivo plasmid-driven packaging systems for production of MS2 PLP.
+In order to combine all the advantages of the available systems and to upgrade and simplify the production and purification of MS2 PLP, a one-plasmid double-expression His-tag system was designed.
+The described system utilizes a unique fusion insertional mutation enabling purification of particles using His-tag affinity.
+Using this new production system, highly pure MS2 PLP can be quickly produced and purified by a fast performance liquid chromatography (FPLC) approach.
+BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is a life-saving therapy in acute respiratory distress syndrome (ARDS) patients but is associated with complications and costs.
+Here, we validate various scores supposed to predict mortality and develop an optimized categorical model.
+METHODS: In a derivation cohort, 108 ARDS patients (2010–2015) on veno-venous ECMO were retrospectively analysed to assess four established risk scores (ECMOnet-Score, RESP-Score, PRESERVE-Score, Roch-Score) for mortality prediction (receiver operating characteristic analysis) and to identify by multivariable logistic regression analysis independent variables for mortality to yield the new PRESET-Score (PREdiction of Survival on ECMO Therapy-Score).
+This new score was then validated both in independent internal (n = 82) and external (n = 59) cohorts.
+RESULTS: The median (25%; 75% quartile) Sequential Organ Failure Assessment score was 14 (12; 16), Simplified Acute Physiology Score II was 62.5 (57; 72.8), median intensive care unit stay was 17 days (range 1–124), and mortality was 62%.
+Only the ECMOnet-Score (area under curve (AUC) 0.69) and the RESP-Score (AUC 0.64) discriminated survivors and non-survivors.
+Admission pH(a), mean arterial pressure, lactate, platelet concentrations, and pre-ECMO hospital stay were independent predictors of death and were used to build the PRESET-Score.
+The score’s internal (AUC 0.845; 95% CI 0.76–0.93; p < 0.001) and external (AUC 0.70; 95% CI 0.56–0.84; p = 0.008) validation revealed excellent discrimination.
+CONCLUSIONS: While our data confirm that both the ECMOnet-Score and the RESP-Score predict mortality in ECMO-treated ARDS patients, we propose a novel model also incorporating extrapulmonary variables, the PRESET-Score.
+This score predicts mortality much better than previous scores and therefore is a more precise choice for decision support in ARDS patients to be placed on ECMO.
+To explore the clinical characteristics of steroid-associated osteonecrosis of the femoral head (ONFH) presenting initially normal magnetic resonance imaging (MRI) results.
+This retrospective study examined data from 23 cases that suffered from ONFH but presented a normal image at the first MRI examination after corticosteroid therapy from June 2005 to December 2013.
+Data on protopathy, age, sex, time of pain onset, MRI examination, and initial diagnosis were collected and analyzed.
+Average time from steroid therapy to first MRI examination was 45.7 ± 25.5 days (range, 10–94 days).
+Of the 23 cases, 21 cases complained of discomfort and were misdiagnosed because of a normal initial MRI scan.
+Twelve hips progressed to collapse and 1 hip received lumbar discectomy when got the final diagnosis.
+Cases with continuous pain (9/21) presented with pain at a later time than those with intermittent pain (12/21), although the continuous pain cases were diagnosed earlier.
+Hantaan virus (HTNV) infections can cause severe hemorrhagic fever with renal syndrome (HFRS) in humans, which is associated with high fatality rates.
+Cytotoxic T cell (CTL) responses contribute to virus elimination; however, to date, HLA class I allele-restricted HTNV glycoprotein (GP) epitopes recognized by CTLs have not been reported, limiting our understanding of CTL responses against HTNV infection in humans.
+In this study, 34 HTNV GP nine-mer epitopes that may bind to HLA-A*0201 molecules were predicted using the BIMAS and SYFPEITHI database.
+Seven of the epitopes were demonstrated to bind to HLA-A*0201 molecules with high affinity via the T2 cell binding assay and were successfully used to synthesize peptide/HLA-A*0201 tetramers.
+The results of tetramer staining showed that the frequencies of each epitope-specific CTL were higher in patients with milder HFRS, which indicated that the epitopes may induce protective CTL responses after HTNV infection.
+IFN-γ-enzyme-linked immunospot analysis further confirmed the immunoreactivity of epitopes by eliciting epitope-specific IFN-γ-producing CTL responses.
+In an HTNV challenge trial, significant inhibition of HTNV replication characterized by lower levels of antigens and RNA loads was observed in major target organs (liver, spleen, and kidneys) of HLA-A2.1/K(b) transgenic mice pre-vaccinated with nonapeptides VV9 (aa8–aa16, VMASLVWPV), SL9 (aa996–aa1004, SLTECPTFL) and LL9 (aa358–aa366, LIWTGMIDL).
+Importantly, LL9 exhibited the best ability to induce protective CTL responses and showed a prominent effect on the kidneys, potentially preventing kidney injury after HTNV infection.
+Taken together, our results highlight that HTNV GP-derived HLA-A*0201-restricted epitopes could elicit protective CTL responses against the virus, and that epitope LL9 functions as an immunodominant protective epitope that may advance the design of safe and effective CTL-based HTNV peptide vaccines for humans.
+An infectious disease characterized with short bills and protruding tongues has attacked to meat ducks in China since March 2015, which has caused ducks poor growth and enormous economic losses to duck industry of China.
+As the genomic sequence analysis showed, this pathogen shared 90.8–94.6% of nucleotide identity with goose parvovirus (GPV), and it was called duck-origin novel goose parvovirus (N-GPV).
+In this study, a quantitative loop-mediated isothermal amplification (qLAMP) assay was developed for the rapid diagnosis of N-GPV.
+A set of four specific primers, two inner and two outer, were designed targeting at VP3 gene, which could be completed within 60 min at 65°C in water bath or on a real-time PCR instrument for quantitative analysis.
+Specificity test of LAMP assay showed that there was no cross-reactivity between N-GPV and other duck pathogens, and the detection limit of qLAMP assay was 1.0 × 10(2) copies/μL.
+The repeatability of this method was confirmed by inter-assay and intra-assay tests with variability ranging from 0.74 to 2.25%.
+The results have indicated that the qLAMP assay was a simple, rapid, accurate, sensitive, and specific method for detecting N-GPV, especially on field detection.
+OBJECTIVES: New point of care diagnostics are urgently needed to reduce the over-prescription of antimicrobials for bacterial respiratory tract infection (RTI).
+We performed a pilot cross sectional study to assess the feasibility of gas-capillary column ion mobility spectrometer (GC-IMS), for the analysis of volatile organic compounds (VOC) in exhaled breath to diagnose bacterial RTI in hospital inpatients.
+METHODS: 71 patients were prospectively recruited from the Acute Medical Unit of the Royal Liverpool University Hospital between March and May 2016 and classified as confirmed or probable bacterial or viral RTI on the basis of microbiologic, biochemical and radiologic testing.
+Breath samples were collected at the patient’s bedside directly into the electronic nose device, which recorded a VOC spectrum for each sample.
+Sparse principal component analysis and sparse logistic regression were used to develop a diagnostic model to classify VOC spectra as being caused by bacterial or non-bacterial RTI.
+RESULTS: Summary area under the receiver operator characteristic curve was 0.73 (95% CI 0.61–0.86), summary sensitivity and specificity were 62% (95% CI 41–80%) and 80% (95% CI 64–91%) respectively (p = 0.00147).
+CONCLUSIONS: GC-IMS analysis of exhaled VOC for the diagnosis of bacterial RTI shows promise in this pilot study and further trials are warranted to assess this technique.
+CD147 is an activation induced glycoprotein that promotes the secretion and activation of matrix metalloproteinases (MMPs) and is upregulated during the differentiation of macrophages.
+Interestingly, some of the molecular functions of CD147 rely on its glycosylation status: the highly glycosylated forms of CD147 induce MMPs whereas the lowly glycosylated forms inhibit MMP activation.
+Statins are hydroxy-methylglutaryl coenzyme A reductase inhibitors that block the synthesis of mevalonate, thereby inhibiting all mevalonate-dependent pathways, including isoprenylation, N-glycosylation and cholesterol synthesis.
+In this study, we investigated the role of statins in the inhibition of macrophage differentiation and the associated process of MMP secretion through modulation of CD147.
+We observed that differentiation of the human monocytic cell line THP-1 to a macrophage phenotype led to upregulation of CD147 and CD14 and that this effect was inhibited by statins.
+At the molecular level, statins altered CD147 expression, structure and function by inhibiting isoprenylation and N-glycosylation.
+In addition, statins induced a shift of CD147 from its highly glycosylated form to its lowly glycosylated form.
+This shift in N-glycosylation status was accompanied by a decrease in the production and functional activity of MMP-2 and MMP-9.
+In conclusion, these findings describe a novel molecular mechanism of immune regulation by statins, making them interesting candidates for autoimmune disease therapy.
+Much progress has been made investigating the role of ubiquitin ligases at the synapse, however very little is known about the deubiquitinating enzymes (DUBs) which remove ubiquitin from target proteins.
+Although there are far fewer DUBs than ubiquitin ligases encoded by the human genome, it is becoming clear that DUBs have very specific physiological functions, suggesting that DUB activity is tightly regulated in vivo.
+Many DUBs function as part of larger protein complexes, and multiple regulatory mechanisms exist to control the expression, localization and catalytic activity of DUBs.
+In this review article, we focus on the role of the DUB USP46 in the nervous system, and illustrate potential mechanisms of regulating DUBs by describing how USP46 is regulated by two WD40-repeat (WDR) proteins, WDR48/UAF1 and WDR20, based on recent structural studies and genetic analyses in vivo.
+Deciphering the way gene expression regulatory aspects are encoded in viral genomes is a challenging mission with ramifications related to all biomedical disciplines.
+Here, we aimed to understand how the evolution shapes the bacteriophage lambda genes by performing a high resolution analysis of ribosomal profiling data and gene expression related synonymous/silent information encoded in bacteriophage coding regions.
+We demonstrated evidence of selection for distinct compositions of synonymous codons in early and late viral genes related to the adaptation of translation efficiency to different bacteriophage developmental stages.
+Specifically, we showed that evolution of viral coding regions is driven, among others, by selection for codons with higher decoding rates; during the initial/progressive stages of infection the decoding rates in early/late genes were found to be superior to those in late/early genes, respectively.
+Moreover, we argued that selection for translation efficiency could be partially explained by adaptation to Escherichia coli tRNA pool and the fact that it can change during the bacteriophage life cycle.
+An analysis of additional aspects related to the expression of viral genes, such as mRNA folding and more complex/longer regulatory signals in the coding regions, is also reported.
+BACKGROUND: Human respiratory syncytial virus usually causes self-limiting upper respiratory infection and occasionally causes pneumonia in immunocompromised hosts.
+Respiratory syncytial virus-induced severe pneumonia or acute respiratory distress syndrome in immunocompetent adults has been rarely described.
+We report a case of respiratory syncytial virus-induced acute respiratory distress syndrome occurring in a previously healthy man successfully treated with orally administered ribavirin.
+CASE PRESENTATION: An 81-year-old previously healthy Korean man presented with cough, dyspnea, and febrile sensation.
+He had hypoxemia with diffuse ground glass opacity evident on chest radiography, which progressed and required mechanical ventilation.
+All microbiological tests were negative except multiplex real-time reverse transcriptase polymerase chain reaction using respiratory specimen, which was positive for human adenovirus.
+Under the diagnosis of respiratory syncytial virus-induced acute respiratory distress syndrome, orally administered ribavirin was administered and he recuperated completely without complications.
+CONCLUSION: This case demonstrates the potential usefulness of orally administered ribavirin as a therapeutic option for severe respiratory syncytial virus infection, at least in an immunocompetent host.
+In recent years, avian influenza virus H9N2 undergoing antigenic drift represents a threat to poultry farming as well as public health.
+In this study, a recombinant H9N2 (H9N2-TM) strain with a replaced H3 hemagglutinin (HA) transmembrane (TM) domain was generated.
+Further, the recombinant TM-replaced H9N2-TM virus could provide better inter-clade protection in both mice and chickens against H9N2, suggesting that the H3-TM-replacement could be considered as a strategy to develop efficient subtype-specific H9N2 influenza vaccines.
+BACKGROUND: Uncertain prediction of outcome in acute respiratory distress syndrome (ARDS) impedes individual patient management and clinical trial design.
+OBJECTIVES: To develop a radiological metric of injurious inflation derived from matched inspiratory and expiratory CT scans, calibrate it in a model of experimental lung injury, and test it in patients with ARDS.
+METHODS: 73 anaesthetised rats (acid aspiration model) were ventilated (protective or non-protective) for up to 4 hours to generate a spectrum of lung injury.
+CT was performed (inspiratory and expiratory) at baseline each hour, paired inspiratory and expiratory images were superimposed and voxels tracked in sequential scans.
+In nine patients with ARDS, paired inspiratory and expiratory CT scans from the first intensive care unit week were analysed.
+RESULTS: In experimental studies, regions of lung with unstable inflation (ie, partial or reversible airspace filling reflecting local strain) were the areas in which subsequent progression of injury was greatest in terms of progressive infiltrates (R=0.77) and impaired compliance (R=0.67, p<0.01).
+In patients with ARDS, a threshold fraction of tissue with unstable inflation was apparent: >28% in all patients who died and ≤28% in all who survived, whereas segregation of survivors versus non-survivors was not possible based on oxygenation or lung mechanics.
+CONCLUSIONS: A single set of superimposed inspiratory–expiratory CT scans may predict progression of lung injury and outcome in ARDS; if these preliminary results are validated, this could facilitate clinical trial recruitment and individualised care.
+Diet-induced obesity is associated with systemic inflammation, which is considered to originate predominantly from the adipose tissue.
+Quercetin and resveratrol are two dietary polyphenols that exhibit anti-inflammatory properties and anti-insulin resistance when administered in isolation or combination (CQR).
+It remains unknown whether CQR reduces high fat diet (HFD)-induced obesity and inflammation in rats.
+In the current study, 46 male Wistar rats were divided into two groups, one of which was fed a normal diet (ND, 5.4% fat, w/w) and one of which was fed a HFD (45% fat, w/w) for 3 weeks.
+Following removal of the 12 most obesity-resistant rats from the HFD group, the remaining rats were divided into two sub-groups: A HFD group and a HFD+CQR group (administered 120 mg/kg/day resveratrol and 240 mg/kg/day quercetin).
+The results revealed that the HFD+CQR group had significantly lower body weights at 11 weeks compared with the HFD group and had significantly reduced visceral adipose tissue weights and adipocyte sizes.
+CQR attenuated the expression of systemic proinflammatory adipokines, including leptin, tumor necrosis factor-α, monocyte chemoattractant protein-1 and interleukin-6.
+Furthermore, CQR reversed the HFD-induced suppression of 5′-adenosine monophosphate-activated protein kinase α1 (AMPKα1) phosphorylation and sirtuin 1 (SIRT1) expression in EAT.
+In conclusion, CQR may suppress obesity and associated inflammation via the AMPKα1/SIRT1 signaling pathway in rats fed a HFD.
+Bacterial and viral co-infections of the respiratory tract are life-threatening and present a global burden to the global community.
+Staphylococcus aureus, Streptococcus pneumoniae, and Streptococcus pyogenes are frequent colonizers of the upper respiratory tract.
+Imbalances through acquisition of seasonal viruses, e.g., Influenza A virus, can lead to bacterial dissemination to the lower respiratory tract, which in turn can result in severe pneumonia.
+In this review, we summarize the current knowledge about bacterial and viral co-infections of the respiratory tract and focus on potential experimental models suitable for mimicking this disease.
+The knowledge gained from these studies led to important discoveries and advances in understanding these infectious diseases.
+Nevertheless, mouse and other infection models have limitations, especially in translation of the discoveries to humans.
+Here, we suggest the use of human engineered lung tissue, human ex vivo lung tissue, and porcine models to study respiratory co-infections, which might contribute to a greater translation of the results to humans and improve both, animal and human health.
+Canine distemper virus (CDV), a paramyxovirus, causes a severe highly contagious lethal disease in carnivores, such as mink.
+Mink lung epithelial cells (Mv.1.Lu cells) are sensitive to CDV infection and are homologous to the natural host system of mink.
+The current study analyzed the response of Mv.1.Lu cells to CDV infection by iTRAQ combined with LC–MS/MS.
+In total, 151 and 369 differentially expressed proteins (DEPs) were markedly up-regulated or down-regulated, respectively.
+Network and KEGG pathway analyses revealed several regulated proteins associated with the NF-κB signaling pathway.
+Further validation was performed by western blot analysis and immunofluorescence assay, which demonstrated that different CDV strains induced NF-κB P65 phosphorylation and nuclear translocation.
+Moreover, the results provided interesting information that some identified DEPs possibly associated with the pathogenesis and the immune response upon CDV infection.
+This study is the first overview of the responses to CDV infection in Mv.1.Lu cells, and the findings will help to analyze further aspects of the molecular mechanisms involved in viral pathogenesis and the immune responses upon CDV infection.
+Since 2012, our understanding of human papillomavirus (HPV) subcellular trafficking has undergone a drastic paradigm shift.
+Work from multiple laboratories has revealed that HPV has evolved a unique means to deliver its viral genome (vDNA) to the cell nucleus, relying on myriad host cell proteins and processes.
+The major breakthrough finding from these recent endeavors has been the realization of L2-dependent utilization of cellular sorting factors for the retrograde transport of vDNA away from degradative endo/lysosomal compartments to the Golgi, prior to mitosis-dependent nuclear accumulation of L2/vDNA.
+An overview of current models of HPV entry, subcellular trafficking, and the role of L2 during initial infection is provided below, highlighting unresolved questions and gaps in knowledge.
+Animal movement impacts the spread of human and wildlife diseases, and there is significant interest in understanding the role of migrations, biological invasions and other wildlife movements in spatial infection dynamics.
+However, the influence of processes acting on infections during transient phases of host movement is poorly understood.
+We propose a conceptual framework that explicitly considers infection dynamics during transient phases of host movement to better predict infection spread through spatial host networks.
+Accounting for host transient movement captures key processes that occur while hosts move between locations, which together determine the rate at which hosts spread infections through networks.
+We review theoretical and empirical studies of host movement and infection spread, highlighting the multiple factors that impact the infection status of hosts.
+Recent technological advances provide disease ecologists unprecedented ability to track the fine-scale movement of organisms.
+These, in conjunction with experimental testing of the factors driving infection dynamics during host movement, can inform models of infection spread based on constituent biological processes.
+BACKGROUND: Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe hypersensitivity drug reaction involving the skin and multiple internal organ systems.
+The symptoms typically present with fever and skin rash, and rapidly progress to multiple organ failures.
+Vancomycin is a rare drug to cause DRESS syndrome with 23 cases reported to date.
+CASE PRESENTATION: We described a case of a 39 year-old man who was treated with vancomycin for osteomyelitis of the foot.
+The patient subsequently developed acute respiratory distress syndrome (ARDS) followed by rash and acute interstitial nephritis.
+According to the European Registry of Severe Cutaneous Adverse Reaction Criteria (RegiSCAR) (Kardaun et al, British Journal of Dermatology, 169:1071-1080, 2013), the probability of vancomycin induced DRESS syndrome was scored as “Definite”.
+A literature search of vancomycin induced DRESS syndrome was also performed and the overall pulmonary involvement was estimated as 5%.
+To our knowledge, this was the first case reported with pulmonary involvement as the initial symptom.
+CONCLUSION: This is the first case to report pulmonary manifestation as the initial symptom in vancomycin induced DRESS syndrome.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12890-017-0564-6) contains supplementary material, which is available to authorized users.
+INTRODUCTION: In low-resource settings, empiric case management of febrile illness is routine as a result of limited access to laboratory diagnostics.
+The use of comprehensive fever syndromic surveillance, with enhanced clinical microbiology, advanced diagnostics and more robust epidemiologic investigation, could enable healthcare providers to offer a differential diagnosis of fever syndrome and more appropriate care and treatment.
+METHODS: We conducted a year-long exploratory study of fever syndrome among patients ≥ 1 year if age, presenting to clinical settings with an axillary temperature of ≥37.5°C and symptomatic onset of ≤5 days.
+Blood and naso-pharyngeal/oral-pharyngeal (NP/OP) specimens were collected and analyzed, respectively, using AFI and respiratory TaqMan Array Cards (TAC) for multi-pathogen detection of 57 potential causative agents.
+Furthermore, we examined numerous epidemiologic correlates of febrile illness, and conducted demographic, clinical, and behavioral domain-specific multivariate regression to statistically establish associations with agent detection.
+RESULTS: From 15 September 2014–13 September 2015, 1007 febrile patients were enrolled, and 997 contributed an epidemiologic survey, including: 14% (n = 139) 1<5yrs, 19% (n = 186) 5-14yrs, and 67% (n = 672) ≥15yrs.
+AFI TAC and respiratory TAC were performed on 842 whole blood specimens and 385 NP/OP specimens, respectively.
+AFI TAC detected nucleic acid for one or more of seven microbial agents in 49% of AFI blood samples, including: Plasmodium (47%), Leptospira (3%), Bartonella (1%), Salmonella enterica (1%), Coxiella burnetii (1%), Rickettsia (1%), and West Nile virus (1%).
+Respiratory TAC detected nucleic acid for 24 different microbial agents, including 12 viruses and 12 bacteria.
+The most common agents detected among our surveyed population were: Haemophilus influenzae (67%), Streptococcus pneumoniae (55%), Moraxella catarrhalis (39%), Staphylococcus aureus (37%), Pseudomonas aeruginosa (36%), Human Rhinovirus (25%), influenza A (24%), Klebsiella pneumoniae (14%), Enterovirus (15%) and group A Streptococcus (12%).
+Our epidemiologic investigation demonstrated both age and symptomatic presentation to be associated with a number of detected agents, including, but not limited to, influenza A and Plasmodium.
+Linear regression of fully-adjusted mean cycle threshold (C(t)) values for Plasmodium also identified statistically significant lower mean C(t) values for older children (20.8), patients presenting with severe fever (21.1) and headache (21.5), as well as patients admitted for in-patient care and treatment (22.4).
+CONCLUSIONS: This study is the first to employ two syndromic TaqMan Array Cards for the simultaneous survey of 57 different organisms to better characterize the type and prevalence of detected agents among febrile patients.
+Additionally, we provide an analysis of the association between adjusted mean C(t) values for Plasmodium and key clinical and demographic variables, which may further inform clinical decision-making based upon intensity of infection, as observed across endemic settings of sub-Saharan Africa.
+Current natural populations face new interactions because of the re‐emergence of ancient microbes and viruses.
+These risks come from the re‐emergence of pathogens kept in laboratories or from pathogens that are retained in the permafrost, which become available upon thawing due to climate change.
+We here focus on the effects of such re‐emergence in natural host populations based on evolutionary theory of virulence and long‐term studies, which investigate host–pathogen adaptations.
+Pathogens tend to be locally and temporally adapted to their co‐occurring hosts, but when pathogens from a different environment or different time enter the host community, the degree to which a new host–pathogen interaction is a threat will depend on the specific genotypic associations, the time lag between the host and the pathogen, and the interactions with native or recent host and pathogen species.
+These long‐term studies based on time‐shift experiments are essential to obtain insight into the mechanisms underlying host–pathogen coevolution at several ecological and temporal scales.
+As past pathogens and their corresponding host(s) can differ in infectivity and susceptibility, strong reciprocal selective pressures can be induced by the pathogen.
+These strong selective pressures often result in an escalating arms race, but do not necessarily result in increased infectivity over time.
+Human health can also be impacted by these resurrected pathogens as the majority of emerging infectious diseases are zoonoses, which are infectious diseases originating from animal populations naturally transmitted to humans.
+The sanitary risk associated with pathogen emergence from different environments (spatial or temporal) depends on a combination of socioeconomic, environmental, and ecological factors that affect the virulence or the pathogenic potential of microbes and their ability to infect susceptible host populations.
+Human metapneumovirus (hMPV) is a leading cause of lower respiratory infection in pediatric populations globally.
+This study examined proteomic profile changes in A549 cells infected with hMPV and two attenuated mutants with deleted PDZ domain-binding motif(s) in the M2-2 protein.
+These motifs are involved in the interruption of antiviral signaling, namely the interaction between the TNF receptor associated factor (TRAF) and mitochondrial antiviral-signaling (MAVS) proteins.
+The aim of this study was to provide insight into the overall and novel impact of M2-2 motifs on cellular responses via an unbiased comparison.
+Tandem mass tagging, stable isotope labeling, and high-resolution mass spectrometry were used for quantitative proteomic analysis.
+Using quantitative proteomics and Venn analysis, 1248 common proteins were detected in all infected samples of both technical sets.
+Hierarchical clustering of the differentiated proteome displayed distinct proteomic signatures that were controlled by the motif(s).
+Bioinformatics and experimental analysis confirmed the differentiated proteomes, revealed novel cellular biological events, and implicated key pathways controlled by hMPV M2-2 PDZ domain-binding motif(s).
+This study documents variation in risk of URI between nine North American shelters; determines whether this reflects variation in pathogen frequency on intake or differences in transmission and expression of disease; and identifies modifiable environmental and group health factors linked to risk for URI.
+This study demonstrated that although periodic introduction of pathogens into shelter populations may be inevitable, disease resulting from those pathogens is not.
+Housing and care of cats, particularly during their first week of stay in an animal shelter environment, significantly affects the rate of upper respiratory infection.
+The hepatitis C virus (HCV) envelope glycoproteins E1 and E2 form a non-covalently linked heterodimer on the viral surface that mediates viral entry.
+E1, E2 and the heterodimer complex E1E2 are candidate vaccine antigens, but are technically challenging to study because of difficulties in producing natively folded proteins by standard protein expression and purification methods.
+To better comprehend the antigenicity of these proteins, a library of alanine scanning mutants comprising the entirety of E1E2 (555 residues) was created for evaluating the role of each residue in the glycoproteins.
+The mutant library was probed, by a high-throughput flow cytometry-based assay, for binding with the co-receptor CD81, and a panel of 13 human and mouse monoclonal antibodies (mAbs) that target continuous and discontinuous epitopes of E1, E2, and the E1E2 complex.
+Together with the recently determined crystal structure of E2 core domain (E2c), we found that several residues in the E2 back layer region indirectly impact binding of CD81 and mAbs that target the conserved neutralizing face of E2.
+These findings highlight an unexpected role for the E2 back layer in interacting with the E2 front layer for its biological function.
+We also identified regions of E1 and E2 that likely located at or near the interface of the E1E2 complex, and determined that the E2 back layer also plays an important role in E1E2 complex formation.
+The conformation-dependent reactivity of CD81 and the antibody panel to the E1E2 mutant library provides a global view of the influence of each amino acid (aa) on E1E2 expression and folding.
+This information is valuable for guiding protein engineering efforts to enhance the antigenic properties and stability of E1E2 for vaccine antigen development and structural studies.
+Disease problems in honeybees have intensified in recent years, despite increasing attention to addressing them.
+Here we argue that we must focus on the principles of disease ecology and evolution to understand disease dynamics, assess the severity of disease threats, and control these threats via honeybee management.
+We cover the ecological context of honeybee disease, including both host and parasite factors driving current transmission dynamics, and then discuss evolutionary dynamics including how beekeeping management practices may drive selection for more virulent parasites.
+We then outline how ecological and evolutionary principles can guide disease mitigation in honeybees, including several practical management suggestions for addressing short- and long-term disease dynamics and consequences.
+The explosive growth of literature and data in the life sciences challenges researchers to keep track of current advancements in their disciplines.
+Novel approaches in the life science like the One Health paradigm require integrated methodologies in order to link and connect heterogeneous information from databases and literature resources.
+Current publications in the life sciences are increasingly characterized by the employment of trans-disciplinary methodologies comprising molecular and cell biology, genetics, genomic, epigenomic, transcriptional and proteomic high throughput technologies with data from humans, plants, and animals.
+The literature search engine LIVIVO empowers retrieval functionality by incorporating various literature resources from medicine, health, environment, agriculture and nutrition.
+It provides a user-friendly and usability-tested search interface with a corpus of 55 Million citations derived from 50 databases.
+The search functions allow for semantic retrieval with filtering options based on life science entities.
+The service oriented architecture of LIVIVO uses four different implementation layers to deliver search services.
+A Knowledge Environment is developed by ZB MED to deal with the heterogeneity of data as an integrative approach to model, store, and link semantic concepts within literature resources and databases.
+Future work will focus on the exploitation of life science ontologies and on the employment of NLP technologies in order to improve query expansion, filters in faceted search, and concept based relevancy rankings in LIVIVO.
+Norovirus infection, a highly prevalent condition associated with a high rate of morbidity, comprises a significant health issue.
+Although norovirus transmission mainly occurs via the fecal-oral and vomit-oral routes, airborne transmission has been proposed in recent decades.
+This paper re-examines a previously described norovirus outbreak in a hotel restaurant wherein airborne transmission was originally inferred.
+Specifically, the original evidence that suggested airborne transmission was re-analyzed by exploring an alternative hypothesis: could this outbreak instead have occurred via fomite transmission?
+This re-analysis was based on whether fomite transmission could have yielded similar attack rate distribution patterns.
+Seven representative serving pathways used by waiters were considered, and the infection risk distributions of the alternative fomite transmission routes were predicted using a multi-agent model.
+These distributions were compared to the reported attack rate distribution in the original study using a least square methods approach.
+The results show that with some reasonable assumptions of human behavior patterns and parameter values, the attack rate distribution corresponded well with that of the infection risk via the fomite route.
+This finding offers an alternative interpretation of the transmission routes that underlay this particular norovirus outbreak and an important consideration in the development of infection control guidelines and the investigation of similar norovirus outbreaks in future.
+PURPOSE: Acute otitis media (AOM) is a common infectious disease in children and usually accompanied by a preceding viral respiratory tract infection, especially in the preschool-age population.
+METHODS: This retrospective cohort study included data for 803,592 children (<10 years old) recorded in Taiwan’s National Health Insurance Research Database.
+AOM incidence and tympanostomy tube insertion incidence in each influenza season before and after the introduction of traditional injectable trivalent influenza vaccine (TIV) were compared using the Poisson regression analysis to estimate the incidence rate ratios (IRRs) and 95% confidence intervals (CIs).
+RESULTS: In children < 2 years old, the age group eligible for free influenza vaccination, there was a significant reduction in seasonal AOM incidence after TIV introduction in 2004 (from 98.4 episodes/1000 person-seasons [95% CI: 96.4–100.5] to 66.1 episodes/1000 person-seasons [95% CI: 64–68.1]).
+In addition, with the increased vaccine coverage rate, the outpatient visits for AOM in the influenza season of 2005 and 2006 were significantly lower than that in 2004 (IRR = 0.85 and 0.80, respectively, p < 0.0001).
+CONCLUSIONS: A significant reduction in primary care consultations for children <2 years old was observed after the introduction of the TIV in Taiwan in 2004.
+In addition of the direct protection provided by the vaccination, we believe that TIV may have induced some herd immunity that further contributed to the reduction in influenza attack rates and the rates of associated AOM in that age group.
+These reductions were observed only in vaccine-eligible children, while older children, who were not enrolled in the influenza vaccination program during the study period, have experienced increases in the AOM incidence during the 2004–2006 period compared to the 2000–2003 period.
+BACKGROUND: Influenza A viruses cause life-threatening pneumonia and lung injury in the lower respiratory tract.
+Application of high GM-CSF levels prior to infection has been shown to reduce morbidity and mortality from pathogenic influenza infection in mice, but the mechanisms of protection and treatment efficacy have not been established.
+Supra-physiologic levels of GM-CSF were induced in the airways using the double transgenic GM-CSF (DTGM) or littermate control mice starting on 3 days post-infection (dpi).
+RESULTS: Supra-physiologic levels of GM-CSF conferred a survival benefit, arrested the deterioration of lung mechanics, and reduced the abundance of protein exudates in bronchoalveolar (BAL) fluid to near baseline levels.
+Transcriptome analysis, and subsequent validation ELISA assays, revealed that excess GM-CSF re-directs macrophages from an “M1-like” to a more “M2-like” activation state as revealed by alterations in the ratios of CXCL9 and CCL17 in BAL fluid, respectively.
+Ingenuity pathway analysis predicted that GM-CSF surplus during IAV infection elicits expression of anti-inflammatory mediators and moderates M1 macrophage pro-inflammatory signaling by Type II interferon (IFN-γ).
+CONCLUSIONS: Our data indicate that application of high levels of GM-CSF in the lung after influenza A virus infection alters pathogenic “M1-like” macrophage inflammation.
+These results indicate a possible therapeutic strategy for respiratory virus-associated pneumonia and acute lung injury.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12931-017-0708-5) contains supplementary material, which is available to authorized users.
+Cardiotoxicity is a well-known side effect of doxorubicin (DOX), but the mechanisms leading to this phenomenon are still not completely clear.
+Prediction of drug-induced dysfunction onset is difficult and is still largely based on detection of cardiac troponin (cTn), a circulating marker of heart damage.
+In the last years, several investigations focused on the possible involvement of microRNAs (miRNAs) in DOX-induced toxicity in vitro, with contrasting results.
+Recently, several groups employed animal models to mimic patient’s condition, investigate the biological pathways perturbed by DOX, and identify diagnostic markers of cardiotoxicity.
+We reviewed the results from several studies investigating cardiac miRNAs expression in rodent models of DOX-treatment.
+We also discussed the data from two publications indicating the possible use of circulating miRNA as biomarkers of DOX-induced cardiotoxicity.
+Unfortunately, limited information was derived from these studies, as selection methods of candidate-miRNAs and heterogeneity in cardiotoxicity assessment greatly hampered the novelty and robustness of the findings.
+Nevertheless, at least one circulating miRNA, miR-1, showed a good potential as early biomarker of drug-mediated cardiac dysfunction onset.
+The use of animal models to investigate DOX-induced cardiotoxicity surely helps narrowing the gap between basic research and clinical practice.
+Despite this, several issues, including selection of relevant miRNAs and less-than-optimal assessment of cardiotoxicity, greatly limited the results obtained so far.
+Nonetheless, the association of patients-based studies with the use of preclinical models may be the key to address the many unanswered questions regarding the pathophysiology and early detection of cardiotoxicity.
+Like all viruses, human immunodeficiency viruses (HIVs) and their primate lentivirus relatives must enter cells in order to replicate and, once produced, new virions need to exit to spread to new targets.
+These processes require the virus to cross the plasma membrane of the cell twice: once via fusion mediated by the envelope glycoprotein to deliver the viral core into the cytosol; and secondly by ESCRT-mediated scission of budding virions during release.
+This physical barrier thus presents a perfect location for host antiviral restrictions that target enveloped viruses in general.
+In this review we will examine the current understanding of innate host antiviral defences that inhibit these essential replicative steps of primate lentiviruses associated with the plasma membrane, the mechanism by which these viruses have adapted to evade such defences, and the role that this virus/host battleground plays in the transmission and pathogenesis of HIV/AIDS.
+Structured RNA elements may control virus replication, transcription and translation, and their distinct features are being exploited by novel antiviral strategies.
+However, the wealth of sequence data, notably from deep viral RNA sequencing, viromes, and metagenomes, necessitates computational approaches being used as an essential discovery tool.
+In this review, we describe practical approaches being used to discover functional RNA elements in viral genomes.
+In addition to success stories in new and emerging viruses, these approaches have revealed some surprising new features of well-studied viruses e.g., human immunodeficiency virus, hepatitis C virus, influenza, and dengue viruses.
+With the exponential growth of computer power we have progressed from stem-loop prediction on single sequences to cutting edge 3D prediction, and from command line to user friendly web interfaces.
+Despite these advances, many powerful, user friendly prediction tools and resources are underutilized by the virology community.
+BACKGROUND: The Ebola outbreak in West-Africa triggered risk communication activities to promote adequate preventive behaviour in the Netherlands.
+METHODS: In December 2014, an online questionnaire was administered to the Dutch population (n = 526) and Health Care Workers (HCW) (n = 760).
+RESULTS: The mean knowledge score (range 0–15) of HCW (m = 13.3;SD = 1.4) was significantly higher than the general public (m = 10.8;SD = 2.0).
+Perceived fear of the general public (m = 2.5; SD = 0.8) was significantly higher than among HCW (m = 2.4; SD = 0.7).
+CONCLUSIONS: While Ebola was perceived severe, it did not lead to excessive fear or perceived susceptibility for developing the disease.
+Nonetheless, our research showed that knowledge with respect to human-to-human transmission is low, while this is crucial to complying with preventive measures.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12879-017-2906-7) contains supplementary material, which is available to authorized users.
+BACKGROUND: Evidence concerning the efficacy and safety of extracorporeal membrane oxygenation (ECMO) in patients with influenza A (H7N9) has been was limited to case reports.
+Our study is aimed to investigate the current application, efficacy and safety of ECMO in for severe H7N9 pneumonia-associated acute respiratory distress syndrome (ARDS) in the Chinese population.
+METHODS: A multicentre retrospective cohort study was conducted at 20 hospitals that admitted patients with avian influenza A (H7N9) viral pneumonia patients’ admission from 9 provinces in China between October 1, 2016, and March 1, 2017.
+Data from the National Health and Family Planning Commission of China, including general conditions, outcomes and ECMO management, were analysed.
+RESULTS: A total of 35 patients, aged 57 ± 1 years, were analysed; 65.7% of patients were male with 63% mortality.
+All patients underwent invasive positive pressure ventilation (IPPV), and rescue ventilation strategies were implemented for 23 cases (65.7%) with an average IPPV duration of 5 ± 1 d, PaO(2)/FiO(2) of 78 ± 23 mmHg, tidal volume (VT) of 439 ± 61 ml and plateau pressure (P(plat)) of 29 ± 8 cmH(2)O pre-ECMO.
+After 48 h on ECMO, PaO(2) improved from 56 ± 21 mmHg to 90 ± 24 mmHg and PaCO(2) declined from 52 ± 24 mmHg to 38 ± 24 mmHg.
+Haemorrhage, ventilator-associated pneumonia (VAP) and barotrauma occurred in 45.7%, 60% and 8.6% of patients, respectively.
+Compared with successfully weaned patients (n = 14), the 21 unsuccessfully weaned patients had a longer duration of IPPV pre-ECMO (6 ± 4 d vs. 2 ± 1 d, P < 0.01) as well as a higher P(plat) (25 ± 5 cmH(2)O vs. 21 ± 3 cmH(2)O, P < 0.05) and VT (343 ± 96 ml vs. 246 ± 93 ml, P < 0.05) after 48 h on ECMO support.
+Furthermore, the unsuccessfully weaned group had a higher mortality (100% vs. 7.1%, P < 0.01) with more haemorrhage (77.3% vs. 28.6%, P < 0.01).
+CONCLUSIONS: ECMO is effective at improving oxygenation and ventilation of patients with avian influenza A (H7N9) induced severe ARDS.
+Early initiation of ECMO with appropriate IPPV settings and anticoagulation strategies are necessary to reduce complications.
+Results: In this study, we found fraction 1 of Toona sinensis leaf (TSL-1) resulted in inhibition of cell viability in MG-63, Saos-2, and U2OS osteosarcoma cell lines, while it only caused a moderate suppressive effect on normal osteoblasts.
+In addition, TSL-1 significantly elevated lactate dehydrogenase leakage and induced apoptosis and necrosis in Saos-2 cells.
+Most important, TSL-1 significantly suppressed Saos-2 xenograft tumor growth in nude mice by increasing caspase-3.
+The IC-50 of TSL-1 for the 3 tested osteosarcoma cells is around 1/9 of that for lung cancer cells.
+Conclusion: We demonstrated that TSL-1, a fractionated extract from TSL, caused significant cytotoxicity to osteosarcoma cells due to apoptosis.
+In vivo xenograft study showed that TSL-1 suppressed the growth of osteosarcoma cells at least in part by inducing apoptosis.
+Our results indicate that TSL-1 has potential to be a promising anti-osteosarcoma adjuvant functional plant extract.
+Great interest has been shown in mesenchymal stem cell (MSC) therapy in a wide variety of clinical domains.
+Chemokine receptors are involved in regulating the proliferation and migration to the specific organs of MSCs in different microenvironments.
+CXC receptor seven (CXCR7), a newly discovered Chemokine ligand 12 (CXCL12) receptor, has organ specificity for tumour migration.
+In present study, we constructed long-term and stable mMSCs lines overexpressing and suppressing CXCR7 modifications with lentiviral vectors.
+CXCR7 gene overexpression promoted mMSCs proliferation and migration, whereas suppressing CXCR7 had the opposite effect.
+The overexpression of CXCR7 increased the MSC-secreted CXCL12, VCAM-1, CD44 and MMP2 levels, which contributed to the improvement of mMSC proliferation and migration.
+Therefore, overexpressing CXCR7 improved the proliferation and migration of mMSCs, which may be attributable to the CXCL12 secreted by MSCs, leading to a positive feedback loop for CXCL12/CXCR7 axis.
+Our results may provide a potential method for improving the treatment effectiveness of mMSCs by overexpressing CXCR7.
+Powassan virus (POWV) is an emerging tick-borne arbovirus presenting a public health threat in North America.
+POWV lineage II, also known as deer tick virus, is the strain of the virus most frequently found in Ixodes scapularis ticks and is implicated in most cases of POWV encephalitis in the United States.
+Currently, no commercial tests are available to detect POWV exposure in tick-borne disease (TBD) patients.
+We describe here the development and analytical validation of a serologic test panel to detect POWV infections.
+The analytical sensitivity of the test panel was 89%, and the limit of detection was a plaque reduction neutralization test (PRNT) titer of 1:20.
+The analytical specificity was 100% for the IgM assay and 65% for the IgG assay when heterologous-flavivirus-positive samples were tested.
+On samples collected from regions where Lyme disease is endemic, seroprevalence for POWV in TBD samples was 9.4% (10 of 106) versus 2% when tested with non-TBD samples (2 of 100, P = 0.034).
+No evidence of POWV infection was seen in samples collected from a region where Lyme disease was not endemic (0 of 22).
+This test panel provides a sensitive and specific platform for detecting a serologic response to POWV early in the course of infection when neutralizing antibodies may not be detectable.
+Combined with clinical history, the panel is an effective tool for identifying acute POWV infection.
+IMPORTANCE Approximately 100 cases of POWV disease were reported in the United States over the past 10 years.
+The prevalence of POWV in ticks and mammals is increasing, and POWV poses an increasing threat in a greater geographical range.
+In areas of the Northeast and Midwest where Lyme disease is endemic, POWV testing is recommended for patients with a recent tick bite, patients with Lyme disease who have been treated with antibiotics, or patients with a tick exposure who have tested negative for Lyme disease or other tick-borne illnesses and have persistent symptoms consistent with posttreatment Lyme disease.
+Testing could also benefit patients with tick exposure and unexplained neurologic symptoms and chronic fatigue syndrome (CFS) patients with known tick exposure.
+Until now, diagnostic testing for Powassan virus has not been commercially available and has been limited to patients presenting with severe, neurologic complications.
+The lack of routine testing for Powassan virus in patients with suspected tick-borne disease means that little information is available regarding the overall prevalence of the virus and the full spectrum of clinical symptoms associated with infection.
+As Ixodes scapularis is the tick vector for Powassan virus and multiple other tick-borne pathogens, including the Lyme disease bacterium, Borrelia burgdorferi, the clinical presentations and long-term outcomes of Powassan virus infection and concurrent infection with other tick-borne disease pathogens remain unknown.
+Microtubule severing enzymes implement a diverse range of tissue-specific molecular functions throughout development and into adulthood.
+Although microtubule severing is fundamental to many dynamic neural processes, little is known regarding the role of the family member Katanin p60 subunit A-like 1, KATNAL1, in central nervous system (CNS) function.
+Recent studies reporting that microdeletions incorporating the KATNAL1 locus in humans result in intellectual disability and microcephaly suggest that KATNAL1 may play a prominent role in the CNS; however, such associations lack the functional data required to highlight potential mechanisms which link the gene to disease symptoms.
+Here we identify and characterise a mouse line carrying a loss of function allele in Katnal1.
+We show that mutants express behavioural deficits including in circadian rhythms, sleep, anxiety and learning/memory.
+Furthermore, in the brains of Katnal1 mutant mice we reveal numerous morphological abnormalities and defects in neuronal migration and morphology.
+Furthermore we demonstrate defects in the motile cilia of the ventricular ependymal cells of mutants, suggesting a role for Katnal1 in the development of ciliary function.
+We believe the data we present here are the first to associate KATNAL1 with such phenotypes, demonstrating that the protein plays keys roles in a number of processes integral to the development of neuronal function and behaviour.
+OBJECTIVE: To translate the English work-related acceptance and action questionnaire (WAAQ), make cross-cultural adaptations, and examine its psychometric properties when used by Chinese oncology nurses.
+METHODS: After translation, the psychometric properties of the Chinese WAAQ were analyzed among 417 nurses, and content validity was determined by six experts.
+RESULTS: Item-level content validity index (CVI) values were between 0.83 and 1.00; scale-level CVI/universal agreement (S-CVI/UA) and S-CVI/average were 0.86 and 0.98, respectively, which implicated a good content validity.
+The correlation of the Chinese WAAQ with AAQ-II (r(s) = −0.247, P < 0.001) suggested criterion validity, and those with General Health Questionnaire-12 (−0.250, <0.001) and general self-efficacy scale (0.491, <0.001) and Utrecht work engagement scale (UWES) (0.439, <0.001) suggested convergent validity.
+The Chinese version of WAAQ had high internal consistency (Cronbach's α = 0.920), with an item-total correlation coefficient of 0.702–0.828 (P < 0.05), split-half reliability of 0.933, and test-retest reliability of 0.772.
+CONCLUSIONS: The Chinese WAAQ is a reliable and valid tool for assessing psychological flexibility in Chinese oncology nurses.
+To study the genetic diversity of enterovirus G (EV-G) among Japanese pigs, metagenomics sequencing was performed on fecal samples from pigs with or without diarrhea, collected between 2014 and 2016.
+By complete VP1 sequence analysis, Japanese EV-G isolates were classified into G1 (17 strains), G2 (four strains), G3 (22 strains), G4 (two strains), G6 (two strains), G9 (six strains), G10 (five strains), and a new genotype (one strain).
+Remarkably, 16 G1 and one G2 strain identified in diarrheic (23.5%; four strains) or normal (76.5%; 13 strains) fecal samples possessed a papain-like cysteine protease (PL-CP) sequence, which was recently found in the USA and Belgium in the EV-G genome, at the 2C–3A junction site.
+This paper presents the first report of the high prevalence of viruses carrying PL-CP in the EV-G population.
+Furthermore, possible inter- and intragenotype recombination events were found among EV-G strains, including G1-PL-CP strains.
+Our findings may advance the understanding of the molecular epidemiology and genetic evolution of EV-Gs.
+A close relative of poliovirus, enterovirus 71 (EV71) is regarded as an important neurotropic virus of serious public health concern.
+EV71 causes Hand, Foot and Mouth Disease and has been associated with neurological complications in young children.
+Our limited understanding of the mechanisms involved in its neuropathogenesis has hampered the development of effective therapeutic options.
+Here, using a two-dimensional proteomics approach combined with mass spectrometry, we have identified a unique panel of host proteins that were differentially and dynamically modulated during EV71 infection of motor-neuron NSC-34 cells, which are found at the neuromuscular junctions where EV71 is believed to enter the central nervous system.
+Meta-analysis with previously published proteomics studies in neuroblastoma or muscle cell lines revealed minimal overlapping which suggests unique host-pathogen interactions in NSC-34 cells.
+Among the candidate proteins, we focused our attention on prohibitin (PHB), a protein that is involved in multiple cellular functions and the target of anti-cancer drug Rocaglamide (Roc-A).
+We demonstrated that cell surface-expressed PHB is involved in EV71 entry into neuronal cells specifically, while membrane-bound mitochondrial PHB associates with the virus replication complex and facilitates viral replication.
+However, the inhibitory effect of Roc-A on PHB in NSC-34 cells was not through blocking the CRAF/MEK/ERK pathway as previously reported.
+Instead, Roc-A treated NSC-34 cells had lower mitochondria-associated PHB and lower ATP levels that correlated with impaired mitochondria integrity.
+In vivo, EV71-infected mice treated with Roc-A survived longer than the vehicle-treated animals and had significantly lower virus loads in their spinal cord and brain, whereas virus titers in their limb muscles were comparable to controls.
+Together, this study uncovers PHB as the first host factor that is specifically involved in EV71 neuropathogenesis and a potential drug target to limit neurological complications.
+Memory CD8 T cells can provide protection from re-infection by respiratory viruses such as influenza and SARS.
+However, the relative contribution of memory CD8 T cells in providing protection against respiratory syncytial virus (RSV) infection is currently unclear.
+To address this knowledge gap, we utilized a prime-boost immunization approach to induce robust memory CD8 T cell responses in the absence of RSV-specific CD4 T cells and antibodies.
+Unexpectedly, RSV infection of mice with pre-existing CD8 T cell memory led to exacerbated weight loss, pulmonary disease, and lethal immunopathology.
+The exacerbated disease in immunized mice was not epitope-dependent and occurred despite a significant reduction in RSV viral titers.
+In addition, the lethal immunopathology was unique to the context of an RSV infection as mice were protected from a normally lethal challenge with a recombinant influenza virus expressing an RSV epitope.
+Memory CD8 T cells rapidly produced IFN-γ following RSV infection resulting in elevated protein levels in the lung and periphery.
+These results demonstrate that in contrast to other respiratory viruses, RSV-specific memory CD8 T cells can induce lethal immunopathology despite mediating enhanced viral clearance.
+Porcine reproductive and respiratory syndrome virus (PRRSV) has been recognized to inhibit the response of type I interferon (IFN) both in vivo and in vitro.
+However, the post-transcriptional mechanism by which PRRSV suppresses type I IFN induction in virus-infected host cells remains unclear.
+The present study first demonstrated that PRRSV inhibited post-transcriptionally the protein induction of IFN-β in primary porcine alveolar macrophages (PAMs) during early infection, and the inhibition effect mediated by the Chinese highly pathogenic (HP)-PRRSV was stronger.
+Next, we analyzed the cellular microRNA (miRNA)-modulated protein expression of porcine IFN-β by dual firefly/Renilla luciferase reporter assay, transfection of miRNA mimics and inhibitor assay and polyinosinic-polycytidylic acid (poly I:C) treatment of PAMs, showing that porcine miRNAs including let-7b, miR-26a, miR-34a and miR-145 are able to inhibit IFN-β protein expression in primary PAMs by directly targeting sequences within the porcine IFN-β 3′UTR locating at 160–181, 9–31, 27–47 and 12–32 bp, respectively.
+Finally, we confirmed that let-7b, miR-26a, miR-34a and miR-145, were upregulated in PRRSV-infected PAMs early in vitro, and the expression level of these miRNAs in HP-PRRSV JXwn06-infected PAMs were higher than those in low pathogenic PRRSV HB-1/3.9-infected PAMs.
+The endogenous cellular miRNA-mediated inhibition of IFN-β induction in PRRSV-infected PAMs early could be relieved by miRNA antagonists.
+Taken together, our findings suggest for the first time that PRRSV can suppress post-transcriptionally protein expression of IFN-β by upregulating cellular miRNAs in PAMs in vitro, providing novel insight into mechanisms in relation to the PRRSV-mediated immunomodulation of porcine innate immunity.
+Chemokine (C-C motif) ligand 5 (CCL5) belongs to a group of chemokines that play a role in the peripheral immune system, mostly as chemoattractant molecules, and mediate tactile allodynia.
+In the central nervous system (CNS), CCL5 and its receptors have multiple functions, including promoting neuroinflammation, insulin signaling, neuromodulator of synaptic activity and neuroprotection against a variety of neurotoxins.
+The multifunctional profile of CCL5 might correlate with its ability to bind different chemokine receptors, as well as with its unique cellular expression.
+In this work, we have used fluorescence in situ hybridization combined with immunohistochemistry to examine the expression profile of CCL5 mRNA in the adult rat brain and provide evidence of its cellular localization.
+We have observed that the highest expression of CCL5 mRNA occurs in all major fiber tracts, including the corpus callosum, anterior commissure, and cerebral peduncle.
+Astrocytic and microglial expression was also evident in several brain areas including the cerebral cortex, caudate/putamen, hippocampus, and thalamus.
+Furthermore, using a specific neuronal marker, we observed CCL5 mRNA expression in discrete layers of the cortex and hippocampus.
+Interestingly, in the midbrain, CCL5 mRNA co-localized with tyrosine hydroxylase (TH) positive cells of the ventral tegmental area, suggesting that CCL5 might be expressed by a subset of dopaminergic neurons of the mesolimbic system.
+The expression of CCL5 mRNA and protein, together with its receptors, in selected brain cell populations proposes that this chemokine could be involved in neuronal/glial communication.
+Background: In Africa, the clinical syndrome of pneumonia remains the leading cause of morbidity and mortality in children in the post-neonatal period.
+The targeted use of oxygen and simple, non-invasive methods of respiratory support may be a highly cost-effective means of improving outcome, but the optimal oxygen saturation threshold that results in benefit and the best strategy for delivery are yet to be tested in adequately powered randomised controlled trials.
+There is, however, an accumulating literature about the harms of oxygen therapy across a range of acute and emergency situations that have stimulated a number of trials investigating permissive hypoxia.
+Liberal oxygenation (recommended care) compared with a strategy that permits hypoxia to SpO (2 )> or = 80% (permissive hypoxia); and 2.
+Discussion: The overarching objective is to address the key research gaps in the therapeutic use of oxygen in resource-limited setting in order to provide a better evidence base for future management guidelines.
+The trial has been designed to address the poor outcomes of children in sub-Saharan Africa, which are associated with high rates of in-hospital mortality, 9-10% (for those with oxygen saturations of 80-92%) and 26-30% case fatality for those with oxygen saturations <80%.
+The highly pathogenic avian influenza (HPAI) H5N1 influenza virus has been a public health concern for more than a decade because of its frequent zoonoses and the high case fatality rate associated with human infections.
+Severe disease following H5N1 influenza infection is often associated with dysregulated host innate immune response also known as cytokine storm but the virological and cellular basis of these responses has not been clearly described.
+We rescued a series of 6:2 reassortant viruses that combined a PR8 HA/NA pairing with the internal gene segments from human adapted H1N1, H3N2, or avian H5N1 viruses and found that mice infected with the virus with H5N1 internal genes suffered severe weight loss associated with increased lung cytokines but not high viral load.
+This phenotype did not map to the NS gene segment, and NS1 protein of H5N1 virus functioned as a type I IFN antagonist as efficient as NS1 of H1N1 or H3N2 viruses.
+Instead we discovered that the internal genes of H5N1 virus supported a much higher level of replication of viral RNAs in myeloid cells in vitro, but not in epithelial cells and that this was associated with high induction of type I IFN in myeloid cells.
+We also found that in vivo during H5N1 recombinant virus infection cells of haematopoetic origin were infected and produced type I IFN and proinflammatory cytokines.
+Taken together our data infer that human and avian influenza viruses are differently controlled by host factors in alternative cell types; internal gene segments of avian H5N1 virus uniquely drove high viral replication in myeloid cells, which triggered an excessive cytokine production, resulting in severe immunopathology.
+Despite of the role of domestic dogs as reservoirs for threatening viral diseases for wild carnivores, few studies have focused to identify circulation of viruses among dogs living in human/wildlife interfaces.
+To identify canine parvovirus (CPV) types circulating in dogs living in an Atlantic forest biome, faecal samples (n = 100) were collected at the same period (one week) corresponding to each of four areas, during 2014 to 2016 and corresponded to 100 different individuals.
+CPV was isolated in cell culture from 67 out 100 (67%) samples from healthy dogs.
+Genome sequences of CPV-2a (10%), CPV-2b (7%) and CPV-2c (50%) were concomitantly detected by PCR and nucleotide sequencing.
+The current study addresses the importance of monitoring CPV circulation among dogs presenting potential contact with wildlife species.
+Malaria fever has been pervasive for quite a while in tropical developing regions causing high morbidity and mortality.
+The causal organism is a protozoan parasite of genus Plasmodium which spreads to the human host by the bite of hitherto infected female Anopheles mosquito.
+In the course of biting, a salivary protein of Anopheles helps in blood feeding behavior and having the ability to elicit the host immune response.
+This study represents a series of immunoinformatics approaches to design multi-epitope subunit vaccine using Anopheles mosquito salivary proteins.
+To enhance the stability of vaccine protein, disulfide engineering was performed in a region of high mobility.
+Codon adaptation and in silico cloning was also performed to ensure the higher expression of designed subunit vaccine in E. coli K12 expression system.
+Finally, molecular docking and simulation study was performed for the vaccine protein and TLR-4 receptor, to determine the binding free energy and complex stability.
+Moreover, the designed subunit vaccine was found to induce anti-salivary immunity which may have the ability to prevent the entry of Plasmodium sporozoites into the human host.
+We create a geometric analysis method (called GenomeLandscaper) to conduct landscape analysis of genome-fingerprints maps (GFM), trace large-scale repetitive regions, and assess their impacts on the global architectures of assembled chromosomes.
+We construct a galaxy of genome-fingerprints maps (GGFM) for them, and a landscape compatibility among relatives is observed.
+But a long sharp straight line on the GGFM breaks such a landscape compatibility, distinguishing GRCh38p1.chrY (and throughout GRCh38p7.chrY) from GRCh37p13.chrY, HuRef.chrY and YH.chrY.
+We delete a 1.30-Mbp target segment to rescue the landscape compatibility, matching the antecedent GRCh37p13.chrY.
+We re-locate it into the modelled centromeric and pericentromeric region of GRCh38p10.chrY, matching a gap placeholder of GRCh37p13.chrY.
+We decompose it into sub-constituents (such as BACs, interspersed repeats, and tandem repeats) and trace their homologues by phylogenetics analysis.
+We elucidate that most examined tandem repeats are of reasonable quality, but the BAC-sized repeats, 173U1020C (176.46 Kbp) and 5U41068C (205.34 Kbp), are likely over-repeated.
+These results offer unique insights into the centromeric and pericentromeric regions of the human Y chromosomes.
+Influenza virus stablishes a network of virus-host functional interactions, which depends on chromatin dynamic and therefore on epigenetic modifications.
+Using an unbiased search, we analyzed the epigenetic changes at DNA methylation and post-translational histone modification levels induced by the infection.
+DNA methylation was unaltered, while we found a general decrease on histone acetylation, which correlates with transcriptional inactivation and may cooperate with the impairment of cellular transcription that causes influenza virus infection.
+A particular increase in H3K79 methylation was observed and the use of an inhibitor of the specific H3K79 methylase, Dot1L enzyme, or its silencing, increased influenza virus replication.
+The antiviral response was reduced in conditions of Dot1L downregulation, since decreased nuclear translocation of NF-kB complex, and IFN-β, Mx1 and ISG56 expression was detected.
+The data suggested a control of antiviral signaling by methylation of H3K79 and consequently, influenza virus replication was unaffected in IFN pathway-compromised, Dot1L-inhibited cells.
+H3K79 methylation also controlled replication of another potent interferon-inducing virus such as vesicular stomatitis virus, but did not modify amplification of respiratory syncytial virus that poorly induces interferon signaling.
+Epigenetic methylation of H3K79 might have an important role in controlling interferon-induced signaling against viral pathogens.
+BACKGROUND: Social media, defined as interactive Web applications, have been on the rise globally, particularly among adults.
+The objective of this study was to investigate the trend of the literature related to the most used social network worldwide (i.e.
+Specifically, this study will assess the growth in publications, citation analysis, international collaboration, author productivity, emerging topics and the mapping of frequent terms in publications pertaining to social media in the field of psychology.
+METHODS: Publications related to social media in the field of psychology published between 2004 and 2014 were obtained from the Web of Science.
+The records extracted were analysed for bibliometric characteristics such as the growth in publications, citation analysis, international collaboration, emerging topics and the mapping of frequent terms in publications pertaining to social media in the field of psychology.
+The number of research publications in social media in the field of psychology showed a steady upward growth.
+Publications from the USA accounted for 57.14% of the total publications and the highest h-index (48).The most common document type was research articles (873; 91.03%).
+The University of Wisconsin–Madison ranked first in terms of the total publications (n = 39).
+A visualisation analysis showed that personality psychology, experimental psychology, psychological risk factors, and developmental psychology were continual concerns of the research.
+CONCLUSIONS: This is the first study reporting the global trends in the research related to social media in the psychology field.
+Based on the raw data from the Web of Science, publication characteristics such as quality and quantity were assessed using bibliometric techniques over 12 years.
+The most preferred topics related to social media in psychology are personality psychology, experimental psychology, psychological risk factors, and developmental psychology.
+As of May 1, 2017, 74 antibody-based molecules have been approved by a regulatory authority in a major market.
+Additionally, there are 70 and 575 antibody-based molecules in phase III and phase I/II clinical trials, respectively.
+These total 719 antibody-based clinical stage molecules include 493 naked IgGs, 87 antibody-drug conjugates, 61 bispecific antibodies, 37 total Fc fusion proteins, 17 radioimmunoglobulins, 13 antibody fragments, and 11 immunocytokines.
+There are over 80 antibodies in clinical trials targeting T cell checkpoints, 26 T-cell-redirected bispecific antibodies, and 145 chimeric antigen receptor (CAR) cell-based candidates (all currently in phase I or II clinical trials), totaling more than 250 T cell interacting clinical stage antibody-based candidates.
+Finally, significant progress has been made recently on routes of delivery, including delivery of proteins across the blood-brain barrier, oral delivery to the gut, delivery to the cellular cytosol, and gene- and viral-based delivery of antibodies.
+Thus, there are currently at least 864 antibody-based clinical stage molecules or cells, with incredible diversity in how they are constructed and what activities they impart.
+These are followed by a next wave of novel molecules, approaches, and new methods and routes of delivery, demonstrating that the field of antibody-based biologics is very innovative and diverse in its approaches to fulfill their promise to treat unmet medical needs.
+BACKGROUND: Acinetobacter species have become increasingly common in the intensive care units (ICU) over the past two decades, causing serious infections.
+At the American University of Beirut Medical Center, the incidence of multi-drug resistant Acinetobacter baumannii (MDR-Ab) infections in the ICU increased sharply in 2007 by around 120%, and these infections have continued to cause a serious problem to this day.
+METHODS: We conducted a seven-year prospective cohort study between 2007 and 2014 in the ICU.
+Early in the epidemic, a case-control study was performed that included MDR-Ab cases diagnosed between 2007 and 2008 and uninfected controls admitted to the ICU during the same time.
+RESULTS: The total number of patients with MDR-Ab infections diagnosed between 2007 and 2014 was 128.
+There were also 99 patients with MDR-Ab colonization without evidence of active infection between 2011 and 2014.
+The majority of infections were considered hospital-acquired (84%) and most consisted of respiratory infections (53.1%).
+CONCLUSION: MDR-Ab infections mostly consisted of ventilator-associated pneumonia and were associated with a very high mortality rate.
+Infection control measures should be reinforced to control the transmission of these organisms in the ICU.
+Here, we confirmed that water-extractable polysaccharides of CD (WPCD) could modulate immune responses in vitro and in vivo.
+In a dose-dependent manner, WPCD significantly promoted the maturation and function of murine marrow-derived dendritic cells (BM-DCs) through up-regulating the expression levels of MHC-II, CD86, CD80, and CD40, allogenic T cell proliferation, and the yields of IL-12 and TNF-α via toll-like receptor4 (TLR4), as indicated by in vitro experiments.
+WPCD effectively improved the titers of IgG, IgG(1) and IgG(2a) and markedly enhanced the proliferation of T and B cells, the production of IFN-γ and IL-4 in CD4(+) T cells and the expression level of IFN-γ in CD8(+) T cells better than Alum.
+Furthermore, WPCD could markedly up-regulate the expression levels of CD40 and CD80 on DCs in spleen and down-regulate the Treg frequency.
+The study suggests that polysaccharides of Cistanche deserticola are a safe and effective vaccine adjuvant for eliciting both humoral immunity and cellular immunity by activating DCs via TLR4 signaling pathway.
+Background Shared seasonal patterns, such as between influenza and some respiratory bacterial infections, can create associations between phenomena not causally related.
+Objectives To estimate the association of influenza with subsequent bacterial infections after full adjustment for confounding by seasonal and long‐term trends.
+Methods Time series of weekly counts of notified cases of invasive infections with Haemophilus influenzae, Neisseria meningitidis, Streptococcus pneumoniae and Streptococcus pyogenes, in Montréal, Canada, 1996–2008, were modelled by negative binomial regression, with terms representing seasonal and long‐term trends and terms for numbers of positive laboratory tests for influenza A and B.
+Results The associations of S. pneumoniae, H. influenzae and N. meningitidis with influenza disappeared after seasonal terms were added to the model.
+However, the influenza B count remained associated with the S. pyogenes counts for the same week and the following week: S. pyogenes incidence rate ratios were 1.0376 (95% CI: 1.0009–1.0757) and 1.0354 (0.9958–1.0766), respectively, for each increase of 1 in the influenza count.
+Conclusions Influenza B accounts for about 8percnt; of the incidence of invasive S. pyogenes infections, over and above any effect associated with modellable seasonal and long‐term trends.
+This association of influenza B with S. pyogenes infections can be attributed largely to the years 1997, 2001, 2007 and 2008, when late peaks in influenza B counts were followed by peaks in S. pyogenes notifications.
+This finding reinforces the case for universal immunization against influenza, as partial protection against the ‘flesh eating disease’.
+Extremely low risk for acquisition of a respiratory viral infection in the emergency room of a large pediatric hospital during the winter season.
+The aim of this study was to investigate the rate of transmission of respiratory viral infections to children visiting the emergency room of a large pediatric hospital during winter.
+Twenty‐two (3·6%) children developed at least one symptom compatible with a respiratory viral infection within 1–7 days after the visit, including cough (12 children), fever (8), rhinorrhea (7), and/or respiratory distress (1).
+These findings indicate that transmission of respiratory viral infections to children visiting an emergency room during the winter season is extremely low.
+Background Surveillance for influenza viruses within live bird markets (LBMs) has been recognized as an effective tool for detecting circulating avian influenza viruses (AIVs).
+In Sub‐Saharan Africa, limited data exist on AIVs in animal hosts, and in Kenya the presence of influenza virus in animal hosts has not been described.
+Objectives This surveillance project aimed to detect influenza A virus in poultry traded in five LBMs in Kenya.
+Methods We visited each market monthly and collected oropharyngeal and cloacal specimens from poultry and environmental specimens for virological testing for influenza A by real time RT‐PCR.
+On each visit, we collected information on the number and types of birds in each market, health status of the birds, and market practices.
+Of the 5199 (99·6%) specimens tested, influenza A virus was detected in 42 (0·8%), including 35/4166 (0·8%) specimens from chickens, 3/381 (0·8%) from turkeys, and 4/335 (1·2%) from geese.
+Influenza was more commonly detected in oropharyngeal [33 (1·3%)] than in cloacal [9 (0·4%)] specimens.
+Ducks and geese were kept longer at the market (median 30 days) than chickens (median 2 days).
+Conclusions Influenza A was detected in a small percentage of poultry traded in LBMs in Kenya.
+Efforts should be made to promote practices that could limit the maintenance and transmission of AIVs in LBMs.
+BACKGROUND: We report a fatal case of disseminated adenovirus infection in a non-transplant haematology adult patient with chronic lymphocytic leukaemia who had completed combination chemoimmunotherapy a few months before developing respiratory symptoms.
+non-blood) site of infection such as the chest, serial adenovirus monitoring in blood for the duration of that illness may be warranted.
+CASE PRESENTATION: This case started with an initial bacterial chest infection that responded to treatment, followed by an adenovirus pneumonitis that disseminated to his blood a week later with levels of up to 92 million adenovirus DNA copies/ml.
+Despite prompt treatment with cidofovir, his respiratory function continued to deteriorate over the next two weeks and he was moved to intensive care.
+However, he died soon after this with a final adenovirus load of 20 million copies/ml in his blood.
+CONCLUSIONS: We recommend that even in non-transplant haematology patients, where such patients present with an acute respiratory adenovirus infection, teams should consider checking the blood for adenovirus to check for signs of disseminated infection.
+The earlier this can be tested, the earlier treatment can be initiated (if adenovirus positive), which may produce more successful clinical outcomes.
+The purpose of this paper is to review the major sources of data on mortality, morbidity and health in Europe and in other developed regions in order to examine their potential for analysing mortality and morbidity levels and trends.
+No attempt is made to draw up an inventory of sources by country; the paper deals instead with the pros and cons of each source for mortality and morbidity studies in demography.
+While each source considered separately can already yield useful, though partial, results, record linkage among data sources can significantly improve the analysis.
+Record linkage can also lead to the detection of possible causal associations that could eventually be confirmed.
+More generally, Big Data can reveal changing mortality and morbidity trends and patterns that could lead to preventive measures being taken rather than more costly curative ones.
+The emergence of Variola virus-like viruses by natural evolution of zoonotic Orthopoxviruses, like Cowpox virus (CPXV), is a global health threat.
+The proteasome is essential for poxvirus replication, making the viral components interacting with the ubiquitin-proteasome system attractive antiviral targets.
+We show that proteasome inhibition impairs CPXV replication by prevention of uncoating, suggesting that uncoating is mediated by proteasomal degradation of viral core proteins.
+Therefore, for the first time, we analyzed globally ubiquitination sites in CPXV mature virion proteins using LC-MS/MS.
+Identification of 137 conserved sites in 54 viral proteins among five CPXV strains revealed extensive ubiquitination of structural core proteins.
+Moreover, since virions contained primarily K48-linked polyubiquitin, we hypothesized that core proteins are modified accordingly.
+However, quantitative analysis of ubiquitinated CPXV proteins early in infection showed no proteasomal degradation of core proteins.
+Instead, our data indicate that the recently suggested proteasomal regulation of the uncoating factor E5 is a prerequisite for uncoating.
+Expanding our understanding of poxvirus uncoating and elucidating a multitude of novel ubiquitination sites in poxvirus proteins, the present study verifies the major biological significance of ubiquitin in poxvirus infection.
+In this work, we developed a miniaturized palmtop high-speed capillary electrophoresis (CE) system integrating whole modules, including picoliter-scale sample injection, short capillary-based fast CE, high-voltage power supply, orthogonal laser induced fluorescence (LIF) detection, battery, system control, on-line data acquisition, processing, storage, and display modules.
+A strategy of minimalist miniaturization combining minimal system design and low-cost system construction was adopted to achieve the instrument miniaturization with extremely low cost, which is differing from the current microfabrication strategy used in most reported miniaturized CE systems.
+With such a strategy, the total size of the bioanalyzer was minimized to 90 × 75 × 77 mm (length × width × height) and the instrument cost was reduced to ca.
+$500, which demonstrated the smallest and lowest-cost CE instrument with LIF detection in so far reported systems.
+Fast separations were achieved for multiple types of samples as amino acids, amino acid enantiomers, DNA fragments, and proteins with high efficiency.
+We applied this instrument in colorectal cancer diagnosis for detecting KRAS mutation status by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method.
+Infections by Enterobacteriaceae producing metallo-β-lactamases (MBLs), e.g., New Delhi metallo-β-lactamase 1 (NDM-1) are very difficult to treat.
+Development of effective MBL inhibitors to revive the efficacy of existing antibiotics is highly desirable.
+Here we show that an anti-Helicobacter pylori drug, colloidal bismuth subcitrate (CBS), and related Bi(III) compounds irreversibly inhibit different types of MBLs via the mechanism, with one Bi(III) displacing two Zn(II) ions as revealed by X-ray crystallography, leading to the release of Zn(II) cofactors.
+CBS restores meropenem (MER) efficacy against MBL-positive bacteria in vitro, and in mice infection model, importantly, also slows down the development of higher-level resistance in NDM-1-positive bacteria.
+This study demonstrates a high potential of Bi(III) compounds as the first broad-spectrum B1 MBL inhibitors to treat MBL-positive bacterial infection in conjunction with existing carbapenems.
+The arthropod-transmitted chikungunya virus (CHIKV) causes a flu-like disease that is characterized by incapacitating arthralgia.
+The re-emergence of CHIKV and the continual risk of new epidemics have reignited research in CHIKV pathogenesis.
+Virus-specific antibodies have been shown to control virus clearance, but antibodies present at sub-neutralizing concentrations can also augment virus infection that exacerbates disease severity.
+To explore this occurrence, CHIKV infection was investigated in the presence of CHIKV-specific antibodies in both primary human cells and a murine macrophage cell line, RAW264.7.
+Enhanced attachment of CHIKV to the primary human monocytes and B cells was observed while increased viral replication was detected in RAW264.7 cells.
+Furthermore, experimental infection in adult mice showed that animals had higher viral RNA loads and endured more severe joint inflammation in the presence of sub-neutralizing concentrations of CHIKV-specific antibodies.
+In addition, CHIKV infection in 11 days old mice under enhancing condition resulted in higher muscles viral RNA load detected and death.
+These observations provide the first evidence of antibody-mediated enhancement in CHIKV infection and pathogenesis and could also be relevant for other important arboviruses such as Zika virus.
+We have produced a new Ebola virus pseudotype, E-S-FLU, that can be handled in biosafety level 1/2 containment for laboratory analysis.
+The E-S-FLU virus is a single-cycle influenza virus coated with Ebolavirus glycoprotein, and it encodes enhanced green fluorescence protein as a reporter that replaces the influenza virus hemagglutinin.
+MDCK-SIAT1 cells were transduced to express Ebolavirus glycoprotein as a stable transmembrane protein for E-S-FLU virus production.
+Infection of cells with the E-S-FLU virus was dependent on the Niemann-Pick C1 protein, which is the well-characterized receptor for Ebola virus entry at the late endosome/lysosome membrane.
+The E-S-FLU virus was neutralized specifically by an anti-Ebolavirus glycoprotein antibody and a variety of small drug molecules that are known to inhibit the entry of wild-type Ebola virus.
+To demonstrate the application of this new Ebola virus pseudotype, we show that a single laboratory batch was sufficient to screen a library (LOPAC(1280); Sigma) of 1,280 pharmacologically active compounds for inhibition of virus entry.
+A total of 215 compounds inhibited E-S-FLU virus infection, while only 22 inhibited the control H5-S-FLU virus coated in H5 hemagglutinin.
+These inhibitory compounds have very dispersed targets and mechanisms of action, e.g., calcium channel blockers, estrogen receptor antagonists, antihistamines, serotonin uptake inhibitors, etc., and this correlates with inhibitor screening results obtained with other pseudotypes or wild-type Ebola virus in the literature.
+The E-S-FLU virus is a new tool for Ebola virus cell entry studies and is easily applied to high-throughput screening assays for small-molecule inhibitors or antibodies.
+IMPORTANCE Ebola virus is in the Filoviridae family and is a biosafety level 4 pathogen.
+These characteristics warrant the development of surrogates for Ebola virus that can be handled in more convenient laboratory containment to study the biology of the virus and screen for inhibitors.
+Here we characterized a new surrogate, named E-S-FLU virus, that is based on a disabled influenza virus core coated with the Ebola virus surface protein but does not contain any genetic information from the Ebola virus itself.
+We show that E-S-FLU virus uses the same cell entry pathway as wild-type Ebola virus.
+As an example of the ease of use of E-S-FLU virus in biosafety level 1/2 containment, we showed that a single production batch could provide enough surrogate virus to screen a standard small-molecule library of 1,280 candidates for inhibitors of viral entry.
+This study was initiated due to the lack of published data concerning the real progress in research output in the use of nicotine replacement therapy (NRT) for tobacco cessation.
+This study was aimed to use bibliometric analysis to estimate the NRT literature indexed in Scopus database at global level.
+METHODS: Core of the search strategy was the documents that contained specific words or phrases regarding NRT as keywords in the title.
+Publication output of most prolific countries was adjusted to the gross domestic product and population size.
+RESULTS: A total of 2138 references were retrieved and published from 56 countries, which were published between 1970 and 2016.
+The USA has the most number of published articles accounted to 986, followed by the UK (312 publications) and then Australia (102 publications), and Sweden (102 publications).
+No significant correlation was found between the country population size or 2016 gross domestic product values and the number of publications of the top-10 most prolific countries in the field of NRT (r = − 0.156, P = 0.664; and r = − 0.173, P = 0.632, respectively).
+Furthermore, there is no correlation between prevalence of tobacco smoking and number of publications of the top-10 most prolific countries in the field of NRT (r = − 0.235, P = 0.514).
+The USA was by far the predominant country in the amount of NRT-based research activity.
+The results of this study delineate a framework for better understanding the situations of current NRT research and prospective directions of the research in this field which could be applied for managing and prioritizing future research efforts in NRT research.
+The present study aimed to determine the cost of childhood pneumococcal infections under 5 years of age and to provide further data for future health economy studies.
+Electronic medical records of children diagnosed with meningitis caused by S. pneumoniae and all-cause pneumonia, and acute otitis media (AOM) between January 2013-April 2014 were retrospectively evaluated.
+Direct costs for the treatments of hospitalized patients (pneumonia and pneumococcal meningitis) including costs of healthcare services consisted of costs of hospital bed, examination, laboratory analyses, scanning methods, consultation, vascular access procedures, and infusion and intravenous treatments.
+Direct costs for patients (AOM) treated in outpatient setting included constant price paid for the examination and cost of prescribed antibiotics.
+Data of 130 children with pneumococcal meningitis (n = 10), pneumonia (n = 53), and AOM (n = 67) were analyzed.
+The total median cost was €4,060.38 (direct cost: €3,346.38 and indirect cost: €829.18) for meningitis, €835.91 (direct cost: €480.66 and indirect cost: €330.09) for pneumonia, and €117.32 (direct cost: €17.59 and indirect cost: €99.73) for AOM.
+The medication cost (p = 0.047), indirect cost (p = 0.032), and total cost (p = 0.011) were significantly higher in pneumonia patients aged ≥36 months than those aged <36 months; however, direct cost of AOM were significantly higher in the patients aged <36 months (p = 0.049).
+Results of the present study revealed that the treatment cost was significantly enhanced for hospitalization and for advanced disease.
+The formulation of accurate clinical case definitions is an integral part of an effective process of public health surveillance.
+Although such definitions should, ideally, be based on a standardized and fixed collection of defining criteria, they often require revision to reflect new knowledge of the condition involved and improvements in diagnostic testing.
+Optimal case definitions also need to have a balance of sensitivity and specificity that reflects their intended use.
+After the 2009–2010 H1N1 influenza pandemic, the World Health Organization (WHO) initiated a technical consultation on global influenza surveillance.
+This prompted improvements in the sensitivity and specificity of the case definition for influenza – i.e.
+The revision process not only modified the definition of influenza-like illness, to include a simplified list of the criteria shown to be most predictive of influenza infection, but also clarified the language used for the definition, to enhance interpretability.
+To capture severe cases of influenza that required hospitalization, a new case definition was also developed for severe acute respiratory infection in all age groups.
+Despite the challenge still posed in the clinical separation of influenza from other respiratory infections, the global use of the new WHO case definitions should help determine global trends in the characteristics and transmission of influenza viruses and the associated disease burden.
+The human interferon (IFN)-induced MxA protein is a key antiviral host restriction factor exhibiting broad antiviral activity against many RNA viruses, including highly pathogenic avian influenza A viruses (IAV) of the H5N1 and H7N7 subtype.
+To date the mechanism for how MxA exerts its antiviral activity is unclear, however, additional cellular factors are believed to be essential for this activity.
+To identify MxA cofactors we performed a genome-wide siRNA-based screen in human airway epithelial cells (A549) constitutively expressing MxA using an H5N1 reporter virus.
+The combined data identified SMARCA2, the ATPase subunit of the BAF chromatin remodeling complex, as a crucial factor required for the antiviral activity of MxA against IAV.
+Intriguingly, our data demonstrate that although SMARCA2 is essential for expression of some IFN-stimulated genes (ISGs), and the establishment of an antiviral state, it is not required for expression of MxA, suggesting an indirect effect on MxA activity.
+Transcriptome analysis of SMARCA2-depleted A549-MxA cells identified a small set of SMARCA2-regulated factors required for activity of MxA, in particular IFITM2 and IGFBP3.
+These findings reveal that several virus-inducible factors work in concert to enable MxA restriction of IAV.
+Activation and regulation of the cascade systems of the blood (the complement system, the coagulation/contact activation/kallikrein system, and the fibrinolytic system) occurs via activation of zymogen molecules to specific active proteolytic enzymes.
+Despite the fact that the generated proteases are all present together in the blood, under physiological conditions, the activity of the generated proteases is controlled by endogenous protease inhibitors.
+This concept review article aims at identifying and describing conditions where the strict system-related control is circumvented.
+These include clinical settings where massive amounts of proteolytic enzymes are released from tissues, e.g., during pancreatitis or post-traumatic tissue damage, resulting in consumption of the natural substrates of the specific proteases and the available protease inhibitor.
+Another example of cascade system dysregulation is disseminated intravascular coagulation, with canonical activation of all cascade systems of the blood, also leading to specific substrate and protease inhibitor elimination.
+The present review explains basic concepts in protease biochemistry of importance to understand clinical conditions with extensive protease activation.
+Exploring biophysical properties of virus-encoded components and their requirement for virus replication is an exciting new area of interdisciplinary virological research.
+To date, spatial resolution has only rarely been analyzed in computational/biophysical descriptions of virus replication dynamics.
+However, it is widely acknowledged that intracellular spatial dependence is a crucial component of virus life cycles.
+The hepatitis C virus-encoded NS5A protein is an endoplasmatic reticulum (ER)-anchored viral protein and an essential component of the virus replication machinery.
+Therefore, we simulate NS5A dynamics on realistic reconstructed, curved ER surfaces by means of surface partial differential equations (sPDE) upon unstructured grids.
+We match the in silico NS5A diffusion constant such that the NS5A sPDE simulation data reproduce experimental NS5A fluorescence recovery after photobleaching (FRAP) time series data.
+Such parameters are needed for spatial models of HCV dynamics, which we are developing in parallel but remain qualitative at this stage.
+Thus, our present study likely provides the first quantitative biophysical description of the movement of a viral component.
+Our spatio-temporal resolved ansatz paves new ways for understanding intricate spatial-defined processes central to specfic aspects of virus life cycles.
+BACKGROUND: During each winter the hospital quality of care (QoC) in pediatric wards decreases due to a surge in pediatric infectious diseases leading to overcrowded units.
+Bed occupancy rates often surpass the good hospital bed management threshold of 85%, which can result in poor conditions in the workplace.
+This study explores how QoC-scores could be improved by investing in additional beds and/or better vaccination programs against vaccine-preventable infectious diseases.
+METHODS: The Cobb–Douglas model was selected to define the improvement in QoC (%) as a function of two strategies (rotavirus vaccination coverage [%] and addition of extra hospital beds [% of existing beds]), allowing improvement-isocurves to be produced.
+Subsequently, budget minimization was applied to determine the combination of the two strategies needed to reach a given QoC improvement at the lowest cost.
+The annual population in the catchment area to be vaccinated was 7000 children; the winter period was 90 days with 34 pediatric beds available.
+Rotavirus vaccination cost per course was €118.26 and the daily cost of a pediatric bed was €436.53.
+RESULTS: The model predicted that a combination of 64% vaccine coverage and 39% extra hospital beds (≈ 13 extra beds) in winter would improve QoC-scores by 50% for the minimum budget allocation.
+CONCLUSION: The model allows determination of the most efficient allocation of the healthcare budget between rotavirus vaccination and bed expansion for improving QoC-scores during the annual epidemic winter seasons.
+The non-specific effects (NSEs) of vaccines have been discussed for their potential long-term beneficial effects beyond direct protection against a specific pathogen.
+Cold-adapted, live attenuated influenza vaccine (CAIV) induces local innate immune responses that provide a broad range of antiviral immunity.
+Herein, we examined whether X-31ca, a donor virus for CAIVs, provides non-specific cross-protection against respiratory syncytial virus (RSV).
+The degree of RSV replication was significantly reduced when X-31ca was administered before RSV infection without any RSV-specific antibody responses.
+The vaccination induced an immediate release of cytokines and infiltration of leukocytes into the respiratory tract, moderating the immune perturbation caused by RSV infection.
+The potency of protection against RSV challenge was significantly reduced in TLR3(-/-) TLR7(-/-) mice, confirming that the TLR3/7 signaling pathways are necessary for the observed immediate and short-term protection.
+The additional benefits of CAIVs in mitigating acute respiratory infections for which vaccines are not yet available need to be assessed in future studies.
+Uropathogenic E. coli (UPEC), which cause urinary tract infections (UTI), utilize type 1 pili, a chaperone usher pathway (CUP) pilus, to cause UTI and colonize the gut.
+The pilus rod, comprised of repeating FimA subunits, provides a structural scaffold for displaying the tip adhesin, FimH.
+We solved the 4.2 Å resolution structure of the type 1 pilus rod using cryo-electron microscopy.
+Residues forming the interactive surfaces that determine the mechanical properties of the rod were maintained by selection based on a global alignment of fimA sequences.
+We identified mutations that did not alter pilus production in vitro but reduced the force required to unwind the rod.
+UPEC expressing these mutant pili were significantly attenuated in bladder infection and intestinal colonization in mice.
+This study elucidates an unappreciated functional role for the molecular spring-like property of type 1 pilus rods in host-pathogen interactions and carries important implications for other pilus-mediated diseases.
+Communication by public authorities during a crisis situation is an essential and indispensable part of any response to a situation that may threaten both life and property.
+In the online connected world possibilities for such communication have grown further, in particular with the opportunity that social media presents.
+As a consequence, communication strategies have become a key plank of responses to crises ranging from epidemics to terrorism to natural disaster.
+Whilst being able to bring about positive effects, they can also bring about a range of harmful unintended side effects.
+This include economic harms produced by incorrect information and a range of social harms that can be fuelled by myths and rumours, worsening negative phenomena such as stigmatisation and discrimination.
+Given the potential for such harms, one might expect that affected or potentially affected individuals would be able to challenge such measures before courts or administrative tribunals.
+More often than not seemingly applicable legal approaches are unlikely to be able to engage such methods.
+This is often because such measures represent activities that are purely expressive in nature and therefore not capable of imposing any binding legal or corporeal changes on individuals.
+Whilst some forms of soft law may pose requirements for public officials involved in such activities (e.g.
+codes of conduct or of professional ethics), they are not likely to offer potentially harmed individuals the chance to to challenge particular communication strategies before courts or legal tribunals.
+The result is that public authorities largely have a free reign to communicate how they wish and do not have to have to comply with a range of requirements (e.g.
+relating to form and substantive) content) that would in general apply to most forms of official administrative act.
+Here, we report that the H5N1 influenza virus encodes a microRNA-like small RNA, miR-HA-3p, which is processed from a stem loop-containing viral RNA precursor by Argonaute 2, and plays a role in enhancing cytokine production during H5N1 infection.
+Consistent with PCBP2 being an important negative regulator of RIG-I/MAVS-mediated antiviral innate immunity, suppression of PCBP2 expression by miR-HA-3p promotes cytokine production in human macrophages and mice infected with H5N1 virus.
+We conclude that miR-HA-3p is the first identified influenza virus-encoded microRNA-like functional RNA fragment and a novel virulence factor contributing to H5N1-induced 'cytokine storm' and mortality.
+A direct approach to prevent airborne transmission is inactivation of airborne pathogens, and the airborne antimicrobial potential of UVC ultraviolet light has long been established; however, its widespread use in public settings is limited because conventional UVC light sources are both carcinogenic and cataractogenic.
+By contrast, we have previously shown that far-UVC light (207–222 nm) efficiently inactivates bacteria without harm to exposed mammalian skin.
+This is because, due to its strong absorbance in biological materials, far-UVC light cannot penetrate even the outer (non living) layers of human skin or eye; however, because bacteria and viruses are of micrometer or smaller dimensions, far-UVC can penetrate and inactivate them.
+We show for the first time that far-UVC efficiently inactivates airborne aerosolized viruses, with a very low dose of 2 mJ/cm(2) of 222-nm light inactivating >95% of aerosolized H1N1 influenza virus.
+Continuous very low dose-rate far-UVC light in indoor public locations is a promising, safe and inexpensive tool to reduce the spread of airborne-mediated microbial diseases.
+Intracellular nucleic acid sensors often undergo sophisticated modifications that are critical for the regulation of antimicrobial responses.
+Upon recognition of DNA, the cytosolic sensor cyclic GMP-AMP (cGAMP) synthase (cGAS) produces the second messenger cGAMP, which subsequently initiates downstream signaling to induce interferon-αβ (IFNαβ) production.
+Here we report that TRIM56 E3 ligase-induced monoubiquitination of cGAS is important for cytosolic DNA sensing and IFNαβ production to induce anti-DNA viral immunity.
+TRIM56 induces the Lys335 monoubiquitination of cGAS, resulting in a marked increase of its dimerization, DNA-binding activity, and cGAMP production.
+Consequently, TRIM56-deficient cells are defective in cGAS-mediated IFNαβ production upon herpes simplex virus-1 (HSV-1) infection.
+Furthermore, TRIM56-deficient mice show impaired IFNαβ production and high susceptibility to lethal HSV-1 infection but not to influenza A virus infection.
+This adds TRIM56 as a crucial component of the cytosolic DNA sensing pathway that induces anti-DNA viral innate immunity.
+Due to the high complexity of this immunological syndrome development of novel therapeutic strategies is urgent.
+Promising drug targets or biomarkers may depict aquaporins (AQPs) as they regulate crucial key mechanisms of sepsis.
+MAIN BODY: Here we report on base of the current literature that several AQPs are involved in different physiological processes of sepsis.
+In immune system mainly AQPs 3, 5 and 9 seem to be important, as they regulate the migration of different immune cells.
+Several studies showed that AQP3 is essential for T cell function and macrophage migration and that AQP5 and AQP9 regulate neutrophil cell migration and impact sepsis survival.
+Additionally, to the function in immune system AQPs 1 and 5 play a role in sepsis induced lung injury and their downregulation after inflammatory stimuli impair lung injury.
+By contrast, AQP4 expression is up-regulated during brain inflammation and aggravates brain edema in sepsis.
+CONCLUSION: In conclusion, AQPs are involved in many physiological dysfunctions in sepsis and their expressions are differently regulated.
+Surfactant protein D (SP-D) is a multimeric collectin that is involved in innate immune defense and expressed in pulmonary, as well as non-pulmonary, epithelia.
+SP-D exerts antimicrobial effects and dampens inflammation through direct microbial interactions and modulation of host cell responses via a series of cellular receptors.
+However, low protein concentrations, genetic variation, biochemical modification, and proteolytic breakdown can induce decomposition of multimeric SP-D into low-molecular weight forms, which may induce pro-inflammatory SP-D signaling.
+Multimeric SP-D can decompose into trimeric SP-D, and this process, and total SP-D levels, are partly determined by variation within the SP-D gene, SFTPD.
+SP-D has been implicated in the development of respiratory diseases including respiratory distress syndrome, bronchopulmonary dysplasia, allergic asthma, and chronic obstructive pulmonary disease.
+Disease-induced breakdown or modifications of SP-D facilitate its systemic leakage from the lung, and circulatory SP-D is a promising biomarker for lung injury.
+Moreover, studies in preclinical animal models have demonstrated that local pulmonary treatment with recombinant SP-D is beneficial in these diseases.
+In recent years, SP-D has been shown to exert antimicrobial and anti-inflammatory effects in various non-pulmonary organs and to have effects on lipid metabolism and pro-inflammatory effects in vessel walls, which enhance the risk of atherosclerosis.
+A common SFTPD polymorphism is associated with atherosclerosis and diabetes, and SP-D has been associated with metabolic disorders because of its effects in the endothelium and adipocytes and its obesity-dampening properties.
+This review summarizes and discusses the reported genetic associations of SP-D with disease and the clinical utility of circulating SP-D for respiratory disease prognosis.
+Moreover, basic research on the mechanistic links between SP-D and respiratory, cardiovascular, and metabolic diseases is summarized.
+Cold-inducible RNA-binding protein (CIRP) is a novel sepsis inflammatory mediator and C23 is a putative CIRP competitive inhibitor.
+First, we confirmed that C23 dose-dependently inhibited TNF-α release, IκBα degradation, and NF-κB nuclear translocation in macrophages stimulated with CIRP.
+Next, we observed that male C57BL/6 mice treated with C23 (8 mg/kg BW) at 2 h after cecal ligation and puncture (CLP) had lower serum levels of LDH, ALT, IL-6, TNF-α, and IL-1β (reduced by ≥39%) at 20 h after CLP compared with mice treated with vehicle.
+C23-treated mice also had improved lung histology, less TUNEL-positive cells, lower serum levels of creatinine (34%) and BUN (26%), and lower kidney expression of NGAL (50%) and KIM-1 (86%).
+The 10-day survival after CLP of vehicle-treated mice was 55%, while that of C23-treated mice was 85%.
+In summary, C23 decreased systemic, lung, and kidney injury and inflammation, and improved the survival rate after CLP, suggesting that it may be developed as a new treatment for sepsis.
+BACKGROUND: Although viruses are known to be the second most common etiological factor in community-acquired pneumonia (CAP), the respiratory viral profile of the patients with healthcare-associated pneumonia (HCAP) has not yet been elucidated.
+We investigated the prevalence and the clinical impact of respiratory virus infection in adult patients with HCAP.
+METHODS: Patients admitted with HCAP or CAP, between January and December 2016, to a tertiary referral hospital in Korea, were prospectively enrolled, and virus identification was performed using reverse-transcription polymerase chain reaction (RT-PCR).
+RESULTS: Among 452 enrolled patients (224 with HCAP, 228 with CAP), samples for respiratory viruses were collected from sputum or endotracheal aspirate in 430 (95.1%) patients and from nasopharyngeal specimens in 22 (4.9%) patients.
+Eighty-seven (19.2%) patients had a viral infection, and the proportion of those with viral infection was significantly lower in the HCAP than in the CAP group (13.8% vs 24.6%, p = 0.004).
+In both the HCAP and CAP groups, influenza A was the most common respiratory virus, followed by entero-rhinovirus.
+In the HCAP group, the viral infection resulted in a similar length of hospital stay and in-hospital mortality as viral–bacterial coinfection and bacterial infection, and the CAP group showed similar results.
+CONCLUSIONS: The prevalence of viral infection in patients with HCAP was lower than that in patients with CAP, and resulted in a similar prognosis as viral–bacterial coinfection or bacterial infection.
+Porcine epidemic diarrhea, a disastrous gastrointestinal disease, causes great financial losses due to its high infectivity, morbidity and mortality in suckling piglets despite the development and application of various vaccines.
+In this study, high-throughput sequencing was used to explore differences in the intestinal microbiota between uninfected piglets and piglets infected with porcine epidemic diarrhea virus (PEDV).
+The results revealed that the small intestinal microbiota of suckling piglets infected with PEDV showed low diversity and was dominated by Proteobacteria (49.1%).
+Additionally, the composition of the small intestinal microbiota of sucking piglets infected with PEDV showed marked differences from that of the uninfected piglets.
+Some of the taxa showing differences in abundance between uninfected piglets and piglets infected with PEDV were associated with cellular transport and catabolism, energy metabolism, the biosynthesis of other secondary metabolites, and amino acid metabolism as determined through the prediction of microbial function based on the bacterial 16S rRNA gene.
+Therefore, adjusting the intestinal microbiota might be a promising method for the prevention or treatment of PEDV.
+The molecular functions of betanodavirus non-structural protein B and its role in host cell survival remain unclear.
+In the present study, we examined the roles of specific nuclear targeting domains in B1 localization as well as the effect of B1 nuclear localization on the cell cycle and host cell survival.
+The B1 protein of the Red spotted grouper nervous necrosis virus (RGNNV) was detected in GF-1 grouper cells as early as 24 hours post-infection (hpi).
+Using an EYFP-B1 fusion construct, we observed nuclear localization of the B1 protein (up to 99%) in GF-1 cells at 48 hpi.
+The nuclear localization of B1 was mediated by two arginine-rich nuclear targeting domains (B domain: (46)RRSRR(51); C domain: (63)RDKRPRR(70)) and domain C was more important than domain B in this process.
+B1 nuclear localization correlated with upregulation of p53 and p21((wef1/cip1)); downregulation of Cyclin D1, CDK4 and Mdm2; and G1/S cell cycle arrest in GF-1 cells.
+In conclusion, nuclear targeting of the RGNNV B1 protein via two targeting domains causes cell cycle arrest by up-regulating p53/p21 and down-regulating Mdm2, thereby regulating host cell survival.
+Peste des petits ruminants virus (PPRV) causes an acute and highly contagious disease of sheep and goats and has spread with alarming speed around the world.
+The pathology of Peste des petits ruminants is linked to retrogressive changes and necrotic lesions in lymphoid tissues and epithelial cells.
+Here, we performed a comprehensive study of the entry mechanism of PPRV into caprine endometrial epithelial cells (EECs).
+We clearly demonstrated that PPRV internalization was inhibited by chloroquine and ammonium chloride, which elevate the pH of various organelles.
+However, PPRV entry was not affected by chlorpromazine and knockdown of the clathrin heavy chain in EECs.
+In addition, we found that the internalization of PPRV was dependent on dynamin and membrane cholesterol and was suppressed by silencing of caveolin-1.
+Macropinocytosis did not play a role, but phosphatidylinositol 3-kinase (PI3K) was required for PPRV internalization.
+Cell type and receptor-dependent differences indicated that PPRV entry into caprine fetal fibroblast cells (FFCs) occurred via a different route.
+Taken together, our findings demonstrate that PPRV enters EECs through a cholesterol-dependent caveolae-mediated uptake mechanism that is pH-dependent and requires dynamin and PI3K but is independent of clathrin.
+BACKGROUND: Respiratory tract infections (RTIs) are a major morbidity factor contributing largely to health care costs and individual quality of life.
+The aim of the study was to test whether obesity (BMI ≥ 30 kg/m(2)) is one of the risk factors underlying frequent RTIs in the German adult population.
+METHODS: We recruited 1455 individuals between 18 to 70 years from a cross-sectional survey on airway infections in Germany and invited them to self-report in diaries incident RTIs experienced during three consecutive winter/spring seasons.
+RTIs reported in these 18 months and summary measures adding-up individual RTIs were the outcomes of interest.
+RESULTS: Compared to individuals with normal weight, obese individuals reported a consistently higher frequency of upper and lower RTIs and predominantly fell in the upper 10% group of a diary sumscore adding-up 10 different RTI symptoms over time.
+Obesity was associated both with lower RTIs ((adjusted)OR = 2.02, 95%CI = 1.36–3.00) and upper RTIs ((adjusted)OR = 1.55, 95%CI = 1.22–1.96).
+Stratified analyses suggested a stronger association for women and effect modifications by sports activity and dietary habits.
+CONCLUSIONS: We confirm the association of obesity with infection burden and present evidence for putative interaction with sports activity and dietary patterns.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12889-018-5172-8) contains supplementary material, which is available to authorized users.
+Background: Ebola virus disease (EVD) health facility transmission can result in infection and death of health workers.
+The World Health Organization (WHO) supports countries in preparing for and responding to public health emergencies, which often require developing new guidance in short timelines with scarce evidence.
+The objective of this study was to understand frontline physicians’ and nurses’ perspectives about personal protective equipment (PPE) use during the 2014-2016 EVD outbreak in West Africa and to incorporate these findings into the development process of a WHO rapid advice guideline.
+Methods : We surveyed frontline physicians and nurses deployed to West Africa between March and September of 2014.
+Results: We developed the protocol, obtained ethics approval, delivered the survey, analysed the data and presented the findings as part of the evidence-to-decision tables at the expert panel meeting where the recommendations were formulated within eight weeks.
+They generally felt at low or extremely low risk of virus transmission with all types of PPE used.
+Eye protection reduced the ability to provide care, mainly due to impaired visibility because of fogging.
+Heat and dehydration were a major issue for 76% of the participants using goggles and for 64% using a hood.
+Conclusion : Our study demonstrated that it was possible to incorporate primary data on end-users’ preferences into a rapid advice guideline for a public health emergency in difficult field conditions.
+Health workers perceived a balance between transmission protection and ability to care for patients effectively while wearing PPE.
+These findings were used by the guideline development expert panel to formulate WHO recommendations on PPE for frontline providers caring for EVD patients in outbreak conditions.
+Rotavirus (RV), belonging to Reoviridae family, is the leading cause of acute severe viral diarrhea in children (under 5 years old) and infant animals worldwide.
+Although vaccines are commonly used to prevent infection, episodes of diarrhea caused by RV frequently occur.
+Thus, this study was conducted to determine whether resveratrol had protective effects against RV infection in piglets.
+Following pretreatment with resveratrol dry suspension through adding into the basal diet for 3 weeks, the piglets were orally challenged with RV.
+Resveratrol-treatment inhibited the TNF-α production, indicating that the anti-RV activity of resveratrol may be achieved by reducing the inflammatory response.
+The IFN-γ level was elevated in 10mg/kg/d resveratrol-treated group and 30mg/kg/d resveratrol-treated group after RV infection.
+The ratios of CD4+/CD8+ in resveratrol-treated groups were the same as that in mock infected group, suggesting that resveratrol could maintain the immune function in RV-infected piglets.
+These results revealed that resveratrol dry suspension could be a new control measure for RV infection.
+Although antiviral drugs are available for the treatment of influenza infection, it is an urgent requirement to develop new antiviral drugs regarding the emergence of drug‐resistant viruses.
+The nucleoprotein (NP) is conserved among all influenza A viruses (IAVs) and has no cellular equivalent.
+In this study, we identified a novel anti‐influenza compound, ZBMD‐1, from a library of 20,000 compounds using cell‐based influenza A infection assays.
+We found that ZBMD‐1 inhibited the replication of H1N1 and H3N2 influenza A virus strains in vitro, with an IC (50) ranging from 0.41–1.14 μM.
+Further investigation indicated that ZBMD‐1 binds to the nuclear export signal 3 (NES3) domain and the dimer interface of the NP pocket.
+ZBMD‐1 also protected mice that were challenged with lethal doses of A/PR/8/1934 (H1N1) virus, effectively relieving lung histopathology changes, as well as strongly inhibiting the expression of pro‐inflammatory cytokines/chemokines, without inducing toxicity effects in mice.
+These results suggest that ZBMD‐1 is a promising anti‐influenza compound which can be further investigated as a useful strategy against IAVs in the future.
+Recycling endosomes maintain plasma membrane homeostasis and are important for cell polarity, migration, and cytokinesis.
+Here we show that the CORVET-specific subunits Vps3 and Vps8 also regulate vesicular transport from early to recycling endosomes.
+Vps3 and Vps8 localise to Rab4-positive recycling vesicles and co-localise with the CHEVI complex on Rab11-positive recycling endosomes.
+Depletion of Vps3 or Vps8 does not affect transferrin recycling, but delays the delivery of internalised integrins to recycling endosomes and their subsequent return to the plasma membrane.
+Consequently, Vps3/8 depletion results in defects in integrin-dependent cell adhesion and spreading, focal adhesion formation, and cell migration.
+These data reveal a role for Vps3 and Vps8 in a specialised recycling pathway important for integrin trafficking.
+Pancreatic cancer is the 5(th) leading cause of cancer deaths, and there are no effective treatments.
+We developed a poxvirus platform vaccine with improved immunogenicity and inserted the mesothelin gene to create an anti-mesothelin cancer vaccine.
+Mesothelin expression is mostly restricted to tumors in adult mammals and thus may be a good target for cancer treatment.
+We show here that the modified vaccinia virus Ankara (MVA) virus expressing mesothelin and the enhanced MVA virus missing the immunosuppressive A35 gene and expressing mesothelin were both safe in mice and were able to induce IFN-gamma secreting T cells in response to mesothelin expressing tumor cells.
+In addition, the MVA virus has oncolytic properties in vitro as it can replicate in and kill Panc02 pancreatic adenocarcinoma cell line tumor cells, even though it is unable to replicate in most mammalian cells.
+However, we were unable to demonstrate inhibition of Panc02 tumor growth in immunocompetent mice with pre-vaccination of mice, boosts, or even intratumoral injections of the recombinant viruses.
+Vaccine efficacy may be limited by shedding of mesothelin from tumor cells thus creating a protective screen from the immune system.
+Several leptospiral proteins that are upregulated during infection have been described, but their utility as a diagnostic marker is still unclear.
+In this study, we undertook a lipidomics approach to determine if there are any differences in the serum lipid profiles of horses naturally infected with pathogenic Leptospira spp.
+Utilizing a high-resolution mass spectrometry serum lipidomics analytical platform, we demonstrate that cyclic phosphatidic acids, diacylglycerols, and hydroperoxide oxidation products of choline plasmalogens are elevated in the serum of naturally infected as well as vaccinated horses.
+Other lipids of interest were triacylglycerols that were only elevated in the serum of infected horses and sphingomyelins that were increased only in the serum of vaccinated horses.
+This is the first report looking at the equine serum lipidome during leptospiral infection and vaccination.
+Numerous bioactive constituents of tea were confirmed to possess healthy benefits via the mechanisms of regulating gene expressions or protein activities.
+However, a complete interacting profile between tea bioactive compounds (TBCs) and their target genes is lacking, which put an obstacle in the study of healthy function of tea.
+To fill this gap, we developed a database of target genes of TBCs (TBC2target, http://camellia.ahau.edu.cn/TBC2target) based on a pharmacophore mapping approach.
+TBC2target contains detailed information about each interacting entry, such as TBC, CAS number, PubChem CID, source of compound (e.g., green, black), compound type, target gene(s) of TBC, gene symbol, gene ID, ENSEMBL ID, PDB ID, TBC bioactivity and the reference.
+Using the TBC-target associations, we constructed a bipartite network and provided users the global network and local sub-network visualization and topological analyses.
+The particular strengths of TBC2target are the inclusion of the comprehensive TBC-target interactions, and the capacity to visualize and analyze the interacting networks, which may help uncovering the beneficial effects of tea on human health as a central resource in tea health community.
+Infectious pathogens are known for their rapid evolutionary rates with new mutations arising over days to weeks.
+The ability to rapidly recover whole genome sequences and analyze the spread and evolution of pathogens using genetic information and pathogen collection dates has lead to interest in real-time tracking of infectious transmission and outbreaks.
+However, the level of temporal resolution afforded by these analyses may conflict with definitions of what constitutes protected health information (PHI) and privacy requirements for de-identification for publication and public sharing of research data and metadata.
+In the United States, dates and locations associated with patient care that provide greater resolution than year or the first three digits of the zip code are generally considered patient identifiers.
+Admission and discharge dates are specifically named as identifiers in Department of Health and Human Services guidance.
+To understand the degree to which one can impute admission dates from specimen collection dates, we examined sample collection dates and patient admission dates associated with more than 270,000 unique microbiological results from the University of Washington Laboratory Medicine Department between 2010 and 2017.
+Across all positive microbiological tests, the sample collection date exactly matched the patient admission date in 68.8% of tests.
+Collection dates and admission dates were identical from emergency department and outpatient testing 86.7% and 96.5% of the time, respectively, with >99% of tests collected within 1 day from the patient admission date.
+Samples from female patients were significantly more likely to be collected closer to admission date that those from male patients.
+We show that PHI-associated dates such as admission date can confidently be imputed from deposited collection date.
+We suggest that publicly depositing microbiological collection dates at greater resolution than the year may not meet routine Safe Harbor-based requirements for patient de-identification.
+We recommend the use of Expert Determination to determine PHI for a given study and/or direct patient consent if clinical laboratories or phylodynamic practitioners desire to make these data available.
+Host restriction factors constitute a formidable barrier for viral replication to which many viruses have evolved counter-measures.
+Human SAMD9, a tumor suppressor and a restriction factor for poxviruses in cell lines, is antagonized by two classes of poxvirus proteins, represented by vaccinia virus (VACV) K1 and C7.
+A paralog of SAMD9, SAMD9L, is also encoded by some mammals, while only one of two paralogs is retained by others.
+Here, we show that SAMD9L functions similarly to SAMD9 as a restriction factor and that the two paralogs form a critical host barrier that poxviruses must overcome to establish infection.
+In mice, which naturally lack SAMD9, overcoming SAMD9L restriction with viral inhibitors is essential for poxvirus replication and pathogenesis.
+While a VACV deleted of both K1 and C7 (vK1L(-)C7L(-)) was restricted by mouse cells and highly attenuated in mice, its replication and virulence were completely restored in SAMD9L(-/-) mice.
+In humans, both SAMD9 and SAMD9L are poxvirus restriction factors, although the latter requires interferon induction in many cell types.
+While knockout of SAMD9 with Crispr-Cas9 was sufficient for abolishing the restriction for vK1L(-)C7L(-) in many human cells, knockout of both paralogs was required for abolishing the restriction in interferon-treated cells.
+Both paralogs are antagonized by VACV K1, C7 and C7 homologs from diverse mammalian poxviruses, but mouse SAMD9L is resistant to the C7 homolog encoded by a group of poxviruses with a narrow host range in ruminants, indicating that host species-specific difference in SAMD9/SAMD9L genes serves as a barrier for cross-species poxvirus transmission.
+BACKGROUND: Until now, there is non-specific treatment, and exploring early and novel biomarkers to determine the disease severity and prognosis of hemorrhagic fever with renal syndrome (HFRS) would be of importance for clinician to take systematic and timely intervention.
+This study observed the expression of plasma sCD138, a soluble component shedding from the glycocalyx (GCX) to the circulating blood, and evaluated its predictive value on disease severity and prognosis of HFRS.
+METHODS: One hundred and seventy-six patients with HFRS who were treated at our center between January 2011 and December 2013 were randomly enrolled in this study.
+The patients were divided into a mild-type group, a moderate-type group, a severe-type group and a critical-type group according to the HFRS criteria for clinical classification.
+The levels of prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (Fib), albumin (ALB), alanine aminotransferase (ALT), aspartate aminotransferase (AST), white blood cells (WBC), platelets (PLT), glucose (GLU), blood urea nitrogen (BUN) and serum creatinine (Scr) in the samples were routinely tested.
+The levels of sCD138 among the different types were compared; the correlation among sCD138 and the laboratory parameters mentioned above were analyzed.
+The predictive effectiveness for prognosis of sCD138 was evaluated using the receiver operating characteristic (ROC) curve analysis.
+RESULTS: Except for the mild-type, the levels of sCD138 in the moderate-, severe- and critical-type patients during the acute stage were significantly higher than that of the convalescent stage and the control (P<0.05).
+With the aggravation of the disease, the levels of sCD138 during the acute stage had an increasing tendency, while demonstrated no significant difference among the moderate-, severe- and critical-type patients (P>0.05).
+sCD138 was negatively correlated with Fib, PLT and ALB, and was positively correlated with WBC and AST (P<0.05).
+sCD138 demonstrated predictive effectiveness for prognosis with the area under the curve (AUC) of 0.778 (P<0.001).
+CONCLUSION: Dynamic detection of plasma sCD138 might be benefit to evaluating the disease severity and prognosis of the patients with HFRS.
+Traditional approaches to assess the immune response of chickens to infection are through animal trials, which are expensive, require enhanced biosecurity, compromise welfare, and are frequently influenced by confounding variables.
+Since the chicken embryo becomes immunocompetent prior to hatch, we here characterized the transcriptional response of selected innate immune genes to Newcastle disease virus (NDV) infection in chicken embryos at days 10, 14, and 18 of embryonic development.
+The results suggest that the innate immune response 72 h after challenge of 18-day chicken embryo is both consistent and robust.
+The expression of CCL5, Mx1, and TLR3 in lung tissues of NDV challenged chicken embryos from the outbred Kuroiler and Tanzanian local ecotype lines showed that their expression was several orders of magnitude higher in the Kuroiler than in the local ecotypes.
+Next, the expression patterns of three additional innate-immunity related genes, IL-8, IRF-1, and STAT1, were examined in the highly congenic Fayoumi (M5.1 and M15.2) and Leghorn (Ghs6 and Ghs13) sublines that differ only at the microchromosome bearing the major histocompatibility locus.
+The results show that the Ghs13 Leghorn subline had a consistently higher expression of all genes except IL-8 and expression seemed to be subline-dependent rather than breed-dependent, suggesting that the innate immune response of chicken embryos to NDV infection may be genetically controlled by the MHC-locus.
+Taken together, the results suggest that the chicken embryo may represent a promising model to studying the patterns and sources of variation of the avian innate immune response to infection with NDV and related pathogens.
+The hydroalcoholic extract of Punica granatum (pomegranate) leaves was previously demonstrated to be anti-inflammatory in a rat model of lipopolysaccharide- (LPS-) induced acute peritonitis.
+Here, we investigated the anti-inflammatory effects of the ethyl acetate fraction obtained from the pomegranate leaf hydroalcoholic extract (EAFPg) on the LPS-induced acute lung injury (ALI) mouse model.
+Male Swiss mice received either EAFPg at different doses or dexamethasone (per os) prior to LPS intranasal instillation.
+Animals were culled at 4 h after LPS challenge, and the bronchoalveolar lavage fluid (BALF) and lung samples were collected for analysis.
+EAFPg and kaempferol effects on NO and cytokine production by LPS-stimulated RAW 264.7 macrophages were also investigated.
+Pretreatment with EAFPg (100–300 mg/kg) markedly reduced cell accumulation (specially neutrophils) and collagen deposition in the lungs of ALI mice.
+The same animals presented with reduced lung and BALF TNF-α and IL-1β expression in comparison with vehicle controls (p < 0.05).
+Additionally, incubation with either EAFPg or kaempferol (100 μg/ml) reduced NO production and cytokine gene expression in cultured LPS-treated RAW 264.7 macrophages.
+Selection of reference genes has become an integral step in any real time quantitative PCR (RT-qPCR) based expression studies.
+The importance of this study stems from the fact that riverine buffaloes are major dairy species of Indian sub-continent and the information generated here will be of great interest to the investigators engaged in functional genomic studies of this important livestock species.
+In addition to overall analysis, tissue wise evaluation of expression stability of individual RG was also performed.
+Three different algorithms provided in geNorm, NormFinder and BestKeeper softwares were used to evaluate the stability of 10 potential reference genes from different functional classes.
+From the most stable to the least stable, genes were ranked as: UXT/RPS9> RPL4> RPS23> EEF1A1> ACTB> HMBS> GAPDH> B2M> RPS15.
+While NormFinder analysis ranked the genes as: UXT> RPS23> RPL4> RPS9> EEF1A1> HMBS> ACTB> β2M> GAPDH> RPS15.
+Based on the crossing point SD value and range of fold change expression, BestKeeper analysis ranked the genes as: RPS9> RPS23/UXT> RPL4> GAPDH> EEF1A1> ACTB> HMBS> β2M> RPS15.
+Overall the study has identified RPS23, RPS9, RPL4 and UXT genes to be the most stable and appropriate RGs that could be utilized for normalization of transcriptional data in various tissues of buffaloes.
+This manuscript thus provide useful information on panel of reference genes that could be helpful for researchers conducting functional genomic studies in riverine buffaloes.
+Viscous sputum specimens usually cannot undergo automated extraction, and thus, a pre-homogenization process is desirable before isolating nucleic acids for real-time reverse transcription PCR.
+In this study, we compared three preprocessing methods [preprocessing with normal saline (NS), dithiothreitol (DTT), and proteinase K (PK)] of sputum specimens on the extraction and detection of influenza A virus (IAV) nucleic acids.
+Based on the experimental results of 217 specimens, we found that DTT and PK could be used to improve the homogenization effects of sputum and increase the positive rates by 5.53–6.91% higher than that of the NS group.
+Comparison of 49 positive specimens in all of the three groups demonstrated that the threshold cycle values of the DTT group and PK group were significantly lower and their nucleic acid concentration and A(260)/A(280) ratio within 1.8–2.0 were higher than those of the NS group.
+Thus, sputum homogenization before nucleic acid extraction is essential for the accurate diagnosis of IAV infection.
+In this study, estimates of the growth rate of new infections, based on the growth rate of new laboratory-confirmed cases, were used to provide a statistical basis for in-depth research into the epidemiological patterns of H7N9 epidemics.
+The incubation period, interval from onset to laboratory confirmation, and confirmation time for all laboratory-confirmed cases of H7N9 avian influenza in Mainland China, occurring between January 2013 and June 2017, were used as the statistical data.
+Stochastic processes theory and maximum likelihood were used to calculate the growth rate of new infections.
+Time-series analysis was then performed to assess correlations between the time series of new infections and new laboratory-confirmed cases.
+Laboratory confirmation was delayed by a period of time longer than that of the infection (average delay, 13 days; standard deviation, 6.8 days).
+At the lags of −7.5 and −15 days, respectively, the time-series of new infections and new confirmed cases were significantly correlated; the cross correlation coefficients (CCFs) were 0.61 and 0.16, respectively.
+The temporal distribution characteristics of new infections and new laboratory-confirmed cases were similar and strongly correlated.
+BACKGROUND/PURPOSE: Acral melanoma is the most common type of melanoma in Asians, and usually results in a poor prognosis due to late diagnosis.
+We applied a convolutional neural network to dermoscopy images of acral melanoma and benign nevi on the hands and feet and evaluated its usefulness for the early diagnosis of these conditions.
+METHODS: A total of 724 dermoscopy images comprising acral melanoma (350 images from 81 patients) and benign nevi (374 images from 194 patients), and confirmed by histopathological examination, were analyzed in this study.
+To perform the 2-fold cross validation, we split them into two mutually exclusive subsets: half of the total image dataset was selected for training and the rest for testing, and we calculated the accuracy of diagnosis comparing it with the dermatologist’s and non-expert’s evaluation.
+RESULTS: The accuracy (percentage of true positive and true negative from all images) of the convolutional neural network was 83.51% and 80.23%, which was higher than the non-expert’s evaluation (67.84%, 62.71%) and close to that of the expert (81.08%, 81.64%).
+Moreover, the convolutional neural network showed area-under-the-curve values like 0.8, 0.84 and Youden’s index like 0.6795, 0.6073, which were similar score with the expert.
+CONCLUSION: Although further data analysis is necessary to improve their accuracy, convolutional neural networks would be helpful to detect acral melanoma from dermoscopy images of the hands and feet.
+HIV-1 arose as the result of spillover of simian immunodeficiency viruses (SIVs) from great apes in Africa, namely from chimpanzees and gorillas.
+The host barriers that drive viral adaptation have predominantly been attributed to restriction factors, rather than cofactors (host proteins exploited to promote viral replication).
+Here, we consider the role of one cofactor, RanBP2, in providing a barrier that drove viral genome evolution during SIV spillover events.
+RanBP2 (also known as Nup358) is a component of the nuclear pore complex known to facilitate nuclear entry of HIV-1.
+Our data suggest that transmission of SIV from monkeys to chimpanzees, and then from chimpanzees to gorillas, both coincided with changes in the viral capsid that allowed interaction with RanBP2 of the new host species.
+However, human RanBP2 subsequently provided no barrier to the zoonotic transmission of SIV from chimpanzees or gorillas, indicating that chimpanzee- and gorilla-adapted SIVs are pre-adapted to humans in this regard.
+Our observations are in agreement with RanBP2 driving virus evolution during cross-species transmissions of SIV, particularly in the transmissions to and between great ape species.
+These exacerbations are associated with elevated lung levels of lactate dehydrogenase (LDH), indicating occurrence of cell necrosis.
+We thus hypothesized that reduced lung IFN-β could contribute to necrotic cell death in a model of asthma exacerbations.
+Wild-type and IFN-β(−/−) mice were given saline or house dust mite (HDM) intranasally for 3 weeks to induce inflammation.
+HDM induced an eosinophilic inflammation, which was not associated with increased expression of cleaved caspase-3, cleaved PARP or elevated bronchoalveolar lavage fluid (BALF) LDH levels in wild-type.
+However, exacerbation evoked by HDM + dsRNA challenges increased BALF levels of LDH, apoptotic markers and the necroptotic markers receptor-interacting protein (RIP)-3 and phosphorylation of mixed linage kinase domain-like protein (pMLKL), compared to HDM + saline.
+Absence of IFN-β at exacerbation further increased BALF LDH and protein expression of pMLKL compared to wild-type.
+We demonstrate that cell death markers are increased at viral stimulus-induced exacerbation in mouse lungs, and that absence of IFN-β augments markers of necroptotic cell death at exacerbation.
+The pathogenesis of autoimmune diseases, such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) is driven by genetic predisposition and environmental triggers that lead to dysregulated immune responses.
+Current therapies for RA and other autoimmune diseases reduce inflammation by targeting inflammatory mediators, most of which are innate response cytokines, resulting in generalized immunosuppression.
+Overall, this strategy has been very successful, but not all patients respond, responses can diminish over time and numerous side effects can occur.
+Therapies that target the germinal center (GC) reaction and/or antibody-secreting plasma cells (PC) potentially provide a novel approach.
+TANK-binding kinase 1 (TBK1) is an IKK-related serine/threonine kinase best characterized for its involvement in innate antiviral responses through the induction of type I interferons.
+In this review, we discuss the role of TBK1 in immunological pathways involved in the development and maintenance of antibody responses, with particular emphasis on its potential relevance in the pathogenesis of humoral autoimmunity.
+Second, we highlight how TBK1 mediates inducible T cell co-stimulator signaling to the GC T follicular B helper population.
+Third, we discuss emerging evidence on the contribution of TBK1 to autophagic pathways and the potential implications for immune cell function.
+Vaccination is the process of administering immunogenic formulations in order to induce or harness antigen (Ag)-specific antibody and T cell responses in order to protect against infections.
+Important successes have been obtained in protecting individuals against many deleterious pathological situations after parenteral vaccination.
+However, one of the major limitations of the current vaccination strategies is the administration route that may not be optimal for the induction of immunity at the site of pathogen entry, i.e., mucosal surfaces.
+It is now well documented that immune responses along the genital, respiratory, or gastrointestinal tracts have to be elicited locally to ensure efficient trafficking of effector and memory B and T cells to mucosal tissues.
+Moreover, needle-free mucosal delivery of vaccines is advantageous in terms of safety, compliance, and ease of administration.
+However, the quest for mucosal vaccines is challenging due to (1) the fact that Ag sampling has to be performed across the epithelium through a relatively limited number of portals of entry; (2) the deleterious acidic and proteolytic environment of the mucosae that affect the stability, integrity, and retention time of the applied Ags; and (3) the tolerogenic environment of mucosae, which requires the addition of adjuvants to elicit efficient effector immune responses.
+In animal models and clinical trials, the use of lipidic structures such as liposomes, virosomes, immune stimulating complexes, gas-filled microbubbles and emulsions has proven efficient for the mucosal delivery of associated Ags and the induction of local and systemic immune reponses.
+Such particles are suitable for mucosal delivery because they protect the associated payload from degradation and deliver concentrated amounts of Ags via specialized sampling cells (microfold cells) within the mucosal epithelium to underlying antigen-presenting cells.
+The review aims at summarizing recent development in the field of mucosal vaccination using lipid-based particles.
+The modularity ensured by tailoring the lipidic design and content of particles, and their known safety as already established in humans, make the continuing appraisal of these vaccine candidates a promising development in the field of targeted mucosal vaccination.
+BACKGROUND: It has been found that health-seeking behavior has a certain impact on influenza infection.
+However, behaviors with/without risk perception on the control of influenza transmission among age groups have not been well quantified.
+OBJECTIVES: The purpose of this study was to assess to what extent, under scenarios of with/without control and preventive/protective behaviors, the age-specific network-driven risk perception influences influenza infection.
+MATERIALS AND METHODS: A behavior-influenza model was used to estimate the spread rate of age-specific risk perception in response to an influenza outbreak.
+A network-based information model was used to assess the effect of network-driven risk perception information transmission on influenza infection.
+A probabilistic risk model was used to assess the infection risk effect of risk perception with a health behavior change.
+RESULTS: The age-specific overlapping percentage was estimated to be 40%–43%, 55%–60%, and 19%–35% for child, teenage and adult, and elderly age groups, respectively.
+Individuals perceive the preventive behavior to improve risk perception information transmission among teenage and adult and elderly age groups, but not in the child age group.
+The population with perceived health behaviors could not effectively decrease the percentage of infection risk in the child age group, whereas for the elderly age group, the percentage of decrease in infection risk was more significant, with a 97.5th percentile estimate of 97%.
+CONCLUSION: The present integrated behavior-infection model can help health authorities in communicating health messages for an intertwined belief network in which health-seeking behavior plays a key role in controlling influenza infection.
+However, we are far from understanding whether this is a cause or consequence of HTN, and how to best translate this fundamental knowledge to advance the management of HTN.
+This review aims to summarize recent advances in the field, illustrate the connections between the gut and hypertension, and establish that the gut microbiota (GM)-gut interaction is centrally positioned for consideration as an innovative approach for HTN therapeutics.
+RECENT FINDINGS: Animal models of HTN have shown that gut pathology occurs in HTN, and provides some clues to mechanisms linking the dysbiosis, gut pathology, and HTN.
+Gut pathology, apparent in animal HTN models, has not been fully investigated in hypertensive patients.
+Objective evidence and an understanding of mechanisms could have a major impact for new antihypertensive therapies and/or improved applications of current ones.
+Although the genetic basis of Duchenne muscular dystrophy has been known for almost thirty years, the cellular and molecular mechanisms characterizing the disease are not completely understood and an efficacious treatment remains to be developed.
+In this study we analyzed proteomics data obtained with the SomaLogic technology from blood serum of a cohort of patients and matched healthy subjects.
+We developed a workflow based on biomarker identification and network-based pathway analysis that allowed us to describe different deregulated pathways.
+In addition to muscle-related functions, we identified other biological processes such as apoptosis, signaling in the immune system and neurotrophin signaling as significantly modulated in patients compared with controls.
+Moreover, our network-based analysis identified the involvement of FoxO transcription factors as putative regulators of different pathways.
+On the whole, this study provided a global view of the molecular processes involved in Duchenne muscular dystrophy that are decipherable from serum proteome.
+The evolution of bias in synonymous codon usage in chosen monkeypox viral genomes and the factors influencing its diversification have not been reported so far.
+In this study, various trends associated with synonymous codon usage in chosen monkeypox viral genomes were investigated, and the results are reported.
+Identification of factors that influence codon usage in chosen monkeypox viral genomes was done using various codon usage indices, such as the relative synonymous codon usage, the effective number of codons, and the codon adaptation index.
+The Spearman rank correlation analysis and a correspondence analysis were used for correlating various factors with codon usage.
+The results revealed that mutational pressure due to compositional constraints, gene expression level, and selection at the codon level for utilization of putative optimal codons are major factors influencing synonymous codon usage bias in monkeypox viral genomes.
+A cluster analysis of relative synonymous codon usage values revealed a grouping of more virulent strains as one major cluster (Central African strains) and a grouping of less virulent strains (West African strains) as another major cluster, indicating a relationship between virulence and synonymous codon usage bias.
+This study concluded that a balance between the mutational pressure acting at the base composition level and the selection pressure acting at the amino acid level frames synonymous codon usage bias in the chosen monkeypox viruses.
+The natural selection from the host does not seem to have influenced the synonymous codon usage bias in the analyzed monkeypox viral genomes.
+BACKGROUND: Oral cholera vaccination is an approach to preventing outbreaks in at-risk settings and controlling cholera in endemic settings.
+However, vaccine-derived herd immunity may be short-lived due to interactions between human mobility and imperfect or waning vaccine efficacy.
+As the supply and utilization of oral cholera vaccines grows, critical questions related to herd immunity are emerging, including: who should be targeted; when should revaccination be performed; and why have cholera outbreaks occurred in recently vaccinated populations?
+METHODS AND FINDINGS: We use mathematical models to simulate routine and mass oral cholera vaccination in populations with varying degrees of migration, transmission intensity, and vaccine coverage.
+We show that migration and waning vaccine efficacy strongly influence the duration of herd immunity while birth and death rates have relatively minimal impacts.
+As compared to either periodic mass vaccination or routine vaccination alone, a community could be protected longer by a blended “Mass and Maintain” strategy.
+We show that vaccination may be best targeted at populations with intermediate degrees of mobility as compared to communities with very high or very low population turnover.
+Using a case study of an internally displaced person camp in South Sudan which underwent high-coverage mass vaccination in 2014 and 2015, we show that waning vaccine direct effects and high population turnover rendered the camp over 80% susceptible at the time of the cholera outbreak beginning in October 2016.
+CONCLUSIONS: Oral cholera vaccines can be powerful tools for quickly protecting a population for a period of time that depends critically on vaccine coverage, vaccine efficacy over time, and the rate of population turnover through human mobility.
+Due to waning herd immunity, epidemics in vaccinated communities are possible but become less likely through complementary interventions or data-driven revaccination strategies.
+The class I major histocompatibility complex (MHC) is capable of binding peptides derived from intracellular proteins and displaying them at the cell surface.
+The recognition of these peptide-MHC (pMHC) complexes by T-cells is the cornerstone of cellular immunity, enabling the elimination of infected or tumoral cells.
+T-cell-based immunotherapies against cancer, which leverage this mechanism, can greatly benefit from structural analyses of pMHC complexes.
+Several attempts have been made to use molecular docking for such analyses, but pMHC structure remains too challenging for even state-of-the-art docking tools.
+To overcome these limitations, we describe the use of an incremental meta-docking approach for structural prediction of pMHC complexes.
+Previous methods applied in this context used specific constraints to reduce the complexity of this prediction problem, at the expense of generality.
+Our strategy makes no assumption and can potentially be used to predict binding modes for any pMHC complex.
+Our method has been tested in a re-docking experiment, reproducing the binding modes of 25 pMHC complexes whose crystal structures are available.
+This study is a proof of concept that incremental docking strategies can lead to general geometry prediction of pMHC complexes, with potential applications for immunotherapy against cancer or infectious diseases.
+Numerous peripheral tissues possess self-sustaining daily biologic rhythms that are regulated at the molecular level by clock genes such as PER1, PER2, CLOCK, and BMAL1.
+Nevertheless, little is known of the expression and distribution pattern of clock genes in nasal mucosa.
+The present study investigates the expression level and distribution pattern of PER1, PER2, CLOCK, and BMAL1 genes in nasal mucosa of healthy controls, allergic rhinitis patients, and normal rats.
+In human and rat nasal mucosa, the levels of these genes are asymmetrically expressed in nasal mucosa derived from right and left cavities in normal controls, allergic patients, and rat.
+In human nasal mucosa, the expression levels of these genes were higher in the decongested side than the congested mucosa.
+In rat nasal mucosa, these clock genes are expressed in a rhythmic circadian manner under the regular light/dark cycles.
+The expression levels of MUC5AC, a key mucin genes produced in superficial epithelium, are higher in decongested side than that congested side in human nasal mucosa.
+In rat nasal mucosa, MUC5AC levels showed a circadian rhythm which was associated with different expression levels in nasal mucosa derived from the right and left nasal cavities.
+Taken together with these results, the present study shows that the clock genes such as PER1, PER2, CLOCK, and BMAL1 are present in human and rat nasal mucosa, and suggest that these clock genes may control the pathophysiological function of nasal mucosa as circadian oscillators and affect the maintenance of the nasal cycle.
+Severe bacterial pneumonia is a major global cause of morbidity and mortality, yet current diagnostic approaches rely on identification of causative pathogens by cultures, which require extended incubation periods and often fail to detect relevant pathogens.
+Consequently, patients are prescribed broad-spectrum antibiotics in a “one-size-fits-all” manner, which may be inappropriate for their individual needs and promote antibiotic resistance.
+My research focuses on leveraging next-generation sequencing of microbial DNA directly from patient samples for the development of new, culture-independent definitions of pneumonia.
+In this perspective article, I discuss the current state of the field and focus on the conceptual and research design challenges for clinical translation.
+With ongoing technological advancements and application of computational biology methods for assessing clinical validity and utility, I anticipate that sequencing-based diagnostics will soon be able to positively disrupt the way we think about, diagnose, and treat pulmonary infections.
+Beyond selection for optimal protein functioning, coding sequences (CDSs) are under selection at the RNA and DNA levels.
+Here, we identify a possible signature of “dual-coding,” namely extensive adenine (A) enrichment at bacterial CDS fourth sites.
+In 99.07% of studied bacterial genomes, fourth site A use is greater than expected given genomic A-starting codon use.
+Arguing for nucleotide level selection, A-starting serine and arginine second codons are heavily utilized when compared with their non-A starting synonyms.
+Further, +1 frameshifts on the initiating ATG encode a stop codon (TGA) provided A is the fourth residue, acting either as a frameshift “catch and destroy” or a frameshift stop and adjust mechanism and hence implicated in translation initiation.
+Sequences lacking a Shine–Dalgarno sequence and those without upstream leader genes, that may be more error prone during initiation, have greater utilization of A, again suggesting a role in initiation.
+The frameshift correction model is consistent with the notion that many genomic features are error-mitigation factors and provides the first evidence for site-specific out of frame stop codon selection.
+We conjecture that the NTG universal start codon may have evolved as a consequence of TGA being a stop codon and the ability of NTGA to rapidly terminate or adjust a ribosome.
+Ingestion has been shown as a natural route of transmission for both Lassa virus (LASV) and Lymphocytic choriomeningitis virus (LCMV).
+Due to the mechanism of transmission, epithelial tissues are among the first host cells to come in contact with the viruses, and as such they potentially play a role in spread of virus to naïve hosts.
+We have utilized a well-established cell culture model, Caco-2, to investigate the role of intestinal epithelia during intragastric infection.
+However, the reassortant virus, ML-29, containing the L segment of MOPV and S segment of LASV, exhibits a unique pattern of viral release relative to LCMV and MOPV.
+Furthermore, we have determined attachment efficacy to Caco-2 cells is potentially responsible for observed replication kinetics of these viruses in a polarized Caco-2 cell model.
+Collectively, our data shows that viral dissemination and interaction with intestinal epithelia may be host, tissue, and viral specific.
+Although flies are known to transmit disease, the effects of cleaning behavior have not been well studied.
+This study quantified the cleaning effectiveness and behavior of three fly species: Sarcophaga bullata, Musca domestica L., and Drosophila virilis.
+Flies were transferred to plates of Escherichia coli or Pseudomonas aeruginosa and allowed to walk on the bacteria for a total of 5 min.
+After the flies were contaminated, they were either immediately collected to quantify bacteria or were placed onto sterile plates to clean for 5 or 10 min.
+After cleaning, flies were placed into tubes with 1 ml of sterile 0.85% saline and were gently shaken for 1 min to remove bacteria.
+Sarcophaga bullata and D. virilis both showed a significant reduction of both bacteria within 10 min, whereas M. domestica only showed a significant reduction in P. aeruginosa.
+Cleaning behavior increased significantly in flies that were exposed to bacteria compared to flies that were not exposed to bacteria.
+This study is important, as it demonstrates that fly cleaning could affect mechanical transmission of disease, and additional studies should look at flies’ abilities to remove other types of microorganisms.
+AIM: To investigate the current state of research output from Chinese studies into severe ulcerative colitis (SUC) using a bibliometric analysis of publications.
+METHODS: The contents of the Chinese periodical databases WANFANG, VIP, and China National Knowledge Infrastructure were searched for all papers regarding UC or SUC published in last the 15 years (from 2001 to 2015).
+The number of publications in each year was recorded to assess the temporal trends of research output.
+All SUC related publications were downloaded and the complexity of this research was evaluated with methods described previously.
+The number of patients with SUC reported each year was recorded and their clinical characteristics were analyzed using information available in the relevant papers.
+RESULTS: There were 13499 publications regarding UC published in Chinese medical journals between 2001 and 2015, of which 201 focused on SUC.
+The number of publications increased rapidly with more than half of all papers being published in the most recent 5-year period.
+There was a significant increase in analytical studies and clinical trials over the study period (P < 0.01), with research into the management of SUC, included pharmacotherapy, nutrition support as well as surgery, predominating.
+Almost half (46.2%) of the observational analytical studies and clinical trials focused on Traditional Chinese Medicine, with little research on the efficacy of cyclosporin and infliximab in disease management.
+About 6222 patients with SUC were reported in the 201 SUC relevant papers, with a ratio of male/female of 1.38.
+CONCLUSION: The output and complexity of research related to SUC in China increased significantly over the previous 15 years, however few of these studies focused on salvage therapy.
+BACKGROUND: More and more cases of human infections with avian influenza A H7N9 have been reported since it was first mentioned in 2013 in China, but concurrence of influenza A H7N9 with Mycoplasma pneumoniae, however, has never been described.
+Here, we reported the case of a woman co-infected by influenza A H7N9 and Mycoplasma pneumoniae, whose treatment process was a little bit longer and a little bit complicated as well.
+CASE PRESENTATION: Our patient was an 80-year-old Chinese woman who presented with fever, cough, chest tightness, and shortness of breath.
+Her sputum and throat swabs were checked for nucleic acid of influenza A and the result was positive for influenza A H7N9.
+She was diagnosed as having severe influenza A H7N9 and acute respiratory distress syndrome, and was admitted to an intensive care unit.
+She was given comprehensive treatment, including oseltamivir, methylprednisolone, immunoglobulin, gastric protection, and noninvasive mechanical ventilation.
+However, some symptoms exacerbated again 2 days later with ground-glass changes appearing in upper area of right lung and the titer of antibody to Mycoplasma pneumoniae rising from 1:80 to 1:640.
+She was reasonably considered to be infected with Mycoplasma pneumoniae as well, and azithromycin and moxifloxacin were added to her treatment.
+Oseltamivir was discontinued because of three consecutive negative results of nucleic acid for influenza A H7N9, but anti-Mycoplasma treatment was continued.
+Although her symptoms and abnormal changes on computed tomography scan slowly went away, she finally recovered from the mixed infection after a total of 33 days of management.
+CONCLUSION: In patients with confirmed influenza A H7N9 infection whose condition worsens again, especially with new infiltration or lung ground-glass infiltration, one should suspect infection by other pathogens such as Mycoplasma pneumoniae.
+BACKGROUND: Hypertension may result from high-fat (HF) diet induced-obesity and overexposure to glucocorticoids in utero.
+Recent studies demonstrated the potent contribution of adipose tissue’s renin-angiotensin system (RAS) to systemic RAS, which plays a key role in regulating blood pressure (BP).
+In this study, we investigated the effects of prenatal dexamethasone (DEX) exposure and postnatal HF diet on RAS of adipose tissue.
+METHODS: RAS and BP of 6-month old rats exposed to prenatal DEX and/or postnatal HF diet were examined.
+Prenatal DEX exposure suppressed plasma angiotensin (ANG) I and ANG II, whereas postnatal HF suppressed plasma ANG-(1–7) level.
+Prenatal DEX increased prorenin receptor and renin levels, but suppressed angiotensinogen (AGT) and angiotensin-converting-enzyme 1 (ACE1) mRNA expressions in adipose tissue.
+Postnatal HF increased AGT mRNA expression, but suppressed prorenin receptor, renin, ACE2, ANG II type 2 receptor (AT2R), and Mas receptor (MasR) mRNA expression levels.
+CONCLUSIONS: Prenatal GC exposure altered the ACE1/ANG II/ANG II type 1 receptor (AT1R) axis, whereas postnatal HF negatively impacted the ACE2/ANG-(1–7)/MasR axis.
+Prenatal DEX exposure and postnatal HF synergistically elevated BP through a distinct programming mechanism of systemic and adipose RAS.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12944-018-0701-0) contains supplementary material, which is available to authorized users.
+BACKGROUND: MEDI8852 is a novel monoclonal antibody (mAb) that neutralizes both group I and group II influenza A viruses (IAVs) in vitro.
+We evaluated whether MEDI8852 was effective for prophylaxis and therapy against representative group I (H5N1) and group II (H7N9) pandemic IAVs in mice and ferrets and could be used to block transmission of influenza H1N1pdm09 in ferrets, compared to an irrelevant control mAb R347 and oseltamivir.
+METHODS: MEDI8852 was administered to mice and ferrets by intraperitoneal injection at varying doses, 24 hours prior to intranasal infection with H5N1 and H7N9 viruses for prophylaxis, and 24, 48, and 72 hours post-infection for treatment.
+A comparison with oseltamivir alone and combination of MEDI8852 and oseltamivir was included in some studies.
+For the transmission study, naive respiratory contact ferrets received MEDI8852 or R347 prior to exposure to ferrets infected with an H1N1pdm09 virus.
+RESULTS: MEDI8852 was effective for prophylaxis and treatment of H7N9 and H5N1 infection in mice, with a clear dose-dependent response and treatment with MEDI8852 24, 48, or 72 hours postinfection was superior to oseltamivir for H5N1.
+MEDI8852 alone was effective treatment for lethal H5N1 infection in ferrets compared to oseltamivir and R347, and MEDI8852 plus oseltamivir was better than oseltamivir alone.
+MEDI8852 or oseltamivir alone early in infection was equally effective for H7N9 infection in ferrets while the combination yielded similar protection when treatment was delayed.
+CONCLUSIONS: MEDI8852, alone or with oseltamivir, shows promise for prophylaxis or therapy of group I and II IAVs with pandemic potential.
+BACKGROUND: Clinically meaningful endpoints for respiratory syncytial virus (RSV) treatment trials are lacking for hematopoietic cell transplant (HCT) recipients.
+METHODS: Subjects were grouped according to the presence of upper respiratory tract infection (URTI) without lower respiratory tract infection (LRTI), URTI progressing to LRTI, and LRTI at presentation.
+LRTI was defined as a positive lower respiratory tract sample with or without radiographic abnormality (defined as proven or probable LRTI, respectively) or a positive upper respiratory tract sample with radiographic abnormality (possible LRTI).
+Supplemental oxygen–free days were defined as any day while alive after diagnosis of RSV infection during which ≤2 L of supplemental oxygen per minute was received.
+RESULTS: Among 230 patients, supplemental oxygen use by day 28 after the first diagnosis of RSV infection was lowest in patients presenting with URTI (31 of 197 [16%]).
+Supplemental oxygen use was lower in patients with possible LRTI (12 of 45 [27%]) than in those with proven/probable LRTI (29 of 42 [69%]).
+Patients presenting with proven/probable LRTI had a median of 16 fewer supplemental oxygen–free days than those presenting with URTI (P < .0001).
+CONCLUSIONS: Confirmation of RSV infection in the lower respiratory tract provides prognostic information that may help prioritize therapies.
+Supplemental oxygen–free days as a clinical endpoint may allow smaller sample sizes for trials evaluating RSV antivirals.
+Recently, novel highly pathogenic avian influenza H5Nx viruses (clade 2.3.4.4) caused outbreaks in US poultry.
+We evaluated the potential of a stockpiled A(H5N1) A/Anhui/1/2005 (clade 2.3.4) vaccine to elicit cross-reactive antibody responses to these emerging viruses.
+Sera from subjects who received 2 doses of MF59-adjuvanted A/Anhui/1/2005, or 1 dose of MF59-adjuvanted A/Anhui/1/2005 following priming with a clade 1 vaccine were characterized by microneutralization assays and modified hemagglutination inhibition (HI) assays.
+Heterologous prime-boost may provide a more effective vaccination strategy to broaden the antibody responses to emerging viruses.
+The first reported outbreak of Ebola virus disease occurred in 1976 in Yambuku, Democratic Republic of Congo.
+However, this report is the first characterization of anti-Ebola virus antibody persistence and neutralization capacity 40 years after infection.
+Using ELISAs we measured survivor’s immunological response to Ebola virus Zaire (EBOV) glycoprotein and nucleoprotein, and assessed VP40 reactivity.
+Neutralization of EBOV was measured using a pseudovirus approach and plaque reduction neutralization test with live EBOV.
+Interestingly, a subset of these survivors’ serum antibodies could still neutralize live virus 40 years postinitial infection.
+These data provide the longest documentation of both anti-Ebola serological response and neutralization capacity within any survivor cohort, extending the known duration of response from 11 years postinfection to at least 40 years after symptomatic infection.
+Pregnancy has been associated with severe influenza, an association highlighted during the 2009 pandemic of influenza A(H1N1) virus (A[H1N1]pdm09) infection.
+To assess the underlying mechanism, we infected pregnant and non-pregnant ferrets with A(H1N1) pdm09 virus.
+Systemically, total CD8(+) T cell counts and A(H1N1)pdm09-specific B-cell responses in blood were significantly lower in pregnant ferrets.
+This model predicts that the poorer outcome for pregnant women during the A(H1N1)pdm09 pandemic was due to an elevated level of viral replication and to a cytokine imbalance that led to a less effective immune response.
+A closed-tube reverse transcription loop-mediated isothermal amplification (CT-RT-LAMP) assay was developed for the detection of yam mosaic virus (YMV, genus Potyvirus) infecting yam (Dioscorea spp.).
+The assay uses a set of six oligonucleotide primers targeting the YMV coat protein region, and the amplification products in YMV-positive samples are visualized by chromogenic detection with SYBR Green I dye.
+The assay is 100 times more sensitive in detecting YMV than standard RT-PCR, while maintaining the same specificity.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00705-018-3706-0) contains supplementary material, which is available to authorized users.
+New genotypes have been described within HRV‐A and HRV‐C species, but only one has been accepted related to HRV‐B.
+From 2003 to 2010, a total of 3987 nasopharyngeal aspirate samples were taken from pediatric patients admitted to the Severo Ochoa Hospital in Madrid (Spain).
+The sequencing of partial VP4/VP2 coding region revealed the spread of 13 of 25 defined HRV‐B serotypes and three putative new genotypes.
+Human mobility is increasing in its volume, speed and reach, leading to the movement and introduction of pathogens through infected travelers.
+An understanding of how areas are connected, the strength of these connections and how this translates into disease spread is valuable for planning surveillance and designing control and elimination strategies.
+While analyses have been undertaken to identify and map connectivity in global air, shipping and migration networks, such analyses have yet to be undertaken on the road networks that carry the vast majority of travellers in low and middle income settings.
+Here we present methods for identifying road connectivity communities, as well as mapping bridge areas between communities and key linkage routes.
+We apply these to Africa, and show how many highly-connected communities straddle national borders and when integrating malaria prevalence and population data as an example, the communities change, highlighting regions most strongly connected to areas of high burden.
+The approaches and results presented provide a flexible tool for supporting the design of disease surveillance and control strategies through mapping areas of high connectivity that form coherent units of intervention and key link routes between communities for targeting surveillance.
+Air sampling as an aid to infection control is still in an experimental stage, as there is no consensus about which air samplers and pathogen detection methods should be used, and what thresholds of specific pathogens in specific exposed populations (staff, patients, or visitors) constitutes a true clinical risk.
+This case report used a button sampler, worn or held by staff or left free-standing in a fixed location, for environmental sampling around a child who was chronically infected by a respiratory adenovirus, to determine whether there was any risk of secondary adenovirus infection to the staff managing the patient.
+Despite multiple air samples taken on difference days, coinciding with high levels of adenovirus detectable in the child’s nasopharyngeal aspirates (NPAs), none of the air samples contained any detectable adenovirus DNA using a clinically validated diagnostic polymerase chain reaction (PCR) assay.
+Although highly sensitive, in-house PCR assays have been developed to detect airborne pathogen RNA/DNA, it is still unclear what level of specific pathogen RNA/DNA constitutes a true clinical risk.
+In this case, the absence of detectable airborne adenovirus DNA using a conventional diagnostic assay removed the requirement for staff to wear surgical masks and face visors when they entered the child’s room.
+We developed a Rapid Diagnostic Test (RDT) kit for detecting IgG/IgM antibodies against Zika virus (ZIKV) using monoclonal antibodies to the envelope (E) and non-structural protein 1 (NS1) of ZIKV.
+Monoclonal antibodies J2G7 to NS1 and J5E1 to E protein were selected and conjugated with colloidal gold to produce the Zika IgG/IgM RDT kit (Zika RDT).
+Comparisons with ELISA, plaque reduction neutralization test (PRNT), and PCR were done to investigate the analytical sensitivity of Zika RDT, which resulted in 100% identical results.
+Sensitivity and specificity of Zika RDT in a field test was determined using positive and negative samples from Brazil and Korea.
+The diagnostic accuracy of Zika RDT was fairly high; sensitivity and specificity for IgG was 99.0 and 99.3%, respectively, while for IgM it was 96.7 and 98.7%, respectively.
+Cross reaction with dengue virus was evaluated using anti-Dengue Mixed Titer Performance Panel (PVD201), in which the Zika RDT showed cross-reactions with DENV in 16.7% and 5.6% in IgG and IgM, respectively.
+Cross reactions were not observed with West Nile, yellow fever, and hepatitis C virus infected sera.
+Zika RDT kit is very simple to use, rapid to assay, and very sensitive, and highly specific.
+Therefore, it would serve as a choice of method for point-of-care diagnosis and large scale surveys of ZIKV infection under clinical or field conditions worldwide in endemic areas.
+Intranasal inoculation of animals with a liquid inoculum is one of the main methods used to experimentally infect animals with influenza virus; however, this method does not reflect the natural infection with influenza virus by contact or aerosol route.
+Aerosol inhalation methods have been established with several influenza viruses for mouse and ferret models, but few studies have evaluated inoculation routes in a nonhuman primates (NHP) model.
+Here, we performed the experimental infection of NHPs with a highly pathogenic H5N1 influenza virus via the aerosol route and demonstrated that aerosol infection had no effect on clinical outcome, but caused broader infection throughout all of the lobes of the lung compared with a non-aerosolized approach.
+Human dengue viruses emerged from primate reservoirs, yet paradoxically dengue does not reach high titers in primate models.
+The dengue virus 2 (DENV2) - encoded protease cleaves human STING, reducing type I interferon production and boosting viral titers in humans.
+We find that both human and sylvatic (reservoir) dengue viruses universally cleave human STING, but not the STING of primates implicated as reservoir species.
+The special ability of dengue to cleave STING is thus specific to humans and a few closely related ape species.
+Conversion of residues 78/79 to the human-encoded ‘RG’ renders all primate (and mouse) STINGs sensitive to viral cleavage.
+Dengue viruses may have evolved to increase viral titers in the dense and vast human population, while maintaining decreased titers and pathogenicity in the more rare animals that serve as their sustaining reservoir in nature.
+BACKGROUND: The majority of critically ill patients do not suffer from acute respiratory distress syndrome (ARDS).
+To improve the treatment of these patients, we aimed to identify potentially modifiable factors associated with outcome of these patients.
+METHODS: The PRoVENT was an international, multicenter, prospective cohort study of consecutive patients under invasive mechanical ventilatory support.
+Compared to patients who died, patients who survived had a lower risk of ARDS according to the ‘Lung Injury Prediction Score’ and received lower maximum airway pressure (P(max)), driving pressure (ΔP), positive end-expiratory pressure, and FiO(2) levels.
+Higher P(max) was a potentially modifiable ventilatory variable associated with in-hospital mortality in multivariable analyses.
+ΔP was not independently associated with in-hospital mortality, but reliable values for ΔP were available for 343 patients only.
+Non-modifiable factors associated with in-hospital mortality were older age, presence of immunosuppression, higher non-pulmonary sequential organ failure assessment scores, lower pulse oximetry readings, higher heart rates, and functional dependence.
+CONCLUSIONS: Higher P(max) was independently associated with higher in-hospital mortality in mechanically ventilated critically ill patients under mechanical ventilatory support for reasons other than ARDS.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13613-018-0385-7) contains supplementary material, which is available to authorized users.
+Identifying effective antivirals for treating Ebola virus disease (EVD) and minimizing transmission of such disease is critical.
+A variety of cell-based assays have been developed for evaluating compounds for activity against Ebola virus.
+However, very few reports discuss the variable assay conditions that can affect the results obtained from these drug screens.
+Here, we describe variable conditions tested during the development of our cell-based drug screen assays designed to identify compounds with anti-Ebola virus activity using established cell lines and human primary cells.
+The effect of multiple assay readouts and variable assay conditions, including virus input, time of infection, and the cell passage number, were compared, and the impact on the effective concentration for 50% and/ or 90% inhibition (EC(50), EC(90)) was evaluated using the FDA-approved compound, toremifene citrate.
+In these studies, we show that altering cell-based assay conditions can have an impact on apparent drug potency as measured by the EC(50).
+These results further support the importance of developing standard operating procedures for generating reliable and reproducible in vitro data sets for potential antivirals.
+The T3SS chaperone CesT is recently shown to interact with the post-transcriptional regulator CsrA to modulate post-attachment signaling in enteropathogenic and enterohemorrhagic Escherichia coli.
+Here, we show that CesT and CsrA both created two ligand binding sites in their homodimers, forming irregular multimeric complexes in solution.
+Through construction of a recombinant CsrA-dimer (Re-CsrA) that contains a single CesT binding site, the atomic binding features between CesT and CsrA are delineated via the structure of the CesT/Re-CsrA complex.
+In contrast to a previously reported N-terminally swapped dimer-form, CesT adopts a dimeric architecture with a swapped C-terminal helix for CsrA engagement.
+In CsrA, CesT binds to a surface patch that extensively overlaps with its mRNA binding site.
+The binding mode therefore justifies a mechanism of CsrA-modulation by CesT via competitive inhibition of the CsrA/mRNA interactions.
+Avian influenza A(H7N9) virus infections frequently lead to acute respiratory distress syndrome and death in humans.
+We aimed to investigate whether primary cultures of human respiratory tract epithelial cells are helpful to understand H7N9 virus pathogenesis and tissue tropism, and to evaluate how patient-related characteristics can affect the host's response to infection.
+Normal human bronchial epithelial cells (isolated from two different donors) and primary epithelial cells (harvested from 27 patients undergoing airway surgery) were experimentally infected with H7N9 and/or H1N1pdm for 72 h. After virus infection, the culture media were collected for viral RNA quantitation and cytokine detection.
+Both H7N9 and H1N1pdm viruses replicated and induced a cytokine response differently for each donor in the normal human bronchial epithelial model.
+H7N9 replicated equivalently in epithelial cells harvested from the inferior turbinate and paranasal sinus, and those from the larynx and bronchus, at 72 h post-infection.
+Viral RNA quantity at 72 h was significantly higher in patients aged 21–64 years than in patients aged ≥ 65 years; however, no effects of sex, medical comorbidities, and obesity were noted.
+H7N9-infected cultured cells released multiple cytokines within 72 h. Levels of interleukin-1β, interleukin-6, interleukin-8, interferon-γ, and tumor necrosis factor-α were associated differently with patient-related characteristics (such as age, sex, obesity, and medical comorbidities).
+In the era of precision medicine, these findings illustrate the potential utility of this primary culture approach to predict a host's response to H7N9 infection or to future infection by newly emerging viral infections, and to dissect viral pathogenesis.
+SIMPLE SUMMARY: Historically, older cats and dogs have been particularly at-risk for euthanasia in animal shelters due to their lower perceived appeal for adoption.
+This study found that the condition at intake had the greatest impact on the outcomes of older cats and dogs.
+Additionally, the application of specialized veterinary care, such as orthopedic surgery or chronic disease maintenance, is discussed as factors that inform higher rates of live outcomes for these senior companion animals.
+These findings demonstrate that if shelters integrate practices that address the specific needs of ageing companion animals, the live outcomes for this population can increase.
+ABSTRACT: With advances in veterinary medicine that can increase the lifespan of cats and dogs and the effectiveness of spay/neuter programs in reducing the juvenile population of pets, animal shelters are experiencing an increasing population of older companion animals in their care.
+The purpose of this study was to assess the factors that inform the outcomes of these older cats and dogs.
+The sample consisted of 124 cats and 122 dogs that were over the age of 84 months (seven years) who were taken into a shelter over a one-year period.
+To assess the impact of condition at intake on the outcome for the senior animals, a multinomial logistic regression was performed.
+These findings indicate that preventative programming that can address the reasons these older animals are surrendered, as well as advancements in specialized medical or behavioral programs for ageing companion animals, may support an increase in live outcomes for older cats and dogs in shelters.
+Further study is needed to evaluate how the quality of life of older animals is impacted by remaining in the care of shelters rather than being euthanized.
+To investigate the factors associated with death and describe the gestational outcomes in pregnant women with influenza A(H1N1)pdm09, we conducted a case-control study (deaths and recovered) in hospitalized pregnant women with laboratory-confirmed influenza A(H1N1)pdm09 with severe acute respiratory illness (SARI) in the state of São Paulo from June 9 to December 1, 2009.
+All cases were evaluated, and four controls that were matched by the epidemiological week of hospitalization of the case were randomly selected for each case.
+The hospital records from 126 hospitals were evaluated, and home interviews were conducted using standardized forms.
+Having had a previous health visit to a healthcare provider for an influenza episode before hospital admission was a risk factor for death (adjusted OR (OR(adj)) of 7.93, 95% CI 2.19–28.69).
+Although not significant in the multiple analysis (OR(adj) of 2.13, 95% CI 0.91–5.00), the 3(rd) trimester deserves attention, with an OR = 2.22, 95% CI 1.13–4.37 in the univariate analysis.
+Antiviral treatment was a protective factor when administered within 48 hours of symptom onset (OR(adj) = 0.16, 95% CI 0.05–0.50) and from 48 to 72 hours (OR(adj) = 0.09, 95% CI 0.01–0.87).
+There was a higher proportion of fetal deaths and preterm births among cases (p = 0.001) and live births with low weight (p = 0.019), compared to control subjects who gave birth during hospitalization.
+Early antiviral treatment during the presence of a flu-like illness is an important factor in reducing mortality from influenza in pregnant women and unfavorable neonatal outcomes.
+It is important to monitor pregnant women, particularly in the 3(rd) trimester of gestation, with influenza illness for diagnosis and early treatment.
+In our previous study, a genetically engineered Lactobacillus casei oral vaccine (pPG-COE-DCpep/L393) expressing a dendritic cell (DC)-targeting peptide fused with porcine epidemic diarrhea virus (PEDV) COE antigen was developed.
+This vaccine induced significant levels of anti-PEDV specific IgG and IgA antibody responses in mice, indicating a potential strategy against PEDV infection.
+An indirect enzyme-linked immunosorbent assay (ELISA) showed that the recombinant Lactobacillus vaccine elicits a specific systemic and mucosal immune response.
+The histopathological results showed that pPG-COE-DCpep/L393 promotes lymphocyte proliferation and effectively protects piglets against PEDV infection.
+The transforming growth factor-β level indicated that the recombinant Lactobacillus vaccine plays a role in anti-inflammatory responses in mesenteric lymph nodes during PEDV infection.
+Codon usage bias (CUB) is an important evolutionary feature in a genome which provides important information for studying organism evolution, gene function and exogenous gene expression.
+The CUB and its shaping factors in the nuclear genomes of four sequenced cotton species, G. arboreum (A(2)), G. raimondii (D(5)), G. hirsutum (AD(1)) and G. barbadense (AD(2)) were analyzed in the present study.
+The effective number of codons (ENC) analysis showed the CUB was weak in these four species and the four subgenomes of the two tetraploids.
+Codon composition analysis revealed these four species preferred to use pyrimidine-rich codons more frequently than purine-rich codons.
+Correlation analysis indicated that the base content at the third position of codons affect the degree of codon preference.
+PR2-bias plot and ENC-plot analyses revealed that the CUB patterns in these genomes and subgenomes were influenced by combined effects of translational selection, directional mutation and other factors.
+The translational selection (P2) analysis results, together with the non-significant correlation between GC12 and GC3, further revealed that translational selection played the dominant role over mutation pressure in the codon usage bias.
+Through relative synonymous codon usage (RSCU) analysis, we detected 25 high frequency codons preferred to end with T or A, and 31 low frequency codons inclined to end with C or G in these four species and four subgenomes.
+Finally, 19 to 26 optimal codons with 19 common ones were determined for each species and subgenomes, which preferred to end with A or T. We concluded that the codon usage bias was weak and the translation selection was the main shaping factor in nuclear genes of these four cotton genomes and four subgenomes.
+Zika virus (ZIKV) is an emerging arbovirus belonging to the genus flavivirus that comprises other important public health viruses, such as dengue (DENV) and yellow fever (YFV).
+In general, ZIKV infection is a self-limiting disease, however cases of Guillain-Barré syndrome and congenital brain abnormalities in newborn infants have been reported.
+Diagnosing ZIKV infection remains a challenge, as viral RNA detection is only applicable until a few days after the onset of symptoms.
+After that, serological tests must be applied, and, as expected, high cross-reactivity between ZIKV and other flavivirus serology is observed.
+Plaque reduction neutralization test (PRNT) is indicated to confirm positive samples for being more specific, however it is laborious intensive and time consuming, representing a major bottleneck for patient diagnosis.
+To overcome this limitation, we developed a high-throughput image-based fluorescent neutralization test for ZIKV infection by serological detection.
+Using 226 human specimens, we showed that the new test presented higher throughput than traditional PRNT, maintaining the correlation between results.
+Furthermore, when tested with dengue virus samples, it showed 50.53% less cross reactivity than MAC-ELISA.
+This fluorescent neutralization test could be used for clinical diagnosis confirmation of ZIKV infection, as well as for vaccine clinical trials and seroprevalence studies.
+Potyviruses (genus Potyvirus; family Potyviridae) are widely distributed and represent one of the most economically important genera of plant viruses.
+However, this can sometimes be problematic particularly in plant species containing high amounts of polysaccharides and polyphenols such as yam (Dioscorea spp.).
+Here, we report the development of a reliable, rapid and cost-effective detection method for the two most important potyviruses infecting yam based on reverse transcription-recombinase polymerase amplification (RT-RPA).
+The developed method, named ‘Direct RT-RPA’, detects each target virus directly from plant leaf extracts prepared with a simple and inexpensive extraction method avoiding laborious extraction of high-quality RNA.
+Direct RT-RPA enables the detection of virus-positive samples in under 30 min at a single low operation temperature (37 °C) without the need for any expensive instrumentation.
+The Direct RT-RPA tests constitute robust, accurate, sensitive and quick methods for detection of potyviruses from recalcitrant plant species.
+The minimal sample preparation requirements and the possibility of storing RPA reagents without cold chain storage, allow Direct RT-RPA to be adopted in minimally equipped laboratories and with potential use in plant clinic laboratories and seed certification facilities worldwide.
+Duchenne muscular dystrophy (DMD) is a lethal disorder caused by mutations in the DMD gene.
+Antisense-mediated exon-skipping is a promising therapeutic strategy that makes use of synthetic nucleic acids to skip frame-disrupting exon(s) and allows for short but functional protein expression by restoring the reading frame.
+In 2016, the U.S. Food and Drug Administration (FDA) approved eteplirsen, which skips DMD exon 51 and is applicable to approximately 13% of DMD patients.
+Multiple exon skipping, which is theoretically applicable to 80–90% of DMD patients in total, have been demonstrated in animal models, including dystrophic mice and dogs, using cocktail antisense oligonucleotides (AOs).
+Although promising, current drug approval systems pose challenges for the use of a cocktail AO.
+For example, both exons 6 and 8 need to be skipped to restore the reading frame in dystrophic dogs.
+Therefore, the cocktail of AOs targeting these exons has a combined therapeutic effect and each AO does not have a therapeutic effect by itself.
+The current drug approval system is not designed to evaluate such circumstances, which are completely different from cocktail drug approaches in other fields.
+Significant changes are needed in the drug approval process to promote the cocktail AO approach.
+Bovine viral diarrhoea virus 1 (BVDV-1) is strongly associated with several important diseases of cattle, such as bovine respiratory disease, diarrhoea and haemoragic lesions.
+To date many subgenotypes have been reported for BVDV-1, currently ranging from subgenotype 1a to subgenotype 1u.
+As an example, BVDV-1 subgenotypes 1a and 1b are frequently detected in North America and Europe, while the subgenotype 1c is rarely detected.
+The aim of this study was to characterise the in vivo properties of five strains of BVDV-1 subgenotype 1c in cattle infection studies.
+No overt respiratory signs were reported in any of the infected cattle regardless of strain.
+Consistent with other subgenotypes, transient pyrexia and leukopenia were commonly identified, while thrombocytopenia was not.
+The quantity of virus detected in the nasal secretions of transiently infected animals suggested the likelihood of horizontal transmission was very low.
+Further studies are required to fully understand the variability and importance of the BVDV-1 subgenotype 1c.
+All over the world, children and adults are severely affected by acute gastroenteritis, caused by one of the emerging enteric pathogens, rotavirus C (RVC).
+At present, no extensive surveillance program is running for RVC in India, and its prevalence is largely unknown except cases of local outbreaks.
+Here, we intended to detect the presence of RVC in diarrheic children visiting or admitted to hospitals in Haldwani (state of Uttarakhand, India), a city located in the foothills of the Himalayas.
+Of these, 38 (31.93%) were found positive, which is higher than the incidence rates reported so far from India.
+The phylogenetic analysis of the derived nucleotide sequences from one of the human RVC (HuRVC) isolates, designated as HuRVC/H28/2013/India, showed that the study isolate belongs to genotype I2, P2 and E2 for RVC structural genes 6 and 4 (VP6, and VP4) and non-structural gene 4 (NSP4), respectively.
+Furthermore, the VP6 gene of HuRVC/H28/2013/India shows the highest similarity to a recently-reported human-like porcine RVC (PoRVC/ASM140/2013/India, KT932963) from India suggesting zoonotic transmission.
+Under the One-health platforms there is a need to launch combined human and animal RVC surveillance programs for a better understanding of the epidemiology of RVC infections and for implementing control strategies.
+Cleavage and activation of hemagglutinin (HA) by trypsin-like proteases in influenza A virus (IAV) are essential prerequisites for its successful infection and spread.
+In host cells, some transmembrane serine proteases such as TMPRSS2, TMPRSS4 and HAT, along with plasmin in the bloodstream, have been reported to cleave the HA precursor (HA(0)) molecule into its active forms, HA(1) and HA(2).
+However, the precise activation mechanism for this process is unclear, because the expression level of the physiological activator of the trypsinogens, the TMPRSS15 enterokinase, is expected to be very low in such cells, with the exception of duodenal cells.
+Here, we show that at least two variant enterokinases are expressed in various human cell lines, including A549 lung-derived cells.
+The exogenous expression of these enterokinases was able to enhance the proliferation of IAV in 293T human kidney cells, but the proliferation was reduced by knocking down the endogenous enterokinase in A549 cells.
+The enterokinase was able to enhance HA processing in the cells, which activated trypsinogen in vitro and in the IAV-infected cells also.
+Therefore, we conclude that enterokinase plays a role in IAV infection and proliferation by activating trypsinogen to process viral HA in human cell lines.
+The avian respiratory system hosts a wide range of commensal and potential pathogenic bacteria and/or viruses that interact with each other.
+Such interactions could be either synergistic or antagonistic, which subsequently determines the severity of the disease complex.
+The intensive rearing methods of poultry are responsible for the marked increase in avian respiratory diseases worldwide.
+The interaction between avian influenza with other pathogens can guarantee the continuous existence of other avian pathogens, which represents a global concern.
+A better understanding of the impact of the interaction between avian influenza virus and other avian respiratory pathogens provides a better insight into the respiratory disease complex in poultry and can lead to improved intervention strategies aimed at controlling virus spread.
+INTRODUCTION: On 17 September 2015, Buliisa District Health Office reported multiple deaths due to haemorrhage to the Uganda Ministry of Health.
+We conducted an investigation to verify the existence of an outbreak and to identify the disease nature, mode of transmission and risk factors.
+METHODS: We defined a suspected case as onset of hematemesis between 1 June 2015 and 15 October 2015 in a resident of Hoima, Buliisa or neighbouring districts.
+We interviewed case-patients and health-care workers and performed descriptive epidemiology to generate hypotheses on possible exposures.
+In a case-control study we compared exposures between 21 cases and 81 controls, matched by age (± 10 years), sex and village of residence.
+We collected 22 biological specimens from 19 case-patients to test for Viral Haemorrhagic Fevers (VHF).
+We analysed the data using the Mantel-Haenszel method to account for the matched study design.
+RESULTS: We identified 56 cases with onset from June to October (attack rate 15/100,000 in Buliisa District and 5.2/100,000 in Hoima District).
+The age-specific attack rate was highest in persons aged 31-60 years (15/100,000 in Hoima and 47/100,000 in Buliisa); no persons below 15 years of age had the illness.
+In the case-control study, 42% (5/12) of cases vs. 0.0% (0/77) of controls had liver disease (OR(M-H) = ∞; 95%CI = 3.7-∞); 71% (10/14) of cases vs. 35% (28/81) of controls had ulcer disease (OR(M-H) = 13; 95% CI = 1.6-98); 27% (3/11) of cases vs. 14% (11/81) of controls used indomethacin prior to disease onset (OR(M-H) = 6.0; 95% CI = 1.0-36).
+CONCLUSION: This reported cluster of hematemesis illness was due to predisposing conditions and use of Non-Steroidal Anti-inflammatory Drugs (NSAID).
+Health education should be conducted on the danger of NSAIDs misuse, especially in persons with pre-disposing conditions.
+BACKGROUND: Hepatic complications of hepatitis C virus (HCV), including fibrosis and cirrhosis are accelerated in human immunodeficiency virus (HIV)-infected individuals.
+Although, liver biopsy remains the gold standard for staging HCV-associated liver disease, this test can result in serious complications and is subject to sampling errors.
+To this end, we compared serum proteome profiles at different stages of fibrosis in HIV/HCV co- and HCV mono-infected patients using surface-enhanced laser desorption ionization time-of-flight mass spectrometry (SELDI-TOF MS).
+METHODS: Sera from 83 HIV/HCV co- and 68 HCV mono-infected subjects in 4 stages of fibrosis were tested.
+Sera were fractionated, randomly applied to protein chip arrays (IMAC, CM10 and H50) and spectra were generated at low and high laser intensities.
+RESULTS: Sixteen biomarkers achieved a p value < 0.01 (ROC values > 0.75 or < 0.25) predictive of fibrosis status in co-infected individuals and 14 in mono infected subjects.
+Candidate diagnostic algorithms were created to distinguish between non-fibrotic and fibrotic individuals using a panel of 4 biomarker peaks.
+CONCLUSION: These data suggest that SELDI MS profiling can identify diagnostic serum biomarkers for fibrosis that are both common and distinct in HIV/HCV co-infected and HCV mono-infected individuals.
+When protein secretion demand exceeds the protein folding capacity of the ER, the unfolded protein response (UPR) is triggered as a consequence of ER stress.
+Due to the secretory function of epithelial cells, UPR plays an important role in maintaining epithelial barrier function at mucosal sites.
+ER stress and activation of the UPR are natural mechanisms by which mucosal epithelial cells combat viral infections.
+In this review, we discuss the important role of UPR in regulating mucosal epithelium homeostasis.
+In addition, we review current insights into how the UPR is involved in viral infection at mucosal barriers and potential therapeutic strategies that restore epithelial cell integrity following acute viral infections via cytokine and cellular stress manipulation.
+Industry-driven voluntary disease control programs for swine diseases emerged in North America in the early 2000’s, and, since then, those programs have been used for monitoring diseases of economic importance to swine producers.
+One example of such initiatives is Dr. Morrison’s Swine Health Monitoring Project, a nation-wide monitoring program for swine diseases including the porcine reproductive and respiratory syndrome (PRRS).
+PRRS has been extensively reported as a seasonal disease in the U.S., with predictable peaks that start in fall and are extended through the winter season.
+However, formal time series analysis stratified by geographic region has never been conducted for this important disease across the U.S.
+The main objective of this study was to use approximately seven years of PRRS incidence data in breeding swine herds to conduct time-series analysis in order to describe the temporal patterns of PRRS outbreaks at the farm level for five major swine-producing states across the U.S. including the states of Minnesota, Iowa, North Carolina, Nebraska and Illinois.
+Data was aggregated retrospectively at the week level for the number of herds containing animals actively shedding PRRS virus.
+Basic descriptive statistics were conducted followed by autoregressive integrated moving average (ARIMA) modelling, conducted separately for each of the above-mentioned states.
+Results showed that there was a difference in the nature of PRRS seasonality among states.
+Of note, when comparing states, the typical seasonal pattern previously described for PRRS could only be detected for farms located in the states of Minnesota, North Carolina and Nebraska.
+For the other two states, seasonal peaks every six months were detected within a year.
+In conclusion, we showed that epidemic patterns are not homogeneous across the U.S, with major peaks of disease occurring through the year.
+These findings highlight the importance of coordinating alternative control strategies in different regions considering the prevailing epidemiological patterns.
+Ebolaviruses comprises 5 species that exert varying degrees of mortality/infectivity in humans with Reston ebolaviruses (REBOV) showing the lowest and Zaire ebolaviruses (ZEBOV) showing the highest.
+Here, we report that the structural features of ebolavirus envelope glycoproteins (GPs) and one of their counter receptors, macrophage galactose-type calcium-type lectin (MGL/CD301), play crucial roles in determining viral infectivity.
+The low infectivity of REBOV mediated by the interaction between GPs and MGL/CD301 dramatically increased when the N-terminal 18 amino acids (33rd through 50th) of GPs were replaced with that of ZEBOV.
+Furthermore, structural analysis of glycans of GPs revealed that N-glycans were more extended in REBOV than in ZEBOV.
+Therefore, these data strongly suggest that extended N-glycans on GPs reduce MGL/CD301-mediated viral infectivity by hindering the interaction between GPs and MGL/CD301 preferentially binds O-glycans.
+This study was conducted to identify risk factors associated with AIV infections in live bird retail stalls (LBRS) in Lahore District, Pakistan.
+A cross-sectional survey of LBRS was conducted from December 2009-February 2010 using two-stage cluster sampling based on probability proportional to size.
+A total of 280 oropharyngeal swab sample pools were collected from 1400 birds in 8 clusters and tested by qRT-PCR for the matrix (M) gene of type A influenza virus and HA gene subtypes H9, H5 and H7.
+Thirty-four (34) samples were positive for the M gene, of which 28 were also positive for H9.
+Data for 36 potential risk factors, collected by questionnaire, were analyzed by survey-weighted logistic regression and prevalence odds ratios (OR) for associated risk factors were calculated.
+A final multivariable model identified three risk factors for H9 infection in LRBS, namely obtaining birds from mixed sources (OR 2.28, CI(95%): 1.4–3.7), keeping birds outside cages (OR 3.10, CI(95%): 1.4–7.0) and keeping chicken breeds other than broilers (OR 6.27, CI(95%): 1.7–23.2).
+Sourcing birds from dealers/wholesalers, keeping birds inside cages and avoiding mixing different breeds in cages could reduce the risk of H9 infections in LRBS.
+We intended to develop a scoring system to predict mechanical ventilator dependence in patients who survive sepsis/septic shock with respiratory failure.
+This study evaluated 251 adult patients in medical intensive care units (ICUs) between August 2013 to October 2015, who had survived for over 21 days and received aggressive treatment.
+The ventilator dependence risk score was calculated as the sum of the following four variables after being adjusted by proportion to the beta coefficient.
+We assigned a history of previous stroke, a score of one point, platelet count less than 150,000/μL a score of one point, pH value less than 7.35 a score of two points, and the fraction of inspired oxygen on admission day 7 over 39% as two points.
+VD risk score could be applied to predict prolonged mechanical ventilation in patients who survive sepsis/septic shock.
+Bovine Respiratory Disease (BRD) is a major source of economic loss within the agricultural industry.
+Vaccination against BRD-associated viruses does not offer complete immune protection and vaccine failure animals present potential routes for disease spread.
+Serological differentiation of infected from vaccinated animals (DIVA) is possible using antigen-deleted vaccines, but during virus outbreaks DIVA responses are masked by wild-type virus preventing accurate serodiagnosis.
+Previous work by the authors has established the potential for metabolomic profiling to reveal metabolites associated with systemic immune responses to vaccination.
+The current study builds on this work by demonstrating for the first time the potential to use plasma metabolite profiling to differentiate between vaccinated and non-vaccinated animals following infection-challenge.
+Male Holstein Friesian calves were intranasally vaccinated (Pfizer RISPOVAL(®)PI3+RSV) and subsequently challenged with Bovine Parainfluenza Virus type-3 (BPI3V) via nasal inoculation.
+Metabolomic plasma profiling revealed that viral challenge led to a shift in acquired plasma metabolite profiles from day 2 to 20 p.i., with 26 metabolites identified whose peak intensities were significantly different following viral challenge depending on vaccination status.
+Elevated levels of biliverdin and bilirubin and decreased 3-indolepropionic acid in non-vaccinated animals at day 6 p.i.
+may be associated with increased oxidative stress and reactive oxygen scavenging at periods of peak virus titre.
+During latter stages of infection, increased levels of N-[(3α,5β,12α)-3,12-dihydroxy-7,24-dioxocholan-24-yl]glycine and lysophosphatidycholine and decreased enterolactone in non-vaccinated animals may reflect suppression of innate immune response mechanisms and progression to adaptive immune responses.
+Levels of hexahydrohippurate were also shown to be significantly elevated in non-vaccinated animals from days 6 to 20 p.i.
+These findings demonstrate the potential of metabolomic profiling to identify plasma markers that can be employed in disease diagnostic applications to both differentially identify infected non-vaccinated animals during disease outbreaks and provide greater information on the health status of infected animals.
+We have used ribosome profiling to characterize viral translation in infected cells and map new translation initiation sites.
+We show here that EBV transcripts are translated with highly variable efficiency, owing to variable transcription and translation rates, variable ribosome recruitment to the leader region and coverage by monosomes versus polysomes.
+Some transcripts were hardly translated, others mainly carried monosomes, showed ribosome accumulation in leader regions and most likely represent non-coding RNAs.
+A similar process was visible for a subset of lytic genes including the key transactivators BZLF1 and BRLF1 in cells infected with weakly replicating EBV strains.
+This suggests that ribosome trapping, particularly in the leader region, represents a new checkpoint for the repression of lytic replication.
+We could identify 25 upstream open reading frames (uORFs) located upstream of coding transcripts that displayed 5′ leader ribosome trapping, six of which were located in the leader region shared by many latent transcripts.
+These uORFs repressed viral translation and are likely to play an important role in the regulation of EBV translation.
+Genome-wide transcriptional profiling provides a global view of cellular state and how this state changes under different treatments (e.g.
+Here, we present ProTINA (Protein Target Inference by Network Analysis), a network perturbation analysis method for inferring protein targets of compounds from gene transcriptional profiles.
+ProTINA uses a dynamic model of the cell-type specific protein–gene transcriptional regulation to infer network perturbations from steady state and time-series differential gene expression profiles.
+A candidate protein target is scored based on the gene network's dysregulation, including enhancement and attenuation of transcriptional regulatory activity of the protein on its downstream genes, caused by drug treatments.
+For benchmark datasets from three drug treatment studies, ProTINA was able to provide highly accurate protein target predictions and to reveal the mechanism of action of compounds with high sensitivity and specificity.
+Further, an application of ProTINA to gene expression profiles of influenza A viral infection led to new insights of the early events in the infection.
+Outbreaks of novel highly pathogenic avian influenza viruses have been reported in poultry species in the United States since 2014.
+These outbreaks have proven the limitations of biosecurity control programs, and new tools are needed to reinforce the current avian influenza control arsenal.
+Some enzootic countries have implemented inactivated influenza vaccine (IIV) in their control programs, but there are serious concerns that a long-term use of IIV without eradication may result in the selection of novel antigenically divergent strains.
+We showed in our previous studies that pc4-LAIV (a variant that encodes a C-terminally truncated NS1 protein) can provide significant protection against heterologous challenge virus in chickens vaccinated at 2–4 weeks of age through upregulation of innate and adaptive immune responses.
+The current study was conducted to compare the performances of pc4-LAIV and IIV in young chickens vaccinated at 1 day of age.
+A single dose of pc4-LAIV was able to induce stronger innate and mucosal IgA responses and protect young immunologically immature chickens better than a single dose of IIV.
+Most importantly, when 1-day-old chickens were intranasally primed with pc4-LAIV and subcutaneously boosted with IIV three weeks later, they showed a rapid, robust, and highly cross-reactive serum antibody response and a high level of mucosal IgA antibody response.
+BACKGROUND: Research has revealed that angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) may prevent cancers such as hepatocellular carcinoma (HCC).
+The comparative chemopreventive effects of ACEIs and ARBs in high-risk populations with hepatitis B virus (HBV) or hepatitis C virus (HCV) infection have yet to be investigated.
+METHODS: From 2005 to 2014, high-risk HBV and HCV cohorts of hypertensive patients without HCC history were recruited from three linked national databases of Taiwan, and were classified into two groups based on the ACEI or ARB exposure within the initial six months after initiating antiviral agent.
+Intergroup differences in clinical characteristics and duration of drug exposure within study period were evaluated.
+Multivariate Cox regression including time-dependent variables for the use of ACEIs or ARBs and other medications was applied to adjust for confounders.
+RESULTS: Among the 7724 patients with HBV and 7873 with HCV, 46.3% and 42.5%, respectively, had an initial exposure to ACEIs or ARBs.
+The median durations of exposure were 36.4 and 38.9 months for the HBV and HCV cohorts, respectively.
+The median durations of ACEI or ARB use during study period between initial exposure and nonexposure groups were 41.8 vs. 18.3 months and 46.4 vs. 22.7 months for the HBV and HCV cohorts, respectively.
+No significant difference was observed in HCC risk within 7 years between the initial exposure and non-exposure groups.
+After adjustment for comorbidities, namely liver cirrhosis, diabetes mellitus (DM), and hyperlipidemia, and medications, namely aspirin, metformin, and statins, the hazard ratios (HRs) for ACEI or ARB exposure for HCC risk were 0.97 (95% confidence interval [CI]: 0.81–1.16) and 0.96 (0.80–1.16) in the HBV and HCV cohorts, respectively.
+In the HCV cohort, the increased HCC risk was associated with ACEI or ARB use in patients without cirrhosis, DM, and hyperlipidemia (HR: 4.53, 95% CI: 1.46–14.1).
+CONCLUSION: Compared with other significant risk and protective factors for HCC, ACEI or ARB use in the HBV and HCV cohorts was not associated with adequate protective effectiveness under standard dosages and may not be completely safe.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12885-018-4292-y) contains supplementary material, which is available to authorized users.
+V920, rVSVΔG-ZEBOV-GP, is a recombinant vesicular stomatitis-Zaire ebolavirus vaccine which has shown an acceptable safety profile and provides a protective immune response against Ebola virus disease (EVD) induced by Zaire ebolavirus in humans.
+The purpose of this study was to determine whether the V920 vaccine is capable of replicating in arthropod cell cultures of relevant vector species and of replicating in live mosquitoes.
+While the V920 vaccine replicated well in Vero cells, no replication was observed in Anopheles or Aedes mosquito, Culicoides biting midge, or Lutzomyia sand fly cells, nor in live Culex or Aedes mosquitoes following exposure through intrathoracic inoculation or feeding on a high-titer infectious blood meal.
+The insect taxa selected for use in this study represent actual and potential epidemic vectors of VSV.
+aegypti mosquitoes demonstrated persistence of replication-competent virus following inoculation, consistent with the recognized biological stability of the vaccine, but no evidence for active virus replication in live mosquitoes was observed.
+quinquefasciatus mosquitoes at a titer several log(10) PFU more concentrated than would be observed in vaccinated individuals, no infection or dissemination of V920 was observed in either mosquito species.
+In vitro and in vivo data gathered during this study support minimal risk of the vector-borne potential of the V920 vaccine.
+BACKGROUND/OBJECTIVE: A novel porous scaffold poly (lactide-co-glycolide) and tricalcium phosphate (PLGA/TCP) was developed by three-dimensional printing technology for bone defect repair.
+As a Class 2 solvent with less severe toxicity, content of residual 1,4-dioxane in this newly developed scaffold should be rigorously controlled when it is translated to clinical use.
+In this study, a headspace gas chromatography-mass spectrometric (HS-GC-MS) method and related testing protocol were developed for quantitative determination of 1,4-dioxane in the PLGA/TCP composite scaffolds.
+The accuracy, precision, and robustness of this newly developed quantitative method were also validated before quantification of 1,4-dioxane in the scaffolds with different drying procedures.
+RESULTS: Dimethyl formamide (DMF) was the optimal solvent for dissolving scaffolds for GC-MS with proper sensitivity and without matrix effect.
+Then, the optimised procedure was determined as: the scaffolds were dissolved in DMF and kept at 90°C for 40 minutes, separated on a HP-5MS column, and detected by mass spectroscopy.
+The linear range for 1,4-dioxane was determined as 1–40 ppm with linear correlation coefficient ≥ 0.9999.
+Intraday and interday precision was determined as being within relative standard deviation of below 0.68%.
+The passable drying procedure was related to lyophilising (−50°C, 50 Pa) the scaffolds for 2 days and drying in vacuum (50 Pa) for 7 days.
+CONCLUSION: This is the first quantitative method established to test 1,4-dixoane in a novel scaffold.
+This method was validated with good accuracy and reproducibility, and met the methodological requirements of the Guideline 9101 documented in the Chinese Pharmacopoeia 2015 Edition.
+THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: This quantitative method for determination of residual 1,4-dioxane in the novel scaffolds is a key technical method during its translation into clinical use because this method is an important and indispensable file in the enterprise standard when the porous scaffold is registered as a Class III implanted medical device for bone defect repair, which is used to guarantee the safety of the scaffolds.
+It is also applied to optimise the drying process of scaffolds and to monitor the quality of scaffolds in the industrialisation process.
+Further, this method provides references for other solvents quantitative determination in porous scaffolds or materials.
+Pneumonia and meningitis continue to present an enormous public health burden and pose a major threat to young children.
+Among the causative organisms of pneumonia and meningitis, bacteria are the most common causes of serious disease and deaths.
+To solve this problem, we developed and validated a 12-plex PCR coupled with matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) method (bacterial pathogen-mass spectrometry, BP-MS) that can be used to simultaneously screen for 11 key bacterial pathogens related to pneumonia and meningitis.
+Forty-six nasopharyngeal swabs and 12 isolates were used to determine the specificity of the method.
+The results showed that, using the BP-MS method, we could accurately identify the expected bacteria without cross-reactivity with other pathogens.
+For the 11 target bacterial pathogens, the analytical sensitivity of the BP-MS method was as low as 10 copies/reaction.
+To further evaluate the clinical effectiveness of this method, 204 nasopharyngeal swabs from hospitalized children with suspected pneumonia were tested using this method.
+In total, 81.9% (167/204) of the samples were positive for at least one of the 11 target pathogens.
+Among the 167 bacteria-positive samples, the rate of multiple infections was 55.7% (93/167), and the most frequent combination was Streptococcus pneumoniae with Haemophilus influenzae, representing 46.2% (43/93) two-pathogen mixed infections.
+We used real-time PCR and nested PCR to confirm positive results, with identical results obtained for 81.4% (136/167) of the samples.
+The BP-MS method is a sensitive and specific molecular detection technique in a multiplex format and with high sample throughput.
+Therefore, it will be a powerful tool for pathogen screening and antibiotic selection at an early stage of disease.
+BACKGROUND: Neonatal male circumcision (NMC) is an alternative approach to adult male circumcision for HIV prevention.
+Recent studies found that NMC was rarely performed in Thailand and that most Thai health professionals did not recognize that NMC could reduce the risk of HIV infection and would not want NMC services in their hospitals.
+This study explored the thoughts and concerns of Thai government health staff regarding the introduction of NMC in government health facilities as a public health measure.
+METHODS: In-depth interviews with physicians, nurses and physician administrators from four different levels of government hospitals in four provinces representing 4 regions of Thailand were conducted after provision of education regarding the benefits and risks of NMC.
+RESULTS: Six themes emerged from the data of 42 respondents: understanding of the benefits of NMC; risks of NMC; need for a pilot project; need for staff training and hospital readiness; need for parental/family education; and need for public awareness educational campaign.
+Major concerns included possible medical complications of NMC, infringement of child rights, and lack of understanding from staff and parents.
+The respondents emphasized the need for a clear policy, proper training of staff, financial and equipment support, and piloting NMC rollout before this measure could be fully implemented.
+CONCLUSIONS: Thai health professionals who took part in this study expressed several concerns if NMC had to be performed in their health care facilities.
+There is significant preparation that needs to be done before NMC can be introduced in the country.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12913-018-3093-y) contains supplementary material, which is available to authorized users.
+High-resolution crystal structures of ZUFSP in complex with ubiquitin reveal several distinctive features of ubiquitin recognition and catalysis.
+Our analyses reveal that ZUFSP is a novel DUB with no homology to any known DUBs, leading us to classify ZUFSP as the seventh DUB family.
+We identify two ubiquitin binding domains in ZUFSP: a ZHA (ZUFSP helical arm) that binds to the distal ubiquitin and an atypical UBZ domain in ZUFSP that binds to polyubiquitin.
+We show that ZUFSP localizes to DNA lesions, where it plays an important role in genome stability pathways, functioning to prevent spontaneous DNA damage and also promote cellular survival in response to exogenous DNA damage.
+Muscle wasting is one of the main features of cancer cachexia, a multifactorial syndrome frequently occurring in oncologic patients.
+The onset of cachexia is associated with reduced tolerance and response to antineoplastic treatments, eventually leading to clinical conditions that are not compatible with survival.
+In this regard, several potential treatments have been proposed, mainly on the basis of promising results obtained in preclinical models.
+However, at present, no treatment yet reached validation to be used in the clinical practice, although several drugs are currently tested in clinical trials for their ability to improve muscle metabolism in cancer patients.
+Along this line, the results obtained in both experimental and clinical studies clearly show that cachexia can be effectively approached by a multidirectional strategy targeting nutrition, inflammation, catabolism, and inactivity at the same time.
+In the present study, approaches aimed to modulate muscle metabolism in cachexia will be reviewed.
+Host shifts, where a pathogen invades and establishes in a new host species, are a major source of emerging infectious diseases.
+They frequently occur between related host species and often rely on the pathogen evolving adaptations that increase their fitness in the novel host species.
+To investigate genetic changes in novel hosts, we experimentally evolved replicate lineages of an RNA virus (Drosophila C Virus) in 19 different species of Drosophilidae and deep sequenced the viral genomes.
+We found a strong pattern of parallel evolution, where viral lineages from the same host were genetically more similar to each other than to lineages from other host species.
+When we compared viruses that had evolved in different host species, we found that parallel genetic changes were more likely to occur if the two host species were closely related.
+This suggests that when a virus adapts to one host it might also become better adapted to closely related host species.
+This may explain in part why host shifts tend to occur between related species, and may mean that when a new pathogen appears in a given species, closely related species may become vulnerable to the new disease.
+However, the extensive applications of GTs in glycosides formation are limited due to their requirements of expensive nucleotide diphosphate (NDP)-sugars or NDP as the substrates.
+Here, in an effort to characterize flexible GTs for glycodiversification of natural products, we isolated a cDNA, designated as OcUGT1 from Ornithogalum caudatum, which encoded a flavonoid GT that was able to catalyze the trans-glycosylation reactions, allowing the formation of glycosides without the additions of NDP-sugars or NDP.
+In addition, OcUGT1 was observed to exhibit additional five types of functions, including classical sugar transfer reaction and three reversible reactions namely NDP-sugar synthesis, sugars exchange and aglycons exchange reactions, as well as enzymatic hydrolysis reaction, suggesting OcUGT1 displays both glycosyltransferase and glycosidase activities.
+Expression profiles revealed that the expression of OcUGT1 was development-dependent and affected by environmental factors.
+The unusual multifunctionality of OcUGT1 broadens the applicability of OcUGT1, thereby generating diverse carbohydrate-containing structures.
+Some viruses within the Caliciviridae family initiate their replication cycle by attachment to cell surface carbohydrate moieties, histo-blood group antigens (HBGAs), and/or terminal sialic acids (SAs).
+Although bovine nebovirus (BNeV), one of the enteric caliciviruses, is an important causative agent of acute gastroenteritis in cattle, its attachment factors and possibly other cellular receptors remain unknown.
+Using a comprehensive series of protein-ligand biochemical assays, we sought to determine whether BNeV recognizes cell surface HBGAs and/or SAs as attachment factors.
+It was found that BNeV virus-like particles (VLPs) bound to A type/H type 2/Le(y) HBGAs expressed in the bovine digestive tract and are related to HBGAs expressed in humans and other host species, suggesting a wide spectrum of HBGA recognition by BNeV.
+BNeV VLPs also bound to a large variety of different bovine and human saliva samples of all ABH and Lewis types, supporting previously obtained results and suggesting a zoonotic potential of BNeV transmission.
+Removal of α1,2-linked fucose and α1,3/4-linked fucose epitopes of target HBGAs by confirmation-specific enzymes reduced the binding of BNeV VLPs to synthetic HBGAs, bovine and human saliva, cultured cell lines, and bovine small intestine mucosa, further supporting a wide HBGA binding spectrum of BNeV through recognition of α1,2-linked fucose and α1,3/4-linked fucose epitopes of targeted HBGAs.
+However, removal of terminal α2,3- and α2,6-linked SAs by their specific enzyme had no inhibitory effects on binding of BNeV VLPs, indicating that BNeV does not use terminal SAs as attachment factors.
+IMPORTANCE Enteric caliciviruses such as noroviruses, sapoviruses, and recoviruses are the most important etiological agents of severe acute gastroenteritis in humans and many other mammalian host species.
+However, the attachment factor(s) for BNeV, a recently classified enteric calicivirus genus/type species, remains unexplored.
+Here, we demonstrate that BNeV VLPs have a wide spectrum of binding to synthetic HBGAs, bovine and human saliva samples, and bovine duodenal sections.
+We further discovered that α1,2-linked fucose and α1,3/4-linked fucose epitopes are essential for binding of BNeV VLPs.
+Continued investigation regarding the proteinaceous receptor(s) will be necessary for better understanding of the tropism, pathogenesis, and host range of this important viral genus.
+Damage of mitochondria in the initial period of tissue injury aggravates the severity of injury.
+Recently, mitochondrial transfer from stem cells has been demonstrated to play a significant role in rescuing injured tissues.
+The possible mechanisms of mitochondria released from stem cells, the pathways of mitochondria transfer between the donor stem cells and recipient cells, and the internalization of mitochondria into recipient cells are discussed.
+Moreover, a novel strategy for tissue injury based on the concept of stem cell-derived mitochondrial transplantation is pointed out, and the advantages and challenges are summarized.
+OBJECTIVE: The Plan of Information on Acute Respiratory Infections in Catalonia (PIDIRAC) included the surveillance of severe hospitalized cases of laboratory-confirmed influenza (SHCLCI) in 2009.
+The objective of this study was to determine the clinical, epidemiological and virological features of SHCLCI recorded in 12 sentinel hospitals during five influenza seasons.
+RESULTS: From a sample of SHCLCI recorded during the 5 influenza epidemics seasons from 2010–2011 to 2014–2015, Cases were confirmed by PCR and/or viral isolation in cell cultures from respiratory samples.
+The median age of cases was 61 years (range 0–101 years); 70.5% were unvaccinated; 80.4% received antiviral treatment (in 79.6 and 24% of cases within 48 h after hospital admission and the onset of symptoms, respectively); influenza virus A [37.9% A (H1N1)pdm09, 29.3% A (H3N2)] was identified in 87.7% of cases.
+Surveillance of SHCLCI provides an estimate of the severity of seasonal influenza epidemics and the identification and characterization of at-risk groups in order to facilitate preventive measures such as vaccination and early antiviral treatment.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13104-018-3349-y) contains supplementary material, which is available to authorized users.
+In order to determine the most reliable bioinformatics tools to assess the likely pathogenicity of PITX2 variants, the results of bioinformatics predictions were compared to the impact of variants on PITX2 structure and function.
+The MutPred, Provean, and PMUT bioinformatic tools were found to have the highest performance in predicting the pathogenicity effects of all 18 characterized missense variants in PITX2, all with sensitivity and specificity >93%.
+Applying these three programs to assess the likely pathogenicity of 13 previously uncharacterized PITX2 missense variants predicted 12/13 variants as deleterious, except A30V which was predicted as benign variant for all programs.
+Molecular modeling of the PITX2 homoedomain predicts that of the 31 known PITX2 variants, L54Q, F58L, V83F, V83L, W86C, W86S, and R91P alter PITX2’s structure.
+The results of molecular modeling, performed on all the PITX2 missense mutations located in the homeodomain, were compared with the findings of eight protein stability programs.
+CUPSAT was found to be the most reliable in predicting the effect of missense mutations on PITX2 stability.
+Our results showed that for PITX2, and likely other members of this homeodomain transcription factor family, MutPred, Provean, PMUT, molecular modeling, and CUPSAT can reliably be used to predict PITX2 missense variants pathogenicity.
+A balanced immune response to infection is essential to prevent the pathology and tissue damage that can occur from an unregulated or hyperactive host defense.
+Interferons (IFNs) are critical mediators of the innate defense to infection, and in this study we evaluated the contribution of a specific gene coding for IFIT2 induced by type I IFNs in a murine model of disseminated Candida albicans.
+Invasive candidiasis is a frequent challenge during immunosuppression or surgical medical interventions, and C. albicans is a common culprit that leads to high rates of mortality.
+When IFIT2 knockout mice were infected systemically with C. albicans, they were found to have improved survival and reduced fungal burden compared to wild-type mice.
+One of the mechanisms by which IFIT2 increases the pathological effects of invasive C. albicans appears to be suppression of NADPH oxidase activation.
+Loss of IFIT2 increases production of reactive oxygen species by leukocytes, and we demonstrate that IFIT2 is a binding partner of a critical regulatory subunit of NADPH oxidase, p67(phox).
+Since the administration of IFN has been used therapeutically to combat viral infections, cancer, and multiple sclerosis, we evaluated administration of IFN-β to mice prior to C. albicans infection.
+We provide evidence that IFIT2 increases the pathological effects of invasive C. albicans and that administration of IFN-β has deleterious effects during infection.
+BACKGROUND: Patients on extracorporeal membrane oxygenation (ECMO) are often among the most severely ill in the intensive care unit.
+They are often receiving broad-spectrum antibiotics; they have multiple entry points for pathogens; and their immune system is impaired by blood circuit interaction.
+We thus aimed to evaluate the prevalence, risk factors, and prognosis of fungal infections in adults on ECMO.
+METHODS: We conducted a retrospective cohort study using the Extracorporeal Life Support Organization registry, which compiles data on ECMO use from hundreds of international centers.
+We included all adult patients from 2006 to 2016 on any mode of ECMO with either a diagnosis of fungal infection or a positive fungal culture.
+Aspergillus involvement (colonization or infection) was present in 272 patients (1.4%), of whom 35.7% survived to hospital discharge.
+Risk factors for Aspergillus involvement included solid organ transplant (OR 1.83; p = 0.008), respiratory support (OR 2.75; p < 0.001), and influenza infection (OR 2.48; p < 0.001).
+Risk factors for candidemia included sepsis (OR 1.60; p = 0.005) and renal replacement therapy (OR 1.55; p = 0.007).
+In multivariable analysis, Aspergillus involvement (OR 0.40; p < 0.001) and candidemia (OR 0.47; p < 0.001) were both independently associated with decreased survival.
+CONCLUSIONS: The prevalence of Aspergillus involvement and Candida invasive bloodstream infection were not higher in patients on ECMO than what has been reported in the general intensive care population.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13054-018-2023-z) contains supplementary material, which is available to authorized users.
+The last 5 years have been marked by profound innovation in the targeted treatment of chronic lymphocytic leukemia (CLL) and indolent lymphomas.
+Using CLL as a case study, we present a timeline and overview of the current treatment landscape for the radiologist, including an overview of clinical and radiological features of CLL, discussion of the targeted agents themselves, and the role of imaging in response and toxicity assessment.
+The goal is to familiarize the radiologist with multiple Food and Drug Administration (FDA)-approved targeted agents used in this setting and associated adverse events which are commonly observed in this patient population.
+BACKGROUND: The FilmArray Respiratory Panel (FARP) (BioFire Diagnostics, Inc.) is a multiplex, polymerase chain reaction (PCR) technique that can detect 17 respiratory viruses and 3 bacterial targets in a single reaction.
+This prospective study aimed to evaluate the yield and concordance of NP and BAL FARP testing when performed on the same patient concurrently.
+METHODS: From February to December 2016, 125 patients (100 ICH and 25 non-ICH) were enrolled.
+RESULTS: The yield of the BAL FARP among ICH and non-ICH was 24% (24/100) and 8% (2/25), respectively.
+The yield of positive NP swabs in ICH was 27% (27/100) versus 4% (1/25) in non-ICH.
+Of the 24 ICH patients who had a positive BAL FARP, the majority (79%) had the same pathogen detected from the NP swab.
+Given the high concordance, in patients whom a pathogen is identified on the NP FARP, a FARP performed on BAL will likely yield the same result.
+However, if the NP FARP is negative, performing the test on a BAL sample may have an incremental yield.
+BACKGROUND: The respiratory syncytial virus (RSV) is recognized as an important cause of respiratory tract infections.
+Immunocompromised patients, healthcare workers (HCWs) and children contacts are at increased risk of acquiring the infection.
+Objectives: this study evaluated the frequency and viral load (VL) of RSV in nasal swab samples of individuals with different risk factors for acquiring infection in a university hospital in Sao Paulo, Brazil.
+METHODS: We included 196 symptomatic children and their 192 asymptomatic caregivers, 70 symptomatic and 95 asymptomatic HCWs, 43 samples from symptomatic HIV‐positive outpatients, and 100 samples of asymptomatic HIV patients in the period of 2009‐2013.
+RESULTS: RSV infection was detected in 10.1% (70/696) of samples, 4.4% (17/387) of asymptomatic patients, and 17.1% (53/309) from symptomatic patients.
+The VL of symptomatic patients (4.7 log copies/mL) was significantly higher compared to asymptomatic patients (2.3 log copies/mL).
+RSV detection among asymptomatic caregivers (6.8%; 13/192) was significantly higher compared to other asymptomatic adults, HIV and HCWs (2.0%; 4/195; P = .0252).
+A close contact with an infected child at home was an important risk to RSV acquisition [OR 22.6 (95% CI 4.8‐106.7)].
+Children who possibly transmitted the virus to their asymptomatic contacts had significantly higher viral load than children who probably did not transmit (P < .0001).
+CONCLUSIONS: According to our results, it is important to know if people circulating inside the hospital have close contact with acute respiratory infected children.
+OBJECTIVES: Complement activation product C5a plays a critical role in systemic inflammatory response syndrome induced by viruses, bacteria, and toxic agents including paraquat poisoning.
+This study is to explore the efficiency of anti-C5a–based intervention on systemic inflammatory responses induced by paraquat poisoning.
+SUBJECTS: Cynomolgus macaque (n = 12) and samples of plasma from patients (n = 16).
+INTERVENTIONS: The neutralizing antihuman C5a antibody (IFX-1) was administered to investigate the new treatment strategy for paraquat-induced systemic inflammatory responses in cynomolgus macaque model.
+In addition, C5a activation in plasma of paraquat patients was blocked by IFX-1 to investigate the blockade role of anti-C5a antibody in activation of inflammatory cells.
+MEASUREMENTS AND MAIN RESULTS: Dysregulated complement activation and the subsequent cytokine storm were found in patients with acute lung injury and in a primate model of paraquat poisoning.
+Targeted inhibition of C5a by IFX-1 led to marked alleviation of systemic inflammatory responses and multiple organ damage in the primate model.
+In addition, blockade of C5a activity in plasma from patients completely inhibited activation of CD11b on blood granulocytes from normal donors, suggesting that IFX-1 may alleviate the excessive activation of inflammatory responses and have clinical utility for patients with acute lung injury.
+CONCLUSIONS: Anti-C5a antibodies such as IFX-1 may be used as effective therapeutics for treatment of those suffering from systemic inflammatory responses induced by chemical poisoning like paraquat.
+Plant pathogen detection systems have been useful tools to monitor inoculum presence and initiate management schedules.
+More recently, a loop-mediated isothermal amplification (LAMP) assay was successfully designed for field use in the grape powdery mildew pathosystem; however, false negatives or false positives were prevalent in grower-conducted assays due to the difficulty in perceiving the magnesium pyrophosphate precipitate at low DNA concentrations.
+A quantitative LAMP (qLAMP) assay using a fluorescence resonance energy transfer-based probe was assessed by grape growers in the Willamette Valley of Oregon.
+Custom impaction spore samplers were placed at a research vineyard and six commercial vineyard locations, and were tested bi-weekly by the lab and by growers.
+Grower-conducted qLAMP assays used a beta-version of the Smart-DART handheld LAMP reaction devices (Diagenetix, Inc., Honolulu, HI, USA), connected to Android 4.4 enabled, Bluetooth-capable Nexus 7 tablets for output.
+Quantification by a quantitative PCR assay was assumed correct to compare the lab and grower qLAMP assay quantification.
+Growers were able to conduct and interpret qLAMP results; however, the Erysiphe necator inoculum quantification was unreliable using the beta-Smart-DART devices.
+The qLAMP assay developed was sensitive to one spore in early testing of the assay, but decreased to >20 spores by the end of the trial.
+The qLAMP assay is not likely a suitable management tool for grape powdery mildew due to losses in sensitivity and decreasing costs and portability for other, more reliable molecular tools.
+Volatile metabolites are currently under investigation as potential biomarkers for the detection and identification of pathogenic microorganisms, including bacteria, fungi, and viruses.
+Unlike bacteria and fungi, which produce distinct volatile metabolic signatures associated with innate differences in both primary and secondary metabolic processes, viruses are wholly reliant on the metabolic machinery of infected cells for replication and propagation.
+In the present study, the ability of volatile metabolites to discriminate between respiratory cells infected and uninfected with virus, in vitro, was investigated.
+Two important respiratory viruses, namely respiratory syncytial virus (RSV) and influenza A virus (IAV), were evaluated.
+Data were analyzed using three different machine learning algorithms (random forest (RF), linear support vector machines (linear SVM), and partial least squares-discriminant analysis (PLS-DA)), with volatile metabolites identified from a training set used to predict sample classifications in a validation set.
+The discriminatory performances of RF, linear SVM, and PLS-DA were comparable for the comparison of IAV-infected versus uninfected cells, with area under the receiver operating characteristic curves (AUROCs) between 0.78 and 0.82, while RF and linear SVM demonstrated superior performance in the classification of RSV-infected versus uninfected cells (AUROCs between 0.80 and 0.84) relative to PLS-DA (0.61).
+A subset of discriminatory features were assigned putative compound identifications, with an overabundance of hydrocarbons observed in both RSV- and IAV-infected cell cultures relative to uninfected controls.
+This finding is consistent with increased oxidative stress, a process associated with viral infection of respiratory cells.
+Discriminating sterile inflammation from infection, especially in cases of aseptic loosening versus an actual prosthetic joint infection, is challenging and has significant treatment implications.
+Our goal was to evaluate a novel human monoclonal antibody (mAb) probe directed against the Gram-positive bacterial surface molecule lipoteichoic acid (LTA).
+We then radiolabeled the anti-LTA mAb and evaluated its effectiveness as a diagnostic imaging tool for detecting infection via immunoPET imaging in an in vivo mouse model of prosthetic joint infection (PJI).
+In vitro and ex vivo binding of the anti-LTA mAb to pathogenic bacteria was measured with Octet, ELISA, and flow cytometry.
+The in vivo PJI mouse model was assessed using traditional imaging modalities, including positron emission tomography (PET) with [(18)F]FDG and [(18)F]NaF as well as X-ray computed tomography (CT), before being evaluated with the zirconium-89-labeled antibody specific for LTA ([(89)Zr]SAC55).
+Results from imaging showed that our model could reliably simulate infection at the surgical site by bioluminescent imaging, conventional PET tracer imaging, and bone morphological changes by CT. One day following injection of both the radiolabeled anti-LTA and isotype control antibodies, the anti-LTA antibody demonstrated significantly greater (P < 0.05) uptake at S. aureus-infected prosthesis sites over either the same antibody at sterile prosthesis sites or of control non-specific antibody at infected prosthesis sites.
+Taken together, the radiolabeled anti-LTA mAb, [(89)Zr]SAC55, may serve as a valuable diagnostic molecular imaging probe to help distinguish between sterile inflammation and infection in the setting of PJI.
+Human norovirus (HuNoV) is a major cause of nonbacterial gastroenteritis worldwide, yet despite its impact on society, vaccines and antivirals are currently lacking.
+A HuNoV replicon system has been widely applied to the evaluation of antiviral compounds and has thus accelerated the process of drug discovery against HuNoV infection.
+Rupintrivir, an irreversible inhibitor of the human rhinovirus 3C protease, has been reported to inhibit the replication of the Norwalk virus replicon via the inhibition of the norovirus protease.
+Here we report, for the first time, the generation of rupintrivir-resistant human Norwalk virus replicon cells in vitro.
+Sequence analysis revealed that these replicon cells contained amino acid substitutions of alanine 105 to valine (A105V) and isoleucine 109 to valine (I109V) in the viral protease NS6.
+The application of a cell-based fluorescence resonance energy transfer (FRET) assay for protease activity demonstrated that these substitutions were involved in the enhanced resistance to rupintrivir.
+Furthermore, we validated the effect of these mutations using reverse genetics in murine norovirus (MNV), demonstrating that a recombinant MNV strain with a single I109V substitution in the protease also showed reduced susceptibility to rupintrivir.
+In summary, using a combination of different approaches, we have demonstrated that, under the correct conditions, mutations in the norovirus protease that lead to the generation of resistant mutants can rapidly occur.
+Latent membrane protein 1 (LMP1) is an Epstein-Barr virus (EBV) oncogenic protein that has no intrinsic enzymatic activity or sequence homology to cellular or viral proteins.
+The oncogenic potential of LMP1 has been ascribed to pleiotropic signaling properties initiated through protein-protein interactions in cytosolic membrane compartments, but the effects of LMP1 extend to nuclear and extracellular processes.
+Although LMP1 is one of the latent genes required for EBV-immortalization of B cells, the biology of LMP1 in the pathogenesis of the epithelial cancer nasopharyngeal carcinoma (NPC) is more complex.
+NPC is prevalent in specific regions of the world with high incidence in southeast China.
+The epidemiology and time interval from seroconversion to NPC onset in adults would suggest the involvement of multiple risk factors that complement the establishment of a latent and persistent EBV infection.
+The contribution of LMP1 to EBV pathogenesis in polarized epithelia has only recently begun to be elucidated.
+Furthermore, the LMP1 gene has emerged as one of the most divergent sequences in the EBV genome.
+This review will discuss the significance of recent advances in NPC research from elucidating LMP1 function in epithelial cells and lessons that could be learned from mining LMP1 sequence diversity.
+The recent 2014–2016 West African Ebola virus epidemic underscores the need for the development of novel anti-Ebola therapeutics, due to the high mortality rates of Ebola virus infections and the lack of FDA-approved vaccine or therapy that is available for the prevention and treatment.
+Traditional Chinese medicines (TCMs) represent a huge reservoir of bioactive chemicals and many TCMs have been shown to have antiviral activities.
+373 extracts from 128 TCMs were evaluated using a high throughput assay to screen for inhibitors of Ebola virus cell entry.
+Extract of Rhodiola rosea displayed specific and potent inhibition against cell entry of both Ebola virus and Marburg virus.
+In addition, twenty commercial compounds that were isolated from Rhodiola rosea were evaluated using the pseudotyped Ebola virus entry assay, and it was found that ellagic acid and gallic acid, which are two structurally related compounds, are the most effective ones.
+The activity of the extract and the two pure compounds were validated using infectious Ebola virus.
+The time-of-addition experiments suggest that, mechanistically, the Rhodiola rosea extract and the effective compounds act at an early step in the infection cycle following initial cell attachment, but prior to viral/cell membrane fusion.
+Our findings provide evidence that Rhodiola rosea has potent anti-filovirus properties that may be developed as a novel anti-Ebola treatment.
+Viruses have a dual nature: particles are “passive substances” lacking chemical energy transformation, whereas infected cells are “active substances” turning-over energy.
+How passive viral substances convert to active substances, comprising viral replication and assembly compartments has been of intense interest to virologists, cell and molecular biologists and immunologists.
+Infection starts with virus entry into a susceptible cell and delivers the viral genome to the replication site.
+Likewise, the egress of progeny virus particles from the replication site to the extracellular space is enhanced by the cytoskeleton and associated motor proteins.
+This overcomes the limitation of thermal diffusion, and transports virions and virion components, often in association with cellular organelles.
+We discuss the methodology enabling researchers to visualize single virions in cells by fluorescence imaging and tracking.
+Virus visualization and tracking are increasingly enhanced by computational analyses of virus trajectories as well as in silico modeling.
+Using select examples of complementary methodology, we highlight the role of actin filaments and microtubules, and their associated motors in virus infections.
+In-depth studies of single virion dynamics at high temporal and spatial resolutions thereby provide deep insight into virus infection processes, and are a basis for uncovering underlying mechanisms of how cells function.
+It has currently been identified in mosquito pools collected in the field in West and Central Africa.
+Emergence in wild birds in Europe and serological evidence in encephalitis patients in India raise questions on its genetic evolution and the diversity of isolates circulating in Africa.
+To better understand genetic diversity and evolution of Bagaza virus, we describe the full-genome characterization of 11 West African isolates, sampled from 1988 to 2014.
+Parameters such as genetic distances, N-glycosylation patterns, recombination events, selective pressures, and its codon adaptation to human genes are assessed.
+Our study is noteworthy for the observation of N-glycosylation and recombination in Bagaza virus and provides insight into its Indian origin from the 13th century.
+Interestingly, evidence of Bagaza virus codon adaptation to human house-keeping genes is also observed to be higher than those of other flaviviruses well known in human infections.
+Genetic variations on genome of West African Bagaza virus could play an important role in generating diversity and may promote Bagaza virus adaptation to other vertebrates and become an important threat in human health.
+Interferons (IFNs) are a group of secreted proteins that play critical roles in antiviral immunity, antitumor activity, activation of cytotoxic T cells, and modulation of host immune responses.
+The major signaling pathway activated by IFNs is the JAK/STAT (Janus kinase/signal transducer and activator of transcription) pathway, a complex pathway involved in both viral and host survival strategies.
+On the one hand, viruses have evolved strategies to escape from antiviral host defenses evoked by IFN-activated JAK/STAT signaling.
+On the other hand, viruses have also evolved to exploit the JAK/STAT pathway to evoke activation of certain STATs that somehow promote viral pathogenesis.
+In this review, recent progress in our understanding of the virus-induced IFN-independent STAT signaling and its potential roles in viral induced inflammation and pathogenesis are summarized in detail, and perspectives are provided.
+We have previously shown that the infection of cell cultures with the arenaviruses Junín (JUNV), Tacaribe (TCRV), and Pichindé promotes the phosphorylation of mitogen-activated protein kinases (MAPKs) extracellular signal-regulated kinases 1 and 2 (ERK1/2) and that this activation is required for the achievement of a productive infection.
+Here we examined the contribution of ERK1/2 in early steps of JUNV and TCRV multiplication.
+JUNV adsorption, internalization, and uncoating were not affected by treatment of cultured cells with U0126, an inhibitor of the ERK1/2 signaling pathway.
+In contrast, U0126 caused a marked reduction in viral protein expression and RNA synthesis, while JUNV RNA synthesis was significantly augmented in the presence of an activator of the ERK1/2 pathway.
+Moreover, U0126 impaired the expression of a reporter gene in a TCRV-based replicon system, confirming the ability of the compound to hinder arenavirus macromolecular synthesis.
+By using a cell-based assay, we determined that the inhibitor did not affect the translation of a synthetic TCRV-like mRNA.
+No changes in the phosphorylation pattern of the translation factor eIF2α were found in U0126-treated cells.
+Our results indicate that U0126 impairs viral RNA synthesis, thereby leading to a subsequent reduction in viral protein expression.
+Thus, we conclude that ERK1/2 signaling activation is required for an efficient arenavirus RNA synthesis.
+Metagenomics poses opportunities for clinical and public health virology applications by offering a way to assess complete taxonomic composition of a clinical sample in an unbiased way.
+This, together with the wealth of different tools and workflows that have been proposed, poses a barrier for new users.
+To this end, we described the methods of existing workflows by breaking them up into five general steps and assessed their ease-of-use and validation experiments.
+Performance scores of previous benchmarks were summarized and correlations between methods and performance were investigated.
+We indicate the potential suitability of the different workflows for (1) time-constrained diagnostics, (2) surveillance and outbreak source tracing, (3) detection of remote homologies (discovery), and (4) biodiversity studies.
+We provide two decision trees for virologists to help select a workflow for medical or biodiversity studies, as well as directions for future developments in clinical viral metagenomics.
+In 2016, the definition and diagnostic criteria for AE-IPF were updated by an international working group.
+The new definition includes any acute, clinically significant respiratory deterioration (both idiopathic and triggered events) characterized by evidence of new widespread alveolar abnormality in patients with IPF.
+This is the first report describing AE-IPF triggered by Aspergillus empyema, which was improved by a combination of corticosteroid, systemic antifungal therapy, local antifungal therapy, and additional pharmacological therapies.
+ARTDs transfer either single or multiple ADP-ribose units to substrates, resulting in mono- or poly-ADP-ribosylation.
+Interactome analyses revealed that TARG1 binds strongly to ribosomes and proteins associated with rRNA processing and ribosomal assembly factors.
+In response to DNA damage, which activates ARTD1/2 (PARP1/2) and promotes synthesis of poly-ADP-ribose chains, TARG1 re-localized to the nucleoplasm.
+These findings are consistent with the observed ability of TARG1 to competitively interact with RNA and PAR chains.
+We propose a nucleolar role of TARG1 in ribosome assembly or quality control that is stalled when TARG1 is re-located to sites of DNA damage.
+The use of fever syndromic surveillance in sub-Saharan Africa is an effective approach to determine the prevalence of both malarial and nonmalarial infectious agents.
+We collected both blood and naso/oro-pharyngeal (NP/OP) swabs from consecutive consenting patients ≥ 1 year of age, with an axillary temperature ≥ 37.5°C, and symptom onset of ≤ 5 days.
+Specimens were analyzed using both acute febrile illness (AFI) and respiratory TaqMan array cards (Resp TAC) for multiagent detection of 56 different bloodstream and respiratory agents.
+We enrolled 205 febrile patients, including 70 children (1 < 15 years of age; 34%) and 135 adults (≥ 15 years of age; 66%).
+AFI TAC and Resp TAC were performed on 191 whole blood specimens and 115 NP/OP specimens, respectively.
+We detected nucleic acid for Plasmodium (57%), Leptospira (2%), and dengue virus (1%) among blood specimens.
+In addition, we detected 17 different respiratory agents, most notably, Haemophilus influenzae (64%), Streptococcus pneumonia (56%), Moraxella catarrhalis (39%), and respiratory syncytial virus (11%) among NP/OP specimens.
+This study provides a proof-of-concept for the use of a multiagent diagnostic approach for exploratory research on febrile illness and underscores the utility of quantitative molecular diagnostics in complex epidemiologic settings of sub-Saharan Africa.
+In comparison with the major histocompatibility complexes (MHCs) of typical mammals, the chicken MHC is simple and compact with a single dominantly expressed class I molecule that can determine the immune response.
+In addition to providing useful information for the poultry industry and allowing insights into the evolution of the adaptive immune system, the simplicity of the chicken MHC has allowed the discovery of phenomena that are more difficult to discern in the more complicated mammalian systems.
+This review discusses the new concept that poorly expressed promiscuous class I alleles act as generalists to protect against a wide variety of infectious pathogens, while highly expressed fastidious class I alleles can act as specialists to protect against new and dangerous pathogens.
+Objectives This study was designed to explore the genetic etiology of deafness in a large Chinese family with autosomal dominant, nonsyndromic, progressive sensorineural hearing loss (ADNSHL).
+Results We identified a cosegregating heterozygous missense mutation, c.296G>A (p.Arg99His) in the gene encoding interferon lambda receptor 1 (IFNLR1) – a protein that functions in the Jak/ STAT pathway– are associated with ADNSHL.
+Morpholino knockdown of ifnlr1 leads to a significant decrease in hair cells and non-inflation of the swim bladder in late-stage zebrafish, which can be reversed by injection with normal Zebrafish ifnlr1 mRNA.
+Knockdown of ifnlr1 in zebrafish causes significant upregulation of cytokine receptor family member b4 (interleukin-10r2), jak1, tyrosine kinase 2, stat3, and stat5b in the Jak1/STAT3 pathway at the mRNA level.
+Conclusion IFNLR1 function is required in the auditory system and that IFNLR1 mutations are associated with ADNSHL.
+To the best of our knowledge, this is the first study implicating an interferon lambda receptor in auditory function.
+HPIVs are serologically and genetically grouped into four species that account for up to 10% of all hospitalizations due to acute respiratory infection in children under the age of five.
+Genetic and epidemiological data for the four HPIVs derived from two pediatric cohorts in Viet Nam are presented.
+We used a hemi-nested PCR approach to generate viral genome sequences from HPIV-positive samples and conducted a comprehensive phylogenetic analysis.
+HPIV3 was most commonly detected in our cohort and 80 co-detections of HPIV with other respiratory viruses were found.
+Phylogenetic analyses suggest local endemic circulation as well as punctuated introductions of new HPIV lineages.
+Viral gene flow analysis revealed that Viet Nam is a net importer of viral genetic diversity.
+HPIV sequences from Viet Nam formed local clusters and were interspersed with sequences from diverse geographic regions.
+Combined, this new knowledge will help to investigate global HPIV circulation patterns in more detail and ultimately define more suitable vaccine strains.
+Leptospirosis is the most widespread zoonotic disease, estimated to cause severe infection in more than one million people each year, particularly in developing countries of tropical areas.
+Several factors such as variable and nonspecific clinical manifestation, existence of large number of serovars and asymptomatic hosts spreading infection, poor sanitation and lack of an effective vaccine make prophylaxis difficult.
+Consequently, there is an urgent need to develop an effective vaccine to halt its spread all over the world.
+In this study, an immunoinformatics approach was employed to identify the most vital and effective immunogenic protein from the proteome of Leptospira interrogans serovar Copenhageni strain L1-130 that may be suitable to stimulate a significant immune response aiding in the development of peptide vaccine against leptospirosis.
+Both B-cell and T-cell (Helper T-lymphocyte (HTL) and cytotoxic T lymphocyte (CTL)) epitopes were predicted for the conserved and most immunogenic outer membrane lipoprotein.
+Further, the binding interaction of CTL epitopes with Major Histocompatibility Complex class I (MHC-I) was evaluated using docking techniques.
+A Molecular Dynamics Simulation study was also performed to evaluate the stability of the resulting epitope-MHC-I complexes.
+Overall, this study provides novel vaccine candidates and may prompt further development of vaccines against leptospirosis.
+The subsequent humanitarian effort spurred extensive research, significantly enhancing our understanding of ebolavirus replication and pathogenicity.
+The main functions of each ebolavirus protein have been studied extensively since the discovery of the virus in 1976; however, the recent expansion of ebolavirus research has led to the discovery of new protein functions.
+These newly discovered roles are revealing new mechanisms of virus replication and pathogenicity, whilst enhancing our understanding of the broad functions of each ebolavirus viral protein (VP).
+Many of these new functions appear to be unrelated to the protein’s primary function during virus replication.
+Such new functions range from bystander T-lymphocyte death caused by VP40-secreted exosomes to new roles for VP24 in viral particle formation.
+This review highlights the newly discovered roles of ebolavirus proteins in order to provide a more encompassing view of ebolavirus replication and pathogenicity.
+Humans constitutively and/or inducibly express α- and β-defensins, which are known for their antiviral and antibacterial activities.
+We discuss the extant experimental results, limited though they are, to consider the potential applicability of human defensins as antiviral agents.
+Given their antiviral effects, we propose that basic research be conducted on human defensins that focuses on RNA viruses, such as human immunodeficiency virus (HIV), influenza A virus (IAV), respiratory syncytial virus (RSV), and dengue virus (DENV), which are considered serious human pathogens but have posed huge challenges for vaccine development for different reasons.
+Concerning the prophylactic and therapeutic applications of defensins, we then discuss the applicability of human defensins as antivirals that has been demonstrated in reports using animal models.
+Finally, we discuss the potential adjuvant-like activity of human defensins and propose an exploration of the ‘defensin vaccine’ concept to prime the body with a controlled supply of human defensins.
+In sum, we suggest a conceptual framework to achieve the practical application of human defensins to combat viral infections.
+Here, we evaluated whether the sequence similarity of various antigens to the microbiota dampens or increases immunogenicity of T cell epitopes.
+Sets of epitopes and control sequences derived from 38 antigenic categories (infectious pathogens, allergens, autoantigens) were retrieved from the Immune Epitope Database (IEDB).
+Dengue and West Nile viruses) likelihood of a peptide being immunogenic as a function of epitope source category.
+Ten-fold cross-validation and validation using sets of manually curated epitopes and non-epitopes derived from allergens were used to confirm these initial observations.
+Furthermore, the genus from which the microbiome homologous sequences were derived influenced whether a tolerogenic versus inflammatory modulatory effect was observed, with Fusobacterium most associated with inflammatory influences and Bacteroides most associated with tolerogenic influences.
+“Tolerogenic” microbiome peptides elicited IL-10 production, “inflammatory” peptides elicited mixed IL-10/IFNγ production, while microbiome epitopes homologous to self were completely unreactive for both cytokines.
+We also tested the sequence similarity of cockroach epitopes to specific microbiome sequences derived from households of cockroach allergic individuals and non-allergic controls.
+Microbiomes from cockroach allergic households were less likely to contain sequences homologous to previously defined cockroach allergens.
+These results are compatible with the hypothesis that microbiome sequences may contribute to the tolerization of T cells for allergen epitopes, and lack of these sequences might conversely be associated with increased likelihood of T cell reactivity against the cockroach epitopes.
+Taken together this study suggests that microbiome sequence similarity influences immune reactivity to homologous epitopes encoded by pathogens, allergens and auto-antigens.
+BACKGROUND: This study aimed to evaluate the demographic, clinical features, laboratory data, pathology and other survey in pediatric patients with cryofibrinogenemia.
+METHODS: A 12-year retrospective chart review identified eight pediatric patients at Mackay Memorial Hospital, Taipei, Taiwan.
+The mean age at symptom onset and of diagnosis was 10.3 ± 4.6 years and 12.3 ± 4 years, respectively.
+All patients had increased anti-thrombin III while 87.5% and 62.5% had abnormal protein S and protein C, respectively.
+One had vertebral artery narrowing, two showed increased T2-weighted signal intensity on the thalamus or white matter, and one had acute hemorrhagic encephalomyelitis on brain magnetic resonance imaging.
+Thermal acclimation is hypothesized to offer a selective advantage in seasonal habitats and may underlie disparities in geographic range size among closely‐related species with similar ecologies.
+Understanding this relationship is also critical for identifying species that are more sensitive to warming climates.
+Here, we study North American plethodontid salamanders to investigate whether acclimation ability is associated with species’ latitudinal extents and the thermal range of the environments they inhabit.
+We quantified variation in thermal physiology by measuring standard metabolic rate (SMR) at different test and acclimation temperatures for 16 species of salamanders with varying latitudinal extents.
+A phylogenetically‐controlled Markov chain Monte Carlo generalized linear mixed model (MCMCglmm) was then employed to determine whether there are differences in SMR between wide‐ and narrow‐ranging species at different acclimation temperatures.
+In addition, we tested for a relationship between the acclimation ability of species and the environmental temperature ranges they inhabit.
+Further, we investigated if there is a trade‐off between critical thermal maximum (CTMax) and thermal acclimation ability.
+MCMCglmm results show a significant difference in acclimation ability between wide and narrow‐ranging temperate salamanders.
+Salamanders with wide latitudinal distributions maintain or slightly increase SMR when subjected to higher test and acclimation temperatures, whereas several narrow‐ranging species show significant metabolic depression.
+We also found significant, positive relationships between acclimation ability and environmental thermal range, and between acclimation ability and CTMax.
+Wide‐ranging salamander species exhibit a greater capacity for thermal acclimation than narrow‐ranging species, suggesting that selection for acclimation ability may have been a key factor enabling geographic expansion into areas with greater thermal variability.
+Further, given that narrow‐ranging salamanders are found to have both poor acclimation ability and lower tolerance to warm temperatures, they are likely to be more susceptible to environmental warming associated with anthropogenic climate change.
+Background: There is uncertainty regarding which factors are associated with in-hospital mortality among patients with pulmonary TB (PTB).
+The aim of this systematic review and meta-analysis is to identify predictors of in-hospital mortality among patients with PTB.
+Methods: We searched MEDLINE, EMBASE, and Global Health, for cohort and case-control studies that reported risk factors for in-hospital mortality in PTB.
+We pooled all factors that were assessed for an association, and presented relative associations as pooled odds ratios (ORs).
+Results: We identified 2,969 records, of which we retrieved 51 in full text; 11 cohort studies that evaluated 5,468 patients proved eligible.
+Moderate quality evidence suggested an association with co-morbid malignancy and in-hospital mortality (OR 1.85; 95% CI 1.01–3.40).
+Low quality evidence showed no association with positive sputum smear (OR 0.99; 95% CI 0.40–2.48), or male sex (OR 1.09, 95% CI 0.84–1.41), and very low quality evidence showed no association with diabetes mellitus (OR 1.31, 95% IC 0.38–4.46), and previous TB infection (OR 2.66, 95% CI 0.48–14.87).
+Conclusion: Co-morbid malignancy was associated with increased risk of in-hospital death among pulmonary TB patients.
+There is insufficient evidence to confirm positive sputum smear, male sex, diabetes mellitus, and previous TB infection as predictors of in-hospital mortality in TB patients.
+Work-related mental health impairment is recognized as a real problem in the context of helping responders, including health professionals, due to adverse health outcomes after a severe disaster.
+The Great East-Japan Earthquake, which occurred on 11 March 2011, was an unprecedented complex disaster that caused a nuclear accident at the Fukushima Daiichi Nuclear Power Plant (NPP).
+In addition to disaster stress and daily work, medical and health-care professionals, particularly nurses, provided counseling services to residents concerned about radiation health risks or mental health issues.
+This review focuses on the psychological aspects of the complex nuclear disaster, which was a combined artificial nuclear accident and natural disaster, and we investigated the psychological effects on hospital nurses associated with their experiences during the disaster.
+We looked at several investigations into the mental health of nurses after a nuclear disaster and in other situations.
+It was shown that mental health of nurses is impacted, not only after nuclear disasters but also in other circumstances.
+Furthermore, we noted the effects of extended periods of a heavy workload and daily life.
+Regarding anxiety about radiation exposure, nurses who had more knowledge of radiation tended to have better mental health, suggesting that education about the health risks of radiation exposure is important for health-care professionals.
+In summary, it is essential that nurses are provided with education about radiation exposure and its associated health risks, and also that there is a comprehensive approach to mental health care for nurses during the chronic phase of a disaster.
+The ability of the host immune response is largely mediated by the proinflammatory cytokine production.
+Physiological and pathological conditions of endoplasmic reticulum (ER) trigger unfolded protein response and contribute to the development or pathology of inflammatory diseases.
+Under ER stress, unfolded protein response (UPR) signaling pathways participate in upregulating inflammatory cytokine production via NF-kappaB, MAPK, and GSK-3β.
+Moreover, it has been suggested that ER stress crosstalks with toll-like receptor (TLR) signaling pathway to promote the production of proinflammatory cytokines.
+In this review, we will cover how proinflammatory cytokine production by UPR signaling can be induced or amplified in the presence or absence of TLR activation.
+One of the daunting challenges facing modern medicine lies in the understanding and treatment of tumor heterogeneity.
+Most tumors show intra-tumor heterogeneity at both genomic and proteomic levels, with marked impacts on the responses of therapeutic targets.
+However, the finding that targets such as eukaryotic initiation factor (eIF) 4E (and its phosphorylated form, p-eIF4E) are generally homogenously expressed throughout tumors, regardless of the presence of hypoxia or other cellular stress conditions, opens the exciting possibility that malignancies could be treated with therapies that combine targeting of eIF4E phosphorylation with immune checkpoint inhibitors or chemotherapy.
+The present study aimed to explore the mechanisms underlying sepsis-induced acute lung injury (ALI) and identify more effective therapeutic strategies to treat it.
+The gene expression data set GSE10474 was downloaded and assessed to identify differentially expressed genes (DEGs).
+A number of DEGs, including zinc finger and BTB domain containing 17 (ZBTB17), heat shock protein 90 kDa β, member 1 (HSP90B1) and major histocompatibility complex, class II, DR α were identified.
+Furthermore, gene ontology terms including antigen processing and presentation, glycerophospholipid metabolism, transcriptional misregulation in cancer, thyroid hormone synthesis and pathways associated with diseases, such as asthma were identified.
+In addition, a differential co-expression network containing ubiquitin-conjugating enzyme E2 D4, putative and tubulin, γ complex associated protein 3 was constructed.
+Furthermore, a number of gene-drug interactions, including between HSP90B1 and adenosine-5′-diphosphate and radicicol, were identified.
+Therefore, DEGs, including ZBTB17 and HSP90B1, may be important in the pathogenesis of sepsis-induced ALI.
+Sodium taurocholate cotransporting polypeptide (NTCP) is a major entry receptor of hepatitis B virus (HBV) and one of the most attractive targets for anti-HBV drugs.
+We developed a cell-mediated drug screening method to monitor NTCP expression on the cell surface by generating a HepG2 cell line with tetracycline-inducible expression of NTCP and a monoclonal antibody that specifically detects cell-surface NTCP.
+Using this system, we screened a small molecule library for compounds that protected against HBV infection by targeting NTCP.
+We found that glabridin, a licorice-derived isoflavane, could suppress viral infection by inducing caveolar endocytosis of cell-surface NTCP with an IC(50) of ~40 μM.
+We also found that glabridin could attenuate the inhibitory effect of taurocholate on type I interferon signaling by depleting the level of cell-surface NTCP.
+These results demonstrate that our screening system could be a powerful tool for discovering drugs targeting HBV entry.
+We sought to evaluate whether a semi-quantitative scoring tool, the Radiologic Severity Index (RSI), predicted mortality after parainfluenza virus (PIV)-associated LRI.
+METHODS: We conducted a retrospective review of consecutively-enrolled adult patients with hematologic malignancy or hematopoietic stem cell transplantation and with PIV detected in nasal wash who subsequently developed radiologically-confirmed LRI.
+We measured RSI (range 0–72) in each chest radiograph during the first 30 days after LRI diagnosis.
+We used extended Cox proportional hazards models to identify factors associated with mortality after onset of LRI with all-cause mortality as our failure event.
+RESULTS: After adjustment for patient characteristics, each 1-point increase in RSI was associated with an increased hazard of death (HR 1.13, 95% confidence interval [CI] 1.05–1.21, p = 0.0008).
+Baseline RSI was not predictive of death, but both peak RSI and the change from baseline to peak RSI (delta-RSI) predicted mortality (odds ratio for mortality, peak: 1.11 [95%CI 1.04–1.18], delta-RSI: 1.14 [95%CI 1.06–1.22]).
+CONCLUSIONS: We conclude that the RSI offers precise, informative and reliable assessments of LRI severity.
+Our results were derived from a cohort of patients with PIV-associated LRI, but can be applied in validated in other populations of patients with LRI.
+During the last two decades, the pharmaceutical industry has progressed from detecting small molecules to designing biologic-based therapeutics.
+Amino acid-based drugs are a group of biologic-based therapeutics that can effectively combat the diseases caused by drug resistance or molecular deficiency.
+Computational techniques play a key role to design and develop the amino acid-based therapeutics such as proteins, peptides and peptidomimetics.
+In this study, it was attempted to discuss the various elements for computational design of amino acid-based therapeutics.
+Protein design seeks to identify the properties of amino acid sequences that fold to predetermined structures with desirable structural and functional characteristics.
+Peptide drugs occupy a middle space between proteins and small molecules and it is hoped that they can target “undruggable” intracellular protein–protein interactions.
+Peptidomimetics, the compounds that mimic the biologic characteristics of peptides, present refined pharmacokinetic properties compared to the original peptides.
+Here, the elaborated techniques that are developed to characterize the amino acid sequences consistent with a specific structure and allow protein design are discussed.
+Moreover, the key principles and recent advances in currently introduced computational techniques for rational peptide design are spotlighted.
+Liver diseases are one of the fatal syndromes due to the vital role of the liver.
+Two natural compounds possessing promising liver protection and with different chemical structures namely; the bioflavonoid hinokiflavone (HF) isolated from Junipers phoenicea family Cupressaceae and the sweet saponin Glycyrrhizin (GL) present in Glycyrrhiza glabra (liquorice) were selected for the current study.
+Since the two compounds are of different nature, they may act by different mechanisms and express synergistic effect.
+Combination of the two compounds using to dose levels were challenged with single doses of HF, GL and SI as well.
+The comparison was monitored via measuring serum biochemical parameters including, aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyltranspeptidase (GGT), alkaline phosphatase (ALP) and total bilirubin, tissue parameters such as MDA, NP-SH and TP, histopathological study using light and electron microscope.
+Protective effect on kidney was also monitored histopathologically and biochemically through observing the levels of LDH, creatinine, creatinine-kinase, urea and uric acid.
+The combinations of HF and GL showed protective effect more than the used single doses of HF and GL alone.
+However, SI was superior to the used combination in the two used doses in all the measured parameters.
+The liver and kidney cells appearance under normal and electron microscope showed that SI treated groups showed almost normal cells with slight toxic signs.
+Cells from group treated with the higher doses of the combination of HF and GL showed slight signs of intoxication under light and electron microscope indicating good level of protection.
+Although the combination of HF and GL expressed good protection in the higher dose, however, the combination did not exceed the protective effect of SI.
+Background: The C allele of the interferon-induced transmembrane protein-3 (IFITM3) SNP rs12252, a common allele in South East Asia and China, is strongly associated with severe influenza infection.
+However, despite the high occurrence of rs12252-CC genotype in Chinese population (~25%), severe influenza infection is rare.
+The aim of study is to determine whether rs12252-CC individuals have pre-existing antibody responses to previous seasonal influenza infections.
+Cohort and Method: A total 99 young healthy volunteers (18–20 years) were recruited and received an influenza seasonal Vaccination [A/Switzerland/9715293/2013(H3N2), A/California/7/2009 (pdm09H1N1) and B/Jeep/3073/2013-like virus (Flu-B)].
+Plasma and gDNA was isolated from each volunteer before, and 14, 28, 180, 360, and 540 days after vaccination.
+Additionally, 68 elderlies (>65 years) were also recruited as a control group to compare the levels of antibodies at baseline between the young adults and the elderly.
+For each sample IFITM3 rs12252 genotype was determined and antibody levels in response to pdmH1N1, H3N2 and Influenza B infection were measured for each time point.
+Results: We found a significantly higher level of pre-existing antibodies to pandemic influenza H1N1/09 virus (pdm09H1N1) but not to H3N2 or FluB in CC donors in comparison with CT/TT donors prior to vaccination.
+No impact of IFITM3 genotype in boosting influenza specific antibodies in young adults within 1 year after receiving seasonal influenza vaccination was observed.
+In addition, there was no difference in pdm09H1N1 specific antibody levels observed in the elderly cohort between volunteers carrying different IFITM3 genotypes.
+Higher levels of antibodies to pdmH1N1 were observed in elderly CC carriers when compared to the young CC carriers, but this trend was not replicated in TT carriers.
+Conclusion: IFITM3-rs12252 CC carriers exhibit a high level of pre-existing immunity to pdm09H1N1 compared to TT carriers in the young cohort.
+This suggests that compensatory mechanisms exist which might contribute to viral control in patients carrying the rs12252-CC genotype who do not become sick after flu infection.
+However, such a potential compensatory effect appears to be lost overtime, as evidenced in the elderly cohort.
+If this compensatory mechanism is lost, it may make the CC carrying elderly more susceptible to severe influenza infection.
+Codon usage bias not only plays an important regulatory role at the level of gene expression, but also helps in improving the accuracy and efficiency of translation.
+Meanwhile, codon usage pattern of Mycobacterium tuberculosis genome is important for interpreting evolutionary characteristics in species.
+In order to investigate the codon usage pattern of the Mycobacterium tuberculosis genome, 12 Mycobacterium tuberculosis genomes from different area are downloaded from the GeneBank.
+The correlations between G(3), GC(12), whole GC content, codon adaptation index, codon bias index, and so on of Mycobacterium tuberculosis genomes are calculated.
+The ENC-plot, relationship between A(3)/(A(3) + T(3)) and G(3)/(G(3) + C(3)), GC(12) versus GC(3) plot, and the RSCU of overall/separated genomes all show that the codon usage bias exists in all 12 Mycobacterium tuberculosis genomes.
+Lastly, relationship between CBI and the equalization of ENC shows a strong negative correlation between them.
+The relationship between protein length and GC content (GC(3) and GC(12)) shows that more obvious differences in the GC content may be in shorter protein.
+These results show that codon usage bias existing in the Mycobacterium tuberculosis genomes could be used for further study on their evolutionary phenomenon.
+Group C serogroup includes members of the Orthobunyavirus genus (family Peribunyaviridae) and comprises 15 arboviruses that can be associated with febrile illness in humans.
+Although previous studies described the genome characterization of Group C orthobunyavirus, there is a gap in genomic information about the other viruses in this group.
+Therefore, in this study, complete genomes of members of Group C serogroup were sequenced or re-sequenced and used for genetic characterization, as well as to understand their phylogenetic and evolutionary aspects.
+Thus, our study reported the genomes of three new members in Group C virus (Apeu strain BeAn848, Itaqui strain BeAn12797 and Nepuyo strain BeAn10709), as well as re-sequencing of original strains of five members: Caraparu (strain BeAn3994), Madrid (strain BT4075), Murucutu (strain BeAn974), Oriboca (strain BeAn17), and Marituba (strain BeAn15).
+Interestingly, all viruses of this serogroup showed an open reading frame (ORF) that encodes the putative nonstructural NSs protein that precedes the nucleoprotein ORF, an unprecedented fact in Group C virus.
+This study expands the genomic information of Group C viruses, as well as revalidates the genomic organization of viruses that were previously reported.
+BACKGROUND: The structural modification of natural products with the aim to improve the anticancer activity is a popular current research direction.
+The pentacyclic triterpenoid compounds oleanolic acid (OA) and glycyrrhetinic acid (GA) are distributed widely in nature.
+METHODS: In this study, various oleanolic acids and glycyrrhetinic acids were designed and synthesized by using the combination principle.
+The in vitro anticancer activities of new OA and GA derivatives were tested by the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) method with SGC-7901 (gastric cancer), MCF-7 (breast cancer), Eca-109 (esophageal cancer), HeLa (cervical cancer), Hep-G2 (hepatoma cancer) and HSF (normal human skin fibroblast) cells.
+RESULTS AND CONCLUSION: The screening results showed that the compound 3m presented the highest inhibitory activities against SGC-7901, MCF-7 and Eca-109 cell lines with IC(50) values of 7.57±0.64 μM, 5.51±0.41 μM and 5.03±0.56 μM, respectively.
+In addition, this compound also showed effective inhibition of Hep-G2 cells with an IC(50) value of 4.11±0.73 μM.
+Moreover, compound 5b showed the strongest inhibitory activity against Hep-G2 cells with an IC(50) value of 3.74±0.18 μM and compound 3l showed strong selective inhibition of the HeLa cells with the lowest IC(50) value of 4.32±0.89 μM.
+A series of pharmacology experiments indicated that compound 5b could induce Hep-G2 cells autophagy and apoptosis.
+These compounds will expand the structural diversity of anti-cancer targets and confirm the prospects for further research.
+China is one of the most dynamic countries of the world and it shelters some amazing levels of biodiversity, including some very special primate species.
+However, primarily as a result of forest loss, most of which occurred in historical times, approximately 70% of China’s primate species have less than 3 000 individuals.
+Here I evaluate one road for future conservation/development that could produce very positive gains for China’s primates; namely forest restoration.
+I argue that for a large scale restoration project to be possible two conditions must be met; the right societal conditions must exist and the right knowledge must be in hand.
+This evaluation suggests that the restoration of native forest to support many of China’s primates holds great potential to advance conservation goals and to promote primate population recovery.
+Noroviruses are the primary cause of nonbacterial diarrheal outbreaks in humans, whilst rotaviruses are a major cause of childhood diarrhea.
+Although both enteric pathogens substantially impact human health and economies, there are no approved drugs against noroviruses and rotaviruses so far.
+On the other hand, whilst the currently licensed rotavirus vaccines have been successfully implemented in over 100 countries, the most advanced norovirus vaccine has recently completed phase-I and II trials.
+METHODS: We performed a structured search of bibliographic databases for peer-reviewed research litera-ture on advances in the fields of norovirus and rotavirus therapeutics and immunoprophylaxis.
+RESULTS: Technological advances coupled with a proper understanding of viral morphology and replication over the past decade has facilitated pioneering research on therapeutics and immunoprophylaxis against noroviruses and rotaviruses, with promising outcomes in human clinical trials of some of the drugs and vaccines.
+CONCLUSIONS: This review provides important insights into the various approaches to therapeutics and im-munoprophylaxis against noroviruses and rotaviruses..
+Cytokines IL-17 and IL-22 play pivotal roles in host defense against microbes and in the development of chronic inflammatory diseases.
+These cytokines are produced by cells that are often located in epithelial barriers, including subsets of T cells and innate lymphoid cells.
+In general, IL-17 and IL-22 can be characterized as important cytokines in the rapid response to infectious agents, both by recruiting neutrophils and by inducing the production of antimicrobial peptides.
+Although each cytokine induces an innate immune response in epithelial cells, their functional spectra are generally distinct: IL-17 mainly induces an inflammatory tissue response and is involved in the pathogenesis of several autoimmune diseases, whereas IL-22 is largely protective and regenerative.
+In this review, we compare IL-17 and IL-22, describing overlaps and differences in their cellular sources as well as their regulation, signaling, biological functions and roles during disease, with a focus on the contribution of these cytokines to the gut mucosal barrier during bacterial infection.
+Autophagy is a common strategy for cell protection; however, some viruses can in turn adopt cellular autophagy to promote viral replication.
+Zika virus (ZIKV) is the pathogen that causes Zika viral disease, and it is a mosquito-borne virus.
+However, its pathogenesis, especially the interaction between ZIKV and target cells during the early stages of infection, is still unclear.
+In this study, we demonstrate that infecting human umbilical vein endothelial cells (HUVEC) with ZIKV triggers cellular autophagy.
+We observed both an increase in the conversion of LC3-I to LC3-II and increased accumulation of fluorescent cells with LC3 dots, which are considered to be the two key indicators of autophagy.
+The ratio of LC3-II/GAPDH in each group was significantly increased at different times after ZIKV infection at different MOIs, indicating that the production of lipidated LC3-II increased.
+Moreover, both the ratio of LC3-II/GAPDH and the expression of viral NS3 protein increased with increasing time of viral infection.
+Expression profile of double fluorescent protein labelling LC3 indicated that the autophagy induced by ZIKV infection was a complete process.
+We demonstrated that either the treatment with inhibitors of autophagosomes formation or short hairpin RNA targeting the Beclin-1 gene, which is critical for the formation of autophagosomes, significantly reduced viral production.
+Taken together, our results indicate that ZIKV infection induces autophagy of HUVEC, and inhibition of ZIKV-induced autophagy restrains viral replication.
+Tetherin/BST-2/CD317 is an interferon-induced host restriction factor that can block the budding of enveloped viruses by tethering them to the cell surface.
+Many viruses use certain proteins to counteract restriction by tetherin from their natural hosts, but not from other species.
+The influenza A virus (FLUAV) has a wide range of subtypes with different host tropisms.
+Human tetherin (huTHN) has been reported to restrict only specific FLUAV strains and the viral hemagglutinin (HA) and neuraminidase (NA) genes determine the sensitivity to huTHN.
+Here, we evaluate the impact of equine tetherin (eqTHN) and huTHN on the replication of A/Sichuan/1/2009 (H1N1) and A/equine/Xinjiang/1/2007 (H3N8) strains.
+Our results show that eqTHN had higher restriction activity towards both viruses, and its shorter cytoplasmic tail contributed to that activity.
+Notably, our results indicate that four amino acids, 13T and 49L of HA and 32T and 80V of NA, were involved in blocking the restriction activity of eqTHN.
+These findings reveal interspecies restriction by eqTHN towards FLUAV, and the role of the HA and NA proteins in overcoming this restriction.
+Increased inflammation and an enhanced thrombotic milieu represent two major complications of CVD, which can culminate into an ischemic event.
+However, reperfusion strategies may result in ischemia–reperfusion injury (I/RI) secondary to various cardiovascular pathologies, including myocardial infarction and stroke, by furthering the inflammatory and thrombotic responses and delivering inflammatory mediators to the affected tissue.
+Annexin A1 (AnxA1) and its mimetic peptides are endogenous anti-inflammatory and pro-resolving mediators, known to have significant effects in resolving inflammation in a variety of disease models.
+Mounting evidence suggests that AnxA1, which interacts with the formyl peptide receptor (FPR) family, may have a significant role in mitigating I/RI associated complications.
+In this review article, we focus on how AnxA1 plays a protective role in the I/R based vascular pathologies.
+Ultraviolet (UV) radiation induces skin injury, and is associated with the development and formation of melanoma, which is a highly lethal form of skin cancer.
+Juglanin is a natural product, which is predominantly extracted from Polygonum aviculare, and is considered a functional component among its various compounds.
+Juglanin has been reported to exert marked protective effects in various diseases via the inhibition of inflammation and tumor cell growth.
+The present study aimed to explore the effects of juglanin on human skin cancer induced by UV and to reveal the underlying molecular mechanism.
+In the present study, immunohistochemical analysis, western blot analysis, RT-qPCR analysis and flow cytometry assays were mainly used in vivo and/or in vitro.
+The results indicated that in mice, UVB exposure increased susceptibility to carcinogens, and accelerated disease pathogenesis.
+Conversely, juglanin was able to ameliorate this condition via inhibition of inflammation, suppression of cell proliferation and induction of apoptosis via p38/c-Jun N-terminal kinase (JNK) blockage, nuclear factor (NF)-κB inactivation and caspase stimulation in vivo.
+In addition, in vitro, the present study demonstrated that treatment of UVB-stimulated B16F10 melanoma cells with juglanin resulted in a dose-dependent decrease in cell viability, as well as increased apoptosis via the upregulation of caspase expression and poly (ADP-ribose) polymerase cleavage.
+In addition, juglanin markedly attenuated p38/JNK signaling, inactivated the phosphoinositide 3-kinase/protein kinase B pathway and suppressed UVB-induced NF-κB activation.
+Taken together, these results indicated the possibility of applying juglanin in combination with UVB as a potential therapeutic strategy for preventing skin cancer.
+GALT is an important antigen of Actinobacillus pleuropneumoniae (APP), which was shown to provide partial protection against APP infection in a previous study in our lab.
+The main purpose of the present study is to investigate GALT induced cross-protection between different APP serotypes and elucidate key mechanisms of the immune response to GALT antigenic stimulation.
+Bioinformatic analysis demonstrated that galT is a highly conserved gene in APP, widely distributed across multiple pathogenic strains.
+Indirect enzyme-linked immunosorbent assay (ELISA) confirmed that GALT specific antibodies could not be induced by inactivated APP L20 or MS71 whole cell bacterin preparations.
+A recombinant fusion GALT protein derived from APP L20, however has proven to be an effective cross-protective antigen against APP sevorar 1 MS71 (50%, 4/8) and APP sevorar 5b L20 (75%, 6/8).
+Histopathological examinations have confirmed that recombinant GALT vaccinated animals showed less severe pathological signs in lung tissues than negative controls after APP challenge.
+Immunohistochemical (IHC) analysis indicated that the infiltration of neutrophils in the negative group is significantly increased compared with that in the normal control (P<0.001) and that in surviving animals is decreased compared to the negative group.
+After interaction with anti-GALT antibodies, survival rate of APP challenged vaccinated animals was significantly reduced (P<0.001).
+This study demonstrated that GALT is an effective cross-protective antigen, which could be used as a potential vaccine candidate against multiple APP serotypes.
+A better understanding of the seroprevalence and specificity of influenza HA stem-directed broadly neutralizing antibodies (bNAbs) in the human population could significantly inform influenza vaccine design efforts.
+Here, we utilized probes comprising headless, HA stabilized stem (SS) to determine the prevalence, binding and neutralization breadth of antibodies directed to HA stem-epitope in a cross-sectional analysis of the general population.
+Eighty-four percent of samples analyzed had specific reactivity to at least one probe, with approximately 60% of the samples reactive to H1 probes, and up to 45% reactive to each of the non-circulating subtypes.
+Thirty percent of analyzed sera had cross-reactivity to at least four of five probes and this reactivity could be blocked by competing with F10 bNAb.
+Our data demonstrate the need to use multiple HA-stem probes to assess for broadly reactive antibodies.
+BACKGROUND: Dual Use Research of Concern (DURC) constitutes a major challenge for research practice and oversight on the local, national and international level.
+The situation in Germany is shaped by two partly competing suggestions of how to regulate security-related research: The German Ethics Council, as an independent political advisory body, recommended a series of measures, including national legislation on DURC.
+Competing with that, the German National Academy of Sciences and the German Research Foundation, as two major professional bodies, presented a strategy which draws on the self-control of science and, inter alia, suggests expanding the scope of research ethics committees (RECs) to an evaluation of DURC.
+MAIN BODY: This situation is taken as an occasion to further discuss the scope and limits of professional self-control with respect to security-related research.
+The role of RECs as professional bodies of science is particularly analyzed, referring to the theoretical backgrounds of professionalism.
+Two key sociological features of professionalism – ethical orientation and professional self-control – are discussed with respect to the practice of biomedical science.
+CONCLUSION: In conclusion, it is stated that issues of biosecurity transcend the boundaries of the scientific community and that a more comprehensive strategy should be implemented encompassing both professional self-control and legal oversight.
+Unlike the traditional fluorescent proteins (FPs), FAPs do not fluoresce unless bound to their specific small-molecule fluorogens.
+When using FAPs/fluorogen probes, a washing step is not required for the removal of free probes from the cells, thus allowing rapid and specific detection of proteins in living cells with high signal-to-noise ratio.
+In this review, we describe about the discovery of FAPs, the design strategy of FAP fluorogens, the application of the FAP technology and the advances of FAP technology in protein labeling systems.
+Numerous living organisms possess biophotonic nanostructures that provide coloration and other diverse functions for survival.
+While such structures have been actively studied and replicated in the laboratory, it remains unclear whether they can be used for biomedical applications.
+Here we show a transparent photonic nanostructure inspired by the longtail glasswing (Chorinea faunus) butterfly and demonstrate its use in intraocular pressure (IOP) sensors in vivo.
+We exploit the phase separation between two immiscible polymers (poly(methyl methacrylate) and polystyrene) to form nanostructured features on top of a Si(3)N(4) substrate.
+The membrane thus formed shows good angle-independent white light transmission, strong hydrophilicity and anti-biofouling properties that prevent adhesion of proteins, bacteria, and eukaryotic cells.
+We then developed a microscale implantable IOP sensor using our photonic membrane as an optomechanical sensing element.
+Finally, we performed in vivo testing on New Zealand white rabbits and show that our device reduces the mean IOP measurement variation compared to conventional rebound tonometry without signs of inflammation.
+Zika virus (ZIKV) has received widespread attention because of its effect on the developing fetus.
+It is becoming apparent, however, that severe neurological sequelae, such as Guillian-Barrë syndrome (GBS), myelitis, encephalitis, and seizures can occur after infection of adults.
+This study demonstrates that a contemporary strain of ZIKV can widely infect astrocytes and neurons in the brain and spinal cord of adult, interferon α/β receptor knockout mice (AG129 strain) and cause progressive hindlimb paralysis, as well as severe seizure-like activity during the acute phase of disease.
+The severity of hindlimb motor deficits correlated with increased numbers of ZIKV-infected lumbosacral spinal motor neurons and decreased numbers of spinal motor neurons.
+Electrophysiological compound muscle action potential (CMAP) amplitudes in response to stimulation of the lumbosacral spinal cord were reduced when obvious motor deficits were present.
+ZIKV immunoreactivity was high, intense, and obvious in tissue sections of the brain and spinal cord.
+Infection in the brain and spinal cord was also associated with astrogliosis as well as T cell and neutrophil infiltration.
+Consequently, motor deficits in these circumstances appear to be primarily due to myelitis and possibly encephalitis as opposed to a peripheral neuropathy or a GBS-like syndrome.
+Thus, acute ZIKV infection of adult AG129 mice may be a useful model for ZIKV-induced myelitis, encephalitis, and seizure activity.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13365-017-0595-z) contains supplementary material, which is available to authorized users.
+It is estimated that 10 million deaths due to AMR will occur every year after 2050.
+International institutions such as G20, World Bank, World Health Organization (WHO), UN General Assembly, European Union, and the UK and USA governments are calling for new antibiotics.
+To underline this emergency, a list of antibiotic-resistant “priority pathogens” has been published by WHO.
+Resistance to multiple antibiotics is particularly relevant for the Gram-negative bacteria present in the list.
+The ability of these bacteria to develop mechanisms to resist treatment could be transmitted with genetic material, allowing other bacteria to become drug resistant.
+Although the search for new antimicrobial drugs remains a top priority, the pipeline for new antibiotics is not promising, and alternative solutions are needed.
+In fact, while antibiotic resistance emerges rapidly, vaccines can lead to a much longer lasting control of infections.
+New technologies, such as the high-throughput cloning of human B cells from convalescent or vaccinated people, allow for finding new protective antigens (Ags) that could not be identified with conventional technologies.
+Antibodies produced by convalescent B cell clones can be screened for their ability to bind, block, and kill bacteria, using novel high-throughput microscopy platforms that rapidly capture digital images, or by conventional technologies such as bactericidal, opsono-phagocytosis and FACS assays.
+Selected antibodies expressed by recombinant DNA techniques can be used for passive immunization in animal models and tested for protection.
+Antibodies providing the best protection can be employed to identify new Ags and then used for generating highly specific recombinant Fab fragments.
+Co-crystallization of Ags bound to Fab fragments will allow us to determine the structure and characteristics of new Ags.
+This structure-based Ag design will bring to a new generation of vaccines able to target previously elusive infections, thereby offering an effective solution to the problem of AMR.
+Systemic amyloid A (AA) amyloidosis is a major cause of morbidity and mortality among captive cheetahs.
+The self-aggregating AA protein responsible for this disease is a byproduct of serum amyloid A (SAA) protein degradation.
+Transcriptional induction of the SAA1 gene is dependent on both C/EBPβ and NF-κB cis-acting elements within the promoter region.
+In cheetahs, 2 alleles exist for a single guanine nucleotide deletion in the putative NF-κB binding site.
+The results show that the SAA1A(−97delG) allele is associated with decreased SAA protein concentrations in the serum of captive cheetahs (n = 58), suggesting genetic differences at this locus may be affecting AA amyloidosis prevalence.
+However, there was no significant difference in the frequency of the SAA1A(−97delG) allele between individuals confirmed AA amyloidosis positive versus AA amyloidosis negative at the time of necropsy (n = 48).
+Thus, even though there is evidence that having more copies of the SAA1A(−97delG) allele results in a potentially protective decrease in serum concentrations of SAA protein in captive cheetahs, genotype is not associated with this disease within the North American population.
+These results suggest that other factors are playing a more significant role in the pathogenesis of AA amyloidosis among captive cheetahs.
+Determining the fitness of viral genotypes has become a standard practice in virology as it is essential to evaluate their evolutionary potential.
+Darwinian fitness, defined as the advantage of a given genotype with respect to a reference one, is a complex property that captures, in a single figure, differences in performance at every stage of viral infection.
+To what extent does viral fitness result from specific molecular interactions with host factors and regulatory networks during infection?
+Here, we compared the transcriptomes of tobacco plants infected with seven genotypes of tobacco etch potyvirus that differ in fitness.
+We found that the larger the fitness differences among genotypes, the more dissimilar the transcriptomic profiles are.
+Consistently, two different mutations, one in the viral RNA polymerase and another in the viral suppressor of RNA silencing, resulted in significantly similar gene expression profiles.
+Moreover, we identified host genes whose expression showed a significant correlation, positive or negative, with the virus' fitness.
+Differentially expressed genes which were positively correlated with viral fitness activate hormone- and RNA silencing-mediated pathways of plant defense.
+In contrast, those that were negatively correlated with fitness affect metabolism, reducing growth, and development.
+Overall, these results reveal the high information content of viral fitness and suggest its potential use to predict differences in genomic profiles of infected hosts.
+The extent and biological significance of viral presence/infection in actual tumor samples is generally unknown but could be measured using human transcriptome (RNA-seq) data from tumor samples.
+We present an open source bioinformatics pipeline viGEN, which allows for not only the detection and quantification of viral RNA, but also variants in the viral transcripts.
+The pipeline includes 4 major modules: The first module aligns and filter out human RNA sequences; the second module maps and count (remaining un-aligned) reads against reference genomes of all known and sequenced human viruses; the third module quantifies read counts at the individual viral-gene level thus allowing for downstream differential expression analysis of viral genes between case and controls groups.
+To the best of our knowledge, there are no publicly available pipelines or packages that would provide this type of complete analysis in one open source package.
+We first demonstrate the working of our pipeline on a large public dataset, the TCGA cervical cancer cohort.
+In the second case study, we performed an in-depth analysis on a small focused study of TCGA liver cancer patients.
+This allowed us to find differentially expressed viral-transcripts and viral-variants between the groups of patients, and connect them to clinical outcome.
+From our analyses, we show that we were able to successfully detect the human papilloma virus among the TCGA cervical cancer patients.
+We were also able to quantify viral-transcripts and extract viral-variants using the liver cancer dataset.
+The results presented corresponded with published literature in terms of rate of detection, and impact of several known variants of HBV genome.
+This pipeline is generalizable, and can be used to provide novel biological insights into microbial infections in complex diseases and tumorigeneses.
+Our viral pipeline could be used in conjunction with additional type of immuno-oncology analysis based on RNA-seq data of host RNA for cancer immunology applications.
+A real-time PCR (qPCR) assay targeting on invA and pagC genes was developed and validated for the detection and quantification of Salmonella enterica strains (Bai et al., 2018) [1].
+A host gene, normally an endogenous housekeeping gene (Beer-Davidson et al., 2018; Poon et al., 2004) [2,3], or an irrelevant exogenous gene (Cheng et al., 2015; Sedlak et al., 2014) [4,5] has been widely used as an internal control to monitor nucleic acid extraction efficiencies and potential PCR inhibitions in PCR-based detection assays.
+An endogenous internal control designed based on the 18S rRNA gene was used in the above-mentioned qPCR assay.
+This 18S rRNA internal control amplifies the target gene in multiple species including bovine, swine, ovine, caprine and cervine.
+Data was generated by the duplex qPCR assay on 138 enriched cattle lymph node samples without the internal control, and compared with data on the same samples tested by the triplex qPCR assay that has the 18S rRNA gene as internal control.
+Threshold cycle (Ct) data for the duplex and the triplex qPCR on the 138 samples were similar, and are presented in this brief report.
+BACKGROUND: Synthetic virology is an important multidisciplinary scientific field, with emerging applications in biotechnology and medicine, aiming at developing methods to generate and engineer synthetic viruses.
+In particular, many of the RNA viruses, including among others the Dengue and Zika, are widespread pathogens of significant importance to human health.
+The ability to design and synthesize such viruses may contribute to exploring novel approaches for developing vaccines and virus based therapies.
+RESULTS: Here we develop a full multidisciplinary pipeline for generation and analysis of synthetic RNA viruses and specifically apply it to Dengue virus serotype 2 (DENV-2).
+The major steps of the pipeline include comparative genomics of endogenous and synthetic viral strains.
+Specifically, we show that although the synthetic DENV-2 viruses were found to have lower nucleotide variability, their phenotype, as reflected in the study of the AG129 mouse model morbidity, RNA levels, and neutralization antibodies, is similar or even more pathogenic in comparison to the wildtype master strain.
+Additionally, the highly variable positions, identified in the analyzed DENV-2 population, were found to overlap with less conserved homologous positions in Zika virus and other Dengue serotypes.
+These results may suggest that synthetic DENV-2 could enhance virulence if the correct sequence is selected.
+CONCLUSIONS: The approach reported in this study can be used to generate and analyze synthetic RNA viruses both on genotypic and on phenotypic level.
+It could be applied for understanding the functionality and the fitness effects of any set of mutations in viral RNA and for editing RNA viruses for various target applications.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12859-018-2132-3) contains supplementary material, which is available to authorized users.
+BACKGROUND: Angiotensin converting enzyme 2 (ACE2) is an endogenous regulator of the renin angiotensin system.
+Increased circulating ACE2 predicts adverse outcomes in patients with heart failure (HF), but it is unknown if elevated plasma ACE2 activity predicts major adverse cardiovascular events (MACE) in patients with obstructive coronary artery disease (CAD).
+METHODS: We prospectively recruited patients with obstructive CAD (defined as ≥50% stenosis of the left main coronary artery and/or ≥70% stenosis in ≥ 1 other major epicardial vessel on invasive coronary angiography) and measured plasma ACE2 activity.
+Patients were followed up to determine if circulating ACE2 activity levels predicted the primary endpoint of MACE (cardiovascular mortality, HF or myocardial infarction).
+Over a median follow up of 10.5 years [9.6–10.8years], MACE occurred in 46% of patients (36 events).
+On Kaplan-Meier analysis, above-median plasma ACE2 activity was associated with MACE (log-rank test, p = 0.035) and HF hospitalisation (p = 0.01).
+After Cox multivariable adjustment, log ACE2 activity remained an independent predictor of MACE (hazard ratio (HR) 2.4, 95% confidence interval (CI) 1.24–4.72, p = 0.009) and HF hospitalisation (HR: 4.03, 95% CI: 1.42–11.5, p = 0.009).
+CONCLUSIONS: Plasma ACE2 activity independently increased the hazard of adverse long-term cardiovascular outcomes in patients with obstructive CAD.
+Because so few viruses in the family Barnaviridae have been reported, we searched for more of them in public sequence databases.
+Here, we report the complete coding sequence of Colobanthus quitensis associated barnavirus 1, mined from a transcriptome of the Antarctic pearlwort Colobanthus quitensis.
+The 4.2-kb plus-strand sequence of this virus encompasses four main open reading frames (ORFs), as expected for barnaviruses, including ORFs for a protease-containing polyprotein, an RNA-dependent RNA polymerase whose translation appears to rely on − 1 ribosomal frameshifting, and a capsid protein that is likely to be translated from a subgenomic RNA.
+The possible derivation of this virus from a fungus associated with C. quitensis is discussed.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00705-018-3794-x) contains supplementary material, which is available to authorized users.
+Angiopoietins, vascular-specific growth factors, are linked to endothelial barrier dysfunction, and elevated Angiopoietin-2 (ANG2) levels are associated with poor outcome of ALI patients.
+Specialized immune cells, referred to as ‘TIE2-expressing monocytes and macrophages’ (TEM), were shown to specifically respond to ANG2 binding.
+Thus, our aim was to assess the dynamics of TEMs in a murine model of ALI.
+RESULTS: Intratracheal instillation of LPS induced a robust pulmonary pro-inflammatory response with endothelial barrier dysfunction and significantly enhanced ANG2 expression.
+The percentage number of TEMs, assessed by FACS analysis, was more than trebled compared to controls, with TEM count in lungs reaching more than 40% of all macrophages.
+Incubation of the monocytic cell line THP-1 with LPS or TNF-α resulted in a dose-dependent, significant upregulation of TIE2, suggesting that not recruitment from extra-pulmonary compartments but TIE2 upregulation in resident macrophages accounts for increased lung TEM frequencies.
+CONCLUSIONS: For the first time, our data provide evidence that the activity of TEMs changes at sites of acute inflammation.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12950-018-0188-5) contains supplementary material, which is available to authorized users.
+Model-based epidemiological assessment is useful to support decision-making at the beginning of an emerging Aedes-transmitted outbreak.
+However, early forecasts are generally unreliable as little information is available in the first few incidence data points.
+The approach was applied to the 2015–2017 Zika virus epidemics in three islands of the French West Indies, with historical data including other Aedes-transmitted diseases (chikungunya and Zika) in the same and other locations.
+Hierarchical models were used to build informative a priori distributions on the reproduction ratio and the reporting rates.
+The accuracy and sharpness of forecasts improved substantially when these a priori distributions were used in models for prediction.
+For example, early forecasts of final epidemic size obtained without historical information were 3.3 times too high on average (range: 0.2 to 5.8) with respect to the eventual size, but were far closer (1.1 times the real value on average, range: 0.4 to 1.5) using information on past CHIKV epidemics in the same places.
+Likewise, the 97.5% upper bound for maximal incidence was 15.3 times (range: 2.0 to 63.1) the actual peak incidence, and became much sharper at 2.4 times (range: 1.3 to 3.9) the actual peak incidence with informative a priori distributions.
+Improvements were more limited for the date of peak incidence and the total duration of the epidemic.
+The framework can adapt to all forecasting models at the early stages of emerging Aedes-transmitted outbreaks.
+BACKGROUND: Severe infections are common complications of immunosuppressive treatment for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) with renal involvement.
+We investigated the clinical characteristics and risk factors of severe infection in Chinese patients with AAV after immunosuppressive therapy.
+METHODS: A total of 248 patients with a new diagnosis of ANCA-associated vasculitis were included in this study.
+The incidence, time, site, and risk factors of severe infection by the induction therapies were analysed.
+Multivariate Cox proportional hazards models were used to calculate hazard ratios (HRs) with 95% confidence intervals (CI).
+RESULTS: A total of 103 episodes of severe infection were identified in 86 (34.7%, 86/248) patients during a median follow-up of 15 months.
+The incidence of infection during induction therapy was 38.5% for corticosteroids (CS), 39.0% for CS+ intravenous cyclophosphamide (IV-CYC), 33.8% for CS+ mycophenolate mofetil and 22.5% for CS + tripterygium glycosides, 76 (73.8%) infection episodes occurred within 6 months, while 66 (64.1%) occurred within 3 months.
+Pneumonia (71.8%, 74/103) was the most frequent type of infection, and the main pathogenic spectrum included bacteria (78.6%), fungi (12.6%), and viruses (8.7%).
+The risk factors associated with infection were age at the time of diagnosis (HR = 1.003, 95% CI = 1.000–1.006), smoking (HR = 2.338, 95% CI = 1.236–4.424), baseline secrum creatinine (SCr) ≥5.74 mg/dl (HR = 2.153, 95% CI = 1.323–3.502), CD4(+) T cell< 281 μl (HR = 1.813, 95% CI = 1.133–2.900), and intravenous cyclophosphamide regimen (HR = 1.951, 95% CI =1.520–2.740).
+Age at the time of diagnosis, smoking, baseline SCr ≥5.74 mg/dl, CD4(+) T cell< 281 μl, and IV-CYC therapy were identified as risk factors for infection.
+The aim of the present study was to investigate long-term outcomes of the offspring in a lipopolysaccharide (LPS)-induced maternal immune activation (MIA) model and the effect of maternal molecular hydrogen (H(2)) administration.
+We have previously demonstrated in the MIA mouse model that maternal administration of H(2) attenuates oxidative damage and neuroinflammation, including induced pro-inflammatory cytokines and microglial activation, in the fetal brain.
+Short-term memory, sociability and social novelty, and sensorimotor gating were evaluated using the Y-maze, three-chamber, and prepulse inhibition (PPI) tests, respectively, at postnatal 3 or 4 weeks.
+The number of neurons and oligodendrocytes was also analyzed at postnatal 5 weeks by immunohistochemical analysis.
+Offspring of the LPS-exposed dams showed deficits in short-term memory and social interaction, following neuronal and oligodendrocytic loss in the amygdala and cortex.
+Moreover, we evaluated the effect of H(2) on LPS-induced astrocytic activation, both in vivo and in vitro.
+The number of activated astrocytes with hypertrophic morphology was increased in LPS-exposed offspring, but decreased in the offspring of H(2)-administered dams.
+Overall, these findings indicate that maternal H(2) administration exerts neuroprotective effects and ameliorates MIA-induced neurodevelopmental deficits of offspring later in life.
+The recent epidemic in the Americas caused by Zika virus (ZIKV), Asian lineage, spurred the research towards a better understanding of how ZIKV infection affects the host immune response.
+The aim of this study was to evaluate the effects of Asian and East African ZIKV strain infection on the induction of IFN and proinflammatory and Th2 cytokines in human PBMC.
+We reported a slight modulation of type II IFN in PBMC exposed to Asian strain, but not to African strain, and a complete lack of type I and III IFN induction by both strains, suggesting the ability of ZIKV to evade the IFN system not only inhibiting the antiviral IFN response but also IFN production.
+Moreover, we highlighted a polyfunctional immune activation only in PBMC exposed to Asian strain, due to the induction of an inflammatory profile (IL-6, IL-8) and of a Th9 (IL-9) response.
+Overall, our data show a different ability of the ZIKV Asian strain, with respect to the African strain, to activate host immune response that may have pathogenetic implications for virus spread in vivo, including mother-to-child transmission and induction of severe fetal complications, as birth defects and neurological disorders.
+BACKGROUND: The emerging zoonotic paramyxovirus Nipah virus (NiV) causes severe respiratory and neurological disease in humans, with high fatality rates.
+Nipah virus can be transmitted via person-to-person contact, posing a high risk for epidemic outbreaks.
+METHODS: We engineered new antiviral lipopeptides and analyzed in vitro fusion inhibition to identify an optimal candidate for prophylaxis of NiV infection in the lower respiratory tract, and we assessed antiviral efficiency in 2 different animal models.
+RESULTS: We show that lethal NiV infection can be prevented with lipopeptides delivered via the respiratory route in both hamsters and nonhuman primates.
+By targeting retention of peptides for NiV prophylaxis in the respiratory tract, we avoid its systemic delivery in individuals who need only prevention, and thus we increase the safety of treatment and enhance utility of the intervention.
+CONCLUSIONS: The experiments provide a proof of concept for the use of antifusion lipopeptides for prophylaxis of lethal NiV.
+These results advance the goal of rational development of potent lipopeptide inhibitors with desirable pharmacokinetic and biodistribution properties and a safe effective delivery method to target NiV and other pathogenic viruses.
+Avian influenza viruses, including highly pathogenic strains, pose severe economic, animal and public health concerns.
+We implemented live bird market surveillance in Bangladesh to identify the subtypes of avian influenza A viruses in domestic waterfowl and market environments.
+We collected waterfowl samples monthly from 4 rural sites from 2007 to 2012 and environmental samples from 4 rural and 16 urban sites from 2009 to 2012.
+Samples were tested through real-time RT-PCR, virus culture, and sequencing to detect and characterize avian influenza A viruses.
+Among 4,308 waterfowl tested, 191 (4.4%) were positive for avian influenza A virus, including 74 (1.9%) avian influenza A/H5 subtype.
+The majority (99%, n = 73) of the influenza A/H5-positive samples were from healthy appearing waterfowl.
+Multiple subtypes, including H1N1, H1N3, H3N2, H3N6, H3N8, H4N1, H4N2, H4N6, H5N1 (clades 2.2.2, 2.3.2.1a, 2.3.4.2), H5N2, H6N1, H7N9, H9N2, H11N2 and H11N3, H11N6 were detected in waterfowl and environmental samples.
+Avian influenza viruses, including H5N1 and H9N2 subtypes were also identified in backyard and small-scale raised poultry.
+Live bird markets could be high-risk sites for harboring the viruses and have the potential to infect naive birds and humans exposed to them.
+Astroviruses (AstVs) are responsible for infection of a large diversity of mammalian and avian species, including bats, aquatic birds, livestock and humans.
+We investigated AstVs circulation in bats in Mozambique and Mayotte, a small island in the Comoros Archipelago located between east Africa and Madagascar.
+Biological material was collected from 338 bats and tested for the presence of the AstV RNA-dependent RNA-polymerase gene with a pan-AstV semi-nested polymerase chain reaction assay.
+None of the 79 samples obtained from Mayotte bats (Pteropus seychellensis comorensis and Chaerephon pusillus) tested positive; however, 20.1% of bats sampled in Mozambique shed AstVs at the time of sampling and significant interspecific variation in the proportion of positive bats was detected.
+Many AstVs sequences obtained from a given bat species clustered in different phylogenetic lineages, while others seem to reflect some level of host-virus association, but also with AstVs previously reported from Malagasy bats.
+Our findings support active circulation of a large diversity of AstVs in bats in the western Indian Ocean islands, including the southeastern African coast, and highlight the need for more detailed assessment of its risk of zoonotic transmission to human populations.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12985-018-1011-x) contains supplementary material, which is available to authorized users.
+This observational study examined the association of temperature, humidity and rainfall with six common climate-sensitive infectious diseases in adults (malaria, diarrheal disease, enteric fever, encephalitis, pneumonia and bacterial meningitis) in northeastern Bangladesh.
+Subjects admitted to the adult medicine ward of a tertiary referral hospital in Sylhet, Bangladesh from 2008 to 2012 with a diagnosis of one of the six chosen climate-sensitive infectious diseases were enrolled in the study.
+Disease incidence was then analyzed against mean temperature, humidity and average rainfall for the Sylhet region.
+All six diseases showed highly significant (p = 0.01) rises in incidence between the study years 2008 (540 cases) and 2012 (1330 cases), compared with no significant rise in overall all-cause hospital admissions in the same period (p = 0.19).
+The highest number of malaria (135), diarrhea (266) and pneumonia (371) cases occurred during the rainy season.
+On the other hand, the maximum number of enteric fever (408), encephalitis (183) and meningitis (151) cases occurred during autumn, which follows the rainy season.
+A positive (P = 0.01) correlation was observed between increased temperature and the incidence of malaria, enteric fever and diarrhea, and a negative correlation with encephalitis, meningitis and pneumonia.
+Higher humidity correlated (P = 0.01) with a higher number of cases of malaria and diarrhea, but inversely correlated with meningitis and encephalitis.
+The findings support a relationship between weather patterns and disease incidence, and provide essential baseline data for future large prospective studies.
+The International Classification of Diseases (ICD) relies on clinical features and lags behind the current understanding of the molecular specificity of disease pathobiology, necessitating approaches that incorporate growing biomedical data for classifying diseases to meet the needs of precision medicine.
+Our analysis revealed that the heterogeneous molecular diversity of disease chapters and the blurred boundary between disease categories in ICD should be further investigated.
+Here, we propose a new classification of diseases (NCD) by developing an algorithm that predicts the additional categories of a disease by integrating multiple networks consisting of disease phenotypes and their molecular profiles.
+With statistical validations from phenotype-genotype associations and interactome networks, we demonstrate that NCD improves disease specificity owing to its overlapping categories and polyhierarchical structure.
+Furthermore, NCD captures the molecular diversity of diseases and defines clearer boundaries in terms of both phenotypic similarity and molecular associations, establishing a rational strategy to reform disease taxonomy.
+To identify the incidence, risk factors and impact on long-term survival of invasive pulmonary aspergillosis (IPA) and Aspergillus colonisation in patients receiving vv-extracorporeal membrane oxygenation (ECMO).
+A retrospective evaluation was performed of patients receiving vv-ECMO at a tertiary hospital in Manchester (UK) between January 2012 and December 2016.
+Cases were classified as proven IPA, putative IPA or Aspergillus colonisation according to a validated clinical algorithm.
+One hundred thirty-four patients were supported with vv-ECMO, median age of 45.5 years (range 16.4–73.4).
+Immunosuppression and influenza A infection were significantly associated with developing IPA in a logistic regression model.
+Patients with putative IPA and colonised patients had a 6-month mortality rate of 80 and 11%, respectively.
+IPA, but not Aspergillus colonisation, is associated with high long-term mortality in patients supported with vv-ECMO.
+The genome of Mycobacterium tuberculosis, the causal organism of tuberculosis (TB), encodes a unique protein family known as the PE/PPE/PGRS family, present exclusively in the genus Mycobacterium and nowhere else in the living kingdom, with largely unexplored functions.
+We describe the functional significance of the PGRS domain of Rv0297, a member of this family.
+In silico analyses revealed the presence of intrinsically disordered stretches and putative endoplasmic reticulum (ER) localization signals in the PGRS domain of Rv0297 (Rv0297PGRS).
+The PGRS domain aids in ER localization, which was shown by infecting macrophage cells with M. tuberculosis and by overexpressing the protein by transfection in macrophage cells followed by activation of the unfolded protein response, as evident from increased expression of GRP78/GRP94 and CHOP/ATF4, leading to disruption of intracellular Ca(2+) homeostasis and increased nitric oxide (NO) and reactive oxygen species (ROS) production.
+The consequent activation of the effector caspase-8 resulted in apoptosis of macrophages, which was Toll-like receptor 4 (TLR4) dependent.
+These results implicate a hitherto-unknown role of the PGRS domain of the PE_PGRS protein family in ER stress-mediated cell death through TLR4.
+Since this protein is already known to be present at later stages of infection in human granulomas it points to the possibility of it being employed by M. tuberculosis for its dissemination via an apoptotic mechanism.
+BACKGROUND: Sepsis morbidity and mortality are aggravated by acute lung injury (ALI) or acute respiratory distress syndrome (ARDS).
+Mouse B-1a cells are a phenotypically and functionally unique sub-population of B cells, providing immediate protection against infection by releasing natural antibodies and immunomodulatory molecules.
+After 20 h of CLP, lungs were harvested and assessed by PCR and ELISA for pro-inflammatory cytokines (IL-6, IL-1β) and chemokine (MIP-2) expression, by histology for injury, by TUNEL and cleaved caspase-3 for apoptosis, and by myeloperoxidase (MPO) assay for neutrophil infiltration.
+RESULTS: We found that septic mice adoptively transferred with B-1a cells significantly decreased the mRNA and protein levels of IL-6, IL-1β and MIP-2 in the lungs compared to PBS-treated mice.
+Mice treated with B-1a cells showed dramatic improvement in lung injury compared to PBS-treated mice after sepsis.
+We found apoptosis in the lungs was significantly inhibited in B-1a cell injected mice compared to PBS-treated mice after sepsis.
+B-1a cell treatment significantly down-regulated MPO levels in the lungs compared to PBS-treated mice in sepsis.
+The protective outcomes of B-1a cells in ALI was further confirmed by using B-1a cell deficient CD19(−/−) mice, which showed significant increase in the lung injury scores following sepsis as compared to WT mice.
+CONCLUSIONS: Our results demonstrate a novel therapeutic potential of B-1a cells to treat sepsis-induced ALI.
+BACKGROUND: Experiences during a stay in the intensive care unit (ICU), including pain, delirium, physical deterioration, and the critical illness itself, may all influence survivors’ health-related quality of life (HRQOL).
+However, few studies have examined the influence of social support, comorbidity, and pain interference on ICU survivors’ HRQOL.
+OBJECTIVES: To investigate possible associations between social support, number of comorbidities, and pain interference on HRQOL in ICU survivors.
+METHODS: ICU survivors responded to a survey 3 months (n = 118) and 1 year (n = 89) after ICU discharge.
+HRQOL was measured using the Short Form Health Survey-12 (v1), social support using the revised Social Provision Scale, pain interference using the Brief Pain Inventory–Short Form, and comorbidities using the Self-Administered Comorbidity Questionnaire.
+RESULTS: Physical and mental HRQOL were reduced at both 3 months and 1 year in ICU survivors compared with the general population.
+This reduction was more pronounced at 3 months for physical HRQOL, while a small reduction in mental HRQOL was not clinically relevant.
+Social support was statistical significantly positively associated with mental HRQOL at 3 months, while number of comorbidities was statistical significantly associated with a reduction in physical HRQOL at 3 months and 1 year and mental HRQOL at 1 year.
+Lastly pain interference was significantly associated with a reduction in physical HRQOL at 3 months and 1 year.
+Social support was positively associated with mental HRQOL, while number of comorbidities, and pain interference were all significantly associated with a reduction in HRQOL.
+An efficient preparative procedure for the separation of four antibacterial diterpenes from a Salvia prattii crude diterpenes-rich sample was developed.
+Firstly, the XION hydrophilic stationary phase was chosen to separate the antibacterial crude diterpenes-rich sample (18.0 g) into three fractions with a recovery of 46.1%.
+Then, the antibacterial fractions I (200 mg), II (200 mg), and III (150 g) were separated by the Megress C18 preparative column, and compounds tanshinone IIA (80.0 mg), salvinolone (62.0 mg), cryptotanshinone (70.0 mg), and ferruginol (68.0 mg) were produced with purities greater than 98%.
+The procedure achieved large-scale preparation of the four diterpenes with high purity, and it could act as a reference for the efficient preparation of active diterpenes from other plant extracts.
+RNA-protein interactions (RPIs) have critical roles in numerous fundamental biological processes, such as post-transcriptional gene regulation, viral assembly, cellular defence and protein synthesis.
+As the number of available RNA-protein binding experimental data has increased rapidly due to high-throughput sequencing methods, it is now possible to measure and understand RNA-protein interactions by computational methods.
+In this study, we integrate a sequence-based derived kernel with regularized least squares to perform prediction.
+The derived kernel exploits the contextual information around an amino acid or a nucleic acid as well as the repetitive conserved motif information.
+We propose a novel machine learning method, called RPiRLS to predict the interaction between any RNA and protein of known sequences.
+For the RPiRLS classifier, each protein sequence comprises up to 20 diverse amino acids but for the RPiRLS-7G classifier, each protein sequence is represented by using 7-letter reduced alphabets based on their physiochemical properties.
+We evaluated both methods on a number of benchmark data sets and compared their performances with two newly developed and state-of-the-art methods, RPI-Pred and IPMiner.
+On the non-redundant benchmark test sets extracted from the PRIDB, the RPiRLS method outperformed RPI-Pred and IPMiner in terms of accuracy, specificity and sensitivity.
+Advances in next-generation sequencing (NGS) have provided the opportunity for development of a comprehensive method to identify infectious agents.
+This study describes the use of target-specific primers for PCR-mediated amplification with the NGS technology in which pathogen genomic regions of interest are enriched and selectively sequenced from clinical samples.
+In the study, 198 primers were designed to target 43 common bovine and small-ruminant bacterial, fungal, viral, and parasitic pathogens, and a bioinformatics tool was specifically constructed for the detection of targeted pathogens.
+The primers were confirmed to detect the intended pathogens by testing reference strains and isolates.
+The method was then validated using 60 clinical samples (including tissues, feces, and milk) that were also tested with other routine diagnostic techniques.
+The detection limits of the targeted NGS method were evaluated using 10 representative pathogens that were also tested by quantitative PCR (qPCR), and the NGS method was able to detect the organisms from samples with qPCR threshold cycle (C(T)) values in the 30s.
+The method was successful for the detection of multiple pathogens in the clinical samples, including some additional pathogens missed by the routine techniques because the specific tests needed for the particular organisms were not performed.
+The results demonstrate the feasibility of the approach and indicate that it is possible to incorporate NGS as a diagnostic tool in a cost-effective manner into a veterinary diagnostic laboratory.
+In 2016 the World Health Organization identified 21 countries that could eliminate malaria by 2020.
+Here we develop methods that estimate individual reproduction numbers and their variation through time and space.
+Individual reproduction numbers, R(c), describe the state of transmission at a point in time and differ from mean reproduction numbers, which are averages of the number of people infected by a typical case.
+We assess elimination progress in El Salvador using data for confirmed cases of malaria from 2010 to 2016.
+Our results demonstrate that whilst the average number of secondary malaria cases was below one (0.61, 95% CI 0.55–0.65), individual reproduction numbers often exceeded one.
+However we also show that if importation is maintained at the same rate, the country may not achieve malaria elimination by 2020.
+The effect of long-distance transport on cattle health has not frequently been studied in Bangladesh.
+The current study investigated the health conditions, and the extent and pattern of cattle injuries, along with haemato-biochemical and hormonal changes, before and after long-distance transportation (≈648 km) from the market of origin to the market of destination.
+A total of 100 adult cattle were selected at the Benapole live cattle market, Bangladesh, for physical examination before and after transportation.
+Fifty of these cattle were randomly selected for additional haemato-biochemical evaluation just before the start of transportation (0 hour), immediately after arrival at the destination market (13.8±0.9 hours after the start of transportation) and 24 hours after arrival at the destination market.
+Animals were fasting in the vehicle during transportation and provided only with paddy straw and water before sale at the destination market.
+Before and after transportation, the overall frequency of cattle injuries varied significantly (26 per cent before v 47 per cent after transportation; P<0.001).
+Cattle health conditions diverged significantly (such as nasal discharge: 15 per cent v 28 per cent; P=0.03).
+The values of haemoglobin (P=0.01), total erythrocyte count (P=0.001), total leucocyte count (P<0.001), lymphocyte (P=0.005), neutrophil (P=0.01) and eosinophil (P=0.01) varied significantly.
+The values of serum total protein (P=0.006), creatine kinase (P<0.001), triglyceride (P=0.04), calcium (P=0.003), phosphorus (P<0.001) and alkaline phosphatase (P=0.04) significantly differed.
+Clinicians are encouraged to avoid FO; however, strategies to avoid FO are not well-described in pediatrics.
+Our aim was to implement a bundle strategy to prevent FO in children with sepsis and pARDS and to compare the outcomes with a historical cohort.
+METHODS: A quality improvement initiative, known as preemptive fluid strategy (PFS) was implemented to prevent early FO, in a 12-bed general PICU.
+For comparison, data from a historical cohort from 2015, with the same inclusion and exclusion criteria, was retrospectively reviewed.
+The PFS bundle consisted of 1. maintenance of intravenous fluids (MIVF) at 50% of requirements; 2. drug volume reduction; 3. dynamic monitoring of preload markers to determine the need for fluid bolus administration; 4. early use of diuretics; and 5. early initiation of enteral feeds.
+PFO was defined as the highest FO during the first 72 h. FO was calculated as (cumulative fluid input – cumulative output)/kg*100.
+Fluid input/output were registered every 12 h for 72 h. RESULTS: Thirty-seven patients were included in the PFS group (54% male, 6 mo (IQR 2,11)) and 39 with SFS (64%male, 3 mo (IQR1,7)).
+FO was lower in PFS compared to CFS as early as 12 h after admission [2.4(1.4,3.7) v/s 4.3(1.5,5.5), p < 0.01] and maintained during the study.
+PRBC requirements were lower during the first 24 h in the PFS (5%) compared to SFS (28%, p < 0.05).
+MV duration was 81 h (58,98) in PFS and 118 h (85154) in SFS(p < 0.05).
+PICU LOS in PFS was 5 (4, 7) and in SFS was 8 (6, 10) days.
+CONCLUSION: Implementation of a bundle to prevent FO in children on MV with pARDS and sepsis resulted in less PFO.
+Future studies are needed to address if PFS might have a positive impact on health outcomes.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12887-018-1188-6) contains supplementary material, which is available to authorized users.
+Social support is a known protective factor against the negative psychological impact of natural disasters.
+Most past research has examined how the effects of exposure to traumatic events influences whether someone meets diagnostic criteria for depression and posttraumatic stress disorder (PTSD); it has also suggested sequelae of disaster exposure depends on whether survivors are displaced from their homes.
+To capture the full range of the psychological impact of natural disasters, we examined the buffering effects of social support on depressive symptoms and cluster‐specific PTSD symptoms, with consideration of displacement status.
+In a survey conducted 18 to 24 months after Hurricane Katrina, 810 adults exposed to the disaster reported the number of Katrina‐related traumatic events experienced, perceived social support 2 months post‐Katrina, and cluster‐specific PTSD and depressive symptoms experienced since Katrina.
+Analyses assessed the moderating effects of social support and displacement and the conditional effects of displacement status.
+Social support significantly buffered the negative effect of Katrina‐related traumatic events on depressive symptoms, B = −0.10, p = .001, and avoidance and arousal PTSD symptoms, B = −0.02, p = .035 and B = −0.02, p = .042, respectively.
+Conditional effects indicated social support buffered development of depressive symptoms across all residents; however, the moderating effects of support on avoidance and arousal symptoms only appeared significant for nondisplaced residents.
+Results highlight the protective effects of disaster‐related social support among nondisplaced individuals, and suggest displaced individuals may require more formal supports for PTSD symptom reduction following a natural disaster.
+Biomolecular mass spectrometry has matured strongly over the past decades and has now reached a stage where it can provide deep insights into the structure and composition of large cellular assemblies.
+Here, we describe a three-tiered hybrid mass spectrometry approach that enables the dissection of macromolecular complexes in order to complement structural studies.
+To demonstrate the capabilities of the approach, we investigate ribosomes, large ribonucleoprotein particles consisting of a multitude of protein and RNA subunits.
+We identify sites of sequence processing, protein post-translational modifications, and the assembly and stoichiometry of individual ribosomal proteins in four distinct ribosomal particles of bacterial, plant and human origin.
+Amongst others, we report extensive cysteine methylation in the zinc finger domain of the human S27 protein, the heptameric stoichiometry of the chloroplastic stalk complex, the heterogeneous composition of human 40S ribosomal subunits and their association to the CrPV, and HCV internal ribosome entry site RNAs.
+Previous transcriptomic analyses suggested that the 1918 influenza A virus (IAV1918), one of the most devastating pandemic viruses of the 20th century, induces a dysfunctional cytokine storm and affects other innate immune response patterns.
+Because all viruses are obligate parasites that require host cells for replication, we globally assessed how IAV1918 induces host protein dysregulation.
+Selected proteins were validated by immunoblotting and phosphorylation levels of members of the PI3K/AKT/mTOR pathway were assessed.
+Proteins mapped to amino sugar metabolism, purine metabolism, steroid biosynthesis, transmembrane receptors, phosphatases and transcription regulation.
+Immunoblotting demonstrated that IAV1918 induced a slight up-regulation of the lamin B receptor whereas all other tested virus strains induced a significant down-regulation.
+IAV1918 also strongly induced Rab5b expression whereas all other tested viruses induced minor up-regulation or down-regulation.
+IAV1918 showed early reduced phosphorylation of PI3K/AKT/mTOR pathway members and was especially sensitive to rapamycin.
+These results suggest the 1918 strain requires mTORC1 activity in early replication events, and may explain the unique pathogenicity of this virus.
+Internet search query data have been identified as a valuable source for the detection of emerging influenza epidemics.
+However, the selection of the search queries and the adoption of prediction methods are crucial challenges when it comes to improving predictions.
+The purpose of this study was to explore the application of the Support Vector Machine (SVM) regression model in merging search engine query data and traditional influenza data.
+METHODS: The official monthly reported number of influenza cases in Liaoning province in China was acquired from the China National Scientific Data Center for Public Health from January 2011 to December 2015.
+Based on Baidu Index, a publicly available search engine database, search queries potentially related to influenza over the corresponding period were identified.
+An SVM regression model was built to be used for predictions, and the choice of three parameters (C, γ, ε) in the SVM regression model was determined by leave-one-out cross-validation (LOOCV) during the model construction process.
+The model’s performance was evaluated by the evaluation metrics including Root Mean Square Error, Root Mean Square Percentage Error and Mean Absolute Percentage Error.
+RESULTS: In total, 17 search queries related to influenza were generated through the initial query selection approach and were adopted to construct the SVM regression model, including nine queries in the same month, three queries at a lag of one month, one query at a lag of two months and four queries at a lag of three months.
+The SVM model performed well when with the parameters (C = 2, γ = 0.005, ɛ = 0.0001), based on the ensemble data integrating the influenza surveillance data and Baidu search query data.
+CONCLUSIONS: The results demonstrated the feasibility of using internet search engine query data as the complementary data source for influenza surveillance and the efficiency of SVM regression model in tracking the influenza epidemics in Liaoning.
+BACKGROUND: Triclosan and triclocarban (TCs) are broad-spectrum antimicrobials that, until recently, were found in a wide variety of household and personal wash products.
+OBJECTIVES: To determine whether use of TC-containing wash products reduces incidence of infection in children less than one year of age.
+METHODS: Starting in 2011, we nested a randomized intervention of wash products with and without TCs within a multiethnic birth cohort.
+Maternal reports of infectious disease symptoms and antibiotic use were collected weekly by automated survey; household visits occurred every four months.
+Differences by intervention group in reported infectious disease (primary outcome) and antibiotic use (secondary outcome) were assessed using mixed effects logistic regression and Fisher’s Exact tests, respectively.
+RESULTS: Infectious illness occurred in 6% of weeks, with upper respiratory illness the predominant syndrome.
+Among 60 (45%) TC-exposed and 73 (55%) non-TC-exposed babies, infectious disease reports did not differ in frequency between groups (likelihood ratio test: p = 0.88).
+Medical visits with antibiotic prescriptions were less common in the TC group than in the non-TC group (7.8% vs. 16.6%, respectively; p = 0.02).
+CONCLUSIONS: Although randomization to TC-containing wash products was not associated with decreased infectious disease reports by mothers, TCs were associated with decreased antibiotic prescriptions, suggesting a benefit against bacterial infection.
+The recent removal of TCs from consumer wash products makes further elucidation of benefits and risks impracticable.
+Differentiating dengue patients from other acute febrile illness patients is a great challenge among physicians.
+The application of specific laboratory tests is still limited due to high cost, lack of equipment, and uncertain validity.
+This study aimed to construct Bayesian network models using basic demographic, clinical, and laboratory profiles of acute febrile illness patients to diagnose dengue.
+Data of 397 acute undifferentiated febrile illness patients who visited the fever clinic of the Bangkok Hospital for Tropical Diseases, Thailand, were used for model construction and validation.
+The two best final models were selected: one with and one without NS1 rapid test result.
+The diagnostic accuracy of the models was compared with that of physicians on the same set of patients.
+The Bayesian network models provided good diagnostic accuracy of dengue infection, with ROC AUC of 0.80 and 0.75 for models with and without NS1 rapid test result, respectively.
+The models had approximately 80% specificity and 70% sensitivity, similar to the diagnostic accuracy of the hospital’s fellows in infectious disease.
+Including information on NS1 rapid test improved the specificity, but reduced the sensitivity, both in model and physician diagnoses.
+The Bayesian network model developed in this study could be useful to assist physicians in diagnosing dengue, particularly in regions where experienced physicians and laboratory confirmation tests are limited.
+Viral pathogens have adapted to the host organism to exploit the cellular machinery for virus replication and to modulate the host cells for efficient systemic dissemination and immune evasion.
+Much of our knowledge of the effects that virus infections have on cells originates from in vitro imaging studies using experimental culture systems consisting of cell lines and primary cells.
+Recently, intravital microscopy using multi-photon excitation of fluorophores has been applied to observe virus dissemination and pathogenesis in real-time under physiological conditions in living organisms.
+Critical steps during viral infection and pathogenesis could be studied by direct visualization of fluorescent virus particles, virus-infected cells, and the immune response to viral infection.
+In this review, I summarize the latest research on in vivo studies of viral infections using multi-photon intravital microscopy (MP-IVM).
+Initially, the underlying principle of multi-photon microscopy is introduced and experimental challenges during microsurgical animal preparation and fluorescent labeling strategies for intravital imaging are discussed.
+I will further highlight recent studies that combine MP-IVM with optogenetic tools and transcriptional analysis as a powerful approach to extend the significance of in vivo imaging studies of viral pathogens.
+Vaccination is one of the most successful immunology applications that has considerably improved human health.
+Although the DNA vaccine is promising, no human DNA vaccine has been approved to date.
+The main problem facing DNA vaccine efficacy is the lack of a DNA vaccine delivery system.
+One of the best DNA vaccine delivery systems uses a live bacterial vector as the carrier.
+The live bacterial vector induces a robust immune response due to its natural characteristics that are recognized by the immune system.
+Moreover, the route of administration used by the live bacterial vector is through the mucosal route that beneficially induces both mucosal and systemic immune responses.
+The mucosal route is not invasive, making the vaccine easy to administer, increasing the patient’s acceptance.
+Lactic acid bacterium is one of the most promising bacteria used as a live bacterial vector.
+Numerous studies showed that live bacterial vectors are a promising candidate to deliver DNA vaccines.
+SIMPLE SUMMARY: Relocation of cats and kittens is a relatively new practice in animal welfare.
+It is one of the many tools used by animal welfare agencies to decrease shelter euthanasia rates across the country.
+However, there are few and sometimes conflicting guidelines for either minimum standards or best practices regarding relocation programs.
+Concerns about the frequency of infectious diseases and the corresponding likelihood of spread are commonly raised in the context of animal relocation.
+In this study, which followed one relocation program over a 7-month period, highly contagious infectious diseases, feline panleukopenia virus (FPV) and ringworm, were uncommon in cats following relocation into one shelter.
+Upper respiratory infection (URI) was, however, relatively more frequent with younger age, increased time in transport during relocation and increased time spent at the shelter following relocation all associated with increased disease frequency.
+Accordingly, even in an established relocation program, steps should be taken to mitigate the risk of upper respiratory infection in relocated cats.
+ABSTRACT: Feline relocation is used increasingly in animal welfare to decrease shelter euthanasia rates and increase positive outcomes.
+Concerns about infectious disease introduction and transmission are often expressed; however, little research has been conducted on even the baseline prevalence of infectious disease following relocation.
+This study, which collected data on 430 cats relocated through an established program over 7 months, evaluated the prevalence of upper respiratory infection (URI), feline panleukopenia virus (FPV) and dermatophytosis at one destination agency.
+Younger age, increased time in transport, and increased length of stay at the destination agency were associated with increased URI prevalence following relocation.
+The findings of this study reveal that certain highly contagious and environmentally persistent infectious diseases, such as FPV and dermatophytosis, are uncommon following relocation in an established program; however, URI in relocated cats should be proactively managed.
+Animal welfare agencies can use this information to guide shelter and relocation operations and mitigate the impact of URI in relocated cats.
+The promise of nucleic acid based oligonucleotides as effective genetic therapies has been held back by their low bioavailability and poor cellular uptake to target tissues upon systemic administration.
+One such strategy to improve upon delivery is the use of short cell-penetrating peptides (CPPs) that can be either directly attached to their cargo through covalent linkages or through the formation of noncovalent nanoparticle complexes that can facilitate cellular uptake.
+In this review, we will highlight recent proof-of-principle studies that have utilized both of these strategies to improve nucleic acid delivery and discuss the prospects for translation of this approach for clinical application.
+However, whether CMV infection or CMV reactivation contributes to mortality of immunocompetent patients remains unclear.
+Studies reporting on CMV infection in immunocompetent patients in ICUs and containing 2 × 2 tables on CMV results and all-cause mortality were included.
+RESULTS: Eighteen studies involving 2398 immunocompetent patients admitted to ICUs were included in the meta-analysis.
+The overall rate of CMV infection was 27% (95%CI 22–34%, I(2) = 89%, n = 2398) and the CMV reactivation was 31% (95%CI 24–39%, I(2) = 74%, n = 666).
+The odds ratio (OR) for all-cause mortality among patients with CMV infection, compared with those without infection, was 2.16 (95%CI 1.70–2.74, I(2) = 10%, n = 2239).
+Moreover, upon exclusion of studies in which antiviral treatment was possibly or definitely provided to some patients, the association of mortality rate with CMV infection was also statistically significant (OR: 1.69, 95%CI 1.01–2.83, I(2) = 37%, n = 912,).
+For CMV seropositive patients, the OR for mortality in patients with CMV reactivation as compared with patients without CMV reactivation was 1.72 (95%CI 1.04–2.85, I(2) = 29%, n = 664).
+Patients with CMV infection required significantly longer mechanical ventilation (mean difference (MD): 9 days (95% CI 5–14, I(2) = 81%, n = 875)) and longer duration of ICU stay (MD: 12 days (95% CI 7–17, I(2) = 70%, n = 949)) than patients without CMV infection.
+When analysis was limited to detection in blood, CMV infection without antiviral drug treatment or reactivation was not significantly associated with higher mortality (OR: 1.69, 95%CI 0.81–3.54, I(2) = 52%, n = 722; OR: 1.49, I(2) = 63%, n = 469).
+CONCLUSION: Critically ill patients without immunosuppression admitted to ICUs show a high rate of CMV infection.
+CMV infection during the natural unaltered course or reactivation in critically ill patients is associated with increased mortality, but have no effect on mortality when CMV in blood.
+More studies are needed to clarify the impact of CMV infection on clinical outcomes in those patients.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12879-018-3195-5) contains supplementary material, which is available to authorized users.
+Identifying mechanisms responsible for such T cell dysfunction is therefore of great importance to understand how to prevent persistent viral infection.
+Here we show using lymphocytic choriomeningitis virus (LCMV) infection that carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is fundamental for recruiting lymphocyte-specific protein kinase (Lck) into the T cell receptor complex to form an efficient immunological synapse.
+CEACAM1 is essential for activation of CD8(+) T cells, and the absence of CEACAM1 on virus-specific CD8(+) T cells limits the antiviral CD8(+) T cell response.
+Treatment with anti-CEACAM1 antibody stabilizes Lck in the immunological synapse, prevents CD8(+) T cell exhaustion, and improves control of virus infection in vivo.
+We conclude that CEACAM1 is an important regulator of virus-specific CD8(+) T cell functions in mice and humans and represents a promising therapeutic target for modulating CD8(+) T cells.
+Although TB pneumonia is one of the causes of disease and death among children worldwide, the literature on TB pneumonia-induced ARDS is limited.
+We report herein on the successful treatment of a two-year-old female child with TB pneumonia-induced severe ARDS complicated with disseminated intravascular coagulation (DIC).
+CASE PRESENTATION: A two-year-old Vietnamese female child with sustained fever and cough for 20 days was transferred to our hospital.
+She had severe dyspnea and a chest X-ray showed bilateral infiltration without findings of heart failure.
+After tracheal intubation, her oxygenation index (OI) and PaO(2)/FiO(2) (PF) ratio were 29 and 60 mmHg, respectively.
+Mycobacterium tuberculosis was detected by real-time polymerase chain reaction (rPCR) assay of tracheal lavage fluid.
+However, her respiratory condition deteriorated despite treatment with high-frequency oscillating ventilation (HFO), vasopressor support, and 1 g/kg of immunoglobulin.
+On the third day after admission, her International Society on Thrombosis and Hemostasis DIC score had increased to 5.
+After the administration of rTM was completed, OI gradually decreased, after which the mechanical ventilation mode was changed from HFO to synchronized intermittent mandatory ventilation.
+Plasma levels of soluble receptor for advanced glycan end products (sRAGE) and high mobility group box 1 (HMGB-1), which are reported to be associated with ARDS severity, also decreased.
+In addition, inflammatory biomarkers, including interferon-gamma (IFN-γ) and interleukin-6 (IL-6), decreased after the administration of rTM.
+Although severe ARDS (P/F ratio ≦ 100 mmHg) continued for 19 days, the patient’s OI and P/F ratio improved gradually, and she was extubated on the 27th day after admission.
+The severe ARDS with DIC was successfully treated, and she was discharged from hospital on day 33 post-admission.
+CONCLUSIONS: We successfully treated a female child suffering from TB pneumonia-induced severe ARDS complicated with DIC using multimodal interventions.
+Since its discovery in 2001, the major focus of TAAR1 research has been on its role in monoaminergic regulation, drug-induced reward and psychiatric conditions.
+More recently, TAAR1 expression and functionality in immune system regulation and immune cell activation has become a topic of emerging interest.
+Here, we review the immunologically-relevant TAAR1 literature and incorporate open-source expression and cancer survival data meta-analyses.
+We provide strong evidence for TAAR1 expression in the immune system and cancers revealed through NCBI GEO datamining and discuss its regulation in a spectrum of immune cell types as well as in numerous cancers.
+We discuss connections and logical directions for further study of TAAR1 in immunological function, and its potential role as a mediator or modulator of immune dysregulation, immunological effects of psychostimulant drugs of abuse, and cancer progression.
+Mesenchymal stem cells (MSCs) have been demonstrated to be anti-inflammatory against various immune disorders through several factors, including indoleamine 2,3-dioxygenase (IDO) and TNF-stimulated gene 6 (TSG-6).
+Here we employed the mouse lipopolysaccharide (LPS)-induced acute lung injury (ALI) model, and found that IDO is necessary to achieve the effect of human umbilical cord-derived MSC (hUC-MSC)-based treatment on ALI.
+This specific IDO-mediated regulation of TSG-6 expression was found to be exerted through its metabolite, kynurenic acid (KYNA), as inhibition of KYNA production led to decreased TSG-6 expression.
+Mechanistically, KYNA activates aryl hydrocarbon receptor (AhR), which directly binds to the TSG-6 promoter to enhance TSG-6 expression.
+Therefore, our study has uncovered a novel link between IDO and TSG-6, and demonstrates that a metabolite of IDO controls the TSG-6-mediated anti-inflammatory therapeutic effects of human MSCs.
+Vaccines represent the discovery of utmost importance for global health, due to both prophylactic action to prevent infections and therapeutic intervention in neoplastic diseases.
+Despite this, current vaccination strategies need to be refined to successfully generate robust protective antigen-specific memory immune responses.
+To address this issue, one possibility is to exploit the high efficiency of dendritic cells (DCs) as antigen-presenting cells for T cell priming.
+DCs functional plasticity allows shaping the outcome of immune responses to achieve the required type of immunity.
+Therefore, the choice of adjuvants to guide and sustain DCs maturation, the design of multifaceted vehicles, and the choice of surface molecules to specifically target DCs represent the key issues currently explored in both preclinical and clinical settings.
+Here, we review advances in DCs-based vaccination approaches, which exploit direct in vivo DCs targeting and activation options.
+We also discuss the recent findings for efficient antitumor DCs-based vaccinations and combination strategies to reduce the immune tolerance promoted by the tumor microenvironment.
+While much research relies upon viruses grown in cultured immortalized cells, human parainfluenza virus 3 (HPIV-3) evolves in culture.
+We present a genome-wide survey of HPIV-3 adaptations to culture using metagenomic next-generation sequencing of matched pairs of clinical samples and primary culture isolates (zero passage virus).
+Nonsynonymous changes arose during primary viral isolation, almost entirely in the genes encoding the two surface glycoproteins—the receptor binding protein hemagglutinin-neuraminidase (HN) or the fusion protein (F).
+We recovered genomes from 95 HPIV-3 primary culture isolates and 23 HPIV-3 strains directly from clinical samples.
+HN mutations arising during primary viral isolation resulted in substitutions at HN’s dimerization/F-interaction site, a site critical for activation of viral fusion.
+Alterations in HN dimer interface residues known to favor infection in culture occurred within 4 days (H552 and N556).
+A novel cluster of residues at a different face of the HN dimer interface emerged (P241 and R242) and imply a role in HPIV-3-mediated fusion.
+Functional characterization of these culture-associated HN mutations in a clinical isolate background revealed acquisition of the fusogenic phenotype associated with cultured HPIV-3; the HN-F complex showed enhanced fusion and decreased receptor-cleaving activity.
+These results utilize a method for identifying genome-wide changes associated with brief adaptation to culture to highlight the notion that even brief exposure to immortalized cells may affect key viral properties and underscore the balance of features of the HN-F complex required for fitness by circulating viruses.
+BACKGROUND: Patients with acute respiratory failure secondary to tuberculous destroyed lung (TDL) have a poor prognosis.
+The aim of the present retrospective study was to develop a mortality prediction model for TDL patients who require mechanical ventilation.
+METHODS: Data from consecutive TDL patients who had received mechanical ventilation at a single university-affiliated tertiary care hospital in Korea were reviewed.
+A TDL on mechanical Ventilation (TDL-Vent) score was calculated by assigning points to variables according to β coefficient values.
+On the basis of multivariate analysis, the following factors were included in the TDL-Vent score: age ≥65 years, vasopressor use, and arterial partial pressure of oxygen/fraction of inspired oxygen ratio <180.
+In a second regression model, a modified score was then calculated by adding brain natriuretic peptide.
+For TDL-Vent scores 0 to 3, the 60-day mortality rates were 11%, 27%, 30%, and 77%, respectively (p<0.001).
+For modified TDL-Vent scores 0 to ≥3, the 60-day mortality rates were 0%, 21%, 33%, and 57%, respectively (p=0.001).
+For both the TDL-Vent score and the modified TDL-Vent score, the areas under the receiver operating characteristic curve were larger than that of other illness severity scores.
+CONCLUSION: The TDL-Vent model identifies TDL patients on mechanical ventilation with a high risk of mortality.
+BACKGROUND: Although 0.8 mg/kg is considered a lethal dose of colchicine, fatal cases of patients who followed a critical disease course after an intake below this lethal dose have been reported.
+CASE PRESENTATION: An 18-year-old Japanese woman who had taken an overdose of prescription colchicine (15 mg; 0.2 mg/kg) was brought to our emergency out-patient department.
+Although her colchicine intake was below 0.8 mg/kg (considered the lethal dose), she reached a critical state and underwent three phases characterizing colchicine poisoning (gastrointestinal symptoms, multiple organ failure, and recovery).
+Her condition was critical, with a Sequential Organ Failure Assessment score of a maximum of 14.
+Thus, it might be necessary to review which dose of colchicine should be considered lethal.
+OBJECTIVE: To evaluate the overall diagnostic value related to magnetic resonance imaging (MRI) in patients with early osteonecrosis of the femoral head.
+METHODS: By searching multiple databases and sources, including PubMed, Cochrane, and Embase database, by the index words updated in December 2017, qualified studies were identified and relevant literature sources were also searched.
+Heterogeneity of the included studies were reviewed to select proper effect model for pooled weighted sensitivity, specificity, and diagnostic odds ratio (DOR).
+RESULTS: Forty-three studies related to diagnostic accuracy of MRI to detect early osteonecrosis of the femoral head were involved in the meta-analysis.
+The global sensitivity and specificity of MRI in early osteonecrosis of the femoral head were 93.0% (95% CI 92.0–94.0%) and 91.0% (95% CI 89.0%–93.0%), respectively.
+The global positive likelihood ratio and global negative likelihood ratio of MRI in early osteonecrosis of the femoral head were 2.74 (95% CI 1.98–3.79) and 0.18 (95% CI 0.14–0.23), respectively.
+The global DOR was 27.27 (95% CI 17.02–43.67), and the area under the SROC was 93.38% (95% CI 90.87%–95.89%).
+CONCLUSIONS: This review provides a systematic review and meta-analysis to evaluate the diagnostic accuracy of MRI in early osteonecrosis of the femoral head.
+Moderate to strong evidence indicated that MRI appears to be significantly associated with higher diagnostic accuracy for early osteonecrosis of the femoral head.
+The peroxisome proliferator-activated receptor gamma (PPAR-γ) agonist rosiglitazone inhibits NF-κB expression and endogenous neural stem cell differentiation into neurons and reduces the inflammatory cascade after spinal cord injury (SCI).
+The aim of this study was to explore the mechanisms underlying rosiglitazone-mediated neuroprotective effects and regulation of the balance between the inflammatory cascade and generation of endogenous spinal cord neurons by using a spinal cord-derived neural stem cell culture system as well as SD rat SCI model.
+Activation of PPAR-γ could promote neural stem cell proliferation and inhibit PKA expression and neuronal formation in vitro.
+In the SD rat SCI model, the rosiglitazone + forskolin group showed better locomotor recovery compared to the rosiglitazone and forskolin groups.
+MAP2 expression was higher in the rosiglitazone + forskolin group than in the rosiglitazone group, NF-κB expression was lower in the rosiglitazone + forskolin group than in the forskolin group, and NeuN expression was higher in the rosiglitazone + forskolin group than in the forskolin group.
+PPAR-γ activation likely inhibits NF-κB, thereby reducing the inflammatory cascade, and PKA activation likely promotes neuronal cell regeneration.
+We sometimes decide to take an offered option that results in apparent loss (e.g., unpaid overtime).
+Mainstream decision theory does not predict or explain this as a choice we want to make, whereas such a choice has long been described and highly regarded by the traditional Chinese dogma “吃亏是福” (suffering a loss is good fortune).
+Our findings suggest that “suffering a loss is good fortune” is not a myth but a certain reality.
+© 2017 The Authors Journal of Behavioral Decision Making Published by John Wiley & Sons Ltd.
+Automated nucleic acid extraction from primary (raw) sputum continues to be a significant technical challenge for molecular diagnostics.
+In this work, we developed a prototype open-architecture, automated nucleic acid workstation that includes a mechanical homogenization and lysis function integrated with heating and TruTip purification; optimized an extraction protocol for raw sputum; and evaluated system performance on primary clinical specimens.
+The system efficiently homogenized primary sputa and doubled nucleic acid recovery relative to an automated protocol that did not incorporate sample homogenization.
+Nucleic acid recovery was at least five times higher from raw sputum as compared to that of matched sediments regardless of smear or culture grade, and the automated workstation reproducibly recovered PCR-detectable DNA to at least 80 CFU mL(-1) raw sputum.
+M. tuberculosis DNA was recovered and detected from 122/123 (99.2%) and 124/124 (100%) primary sputum and sediment extracts, respectively.
+There was no detectable cross-contamination across 53 automated system runs and amplification or fluorescent inhibitors (if present) were not detectable.
+The open fluidic architecture of the prototype automated workstation yields purified sputum DNA that can be used for any molecular diagnostic test.
+The ability to transfer TruTip protocols between personalized, on-demand pipetting tools and the fully automated workstation also affords public health agencies an opportunity to standardize sputum nucleic acid sample preparation procedures, reagents, and quality control across multiple levels of the health care system.
+BACKGROUND: Influenza infections are often complicated by secondary infections, which are associated with high morbidity and mortality, suggesting that influenza profoundly influences the immune response towards a subsequent pathogenic challenge.
+However, data on the immunological interplay between influenza and secondary infections are equivocal, with some studies reporting influenza-induced augmentation of the immune response, whereas others demonstrate that influenza suppresses the immune response towards a subsequent challenge.
+These contrasting results may be due to the use of various types of live bacteria as secondary challenges, which impedes clear interpretation of causal relations, and to differences in timing of the secondary challenge relative to influenza infection.
+Herein, we investigated whether influenza infection results in an enhanced or suppressed innate immune response upon a secondary challenge with bacterial lipopolysaccharide (LPS) in either the acute or the recovery phase of infection.
+METHODS: Male C57BL/6J mice were intranasally inoculated with 5 × 10(3) PFU influenza virus (pH1N1, strain A/Netherlands/602/2009) or mock treated.
+After 4 (acute phase) or 10 (recovery phase) days, 5 mg/kg LPS or saline was administered intravenously, and mice were sacrificed 90 min later.
+RESULTS: LPS administration 4 days after influenza infection resulted in a synergistic increase in TNF-α, IL-1β, and IL-6 concentrations in lung tissue, but not in plasma.
+This effect was also observed 10 days after influenza infection, albeit to a lesser extent.
+LPS-induced plasma levels of the anti-inflammatory cytokine IL-10 were enhanced 4 days after influenza infection, whereas a trend towards increased pulmonary IL-10 concentrations was found.
+LPS-induced increases in pulmonary MPO content tended to be enhanced as well, but only at 4 days post-infection.
+CONCLUSIONS: An LPS challenge in the acute phase of influenza infection results in an enhanced pulmonary pro-inflammatory innate immune response.
+Combing data of the present study with previous findings, it appears that this enhanced response is not beneficial in terms of protection against secondary infections, but rather damaging by increasing immunopathology.
+The sharp increase in antibiotic resistance imposes a global threat to human health and the discovery of effective antimicrobial alternatives is needed.
+Pathogenic Escherichia coli is causative of multiple clinical syndromes such as diarrheal diseases, meningitis and urinary tract infections.
+In this work, we evaluated the efficacy of probiotics to control multidrug-resistant E. coli and reduce their ability to form biofilms.
+Six E. coli resistant to at least five antibiotics (Ceftazidime, Ampicillin, Clarithromycin, Amoxicillin + Clavulanic Acid and Ceftriaxone) were isolated in this work.
+Preparations of cell-free spent media (CFSM) of six probiotics belonging to the genus Bifidobacterium and Lactobacillus which were grown in Man-Rogosa-Sharpe (MRS) broth exhibited strong antibacterial activity (inhibition zones of 11.77–23.10 mm) against all E. coli isolates.
+Two E. coli isolates, namely E. coli WW1 and IC2, which were most resistant to all antibiotics were subjected to antibiofilm experiments.
+Interestingly, the CFSM of MRS fermented by all probiotics resulted in inhibition of biofilm formation while B. longum caused highest inhibition (57.94%) in case of E. coli IC2 biofilms and L. plantarum was responsible for 64.57% reduction of E. coli WW1 biofilms.
+On the other hand, CFSM of skim milk fermented by L. helveticus and L. rhamnosus exhibited a slight inhibitory activity against IC2 isolate (inhibition percentage of 31.52 and 17.
+68, respectively) while WW1 isolate biofilms was reduced by CFSM of milk fermented by B. longum and L. helveticus (70.81 and 69.49 reduction percentage, respectively).
+These results support the effective use of probiotics as antimicrobial alternatives and to eradicate biofilms formed by multidrug-resistant E. coli.
+Geminiviruses (family Geminiviridae) possess single-stranded circular DNA genomes that are replicated by cellular polymerases in plant host cell nuclei.
+In their hosts, geminivirus populations behave as ensembles of mutant and recombinant genomes, known as viral quasispecies.
+This favors the emergence of new geminiviruses with altered host range, facilitating new or more severe diseases or overcoming resistance traits.
+In warm and temperate areas several whitefly-transmitted geminiviruses of the genus Begomovirus cause the tomato yellow leaf curl disease (TYLCD) with significant economic consequences.
+Over a 45 day period we have studied the diversification of three begomoviruses causing TYLCD: tomato yellow leaf curl virus (TYLCV), tomato yellow leaf curl Sardinia virus (TYLCSV) and tomato yellow leaf curl Malaga virus (TYLCMaV, a natural recombinant between TYLCV and TYLCSV).
+Viral quasispecies resulting from inoculation of geminivirus infectious clones were examined in plants of susceptible tomato (ty-1/ty-1), heterozygous resistant tomato (Ty-1/ty-1), common bean, and the wild reservoir Solanum nigrum.
+However, the complexity and heterogeneity of the quasispecies were high, especially in common bean and the wild host.
+Interestingly, the presence or absence of the Ty-1 allele in tomato did not lead to differences in begomovirus mutant spectra.
+However, the fitness decrease of TYLCSV and TYLCV in tomato at 45 dpi might be related to an increase in CP (Coat protein) mutation frequency.
+In Solanum nigrum the recombinant TYLCMaV, which showed lower fitness than TYLCSV, at 45 dpi actively explored Rep (Replication associated protein) ORF but not the overlapping C4.
+This is especially relevant in the wild reservoir of the viruses, which has the potential to maintain highly diverse mutant spectra without modifying their consensus sequences.
+BACKGROUND: The acute respiratory distress syndrome (ARDS) is one of the main causes of mortality in adults admitted to intensive care units.
+Previous studies have demonstrated the existence of genetic variants involved in the susceptibility and outcomes of this syndrome.
+METHODS: We first performed a prioritization of candidate genes by integrating our own genomic data from a transcriptomic study in an animal model of ARDS and from the only published genome-wide association study of ARDS study in humans.
+Then, we selected single nucleotide polymorphisms (SNPs) from prioritized genes to conduct a case-control discovery association study in patients with sepsis-induced ARDS (n = 225) and population-based controls (n = 899).
+Finally, we validated our findings in an independent sample of 661 sepsis-induced ARDS cases and 234 at-risk controls.
+RESULTS: Three candidate genes were prioritized: dynein cytoplasmic-2 heavy chain-1, fms-related tyrosine kinase 1 (FLT1), and integrin alpha-1.
+Of those, a SNP from FLT1 gene (rs9513106) was associated with ARDS in the discovery study, with an odds ratio (OR) for the C allele of 0.76, 95% confidence interval (CI) 0.58–0.98 (p = 0.037).
+This result was replicated in an independent study (OR = 0.78, 95% CI = 0.62–0.98, p = 0.039), showing consistent direction of effects in a meta-analysis (OR = 0.77, 95% CI = 0.65–0.92, p = 0.003).
+CONCLUSIONS: We identified FLT1 as a novel ARDS susceptibility gene and demonstrated that integration of genomic data can be a valid procedure to identify novel susceptibility genes.
+These results contribute to previous firm associations and functional evidences implicating FLT1 gene in other complex traits that are mechanistically linked, through the key role of endothelium, to the pathophysiology of ARDS.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s40635-018-0181-6) contains supplementary material, which is available to authorized users.
+Mutation rates can evolve through genetic drift, indirect selection due to genetic hitchhiking, or direct selection on the physicochemical cost of high fidelity.
+However, for many systems, it has been difficult to disentangle the relative impact of these forces empirically.
+In RNA viruses, an observed correlation between mutation rate and virulence has led many to argue that their extremely high mutation rates are advantageous because they may allow for increased adaptability.
+This argument has profound implications because it suggests that pathogenesis in many viral infections depends on rare or de novo mutations.
+Here, we present data for an alternative model whereby RNA viruses evolve high mutation rates as a byproduct of selection for increased replicative speed.
+We find that a poliovirus antimutator, 3D(G64S), has a significant replication defect and that wild-type (WT) and 3D(G64S) populations have similar adaptability in 2 distinct cellular environments.
+Experimental evolution of 3D(G64S) under selection for replicative speed led to reversion and compensation of the fidelity phenotype.
+Mice infected with 3D(G64S) exhibited delayed morbidity at doses well above the lethal level, consistent with attenuation by slower growth as opposed to reduced mutational supply.
+Furthermore, compensation of the 3D(G64S) growth defect restored virulence, while compensation of the fidelity phenotype did not.
+Our data are consistent with the kinetic proofreading model for biosynthetic reactions and suggest that speed is more important than accuracy.
+In contrast with what has been suggested for many RNA viruses, we find that within-host spread is associated with viral replicative speed and not standing genetic diversity.
+Drug delivery by nanocarriers (NCs) has long been stymied by dominant liver uptake and limited target organ deposition, even when NCs are targeted using affinity moieties.
+Here we report a universal solution: red blood cell (RBC)-hitchhiking (RH), in which NCs adsorbed onto the RBCs transfer from RBCs to the first organ downstream of the intravascular injection.
+For example, RH injected intravenously increases liposome uptake in the first downstream organ, lungs, by ~40-fold compared with free NCs.
+Intra-carotid artery injection of RH NCs delivers >10% of the injected NC dose to the brain, ~10× higher than that achieved with affinity moieties.
+Further, RH works in mice, pigs, and ex vivo human lungs without causing RBC or end-organ toxicities.
+Thus, RH is a clinically translatable platform technology poised to augment drug delivery in acute lung disease, stroke, and several other diseases.
+The birth and subsequent evolution of optogenetics has resulted in an unprecedented advancement in our understanding of the brain.
+Its outstanding success does usher wider applications; however, the tool remains still largely relegated to neuroscience.
+Here, we introduce selected aspects of optogenetics with potential applications in infection biology that will not only answer long-standing questions about intracellular pathogens (parasites, bacteria, viruses) but also broaden the dimension of current research in entwined models.
+In this essay, we illustrate how a judicious integration of optogenetics with routine methods can illuminate the host–pathogen interactions in a way that has not been feasible otherwise.
+An outbreak of West Nile Virus (WNV) like the recent Ebola can be more epidemic and fatal to public health throughout the world.
+WNV possesses utmost threat as no vaccine or drug is currently available for its treatment except mosquito control.
+The current study applied the combined approach of immunoinformatics and pharmacoinformatics to design potential epitope-based vaccines and drug candidates against WNV.
+By analyzing the whole proteome of 2994 proteins, the WNV envelope glycoprotein was selected as a therapeutic target based on its highest antigenicity.
+After proper assessment “KSFLVHREW” and “ITPSAPSYT” were found to be the most potential T and B-cell epitopes, respectively.
+Besides, we have designed and validated four novel drugs from a known WNV inhibitor, AP30451 by adopting computational approaches.
+This in silico research might greatly facilitate the wet lab experiments to develop vaccine and drug against WNV.
+[Image: see text] In this study, we report the fabrication of aluminum oxide-coated glass (ACG) slides for the preparation of glycan microarrays.
+Pure aluminum (Al, 300 nm) was coated on glass slides via electron-beam vapor deposition polymerization (VDP), followed by anodization to form a thin layer (50–65 nm) of aluminum oxide (Al-oxide) on the surface.
+The ACG slides prepared this way provide a smooth surface for arraying sugars covalently via phosphonate formation with controlled density and spatial distance.
+To evaluate this array system, a mannose derivative of α-5-pentylphosphonic acid was used as a model for the optimization of covalent arraying based on the fluorescence response of the surface mannose interacting with concanavalin A (ConA) tagged with the fluorescence probe A488.
+The ACG slide was characterized using scanning electron microscopy, atomic force microscopy (AFM), and ellipsometry, and the sugar loading capacity, uniformity, and structural conformation were also characterized using AFM, a GenePix scanner, and a confocal microscope.
+This study has demonstrated that the glycan array prepared from the ACG slide is more homogeneous with better spatial control compared with the commonly used glycan array prepared from the N-hydroxysuccinimide-activated glass slide.
+Here, we investigated the nutritional functions of preserved eggs by in vivo and in vitro experiments.
+The results of in vivo studies showed that the levels of triglycerides (TG), total cholesterol (TCHO) and low-density lipoprotein cholesterol/high density lipoprotein cholesterol (LDL-C/HDL-C) were significantly decreased (p<0.05) in the liver of rats treated with preserved eggs.
+Meanwhile, the levels of two important cancer markers, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), were also significantly decreased (p<0.05) in treated rats.
+In vitro studies were performed on Caco-2 cells, a human epithelial colorectal adenocarcinoma cell line.
+It demonstrated that the gastrointestinal (GI) digests of preserved eggs significantly accelerated (p<0.05) the apoptosis by upregulating caspase-3 in the Caco-2 cells.
+Besides, after treated with preserved eggs, the half maximal inhibitory concentration (IC50) of preserved eggs digests to Caco-2 cells was 5.75 mg/mL, indicating the significant inhibition of cell proliferation provided by preserved eggs (p<0.05).
+The results shown in this study demonstrated that preserved eggs may be a novel functional food involved with antilipemic, anti-inflammatory activity as well as the effect on accelarating the apoptosis of Caco-2 cells.
+Herein, meta-analysis, using publicly available microarray data, was conducted identify the differentially expressed genes (DEGs) between pre- and post-peak milk production.
+Samples related to pre-peak (n = 85) and post-peak (n = 24) milk production were selected.
+Interestingly, 10 genes, including MRPS18B, SF1, UQCRC1, NUCB1, RNF126, ADSL, TNNC1, FIS1, HES5 and THTPA, were not detected in original studies that highlights meta-analysis power in biosignature discovery.
+Common target and regulator analysis highlighted the high connectivity of CTNNB1, CDD4 and LPL as gene network hubs.
+As data originally came from three different species, to check the effects of heterogeneous data sources on DEGs, 10 attribute weighting (machine learning) algorithms were applied.
+Attribute weighting results showed that the type of organism had no or little effect on the selected gene list.
+Systems biology analysis suggested that these DEGs affect the milk production by improving the immune system performance and mammary cell growth.
+This is the first study employing both meta-analysis and machine learning approaches for comparative analysis of gene expression pattern of mammary glands in two important time points of lactation process.
+The finding may pave the way to use of publically available to elucidate the underlying molecular mechanisms of physiologically complex traits such as lactation in mammals.
+Epstein-Barr virus (EBV) is a ubiquitous gammaherpesvirus that establishes a latent reservoir in peripheral B-lymphocytes with sporadic reactivation.
+EBV also infects epithelial cells, predominantly resulting in a lytic infection, which may contribute to EBV transmission from saliva.
+In the nasopharynx, EBV infection can lead to the clonal expansion of a latently infected cell and the development of nasopharyngeal carcinoma (NPC).
+An advanced understanding would depend on a physiologically relevant culture model of polarized airway epithelium.
+The recent application of the organotypic raft culture in keratinocytes has demonstrated great promise for the use of polarized cultures in the study of EBV permissive replication.
+In this study, the adaptation of an air-liquid interface (ALI) culture method using transwell membranes was explored in an EBV-infected NPC cell line.
+In the EBV-infected NPC HK1 cell line, ALI culture resulted in the completion of EBV reactivation, with global induction of the lytic cascade, replication of EBV genomes, and production of infectious progeny virus.
+We propose that the ALI culture method can be widely adopted as a physiologically relevant model to study EBV pathogenesis in polarized nasal epithelial cells.
+IMPORTANCE Lifting adherent cells to the air-liquid interface (ALI) is a method conventionally used to culture airway epithelial cells into polarized apical and basolateral surfaces.
+Reactivation of Epstein-Barr virus (EBV) from monolayer epithelial cultures is sometimes abortive, which may be attributed to the lack of authentic reactivation triggers that occur in stratified epithelium in vivo.
+In the present work, the ALI culture method was applied to study EBV reactivation in nasopharyngeal epithelial cells.
+The ALI culture of an EBV-infected cell line yielded high titers and can be dissected by a variety of molecular virology assays that measure induction of the EBV lytic cascade and EBV genome replication and assembly.
+EBV infection of polarized cultures of primary epithelial cells can be challenging and can have variable efficiencies.
+However, the use of the ALI method with established EBV-infected cell lines offers a readily available and reproducible approach for the study of EBV permissive replication in polarized epithelia.
+OBJECTIVE: To provide an update on the current understanding, evaluation, and management of febrile seizures.
+METHODS: A PubMed search was completed in Clinical Queries using the key terms ‘febrile convulsions’ and ‘febrile seizures’.
+RESULTS: Febrile seizures, with a peak incidence between 12 and 18 months of age, likely result from a vulnerability of the developing central nervous system to the effects of fever, in combination with an underlying genetic predisposition and environmental factors.
+The majority of febrile seizures occur within 24 hours of the onset of the fever.
+Clinical judgment based on variable presentations must direct the diagnostic studies which are usually not necessary in the majority of cases.
+A lumbar puncture should be considered in children younger than 12 months of age or with suspected meningitis.
+Approximately 30–40% of children with a febrile seizure will have a recurrence during early childhood.
+CONCLUSION: Continuous preventative antiepileptic therapy for the prevention of recurrent febrile seizures is not recommended.
+Isopeptide bond-tethered triple-stranded coiled coils of HIV-1 gp41 N-terminal heptad repeat (NHR) peptides have been designed with de novo auxiliaries to guide site-directed trimerized cross-linking.
+The presence of isopeptide bridges in the rationally designed trimerization motifs provides extraordinary stability to withstand thermal and chemical denaturation.
+As a result, these ultra-stable and well-folded trimeric coiled coils direct and yield proteolysis-resistant and remarkably potent N-peptide chimeric trimers with HIV-1 fusion inhibitory activities in the low nanomolar range, much more effective than the corresponding unstructured N-peptide monomers and reaching the potency of clinically used T20 peptide (enfuvirtide).
+Thus, these isopeptide bond-crosslinked de novo coiled coils may also be used as attractive scaffolds for isolating NHR-trimers in other class I enveloped viruses for therapeutic intervention.
+Furthermore, this isopeptide bridge-tethering strategy could be extendable to the construction of ultra-stable proteins interfering with certain biological processes.
+We present two probabilistic models to estimate the risk of introducing infectious diseases into previously unaffected countries/regions by infective travellers.
+We analyse two distinct situations, one dealing with a directly transmitted infection (measles in Italy in 2017) and one dealing with a vector-borne infection (Zika virus in Rio de Janeiro, which may happen in the future).
+To calculate the risk in the first scenario, we used a simple, nonhomogeneous birth process.
+The second model proposed in this paper provides a way to calculate the probability that local mosquitoes become infected by the arrival of a single infective traveller during his/her infectiousness period.
+The result of the risk of measles invasion of Italy was of 93% and the result of the risk of Zika virus invasion of Rio de Janeiro was of 22%.
+Plasmodium falciparum erythrocyte invasion is a multistep process that involves a spectrum of interactions that are not well characterized.
+The protein is localized on the surfaces of both merozoites and gametocytes, hence the name Plasmodium falciparum surface-related antigen (PfSRA).
+The processed 32-kDa fragment of PfSRA binds normal human erythrocytes with different sensitivities to enzyme treatments.
+Temporal imaging from initial attachment to internalization of viable merozoites revealed that a fragment of PfSRA, along with PfMSP1(19,) is internalized after invasion.
+Moreover, parasite growth inhibition assays showed that PfSRA P1 antibodies potently inhibited erythrocyte invasion of both sialic acid–dependent and –independent parasite strains.
+Overall, the results demonstrate that PfSRA has the structural and functional characteristics of a very promising target for vaccine development.
+To transfer the viral genome into the host cell cytoplasm, internalized influenza A virus (IAV) particles depend on the fusion of the IAV envelope with host endosomal membranes.
+The antiviral host interferon (IFN) response includes the upregulation of interferon-induced transmembrane protein 3 (IFITM3), which inhibits the release of the viral content into the cytosol.
+Although IFITM3 induction occurs concomitantly with late endosomal/lysosomal (LE/L) cholesterol accumulation, the functional significance of this process is not well understood.
+Here we report that LE/L cholesterol accumulation itself plays a pivotal role in the early antiviral defense.
+We demonstrate that inducing LE/L cholesterol accumulation is antiviral in non-IFN-primed cells, restricting incoming IAV particles and impairing mixing of IAV/endosomal membrane lipids.
+Our results establish a protective function of LE/L cholesterol accumulation and suggest endosomal cholesterol balance as a possible antiviral target.
+Individual patients with life-threatening or severely debilitating diseases can petition the U.S. Food and Drug Administration (FDA) through their physicians to have expanded access (EA) to drugs that are in clinical trials but have not reached full FDA approval (the “single-patient” investigational new drug [IND] application).
+Additionally, recent state and federal laws—so-called “right to try legislation”—allow patients to approach drug companies directly for access prior to FDA approval.
+While these pathways provide potential access for individual patients to investigational drugs, different EA pathways permit entire groups of certain patients to access investigational drugs prior to FDA approval.
+This review focuses on special categories of EA INDs intended for multiple patients—the intermediate-group IND and the widespread-treatment IND—as well as emergency authorization for use of investigational drugs and biological products (e.g., vaccines) in public health emergencies.
+BACKGROUND: Imported horses that have undergone recent long distance transport might represent a serious risk for spreading infectious respiratory pathogens into populations of horses.
+ANIMALS: All imported horses with signed owner consent (n = 167) entering a USDA quarantine for contagious equine metritis from October 2014 to June 2016 were enrolled in the study.
+Enrolled horses had a physical examination performed and nasal secretions collected at the time of entry and subsequently if any horse developed signs of respiratory disease during quarantine.
+Samples were assayed for equine influenza virus (EIV), equine herpesvirus type‐1, −2, −4, and −5 (EHV‐1, −2, −4, −5), equine rhinitis virus A (ERAV), and B (ERBV) and Streptococcus equi subspecies equi (S. equi) using quantitative PCR (qPCR).
+RESULTS: Equine herpesviruses were detected by qPCR in 52% of the study horses including EHV‐2 (28.7%), EHV‐5 (40.7%), EHV‐1 (1.2%), and EHV‐4 (3.0%).
+CONCLUSIONS AND CLINICAL IMPORTANCE: Clinical signs of respiratory disease were poorly correlated with qPCR positive status for EHV‐2, −4, and −5.
+Equine herpesvirus type‐1 or 4 (EHV‐1 or EHV‐4) were detected in 4.2% of horses, which could have serious consequences if shedding animals entered a population of susceptible horses.
+Biosecurity measures are important when introducing recently imported horses into resident US populations of horses.
+Crimean-Congo hemorrhagic fever (CCHF) is an acute, often fatal viral disease characterized by rapid onset of febrile symptoms followed by hemorrhagic manifestations.
+The etiologic agent, CCHF orthonairovirus (CCHFV), can infect several mammals in nature but only seems to cause clinical disease in humans.
+Over the past two decades there has been an increase in total number of CCHF case reports, including imported CCHF patients, and an expansion of CCHF endemic areas.
+Despite its increased public health burden there are currently no licensed vaccines or treatments to prevent CCHF.
+We here report the development and assessment of the protective efficacy of an adenovirus (Ad)-based vaccine expressing the nucleocapsid protein (N) of CCHFV (Ad-N) in a lethal immunocompromised mouse model of CCHF.
+The results show that Ad-N can protect mice from CCHF mortality and that this platform should be considered for future CCHFV vaccine strategies.
+Although B cell depletion is an effective therapy of multiple sclerosis (MS), the pathogenic functions of B cells in MS remain incompletely understood.
+We asked whether cerebrospinal fluid (CSF) B cells in MS secrete different cytokines than control-subject B cells and whether cytokine secretion affects MS phenotype.
+We blindly studied CSF B cells after their immortalization by Epstein-Barr Virus (EBV) in prospectively-collected MS patients and control subjects with other inflammatory-(OIND) or non-inflammatory neurological diseases (NIND) and healthy volunteers (HV).
+The pilot cohort (n = 80) was analyzed using intracellular cytokine staining (n = 101 B cell lines [BCL] derived from 35 out of 80 subjects).
+We validated differences in cytokine production in newly-generated CSF BCL (n = 207 BCL derived from subsequent 112 prospectively-recruited subjects representing validation cohort), using ELISA enhanced by objective, flow-cytometry-based B cell counting.
+After unblinding the pilot cohort, the immortalization efficiency was almost 5 times higher in MS patients compared to controls (p < 0.001).
+MS subjects' BCLs produced significantly more vascular endothelial growth factor (VEGF) compared to control BCLs.
+Progressive MS patients BCLs produced significantly more tumor necrosis factor (TNF)-α and lymphotoxin (LT)-α than BCL from relapsing-remitting MS (RRMS) patients.
+In the validation cohort, we observed lower secretion of IL-1β in RRMS patients, compared to all other diagnostic categories.
+The validation cohort validated enhanced VEGF-C production by BCL from RRMS patients and higher TNF-α and LT-α secretion by BCL from progressive MS. No significant differences among diagnostic categories were observed in secretion of IL-6 or GM-CSF.
+However, B cell secretion of IL-1β, TNF-α, and GM-CSF correlated significantly with the rate of accumulation of disability measured by MS disease severity scale (MS-DSS).
+Finally, all three cytokines with increased secretion in different stages of MS (i.e., VEGF-C, TNF-α, and LT-α) enhance lymphangiogenesis, suggesting that intrathecal B cells directly facilitate the formation of tertiary lymphoid follicles, thus compartmentalizing inflammation to the central nervous system.
+This uncommon RNA virus trait provides influenza with the advantage of access to the nuclear machinery during replication.
+However, it also increases the complexity of the intracellular trafficking that is required for the viral components to establish a productive infection.
+The segmentation of the influenza genome makes these additional trafficking requirements especially challenging, as each viral RNA (vRNA) gene segment must navigate the network of cellular membrane barriers during the processes of entry and assembly.
+To accomplish this goal, influenza A viruses (IAVs) utilize a combination of viral and cellular mechanisms to coordinate the transport of their proteins and the eight vRNA gene segments in and out of the cell.
+The aim of this review is to present the current mechanistic understanding for how IAVs facilitate cell entry, replication, virion assembly, and intercellular movement, in an effort to highlight some of the unanswered questions regarding the coordination of the IAV infection process.
+Along with tRNAs, enzymes that modify anticodon bases are a key aspect of translation across the tree of life.
+tRNA modifications extend wobble pairing, allowing specific (“target”) tRNAs to recognize multiple codons and cover for other (“nontarget”) tRNAs, often improving translation efficiency and accuracy.
+However, the detailed evolutionary history and impact of tRNA modifying enzymes has not been analyzed.
+Using ancestral reconstruction of five tRNA modifications across 1093 bacteria, we show that most modifications were ancestral to eubacteria, but were repeatedly lost in many lineages.
+Most modification losses coincided with evolutionary shifts in nontarget tRNAs, often driven by increased bias in genomic GC and associated codon use, or by genome reduction.
+Our work thus traces the complex history of bacterial tRNA modifications, providing the first clear evidence for their role in the evolution of bacterial translation.
+They have demonstrated higher susceptibility to a wider variety of human pathogens than other rodents and are also the animal model of choice for pre-clinical evaluations of some vaccine candidates.
+However, the genome of cotton rats remains to be fully sequenced, with much fewer genes cloned and characterised compared to other rodent species.
+Here we report the cloning and characterization of CD40 ligand, whose human and murine counterparts are known to be expressed on a range of cell types including activated T cells and B cells, dendritic cells, granulocytes, macrophages and platelets and exerts a broad array of immune responses.
+The cDNA for cotton rat CD40L we isolated is comprised of 1104 nucleotides with an open reading frame (ORF) of 783bp coding for a 260 amino acid protein.
+Moreover, it demonstrated functional activities on immature bone marrow dendritic cells by upregulating surface maturation markers (CD40, CD54, CD80, and CD86), and increasing IL-6 gene and protein expression.
+The availability of CD40L gene identity could greatly facilitate mechanistic research on pathogen-induced-immunopathogenesis and vaccine-elicited immune responses.
+We aimed to present Influenza Like Illness (ILI) and Severe Acute Respiratory Infection (SARI) surveillance data and characterize influenza viruses circulating in the country over three influenza seasons.
+METHODS: We analyzed sentinel site ILI and SARI data for the 2014–2017 seasons in Georgia.
+Patients’ samples were screened by real-time RT-PCR and influenza viruses isolated were characterized antigenically by haemagglutination inhibition assay and genetically by sequencing of HA and NA genes.
+RESULTS: 32% (397/1248) of ILI and 29% (581/1997) of SARI patients tested were positive for influenza viruses.
+In 2014–2015 the median week of influenza detection was week 7/2015 with B/Yamagata lineage viruses dominating (79%); in 2015–2016—week 5/2016 was the median with A/H1N1pdm09 viruses prevailing (83%); and in 2016–2017 a bimodal distribution of influenza activity was observed—the first wave was caused by A/H3N2 (55%) with median week 51/2016 and the second by B/Victoria lineage viruses (45%) with median week 9/2017.
+For ILI, influenza virus detection was highest in children aged 5–14 years while for SARI patients most were aged >15 years and 27 (4.6%) of 581 SARI cases died during the three seasons.
+Persons aged 30–64 years had the highest risk of fatal outcome, notably those infected with A/H1N1pdm09 (OR 11.41, CI 3.94–33.04, p<0.001).
+A/H1N1pdm09 viruses analyzed by gene sequencing fell into genetic groups 6B and 6B.1; A/H3N2 viruses belonged to genetic subclades 3C.3b, 3C.3a, 3C.2a and 3C.2a1; B/Yamagata lineage viruses were of clade 3 and B/Victoria lineage viruses fell in clade1A.
+CONCLUSION: In Georgia influenza virus activity occurred mainly from December through March in all seasons, with varying peak weeks and predominating viruses.
+Around one third of ILI/ SARI cases were associated with influenza caused by antigenically and genetically distinct influenza viruses over the course of the three seasons.
+Monkeys demonstrate gastrointestinal barrier dysfunction (leaky gut) as evidenced by higher biomarkers of microbial translocation (MT) and inflammation with ageing despite equivalent health status, and lifelong diet and environmental conditions.
+We evaluated colonic structural, microbiomic and functional changes in old female vervet monkeys (Chlorocebus aethiops sabeus) and how age-related leaky gut alters responses to Western diet.
+Microbiome profiles from 16S sequencing did not show large differences by age grouping, but there was evidence for higher mucosal bacterial loads using qPCR.
+Western diet challenge led to elevations in glycemic and hepatic biochemistry values only in old monkeys, and immunoglobulin therapy was not effective in reducing MT markers or improving metabolic health.
+We interpret these findings to suggest that ageing may lead to lower control over colonization at the mucosal surface, and reduced clearance of pathogens resulting in MT and inflammation.
+Leaky gut in ageing, which is not readily rescued by innate immune support with immunoglobulin, primes the liver for negative consequences of high fat, high sugar diets.
+We evaluated characteristics of the 2014 West African Ebola outbreak to elucidate lessons learned for managing transnational public health security threats.
+METHODS: We used publically available data to compare demographic and outbreak-specific data for Guinea, Sierra Leone, and Liberia, including key indicator data by the World Health Organization.
+Pearson correlation statistics were calculated to compare country-level infrastructure characteristics with outbreak size and duration.
+RESULTS: Hospital bed density was inversely correlated with longer EVD outbreak duration (r = − 0.99).
+Country-specific funding amount allocations were more likely associated with number of incident cases than the population at-risk or infrastructure needs.
+Key indicators demonstrating challenges for Guinea included: number of unsafe burials, percent of EVD-positive samples, and days between symptom onset and case hospitalization.
+CONCLUSION: Many of the country-level factors, particularly the WHO key indicators were associated with controlling the epidemic.
+The infrastructure of countries affected by communicable diseases should be assessed by international political and public health leaders.
+BACKGROUND: American cockroaches (Periplaneta americana) are an important indoor allergen source and a major risk factor for exacerbations and poor control of asthma.
+Sensitization to major American cockroach allergen, Per a 2, correlated with more severe clinical phenotypes among patients with allergic airway diseases.
+MATERIALS AND METHODS: In this study, we examined whether oral plant vaccine-encoding full-length Per a 2 clone-996 or its hypoallergenic clone-372 could exert a prophylactic role in Per a 2-sensitized mice.
+The cDNAs coding Per a 2–996 and Per a 2–372 were inserted into TuMV vector and expressed in Chinese cabbage.
+Adult female BALB/c mice were fed with the cabbage extracts for 21 days and subsequently underwent two-step sensitization with recombinant Per a 2.
+RESULTS: Per a 2-specific IgE measured by in-house ELISA in the sera of Per a 2-372-treated groups were significantly lower than in the control groups after allergen challenge but not the Per a 2-996-treated group.
+Moreover, Per a 2–372 vaccine markedly decreased airway hyper-responsiveness and infiltration of inflammatory cells into the lungs, as well as reduced mRNA expression of IL-4 and IL-13 in comparison with the control mice.
+CONCLUSION: Our data suggest that oral administration of edible plant vaccine encoding Per a 2 hypo-allergen may be used as a prophylactic strategy against the development of cockroach allergy.
+Synthetic aperture radar (SAR) has been widely used to detect oil-spill areas through the backscattering intensity difference between oil and background pixels.
+However, since the signal is similar to that produced by other phenomena, positive identification can be challenging.
+In this study we developed an algorithm to effectively analyze large-scale oil spill areas in SAR images by focusing on optimizing the input layer to artificial neural network (ANN) through removal the factor of lowering the accuracy.
+Highly accurate pixel-based data processing was conducted through false or un-detection element reduction by normalizing the image or applying a non-local (NL) means filter and median filter to the input neurons for ANN.
+In addition, the standard deviation of co-polarized phase difference (CPD) was used to reduce false detection from the look-alike with weak damping effect.
+The algorithm was validated using TerraSAR-X images of an oil spill caused by stranded oil tanker Volganefti-139 in the Kerch Strait in 2007.
+According to the validation results of the receiver operating characteristic (ROC) curve, the oil spill was detected with an accuracy of about 95.19% and un-detection or false detection by look-alike and speckle noise was greatly reduced.
+Chemokines have been demonstrated to serve an important role in a variety of diseases, particularly in tumor progression.
+There have been numerous studies that have reported that T cells serve major roles in tumor progression.
+However, the function of CXC motif chemokine ligand 9 (CXCL9) in prostate cancer remains unknown.
+A prostate cancer mouse model was generated by treating C57/BL-6 and B6.Cg-Selplgtm1Fur/J mice with 3,2′-dimethyl 4-aminobiphenyl (DMAB).
+Flow cytometry was used to detect the alterations of T cells in C57+DMAB or CXCL9+DMAB mice.
+Immunofluorescence revealed that there was positive expression of interleukin-6 (IL-6) and transforming growth factor (TGF)-β in the mouse tissues.
+Results revealed that prostate cancer pathology and cell proliferation in CXCL9+DMAB mice were significantly greater compared with the C57+DMAB mice.
+Compared with C57+DMAB mice, the number of T cells in peripheral blood and spleen of CXCL9+DMAB mice was significantly reduced.
+IHC demonstrated that the expression of IL-6 and TGF-β was significantly downregulated in the CXCL9+DMAB mice.
+In addition, reverse transcription-quantitative polymerase chain reaction analysis demonstrated that CXCL9 mRNA expression in clinical samples was positively associated with clinical pathological stages of prostate cancer.
+In conclusion, CXCL9 may promote prostate cancer progression via inhibition of cytokines from T cells.
+The World Health Organization (WHO) estimates that zoonotic diseases transmitted from animals to humans account for 75 percent of new and emerging infectious diseases.
+Globally, high-consequence pathogens that impact livestock and have the potential for human transmission create research paradoxes and operational challenges for the high-containment laboratories that conduct work with them.
+These specialized facilities are required for conducting all phases of research on high-consequence pathogens (basic, applied, and translational) with an emphasis on both the generation of fundamental knowledge and product development.
+To achieve this research mission, a highly-trained workforce is required and flexible operational methods are needed.
+In addition, working with certain pathogens requires compliance with regulations such as the Centers for Disease Control (CDC) and the U.S. Department of Agriculture (USDA) Select Agent regulations, which adds to the operational burden.
+The vast experience from the existing studies at Plum Island Animal Disease Center, other U.S. laboratories, and those in Europe and Australia with biosafety level 4 (BSL-4) facilities designed for large animals, clearly demonstrates the valuable contribution this capability brings to the efforts to detect, prepare, prevent and respond to livestock and potential zoonotic threats.
+To raise awareness of these challenges, which include biosafety and biosecurity issues, we held a workshop at the 2018 American Society for Microbiology (ASM) Biothreats conference to further discuss the topic with invited experts and audience participants.
+The workshop covered the subjects of research funding and metrics, economic sustainment of drug and vaccine development pipelines, workforce turnover, and the challenges of maintaining operational readiness of high containment laboratories.
+Gold nanoparticles (GNPs) have been widely utilized to develop various biosensors for molecular diagnosis, as they can be easily functionalized and exhibit unique optical properties explained by plasmonic effects.
+These unique optical properties of GNPs allow the expression of an intense color under light that can be tuned by altering their size, shape, composition, and coupling with other plasmonic nanoparticles.
+Additionally, they can also enhance other optical signals, such as fluorescence and Raman scattering, making them suitable for biosensor development.
+In this review, we provide a detailed discussion of the currently developed biosensors based on the aforementioned unique optical features of GNPs.
+Mainly, we focus on four different plasmonic biosensing methods, including localized surface plasmon resonance (LSPR), surface-enhanced Raman spectroscopy (SERS), fluorescence enhancement, and quenching caused by plasmon and colorimetry changes based on the coupling of GNPs.
+We believe that the topics discussed here are useful and able to provide a guideline in the development of novel GNP-based biosensors in the future.
+AIMS: The chronic consumption of alcohol is known to result in neurodegeneration and impairment of cognitive function.
+Pathological and neuroimaging studies have confirmed that brain atrophy in alcoholics is mainly due to widespread white matter (WM) loss with neuronal loss restricted to specific regions, such as the prefrontal cortex.
+Neuroimaging studies of cigarette smokers also suggest that chronic inhalation of tobacco smoke leads to brain atrophy, although the neurotoxic component is unknown.
+As a high proportion of chronic alcoholics also smoke cigarettes it has been hypothesized that at least some alcohol-related brain damage is due to tobacco smoke exposure.
+METHODS: 39 Long Evans rats were subjected to 8 weeks exposure to alcohol and/or 5 weeks co-exposure to nicotine-specific nitrosamine ketone (NNK), a proxy for tobacco smoke.
+Furthermore, NNK treatment led to a greater reduction in myelin sheath thickness than ethanol whereas only the ethanol-treated animals showed a decrease in unmyelinated fibre density.
+CONCLUSION: These data suggest that NNK causes WM degeneration, an effect that is exacerbated by alcohol, but unlike alcohol, it has little impact on the neuronal components of the brain.
+However, its effectiveness in preventing acute respiratory illness (ARI) during field training in military training facilities has been not studied.
+A quasi-interventional study was performed to evaluate the prevalence of ARIs over 4 weeks in a Korean army training center in South Korea from January 2009 to February 2009.
+A total of 1291 recruits participating in military training for 4 weeks were randomly distributed to 2 battalions (one with 631 and the other with 660).
+After noticing there is a difference between the 2 battalions in terms of the development of ARIs at the end of 2 weeks of training, we conducted interviews with the battle commanders to determine factors that may be related to one battalion having a higher incidence of ARI.
+Thereafter, we performed an intervention, which consists of instructing the battalion having a higher incidence of ARI to implement field hand washing from the third week.
+Following the intervention, we compared the cumulative rate of ARI during 4 weeks of training.
+The interviews revealed that there were no major differences between the 2 battalions in terms of the training schedules, living environments, or indoor hand washing methods.
+However, there was difference in terms of hand washing during field training for the first 2 weeks; whereas one battalion (the early hand washing group) implemented hand washing during field training starting in the first week, the other battalion did not implement hand washing for the first 2 weeks but instead began in the third week (the late hand washing group).
+The cumulative incidence rate of ARI during 4 weeks of training was significantly lower in the early hand washing group (13.0%, 95% confidence interval [CI]: 10.6%–15.9%) than in the late hand washing group (28.0%, 95% CI, 24.7%–31.5%).
+Our study suggests that outdoor hand washing during field training may be an effective precaution for reducing ARI incidence among recruits participating in military training.
+Acute respiratory tract infection (ARTI) is the most common causes of outpatient visit and hospital admission for children.
+The study aimed to report epidemiological data on respiratory viruses in a university-affiliated children's hospital.
+The study was a retrospective study conducted in a university affiliated children's hospital from 2016 May to 2017 April.
+The results of all nasopharyngeal swab and sputum samples sent for the test for respiratory viruses (adenovirus, influenza A, influenza B, and respiratory syncytial virus) were extracted from the electronic healthcare records.
+Multivariable regression models were employed by including age, gender, type of sample (swab vs sputum), source (emergency department vs others), and season to explore the independent factors associated with positive results for respiratory viruses.
+A total of 3102 (8.9%) samples were positive for adenovirus, 2811 (8.0%) were positive for influenza A, 3460 (9.9%) were positive for influenza B, and 4527 (13.0%) were positive for respiratory syncytial virus.
+The positive rate of adenovirus was highest in April (50.8%), and lowest in November (3%).
+The absolute number of positive samples for adenovirus was highest in June (n = 587) and April (n = 544).
+With 1 year increase in age, the odds of positive result increased by 12% (odds ratio [OR]: 1.12; 95% confidence interval [CI]: 1.11–1.13; P < .001).
+As compared with the autumn, the summer showed significantly lower rate of positive for RSV (OR: 0.49; 95% CI: 0.38–0.62; P < .001), whereas the winter had higher risk of positive result (OR: 3.88; 95% CI: 3.37–4.50; P < .001).
+The study reported epidemiological data on the prevalence of respiratory viruses in a large tertiary care children's hospital.
+Age, gender, type of sample, source, and season were associated with the positive rates for respiratory viruses.
+We conducted a retrospective study of children with histologically confirmed ELP at Red Cross Children’s Hospital, South Africa.
+Repeated oral administration of plant‐based oil for cultural reasons was reported by 10 of 11 caregivers.
+Cough (12/12), tachypnoea (11/12), hypoxia (9/12), and diffuse alveolar infiltrates on chest radiography (12/12) were common at presentation.
+Chest computed tomography revealed ground‐glass opacification with lower zone predominance (9/9) and interlobular septal thickening (8/9).
+Bronchoalveolar lavage specimens appeared cloudy/milky, with abundant lipid‐laden macrophages and extracellular lipid on Oil‐Red‐O staining (12/12), with polymicrobial (6/12) and Mycobacterium abscessus (2/12) co‐infection.
+Antibiotics, systemic corticosteroids, and therapeutic lavage were interventions in all eight and five patients, respectively.
+BACKGROUND: Although the use of induced blood stage malaria infection has proven to be a valuable tool for testing the efficacy of vaccines and drugs against Plasmodium falciparum, a limiting factor has been the availability of Good Manufacturing Practice (GMP)—compliant defined P. falciparum strains for in vivo use.
+The aim of this study was to develop a cost-effective method for the large-scale production of P. falciparum cell banks suitable for use in clinical trials.
+METHODS: Genetically-attenuated parasites (GAP) were produced by targeted deletion of the gene encoding the knob associated histidine rich protein (kahrp) from P. falciparum strain 3D7.
+A GAP master cell bank (MCB) was manufactured by culturing parasites in an FDA approved single use, closed system sterile plastic bioreactor.
+All components used to manufacture the MCB were screened to comply with standards appropriate for in vivo use.
+The cryopreserved MCB was subjected to extensive testing to ensure GMP compliance for a phase 1 investigational product.
+At harvest, the GAP MCB had a parasitaemia of 6.3%, with 96% of parasites at ring stage.
+Testing confirmed that all release criteria were met (sterility, absence of viral contaminants and endotoxins, parasite viability following cryopreservation, identity and anti-malarial drug sensitivity of parasites).
+CONCLUSION: Large-scale in vitro culture of P. falciparum parasites using a wave bioreactor can be achieved under GMP-compliant conditions.
+This provides a cost-effective methodology for the production of malaria parasites suitable for administration in clinical trials.
+Extracellular matrix stiffness (ECM) is one of the many mechanical forces acting on mammalian adherent cells and an important determinant of cellular function.
+While the effect of ECM stiffness on many aspects of cellular behavior has been studied previously, how ECM stiffness might mediate susceptibility of host cells to infection by bacterial pathogens is hitherto unexplored.
+To address this open question, we manufactured hydrogels of varying physiologically relevant stiffness and seeded human microvascular endothelial cells (HMEC-1) on them.
+We then infected HMEC-1 with the bacterial pathogen Listeria monocytogenes (Lm) and found that adhesion of Lm to host cells increases monotonically with increasing matrix stiffness, an effect that requires the activity of focal adhesion kinase (FAK).
+We identified cell surface vimentin as a candidate surface receptor mediating stiffness-dependent adhesion of Lm to HMEC-1 and found that bacterial infection of these host cells is decreased when the amount of surface vimentin is reduced.
+Our results provide the first evidence that ECM stiffness can mediate the susceptibility of mammalian host cells to infection by a bacterial pathogen.
+Following injury, mesenchymal repair cells are activated to function as leader cells that modulate wound healing.
+The ex vivo mock cataract surgery cultures are an attractive model with which to address this question.
+With this model we study, concurrently, the mechanisms that control mesenchymal leader cell function in injury repair within their native microenvironment and the signals that induce this same cell population to acquire a myofibroblast phenotype when these cells encounter the environment of the adjacent tissue culture platform.
+Here we show that on injury, the cytoskeletal protein vimentin is released into the extracellular space, binds to the cell surface of the mesenchymal leader cells located at the wound edge in the native matrix environment, and supports wound closure.
+In profibrotic environments, the extracellular vimentin pool also links specifically to the mesenchymal leader cells and has an essential role in signaling their fate change to a myofibroblast.
+These findings suggest a novel role for extracellular, cell-surface–associated vimentin in mediating repair-cell function in wound repair and in transitioning these cells to a myofibroblast phenotype.
+Like most viruses that replicate in the cytoplasm, mammalian reoviruses assemble membranous neo-organelles called inclusions that serve as sites of viral genome replication and particle morphogenesis.
+Viral inclusion formation is essential for viral infection, but how these organelles form is not well understood.
+Correlative light and electron microscopy showed that endoplasmic reticulum (ER) membranes are in contact with nascent inclusions, which form by collections of membranous tubules and vesicles as revealed by electron tomography.
+Live-cell imaging showed that early in infection, the ER is transformed into thin cisternae that fragment into small tubules and vesicles.
+We discovered that ER tubulation and vesiculation are mediated by the reovirus σNS and μNS proteins, respectively.
+Our results enhance an understanding of how viruses remodel cellular compartments to build functional replication organelles.
+Against a backdrop of seasonal influenza virus epidemics, emerging avian influenza viruses (AIVs) occasionally jump from birds to humans, posing a public health risk, especially with the recent sharp increase in H7N9 infections.
+Evaluations of cross-reactive T-cell immunity to seasonal influenza viruses and human-infecting AIVs have been reported previously.
+However, the roles of influenza A virus-derived epitopes in the cross-reactive T-cell responses and heterosubtypic protections are not well understood; understanding those roles is important for preventing and controlling new emerging AIVs.
+Here, among the members of a healthy population presumed to have previously been infected by pandemic H1N1 (pH1N1), we found that pH1N1-specific T cells showed cross- but biased reactivity to human-infecting AIVs, i.e., H5N1, H6N1, H7N9, and H9N2, which correlates with distinct protections.
+Through a T-cell epitope-based phylogenetic analysis, the cellular immunogenic clustering expanded the relevant conclusions to a broader range of virus strains.
+We defined the potential key conserved epitopes required for cross-protection and revealed the molecular basis for the immunogenic variations.
+Our study elucidated an overall profile of cross-reactivity to AIVs and provided useful recommendations for broad-spectrum vaccine development.
+Significant differences exist between the highly pathogenic (HP) porcine reproductive and respiratory syndrome virus (PRRSV) and its attenuated pathogenic (AP) strain in the ability to infect host cells.
+In this study, pulmonary alveolar macrophages (PAMs) are infected with HP‐PRRSV (HuN4) and AP‐PRRSV (HuN4‐F112) for 24 h, then harvested and subjected to label‐free quantitative MS. A total of 2849 proteins are identified, including 95 that are differentially expressed.
+The most differentially expressed proteins are involved in response to stimulus, metabolic process, and immune system process, which mainly have the function of binding and catalytic activity.
+Cluster of differentiation CD163, vimentin (VIM), and nmII as well as detected proteins are assessed together by string analysis, which elucidated a potentially different infection mechanism.
+According to the function annotations, PRRSV with different virulence may mainly differ in immunology, inflammation, immune evasion as well as cell apoptosis.
+This is the first attempt to explore the differential characteristics between HP‐PRRSV and its attenuated PRRSV infected PAMs focusing on membrane proteins which will be of great help to further understand the different infective mechanisms of HP‐PRRSV and AP‐PRRSV.
+BACKGROUND: Little is known about the correlation between microbiological yield and radiographic activity, on chest computed tomography (CT), in suspected pulmonary tuberculosis (PTB) cases, despite CT being widely used, clinically.
+METHODS: We used multicenter retrospective data, obtained from medical records, focusing on the diagnostic performance for definite PTB.
+We categorized patients into four groups, by radiographic activity: definitely active, probably active, indeterminate activity, and probably inactive.
+RESULTS: Of the 650 patients included, 316 had culture-confirmed PTB; 190 (29.2%), 323 (49.7%), 70 (10.8%), and 67 (10.3%) were classified into the definitely active, probably active, indeterminate activity, and probably inactive groups, respectively.
+The corresponding observed culture rates for CT radiographic activity were 61.6%, 60.7%, 4.3% and 0%, respectively.
+When not only culture rates but TB-PCR and histological results were taken into consideration as definite PTB, it showed 66.6%, 67.2%, 14.3%, and 0% of each CT radiographic activity, respectively.
+Regarding the diagnostic performance for definite PTB, radiographic activity displayed high sensitivity (97.1%, 95% confidence interval (CI), 94.6–98.5) and negative predictive values (92.7%, 95% CI, 86.6–96.2), considered definitely and probably active PTB.
+Apart from PTB, other etiologies, according to radiographic activity, were predominantly respiratory infections such as bacterial pneumonia and non-tuberculous mycobacterial infection.
+CONCLUSIONS: Radiographic activity showed good diagnostic performance, and can be used easily in clinical practice.
+As the target organ for numerous pathogens, the lung epithelium exerts critical functions in health and disease.
+However, research in this area has been hampered by the quiescence of the alveolar epithelium under standard culture conditions.
+Long-term, robust growth of human DAECs was achieved using co-culture with feeder cells and supplementation with epidermal growth factor (EGF), Rho-associated protein kinase inhibitor Y27632, and the Notch pathway inhibitor dibenzazepine (DBZ).
+Removal of feeders and priming with DBZ and a cocktail of lung maturation factors prevented the spontaneous differentiation into airway club cells and instead induced differentiation to alveolar epithelial cells.
+We successfully transferred this approach to chicken distal airway cells, thus generating a zoonotic infection model that enables studies on influenza A virus replication.
+These cells are also amenable for gene knockdown using RNAi technology, indicating the suitability of the model for mechanistic studies into lung function and disease.
+Peste des petits ruminants (PPR) is an acute and highly contagious disease in small ruminants that causes significant economic losses in developing countries.
+An increasing number of studies have demonstrated that both autophagy and apoptosis are important cellular mechanisms for maintaining homeostasis, and they participate in the host response to pathogens.
+However, the crosstalk between apoptosis and autophagy in host cells during PPRV infection has not been clarified.
+In this study, autophagy was induced upon virus infection in caprine endometrial epithelial cells (EECs), as determined by the appearance of double- and single-membrane autophagy-like vesicles, LC3-I/LC3-II conversion, and p62 degradation.
+We also found that PPRV infection triggered a complete autophagic response, most likely mediated by the non-structural protein C and nucleoprotein N. Moreover, our results suggest that autophagy not only promotes the replication of PPRV in EECs but also provides a potential mechanism for inhibiting PPRV-induced apoptosis.
+Inhibiting autophagosome formation by wortmannin and knocking down the essential autophagic proteins Beclin-1 and ATG7 induces caspase-dependent apoptosis in EECs in PPRV infection.
+However, inhibiting autophagosome and lysosome fusion by NH(4)Cl and chloroquine did not increase the number of apoptotic cells.
+Collectively, these data are the first to indicate that PPRV-induced autophagy inhibits caspase-dependent apoptosis and thus contributes to the enhancement of viral replication and maturity in host cells.
+Infectious bronchitis virus (IBV) causes a highly contagious respiratory, reproductive and urogenital tract disease in chickens worldwide, resulting in substantial economic losses for the poultry industry.
+Several studies indicate that attenuated IBV vaccine strains contribute to the emergence of variant viruses in the field due to mutations and recombination.
+Therefore, there is a need to develop a stable and safe IBV vaccine that will not create variant viruses.
+In this study, we generated recombinant Newcastle disease viruses (rNDVs) expressing the S1, S2 and S proteins of IBV using reverse genetics technology.
+Our results showed that the rNDV expressing the S protein of IBV provided better protection than the rNDV expressing S1 or S2 protein of IBV, indicating that the S protein is the best protective antigen of IBV.
+Immunization of 4-week-old SPF chickens with the rNDV expressing S protein elicited IBV-specific neutralizing antibodies and provided complete protection against virulent IBV and virulent NDV challenges.
+These results suggest that the rNDV expressing the S protein of IBV is a safe and effective bivalent vaccine candidate for both IBV and NDV.
+Macrophage-mediated programmed cell removal (PrCR) is a process essential for the clearance of unwanted (damaged, dysfunctional, aged, or harmful) cells.
+The detection and recognition of appropriate target cells by macrophages is a critical step for successful PrCR, but its molecular mechanisms have not been delineated.
+Here using the models of tissue turnover, cancer immunosurveillance, and hematopoietic stem cells, we show that unwanted cells such as aging neutrophils and living cancer cells are susceptible to “labeling” by secreted calreticulin (CRT) from macrophages, enabling their clearance through PrCR.
+Importantly, we identified asialoglycans on the target cells to which CRT binds to regulate PrCR, and the availability of such CRT-binding sites on cancer cells correlated with the prognosis of patients in various malignancies.
+Our study reveals a general mechanism of target cell recognition by macrophages, which is the key for the removal of unwanted cells by PrCR in physiological and pathophysiological processes.
+BACKGROUND: In Bangladesh, backyard poultry raisers lack awareness of avian influenza and infrequently follow government recommendations for its prevention.
+Identifying where poultry raisers seek care for their ill poultry might help the government better plan how to disseminate avian influenza prevention and control recommendations.
+METHODS: In order to identify where backyard poultry raisers seek care for their ill poultry, we conducted in-depth and informal interviews: 70 with backyard poultry raisers and six with local poultry healthcare providers in two villages, and five with government veterinary professionals at the sub-district and union levels in two districts during June–August 2009.
+RESULTS: Most (86% [60/70]) raisers sought care for their backyard poultry locally, 14% used home remedies only and none sought care from government veterinary professionals.
+Four local care providers had shops in the village market where raisers sought healthcare for their poultry and the remaining two visited rural households to provide poultry healthcare services.
+Five of the six local care providers did not have formal training in veterinary medicine.
+Local care providers either did not know about avian influenza or considered avian influenza to be a disease common among commercial but not backyard poultry.
+The government professionals had degrees in veterinary medicine and experience with avian influenza and its prevention.
+They had their offices at the sub-district or union level and lacked staffing to reach the backyard raisers at the village level.
+CONCLUSIONS: The local poultry care providers provided front line healthcare to backyard poultry in villages and were a potential source of information for the rural raisers.
+Integration of these local poultry care providers in the government’s avian influenza control programs is a potentially useful approach to increase poultry raisers’ and local poultry care providers’ awareness about avian influenza.
+Objectives: In this study, we investigated the antimicrobial activity of resveratrol in combination with colistin, a last-resort agent for the treatment of severe infections caused by multidrug resistant Gram-negative pathogens.
+Methods: The synergistic activity and the bactericidal activity of colistin in combination with resveratrol was investigated by checkerboard assays and time-kill assays, respectively.
+A total of 21 strains were investigated, including 16 strains of different species (Klebsiella pneumoniae, n = 6, Escherichia coli, n = 6; Citrobacter braakii, n = 1; Stenotrophomonas malthophilia, n = 1; Enterobacter cloaceae, n = 1; Acinetobacter baumannii, n = 1) with acquired colistin resistance, three colistin-susceptible K. pneumoniae precursors, and two strains of intrinsically colistin-resistant species (Serratia marcescens, n = 1; Proteus mirabilis, n = 1).
+Mechanisms of acquired colistin resistance included chromosomal mutations (i.e., mgrB, pmrAB) and plasmid genes (mcr-1, mcr-1.2).
+Overall, a relevant synergistic antimicrobial activity of resveratrol in combination with colistin was observed with all tested strains, except for the three colistin-susceptible K. pneumoniae strains, and for two mcr-1-positive E. coli strains.
+In time-kill assays, performed with 15 selected strains, the combination of colistin 2 mg/L plus resveratrol 128 mg/L was bactericidal with 11 strains, and bacteriostatic for the remaining ones.
+Conclusions: Resveratrol was found to potentiate colistin activity against a wide panel of colistin-resistant strains, regardless of species and resistance mechanisms, which would deserve further investigation for potential clinical applications.
+Formation and regulation mechanism of migration behavior has resulted in a large number of fundamental researches involving quantitative studies of gene expression in this species.
+In this paper, expression stabilities of ten candidate reference genes were evaluated in M. separata under various biotic and abiotic conditions by employing four different software geNorm, NormFinder, BestKeeper, and the comparative ΔCT method.
+PKG as a target gene was employed to justify the number of reference genes in four larval tissues and two photoperiod treatments.
+Results demonstrate that the first three most stable genes were as follows: EF, CypA, and β-TUB for developmental stages; EF, CypA, and RPL12 for larval tissues; EF, TBP, and β-TUB for adult tissues.
+RPL12, β-TUB, and EF for densities; EF, RPL12, and GAPDH for photoperiod treatments; β-TUB, EF, and ATPase for temperature treatments.
+This work provides for the first time a comprehensive list of appropriate reference genes and facilitates future studies on gene function of M. separata.
+Children born preterm, less than 37 weeks’ gestation, are at increased risk of viral respiratory infections and associated complications both during their initial birth hospitalisation and in their first years following discharge.
+This increased burden of viral respiratory infections is likely to have long term implications for lung health and function in individuals born preterm, particularly those with bronchopulmonary dysplasia.
+Several hypotheses have been put forward to explain the association between early life viral respiratory infection and development of suboptimal lung health and function later in life following preterm birth.
+Although preterm infants with diminished lung function, particularly small airways, might be particularly susceptible to asthma and wheezing disorders following viral infection, there is evidence that respiratory viruses can activate number of inflammatory and airway re-modelling pathways.
+Therefore, the aim of this review is to highlight the perinatal and early life risk factors that may contribute to increased susceptibility to viral respiratory infections among preterm infants during early life and to understand how respiratory viral infection may influence the development of abnormal lung health and function later in life.
+Ebola virus (EBOV), a member of the family Filoviridae, is responsible for causing Ebola virus disease (EVD) (formerly named Ebola hemorrhagic fever).
+This is a severe, often fatal illness with mortality rates varying from 50 to 90% in humans.
+Although the virus and associated disease has been recognized since 1976, it was only when the recent outbreak of EBOV in 2014–2016 highlighted the danger and global impact of this virus, necessitating the need for coming up with the effective vaccines and drugs to counter its pandemic threat.
+Albeit no commercial vaccine is available so far against EBOV, a few vaccine candidates are under evaluation and clinical trials to assess their prophylactic efficacy.
+These include recombinant viral vector (recombinant vesicular stomatitis virus vector, chimpanzee adenovirus type 3-vector, and modified vaccinia Ankara virus), Ebola virus-like particles, virus-like replicon particles, DNA, and plant-based vaccines.
+Due to improvement in the field of genomics and proteomics, epitope-targeted vaccines have gained top priority.
+Correspondingly, several therapies have also been developed, including immunoglobulins against specific viral structures small cell-penetrating antibody fragments that target intracellular EBOV proteins.
+Other treatment options include viral entry inhibitors, transfusion of convalescent blood/serum, neutralizing antibodies, and gene expression inhibitors.
+Repurposed drugs, which have proven safety profiles, can be adapted after high-throughput screening for efficacy and potency for EVD treatment.
+Further studies to better understand the pathogenesis and antigenic structures of the virus can help in developing an effective vaccine and identifying appropriate antiviral targets.
+This review presents the recent advances in designing and developing vaccines, drugs, and therapies to counter the EBOV threat.
+Neurotropic herpesviruses can establish lifelong infection in humans and contribute to severe diseases including encephalitis and neurodegeneration.
+However, the mechanisms through which the brain’s immune system recognizes and controls viral infections propagating across synaptically linked neuronal circuits have remained unclear.
+Using a well-established model of alphaherpesvirus infection that reaches the brain exclusively via retrograde transsynaptic spread from the periphery, and in vivo two-photon imaging combined with high resolution microscopy, we show that microglia are recruited to and isolate infected neurons within hours.
+Selective elimination of microglia results in a marked increase in the spread of infection and egress of viral particles into the brain parenchyma, which are associated with diverse neurological symptoms.
+Microglia recruitment and clearance of infected cells require cell-autonomous P2Y12 signalling in microglia, triggered by nucleotides released from affected neurons.
+In turn, we identify microglia as key contributors to monocyte recruitment into the inflamed brain, which process is largely independent of P2Y12.
+P2Y12-positive microglia are also recruited to infected neurons in the human brain during viral encephalitis and both microglial responses and leukocyte numbers correlate with the severity of infection.
+Thus, our data identify a key role for microglial P2Y12 in defence against neurotropic viruses, whilst P2Y12-independent actions of microglia may contribute to neuroinflammation by facilitating monocyte recruitment to the sites of infection.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00401-018-1885-0) contains supplementary material, which is available to authorized users.
+The black yeast genus Exophiala includes numerous potential opportunistic species that potentially cause systematic and disseminated infections in immunocompetent individuals.
+Species causing systemic disease have ability to grow at 37–40 °C, while others consistently lack thermotolerance and are involved in diseases of cold-blooded, waterborne vertebrates and occasionally invertebrates.
+We explain a fast and sensitive assay for recognition and identification of waterborne Exophiala species without sequencing.
+The ITS rDNA region of seven Exophiala species (E. equina, E. salmonis, E. opportunistica, E. pisciphila, E. aquamarina, E. angulospora and E. castellanii) along with the close relative Veronaea botryosa was sequenced and aligned for the design of specific padlock probes for the detection of characteristic single-nucleotide polymorphisms.
+The assay demonstrated to successfully amplify DNA of target fungi, allowing detection at the species level.
+The simplicity, tenderness, robustness and low expenses provide padlock probe assay (RCA) a definite place as a very practical method among isothermal approaches for DNA diagnostics.
+Within PPs, Dendritic cells (DCs) can uptake antigens from the gut lumen by extending dendrites into epithelium, and process it and then present to lymphocytes, which effectively antigen produces an immune response.
+Porcine epidemic diarrhea virus (PEDV) is the causative agent of porcine epidemic diarrhea (PED), an acute and highly contagious enteric viral disease.
+The interaction between inactivated porcine epidemic diarrhea virus and porcine monocyte-derived dendritic cells (Mo-DCs) has been reported.
+However, little is known about the interaction between inactivated PEDV and DCs in porcine PPs.
+RESULTS: In this study, for the first time we investigated the role of DCs in porcine PPs after oral administration inactivated PEDV.
+Firstly, a method to isolate DCs from porcine PPs was established, in which the purity of SWC3a(+)/MHC-II(+) DCs was more than 90%.
+Our findings clearly indicate that DCs in porcine PPs after oral administration of inactivated PEDV not only stimulated the proliferation of allogeneic lymphocytes, but also secreted cytokines (IL-1, IL-4).
+Furthermore, the number of DCs and IgA(+) cells in porcine intestinal mucosal significantly increased and the levels of anti-PEDV specific IgG antibody in the serum and SIgA antibody in the feces increased after oral administration inactivated PEDV.
+CONCLUSIONS: Our findings indicate that oral administration of inactivated PEDV activate DCs in porcine Peyer’s patches and inactivated PEDV may be a useful and safe vaccine to trigger adaptive immunity.
+Infectious HCV carrying reporter genes have further applications in understanding the HCV life cycle including replication, viral assembly and release.
+In this study, a full-length 3039bp LacZ gene was inserted into the derivative of JFH1-AM120 to develop an additional reporter virus.
+The results showed that the recombinant reporter virus JFH1-AM120-LacZ can replicate and produce lower titers of infectious virus.
+However, insertion of the LacZ gene in the C-terminal region of the NS5A in HCV JFH1-AM120-LacZ decreased viral replication and dramatically impaired the production of infectious viral particles.
+Nevertheless, the JFH1-AM120-LacZ reporter virus displayed the entire life cycle of HCV, from replication to production of infectious virus, in Huh7.5 cells.
+This study demonstrates that the NS5A region of HCV JFH1-AM120 has the capacity to accommodate large foreign genes up to 3,039 bp and suggests that other relatively large gene inserts can be accommodated at this site.
+Macrocyclic peptides are privileged scaffolds for drug development and constitute a significant portion of macrocyclic drugs on the market today in fields spanning from infectious disease to oncology.
+Developing orally bioavailable peptide-based drugs remains a challenging task; however, macrocyclization of linear peptides can be an effective strategy to improve membrane permeability, proteolytic stability, oral bioavailability, and overall drug-like characteristics for this class.
+Significant advances in solid-phase peptide synthesis (SPPS) have enabled the efficient construction of macrocyclic peptide and peptidomimetic libraries with macrolactamization being performed on-resin or in solution phase.
+The primary goal of this review is to summarize solid-phase cyclohexapeptide synthesis using the on-resin and solution-phase macrocyclization methodologies published since 2013.
+We also highlight their broad applications ranging from natural product total synthesis, synthetic methodology development, and medicinal chemistry, to drug development and analyses of conformational and physiochemical properties.
+The advent of the genomic era has made elucidating gene function on a large scale a pressing challenge.
+ORFeome collections, whereby almost all ORFs of a given species are cloned and can be subsequently leveraged in multiple functional genomic approaches, represent valuable resources toward this endeavor.
+Here we provide novel, genome-scale tools for the study of Candida albicans, a commensal yeast that is also responsible for frequent superficial and disseminated infections in humans.
+We have generated an ORFeome collection composed of 5099 ORFs cloned in a Gateway™ donor vector, representing 83% of the currently annotated coding sequences of C. albicans.
+We also engineered 49 expression vectors with a choice of promoters, tags and selection markers and demonstrated their applicability to the study of target ORFs transferred from the C. albicans ORFeome.
+In addition, the use of the ORFeome in the detection of protein–protein interaction was demonstrated.
+Mating-compatible strains as well as Gateway™-compatible two-hybrid vectors were engineered, validated and used in a proof of concept experiment.
+These unique and valuable resources should greatly facilitate future functional studies in C. albicans and the elucidation of mechanisms that underlie its pathogenicity.
+Severe Fever with Thrombocytopenia Syndrome (SFTS), an emerging infectious disease caused by a novel phlebovirus, is associated with high fatality.
+The anti-viral immune response has been reported, but humoral involvement in viral pathogenesis is poorly understood.
+Here we show defective serological responses to SFTSV is associated with disease fatality and a combination of B-cell and T-cell impairment contribute to disruption of anti-viral immunity.
+The serological profile in deceased patients is characterized by absence of specific IgG to viral nucleocapsid and glycoprotein due to failure of B-cell class switching.
+Apoptosis of monocytes in the early stage of infection diminishes antigen-presentation by dendritic cells, impedes differentiation and function of T follicular helper cells, and contributes to failure of the virus-specific humoral response.
+Objectives: We evaluated the usefulness of an Aspergillus fumigatus quantitative PCR assay performed in bronchoalveolar lavage fluid (BAL) for the diagnosis and prognosis of both invasive and non-invasive aspergillosis.
+Methods: This 4-year retrospective study involved 613 at-risk patients who had either hematological disorders or other immunosuppressive conditions, notably solid organ transplants.
+Results: For invasive aspergillosis (IA), PCR performed in BAL yielded 88.6% sensitivity and 95.5% specificity.
+Comparatively, galactomannan index and mycological examination yielded only 56.3 and 63.6% sensitivity and 97.6 and 94.5% specificity, respectively.
+Considering the 13 chronic aspergillosis cases, PCR, galactomannan index and mycological examination yielded 76.9, 15.4, and 84.6% sensitivity and 92.2, 94.9, and 93% specificity, respectively.
+Fungal load in BAL evaluated by PCR was able to discriminate between aspergillosis and contamination, but not between invasive and non-invasive forms.
+Finally, fungal load was predictive of 90-day mortality, with 23.1% mortality for patients with less than 500 copies/mL versus 68.4% for patients above that cut-off (p < 0.05).
+Conclusion: Our results indicate that Aspergillus PCR in BAL is of particular interest for both the diagnosis and the prognosis of IA.
+This article reviews immunological memory cells, currently represented by T and B lymphocytes and natural killer (NK) cells, which determine a rapid and effective response against a second encounter with the same antigen.
+Among T lymphocytes, functions of memory cells are provided by their subsets: central memory, effector memory, tissue-resident memory, regulatory memory and stem memory T cells.
+Memory T and B lymphocytes have an essential role in the immunity against microbial pathogens but are also involved in autoimmunity and maternal-fetal tolerance.
+NK cells can respond to haptens or viruses, which results in generation of antigen-specific memory cells.
+T, B and NK cells, which have a role in immunological memory, have been characterized phenotypically and functionally.
+During the secondary immune response, these cells are involved in the reaction against foreign antigens, including pathogens, and take part in autoimmune diseases, but also are crucial to immunological tolerance and vaccine therapy.
+Naturally occurring plant compounds including tannins, saponins and essential oils are extensively assessed as natural alternatives to in-feed antibiotics.
+Tannins are a group of polyphenolic compounds that are widely present in plant region and possess various biological activities including antimicrobial, anti-parasitic, anti-viral, antioxidant, anti-inflammatory, immunomodulation, etc.
+Strong protein affinity is the well-recognized property of plant tannins, which has successfully been applied to ruminant nutrition to decrease protein degradation in the rumen, and thereby improve protein utilization and animal production efficiency.
+Incorporations of tannin-containing forage in ruminant diets to control animal pasture bloat, intestinal parasite and pathogenic bacteria load are another 3 important applications of tannins in ruminant animals.
+Tannins have traditionally been regarded as “anti-nutritional factor” for monogastric animals and poultry, but recent researches have revealed some of them, when applied in appropriate manner, improved intestinal microbial ecosystem, enhanced gut health and hence increased productive performance.
+The applicability of plant tannins as an alternative to in-feed antibiotics depends on many factors that contribute to the great variability in their observed efficacies.
+Using the isolated virus, we could obtain not only genomic information, but also several biological characteristics of the virus.
+In the phylogenetic analysis, the virus was found to belong to the recently proposed genus Shaanvirus.
+Through sequence analyses and in vitro testing, the isolated virus was also found to have haemagglutinin-neuraminidase (HN) protein as one of the structural proteins.
+When mouse antiserum was generated against the isolated virus and tested, it was cross-reactive to human parainfluenza virus 1 in an indirect immunofluorescence assay but could not cross-neutralize human parainfluenza virus 1.
+Collectively, this study provided basic information on further classification of the bat paramyxovirus B16-40 and related viruses in the proposed genus Shaanvirus.
+During Coxsackievirus B3 (CVB3) infection hepatitis is a potentially life threatening complication, particularly in newborns.
+Studies with type I interferon (IFN-I) receptor (IFNAR)-deficient mice revealed a key role of the IFN-I axis in the protection against CVB3 infection, whereas the source of IFN-I and cell types that have to be IFNAR triggered in order to promote survival are still unknown.
+We found that CVB3 infected IFN-β reporter mice showed effective reporter induction, especially in hepatocytes and only to a minor extent in liver-resident macrophages.
+Accordingly, upon in vitro CVB3 infection of primary hepatocytes from murine or human origin abundant IFN-β responses were induced.
+To identify sites of IFNAR-triggering we performed experiments with Mx reporter mice, which upon CVB3 infection showed massive luciferase induction in the liver.
+Immunohistological studies revealed that during CVB3 infection MX1 expression of hepatocytes was induced primarily by IFNAR-, and not by IFN-III receptor (IFNLR)-triggering.
+CVB3 infection studies with primary human hepatocytes, in which either the IFN-I or the IFN-III axis was inhibited, also indicated that primarily IFNAR-, and to a lesser extent IFNLR-triggering was needed for ISG induction.
+Interestingly, CVB3 infected mice with a hepatocyte-specific IFNAR ablation showed severe liver cell necrosis and ubiquitous viral dissemination that resulted in lethal disease, as similarly detected in classical IFNAR(-/-) mice.
+In conclusion, we found that during CVB3 infection hepatocytes are major IFN-I producers and that the liver is also the organ that shows strong IFNAR-triggering.
+Importantly, hepatocytes need to be IFNAR-triggered in order to prevent virus dissemination and to assure survival.
+These data are compatible with the hypothesis that during CVB3 infection hepatocytes serve as important IFN-I producers and sensors not only in the murine, but also in the human system.
+Interactions of influenza A virus (IAV) with sialic acid (SIA) receptors determine viral fitness and host tropism.
+Binding to mucus decoy receptors and receptors on epithelial host cells is determined by a receptor-binding hemagglutinin (HA), a receptor-destroying neuraminidase (NA) and a complex in vivo receptor-repertoire.
+The crucial but poorly understood dynamics of these multivalent virus-receptor interactions cannot be properly analyzed using equilibrium binding models and endpoint binding assays.
+In this study, the use of biolayer interferometric analysis revealed the virtually irreversible nature of IAV binding to surfaces coated with synthetic sialosides or engineered sialoglycoproteins in the absence of NA activity.
+In addition to HA, NA was shown to be able to contribute to the initial binding rate while catalytically active.
+Multiple low-affinity HA-SIA interactions resulted in overall extremely high avidity but also permitted a dynamic binding mode, in which NA activity was driving rolling of virus particles over the receptor-surface.
+Virus dissociation only took place after receptor density of the complete receptor-surface was sufficiently decreased due to NA activity of rolling IAV particles.
+The results indicate that in vivo IAV particles, after landing on the mucus layer, reside continuously in a receptor-bound state while rolling through the mucus layer and over epithelial cell surfaces driven by the HA-NA-receptor balance.
+Quantitative BLI analysis enabled functional examination of this balance which governs this dynamic and motile interaction that is expected to be crucial for penetration of the mucus layer and subsequent infection of cells by IAV but likely also by other enveloped viruses carrying a receptor-destroying enzyme in addition to a receptor-binding protein.
+Background: Although WU polyomavirus (WU) and KI polyomavirus (KI) have been demonstrated to infect the human respiratory tract, it remains unclear if WU or KI cause human disease.
+We sought to further investigate the relationship between WU and KI infection and respiratory disease in a pediatric population with respiratory symptoms in Singapore.
+Methods: We conducted a cross-sectional study of pediatric patients with respiratory symptoms in a Singaporean pediatrics hospital.
+Upon consent, residual respiratory samples from pediatric inpatients, previously screened for common respiratory viruses, were collected and further screened for WU and KI using qPCR.
+The severity of a patient's illness was assessed by chart review post-discharge looking for clinical markers of respiratory status such as presenting symptoms, diagnoses, and interventions.
+Results: From December 2016 to April 2017, 201 patients with residual respiratory samples were enrolled in the study.
+Conducting bivariate and multivariate modeling, patients with WU or KI positivity were not at increased risk of SARI, need for additional oxygen, intravenous fluids, and did not receive additional oral antibiotics or bronchodilators during admission.
+In contrast, patients with RSV detections were at increased risk of requiring supplemental oxygen during hospital admission.
+Conclusion: While limited in sample size, our pilot study data do not support the hypothesis that molecular evidence of WU or KI was associated with increased morbidity among a sample of general, pediatric patients with respiratory illness in Singapore.
+METHODS: Hemagglutinin inhibition (HAI) assays against historical human and recent avian influenza A(H2N2) viruses were performed across age groups in Rochester, New York, and Hong Kong, China.
+RESULTS: One hundred fifty individual sera from Rochester and 295 from Hong Kong were included.
+Eighty-five percent of patients born in Rochester and Hong Kong before 1968 had HAI titers ≥1:40 against A/Singapore/1/57, and >50% had titers ≥1:40 against A/Berkeley/1/68.
+The frequency of titers ≥1:40 to avian H2N2 A/mallard/England/727/06 and A/mallard/Netherlands/14/07 in subjects born before 1957 was 62% and 24%, respectively.
+These levels of seroprevalence reduce the initial reproduction number of A/Singapore/1/1957 or A/Berkeley/1/68 by 15%–20%.
+A basic reproduction number (R(0)) of the emerging transmissible virus <1.2 predicts a preventable pandemic.
+CONCLUSIONS: Population immunity to H2 viruses is insufficient to block epidemic spread of H2 virus.
+The characteristics of disease propagation evolve with time, as a result of a multitude of environmental and anthropic factors, this non-stationarity is a key factor in this huge complexity.
+In the absence of appropriate external data sources, to correctly describe the disease propagation, we explore a flexible approach, based on stochastic models for the disease dynamics, and on diffusion processes for the parameter dynamics.
+Using such a diffusion process has the advantage of not requiring a specific mathematical function for the parameter dynamics.
+Coupled with particle MCMC, this approach allows us to reconstruct the time evolution of some key parameters (average transmission rate for instance).
+Thus, by capturing the time-varying nature of the different mechanisms involved in disease propagation, the epidemic can be described.
+Firstly we demonstrate the efficiency of this methodology on a toy model, where the parameters and the observation process are known.
+Applied then to real datasets, our methodology is able, based solely on simple stochastic models, to reconstruct complex epidemics, such as flu or dengue, over long time periods.
+Hence we demonstrate that time-varying parameters can improve the accuracy of model performances, and we suggest that our methodology can be used as a first step towards a better understanding of a complex epidemic, in situation where data is limited and/or uncertain.
+BACKGROUND: Foodborne norovirus outbreak data in Japan from 2005–2006, involving virological surveillance of all symptomatic and asymptomatic individuals, were reanalyzed to estimate the asymptomatic ratio of norovirus infection along with the risk of infection and the probability of virus shedding.
+METHODS: Employing a statistical model that is considered to capture the data-generating process of the outbreak and virus surveillance, maximum likelihood estimation of the asymptomatic ratio was implemented.
+RESULTS: Assuming that all norovirus outbreaks (n = 55) were the result of random sampling from an identical distribution and ignoring genogroup and genotype specificities, the asymptomatic ratio was estimated at 32.1% (95% confidence interval [CI], 27.7–36.7).
+Although not significant, separate estimation of the asymptomatic ratio of the GII.4 genotype appeared to be greater than other genotypes and was estimated at 40.7% (95% CI, 32.8–49.0).
+CONCLUSION: The present study offered the first explicit empirical estimates of the asymptomatic ratio of norovirus infection in natural infection settings.
+Practical difficulty in controlling GII.4 outbreaks was supported by the data, considering that a large estimate of the asymptomatic ratio was obtained for the GII.4 genotype.
+OBJECTIVE: This study aimed to evaluate psychometric properties of the Munich ChronoType Questionnaire (MCTQ) in a sample of Korean older adults.
+METHODS: One-hundred ninety two participants aged 65 and over completed interview-based questionnaires about chronotype, insomnia, depression, and anxiety.
+RESULTS: Morningness-Eveningness Questionnaire (MEQ) scores were significantly negatively correlated with Midpoint of sleep on free days corrected for sleep debt accumulated through weekdays (MSFsc) (r=-0.45, p<0.01) assessed by the MCTQ.
+MSFsc using the MCTQ was significantly positively correlated with MSFsc assessed by both the sleep diary (r=0.74, p<0.05) and actigraphy (r=0.76, p<0.05).
+Additionally, MSFsc assessed by the MCTQ was significantly positively correlated with insomnia (r=0.26, p<0.01), depression (r=0.25, p<0.01), and anxiety (r=0.18, p<0.05).
+Finally, based on MEQ scores, we derived a cut-off score for the MCTQ that distinguishes morning type and other types (intermediate/evening types) in older adults.
+CONCLUSION: The results of these studies supported the validity of the MCTQ in Korean older adults.
+Additionally, while sleep rhythms in elder adults may be more advanced, eveningness tendency may be still important and indicative of sleep and psychological disturbance.
+The aim of the present study was to evaluate the cytotoxic effect of emodin on HepaRG cells and to define the underlying mechanism.
+The results demonstrated that emodin evidently inhibited HepaRG cell growth in a dose- and time-dependent manner by blocking cell cycle progression in the S and G2/M phase and by inducing apoptosis.
+Emodin treatment also resulted in generation of reactive oxygen species (ROS), which abrogated mitochondrial membrane potential (MMP).
+Further studies by western blot analysis howed that emodin upregulated p53, p21, Bax, cyclin E, cleaved caspase-3, 8 and 9, and cleaved poly(ADP-ribose)polymerase (PARP).
+Taken together, our results suggest that emodin induces apoptosis via the mitochondrial apoptosis pathway through cell cycle arrest and ROS generation in HepaRG cells.
+Hepatitis C Virus (HCV) infection treatment has dramatically changed with the advent of direct-acting antiviral agents (DAAs).
+However, the efficacy of DAAs can be attenuated by the presence of resistance-associated substitutions (RASs) before and after treatment.
+Indeed, RASs detected in DAA treatment-naïve HCV-infected patients could be useful for clinical management and outcome prediction.
+Although the frequency of naturally occurring HCV NS5A and NS5B RASs has been addressed in many countries, there are only a few reports on their prevalence in the South American region.
+The aim of this study was to investigate the presence of RASs to NS5A and NS5B inhibitors in a DAA treatment naïve cohort of Uruguayan patients infected with chronic hepatitis C and compare them with reports from other South American countries.
+Here, we found that naturally occurring substitutions conferring resistance to NS5A and NS5B inhibitors were present in 8% and 19.2%, respectively, of treatment-naïve HCV genotype 1 infected patients.
+Importantly, the baseline substitutions in NS5A and NS5B herein identified differ from the studies previously reported in Brazil.
+Furthermore, Uruguayan strains subtype 1a clustered within all major world clades, showing that HCV variants currently circulating in this country are characterized by a remarkable genetic diversity.
+Phagocytic cells are the first line of innate defense against intracellular pathogens, and yet Toxoplasma gondii is renowned for its ability to survive in macrophages, although this paradigm is based on virulent type I parasites.
+Surprisingly, we find that avirulent type III parasites are preferentially cleared in naive macrophages, independent of gamma interferon (IFN-γ) activation.
+The ability of naive macrophages to clear type III parasites was dependent on enhanced activity of NADPH oxidase (Nox)-generated reactive oxygen species (ROS) and induction of guanylate binding protein 5 (Gbp5).
+Macrophages infected with type III parasites (CTG strain) showed a time-dependent increase in intracellular ROS generation that was higher than that induced by type I parasites (GT1 strain).
+The absence of Nox1 or Nox2, gp91 subunit isoforms of the Nox complex, reversed ROS-mediated clearance of CTG parasites.
+Consistent with this finding, both Nox1(−/−) and Nox2(−/−) mice showed higher susceptibility to CTG infection than wild-type mice.
+Additionally, Gbp5 expression was induced upon infection and the enhanced clearance of CTG strain parasites was reversed in Gbp5(−/−) macrophages.
+Expression of a type I ROP18 allele in CTG prevented clearance in naive macrophages, suggesting that it plays a role counteracting Gbp5.
+Although ROS and Gbp5 have been linked to activation of the NLRP3 inflammasome, clearance of CTG parasites did not rely on induction of pyroptosis.
+Collectively, these findings reveal that not all strains of T. gondii are adept at avoiding clearance in macrophages and define new roles for ROS and Gbps in controlling this important intracellular pathogen.
+The mycotoxin, ochratoxin-A (OTA), produced by some fungi, and is a natural contaminant of many foods and animal feeds worldwide.
+Due to its toxic effects, the recommended maximum daily intake of OTA for poultry feeds is 0.1 mg OTA/kg (ECR2006/575/EC); this dose does not induce changes in hepatic/renal parameters, but decreases thymus size and serum globulin concentrations.
+Accordingly, in this study, we assessed quantitatively the total circulating IgY and IgA serum levels, in chicks consuming a 0.1 mg OTA/kg diet (limit) and higher doses (0.3–1.1 mg OTA/kg diet) for 14 or 21 days.
+We also evaluated other immunological parameters (thymus, bursa of Fabricius, and spleen weights and leukocyte profiles) at day 21.
+In the low-dose group, IgA levels were decreased on day 21, but not on day 14.
+The size of the thymus and the bursa of Fabricius was decreased in all OTA-treated groups (p < 0.05), whereas reduced spleen size and altered leukocyte profiles were detected only in the high-dose group (p < 0.05).
+We concluded that chronic exposure to OTA, even at the recommended highest dose, affected IgY and IgA production in chicks.
+A disease with a sudden drop in egg production and shell-less eggs called, shell-less egg syndrome (SES) has been observed in Western Canada egg layer flocks since 2010.
+We hypothesize that SES is caused by an infectious bronchitis virus (IBV) strain since it is known that IBV replicates in the shell gland causing various eggshell abnormalities.
+In this study, we screened egg layer flocks, in the provinces of Alberta (AB) and Saskatchewan (SK), with and without a history of SES for the presence of IBV infection.
+During 2015–2016, a total of 27 egg layer flocks were screened in AB (n = 7) and SK (n = 20).
+Thirty of these isolates were successfully characterized using molecular tools targeting the most variable spike (S) 1 gene.
+IBV isolates from this study clustered into three genotypes based on partial S1 gene variability.
+The majority of the IBV isolates (70%) were Massachusetts (Mass) type, and the rest were either Connecticut (Conn) type or an uncharacterized genotype with genetic characteristics of Mass and Conn types.
+Since the majority of the IBV isolates included within the Mass type, we used a Mass type IBV isolate to reproduce SES in specific pathogen free (SPF) white leghorn chickens in lay.
+Further studies are warranted to investigate whether other IBV isolates can cause SES, to clarify the pathogenesis of SES and to develop a vaccine in order to prevent SES as observed in Western Canadian layer flocks.
+Manipulation of natural mosquito populations using the endosymbiotic bacteria Wolbachia is being investigated as a novel strategy to reduce the burden of mosquito-borne viruses.
+To evaluate the efficacy of these interventions, it will be critical to determine Wolbachia infection frequencies in Aedes aegypti mosquito populations.
+Morphological methods cannot identify Wolbachia, immunoassays often suffer from low sensitivity and poor throughput, while PCR and spectroscopy require complex instruments and technical expertise, which restrict their use to centralized laboratories.
+To address this unmet need, we have used loop-mediated isothermal amplification (LAMP) and oligonucleotide strand displacement (OSD) probes to create a one-pot sample-to-answer nucleic acid diagnostic platform for vector and symbiont surveillance.
+LAMP-OSD assays can directly amplify target nucleic acids from macerated mosquitoes without requiring nucleic acid purification and yield specific single endpoint yes/no fluorescence signals that are observable to eye or by cellphone camera.
+We demonstrate cellphone-imaged LAMP-OSD tests for two targets, the Aedes aegypti cytochrome oxidase I (coi) gene and the Wolbachia surface protein (wsp) gene, and show a limit of detection of 4 and 40 target DNA copies, respectively.
+In a blinded test of 90 field-caught mosquitoes, the coi LAMP-OSD assay demonstrated 98% specificity and 97% sensitivity in identifying Ae.
+Similarly, the wsp LAMP-OSD assay readily identified the wAlbB Wolbachia strain in field-collected Aedes albopictus mosquitoes without generating any false positive signals.
+Modest technology requirements, minimal execution steps, simple binary readout, and robust accuracy make the LAMP-OSD-to-cellphone assay platform well suited for field vector surveillance in austere or resource-limited conditions.
+PURPOSE: Molecular biomarkers, especially serologic factors, have been widely applied in cancer diagnosis and patient follow-up.
+Here, the authors investigated whether laminin gamma 2 (LAMC2) expression, especially serum LAMC2 (sLAMC2) level, was a suitable prognostic factor that could aid in the prediction of survival in PSCC.
+Reverse transcription-quantitative polymerase chain reaction, Western blotting, and immunohistochemistry were performed to detect LAMC2 expression; enzyme-linked immunosorbent assays were used to test sLAMC2 concentration; and a Transwell assay and an in vivo experiment in nude mice were used to test PSCC cell migration, invasion, and metastasis.
+The chi-squared test was used to analyze the association between LAMC2 level and clinical parameters, the Cox proportional hazards regression model was used to evaluate the hazard ratio for death, and Kaplan–Meier analysis with a log-rank test was used for the survival analysis.
+RESULTS: LAMC2 was overexpressed in PSCC tissues, and the LAMC2 expression level was higher in metastatic lymph node (LN) tissues than in primary cancer tissues; moreover, the LAMC2 levels in primary cancer tissues and sLAMC2 were higher in patients with LN metastasis than in those without LN metastasis.
+Upregulated LAMC2 facilitated the migration, invasion, and epithelial-to-mesenchymal transition of PSCC cells in vitro and promoted LN metastasis of PSCC cells in nude mice.
+Elevated LAMC2 levels were strongly correlated with advanced clinicopathologic parameters, especially LN metastasis, in PSCC patients and predicted shorter disease-specific survival.
+The predictive value of sLAMC2 is superior to that of C-reactive protein and squamous cell carcinoma antigen previously reported in PSCC patients, and a stratification analysis revealed that the level of sLAMC2 had a higher predictive value for disease-specific survival in early penile cancer (especially at the N(0/X) stage) than in later-stage penile cancer.
+CONCLUSION: These findings suggest that sLAMC2 is a potential serologic prognostic marker in PSCC and could aid in risk stratification in early-stage PSCC patients.
+Metabarcoding diet analysis has become a valuable tool in animal ecology; however, co‐amplified predator sequences are not generally used for anything other than to validate predator identity.
+Exemplified by the common vampire bat, we demonstrate the use of metabarcoding to infer predator population structure alongside diet assessments.
+Growing populations of common vampire bats impact human, livestock and wildlife health in Latin America through transmission of pathogens, such as lethal rabies viruses.
+Techniques to determine large‐scale variation in vampire bat diet and bat population structure would empower locality‐ and species‐specific projections of disease transmission risks.
+Using bloodmeal and faecal samples from common vampire bats from coastal, Andean and Amazonian regions of Peru, we showcase metabarcoding as a scalable tool to assess vampire bat population structure and feeding preferences.
+Using the same data, we document mitochondrial geographic population structure in the common vampire bat in Peru.
+Such simultaneous inference of vampire bat diet and population structure can enable new insights into the interplay between vampire bat ecology and disease transmission risks.
+Importantly, the methodology can be incorporated into metabarcoding diet studies of other animals to couple information on diet and population structure.
+Duck is a major waterfowl species in China, providing high-economic benefit with a population of up to 20–30 billion per year.
+Ducks are commonly affected by severe diseases, including egg-drop syndrome caused by duck Tembusu virus (DTMUV).
+In this study, duck embryo fibroblasts (DEFs) were infected with DTMUV and harvested at 12 and 24 h post-infection (hpi), and their genomes were sequenced.
+In total, 911 (764 upregulated and 147 downregulated genes) and 3008 (1791 upregulated and 1217 downregulated) differentially expressed genes (DEGs) were identified at 12 and 24 hpi, respectively.
+Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed that DEGs were considerably enriched in immune-relevant pathways, including Toll-like receptor signaling pathway, Cytosolic DNA-sensing pathway, RIG-I-like receptor signaling pathway, Chemokine signaling pathway, NOD-like receptor signaling pathway, and Hematopoietic cell lineage at both time points.
+The key DEGs in immune system included those of the cytokines (IFN α2, IL-6, IL-8L, IL-12B, CCR7, CCL19, and CCL20), transcription factors or signaling molecules (IRF7, NF-κB, STAT1, TMEM173, and TNFAIP3), pattern recognition receptors (RIG-I and MDA5), and antigen-presenting proteins (CD44 and CD70).
+Our data revealed valuable transcriptional information regarding DTMUV-infected DEFs, thereby broadening our understanding of the immune response against DTMUV infection; this information might contribute in developing strategies for controlling the prevalence of DTMUV infection.
+Influenza A viruses result in the deaths of hundreds of thousands of individuals worldwide each year.
+In this study, influenza A transmission in a graduate student office is simulated via long-range airborne, fomite, and close contact routes based on real data from more than 3500 person-to-person contacts and 127,000 surface touches obtained by video-camera.
+The long-range airborne, fomite and close contact routes contribute to 54.3%, 4.2% and 44.5% of influenza A infections, respectively.
+For the fomite route, 59.8%, 38.1% and 2.1% of viruses are transmitted to the hands of students from private surfaces around the infected students, the students themselves and other susceptible students, respectively.
+The intranasal dose via fomites of the students’ bodies, belongings, computers, desks, chairs and public facilities are 8.0%, 6.8%, 13.2%, 57.8%, 9.3% and 4.9%, respectively.
+The intranasal dose does not monotonously increase or decrease with the virus transfer rate between hands and surfaces.
+Mask wearing is much more useful than hand washing for control of influenza A in the tested office setting.
+Regular cleaning of high-touch surfaces, which can reduce the infection risk by 2.14%, is recommended and is much more efficient than hand-washing.
+Rabies virus (RABV) and other lyssaviruses can cause rabies and rabies-like diseases, which are a persistent public health threat to humans and other mammals.
+Lyssaviruses exhibit distinct characteristics in terms of geographical distribution and host specificity, indicative of a long-standing diversification to adapt to the environment.
+We found that RABV has the lowest codon usage bias among lyssaviruses strains, evidenced by its high mean effective number of codons (ENC) (53.84 ± 0.35).
+Moreover, natural selection is the driving force in shaping the codon usage pattern of these strains.
+In summary, our study sheds light on the codon usage patterns of lyssaviruses, which can aid in the development of control strategies and experimental research.
+Flaviviruses constitute an increasing source of public health concern, with growing numbers of pathogens causing disease and geographic spread to temperate climates.
+Despite a large body of evidence supporting mutagenesis as a conceivable antiviral strategy, there are currently no data on the sensitivity to increased mutagenesis for Zika virus (ZIKV) and Usutu virus (USUV), two emerging flaviviral threats.
+In this study, we demonstrate that both viruses are sensitive to three ribonucleosides, favipiravir, ribavirin, and 5-fluorouracil, that have shown mutagenic activity against other RNA viruses while remaining unaffected by a mutagenic deoxyribonucleoside.
+Serial cell culture passages of ZIKV in the presence of these compounds resulted in the rapid extinction of infectivity, suggesting elevated sensitivity to mutagenesis.
+USUV extinction was achieved when a 10-fold dilution was applied between every passage, but not in experiments involving undiluted virus, indicating an overall lower susceptibility than ZIKV.
+Although the two viruses are inhibited by the same three drugs, ZIKV is relatively more susceptive to serial passage in the presence of purine analogues (favipiravir and ribavirin), while USUV replication is suppressed more efficiently by 5-fluorouracil.
+These differences in sensitivity typically correlate with the increases in the mutation frequencies observed in each nucleoside treatment.
+These results are relevant to the development of efficient therapies based on lethal mutagenesis and support the rational selection of different mutagenic nucleosides for each pathogen.
+We will discuss the implications of these results to the fidelity of flavivirus replication and the design of antiviral therapies based on lethal mutagenesis.
+Double-stranded RNA (dsRNA) structures form triplexes and RNA-protein complexes through binding to single-stranded RNA (ssRNA) regions and proteins, respectively, for diverse biological functions.
+Hence, targeting dsRNAs through major-groove triplex formation is a promising strategy for the development of chemical probes and potential therapeutics.
+Short (e.g., 6–10 mer) chemically-modified Peptide Nucleic Acids (PNAs) have been developed that bind to dsRNAs sequence specifically at physiological conditions.
+For example, a PNA incorporating a modified base thio-pseudoisocytosine (L) has an enhanced recognition of a G–C pair in an RNA duplex through major-groove L·G–C base triple formation at physiological pH, with reduced pH dependence as observed for C(+)·G–C base triple formation.
+Currently, an unmodified T base is often incorporated into PNAs to recognize a Watson–Crick A–U pair through major-groove T·A–U base triple formation.
+A substitution of the 5-methyl group in T by hydrogen and halogen atoms (F, Cl, Br, and I) causes a decrease of the pK(a) of N3 nitrogen atom, which may result in improved hydrogen bonding in addition to enhanced base stacking interactions.
+Here, we synthesized a series of PNAs incorporating uracil and halouracils, followed by binding studies by non-denaturing polyacrylamide gel electrophoresis, circular dichroism, and thermal melting.
+Our results suggest that replacing T with uracil and halouracils may enhance the recognition of an A–U pair by PNA·RNA(2) triplex formation in a sequence-dependent manner, underscoring the importance of local stacking interactions.
+Incorporating bromouracils and chlorouracils into a PNA results in a significantly reduced pH dependence of triplex formation even for PNAs containing C bases, likely due to an upshift of the apparent pK(a) of N3 atoms of C bases.
+Thus, halogenation and other chemical modifications may be utilized to enhance hydrogen bonding of the adjacent base triples and thus triplex formation.
+Furthermore, our experimental and computational modelling data suggest that PNA·RNA(2) triplexes may be stabilized by incorporating a (Br)UL step but not an L(Br)U step, in dsRNA-binding PNAs.
+OBJECTIVES: The objectives were to collect baseline data on the occurrence, testing and vaccination practices, and clinical outcomes of feline leukaemia virus (FeLV) and feline immunodeficiency virus (FIV) in New Zealand METHODS: A cross-sectional survey of 423 veterinary practices in New Zealand was performed to collect data on FeLV and FIV testing and vaccination during the 2015 calendar year.
+Clinical records from 572 cats tested using a point-of-care ELISA at a first-opinion veterinary practice between 7 April 2010 and 23 June 2016 were also obtained and multivariable logistic regression models were constructed to identify risk factors for test positivity.
+RESULTS: The survey was completed by 112 clinics (26.4%) of which 72 performed in-house testing.
+Of the 2125 tests performed, 56 (2.6%) were positive for FeLV and 393 (18.5%) were positive for FIV.
+Fewer than 1% of cats were vaccinated for FeLV, with veterinarians citing low perceived prevalence as the primary reason for not vaccinating.
+Being male compared with being female and having clinical evidence of immunosuppression were significant risk factors for both FeLV and FIV test positivity.
+The median survival times of FeLV and FIV test-positive cats were 10 days (95% confidence interval [CI] 0–16) and 650 days (95% CI 431–993), respectively.
+CONCLUSIONS AND RELEVANCE: Testing and vaccination for FeLV and FIV in New Zealand appears targeted towards high-risk animals, which may bias prevalence estimates.
+Baseline data should be monitored for changes in FeLV epidemiology now commercial vaccines are no longer available.
+Porcine respiratory disease complex (PRDC), a common piglet disease, causes substantive economic losses in pig farming.
+To investigate the viral diversity associated with PRDC, the viral communities in serum and nasal swabs from 26 PRDC-affected piglets were investigated using metagenomics.
+By deep sequencing and de novo assembly, 17 viruses were identified in two pooled libraries (16 viruses from serum, nine from nasal swabs).
+Porcine circovirus (PCV)-2, porcine reproductive and respiratory syndrome virus (PRRSV) and pseudorabies virus, all commonly associated with PRDC, were identified in the two pooled samples by metagenomics, but most viruses comprised small linear and circular DNAs (e.g.
+PCR was used to compare the detection rates of each virus in the serum samples from 36 PRDC-affected piglets versus 38 location-matched clinically healthy controls.
+The average virus category per sample was 6.81 for the PRDC-affected piglets and 4.09 for the controls.
+Single or co-infections with PCV-2 or PRRSV had very high detection rates in the PRDC-affected piglets.
+Interestingly, porcine parvovirus (PPV)-2, PPV-3, PPV-6 and torque teno sus virus 1a were significantly associated with PRDC.
+These results illustrate the complexity of viral communities in the PRDC-affected piglets and highlight the candidate viruses associated with it.
+Methods to protect against radiation-induced lung injury (RILI) will facilitate the development of more effective radio-therapeutic protocols for lung cancer and may provide the means to protect the wider population in the event of a deliberate or accidental nuclear or radiological event.
+We hypothesised that supplementing lipid membranes through nebulization of synthetic lamellar lipids would mitigate RILI.
+Following pre-treatment with either nebulised lamellar lipids or saline, anaesthetised sheep were prescribed fractionated radiotherapy (30 Gray (Gy) total dose in five 6 Gy fractions at 3–4 days intervals) to a defined unilateral lung volume.
+Gross pathology in radio-exposed lung 37 days after the first radiation treatment was consistent between treatment groups and consisted of deep red congestion evident on the pleural surface and firmness on palpation.
+Consistent histopathological features in radio-exposed lung were subpleural, periarteriolar and peribronchial intra-alveolar oedema, alveolar fibrosis, interstitial pneumonia and type II pneumocyte hyperplasia.
+The synthetic lamellar lipids abrogated radiation-induced alveolar fibrosis and reduced alpha-smooth muscle actin (ASMA) expression in radio-exposed lung compared to saline treated sheep.
+Administration of synthetic lamellar lipids was also associated with an increased number of cells expressing dendritic cell-lysosomal associated membrane protein throughout the lung.
+Given the disease severity, associated economic costs, and recent appearance of novel IAV strains, there is a renewed interest in developing novel and efficacious “universal” IAV vaccination strategies.
+Recent studies have highlighted that immunizations capable of generating local (i.e., nasal mucosa and lung) tissue-resident memory T and B cells in addition to systemic immunity offer the greatest protection against future IAV encounters.
+Current IAV vaccines are designed to largely stimulate IAV-specific antibodies, but do not generate the lung-resident memory T and B cells induced during IAV infections.
+Herein, we report on an intranasally administered biocompatible polyanhydride nanoparticle-based IAV vaccine (IAV-nanovax) capable of providing protection against subsequent homologous and heterologous IAV infections in both inbred and outbred populations.
+Our findings also demonstrate that vaccination with IAV-nanovax promotes the induction of germinal center B cells within the lungs, both systemic and lung local IAV-specific antibodies, and IAV-specific lung-resident memory CD4 and CD8 T cells.
+Altogether our findings show that an intranasally administered nanovaccine can induce immunity within the lungs, similar to what occurs during IAV infections, and thus could prove useful as a strategy for providing “universal” protection against IAV.
+In addition to its antiviral activities against herpes and fowlpox, the anti-HBV efficacy is very recently reported.
+Objective: To develop and validate simple, sensitive RP-/NP-HPTLC methods for quantitative determination of biomarkers rutin, quercetin, naringenin, and gallic acid in the anti-HBV active G. senegalensis leaves ethanol-extract.
+Materials and methods: RP-HPTLC (rutin & quercetin; phase- acetonitrile:water, 4:6) and NP-HPTLC (naringenin & gallic acid; phase- toluene:ethyl acetate:formic acid, 6:4:0.8) were performed on glass-backed silica gel plates 60F(254)-RP18 and 60F(254), respectively.
+Results: Well-separated and compact spots (R(f)) of rutin (0.52 ± 0.006), quercetin (0.23 ± 0.005), naringenin (0.56 ± 0.009) and gallic acid (0.28 ± 0.006) were detected.
+The regression equations (Y) were 12.434x + 443.49, 10.08x + 216.85, 11.253x + 973.52 and 11.082x + 446.41 whereas the coefficient correlations (r(2)) were 0.997 ± 0.0004, 0.9982 ± 0.0001, 0.9974 ± 0.0004 and 0.9981 ± 0.0001, respectively.
+Gallic acid (7.01 μg/mg) was the most abundant biomarker compared to rutin (2.42 μg/mg), quercetin (1.53 μg/mg) and naringenin (0.14 μg/mg) in the extract.
+Conclusion: The validated NP-/RP-HPTLC methods were simple, accurate, and sensitive for separating and quantifying antiviral biomarkers in G. senegalensis, and endorsed its anti-HBV activity.
+The developed methods could be further employed in the standardization and quality-control of herbal formulations.
+Context: Torilidis fructus, fruits of Torilis japonica Decadolle (Umbelliferae), is a medicinal herb traditionally used as a pesticide, an astrictive, or a medicine for various inflammatory diseases.
+Objectives: Due to the lack of pharmacological studies on this herbal medicine, we explored the inhibitory activity of torilidis fructus on the macrophage-mediated inflammatory response using its ethanol extract (Tf-EE).
+Material and methods: The Griess assay and prostaglandin (PGE(2)) ELISA assay were conducted with Tf-EE (0-75 µg/mL) and LPS (1 µg/mL) treated RAW264.7 cells in cultured media.
+Tf-EE pretreated RAW264.7 cells were incubated with LPS for 6 h and semi-quantitative PCR was performed.
+Reporter gene assays, overexpression of target enzymes and immunoblotting were performed on macrophages to determine the molecular targets of Tf-EE.
+Results: Tf-EE markedly suppressed the inflammatory response of macrophages, such as lipopolysaccharide (LPS)-induced nitric oxide (NO) and PGE(2) production with IC(50) values of 35.66 and 62.47 µg/mL, respectively.
+It was also found that Tf-EE reduced the expression of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 by 80%.
+Nuclear translocation and activation of nuclear factor (NF)-κB (p65 and p50) were declined by 60% and 30% respectively, and their regulatory events including the phosphorylation of AKT, IκBα, Src, and the formation of complexes between Src and p-p85 were also recognized to be diminished.
+Conclusions: The signalling events managed by Src and p85 complex seemed to be critically involved in Tf-EE-mediated anti-inflammatory response.
+Hypercapnia, the elevation of CO(2) in blood and tissues, commonly occurs in severe acute and chronic respiratory diseases, and is associated with increased risk of mortality.
+Recent studies have shown that hypercapnia adversely affects innate immunity, host defense, lung edema clearance and cell proliferation.
+Airway epithelial dysfunction is a feature of advanced lung disease, but the effect of hypercapnia on airway epithelium is unknown.
+Thus, in the current study we examined the effect of normoxic hypercapnia (20% CO(2) for 24 h) vs normocapnia (5% CO(2)), on global gene expression in differentiated normal human airway epithelial cells.
+Gene expression was assessed on Affymetrix microarrays, and subjected to gene ontology analysis for biological process and cluster-network representation.
+Among these, major gene clusters linked to immune responses and nucleosome assembly were largely downregulated, while lipid metabolism genes were largely upregulated.
+The overwhelming majority of these genes were not previously known to be regulated by CO(2).
+These changes in gene expression indicate the potential for hypercapnia to impact bronchial epithelial cell function in ways that may contribute to poor clinical outcomes in patients with severe acute or advanced chronic lung diseases.
+The black tiger shrimp (Penaeus monodon) remains the second most widely cultured shrimp species globally; however, issues with disease and domestication have seen production levels stagnate over the past two decades.
+To help identify innovative solutions needed to resolve bottlenecks hampering the culture of this species, it is important to generate genetic and genomic resources.
+Towards this aim, we have produced the most complete publicly available P. monodon transcriptome database to date based on nine adult tissues and eight early life-history stages (BUSCO - Complete: 98.2% [Duplicated: 51.3%], Fragmented: 0.8%, Missing: 1.0%).
+The assembly resulted in 236,388 contigs, which were then further segregated into 99,203 adult tissue specific and 58,678 early life-history stage specific clusters.
+While annotation rates were low (approximately 30%), as is typical for a non-model organisms, annotated transcript clusters were successfully mapped to several hundred functional KEGG pathways.
+Transcripts were clustered into groups within tissues and early life-history stages, providing initial evidence for their roles in specific tissue functions, or developmental transitions.
+We expect the transcriptome to provide an essential resource to investigate the molecular basis of commercially relevant-significant traits in P. monodon and other shrimp species.
+BACKGROUND: Anti-synthetase (AS) and dermato-pulmonary associated with anti-MDA-5 antibodies (aMDA-5) syndromes are near one of the other autoimmune inflammatory myopathies potentially responsible for severe acute interstitial lung disease.
+We undertook a 13-year retrospective multicenter study in 35 French ICUs in order to describe the clinical presentation and the outcome of patients admitted to the ICU for acute respiratory failure (ARF) revealing AS or aMDA-5 syndromes.
+RESULTS: From 2005 to 2017, 47 patients (23 males; median age 60 [1st–3rd quartiles 52–69] years, no comorbidity 85%) were admitted to the ICU for ARF revealing AS (n = 28, 60%) or aMDA-5 (n = 19, 40%) syndromes.
+Muscular, articular and cutaneous manifestations occurred in 11 patients (23%), 14 (30%) and 20 (43%) patients, respectively.
+Forty-two patients (89%) had ARDS, which was severe in 86%, with a rate of 17% (n = 8/47) of extra-corporeal membrane oxygenation requirement.
+Proportion of patients who received corticosteroids, cyclophosphamide, rituximab, intravenous immunoglobulins and plasma exchange were 100%, 72%, 15%, 21% and 17%, respectively.
+ICU and hospital mortality rates were 45% (n = 21/47) and 51% (n = 24/47), respectively.
+Patients with aMDA-5 dermato-pulmonary syndrome had a higher hospital mortality than those with AS syndrome (n = 16/19, 84% vs. n = 8/28, 29%; p = 0.001).
+Neurotropic strains of mouse hepatitis virus (MHV) induce acute inflammation and chronic demyelination in the spinal cord and optic nerves mediated by axonal spread following intracranial inoculation in mice, with pathologic features similar to the human demyelinating disease multiple sclerosis.
+Spinal cord demyelination is also induced following intranasal inoculation with neurotropic MHV strains, however much higher viral doses are required as compared to intracranial inoculation.
+Recently, it was shown that intranasal administration of low concentrations of proteins leads to significant, rapid accumulation of protein in the optic nerve and in the eye, with only low levels reaching spinal cord and other brain regions.
+Thus, we examined whether intranasal inoculation with MHV at doses equivalent to those given intracranially could induce optic neuritis—inflammation, demyelination and loss of retinal ganglion cells (RGCs) in the optic nerve with or without inducing spinal cord demyelination.
+Four week old male C57BL/6J mice were inoculated intracranially with the recombinant demyelinating strain RSA59, or intranasally with RSA59 or the non-demyelinating strain RSMHV2 as control.
+One month post-inoculation, mice inoculated intracranially with RSA59 had significant myelin loss in both spinal cord and optic nerves, with significant loss of RGCs as well, consistent with prior studies.
+As expected, intranasal inoculation with RSA59 failed to induce demyelination in spinal cord; however, it also did not induce optic nerve demyelination.
+No acute inflammation was found, and no viral antigen was detected, in the optic nerve or retina 1 day after inoculation.
+Results confirm the neurotropic effects of RSA59 following intracranial inoculation, and suggest that direct infection with axonal transport of virus from brain to spinal cord and optic nerve is required to induce demyelinating disease.
+These studies suggest that MHV does not selectively concentrate in optic nerve and retina to sufficient levels to induce demyelination following intranasal inoculation.
+Intracranial inoculation should continue to be considered a preferred method for studies of MHV-induced optic neuritis and central nervous system (CNS) demyelinating disease.
+At present, no established biomarkers exist to support diagnosis for respiratory viral infections and more importantly for severe IV disease.
+Studies in animal models are extremely important to understand the biological, genetic, and environmental factors that contribute to severe IV disease and to validate biomarker candidates from human studies.
+However, mouse human cross-species comparisons are often compromised by the fact that animal studies concentrate on the infected lungs, whereas in humans almost all studies use peripheral blood from patients.
+In addition, human studies do not consider genetic background as variable although human populations are genetically very diverse.
+Therefore, in this study, we performed a cross-species gene expression study of the peripheral blood from human patients and from the highly genetically diverse Collaborative Cross (CC) mouse population after IV infection.
+Our results demonstrate that changes of gene expression in individual genes are highly similar in mice and humans.
+We conclude that the mouse is a highly valuable in vivo model system to validate and to discover gene candidates which can be used as biomarkers in humans.
+Furthermore, mouse studies allow confirmation of findings in humans in a well-controlled experimental system adding enormous value to the understanding of expression and function of human candidate genes.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00335-018-9750-y) contains supplementary material, which is available to authorized users.
+The vacuolar-type H(+)-ATPase (v-ATPase) is the major proton pump that acidifies intracellular compartments of eukaryotic cells.
+Since the inhibition of v-ATPase resulted in anti-tumor and anti-metastatic effects in different tumor models, this enzyme has emerged as promising strategy against cancer.
+Here, we used the well-established v-ATPase inhibitor archazolid, a natural product first isolated from the myxobacterium Archangium gephyra, to study the consequences of v-ATPase inhibition in endothelial cells (ECs), in particular on the interaction between ECs and cancer cells, which has been neglected so far.
+Human endothelial cells treated with archazolid showed an increased adhesion of tumor cells, whereas the transendothelial migration of tumor cells was reduced.
+The adhesion process was independent from the EC adhesion molecules ICAM-1, VCAM-1, E-selectin and N-cadherin.
+Instead, the adhesion was mediated by β1-integrins expressed on tumor cells, as blocking of the integrin β1 subunit reversed this process.
+Tumor cells preferentially adhered to the β1-integrin ligand collagen and archazolid led to an increase in the amount of collagen on the surface of ECs.
+The accumulation of collagen was accompanied by a strong decrease of the expression and activity of the protease cathepsin B. Overexpression of cathepsin B in ECs prevented the capability of archazolid to increase the adhesion of tumor cells onto ECs.
+Our study demonstrates that the inhibition of v-ATPase by archazolid induces a pro-adhesive phenotype in endothelial cells that promotes their interaction with cancer cells, whereas the transmigration of tumor cells was reduced.
+Although annual influenza epidemics affect around 10% of the global population, current treatment options are limited and development of new antivirals is needed.
+Here, using quantitative phosphoproteomics, we reveal the unique phosphoproteome dynamics that occur in the host cell within minutes of influenza A virus (IAV) infection.
+We uncover cellular kinases required for the observed signaling pattern and find that inhibition of selected candidates, such as the G protein-coupled receptor kinase 2 (GRK2), leads to decreased IAV replication.
+As GRK2 has emerged as drug target in heart disease, we focus on its role in IAV infection and show that it is required for viral uncoating.
+Replication of seasonal and pandemic IAVs is severely decreased by specific GRK2 inhibitors in primary human airway cultures and in mice.
+Our study reveals the IAV-induced changes to the cellular phosphoproteome and identifies GRK2 as crucial node of the kinase network that enables IAV replication.
+Bats are the only mammals capable of true, powered flight, which drives an extremely high metabolic rate.
+The “Free Radical Theory of Ageing” (FTRA) posits that a high metabolic rate causes mitochondrial heteroplasmy and the progressive ageing phenotype.
+Contrary to this, bats are the longest-lived order of mammals given their small size and high metabolic rate.
+To investigate if bats exhibit increased mitochondrial heteroplasmy with age, we performed targeted, deep sequencing of mitogenomes and measured point heteroplasmy in wild, long lived Myotis myotis.
+Blood was sampled from 195 individuals, aged between <1 and at 6+ years old, and whole mitochondria deep-sequenced, with a subset sampled over multiple years.
+Oxidative mutations were present in only a small number of individuals, suggesting local oxidative stress events.
+Cohort data showed no significant increase in heteroplasmy with age, while longitudinal data from recaptured individuals showed heteroplasmy is dynamic, and does not increase uniformly over time.
+We show that bats do not suffer from the predicted, inevitable increase in heteroplasmy as posited by the FRTA, instead heteroplasmy was found to be dynamic, questioning its presumed role as a primary driver of ageing.
+BACKGROUND: Postgraduate year training programs play an important role in the development of a comprehensive medical education.
+The goal of these training programs is to inculcate in physicians the expected level of skill in patient care.
+After the initiation of such programs in the USA, Europe, and Japan, studies were conducted in Taiwan to investigate relevant training methods, and a training system was established in 2003.
+Beginning with 3-month programs, followed by 6-month programs, the programs were constantly modified and enhanced by the establishment of the 1-year training program in 2011.
+METHODS: We used a 50-item multiple choice question (MCQ) test and six 10-min stations for objective structured clinical examination (OSCE), which was composed of four stations relating to standardized patients and two stations concerning the clinical skill evaluation, to evaluate the learning results of the trainees.
+RESULTS: There was no significant difference between the performance of the 6 months and 1-year groups.
+The p values were 0.424 in the MCQ test and 0.082 in the OSCE evaluation.
+The results of this study may provide useful insight for ways to improve the design of training programs.
+The streptococcal toxic shock syndrome is a severe complication associated with invasive infections by group A streptococci.
+In spite of medical progresses in the care of patients with septic shock during the last decades, this condition has remained associated with a high mortality.
+Early recognition and multidisciplinary management are key to the care of patients with streptococcal toxic shock syndrome, with intensive and appropriate intensive support of failing organs, rapid diagnosis of infectious source(s), and surgical management.
+The epidemiology and risk factors for streptococcal toxic shock syndrome remain to be better studied, including the possible causal role of exposure to nonsteroidal anti-inflammatory drugs.
+In this review article, the authors review the current knowledge of streptococcal toxic shock syndrome and discuss the pathophysiology as well as its supportive and specific treatment.
+BACKGROUND: Infectious bronchitis (IB) caused by the IB virus (IBV) can cause acute damage to chickens around the world.
+Enzyme-linked immunosorbent assays (ELISAs) have been widely used in the detection of IBV antibodies in the early infection and continuous infection of IB because they are more sensitive and quicker than other diagnostic methods.
+RESULTS: We have developed two indirect microarray methods to detect antibodies against IBV: a chemiluminescent immunoassay test (CIT) and a rapid diagnostic test (RDT).
+IBV nonstructural protein 5 (nsp5) was expressed, purified from Escherichia coli, and used to spot the initiator integrated poly(dimethylsiloxane), which can provide a near “zero” background for serological assays.
+Compared with the IDEXX IBV Ab Test kit, CIT and RDT have a sensitivity and specificity of at least 98.88% and 91.67%, respectively.
+No cross-reaction was detected with antibodies against avian influenza virus subtypes (H5, H7, and H9), Newcastle disease virus, Marek’s disease virus, infectious bursal disease virus, and chicken anemia virus.
+The coefficients of variation of the reproducibility of the intra- and inter-assays for CIT ranged from 0.8 to 18.63%.
+The application of the IBV nsp5 protein microarray showed that the positive rate of the CIT was 96.77%, that of the nsp5 ELISA was 91.40%, and that of the RDT was 90.32%.
+Furthermore, the RDT, which was visible to the naked eye, could be completed within 15 min.
+Our results indicated that compared with nsp5 ELISA, the CIT was more sensitive, and the RDT had similar positive rates but was faster.
+CONCLUSIONS: Two microarray assays, which were rapid, specific, sensitive, and relatively simple, were developed for the detection of an antibody against IBV.
+These methods can be of great value for the surveillance of pathogens and monitoring the efficiency of vaccination.
+Mesenchymal stromal cells (MSC) for cellular therapy in European Union are classified as advanced therapy medicinal products (ATMPs), and their production must fulfill the requirements of Good Manufacturing Practice (GMP) rules.
+Despite their classification as medicinal products is already well recognized, there is still a lack of information and indications to validate methods and to adapt the noncompendial and compendial methods to these peculiar biological products with intrinsic characteristics that differentiate them from classic synthetic or biologic drugs.
+In the present paper, we present the results of the validation studies performed in the context of MSC development as ATMPs for clinical experimental use.
+Specifically, we describe the validation policies followed for sterility testing, endotoxins, adventitious viruses, cell count, and immunophenotyping.
+Our work demonstrates that it is possible to fully validate analytical methods also for ATMPs and that a risk-based approach can fill the gap between the prescription of the available guidelines shaped on traditional medicinal products and the peculiar characteristics of these novel and extremely promising new drugs.
+In Brazil, there were reports of several enteric disease outbreaks in chickens in which avian nephritis virus (ANV) was detected; however, the role of ANV in the outbreaks and whether the virus was a causative agent of these cases of enteric diseases were not determined.
+The aim of this study was to isolate ANV in specific pathogen-free (SPF) chicken embryonated eggs (CEE) from the enteric contents of chickens showing signs of RSS.
+For this purpose, 22 samples of chicken enteric contents that were positive only for ANV were inoculated into 7 and 14-day-old SPF-CEE via the yolk sac route and incubated for 5 d, with a total of 3 passages.
+Virus isolation was confirmed by the presence of embryo injuries, detection of viral RNA by RT-PCR, and visualization of viral particles using electron microscopy.
+Therefore, the 7-day-old inoculated embryos showed dwarfism, gelatinous consistency, hemorrhage, and edema in the embryos, whereas the 14-day-old did not show any alteration.
+Viral RNA was detected in the embryos of both ages of inoculation, and the same viral particles were visualized.
+The embryos from the mock group showed no alteration and were negative for all the tests.
+The viral cDNA was sequenced, and the molecular and phylogenetic analyses showed that the Brazilian isolates are more related with the ANV-1 serotype group; the sequences of these isolates showed a high percentage of nucleotide (86.4 to 94.9%) and amino acid (92.3 to 98.7%) similarity with other sequences from China, Japan, Australia, and the United States that belong to this serotype previously classified group.
+In this study, we isolated 8 samples of ANV in SPF-CEE from enteric content samples from chickens with RSS.
+In doing so, we showed the pathological injuries to the embryo caused by the virus and the molecular characterization of a part of the ORF 1b gene of the virus.
+Human siglecs are a family of 14 sialic acid-binding proteins, most of which are expressed on subsets of immune cells where they regulate immune responses.
+Siglec-8 is expressed selectively on human allergic inflammatory cells—primarily eosinophils and mast cells—where engagement causes eosinophil apoptosis and inhibits mast cell mediator release.
+Evidence supports a model in which human eosinophils and mast cells bind to Siglec-8 sialoglycan ligands on inflammatory target tissues to resolve allergic inflammation and limit tissue damage.
+To identify Siglec-8-binding sialoglycans from human airways, proteins extracted from postmortem human trachea were resolved by size-exclusion chromatography and composite agarose–acrylamide gel electrophoresis, blotted and probed by Siglec-8-Fc blot overlay.
+Three size classes of Siglec-8 ligands were identified: 250 kDa, 600 kDa and 1 MDa, each of which was purified by affinity chromatography using a recombinant pentameric form of Siglec-8.
+Proteomic mass spectrometry identified all size classes as the proteoglycan aggrecan, a finding validated by immunoblotting.
+Glycan array studies demonstrated Siglec-8 binding to synthetic glycans with a terminal Neu5Acα2-3(6-sulfo)-Gal determinant, a quantitatively minor terminus on keratan sulfate (KS) chains of aggrecan.
+Treating human tracheal extracts with sialidase or keratanase eliminated Siglec-8 binding, indicating sialylated KS chains as Siglec-8-binding determinants.
+Finally, Siglec-8 ligand purified from human trachea extracts induced increased apoptosis of freshly isolated human eosinophils in vitro.
+We conclude that sialylated KS proteoglycans are endogenous human airway ligands that bind Siglec-8 and may regulate allergic inflammation.
+Myocardial infarction is one of the most common human cerebrovascular conditions and frequently leads to ischemic stroke.
+Evidence has indicated that magnetic resonance imaging (MRI) is a potential method for the diagnosis of patients with cardiovascular injury.
+However, the efficacy of MRI in diagnosing patients with myocardial infarction requires to be improved.
+In the present study, a novel nano-size contrast agent, a chitosan/Fe(3)O(4)-enclosed albumin (CFEA), was introduced that was used to quantify blood volume and permeability in the infarcted myocardium.
+A total of 68 patients with suspected myocardial infarction were recruited to analyze the efficacy of MRI combined with CFEA (MRI-CFEA).
+It was revealed that MRI-CFEA provided a higher signal intensity than MRI in the same patients.
+It was demonstrated that the diagnostic efficacy of MRI-CFEA for patients with myocardial infarction was higher than that of MRI (P<0.05).
+By MRI-CFEA, 50/68 of cases with myocardial infarction were diagnosed, providing a significantly higher diagnostic rate compared with the 38/68 of cases diagnosed by contrast-enhanced MRI (P<0.01).
+MRI-CFEA successfully discriminated the infarcted regions based on a decreased fractional blood volume and increased permeability-surface (PS) area product in the infarcted myocardium.
+In conclusion, the present study provided a novel method to diagnose infarcted myocardium for patients with myocardial infarction, providing an imaging biomarker for the assessment of endothelial dysfunction in the clinic.
+Programmed –1 ribosomal frameshifting (−1PRF) is a recoding mechanism to make alternative proteins from a single mRNA transcript.
+−1PRF is stimulated by cis-acting signals in mRNA, a seven-nucleotide slippery sequence and a downstream secondary structure element, which is often a pseudoknot.
+In this study we engineered the frameshifting pseudoknot from the mouse mammary tumor virus to respond to a rationally designed small molecule naphthyridine carbamate tetramer (NCTn).
+We demonstrate that NCTn can stabilize the pseudoknot structure in mRNA and activate –1PRF both in vitro and in human cells.
+The results illustrate how NCTn-inducible –1PRF may serve as an important component of the synthetic biology toolbox for the precise control of gene expression using small synthetic molecules.
+Porcine circovirus 3 (PCV3) is a novel virus associated with acute PDNS (porcine dermatitis and nephropathy syndrome)‐like clinical signs identified by metagenomic sequencing from swine.
+Herein, the possible origin, genotypes, and evolutionary dynamics of PCV3 based on available genomic sequences are determined.
+The closest ancestor of PCV3 is found to be within the clade 1 bat CVs.
+It is found that the effective population size of PCV3 increased rapidly during late 2013 to early 2014 and this is associated with the diversification of PCV3a and PCV3b.
+A relatively high effective reproductive number (Re) value and higher evolutionary rate were found compared to other single‐stranded DNA viruses, and positive selection on codons 122 and 320 (24 of ORF2) is identified.
+It is hypothesized that this, together with the prediction of a potential change of an antigenic epitope at position 320, might have allowed PCV3 to escape from the host immune response.
+Overall, this study has important implications for understanding the ongoing PCV3 cases worldwide and will guide future efforts to develop effective preventive and control measures.
+Expression profiles of CXC- and CC-chemokines in various forms of tonsillar disease were studied to evaluate whether certain chemokines play a predominant role in a specific subset of tonsillar disease.
+Total RNA was isolated from 89 biopsies (21 hyperplastic palatine tonsils, 25 adenoids, 16 chronic inflammatory palatine tonsils and 27 chronic inflammatory palatine tonsils with histological prove of acute inflammation), reverse transcribed and subjected to PCR amplifying IL-8, Gro-alpha, eotaxin-1, eotaxin-2, MCP-3, MCP-4 and RANTES.
+2% agarose gel electrophoresis revealed a predominance of IL-8 in the chronic inflammatory palatine tonsil group compared to tonsillar hyperplasia.
+Our data suggest that the majority of diseases related to adenoid formation are mediated via an eotaxin-2 expression, whereas chronic inflammatory tonsillitis is associated with IL-8 upregulation.
+These data imply that adenoids are related to a Th-2, and chronic inflammatory tonsillitis to a Th-1 based immune response.
+Avian avulaviruses serotype 1 (abbreviated as APMV-1 for the historical name avian paramyxovirus 1) are capable of infecting a wide spectrum of avian species with variable clinical symptoms and outcomes.
+Ease of transmission has allowed the virus to spread worldwide with varying degrees of virulence depending upon the virus strain and host species.
+The emergence of new virulent genotypes from global epizootics, and the year-to-year genomic changes in low and high virulence APMV-1 imply that distinct genotypes of APMV-1 are simultaneously evolving at different geographic locations across the globe.
+This vast genomic diversity may be favoured by large variety of avian species susceptibility to APMV-1 infection, and by the availability of highly mobile wild birds.
+It has long been considered that waterfowls are not sensitive to APMV-1 and are unable to show any clinical signs, however, outbreaks from the 90′s contradict these concepts.
+Waterfowl have strong innate immune responses, which minimize the impact of virus infection, however, are unable to prevent the viral shedding.
+Therefore, commercial ducks and geese should be vaccinated against APMV-1 to minimize the virus shedding and for the prevention the transmission.
+Genetic diversity within APMV-1 demonstrates the need for continual monitoring of viral evolution and periodic updates of vaccine seed-strains to achieve efficient control and eradication of APMV-1 in waterfowls.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13567-018-0587-x) contains supplementary material, which is available to authorized users.
+Phytochemical investigations have revealed the presence of diarylheptanoids, polyphenols, flavonoids, terpenoids, steroids and other compounds.
+Diarylheptanoids, natural products with a 1,7-diphenylheptane structural skeleton, are the dominant constituents in the genus, whose anticancer effect has been brought into focus.
+Pure compounds and crude extracts from the genus exhibit a wide spectrum of pharmacological activities both in vitro and in vivo.
+This paper compiles 273 naturally occurring compounds from the genus Alnus along with their structures and pharmacological activities, as reported in 138 references.
+Estimating the transmissibility, which is usually characterized by the basic reproductive number R(0), the mean number of secondary infectious cases generated by a single primary infectious case introduced into a totally susceptible population, provides crucial information for the effort required to stop infection spreading.
+An outbreak from March to June 2011 was reported to have occurred at an elementary school of 698 pupils in China and it was found that the outbreak was due to direct transmission between school children.
+Based on the symptom onset date and the social contact network of the children, in this study we estimate the serial interval (i.e.
+the gap in symptom onset between an infectee and its infector) and use different statistical methods to estimate R(0).
+Combining with the positivity of IgG antibodies tests, we develop a compartmental transmission dynamics model which includes both asymptomatic and symptomatic infections to estimate the overall R(0).
+Our analysis suggests a serial interval of mean = 23.9 days and standard deviation = 20.9 days.
+The different statistical methods suggest estimates for R(0) in the outbreak varying from 2.1 to 2.8, and the estimates from the transmission dynamics model are consistent with this range.
+Our estimates are in agreement with that from one study in England but are higher than that from one study in the United States.
+Our transmission dynamics model suggests that the proportion of symptomatic infections is about 9%, implying that there were about 344 asymptomatic infections along with the 32 observed symptomatic cases.
+Furthermore, it is shown that the inclusion of asymptomatic infection in the epidemic process increases the estimate of R(0) but does not do so greatly provided that the proportion of symptomatic infections is constant over the outbreak and there is no difference in transmissibility between symptomatic and asymptomatic infections.
+BACKGROUND: Patients with influenza complicated with pneumonia are at high risk of rapid progression to acute respiratory distress syndrome (ARDS).
+Prone positioning with longer duration and lung-protective strategies might reduce the mortality level in ARDS.
+The aim of this study is to investigate the survival predictors of prone positioning in patients with ARDS caused by influenza pneumonia.
+From January 1 to March 31 in 2016, all of the patients in intensive care units with virology-proven influenza pneumonia were collected, while all of those patients with ARDS and receiving prone positioning were enrolled.
+Demographic data, laboratory examinations, management records, ventilator settings and clinical outcomes were collected for analysis.
+RESULTS: During the study period, 336 patients with severe influenza pneumonia were screened and 263 patients met the diagnosis of ARDS.
+The 60-day survivors had lower Acute Physiology and Chronic Health Evaluation (APACHE) II score, pneumonia severity index (PSI), creatinine level and lower rate of receiving renal replacement therapy than non-survivors (22.4 ± 8.5 vs. 29.2 ± 7.4, p = 0.003; 106.6 ± 40.9 vs. 135.3 ± 48.6, p = 0.019; 1.2 ± 0.9 mg/dL vs. 3.1 ± 3.6 mg/dL, p = 0.040; and 4% vs. 42%, p < 0.005).
+Multivariate Cox regression analysis identified PSI (hazard ratio 1.020, 95% confidence interval 1.009–1.032; p < 0.001), renal replacement therapy (hazard ratio 6.248, 95% confidence interval 2.245–17.389; p < 0.001), and increase in dynamic driving pressure (hazard ratio 1.372, 95% confidence interval 1.095–1.718; p = 0.006) which were independent predictors associated with 60-day mortality.
+CONCLUSIONS: In the present study, in evaluating the effect of prone positioning in patients with influenza pneumonia-related ARDS, pneumonia severity index, renal replacement therapy and increase in dynamic driving pressure were associated with 60-day mortality in patients with influenza pneumonia-related ARDS receiving prone positioning.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13613-018-0440-4) contains supplementary material, which is available to authorized users.
+Thrombotic microangiopathy (TMA) refers to phenotypically similar disorders, including hemolytic uremic syndromes (HUS) and thrombotic thrombocytopenic purpura (TTP).
+This review explores the role of the influenza virus as trigger of HUS or TTP.
+We conducted a literature survey in PubMed and Google Scholar using HUS, TTP, TMA, and influenza as keywords, and extracted and analyzed reported epidemiological and clinical data.
+Influenza A was found in 83%, 10 out of 25 during the 2009 A(H1N1) pandemic.
+Serum C3 was reduced in 5 out of 14 patients (36%); Coombs test was negative in 7 out of 7 and elevated fibrin/fibrinogen degradation products were documented in 6 out of 8 patients.
+Pathogenic complement gene mutations were found in 7 out of 8 patients tested (C3, MCP, or MCP combined with CFB or clusterin).
+A sizable proportion of tested patients demonstrated mutations associated with alternative pathway of complement dysregulation that was uncovered by this infection.
+Further research is warranted targeting the roles of viral neuraminidase, enhanced virus-induced complement activation and/or ADAMTS13 antibodies, and rational treatment approaches.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00467-017-3783-4) contains supplementary material, which is available to authorized users
+Although many studies have investigated the association of single nucleotide polymorphisms (SNPs) in transforming growth factor beta1 (TGF-β1) gene with pulmonary fibrosis (PF), but their association is still controversial.
+Studies related to TGF-β1 and PF were retrieved from PubMed, Medline, Embase, Scopus, and Wanfang (up to November 30, 2017).
+We targeted TGF-β1 SNPs that have been reported by ≥3 studies to be included in the current meta-analysis, resulting in only 1 final SNP (rs1800470).
+The odds ratios (ORs) and 95% confidence intervals (CIs) were estimated in the models of allele comparison (T vs C), homozygote comparison (TT vs CC), dominant (TT vs TC + CC), recessive (TT + TC vs CC) to evaluate the strength of the associations.
+Overall, no significant association between TGF-β1 rs1800470 and PF was found (T vs C: OR [95% CI] = 0.96 [0.80, 1.15]; TT vs CC: 0.87 [0.61, 1.22]; TT vs TC + CC: 0.80 [0.62, 1.04]; TT + TC vs CC: 1.13 [0.83, 1.54]).
+In subgroup analyses by ethnicity or original disease, no statistically significant association between TGF-β1 rs1800470 polymorphisms and PF was demonstrated.
+This meta-analysis revealed that TGF-β1 rs1800470 polymorphism was not associated with susceptibility to PF development.
+The unique ornamental features and extreme sexual traits of Peacock have always intrigued scientists and naturalists for centuries.
+Here, we report the first genome sequence and comparative analysis of peacock with the high quality genomes of chicken, turkey, duck, flycatcher and zebra finch.
+Genes involved in early developmental pathways including TGF-β, BMP, and Wnt signaling, which have been shown to be involved in feather patterning, bone morphogenesis, and skeletal muscle development, revealed signs of adaptive evolution and provided useful clues on the phenotypes of peacock.
+Innate and adaptive immune genes involved in complement system and T-cell response also showed signs of adaptive evolution in peacock suggesting their possible role in building a robust immune system which is consistent with the predictions of the Hamilton–Zuk hypothesis.
+This study provides novel genomic and evolutionary insights into the molecular understanding toward the phenotypic evolution of Indian peacock.
+MOTIVATION: To understand protein structure, folding and function fully and to design proteins de novo reliably, we must learn from natural protein structures that have been characterized experimentally.
+The number of protein structures available is large and growing exponentially, which makes this task challenging.
+Here, we use tools from graph theory to define an Atlas classification scheme for automatically categorizing certain protein substructures.
+RESULTS: Focusing on the α-helical coiled coils, which are ubiquitous protein-structure and protein–protein interaction motifs, we present a suite of computational resources designed for analyzing these assemblies.
+iSOCKET enables interactive analysis of side-chain packing within proteins to identify coiled coils automatically and with considerable user control.
+Applying a graph theory-based Atlas classification scheme to structures identified by iSOCKET gives the Atlas of Coiled Coils, a fully automated, updated overview of extant coiled coils.
+The utility of this approach is illustrated with the first formal classification of an emerging subclass of coiled coils called α-helical barrels.
+Furthermore, in the Atlas, the known coiled-coil universe is presented alongside a partial enumeration of the ‘dark matter’ of coiled-coil structures; i.e.
+those coiled-coil architectures that are theoretically possible but have not been observed to date, and thus present defined targets for protein design.
+AVAILABILITY AND IMPLEMENTATION: iSOCKET is available as part of the open-source GitHub repository associated with this work (https://github.com/woolfson-group/isocket).
+BACKGROUND: Human Bocavirus (HBoV) is an emerging virus discovered in 2005 from individuals suffering gastroenteritis and respiratory tract infections.
+This review reports on HBoV studies in individuals with acute gastroenteritis, with and without respiratory tract infections in Africa between 2005 and 2016.
+MATERIAL AND METHOD: The search engines of PubMed, Google Scholar, and Embase database for published articles of HBoV were used to obtain data between 2005 and 2016.
+The search words included were as follows: studies performed in Africa or/other developing countries or/worldwide; studies for the detection of HBoV in patients with/without diarrhea and respiratory tract infection; studies using standardized laboratory techniques for detection.
+RESULTS: The search yielded a total of 756 publications with 70 studies meeting the inclusion criteria.
+Therefore, surveillance of individuals suffering from infections in Africa is required to monitor the prevalence of HBoV and help understand the role of HBoV in individuals suffering from gastroenteritis with/without respiratory tract infection.
+It has been reported that single-nucleotide polymorphisms (SNPs) in Aurora kinase A (AURKA) or Aurora kinase B (AURKB) are associated with the risk and survival of several cancers.
+MATERIALS AND METHODS: In this study, we investigated the association between polymorphisms in AURKA or AURKB gene and prognosis of TNBC patients treated with taxane-based adjuvant chemotherapy.
+RESULTS: We found that AURKA rs6099128 GG genotype carriers had significantly worse overall survival (OS) than TT+ TG genotype carriers (P = 0.003, HR = 12.499, 95% CI = 2.357–66.298).
+AURKB rs11651993 TT genotype carriers had better disease-free survival (DFS) than TC + CC genotype carriers (P = 0.018, HR = 1.876, 95% CI = 1.116–3.154).
+AURKB rs2289590 CC genotype carriers had worse DFS than CA + AA genotype carriers (P = 0.021, HR = 0.536, 95% CI = 0.315–0.912).
+After subgroup analysis, rs11651993 TC + CC genotype predicted worse DFS in subgroups of age ≤ 50, post-menopausal, grade unknown (UK), tumor size >2 cm, and lymph node negative.
+Rs2289590 CA + AA genotype could predict favorable DFS in pre-menopausal, grade 3 and lymph node-positive patients.
+CONCLUSION: We first demonstrated that polymorphisms in AURKA or AURKB gene might predict the OS or DFS of TNBC patients treated with taxane-based adjuvant chemotherapy.
+Camels have cultural value in the Arab society and are considered one of the most important animals in the Arabian Peninsula and arid environments, due to the distinct characteristics of their meat and milk.
+Therefore, treatment of elite animals, increasing the number of camels as well as genetic improvement is an essential demand.
+Because there are unique camels for milk production, meat, or in racing, the need to propagate genetically superior camels is urgent.
+Recent biotechnological approaches such as stem cells hold great promise for biomedical research, genetic engineering, and as a model for studying early mammalian developmental biology.
+Establishment of stem cells lines from camels would tremendously facilitate regenerative medicine for genetically superior camels, permit the gene targeting of the camel genome and the generation of genetically modified animal and be a mean for genome conservation for the elite breeds.
+In this mini-review, we show the current research, future horizons and potential applications for camel stem cells.
+In the context of respiratory disease, chronic obstructive pulmonary disease (COPD) is the leading cause of mortality worldwide.
+Despite much development in the area of drug development, currently there are no effective medicines available for the treatment of this disease.
+An imbalance in the protease: Antiprotease ratio in the COPD lung remains an important aspect of COPD pathophysiology and several studies have shown the efficacy of antiprotease therapy in both in vitro and in vivo COPD models.
+However more in-depth studies will be required to validate the efficacy of lead drug molecules targeting these proteases.
+This review discusses the current status of protease-directed drugs used for treating COPD and explores the future prospects of utilizing the potential of antiprotease-based therapeutics as a treatment for this disease.
+Glycoproteins are major players in the mucus protective barrier in the gastrointestinal and other mucosal surfaces.
+They are characterized by their high carbohydrate content, present in their variable number, tandem repeat domains.
+Throughout evolution the mucins have been maintained as integral components of the mucosal barrier, emphasizing their essential biological status.
+The glycosylation of the mucins is achieved through a series of biosynthetic pathways processes, which generate the wide range of glycans found in these molecules.
+The enteric microbiota interacts with the mucosal mucus barrier in a variety of ways in order to fulfill its many normal processes.
+How bacteria read the glycocode and link to normal and pathological processes is outlined in the review.
+The discovery of new antivirals is a good approach to control new outbreaks that cause such death.
+In this study, we tested the antiviral activity against Measles virus (MeV) of Polyphenol-rich extracts (PPs) coming from five seaweeds collected and cultivated in Mexico.
+An MTT assay was performed to determine cytotoxicity effect, and antiviral activity was measured by syncytia reduction assay and confirmed by qPCR.
+PPs from Ecklonia arborea (formerly Eisenia arborea, Phaeophyceae) and Solieria filiformis (Rhodophyta) showed the highest Selectivity Index (SI), >3750 and >576.9 respectively.
+Both PPs extracts were selected to the subsequent experiments owing to their high efficacy and low cytotoxicity compared with ribavirin (SI of 11.57).
+The combinational effect of PPs with sulphated polysaccharides (SPs) and ribavirin were calculated by using Compusyn software.
+Synergistic activity was observed by combining both PPs with low concentrations of Solieria filiformis SPs (0.01 µg/mL).
+Virucidal assay, time of addition, and viral penetration evaluations suggested that PPs act mainly by inactivating the viral particle.
+To our knowledge, this is the first report of the virucidal effect of Polyphenol-rich extracts of seaweeds.
+Background: Plants and their derived natural compounds possess various biological and therapeutic properties, which turns them into an increasing topic of interest and research.
+Juniperus genus is diverse in species, with several traditional medicines reported, and rich in natural compounds with potential for development of new drugs.
+Methods: The research for this review were based in the Scopus and Web of Science databases using terms combining Juniperus, secondary metabolites names, and biological activities.
+This is not an exhaustive review of Juniperus compounds with biological activities, but rather a critical selection taking into account the following criteria: (i) studies involving the most recent methodologies for quantitative evaluation of biological activities; and (ii) the compounds with the highest number of studies published in the last four years.
+Results: From Juniperus species, several diterpenes, flavonoids, and one lignan were emphasized taking into account their level of activity against several targets.
+Antitumor activity is by far the most studied, being followed by antibacterial and antiviral activities.
+Conclusions: This review demonstrates the Juniperus species value as a source of secondary metabolites with relevant pharmaceutical potential.
+Background: Heparin and heparin-related sulphated carbohydrates inhibit ligand binding of the receptor for advanced glycation end products (RAGE).
+Here, we have studied the ability of heparin to inhibit homophilic interactions of RAGE in living cells and studied how heparin related structures interfere with RAGE–ligand interactions.
+Methods: Homophilic interactions of RAGE were studied with bead aggregation and living cell protein-fragment complementation assays.
+Cell surface advanced glycation end product binding to RAGE was studied using PC3 cell adhesion assay.
+Results: Homophilic binding of RAGE was mediated by V(1)- and modulated by C(2)-domain in bead aggregation assay.
+The inhibition was dependent on the level of sulfation and the length of the carbohydrate backbone.
+α-d-Glucopyranosiduronic acid (glycyrrhizin) inhibited RAGE binding to advanced glycation end products in PC3 cell adhesion and protein binding assays.
+Conclusions: Our results show that K5 polysaccharides and glycyrrhizin are promising candidates for RAGE targeting drug development.
+Selenium nanoparticles (SeNPs) attract much attention in the biomedical field and are used as carriers of drugs in current research studies.
+In this study, SeNPs were decorated by RBV, and the novel nanoparticle system was well characterized.
+Madin-Darby Canine Kidney cells were infected with H1N1 influenza virus before treatment with RBV, SeNPs, and SeNPs loaded with RBV (Se@RBV).
+METHODS AND RESULTS: MTT assay showed that Se@RBV nanoparticles protect cells during H1N1 infection in vitro.
+Intracellular localization detection revealed that Se@RBV accumulated in lysosome and escaped to cytoplasm as time elapsed.
+Expressions of proteins related to caspase-3, including cleaved poly-ADP-ribose polymerase, caspase-8, and Bax, were downregulated evidently after treatment with Se@RBV compared with the untreated infection group.
+In addition, phosphorylations of phosphorylated 38 (p38), JNK, and phosphorylated 53 (p53) were inhibited as well.
+In vivo experiments indicated that Se@RBV was found to prevent lung injury in H1N1-infected mice through hematoxylin and eosin staining.
+Tunel test of lung tissues present that DNA damage reached a high level but reduced substantially when treated with Se@RBV.
+Immunohistochemical test revealed an identical result with the in vitro experiment that activations of caspase-3 and proteins on the apoptosis pathway were restrained by Se@RBV treatment.
+CONCLUSION: Taken together, this study elaborates that Se@RBV is a novel promising agent against H1N1 influenza virus infection.
+Inflammasomes have emerged as critical innate sensors of host immune that defense against pathogen infection, metabolism syndrome, cellular stress and cancer metastasis in the liver.
+The assembly of inflammasome activates caspase-1, which promotes the maturation of interleukin-1β (IL-1β) and interleukin-18 (IL-18), and initiates pyroptotic cell death (pyroptosis).
+IL-18 exerts pleiotropic effects on hepatic NK cells, priming FasL-mediated cytotoxicity, and interferon-γ (IFN-γ)-dependent responses to prevent the development of liver diseases.
+However, considerable attention has been attracted to the pathogenic role of inflammasomes in various acute and chronic liver diseases, including viral hepatitis, nanoparticle-induced liver injury, alcoholic and non-alcoholic steatohepatitis.
+In this review, we summarize the latest advances on the physiological and pathological roles of inflammasomes for further development of inflammasome-based therapeutic strategies for human liver diseases.
+This study aims to describe the patterns of mortality in children presenting to the pediatric emergency department.
+METHODS: This was a five-year chart review of deaths in pediatric patients aged 7 days to 13 years presenting to the Tikur Anbessa Specialized Tertiary Hospital (TASTH) from January 2012 to December 2016.
+Data were collected using a pretested, structured checklist, and analyzed using the SPSS Version 20.
+Multivariate analysis by logistic regression was carried out to estimate any measures of association between variables of interest and the primary outcome of death.
+RESULTS: The proportion of pediatric emergency department (PED) deaths was 4.1% (499 patients) out of 12,240 PED presentations.
+Thirty two percent of the deaths occurred within 24 h of presentation with 6.5% of the deaths being neonates and the most common co-morbid illness was malnutrition (41.1%).
+Multivariate analysis revealed that shortness of breath [AOR=2.45, 95% CI (1.22-4.91)], late onset of signs and symptoms [AOR=3.22, 95% CI (1.34-7.73)], fever [AOR=3.17, 95% CI (1.28-7.86)], and diarrhea [AOR=3.36, 95% CI (1.69-6.67)] had significant association with early mortality.
+A delay in presentation of more than 48 hours, diarrheal diseases and shortness of breath were significantly associated with early pediatric mortality.
+Human cytomegalovirus (HCMV) infects most of the population worldwide, persisting throughout the host's life in a latent state with periodic episodes of reactivation.
+While typically asymptomatic, HCMV can cause fatal disease among congenitally infected infants and immunocompromised patients.
+These clinical issues are compounded by the emergence of antiviral resistance and the absence of an effective vaccine, the development of which is likely complicated by the numerous immune evasins encoded by HCMV to counter the host's adaptive immune responses, a feature that facilitates frequent super-infections.
+Understanding the evolutionary dynamics of HCMV is essential for the development of effective new drugs and vaccines.
+By comparing viral genomes from uncultivated or low-passaged clinical samples of diverse origins, we observe evidence of frequent homologous recombination events, both recent and ancient, and no structure of HCMV genetic diversity at the whole-genome scale.
+Analysis of individual gene-scale loci reveals a striking dichotomy: while most of the genome is highly conserved, recombines essentially freely and has evolved under purifying selection, 21 genes display extreme diversity, structured into distinct genotypes that do not recombine with each other.
+Most of these hyper-variable genes encode glycoproteins involved in cell entry or escape of host immunity.
+Evidence that half of them have diverged through episodes of intense positive selection suggests that rapid evolution of hyper-variable loci is likely driven by interactions with host immunity.
+It appears that this process is enabled by recombination unlinking hyper-variable loci from strongly constrained neighboring sites.
+It is conceivable that viral mechanisms facilitating super-infection have evolved to promote recombination between diverged genotypes, allowing the virus to continuously diversify at key loci to escape immune detection, while maintaining a genome optimally adapted to its asymptomatic infectious lifecycle.
+Early growth response gene-1 (EGR1) is a multifunctional transcription factor that is implicated in viral infection.
+In this study, we observed that foot-and-mouth disease virus (FMDV) infection significantly triggered EGR1 expression.
+Overexpression of EGR1 suppressed FMDV replication in porcine cells, and knockdown of EGR1 considerably promoted FMDV replication.
+A previously reported FMDV mutant virus (with two amino acids mutations in SAP domain) that displays a strong type I interferon (IFN) induction activity was used in this study.
+We found that SAP mutant FMDV infection induced a higher expression of EGR1 than wildtype FMDV infection, and also triggered higher IFN-β and IFN-stimulated genes (ISGs) expression than wildtype FMDV infection.
+Further study showed that overexpression of EGR1 resulted in Sendai virus (SeV)-induced IFN-stimulated response element (ISRE) and NF-κB promoter activation.
+EGR1 upregulation promoted type I IFN signaling activation and suppressed FMDV and Seneca Valley virus replication.
+Suppression of the transcriptional activity of EGR1 did not affect its antiviral effect against FMDV.
+This study reveals a new mechanism evolved by EGR1 to enhance type I IFN signaling and suppress FMDV replication.
+In this study, we report that human plantar fascia consists of two distinct tissues with differential structural properties.
+The mechanobiological responses of these two plantar fascia stem cells also differ in terms of expression of collagen I and IV, non-ligament-related genes, and proinflammatory genes.
+The production of inflammatory agents (prostaglandin E(2), interleukin-6) and matrix degradative enzymes (matrix metalloproteinase-1, matrix metalloproteinase-2) are also different between the two types of plantar fascia stem cells.
+Based on the findings from this study, we suggest that plantar fasciitis results from the aberrant mechanobiological responses of the stem cells from plantar fascia sheath and core tissues.
+Our findings may also be used to devise tissue engineering approaches to treat plantar fascia injury effectively.
+The cellular dispersion and therapeutic control of glioblastoma, the most aggressive type of primary brain cancer, depends critically on the migration patterns after surgery and intracellular responses of the individual cancer cells in response to external biochemical cues in the microenvironment.
+Recent studies have shown that miR-451 regulates downstream molecules including AMPK/CAB39/MARK and mTOR to determine the balance between rapid proliferation and invasion in response to metabolic stress in the harsh tumor microenvironment.
+Surgical removal of the main tumor is inevitably followed by recurrence of the tumor due to inaccessibility of dispersed tumor cells in normal brain tissue.
+In order to address this complex process of cell proliferation and invasion and its response to conventional treatment, we propose a mathematical model that analyzes the intracellular dynamics of the miR-451-AMPK- mTOR-cell cycle signaling pathway within a cell.
+The model identifies a key mechanism underlying the molecular switches between proliferative phase and migratory phase in response to metabolic stress in response to fluctuating glucose levels.
+We show how up- or down-regulation of components in these pathways affects the key cellular decision to infiltrate or proliferate in a complex microenvironment in the absence and presence of time delays and stochastic noise.
+Glycosylated chondroitin sulfate proteoglycans (CSPGs), a major component of the extracellular matrix (ECM) in the brain, contribute to the physical structure of the local brain microenvironment but also induce or inhibit glioma invasion by regulating the dynamics of the CSPG receptor LAR as well as the spatiotemporal activation status of resident astrocytes and tumor-associated microglia.
+Using a multi-scale mathematical model, we investigate a CSPG-induced switch between invasive and non-invasive tumors through the coordination of ECM-cell adhesion and dynamic changes in stromal cells.
+We show that the CSPG-rich microenvironment is associated with non-invasive tumor lesions through LAR-CSGAG binding while the absence of glycosylated CSPGs induce the critical glioma invasion.
+We illustrate how high molecular weight CSPGs can regulate the exodus of local reactive astrocytes from the main tumor lesion, leading to encapsulation of non-invasive tumor and inhibition of tumor invasion.
+The complex distribution of CSPGs in the tumor microenvironment can determine the nonlinear invasion behaviors of glioma cells, which suggests the need for careful therapeutic strategies.
+BACKGROUND: It is not unusual for systemic diseases to mimic sepsis and, in any case, the clinician should thoroughly investigate this possibility.
+CASE PRESENTATION: We present the case of a 21-year-old Greek woman who presented to the Intensive Care Unit of our hospital with severe septic shock – multiple organ failure as a result of a suspected gynecological infection of the ovaries.
+An immediate improvement of her clinical condition in combination with strong clinical suspicion and negative cultures led to the differential diagnosis of diseases other than sepsis.
+Based on the results of the biopsies that were obtained by research laparotomy, our patient suffered from primary Burkitt ovarian lymphoma.
+Chemotherapy is the dominant treatment for Burkitt’s lymphoma, while surgery or radiotherapy has no place.
+CONCLUSIONS: All intensivists should be aware of clinical conditions that mimic sepsis as early diagnosis can lead to appropriate therapy and avoid unnecessary diagnostic tests and antibiotic abuse.
+BACKGROUND: Mathematical models are increasingly being used to evaluate strategies aiming to achieve the control or elimination of parasitic diseases.
+Recently, owing to growing realization that process-oriented models are useful for ecological forecasts only if the biological processes are well defined, attention has focused on data assimilation as a means to improve the predictive performance of these models.
+METHODOLOGY AND PRINCIPAL FINDINGS: We report on the development of an analytical framework to quantify the relative values of various longitudinal infection surveillance data collected in field sites undergoing mass drug administrations (MDAs) for calibrating three lymphatic filariasis (LF) models (EPIFIL, LYMFASIM, and TRANSFIL), and for improving their predictions of the required durations of drug interventions to achieve parasite elimination in endemic populations.
+The relative information contribution of site-specific data collected at the time points proposed by the WHO monitoring framework was evaluated using model-data updating procedures, and via calculations of the Shannon information index and weighted variances from the probability distributions of the estimated timelines to parasite extinction made by each model.
+Results show that data-informed models provided more precise forecasts of elimination timelines in each site compared to model-only simulations.
+Data streams that included year 5 post-MDA microfilariae (mf) survey data, however, reduced each model’s uncertainty most compared to data streams containing only baseline and/or post-MDA 3 or longer-term mf survey data irrespective of MDA coverage, suggesting that data up to this monitoring point may be optimal for informing the present LF models.
+We show that the improvements observed in the predictive performance of the best data-informed models may be a function of temporal changes in inter-parameter interactions.
+Such best data-informed models may also produce more accurate predictions of the durations of drug interventions required to achieve parasite elimination.
+SIGNIFICANCE: Knowledge of relative information contributions of model only versus data-informed models is valuable for improving the usefulness of LF model predictions in management decision making, learning system dynamics, and for supporting the design of parasite monitoring programmes.
+The present results further pinpoint the crucial need for longitudinal infection surveillance data for enhancing the precision and accuracy of model predictions of the intervention durations required to achieve parasite elimination in an endemic location.
+Monitoring of transmissions of individuals from different age groups could offer information that would be valuable for planning adequate disease control strategies.
+We compared the age-specific effective reproductive numbers (R) of measles during 2009–2016 in Guangdong, China.
+METHODS: We estimated the age-specific R values for 7 age groups: 0–8 months, 9–18 months, 19 months to 6 years, 7–15 years, 16–25 years, 26–45 years, and ≥46 years adapting the contact matrix of China.
+The daily numbers of laboratory and clinically confirmed cases reported to the Center for Disease Control and Prevention of Guangdong were used.
+RESULTS: The peak R values of the entire population were above unity from 2012 to 2016, indicating the persistence of measles in the population.
+In general, children aged 0–6 years and adults aged 26–45 years had larger values of R when comparing with other age groups after 2012.
+While the peaks of R values for children aged 0–6 years dropped steadily after 2013, the peaks of R values for adults aged 26–45 years kept at a high range every year.
+CONCLUSIONS: Although the provincial supplementary immunization activities (SIAs) conducted in 2009 and 2010 were able to reduce the transmissions from 2009 to 2011, larger values of R for children aged 0–6 years were observed after 2012, indicating that the benefits of the SIAs were short-lived.
+In addition, the transmissions from adults aged between 26 and 45 years increased over time.
+Disease control strategies should target children and adult groups that carry high potential for measles transmission.
+Porcine circovirus 3 (PCV3) was found to be associated with reproductive disease in pigs, and since its first identification in the United States, it subsequently spread worldwide, especially in China, where it might pose a potential threat to the porcine industry.
+However, no exhaustive analysis was performed to understand its evolution in the prospect of codon usage pattern.
+PCV3 sequences were classified into two clades: PCV3a and PCV3b, confirmed by principal component analysis.
+Additionally, the degree of codon usage bias of PCV3 was slightly low as inferred from the analysis of the effective number of codons.
+The codon usage pattern was mainly affected by natural selection, but there was a co-effect of mutation pressure and dinucleotide frequency.
+Moreover, based on similarity index analysis, codon adaptation index analysis and relative codon deoptimization index analysis, we found that PCV3 might pose a potential risk to public health though with unknow pathogenicity.
+In conclusion, this work reinforces the systematic understanding of the evolution of PCV3, which was reflected by the codon usage patterns and fitness of this novel emergent virus.
+Glutathione S‒transferases (GSTs) are multifunctional enzymes that play an important role in detoxification, cellular signalling, and the stress response.
+Camelus dromedarius is well-adapted to survive in extreme desert climate and it has GSTs, for which limited information is available.
+This study investigated the structure-function and thermodynamic properties of a mu-class camel GST (CdGSTM1) at different pH.
+Conformational and thermodynamic changes during the thermal unfolding pathway of dimeric and monomeric CdGSTM1 were characterised via a thermal shift assay and dynamic multimode spectroscopy (DMS).
+The thermal shift assay based on intrinsic tryptophan fluorescence revealed that CdGSTM1 underwent a two-state unfolding pathway at pH 1.0–10.0.
+Another orthogonal technique based on far-UV CD also exhibited two-state unfolding in the dimeric and monomeric states.
+Generally, proteins tend to lose structural integrity and stability at low pH; however, monomeric CdGSTM1 at pH 2.0 was thermally more stable and unfolded with lower van't Hoff enthalpy.
+The present findings provide essential information regarding the structural, functional, and thermodynamic properties of CdGSTM1 at pH 1.0–10.0.
+Due to emergence of new variants of pathogenic micro-organisms the treatment and immunization of infectious diseases have become a great challenge in the past few years.
+In the context of vaccine development remarkable efforts have been made to develop new vaccines and also to improve the efficacy of existing vaccines against specific diseases.
+To date, some vaccines are developed from protein subunits or killed pathogens, whilst several vaccines are based on live-attenuated organisms, which carry the risk of regaining their pathogenicity under certain immunocompromised conditions.
+To avoid this, the development of risk-free effective vaccines in conjunction with adequate delivery systems are considered as an imperative need to obtain desired humoral and cell-mediated immunity against infectious diseases.
+In the last several years, the use of nanoparticle-based vaccines has received a great attention to improve vaccine efficacy, immunization strategies, and targeted delivery to achieve desired immune responses at the cellular level.
+To improve vaccine efficacy, these nanocarriers should protect the antigens from premature proteolytic degradation, facilitate antigen uptake and processing by antigen presenting cells, control release, and should be safe for human use.
+Nanocarriers composed of lipids, proteins, metals or polymers have already been used to attain some of these attributes.
+In this context, several physico-chemical properties of nanoparticles play an important role in the determination of vaccine efficacy.
+This review article focuses on the applications of nanocarrier-based vaccine formulations and the strategies used for the functionalization of nanoparticles to accomplish efficient delivery of vaccines in order to induce desired host immunity against infectious diseases.
+Zika virus (ZIKV) infection in humans has been associated with congenital malformations and other neurological disorders, such as Guillain-Barré syndrome.
+The mechanism(s) of ZIKV intrauterine transmission, the cell types involved, the most vulnerable period of pregnancy for severe outcomes from infection and other physiopathological aspects are not completely elucidated.
+In this study, we analyzed placental samples obtained at the time of delivery from a group of 24 women diagnosed with ZIKV infection during the first, second or third trimesters of pregnancy.
+Villous immaturity was the main histological finding in the placental tissues, although placentas without alterations were also frequently observed.
+Significant enhancement of the number of syncytial sprouts was observed in the placentas of women infected during the third trimester, indicating the development of placental abnormalities after ZIKV infection.
+Hyperplasia of Hofbauer cells (HCs) was also observed in these third-trimester placental tissues, and remarkably, HCs were the only ZIKV-positive fetal cells found in the placentas studied that persisted until birth, as revealed by immunohistochemical (IHC) analysis.
+Thirty-three percent of women infected during pregnancy delivered infants with congenital abnormalities, although no pattern correlating the gestational stage at infection, the IHC positivity of HCs in placental tissues and the presence of congenital malformations at birth was observed.
+Placental tissue analysis enabled us to confirm maternal ZIKV infection in cases where serum from the acute infection phase was not available, which reinforces the importance of this technique in identifying possible causal factors of birth defects.
+The results we observed in the samples from naturally infected pregnant women may contribute to the understanding of some aspects of the pathophysiology of ZIKV.
+OBJECTIVE: To characterize the transport of severely ill patients with extracorporeal respiratory or cardiovascular support.
+METHODS: A series of 18 patients in the state of São Paulo, Brazil is described.
+RESULTS: From 2011 to 2017, 18 patients aged 29 (25 - 31) years with a SAPS 3 of 84 (68 - 92) and main primary diagnosis of leptospirosis and influenza A (H1N1) virus were transported to three referral hospitals in São Paulo.
+A median distance of 39 (15 - 82) km was traveled on each rescue mission during a period of 360 (308 - 431) min.
+A median of one (0 - 2) nurse, three (2 - 3) physicians, and one (0 - 1) physical therapist was present per rescue.
+The observed complications were interruption in the energy supply to the pump in two cases (11%) and oxygen saturation < 70% in two cases.
+Among the nonsurvivors, there were two cases of brain death, two cases of multiple organ dysfunction syndrome, and one case of irreversible pulmonary fibrosis.
+CONCLUSIONS: Transportation with extracorporeal support occurred without serious complications, and the hospital survival rate was high.
+As antimicrobial signalling molecules, type III or lambda interferons (IFNλs) are critical for defence against infection by diverse pathogens, including bacteria, fungi and viruses.
+Counter-intuitively, expression of one member of the family, IFNλ4, is associated with decreased clearance of hepatitis C virus (HCV) in the human population; by contrast, a natural frameshift mutation that abrogates IFNλ4 production improves HCV clearance.
+To further understand how genetic variation between and within species affects IFNλ4 function, we screened a panel of all known extant coding variants of human IFNλ4 for their antiviral potential and identify three that substantially affect activity: P70S, L79F and K154E.
+The most notable variant was K154E, which was found in African Congo rainforest ‘Pygmy’ hunter-gatherers.
+K154E greatly enhanced in vitro activity in a range of antiviral (HCV, Zika virus, influenza virus and encephalomyocarditis virus) and gene expression assays.
+Remarkably, E154 is the ancestral residue in mammalian IFNλ4s and is extremely well conserved, yet K154 has been fixed throughout evolution of the hominid genus Homo, including Neanderthals.
+Compared to chimpanzee IFNλ4, the human orthologue had reduced activity due to amino acid K154.
+Comparison of published gene expression data from humans and chimpanzees showed that this difference in activity between K154 and E154 in IFNλ4 correlates with differences in antiviral gene expression in vivo during HCV infection.
+Mechanistically, our data show that the human-specific K154 negatively affects IFNλ4 activity through a novel means by reducing its secretion and potency.
+We thus demonstrate that attenuated activity of IFNλ4 is conserved among humans and postulate that differences in IFNλ4 activity between species contribute to distinct host-specific responses to—and outcomes of—infection, such as HCV infection.
+The driver of reduced IFNλ4 antiviral activity in humans remains unknown but likely arose between 6 million and 360,000 years ago in Africa.
+Overlapping genes in viruses maximize the coding capacity of their genomes and allow the generation of new genes without major increases in genome size.
+Despite their importance, the evolution and function of overlapping genes are often not well understood, in part due to difficulties in their detection.
+In addition, most bioinformatic approaches for the detection of overlapping genes require the comparison of multiple genome sequences that may not be available in metagenomic surveys of virus biodiversity.
+We introduce a simple new method for identifying candidate functional overlapping genes using single virus genome sequences.
+Our method uses randomization tests to estimate the expected length of open reading frames and then identifies overlapping open reading frames that significantly exceed this length and are thus predicted to be functional.
+We applied this method to 2548 reference RNA virus genomes and find that it has both high sensitivity and low false discovery for genes that overlap by at least 50 nucleotides.
+Notably, this analysis provided evidence for 29 previously undiscovered functional overlapping genes, some of which are coded in the antisense direction suggesting there are limitations in our current understanding of RNA virus replication.
+BACKGROUND: This study investigated the role and mechanism of alprostadil in acute respiratory distress syndrome (ARDS) induced by oleic acid (OA) in rats.
+MATERIAL/METHODS: Sprague-Dawley rats were randomly divided into control, OA model, and OA + Alprostadil (2.5, 5, and 10 μg/kg, respectively) groups.
+The ARDS model was induced by femoral vein injection of OA, and alprostadil was administrated immediately.
+Expressions of ACE, inflammatory mediators, apoptotic-related proteins, and proteins in the MAPKs and NF-κB signaling pathways were determined by Western blot or immunohistochemical staining.
+RESULTS: Compared with the control group, the OA model group had significantly increased W/D, lung injury score, and collagen deposition at 3 h after OA injection.
+Furthermore, we found that Alprostadil had an inhibitory effect on the phosphorylation of JNK, ERK1/2, and p38 MAPKs.
+Remarkably increased expression of ACE in the OA model group was observed, which was decreased by alprostadil.
+CONCLUSIONS: Alprostadil has a protective effect on ARDS induced by OA in rats, possibly through inhibiting apoptosis, suppressing the activation of MAPKs and NF-κB signaling pathways, and decreasing ACE protein expression.
+The implementation of the United Nations (UN) Millennium Development Goals (MDGs) and Sustainable Development Goals (SDGs) has resulted in an increased focus on developing innovative, sustainable sanitation techniques to address the demand for adequate and equitable sanitation in low-income areas.
+We used bibliometric analysis and word cluster analysis to evaluate sanitation research from 1992 to 2016 based on the Science Citation Index EXPANDED (SCI-EXPANDED) and Social Sciences Citation Index (SSCI) databases.
+Our results show that sanitation is a comprehensive field connected with multiple categories, and the increasing number of publications reflects a strong interest in this research area.
+Most of the research took place in developed countries, especially the USA, although sanitation problems are more serious in developing countries.
+Innovations in sanitation techniques may keep susceptible populations from contracting diseases caused by various kinds of contaminants and microorganisms.
+Hence, the hygienization of human excreta, resource recovery, and removal of micro-pollutants from excreta can serve as effective sustainable solutions.
+Commercialized technologies, like composting, anaerobic digestion, and storage, are reliable but still face challenges in addressing the links between the political, social, institutional, cultural, and educational aspects of sanitation.
+Innovative technologies, such as Microbial Fuel Cells (MFCs), Microbial Electrolysis Cells (MECs), and struvite precipitation, are at the TRL (Technology readiness levels) 8 level, meaning that they qualify as “actual systems completed and qualified through test and demonstration.” Solutions that take into consideration economic feasibility and all the different aspects of sanitation are required.
+There is an urgent demand for holistic solutions considering government support, social acceptability, as well as technological reliability that can be effectively adapted to local conditions.
+Infectious diseases continue to pose a significant public health burden despite the great progress achieved in their prevention and control over the last few decades.
+Our ability to disentangle the factors and mechanisms driving their propagation in space and time has dramatically advanced in recent years.
+The current era is rich in mathematical and computational tools and detailed geospatial information, including sociodemographic, geographic, and environmental data, which are essential to elucidate key drivers of infectious disease transmission from epidemiological and genetic data.
+Indeed, this paradigm shift was driven by dramatic advances in complex systems approaches along with substantial improvements in data availability and computational power.
+The burgeoning output of infectious disease spatial modeling suggests that we are close to a fully integrated approach for early epidemic detection and intervention.
+This special collection in BMC Medicine aims to bring together a broad range of quantitative investigations that improve our understanding of the spatiotemporal transmission dynamics of infectious diseases in order to mitigate their impact on the human population.
+BACKGROUND: We aimed to compare the therapeutic efficacy of prolonged macrolide (PMC), corticosteroids (CST), doxycycline (DXC), and levofloxacin (LFX) against macrolide-unresponsive Mycoplasma pneumoniae (MP) pneumonia in children and to evaluate the safety of the secondary treatment agents.
+METHODS: We retrospectively analyzed the data of patients with MP pneumonia hospitalized between January 2015 and April 2017.
+Macrolide-unresponsiveness was clinically defined with a persistent fever of ≥ 38.0°C at ≥ 72 hours after macrolide treatment.
+We compared the time to defervescence (TTD) after secondary treatment and the TTD after initial macrolide treatment in each group with adjustment using propensity score-matching analysis.
+The proportion of patients who achieved defervescence within 48 hours in CST, DXC, and LFX groups were 96.9% (31/33), 85.7% (12/14), and 83.3% (5/6), respectively.
+The TTD after initial macrolide treatment did not differ between PMC and CST groups (5.1 vs. 4.2 days, P = 0.085), PMC and DXC groups (4.9 vs. 5.7 days, P = 0.453), and PMC and LFX groups (4.4 vs. 5.0 days, P = 0.283).
+CONCLUSION: The change to secondary treatment did not show better efficacy compared to PMC in children with macrolide-unresponsive MP pneumonia.
+Surfactant protein D (SP-D) expressed in lung and kidney plays important roles in innate immunity.
+The current study uses wild type (WT), SP-D knockout (KO), and humanized SP-D transgenic (hTG, lung-specific SP-D expression) mice to study organ-specific role of SP-D in pneumonia-induced sepsis.
+After infection, KO mice showed higher injurious scores in both lung and kidney, and decreased renal function than WT and hTG mice.
+hTG mice exhibited comparable lung injury but more severe kidney injury compared to WT mice.
+Increased renal tubular apoptosis, NF-κB activation and proinflammatory cytokines in the kidney of KO mice were found when compared with WT and hTG mice.
+Furthermore, in vitro primary proximal tubular epithelial cells from KO mice showed more apoptosis with higher level of activated caspase-3 than those from WT mice after LPS treatment.
+Collectively, SP-D attenuates AKI in the sepsis by modulating renal apoptosis, inflammation and NF-κB signaling.
+BACKGROUND: Past and present national initiatives advocate for electronic exchange of health data and emphasize interoperability.
+The critical role of public health in the context of disease surveillance was recognized with recommendations for electronic laboratory reporting (ELR).
+Many public health agencies have seen a trend towards centralization of information technology services which adds another layer of complexity to interoperability efforts.
+OBJECTIVES: The study objective was to understand the process of data exchange and its impact on the quality of data being transmitted in the context of electronic laboratory reporting to public health.
+This was conducted in context of Minnesota Electronic Disease Surveillance System (MEDSS), the public health information system for supporting infectious disease surveillance in Minnesota.
+Data Quality (DQ) dimensions by Strong et al., was chosen as the guiding framework for evaluation.
+METHODS: The process of assessing data exchange for electronic lab reporting and its impact was a mixed methods approach with qualitative data obtained through expert discussions and quantitative data obtained from queries of the MEDSS system.
+Based on these discussions, two high level categories of data exchange process which could impact data quality were identified: onboarding for electronic lab reporting and internal data exchange routing.
+This in turn comprised of ten critical steps and its impact on quality of data was identified through expert input.
+This was followed by analysis of data in MEDSS by various criteria identified by the informatics team.
+RESULTS: All DQ metrics (Intrinsic DQ, Contextual DQ, Representational DQ, and Accessibility DQ) were impacted in the data exchange process with varying influence on DQ dimensions.
+Some errors such as improper mapping in electronic health records (EHRs) and laboratory information systems had a cascading effect and can pass through technical filters and go undetected till use of data by epidemiologists.
+Some DQ dimensions such as accuracy, relevancy, value-added data and interpretability are more dependent on users at either end of the data exchange spectrum, the relevant clinical groups and the public health program professionals.
+The study revealed that data quality is dynamic and on-going oversight is a combined effort by MEDSS Informatics team and review by technical and public health program professionals.
+CONCLUSION: With increasing electronic reporting to public health, there is a need to understand the current processes for electronic exchange and their impact on quality of data.
+This study focused on electronic laboratory reporting to public health and analyzed both onboarding and internal data exchange processes.
+Insights gathered from this research can be applied to other public health reporting currently (e.g.
+Cardioviruses are members of the Picornaviridae family and infect a variety of mammals, from mice to humans.
+Replication of cardioviruses produces double stranded RNA that is detected by helicases in the RIG-I-like receptor family and leads to a signaling cascade to produce type I interferon.
+Like other viruses within Picornaviridae, however, cardioviruses have evolved several mechanisms to inhibit interferon production.
+In this review, we summarize recent findings that have uncovered several proteins enabling efficient detection of cardiovirus dsRNA and discuss which cell types may be most important for interferon production in vivo.
+Additionally, we describe how cardiovirus proteins L, 3C and L(∗) disrupt interferon production and antagonize the antiviral activity of interferon effector molecules.
+OBJECTIVE: Salmonella enterica remains a major cause of food-borne disease in humans, and Salmonella Typhimurium (ST) contamination of poultry products is a worldwide problem.
+Since macrophages play an essential role in controlling Salmonella infection, the aim of this study was to evaluate the effect of glycyrrhizic acid (GA) on immune function of chicken HD11 macrophages.
+RESULTS: GA increased the internalization of both fluorescein isothiocyanate (FITC)-dextran and ST by HD11 cells and markedly decreased the intracellular survival of ST. We found that the messenger RNA (mRNA) expression of cell surface molecules (CD40, CD80, CD83, and CD197) and cytokines (IFN-γ, IL-6, and IL-10) of HD11 cells was up-regulated following GA exposure.
+The expression of iNOS and NOX-1 was induced by GA and thereby the productions of NO and H(2)O(2) in HD11 cells were enhanced.
+Notably, it was verified that nuclear factor-κB (NF-κB) and c-Jun N-terminal kinase (JNK) pathways were responsible for GA-induced synthesis of NO and IFN-γ gene expression.
+CONCLUSIONS: Taken together, these results suggested that GA exhibits a potent immune regulatory effect to activate chicken macrophages and enhances Salmonella-killing capacity.
+ELECTRONIC SUPPLEMENTARY MATERIAL: Supplementary material is available for this article at 10.1631/jzus.B1700506 and is accessible for authorized users.
+Overlapping genes represent a fascinating evolutionary puzzle, since they encode two functionally unrelated proteins from the same DNA sequence.
+They originate by a mechanism of overprinting, in which point mutations in an existing frame allow the expression (the "birth") of a completely new protein from a second frame.
+In viruses, in which overlapping genes are abundant, these new proteins often play a critical role in infection, yet they are frequently overlooked during genome annotation.
+This results in erroneous interpretation of mutational studies and in a significant waste of resources.
+Therefore, overlapping genes need to be correctly detected, especially since they are now thought to be abundant also in eukaryotes.
+Developing better detection methods and conducting systematic evolutionary studies require a large, reliable benchmark dataset of known cases.
+We thus assembled a high-quality dataset of 80 viral overlapping genes whose expression is experimentally proven.
+We found that overall, overlapping genes differ significantly from non-overlapping genes in their nucleotide and amino acid composition.
+In particular, the proteins they encode are enriched in high-degeneracy amino acids and depleted in low-degeneracy ones, which may alleviate the evolutionary constraints acting on overlapping genes.
+Principal component analysis revealed that the vast majority of overlapping genes follow a similar composition bias, despite their heterogeneity in length and function.
+We propose that this apparently near-universal composition bias may either favour the birth of overlapping genes, or/and result from selection pressure acting on them.
+Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) has been reported to mediate both tumorigenic and anti-tumor effects in vivo.
+Blockade of the CEACAM1 signaling pathway has recently been implicated as a novel mechanism for cancer immunotherapy.
+CC1, a mouse anti-CEACAM1 monoclonal antibody (mAb), has been widely used as a pharmacological tool in preclinical studies to inform on CEACAM1 pathway biology although limited data are available on its CEACAM1 blocking characteristics or pharmacodynamic-pharmacokinetic profiles.
+We sought to investigate CEACAM1 expression on mouse tumor and immune cells, characterize CC1 mAb binding, and evaluate CC1 in syngeneic mouse oncology models as a monotherapy and in combination with an anti-PD-1 mAb.
+CEACAM1 expression was observed at high levels on neutrophils, NK cells and myeloid-derived suppressor cells (MDSCs), while the expression on tumor-infiltrating CD8+ T cells was low.
+No anti-tumor effects were observed in CT26, MBT2 or A20 models when tested up to 30 mg/kg dose, a dose that was estimated to achieve >90% target engagement in vivo.
+Taken together, tumor infiltrating CD8+ T cells express low levels of CEACAM1 and CC1 Ab mediates no or minimal anti-tumor effects in vivo, as a monotherapy or in combination with anti-PD-1 treatment.
+Given variable rates of vaccine efficacy and antiviral resistance, alternative strategies are urgently required to improve disease outcomes.
+Here we describe the use of HiSeq deep sequencing to analyze host gene expression in primary human alveolar epithelial type II cells infected with highly pathogenic avian influenza H5N1 virus.
+At 24 hours post-infection, 623 host genes were significantly upregulated, including the cell adhesion molecule CEACAM1.
+H5N1 virus infection stimulated significantly higher CEACAM1 protein expression when compared to influenza A PR8 (H1N1) virus, suggesting a key role for CEACAM1 in influenza virus pathogenicity.
+Furthermore, silencing of endogenous CEACAM1 resulted in reduced levels of proinflammatory cytokine/chemokine production, as well as reduced levels of virus replication following H5N1 infection.
+Our study provides evidence for the involvement of CEACAM1 in a clinically relevant model of H5N1 infection and may assist in the development of host-oriented antiviral strategies.
+The spreading of epidemics is very much determined by the structure of the contact network, which may be impacted by the mobility dynamics of the individuals themselves.
+In confined scenarios where a small, closed population spends most of its time in localized environments and has easily identifiable mobility patterns—such as workplaces, university campuses, or schools—it is of critical importance to identify the factors controlling the rate of disease spread.
+Here, we present a discrete-time, metapopulation-based model to describe the transmission of susceptible-infected-susceptible-like diseases that take place in confined scenarios where the mobilities of the individuals are not random but, rather, follow clear recurrent travel patterns.
+This model allows analytical determination of the onset of epidemics, as well as the ability to discern which contact structures are most suited to prevent the infection to spread.
+It thereby determines whether common prevention mechanisms, as isolation, are worth implementing in such a scenario and their expected impact.
+BACKGROUND: It is a challenge in low-resource settings to ensure the availability of complete, timely disease surveillance information.
+METHODS: The Central African Republic (CAR) Ministry of Health and Médecins Sans Frontières (MSF) conducted a 15-week pilot project to test a disease surveillance app, Argus, for 20 conditions in 21 health centers in Mambéré Kadéi district (MK 2016).
+Results were compared to the usual paper-based surveillance in MK the year prior (MK 2015) and simultaneously in an adjacent health district, Nana-Mambére (NM 2016).
+Wilcoxon rank sum and Kaplan-Meier analyses compared report completeness and timeliness; the cost of the app, and users’ perceptions of its usability were assessed.
+RESULTS: Two hundred seventy-one weekly reports sent by app identified 3403 cases and 63 deaths; 15 alerts identified 28 cases and 4 deaths.
+Median completeness (IQR) for MK 2016, 81% (81–86%), was significantly higher than in MK 2015 (31% (24–36%)), and NM 2016 (52% (48–57)) (p < 0.01).
+Median timeliness (IQR) for MK 2016, 50% (39–57%) was also higher than in MK 2015, 19% (19–24%), and NM 2016 29% (24–36%) (p < 0.01).
+Kaplan-Meier Survival Analysis showed a significant progressive reduction in the time taken to transmit reports over the 15-week period (p < 0.01).
+It is estimated that to maintain the app in the 21 health facilities of MK will cost approximately US$18,800 in communication fees per year.
+CONCLUSIONS: The app-based data transmission system more than doubled the completeness and timeliness of disease surveillance reports.
+This simple, low-cost intervention may permit the early detection of disease outbreaks in similar low-resource settings elsewhere.
+Human papillomaviruses (HPVs) are a group of circular double-stranded DNA viruses, showing severe tropism to mucosal tissues.
+A subset of HPVs, especially HPV16 and 18, are the primary etiological cause for several epithelial cell malignancies, causing about 5.2% of all cancers worldwide.
+Due to the high prevalence and mortality, HPV-associated cancers have remained as a significant health problem in human society, making an urgent need to develop an effective therapeutic vaccine against them.
+Achieving this goal is primarily dependent on the identification of efficient tumor-associated epitopes, inducing a robust cell-mediated immune response.
+Previous information has shown that E5, E6, and E7 early proteins are responsible for the induction and maintenance of HPV-associated cancers.
+Therefore, the prediction of major histocompatibility complex (MHC) class I T cell epitopes of HPV16, 18, 31 and 45 oncoproteins was targeted in this study.
+For this purpose, a two-step plan was designed to identify the most probable CD8+ T cell epitopes.
+In the first step, MHC-I and II binding, MHC-I processing, MHC-I population coverage and MHC-I immunogenicity prediction analyses, and in the second step, MHC-I and II protein-peptide docking, epitope conservation, and cross-reactivity with host antigens’ analyses were carried out successively by different tools.
+Finally, we introduced five probable CD8+ T cell epitopes for each oncoprotein of the HPV genotypes (60 epitopes in total), which obtained better scores by an integrated approach.
+These predicted epitopes are valuable candidates for in vitro or in vivo therapeutic vaccine studies against the HPV-associated cancers.
+Additionally, this two-step plan that each step includes several analyses to find appropriate epitopes provides a rational basis for DNA- or peptide-based vaccine development.
+However, a significant subset of patient’s progress to nonalcoholic steatohepatitis (NASH) that is defined by the presence of steatosis, inflammation and hepatocyte injury with fibrosis.
+Unfortunately, there are no approved therapies for NAFLD or NASH and therefore therapeutic approaches are urgently needed.
+Niclosamide is an U.S. Food and Drug Administration (FDA)-approved anthelmintic drug that mediates its effect by uncoupling oxidative phosphorylation.
+Niclosamide and its salt forms, Niclosamide Ethanolamine (NEN), and Niclosamide Piperazine (NPP) have shown efficacy in murine models of diet induced obesity characterized by attenuation of the prominent fatty liver disease phenotype and improved glucose metabolism.
+While the exact mechanism(s) underlying these changes remains unclear, the ability to uncouple oxidative phosphorylation leading to increased energy expenditure and lipid metabolism or attenuation of PKA mediated glucagon signaling in the liver have been proposed.
+This, in addition to mitochondrial uncoupling activity and potential genotoxicity have reduced enthusiasm for its clinical use.
+More recently, salt forms of niclosamide, NEN and NPP, have demonstrated improved oral bioavailability while retaining activity.
+This suggests that development of safer more effective niclosamide derivatives for the treatment of NAFLD and Type 2 Diabetes may be possible.
+Herein we explored the ability of a series of N-substituted phenylbenzamide derivatives of the niclosamide salicylanilide chemotype to attenuate hepatic steatosis using a novel phenotypic in vitro model of fatty liver and the high fat diet-fed mouse model of diet induced obesity.
+These studies identified novel compounds with improved pre-clinical properties that attenuate hepatic steatosis in vitro and in vivo.
+These compounds with improved drug properties may be useful in alleviating symptoms and protection against disease progression in patients with metabolic syndrome and NAFLD.
+Although infrequent, respiratory viral infections (RVIs) during birth hospitalization have a significant impact on short- and long-term morbidity in term and preterm neonates.
+RVI have been associated with increased length of hospital stay, severe disease course, unnecessary antimicrobial exposure and nosocomial outbreaks in the neonatal intensive care unit (NICU).
+Virus transmission has been described to occur via health care professionals, parents and other visitors.
+Most at risk are infants born prematurely, due to their immature immune system and the fact that they stay in the NICU for a considerable length of time.
+A prevalence of RVIs in the NICU in symptomatic infants of 6–30% has been described, although RVIs are most probably underdiagnosed, since testing for viral pathogens is not performed routinely in symptomatic patients in many NICUs.
+Additional challenges are the wide range of clinical presentation of RVIs, their similarity to bacterial infections and the unreliable detection methods prior to the era of molecular biology based technologies.
+Reviewed viral pathogens include human rhinovirus, respiratory syncytial virus and influenza virus, and discussed literature is restricted to reports based on modern molecular biology techniques.
+Furthermore, short- and long-term consequences of RVIs in infants hospitalized in the NICU are discussed.
+BACKGROUND: Mesenchymal stem cells (MSCs) derived from bone marrow have potent stabilizing effects for the treatment of acute respiratory distress syndrome (ARDS).
+However, low efficiency and survival in MSC homing to injured lung tissue remains to be solved.
+Therefore, the aim of this study was to assess whether large intergenic noncoding RNA (LincRNA)-p21 promote MSC migration and survival capacity through hypoxic preconditioning in vitro.
+METHODS: MSCs were cultured and divided into the normoxia culture group (20% O2) and hypoxia culture group (1% O2).
+To determine roles and mechanisms, lentivirus vector-mediated LincRNA-p21 knockdown of MSCs and hypoxia-inducible factor (HIF-1α) inhibitor KC7F2 were introduced.
+Moreover, LincRNA-p21 and HIF-1α mRNA was measured by reverse transcription-polymerase chain reaction, and HIF-1α and CXCR4/7 protein were assayed by western blot (WB) or enzyme-linked immunosorbent assay (ELISA).
+MSCs induced by hypoxic preconditioning evoked an increase in expression of LincRNA-p21, HIF-1α, and CXCR4/7(both were chemokine stromal-derived factor-1(SDF-1) receptors).
+Contrarily, blockade of LincRNA-p21 by shRNA and HIF-1α inhibitor KC7F2 abrogated upregulation of hypoxic preconditioning induced CXCR4/7 in MSCs, cell migration, and survival.
+Furthermore, co-immunoprecipitation assay revealed that hypoxic preconditioning isolated VHL and HIF-1α protein by increasing HIF-1α expression.
+CONCLUSIONS: Hypoxic preconditioning was identified as a promoting factor of MSC migration and survival capacity.
+LincRNA-p21 promotes MSC migration and survival capacity through HIF-1α/CXCR4 and CXCR7 pathway under hypoxic preconditioning in vitro.
+Recent studies of viral transmission have used genome sequence data to evaluate the number of particles transmitted between hosts, and the role of selection as it operates during the transmission process.
+We here present a novel and comprehensive framework for using short-read sequence data to understand viral transmission events, designed for influenza virus, but adaptable to other viral species.
+Our approach solves multiple shortcomings of previous methods for this purpose; for example, we consider transmission as an event involving whole viruses, rather than sets of independent alleles.
+We demonstrate how selection during transmission and noisy sequence data may each affect naive inferences of the population bottleneck, accounting for these in our framework so as to achieve a correct inference.
+We identify circumstances in which selection for increased viral transmission may or may not be identified from data.
+Applying our method to experimental data in which transmission occurs in the presence of strong selection, we show that our framework grants a more quantitative insight into transmission events than previous approaches, inferring the bottleneck in a manner that accounts for selection, both for within-host virulence, and for inherent viral transmissibility.
+Our work provides new opportunities for studying transmission processes in influenza, and by extension, in other infectious diseases.
+In the United States, more than 3,00,000 patients are admitted and about 20,000 die from acute pancreatitis per year.
+In Taiwan, the incidence rate of acute pancreatitis is 0.03% and the mortality rate among severe acute pancreatitis is 16.3%.
+The aim of the study was to evaluate the impact of the global budgeting system on health service utilization, health care expenditures, and quality of care among patients with acute pancreatitis in Taiwan.
+Data on patients with acute pancreatitis diagnosed during the period 2000 and 2001 were used as baseline data, and data from 2004 and 2005 were used as post-intervention data.
+The length of stay (LOS), diagnostic costs, drug cost, therapy costs, total costs, risk of readmission within 14 days, and risk of revisiting the emergency department (ED) within 3 days of discharge before and after implementation of the global budgeting system were compared and analyzed.
+There was a significant difference in mean LOS before and after introduction of the global budget system (7.34 ± 0.22 days and 7.82 ± 0.22 days, respectively; P < .001)).
+The mean total costs before and after implementation of the global budget system were Taiwan dollars (NT$) 28,290.66 ± 1576.32 and NT$ 42,341.83 ± 2285.23, respectively.
+The mean rate of revisiting the ED within 3 days decreased from 9.9 ± 0.9% before adoption of global budgeting to 7.2 ± 0.6% after implementation of the system.
+The mean 14-day re-admission rates before and after introduction of global budgeting were 11.6 ± 1.0% and 7.9 ± 0.7%, respectively.
+CONCLUSION: The global budget system was associated with significantly longer length of stay, higher health care expenditures, and better quality of care in patients treated for acute pancreatitis.
+BACKGROUND: Fomite mediated transmission can be an important pathway causing significant disease transmission in number of settings such as schools, daycare centers, and long-term care facilities.
+The importance of these pathways relative to other transmission pathways such as direct person-person or airborne will depend on the characteristics of the particular pathogen and the venue in which transmission occurs.
+Here we analyze fomite mediated transmission through a comparative analysis across multiple pathogens and venues.
+METHODS: We developed and analyzed a compartmental model that explicitly accounts for fomite transmission by including pathogen transfer between hands and surfaces.
+We consider two sub-types of fomite-mediated transmission: direct fomite (e.g., shedding onto fomites) and hand-fomite (e.g., shedding onto hands and then contacting fomites).
+We use this model to examine three pathogens with distinct environmental characteristics (influenza, rhinovirus, and norovirus) in four venue types.
+RESULTS: Based on parameter estimates from the literature the reproductive number ([Formula: see text] ) for the fomite route for rhinovirus and norovirus is greater than 1 in nearly all venues considered, suggesting that this route can sustain transmission.
+For influenza, on the other hand, [Formula: see text] for the fomite route is smaller suggesting many conditions in which the pathway may not sustain transmission.
+Additionally, the direct fomite route is more relevant than the hand-fomite route for influenza and rhinovirus, compared to norovirus.
+The relative importance of the hand-fomite vs. direct fomite route for norovirus is strongly dependent on the fraction of pathogens initially shed to hands.
+Sensitivity analysis stresses the need for accurate measurements of environmental inactivation rates, transfer efficiencies, and pathogen shedding.
+While fomite-based interventions may be able to lower [Formula: see text] for fomites below 1 and interrupt transmission, rhinovirus and norovirus are so infectious ([Formula: see text] ) that single environmental interventions are unlikely to interrupt fomite transmission for these pathogens.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12879-018-3425-x) contains supplementary material, which is available to authorized users.
+Infection with human BK polyomavirus, a small double-stranded DNA virus, potentially results in severe complications in immunocompromised patients.
+Here, we describe the in vivo variability and evolution of the BK polyomavirus by deep sequencing.
+Our data reveal the highest genomic evolutionary rate described in double-stranded DNA viruses, i.e., 10(−3)–10(−5) substitutions per nucleotide site per year.
+High mutation rates in viruses allow their escape from immune surveillance and adaptation to new hosts.
+By combining mutational landscapes across viral genomes with in silico prediction of viral peptides, we demonstrate the presence of significantly more coding substitutions within predicted cognate HLA-C-bound viral peptides than outside.
+This finding suggests a role for HLA-C in antiviral immunity, perhaps through the action of killer cell immunoglobulin-like receptors.
+The present study provides a comprehensive view of viral evolution and immune escape in a DNA virus.
+Fatty acids (FAs) are of interest to the areas of food science and medicine because they are important dietary sources of fuel for animals and play important roles in many biological processes.
+The health effects of FAs are different due to the diversity of olefinic bonds in the alkyl chains including number, position and configuration.
+However, the discrimination of FAs is difficult from a chemical sensing perspective due to the lack of diversity in terms of functional groups.
+Until now, only a few chemosensors have been developed for selective sensing of FAs based on their overall shape, however they are still limited in discrimination of FAs with subtle structural differences, moreover, they cannot be used for rapid and in situ inspections.
+Herein, for the first time, we designed a test paper for in situ colorimetric inspection for FAs based on the combination of the highly selective binding of Ag(+) to olefinic bonds and Ag(+) mediated color variation of 3,3′,5,5′,-tetramethylbenzidine.
+As a result, the sensor exhibited high sensitivity and good selectivity for five FAs with subtle structural differences.
+Furthermore, our method described herein was successfully applied to monitor the structural variations of FAs and quality changes in mixture edible hot pot oils with heat treatment in time course.
+Hence, the test paper presented herein holds great potential in the inspection of fats and edible oils in food industries.
+Drug repurposing offers an expedited and economical route to develop new clinical therapeutics in comparison to traditional drug development.
+Growth-based high-throughput screening is concomitant with drug repurposing and enables rapid identification of new therapeutic uses for investigated drugs; however, this traditional method is not compatible with microorganisms with abnormal growth patterns such as Staphylococcus aureus small-colony variants (SCV).
+SCV subpopulations are auxotrophic for key compounds in biosynthetic pathways, which result in low growth rate.
+SCV formation is also associated with reduced antibiotic susceptibility, and the SCV’s ability to revert to the normal cell growth state is thought to contribute to recurrence of S. aureus infections.
+Thus, there is a critical need to identify antimicrobial agents that are potent against SCV in order to effectively treat chronic infections.
+Accordingly, here we describe adapting an adenylate kinase (AK)-based cell death reporter assay to identify members of a Food and Drug Administration (FDA)-approved drug library that display bactericidal activity against S. aureus SCV.
+Four library members, daunorubicin, ketoconazole, rifapentine, and sitafloxacin, exhibited potent SCV bactericidal activity against a stable S. aureus SCV.
+Further investigation showed that sitafloxacin was potent against methicillin-susceptible and -resistant S. aureus, as well as S. aureus within an established biofilm.
+Taken together, these results demonstrate the ability to use the AK assay to screen small-molecule libraries for SCV bactericidal agents and highlight the therapeutic potential of sitafloxacin to be repurposed to treat chronic S. aureus infections associated with SCV and/or biofilm growth states.
+IMPORTANCE Conventional antibiotics fail to successfully treat chronic osteomyelitis, endocarditis, and device-related and airway infections.
+These recurring infections are associated with the emergence of SCV, which are recalcitrant to conventional antibiotics.
+Studies have investigated antibiotic therapies to treat SCV-related infections but have had little success, emphasizing the need to identify novel antimicrobial drugs.
+An alternative strategy is drug repurposing, which could identify FDA-approved and well-characterized drugs that could have off-label utility in treating SCV.
+In this study, we adapted a high-throughput AK-based assay to identify 4 FDA-approved drugs, daunorubicin, ketoconazole, rifapentine, and sitafloxacin, which display antimicrobial activity against S. aureus SCV, suggesting an avenue for drug repurposing in order to effectively treat SCV-related infections.
+Additionally, this screening paradigm can easily be adapted for other drug/chemical libraries to identify compounds bactericidal against SCV.
+Designing novel antimicrobial peptides is a hot area of research in the field of therapeutics especially after the emergence of resistant strains against the conventional antibiotics.
+In the past number of in silico methods have been developed for predicting the antimicrobial property of the peptide containing natural residues.
+This study describes models developed for predicting the antimicrobial property of a chemically modified peptide.
+Our models have been trained, tested and evaluated on a dataset that contains 948 antimicrobial and 931 non-antimicrobial peptides, containing chemically modified and natural residues.
+Secondly, a wide range of features was computed from the structure of these peptides using software PaDEL.
+Finally, models were developed for predicting the antimicrobial potential of chemically modified peptides using a wide range of structural features of these peptides.
+Our best model based on support vector machine achieve maximum MCC of 0.84 with an accuracy of 91.62% on training dataset and MCC of 0.80 with an accuracy of 89.89% on validation dataset.
+To assist the scientific community, we have developed a web server called “AntiMPmod” which predicts the antimicrobial property of the chemically modified peptide.
+This study aimed to identify clinical characteristics, etiology, and laboratory findings in childhood Bell’s palsy, and to evaluate the efficacy of corticosteroid treatment.
+METHODS: We conducted a retrospective analysis of children under 19 years of age treated for Bell’s palsy between January 2009 and June 2017, and followed up for over 1 month.
+Patients with Bell’s palsy were divided into groups with (group 1) and without (group 2) corticosteroid treatment.
+Differences in onset age, sex, laterality, infection and vaccination history, degree of facial nerve palsy, and prognosis after treatment between the groups were analyzed.
+A total of 73 patients (73%) received corticosteroids with or without intravenous antiviral agents, and 27 (27%) received only supportive treatment.
+There was no significant difference in the severity, laboratory findings, or neuroimaging findings between the groups.
+Significant improvement was observed in 68 (93.2%) and 26 patients (96.3%) in groups 1 and 2, respectively; this rate was not significantly different between the groups (P=0.48).
+CONCLUSION: Childhood Bell’s palsy showed good prognosis with or without corticosteroid treatment; there was no difference in prognosis between treated and untreated groups.
+Tetraspanins are suggested to regulate the composition of cell membrane components and control intracellular transport, which leaves them vulnerable to utilization by pathogens such as human papillomaviruses (HPV) and cytomegaloviruses (HCMV) to facilitate host cell entry and subsequent infection.
+In this study, by means of cellular depletion, the cluster of differentiation (CD) tetraspanins CD9, CD63, and CD151 were found to reduce HPV16 infection in HeLa cells by 50 to 80%.
+Moreover, we tested recombinant proteins or peptides of specific tetraspanin domains on their effect on the most oncogenic HPV type, HPV16, and HCMV.
+We found that the C-terminal tails of CD63 and CD151 significantly inhibited infections of both HPV16 and HCMV.
+Although CD9 was newly identified as a key cellular factor for HPV16 infection, the recombinant CD9 C-terminal peptide had no effect on infection.
+Based on the determined half-maximal inhibitory concentration (IC(50)), we classified CD63 and CD151 C-terminal peptides as moderate to potent inhibitors of HPV16 infection in HeLa and HaCaT cells, and in EA.hy926, HFF (human foreskin fibroblast) cells, and HEC-LTT (human endothelial cell-large T antigen and telomerase) cells for HCMV, respectively.
+These results indicate that HPV16 and HCMV share similar cellular requirements for their entry into host cells and reveal the necessity of the cytoplasmic CD151 and CD63 C-termini in virus infections.
+Furthermore, this highlights the suitability of these peptides for functional investigation of tetraspanin domains and as inhibitors of pathogen infections.
+The recent outbreaks of Zika virus (ZIKV), its association with Guillain–Barré syndrome and fetal abnormalities, and the lack of approved vaccines and antivirals, highlight the importance of developing countermeasures to combat ZIKV disease.
+However, flavivirus infectious clones are often difficult to work with due to the toxicity of some flavivirus sequences in bacteria.
+To bypass this problem, several alternative approaches have been applied for the generation of ZIKV clones including, among others, in vitro ligation, insertions of introns and using infectious subgenomic amplicons.
+Here, we report a simple and novel DNA-launched approach based on the use of a bacterial artificial chromosome (BAC) to generate a cDNA clone of Rio Grande do Norte Natal ZIKV strain.
+The BAC clone was fully stable in bacteria and the infectious virus was efficiently recovered in Vero cells through direct delivery of the cDNA clone.
+The rescued virus yielded high titers in Vero cells and was pathogenic in a validated mouse model (A129 mice) of ZIKV infection.
+Furthermore, using this infectious clone we have generated a mutant ZIKV containing a single amino acid substitution (A175V) in the NS2A protein that presented reduced viral RNA synthesis in cell cultures, was highly attenuated in vivo and induced fully protection against a lethal challenge with ZIKV wild-type.
+This BAC approach provides a stable and reliable reverse genetic system for ZIKV that will help to identify viral determinants of virulence and facilitate the development of vaccine and therapeutic strategies.
+The high human cost of Zika virus infections and the rapid establishment of virus circulation in novel areas, including the United States, present an urgent need for countermeasures against this emerging threat.
+The development of an effective vaccine against Zika virus may be problematic because of the cross reactivity of the antibodies with other flaviviruses leading to antibody-dependent enhancement of infection.
+Moreover, rapidly replicating positive strand RNA viruses, including Zika virus, generate large spectrum of mutant genomes (quasi species) every replication round, allowing rapid selection of variants resistant to drugs targeting virus-specific proteins.
+On the other hand, viruses are ultimate cellular parasites and rely on the host metabolism for every step of their life cycle, thus presenting an opportunity to manipulate host processes as an alternative approach to suppress virus replication and spread.
+Zika and other flaviviruses critically depend on the cellular secretory pathway, which transfers proteins and membranes from the ER through the Golgi to the plasma membrane, for virion assembly, maturation and release.
+In this review, we summarize the current knowledge of interactions of Zika and similar arthropod-borne flaviviruses with the cellular secretory machinery with a special emphasis on virus-specific changes of the secretory pathway.
+Identification of the regulatory networks and effector proteins required to accommodate the trafficking of virions, which represent a highly unusual cargo for the secretory pathway, may open an attractive and virtually untapped reservoir of alternative targets for the development of superior anti-viral drugs.
+Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is a transmembrane glycoprotein that is expressed on epithelial, endothelial and immune cells.
+CEACAM1 is a differentiation antigen involved in the maintenance of epithelial polarity that is induced during hepatocyte differentiation and liver regeneration.
+CEACAM1 regulates insulin sensitivity by promoting hepatic insulin clearance, and controls liver tolerance and mucosal immunity.
+In mice, deletion or functional inactivation of CEACAM1 impairs insulin clearance and compromises metabolic homeostasis which initiates the development of obesity and hepatic steatosis and fibrosis with other features of non-alcoholic steatohepatitis, and adipogenesis in white adipose depot.
+In obstructive and inflammatory liver diseases, soluble CEACAM1 is shed into human bile where it can serve as an indicator of liver disease.
+On immune cells, CEACAM1 acts as an immune checkpoint regulator, and deletion of Ceacam1 gene in mice causes exacerbation of inflammation and hyperactivation of myeloid cells and lymphocytes.
+Hence, hepatic CEACAM1 resides at the central hub of immune and metabolic homeostasis in both humans and mice.
+This review focuses on the regulatory role of CEACAM1 in liver and biliary tract architecture in health and disease, and on its metabolic role and function as an immune checkpoint regulator of hepatic inflammation.
+Eukaryotic lysyl-tRNA synthetases (LysRS) have an N-terminal appended tRNA-interaction domain (RID) that is absent in their prokaryotic counterparts.
+The disorder-to-order transition is induced by tRNA binding and has implications on folding and subsequent assembly into multi-tRNA synthetase complexes.
+Here, we expressed and purified RID from human LysRS (hRID) in Escherichia coli and performed a detailed mutagenesis of the appended domain.
+hRID was co-purified with nucleic acids during Ni-affinity purification, and cumulative mutations on critical amino acid residues abolished RNA binding.
+Furthermore, we identified a structural ensemble between disordered and helical structures in non-RNA-binding mutants and an equilibrium shift for wild-type into the helical conformation upon RNA binding.
+Since mutations that disrupted RNA binding led to an increase in non-functional soluble aggregates, a stabilized RNA-mediated structural transition of the N-terminal appended domain may have implications on the functional organization of human LysRS and multi-tRNA synthetase complexes in vivo.
+The maintenance mechanisms of ebolaviruses in African forest ecosystems are still unknown, but indirect evidences point at the involvement of some bat species.
+The alternative hypotheses of a non-bat maintenance host or a maintenance community including, or not, several bat and other species, deserves more investigation.
+Since recent studies have revealed that several bat species have been exposed to ebolaviruses, the common denominator to these hypotheses is that within the epidemiological cycle, some bats species must be exposed to the viruses and infected by these potential alternative hosts.
+Under this constraint, and given the peculiar ecology of bats (roosting behaviour, habitat utilisation, and flight mode), we review the hosts and transmission pathways that can lead to bat exposure and infection to ebolaviruses.
+In contrast to the capacity of bats to transmit ebolaviruses and other pathogens to many hosts, our results indicate that only a limited number of hosts and pathways can lead to the transmission of ebolaviruses to bats, and that the alternative maintenance host, if it exists, must be amongst them.
+A list of these pathways is provided, along with protocols to prioritise and investigate these alternative hypotheses.
+In conclusion, taking into account the ecology of bats and their known involvement in ebolaviruses ecology drastically reduces the list of potential alternative maintenance hosts for ebolaviruses.
+Understanding the natural history of ebolaviruses is a health priority, and investigating these alternative hypotheses could complete the current effort focused on the role of bats.
+Live attenuated influenza vaccines (LAIV) have prevented morbidity and mortality associated with influenza viral infections for many years and represent the best therapeutic option to protect against influenza viral infections in humans.
+However, the development of LAIV has traditionally relied on empirical methods, such as the adaptation of viruses to replicate at low temperatures.
+These approaches require an extensive investment of time and resources before identifying potential vaccine candidates that can be safely implemented as LAIV to protect humans.
+In addition, the mechanism of attenuation of these vaccines is poorly understood in some cases.
+Importantly, LAIV are more efficacious than inactivated vaccines because their ability to mount efficient innate and adaptive humoral and cellular immune responses.
+Therefore, the design of potential LAIV based on known properties of viral proteins appears to be a highly appropriate option for the treatment of influenza viral infections.
+For that, the viral RNA synthesis machinery has been a research focus to identify key amino acid substitutions that can lead to viral attenuation and their use in safe, immunogenic, and protective LAIV.
+In this review, we discuss the potential to manipulate the influenza viral RNA-dependent RNA polymerase (RdRp) complex to generate attenuated forms of the virus that can be used as LAIV for the treatment of influenza viral infections, one of the current and most effective prophylactic options for the control of influenza in humans.
+Lack of endothelial nitric oxide causes endothelial dysfunction and circulating monocyte infiltration, contributing to systemic atheroma plaque formation in arterial territories.
+Among the different inflammatory products, macrophage-derived foam cells and smooth muscle cells synthesize matrix metalloproteinases (MMPs), playing a pivotal role in early plaque formation and enlargement.
+We found increased levels of MMP-9 and MMP-13 in human endarterectomies with advanced atherosclerosis, together with significant amounts of extracellular matrix (ECM) metalloproteinase inducer EMMPRIN.
+To test whether the absence of NO may aggravate atherosclerosis through EMMPRIN activation, double NOS3/apoE knockout (KO) mice expressed high levels of EMMPRIN in carotid plaques, suggesting that targeting extracellular matrix degradation may represent a new mechanism by which endothelial NO prevents atherosclerosis.
+Based on our previous experience, by using gadolinium-enriched paramagnetic fluorescence micellar nanoparticles conjugated with AP9 (NAP9), an EMMPRIN-specific binding peptide, magnetic resonance sequences allowed non-invasive visualization of carotid EMMPRIN in NOS3/apoE over apoE control mice, in which atheroma plaques were significantly reduced.
+Taken together, these results point to EMMPRIN as a new therapeutic target of NO-mediated protection against atherosclerosis, and NAP9 as a non-invasive molecular tool to target atherosclerosis.
+BACKGROUND: Pneumonia during pregnancy has been proven to be associated with increased maternal and fetal morbidity and mortality.
+Thus, we summarized the characteristics and pregnancy outcomes of these patients and explored the probable risk factors and predictive factors for pneumonia during pregnancy and the appropriate timing of delivery in severe pneumonia patients.
+METHODS: A retrospective cohort study was conducted with 12 patients who were diagnosed with severe pneumonia complicating pregnancy at Peking Union Medical College Hospital between January 2010 and June 2017.
+The clinical features, treatment strategies, and pregnancy outcomes were collected from medical records and telephone calls.
+The patients had a higher prevalence of anemia (50%) and preeclampsia (25%) than ordinary pregnant women.
+Elective delivery was not performed in any of the four patients in their second trimester.
+Six of the seven patients who presented after 28 weeks of gestation and had live fetuses underwent emergency deliveries.
+Preterm births (6/7) and cesarean sections (5/7) were the two leading adverse outcomes in newborns.
+CONCLUSIONS: Anemia, advanced gestational age, and preeclampsia might be associated with the severity of pneumonia.
+Chest radiographs should be taken as soon as pneumonia is highly suspected to facilitate an early diagnosis.
+High incidences of adverse fetal outcomes were observed; thus, termination of the pregnancy is recommended for patients in their third trimester when respiratory function deteriorates progressively.
+However, it might be reasonable to continue pregnancy for those in their first or second trimester.
+Sporadic amyotrophic lateral sclerosis (sALS) is the most common form of ALS, however, the molecular mechanisms underlying cellular damage and motor neuron degeneration remain elusive.
+To identify molecular signatures of sALS we performed genome-wide expression profiling in laser capture microdissection-enriched surviving motor neurons (MNs) from lumbar spinal cords of sALS patients with rostral onset and caudal progression.
+After correcting for immunological background, we discover a highly specific gene expression signature for sALS that is associated with phosphorylated TDP-43 (pTDP-43) pathology.
+Transcriptome–pathology correlation identified casein kinase 1ε (CSNK1E) mRNA as tightly correlated to levels of pTDP-43 in sALS patients.
+Enhanced crosslinking and immunoprecipitation in human sALS patient- and healthy control-derived frontal cortex, revealed that TDP-43 binds directly to and regulates the expression of CSNK1E mRNA.
+CK1E, the protein product of CSNK1E, in turn interacts with TDP-43 and promotes cytoplasmic accumulation of pTDP-43 in human stem-cell-derived MNs.
+Our framework of transcriptome–pathology correlations identifies candidate genes with relevance to novel mechanisms of neurodegeneration.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00401-018-1870-7) contains supplementary material, which is available to authorized users.
+Microglia are specialized parenchymal‐resident phagocytes of the central nervous system (CNS) that actively support, defend and modulate the neural environment.
+Dysfunctional microglial responses are thought to worsen CNS diseases; nevertheless, their impact during neuroinflammatory processes remains largely obscure.
+Here, using a combination of single‐cell RNA sequencing and multicolour flow cytometry, we comprehensively profile microglia in the brain of lipopolysaccharide (LPS)‐injected mice.
+By excluding the contribution of other immune CNS‐resident and peripheral cells, we show that microglia isolated from LPS‐injected mice display a global downregulation of their homeostatic signature together with an upregulation of inflammatory genes.
+Notably, we identify distinct microglial activated profiles under inflammatory conditions, which greatly differ from neurodegenerative disease‐associated profiles.
+These results provide insights into microglial heterogeneity and establish a resource for the identification of specific phenotypes in CNS disorders, such as neuroinflammatory and neurodegenerative diseases.
+Marek’s Disease Virus (MDV) is the causative agent of a lymphoproliferative disease, Marek’s disease (MD) in chickens.
+MD is only controlled by mass vaccination; however, immunity induced by MD vaccines is unable to prevent MDV replication and transmission.
+The herpesvirus of turkey (HVT) vaccine is one of the most widely used MD vaccines in poultry industry.
+In this study, we examined whether combining TLR-Ls with HVT can boost host immunity against MD and improve its efficacy.
+Results demonstrated that HVT alone or HVT combined with encapsulated CpG-ODN partially protected chickens from tumor incidence and reduced virus replication compared to the control group.
+However, encapsulated CpG-ODN only moderately, but not significantly, improved HVT efficacy and reduced tumor incidence from 53% to 33%.
+Further investigation of cytokine gene profiles in spleen and bursa of Fabricius revealed an inverse association between interleukin (IL)-10 and IL-18 expression and protection conferred by different treatments.
+In addition, the results of this study raise the possibility that interferon (IFN)-β and IFN-γ induced by the treatments may exert anti-viral responses against MDV replication in the bursa of Fabricius at early stage of MDV infection in chickens.
+Prevention of serious infections in pregnant mothers, newborns, and young infants through immunization during pregnancy and in early life has the potential to further reduce maternal and neonatal morbidity and mortality worldwide.
+In the past decade, research in this field has advanced substantially, from the understanding of the biology and immunology of pregnancy and early life, to the active development of several candidate vaccines, for which challenges and opportunities for global implementation are under consideration.
+Experts from academia, industry, regulatory and funding agencies, public health, and international organizations met in Brussels (Belgium) from 10 to 12 September 2017, at the 4th International Neonatal and Maternal Immunization Symposium (INMIS), to review the most relevant advances in maternal and neonatal immunization.
+The overarching focus of the conference was to identify the path forward to achieve integration of maternal and early life immunization strategies for the successful implementation of vaccines in antenatal care and pediatric programs for reduction of maternal and infant mortality worldwide.
+IMPORTANCE This report provides an overview of the proceedings of the 4th International Maternal and Neonatal Immunization Symposium, where presentations focused on the state-of-the-art research on the development and implementation of vaccines given during pregnancy for the protection of mothers and infants.
+The automated comparison of protein-ligand binding sites provides useful insights into yet unexplored site similarities.
+The search for putative off-targets and the establishment of polypharmacological effects by comparing binding sites led to promising results for numerous projects.
+Although many cavity comparison methods are available, a comprehensive analysis to guide the choice of a tool for a specific application is wanting.
+Moreover, the broad variety of binding site modeling approaches, comparison algorithms, and scoring metrics impedes this choice.
+A detailed benchmark study is the only possibility to rationalize the selection of appropriate tools for different scenarios.
+Specific evaluation data sets were developed to shed light on multiple aspects of binding site comparison.
+An assembly of all applied benchmark sets (ProSPECCTs–Protein Site Pairs for the Evaluation of Cavity Comparison Tools) is made available for the evaluation and optimization of further and still emerging methods.
+The results indicate the importance of such analyses to facilitate the choice of a methodology that complies with the requirements of a specific scientific challenge.
+A combined in silico method was developed to predict potential protein targets that are involved in cardiotoxicity induced by aconitine alkaloids and to study the quantitative structure–toxicity relationship (QSTR) of these compounds.
+For the prediction research, a Protein-Protein Interaction (PPI) network was built from the extraction of useful information about protein interactions connected with aconitine cardiotoxicity, based on nearly a decade of literature and the STRING database.
+The software Cytoscape and the PharmMapper server were utilized to screen for essential proteins in the constructed network.
+The Calcium-Calmodulin-Dependent Protein Kinase II alpha (CAMK2A) and gamma (CAMK2G) were identified as potential targets.
+To obtain a deeper insight on the relationship between the toxicity and the structure of aconitine alkaloids, the present study utilized QSAR models built in Sybyl software that possess internal robustness and external high predictions.
+The molecular dynamics simulation carried out here have demonstrated that aconitine alkaloids possess binding stability for the receptor CAMK2G.
+In conclusion, this comprehensive method will serve as a tool for following a structural modification of the aconitine alkaloids and lead to a better insight into the cardiotoxicity induced by the compounds that have similar structures to its derivatives.
+Background Countries in the southern hemisphere experienced sizable epidemics of pandemic influenza H1N1 in their winter season during May–August, 2009.
+Methods We make use of the Richards model to fit the publicly available epidemic data (confirmed cases, hospitalizations, and deaths) of six southern hemisphere countries (Argentina, Brazil, Chile, Australia, New Zealand, and South Africa) to draw useful conclusions, in terms of its reproduction numbers and outbreak turning points, regarding the new pH1N1 virus in a typical winter influenza season.
+Results The estimates for the reproduction numbers of these six countries range from a high of 1·53 (95% CI: 1·22, 1·84) for confirmed case data of Brazil to a low of 1·16 (1·09, 1·22) for pH1N1 hospitalizations in Australia.
+For each country, model fits using confirmed cases, hospitalizations, or deaths data always yield similar estimates for the reproduction number.
+Moreover, the turning points for these closely related outbreak indicators always follow the correct chronological order, i.e., case–hospitalization–death, whenever two or more of these three indicators are available.
+Conclusions The results suggest that the winter pH1N1 outbreaks in the southern hemisphere were similar to the earlier spring and later winter outbreaks in North America in its severity and transmissibility, as indicated by the reproduction numbers.
+Therefore, the current strain has not become more severe or transmissible while circulating around the globe in 2009 as some experts had cautioned.
+The results will be useful for global preparedness planning of possible tertiary waves of pH1N1 infections in the fall/winter of 2010.
+Seasonal influenza causes millions of illnesses and tens of thousands of deaths per year in the USA alone.
+While the morbidity and mortality associated with influenza is substantial each year, the timing and magnitude of epidemics are highly variable which complicates efforts to anticipate demands on the healthcare system.
+The US Centers for Disease Control and Prevention (CDC) has recognized the importance of improving influenza forecasting and hosts an annual challenge for predicting influenza-like illness (ILI) activity in the USA.
+The CDC data serve as the reference for ILI in the USA, but this information is aggregated by epidemiological week and reported after a one-week delay (and may be subject to correction even after this reporting lag).
+Therefore, there has been substantial interest in whether real-time Internet search data, such as Google, Twitter or Wikipedia could be used to improve influenza forecasting.
+In this study, we combine a previously developed calibration and prediction framework with an established humidity-based transmission dynamic model to forecast influenza.
+We then compare predictions based on only CDC ILI data with predictions that leverage the earlier availability and finer temporal resolution of Wikipedia search data.
+We find that both the earlier availability and the finer temporal resolution are important for increasing forecasting performance.
+Using daily Wikipedia search data leads to a marked improvement in prediction performance compared to weekly data especially for a three- to four-week forecasting horizon.
+Sandfly fever Sicilian virus (SFSV) is one of the most widespread and frequently identified members of the genus Phlebovirus (order Bunyavirales, family Phenuiviridae) infecting humans.
+Being transmitted by Phlebotomus sandflies, SFSV causes a self-limiting, acute, often incapacitating febrile disease (“sandfly fever,” “Pappataci fever,” or “dog disease”) that has been known since at least the beginning of the 20th century.
+We show that, similarly to other pathogenic phleboviruses, SFSV suppresses the induction of the antiviral type I interferon (IFN) system in an NSs-dependent manner.
+SFSV NSs interfered with the TBK1-interferon regulatory factor 3 (IRF3) branch of the RIG-I signaling pathway but not with NF-κB activation.
+In contrast to IRF3, neither the IFN master regulator IRF7 nor any of the related transcription factors IRF2, IRF5, and IRF9 were bound by SFSV NSs.
+In spite of this specificity for IRF3, NSs did not inhibit its phosphorylation, dimerization, or nuclear accumulation, and the interaction was independent of the IRF3 activation or multimerization state.
+In further studies, we identified the DNA-binding domain of IRF3 (amino acids 1 to 113) as sufficient for NSs binding and found that SFSV NSs prevented the association of activated IRF3 with the IFN-β promoter.
+Thus, unlike highly virulent phleboviruses, which either destroy antiviral host factors or sequester whole signaling chains into inactive aggregates, SFSV modulates type I IFN induction by directly masking the DNA-binding domain of IRF3.
+IMPORTANCE Phleboviruses are receiving increased attention due to the constant discovery of new species and the ongoing spread of long-known members of the genus.
+Outbreaks of sandfly fever were reported in the 19th century, during World War I, and during World War II.
+Currently, SFSV is recognized as one of the most widespread phleboviruses, exhibiting high seroprevalence rates in humans and domestic animals and causing a self-limiting but incapacitating disease predominantly in immunologically naive troops and travelers.
+We show how the nonstructural NSs protein of SFSV counteracts the upregulation of the antiviral interferon (IFN) system.
+SFSV NSs specifically inhibits promoter binding by IFN transcription factor 3 (IRF3), a molecular strategy which is unique among phleboviruses and, to our knowledge, among human pathogenic RNA viruses in general.
+This IRF3-specific and stoichiometric mechanism, greatly distinct from the ones exhibited by the highly virulent phleboviruses, correlates with the intermediate level of pathogenicity of SFSV.
+Background: The human bocavirus (HBoV) is known to persist latently in the infected host cells and seems to replicate its DNA via the DNA damage response system, which is frequently defect in tumors and correlates with microsatellite instability (MSI).
+Because HBoV is able to persist in the infected tissues, induces pro-fibrotic and pro- cancerogenic cytokines in vivo and in vitro, and is detected in colorectal and lung tumors, the virus may be involved in cancerogenesis at least as a cofactor.
+Recently it was shown that the adenotonsillar tissue is an important site of HBoV1 persistence and replication.
+Considering the background that approximately 60% of oropharyngeal cancers were thought to be attributable to a HPV infection, a co-participation of HBoV in terms of a chronic virus infection might play a role in the cancerogenesis of tonsil tumors.
+Positive tissue sections were afterward subjected to fluorescence in situ hybridization (FISH) analysis to identify HBoV and HPV infected cells.
+By use of an in vitro cell culture model with primary tonsil fibroblasts, keratinocytes, and lymphocytes infected by HBoV we tried to find the target cells of virus replication.
+MSI testing was based on a previously published protocol using a de-multiplexed PCR followed by fluorescent detection of PCR products in a capillary sequencing device.
+Results: In total 62 of 103 (60, 19%) of the tonsil squamous cell carcinomas tested positive for HBoV DNA and 66 of 103 (66%) samples were identified as HPV positive.
+The FISH analysis revealed both double infection of HPV and HBoV in the same cells as well as single infections of both viruses within the tumor tissue.
+Twenty-two of 62 HBoV positive tumors tested HPV negative, 40 of 62 tissue sections were HBoV and HPV positive.
+Conclusion: Our findings support the hypothesis that human bocavirus infections as a cofactor may have an impact on tumor development in tonsils, although it still remains possible that HBoV solely displays a tumor tropism.
+It has been replicated in mice and might be due to greater tolerance of infection, not greater resistance.
+statins and angiotensin receptor blockers) might change the damaging host response in adults to a more tolerant response in children.
+Treating the host response might be the only practical way to reduce global mortality during the next influenza pandemic.
+It might also help reduce mortality due to seasonal influenza and other forms of acute critical illness.
+To realize these benefits, we need laboratory and clinical studies of host response treatment before and after puberty.
+Background: Human rhinovirus (HRV) is the predominant cause of upper respiratory tract infections, resulting in a significant public health burden.
+The virus circulates as many different types (168), each generating strong homologous, but weak heterotypic, immunity.
+The influence of these features on transmission patterns of HRV in the community is understudied.
+Methods: Nasopharyngeal swabs were collected from patients with symptoms of acute respiratory infection (ARI) at nine out-patient facilities across a Health and Demographic Surveillance System between December 2015 and November 2016.
+HRV was diagnosed by real-time RT-PCR, and the VP4/VP2 genomic region of the positive samples sequenced.
+Results: Of 5,744 NPS samples collected, HRV was detected in 1057 (18.4%), of which 817 (77.3%) were successfully sequenced.
+HRV species A, B and C were identified in 360 (44.1%), 67 (8.2%) and 390 (47.7%) samples, respectively.
+In total, 87 types were determined: 39, 10 and 38 occurred within species A, B and C, respectively.
+Spatially, identical types occurred over a wide distance at similar times, but there was statistically significant evidence for clustering of types between health facilities in close proximity or linked by major road networks.
+Conclusion: This study records a high prevalence of HRV in out-patient presentations exhibiting high type diversity.
+Spatial patterns suggest either rapid spread or multiple invasions of the same type, but evidence of similar types amongst close health facilities, or along road systems, indicate type partitioning structured by local spread.
+Multipotent mesenchymal stem/stromal cells (MSCs) possess robust self-renewal characteristics and the ability to differentiate into tissue-specific cells.
+Their therapeutic potential appears promising as evident from their efficacy in several animal models of pulmonary disorders as well as early-phase clinical trials of acute respiratory distress syndrome (ARDS) and chronic obstructive pulmonary disease (COPD).
+Such therapeutic efficacy might be attributed to MSC-derived products (the “secretome”), namely conditioned media (CM) and extracellular vesicles (EVs), which have been shown to play pivotal roles in the regenerative function of MSCs.
+Importantly, the EVs secreted by MSCs can transfer a variety of bioactive factors to modulate the function of recipient cells via various mechanisms, including ligand-receptor interactions, direct membrane fusion, endocytosis, or phagocytosis.
+Herein, we review the current state-of-the-science of MSC-derived CM and EVs as potential therapeutic agents in lung diseases.
+We suggest that the MSC-derived secretome might be an appropriate therapeutic agent for treating aggressive pulmonary disorders because of biological and logistical advantages over live cell therapy.
+Nonetheless, further studies are warranted to elucidate the safety and efficacy of these components in combating pulmonary diseases.
+Typically not assisted by proofreading, the RNA-dependent RNA polymerases (RdRPs) encoded by the RNA viruses may need to independently control its fidelity to fulfill virus viability and fitness.
+However, the precise mechanism by which the RdRP maintains its optimal fidelity level remains largely elusive.
+By solving 2.1–2.5 Å resolution crystal structures of the classical swine fever virus (CSFV) NS5B, an RdRP with a unique naturally fused N-terminal domain (NTD), we identified high-resolution intra-molecular interactions between the NTD and the RdRP palm domain.
+In order to dissect possible regulatory functions of NTD, we designed mutations at residues Y471 and E472 to perturb key interactions at the NTD–RdRP interface.
+When crystallized, some of these NS5B interface mutants maintained the interface, while the others adopted an ‘open’ conformation that no longer retained the intra-molecular interactions.
+Data from multiple in vitro RdRP assays indicated that the perturbation of the NTD–RdRP interactions clearly reduced the fidelity level of the RNA synthesis, while the processivity of the NS5B elongation complex was not affected.
+Collectively, our work demonstrates an explicit and unique mode of polymerase fidelity modulation and provides a vivid example of co-evolution in multi-domain enzymes.
+Background: Chemotherapy is the main treatment for triple-negative breast cancer (TNBC), which lack molecular markers for diagnosis and therapy.
+However, the involvement of kinases in the chemoresistance in TNBC cells is not fully understood.
+Methods: We employed a kinome siRNA library to screen whether targeting any kinases could increase the chemosensitivity of TNBC cell lines.
+The effects of kinase on cell viability in various breast cancer cells were validated with ATP level and colony formation.
+The Cancer Genome Atlas (TCGA) dataset was collected to analyze the correlation of Src expression with prognosis of TNBC patients.
+Results: Primary screening and validation for the initial hits showed that Src kinase was a potential doxorubicin-resistant kinase in the TNBC cell lines MDA-MB-231 and Hs578T.
+Both siRNA against Src and the Src inhibitor dasatinib enhanced the cytotoxic effects of doxorubicin in TNBC cells.
+Moreover, phosphorylation of AKT and signal transducer and activator of transcription 3 (STAT3), downstream effectors of Src, were accordingly decreased in Src-silenced or -inhibited TNBC cells.
+Additionally, TCGA data analysis indicated that Src expression levels in tumor tissues were higher than those in tumor-adjacent normal tissues in patients with TNBC.
+High co-expression level of Src and STAT3 was also significantly correlated with poor prognosis in patients.
+Conclusion: Our results showed that Src-STAT3 axis might be involved in chemoresistance of TNBC cells.
+BACKGROUND: Despite modern intensive care with standardized strategies against acute respiratory distress syndrome (ARDS), Pneumocystis pneumonia (PcP) remains a life-threatening disease with a high mortality rate.
+Here, we analyzed a large mixed cohort of immunocompromised patients with PcP, with regard to clinical course and treatment, and aimed at identifying predictors of outcome.
+METHODS: This was a single-center retrospective analysis in a tertiary care institution across 17 years.
+RESULTS: A total of 52,364 specimens from 7504 patients were sent for microbiological assessment (3653 with clinical suspicion of Pneumocystis pneumonia).
+The remaining subjects were either solid organ transplant recipients (16.3%) or suffered from malignancy (15.8%) or autoimmune diseases (11.7%).
+Multivariable regression identified lactate dehydrogenase (LDH) as predictor of in-hospital mortality (adjusted OR 1.17 (95% CI 1.09–1.27), p < 0.0001).
+Mortality in LDH quartiles increased from 8% to 49%, and a cutoff value of 495 U/L predicted mortality with sensitivity and specificity of 70%.
+With regard to treatment, 40% of patients received trimethoprim-sulfamethoxazole at doses that were lower than recommended, and these patients had a higher mortality risk (HR 1.80 (95% CI 1.10–3.44), p = 0.02).
+Initial LDH values might serve as a stratifying tool to identify those patients at high risk of death among patients with HIV and without HIV infection.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13054-018-2221-8) contains supplementary material, which is available to authorized users.
+OBJECTIVE: To follow up the refractory juvenile dermatomyositis (JDM) with autologous hematopoietic stem cell transplantation (AHSCT) in a long time and to investigate whether AHSCT is effective and safe to treat refractory JDM.
+METHODS: We collected the AHSCT and follow-up data of three patients with refractory JDM who received autologous peripheral blood CD34+ cell transplantation in our hospital between June 2004 and July 2015.
+Those data include: hight, weight, routine blood and urine tests, ESR, CK, ALT, AST, LDH, renal functional tests, lymphocyte subpopulations, HRCT and muscle MRI.
+Twelve months after their AHSCT, all of their monitoring indexes have returned to normal and they have stopped all medications.
+CONCLUSION: Our study suggests that AHSCT is safe and effective in treating refractory JDM, and it can provides long term drug-free survival.
+Metals are a limiting resource for pathogenic bacteria and must be scavenged from host proteins.
+Hemoglobin provides the most abundant source of iron in the human body and is required by several pathogens to cause invasive disease.
+Here we show that the α- and β-globin genes exhibit strikingly parallel signatures of adaptive evolution across simian primates.
+Rapidly evolving sites in hemoglobin correspond to binding interfaces of IsdB, a bacterial hemoglobin receptor harbored by pathogenic Staphylococcus aureus.
+Using an evolution-guided experimental approach, we demonstrate that the divergence between primates and staphylococcal isolates governs hemoglobin recognition and bacterial growth.
+The reintroduction of putative adaptive mutations in α- or β-globin proteins was sufficient to impair S. aureus binding, providing a mechanism for the evolution of disease resistance.
+These findings suggest that bacterial hemoprotein capture has driven repeated evolutionary conflicts with hemoglobin during primate descent.
+Recent studies have suggested that cell factors involved in autophagy, an evolutionally conserved pathway leading to the lysosomal degradation of protein aggregates and organelles during cellular stress, also have roles in macropinocytosis.
+Here, we demonstrate that autophagy-associated proteins are required for trafficking of EBOV into the cell body.
+Depleting cells of beclin 1, autophagy-related protein 7, or microtubule-associated protein 1A/B light chain 3B (LC3B) abolished EBOV uptake, owing to a block in vesicle formation at the cell surface.
+Our work indicates that, although various forms of LC3B possess an inherent ability to associate with forming macropinosomes, LC3B-II is critical for internalization of macropinocytic vesicles and, therefore, EBOV from the cell surface.
+BACKGROUND: Ebola virus (EBOV) mainly targets myeloid cells; however, extensive death of T cells is often observed in lethal infections.
+METHODS: Using VP40-producing clones, we analyzed donor cell cycle, extracellular vesicle (EV) biogenesis, and recipient immune cell death.
+Transcription of cyclin D1 and nuclear localization of VP40 were examined via kinase and chromatin immunoprecipitation assays.
+VP40 clones were accelerated in growth due to cyclin D1 upregulation, and nuclear VP40 was found bound to the cyclin D1 promoter.
+VP40 EV contents were enriched in ribonucleic acid-binding proteins and cytokines (interleukin-15, transforming growth factor-β1, and interferon-γ).
+CONCLUSIONS: Nuclear VP40 upregulates cyclin D1 levels, resulting in dysregulated cell cycle and EV biogenesis.
+Packaging of cytokines and EBOV proteins into EVs from infected cells may be responsible for the decimation of immune cells during EBOV pathogenesis.
+BACKGROUND: For most classes of drugs, rapid development of therapeutics to treat emerging infections is challenged by the timelines needed to identify compounds with the desired efficacy, safety, and pharmacokinetic profiles.
+Fully human monoclonal antibodies (mAbs) provide an attractive method to overcome many of these hurdles to rapidly produce therapeutics for emerging diseases.
+METHODS: In this study, we deployed a platform to generate, test, and develop fully human antibodies to Zaire ebolavirus.
+We obtained specific anti-Ebola virus (EBOV) antibodies by immunizing VelocImmune mice that use human immunoglobulin variable regions in their humoral responses.
+RESULTS: Of the antibody clones isolated, 3 were selected as best at neutralizing EBOV and triggering FcγRIIIa.
+Binding studies and negative-stain electron microscopy revealed that the 3 selected antibodies bind to non-overlapping epitopes, including a potentially new protective epitope not targeted by other antibody-based treatments.
+When combined, a single dose of a cocktail of the 3 antibodies protected nonhuman primates (NHPs) from EBOV disease even after disease symptoms were apparent.
+CONCLUSIONS: This antibody cocktail provides complementary mechanisms of actions, incorporates novel specificities, and demonstrates high-level postexposure protection from lethal EBOV disease in NHPs.
+It is now undergoing testing in normal healthy volunteers in preparation for potential use in future Ebola epidemics.
+Unlike mouse and human type I IFNs (IFN-α/β), which exhibit strong species specificity, type III IFNs were reported to act in a cross-specific manner.
+We reexamined the cross-specificity and observed that mouse and human IFN-λ exhibit some species specificity, although much less than type I IFNs.
+Mouse IFN-λ3 displayed clear species specificity, being 25-fold less active in human cells than the closely related mouse IFN-λ2.
+This specificity likely depends on amino acids in α helices A and F that diverged from other IFN-λ sequences.
+We next developed a firefly luciferase-based reporter cell line, named Fawa-λ-luc, to detect IFN-λ in biological fluids with high specificity and sensitivity.
+Fawa-λ-luc cells, derived from mouse epithelial cells that are responsive to IFN-λ, were made nonresponsive to type I IFNs by inactivation of the Ifnar2 gene and strongly responsive to IFN-λ by overexpression of the mouse IFNLR1.
+This bioassay was as sensitive as a commercially available enzyme-linked immunosorbent assay in detecting mouse IFN-λ in cell culture supernatant, as well as in serum and bronchoalveolar lavage samples of virus-infected mice.
+The assay also enabled the sensitive detection of human IFN-λ activity, including that of the divergent IFN-λ4 with a bias, however, due to variable activity of IFN-λ subtypes.
+Limiting infections and providing patients with optimal drug regimens require timely strain identification as well as virulence and drug-resistance profiling.
+Additionally, prophylactic interventions based on the identification of environmental sources of recurrent infections (e.g., contaminated sinks) and reconstruction of transmission chains (i.e., who infected whom) could help to reduce the incidence of nosocomial infections.
+Some major scientific and logistical challenges need to be solved before WGS fulfils its potential in clinical microbial diagnostics.
+In this review we identify major bottlenecks that need to be resolved for WGS to routinely inform clinical intervention and discuss possible solutions.
+DNA replication stress is often defined by the slowing or stalling of replication fork progression leading to local or global DNA synthesis inhibition.
+Failure to resolve replication stress in a timely manner contribute toward cell cycle defects, genome instability and human disease; however, the mechanism for fork recovery remains poorly defined.
+Here, we show that the translesion DNA polymerase (Pol) kappa, a DinB orthologue, has a unique role in both protecting and restarting stalled replication forks under conditions of nucleotide deprivation.
+Importantly, Pol kappa-mediated DNA synthesis during hydroxyurea (HU)-dependent fork restart is regulated by both the Fanconi Anemia (FA) pathway and PCNA polyubiquitination.
+Loss of Pol kappa prevents timely rescue of stalled replication forks, leading to replication-associated genomic instability, and a p53-dependent cell cycle defect.
+Taken together, our results identify a previously unanticipated role for Pol kappa in promoting DNA synthesis and replication stress recovery at sites of stalled forks.
+Herein we describe the discovery and functional characterization of a steroidal glycosyltransferase (SGT) from Ornithogalum saundersiae and a steroidal glycoside acyltransferase (SGA) from Escherichia coli and their application in the biosynthesis of acylated steroidal glycosides (ASGs).
+OsSGT1-containing cell free extract was then used as the biocatalyst to react with 49 structurally diverse drug-like compounds.
+Unexpectedly, in an effort to identify OsSGT1, we found the bacteria lacA gene in lac operon actually encoded an SGA, specifically catalyzing the acetylations of sugar moieties of steroid 17β-glucosides.
+Finally, a novel enzymatic two-step synthesis of two ASGs, acetylated testosterone-17-O-β-glucosides (AT-17β-Gs) and acetylated estradiol-17-O-β-glucosides (AE-17β-Gs), from the abundantly available free steroids using OsSGT1 and EcSGA1 as the biocatalysts was developed.
+The two-step process is characterized by EcSGA1-catalyzed regioselective acylations of all hydroxyl groups on the sugar unit of unprotected steroidal glycosides (SGs) in the late stage, thereby significantly streamlining the synthetic route towards ASGs and thus forming four monoacylates.
+The improved cytotoxic activities of 3′-acetylated testosterone17-O-β-glucoside towards seven human tumor cell lines were thus observable.
+Type 1 regulatory CD4(+) T (Tr1) cells express high levels of the immunosuppressive cytokine IL-10 but not the master transcription factor Foxp3, and can suppress inflammation and promote immune tolerance.
+In order to identify and obtain viable Tr1 cells for research and clinical applications, co-expression of CD49b and LAG3 has been proposed as a unique surface signature for both human and mouse Tr1 cells.
+However, recent studies have revealed that this pattern of co-expression is dependent on the stimulating conditions and the differentiation stage of the CD4(+) T cells.
+Here, using an IL-10(GFP)/Foxp3(RFP) dual reporter transgenic murine model, we demonstrate that co-expression of CD49b and LAG3 is not restricted to the Foxp3(−) Tr1 cells, but is also observed in Foxp3(+) T regulatory (Treg) cells and CD8(+) T cells that produce IL-10.
+Our data indicate that IL-10-producing Tr1 cells, Treg cells and CD8(+) T cells are all capable of co-expressing LAG3 and CD49b in vitro following differentiation under IL-10-inducing conditions, and in vivo following pathogenic insult or infection in the pulmonary mucosa.
+Our findings urge caution in the use of LAG3/CD49b co-expression as sole markers to identify Tr1 cells, since it may mark IL-10-producing T cell lineages more broadly, including the Foxp3(−) Tr1 cells, Foxp3(+) Treg cells, and CD8(+) T cells.
+This has limited the use of antisense to systems where techniques have been worked out to introduce the molecules into cells, such as embryos and cell cultures.
+Uncharged antisense bearing a group of guanidinium moieties on either a linear peptide or dendrimer scaffold can enter cells by endocytosis and subsequently escape from endosomes into the cytosol/nuclear compartment of cells.
+These technologies allow systemic administration of antisense, making gene knockdowns and splice modification feasible in adult animals; this review presents examples of such animal studies.
+Techniques developed with PPMOs, which are an arginine-rich cell-penetrating peptide linked to a Morpholino oligo, can also be performed using commercially available Vivo-Morpholinos, which are eight guanidinium groups on a dendrimeric scaffold linked to a Morpholino oligo.
+Antisense-based techniques such as blocking translation, modifying pre-mRNA splicing, inhibiting miRNA maturation and inhibiting viral replication can be conveniently applied in adult animals by injecting PPMOs or Vivo-Morpholinos.
+IL-35, a relatively newly discovered cytokine belonging to the larger IL-12 family, shows unique anti-inflammatory properties, believed to be associated with dedicated receptors and signaling pathways.
+IL-35 plays a pivotal role in the development and the function of both regulatory B (Bregs) and T cells (Tregs).
+In order to further its therapeutic potential, a dairy Lactococcus lactis strain was engineered to express murine IL-35 (LL-IL35), and this recombinant strain was applied to suppress collagen-induced arthritis (CIA).
+When administered therapeutically, LL-IL35 abruptly halted CIA progression with no increase in disease severity by reducing neutrophil influx into the joints.
+LL-IL35 treatment reduced IFN-γ and IL-17 3.7- and 8.5-fold, respectively, and increased IL-10 production compared to diseased mice.
+Foxp3(+) and Foxp3(−) CD39(+) CD4(+) T cells were previously shown to be the Tregs responsible for conferring protection against CIA.
+Inquiry into their induction revealed that both CCR6(+) and CCR6(−) Foxp3(+or−) CD39(+) CD4(+) T cells act as the source of the IL-10 induced by LL-IL35.
+Thus, this study demonstrates the feasibility and benefits of engineered probiotics for treating autoimmune diseases.
+We conducted a cross-sectional study in live bird markets (LBMs) in Dhaka and Chittagong, Bangladesh, to estimate the prevalence of avian influenza A(H5) and A(H9) viruses in different types of poultry and environmental areas by using Bayesian hierarchical logistic regression models.
+Prevalence of A(H5) virus was higher in waterfowl than in chickens, whereas prevalence of A(H9) virus was higher in chickens than in waterfowl and, among chicken types, in industrial broilers than in cross-breeds and indigenous breeds.
+Prevalence of A(H9) virus in poultry and level of environmental contamination were also higher in LBMs with >1 wholesaler.
+We found a high level of circulation of both avian influenza viruses in surveyed LBMs.
+Immune checkpoints play important roles in immune regulation, and blocking immune checkpoints on the cell membrane is a promising strategy in the treatment of cancer.
+Based on this, monoclonal antibodies are having much rapid development, such as those against CTLA-4 (cytotoxic T lymphocyte antigen 4) and PD-1 (programmed cell death protein 1).But the cost of preparation of monoclonal antibodies is too high and the therapeutic effect is still under restrictions.
+Recently, a series of soluble immune checkpoints have been found such as sCTLA-4 (soluble CTLA-4) and sPD-1 (soluble PD-1).
+They are functional parts of membrane immune checkpoints produced in different ways and can be secreted by immune cells.
+Much evidence has demonstrated that these soluble checkpoints are involved in positive or negative immune regulation and that changes in their plasma levels affect the development, prognosis and treatment of cancer.
+Since they are endogenous molecules, they will not induce immunological rejection in human beings, which might make up for the deficiencies of monoclonal antibodies and enhance the utility value of these molecules.
+Therefore, there is an increasing need for investigating novel soluble checkpoints and their functions, and it is promising to develop relevant therapies in the future.
+In this review, we describe the production mechanisms and functions of various soluble immune checkpoint receptors and ligands and discuss their biological significance in regard to biomarkers, potential candidate drugs, therapeutic targets, and other topics.
+The purpose of this study was to detect porcine epidemic diarrhea virus (PEDV) subclinically infected pigs shipped from non-case farms to slaughterhouses.
+A total of 1,556 blood samples were collected from 80 case and non-case farms from pigs over 6 months old.
+Serial serum dilutions were subjected to serological examination for PEDV presence using Neutralization test (NT).
+The cut-off titer was set at titer of 1:2 dilution and farms with at least one positive sample in duplicate were classified as PED-positive farms.
+Several non-case farms (9.4%, 6/64) and 100% (16/16) of the case farms were indeed positive for PEDV.
+The proportion of seropositive animals from case farms was 63.7%, significantly different from that of non-case farms (4.3%, P<0.05).
+In both case and non-case farms, the proportion of seropositive animals in farrow-to-finish farms was significantly higher than in wean-to-finish farms (P<0.05).
+Seropositive animals in non-case farms were detected by NT in a sero-survey by sampling at slaughterhouses.
+The essential requirement of the lymphotoxin beta receptor (LTβR) in the development and maintenance of peripheral lymphoid organs is well recognized.
+Evidence shows that LTβR is involved in various cellular processes; however, whether it plays a role in maintaining the cellular function of intestinal porcine enterocytes (IPEC-J2), specifically during porcine epidemic diarrhea virus (PEDV) infection, remains unknown.
+In this study, we generated LTβR null IPEC-J2 cells using CRISPR/Cas9 to examine the importance of LTβR in cell proliferation, apoptosis, and the response to PEDV infection.
+Our results showed that the lack of LTβR leads to significantly decreased cell proliferation, potentially due to S phase arrest in LTβR(−/−) IPEC-J2 cells.
+Label-free digital holographic microscopy was used to record the three-dimensional morphology of both cell types for up to 72 hours and revealed significantly increased numbers of LTβR(−/−) cells undergoing apoptosis.
+Furthermore, we found that PEDV-infected LTβR(−/−) null IPEC-J2 cells exhibited significant suppression of nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) target genes (interleukin (IL)-6 and IL-8) and mucosal barrier integrity-related genes (vascular cell adhesion molecule 1 (VCAM1) and IL-22), which may explain why LTβR(−/−) cells are more susceptible to PEDV infection.
+Collectively, our data not only demonstrate the key role of LTβR in intestinal porcine enterocytes, but also provide data for the improved understanding of the cellular response to PEDV infection.
+In the present study, the anti-influenza A (H2N2) virus activity of patchouli alcohol was studied in vitro, in vivo and in silico.
+MTT assay showed that the inhibition by patchouli alcohol appears strongly after penetration of the virus into the cell.
+In the influenza mouse model, patchouli alcohol showed obvious protection against the viral infection at a dose of 5 mg/kg/day.
+Flexible docking and molecular dynamic simulations indicated that patchouli alcohol was bound to the neuraminidase protein of influenza virus, with an interaction energy of –40.38 kcal mol(–1).
+The invariant key active-site residues Asp151, Arg152, Glu119, Glu276 and Tyr406 played important roles during the binding process.
+Results presented here suggest that patchouli alcohol possesses anti-influenza A (H2N2) virus properties, and therefore is a potential source of anti-influenza agents for the pharmaceutical industry.
+Usb1 is an exoribonuclease that shortens the oligo-uridine tail of U6 snRNA, resulting in a terminal 2′,3′ cyclic phosphate group in most eukaryotes, including humans.
+Loss of function mutations in human Usb1 cause the rare disorder poikiloderma with neutropenia (PN), and result in U6 snRNAs with elongated 3′ ends that are aberrantly adenylated.
+Here, we show that human Usb1 removes 3′ adenosines with 20-fold greater efficiency than uridines, which explains the presence of adenylated U6 snRNAs in cells lacking Usb1.
+We determined three high-resolution co-crystal structures of Usb1: wild-type Usb1 bound to the substrate analog adenosine 5′-monophosphate, and an inactive mutant bound to RNAs with a 3′ terminal adenosine and uridine.
+These structures, along with QM/MM MD simulations of the catalytic mechanism, illuminate the molecular basis for preferential deadenylation of U6 snRNA.
+Pigeon circovirus (PiCV) is the most frequently diagnosed virus in pigeons and is thought to be one of the causative factors of a complex disease called the young pigeon disease syndrome (YPDS).
+The development of a vaccine against this virus could be a strategy for YPDS control.
+Since laboratory culture of PiCV is impossible, its recombinant capsid protein (rCP) can be considered as a potential antigen candidate in sub-unit vaccines.
+The aim of this basic research was to evaluate the immune response of pigeons to PiCV rCP.
+Sixty six-week-old carrier pigeons were divided into two groups (experimental immunized with PiCV rCP mixed with an adjuvant, and control immunized with an adjuvant only), and immunized twice in a 21-day interval.
+On the day of immunization and on two, 23, 39, and 46 days post first immunization (dpv), samples of blood, spleen, and bursa of Fabricius were collected from six birds from each group to examine anti-PiCV rCP IgY, anti-PiCV rCP IgY-secreting B cells (SBC), IFN-γ gene expression, and percentage of T CD3(+), CD4(+), CD8(+), and B IgM(+) lymphocytes.
+The results indicated a correct immune response to PiCV rCP both in humoral and cell-mediated immunity, which was manifested by seroconversion since 23 dpv, by a significantly higher anti-PiCV rCP IgY-SBC number on two and 23 dpv, and significantly higher IFN-γ gene expression since two dpv.
+There were no significant differences or trends noted between particular T and B lymphocyte subpopulations.
+To conclude, PiCV rCP may be deemed immunogenic and could be considered as an antigen candidate in sub-unit vaccines against PiCV infections in pigeons.
+To complement traditional antivirals, natural compounds that act via host targets and present high barriers to resistance are of increasing interest.
+HHT completely inhibited infections of vesicular stomatitis virus (VSV), Newcastle disease virus (NDV), and porcine epidemic diarrhea virus (PEDV) at concentrations of 50, 100, and 500 nM in cell cultures, respectively.
+Treatment with HHT at doses of 0.05 or 0.2 mg/kg significantly reduced viral load and relieved severe symptoms in PEDV- or NDV-infected animals.
+HHT treatment, however, moderately inhibited avian influenza virus (AIV) infection, suggesting its potent antiviral action is restricted to a number of classes of RNA viruses.
+In this study, we also observed that HHT actively inhibited herpes simplex virus type 1 (HSV-1) replication with a 50% inhibitory concentration (IC(50)) of 139 nM; the treatment with HHT at 1000 nM led to reductions of three orders of magnitude.
+Moreover, HHT antagonized the phosphorylation level of endogenous and exogenous eukaryotic initiation factor 4E (p-eIF4E), which might regulate the selective translation of specific messenger RNA (mRNA).
+HHT provides a starting point for further progress toward the clinical development of broad-spectrum antivirals.
+ERBs develop a productive MARV infection with low viremia and shedding but no overt disease, suggesting this virus is efficiently controlled by ERB antiviral responses.
+This dynamic would contrast with humans, where MARV-mediated interferon (IFN) antagonism early in infection is thought to contribute to the severe, often fatal disease.
+The newly-annotated ERB genome and transcriptome have now enabled us to use a custom-designed NanoString nCounter ERB CodeSet in conjunction with RNA-seq to investigate responses in a MARV-infected ERB cell line.
+Both transcriptomic platforms correlated well and showed that MARV inhibited the antiviral program in ERB cells, while an IFN antagonism-impaired MARV was less efficient at suppressing the response gene induction, phenotypes previously reported for primate cells.
+Interestingly, and despite the expansion of IFN loci in the ERB genome, neither MARV showed specific induction of almost any IFN gene.
+However, we detected an upregulation of putative, unannotated ERB antiviral paralogs, as well as an elevated basal expression in uninfected ERB cells of key antiviral genes.
+The in ovo delivery of cytosine-guanosine (CpG) oligodeoxynucleotides (ODNs) protects chickens against many bacterial and viral infections, by activating the toll-like receptor (TLR)21 signaling pathway.
+Although the delivery of CpG ODNs in ovo at embryo day (ED) 18 has been shown to reduce infectious bronchitis virus (IBV) loads in embryonic chicken lungs pre-hatch, whether in ovo delivered CpG ODNs are capable of protecting chickens against a post-hatch challenge is unknown.
+Thus, our objectives were to determine the protective effect of the in ovo delivery of CpG ODNs at ED 18 against IBV infection encountered post-hatch and, then, to investigate the mechanisms of protection.
+We found significantly higher survival rates and reduced IBV infection in the chickens following the pre-treatment of the ED 18 eggs with CpG ODNs.
+At 3 days post infection (dpi), we found an increased recruitment of macrophages, cluster of differentiation (CD)8α+ and CD4+ T lymphocytes, and an up-regulation of interferon (IFN)-γ mRNA in the respiratory tract of the chickens.
+Overall, it may be inferred that CpG ODNs, when delivered in ovo, provide protection against IBV infection induced morbidity and mortality with an enhanced immune response.
+BACKGROUND: Tuberculosis (TB) is one of the world’s major communicable infectious diseases, and it still imposes a great health burden in developing countries.
+The development of drug-resistant TB during the treatment increases the treatment complexity, and the long-term pulmonary complications after completing treatment raise the epidemic health burden.
+This study intended to investigate the utilization of Chinese medicine (CM) for respiratory symptoms by patients with a medical history of TB in Taiwan.
+METHODS: We analyzed a cohort of one million individuals who were randomly selected from the National Health Insurance Research Database in Taiwan.
+The inclusion criteria of patients (n = 7905) with history of TB (ICD-9-CM codes 010–018 and A02) were: (1) TB diagnosed between January 1, 1997 and December 31, 2010 (2) 18 years old or over (3) Clinical records for at least 2 months with complete demographic information (4) Record of treatment with first-line TB medication prescriptions.
+Finally, a total of 3925 TB patients were categorized as: CM users for respiratory discomforts (n = 2051) and non-CM users (n = 1874).
+RESULTS: Among the 3925 subjects, 2051 (52.25%) were CM users, and 1874 (44.753%) were non-CM users.
+Female patients and those who were younger (18–39 y/o) and who lived in urbanized areas relatively tended to be CM users (p < .0001).
+The most commonly prescribed herbal formulas and single herbs were Xiao-Qing-Long-Tang and Radix Platycodonis (Jie-Geng), respectively.
+The core pattern of Chinese medicines for TB patients consisted of Ma-Xing-Gan-Shi-Tang, Bulbus Fritillariae Thunbergii (Bei-Mu), Radix Platycodonis (Jie-Geng) and Semen Armeniacae (Xing-Ren).
+CONCLUSIONS: The use of CM is popular among patients with a medical history of TB complicated with long-term respiratory discomforts in Taiwan.
+BACKGROUND: Bordetella pertussis can cause fatal illness with severe acute respiratory distress syndrome (ARDS) and pulmonary hypertension (PHT).
+CASE PRESENTATION: A 6-month-old non-vaccinated boy with B. pertussis infection who developed ARDS was treated by extracorporeal membrane oxygenation (ECMO).
+During his ECMO support stage, sudden occurred decreasing of ECMO flow implied increasing intrathoracic pressure.
+The airway spasm followed caused sudden drop of ventilator tidal volume as well as poor lung compliance.
+After 297-h of ECMO support, the patient was weaned off ECMO, and extubated one week later.
+CONCLUSIONS: In this patient with severe ARDS caused by Bordetella pertussis, ECMO was performed for cardiopulmonary support and rescued the infant with severe pertussis.
+During ECMO support period, prone position ventilation and care bundle nursing strategy contributed to the relief of continuous airway spasm.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12887-018-1351-0) contains supplementary material, which is available to authorized users.
+Newcastle disease is considered the number one disease constraint to poultry production in low and middle-income countries, however poultry that is raised in resource-poor areas often experience multiple environmental challenges.
+Heat stress has a negative impact on production, and immune response to pathogens can be negatively modulated by heat stress.
+Candidate genes and regions chosen for this study were based on previously reported associations with response to immune stimulants, pathogens, or heat, including: TLR3, TLR7, MX, MHC-B (major histocompatibility complex, gene complex), IFI27L2, SLC5A1, HSPB1, HSPA2, HSPA8, IFRD1, IL18R1, IL1R1, AP2A2, and TOLLIP.
+Chickens of a commercial egg-laying line were infected with a lentogenic strain of NDV (Newcastle disease virus); half the birds were maintained at thermoneutral temperature and the other half were exposed to high ambient temperature before the NDV challenge and throughout the remainder of the study.
+Selected SNPs (single nucleotide polymorphisms) within 14 target genes or regions were genotyped; and genotype effects on phenotypic responses to NDV or heat + NDV were tested in each individual treatment group and the combined groups.
+Seventeen significant haplotype effects, among seven genes and seven phenotypes, were detected for response to NDV or heat or NDV + heat.
+These findings identify specific genetic variants that are associated with response to heat and/or NDV which may be useful in the genetic improvement of chickens to perform favorably when faced with pathogens and heat stress.
+Two different sizes of siRNAs, of which one type was 21-nucleotide (nt) siRNA containing 2-nt dangling ends and the other type was 27-nt siRNA with blunt ends, were conjugated with a nuclear export signal peptide of HIV-1 Rev at the 5′-sense end.
+Processing by Dicer enzyme, cell membrane permeability, and RNAi efficiency of the peptide-conjugated siRNAs were examined.
+Dicer cleaved the peptide-conjugated 27-nt siRNA leading to the release of 21-nt siRNA, whereas the peptide-conjugated 21-nt siRNA was not cleaved.
+Moreover, the peptide-conjugated 27-nt siRNA showed increased potency of RNAi in comparison with the nonmodified 21-nt and 27-nt siRNAs, whereas the peptide-conjugated 21-nt siRNA showed decreased RNAi efficacy.
+This potent RNAi efficacy is probably owing to acceleration of RISC through recognition by Dicer, as well as to the improvement of cell membrane permeability and intracellular accumulation.
+How influenza A viruses host-jump from animal reservoir species to humans, which can initiate global pandemics, is a central question in pathogen evolution.
+The zoonotic and spatial origins of the influenza virus associated with the “Spanish flu” pandemic of 1918 have been debated for decades.
+Outbreaks of respiratory disease in US swine occurred concurrently with disease in humans, raising the possibility that the 1918 virus originated in pigs.
+Swine also were proposed as “mixing vessel” intermediary hosts between birds and humans during the 1957 Asian and 1968 Hong Kong pandemics.
+Swine have presented an attractive explanation for how avian viruses overcome the substantial evolutionary barriers presented by different cellular environments in humans and birds.
+However, key assumptions underpinning the swine mixing-vessel model of pandemic emergence have been challenged in light of new evidence.
+Increased surveillance in swine has revealed that human-to-swine transmission actually occurs far more frequently than the reverse, and there is no empirical evidence that swine played a role in the emergence of human influenza in 1918, 1957, or 1968.
+But swine are not necessary to mediate the establishment of avian viruses in humans, which invites new perspectives on the evolutionary processes underlying pandemic emergence.
+A large body of epidemiologic research has concentrated on the 1918 influenza pandemic, but more work is needed to understand spatial variation in pandemic mortality and its effects on natality.
+We collected and analyzed 35,151 death records from Arizona for 1915–1921 and 21,334 birth records from Maricopa county for 1915–1925.
+We estimated the number of excess deaths and births before, during, and after the pandemic period, and we found a significant decline in the number of births occurring 9–11 months after peak pandemic mortality.
+Moreover, excess mortality rates were highest in northern Arizona counties, where Native Americans were historically concentrated, suggesting a link between ethnic and/or sociodemographic factors and risk of pandemic-related death.
+The relationship between birth patterns and pandemic mortality risk should be further studied at different spatial scales and in different ethnic groups.
+The NS2B-NS3 protease (NS2B-NS3(pro)) of dengue fever virus carries out all enzymatic activities needed for polyprotein processing and is considered to be amenable to antiviral inhibition by analogy.
+Virtual screening of 300,000 compounds using Autodock 3 on the GVSS platform was conducted to identify novel inhibitors against the NS2B-NS3(pro).
+Seven novel compounds were identified as inhibitors with IC(50) values of 3.9 ± 0.6–86.7 ± 3.6 μM.
+Three strong NS2B-NS3(pro) inhibitors were further confirmed as competitive inhibitors with K(i) values of 4.0 ± 0.4, 4.9 ± 0.3, and 3.4 ± 0.1 μM, respectively.
+Hydrophobic and hydrogen bond interactions between amino acid residues in the NS3(pro) active site with inhibition compounds were also identified.
+The technique of loop-mediated isothermal amplification (LAMP) utilizes four (or six) primers targeting six (or eight) regions within a fairly small segment of a genome for amplification, with concentration higher than that used in traditional PCR methods.
+The high concentrations of primers used leads to an increased likelihood of non-specific amplification induced by primer dimers.
+In this study, a set of LAMP primers were designed targeting the prfA gene sequence of Listeria monocytogenes, and dimethyl sulfoxide (DMSO) as well as Touchdown LAMP were employed to increase the sensitivity and specificity of the LAMP reactions.
+The results indicate that the detection limit of this novel LAMP assay with the newly designed primers and additives was 10 fg per reaction, which is ten-fold more sensitive than a commercial Isothermal Amplification Kit and hundred-fold more sensitive than previously reported LAMP assays.
+This highly sensitive LAMP assay has been shown to detect 11 strains of Listeria monocytogenes, and does not detect other Listeria species (including Listeria innocua and Listeria invanovii), providing some advantages in specificity over commercial Isothermal Amplification Kits and previously reported LAMP assay.
+Duchenne muscular dystrophy (DMD) is a genetic muscle disorder caused by mutations in the Dmd gene resulting in the loss of the protein dystrophin.
+Patients do not only experience skeletal muscle degeneration, but also develop severe cardiomyopathy by their second decade, one of the main causes of death.
+Moreover, it pathologically alters intracellular calcium (Ca(2+)) concentration, neuronal nitric oxide synthase (nNOS) localization and mitochondrial function and leads to inflammation and necrosis, all contributing to the development of cardiomyopathy.
+Current therapies only treat symptoms and therefore the need for targeting the genetic defect is immense.
+Several preclinical therapies are undergoing development, including utrophin up-regulation, stop codon read-through therapy, viral gene therapy, cell-based therapy and exon skipping.
+Some of these therapies are undergoing clinical trials, but these have predominantly focused on skeletal muscle correction.
+However, improving skeletal muscle function without addressing cardiac aspects of the disease may aggravate cardiomyopathy and therefore it is essential that preclinical and clinical focus include improving heart function.
+This review consolidates what is known regarding molecular pathology of the DMD heart, specifically focusing on intracellular Ca(2+), nNOS and mitochondrial dysregulation.
+It briefly discusses the current treatment options and then elaborates on the preclinical therapeutic approaches currently under development to restore dystrophin thereby improving pathology, with a focus on the heart.
+Analogues or isosteres of α,γ-diketoacid (DKA) 1a show potent inhibition of hepatitis C virus (HCV) NS5B polymerase through chelation of the two magnesium ions at the active site.
+The anti-HCV activity of the flavonoid quercetin (2) could partly be attributed to it being a structural mimic of DKAs.
+In order to delineate the structural features required for the inhibitory effect and improve the anti-HCV potency, two novel types of quercetin analogues, 7-O-arylmethylquercetins and quercetin-3-O-benzoic acid esters, were designed, synthesized and evaluated for their anti-HCV properties in cell-based assays.
+Among the 38 newly synthesized compounds, 7-O-substituted derivative 3i and 3-O-substituted derivative 4f were found to be the most active in the corresponding series (EC(50) = 3.8 μM and 9.0 μΜ, respectively).
+Docking studies suggested that the quercetin analogues are capable of establishing key coordination with the two magnesium ions as well as interactions with residues at the active site of HCV NS5B.
+Proteins entering the secretory pathway are translocated across the endoplasmic reticulum (ER) membrane in an unfolded form.
+In the ER they are restricted to a quality control system that ensures correct folding or eventual degradation of improperly folded polypeptides.
+Mannose trimming of N-glycans on newly synthesized proteins plays an important role in the recognition and sorting of terminally misfolded glycoproteins for ER-associated protein degradation (ERAD).
+In this process misfolded proteins are retrotranslocated into the cytosol, polyubiquitinated, and eventually degraded by the proteasome.
+The mechanism by which misfolded glycoproteins are recognized and recruited to the degradation machinery has been extensively studied during last decade.
+In this review, we focus on ER degradation-enhancing α-mannosidase-like protein (EDEM) family proteins that seem to play a key role in the discrimination between proteins undergoing a folding process and terminally misfolded proteins directed for degradation.
+We describe interactions of EDEM proteins with other components of the ERAD machinery, as well as with various protein substrates.
+Carbohydrate-dependent interactions together with N-glycan-independent interactions seem to regulate the complex process of protein recognition and direction for proteosomal degradation.
+A Quantitative Structure-Activity Relationship (QSAR) approach for classification was used for the prediction of compounds as active/inactive relatively to overall biological activity, antitumor and antibiotic activities using a data set of 1746 compounds from PubChem with empirical CDK descriptors and semi-empirical quantum-chemical descriptors.
+A data set of 183 active pharmaceutical ingredients was additionally used for the external validation of the best models.
+The best classification models for antibiotic and antitumor activities were used to screen a data set of marine and microbial natural products from the AntiMarin database—25 and four lead compounds for antibiotic and antitumor drug design were proposed, respectively.
+The present work enables the presentation of a new set of possible lead like bioactive compounds and corroborates the results of our previous investigations.
+By other side it is shown the usefulness of quantum-chemical descriptors in the discrimination of biologically active and inactive compounds.
+None of the compounds suggested by our approach have assigned non-antibiotic and non-antitumor activities in the AntiMarin database and almost all were lately reported as being active in the literature.
+A novel Schiff base, ethyl 4-[(E)-(2-hydroxy-4-methoxyphenyl)methylene-amino]benzoate (HL), was prepared and structurally characterized on the basis of elemental analyses, (1)H NMR, (13)C NMR, UV-Vis and IR spectral data.
+Six new copper(II) complexes, [Cu(L)(NO(3))(H(2)O)(2)] (1), [Cu(L)(2)] (2), [Cu(L)(OAc)] (3), [Cu(2) (L)(2)Cl(2)(H(2)O)(4)] (4), [Cu(L)(ClO(4))(H(2)O)] (5) and [Cu(2)(L(2)S)(ClO(4))(H(2)O)]ClO(4)·H(2)O (6) have been synthesized.
+The characterization of the newly formed compounds was done by IR, UV-Vis, EPR, FAB mass spectroscopy, elemental and thermal analysis, magnetic susceptibility measurements and molar electric conductivity.
+The crystal structures of Schiff base and the complex [Cu(2)(L(2)S)(ClO(4))(H(2)O)]ClO(4)·H(2)O (6) have been determined by single crystal X-ray diffraction studies.
+This coordination is ensured by three phenol oxygen, two of which being related to the µ-oxo-bridge, the nitrogen atoms of the azomethine group and the sulfur atoms that come from the polydentate ligand.
+The in vitro antimicrobial activity against Escherichia coli ATCC 25922, Salmonella enteritidis, Staphylococcus aureus ATCC 25923, Enterococcus and Candida albicans strains was studied and compared with that of free ligand.
+The complexes 1, 2, 5 showed a better antimicrobial activity than the Schiff base against the tested microorganisms.
+In this study we investigate the molecular mechanisms of caspases and mitochondria in the extrinsic and intrinsic signal apoptosis pathways in human leukemia HL-60 cells after in vitro exposure to 18α-glycyrrhetinic acid (18α-GA).
+Cells were exposed to 18α-GA at various concentrations for various time periods and were harvested for flow cytometry total viable cell and apoptotic cell death measurements.
+Cells treated with 18α-GA significantly inhibited cell proliferation and induced cell apoptosis in a dose-dependent manner, with an IC(50) value of 100 μM at 48 h. The cell growth inhibition resulted in induction of apoptosis and decreased the mitochondria membrane potential (ΔΨ(m)) and increased caspase-8, -9 and -3 activities.
+Furthermore, cytochrome c and AIF were released from mitochondria, as shown by western blotting and confirmed by confocal laser microscopy.
+Western blotting showed that 18α-GA increased the levels of pro-apoptotic proteins such as Bax and Bid and decreased the anti-apoptotic proteins such as Bcl-2 and Bcl-xl, furthermore, results also showed that 18α-GA increased Fas and Fas-L which are associated with surface death receptor in HL-60 cells.
+Based on those observations, the present study supports the hypothesis that 18α-GA-induced apoptosis in HL-60 cells involves the activation of the both extrinsic and intrinsic apoptotic pathways.
+Two decades ago successful transfection of antigen presenting cells (APC) in vivo was demonstrated which resulted in the induction of primary adaptive immune responses.
+Due to the good biocompatibility of plasmid DNA, their cost-efficient production and long shelf life, many researchers aimed to develop DNA vaccine-based immunotherapeutic strategies for treatment of infections and cancer, but also autoimmune diseases and allergies.
+This review aims to summarize our current knowledge on the course of action of DNA vaccines, and which factors are responsible for the poor immunogenicity in human so far.
+Important optimization steps that improve DNA transfection efficiency comprise the introduction of DNA-complexing nano-carriers aimed to prevent extracellular DNA degradation, enabling APC targeting, and enhanced endo/lysosomal escape of DNA.
+Improvements in DNA vaccine design include the use of APC-specific promotors for transcriptional targeting, the arrangement of multiple antigen sequences, the co-delivery of molecular adjuvants to prevent tolerance induction, and strategies to circumvent potential inhibitory effects of the vector backbone.
+Successful clinical use of DNA vaccines may require combined employment of all of these parameters, and combination treatment with additional drugs.
+The term Interactome describes the set of all molecular interactions in cells, especially in the context of protein-protein interactions.
+These interactions are crucial for most cellular processes, so the full representation of the interaction repertoire is needed to understand the cell molecular machinery at the system biology level.
+In this short review, we compare various methods for predicting protein-protein interactions using sequence and structure information.
+The ultimate goal of those approaches is to present the complete methodology for the automatic selection of interaction partners using their amino acid sequences and/or three dimensional structures, if known.
+Apart from a description of each method, details of the software or web interface needed for high throughput prediction on the whole genome scale are also provided.
+The proposed validation of the theoretical methods using experimental data would be a better assessment of their accuracy.
+Hand disinfection is frequently recommended for prevention of rhinovirus (RV) infection and RV-associated common colds.
+The purpose of this study was to determine the effect of hand disinfection on RV infection and RV-associated common cold illness in a natural setting.
+A controlled clinical trial was done in young adult volunteers during 9 weeks of the fall 2009 RV season.
+Volunteers were randomized to either an antiviral hand treatment containing 2% citric acid and 2% malic acid in 62% ethanol (n = 116) or to a no-treatment control group (n = 96).
+All volunteers kept a daily diary of symptoms and had a nasal lavage for polymerase chain reaction once each week and 2 additional lavages around the time of each common cold illness.
+The incidence of RV infection and of common cold illnesses were evaluated as secondary endpoints.
+The total number of common cold illnesses was significantly reduced in the intent-to-treat analysis, but this effect was not seen in the per protocol analysis.
+In this study, hand disinfection did not reduce RV infection or RV-related common cold illnesses.
+Artificial microRNA (amiRNA)-mediated inhibition of viral replication has recently gained importance as a strategy for antiviral therapy.
+In this study, we evaluated the benefit of using the amiRNA vector against Japanese encephalitis virus (JEV).
+We designed three single amiRNA sequences against the consensus sequence of 3′ untranslated region (3′UTR) of JEV and tested their efficacy against cell culture-grown JEV Vellore strain (P20778) in neuronal cells.
+The binding ability of three amiRNAs on 3′UTR region was tested in vitro in HEK293T cells using a JEV 3′UTR tagged with luciferase reporter vector.
+Transient transfection of amiRNAs was nontoxic to cells as evident from the MTT assay and caused minimal induction in interferon-stimulated gene expression.
+Furthermore, our result suggested that transient expression of two amiRNAs (amiRNA #1 and amiRNA #2) significantly reduced intracellular viral RNA and nonstructural 1 (NS1) protein, as well as diminished infectious viral particle release up to 95% in the culture supernatant as evident from viral plaque reduction assay.
+Overall, our results indicated that RNA interference based on amiRNAs targeting viral conserved regions at 3′UTR was a useful approach for improvements of nucleic acid inhibitors against JEV.
+Nonsense-mediated decay (NMD) is a host RNA control pathway that removes aberrant transcripts with long 3’ untranslated regions (UTRs) due to premature termination codons (PTCs) that arise through mutation or defective splicing.
+To maximize coding potential, RNA viruses often contain internally located stop codons that should also be prime targets for NMD.
+Using an agroinfiltration-based NMD assay in Nicotiana benthamiana, we identified two segments conferring NMD-resistance in the carmovirus Turnip crinkle virus (TCV) genome.
+The ribosome readthrough structure just downstream of the TCV p28 termination codon stabilized an NMD-sensitive reporter as did a frameshifting element from umbravirus Pea enation mosaic virus.
+In addition, a 51-nt unstructured region (USR) at the beginning of the TCV 3’ UTR increased NMD-resistance 3-fold when inserted into an unrelated NMD-sensitive 3’ UTR.
+Several additional carmovirus 3’ UTRs also conferred varying levels of NMD resistance depending on the construct despite no sequence similarity in the analogous region.
+Instead, these regions displayed a marked lack of RNA structure immediately following the NMD-targeted stop codon.
+NMD-resistance was only slightly reduced by conversion of 19 pyrimidines in the USR to purines, but resistance was abolished when a 2-nt mutation was introduced downstream of the USR that substantially increased the secondary structure in the USR through formation of a stable hairpin.
+The same 2-nt mutation also enhanced the NMD susceptibility of a subgenomic RNA expressed independently of the genomic RNA.
+The conserved lack of RNA structure among most carmoviruses at the 5’ end of their 3’ UTR could serve to enhance subgenomic RNA stability, which would increase expression of the encoded capsid protein that also functions as the RNA silencing suppressor.
+These results demonstrate that the TCV genome has features that are inherently NMD-resistant and these strategies could be widespread among RNA viruses and NMD-resistant host mRNAs with long 3’ UTRs.
+Background: Respiratory infections pose a great challenge in global health, and the prevalence of viral infection in adult patients has been poorly understood in northeast China.
+Harbin is one of the major cities in northeast China, and more than half of any given year in Harbin is occupied by winter.
+To reveal the viral etiology and seasonality in adult patients from Harbin, a 4-year consecutive survey was conducted in Harbin, China.
+Methods: From January 2014 to December 2017, specimens were obtained from adult patients admitted to the Second Affiliated Hospital of Harbin Medical University with lower respiratory tract infections.
+Sputum samples were examined by direct immunofluorescence assays to detect seven common respiratory viruses, including influenza virus (type A and B), parainfluenza virus (type 1 to 3), respiratory syncytial virus and adenovirus.
+Results: A total of 1,300 hospitalized adult patients with lower respiratory tract infections were enrolled, in which 189 patients (14.5%) were detected as having at least one viral infection.
+The dominant viral pathogen from 2014 to 2017 was parainfluenza virus, with a detection rate of 7.2%, followed by influenza virus, respiratory syncytial virus and adenovirus.
+Based on the climate seasons determined by daily average temperature, the highest overall viral detection rate was detected in spring (22.0%, 52/236), followed by winter (13.4%, 109/813), autumn (11.4%, 13/114) and summer (10.9%, 15/137).
+Adenovirus type 3 strains with slight variations were isolated from positive cases, which were closely related to the GB strain from the United States, as well as the Harbin04B strain isolated locally.
+Conclusion: This study demonstrated that common respiratory viruses were partially responsible for hospitalized lower respiratory tract infections in adult patients from Harbin, China, with parainfluenza virus as the dominant viral pathogen.
+Future surveillance on viral mutations would be necessary to reveal the evolutionary history of respiratory viruses.
+BACKGROUND: Phlebotomus orientalis is a vector of Leishmania donovani, the causative agent of life threatening visceral leishmaniasis spread in Eastern Africa.
+Sand fly saliva contains a large variety of proteins, some of which elicit specific antibody responses in the bitten hosts.
+To evaluate the exposure to sand fly bites in human populations from disease endemic areas, we tested the antibody reactions of volunteers' sera against recombinant P. orientalis salivary antigens.
+METHODOLOGY/PRINCIPAL FINDINGS: Recombinant proteins derived from sequence data on P. orientalis secreted salivary proteins, were produced using either bacterial (five proteins) or mammalian (four proteins) expression systems and tested as antigens applicable for detection of anti-P. orientalis IgG in human sera.
+Using these recombinant proteins, human sera from Sudan and Ethiopia, countries endemic for visceral leishmaniasis, were screened by ELISA and immunoblotting to identify the potential markers of exposure to P. orientalis bites.
+Two recombinant proteins; mAG5 and mYEL1, were identified as the most promising antigens showing high correlation coefficients as well as good specificity in comparison to the whole sand fly salivary gland homogenate.
+Combination of both proteins led to a further increase of correlation coefficients as well as both positive and negative predictive values of P. orientalis exposure.
+CONCLUSIONS/SIGNIFICANCE: This is the first report of screening human sera for anti-P. orientalis antibodies using recombinant salivary proteins.
+The recombinant salivary proteins mYEL1 and mAG5 proved to be valid antigens for screening human sera from both Sudan and Ethiopia for exposure to P. orientalis bites.
+The utilization of equal amounts of these two proteins significantly increased the capability to detect anti-P. orientalis antibody responses.
+Here we report that in the fission yeast Schizosaccharomyces pombe and the budding yeast Saccharomyces cerevisiae, the lipidation-independent roles of Atg8 in maintaining normal morphology and functions of the vacuole require its interaction with a vacuole membrane protein Hfl1 (homolog of human TMEM184 proteins).
+Crystal structures revealed that the Atg8-Hfl1 interaction is not mediated by the typical Atg8-family-interacting motif (AIM) that forms an intermolecular β-sheet with Atg8.
+Instead, the Atg8-binding regions in Hfl1 proteins adopt a helical conformation, thus representing a new type of AIMs (termed helical AIMs here).
+These results deepen our understanding of both the functional versatility of Atg8 and the mechanistic diversity of Atg8 binding.
+Singapore implements a school closure policy for institutional hand, foot, and mouth disease (HFMD) outbreaks, but there is a lack of empirical evidence on the effect of closure on HFMD transmission.
+We conducted a retrospective analysis of 197,207 cases of HFMD over the period 2003–2012 at the national level and of 57,502 cases in 10,080 institutional outbreaks over the period 2011–2016 in Singapore.
+The effects of school closure due to 1) institutional outbreaks, 2) public holidays, and 3) school vacations were assessed using a Bayesian time series modeling approach.
+During public holidays, average numbers of secondary cases having onset the week after dropped by 53% (95% credible interval 44–62%), and during school vacations, the number of secondary cases dropped by 7% (95% credible interval 3–10%).
+Schools being temporarily closed in response to an institutional outbreak reduced the average number of new cases by 1,204 (95% credible interval 1,140–1,297).
+Despite the positive effect in reducing transmission, the effect of school closure is relatively small and may not justify the routine use of this measure.
+The skin represents one of the tissues that are most profoundly influenced by alterations in the quality of lipids (lipoquality).
+Lipids not only constitute cellular membranes, but also serve as bioactive lipid mediators and essential components of the skin barrier.
+Phospholipase A(2) (PLA(2)) enzymes supply fatty acids and lysophospholipids from membrane phospholipids, thereby variably affecting cutaneous homeostasis.
+Accordingly, perturbation of particular PLA(2)-driven lipid pathways can be linked to various forms of skin disease.
+In this review article, we highlight the roles of several PLA(2) subtypes in cutaneous pathophysiology, as revealed by transgenic/knockout studies in combination with comprehensive lipidomics.
+We focus mainly on secreted PLA(2) group IIF (sPLA(2)-IIF), which is associated with epidermal hyperplasia through mobilization of a unique lipid metabolite.
+We also address the distinct roles of sPLA(2)-IIE in hair follicles and sPLA(2)-IID in lymphoid immune cells that secondarily affect cutaneous inflammation, and provide some insights into species differences in sPLA(2)s. Additionally, we briefly overview the patatin-like phospholipase PNPLA1, which belongs to the Ca(2+)-independent PLA(2) (iPLA(2)) family, as a key regulator of skin barrier function through catalysis of a unique non-PLA(2) reaction.
+These knowledges on lipid metabolism driven by various PLA(2) subtypes will open novel opportunities for translated studies toward diagnosis and therapy of human skin diseases.
+Chikungunya fever is caused by Chikungunya virus (CHIKV) and is generally considered a self-limiting disease.
+However, severe clinical presentations with a high mortality rate have been reported in association with underlying medical conditions.
+This study reports the molecular characterization of the virus and an abnormal pattern of circulating cytokines in a unique lethal CHIKV case during the 2017 outbreak in Italy, which involved an elderly patient with underlying cardiac disease.
+Analysis of inflammatory cytokines revealed a strong increase of interferon (IFN)-α and IFN-β, as well as interleukin-6, suggesting a possible role of type-I IFN in the cytokine storm, which may be correlated with unfavorable prognosis of CHIKV infection.
+BACKGROUND: The aim of this study was to estimate the prevalence of pneumonia and secondary bacterial infections during the pandemic of influenza A(H1N1)pdm09.
+METHODS: A systematic review was conducted to identify relevant literature in which clinical outcomes of pandemic influenza A(H1N1)pdm09 infection were described.
+Published studies (between 01/01/2009 and 05/07/2012) describing cases of fatal or hospitalised A(H1N1)pdm09 and including data on bacterial testing or co-infection.
+Fatal cases with autopsy specimen testing were reported in 11 studies, in which any co-infection was identified in 23% of cases (Streptococcus pneumoniae 29%).
+Eleven studies reported bacterial co-infection among hospitalised cases of A(H1N1)2009pdm with confirmed pneumonia, with a mean of 19% positive for bacteria (Streptococcus pneumoniae 54%).
+Of 16 studies of intensive care unit (ICU) patients, bacterial co-infection identified in a mean of 19% of cases (Streptococcus pneumoniae 26%).
+The mean prevalence of bacterial co-infection was 12% in studies of hospitalised patients not requiring ICU (Streptococcus pneumoniae 33%) and 16% in studies of paediatric patients hospitalised in general or pediatric intensive care unit (PICU) wards (Streptococcus pneumoniae 16%).
+CONCLUSION: We found that few studies of the 2009 influenza pandemic reported on bacterial complications and testing.
+Of studies which did report on this, secondary bacterial infection was identified in almost one in four patients, with Streptococcus pneumoniae the most common bacteria identified.
+Bacterial complications were associated with serious outcomes such as death and admission to intensive care.
+Prevention and treatment of bacterial secondary infection should be an integral part of pandemic planning, and improved uptake of routine pneumococcal vaccination in adults with an indication may reduce the impact of a pandemic.
+Aims: The purpose of this study was to assess the relationship between genetic variants and steroid-induced osteonecrosis of the femoral head (SONFH) in steroid use populations.
+This study analyzed only the single-nucleotide polymorphisms (SNPs) that have appeared in more than three studies and assessed the level of evidence by classifying the outcomes according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach.
+Results: The ABCB1 rs1045642 C>T mutation had a protective effect against SONFH in the allelic model (I(2) = 50.2%; OR: 0.74; 95% CI: 0.55–1.00; p = 0.046).
+The rs2032582 mutation in the ABCB1 gene showed no relationship to SONFH (allelic model: I(2) = 63.4%; OR: 0.85; 95% CI: 0.58–1.23; p = 0.382).
+In ApoB rs693, four models showed that mutations can increase SONFH risk, but the allelic model did not.
+The ApoB rs1042031 mutation increased SONFH risk in the dominant model (I(2) = 50.3%; OR: 2.90; 95% CI: 1.49–5.66; p = 0.002).
+Conclusion: An allelic model of ABCB1 rs1045642 showed that mutations have a protective effect against SONFH at a very low level of evidence.
+The mutations in ApoB rs693 and rs1042031 increase the SONFH risk with moderate levels of evidence.
+Given the high mortality rate (>50%) and potential danger of intrapersonal transmission, highly pathogenic avian influenza (HPAI) H5N1 epidemics still pose a significant threat to humans.
+γδ T cells, which participate on the front line of the host immune defense, demonstrate both innate, and adaptive characteristics in their immune response and have potent antiviral activity against various viruses.
+In this study, we found that γδ T cells provided a crucial protective function in the defense against HPAI H5N1 viral infection.
+HPAI H5N1 viruses could directly activate γδ T cells, leading to enhanced CD69 expression and IFN-γ secretion.
+Importantly, we found that the trimer but not the monomer of HPAI H5N1 virus hemagglutinin (HA) proteins could directly activate γδ T cells.
+HA-induced γδ T cell activation was dependent on both sialic acid receptors and HA glycosylation, and this activation could be inhibited by the phosphatase calcineurin inhibitor cyclosporin A but not by the phosphatidylinositol 3-kinase (PI3-K) inhibitors wortmannin and LY294002.
+Our findings provide a further understanding the mechanism underlying γδ T cell-mediated innate and adoptive immune responses against HPAI H5N1 viral infection, which helps to develop novel therapeutic strategies for the treatment of H5N1 infection in the future.
+BACKGROUND: Since the acute fibrinous and organizing pneumonia (AFOP) was first described by Beasley in 2002, some case reports of patients aged from 38 d to 80 years have been published worldwide, but there is still no standard therapy for this disease and the treatment methods remain controversial.
+Both steroid and immunosuppressive agents, such as cyclophosphamide or mycophenolate mofetil, have been reported to be effective in some studies, but with many side effects, especially in patients of advanced age.
+CASE SUMMARY: We herein report an 81-year-old female patient who was admitted to our hospital due to dry cough, and breathlessness for 1 mo.
+She was treated with broad-spectrum antibiotics and anti-fungal therapy, but without improvement in both symptoms and radiological findings, and her respiratory status worsened, and she required bed rest almost the whole day.
+Computed tomography-guided percutaneous needle lung biopsy was performed and histopathology examination confirmed the diagnosis of AFOP.
+She was then successfully treated with a steroid monotherapy, which resulted in a satisfactory clinical outcome without serious complications.
+CONCLUSION: We conclude that complete remission of AFOP can be achieved by steroid monotherapy in patients of advanced age.
+A novel vaccine against bovine viral diarrhea (BVD) induced pathogenic antibody production in 5–10% of BVD-vaccinated cows.
+Transfer of these antibodies via colostrum caused Bovine neonatal pancytopenia (BNP) in calves, with a lethality rate of 90%.
+The exact immunological mechanisms behind the onset of BNP are not fully understood to date.
+To gain further insight into these mechanisms, we analyzed the immune proteome from alloreactive antibody producers (BNP cows) and non-responders.
+After in vitro stimulation of peripheral blood derived lymphocytes (PBL), we detected distinctly deviant expression levels of several master regulators of immune responses in BNP cells, pointing to a changed immune phenotype with severe dysregulation of immune response in BNP cows.
+Interestingly, we also found this response pattern in 22% of non-BVD-vaccinated cows, indicating a genetic predisposition of this immune deviant (ID) phenotype in cattle.
+We additionally analyzed the functional correlation of the ID phenotype with 10 health parameters and 6 diseases in a retrospective study over 38 months.
+The significantly increased prevalence of mastitis among ID cows emphasizes the clinical relevance of this deviant immune response and its potential impact on the ability to fight infections.
+Glycosylation is a biologically important protein modification process by which a carbohydrate chain is enzymatically added to a protein at a specific amino acid residue.
+This process plays roles in many cellular functions, including intracellular trafficking, cell–cell signaling, protein folding and receptor binding.
+While glycosylation is a common host cell process, it is utilized by many pathogens as well.
+Protein glycosylation is widely employed by viruses for both host invasion and evasion of host immune responses.
+Thus better understanding of viral glycosylation functions has potential applications for improved antiviral therapeutic and vaccine development.
+Here, we summarize our current knowledge on the broad biological functions of glycans for the Mononegavirales, an order of enveloped negative-sense single-stranded RNA viruses of high medical importance that includes Ebola, rabies, measles and Nipah viruses.
+We discuss glycobiological findings by genera in alphabetical order within each of eight Mononegavirales families, namely, the bornaviruses, filoviruses, mymonaviruses, nyamiviruses, paramyxoviruses, pneumoviruses, rhabdoviruses and sunviruses.
+The parasite Toxoplasma gondii causes an opportunistic infection, that is, particularly severe in immunocompromised patients, infants, and neonates.
+Current antiparasitic drugs are teratogenic and cause hypersensitivity-based toxic side effects especially during prolonged treatment.
+Furthermore, the recent emergence of drug-resistant toxoplasmosis has reduced the therapeutic impact of such drugs.
+In an effort to develop recombinant antibodies as a therapeutic alternative, a panel of affinity-matured, T. gondii tachyzoite-specific single-chain variable fragment (scFv) antibodies was selected by phage display and bioinformatic analysis.
+Further affinity optimization was attempted by introducing point mutations at hotspots within light chain complementarity-determining region 2.
+This strategy yielded four mutated scFv sequences and a parental scFv that were used to produce five mouse–human chimeric IgGs in Nicotiana benthamiana plants, with yields of 33–72 mg/kg of plant tissue.
+Immunological analysis confirmed the specific binding of these plant-derived antibodies to T. gondii tachyzoites, and in vitro efficacy was demonstrated by their ability to inhibit the invasion of human fibroblasts and impair parasite infectivity.
+These novel recombinant antibodies could therefore be suitable for the development of plant-derived immunotherapeutic interventions against toxoplasmosis.
+Current clinical diagnosis is typically based on a combination of approaches including clinical examination of the patient, clinical experience, physiologic and/or genetic parameters, high-tech diagnostic medical imaging, and an extended list of laboratory values mostly determined in biofluids such as blood and urine.
+However, recent advances in technology and better understanding of molecular mechanisms underlying disease will allow us to better characterize patients in the future.
+These improvements will enable us to distinguish patients who have similar clinical presentations but different cellular and molecular responses.
+Treatments will be able to be chosen more “precisely”, resulting in more appropriate therapy, precision medicine v2.0.
+In this review, we will reflect on the potential added value of recent advances in technology and a better molecular understanding of necrosis and inflammation for improving diagnosis and treatment of critically ill patients.
+We give a brief overview on the mutual interplay between necrosis and inflammation, which are two crucial detrimental factors in organ and/or systemic dysfunction.
+One of the challenges for the future will thus be the cellular and molecular profiling of necroinflammation in biofluids.
+The huge amount of data generated by profiling biomolecules and single cells through, for example, different omic-approaches is needed for data mining methods to allow patient-clustering and identify novel biomarkers.
+The real-time monitoring of biomarkers will allow continuous (re)evaluation of treatment strategies using machine learning models.
+Ultimately, we may be able to offer precision therapies specifically designed to target the molecular set-up of an individual patient, as has begun to be done in cancer therapeutics.
+BACKGROUND: Nontuberculous mycobacteria (NTM) lung diseases are increasingly recognized as chronic opportunistic infections, occurring in individuals with a wide variety of underlying conditions.
+In the absence of systemic immunodeficiency, decision of NTM lung disease treatment must relies on a careful risk/benefit assessment, given the requirement of long-term administration of multidrug therapies supported by limited evidence.
+METHODS: This retrospective, single center study (2013–2016, 45 months) addressed the criteria supporting treatment decision among adults with NTM lung disease without systemic immunodeficiency at our institution, with the assigned goal to harmonize the practice.
+All patients matched the current international definitions of NTM lung disease according to the American Thoracic Society criteria.
+An expert radiologist conducted a blinded computed tomography (CT)-scan review of the treated and untreated patients.
+In univariate analysis, a body mass index (BMI) < 18 kg/m(2) (odds ratio (OR), 4.2 [95% confidence interval (CI) 1.2–15.2]; p = 0.042), hemoptysis (OR, 11.8 [95% CI 1.35–12.9]; p = 0.026), excavation(s) (OR, 4.8 [95% CI 1.4–16.4], p = 0.012), prior anti-NTM treatment (OR, 5.65 [95% CI 1.06–29.9]; p = 0.042), Aspergillus spp.
+co-infection was the only independent determinant of treatment initiation (OR, 5.3 [95% CI 1.1–25.4]; p = 0.036).
+Median treatment duration and follow-up were 36.3 (interquartile range [IQR], 13.1–64.4) weeks and 17.1 (IQR, 8.7–27.1) months, respectively.
+Regarding radiological outcome, 85 CT-scans were reviewed, showing similar rates of regression or stabilization in treated and untreated patients.
+Radiological regression or stabilization of pulmonary lesions was not different between the treated and untreated patients.
+BACKGROUND: Critical illness polyneuromyopathy (CIPNM) is a major cause of weakness in intensive care unit (ICU) patients, but current diagnostic tests are limited.
+We evaluated the generalizability and validity of single nerve conduction studies (NCS) and muscle ultrasound testing to identify CIPNM, and we also assessed the ability of muscle ultrasound to prognosticate patient outcomes.
+METHODS: This was a prospective cohort study of mechanically ventilated medical, cardiac, surgical, and neurosurgical ICU patients.
+We calculated the sensitivity, specificity, and other test characteristics of single NCS and muscle ultrasound, and we used multivariable regression models to assess the prognostic ability of muscle ultrasound.
+The incidence of probable CIPNM was 18% and did not differ significantly by type of ICU (p = 0.49).
+For diagnosing probable CIPNM, the peroneal motor NCS had a sensitivity of 94% (95% confidence interval (CI) 71–100%) and specificity of 91% (95% CI 82–96%), the sural sensory NCS had a sensitivity of 100% (95% CI 80–100%) and specificity of 42% (95% CI 31–54%), and abnormal muscle ultrasound echogenicity had a sensitivity of 82% (95% CI 48–98%) and specificity of 57% (95% CI 43–70%).
+Abnormal echogenicity was associated with reduced likelihood of discharge to home (9% vs 50%, p = 0.0001), fewer ICU-free days (median 3 (interquartile range 0–15) days vs 16 (9.3–19.3) days, p = 0.0002), and increased ICU mortality (42% vs 12%, p = 0.004).
+CONCLUSIONS: In a diverse cohort of critically ill patients, single NCS and muscle ultrasound achieved diagnostic accuracy for patients at risk for CIPNM.
+The routine utilization of these tests could be beneficial for all critically ill patients at risk for CIPNM.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13054-018-2281-9) contains supplementary material, which is available to authorized users.
+Methicillin-resistant Staphylococcus aureus (MRSA) is a continued threat to human health in both community and healthcare settings.
+In hospitals, control efforts would benefit from accurate estimation of asymptomatic colonization and infection importation rates from the community.
+However, developing such estimates remains challenging due to limited observation of colonization and complicated transmission dynamics within hospitals and the community.
+Here, we develop an inference framework that can estimate these key quantities by combining statistical filtering techniques, an agent-based model, and real-world patient-to-patient contact networks, and use this framework to infer nosocomial transmission and infection importation over an outbreak spanning 6 years in 66 Swedish hospitals.
+In particular, we identify a small number of patients with disproportionately high risk of colonization.
+In retrospective control experiments, interventions targeted to these individuals yield a substantial improvement over heuristic strategies informed by number of contacts, length of stay and contact tracing.
+BACKGROUND: Cytomegalovirus (CMV) reactivation in previously immunocompetent critically ill patients is associated with increased mortality, which has been hypothesized to result from virus-induced immunomodulation.
+Therefore, we studied the effects of CMV reactivation on the temporal course of host response biomarkers in patients with sepsis.
+METHODS: In this matched cohort study, each sepsis patient developing CMV reactivation between day 3 and 17 (CMV+) was compared with one CMV seropositive patient without reactivation (CMVs+) and one CMV seronegative patient (CMVs−).
+CMV serostatus and plasma loads were determined by enzyme-linked immunoassays and real-time polymerase chain reaction, respectively.
+Systemic interleukin-6 (IL-6), IL-8, IL-18, interferon-gamma–induced protein-10 (IP-10), neutrophilic elastase, IL-1 receptor antagonist (RA), and IL-10 were measured at five time points by multiplex immunoassay.
+The effects of CMV reactivation on sequential concentrations of these biomarkers were assessed in multivariable mixed models.
+RESULTS: Among 64 CMV+ patients, 45 could be matched to CMVs+ or CMVs− controls or both.
+The two baseline characteristics and host response biomarker levels at viremia onset were similar between groups.
+CMV+ patients had increased IP-10 on day 7 after viremia onset (symmetric percentage difference +44% versus −15% when compared with CMVs+ and +37% versus +4% when compared with CMVs−) and decreased IL-1RA (−41% versus 0% and −49% versus +10%, respectively).
+However, multivariable analyses did not show an independent association between CMV reactivation and time trends of IL-6, IP-10, IL-10, or IL-1RA.
+CONCLUSION: CMV reactivation was not independently associated with changes in the temporal trends of host response biomarkers in comparison with non-reactivating patients.
+Therefore, these markers should not be used as surrogate clinical endpoints for interventional studies evaluating anti-CMV therapy.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13054-018-2261-0) contains supplementary material, which is available to authorized users.
+In the past two decades, avian influenzas have posed an increasing international threat to human and livestock health.
+In particular, highly pathogenic avian influenza H5N1 has spread across Asia, Africa, and Europe, leading to the deaths of millions of poultry and hundreds of people.
+The two main means of international spread are through migratory birds and the live poultry trade.
+We focus on the role played by the live poultry trade in the spread of H5N1 across three regions widely infected by the disease, which also correspond to three major trade blocs: the European Union (EU), the Economic Community of West African States (ECOWAS), and the Association of Southeast Asian Nations (ASEAN).
+Across all three regions, we found per-capita GDP (a proxy for modernization, general biosecurity, and value-at-risk) to be risk reducing.
+A more specific biosecurity measure–general surveillance–was also found to be mitigating at the all-regions level.
+For the EU and ASEAN, intra-bloc live poultry imports were risk reducing while extra-bloc imports were risk increasing; for ECOWAS the reverse was true.
+This is likely due to the fact that while the EU and ASEAN have long-standing biosecurity standards and stringent enforcement (pursuant to the World Trade Organization’s Agreement on the Application of Sanitary and Phytosanitary Measures), ECOWAS suffered from a lack of uniform standards and lax enforcement.
+Background: Fulminant hepatitis (FH) is a serious threat to human life, accompanied by massive and rapid necroinflammation.
+Kupffer cells, the major immune cell population involved in innate immune responses, are considered to be central for FH.
+Fibrinogen-like protein 2 (Fgl2) is a pro-coagulant protein that is substantially induced in macrophages upon viral infection, and Fgl2 depletion represses murine hepatitis virus strain 3 (MHV-3) infection.
+Clara cell 10 kDa (CC10) protein is a secretory protein with anti-inflammatory properties in allergic rhinitis and asthma.
+In this study, we aimed to determine the role of CC10 in FH and the regulation of Fgl2 by CC10.
+The regulatory effect of CC10 on Fgl2 expression was investigated using THP-1 cells and mouse peritoneal macrophages in vitro.
+Results: In the mouse FH model induced by MHV-3, the survival rate increased from 0 to 12.5% in the CC10 group compared to that in the saline-only control group.
+Meanwhile, the levels of ALT and AST in serum were significantly decreased and liver damage was reduced.
+Furthermore, hepatic Fgl2, TNF-α, and IL-1β expression was obviously downregulated together with fibrin deposition, and hepatocyte apoptosis was reduced after administration of CC10 protein.
+In vitro, CC10 was found to significantly inhibit the expression of Fgl2 in IFN-γ-treated THP-1 cells and MHV-3-infected mouse peritoneal macrophages by western blot and real-time PCR.
+Microarray investigations suggested that HMG-box transcription factor 1 (HBP1) was significantly low in CC10-treated and IFN-γ-primed THP-1 cells.
+HBP1-siRNA treatment abrogated the inhibitory effect of CC10 on Fgl2 expression in Human Umbilical Vein Endothelial cells (HUVECs).
+Type VI secretion systems (T6SSs) translocate effectors into target cells and are made of a contractile sheath and a tube docked onto a multi-protein transmembrane complex via a baseplate.
+Although some information is available about the mechanisms of tail contraction leading to effector delivery, the detailed architecture and function of the baseplate remain unknown.
+Here, we report the 3.7 Å resolution cryo-electron microscopy reconstruction of an enteroaggregative Escherichia coli baseplate subcomplex assembled from TssK, TssF and TssG.
+The structure reveals two TssK trimers interact with a locally pseudo-3-fold symmetrical complex comprising two copies of TssF and one copy of TssG.
+TssF and TssG are structurally related to each other and to components of the phage T4 baseplate and of the type IV secretion system, strengthening the evolutionary relationships among these macromolecular machines.
+These results, together with bacterial two-hybrid assays, provide a structural framework to understand the T6SS baseplate architecture.
+However, it remains poorly understood how rickettsiae remain free in macrophages prior to establishing their infection in microvascular endothelial cells.
+Here, we demonstrated that the concentration of Rickettsia australis was significantly greater in infected tissues of Atg5(flox/flox) mice than in the counterparts of Atg5(flox/flox) Lyz-Cre mice, in association with a reduced level of interleukin-1β (IL-1β) in serum.
+The greater concentration of R. australis in Atg5(flox/flox) bone marrow-derived macrophages (BMMs) than in Atg5(flox/flox) Lyz-Cre BMMs in vitro was abolished by exogenous treatment with recombinant IL-1β.
+Rickettsia australis induced significantly increased levels of light chain 3 (LC3) form II (LC3-II) and LC3 puncta in Atg5-competent BMMs but not in Atg5-deficient BMMs, while no p62 turnover was observed.
+Further analysis found the colocalization of LC3 with a small portion of R. australis and Rickettsia-containing double-membrane-bound vacuoles in the BMMs of B6 mice.
+Moreover, treatment with rapamycin significantly increased the concentrations of R. australis in B6 BMMs compared to those in the untreated B6 BMM controls.
+Taken together, our results demonstrate that Atg5 favors R. australis infection in mouse macrophages in association with a suppressed level of IL-1β production but not active autophagy flux.
+These data highlight the contribution of Atg5 in macrophages to the pathogenesis of rickettsial diseases.
+Plasmacytoid dendritic cells (PDCs) are critical for defense against respiratory viruses because of their propensity to secrete high levels of type I interferons (IFN).
+We examined the effect of human primary bronchial epithelial cells (PBECs) on PDC functions by performing RNA-sequencing of PDCs after co-culture with air liquid interface differentiated PBECs.
+Functional analysis revealed that PDCs co-cultured with PBECs displayed upregulation of type I IFN production and response genes.
+Upregulated transcripts included those encoding cytosolic sensors of DNA, ZBP-1,IRF-3, and NFkB as well as genes involved in amplification of the IFN response, such as IFNAR1, JAK/STAT, ISG15.
+In keeping with the RNA-seq data, we observe increased secretion of type I IFN and other cytokines in response to influenza in PDCs co-cultured with PBECs.
+The enhanced response of PDCs co-cultured with PBECs was due to the action of growth factors, GMCSF, GCSF, and VEGF, which were secreted by PBECs on differentiation.
+These data highlight possible mechanisms to enhance the production of type-I IFN in the airways, which is critical for host defense against respiratory infections.
+The genetic variability of Infectious bronchitis virus (IBV) is one of the main challenges for its control, hindering not only the development of effective vaccination strategies but also its classification and, consequently, epidemiology understanding.
+The 624/I and Q1 genotypes, now recognized to be part of the GI-16 lineage, represent an excellent example of the practical consequences of IBV molecular epidemiology limited knowledge.
+In fact, being their common origin unrecognized for a long time, independent epidemiological pictures were drawn for the two genotypes.
+To fix this misinterpretation, the present study reconstructs the history, population dynamics and spreading patterns of GI-16 lineage as a whole using a phylodynamic approach.
+A collection of worldwide available hypervariable region 1 and 2 (HVR12) and 3 (HVR3) sequences of the S1 protein was analysed together with 258 HVR3 sequences obtained from samples collected in Italy (the country where this genotype was initially identified) since 1963.
+The results demonstrate that after its emergence at the beginning of the XX century, GI-16 was able to persist until present days in Italy.
+Approximately in the late 1980s, it migrated to Asia, which became the main nucleus for further spreading to Middle East, Europe and especially South America, likely through multiple introduction events.
+Interestingly, although most of the recent Italian GI-16 strains originated from ancestral viruses detected in the same country, a couple were closely related to Chinese ones, supporting a backward viral flow from China to Italy.
+Besides to the specific case-study results, this work highlights the misconceptions that originate from the lack of a unified nomenclature and poor molecular epidemiology data generation and sharing.
+This shortcoming appears particularly relevant since the described scenario could likely be shared by many other IBV genotypes and pathogens in general.
+BACKGROUND: The emerging avian influenza A (H7N9) virus, a subtype of influenza viruses, was first discovered in March 2013 in China.
+Infected patients frequently present with pneumonia and acute respiratory disorder syndrome with high rates of intensive care unit admission and death.
+Neurological complications, such as Guillain–Barré syndrome(GBS), and intensive care unit-acquired weakness, including critical illness polyneuropathy and myopathy, have only rarely been reported previously.
+CASE PRESENTATION: In this study, we report on two Chinese patients with H7N9 severe pneumonia presenting neurological complications.
+A 56-year-old female patient (case 1) and a 78-year-old female patient (case 2) were admitted because of fever, cough, chest tightness and shortness of breath.
+These patients were confirmed to have H7N9 infection soon after admission followed by the development of acute respiratory distress syndrome and various severe bacterial and fungal infections.
+The case 1 patient was found to have muscle weakness in all extremities after withdrawing the mechanical ventilator, and the case 2 patient was found when withdrawing extracorporeal membrane oxygenation, both of these conditions prolonged ventilator-weaning time.
+Furthermore, the case 1 patient carried the H7N9 virus for a prolonged period, reaching 28 days, and both of them stayed in the hospital for more than two months.
+However, based on results from electrophysiological testing and needle electromyography of these 2 patients, it is difficult to differentiate critical illness polyneuropathy from GBS, since no lumbar puncture or muscle and nerve biopsy were conducted during hospitalization.
+CONCLUSIONS: Although there is great improvement in saving severe patients’ lives from fatal respiratory and blood infections, it is necessary to pay sufficient attention and to use more methods to differentiate GBS from intensive care unit-acquired weakness.
+This unusual neurological complication could result in additional complications including ventilator associated pneumonia, prolonged hospital stay and then would further increase the death rate, and huge costs.
+The endangered Florida panther (Puma concolor coryi) had an outbreak of infection with feline leukemia virus (FeLV) in the early 2000s that resulted in the deaths of 3 animals.
+A vaccination campaign was instituted during 2003–2007 and no additional cases were recorded until 2010.
+We characterized FeLV genomes isolated from Florida panthers from both outbreaks and compared them with full-length genomes of FeLVs isolated from contemporary Florida domestic cats.
+Phylogenetic analyses identified at least 2 circulating FeLV strains in panthers, which represent separate introductions from domestic cats.
+The original FeLV virus outbreak strain is either still circulating or another domestic cat transmission event has occurred with a closely related variant.
+We also report a case of a cross-species transmission event of an oncogenic FeLV recombinant (FeLV-B).
+Evidence of multiple FeLV strains and detection of FeLV-B indicate Florida panthers are at high risk for FeLV infection.
+Flaviviruses continue to cause globally relevant epidemics and have emerged or re-emerged in regions that were previously unaffected.
+Here we identify potential sylvatic reservoirs of flaviviruses and characterize the macro-ecological traits common to known wildlife hosts to predict the risk of sylvatic flavivirus transmission among wildlife and identify regions that could be vulnerable to outbreaks.
+We evaluate variability in wildlife hosts for zoonotic flaviviruses and find that flaviviruses group together in distinct clusters with similar hosts.
+Models incorporating ecological and climatic variables as well as life history traits shared by flaviviruses predict new host species with similar host characteristics.
+The combination of vector distribution data with models for flavivirus hosts allows for prediction of global vulnerability to flaviviruses and provides potential targets for disease surveillance in animals and humans.
+Olive flounder (Paralichthys olivaceus) is one of economically valuable fish species in the East Asia.
+In comparison with its economic importance, available genomic information of the olive flounder is very limited.
+The mass mortality caused by variety of pathogens (virus, bacteria and parasites) is main problem in aquaculture industry, including in olive flounder culture.
+In this study, we carried out transcriptome analysis using the olive flounder gill tissues after infection of three types of pathogens (Virus; Viral hemorrhagic septicemia virus, Bacteria; Streptococcus parauberis, and Parasite; Miamiensis avidus), respectively.
+As a result, we identified total 12,415 differentially expressed genes (DEG) from viral infection, 1,754 from bacterial infection, and 795 from parasite infection, respectively.
+To investigate the effects of pathogenic infection on immune response, we analyzed Gene ontology (GO) enrichment analysis with DEGs and sorted immune-related GO terms per three pathogen groups.
+Especially, we verified various GO terms, and genes in these terms showed down-regulated expression pattern.
+In addition, we identified 67 common genes (10 up-regulated and 57 down-regulated) present in three pathogen infection groups.
+Our goals are to provide plenty of genomic knowledge about olive flounder transcripts for further research and report genes, which were changed in their expression after specific pathogen infection.
+BACKGROUND: The human immunodeficiency virus type 1 (HIV-1) is an infectious viral agent that gradually extinguishes the immune system, resulting in acquired immune deficiency syndrome (AIDS).
+The aim of this study was to construct an RNA-positive control based on armored (AR) RNA technology, using HIV-1 RNA as a model.
+METHODS: The MS2 maturase, a coat protein gene (at positions 1765 to 1787) and HIV-1 pol gene were cloned into pET-32a plasmid.
+The prepared plasmid was transformed into Escherichia coli strain BL2 (DE3), and the expression of the construct was induced by 1 mM of isopropyl-L-thio-D-galactopyranoside (IPTG) at 37 °C for 16 h to obtain the fabricated AR RNA.
+RESULTS: The stability of AR RNA was evaluated by treatment with DNase I and RNase A and confirmed by transmission electron microscopy and gel agarose electrophoresis.
+In addition, R(2) value was 0.998, and the slope of the standard curve was -3.33.
+CONCLUSION: Prepared AR RNA, as a positive control, could be used as a basis for launching an in-house HIV-1 virus assay and other infectious agents.
+The AR RNA is non-infectious and highly resistant to ribonuclease enzyme and can reduce the risk of infection in the clinical laboratory.
+BACKGROUND: The study of Onchocerca volvulus has been limited by its host range, with only humans and non-human primates shown to be susceptible to the full life cycle infection.
+METHODOLOGY/PRINCIPAL FINDINGS: We hypothesized that highly immunodeficient NSG mice would support the survival and maturation of O. volvulus and alteration of the host microenvironment through the addition of various human cells and tissues would further enhance the level of parasite maturation.
+NSG mice were humanized with: (1) umbilical cord derived CD34(+) stem cells, (2) fetal derived liver, thymus and CD34(+) stem cells or (3) primary human skeletal muscle cells.
+NSG and humanized NSG mice were infected with 100 O. volvulus infective larvae (L3) for 4 to 12 weeks.
+When necropsies of infected animals were performed, it was observed that parasites survived and developed throughout the infection time course.
+In each of the different humanized mouse models, worms matured from L3 to advanced fourth stage larvae, with both male and female organ development.
+Serum and urine, collected from humanized mice for identification of potential biomarkers of infection, allowed for the identification of 10 O. volvulus-derived proteins found specifically in either the urine or the serum of the humanized O. volvulus-infected NSG mice.
+CONCLUSIONS/SIGNIFICANCE: The newly identified mouse models for onchocerciasis will enable the development of O. volvulus specific biomarkers, screening for new therapeutic approaches and potentially studying the human immune response to infection with O. volvulus.
+AIM: To evaluate the uptake of a mandatory meningococcal, a highly recommended influenza, and an optional pneumococcal vaccine, and to explore the key factors affecting vaccination rate among health care workers (HCWs) during the Hajj.
+METHODS: An anonymous cross-sectional online survey was distributed among HCWs and trainees who worked or volunteered at the Hajj 2015-2017 through their line managers, or by visiting their hospitals and healthcare centres in Makkah and Mina.
+Overseas HCWs who accompanied the pilgrims or those who work in foreign Hajj medical missions were excluded.
+Pearson’s χ(2) test was used to compare categorical variables and odds ratio (OR) was calculated by “risk estimate” statistics along with 95% confidence interval (95%CI).
+RESULTS: A total of 138 respondents aged 20 to 59 (median 25.6) years with a male to female ratio of 2.5:1 participated in the survey.
+Only 11.6% (16/138) participants reported receiving all three vaccines, 15.2% (21/138) did not receive any vaccine, 76.1% (105/138) received meningococcal, 68.1% (94/138) influenza and 13.8% (19/138) pneumococcal vaccine.
+Females were more likely to receive a vaccine than males (OR 3.6, 95%CI: 1.0-12.7, P < 0.05).
+Willingness to follow health authority’s recommendation was the main reason for receipt of vaccine (78.8%) while believing that they were up-to-date with vaccination (39.8%) was the prime reason for non-receipt.
+CONCLUSION: Some HCWs at Hajj miss out the compulsory and highly recommended vaccines; lack of awareness is a key barrier and authority’s advice is an important motivator.
+Despite the country’s improved dengue surveillance, it still suffers from various setbacks and needs to be complemented with alternative approaches.
+Previous studies have demonstrated the potential of Internet-based surveillance such as Google Dengue Trends (GDT) in supplementing current epidemiological methods for predicting future dengue outbreaks and patterns.
+With this, our study has two objectives: (1) assess the temporal relationship of weekly GDT and dengue incidence in Metropolitan Manila from 2009–2014; and (2) examine the health-seeking behavior based on dengue-related search queries of the population.
+The study collated the population statistics and reported dengue cases in Metropolitan Manila from respective government agencies to calculate the dengue incidence (DI) on a weekly basis for the entire region and annually per city.
+Data processing of GDT and dengue incidence was performed by conducting an ‘adjustment’ and scaling procedures, respectively, and further analyzed for correlation and cross-correlation analyses using Pearson’s correlation.
+The relative search volume of the term ‘dengue’ and top dengue-related search queries in Metropolitan Manila were obtained and organized from the Google Trends platform.
+Afterwards, a thematic analysis was employed, and word clouds were generated to examine the health behavior of the population.
+Results showed that weekly temporal GDT pattern are closely similar to the weekly DI pattern in Metropolitan Manila.
+Further analysis showed that GDT has a moderate and positive association with DI when adjusted or scaled, respectively.
+Thematic analysis of dengue-related search queries indicated 5 categories namely; (a) dengue, (b) sign and symptoms of dengue, (c) treatment and prevention, (d) mosquito, and (e) other diseases.
+The majority of the search queries were classified in ‘signs and symptoms’ which indicate the health-seeking behavior of the population towards the disease.
+Therefore, GDT can be utilized to complement traditional disease surveillance methods combined with other factors that could potentially identify dengue hotspots and help in public health decisions.
+BACKGROUND: Sepsis is a severe condition characterised by the body’s systemic inflammatory response to infection.
+The specific sepsis-related biomarkers should be used in clinical diagnosis, therapeutic response monitoring, rational use of antibiotics, and prognosis (risk stratification), etc.
+RESULTS: In this study, we investigated the expression level of Decoy Receptor 3 (DcR3) and the mechanism of high expression in sepsis patients.
+Septic cell model experiments were performed by treating human umbilical vein endothelial cells (HUVECs) and Jurkat cells with lipopolysaccharide (LPS), lipoteichoic acid (LTA) and zymosan, respectively.
+SP600125, SB203580 and ammonium pyrrolidinedithiocarbamate (PDTC) were used to inhibit JNK1/2, p38MAPK and NF-κB signalling pathways in septic cell model, respectively.
+DcR3 mRNA and protein levels in HUVECs were increased following treatment with LPS, LTA and zymosan, and also increased in Jurkat cells treated by LPS, but not by LTA or zymosan.
+When HUVECs were treated with the NF-κB inhibitor PDTC, DcR3 expression was decreased compared with controls.
+CONCLUSIONS: The results indicated that DcR3 secretion proceeded through the NF-κB signalling pathway in HUVECs.
+BACKGROUND: Highly active antiretroviral therapy has significantly changed the natural history of HIV infection, leading to a dramatic reduction of HIV-related morbidity and mortality.
+Late Presenters, Very Late Presenters and AIDS presenters still represent, also in Europe, including Italy, a huge challenge in terms of diagnostic and therapeutic management.
+HIV test resulted positive with a high HIV Viral Load and a very low T-CD4 number of cells (5 cells/mm(3)).
+Although we performed antiretroviral therapy and specific-therapies for each disease, he was transferred to intensive care unit where he died due to an Acute Respiratory Distress Syndrome.
+CONCLUSION: The reported case is unusual due to the relevant number of opportunistic diseases (both infectious and tumoral) emerging not long after the HIV infection had been diagnosed.
+Late presenters HIV patients and AIDS presenters still represent a challenge, which is often too complex for clinicians to deal with.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12879-018-3573-z) contains supplementary material, which is available to authorized users.
+BACKGROUND: The neutral theory of Motoo Kimura stipulates that evolution is mostly driven by neutral mutations.
+The relation between neutrality and adaptation has been studied in the context of RNA before and here we further study transitional mutations in the context of degenerate (plastic) RNA sequences and genetic assimilation.
+mutations which preserve an element of the phenotype set, as minimal mutations and study their properties.
+We also propose a general probabilistic interpretation of genetic assimilation and specialize it to the Boltzmann ensemble of RNA sequences.
+sequences with more than one structure at the MFE level have the highest evolvability among all sequences and are central to evolutionary innovation.
+The selective pressure in an evolutionary simulation causes the population to move towards regions with more degenerate sequences, i.e.
+regions at the intersection of different neutral networks, and this causes the number of such sequences to increase well beyond the average percentage of degenerate sequences in the sequence space.
+We also observe that evolution by quasineutral mutations tends to conserve the number of base pairs in structures and thereby maintains structural integrity even in the presence of pressure to the contrary.
+The seasonal outbreaks of influenza infection cause globally respiratory illness, or even death in all age groups.
+Given early‐warning signals preceding the influenza outbreak, timely intervention such as vaccination and isolation management effectively decrease the morbidity.
+However, it is usually a difficult task to achieve the real‐time prediction of influenza outbreak due to its complexity intertwining both biological systems and social systems.
+By exploring rich dynamical and high‐dimensional information, our dynamic network marker/biomarker (DNM/DNB) method opens a new way to identify the tipping point prior to the catastrophic transition into an influenza pandemics.
+In order to detect the early‐warning signals before the influenza outbreak by applying DNM method, the historical information of clinic hospitalization caused by influenza infection between years 2009 and 2016 were extracted and assembled from public records of Tokyo and Hokkaido, Japan.
+The early‐warning signal, with an average of 4‐week window lead prior to each seasonal outbreak of influenza, was provided by DNM‐based on the hospitalization records, providing an opportunity to apply proactive strategies to prevent or delay the onset of influenza outbreak.
+Moreover, the study on the dynamical changes of hospitalization in local district networks unveils the influenza transmission dynamics or landscape in network level.
+We describe a patient with rapidly progressing ARDS and myocarditis secondary to spotted fever caused by Rickettsia conorii.
+ARDS and myocarditis are rare complications of Rickettsia conorii infections and only a few cases are reported to date.
+CASE PRESENTATION: A 53 years old manual worker presented with fever for 5 days and a skin rash.
+He was in circulatory failure on admission and developed severe hypoxaemia with gross changes in chest radiograph by next day requiring assisted ventilation.
+He was confirmed to have spotted fever rickettsial infection with rising titre of indirect immunofluorescence antibodies to Ricketssia conorii and made a complete recovery with appropriate antibiotic therapy and supportive care.
+Even the patients with severe organ involvements such as myocarditis and ARDS can be completely cured if timely identified and treated.
+Reactive species (RS), generally known as reactive oxygen species (ROS) and reactive nitrogen species (RNS), are produced during regular metabolism in the host and are required for many cellular processes such as cytokine transcription, immunomodulation, ion transport, and apoptosis.
+Intriguingly, both RNS and ROS are commonly triggered by the pathogenic viruses and are famous for their dual roles in the clearance of viruses and pathological implications.
+Uncontrolled production of reactive species results in oxidative stress and causes damage in proteins, lipids, DNA, and cellular structures.
+In this review, we describe the production of RS, their detoxification by a cellular antioxidant system, and how these RS damage the proteins, lipids, and DNA.
+Given the widespread importance of RS in avian viral diseases, oxidative stress pathways are of utmost importance for targeted therapeutics.
+Finally, future research perspectives are discussed on the exploitation of these pathways to treat viral diseases of poultry.
+Early assessment of infectious disease outbreaks is key to implementing timely and effective control measures.
+In particular, rapidly recognising whether infected individuals stem from a single outbreak sustained by local transmission, or from repeated introductions, is crucial to adopt effective interventions.
+temporal, spatial and genetic data, to identify clusters of related cases of an infectious disease.
+Our method explicitly accounts for underreporting, and allows incorporating preexisting information about the disease, such as its serial interval, spatial kernel, and mutation rate.
+We define, for each data stream, a graph connecting all cases, with edges weighted by the corresponding pairwise distance between cases.
+Each graph is then pruned by removing distances greater than a given cutoff, defined based on preexisting information on the disease and assumptions on the reporting rate.
+The pruned graphs corresponding to different data streams are then merged by intersection to combine all data types; connected components define clusters of cases related for all types of data.
+Estimates of the reproduction number (the average number of secondary cases infected by an infectious individual in a large population), and the rate of importation of the disease into the population, are also derived.
+We test our approach on simulated data and illustrate it using data on dog rabies in Central African Republic.
+We show that the outbreak clusters identified using our method are consistent with structures previously identified by more complex, computationally intensive approaches.
+BACKGROUND: The required efforts, feasibility and predicted success of an intervention strategy against an infectious disease are partially determined by its basic reproduction number, R(0).
+In its simplest form R(0) can be understood as the product of the infectious period, the number of infectious contacts and the per-contact transmission probability, which in the case of vector-transmitted diseases necessarily extend to the vector stages.
+As vectors do not usually recover from infection, they remain infectious for life, which places high significance on the vector’s life expectancy.
+Current methods for estimating the R(0) for a vector-borne disease are mostly derived from compartmental modelling frameworks assuming constant vector mortality rates.
+We hypothesised that some of the assumptions underlying these models can lead to unrealistic high vector life expectancies with important repercussions for R(0) estimates.
+METHODOLOGY AND PRINCIPAL FINDINGS: Here we used a stochastic, individual-based model which allowed us to directly measure the number of secondary infections arising from one index case under different assumptions about vector mortality.
+Our results confirm that formulas based on age-independent mortality rates can overestimate R(0) by nearly 100% compared to our own estimate derived from first principles.
+We further provide a correction factor that can be used with a standard R(0) formula and adjusts for the discrepancies due to erroneous vector age distributions.
+CONCLUSION: Vector mortality rates play a crucial role for the success and general epidemiology of vector-transmitted diseases.
+Many modelling efforts intrinsically assume these to be age-independent, which, as clearly demonstrated here, can lead to severe over-estimation of the disease’s reproduction number.
+Our results thus re-emphasise the importance of obtaining field-relevant and species-dependent vector mortality rates, which in turn would facilitate more realistic intervention impact predictions.
+Lassa mammarenavirus (LASV) is an enveloped RNA virus that can cause Lassa fever, an acute hemorrhagic fever syndrome associated with significant morbidity and high rates of fatality in endemic regions of western Africa.
+The arenavirus matrix protein Z has several functions during the virus life cycle, including coordinating viral assembly, driving the release of new virus particles, regulating viral polymerase activity, and antagonizing the host antiviral response.
+To investigate possible means of regulation, mass spectrometry was used to identify potential sites of phosphorylation in the LASV Z protein.
+This analysis revealed that two serines (S18, S98) and one tyrosine (Y97) are phosphorylated in the flexible N- and C-terminal regions of the protein.
+Notably, two of these sites, Y97 and S98, are located in (Y97) or directly adjacent to (S98) the PPXY late domain, an important motif for virus release.
+Studies with non-phosphorylatable and phosphomimetic Z proteins revealed that these sites are important regulators of the release of LASV particles and that host-driven, reversible phosphorylation may play an important role in the regulation of LASV Z protein function.
+The standardised data set of an accident insurer was used to analyse the time trends of infection-related claims and confirmed occupational diseases (ODs) in HWs.
+The numbers of claims and confirmed claims for different infections were analysed for the years 1996 to 2017.
+The decrease was most pronounced for hepatitis B and hepatitis C infections, which were the most frequent infections for which claims were made at the start of the period.
+In 2017, tuberculosis (TB)-related claims were more frequent than those related to blood-borne virus infections.
+However, the growing number of TB claims does not reflect an increased infection risk, but rather improved methods for the diagnosis of latent TB infection (LTBI).
+Measures to prevent blood-borne virus infections in HWs were successful in the last 22 years, but attention should be paid to newly emerging infections.
+From the perspective of vaccine development, it is imperative to accurately diagnose target infections in order to exclude subjects with prior exposure from evaluations of vaccine effectiveness, to track incident infection during the course of a clinical trial and to differentiate immune reactions due to natural infections from responses that are vaccine related.
+When vaccine development is accelerated to a rapid pace in response to emerging infectious disease threats, the challenges to develop such diagnostic tools is even greater.
+This was observed through the recent expansion of Zika virus infections into the Western Hemisphere in 2014–2017.
+When initial Zika vaccine clinical trials were being designed and launched in response to the outbreak, there were no standardized sets of viral and immunological assays, and no approved diagnostic tests for Zika virus infection.
+The diagnosis of Zika virus infection is still an area of active research and development on many fronts.
+Here we review emerging infectious disease vaccine clinical assay development and trial execution with a special focus on the state of Zika virus clinical assays and diagnostics.
+Glucose-6-phosphate dehydrogenase (G6PD) deficiency may affect the clinical presentation of dengue due to the altered redox state in immune cells.
+We aimed to determine the association between G6PD deficiency and severity of dengue infection in paediatric patients in Myanmar.
+A cross-sectional study was conducted among paediatric patients aged 2–13 years with dengue in Yankin Children Hospital, Myanmar.
+One hundred and ninety-six patients positive for dengue infection, as determined via PCR or ELISA, were enrolled.
+The adjusted median G6PD value of males in the study population was used to define various cut-off points according to the WHO classification guidelines.
+G6PD genotyping for Mahidol, Kaiping and Mediterranean mutations was performed for 128 out of 196 samples by real-time multiplex PCR.
+The prevalence of G6PD phenotype deficiency (< 60% activity) in paediatric patients was 14.8% (29/196), specifically, 13.6% (14/103) in males and 16.2% (15/93) in females.
+Severe deficiency (< 10% activity) accounted for 7.1% (14/196) of our cohort, occurring 11.7% (12/103) in males and 2.2% (2/93) in females.
+Among 128 samples genotyped, the G6PD gene mutations were detected in 19.5% (25/128) of patients, with 20.3% (13/ 64) in males and 18.8% (12/64) in females.
+The G6PD Mahidol mutation was 96.0% (24/25) while the G6PD Kaiping mutation was 4.0% (1/25).
+Severe dengue was not associated with G6PD enzyme deficiency or presence of the G6PD gene mutation.
+Trial registration: The study was registered following the WHO International Clinical Trials Registry Platform (WHO-ICTRP) on Thai Clinical Trials Registry (TCTR) website, registration number # TCTR20180720001
+CD8(+) T cell immunity largely correlates with enhanced survival, whereas inflammation is associated with poor prognosis.
+Previous studies have shown polystyrene nanoparticles (PSNPs) are biocompatible, do not induce inflammation and when used as vaccine carriers for model peptides induce CD8(+) T cell responses.
+Herein we test the immunogenicity of 24 different peptides, from three leading vaccine target proteins in gynecological cancers: the E7 protein of human papilloma virus (HPV); Wilms Tumor antigen 1 (WT1) and survivin (SV), in PSNP conjugate vaccines.
+Of relevance to vaccine development was the finding that a minimal CD8(+) T cell peptide epitope from HPV was not able to induce HLA-A2.1 specific CD8(+) T cell responses in transgenic humanized mice using conventional adjuvants such as CpG, but was nevertheless able to generate strong immunity when delivered as part of a specific longer peptide conjugated to PSNPs vaccines.
+Conversely, in most cases, when the minimal CD8(+) T cell epitopes were able to induce immune responses (with WT1 or SV super agonists) in CpG, they also induced responses when conjugated to PSNPs.
+In this case, extending the sequence around the CD8(+) T cell epitope, using the natural protein context, or engineering linker sequences proposed to enhance antigen processing, had minimal effects in enhancing or changing the cross-reactivity pattern induced by the super agonists.
+Nanoparticle approaches, such as PSNPs, therefore may offer an alternative vaccination strategy when conventional adjuvants are unable to elicit the desired CD8(+) T cell specificity.
+The findings herein also offer sequence specific insights into peptide vaccine design for nanoparticle-based vaccine carriers.
+The lethality of Ebola virus infection is about 50%, supporting the urgent need to develop anti-Ebola drugs.
+Glycoprotein (GP) is the only surface protein of the Ebola virus, which is functionally critical for the virus to attach and enter the host cells, and is a promising target for anti-Ebola virus drug development.
+In this study, using the recombinant HIV-1/Ebola pseudovirus platform we previously established, we evaluated a small molecule library containing various quinoline compounds for anti-Ebola virus entry inhibitors.
+Among them, compound SYL1712 was the most potent Ebola virus entry inhibitor with an IC(50) of ~1 μM.
+The binding of SYL1712 to the vial glycoprotein was computationally modeled and was predicted to interact with specific residues of GP.
+We used the time of the addition assay to show that compound SYL1712 blocks Ebola GP-mediated entry.
+Finally, consistent with being an Ebola virus entry inhibitor, compound SYL1712 inhibited infectious Ebola virus replication in tissue culture under biosafety level 4 containment, with an IC(50) of 2 μM.
+In conclusion, we identified several related molecules with a diaryl-quinoline scaffold as potential anti-EBOV entry inhibitors, which can be further optimized for anti-Ebola drug development.
+Hepatitis C Virus (HCV) remains an important public health threat with approximately 170 million carriers worldwide who are at risk of developing hepatitis C-associated end-stage liver diseases.
+Despite improvement of HCV treatment using the novel direct-acting antivirals (DAAs) targeting viral replication, there is a lack of prophylactic measures for protection against HCV infection.
+Identifying novel antivirals such as those that target viral entry could help broaden the therapeutic arsenal against HCV.
+Herein, we investigated the anti-HCV activity of the methanolic extract from Rhizoma coptidis (RC), a widely used traditional Chinese medicine documented by the WHO and experimentally reported to possess several pharmacological functions including antiviral effects.
+Using the cell culture-derived HCV system, we demonstrated that RC dose-dependently inhibited HCV infection of Huh-7.5 cells at non-cytotoxic concentrations.
+In particular, RC blocked HCV attachment and entry/fusion into the host cells without exerting any significant effect on the cell-free viral particles or modulating key host cell entry factors to HCV.
+Moreover, RC robustly suppressed HCV pseudoparticles infection of Huh-7.5 cells and impeded infection by several HCV genotypes.
+Collectively, our results identified RC as a potent antagonist to HCV entry with potential pan-genotypic properties, which deserves further evaluation for use as an anti-HCV agent.
+Hepatitis E virus (HEV) is responsible for large waterborne epidemics of hepatitis in endemic countries and is an emerging zoonotic pathogen worldwide.
+In endemic regions, HEV-1 or HEV-2 genotypes are frequently associated with fulminant hepatitis in pregnant women, while with zoonotic HEV (HEV-3 and HEV-4), chronic cases of hepatitis and severe neurological disorders are reported.
+Here, we investigated the ability of the nonstructural polyprotein encoded by the first open reading frame (ORF1) of HEV to modulate the host early antiviral response and, in particular, the type I interferon (IFN-I) system.
+We found that the amino-terminal region of HEV-3 ORF1 (MetYPCP), containing a putative methyltransferase (Met) and a papain-like cysteine protease (PCP) functional domain, inhibited IFN-stimulated response element (ISRE) promoter activation and the expression of several IFN-stimulated genes (ISGs) in response to IFN-I.
+We showed that the MetYPCP domain interfered with the Janus kinase (JAK)/signal transducer and activator of the transcription protein (STAT) signalling pathway by inhibiting STAT1 nuclear translocation and phosphorylation after IFN-I treatment.
+In contrast, MetYPCP had no effect on STAT2 phosphorylation and a limited impact on the activation of the JAK/STAT pathway after IFN-II stimulation.
+This inhibitory function seemed to be genotype-dependent, as MetYPCP from HEV-1 had no significant effect on the JAK/STAT pathway.
+Overall, this study provides evidence that the predicted MetYPCP domain of HEV ORF1 antagonises STAT1 activation to modulate the IFN response.
+Advances in next-generation sequencing have facilitated the discovery of a multitude of long non-coding RNAs (lncRNAs) with pleiotropic functions in cellular processes, disease, and viral pathogenesis.
+It came as no surprise when viruses were also revealed to transcribe their own lncRNAs.
+Among them, gammaherpesviruses, one of the three subfamilies of the Herpesviridae, code their largest number.
+These structurally and functionally intricate non-coding (nc) transcripts modulate cellular and viral gene expression to maintain viral latency or prompt lytic reactivation.
+These lncRNAs allow for the virus to escape cytosolic surveillance, sequester, and re-localize essential cellular factors and modulate the cell cycle and proliferation.
+Some viral lncRNAs act as “messenger molecules”, transferring information about viral infection to neighboring cells.
+This broad range of lncRNA functions is achieved through lncRNA structure-mediated interactions with effector molecules of viral and host origin, including other RNAs, proteins and DNAs.
+In this review, we discuss examples of gammaherpesvirus-encoded lncRNAs, emphasize their unique structural attributes, and link them to viral life cycle, pathogenesis, and disease progression.
+We will address their potential as novel targets for drug discovery and propose future directions to explore lncRNA structure and function relationship.
+We have developed a generalizable “smart molecular diagnostic” capable of accurate point-of-care (POC) detection of variable nucleic acid targets.
+Our isothermal assay relies on multiplex execution of four loop-mediated isothermal amplification reactions, with primers that are degenerate and redundant, thereby increasing the breadth of targets while reducing the probability of amplification failure.
+An easy-to-read visual answer is computed directly by a multi-input Boolean OR logic gate (gate output is true if either one or more gate inputs is true) signal transducer that uses degenerate strand exchange probes to assess any combination of amplicons.
+We demonstrate our methodology by using the same assay to detect divergent Asian and African lineages of the evolving Zika virus (ZIKV), while maintaining selectivity against non-target viruses.
+Direct analysis of biological specimens proved possible, with crudely macerated ZIKV-infected Aedes aegypti mosquitoes being identified with 100% specificity and sensitivity.
+The ease-of-use with minimal instrumentation, broad programmability, and built-in fail-safe reliability make our smart molecular diagnostic attractive for POC use.
+In the healthcare environment, microorganisms’ cross-transmission between inanimate surfaces and patients or healthcare workers can lead to healthcare-associated infections.
+A recent interest has grown to create antimicrobial copper touch surfaces, in order to counteract microbial spread in the healthcare environment.
+For the first time, five French long-term care facilities were at 50% fitted with copper alloys door handles and handrails.
+Related to the environmental bacterial contamination, 1400 samples were carried out on copper and control surfaces over three years after copper installation.
+In addition, some copper door handles were taken from the different facilities, and their specific activity against methicillin-resistant S. aureus (MRSA) was tested in vitro.
+In comparison to control surfaces, copper door handles and handrails revealed significantly lower contamination levels.
+This difference was observed in the five long-term care facilities and it persists through the three years of the study.
+Although, the antibacterial activity of copper surfaces against MRSA was lowered after three years of regular use, it was still significant as compared to inert control surfaces.
+Therefore, copper containing surfaces are promising actors in the non-spreading of environmental bacterial contamination in healthcare facilities.
+are pathogenic bacteria that cause bacillary dysentery in humans by invading the colonic and rectal mucosa where they induce dramatic inflammation.
+Here, we have analyzed the role of the soluble PRR Pentraxin 3 (PTX3), a key component of the humoral arm of innate immunity.
+Mice that had been intranasally infected with S. flexneri were rescued from death by treatment with recombinant PTX3.
+In vitro PTX3 exerts the antibacterial activity against Shigella, impairing epithelial cell invasion and contributing to the bactericidal activity of serum.
+PTX3 is produced upon LPS-TLR4 stimulation in accordance with the lipid A structure of Shigella.
+In the plasma of infected patients, the level of PTX3 amount only correlates strongly with symptom severity.
+These results signal PTX3 as a novel player in Shigella pathogenesis and its potential role in fighting shigellosis.
+Finally, we suggest that the plasma level of PTX3 in shigellosis patients could act as a biomarker for infection severity.
+Serving over three billion passengers annually, air travel serves as a conduit for infectious disease spread, including emerging infections and pandemics.
+Our study team collected 229 environmental samples on ten transcontinental US flights with subsequent 16S rRNA sequencing.
+We found that bacterial communities were largely derived from human skin and oral commensals, as well as environmental generalist bacteria.
+We identified clear signatures for air versus touch surface microbiome, but not for individual types of touch surfaces.
+We also found large flight-to-flight beta diversity variations with no distinguishing signatures of individual flights, rather a high between-flight diversity for all touch surfaces and particularly for air samples.
+Our findings are similar to those of other recent studies of the microbiome of built environments.
+The vast majority of airplane-associated microbes are human commensals or non-pathogenic, and the results provide a baseline for non-crisis-level airplane microbiome conditions.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00248-018-1191-3) contains supplementary material, which is available to authorized users.
+BACKGROUND: Although the utilization of extracorporeal membrane oxygenation (ECMO) is increasing and its technology is evolving, only a few epidemiologic reports have described the uses and outcomes of ECMO.
+The aim of this study was to investigate the changes in utilization and survival rate in patients supported with ECMO for severe respiratory failure in Korea.
+METHODS: This was a multicenter study on consecutive patients who underwent ECMO across 16 hospitals in Korea.
+The records of all patients who required ECMO for acute respiratory failure between 2012 and 2015 were retrospectively reviewed, and the utilization of ECMO was analyzed over time.
+RESULTS: During the study period, 5552 patients received ECMO in Korea as a whole, and a total of 2472 patients received ECMO at the participating 16 hospitals.
+The number of ECMO procedures provided for respiratory failure increased from 104 to 153 during the study period.
+The use of prone positioning increased from 6.8% to 49.0% (p < 0.001), and the use of neuromuscular blockers also increased from 28.2% to 58.2% (p < 0.001).
+Multiple regression analysis showed that old age (OR 1.038 (95% CI 1.022, 1.054)), use of corticosteroid (OR 2.251 (95% CI 1.153, 4.397)), continuous renal replacement therapy (OR 2.196 (95% CI 1.135, 4.247)), driving pressure (OR 1.072 (95% CI 1.031, 1.114)), and prolonged ECMO duration (OR 1.020 (95% CI 1.003, 1.038)) were associated with increased odds of mortality.
+CONCLUSIONS: Utilization of ECMO and survival rates of patients who received ECMO for respiratory failure increased over time in Korea.
+The use of pre-ECMO prone positioning and neuromuscular blockers also increased during the same period.
+BACKGROUND: The post-disaster mental health crisis intervention (MHCI) system in China remains immature and unsystematic.
+We aim to report the perceptions of a large sample of MHCI workers and government administrators and provide recommendations for developing a national mental health disaster response management plan in China.
+METHODS: An in-depth qualitative study was conducted, collecting data from 20 focus-group discussions and 25 key stakeholder interviews.
+These recruited participants who had been involved in different types of disaster rescue across 7 provinces/cities where disasters have recently occurred.
+We used thematic analysis to analyze the data and relevant findings were extracted for policy recommendation.
+RESULTS: Mental health workers’ perspectives were examined in detailed according to four core themes: forms of organization, intervention pathway, intervention strategy and technique, and public health information.
+Post-disaster MHCI should be approached in teams that are integrated with emergency medicine systems, and be led by unified command management.
+All levels of local health and family planning commission should prepare post-disaster MHCI work plans and build response teams/emergency centres.
+Future training for MHCI workers should focus on: building a sense of trust within the team; clarifying each member’s role; strengthening the screening, assessment and referrals training for psychological professionals; and providing psychological intervention training for Chinese psychiatrists.
+It is necessary to set up guiding principles for disaster research ethics, mental health rehabilitation and media interaction.
+CONCLUSIONS: Through exploring and analyzing the perceptions of current disaster response mental health workers and government administrators, our findings provide essential recommendations for developing a national to county level post-disaster MHCI emergency management plan and can guide the formulation of relevant laws and regulation in China.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12889-018-6313-9) contains supplementary material, which is available to authorized users.
+Infusion reactions (IRs) are complex, immune-mediated side effects that mainly occur within minutes to hours of receiving a therapeutic dose of intravenously administered pharmaceutical products.
+These products are diverse and include both traditional pharmaceuticals (for example biological agents and small molecules) and new ones (for example nanotechnology-based products).
+Although IRs are not unique to nanomedicines, they represent a hurdle for the translation of nanotechnology-based drug products.
+This Perspective offers a big picture of the pharmaceutical field and examines current understanding of mechanisms responsible for IRs to nanomedicines.
+We outline outstanding questions, review currently available experimental evidence to provide some answers and highlight the gaps.
+We review advantages and limitations of the in vitro tests and animal models used for studying IRs to nanomedicines.
+Finally, we propose a roadmap to improve current understanding, and we recommend a strategy for overcoming the problem.
+Chloroquine diphosphate (CQ) is a hydrophilic drug with low entrapment efficiency in hydrophobic nanoparticles (NP).
+Herpes simplex virus type 1 (HSV-1) is an enveloped double-stranded DNA virus worldwide known as a common human pathogen.
+This study aims to develop chloroquine-loaded poly(lactic acid) (PLA) nanoparticles (CQ-NP) to improve the chloroquine anti- HSV-1 efficacy.
+Physicochemical properties of the NP were monitored using dynamic light scattering, atomic force microscopy, drug loading efficiency, and drug release studies.
+Spherical nanoparticles were produced with modal diameter of <300 nm, zeta potential of −20 mv and encapsulation efficiency of 64.1%.
+In vitro assays of CQ-NP performed in Vero E6 cells, using the MTT-assay, revealed different cytotoxicity levels.
+Finally, the antiviral activity tested by the plaque reduction assay revealed greater efficacy for CQ-NP compared to CQ at concentrations equal to or lower than 20 µg mL(−1) (p < 0.001).
+The CQ-NP has shown feasible properties and great potential to improve the antiviral activity of drugs.
+In contrast to −1 programmed ribosomal frameshifting (PRF) stimulation by an RNA pseudoknot downstream of frameshifting sites, a refolding upstream RNA hairpin juxtaposing the frameshifting sites attenuates −1 PRF in human cells and stimulates +1 frameshifting in yeast.
+This eukaryotic functional mimicry of the internal Shine-Dalgarno (SD) sequence-mediated duplex was confirmed directly in the 70S translation system, indicating that both frameshifting regulation activities of upstream hairpin are conserved between 70S and 80S ribosomes.
+Unexpectedly, a downstream pseudoknot also possessed two opposing hungry codon-mediated frameshifting regulation activities: attenuation of +1 frameshifting and stimulation of a non-canonical −1 frameshifting within the +1 frameshift-prone CUUUGA frameshifting site in the absence of release factor 2 (RF2) in vitro.
+However, the −1 frameshifting activity of the downstream pseudoknot is not coupled with its +1 frameshifting attenuation ability.
+Similarly, the +1 frameshifting activity of the upstream hairpin is not required for its −1 frameshifting attenuation function Thus, each of the mRNA duplexes flanking the two ends of a ribosomal mRNA-binding channel possesses two functions in bi-directional ribosomal frameshifting regulation: frameshifting stimulation and counteracting the frameshifting activity of each other.
+Circular RNAs (CircRNAs), as a new class of non-coding RNA molecules that, unlike linear RNAs, have covalently closed loop structures from the ligation of exons, introns, or both.
+CircRNAs are widely expressed in various organisms in a specie-, tissue-, disease- and developmental stage-specific manner, and have been demonstrated to play a vital role in the pathogenesis and progression of human diseases.
+An increasing number of recent studies has revealed that circRNAs are intensively associated with different respiratory diseases, including lung cancer, acute respiratory distress syndrome, pulmonary hypertension, pulmonary tuberculosis, and silicosis.
+However, to the best of our knowledge, there has been no systematic review of studies on the role of circRNAs in respiratory diseases.
+In this review, we elaborate on the biogenesis, functions, and identification of circRNAs and focus particularly on the potential implications of circRNAs in respiratory diseases.
+BACKGROUND: Increased vascular permeability is a key feature in the pathophysiology of sepsis and the development of organ failure.
+Shedding of the endothelial glycocalyx is increasingly being recognized as an important pathophysiological mechanism but at present it is unclear if glypicans contribute to this response.
+METHODS: Plasma GPC 1–6 levels were measured by ELISA in 10 patients with sepsis and 10 healthy controls as an initial screening.
+Plasma GPC 1, 3, and 4 were further measured in a cohort of 184 patients with a clinically confirmed infection.
+Patients were divided into groups of those who had sepsis and those who had an infection without organ failure.
+To determine whether plasma glypicans could predict the development of organ failure, patients were further subdivided to those who had organ failure at enrolment and those who developed it after enrollment.
+The association of plasma GPC 1, 3, and 4 with organ failure and with various markers of inflammation, disease severity, and glycocalyx shedding was investigated.
+RESULTS: In the pilot study, only GPC 1, 3, and 4 were detectable in the plasma of sepsis patients.
+In the larger cohort, GPC 1, 3, and 4 levels were significantly higher (p < 0.001) in patients with sepsis than in those with infection without organ failure.
+GPC 1, 3, and 4 were significantly positively correlated with plasma levels of the disease severity markers C-reactive protein, lactate, procalcitonin, and heparin binding protein, and with the marker of glycocalyx degradation syndecan 1.
+They were significantly negatively correlated with plasma levels of the glycocalyx-protective factors apolipoprotein M and sphingosine-1-phosphate.
+CONCLUSIONS: We show that GPC 1, 3, and 4 are elevated in plasma of patients with sepsis and correlate with markers of disease severity, systemic inflammation, and glycocalyx damage.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s40635-018-0216-z) contains supplementary material, which is available to authorized users.
+The Integrated Microbial Genome/Virus (IMG/VR) system v.2.0 (https://img.jgi.doe.gov/vr/) is the largest publicly available data management and analysis platform dedicated to viral genomics.
+Since the last report published in the 2016, NAR Database Issue, the data has tripled in size and currently contains genomes of 8389 cultivated reference viruses, 12 498 previously published curated prophages derived from cultivated microbial isolates, and 735 112 viral genomic fragments computationally predicted from assembled shotgun metagenomes.
+Nearly 60% of the viral genomes and genome fragments are clustered into 110 384 viral Operational Taxonomic Units (vOTUs) with two or more members.
+To improve data quality and predictions of host specificity, IMG/VR v.2.0 now separates prokaryotic and eukaryotic viruses, utilizes known prophage sequences to improve taxonomic assignments, and provides viral genome quality scores based on the estimated genome completeness.
+Finally, geographic map visualization to locate user-selected viral genomes or genome fragments has been implemented and download options have been extended.
+All of these features make IMG/VR v.2.0 a key resource for the study of viruses.
+BACKGROUND: Human adenovirus type 3 (HAdV-3) and 7 (HAdV-7) cause significant morbidity and develop severe complications and long-term pulmonary sequelae in children.
+However, epidemiologic reports have suggested that nearly all highly severe or fatal adenoviral diseases in children are associated with HAdV-7 rather than HAdV-3.
+Here, we conduct in-depth investigations to confirm and extend these findings through a comprehensive series of assays in vitro and in vivo as well as clinical correlates.
+METHODS: A total of 8248 nasopharyngeal aspirate (NPA) samples were collected from hospitalized children with acute respiratory infections in Children’s Hospital of Chongqing Medical University from June 2009 to May 2015.
+Among 289 samples that tested positive for HAdVs, clinical data of 258 cases of HAdV-3 (127) and HAdV-7 (131) infections were analyzed.
+All HAdV-positive samples were classified by sequencing the hexon and fiber genes, and compared with clinical data and virological assays.
+We also performed in vitro assays of virus quantification, viral growth kinetics, competitive fitness, cytotoxicity and C3a assay of the two strains.
+RESULTS: Clinical characteristics revealed that HAdV-7 infection caused more severe pneumonia, toxic encephalopathy, respiratory failure, longer mean hospitalization, significantly lower white blood cell (WBC) and platelet counts, compared to those of HAdV-3.
+In cell culture, HAdV-7 replicated at a higher level than HAdV-3, and viral fitness showed significant differences as well.
+HAdV-7 also exhibited higher C3a production and cytotoxic effects, and HAdV-7-infected mice showed aggravated pathology and higher pulmonary virus loads, compared to HAdV-3-infected mice.
+Macrophages in BALF remained markedly high during infection, with concomitant increase in pro-inflammatory cytokines (TNF-α, IL-1β, IFN-γ, and IL-6), compared HAdV-3 infection.
+CONCLUSIONS: These results document that HAdV-7 replicates more robustly than HAdV-3, and promotes an exacerbated cytokine response, causing a more severe airway inflammation.
+The findings merit further mechanistic studies that offer the pediatricians an informed decision to proceed with early diagnosis and treatment of HAdV-7 infection.
+Apoptosis is a form of cell death by which the body maintains the homeostasis of the internal environment.
+Apoptosis is an initiative cell death process that is controlled by genes and is mainly divided into endogenous pathways (mitochondrial pathway), exogenous pathways (death receptor pathway), and apoptotic pathways induced by endoplasmic reticulum (ER) stress.
+Under specific conditions, ER stress can be beneficial to the body; however, if ER protein homeostasis is not restored, the prolonged activation of the unfolded protein response may initiate apoptotic cell death via the up-regulation of the C/EBP homologous protein (CHOP).
+CHOP plays an important role in ER stress-induced apoptosis and this review focuses on its multifunctional roles in that process, as well as its role in apoptosis during microbial infection.
+We also focus on the newest discoveries in the functions of CHOP-induced apoptosis during microbial infection, including DNA and RNA viruses and some species of bacteria.
+Understanding how CHOP functions during microbial infection will assist with the development of antimicrobial therapies.
+Eight novel N′-(2-oxoindolin-3-ylidene)-2-propylpentane hydrazide-hydrazone derivatives 4a–h were synthesized and fully characterized by IR, NMR ((1)H-NMR and (13)C-NMR), elemental analysis, and X-ray crystallography.
+The cyto-toxicity and in vitro anti-cancer evaluation of the prepared compounds have been assessed against two different human tumour cell lines including human liver (HepG2) and leukaemia (Jurkat), as well as in normal cell lines derived from human embryonic kidney (HEK293) using MTT assay.
+The compounds 3e, 3f, 4a, 4c, and 4e revealed promising anti-cancer activities in tested human tumour cells lines (IC(50) values between 3 and 7 μM) as compared to the known anti-cancer drug 5-Fluorouracil (IC(50) 32–50 μM).
+Among the tested compounds, 4a showed specificity against leukaemia (Jurkat) cells, with an IC(50) value of 3.14 μM, but this compound was inactive in liver cancer and normal cell lines.
+The functionalisation of microbeads with oligonucleotides has become an indispensable technique for high-throughput aptamer selection in SELEX protocols.
+In addition to simplifying the separation of binding and non-binding aptamer candidates, microbeads have facilitated the integration of other technologies such as emulsion PCR (ePCR) and Fluorescence Activated Cell Sorting (FACS) to high-throughput selection techniques.
+Within these systems, monoclonal aptamer microbeads can be individually generated and assayed to assess aptamer candidate fitness thereby helping eliminate stochastic effects which are common to classical SELEX techniques.
+Such techniques have given rise to aptamers with 1000 times greater binding affinities when compared to traditional SELEX.
+Another emerging technique is Fluorescence Activated Droplet Sorting (FADS) whereby selection does not rely on binding capture allowing evolution of a greater diversity of aptamer properties such as fluorescence or enzymatic activity.
+Within this review we explore examples and applications of oligonucleotide functionalised microbeads in aptamer selection and reflect upon new opportunities arising for aptamer science.
+Acute lung injury (ALI) affects over 10% of patients hospitalised in critical care, with acute respiratory distress syndrome (ARDS) being the most severe form of ALI and having a mortality rate in the region of 40%.
+There has been slow but incremental progress in identification of biomarkers that contribute to the pathophysiology of ARDS, have utility in diagnosis and monitoring, and that are potential therapeutic targets (Calfee CS, Delucchi K, Parsons PE, Thompson BT, Ware LB, Matthay MA, Thompson T, Ware LB, Matthay MA, Lancet Respir Med 2014, 2:611–-620).
+However, a major issue is that ARDS is such a heterogeneous, multi-factorial, end-stage condition that the strategies for “lumping and splitting” are critical (Prescott HC, Calfee CS, Thompson BT, Angus DC, Liu VX, Am J Respir Crit Care Med 2016, 194:147–-155).
+Nevertheless, sequencing of the human genome, the availability of improved methods for analysis of transcription to mRNA (gene expression), and development of sensitive immunoassays has allowed the application of network biology to ARDS, with these biomarkers offering potential for personalised or precision medicine (Sweeney TE, Khatri P, Toward precision medicine Crit Care Med; 2017 45:934-939).
+Biomarker panels have potential applications in molecular phenotyping for identifying patients at risk of developing ARDS, diagnosis of ARDS, risk stratification and monitoring.
+Two subphenotypes of ARDS have been identified on the basis of blood biomarkers: hypo-inflammatory and hyper-inflammatory.
+Biomarkers of particular interest have included interleukins (IL-6 and IL-8), interferon gamma (IFN-γ), surfactant proteins (SPD and SPB), von Willebrand factor antigen, angiopoietin 1/2 and plasminogen activator inhibitor-1 (PAI-1).
+In terms of gene expression (mRNA) in blood there have been found to be increases in neutrophil-related genes in sepsis-induced and influenza-induced ARDS, but whole blood expression does not give a robust diagnostic test for ARDS.
+Despite improvements in management of ARDS on the critical care unit, this complex disease continues to be a major life-threatening event.
+However, there have been major advances in methods of mechanical ventilation, a neuromuscular blocker (cisatracurium besilate) has shown some benefit, and stem cell therapy is being developed.
+In the future, by understanding the role of biomarkers in the pathophysiology of ARDS and lung injury, it is hoped that this will provide rational therapeutic targets and ultimately improve clinical care (Seymour CW, Gomez H, Chang CH, Clermont G, Kellum JA, Kennedy J, Yende S, Angus DC, Crit Care 2017, 21:257).
+Interferon-induced transmembrane protein 3 (IFITM3) is a potent antiviral protein that enhances cellular resistance to a variety of pathogens, including influenza virus.
+Classically defined as an interferon-stimulated gene, expression of IFITM3 on cells is rapidly up-regulated in response to type I and II interferon.
+Here we found that IFITM3 is rapidly up-regulated by T cells following their activation and this occurred independently of type I and II interferon and the interferon regulatory factors 3 and 7.
+Up-regulation of IFITM3 on effector T cells protected these cells from virus infection and imparted a survival advantage at sites of virus infection.
+Our results show that IFITM3 expression on effector T cells is crucial for these cells to mediate their effector function and highlights an interferon independent pathway for the induction of IFITM3 which, if targeted, could be an effective approach to harness the activity of IFITM3 for infection prevention.
+Many viruses interface with the autophagy pathway, a highly conserved process for recycling cellular components.
+For three viral infections in which autophagy constituents are proviral (poliovirus, dengue, and Zika), we developed a panel of knockouts (KOs) of autophagy-related genes to test which components of the canonical pathway are utilized.
+We discovered that each virus uses a distinct set of initiation components; however, all three viruses utilize autophagy-related gene 9 (ATG9), a lipid scavenging protein, and LC3 (light-chain 3), which is involved in membrane curvature.
+By measuring viral RNA abundance, we also found that poliovirus utilizes these autophagy components for intracellular growth, while dengue and Zika virus only use autophagy components for post-RNA replication processes.
+Comparing how RNA viruses manipulate the autophagy pathway reveals new noncanonical autophagy routes, explains the exacerbation of disease by starvation, and uncovers common targets for antiviral drugs.
+BACKGROUND: The 2009 influenza pandemic was caused by the A/H1N1pdm09 virus, which was subsequently included in the seasonal vaccine, up to 2016/2017, as the A/H1N1 strain.
+METHODS: Healthcare workers (HCWs) were immunized with the AS03-adjuvanted H1N1pdm09 vaccine in 2009 (N = 250), and subsequently vaccinated with seasonal vaccines containing H1N1pdm09 for 4 seasons (repeated group), <4 seasons (occasional group), or no seasons (single group).
+Blood samples were collected pre and at 21 days and 3, 6, and 12 months after each vaccination, or annually (pre-season) from 2010 in the single group.
+RESULTS: Pandemic vaccination robustly induced HI antibodies that persisted above the 50% protective threshold (HI titers ≥ 40) over 12 months post-vaccination.
+Previous seasonal vaccination and the duration of adverse events after the pandemic vaccination influenced the decision to vaccinate in subsequent seasons.
+During 2010/2011–2013/2014, antibodies were boosted after each seasonal vaccination, although no significant difference was observed between the repeated and occasional groups.
+In the single group without seasonal vaccination, 32% of HCWs seroconverted (≥4-fold increase in HI titers) during the 4 subsequent years, most of whom had HI titers <40 prior to seroconversion.
+When excluding these seroconverted HCWs, HI titers gradually declined from 12 to 60 months post–pandemic vaccination.
+To replicate and disseminate, viruses need to manipulate and modify the cellular machinery for their own benefit.
+We are interested in translation, which is one of the key steps of gene expression and viruses that have developed several strategies to hijack the ribosomal complex.
+The type 1 human immunodeficiency virus is a good paradigm to understand the great diversity of translational control.
+Indeed, scanning, leaky scanning, internal ribosome entry sites, and adenosine methylation are used by ribosomes to translate spliced and unspliced HIV-1 mRNAs, and some require specific cellular factors, such as the DDX3 helicase, that mediate mRNA export and translation.
+In addition, some viral and cellular proteins, including the HIV-1 Tat protein, also regulate protein synthesis through targeting the protein kinase PKR, which once activated, is able to phosphorylate the eukaryotic translation initiation factor eIF2α, which results in the inhibition of cellular mRNAs translation.
+Finally, the infection alters the integrity of several cellular proteins, including initiation factors, that directly or indirectly regulates translation events.
+In this review, we will provide a global overview of the current situation of how the HIV-1 mRNAs interact with the host cellular environment to produce viral proteins.
+BACKGROUND: Epidemiological surveillance of HIV infection in Japan involves two technical problems for directly applying a classical backcalculation method, i.e., (i) all AIDS cases are not counted over time and (ii) people diagnosed with HIV have received antiretroviral therapy, extending the incubation period.
+The present study aimed to address these issues and estimate the HIV incidence and the proportion of diagnosed HIV infections, using a simple statistical model.
+METHODS: From among Japanese nationals, yearly incidence data of HIV diagnoses and patients with AIDS who had not previously been diagnosed as HIV positive, from 1985 to 2017, were analyzed.
+Using the McKendrick partial differential equation, general convolution-like equations were derived, allowing estimation of the HIV incidence and the time-dependent rate of diagnosis.
+RESULTS: Assuming that the median incubation period was 10.0 years, the cumulative number of HIV infections was estimated to be 29,613 (95% confidence interval (CI): 29,059, 30,167) by the end of 2017, and the proportion of diagnosed HIV infections was estimated at 80.3% (95% CI [78.7%–82.0%]).
+Allowing the median incubation period to range from 7.5 to 12.3 years, the estimate of the proportion diagnosed can vary from 77% to 84%.
+DISCUSSION: The proportion of diagnosed HIV infections appears to have not yet reached 90% among Japanese nationals.
+Compared with the peak incidence from 2005–2008, new HIV infections have clearly been in a declining trend; however, there are still more than 1,000 new HIV infections per year in Japan.
+To increase the diagnosed proportion of HIV infections, it is critical to identify people who have difficulty accessing consultation, testing, and care, and to explore heterogeneous patterns of infection.
+While active immunization elicits a lasting immune response by the body, passive immunotherapy transiently equips the body with exogenously generated immunological effectors in the form of either target-specific antibodies or lymphocytes functionalized with target-specific receptors.
+mRNA prepared by in vitro transcription (IVT) is increasingly appreciated as a drug substance for delivery of recombinant proteins.
+With its biological role as transient carrier of genetic information translated into protein in the cytoplasm, therapeutic application of mRNA combines several advantages.
+It is not associated with the risk of inducing genomic changes and potential adverse effects are only temporary due to its transient nature.
+Compared to the administration of recombinant proteins produced in bioreactors, mRNA allows supplying proteins that are difficult to manufacture and offers extended pharmacokinetics for short-lived proteins.
+Based on great progress in understanding and manipulating mRNA properties, efficacy data in various models have now demonstrated that IVT mRNA constitutes a potent and flexible platform technology.
+Starting with an introduction into passive immunotherapy, this review summarizes the current status of IVT mRNA technology and its application to such immunological interventions.
+Chikungunya virus (CHIKV) is a reemerging global health threat that produces debilitating arthritis in people.
+Like other RNA viruses with high mutation rates, CHIKV produces populations of genetically diverse genomes within a host.
+While several known CHIKV mutations influence disease severity in vertebrates and transmission by mosquitoes, the role of intrahost diversity in chikungunya arthritic disease has not been studied.
+In this study, high- and low-fidelity CHIKV variants, previously characterized by altered in vitro population mutation frequencies, were used to evaluate how intrahost diversity influences clinical disease, CHIKV replication, and antibody neutralization in immunocompetent adult mice inoculated in the rear footpads.
+Both high- and low-fidelity mutations were hypothesized to attenuate CHIKV arthritic disease, replication, and neutralizing antibody levels compared to wild-type (WT) CHIKV.
+Unexpectedly, high-fidelity mutants elicited more severe arthritic disease than the WT despite comparable CHIKV replication, whereas a low-fidelity mutant produced attenuated disease and replication.
+Serum antibody developed against both high- and low-fidelity CHIKV exhibited reduced neutralization of WT CHIKV.
+Using next-generation sequencing (NGS), the high-fidelity mutations were demonstrated to be genetically stable but produced more genetically diverse populations than WT CHIKV in mice.
+The NGS results contrast with previously reported population diversities for fidelity variants, which focused mainly on part of the E1 gene, and highlight the need for direct measurements of mutation rates to clarify CHIKV fidelity phenotypes.
+Like other RNA viruses, CHIKV has a high mutation rate and is capable of rapid intrahost diversification during an infection.
+In other RNA viruses, virus population diversity associates with disease progression; however, potential impacts of intrahost viral diversity on CHIKV arthritic disease have not been studied.
+Using previously characterized CHIKV fidelity variants, we addressed whether CHIKV population diversity influences the severity of arthritis and host antibody response in an arthritic mouse model.
+Our findings show that CHIKV populations with greater genetic diversity can cause more severe disease and stimulate antibody responses with reduced neutralization of low-diversity virus populations in vitro.
+The discordant high-fidelity phenotypes in this study highlight the complexity of inferring replication fidelity indirectly from population diversity.
+Memory B cells that are generated during an infection or following vaccination act as sentinels to guard against future infections.
+Upon repeat antigen exposure memory B cells differentiate into new antibody-secreting plasma cells to provide rapid and sustained protection.
+Some pathogens evade or suppress the humoral immune system, or induce memory B cells with a diminished ability to differentiate into new plasma cells.
+Single cell approaches coupled with next generation antibody gene sequencing facilitate a detailed analysis of the pathogen-specific memory B cell repertoire.
+Monoclonal antibodies that are generated from antibody gene sequences allow a functional analysis of the repertoire.
+This review discusses what has been learned thus far from analysis of diverse pathogen-specific memory B cell compartments and describes major differences in their repertoires.
+Such information may illuminate ways to advance the goal of improving vaccine and therapeutic antibody design.
+BACKGROUND: The acute respiratory distress syndrome (ARDS) is characterized by the acute onset of hypoxemia and bilateral lung infiltrates in response to an inciting event, and is associated with high morbidity and mortality.
+We hypothesized that HSCT patients with ARDS would have a unique transcriptomic profile identifiable in peripheral blood compared to those that did not undergo HSCT.
+METHODS: We isolated RNA from banked peripheral blood samples from a biorepository of critically ill ICU patients.
+RNA-Seq was performed on 11 patients with ARDS (5 that had undergone HSCT and 6 that had not) and 12 patients with sepsis without ARDS (5 that that had undergone HCST and 7 that had not).
+RESULTS: We identified 687 differentially expressed genes between ARDS and ARDS-HSCT (adjusted p-value < 0.01), including IFI44L, OAS3, LY6E, and SPATS2L that had increased expression in ARDS vs. ARDS-HSCT; these genes were not differentially expressed in sepsis vs sepsis-HSCT.
+Gene ontology enrichment analysis revealed that many differentially expressed genes were related to response to type I interferon.
+CONCLUSIONS: Our findings reveal significant differences in whole blood transcriptomic profiles of patients with non-HSCT ARDS compared to ARDS-HSCT patients and point toward different immune responses underlying ARDS and ARDS-HSCT that contribute to lung injury.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12931-019-0981-6) contains supplementary material, which is available to authorized users.
+Basal cell carcinoma (BCC) is the most common type of human skin cancer, which is driven by the aberrant activation of Hedgehog signaling.
+Previous evidence indicated that sex determining region Y-box 2 (SOX2) is associated with the tumor metastasis.
+Therefore, the aim of the current study was to analyze the possible mechanism of SOX2 in the progression of BCC.
+The levels of SOX2 in BCC cells were detected by reverse transcription-quantitative polymerase chain reaction.
+Immunoblotting and immunofluorescence were used for analyzing the role of SOX2 knockdown in the serine-arginine protein kinase 1 (SRPK1)-mediated phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) signaling pathway in BCC cells.
+In addition, SOX2 knockdown inhibited the migration and invasion of BCC cells, and the epithelial-mesenchymal transition (EMT) progress of BCC cells.
+It was also observed that SOX2 knockdown decreased SRPK1 expression, which further led to the downregulation of PI3K and AKT expression levels in BCC cells.
+Furthermore, SRPK1 transfection or PI3K/AKT pathway activation abolished the inhibitory effects of SOX2 knockdown on the migration, invasion and EMT progress of BCC cells.
+In conclusion, these results indicated that SOX2 may potentially serve as a target for BCC therapy by targeting the SRPK1-mediated PI3K/AKT signaling pathway.
+Recent evidence has confirmed that a mutation of the isocitrate dehydrogenase (IDH) gene occurs early in gliomagenesis and contributes to suppressed immunity.
+The present study aimed to determine the candidate genes associated with IDH mutation status that could serve as biomarkers of immune suppression for improved prognosis prediction.
+Clinical information and RNA-seq gene expression data were collected for 932 glioma samples from the CGGA and TCGA databases, and differentially expressed genes in both lower-grade glioma (LGG) and glioblastoma (GBM) samples were identified according to IDH mutation status.
+Only one gene, interferon-stimulated exonuclease gene 20 (ISG20), with reduced expression in IDH mutant tumors, demonstrated significant prognostic value.
+ISG20 expression level significantly increased with increasing tumor grade, and its high expression was associated with a poor clinical outcome.
+Moreover, increased ISG20 expression was associated with increased infiltration of monocyte-derived macrophages and neutrophils, and suppressed adaptive immune response.
+ISG20 expression was also positively correlated with PD-1, PD-L1, and CTLA4 expression, along with the levels of several chemokines.
+We conclude that ISG20 is a useful biomarker to identify IDH-mediated immune processes in glioma and may serve as a potential therapeutic target.
+Post-translational modification of host and viral proteins by ubiquitin (Ub) and Ub-like proteins, such as interferon stimulated gene product 15 (ISG15), plays a key role in response to infection.
+This includes viruses in the Nairoviridae family that encode a viral homologue of the ovarian tumor protease (vOTU).
+vOTU activity was recently demonstrated to be critical for replication of the often-fatal Crimean-Congo hemorrhagic fever virus, with DUB activity suppressing the type I interferon responses and deISGylase activity broadly removing ISG15 conjugated proteins.
+Recent genomic characterization has revealed a high degree of diversity, with vOTUs showing less than 25% amino acids identities within the family.
+Previous investigations have been limited to only a few closely related nairoviruses, leaving it unclear what impact this diversity has on vOTU function.
+To probe the effects of vOTU diversity on enzyme activity and specificity, we assessed representative vOTUs spanning the Nairoviridae family towards Ub and ISG15 fluorogenic substrates.
+A subset of the vOTUs were further assayed against eight biologically relevant di-Ub substrates, uncovering both common trends and distinct preferences of poly-Ub linkages by vOTUs.
+Four novel X-ray crystal structures were obtained that provide a biochemical rationale for vOTU substrate preferences and elucidate structural features that distinguish the vOTUs, including a motif in the Hughes orthonairovirus species that has not been previously observed in OTU domains.
+Additionally, structure-informed mutagenesis provided the first direct evidence of a second site involved in di-Ub binding for vOTUs.
+These results provide new insight into nairovirus evolution and pathogenesis, and further enhances the development of tools for therapeutic purposes.
+To address the unmet needs for human polyclonal antibodies both as therapeutics and diagnostic reagents, building upon our previously established transchromosomic (Tc) cattle platform, we report herein the development of a Tc goat system expressing human polyclonal antibodies in their sera.
+In the Tc goat system, a human artificial chromosome (HAC) comprising the entire human immunoglobulin (Ig) gene repertoire in the germline configuration was introduced into the genetic makeup of the domestic goat.
+We achieved this by transferring the HAC into goat fetal fibroblast cells followed by somatic cell nuclear transfer for Tc goat production.
+Gene and protein expression analyses in the peripheral blood mononuclear cells (PBMC) and the sera, respectively, of Tc caprine demonstrated the successful expression of human Ig genes and antibodies.
+Furthermore, immunization of Tc caprine with inactivated influenza A (H7N9) viruses followed by H7N9 Hemagglutinin 1 (HA1) boosting elicited human antibodies with high neutralizing activities against H7N9 viruses in vitro.
+As a small ungulate, Tc caprine offers the advantages of low cost and quick establishment of herds, therefore complementing the Tc cattle platform in responses to a range of medical needs and diagnostic applications where small volumes of human antibody products are needed.
+Sublingual immunization is emerging as an alternative to nasal immunization and induction of mucosal IgA responses.
+Using Bacillus anthracis edema toxin (EdTx) as an adjuvant, we previously showed that innate responses triggered after sublingual immunization could limit generation of IgA responses.
+We tested whether co-administration of a neutrophil elastase inhibitor (NEI) could rescue the ability of EdTx to induce broad antibody responses, including mucosal IgA.
+NEI supplementation of sublingual vaccines containing EdTx promoted antigen-specific serum IgA responses but also enhanced serum IgG1, and IgG2b responses.
+This enhancing effect of NEI did not extend to all antibody isotypes and IgG sublclasses, since NEI reduced serum IgE responses and did not affect IgG2a/c and IgG3 responses.
+NEI supplementation also promoted anti-Bacillus anthracis protective antigen (PA) neutralizing antibodies and enhanced high affinity IgG1 and IgA antibodies.
+In addition to serum IgA, NEI supplementation stimulated antigen-specific mucosal IgA responses in the GI tract, and enhanced antigen-specific IgG responses in vaginal washes.
+Analysis of CD4(+) T helper cell responses revealed that co-administration of NEI broadened the profile of cytokine responses, by stimulating Th1, Th2, Th17, and Tfh cytokines.
+We also noted that NEI had a higher stimulatory effect on IL-5, IL-10, IL-17 responses.
+BACKGROUND: China, which used to be an export country for migrants, has become a new destination for international migrants due to its rapid economic growth.
+However, little empirical data is available on the health status of and health service access barriers faced by these international migrants.
+METHODS: Foreigners who visited the Guangzhou Municipal Exit-Entry Administration Office to extend their visas were invited to participate in the study.
+The participants were characterised by the income level of their country of origin (high-, middle- and low-income countries (HICs, MICs and LICs, respectively)), and the key factors associated with their health status, medical insurance coverage and perceptions of health services in China were examined.
+RESULTS: Overall, 1146 participants from 119 countries participated in the study, 57.1, 25.1 and 17.8% of whom were from MICs, HICs and LICs, respectively.
+Over one fifth of the participants experienced health problems while staying in China, and about half had no health insurance.
+Although the participants from HICs were more likely than those from MICs and LICs to have medical insurance, they were also more likely to have health problems.
+Furthermore, 43.0, 45.0 and 12.0% of the participants thought that the health services in China were good, fair and poor, respectively.
+CONCLUSIONS: Our study is the first to report a quantitative survey of the health status, health insurance coverage, and health service perceptions of a diverse and surging population of international migrants in China.
+The findings call for more in-depth studies on the challenges presented by the increasing global migration to the health system.
+A 79-year-old gentleman presented with spontaneous pneumomediastinum and subcutaneous emphysema with pneumonia but no pre-existing lung disease.
+He presented with a 4-day history of increased shortness of breath, pleuritic chest pain, fevers, and non-productive cough.
+It has previously been associated with cases of pneumonia but often with rare strains such as P. jirovecii pneumonia in immunocompromised patients.
+Treatment of pneumomediastinum is typically conservative, and although options may be limited, aggressive management of any causative factor may be essential in selected cases.
+Computerised tomography is a valuable diagnostic tool for identifying pneumomediastinum in patients with subcutaneous emphysema.
+Evidence regarding use of non-invasive/invasive ventilation remains limited but it may theoretically aggravate any air leakage.
+Introduction and expansion of pig production systems in this biodiverse landscape may create new risks, including zoonotic pathogen transmission.
+Historically, biosecurity measures have primarily been focused at farm level, ignoring the important function pig traders fulfill between farmers and consumers.
+This study interviewed pig traders operating at Uganda’s only registered pork abattoir to describe their characteristics, business practices, biosecurity practices, and pig health management and reporting practices.
+All the traders were male, and nearly all (90.5%) relied on pig trading as their primary source of income.
+Most of the pigs brought for processing at the slaughterhouse were purchased from smallholder farms (87.3%).
+In addition, there was a significant difference in the high price paid per kilogram at farm gate by region (P = 0.005).
+High prices paid at farm gate were associated with holiday periods (P < 0.001), harvest season (P < 0.001), and drought (P < 0.001).
+Traders preferred buying live pigs from male farmers (88.9%) because they were considered the final decision makers and owned the pigs being sold.
+Improvements in local pork slaughterhouses and markets will benefit not only pig traders in accessing consistent customers but also individual pig farmers by increasing their market access.
+Finally, given their role as a link between farmers and consumers, traders would benefit from targeted inclusion in disease control and prevention strategies.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11250-018-1668-6) contains supplementary material, which is available to authorized users.
+Healthcare workers (HCWs) have elevated risk of contact with EBOV-infected patients, particularly if safety precautions are not rigorously practiced.
+We conducted a serosurvey to determine seroprevalence against multiple EBOV antigens among HCWs of Boende Health Zone, Democratic Republic of the Congo, the site of a 2014 EBOV outbreak.
+Overall, 234 (41.4%) of enrolled HCWs were reactive to at least 1 EBOV protein: 159 (28.1%) were seroreactive for anti-glycoprotein immunoglobulin G (IgG), 89 (15.8%) were seroreactive for anti-nucleoprotein IgG, and 54 (9.5%) were VP40 positive.
+These data demonstrate that a significant proportion of HCWs have the ability to neutralize virus, despite never having developed Ebola virus disease symptoms, highlighting an important and poorly documented aspect of EBOV infection and progression.
+INTRODUCTION: Robust metrics for national-level preparedness are critical for assessing global resilience to epidemic and pandemic outbreaks.
+However, existing preparedness assessments focus primarily on public health systems or specific legislative frameworks, and do not measure other essential capacities that enable and support public health preparedness and response.
+It consists of five subindices measuring each country’s economic resources, public health communications, infrastructure, public health systems and institutional capacity.
+To evaluate the construct validity of the EPI, we tested its correlation with proxy measures for preparedness and response capacity, including the timeliness of outbreak detection and reporting, as well as vaccination rates during the 2009 H1N1 influenza pandemic.
+RESULTS: The most prepared countries were concentrated in Europe and North America, while the least prepared countries clustered in Central and West Africa and Southeast Asia.
+Better prepared countries were found to report infectious disease outbreaks more quickly and to have vaccinated a larger proportion of their population during the 2009 pandemic.
+CONCLUSION: The EPI measures a country’s capacity to detect and respond to infectious disease events.
+Existing tools, such as the Joint External Evaluation (JEE), have been designed to measure preparedness within a country over time.
+The EPI complements the JEE by providing a holistic view of preparedness and is constructed to support comparative risk assessment between countries.
+The index can be updated rapidly to generate global estimates of pandemic preparedness that can inform strategy and resource allocation.
+To effectively study camel traits, a biobank of camel DNA specimens with associated biological information is needed.
+We examined whole-blood, saliva (buccal swabs), and tail-hair follicle samples to determine which is the best source for establishing a DNA biobank.
+We inspected five amounts of each of whole-blood, buccal swabs, and tail-hair follicles in nine camels, both qualitatively via gel electrophoresis and quantitatively using a NanoDrop spectrophotometer.
+We also tested the effects of long term-storage on the quality and quantity of DNA, and measured the rate of degradation, by analyzing three buccal swab samples and 30 tail-hair follicles over a period of nine months.
+Good quality DNA, in the form of visible large size DNA bands, was extracted from all three sources, for all five amounts.
+The five volumes of whole-blood samples (20–100μl) provided ~0.4–3.6 μg, the five quantities of buccal swabs (1–5) produced ~0.1–12 μg, while the five amounts of tail-hair follicles (10–50) resulted in ~0.7–25 μg.
+No differences in the rate of degradation of buccal swab and tail-hair follicle DNA were detected, but there was clearly greater deterioration in the quality of DNA extracted from buccal swabs when compared to tail-hair follicles.
+We recommend using tail-hair samples for camel DNA biobanking, because it resulted in both an adequate quality and quantity of DNA, along with its ease of collection, transportation, and storage.
+Compared to its success in studies of other domesticated animals, we anticipate that using ~50 tail-hair follicles will provide sufficient DNA for sequencing or SNP genotyping.
+Zika virus (ZIKV) has been associated with serious health conditions, and an intense search to discover different ways to prevent and treat ZIKV infection is underway.
+Berberine and emodin possess several pharmacological properties and have been shown to be particularly effective against the entry and replication of several viruses.
+When the virus was exposed to 160 µM of berberine, a reduction of 77.6% in the infectivity was observed; when emodin was used (40 µM), this reduction was approximately 83.3%.
+Dynamic light scattering data showed that both compounds significantly reduce the hydrodynamic radius of virus particle in solution.
+We report here that berberine and emodin, two natural compounds, have strong virucidal effect in Zika virus.
+The recombinant antibody fragments generated against the toxic components of scorpion venoms are considered a promising alternative for obtaining new antivenoms for therapy.
+Using directed evolution and site-directed mutagenesis, it was possible to generate a human single-chain antibody fragment with a broad cross-reactivity that retained recognition for its original antigen.
+This variant is the first antibody fragment that neutralizes the effect of an estimated 13 neurotoxins present in the venom of nine species of Mexican scorpions.
+These results represent a significant advance in the development of new antivenoms against scorpion stings, since the number of components would be minimized due to their broad cross-neutralization capacity, while at the same time bypassing animal immunization.
+Many plant viruses express their proteins through a polyprotein strategy, requiring the acquisition of protease domains to regulate the release of functional mature proteins and/or intermediate polyproteins.
+Positive-strand RNA viruses constitute the vast majority of plant viruses and they are diverse in their genomic organization and protein expression strategies.
+Until recently, proteases encoded by positive-strand RNA viruses were described as belonging to two categories: (1) chymotrypsin-like cysteine and serine proteases and (2) papain-like cysteine protease.
+However, the functional characterization of plant virus cysteine and serine proteases has highlighted their diversity in terms of biological activities, cleavage site specificities, regulatory mechanisms, and three-dimensional structures.
+The recent discovery of a plant picorna-like virus glutamic protease with possible structural similarities with fungal and bacterial glutamic proteases also revealed new unexpected sources of protease domains.
+We also highlight possible evolution scenarios of these viral proteases, including evidence for the exchange of protease domains amongst unrelated viruses.
+It has been demonstrated that cholinergic synaptic transmission in the RVLM is enhanced in hypertensive rats.
+Angiotensin-converting enzyme 2 (ACE2) in the brain plays beneficial roles in cardiovascular function in hypertension.
+The purpose of this study was to determine the effect of ACE2 overexpression in the RVLM on cholinergic synaptic transmission in spontaneously hypertensive rats (SHRs).
+Four weeks after injecting lentiviral particles containing enhanced green fluorescent protein and ACE2 bilaterally into the RVLM, the blood pressure and heart rate were notably decreased.
+ACE2 overexpression significantly reduced the concentration of acetylcholine in microdialysis fluid from the RVLM and blunted the decrease in blood pressure evoked by bilateral injection of atropine into the RVLM in SHRs.
+In conclusion, we suggest that ACE2 overexpression in the RVLM attenuates the enhanced cholinergic synaptic transmission in SHRs.
+The course of viral infections in patients with acute bronchitis, asthma and COPD can be improved by oral application of Pelargonium sidoides radix extract; however, the mechanism is not well understood.
+This study investigated the in vitro effect of Pelargonium sidoides radix extract (EPs 7630) on the expression of virus binding cell membrane and host defence supporting proteins on primary human bronchial epithelial cells (hBEC).
+Cells were isolated from patients with severe asthma (n = 6), moderate COPD (n = 6) and non-diseased controls (n = 6).
+The results show that EPs 7630 concentration-dependently and significantly increased hBEC survival after rhinovirus infection.
+This effect was paralleled by decreased expression of the inducible co-stimulator (ICOS), its ligand ICOSL and cell surface calreticulin (C1qR).
+In contrast, EPs 7630 up-regulated the expression of the host defence supporting proteins β-defensin-1 and SOCS-1, both in rhinovirus infected and un-infected hBEC.
+The expression of other virus interacting cell membrane proteins such as MyD88, TRL2/4 or ICAM-1 was not altered by EPs 7630.
+The results indicate that EPs 7630 may reduce rhinovirus infection of human primary BEC by down-regulating cell membrane docking proteins and up-regulating host defence proteins.
+Checkpoint protein inhibitor antibodies (CPI), including cytotoxic T-lymphocyte-associated antigen 4 inhibitors (ipilimumab, tremelimumab) and the programmed cell death protein 1 pathway/programmed cell death protein 1 ligand inhibitors (pembrolizumab, nivolumab, durvalumab, atezolizumab), have entered routine practice for the treatment of many cancers.
+They improve the outcome for many cancers, and more patients will be treated with CPI in the future.
+Although CPI can lead to adverse events (AE) less frequently than for chemotherapy, their use can require intensive care unit admission in case of severe immune-related adverse events (IrAE).
+Moreover, some of these events, particularly late events, are poorly documented, so a high level of suspicion should be maintained for patients receiving CPI.
+Intensivists should be aware in general of the known complications and appropriate management of these AE.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13613-019-0487-x) contains supplementary material, which is available to authorized users.
+BACKGROUND: Porcine circovirus type 2 (PCV2) is the causal agent of postweaning multisystemic wasting syndrome (PMWS), causing large economical losses of the global swine industry.
+RESULTS: We used indirect fluorescence assay (IFA), TCID(50), real-time RT-qPCR and western blot assay to reveal the role of NO in restricting PCV2 replication.
+PCV2 replication was inhibited by a form of NO, NO(•), whereas PCV2 was not susceptible to another form of NO, NO(+).
+CONCLUSION: Our findings indicate that the form of NO(•) has a potential role in the fight against PCV2 infection.
+BACKGROUND: To investigate the status of anti-tuberculosis treatment in critically ill patients, and to explore the value of APACHE-II score in guiding anti-tuberculosis treatment.
+The utility of APACHE-II score for predicting drug withdrawal was evaluated using receiver operating characteristic (ROC) curve analysis.
+RESULTS: Among 320 patients enrolled (58 ± 22 years; 256 males), 147 (45.9%) had drugs withdrawn.
+The drug withdrawal group had higher APACHE-II score (median [interquartile range]: 21 [3–52] vs. 17 [4–42] points), higher CD4%, lower hemoglobin level, higher rates of chronic obstructive pulmonary disease (COPD) and chronic renal failure, and lower rate of extrapulmonary tuberculosis (P < 0.05).
+Logistic regression identified APACHE-II score > 18 (odds ratio [95% confidence interval]: 2.099 [1.321–3.334], P < 0.01), COPD (1.913 [1.028–3.561], P < 0.05) and hemoglobin level (0.987 [0.977–0.997], P < 0.05) as independent factors associated with drug withdrawal.
+At an optimal cutoff of 18.5, the sensitivity, specificity, positive predictive value and negative predictive value of APACHE-II score for predicting drug withdrawal was 59.2, 61.8, 56.9 and 64.1%, respectively.
+Understanding the effect of media on disease spread can help improve epidemic forecasting and uncover preventive measures to slow the spread of disease.
+Most previously introduced models have approximated media effect through disease incidence, making media influence dependent on the size of epidemic.
+We propose an alternative approach, which relies on real data about disease coverage in the news, allowing us to model low incidence/high interest diseases, such as SARS, Ebola or H1N1.
+We introduce a network-based model, in which disease is transmitted through local interactions between individuals and the probability of transmission is affected by media coverage.
+We apply the model to the case of H1N1 transmission in Mexico City in 2009 and show how media influence—measured by the time series of the weekly count of news articles published on the outbreak—helps to explain the observed transmission dynamics.
+We show that incorporating the media attention based on the observed media coverage of the outbreak better estimates the disease dynamics from what would be predicted by using media function that approximate the media impact using the number of cases and rate of spread.
+Finally, we apply the model to a typical influenza season in Washington, DC and estimate how the transmission pattern would have changed given different levels of media coverage.
+Macromolecular crowding decreases the diffusion rate, shifts the equilibrium of protein–protein and protein–substrate interactions, and changes protein conformational dynamics.
+Here we describe how crowding may bias the conformational change and dynamics of enzyme populations and in this way affect catalysis.
+Uniform crowding represents random crowding conditions created by synthetic particles with a narrow size distribution.
+Structured crowding refers to the highly coordinated cellular environment, where proteins and other macromolecules are clustered and organized.
+In structured crowded environments the perturbation of protein thermal stability may be lower; however, it may still be able to modulate functions effectively and dynamically.
+Dynamic, allosteric enzymes could be more sensitive to cellular perturbations if their free energy landscape is flatter around the native state; on the other hand, if their free energy landscape is rougher, with high kinetic barriers separating deep minima, they could be more robust.
+Above all, cells are structured; and this holds both for the cytosol and for the membrane environment.
+The crowded environment is organized, which limits the search, and the crowders are not necessarily inert.
+Data on the genetic diversity of Pneumocystis jirovecii causing Pneumocystis pneumonia (PCP) among children are still limited, and there are no available data from the Indian subcontinent, particularly associations between genotypes and clinical characteristics.
+A total of 37 children (62 days-12 years [median 5.5 years]) were included in this study.
+Pneumocystis was diagnosed by microscopy using Grocott-Gomori methenamine silver stain in 12 cases and by nested PCR using mtLSUrRNA in 25 cases.
+Genotyping was performed using three different genes, mitochondrial large subunit ribosomal RNA (mtLSUrRNA), dihydropteroate synthase (DHPS) and dihydrofolate reductase (DHFR).
+mtLSUrRNA genotype 3 and novel mutations at the gene target DHFR (401 T > C) and DHPS 96/98 were frequently observed and clinically associated with severe PCP and treatment failure.
+Two STs (i) 3-DHFR 401 T > C-DHPS 96/98 – PJ1 and (ii) 3-DHFR 401 T > C-DHPS 96- PJ3 were significantly associated with treatment failure and high mortality among PCP-positive patients.
+In conclusion, the present study strongly suggests the emergence of virulent P. jirovecii strains or genetic polymorphisms, leading to treatment failure and high mortality.
+Our study is the first of its kind from the Indian subcontinent and has highlighted the genetic diversity of Pneumocystis jirovecii among children and their clinical outcomes.
+These findings emphasize the need to focus more on genotypes to better understand the epidemiology of Pneumocystis pneumonia.
+Due to the chronic course of the disease combining with devastating complications, this disorder could easily carry a financial burden.
+The early diagnosis of diabetes remains as one of the major challenges medical providers are facing, and the satisfactory screening tools or methods are still required, especially a population- or community-based tool.
+METHODS: This is a retrospective cross-sectional study involving 15,323 subjects who underwent the annual check-up in the Department of Family Medicine of Shengjing Hospital of China Medical University from January 2017 to June 2017.
+With a strict data filtration, 10,436 records from the eligible participants were utilized to develop a prediction model using the J48 decision tree algorithm.
+Nine variables, including age, gender, body mass index (BMI), hypertension, history of cardiovascular disease or stroke, family history of diabetes, physical activity, work-related stress, and salty food preference, were considered.
+RESULTS: The accuracy, precision, recall, and area under the receiver operating characteristic curve (AUC) value for identifying potential diabetes were 94.2%, 94.0%, 94.2%, and 94.8%, respectively.
+The decision tree demonstrated that among those participants with age ≤ 49, 5497 participants (97%) of the individuals were identified as nondiabetic, while age > 49, 771 participants (50%) of the individuals were identified as nondiabetic.
+In the subgroup where people were 34 < age ≤ 49 and BMI ≥ 25, when with positive family history of diabetes, 89 (92%) out of 97 individuals were identified as diabetic and, when without family history of diabetes, 576 (58%) of the individuals were identified as nondiabetic.
+In individuals with 34 < age ≤ 49 and BMI ≥ 25 and without family history of diabetes, 22 (51%) of the individuals with high work-related stress were identified as nondiabetic while 349 (88%) of the individuals with low or moderate work-related stress were identified as not having diabetes.
+CONCLUSIONS: We proposed a classifier based on a decision tree which used nine features of patients which are easily obtained and noninvasive as predictor variables to identify potential incidents of diabetes.
+The classifier indicates that a decision tree analysis can be successfully applied to screen diabetes, which will support clinical practitioners for rapid diabetes identification.
+The model provides a means to target the prevention of diabetes which could reduce the burden on the health system through effective case management.
+Based on studies of isolated BAR domains in vitro, the current paradigm is that BAR domain–containing proteins polymerize into cylindrical scaffolds that stabilize lipid tubules.
+But in nature, proteins that contain BAR domains often also contain large intrinsically disordered regions.
+Using in vitro and live cell assays, here we show that full-length BAR domain–containing proteins, rather than stabilizing membrane tubules, are instead surprisingly potent drivers of membrane fission.
+Specifically, when BAR scaffolds assemble at membrane surfaces, their bulky disordered domains become crowded, generating steric pressure that destabilizes lipid tubules.
+More broadly, we observe this behavior with BAR domains that have a range of curvatures.
+These data suggest that the ability to concentrate disordered domains is a key driver of membrane remodeling and fission by BAR domain–containing proteins.
+BACKGROUND: In the spring of 1918, the “War to End All Wars”, which would ultimately claim more than 37 million lives, had entered into its final year and would change the global political and economic landscape forever.
+At the same time, a new global threat was emerging and would become one of the most devastating global health crises in recorded history.
+MAIN TEXT: The 1918 H1N1 pandemic virus spread across Europe, North America, and Asia over a 12-month period resulting in an estimated 500 million infections and 50–100 million deaths worldwide, of which ~ 50% of these occurred within the fall of 1918 (Emerg Infect Dis 12:15-22, 2006, Bull Hist Med 76:105-115, 2002).
+However, the molecular factors that contributed to the emergence of, and subsequent public health catastrophe associated with, the 1918 pandemic virus remained largely unknown until 2005, when the characterization of the reconstructed pandemic virus was announced heralding a new era of advanced molecular investigations (Science 310:77-80, 2005).
+In the century following the emergence of the 1918 pandemic virus we have landed on the Moon, developed the electronic computer (and a global internet), and have eradicated smallpox.
+In contrast, we have a largely remedial knowledge and understanding of one of the greatest scourges in recorded history.
+CONCLUSION: Here, we reflect on the 1918 influenza pandemic, including its emergence and subsequent rapid global spread.
+In addition, we discuss the pathophysiology associated with the 1918 virus and its predilection for the young and healthy, the rise of influenza therapeutic research following the pandemic, and, finally, our level of preparedness for future pandemics.
+When analysing new emerging infectious disease outbreaks, one typically has observational data over a limited period of time and several parameters to estimate, such as growth rate, the basic reproduction number R(0), the case fatality rate and distributions of serial intervals, generation times, latency and incubation times and times between onset of symptoms, notification, death and recovery/discharge.
+These parameters form the basis for predicting a future outbreak, planning preventive measures and monitoring the progress of the disease outbreak.
+We study inference problems during the emerging phase of an outbreak, and point out potential sources of bias, with emphasis on: contact tracing backwards in time, replacing generation times by serial intervals, multiple potential infectors and censoring effects amplified by exponential growth.
+These biases directly affect the estimation of, for example, the generation time distribution and the case fatality rate, but can then propagate to other estimates such as R(0) and growth rate.
+[Image: see text] APOBEC3 enzymes form part of the innate immune system by deaminating cytosine to uracil in single-stranded DNA (ssDNA) and thereby preventing the spread of pathogenic genetic information.
+However, APOBEC mutagenesis is also exploited by viruses and cancer cells to increase rates of evolution, escape adaptive immune responses, and resist drugs.
+This raises the possibility of APOBEC3 inhibition as a strategy for augmenting existing antiviral and anticancer therapies.
+Here we show that, upon incorporation into short ssDNAs, the cytidine nucleoside analogue 2′-deoxyzebularine (dZ) becomes capable of inhibiting the catalytic activity of selected APOBEC variants derived from APOBEC3A, APOBEC3B, and APOBEC3G, supporting a mechanism in which ssDNA delivers dZ to the active site.
+Multiple experimental approaches, including isothermal titration calorimetry, fluorescence polarization, protein thermal shift, and nuclear magnetic resonance spectroscopy assays, demonstrate nanomolar dissociation constants and low micromolar inhibition constants.
+These dZ-containing ssDNAs constitute the first substrate-like APOBEC3 inhibitors and, together, comprise a platform for developing nucleic acid-based inhibitors with cellular activity.
+Membrane proteins (such as ion channels, transporters, and receptors) and secreted proteins are essential for cellular activities.
+N-linked glycosylation is involved in stability and function of these proteins and occurs at Asn residues.
+Nevertheless, the cochlea of the mammalian inner ear, a tiny organ mediating hearing, has yet to be examined.
+Here, we focused on the stria vascularis, an epithelial-like tissue in the cochlea, and characterised N-glycans by liquid chromatography with mass spectrometry.
+This hypervascular tissue not only expresses several ion transporters and channels to control the electrochemical balance in the cochlea but also harbours different transporters and receptors that maintain structure and activity of the organ.
+Among these, in 55 glycans, the complete structures were determined; in the other 24 species, partial glycosidic linkage patterns and full profiles of the monosaccharide composition were identified.
+In the process of characterisation, several sialylated glycans were subjected sequentially to two different alkylamidation reactions; this derivatisation helped to distinguish α2,3-linkage and α2,6-linkage sialyl isomers with mass spectrometry.
+The amyloid precursor protein plus presenilin-1 (APP/PS1) mice are a frequently-used model for Alzheimer's disease studies (AD).
+However, the data relevant to which proteins are involved in inflammatory mechanism are not sufficiently well-studied using the AD mouse model.
+Using behavioral studies, quantitative RT-PCR and Western-blot techniques, significant findings were determined by the expression of proteins involved in inflammation comparing APP/PS1 and Wild type mice.
+IL-3 is involved in inflammation and ABDF1 intervenes normally in the transport across cell membranes and both were found up-regulated in APP/PS1 mice compared to Wild type mice.
+Furthermore, CCR5 expression was decreased and both CCL3 and CCL4 chemokines were highly expressed indicating a possible gliosis and probably an increase in chemotaxis from lymphocytes and T cell generation.
+We also noted for the first time, a CCR8 increase expression with diminution of its CCL1 chemokine, both normally involved in protection from bacterial infection and demyelination.
+Control of inflammatory proteins will be the next step in understanding the progression of AD and also in determining the mechanisms that can develop in this disease.
+PURPOSE: The aim of the present study was to develop a serodiagnostic test for differentiation infected from vaccinated animal (DIVA) strategy accompanying the marker vaccine lacking an immunodominant epitope (IDE) of nucleoprotein of Newcastle disease virus (NDV).
+MATERIALS AND METHODS: Recombinant epitope-repeat protein (rERP) gene encoding eight repeats of the IDE sequence (ETQFLDLMRAVANSMR) by tetra-glycine linker was synthesized.
+Recombinant baculovirus carrying the rERP gene was generated to express the rERP in insect cells.
+Specificity and sensitivity of an indirect enzyme-linked immunosorbent assay (ELISA) employing the rERP was evaluated.
+RESULTS: The rERP with molecular weight of 20 kDa was successfully expressed by the recombinant baculovirus in an insect-baculovirus system.
+An indirect ELISA employing the rERP was developed and its specificity and sensitivity was determined.
+The ELISA test allowed discrimination of NDV infected sera from epitope deletion virus vaccinated sera.
+Central players of the adaptive immune system are the groups of proteins encoded in the major histocompatibility complex (MHC), which shape the immune response against pathogens and tolerance to self-peptides.
+The corresponding genomic region is of particular interest, as it harbors more disease associations than any other region in the human genome, including associations with infectious diseases, autoimmune disorders, cancers, and neuropsychiatric diseases.
+Certain MHC molecules can bind to a much wider range of epitopes than others, but the functional implication of such an elevated epitope-binding repertoire has remained largely unclear.
+It has been suggested that by recognizing more peptide segments, such promiscuous MHC molecules promote immune response against a broader range of pathogens.
+If so, the geographical distribution of MHC promiscuity level should be shaped by pathogen diversity.
+First, we found that in pathogen-rich geographical regions, humans are more likely to carry highly promiscuous MHC class II DRB1 alleles.
+Second, the switch between specialist and generalist antigen presentation has occurred repeatedly and in a rapid manner during human evolution.
+Third, molecular positions that define promiscuity level of MHC class II molecules are especially diverse and are under positive selection in human populations.
+Taken together, our work indicates that pathogen load maintains generalist adaptive immune recognition, with implications for medical genetics and epidemiology.
+The enterovirus genus of the picornavirus family includes a large number of important human pathogens such as poliovirus, coxsackievirus, enterovirus A71, and rhinoviruses.
+Like all other positive-strand RNA viruses, genome replication of enteroviruses occurs on rearranged membranous structures called replication organelles (ROs).
+Here, we investigated the role of acyl-coenzyme A binding domain containing 3 (ACBD3) in PI4KB recruitment upon enterovirus replication using ACBD3 knockout (ACBD3(KO)) cells.
+ACBD3 knockout impaired replication of representative viruses from four enterovirus species and two rhinovirus species.
+The lack of ACBD3 also affected the localization of individually expressed 3A, causing 3A to localize to the endoplasmic reticulum instead of the Golgi.
+Reconstitution of wild-type (wt) ACBD3 restored PI4KB recruitment and 3A localization, while an ACBD3 mutant that cannot bind to PI4KB restored 3A localization, but not virus replication.
+Consistently, reconstitution of a PI4KB mutant that cannot bind ACBD3 failed to restore virus replication in PI4KB(KO) cells.
+Finally, by reconstituting ACBD3 mutants lacking specific domains in ACBD3(KO) cells, we show that acyl-coenzyme A binding (ACB) and charged-amino-acid region (CAR) domains are dispensable for 3A-mediated PI4KB recruitment and efficient enterovirus replication.
+Altogether, our data provide new insight into the central role of ACBD3 in recruiting PI4KB by enterovirus 3A and reveal the minimal domains of ACBD3 involved in recruiting PI4KB and supporting enterovirus replication.
+While current therapies for these diseases slow disease progression, stem cell and gene therapy may also reverse the effects of these, and other, degenerative retinal conditions.
+Novel therapies being investigated include the use of various types of stem cells in the regeneration of atrophic or damaged retinal tissue, the prolonged administration of neurotrophic factors and/or drug delivery, immunomodulation, as well as the replacement of mutant genes, and immunomodulation through viral vector delivery.
+This review will update the reader on aspects of stem cell and gene therapy in diabetic retinopathy, age-related macular degeneration, retinitis pigmentosa and other less common inherited retinal dystrophies.
+These therapies include the use of adeno-associated viral vector-based therapies for treatment of various types of retinitis pigmentosa and dry age-related macular degeneration.
+Other potential therapies reviewed include the use of mesenchymal stem cells in local immunomodulation, and the use of stem cells in generating structures like three-dimensional retinal sheets for transplantation into degenerative retinas.
+Finally, aspects of stem cell and gene therapy in diabetic retinopathy, age-related macular degeneration, retinitis pigmentosa, and other less common inherited retinal dystrophies will be reviewed.
+Different countries have legislated or promoted the ban of antibiotics as growth promoters in livestock and aquaculture to reduce this phenomenon.
+Therefore, to improve animal growth and reproduction performance and to control multiple bacterial infections, there is a potential to use probiotics as non-antibiotic growth promoters.
+Lactic acid bacteria (LAB) offer various advantages as potential probiotics and can be considered as alternatives to antibiotics during food-animal production.
+LAB are safe microorganisms with abilities to produce different inhibitory compounds such as bacteriocins, organic acids as lactic acid, hydrogen peroxide, diacetyl, and carbon dioxide.
+LAB can inhibit harmful microorganisms with their arsenal, or through competitive exclusion mechanism based on competition for binding sites and nutrients.
+LAB endowed with specific enzymatic functions (amylase, protease…) can improve nutrients acquisition as well as animal immune system stimulation.
+This review aimed at underlining the benefits and inputs from LAB as potential alternatives to antibiotics in poultry, pigs, ruminants, and aquaculture production.
+While high‐throughput metabarcoding has revolutionized the study of bacterial communities, generating comparable viral communities has proven elusive, particularly in wildlife samples where the diversity of viruses and limited quantities of viral nucleic acid present distinctive challenges.
+Metagenomic sequencing is a promising solution for studying viral communities, but the lack of standardized methods currently precludes comparisons across host taxa or localities.
+Here, we developed an untargeted shotgun metagenomic sequencing protocol to generate comparable viral communities from noninvasively collected faecal and oropharyngeal swabs.
+Using samples from common vampire bats (Desmodus rotundus), a key species for virus transmission to humans and domestic animals, we tested how different storage media, nucleic acid extraction procedures and enrichment steps affect viral community detection.
+Based on finding viral contamination in foetal bovine serum, we recommend storing swabs in RNAlater or another nonbiological medium.
+We recommend extracting nucleic acid directly from swabs rather than from supernatant or pelleted material, which had undetectable levels of viral RNA.
+Results from a low‐input RNA library preparation protocol suggest that ribosomal RNA depletion and light DNase treatment reduce host and bacterial nucleic acid, and improve virus detection.
+Finally, applying our approach to twelve pooled samples from seven localities in Peru, we showed that detected viral communities saturated at the attained sequencing depth, allowing unbiased comparisons of viral community composition.
+Future studies using the methods outlined here will elucidate the determinants of viral communities across host species, environments and time.
+The introduction and spread of emerging infectious diseases is increasing in both prevalence and scale.
+Whether naturally, accidentally or maliciously introduced, the substantial uncertainty surrounding the emergence of novel viruses, specifically where they may come from and how they will spread, demands robust and quantifiably validated outbreak control policies that can be implemented in real time.
+This work presents a novel mathematical modeling framework that integrates both outbreak dynamics and outbreak control into a decision support tool for mitigating infectious disease pandemics that spread through passenger air travel.
+An ensemble of border control strategies that exploit properties of the air traffic network structure and expected outbreak behavior are proposed.
+A stochastic metapopulation epidemic model is developed to evaluate and rank the control strategies based on their effectiveness in reducing the spread of outbreaks.
+Sensitivity analyses are conducted to illustrate the robustness of the proposed control strategies across a range of outbreak scenarios, and a case study is presented for the 2009 H1N1 influenza pandemic.
+This study highlights the importance of strategically allocating outbreak control resources, and the results can be used to identify the most robust border control policy that can be implemented in the early stages of an outbreak.
+BACKGROUND: Data on the methods used for microbiological diagnosis of hospital-acquired pneumonia (HAP) are mainly extrapolated from ventilator-associated pneumonia.
+HAP poses additional challenges for respiratory sampling, and the utility of sputum or distal sampling in HAP has not been comprehensively evaluated, particularly in HAP admitted to the ICU.
+METHODS: We analyzed 200 patients with HAP from six ICUs in a teaching hospital in Barcelona, Spain.
+The respiratory sampling methods used were divided into non-invasive [sputum and endotracheal aspirate (EAT)] and invasive [fiberoptic-bronchoscopy aspirate (FBAS), and bronchoalveolar lavage (BAL)].
+At least one respiratory sampling method was applied in 93% of patients, and two or more were applied in 40%.
+Microbiological diagnosis was achieved in 99 (50%) patients, 69 (70%) by only one method (42% FBAS, 23% EAT, 15% sputum, 9% BAL, 7% blood culture, and 4% urinary antigen).
+Higher rates of microbiological diagnosis were observed in the invasive group (56 vs. 39%, p = 0.018).
+Patients with microbiological diagnosis more frequently presented changes in their empirical antibiotic scheme, mainly de-escalation.
+CONCLUSIONS: A comprehensive approach might be undertaken for microbiological diagnosis in critically ill nonventilated HAP.
+Sputum sampling determined one third of microbiological diagnosis in HAP patients who were not subsequently intubated.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13054-019-2348-2) contains supplementary material, which is available to authorized users.
+The timing and location of the first cases of the 1918 influenza pandemic are still controversial, a century after the pandemic became widely recognized.
+Here, we critically review competing hypotheses on the timing and geographical origin of this important outbreak and provide new historical insights into debates within military circles as to the nature of putative pre-1918 influenza activity.
+We also synthesize current knowledge about why the 1918 pandemic was so intense in young adults.
+Although it is still not clear precisely when and where the outbreak began and symptom-based reports are unlikely to reveal the answer, indirect methods including phylogenetics provide important clues, and we consider whether intense influenza activity as far back as 1915 in the USA may have been caused by viral strains closely related to the 1918 one.
+With rapidly increasing animal pathogen surveillance requirements, new technologies are needed for a comprehensive understanding of the roles of pathogens in the occurrence and development of animal diseases.
+We applied metagenomic technology to avian virus surveillance to study the main viruses infecting six poultry farms in two provinces in eastern China.
+Cloacal/throat double swabs were collected from 60 birds at each farm according to a random sampling method.
+The results showed that the method could simultaneously detect major viruses infecting farms, including avian influenza virus, infectious bronchitis virus, Newcastle disease virus, rotavirus G, duck hepatitis B virus, and avian leukemia virus subgroup J in several farms.
+The test results were consistent with the results from traditional polymerase chain reaction (PCR) or reverse transcription-PCR analyses.
+Five H9N2 and one H3N8 avian influenza viruses were detected at the farms and were identified as low pathogenic avian influenza viruses according to HA cleavage sites analysis.
+One detected Newcastle disease virus was classified as Class II genotype I and avirulent type according to F0 cleavage sites analysis.
+Three avian infectious bronchitis viruses were identified as 4/91, CK/CH/LSC/99I and TC07-2 genotypes by phylogenetic analysis of S1 genes.
+The viral infection surveillance method using metagenomics technology enables the monitoring of multiple viral infections, which allows the detection of main infectious viruses.
+The emergence of Zika virus (ZIKV) in the New World has led to more than 200,000 human infections.
+Perinatal infection can cause severe neurological complications, including fetal and neonatal microcephaly, and in adults there is an association with Guillain-Barré syndrome (GBS).
+mosquitoes, yet little is known about its enzootic cycle in which transmission is thought to occur between arboreal Aedes sp.
+In the 1950s and ‘60s, several bat species were shown to be naturally and experimentally susceptible to ZIKV with acute viremia and seroconversion, and some developed neurological disease with viral antigen detected in the brain.
+Because of ZIKV emergence in the Americas, we sought to determine susceptibility of Jamaican fruit bats (Artibeus jamaicensis), one of the most common bats in the New World.
+Bats held to 28 days post-inoculation (PI) had detectable antibody by ELISA and viral RNA was detected by qRT-PCR in the brain, saliva and urine in some of the bats.
+Immunoreactivity using polyclonal anti-ZIKV antibody was detected in testes, brain, lung and salivary glands plus scrotal skin.
+Tropism for mononuclear cells, including macrophages/microglia and fibroblasts, was seen in the aforementioned organs in addition to testicular Leydig cells.
+Jamaican fruit bats, therefore, may be a useful animal model for the study of ZIKV infection.
+This work also raises the possibility that bats may have a role in Zika virus ecology in endemic regions, and that ZIKV may pose a wildlife disease threat to bat populations.
+The quarantine of people suspected of being exposed to an infectious agent is one of the most basic public health measure that has historically been used to combat the spread of communicable diseases in human communities.
+This study presents a new deterministic model for assessing the population-level impact of the quarantine of individuals suspected of being exposed to disease on the spread of the 2014–2015 outbreaks of Ebola viral disease.
+In the absence of quarantine, the model is shown to exhibit global dynamics with respect to the disease-free and its unique endemic equilibrium when a certain epidemiological threshold (denoted by [Formula: see text]) is either less than or greater than unity.
+Thus, unlike the full model with imperfect quarantine (which is known to exhibit the phenomenon of backward bifurcation), the version of the model with no quarantine does not undergo a backward bifurcation.
+Using data relevant to the 2014–2015 Ebola transmission dynamics in the three West African countries (Guinea, Liberia and Sierra Leone), uncertainty analysis of the model show that, although the current level and effectiveness of quarantine can lead to significant reduction in disease burden, they fail to bring the associated quarantine reproduction number ([Formula: see text]) to a value less than unity (which is needed to make effective disease control or elimination feasible).
+This reduction of [Formula: see text] is, however, very possible with a modest increase in quarantine rate and effectiveness.
+It is further shown, via sensitivity analysis, that the parameters related to the effectiveness of quarantine (namely the parameter associated with the reduction in infectiousness of infected quarantined individuals and the contact rate during quarantine) are the main drivers of the disease transmission dynamics.
+Overall, this study shows that the singular implementation of a quarantine intervention strategy can lead to the effective control or elimination of Ebola viral disease in a community if its coverage and effectiveness levels are high enough.
+The objective of this study was to evaluate the effectiveness of the SurePure Turbulator ultraviolet-C (UV-C, 254 nm wavelength) irradiation equipment on inactivation of different enveloped and non-enveloped viruses in commercially collected liquid animal plasma.
+The enveloped viruses tested were inactivated at < 3000 J/L of UV-C, being the dose needed to inactivate 4 log TCID(50) (4D) of 1612 J/L for PRV,1004 J/L for PRRSV, 1953 J/L for PEDV, 1639 J/L for SIV, 1641 J/L for CSFV and 1943 J/L for BVDV.
+The non-enveloped viruses tended to have higher 4D values: 2161 J/L for PPV, 3223 J/L for SVA and 3708 J/L for SVDV.
+Because the initial viral concentration was <4.0 Log for PCV-2, it was not possible to calculate the 4D value for this virus.
+In conclusion, these results demonstrated that the SurePure Turbulator UV-C treatment system is capable of inactivating significant levels of swine viruses inoculated in commercially collected porcine or bovine plasma.
+It was concluded that irradiation with UV-C can provide an additional redundant biosafety feature in the manufacturing process of spray-dried animal plasma.
+Misfolding and aggregation of prion protein (PrP) causes neurodegenerative diseases like Creutzfeldt-Jakob disease (CJD) and scrapie.
+Besides the consensus that spontaneous conversion of normal cellular PrP(C) into misfolded and aggregating PrP(Sc) is the central event in prion disease, an alternative hypothesis suggests the generation of pathological PrP(Sc) by rare translational frameshifting events in the octa-repeat domain of the PrP mRNA.
+Ribosomal frameshifting most commonly relies on a slippery site and an adjacent stable RNA structure to stall translating ribosome.
+Hence, it is crucial to unravel the secondary structure of the octa-repeat domain of PrP mRNA.
+Each of the five octa-repeats contains a motif (GGCGGUGGUGGCUGGG) which alone in vitro forms a G-quadruplex.
+Since the propensity of mRNA to form secondary structure depends on the sequence context, we set to determine the structure of the complete octa-repeat region.
+We assessed the structure of full-length octa-repeat domain of PrP mRNA using dynamic light scattering (DLS), small angle X-ray scattering (SAXS), circular dichroism (CD) spectroscopy and selective 2′-hydroxyl acylation analysis by primer extension (SHAPE).
+Our data show that the PrP octa-repeat mRNA forms stable A-helical hairpins with no evidence of G-quadruplex structure even in the presence of G-quadruplex stabilizing agents.
+In Japan, as part of surveillance for seasonal influenza, the number of patients per influenza sentinel site is counted on a weekly basis.
+Currently, reference values are set for the weekly reported number of influenza cases per sentinel, and pre-epidemic and epidemic warnings are issued based on these values.
+In this study, we examined the association between these reference values and the effective reproduction number (R(t)) using surveillance data for Miyazaki Prefecture collected from 2010 to 2011.
+There are nine public health centre jurisdictions in this prefecture, and R(t) exceeded 1.0 at the time when pre-epidemic warnings were issued in almost all the jurisdictions.
+Thus, it was indicated that the validity of the reference value was also high for influenza transmission.
+However, our results indicated the presence of secondary epidemic caused by infections originating both from other jurisdictions and inner jurisdictions, and it is occasionally not possible to evaluate the end of an epidemic in a jurisdiction using only the reference value of termination.
+It is necessary to establish new methods after considering the situation in the surrounding jurisdictions for more detailed epidemic predictions.
+BACKGROUND: Liver weight is a complex trait, controlled by polygenic factors and differs within populations.
+Dissecting the genetic architecture underlying these variations will facilitate the search for key role candidate genes involved directly in the hepatomegaly process and indirectly involved in related diseases etiology.
+METHODS: Liver weight of 506 mice generated from 39 different Collaborative Cross (CC) lines with both sexes at age 20 weeks old was determined using an electronic balance.
+RESULTS: Statistical analysis revealed a significant (P < 0.05) variation of liver weight between the CC lines, with broad sense heritability (H (2)) of 0.32 and genetic coefficient of variation (CV(G)) of 0.28.
+Subsequently, quantitative trait locus (QTL) mapping was performed, and results showed a significant QTL only for females on chromosome 8 at genomic interval 88.61‐93.38 Mb (4.77 Mb).
+The four QTL were designated as LWL1‐LWL4 referring to liver weight loci 1‐4 on chromosomes 8, 4, 12 and 13, respectively.
+CONCLUSION: To our knowledge, this report presents, for the first time, the utilization of the CC for mapping QTL associated with baseline liver weight in mice.
+Our findings demonstrate that liver weight is a complex trait controlled by multiple genetic factors that differ significantly between sexes.
+BACKGROUND: Analysis of respiratory mechanics during mechanical ventilation (MV) is able to estimate resistive, elastic and inertial components of the working pressure of the respiratory system.
+Our aim was to discriminate the components of the working pressure of the respiratory system in infants on MV with severe bronchiolitis admitted to two PICU’s.
+METHODS: Infants younger than 1 year old with acute respiratory failure caused by severe bronchiolitis underwent neuromuscular blockade, tracheal intubation and volume controlled MV.
+Shortly after intubation studies of pulmonary mechanics were performed using inspiratory and expiratory breath hold.
+The maximum inspiratory and expiratory flow (QI and QE) as well as peak inspiratory (PIP), plateau (PPL) and total expiratory pressures (tPEEP) were measured.
+Inspiratory and expiratory resistances (RawI and RawE) and Time Constants (K(TI) and K(TE)) were calculated.
+Bronchiolitis due to respiratory syncytial virus was the main etiology (93.8%) and 31.3% had comorbidities.
+Elastic component of the working pressure was significantly higher than resistive and both higher than threshold (tPEEP – PEEP) (P < 0.01).
+RawI and RawE were 38.8 (32–53) and 40.5 (22–55) cmH2O/L/s; K(TI) and K(TE) [0.18 (0.12–0.30) v/s 0.18 (0.13–0.22) s], and K(TI):K(TE) ratio was 1:1.04 (1:0.59–1.42).
+CONCLUSIONS: Analysis of respiratory mechanics of infants with severe bronchiolitis receiving MV shows that the elastic component of the working pressure of the respiratory system is the most important.
+The elastic and resistive components in conjunction with flow profile are characteristic of restrictive diseases.
+A better understanding of lung mechanics in this group of patients may lead to change the traditional ventilatory approach to severe bronchiolitis.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12890-017-0475-6) contains supplementary material, which is available to authorized users.
+Salmonella Typhimurium is one of the most important zoonotic pathogens worldwide and a major cause of economic losses in the pig production chain.
+The emergence of multi-drug resistant strains over the past years has led to considerations about an enhanced surveillance of bacterial food contamination.
+The sensitivity and specificity of this assay might be improved by application of new diagnostic antibodies.
+We focused on plant-based expression of candidate diagnostic TM43-E10 antibodies discovered using as antigen the S. Typhimurium OmpD protein.
+The scFv-TM43-E10 and scFv-Fc-TM43-E10 antibody derivatives have been successfully produced in N. benthamiana using a deconstructed movement-deficient PVX vector supplemented with the γb silencing suppressor from Poa semilatent virus.
+The plant-made antibodies showed the same antigen-binding specificity as that of the microbial/mammalian cell-produced counterparts and could recognize the OmpD antigen in S. Typhimurium infected plant samples.
+The current investigation applied a Bayesian modeling approach to a unique experimental transmission study to estimate the occurrence of transmission of foot-and-mouth disease (FMD) during the incubation phase amongst group-housed pigs.
+The primary outcome was that transmission occurred approximately one day prior to development of visible signs of disease (posterior median 21 hours, 95% CI: 1.1–45.0).
+Updated disease state durations were incorporated into a simulation model to examine the importance of addressing preclinical transmission in the face of robust response measures.
+Simulation of FMD outbreaks in the US pig production sector demonstrated that including a preclinical infectious period of one day would result in a 40% increase in the median number of farms affected (166 additional farms and 664,912 pigs euthanized) compared to the scenario of no preclinical transmission, assuming suboptimal outbreak response.
+These findings emphasize the importance of considering transmission of FMD during the incubation phase in modeling and response planning.
+BACKGROUND: T helper (Th) cells regulate sepsis processes, including primary pathogen clear and secondary pathogen defence.
+The objectives of this study were to determine the early and dynamic alterations of Th1 and Th2 populations to community-acquired severe sepsis upon onset among previously immunocompetent patients and whether it was related to clinical outcomes.
+METHODS: This prospective observational cohort study was conducted at a general intensive care unit (ICU) of a tertiary teaching hospital in China.
+Immunocompetent patients with community-acquired severe sepsis within 24 h upon onset were included as septic group.
+Whole blood was collected on D0, 3rd day (D3) and 7th day (D7) for septic group and once upon enrollment for controls.
+Th1 and Th2 populations were measured by flow cytometry and assessed for associations with 28-day mortality using cox proportional hazard models.
+RESULTS: This study demonstrated that community-acquired severe sepsis patients (n = 71) had increased Th2/Th1 and Th2 populations, compared to healthy controls (n = 7) and critically ill patients without severe sepsis (n = 7) at admission.
+Among the septic cohort, values of Th2/Th1 were significantly higher in non-survivors than survivors on D0 (p = 0.04), D3 (p < 0.001) and D7 (p < 0.001).
+Patients with persistently increasing Th2/Th1 demonstrated the highest mortality (47.1%) and incidence of ICU-acquired infections (64.7%).
+CONCLUSIONS: Th2/Th1 was markedly up-regulated with Th2 dominance upon community-acquired severe sepsis onset among previously immunocompetent patients and its persistently dynamic increase was associated with ICU-acquired infections and 28-day death.
+Trial registration Institutional Ethics Committee of Zhongda Hospital, 2014ZDSYLL086, registered in June 2014-prospectively registered; ClinicalTrials.gov, NCT02883218, registered on 25 Aug 2016-retrospectively registered, https://www.clinicaltrials.gov/ct2/show/NCT02883218?cond=NCT02883218&rank=1 ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12967-019-1811-9) contains supplementary material, which is available to authorized users.
+The porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most important swine diseases in the world.
+It is causing an enormous economic burden due to reproductive failure in sows and a complex respiratory syndrome in pigs of all ages, with mortality varying from 2 to 100% in the most extreme cases of emergent highly pathogenic strains.
+PRRSV displays complex interactions with the immune system and a high mutation rate, making the development, and implementation of control strategies a major challenge.
+In this review, the biology of the virus will be addressed focusing on newly discovered functions of non-structural proteins and novel dissemination mechanisms.
+Secondly, the role of different cell types and viral proteins will be reviewed in natural and vaccine-induced immune response together with the role of different immune evasion mechanisms focusing on those gaps of knowledge that are critical to generate more efficacious vaccines.
+Finally, novel strategies for antigen discovery and vaccine development will be discussed, in particular the use of exosomes (extracellular vesicles of endocytic origin).
+As nanocarriers of lipids, proteins and nucleic acids, exosomes have potential effects on cell activation, modulation of immune responses and antigen presentation.
+The pathophysiologic mechanisms of hepatocyte damage associated with chronic HCV infection are not fully understood yet, mainly due to the lack of an in vitro system able to recapitulate the stages of infection in vivo.
+Several studies underline that HCV virus replication depends on redox-sensitive cellular pathways; in addition, it is known that virus itself induces alterations of the cellular redox state.
+In particular, the role of reduced glutathione (GSH) in HCV replication and infection is still not clear.
+of Huh7.5 cell line with a HCV infectious clone (J6/JFH1), that reproduced the acute and persistent phases of HCV infection up to 76 days of culture.
+We demonstrated that the acute phase of HCV infection is characterized by the elevated levels of reactive oxygen species (ROS) associated in part with an increase of NADPH-oxidase transcripts and activity and a depletion of GSH accompanied by high rates of viral replication and apoptotic cell death.
+Conversely, the chronic phase is characterized by a reestablishment of reduced environment due to a decreased ROS production and increased GSH content in infected cells that might concur to the establishment of viral persistence.
+Treatment with the prooxidant auranofin of the persistently infected cultures induced the increase of viral RNA titer, suggesting that a prooxidant state could favor the reactivation of HCV viral replication that in turn caused cell damage and death.
+Our results suggest that targeting the redox-sensitive host-cells pathways essential for viral replication and/or persistence may represent a promising option for contrasting HCV infection.
+Respiratory tract infections (RTI) are more commonly caused by viral pathogens in children than in adults.
+Surprisingly, little is known about antibiotic use in children as compared to adults with RTI.
+This prospective study aimed to determine antibiotic misuse in children and adults with RTI, using an expert panel reference standard, in order to prioritise the target age population for antibiotic stewardship interventions.
+We recruited children and adults who presented at the emergency department or were hospitalised with clinical presentation of RTI in The Netherlands and Israel.
+bacterial or viral infection) for all the patients using all available clinical and laboratory information, including a 28-day follow-up assessment.
+The cohort included 284 children and 232 adults with RTI (median age, 1.3 years and 64.5 years, respectively).
+The proportion of viral infections was larger in children than in adults (209(74%) versus 89(38%), p < 0.001).
+overuse) less frequently in children than in adults (77/209 (37%) versus 74/89 (83%), p < 0.001).
+One (1%) child and three (2%) adults with bacterial infection were not treated with antibiotics (i.e.
+Viral infection is more common in children, but antibiotic overuse is more frequent in adults with viral RTI.
+Together, these findings support the need for effective interventions to decrease antibiotic overuse in RTI patients of all ages.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10096-018-03454-2) contains supplementary material, which is available to authorized users.
+Schmallenberg virus (SBV), discovered in 2011 in Germany, is associated with clinical manifestations of fever, diarrhea, reduced milk yield, abortions and congenital malformations in ruminants.
+Despite many studies performed for SBV, there is no detailed research on in vitro apoptotic effect of SBV.
+This study is aimed to determine apoptosis pathways and role of pro-apoptotic and anti-apoptotic molecules in Vero cells infected with SBV.
+The study results showed that SBV induced apoptosis via both extrinsic and intrinsic pathways by activating both caspase-8 and caspase-9, respectively.
+Expression analyses of pro-apoptotic (Bax, Bak and Puma) and anti-apoptotic (Bcl-2 and Bcl-XL) genes revealed that SBV-induced apoptosis causes upregulation of pro-apoptotic genes, dominantly via Puma gene, whereas Bcl-2 and Bcl-XL genes were downregulated.
+In conclusion, this is the first detailed report about SBV induced apoptosis in the Vero cells via both extrinsic and intrinsic cascades and apoptosis induction is seem to be regulated by Puma.
+During infection, their genomes are carried in capsids across the membranes of host cells to sites of virion production by exploiting cellular behaviour and resources to guide and achieve all aspects of delivery and the downstream virus manufacturing process.
+Successful entry hinges on execution of a precisely tuned viral uncoating program where incoming capsids disassemble in consecutive steps to ensure that genomes are released at the right time, and in the right place for replication to occur.
+Each step of disassembly is cell-assisted, involving individual pathways that transmit signals to regulate discrete functions, but at the same time, these signalling pathways are organized into larger networks, which communicate back and forth in complex ways in response to the presence of virus.
+In this review, we consider the elegant strategy by which adenoviruses (AdVs) target and navigate cellular networks to initiate the production of progeny virions.
+There are many remarkable aspects about the AdV entry program; for example, the virus gains targeted control of a large well-defined local network neighbourhood by coupling several interacting processes (including endocytosis, autophagy and microtubule trafficking) around a collective reference state centred on the interactional topology and multifunctional nature of protein VI.
+Understanding the network targeting activity of protein VI, as well as other built-in mechanisms that allow AdV particles to be efficient at navigating the subsystems of the cell, can be used to improve viral vectors, but also has potential to be incorporated for use in entirely novel delivery systems.
+Resting Ifitm‐family‐deficient CD4(+) T cells had higher expression of Th1‐associated genes than WT and purified naive Ifitm‐family‐deficient CD4(+) T cells differentiated more efficiently to Th1, whereas Th2 differentiation was inhibited.
+Ifitm‐family‐deficient mice, but not Ifitm3‐deficient mice, were less susceptible than WT to induction of allergic airways disease, with a weaker Th2 response and less severe disease and lower Il4 but higher Ifng expression and IL‐27 secretion.
+Thus, the Ifitm family is important in adaptive immunity, influencing Th1/Th2 polarization, and Th2 immunopathology.
+Influenza A virus (IAV) infection poses a serious health threat and novel antiviral strategies are needed.
+Defective interfering particles (DIPs) can be generated in IAV infected cells due to errors of the viral polymerase and may suppress spread of wild type (wt) virus.
+The antiviral activity of DIPs is exerted by a DI genomic RNA segment that usually contains a large deletion and suppresses amplification of wt segments, potentially by competing for cellular and viral resources.
+DI-244 is a naturally occurring prototypic segment 1-derived DI RNA in which most of the PB2 open reading frame has been deleted and which is currently developed for antiviral therapy.
+At present, coinfection with wt virus is required for production of DI-244 particles which raises concerns regarding biosafety and may complicate interpretation of research results.
+Here, we show that cocultures of 293T and MDCK cell lines stably expressing codon optimized PB2 allow production of DI-244 particles solely from plasmids and in the absence of helper virus.
+Finally, we report that the DI-244 particles produced in this novel system exert potent antiviral activity against H1N1 and H3N2 IAV but not against the unrelated vesicular stomatitis virus.
+This is the first report of DIP production in the absence of infectious IAV and may spur efforts to develop DIPs for antiviral therapy.
+Objectives: To investigate the effectiveness of integrative therapy on prevalence and length of hospitalization and management of major complications of Parkinson’s disease (PD) in the South Korea.
+Methods: This study was a retrospective cohort analysis conducted using the National Health Insurance Service-National Sample Cohort in the South Korea.
+Patients over 65 years old who were newly diagnosed with PD during 2007–2011 were identified.
+The integrative therapy group was defined as patients treated with both Korean medicine (KM) and biomedicine, and the monotherapy group consisted of patients treated with biomedicine alone.
+From PD diagnosis to 2013, the prevalence and annual length of hospitalization because of PD and major complications (dementia, depression and pneumonia/sepsis) were analyzed using logistic regression, ANOVA and t-tests after propensity score (PS) matching with a 1:1 ratio.
+Results: After PS estimation and matching, the cohort used in the analysis included 228 subjects (114 integrative therapy group, 114 monotherapy group).
+Sex, age, index year, comorbidity, severity of disability, neurologic care, and anti-parkinsonism medication (levodopa, ropinirole, pramipexole, selegiline) were adjusted in both groups.
+: 0.26–0.96) lower in the integrative therapy group than the monotherapy group, which was statistically significant (p = 0.038).
+The prevalence and annual length of total hospitalization and hospitalization because of PD, dementia, and depression in the integrative therapy group showed positive results compared to the monotherapy group, but these differences were not statistically significant.
+Conclusion: It has not been clearly identified that integrative therapy with KM and biomedicine for PD management is better treatment for patients compared to biomedicine monotherapy; however, we found a clue of better result in integrated therapy.
+Therefore, further investigation by increasing the number of subjects is needed to confirm the findings presented herein.
+The introduction of high-throughput sequencing (HTS)-based methods has paved the way for genomics-based detection of pathogens without any prior assumptions about the characteristics of the organisms.
+However, the use of HTS for the characterization of viral pathogens from clinical samples remains limited.
+Following enrichment in cell culture, RNA was extracted from the growth medium and rapid library preparation, HTS and primary bioinformatic analyses were performed in less than 12 hours.
+Taxonomical profiling of the sequencing reads did not reveal sequence similarities to any known virus.
+Subsequent application of de novo assembly tools to the sequencing reads produced contigs, of which three showed some similarity to the L, M, and S segments of viruses belonging to the Orthobunyavirus genus.
+Further refinement of these contigs resulted in high-quality, full-length genomic sequences of the three genomic segments (L, M and S) of a novel Orthobunyavirus.
+Characterization of the genomic sequence, including the prediction of open reading frames and the inspection of consensus genomic termini and phylogenetic analysis, further confirmed that the novel virus is indeed a new species, which we named Ness Ziona virus.
+The potential inverse relation of HDL to coronary artery disease (CAD) and the effects of HDL on myriad other inflammatory conditions warrant a better understanding of the genetic basis of the HDL proteome.
+We conducted a comprehensive genetic analysis of the regulation of the proteome of HDL isolated from a panel of 100 diverse inbred strains of mice (the hybrid mouse diversity panel) and examined protein composition and efflux capacity to identify novel factors that affect the HDL proteome.
+Some of this variation was explained by local cis-acting regulation, termed cis-protein quantitative trait loci (QTLs).
+Variations in apoA-II and apoC-3 affected the abundance of multiple HDL proteins, indicating a coordinated regulation.
+We identified modules of covarying proteins and defined a protein-protein interaction network that describes the protein composition of the naturally occurring subspecies of HDL in mice.
+Sterol efflux capacity varied up to 3-fold across the strains, and HDL proteins displayed distinct correlation patterns with macrophage and ABCA1-specific cholesterol efflux capacity and cholesterol exchange, suggesting that subspecies of HDL participate in discrete functions.
+The baseline and stimulated sterol efflux capacity phenotypes were associated with distinct QTLs with smaller effect size, suggesting a multigenetic regulation.
+Our results highlight the complexity of HDL particles by revealing the high degree of heterogeneity and intercorrelation, some of which is associated with functional variation, and support the concept that HDL-cholesterol alone is not an accurate measure of HDL’s properties, such as protection against CAD.
+We present an epidemic model called SIQ with an isolation protocol, focusing on the consequences of delays and incomplete identification of infected hosts.
+The continuum limit of this model is a system of Delay Differential Equations, the analysis of which reveals clearly the dependence of epidemic evolution on model parameters including disease reproductive number, isolation probability, speed of identification of infected hosts and recovery rates.
+Our model offers estimates on minimum response capabilities needed to curb outbreaks, and predictions of endemic states when containment fails.
+Critical response capability is expressed explicitly in terms of parameters that are easy to obtain, to assist in the evaluation of funding priorities involving preparedness and epidemics management.
+The porcine epidemic diarrhea virus (PEDV) that emerged and spread throughout Taiwan in 2014 triggered significant concern in the country’s swine industry.
+Acknowledging the absence of a thorough investigation at the geographic level, we used 2014 outbreak sequence information from the Taiwan government’s open access databases plus GenBank records to analyze PEDV dissemination among Taiwanese pig farms.
+Genetic sequences, locations, and dates of identified PEDV-positive cases were used to assess spatial, temporal, clustering, GIS, and phylogeographic factors affecting PEDV dissemination.
+Our conclusion is that S gene sequences from 2014 PEDV-positive clinical samples collected in Taiwan were part of the same Genogroup 2 identified in the US in 2013.
+According to phylogenetic and phylogeographic data, viral strains collected in different areas were generally independent of each other, with certain clusters identified across different communities.
+Data from GIS and multiple potential infection factors were used to pinpoint cluster dissemination in areas with large numbers of swine farms in southern Taiwan.
+The data indicate that the 2014 Taiwan PEDV epidemic resulted from the spread of multiple strains, with strong correlations identified with pig farm numbers and sizes (measured as animal concentrations), feed mill numbers, and the number of slaughterhouses in a specifically defined geographic area.
+Bacillus Calmette-Guérin (BCG) is the only licensed vaccine for tuberculosis (TB), and is also used as an immunotherapy for bladder cancer and other malignancies due to its immunostimulatory properties.
+Mycobacteria spp., however, are well known for their numerous immune evasion mechanisms that limit the true potential of their therapeutic use.
+One such major mechanism is the induction of programmed death ligand-1 (PD-L1), which mitigates adaptive immune responses.
+Here, we sought to unravel the molecular pathways behind PD-L1 up-regulation on antigen-presenting cells (APCs) by BCG.
+We found that infection of APCs with BCG induced PD-L1 up-regulation, but that this did not depend on direct infection, suggesting a soluble mediator for this effect.
+BCG induced potent quantities of IL-6 and IL-10, and the downstream transcription factor STAT3 was hyper-phosphorylated.
+Intracellular analyses revealed that levels of PD-L1 molecules were associated with the STAT3 phosphorylation state, suggesting a causal link.
+Neutralisation of the IL-6 or IL-10 cytokine receptors dampened STAT3 phosphorylation and BCG-mediated up-regulation of PD-L1 on APCs.
+Pharmacological inhibition of STAT3 achieved the same effect, confirming an autocrine-paracrine cytokine loop as a mechanism for BCG-mediated up-regulation of PD-L1.
+Finally, an in vivo immunisation model showed that BCG vaccination under PD-L1 blockade could enhance antigen-specific memory CD4 T-cell responses.
+These novel findings could lead to refinement of BCG as both a vaccine for infectious disease and as a cancer immunotherapy.
+Leishmaniasis and Chagas disease are endemic in many countries, and re-emerging in the developed countries.
+A rapid and accurate diagnosis is important for early treatment for reducing the duration of infection as well as for preventing further potential health complications.
+In this work, we have developed a novel colorimetric molecular assay that integrates nucleic acid analysis by dynamic chemistry (ChemNAT) with reverse dot-blot hybridization in an array format for a rapid and easy discrimination of Leishmania major and Trypanosoma cruzi.
+The assay consists of a singleplex PCR step that amplifies a highly homologous DNA sequence which encodes for the RNA component of the large ribosome subunit.
+The amplicons of the two different parasites differ between them by single nucleotide variations, known as “Single Nucleotide Fingerprint” (SNF) markers.
+The SNF markers can be easily identified by naked eye using a novel micro Spin-Tube device "Spin-Tube", as each of them creates a specific spot pattern.
+Moreover, the direct use of ribosomal RNA without requiring the PCR pre-amplification step is also feasible, further increasing the simplicity of the assay.
+The molecular assay delivers sensitivity capable of identifying up to 8.7 copies per µL with single mismatch specificity.
+The Spin-Tube thus represents an innovative solution providing benefits in terms of time, cost, and simplicity, all of which are crucial for the diagnosis of infectious disease in developing countries.
+Avian leukosis virus subgroup J (ALV-J) infection can cause tumors and immunosuppression in infected chickens.
+In this study, we discovered an interesting phenomenon: ALV-J replication is weakened from 3 hours post-infection (hpi) to 36 hpi, which was verified using Western blotting and RT-PCR.
+To further investigate the interaction between ALV-J and macrophages, transcriptome analysis was performed to analyze the host genes’ function in chicken primary monocyte-derived macrophages (MDM).
+Compared to the uninfected control, 624 up-regulated differentially expressed genes (DEG) and 341 down-regulated DEG at 3 hpi, and 174 up-regulated DEG and 87 down-regulated DEG at 36 hpi were identified in chicken MDM, respectively.
+ALV-J infection induced strong innate immune responses in chicken MDM at 3 hpi, instead of 36 hpi, according to the analysis results of Gene Ontology and KEGG pathway.
+Importantly, the host factors, such as up-regulated MIP-3α, IL-1β, iNOS, K60, IRG1, CH25H, NFKBIZ, lysozyme and OASL were involved in the host defense response during the course of ALV-J infection.
+On the contrary, up-regulated EX-FABP, IL4I1, COX-2, NFKBIA, TNFAIP3 and the Jak STAT pathway inhibitors including CISH, SOCS1 and SOCS3 are beneficial to ALV-J survival in chicken macrophages.
+We speculated that ALV-J tropism for macrophages helps to establish a latent infection in chicken MDM from 6 to 36 hpi.
+It suggests the mechanisms of defense of chicken macrophages against ALV-J invasion and how ALV-J escape the host innate immune responses.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13567-019-0638-y) contains supplementary material, which is available to authorized users.
+As of May 27, 2018, 6 suspected, 13 probable and 35 confirmed cases of Ebola virus disease (EVD) had been reported in Équateur Province, Democratic Republic of Congo.
+We used reported case counts and time series from prior outbreaks to estimate the total outbreak size and duration with and without vaccine use.
+We modeled Ebola virus transmission using a stochastic branching process model that included reproduction numbers from past Ebola outbreaks and a particle filtering method to generate a probabilistic projection of the outbreak size and duration conditioned on its reported trajectory to date; modeled using high (62%), low (44%), and zero (0%) estimates of vaccination coverage (after deployment).
+Additionally, we used the time series for 18 prior Ebola outbreaks from 1976 to 2016 to parameterize the Thiel-Sen regression model predicting the outbreak size from the number of observed cases from April 4 to May 27.
+We used these techniques on probable and confirmed case counts with and without inclusion of suspected cases.
+Probabilistic projections were scored against the actual outbreak size of 54 EVD cases, using a log-likelihood score.
+With the stochastic model, using high, low, and zero estimates of vaccination coverage, the median outbreak sizes for probable and confirmed cases were 82 cases (95% prediction interval [PI]: 55, 156), 104 cases (95% PI: 58, 271), and 213 cases (95% PI: 64, 1450), respectively.
+With the Thiel-Sen regression model, the median outbreak size was estimated to be 65.0 probable and confirmed cases (95% PI: 48.8, 119.7).
+Among our three mathematical models, the stochastic model with suspected cases and high vaccine coverage predicted total outbreak sizes closest to the true outcome.
+Relatively simple mathematical models updated in real time may inform outbreak response teams with projections of total outbreak size and duration.
+The relationship between females with low glucose-6-phosphate dehydrogenase activity level (LG6PD) and HBV infection is unclear.
+We conducted a cross sectional study of 124 406 reproductive-age Chinese females who participated in the National Free Pre-conception Check-up Projects to investigate the risk of HBV infection among females with LG6PD and its effect on liver enzyme.
+Based on HBV serological test results, the participants were divided into the susceptible, immunized, and HBV infected groups.
+The multivariable-adjusted odds ratios (ORs) for HBV infection in LG6PD participants were 1.71 (95% confidence interval (CI): 1.45–2.01) and 1.41 (95% CI: 1.23–1.62), respectively with the susceptible and immunized participants as references, compared to those without LG6PD.
+Participants with HBV infection only and combined with HBV infection and LG6PD had 184% and 249% significantly higher risks of elevated alanine transaminase (ALT) (susceptible participants as reference).
+If the immunized participants were used as reference, significant higher odds of elevated ALT occurred (3.48 (95% CI: 3.18–3.80), 4.28 (95% CI: 2.92–6.28)).
+Thus, reproductive-age females with LG6PD had a higher prevalence of HBV infection, and LG6PD might exacerbate ALT elevation in HBV infected females.
+Our findings underscore the need to explore collaborative management approaches for these two diseases among reproductive-age females for maternal and child health.
+Most Ad-based therapies utilize species C serotypes, with Adenovirus type 5 (Ad5) most commonly employed.
+Prior clinical trials demonstrated low efficiency of oncolytic Ad5 vectors, mainly due to the absence of Ad5 primary receptor (Coxsackie and Adenovirus Receptor, CAR) on cancer cells.
+Engineering serotype chimeric vectors (Ad5/3) to utilize Adenovirus type 3 (Ad3) receptors has greatly improved their oncolytic potential.
+Clinical translation of these infectivity-enhanced vectors has been challenging due to a lack of replication permissive animal models.
+In this study, we explored pigs as a model to study the performance of fiber-modified Ad5/3 chimeric vectors.
+We analyzed binding, gene transfer, replication, and cytolytic ability of Ad5 and Ad5/3 in various non-human cell lines (murine, hamster, canine, porcine).
+Among all tested cell lines only porcine cells supported active binding and replication of Ad5/3.
+Syrian hamster cells supported Ad5 replication but showed no evidence of productive viral replication after infection with Ad5/3 vectors.
+Transduction and replication ability of Ad5/3 in porcine cells outperformed Ad5, a phenomenon often observed in human cancer cell lines.
+Quantitative PCR analyses 7 days post infection revealed Ad5 and Ad5/3 DNA and replication-dependent luciferase activity in the swine lungs and spleen indicating active replication in these tissues.
+These studies demonstrated the flaws in using Syrian hamsters for testing serotype chimeric Ad5/3 vectors.
+This is the first report to validate the pig as a valuable model for preclinical testing of oncolytic adenoviruses utilizing Adenovirus type 3 receptors.
+We hope that these data will help to foster the clinical translation of oncolytic adenoviruses including those with Ad3 retargeted tropism.
+Crimean-Congo haemorrhagic fever (CCHF) is a widespread tickborne disease that circulates in wild and domestic animal hosts, and causes severe and often fatal haemorrhagic fever in infected humans.
+Due to the lack of treatment options or vaccines, and a high fatality rate, CCHF virus (CCHFV) is considered a high-priority pathogen according to the WHO R&D Blueprint.
+Several commercial reverse transcriptase PCR (RT-PCR) and serological diagnostic assays for CCHFV are already available, including febrile agent panels to distinguish CCHFV from other viral haemorrhagic fever agents; however, the majority of international laboratories use inhouse assays.
+As CCHFV has numerous amplifying animal hosts, a cross-sectoral ‘One Health’ approach to outbreak prevention is recommended to enhance notifications and enable early warning for genetic and epidemiological shifts in the human, animal and tick populations.
+However, a lack of guidance for surveillance in animals, harmonisation of case identification and validated serodiagnostic kits for animal testing hinders efforts to strengthen surveillance systems.
+Additionally, as RT-PCR tests tend to be lineage-specific for regional circulating strains, there is a need for pan-lineage sensitive diagnostics.
+Adaptation of existing tests to point-of-care molecular diagnostic platforms that can be implemented in clinic or field-based settings would be of value given the potential for CCHFV outbreaks in remote or low-resource areas.
+Finally, improved access to clinical specimens for validation of diagnostics would help to accelerate development of new tests.
+Lassa fever virus (LASV) causes acute viral haemorrhagic fever with symptoms similar to those seen with Ebola virus infections.
+LASV is endemic to West Africa and is transmitted through contact with excretions of infected Mastomys natalensis rodents and other rodent species.
+Due to a high fatality rate, lack of treatment options and difficulties with prevention and control, LASV is one of the high-priority pathogens included in the WHO R&D Blueprint.
+Current diagnostics for LASV include in-house and commercial (primarily research-only) laboratory-based serological and nucleic acid amplification tests.
+There are two commercially available (for research use only) rapid diagnostic tests (RDTs), and a number of multiplex panels for differential detection of LASV infection from other endemic diseases with similar symptoms have been evaluated.
+Lineage detection is a challenge due to the genomic diversity of LASV, as pan-lineage sensitivity for both molecular and immunological detection is necessary for surveillance and outbreak response.
+While pan-lineage ELISA and RDTs are commercially available (for research use only), validation and external quality assessment (EQA) is needed to confirm detection sensitivity for all known or relevant strains.
+Variable sensitivity of LASV PCR tests also highlights the need for improved validation and EQA.
+Given that LASV outbreaks typically occur in low-resource settings, more options for point-of-care testing would be valuable.
+These requirements should be taken into account in target product profiles for improved LASV diagnostics.
+RATIONALE: Acute fibrinous and organizing pneumonia (AFOP) is an uncommon type of acute lung injury associated with infection, connective tissue disorders, drug exposure, and hematologic malignancies.
+PATIENT CONCERNS: A 53-year-old female presented with intermittent fever, chills, and dry cough since 10 days.
+DIAGNOSES: Histologic examination revealed massive fibrinous exudation with organization within alveolar spaces and scattered neutrophilic infiltrates, which was consistent with AFOP.
+OUTCOMES: Chest radiograph improvement and symptom improvement, including fever and respiratory symptoms, was observed after 2 week of oral prednisolone treatment.
+After 9-month of treatment, the patient was asymptomatic with stable disease and improved quality of life.
+LESSONS: AFOP has unique pathologic manifestations; however, the condition is liable to be misdiagnosed as community-acquired pneumonia ortuberculosis.
+Interferons (IFNs) are pleiotropic cytokines that establish a first line of defense against viral infections in vertebrates.
+Several types of IFN have been identified; however, limited information is available in poultry, especially using live animal experimental models.
+IFN-lambda (IFN-λ) has recently been shown to exert a significant antiviral impact against viral pathogens in mammals.
+In order to investigate the in vivo potential of chicken IFN-λ (chIFN-λ) as a regulator of innate immunity, and potential antiviral therapeutics, we profiled the transcriptome of chIFN-λ-stimulated chicken immune organs (in vivo) and compared it with primary chicken embryo fibroblasts (in vitro).
+Employing the baculovirus expression vector system (BEVS), recombinant chIFN-λ3 (rchIFN-λ3) was produced and its biological activities were demonstrated.
+The transcriptional profiling using RNA-seq and subsequent bioinformatics analysis (gene ontology, differential expressed genes, and KEGGs analysis) of the bursa of Fabricious and the thymus demonstrated an upregulation of crucial immune genes (viperin, IKKB, CCL5, IL1β, and AP1) as well as the antiviral signaling pathways.
+Interestingly, this experimental approach revealed contrasting evidence of the antiviral potential of chIFN-λ in both in vivo and in vitro models.
+Taken together, our data signifies the potential of chIFN-λ as a potent antiviral cytokine and highlights its future possible use as an antiviral therapeutic in poultry.
+Influenza viruses are a threat to global public health resulting in ~500,000 deaths each year.
+Despite an intensive vaccination program, influenza infections remain a recurrent, yet unsolved public health problem.
+Secondary bacterial infections frequently complicate influenza infections during seasonal outbreaks and pandemics, resulting in increased morbidity and mortality.
+Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA), is frequently associated with these co-infections, including the 2009 influenza pandemic.
+Damage to alveolar epithelium is a major contributor to severe influenza-bacterial co-infections and can result in gas exchange abnormalities, fluid leakage, and respiratory insufficiency.
+However, there is a paucity of information regarding the mechanisms (pathogen- and/or host-mediated) underlying influenza-bacterial co-infection pathogenesis.
+To address this, we characterized the contributions of viral-, bacterial-, and host-mediated factors to the altered structure and function of alveolar epithelial cells during co-infection with a focus on the 2009 pandemic influenza (pdm2009) and MRSA.
+Here, we characterized pdm2009 and MRSA replication kinetics, temporal host kinome responses, modulation of MRSA virulence factors, and disruption of alveolar barrier integrity in response to pdm2009-MRSA co-infection.
+Our results suggest that alveolar barrier disruption during co-infection is mediated primarily through host response dysregulation, resulting in loss of alveolar barrier integrity.
+Human adenovirus type 4 (HAdV-E4), which is intriguingly limited to military populations, causes acute respiratory disease with demonstrated morbidity and mortality implications.
+A signature of these “old” HAdV-E4 is the absence of a critical replication motif, NF-I, which is found in all HAdV respiratory pathogens and most HAdVs.
+However, our recent survey of flu-like disease in children in Hong Kong reveals that the emergent HAdV-E4 pathogens circulating in civilian populations contain NF-I, indicating recombination and reflecting host-adaptation that enables the “new” HAdV-E4 to replicate more efficiently in human cells and foretells more potential HAdV-E4 outbreaks in immune-naïve civilian populations.
+Special attention should be paid by clinicians to this emergent and recombinant HAdV-E4 circulating in civilian populations.
+Zika virus (ZIKV) infection can cause severe congenital diseases, such as microcephaly, ocular defects and arthrogryposis in fetuses, and Guillain–Barré syndrome in adults.
+Efficacious therapeutic treatments for infected patients, as well as prophylactic treatments to prevent new infections are needed for combating ZIKV infection.
+Here, we report that ZIKV-specific human polyclonal antibodies (SAB-155), elicited in transchromosomal bovine (TcB), provide significant protection from infection by ZIKV in STAT2 knockout (KO) golden Syrian hamsters both prophylactically and therapeutically.
+Because suitable quantities of highly potent human polyclonal antibodies can be quickly produced from the TcB system against ZIKV and have demonstrated therapeutic efficacy in a small animal model, they have the potential as an effective countermeasure against ZIKV infection.
+BACKGROUND: To develop a more effective vaccination strategy for reducing the impact of respiratory syncytial virus (RSV) infection, especially in young infants (<6 months old), it is necessary to understand the transmission dynamics of RSV.
+METHODS: We conducted a community-based prospective cohort study from 2014 to 2016 in Biliran Province, the Philippines, on children <5 years old.
+We collected nasopharyngeal swabs from symptomatic children with acute respiratory infection (ARI) during household visits and at health facilities.
+In households (n = 181) with RSV-positive ARI cases (RSV-ARI), we also identified ARI episodes among other children <5 years old in the same household.
+In addition, we determined the serial interval to estimate the basic reproduction number (R(0)), the average number of secondary cases generated by a single primary case.
+RESULTS: In the 181 households analyzed, we found 212 RSV-ARI in 152 households with a single case and 29 households with multiple cases, which included 29 1st RSV-ARI and 31 2nd RSV-ARI.
+We also found possible index cases among children <5 years old in the same household for 29.0% (18 of 62) of young infants with RSV-ARI.
+The estimated mean serial interval was 3.2 days, and R(0) was estimated to be 0.92–1.33 for RSV-A and 1.04–1.76 for RSV-B, which varied between different times (2014 and 2015) and places.
+CONCLUSIONS: Young infants are likely to acquire RSV infection from older children in the same household.
+Here, we present the first generation of the chimeric cytoplasmic capping-prone phage polymerase (C3P3-G1) expression system developed by biological engineering, which generates capped and polyadenylated transcripts in host-cell cytoplasm by means of two components.
+First, an artificial single-unit chimeric enzyme made by fusing an mRNA capping enzyme and a DNA-dependent RNA polymerase.
+Second, specific DNA templates designed to operate with the C3P3-G1 enzyme, which encode for the transcripts and their artificial polyadenylation.
+This system, which can potentially be adapted to any in cellulo or in vivo eukaryotic expression applications, was optimized for transient expression in mammalian cells.
+Objectives: The objectives of this study were to evaluate the clinical and nutritional correlates of high free fatty acids (FFAs) level in critically ill patients and the association with outcomes, and to study the effect of short-term caloric restriction (permissive underfeeding) on FFAs level during critical illness.
+Patients/Method: In this pre-planned sub-study of the PermiT (Permissive Underfeeding vs. Target Enteral Feeding in Adult Critically Ill Patients) trial, we included critically ill patients who were expected to stay for ≥14 days in the intensive care unit.
+Of 70 enrolled patients, 23 (32.8%) patients had high FFAs level (baseline FFAs level >0.45 mmol/L in females and >0.6 mmol/L in males).
+Results: Patients with high FFAs level were significantly older and more likely to be females and diabetics and they had lower ratio of partial pressure of oxygen to the fraction of inspired oxygen, higher creatinine, and higher total cholesterol levels than those with normal FFAs level.
+During the study period, patients with high FFAs level had higher blood glucose and required more insulin.
+On multivariable logistic regression analysis, the predictors of high baseline FFAs level were diabetes (adjusted odds ratio (aOR): 5.36; 95% confidence interval (CI): 1.56, 18.43, p = 0.008) and baseline cholesterol level (aOR, 4.29; 95% CI: 11.64, 11.19, p = 0.003).
+Serial levels of FFAs did not differ with time between permissive underfeeding and standard feeding groups.
+FFAs level was not associated with 90-day mortality (aOR: 0.49; 95% CI: 0.09, 2.60, p = 0.40).
+Conclusion: We conclude that high FFAs level in critically ill patients is associated with features of metabolic syndrome and is not affected by short-term permissive underfeeding.
+Solubility is the prime criterion for determining the quality of recombinant proteins, yet it often fails to represent functional activity due to the involvement of non-functional, misfolded, soluble aggregates, which compromise the quality of recombinant proteins.
+However, guidelines for the quality assessment of soluble proteins have neither been proposed nor rigorously validated experimentally.
+Using the aggregation-prone enhanced green-fluorescent protein (EGFP) folding reporter system, we evaluated the folding status of recombinant proteins by employing the commonly used sonication and mild lysis of recombinant host cells.
+We showed that the differential screening of solubility and folding competence is crucial for improving the quality of recombinant proteins without sacrificing their yield.
+These results highlight the importance of screening out incorrectly folded soluble aggregates at the initial purification step to ensure the functional quality of recombinant proteins.
+OBJECTIVE: To investigate scaling approaches for evaluating the development of peak VO(2) and improving the identification of low cardiopulmonary fitness in Southern Chinese children and adolescents.
+METHODS: Nine hundred and twenty Chinese children and adolescents (8 to 16 years) underwent graded cardiopulmonary exercise test on a treadmill until volitional exhaustion.
+Peak VO(2) was corrected for the effects of body mass by ratio or allometric scaling.
+Correlations between scaled peak VO(2), z scores, body size and age were tested to examine the effectiveness of the approach.
+Absolute peak VO(2) significantly increased with age in both sexes (both P<0.05), while ratio-scaled peak VO(2) increased only in males (P<0.05).
+Allometrically scaled peak VO(2) increased from 11 years in both sexes, plateauing by 12 years in girls and continuing to rise until 15 years in boys.
+Allometically scaled peak VO(2) was not correlated with body mass, but remained correlated with height and age in all but the older girls.
+CONCLUSIONS: Absolute and allometric scaled peak VO(2) values are provided for Hong Kong Chinese children and adolescents by age and sex.
+Peak VO(2) z scores improve the evaluation of cardiopulmonary fitness, allowing comparisons across ages and sex and will likely provide a better metric for tracking change over time in children and adolescents, regardless of body size and age.
+INTRODUCTION: Recent data on influenza C virus indicate a possible higher clinical impact in specified patient populations than previously thought.
+METHODS: A total of 1,588 samples from 0 to 4 year-old children presenting as outpatients with influenza-like illness (ILI) or acute respiratory infection were analysed retrospectively.
+The samples represented a subset of all samples from the German national surveillance system for influenza in this age group in 2012–14.
+For positive samples, information on symptoms as well as other respiratory virus co-infections was considered.
+RESULTS: Influenza C viral RNA was detected in 20 (1.3% of) samples, including 16 during the 2012/13 season.
+The majority (18/20) of influenza C-positive patients had ILI according to the European Union definition, one patient had pneumonia.
+CONCLUSION: Our data are the first on influenza C virus circulation in Germany and notably from a European national surveillance system.
+The low detection frequency and the identified virus variants confirm earlier observations outside a surveillance system.
+More virus detections during the 2012/13 season indicate a variable circulation intensity in the different years studied.
+Hemagglutinin (HA) is an important target in the therapeutic treatment and diagnostic detection of the influenza virus.
+Influenza A virus encompasses several different HA subtypes with different strains, which are constantly changing.
+In this study, we identified a fully human H1N1 neutralizing antibody (32D6) via an Epstein-Barr virus-immortalized B cell-based technology.
+32D6 specifically neutralizes the clinically isolated H1N1 strains after the 2009 pandemic but not the earlier strains.
+The epitope was identified through X-ray crystallographic analysis of the 32D6-Fab/HA1 complex structure, which revealed a unique loop conformation located on the top surface of HA.
+The major region is composed of two peptide segments (residues 172–177 and 206–213), which form an abreast loop conformation.
+The residue T262 between the two loops forms a conformational epitope for recognition by 32D6.
+Three water molecules were observed at the interface of HA and the heavy chain, and they may constitute a stabilizing element for the 32D6-HA association.
+This study provides important information on the strain specificity of 32D6 for the therapeutic treatment and detection of viral infection.
+BACKGROUND: We report hereby a severe case of Hantavirus Pulmonary Syndrome” (HPS) induced by Maripa virus in French Guiana and describe the mechanism of severity of the human disease.
+CASE PRESENTATION: A 47-year- old patient started presenting a prodromic period with fever, dyspnea, cough and head ache.
+This clinical presentation was followed by a rapid respiratory, hemodynamic and renal failure leading to admission in the ICU.
+Echocardiographic and hemodynamic monitoring showed a normal left ventricular function with low filling pressures, an elevated extravascular lung water index and pulmonary vascular permeability index.
+CONCLUSIONS: The severity of HPS caused by the virus Maripa in French Guiana can be explained by the tropism of hantavirus for the microvascular endothelial cell leading to a CLS.
+Inflammation is a common and important pathological process, and nuclear factor-κB (NF-κB) is a key mediator of it.
+Moutan Cortex (MC), the dried root cortex of Paeonia suffruticosa Andr., is widely used as a remedy for the treatment of inflammatory diseases in Asian region.
+In this study, the effect of inhibiting NF-κB activation of MC was assessed at the cellular level using a tumor necrosis factor-α (TNF-α) induced inflammatory model.
+Subsequently, ultra-performance liquid chromatography-quadrupole/time of flight-mass spectrometry (UPLC-Q/TOF-MS) combined with biological activity assay was established to screen and identify potential anti-inflammatory ingredients in MC.
+Seven potential NF-κB inhibitors were screened from MC, including oxypaeoniflorin, paeoniflorin, galloylpaeoniflorin, benzoyloxypaeoniflorin, mudanpioside C, gallic acid, and paeonol.
+Among them, the NF-κB inhibitor activity of galloylpaeoniflorin, benzoyloxypaeoniflorin, and mudanpioside C is first reported here.
+In conclusion, the anti-inflammatory activity of MC was associated with the seven components mentioned above.
+And the bioactivity-integrated UPLC-Q/TOF which contains both chemical and bioactive details is suitable for screening active ingredients from natural medicines.
+PURPOSE: Distinguishing urinary tract infection (UTI) from urinary tract colonization (UTC) in children with neurogenic bladders who require clean intermittent catheterization (CIC) is challenging.
+Our objective was to identify urinary proteins to distinguish UTI from UTC in CIC-dependent children that have potential to serve as objective markers of UTI.
+EXPERIMENTAL DESIGN: A total of 10 CIC-dependent children were included in the mass spectrometry analysis (UTI = 5, UTC = 5).
+Quantitative profiling of urine proteins with isobaric protein labeling was performed using tandem mass spectrometry.
+Proteins with >50% change in the average abundance were identified as proteins of interest, which were then measured using enzyme-linked immunosorbent assay (ELISA) in an additional 40 samples (no growth = 10, UTC = 15, UTI = 15).
+Of these, apolipoprotein D, alpha-amylase 2B, non-secretory ribonuclease, CD44 antigen, and prosaposin were measurable by ELISA.
+Concentrations of both CD44 and prosaposin were significantly higher in UTI, with area under the curves (AUCs) of 0.72 and 0.78, respectively.
+CONCLUSION: Urinary CD44 and prosaposin are candidate markers that may assist with the diagnosis of UTI in CIC-dependent children.
+Many ‘non-enveloped’ viruses, including hepatitis A virus (HAV), are released non-lytically from infected cells as infectious, quasi-enveloped virions cloaked in host membranes.
+Quasi-enveloped HAV (eHAV) mediates stealthy cell-to-cell spread within the liver, whereas stable naked virions shed in feces are optimized for environmental transmission.
+We show both virion types enter by clathrin- and dynamin-dependent endocytosis, facilitated by integrin β(1), and traffic through early and late endosomes.
+Uncoating of naked virions occurs in late endosomes, whereas eHAV undergoes ALIX-dependent trafficking to lysosomes where the quasi-envelope is enzymatically degraded and uncoating ensues coincident with breaching of endolysosomal membranes.
+Thus naked and quasi-enveloped virions enter via similar endocytic pathways, but uncoat in different compartments and release their genomes to the cytosol in a manner mechanistically distinct from other Picornaviridae.
+Yersinia pestis, a Gram-negative bacterium and the etiologic agent of plague, has evolved from Yersinia pseudotuberculosis, a cause of a mild enteric disease.
+However, the molecular and biological mechanisms of how Y. pseudotuberculosis evolved to such a remarkably virulent pathogen, Y. pestis, are not clear.
+The ability to initiate a rapid bacterial dissemination is a characteristic hallmark of Y. pestis infection.
+A distinguishing characteristic between the two Yersinia species is that Y. pseudotuberculosis strains possess an O-antigen of lipopolysaccharide (LPS) while Y. pestis has lost the O-antigen during evolution and therefore exposes its core LPS.
+In this study, we showed that Y. pestis utilizes its core LPS to interact with SIGNR1 (CD209b), a C-type lectin receptor on antigen presenting cells (APCs), leading to bacterial dissemination to lymph nodes, spleen and liver, and the initiation of a systemic infection.
+We therefore propose that the loss of O-antigen represents a critical step in the evolution of Y. pseudotuberculosis into Y. pestis in terms of hijacking APCs, promoting bacterial dissemination and causing the plague.
+In the clinical setting with limited resources, high degree of suspicion is needed to diagnose cardiac involvement including myocarditis.
+Although myocarditis is not reported as a common complication due to lack of diagnostic facilities, there are evidence to support myocarditis is more prevalent in post mortem studies of patients died due to leptospirosis.
+We present a case series of severe leptospirosis with cardiac involvement observed during a period of one month at Colombo-North Teaching Hospital, Sri Lanka.
+CASE PRESENTATION: We report here five patients with severe leptospirosis complicated with cardiac involvement, admitted to a single medical ward, Colombo-North Teaching Hospital, Sri Lanka during a one-month period.
+Out of six suspected leptospirosis patients admitted during that period, five in a raw developed severe leptospirosis with cardiac involvement.
+In this case series, four patients were confirmed serologically or quantitative PCR and one patient had possible leptospirosis.
+One patient had dynamic T wave changes in ECG and the other two had sinus tachycardia.
+Two patients had evidence of myocarditis in 2D echocardiogram, whereas other two patients had nonspecific findings and one patient had normal 2D echocardiogram.
+All five patients had elevated cardiac troponin I titre and it was normalized with the recovery.
+Four patients needed inotropic/vasopressor support to maintain mean arterial pressure and one patient recovered from shock with fluid resuscitation.
+All patients were recovered from their illness and repeat 2D echocardiograms after recovery did not show residual complications.
+CONCLUSIONS: Myocarditis and cardiac involvement in leptospirosis may be overlooked due to non-specific clinical findings and co-existing multi-organ dysfunction.
+Atypical presentation of this case series may be due to micro-geographic variation and unusual outbreak of leptospirosis.
+Co-infection of dengue with leptospirosis should be considered in managing patients especially in endemic areas.
+Hemorrhagic fevers (HF) resulting from pathogenic arenaviral infections have traditionally been neglected as tropical diseases primarily affecting African and South American regions.
+There are currently no FDA-approved vaccines for arenaviruses, and treatments have been limited to supportive therapy and use of non-specific nucleoside analogs, such as Ribavirin.
+Outbreaks of arenaviral infections have been limited to certain geographic areas that are endemic but known cases of exportation of arenaviruses from endemic regions and socioeconomic challenges for local control of rodent reservoirs raise serious concerns about the potential for larger outbreaks in the future.
+This review synthesizes current knowledge about arenaviral evolution, ecology, transmission patterns, life cycle, modulation of host immunity, disease pathogenesis, as well as discusses recent development of preventative and therapeutic pursuits against this group of deadly viral pathogens.
+BACKGROUND: Social contact surveys can greatly help in quantifying the heterogeneous patterns of infectious disease transmission.
+The present study aimed to conduct a contact survey in Japan, offering estimates of contact by age and location and validating a social contact matrix using a seroepidemiological dataset of influenza.
+METHODS: An internet-based questionnaire survey was conducted, covering all 47 prefectures in Japan and including a total of 1476 households.
+By imposing several parametric assumptions for the next-generation matrix, the empirical seroepidemiological data of influenza A (H1N1) 2009 was analysed and we estimated the basic reproduction number, R(0).
+RESULTS: In total, the reported number of contacts on weekdays was 10,682 whereas that on weekend days was 8867.
+Forty percent of weekday contacts took place at schools or workplaces, but that declined to 14% on weekends.
+Accounting for the age-dependent heterogeneity with the known social contact matrix, the minimum value of the Akaike information criterion was obtained and R(0) was estimated at 1.45 (95% confidence interval: 1.42, 1.49).
+CONCLUSIONS: Survey datasets will be useful for parameterizing the heterogeneous transmission model of various directly transmitted infectious diseases in Japan.
+Age-dependent assortativity, especially among children, along with numerous contacts in school settings on weekdays implies the potential effectiveness of school closure.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12976-019-0102-8) contains supplementary material, which is available to authorized users.
+Pericytes, as a key cellular part of the blood-brain barrier, play an important role in the maintenance of brain neurovascular unit.
+These cells participate in brain homeostasis by regulating vascular development and integrity mainly through secreting various factors.
+Upon the occurrence of brain acute and chronic diseases, pericytes provoke immune cells to regulate neuro-inflammatory conditions.
+Loss of pericytes in distinct neurologic disorders intensifies blood-brain barrier permeability and leads to vascular dementia.
+The therapeutic potential of pericytes is originated from the unique morphological shape, location, and their ability in providing vast paracrine and juxtacrine interactions.
+A subset of pericytes possesses multipotentiality and exhibit trans-differentiation capacity in the context of damaged tissue.
+This review article aimed to highlight the critical role of pericytes in restoration of the blood-brain barrier after injury by focusing on the dynamics of pericytes and cross-talk with other cell types.
+Clinical application of siRNA-based therapeutics outside of the liver has been hindered by the inefficient delivery of siRNA effector molecules into extra-hepatic organs and cells of interest.
+To understand the parameters that enable RNAi activity in vivo, it is necessary to develop a systematic approach to identify which cells within a tissue are permissive to oligonucleotide internalization and activity.
+In the present study, we evaluate the distribution and activity within the lung of chemically stabilized siRNA to characterize cell-type tropism and structure-activity relationship.
+We demonstrate intratracheal delivery of fully modified siRNA for RNAi-mediated target knockdown in lung CD11c(+) cells (dendritic cells, alveolar macrophages) and alveolar epithelial cells.
+Finally, we use an allergen-induced model of lung inflammation to demonstrate the capacity of inhaled siRNA to induce target knockdown in dendritic cells and ameliorate lung pathology.
+DiNap [(E)-1-(2-hydroxy-4,6-dimethoxyphenyl)-3-(naphthalen-1-yl)prop-2-en-1-one], an analog of a natural product (the chalcone flavokawain), was synthesized and characterized in this study.
+Porcine reproductive and respiratory syndrome virus (PRRSV) is the most challenging threat to the swine industry worldwide.
+Currently, commercially available vaccines are ineffective for controlling porcine reproductive and respiratory syndrome (PRRS) in pigs.
+Hence, the present study evaluated the effects of DiNap on the replication of VR2332 (a prototype strain of type 2 PRRSV).
+Initially, in vitro antiviral assays against VR2332 were performed in MARC-145 cells and porcine alveolar macrophages (PAMs).
+Following this, a pilot study was conducted in a pig model to demonstrate the effects of DiNap following VR2332 infection.
+DiNap inhibited VR2332 replication in both cell lines in a dose-dependent manner, and viral growth was completely suppressed at concentrations ≥0.06 mM, without significant cytotoxicity.
+Consistent with these findings, in the pig study, DiNap also reduced viral loads in the serum and lungs and enhanced the weight gain of pigs following VR2332 infection, as indicated by comparison of the DiNap-treated groups to the untreated control (NC) group.
+In addition, DiNap-treated pigs had fewer gross and microscopic lesions in their lungs than NC pigs.
+Notably, virus transmission was also delayed by approximately 1 week in uninfected contact pigs within the same group after treatment with DiNap.
+Taken together, these results suggest that DiNap has potential anti-PRRSV activity and could be useful as a prophylactic or post-exposure treatment drug to control PRRSV infection in pigs.
+Emodin is a cell arrest and apoptosis-inducing compound that is widely distributed in different plants (rhubarb, aloe), lichens and terrestrial fungi, and also isolated from marine-derived fungi and marine sponge-associated fungi.
+In this study, we designed and synthesized a novel series of emodin derivatives by binding emodin to an amino acid using linkers of varying lengths and composition, and evaluated their anti-proliferative activities using HepG2 cells (human hepatic carcinoma), MCF-7 cells (human breast cancer) and human normal liver L02 cells.
+Notably, compound 7a exhibited potent anti-proliferative activity against HepG2 cells with the half maximal inhibitory concentration (IC(50)) value of 4.95 µM, which was enhanced 8.8-fold compared to the parent compound emodin (IC(50) = 43.87 µM), and it also exhibited better selective anti-proliferative activity and specificity than emodin.
+Moreover, further experiments demonstrated that compound 7a displayed a significant efficacy of inducing apoptosis through mitochondrial pathway via release of cytochrome c from mitochondria and subsequent activation of caspase-9 and caspase-3, inducing cell arrest at G0/G1 phase, as well as suppression of cell migration of tumor cells.
+The preliminary results suggested that compound 7a could be a promising lead compound for the discovery of novel anti-tumor drugs and has the potential for further investigations as an anti-cancer drug.
+Emerging mosquito-transmitted RNA viruses, such as Zika virus (ZIKV) and Chikungunya represent human pathogens of an immense global health problem.
+In particular, ZIKV has emerged explosively since 2007 to cause a series of epidemics in the South Pacific and most recently in the Americas.
+Although typical ZIKV infections are asymptomatic, ZIKV infection during pregnancy is increasingly associated with microcephaly and other fetal developmental abnormalities.
+In the last few years, genomic and molecular investigations have established a remarkable progress on the pathogenic mechanisms of ZIKV infection using in vitro and in vivo models.
+Here, we highlight recent advances in ZIKV-host cell interaction studies, including cellular targets of ZIKV, ZIKV-mediated cell death mechanisms, host cell restriction factors that limit ZIKV replication, and immune evasion mechanisms utilized by ZIKV.
+Understanding of the mechanisms of ZIKV–host interaction at the cellular level will contribute crucial insights into the development of ZIKV therapeutics and vaccines.
+The pathogenesis of life-threatening influenza A virus (IAV) disease remains elusive, as infection is benign in most individuals.
+We Sanger sequenced GATA2 and evaluated the mutation by gene transfer, measured serum cytokine levels, and analyzed circulating T- and B-cells.
+Both patients (father and son, P1 and P2) died in 2011 of H1N1pdm IAV infection at the ages of 54 and 31 years, respectively.
+They had not suffered from severe or moderately severe infections in the last 17 (P1) and 15 years (P2).
+B- and T-cell rearrangement in peripheral blood from P1 during the influenza episode showed expansion of one major clone.
+No T-cell receptor excision circles were detected in P1 and P3 since they were 35 and 18 years, respectively.
+Two previously reported adult GATA2-deficient patients died from severe H1N1 IAV infection; GATA2 deficiency may predispose to life-threatening influenza in adulthood.
+However, a role of other genetic variants involved in immune responses cannot be ruled out.
+Patients with GATA2 deficiency can reach young adulthood without severe infections, including influenza, despite long-lasting complete B-cell and natural killer (NK) cell deficiency, as well as profoundly diminished T-cell thymic output.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10875-018-0512-0) contains supplementary material, which is available to authorized users.
+IMHA is considered secondary when it can be attributed to an underlying disease, and as primary (idiopathic) if no cause is found.
+Eliminating diseases that cause IMHA may attenuate or stop immune‐mediated erythrocyte destruction, and adverse consequences of long‐term immunosuppressive treatment can be avoided.
+We identified and extracted data from studies published in the veterinary literature and developed a novel tool for evaluation of evidence quality, using it to assess study design, diagnostic criteria for IMHA, comorbidities, and causality.
+Statements were refined by conducting 3 iterations of Delphi review with panel and task force members.
+Commentary was solicited from several professional bodies to maximize clinical applicability before the recommendations were submitted.
+The resulting document is intended to provide clinical guidelines for diagnosis of, and underlying disease screening for, IMHA in dogs and cats.
+CASE PRESENTATION: This clinical case presents the history of a woman hospitalized for acute respiratory distress syndrome (ARDS).
+A 62-year-old woman, with regular physical activity and no history of respiratory disease or smoking, was hospitalized for moderate ARDS with bilateral pneumonitis.
+Fourteen days later, she was discharged from the intensive care unit and received respiratory physical therapy.
+A reduction in alveolar-capillary transfer, inappropriate hyperventilation upon exercise, and impairment of gas exchanges at maximal effort, suggestive of pulmonary shunt, were demonstrated.
+The persistence of bilateral basal interstitial syndrome associated with bronchial dilatation and pleural-based consolidations was noted, as well as a stable impaired alveolar-capillary diffusing capacity.
+Moreover, pulmonary function testing at rest and exercise is advised as soon as possible to evaluate the respiratory sequelae.
+This will help to limit the severity of complications through adapted exercise rehabilitation and then regular physical activity.
+BACKGROUND: Dengue fever, a mosquito-borne disease, is caused by dengue virus (DENV) which includes four major serotypes (DENV-1, -2, -3, and -4).
+Some serotypes cause more severe diseases than the other; severe dengue is associated with secondary infections by a different serotype.
+Timely serotyping can provide early warning of dengue epidemics to improve management of patients and outbreaks.
+A mobile insulated isothermal PCR (iiPCR) system is available to allow molecular detection of pathogens near points of need.
+METHODOLOGY/PRINCIPLE FINDINGS: In this study, side-by-side comparison with the CDC DENV-1-4 Real Time RT-PCR (qRT-PCR) was performed to evaluate the performance of four singleplex DENV-1–4 serotyping reverse transcription-iiPCR (RT-iiPCR) reagents for DENV subtyping on the mobile PCR system.
+The four RT-iiPCRs did not react with Zika virus and chikungunya virus; tests with serial dilutions of the four DENV serotypes made in human serum showed they had detection endpoints comparable to those of the reference method, indicating great analytical sensitivity and specificity.
+Clinical performance of the RT-iiPCR reagents was evaluated by testing 40 serum samples each (around 20 target serotype-positive and 20 DENV-negative); all four reagents had high agreement (97.5–100%) with the reference qRT-PCR.
+Moreover, testing of mosquitoes separately infected experimentally with each serotype showed that the four reagents detected specifically their target DENV serotypes in mosquito.
+CONCLUSIONS/SIGNIFICANCE: With analytical and clinical performance comparable to the reference qRT-PCR assay, the four index RT-iiPCR reagents on the field-deployable PCR system can serve as a useful tool for DENV detection near points of needs.
+In this study, we cloned and characterized Atg5, a key gene in the autophagy gene superfamily, from orange-spotted grouper (Epinephelus coioides) (EcAtg5).
+EcAtg5 encoded a 275-amino acid protein that shared 94 and 81% identity to seabass (Lates calcarifer) and humans (Homo sapiens), respectively.
+The transcription level of EcAtg5 was significantly increased in cells infected with red-spotted grouper nervous necrosis virus (RGNNV).
+In cells infected with Singapore grouper iridovirus (SGIV), EcAtg5 expression declined during the early stage of infection and increased in the late stage.
+Fluorescence microscopy revealed that EcAtg5 mainly localized with a dot-like pattern in the cytoplasm of grouper cells.
+Overexpression of EcAtg5 significantly increased the replication of RGNNV and SGIV at different levels of detection, as indicated by increased severity of the cytopathic effect, transcription levels of viral genes, and levels of viral proteins.
+Further studies showed that overexpression EcAtg5 activated autophagy, decreased expression levels of interferon related cytokines or effectors and pro-inflammatory factors, and inhibited the activation of nuclear factor κB, IFN-sensitive response element, and IFNs.
+In addition, ectopic expression of EcAtg5 affected cell cycle progression by hindering the G1/S transition.
+Taken together, our results demonstrated that fish Atg5 exerted a crucial role in virus replication by promoting autophagy, down-regulating antiviral IFN responses, and affecting the cell cycle.
+Vibrio anguillarum is a pathogenic bacterium that infects flounder resulting in significant losses in the aquaculture industry.
+The VAA protein previously identified in flounder is associated with a role in immune protection within these fish.
+In the present study, a recombinant DNA plasmid encoding the VAA gene of V. anguillarum was constructed and its potential as a DNA vaccine, to prevent the infection of V. anguillarum in flounder fish, investigated.
+We verified the expression of the VAA protein both in vitro in cell lines and in vivo in flounder fish.
+The protective effects of pcDNA3.1-VAA (pVAA) were analyzed by determination of the percentage of sIgM(+), CD4-1(+), CD4-2(+), CD8β(+) lymphocytes, and the production of VAA-specific antibodies in flounder following their immunization with the DNA vaccine.
+Histopathological changes in immune related tissues, bacterial load, and relative percentage survival rates of flounder post-challenge with V. anguillarum, were all investigated to assess the efficacy of the pVAA DNA vaccine candidate.
+Fish intramuscularly immunized with pVAA showed a significant increase in CD4-1(+), CD4-2(+), and CD8β(+) T lymphocytes at days 9, 11, and 14 post-vaccination, reaching peak T-cell levels at days 11 or 14 post-immunization.
+Specific anti-V. anguillarum or anti-rVAA antibodies were induced in inoculated fish at days 28–35 post-immunization.
+The liver of vaccinated flounder exhibited only slight histopathological changes compared with a significant pathology observed in control immunized fish.
+Additionally, a lower bacterial burden in the liver, spleen, and kidney were observed in pVAA protected fish in response to bacterial challenge, compared with pcDNA3.1 vector control injected fish.
+Moreover, the pVAA vaccine confers a relative percentage survival of 50.00% following V. anguillarum infection.
+In summary, this is the first study indicating an initial induction of the T lymphocyte response, followed by B lymphocyte induction of specific antibodies as a result of DNA immunization of flounder.
+This signifies the important potential of pVAA as a DNA vaccine candidate for the control of V. anguillarum infection.
+Spinal muscular atrophy (SMA), the leading genetic cause of infant mortality, is caused by reduced levels of functional survival motor neuron (SMN) protein.
+To identify therapeutic agents for SMA, we established a versatile SMN2-GFP reporter line by targeting the human SMN2 gene.
+Z-FA-FMK, a cysteine protease inhibitor, increased functional SMN through inhibiting the protease-mediated degradation of both full-length and exon 7–deleted forms of SMN.
+Further studies reveal that CAPN1, CAPN7, CTSB, and CTSL mediate the degradation of SMN proteins, providing novel targets for SMA.
+Notably, Z-FA-FMK mitigated mitochondriopathy and neuropathy in SMA patient–derived motor neurons and showed protective effects in SMA animal model after intracerebroventricular injection.
+E64d, another cysteine protease inhibitor which can pass through the blood–brain barrier, showed even more potent therapeutic effects after subcutaneous delivery to SMA mice.
+Taken together, we have successfully established a human SMN2 reporter for future drug discovery and identified the potential therapeutic value of cysteine protease inhibitors in treating SMA via stabilizing SMN proteins.
+Porcine gamma interferon is a cytokine produced by activated T cells and NK cells with broad-spectrum antiviral activity and immunomodulatory function.
+However, pIFN-γ is a secretory protein that has a short half-life in organisms and is easily inactivated, making it difficult to apply widely in clinics.
+Therefore, we tried to optimize the expression of pIFN-γ in Pichia pastoris to obtain a large amount of highly active, easily purified pIFN-γ protein in vitro.
+Through C-terminal sequence analysis, we found a signal sequence (EKREAEAE) that was easily enzymolysed by a signal peptide enzyme, resulting in degradation and inactivation of the pIFN-γ protein.
+In this study, we optimized the pIFN-γ gene recombination sequence and mutated the 3' end of the pIFN-γ gene, resulting in a higher expression level and stronger biological activity, as well as a significant upregulation in the expression of the interferon-stimulated genes Mx1 and OAS1 in IPEC-J2 jejunal epithelial cells.
+A recombinant Pichia pastoris strain with the optimized pIFN-γ gene could obtain a high yield of pIFN-γ protein, up to 9536 mg/L, after staged incubation for 0–24 h at 28°C, pH 6.0, and 50% dissolved oxygen (DO), followed by incubation for 24–72 h at 25°C, pH 6.0 and 30% DO.
+These data demonstrated, for the first time, that the expression level of pIFN-γ in Pichia pastoris was improved significantly by gene optimization with 3' end mutation and a fermentation process that maintained good biological activity, which is beneficial to the application of pIFN-γ in animal husbandry.
+Targeting S1PR1, which is known to modulate the immune response, provides protection against pathogenic influenza virus.
+The functional role and molecular mechanism of S1PR1 were analysed by generating inducible endothelial cell-specific S1PR1 knockout mice and assessing the therapeutic efficacy of the selective S1PR1 agonist CYM5442 against acute lung injury (ALI) induced by the 2009 influenza A H1N1 virus.
+Immune-mediated pulmonary injury is aggravated by the absence of endothelial S1PR1 and alleviated by treatment with CYM-5442, suggesting a protective function of S1PR1 signaling during H1N1 infection.
+Mechanistically, the MAPK and NF-kB signaling pathways are involved in the ALI mediated by S1PR1 in infected mice.
+Combined administration of the S1PR1 agonist CYM-5442 and the antiviral drug oseltamivir provides maximum protection from ALI.
+Our current study provides insight into the molecular mechanism of S1PR1 mediating the ALI induced by H1N1 infection and indicates that the combination of S1PR1 agonist with antiviral drug could potentially be used as a therapeutic remedy for future H1N1 virus pandemics.
+Human metapneumovirus (hMPV) is a widely distributed pathogen responsible for acute upper and lower respiratory infections of varying severity.
+Previously, we reported that N-sulfonated derivatives of poly(allylamine hydrochloride) (NSPAHs) efficiently inhibit replication of the influenza virus in vitro and ex vivo.
+Here, we show a dose dependent inhibition of hMPV infection by NSPAHs in LLC-MK2 cells.
+While the activity of NSPAHs is comparable to those of carrageenans, they show better physicochemical properties and may be delivered at high concentrations.
+The functional assays showed that tested polymers block hMPV release from infected cells and, consequently, constrain virus spread.
+Moreover, further studies on viruses utilizing different egress mechanisms suggest that observed antiviral effect depend on selective inhibition of viruses budding from the cell surface.
+Their genome is segmented into two or more parts, and encapsidated in separate particles that appear to propagate independently.
+Completing the replication cycle, however, requires the full genome, so that a systemic infection of a host requires the concurrent presence of several particles.
+A transition from monopartite to multipartite viral forms has been described in vitro under conditions of high multiplicity of infection, suggesting that cooperation between defective mutants is a plausible evolutionary pathway towards multipartitism.
+However, it is unknown how the putative advantages that multipartitism might enjoy at the microscopic level affect its epidemiology, or if an explicit advantange is needed to explain its ecological persistence.
+In order to disentangle which mechanisms might contribute to the rise and fixation of multipartitism, we here investigate the interaction between viral spreading dynamics and host population structure.
+We set up a compartmental model of the spread of a virus in its different forms and explore its epidemiology using both analytical and numerical techniques.
+We uncover that the impact of host contact structure on spreading dynamics entails a rich phenomenology of ecological relationships that includes cooperation, competition, and commensality.
+Furthermore, we find out that multipartitism might rise to fixation even in the absence of explicit microscopic advantages.
+Multipartitism allows the virus to colonize environments that could not be invaded by the monopartite form, while homogeneous contacts between hosts facilitate its spread.
+We conjecture that these features might have led to an increase in the diversity and prevalence of multipartite viral forms concomitantly with the expansion of agricultural practices.
+Despite high anti-HBV efficacies, while the nucleoside analogs (e.g., lamivudine) lead to the emergence of drug-resistance, interferons (e.g., IFN-α causes adverse side-effects.
+Hence, new antiviral strategies must focus not only on synthetic molecules but also on potential natural compounds.
+In this report, we have combined the in vitro cell culture and in silico molecular docking methods to assess the novel anti-HBV activity and delineate the inhibitory mechanism of selected plant-derived pure compounds of different classes.
+Of the tested (2.5-50 μg/ml) twelve non-cytotoxic compounds, ten (10 μg/ml) were found to maximally inhibit HBsAg production at day 5.
+Compared to quercetin (73%), baccatin III (71%), psoralen (67%), embelin (65%), menisdaurin (64%) and azadirachtin (62%) that showed high inhibition of HBeAg synthesis, lupeol (52%), rutin (47%), β-sitosterol (43%) and hesperidin (41%) had moderate efficacies against HBV replication.
+Further assessment of quercetin in combination with the highly active compounds, enhanced its anti-HBV activity up to 10%.
+Being the most important drug target, a 3-D structure of HBV polymerase (Pol/RT) was modeled and docked with the active compounds, including lamivudine as standard.
+Docking of lamivudine indicated strong interaction with the modeled HBV Pol active-site residues that formed stable complex (∆G = −5.2 kcal/mol).
+Similarly, all the docked antiviral compounds formed very stable complexes with HBV Pol (∆G = −6.1 to −9.3 kcal/mol).
+Taken together, our data suggest the anti-HBV potential of the tested natural compounds as novel viral Pol/RT inhibitors.
+Traumatic spinal cord injury (SCI) is a life changing neurological condition with substantial socioeconomic implications for patients and their care-givers.
+Recent advances in medical management of SCI has significantly improved diagnosis, stabilization, survival rate and well-being of SCI patients.
+However, there has been small progress on treatment options for improving the neurological outcomes of SCI patients.
+This incremental success mainly reflects the complexity of SCI pathophysiology and the diverse biochemical and physiological changes that occur in the injured spinal cord.
+Therefore, in the past few decades, considerable efforts have been made by SCI researchers to elucidate the pathophysiology of SCI and unravel the underlying cellular and molecular mechanisms of tissue degeneration and repair in the injured spinal cord.
+To this end, a number of preclinical animal and injury models have been developed to more closely recapitulate the primary and secondary injury processes of SCI.
+In this review, we will provide a comprehensive overview of the recent advances in our understanding of the pathophysiology of SCI.
+We will also discuss the neurological outcomes of human SCI and the available experimental model systems that have been employed to identify SCI mechanisms and develop therapeutic strategies for this condition.
+INTRODUCTION: With growing amounts of data available, identification of clusters of persons linked to each other by transmission of an infectious disease increasingly relies on automated algorithms.
+We propose cluster finding to be a two-step process: first, possible transmission clusters are identified using a cluster algorithm, second, the plausibility that the identified clusters represent genuine transmission clusters is evaluated.
+METHODS: We developed tools to visualise: (i) clusters found in dimensions of time, geographical location and genetic data; (ii) nested sub-clusters within identified clusters; (iii) intra-cluster pairwise dissimilarities per dimension; (iv) intra-cluster correlation between dimensions.
+We applied our tools to notified mumps cases in the Netherlands with available disease onset date (January 2009 – June 2016), geographical information (location of residence), and pathogen sequence data (n = 112).
+One was questionable because, in phylogenetic analysis, genetic sequences related to it segregated in two groups.
+One was implausible with no smaller nested clusters, high intra-cluster dissimilarities on all dimensions, and low intra-cluster correlation between dimensions.
+The NEWC reports concurred with our findings: the plausible/questionable clusters corresponded to reported outbreaks; the implausible cluster did not.
+CONCLUSION: Our tools for assessing automatically identified clusters allow outbreak investigators to rapidly spot plausible transmission clusters for mumps and other human-to-human transmissible diseases.
+Cyclophilin (Cyp), a peptidyl-prolyl cis-trans isomerase (PPIase), acts as a virulence factor in many bacteria including Staphylococcus aureus.
+To precisely determine the unfolding mechanism and the domain structure of Cyp, we have investigated a chimeric S. aureus Cyp (rCyp) using various probes.
+Our limited proteolysis and the consequent analysis of the proteolytic fragments indicate that rCyp is composed of one domain with a short flexible tail at the C-terminal end.
+We also show that the urea-induced unfolding of both rCyp and rCyp-CsA is completely reversible and proceeds via the synthesis of at least one stable intermediate.
+Both the secondary structure and the tertiary structure of each intermediate appears very similar to those of the corresponding native protein.
+The thermodynamic stability of rCyp was also significantly increased in the presence of CsA, recommending that this protein could be employed to screen new CsA derivatives in the future.
+EIT is a radiation-free functional modality that enables bedside imaging and monitoring of lung function and expansion.
+Clinical interest in this method has been driven by the need for bedside monitoring of the dynamics of the lungs and the effects of ventilatory manoeuvres, including changes in ventilator settings, suctioning, chest drains, positioning and physiotherapy.
+We aimed to describe the use of Electrical Impedance Tomography (EIT) as a clinical tool in a tertiary Paediatric Intensive Care unit.
+Children requiring intensive care with a variety of clinical conditions had an electrode belt with 16 electrodes wrapped around the chest, which sequentially applied a small alternating current from each electrode pair.
+With the correct application, and understanding of the monitor, much clinical information can be gained, with potentially significant patient benefit.
+We present the clinical use of EIT in six conditions: Asthma, Ventilation weaning and expansion recoil, Sequential Lobar Collapse, Targeted Physiotherapy, Pleural Effusion assessment, and PEEP optimisation.
+It allows monitoring of a patient’s respiratory function in ways which are not possible through any other means.
+An understanding of respiratory physiology will allow use of this information to improve patient outcomes.
+The goal of this review is to provide an overview on how microglia respond to bacterial pathogens targeting the brain, how the interplay between microglia and bacteria can be studied experimentally, and possible ways to use gained knowledge to identify novel preventive and therapeutic strategies.
+We discuss the dual role of microglia in disease development, the beneficial functions crucial for bacterial clearing, and the destructive properties through triggering neuroinflammation, characterized by cytokine and chemokine release which leads to leukocyte trafficking through the brain vascular endothelium and breakdown of the blood-brain barrier integrity.
+Due to intrinsic complexity of microglia and up until recently lack of specific markers, the study of microglial response to bacterial pathogens is challenging.
+Finally, we summarize recent findings where bacterial virulence factors are identified to be important for the microglial response, and how manipulation of evoked responses could be used for therapeutic or preventive purposes.
+Among promising approaches are: modulations of microglia phenotype switching toward anti-inflammatory and phagocytic functions, the use of non-bacterolytic antimicrobials, preventing release of bacterial components into the neural milieu and consequential amplification of immune activation, and protection of the blood-brain barrier integrity.
+Upon viral infection, the 2′, 5′-oligoadenylate synthetase (OAS)-ribonuclease L (RNaseL) system works to cleave viral RNA, thereby blocking viral replication.
+Here, we show that OAS1 and OAS3 act as negative regulators of the expression of chemokines and interferon-responsive genes in human macrophages.
+Clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein-9 nuclease (Cas9) technology was used to engineer human myeloid cell lines in which the OAS1 or OAS3 gene was deleted.
+Neither OAS1 nor OAS3 was exclusively responsible for the degradation of rRNA in macrophages stimulated with poly(I:C), a synthetic surrogate for viral double-stranded (ds)RNA.
+An mRNA sequencing analysis revealed that genes related to type I interferon signaling and chemokine activity were increased in OAS1(−/−) and OAS3(−/−) macrophages treated with intracellular poly(I:C).
+Indeed, retinoic-acid-inducible gene (RIG)-I- and interferon-induced helicase C domain-containing protein (IFIH1 or MDA5)-mediated induction of chemokines and interferon-stimulated genes was regulated by OAS3, but Toll-like receptor 3 (TLR3)- and TLR4-mediated induction of those genes was modulated by OAS1 in macrophages.
+However, stimulation of these cells with type I interferons had no effect on OAS1- or OAS3-mediated chemokine secretion.
+These data suggest that OAS1 and OAS3 negatively regulate the expression of chemokines and interferon-responsive genes in human macrophages.
+Forkhead box P (FoxP) proteins are members of the versatile Fox transcription factors, which control the timing and expression of multiple genes for eukaryotic cell homeostasis.
+Compared to other Fox proteins, they can form domain-swapped dimers through their DNA-binding –forkhead– domains, enabling spatial reorganization of distant chromosome elements by tethering two DNA molecules together.
+Experimental evidence suggests that the protonation state of a histidine residue conserved in all Fox proteins is responsible for pH-dependent modulation of these interactions.
+Here, we explore the consequences of the protonation state of another histidine (H59), only conserved within FoxM/O/P subfamilies, on folding and dimerization of the forkhead domain of human FoxP1.
+Dimer dissociation kinetics and equilibrium unfolding experiments demonstrate that protonation of H59 leads to destabilization of the domain-swapped dimer due to an increase in free energy difference between the monomeric and transition states.
+Furthermore, anisotropy measurements and molecular dynamics evidence that H59 has a direct impact in the local stability of helix H3.
+Altogether, our results highlight the relevance of H59 in domain swapping and folding stability of FoxP1.
+We previously reported that interleukin-1 receptor antagonist (IL-1Ra) was involved in PRRSV-induced immunosuppression during an early phase of infection.
+To explore the immunomodulatory properties of PRRSV-induced IL-1Ra on porcine immune functions, monocyte-derived dendritic cells (MoDC) and leukocytes were cultured with type 2 PRRSV, and the immunological role of IL-1Ra was assessed by addition of anti-porcine IL-1Ra Ab.
+The results demonstrated that PRRSV-induced IL-1Ra reduced phagocytosis, surface expression of MHC II (SLA-DR) and CD86, as well as downregulation of IFNA and IL1 gene expression in the MoDC culture system.
+Interestingly, IL-1Ra secreted by the PRRSV-infected MoDC also inhibited T lymphocyte differentiation and proliferation, but not IFN-γ production.
+Although PRRSV-induced IL-1Ra was not directly linked to IL-10 production, it contributed to the differentiation of regulatory T lymphocytes (Treg) within the culture system.
+Taken together, our results demonstrated that PRRSV-induced IL-1Ra downregulates innate immune functions, T lymphocyte differentiation and proliferation, and influences collectively with IL-10 in the Treg induction.
+The immunomodulatory roles of IL-1Ra elucidated in this study increase our understanding of the immunobiology of PRRSV.
+Since 2014, acute flaccid myelitis (AFM), a long-recognized condition associated with polioviruses, nonpolio enteroviruses, and various other viral and nonviral causes, has been reemerging globally in epidemic form.
+This unanticipated reemergence is ironic, given that polioviruses, once the major causes of AFM, are now at the very threshold of global eradication and cannot therefore explain any aspect of AFM reemergence.
+Instead, the new AFM epidemic has been temporally associated with reemergences of nonpolio enteroviruses such as EV-D68, until recently thought to be an obscure virus of extremely low endemicity.
+This perspective reviews the enigmatic epidemiologic, virologic, and diagnostic aspects of epidemic AFM reemergence; examines current options for clinical management; discusses future research needs; and suggests that the AFM epidemic offers important clues to mechanisms of viral disease emergence.
+BACKGROUND: A/H5N1 influenza viruses have high pandemic potential; consequently, vaccines need to be produced rapidly.
+MF59® adjuvant reduces the antigen required per dose, allowing for dose sparing and more rapid vaccine availability.
+METHODS: Two multicenter, phase II trials were conducted to evaluate the safety and immunogenicity of an MF59-adjuvanted, cell culture–derived, A/H5N1 vaccine (aH5N1c) among 979 adult (18–64 years old) and 1393 elderly (≥65 years old) subjects.
+Participants were equally randomized to receive 2 full-dose (7.5 μg of hemagglutinin antigen per dose) or 2 half-dose aH5N1c vaccinations 3 weeks apart.
+Outcomes were based on Center for Biologics Evaluation Research and Review (CBER) and Committee for Medicinal Products for Human Use (CHMP) licensure criteria (titers ≥1:40 and seroconversions on day 43).
+Solicited reaction frequencies tended to be higher in the full-dose group and were of mild to moderate intensity.
+CONCLUSIONS: In adult and elderly participants, the full-dose aH5N1c vaccine formulation was well tolerated and met US and European licensure criteria for pandemic vaccines.
+The first human Zika virus (ZIKV) outbreak was reported in Micronesia in 2007, followed by one in Brazil in 2015.
+In 2016, ZIKV transmission was also reported in the US and the World Health Organization declared it a Public Health Emergency of International Concern.
+Because various neurological conditions are associated with ZIKV, such as microcephaly, Guillain-Barré syndrome, and other disorders of both the central and peripheral nervous systems, including encephalopathy, (meningo)encephalitis and myelitis, and because of the lack of reliable patient diagnosis, numerous ongoing studies seek to understand molecular mechanisms underlying ZIKV pathogenesis.
+They control axonal guidance, synaptic signaling, neurotransmitter trafficking and maintenance of neurons, and are targeted by ZIKV.
+In this study, we used a newly developed multiplexed aptamer-based technique (SOMAScan) to examine > 1300 human astrocyte cell proteins.
+We identified almost 300 astrocyte proteins significantly dysregulated by ZIKV infection that span diverse functions and signaling pathways, including protein translation, synaptic control, cell migration and differentiation.
+Therefore, it is essential to develop better strategies to enhance vaccine design and predict parameters that identify susceptible humans.
+CD4 T cells are a central component of protective immunity to influenza, delivering direct effector function and potentiating responses of other lymphoid cells.
+Humans have highly diverse influenza-specific CD4 T-cell populations that vary in stimulation history, specificity, and functionality.
+These complexities constitute a formidable obstacle to predicting immune responses to pandemic strains of influenza and derivation of optimal vaccine strategies.
+We suggest that more precise efforts to identify and enumerate both the positive and negative contributors of immunity in the CD4 T-cell compartment will aid in both predicting susceptible hosts and in development of vaccination strategies that will poise most human subjects to respond to pandemic influenza strains with protective immune responses.
+In 1918–1919, pandemic influenza spread globally and caused an estimated 50–100 million deaths associated with unexpected clinical and epidemiological features.
+The descendants of the 1918 virus continue to circulate as annual epidemic viruses causing significant mortality each year.
+The 1918 influenza pandemic serves as a benchmark for the development of universal influenza vaccines.
+Challenges to producing a truly universal influenza vaccine include eliciting broad protection against antigenically different influenza viruses that can prevent or significantly downregulate viral replication and reduce morbidity by preventing development of viral and secondary bacterial pneumonia.
+Perhaps the most important goal of such vaccines is not to prevent influenza, but to prevent influenza deaths.
+In commemoration of the centennial of the 1918 influenza pandemic, the American Journal of Epidemiology has convened a collection of 12 articles that further illuminate the epidemiology of that pandemic and consider whether we would be more prepared if an equally deadly influenza virus were to emerge again.
+In the present commentary, we place these 12 articles in the context of a growing body of work on the archeo-epidemiology of past pandemics, the socioeconomic and geographic drivers of influenza mortality and natality impact, and renewed interest in immune imprinting mechanisms and the development of novel influenza vaccines.
+We also highlight persisting mysteries in the origins and severity of the 1918 pandemic and the need to preserve rapidly decaying information that may provide treasure troves for future generations.
+Although much progress has been made to uncover age-specific mortality patterns of the 1918 influenza pandemic in populations around the world, more studies in different populations are needed to make sense of the heterogeneous death impact of this pandemic.
+We assessed the absolute and relative magnitudes of 3 pandemic waves in the city of Madrid, Spain, between 1918 and 1920, on the basis of age-specific all-cause and respiratory excess death rates.
+Excess death rates were estimated using a Serfling model with a parametric bootstrapping approach to calibrate baseline death levels with quantified uncertainty.
+Excess all-cause and pneumonia and influenza mortality rates were estimated for different pandemic waves and age groups.
+The youngest and oldest persons experienced the highest excess mortality rates, and young adults faced the highest standardized mortality risk.
+Waves differed in strength; the peak standardized mortality risk occurred during the herald wave in spring 1918, but the highest excess rates occurred during the fall and winter of 1918/1919.
+Acquired immunity may have tempered a protracted fall wave, but recrudescent waves following the initial 2 outbreaks heightened the total pandemic mortality impact.
+It is, therefore, particularly important to develop a universal vaccine against conserved proteins or conserved regions of the virus.
+In this study, we used N-terminal extracellular region of the influenza virus M2 protein (M2e) as the target antigen and constructed two optimized M2e DNA vaccines (p-tPA-p3M2e and p-p3M2e) with increased antigenic epitope density and enhanced antigen secretion.
+These two vaccines also conferred protection against a lethal infection of homo-subtypic H1N1 virus, with p-tPA-p3M2e being the most effective.
+In addition, p-tPA-p3M2e also showed cross-protection against different subtypes of the influenza virus (H9N2, H6N6, and H10N8) at varying rates (80%, 40%, and 20%, respectively).
+After passive immunization, M2e DNA vaccine-induced antibodies in the sera provided complete protection against homologous virus challenge.
+An analysis of the mechanism underlying this immunization-mediated protection indicates that M2e-specific IgG and T-cell immune responses may play critical roles in the prevention of infection and viral clearance.
+Taken together, our results indicate that this optimized M2e DNA vaccine is a promising candidate for the development of a universal, broad-spectrum influenza virus vaccine.
+Disasters may have significant and lasting impacts on educational programs and academic achievement, yet the examination of differing patterns of school recovery after disasters is understudied.
+This paper focused on two aims: (i) identification of school academic recovery trajectories; and (ii) examination of potential risk factors associated with these trajectories.
+We used latent class growth analysis to identify school academic recovery trajectories for a cohort of 462 Texas public schools that were in the path of Hurricane Ike in 2008.
+Using Texas Assessment of Knowledge and Skills (TAKS) data from 2005 to 2011, we found that attendance and percent of economically disadvantaged youth emerged as significant risk factors for two identified academic recovery trajectories (High‐Stable and Low‐Interrupted).
+Higher levels of economically disadvantaged youth were associated with lower likelihood of falling in the High‐Stable trajectory, relative to the Low‐Interrupted trajectory.
+Higher levels of attendance were associated with higher likelihood of membership in the High‐Stable trajectory, relative to the Low‐Interrupted trajectory.
+These findings are consistent with the notion that disasters do not affect all people or communities equally.
+Findings highlight the need for policy initiatives that focus on low performing schools, as these schools are at highest risk for adverse outcomes post‐disaster.
+BACKGROUND: This study sought to analyze the cases of clinical misdiagnosis of scrub typhus complicated by hemophagocytic syndrome.
+METHODS: We retrospectively reviewed the medical records for diagnoses, clinical course, chest X-ray findings, laboratory data, and antibiotic therapy.
+They were diagnosed with septicemia and hemophagocytic syndrome, sepsis and hemophagocytic syndrome, severe infection, hepatitis and hemophagocytic syndrome, or upper respiratory tract infection.
+Among the nine patients, hepatic function examination showed decreased albumin and elevated C-reactive protein levels in all patients; alanine aminotransferase was increased and platelets were decreased in eight patients.
+Indirect immunofluorescence demonstrated positive IgM antibody and EB virus-IgM in all nine patients; Mycoplasma pneumoniae antibody was positive in seven patients.
+Patch shadow with increased density was found in seven patients, including four patients with right pleural effusion and two with bilateral pleural effusion.
+The nine misdiagnosed cases were given multiple broad-spectrum antibiotics either successively or concomitantly before and after admission, but no effective antibiotics against Orientis tsutsugamushi were applied.
+After diagnosis was corrected to scrub typhus, five patients were switched to chloramphenicol and dexamethasone, two patients were given azithromycin and dexamethasone, and two patients were treated with chloramphenicol.
+Body temperature returned to normal within 2–3 days and the children were quickly relieved from their condition.
+CONCLUSION: Hemophagocytic syndrome may be the presenting clinical feature of scrub typhus and initially mask the disease.
+The eschar is a useful diagnostic clue and febrile patients without any localizing signs should be thoroughly examined for its presence.
+In this research, we propose new CPU-based parallel implementations that can provide significant advantages in terms of execution times, monetary cost, and pervasiveness in finding LCS of DNA sequences in an environment where Graphics Processing Units are not available.
+For general purpose use, we also make the OpenMP-based tool publicly available to end users.
+RESULT: In this study, we develop three novel parallel versions of the LCS algorithm on: (i) distributed memory machine using message passing interface (MPI); (ii) shared memory machine using OpenMP, and (iii) hybrid platform that utilizes both distributed and shared memory using MPI-OpenMP.
+The experimental results with both simulated and real DNA sequence data show that the shared memory OpenMP implementation provides at least two-times absolute speedup than the best sequential version of the algorithm and a relative speedup of almost 7.
+We provide a detailed comparison of the execution times among the implementations on different platforms with different versions of the algorithm.
+We also show that removing branch conditions negatively affects the performance of the CPU-based parallel algorithm on OpenMP platform.
+These molecules are involved in innate immune responses by recognizing microbial moieties and damaged tissues, activating complement, exerting opsonic activity and facilitating phagocytosis, and regulating inflammation.
+The long pentraxin PTX3 is a prototypic humoral pattern recognition molecule that, in addition to providing defense against infectious agents, plays several functions in tissue repair and regulation of cancer-related inflammation.
+Characterization of the PTX3 molecular structure and biochemical properties, and insights into its interactome and multiple roles in tissue damage and remodeling support the view that microbial and matrix recognition are evolutionarily conserved functions of humoral innate immunity molecules.
+BACKGROUND: In the past few years, significant progress has been made in inhibiting neovascularization at the tumor site, cutting off the nutrient supply of the tumor, and inhibiting tumor growth and metastasis.
+However, many proteins/peptides have the disadvantage of poor stability, short half-life, and uncertain targeting ability.
+Chemical modification can be used to overcome these disadvantages; many polyethylene glycol-modified proteins/peptides have been approved by US FDA.
+The purpose of this study was to obtain a novel anti-angiogenic chondroitin sulfate (CS)-peptide nanoparticle conjugate with efficient anti-neovascularization and tumor targeting ability and an acceptable half-life.
+MATERIALS AND METHODS: The CS-ES2-AF nanoparticle conjugate was synthesized and characterized using (1)H-nuclear magnetic resonance spectroscopy, transmission electron microscopy, and particle size and zeta potential analyzer.
+The anti-angiogenic ability was studied using MTT, migration, tube formation, and chick chorioallantoic membrane assays.
+RESULTS: The CS-ES2-AF could self-assemble into stable nanoparticles in aqueous solution, which significantly enhances its anti-neovascularization activity, tumor targeting more explicit, and prolongs its half-life.
+CONCLUSION: CS is an effective protein/peptide modifier, and CS-ES2-AF displayed good potential in tumor targeting therapy.
+The Center for Disease Control and Prevention has issued guidelines reminding healthcare workers about the importance of taking steps to prevent the spread of Zika virus, how to test and isolate patients suspected of carrying the Zika virus, and how to protect themselves from infection.
+Therefore, it is of utmost importance for healthcare professionals to be fully aware of Zika virus preparedness, and response measures should an outbreak occur in Malaysia in order to quickly and efficiently contain the outbreak, ensure the safety of individual or healthcare personnel safety, as well as to prevent further spreading of the disease.
+This research aims to show how prepared Malaysian healthcare professionals are against Zika virus and how well can they respond during an outbreak.
+In total, 504 healthcare professionals (128 general practitioners, 215 community pharmacists, 161 nurses) from private health clinics were the target population of the four states of Malaysia where Zika cases suspected.
+The sample size of each category was calculated by using a formula for estimating the population proportion.
+An additional 10% of the calculated sample size was added to compensate the non-response rate.
+The Center For Disease Control and Prevention and World Health Organisation provided a checklist to assess how prepared healthcare professionals are for an Zika outbreak.
+This checklist was modified to a questionnaire in order to assess health care professionals’ preparedness and response to the Zika outbreak.
+Community pharmacists are still lacking in their preparedness and perceived response to the Zika outbreak compared to the general practitioners in the private sector.
+Hence community pharmacists should attend training given by the Ministry of Health Malaysia as a continuing education, which may help them to respond during a Zika outbreak.
+Nipah Virus (NiV) is a re-emerging zoonotic pathogen in the genus Henipavirus of the Paramyxoviridae family of viruses.
+NiV is endemic to Bangladesh and Malaysia and is highly fatal to both livestock and humans (human case fatality rate = 74.5%).
+The goal of this study was to use a recombinant RABV vector expressing NiV glycoprotein (NiV G) to develop a bivalent candidate vaccine against NiV disease and rabies virus (RABV) disease, which is also a significant health burden in the regions where NiV is endemic.
+The rabies vector is a well-established vaccine strain that lacks neurovirulence and can stably expresses foreign antigens that are immunogenic in various animal models.
+Mice inoculated intranasally with the live recombinant RABV/NiV vaccine (NIPARAB) showed no signs of disease.
+To test the immunogenicity of the vaccine candidate, groups of C57BL/6 mice were immunized intramuscularly with a single dose of live vaccine particles or two doses of chemically inactivated viral particles.
+Both vaccination groups showed NiV G-specific seroconversion, and the inactivated (INAC) vaccine group yielded higher titers of NiV G-specific antibodies.
+Furthermore, cross-reactivity of NiV G-specific immune sera against Hendra virus (HeV), was confirmed by immunofluorescence (IF) and indirect ELISA against soluble recombinant HeV glycoprotein (HeV G).
+These results indicate that NIPARAB may be used as a killed virus vaccine to protect humans against NiV and RABV, and possibly as a preventative measure against HeV as well.
+Mallard ducks are important natural hosts of low pathogenic avian influenza (LPAI) viruses and many strains circulate in this reservoir and cause little harm.
+Some strains can be transmitted to other hosts, including chickens, and cause respiratory and systemic disease.
+Rarely, these highly pathogenic avian influenza (HPAI) viruses cause disease in mallards, while chickens are highly susceptible.
+The long co-evolution of mallard ducks with influenza viruses has undoubtedly fine-tuned many immunological host–pathogen interactions to confer resistance to disease, which are poorly understood.
+Here, we compare innate responses to different avian influenza viruses in ducks and chickens to reveal differences that point to potential mechanisms of disease resistance.
+Mallard ducks are permissive to LPAI replication in their intestinal tissues without overtly compromising their fitness.
+In contrast, the mallard response to HPAI infection reflects an immediate and robust induction of type I interferon and antiviral interferon stimulated genes, highlighting the importance of the RIG-I pathway.
+Ducks also appear to limit the duration of the response, particularly of pro-inflammatory cytokine expression.
+Chickens lack RIG-I, and some modulators of the signaling pathway and may be compromised in initiating an early interferon response, allowing more viral replication and consequent damage.
+We review current knowledge about innate response mediators to influenza infection in mallard ducks compared to chickens to gain insight into protective immune responses, and open questions for future research.
+Respiratory syncytial virus (RSV) is one of the leading causes of lower respiratory tract infection in infants.
+Immunoprophylaxis with the anti-RSV monoclonal antibody, palivizumab, reduces the risk for RSV-related hospitalizations, but its use is restricted to high-risk infants due to the high costs.
+In this study, we investigated if genetic delivery of anti-RSV antibody to neonatal mice by chimpanzee adenovirus type 7 expressing the murine form of palivizumab (AdC7αRSV) can provide protection against RSV.
+Intranasal and intramuscular administration of AdC7αRSV to adult mice resulted in similar levels of anti-RSV IgG in the serum.
+However, only intranasal administration resulted in detectable levels of anti-RSV IgG in the bronchoalveolar lavage fluid.
+Expression of the anti-RSV antibody was prolonged following intranasal administration of AdC7αRSV to neonatal mice.
+These data suggest that neonatal genetic delivery of anti-RSV antibody by AdC7αRSV can provide protection against RSV.
+Rhinoviruses (RVs) are classified into three species: RV-A, B, and C. Unlike RV-A and -B, RV-C cannot be propagated using standard cell culture systems.
+In order to isolate RV-Cs from clinical specimens and gain a better understanding of their biological properties and pathogenesis, we established air–liquid-interface (ALI) culture methods using HBEC3-KT and HSAEC1-KT immortalized human airway epithelial cells.
+Two fully sequenced clinical RV-C isolates, RV-C9 and -C53, were propagated in HBEC3-ALI cultures, and increases in viral RNA ranging from 1.71 log(10) to 7.06 log(10) copies were observed.
+Using the HBEC3-ALI culture system, 11 clinical strains of RV-C were isolated from 23 clinical specimens, and of them, nine were passaged and re-propagated.
+The 11 clinical isolates were classified as RV-C2, -C6, -C9, -C12, -C18, -C23, -C40, and -C53 types according to their VP1 sequences.
+Our stable HBEC3-ALI culture system is the first cultivable cell model that supports the growth of multiple RV-C virus types from clinical specimens.
+Thus, the HBEC3-ALI culture system provides a cheap and easy-to-use alternative to existing cell models for isolating and investigating RV-Cs.
+The packaging of genomic RNA in positive-sense single-stranded RNA viruses is a key part of the viral infectious cycle, yet this step is not fully understood.
+The specificity of RNA packaging depends on multiple factors: (i) one or more packaging signals, (ii) RNA replication, (iii) translation, (iv) viral factories, and (v) the physical properties of the RNA.
+The relative contribution of each of these factors to packaging specificity is different for every virus.
+In vitro and in vivo data show that there are different packaging mechanisms that control selective packaging of the genomic RNA during nucleocapsid assembly.
+The goals of this article are to explain some of the key experiments that support the contribution of these factors to packaging selectivity and to draw a general scenario that could help us move towards a better understanding of this step of the viral infectious cycle.
+Ebola Virus Disease (EVD) is one of the most lethal transmissible infections, characterized by a high fatality rate, and caused by a member of the Filoviridae family.
+The recent large outbreak of EVD in Western Africa (2013–2016) highlighted the worldwide threat represented by the disease and its impact on global public health and the economy.
+The development of highly needed anti-Ebola virus antivirals has been so far hampered by the shortage of tools to study their life cycle in vitro, allowing to screen for potential active compounds outside a biosafety level-4 (BSL-4) containment.
+Importantly, the development of surrogate models to study Ebola virus entry in a BSL-2 setting, such as viral pseudotypes and Ebola virus-like particles, tremendously boosted both our knowledge of the viral life cycle and the identification of promising antiviral compounds interfering with viral entry.
+In this context, the combination of such surrogate systems with large-scale small molecule compounds and haploid genetic screenings, as well as rational drug design and drug repurposing approaches will prove priceless in our quest for the development of a treatment for EVD.
+LASV causes severe hemorrhagic fever with high mortality in humans, whereas no case of MOPV infection has been reported.
+Comparing MOPV and LASV is a powerful strategy to unravel pathogenic mechanisms that occur during the course of pathogenic arenavirus infection.
+We used a yeast two-hybrid approach to identify cell partners of MOPV and LASV Z matrix protein in which two autophagy adaptors were identified, NDP52 and TAX1BP1.
+Autophagy has emerged as an important cellular defense mechanism against viral infections but its role during arenavirus infection has not been shown.
+Here, we demonstrate that autophagy is transiently induced by MOPV, but not LASV, in infected cells two days after infection.
+Impairment of the early steps of autophagy significantly decreased the production of MOPV and LASV infectious particles, whereas a blockade of the degradative steps impaired only MOPV infectious particle production.
+Our study provides insights into the role played by autophagy during MOPV and LASV infection and suggests that this process could partially explain their different pathogenicity.
+BACKGROUND: Porcine epidemic diarrhea virus (PEDV) is a major etiological agent of porcine epidemic diarrhea around the world.
+Point-of-care testing in the field is lacking owing to the requirement for a simple, robust field applicable test that does not require professional laboratory equipment.
+The aim of this study was to establish a novel reverse transcription polymerase spiral reaction (RT-PSR) assay for the rapid detection of porcine epidemic diarrhea virus (PEDV).
+For the assay, a specific RT-PSR primer pair was designed against a conserved region in PEDV ORF3.
+RESULTS: The RT-PSR was optimized, and PEDV could be detected after a 50 min incubation at 62 °C, in addition to the 15 min required for reverse transcription.
+This new method for PEDV detection was 10 times more sensitive than the conventional reverse transcription-polymerase chain reaction (RT-PCR) assay.
+The positive rates for 65 clinical samples using the new RT-PSR assay and the conventional RT-PCR assay were 58.46% (38/65) and 53.84% (35/65), respectively.
+In the RT-PSR assay, the addition of a mixture of dyes allowed a positive reaction to be directly observed by the naked eye.
+CONCLUSIONS: These results indicate that this RT-PSR assay is capable of accurately detecting PEDV, and has the advantages of high specificity and sensitivity for the detection of PEDV.
+Fetal airway smooth muscle (ASM) exhibits phasic contractile behavior, which transitions to a more sustained “tonic” contraction after birth.
+The timing and underlying mechanisms of ASM transition from a phasic to a tonic contractile phenotype are yet to be established.
+We characterized phasic ASM contraction in preterm (128 day gestation), term (∼150 day gestation), 1–4 month, 1 yr, and adult sheep (5yr).
+The mechanism of phasic ASM contraction was investigated further with a computational model of ASM force development and lumen narrowing.
+The computational model comprised a two-dimensional cylindrical geometry of a network of contractile units and the activation of neighboring cells was dependent on the strength of coupling between cells.
+As expected, phasic contractions were most prominent in fetal airways and decreased with advancing age, to a level similar to the level in the 1–4 month lambs.
+Computational predictions demonstrated phasic contraction through the generation of a wave of activation events, the magnitude of which is determined by the number of active cells and the strength of cell–cell interactions.
+Results show that phasic activity is suppressed rapidly after birth, then sustained at a lower intensity from the preweaning phase until adulthood in an ovine developmental model.
+Cell–cell coupling is proposed as a key determinant of phasic ASM contraction and if reduced could explain the observed maturational changes.
+While some PIDs can manifest with more than one phenotype, signs, and symptoms of various PIDs overlap considerably.
+Recently, novel defects in immune-related genes and additional variants in previously reported genes responsible for PIDs have been successfully identified by Next Generation Sequencing (NGS), allowing the recognition of a broad spectrum of disorders.
+Objective: To evaluate the strength and weakness of targeted NGS sequencing using custom-made Ion Torrent and Haloplex (Agilent) panels for diagnostics and research purposes.
+Methods: Five different panels including known and candidate genes were used to screen 105 patients with distinct PID features divided in three main PID categories: T cell defects, Humoral defects and Other PIDs.
+Among these, 18 selected patients without a molecular diagnosis and 32 additional patients were analyzed by Haloplex enrichment technology.
+Results: The complementary use of the two custom-made targeted sequencing approaches allowed the identification of causative variants in 28.6% (n = 30) of patients.
+Ion Torrent method was highly successful for those cases with well-defined phenotypes for immunological and clinical presentation.
+The Haloplex approach was able to diagnose 4 SCID/CID patients and 4 additional patients with complex and extended phenotypes, embracing all three PID categories in which this approach was more efficient.
+Conclusions: NGS technology represents a powerful approach in the complex field of rare disorders but its different application should be weighted.
+A relatively small NGS target panel can be successfully applied for a robust diagnostic suspicion, while when the spectrum of clinical phenotypes overlaps more than one PID an in-depth NGS analysis is required, including also whole exome/genome sequencing to identify the causative gene.
+Modern pharmacological studies and clinical practices indicate that AR possesses various biological functions, including potent immunomodulation, antioxidant, anti-inflammation and antitumor activities.
+Among them, isoflavonoids, saponins and polysaccharides are the three main types of beneficial compounds responsible for its pharmacological activities and therapeutic efficacy.
+After ingestion of AR, the metabolism and biotransformation of the bioactive compounds were extensive in vivo.
+The isoflavonoids and saponins and their metabolites are the major type of constituents absorbed in plasma.
+The bioavailability barrier (BB), which is mainly composed of efflux transporters and conjugating enzymes, is expected to have a significant impact on the bioavailability of AR.
+Additionally, the use of AR as a personalized medicine based on the BB is also discussed, which may provide beneficial information to achieve a better and more accurate therapeutic response of AR in clinical practice.
+Ecklonia cava is edible seaweed that is found in Asian countries, such as Japan and Korea; and, its major components include fucoidan and phlorotannins.
+Phlorotannins that are isolated from E. cava are well-known to have an antioxidant effect and strong antiviral activity against porcine epidemic diarrhea virus (PEDV), which has a high mortality rate in piglets.
+In this study, the bioactive components were determined based on two different approaches: (i) bio-guided isolation using the antiviral activity against the H1N1 viral strain, which is a representative influenza virus that originates from swine and (ii) high-resolution mass spectrometry-based dereplication, including relative mass defects (RMDs) and HPLC-qTOFMS fragmentation analysis.
+The EC70 fraction showed the strongest antiviral activity and contained thirteen phlorotannins, which were predicted by dereplication.
+The structures of these two isolated compounds were elucidated using NMR techniques and HPLC-qTOFMS fragmentation analysis.
+In addition, molecular modelling was applied to determine the absolute configurations of the two new compounds.
+The antiviral activities of seven major phlorotannins in active fraction were evaluated against two influenza A viral strains (H1N1 and H9N2).
+Six of the compounds showed moderate to strong effects on both of the viruses and phlorofucofuroeckol A (12), which showed an EC(50) value of 13.48 ± 1.93 μM, is a potential active antiviral component of E. cava.
+Infants with CFTR mutations show a peribronchial neutrophil infiltration prior to the establishment of infection in their lung.
+Infectious and inflammatory response leads to an increase in mucus viscosity and mucus plugging of small and medium-size bronchioles.
+Perpetual infection and airway inflammation destroy the lungs, which leads to increased morbidity and eventual mortality in most of the patients with CF.
+Studies have now established that neutrophil cytotoxins, extracellular DNA, and neutrophil extracellular traps (NETs) are associated with increased mucus clogging and lung injury in CF.
+In addition to opportunistic pathogens, various aspects of the CF airway milieux (e.g., airway pH, salt concentration, and neutrophil phenotypes) influence the NETotic capacity of neutrophils.
+CF airway milieu may promote the survival of neutrophils and eventual pro-inflammatory aberrant NETosis, rather than the anti-inflammatory apoptotic death in these cells.
+Degrading NETs helps to manage CF airway disease; since DNAse treatment release cytotoxins from the NETs, further improvements are needed to degrade NETs with maximal positive effects.
+Neutrophil-T cell interactions may be important in regulating viral infection-mediated pulmonary exacerbations in patients with bacterial infections.
+Therefore, clarifying the role of neutrophils and NETs in CF lung disease and identifying therapies that preserve the positive effects of neutrophils, while reducing the detrimental effects of NETs and cytotoxic components, are essential in achieving innovative therapeutic advances.
+Traumatic temporomandibular joint ankylosis (TMJA) is a common disease and disorder of the temporomandibular joint (TMJ); however, its pathogenesis has yet to be completely elucidated.
+In the authors' previous studies, the lateral pterygoid muscle (LPM) was confirmed to exert a function in distraction osteogenesis (DO) during the healing of a condylar fracture, which resulted in the formation of excess bone.
+The aim of the present study was to investigate alterations in the expression of any associated genes via an Affymetrix GeneChip method.
+The traumatic TMJA model was fabricated by a condylar fracture in the TMJ area of sheep with either a dissected LPM (LPD) or normal (LPN).
+At 4- and 12 weeks post-surgery, the condylar zone was isolated to perform the gene chip analysis, which was performed according to a standard Affymetrix protocol.
+The gene chip analysis indicated that the LPN gene expression pattern was similar compared with the DO process, while LPD was similar to that of normal bone fracture healing.
+The validated genes were collagen type II α1 chain, C-type lectin domain family 3 member A, interleukin 1A, cartilage oligomeric matrix protein, chondromodulin (LECT1), calcitonin receptor (CALCR), transforming growth factor (TGF)-β1, Fos proto-oncogene (FOS), bone γ-carboxyglutamate protein and bone morphogenic protein (BMP)7, among which, BMP7, LECT1, CALCR and FOS were confirmed by RT-qPCR.
+In conclusion, the present study demonstrated that LPM exerts a DO effect during the pathogenesis of traumatic TMJA, which may provide a novel target for preventing TMJA.
+Several self-report measures of conspiracist beliefs have been developed in Western populations, but examination of their psychometric properties outside Europe and North America is limited.
+This study aimed to examine the psychometric properties of three widely-used measures of conspiracist beliefs in Iran.
+We translated the Belief in Conspiracy Theory Inventory (BCTI), Conspiracy Mentality Questionnaire (CMQ), and Generic Conspiracist Belief Scale (GCBS) into Persian.
+Factorial validity was examined using principal-axis factor analysis in a community sample from Tehran, Iran (N = 544).
+Further, the relationships between scores on these measures and hypothesized antecedents (i.e., education, schizotypal personality, information processing style, superstitious beliefs, religiosity, and political orientation) were examined.
+Overall, we failed to find support for the parent factor structures of two of the three scales (BCTI and GCBS) and evidence of construct validity for all three scales was limited.
+These results highlight the necessity of further psychometric work on existing measures of conspiracy theories in diverse culturo-linguistic groups and the development of context-specific measures of conspiracist beliefs.
+Infectious disease nucleic acid amplification technologies (NAAT) have superior sensitivity, specificity, and rapid time to result compared to traditional microbiological methods.
+Recovery of concentrated, high quality pathogen nucleic acid (NA) from complex specimen matrices is required for optimal performance of several NA amplification/detection technologies such as polymerase chain reaction (PCR).
+Fully integrated NAAT platforms that enable rapid sample-to-result workflows with minimal user input are generally restricted to larger reference lab settings, and their complexity and cost are prohibitive to widespread implementation in resource limited settings (RLS).
+Identification of component technologies for incorporation of reliable and affordable sample preparation with pathogen NA amplification/detection into an integrated platform suitable for RLS, is a necessary first step toward achieving the overarching goal of reducing infectious disease-associated morbidity and mortality globally.
+In the current study, we evaluate the performance of six novel NA extraction technologies from different developers using blinded panels of stool, sputum and blood spiked with variable amounts of quality-controlled DNA- and/or RNA-based microbes.
+The extraction efficiencies were semi-quantitatively assessed using validated real-time reverse transcription (RT)-PCR assays specific for each microbe and comparing target-specific RT-PCR results to those obtained with reference NA extraction methods.
+Sample input and output volumes, total processing time, user-required manual steps and cost estimates were also examined for suitability in RLS.
+Together with the performance analysis, these metrics were used to select the more suitable candidate technologies for further optimization of integrated NA amplification and detection technologies for RLS.
+As an attractive alternative to plasmid DNA, messenger RNA (mRNA) has recently emerged as a promising class of nucleic acid therapeutics for biomedical applications.
+Advances in addressing the inherent shortcomings of mRNA and in the development of nanoparticle-based delivery systems have prompted the development and clinical translation of mRNA-based medicines.
+In this review, we discuss the chemical modification strategies of mRNA to improve its stability, minimize immune responses, and enhance translational efficacy.
+Considerable attention is given to the increasingly widespread applications of mRNA nanomedicine in the biomedical fields of vaccination, protein-replacement therapy, gene editing, and cellular reprogramming and engineering.
+Respiratory infections are common precursors to asthma exacerbations in children, but molecular immune responses that determine whether and how an infection causes an exacerbation are poorly understood.
+By using systems-scale network analysis, we identify repertoires of cellular transcriptional pathways that lead to and underlie distinct patterns of asthma exacerbation.
+Specifically, in both virus-associated and nonviral exacerbations, we demonstrate a set of core exacerbation modules, among which epithelial-associated SMAD3 signaling is upregulated and lymphocyte response pathways are downregulated early in exacerbation, followed by later upregulation of effector pathways including epidermal growth factor receptor signaling, extracellular matrix production, mucus hypersecretion, and eosinophil activation.
+We show an additional set of multiple inflammatory cell pathways involved in virus-associated exacerbations, in contrast to squamous cell pathways associated with nonviral exacerbations.
+Our work introduces an in vivo molecular platform to investigate, in a clinical setting, both the mechanisms of disease pathogenesis and therapeutic targets to modify exacerbations.
+Despite causing pandemics and yearly epidemics that result in significant morbidity and mortality, our arsenal of options to treat influenza A virus (IAV) infections remains limited and is challenged by the virus itself.
+While vaccination is the preferred intervention strategy against influenza, its efficacy is reduced in the elderly and infants who are most susceptible to severe and/or fatal infections.
+Similarly, effectiveness of currently used antiviral drugs is jeopardized by the development of resistance to these drugs.
+Like many viruses, IAV is reliant on host factors and signaling-pathways for its replication, which could potentially offer alternative options to treat infections.
+While host-factors have long been recognized as attractive therapeutic candidates against other viruses, only recently they have been targeted for development as IAV antivirals.
+Future strategies to combat IAV infections will most likely include approaches that alter host-virus interactions on the one hand or dampen harmful host immune responses on the other, with the use of biological response modifiers (BRMs).
+In principle, BRMs are biologically active agents including antibodies, small peptides, and/or other (small) molecules that can influence the immune response.
+Repurposing such agents would allow for accelerated use against severe and potentially fatal IAV infections.
+In this review, we will address the potential therapeutic use of different BRM classes to modulate the immune response induced after IAV infections.
+Viruses in the family Papillomaviridae have circular dsDNA genomes of approximately 5.7–8.6 kb that are packaged within non-enveloped, icosahedral capsids.
+The known papillomavirus (PV) representatives infect vertebrates, and there are currently more than 130 recognized PV species in more than 50 genera.
+We identified 12 novel avian papillomavirus (APV) types in wild birds that could represent five distinct species and two genera.
+Viruses were detected in paired oropharyngeal/cloacal swabs collected from six bird species, increasing the number of avian species known to harbor PVs by 40%.
+A new duck PV (DuPV-3) was found in mallard and American black duck (27.6% estimated prevalence) that was monophyletic with other known DuPVs.
+A single viral type was identified in Atlantic puffin (PuPV-1, 9.8% estimated prevalence), while a higher genetic diversity was found in other Charadriiformes.
+Specifically, three types [gull PV-1 (GuPV-1), -2, and -3] were identified in two gull species (estimated prevalence of 17% and 2.6% in American herring and great black-backed gull, respectively), and seven types [kittiwake PV-1 (KiPV-1) through -7] were found in black-legged kittiwake (81.3% estimated prevalence).
+Significantly higher DuPV-3 circulation was observed in spring compared to fall and in adults compared to juveniles.
+The studied host species’ tendencies to be in crowded environments likely affect infection rates and their migratory behaviors could explain the high viral diversity, illustrating how host behavior can influence viral ecology and distribution.
+For DuPV-3, GuPV-1, PuPV-1, and KiPV-2, we obtained the complete genomic sequences, which showed the same organization as other known APVs.
+Phylogenetic analyses showed evidence for virus–host co-divergence at the host taxonomic levels of family, order, and inter-order, but we also observed that host-specificity constraints are relaxed among highly related hosts as we found cross-species transmission within ducks and within gulls.
+Furthermore, the phylogeny of viruses infecting the Charadriiformes did not match the host phylogeny and gull viruses formed distinct monophyletic clades with kittiwake viruses, possibly reflecting past host-switching events.
+Considering the vast PV genotype diversity in other hosts and the large number of bird species, many more APVs likely remain to be discovered.
+OBJECTIVES: Glucose-6-phosphate dehydrogenase (G6PD) deficiency, theoretically, renders red blood cells (RBC) susceptible to oxidative stress.
+G6PD deficiency has also been found in other types of cells than RBC, such as leukocytes and myocytes, where an inefficient protection against oxidative stress may occur too.
+Glutathione (GSH), a significant antioxidant molecule, levels are lower in G6PD individuals, and theoretically, the probability of oxidative stress and haemolysis due to exercise in individuals with G6PD deficiency is increased, whereas dietary supplementation with antioxidants may have beneficial effects on various aspects of this enzymopathy.
+METHODS: A search of the available literature was conducted using the keywords glucose-6-phosphate dehydrogenase (G6PD), deficiency, disease, exercise, muscle, antioxidant, vitamin, supplement, and supplementation.
+The search was limited to publications in English, conducted on humans, and published until August 2018.
+RESULTS: There is little evidence indicating that G6PD deficiency can cause perturbations in redox status, haemolysis, and clinical symptoms such as fatigability and myoglobinuria, especially after intense exercise, compared to individuals with normal enzyme levels.
+CONCLUSIONS: Exercise could be used by G6PD-deficient individuals as a tool to improve their quality of life.
+However, there is a lack of training studies, and assessment of the effects of regular and systematic exercise in G6PD-deficient individuals is warranted.
+Finally, since GSH levels are lower in G6PD deficiency, it would be interesting to examine the effects of antioxidant or cysteine donor supplements on redox status after exercise in these individuals.
+Glioblastoma multiforme is one of the most invasive type of glial tumors, which rapidly grows and commonly spreads into nearby brain tissue.
+It is a devastating brain cancer that often results in death within approximately 12 to 15 months after diagnosis.
+In this work, optimal control theory was applied to regulate intracellular signaling pathways of miR-451–AMPK–mTOR–cell cycle dynamics via glucose and drug intravenous administration infusions.
+A potential drug blocking the inhibitory pathway of mTOR by AMPK complex is incorporated to explore regulation of the down-stream pathway to the cell cycle.
+Both miR-451 and mTOR levels are up-regulated inducing cell proliferation and reducing invasion in the neighboring tissues.
+Concomitant and alternating glucose and drug infusions are explored under various circumstances to predict best clinical outcomes with least administration costs.
+We investigate chloroplast DNA variation in a hyperdiverse community of tropical rainforest trees in French Guiana, focusing on patterns of intraspecific and interspecific variation.
+We test whether a species genetic diversity is higher when it has congeners in the community with which it can exchange genes and if shared haplotypes are more frequent in genetically diverse species, as expected in the presence of introgression.
+We sampled a total of 1,681 individual trees from 472 species corresponding to 198 genera and sequenced them at a noncoding chloroplast DNA fragment.
+Polymorphism was more frequent in species that have congeneric species in the study site than in those without congeners (30% vs. 12%).
+Moreover, more chloroplast haplotypes were shared with congeners in polymorphic species than in monomorphic ones (44% vs. 28%).
+Despite large heterogeneities caused by genus‐specific behaviors in patterns of hybridization, these results suggest that the higher polymorphism in the presence of congeners is caused by local introgression rather than by incomplete lineage sorting.
+Our findings suggest that introgression has the potential to drive intraspecific genetic diversity in species‐rich tropical forests.
+Human Respiratory Syncytial Virus (RSV) is the primary cause of bronchopneumonia in infants and children worldwide.
+Clinical studies have shown that early treatments of RSV patients with ribavirin improve prognosis, even if the use of this drug is limited due to myelosuppression and toxicity effects.
+Thus, the development of highly effective and specific antiviral drugs for pre-exposure prophylaxis and/or treatment of RSV infections is a compelling need.
+In the quest of new RSV inhibitors, in this work we evaluated the antiviral activity of a series of variously substituted 5,6-dichloro-1-phenyl-1(2)H-benzo[d][1,2,3]triazole derivatives in cell-based assays.
+Several 1- and 2-phenyl-benzotriazoles resulted fairly potent (μM concentrations) inhibitors of RSV infection in plaque reduction assays, accompanied by low cytotoxicity in human highly dividing T lymphoid-derived cells and primary cell lines.
+Contextually, no inhibitory effects were observed against other RNA or DNA viruses assayed, suggesting specific activity against RSV.
+Further results revealed that the lead compound 10d was active during the early phase of the RSV infection cycle.
+To understand whether 10d interfered with virus attachment to target cells or virus-cell fusion events, inhibitory activity tests against the RSV mutant strain B1 cp-52—expressing only the F envelope glycoprotein—and a plasmid-based reporter assay that quantifies the bioactivity of viral entry were also performed.
+The overall biological results, in conjunction with in silico modeling studies, supported the conclusion that the RSV fusion process could be the target of this new series of compounds.
+METHODS: We retrospectively reviewed the medical records of patients aged less than 15 years with laboratory-confirmed RSV infections and seizures between January 2011 and December 2016 in a regional hospital in South Korea.
+Of these, 35 (35 of 1,193, 2.93%; boys, 19; girls, 16; mean age: 20.8±16.6 months) presented with seizure.
+Febrile seizure was the most common diagnosis (27 of 35, 77.1%); simple febrile seizures in 13 patients (13 of 27, 48.1%) and complex febrile seizures in 14 (14 of 27, 51.9%).
+Afebrile seizures without meningitis or encephalopathy were observed in 5 patients (5 of 35, 14.3%), seizures with meningitis in 2 (2 of 35, 5.7%), and seizure with encephalopathy in 1 (1 of 35, 2.9%) patient.
+In a patient with encephalopathy, brain diffusion-weighted magnetic resonance imaging revealed transient changes in white matter, suggesting cytotoxic edema as the mechanism underlying encephalopathy.
+Most patients recovered with general management, and progression to epilepsy was noted in only 1 patient.
+CONCLUSION: Although febrile seizures are the most common type of seizure associated with RSV infection, the proportion of patients with complex febrile seizures was higher than that of those with general febrile seizures.
+Human metapneumovirus (HMPV) has been a notable etiological agent of acute respiratory infection in humans, but it was not discovered until 2001, because HMPV replicates only in a limited number of cell lines and the cytopathic effect (CPE) is often mild.
+To promote the study of HMPV, several groups have generated green fluorescent protein (GFP)-expressing recombinant HMPV strains (HMPV(GFP)).
+However, the growing evidence has complicated the understanding of cell line specificity of HMPV, because it seems to vary notably among HMPV strains.
+In addition, unique A2b clade HMPV strains with a 180-nucleotide duplication in the G gene (HMPV A2b(180nt-dup) strains) have recently been detected.
+In this study, we re-evaluated and compared the cell line specificity of clinical isolates of HMPV strains, including the novel HMPV A2b(180nt-dup) strains, and six recombinant HMPV(GFP) strains, including the newly generated recombinant HMPV A2b(180nt-dup) strain, MG0256-EGFP.
+Our data demonstrate that VeroE6 and LLC-MK2 cells generally showed the highest infectivity with any clinical isolates and recombinant HMPV(GFP) strains.
+Other human-derived cell lines (BEAS-2B, A549, HEK293, MNT-1, and HeLa cells) showed certain levels of infectivity with HMPV, but these were significantly lower than those of VeroE6 and LLC-MK2 cells.
+The variations were not directly related to HMPV genotypes, cell lines used for isolation and propagation, specific genome mutations, or nucleotide duplications in the G gene.
+In Europe, members of the genus Culex are often the most abundant insects on cave walls.
+Culex pipiens L., the common house mosquito, exists in two physically very similar, yet genetically and ecologically distinct biotypes (or forms, ‘f.’), namely Cx.
+Autogeny and stenogamy of the latter form have been interpreted as adaptations to underground habitats.
+The epigean occurrence of the two biotypes and their hybrids was recently examined in Eastern Austria, but the hypogean distribution of the Cx.
+Considering the key role of Culex mosquitoes in the epidemiology of certain zoonotic pathogens, the general paucity of data on species composition and relative abundance in subterranean shelters appears unfortunate.
+For a first pertinent investigation in Austria, we collected mosquitoes in four eastern federal states.
+Based on analyses of the ACE2 gene and the CQ11 microsatellite locus, 150 female and three male mosquitoes of the genus Culex, two females of the genus Culiseta and a single female of the genus Anopheles were determined to species level or below.
+territans, two species rarely collected in Austria, lead us to infer that underground habitats host a higher diversity of culicine mosquitoes than previously thought.
+Protein kinase R (PKR) plays a major role in activating host immunity during infection by sensing double-stranded RNA (dsRNA) produced by viruses.
+Once activated by dsRNA, PKR phosphorylates the translation factor eukaryotic initiation factor 2α (eIF2α), halting cellular translation.
+Many viruses have methods of inhibiting PKR activation or its downstream effects, circumventing protein synthesis shutdown.
+Here we describe our finding that in multiple cell types, PKR was depleted during mouse adenovirus type 1 (MAV-1) infection.
+MAV-1 did not appear to be targeting PKR at the transcriptional or translational level, because total PKR mRNA levels and levels of PKR mRNA bound to polysomes were unchanged or increased during MAV-1 infection.
+However, inhibiting the proteasome reduced the PKR depletion seen in MAV-1-infected cells, whereas inhibiting the lysosome had no effect.
+Infecting cells with UV-inactivated virus prevented PKR degradation, whereas inhibiting viral DNA replication did not.
+Degradation of PKR is a rare mechanism to oppose PKR activity, and it has been described in only six RNA viruses.
+To our knowledge, this is the first example of a DNA virus counteracting PKR by degrading it.
+Plasmid DNA (pDNA) gene delivery is a highly versatile technology that has the potential to address a multitude of unmet medical needs.
+Advances in pDNA delivery to host tissue with the employment of in vivo electroporation (EP) have led to significantly enhanced gene expression and the recent demonstration of clinical efficacy with the platform.
+Building upon this platform, this study reports that enzyme-mediated modification of the muscle tissue extracellular matrix structure at the site of pDNA delivery operates in a synergistic manner with EP to enhance both local and systemic gene expression further.
+Specifically, administration of chondroitinase ABC (Cho ABC) to the site of intramuscular delivery of pDNA led to transient disruption of chondroitin sulfate scaffolding barrier, permitting enhanced gene distribution and expression across the tissue.
+The employment of Cho ABC in combination with CELLECTRA(®) intramuscular EP resulted in increased gene expression by 5.5-fold in mice and 17.98-fold in rabbits.
+The study demonstrates how this protocol can be universally applied to an active prophylaxis platform to increase the in vivo production of functional immunoglobulin G, and to DNA vaccine protocols to permit drug dose sparing.
+The data indicate the Cho ABC formulation to be of significant value upon combination with EP to drive enhanced gene expression levels in pDNA delivery protocols.
+Quinones are secondary metabolites of higher plants associated with many biological activities, including antiviral effects and cytotoxicity.
+In this study, the anti-herpetic and anti-dengue evaluation of 27 terpenyl-1,4-naphthoquinone (NQ), 1,4-anthraquinone (AQ) and heterocycle-fused quinone (HetQ) derivatives was done in vitro against Human Herpesvirus (HHV) type 1 and 2, and Dengue virus serotype 2 (DENV-2).
+Using plaque forming unit assays, cell viability assays and molecular docking, we found that NQ 4 was the best antiviral compound, while AQ 11 was the most active and selective molecule on the tested tumor cells.
+NQ 4 showed a fair antiviral activity against Herpesviruses (EC(50): <0.4 µg/mL, <1.28 µM) and DENV-2 (1.6 µg/mL, 5.1 µM) on pre-infective stages.
+Additionally, NQ 4 disrupted the viral attachment of HHV-1 to Vero cells (EC(50): 0.12 µg/mL, 0.38 µM) with a very high selectivity index (SI = 1728).
+The in silico analysis predicted that this quinone could bind to the prefusion form of the E glycoprotein of DENV-2.
+These findings demonstrate that NQ 4 is a potent and highly selective antiviral compound, while suggesting its ability to prevent Herpes and Dengue infections.
+Additionally, AQ 11 can be considered of interest as a leader for the design of new anticancer agents.
+Social media has been used as data resource in a growing number of health-related research.
+The objectives of this study were to identify content volume and sentiment polarity of social media records relevant to healthcare services in China.
+A list of the key words of healthcare services were used to extract data from WeChat and Qzone, between June 2017 and September 2017.
+The data were put into a corpus, where content analyses were performed using Tencent natural language processing (NLP).
+Records on patient safety were the most frequently mentioned topic (approximately 8.73 million, 30.1% of the corpus), with the contents on humanistic care having received the least social media references (0.43 Million, 1.5%).
+The doctor-patient relationship category had the highest proportion of negative contents (74.9%), followed by service efficiency (59.5%), and nursing service (53.0%).
+Neutral disposition was found to be the highest (30.4%) in the contents on appointment-booking services.
+This study added evidence to the magnitude and direction of public perceptions on healthcare services in China’s hospital and pointed to the possibility of monitoring healthcare service improvement, using readily available data in social media.
+The eIF4F complex is a translation initiation factor that closely regulates translation in response to a multitude of environmental conditions including viral infection.
+In this study, the knockdown of the components of the eIF4F complex using shRNA and CRISPR/Cas9 were performed, respectively.
+We have demonstrated that loss-of-function of the three components of eIF4F, including eIF4A, eIF4E and eIF4G, remarkably promotes the levels of rotavirus genomic RNA and viral protein VP4.
+Consistently, knockdown of the negative regulator of eIF4F and programmed cell death protein 4 (PDCD4) inhibits the expression of viral mRNA and the VP4 protein.
+Mechanically, we confirmed that the silence of the eIF4F complex suppressed the protein level of IRF1 and IRF7 that exert potent antiviral effects against rotavirus infection.
+Thus, these results demonstrate that the eIF4F complex is an essential host factor restricting rotavirus replication, revealing new targets for the development of new antiviral strategies against rotavirus infection.
+The present study investigated the expression of type I interferon (IFN-I) pathway members in CDV-induced cerebellar lesions to gain an insight into their role in lesion development.
+Gene expression of 110 manually selected genes in acute, subacute and chronic lesions was analyzed using pre-existing microarray data.
+Interferon regulatory factor (IRF) 3, IRF7, signal transducer and activator of transcription (STAT) 1, STAT2, MX protein, protein kinase R (PKR), 2′-5′-oligoadenylate synthetase (OAS) 1 and interferon-stimulated gene (ISG) 15 expression were also evaluated using immunohistochemistry.
+CDV infection caused an increased expression of the antiviral effector proteins MX, PKR, OAS1 and ISG15, which probably contributed to a restricted viral replication, particularly in neurons and oligodendrocytes.
+This increase might be partly mediated by IRF-dependent pathways due to the lack of changes in IFN-I levels and absence of STAT2 in astrocytes.
+Nevertheless, activated microglia/macrophages showed a strong expression of STAT1, STAT2 and MX proteins in later stages of the disease, indicating a strong activation of the IFN-I signaling cascade, which might be involved in the aggravation of bystander demyelination.
+With improvements in personnel and vehicular body armor, robust casualty evacuation capabilities, and damage control resuscitation strategies, more combat casualties are surviving to reach higher levels of care throughout the casualty evacuation system.
+As such, medical centers are becoming more accustomed to managing the deleterious late consequences of combat trauma related to the dysregulation of the immune system.
+In this review, we aim to highlight these late consequences and identify areas for future research and therapeutic strategies.
+Trauma leads to the dysregulation of both the innate and adaptive immune responses, which places the injured at risk for several late consequences, including delayed wound healing, late onset sepsis and infection, multi-organ dysfunction syndrome, and acute respiratory distress syndrome, which are significant for their association with the increased morbidity and mortality of wounded personnel.
+The mechanisms by which these consequences develop are complex but include an imbalance of the immune system leading to robust inflammatory responses, triggered by the presence of damage-associated molecules and other immune-modifying agents following trauma.
+Treatment strategies to improve outcomes have been difficult to develop as the immunophenotype of injured personnel following trauma is variable, fluid and difficult to determine.
+As more information regarding the triggers that lead to immune dysfunction following trauma is elucidated, it may be possible to identify the immunophenotype of injured personnel and provide targeted treatments to reduce the late consequences of trauma, which are known to lead to significant morbidity and mortality.
+It is very important to explore novel biomarkers to better clarify the characteristics of TNBC.
+It has been reported that polymorphisms in claudin 1 (CLDN1) are associated with risk of several cancers.
+Patients and methods: Between January 2004 and December 2013, 267 patients with stage I–III primary TNBC were included in our study.
+We investigated the association between polymorphisms in CLDN1 gene and clinicopathological characteristics or survival of these patients.
+Results: We found that rs10513846 GA genotype was associated with older age [P=0.013, hazard ratios (HR) = 2.231, 95% confidence interval (CI): 1.186–4.195].
+Rs10513846 AA genotype carriers were more likely to develop grade 3 tumors (P=0.005, HR = 2.889, 95% CI: 1.389–6.007).
+And rs9283658 genotypes were also related to grade, more patients with grade 3 tumors were rs9283658 CC genotype carriers (P=0.023, HR = 0.446, 95% CI: 0.222–0.894).
+After multivariate analysis, tumor size (P=0.021, HR = 3.146, 95% CI: 1.185–8.354) and lymph node status (P<0.001, HR = 10.930, 95% CI: 3.276–36.470) were demonstrated to be independent prognostic factors.
+Conclusion: We first demonstrated that polymorphisms in CLDN1 gene were associated with age and differentiation of TNBC patients.
+In 2016 and 2017, there were earthquakes greater than 5.0 in magnitude on the Korean Peninsula, which has previously been considered an earthquake-free zone.
+Patients with chronic kidney disease are particularly vulnerable to earthquakes, as the term “renal disaster” suggests.
+In the event of a major earthquake, patients on hemodialysis face the risk of losing maintenance dialysis due to infrastructure disruption.
+In this review, we share the experience of an earthquake in Pohang that posed a serious risk to patients on hemodialysis.
+We review the disaster response system in Japan and propose a disaster preparedness plan with respect to hemodialysis.
+Korean nephrologists and staff in dialysis facilities should be trained in emergency response to mitigate risk from natural disasters.
+Dialysis staff should be familiar with the action plan for natural disaster events that disrupt hemodialysis, such as outages and water treatment system failures caused by earthquakes.
+In the event of a disaster situation that results in dialysis failure, patients need to know what to do.
+At the local and national government level, long-term preparations should be made to handle renal disaster and patient safety logistics.
+Moreover, Korean nephrologists should also be prepared to manage cardiovascular disease and diabetes in disaster situations.
+Further evaluation and management of social and national disaster preparedness of hemodialysis units to earthquakes in Korea are needed.
+Mycetoma is a neglected tropical disease, endemic in many tropical and subtropical regions, characterised by massive deformity and disability and can be fatal if untreated early and appropriately.
+Interleukins (IL) -35 and IL-37 are newly discovered cytokines that play an important role in suppressing the immune system.
+However, the expression of these interleukins in patients with Madurella mycetomatis (M. mycetomatis) induced eumycetoma has not yet been explored.
+The aim of this study is to determine the levels of IL-1 family (IL-1β, IL-37) and IL-12 family (IL-12, IL-35) in a group of these patients and the association between these cytokines levels and the patients’ demographic characteristics.
+The present, case-control study was conducted at the Mycetoma Research Centre, Soba University Hospital, University of Khartoum, Sudan and it included 140 individuals.
+They were divided into two groups; group I: healthy controls [n = 70; median age 25 years (range 12 to 70 years)].
+Group II: mycetoma patients [n = 70 patients; median age 25 (range 13 to 70 years)].
+There was a significant negative correlation between IL-1β and IL-12 levels and lesion size and disease duration, while IL-37 and IL-35 levels were significantly positively correlated with both lesion size and disease duration.
+The analysis of the risk factors of higher circulatory levels of IL-37 in patients of mycetoma showed a negative significant association with IL-1β cytokine, where a unit increment in IL-1β will decrease the levels of IL-37 by 35.28 pg/ml.
+The levels of IL-37 among the patients with a duration of mycetoma infection ≤ 1 year were significantly low by an average of 18.45 pg/ml compared to patients with a mycetoma infection’s duration of ≥ 5years (reference group).
+Furthermore, the risk factors of higher levels of IL-35 in mycetoma patients revealed a negative significant association with IL-12, as a unit increment in IL-12 decreases the levels of IL-35 by 8.99 pg/ml (p < 0.001).
+Levels of IL-35 among the patients with duration of mycetoma infection ≤ one year were significantly low on average by 41.82 pg/ml (p value = 0.002) compared to patients with a duration of mycetoma infection ≥ 5 years (reference group).
+In conclusion, this study indicates that both IL-35 and IL-37 are negatively associated with the levels of IL-1β and IL-12 in eumycetoma mycetoma infection; and high levels of IL-37 and IL-35 may have a negative impact on disease progression.
+Bovine viral diarrhea (BVD) is a chronic disease of cattle caused by infection with BVD virus (BVDV) and can result in economic losses within the livestock industry.
+In Japan, the test and culling policy is a basic control measure, and implementation of an adequate vaccination program is recommended as a national policy.
+In addition, optional control measures, including compulsory testing of introduced animals and bulk tank milk (BTM) testing as a mass screening method, are used in several provinces, but their efficacy has not been completely assessed.
+We evaluated these control measures using the scenario tree model of BVD in Japan, developed in the previous study.
+The model outputs indicated that compulsory testing of all introduced cattle, rather than only heifers and/or non-vaccinated cattle, was cost effective and reduced the risk of BVDV introduction due to animal movement and that BTM testing could effectively monitor most part of the cattle population.
+Vaccination coverage and BVDV prevalence among introduced cattle could also affect the cost effectiveness of compulsory testing of targeted cattle, particularly under low vaccination coverage or high BVDV prevalence.
+However, even with the implementation of a highly effective monitoring scheme for many years, BVD risk could not be eliminated; it instead converged at a very low level (0.02%).
+Disease models with a cost-effective output could be a powerful tool in developing a control scheme for chronic animal diseases, including BVD, with the consent of relevant stakeholders.
+Marine viruses impact global biogeochemical cycles via their influence on host community structure and function, yet our understanding of viral ecology is constrained by limitations in host culturing and a lack of reference genomes and ‘universal’ gene markers to facilitate community surveys.
+Short-read viral metagenomic studies have provided clues to viral function and first estimates of global viral gene abundance and distribution, but their assemblies are confounded by populations with high levels of strain evenness and nucleotide diversity (microdiversity), limiting assembly of some of the most abundant viruses on Earth.
+Such features also challenge assembly across genomic islands containing niche-defining genes that drive ecological speciation.
+These populations and features may be successfully captured by single-virus genomics and fosmid-based approaches, at least in abundant taxa, but at considerable cost and technical expertise.
+Here we established a low-cost, low-input, high throughput alternative sequencing and informatics workflow to improve viral metagenomic assemblies using short-read and long-read technology.
+The ‘VirION’ (Viral, long-read metagenomics via MinION sequencing) approach was first validated using mock communities where it was found to be as relatively quantitative as short-read methods and provided significant improvements in recovery of viral genomes.
+We then then applied VirION to the first metagenome from a natural viral community from the Western English Channel.
+In comparison to a short-read only approach, VirION: (i) increased number and completeness of assembled viral genomes; (ii) captured abundant, highly microdiverse virus populations, and (iii) captured more and longer genomic islands.
+Together, these findings suggest that VirION provides a high throughput and cost-effective alternative to fosmid and single-virus genomic approaches to more comprehensively explore viral communities in nature.
+Tangminling pill, consisting of ten Chinese herbal medications, is usually prescribed for T2DM in mainland China.
+Four studies comparing Tangminling vs. placebo treatment in T2DM patients were included and 767 T2DM patients were enrolled in our analyses.
+Tangminling pill might reduce glucose level and body weight and improve β-cell function in T2DM patients.
+With the exception of Reston and Bombali viruses, the marburgviruses and ebolaviruses (family Filoviridae) cause outbreaks of viral hemorrhagic fever in sub-Saharan Africa.
+The Egyptian rousette bat (ERB) is a natural reservoir host for the marburgviruses and evidence suggests that bats are also natural reservoirs for the ebolaviruses.
+Although the search for the natural reservoirs of the ebolaviruses has largely involved serosurveillance of the bat population, there are no validated serological assays to screen bat sera for ebolavirus-specific IgG antibodies.
+Here, we generate filovirus-specific antisera by prime-boost immunization of groups of captive ERBs with all seven known culturable filoviruses.
+After validating a system of filovirus-specific indirect ELISAs utilizing infectious-based virus antigens for detection of virus-specific IgG antibodies from bat sera, we assess the level of serological cross-reactivity between the virus-specific antisera and heterologous filovirus antigens.
+This data is then used to generate a filovirus antibody fingerprint that can predict which of the filovirus species in the system is most antigenically similar to the species responsible for past infection.
+Our filovirus IgG indirect ELISA system will be a critical tool for identifying bat species with high ebolavirus seroprevalence rates to target for longitudinal studies aimed at establishing natural reservoir host-ebolavirus relationships.
+We tested for pollination syndromes in Merianieae (Melastomataceae), which contain bee‐ (buzz‐), hummingbird‐, flowerpiercer‐, passerine‐, bat‐ and rodent‐pollinated species.
+Further, we explored trait changes correlated with the repeated shifts away from buzz‐pollination, which represents an ‘adaptive plateau’ in Melastomataceae.
+We used random forest analyses to identify key traits associated with the different pollinators of 19 Merianieae species and estimated the pollination syndromes of 42 more species.
+We identified three pollination syndromes (‘buzz‐bee’, ‘mixed‐vertebrate’ and ‘passerine’), characterized by different pollen expulsion mechanisms and reward types, but not by traditional syndrome characters.
+Contrary to syndrome theory, our study supports the pooling of different pollinators (hummingbirds, bats, rodents and flowerpiercers) into the ‘mixed‐vertebrate’ syndrome, and we found that disparity was highest in the ‘buzz‐bee’ syndrome.
+We conclude that the highly adaptive buzz‐pollination system may have prevented shifts towards classical pollination syndromes, but provided the starting point for the evolution of a novel set of distinct syndromes, all having retained multifunctional stamens that provide pollen expulsion, reward and attraction.
+Bats are the second most diverse mammalian group, playing keystone roles in ecosystems but also act as reservoir hosts for numerous pathogens.
+Due to their colonial habits which implies close contacts between individuals, bats are often parasitized by multiple species of micro- and macroparasites.
+The particular ecology, behavior, and environment of bat species may shape patterns of intra- and interspecific pathogen transmission, as well as the presence of specific vectorial organisms.
+This review synthetizes information on a multi-level parasitic system: bats, bat flies and their microparasites.
+Bat flies (Diptera: Nycteribiidae and Streblidae) are obligate, hematophagous ectoparasites of bats consisting of ~500 described species.
+Diverse parasitic organisms have been detected in bat flies including bacteria, blood parasites, fungi, and viruses, which suggest their vectorial potential.
+We discuss the ecological epidemiology of microparasites, their potential physiological effects on both bats and bat flies, and potential research perspectives in the domain of bat pathogens.
+For simplicity, we use the term microparasite throughout this review, yet it remains unclear whether some bacteria are parasites or symbionts of their bat fly hosts.
+Antibiotics are losing their effectiveness due to the emerging infectious diseases, the scarcity of novel antibiotics, and the contributions of antibiotic misuse and overuse to resistance.
+Characterization of the lipidomic response to pneumonia and exploring the “lipidomic phenotype” can provide new insight into the underlying mechanisms of pathogenesis and potential avenues for diagnostic and therapeutic treatments.
+METHODS: Lipid profiles of bronchoalveolar lavage fluid (BALF) samples were generated through untargeted lipidomic profiling analysis using high-performance liquid chromatography with mass spectrometry (HPLC-MS).
+RESULTS: PCA showed that BALF lipidomes differed significantly between CAP (n = 52) and controls (n = 68, including 35 healthy volunteers and 33 patients with non-infectious lung diseases); while no clear separation was found between severe CAP and non-severe CAP cases.
+Clustering analysis revealed three separate lipid profiles; subjects in each cluster exhibited significant differences in disease severity, incidence of hypoxemia, percentages of phagocytes in BALF, and serum concentrations of albumin and total cholesterol (all p < 0.05).
+In addition, SM (d34:1) was negatively related to macrophage (adjusted r = − 0.462, p < 0.0001) and PE (18:1p/20:4) was positively correlated with polymorphonuclear neutrophil (PMN) percentages of BALF (adjusted r = 0.541, p < 0.0001).
+CONCLUSIONS: Our data suggest that specific lower airway lipid composition is related to different intensities of host inflammatory responses, and may contribute to functionally relevant shifts in disease pathogenesis in CAP individuals.
+These findings argue for the need to tailor therapy based on specific lipid profiles and related inflammatory status.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12931-019-1028-8) contains supplementary material, which is available to authorized users.
+In 2012, the genome of a novel rhabdovirus, Bas-Congo virus (BASV), was discovered in the acute-phase serum of a Congolese patient with presumed viral hemorrhagic fever.
+In the absence of a replicating virus isolate, fulfilling Koch’s postulates to determine whether BASV is indeed a human virus and/or pathogen has been impossible.
+However, experiments with vesiculoviral particles pseudotyped with Bas-Congo glycoprotein suggested that BASV particles can enter cells from multiple animals, including humans.
+In 2015, genomes of two related viruses, Ekpoma virus 1 (EKV-1) and Ekpoma virus 2 (EKV-2), were detected in human sera in Nigeria.
+Phylogenetic analyses led to the classification of BASV, EKV-1, and EKV-2 in the same genus, Tibrovirus, together with five biting midge-borne rhabdoviruses [i.e., Beatrice Hill virus (BHV), Bivens Arm virus (BAV), Coastal Plains virus (CPV), Sweetwater Branch virus (SWBV), and Tibrogargan virus (TIBV)] not known to infect humans.
+Using individual recombinant vesiculoviruses expressing the glycoproteins of all eight known tibroviruses and more than 75 cell lines representing different animal species, we demonstrate that the glycoproteins of all tibroviruses can mediate vesiculovirus particle entry into human, bat, nonhuman primate, cotton rat, boa constrictor, and Asian tiger mosquito cells.
+Using four of five isolated authentic tibroviruses (i.e., BAV, CPV, SWBV, and TIBV), our experiments indicate that many cell types may be partially resistant to tibrovirus replication after virion cell entry.
+Consequently, experimental data solely obtained from experiments using tibrovirus surrogate systems (e.g., vesiculoviral pseudotypes, recombinant vesiculoviruses) cannot be used to predict whether BASV, or any other tibrovirus, infects humans.
+BACKGROUND: Human metapneumovirus (hMPV) is a Paramyxovirus known to cause acute respiratory tract infections in children and young adults.
+To date, there is no study from the Aseer region of Saudi Arabia determining the proportion and severity of hMPV infection among pediatric hospitalized patients with respiratory infections.
+OBJECTIVES: The objective of this study is to determine the presence of hMPV antigens in the nasopharyngeal secretions of pediatric patients hospitalized with respiratory tract infections in the Aseer region of Saudi Arabia.
+MATERIALS AND METHODS: This prospective, serological hospital-based study included all pediatric patients who were admitted to Aseer Central Hospital, Abha, Saudi Arabia, from July 2016 to November 2017 with upper and/or lower respiratory tract infections.
+Direct fluorescent antibody assay was used to detect the presence of hMPV antigens in the obtained nasopharyngeal secretion specimens.
+RESULTS: During the study, 91 pediatric patients were hospitalized due to upper and/or lower respiratory tract infections, of which 9.9% were positive for hMPV.
+These patients were aged 9 months to 16 years, were from Abha city or its surrounding localities and were mostly (77.8%) hospitalized during autumn or winter.
+The most common diagnosis on admission was bronchopneumonia (55.5%) and aspiration pneumonia (22.2%), and some patients also had underlying chronic conditions such as chronic heart disease (22.2%) and bronchial asthma (11.1%).
+CONCLUSIONS: The results obtained indicated that hMPV is a potential etiologic factor for the commonly occurring acute respiratory infections in hospitalized children from the Aseer region of Saudi Arabia.
+hMPV infection was also found to be associated with complicated respiratory conditions such as bronchopneumonia, chronic heart disease and bronchial asthma.
+Defective viral genomes of the copy-back type (cbDVGs) are the primary initiators of the antiviral immune response during infection with respiratory syncytial virus (RSV) both in vitro and in vivo.
+However, the mechanism governing cbDVG generation remains unknown, thereby limiting our ability to manipulate cbDVG content in order to modulate the host response to infection.
+Here we report a specific genomic signal that mediates the generation of a subset of RSV cbDVG species.
+Using a customized bioinformatics tool, we identified regions in the RSV genome frequently used to generate cbDVGs during infection.
+We then created a minigenome system to validate the function of one of these sequences and to determine if specific nucleotides were essential for cbDVG generation at that position.
+Further, we created a recombinant virus unable to produce a subset of cbDVGs due to mutations introduced in this sequence.
+The identified sequence was also found as a site for cbDVG generation during natural RSV infections, and common cbDVGs originated at this sequence were found among samples from various infected patients.
+These data demonstrate that sequences encoded in the viral genome determine the location of cbDVG formation and, therefore, the generation of cbDVGs is not a stochastic process.
+It is considered the most common zoonosis in the world and is usually transmitted by urine of rodents and dogs with an incubation time of 7–14 days.
+CASE PRESENTATION: Here, we report the case of a German patient with acute pancreatitis associated with Leptospira interrogans causing fulminant septic shock.
+The patient was successfully treated with intravenous antibiotics and left the hospital fully recovered after 18 days.
+CONCLUSIONS: To our knowledge, this is the first case of leptospirosis with acute pancreatitis as the leading clinical manifestation in Central Europe.
+Serologic and molecular genetic tests for leptospirosis should be considered, if no other causes for pancreatitis can be identified.
+Background: The Ebola epidemic in West Africa caused global fear and stirred up worldwide preparedness activities in countries sharing borders with those affected, and in geographically far-away countries such as Iceland.
+Objective: To describe and analyse Ebola preparedness activities within the Icelandic healthcare system, and to explore the perspectives and experiences of managers and frontline health workers.
+Methods: A qualitative case study, based on semi-structured interviews with 21 staff members in the national Ebola Treatment Team, Emergency Room at Landspitali University Hospital, and managers of the response team.
+Results: Contextual factors such as culture and demography influenced preparedness, and contributed to the positive state of mind of participants, and ingenuity in using available resources for preparedness.
+While participants believed they were ready to take on the task of Ebola, they also had doubts about the chances of Ebola ever reaching Iceland.
+Yet, factors such as fear of Ebola and the perceived stigma associated with caring for a potentially infected Ebola patient, influenced the preparation process and resulted in plans for specific precautions by staff to secure the safety of their families.
+There were also concerns about the teamwork and lack of commitment by some during training.
+Being a ‘tiny’ nation was seen as both an asset and a weakness in the preparation process.
+Honest information sharing and scenario-based training contributed to increased confidence amongst participants in the response plans.
+Conclusions: Communication and training were important for preparedness of health staff in Iceland, in order to receive, admit, and treat a patient suspected of having Ebola, while doubts prevailed on staff capacity to properly do so.
+For optimal preparedness, likely scenarios for future global security health threats need to be repeatedly enacted, and areas plagued by poverty and fragile healthcare systems require global support.
+Stroke attracts neutrophils to the injured brain tissue where they can damage the integrity of the blood–brain barrier and exacerbate the lesion.
+However, the mechanisms involved in neutrophil transmigration, location and accumulation in the ischemic brain are not fully elucidated.
+Neutrophils can reach the perivascular spaces of brain vessels after crossing the endothelial cell layer and endothelial basal lamina of post-capillary venules, or migrating from the leptomeninges following pial vessel extravasation and/or a suggested translocation from the skull bone marrow.
+Based on previous observations of microglia phagocytosing neutrophils recruited to the ischemic brain lesion, we hypothesized that microglial cells might control neutrophil accumulation in the injured brain.
+We studied a model of permanent occlusion of the middle cerebral artery in mice, including microglia- and neutrophil-reporter mice.
+Using various in vitro and in vivo strategies to impair microglial function or to eliminate microglia by targeting colony stimulating factor 1 receptor (CSF1R), this study demonstrates that microglial phagocytosis of neutrophils has fundamental consequences for the ischemic tissue.
+We found that reactive microglia engulf neutrophils at the periphery of the ischemic lesion, whereas local microglial cell loss and dystrophy occurring in the ischemic core are associated with the accumulation of neutrophils first in perivascular spaces and later in the parenchyma.
+Accordingly, microglia depletion by long-term treatment with a CSF1R inhibitor increased the numbers of neutrophils and enlarged the ischemic lesion.
+Hence, microglial phagocytic function sets a critical line of defense against the vascular and tissue damaging capacity of neutrophils in brain ischemia.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00401-018-1954-4) contains supplementary material, which is available to authorized users.
+During human immunodeficiency virus (HIV) infection, type I interferon (IFN-I) signaling induces an antiviral state that includes the production of restriction factors that inhibit virus replication, thereby limiting the infection.
+As seen in other viral infections, type I IFN can also increase systemic immune activation which, in HIV disease, is one of the strongest predictors of disease progression to acquired immune deficiency syndrome (AIDS) and non-AIDS morbidity and mortality.
+Moreover, IFN-I is associated with CD4 T cell depletion and attenuation of antigen-specific T cell responses.
+Therefore, therapeutic manipulation of IFN-I signaling to improve HIV disease outcome is a source of much interest and debate in the field.
+Recent studies have highlighted the importance of timing (acute vs. chronic infection) and have suggested that specific targeting of type I IFNs and their subtypes may help harness the beneficial roles of the IFN-I system while avoiding its deleterious activities.
+Infection of cattle by bovine herpesvirus 1 (BoHV-1) can culminate in upper respiratory tract disorders, conjunctivitis, or genital disorders.
+BoHV-1 is the number one infectious agent in cattle that is associated with abortions in cattle.
+Stressful stimuli, mimicked by the synthetic corticosteroid dexamethasone, consistently induce reactivation from latency in latently infected calves and rabbits.
+Increased corticosteroid levels due to stress have a two-pronged effect on reactivation from latency by: (1) directly stimulating viral gene expression and replication, and (2) impairing antiviral immune responses, thus enhancing virus spread and transmission.
+BoHV-1 encodes several proteins, bICP0, bICP27, gG, UL49.5, and VP8, which interfere with key antiviral innate immune responses in the absence of other viral genes.
+Furthermore, the ability of BoHV-1 to infect lymphocytes and induce apoptosis, in particular CD4+ T cells, has negative impacts on immune responses during acute infection.
+BoHV-1 induced immune-suppression can initiate the poly-microbial disorder known as bovine respiratory disease complex, which costs the US cattle industry more than one billion dollars annually.
+Furthermore, interfering with antiviral responses may promote viral spread to ovaries and the developing fetus, thus enhancing reproductive issues associated with BoHV-1 infection of cows or pregnant cows.
+The focus of this review is to describe the known mechanisms, direct and indirect, by which BoHV-1 interferes with antiviral immune responses during the course of infection.
+In this study, we hypothesized that diffusion of inhaled anesthetics from airway lumen to smooth muscle would yield significant bronchodilation in vivo, and systemic recirculation would not be necessary to reduce lung resistance (R(L)) and elastance (E(L)) during sustained bronchoconstriction.
+To test this hypothesis, we designed a delivery system for precise timing of inhaled volatile anesthetics during the course of a positive pressure breath.
+We compared changes in R(L), E(L), and anatomic dead space (V(D)) in canines (N = 5) during pharmacologically induced bronchoconstriction with intravenous methacholine, and following treatments with: (1) targeted anesthetic delivery to V(D) and (2) continuous anesthetic delivery throughout inspiration.
+Compared to continuous delivery, targeted delivery resulted in significantly lower doses of delivered anesthetic and decreased end-expiratory concentrations.
+However, we did not detect significant reductions in R(L) or E(L) for either anesthetic delivery regimen.
+This lack of response may have resulted from an insufficient dose of the anesthetic to cause bronchodilation, or from the preferential distribution of air flow with inhaled anesthetic delivery to less constricted, unobstructed regions of the lung, thereby enhancing airway heterogeneity and increasing apparent R(L) and E(L).
+Influenza A virus (IAV) enters cells by binding to sialic acid on the cell surface.
+To accomplish this while avoiding immobilization by sialic acid in host mucus, viruses rely on a balance between the receptor-binding protein hemagglutinin (HA) and the receptor-cleaving protein neuraminidase (NA).
+Although genetic aspects of this balance are well-characterized, little is known about how the spatial organization of these proteins in the viral envelope may contribute.
+Using site-specific fluorescent labeling and super-resolution microscopy, we show that HA and NA are asymmetrically distributed on the surface of filamentous viruses, creating a spatial organization of binding and cleaving activities that causes viruses to step consistently away from their NA-rich pole.
+This Brownian ratchet-like diffusion produces persistent directional mobility that resolves the virus’s conflicting needs to both penetrate mucus and stably attach to the underlying cells, potentially contributing to the prevalence of the filamentous phenotype in clinical isolates of IAV.
+Background: Bioaerosols are a major concern for public health and sampling for exposure assessment purposes is challenging.
+This study aimed to evaluate the correlation between nasopharyngeal bacterial flora of swine workers and the swine barns bioaerosol biodiversity.
+Methods: Air samples from eight swine barns as well as nasopharyngeal swabs from pig workers (n = 25) and from a non-exposed control group (n = 29) were sequenced using 16S rRNA gene high-throughput sequencing.
+Wastewater treatment plants were used as the industrial, low-dust, non-agricultural environment control to validate the microbial link between the bioaerosol content (air) and the nasopharynxes of workers.
+Results: A multivariate analysis showed air samples and nasopharyngeal flora of pig workers cluster together, compared to the non-exposed control group.
+Unlike the farm environment, nasopharynx samples from wastewater workers did not cluster with air samples from wastewater treatment plants.
+The difference in the microbial community of nasopharynx of swine workers and a control group suggest that swine workers are carriers of germs found in bioaerosols.
+Conclusion: Nasopharynx sampling and microbiota could be used as a proxy of air sampling for exposure assessment studies or for the determination of exposure markers in highly contaminated agricultural environments.
+In several lately published studies, the association between single-nucleotide polymorphism (SNP, rs12252) of IFITM3 and the risk of influenza is inconsistent.
+To further understand the association between the SNP of IFITM3 and the risk of influenza, we searched related studies in five databases including PubMed published earlier than 9 November 2017.
+Ten sets of data from nine studies were included and data were analysed by Revman 5.0 and Stata 12.0 in our updated meta-analysis, which represented 1365 patients and 5425 no-influenza controls from four different ethnicities.
+The significant differences in the allelic model (C vs. T: odds ratio (OR) = 1.35, 95% confidence interval (CI) (1.03–1.79), P = 0.03) and homozygote model (CC vs. TT: OR = 10.63, 95% CI (3.39–33.33), P < 0.00001) in the Caucasian subgroup were discovered, which is very novel and striking.
+Also novel discoveries were found in the allelic model (C vs. T: OR = 1.37, 95% CI (1.08–1.73), P = 0.009), dominant model (CC + CT vs. TT: OR = 1.48, 95% CI (1.08–2.02), P = 0.01) and homozygote model (CC vs. TT: OR = 2.84, 95% CI (1.36–5.92), P = 0.005) when we compared patients with mild influenza with healthy individuals.
+Our meta-analysis suggests that single-nucleotide T to C polymorphism of IFITM3 associated with increasingly risk of severe and mild influenza in both Asian and Caucasian populations.
+Vaccinia virus (VACV) has numerous immune evasion strategies, including multiple mechanisms of inhibition of interferon regulatory factor 3 (IRF-3), nuclear factor κB (NF-κB), and type I interferon (IFN) signaling.
+Here, we use highly multiplexed proteomics to quantify ∼9,000 cellular proteins and ∼80% of viral proteins at seven time points throughout VACV infection.
+A total of 265 cellular proteins are downregulated >2-fold by VACV, including putative natural killer cell ligands and IFN-stimulated genes.
+Two-thirds of these viral targets, including class II histone deacetylase 5 (HDAC5), are degraded proteolytically during infection.
+In follow-up analysis, we demonstrate that HDAC5 restricts replication of both VACV and herpes simplex virus type 1.
+By generating a protein-based temporal classification of VACV gene expression, we identify protein C6, a multifunctional IFN antagonist, as being necessary and sufficient for proteasomal degradation of HDAC5.
+Our approach thus identifies both a host antiviral factor and a viral mechanism of innate immune evasion.
+The aim of this article is to provide a detailed description of the SWEDE-I cohort, a prospective study designed to investigate work-related risk factors for transmission of viral infections.
+A total of 2,237 subjects aged 25–64, working and residing in Eskilstuna (central Sweden), enrolled in the study in August 2011.
+They filled in five detailed questionnaires including information on demography, personal characteristics, work tasks, work place, contact patterns, family structure, health status, physical activity and diet.
+During a 9-month follow-up period, the participants self-reported—via internet or telephone—any onset of fever, upper respiratory tract infection, or gastroenteritis immediately as they occurred.
+For each disease episode, the participants were asked to submit a self-sampled nasal swab for viral diagnosis.
+In total, 1,733 disease reports were recorded and 1,843 nasal swabs were received, of which 48% tested positive for one or more of 14 analyzed viruses.
+The cohort has been used to date to study diet, sleep and physical activity as determinants for upper respiratory tract infections.
+Analyses of contact patterns and occupational circumstances as risk factors for the transmission of infections are ongoing.
+The SWEDE-I study should be seen as a first pioneering effort to provide new insight in the epidemiology and prevention of viral infections.
+Remdesivir (GS-5734) is a 1′-cyano-substituted adenosine nucleotide analogue prodrug that shows broad-spectrum antiviral activity against several RNA viruses.
+This compound is currently under clinical development for the treatment of Ebola virus disease (EVD).
+While antiviral effects have been demonstrated in cell culture and in non-human primates, the mechanism of action of Ebola virus (EBOV) inhibition for remdesivir remains to be fully elucidated.
+The EBOV RNA-dependent RNA polymerase (RdRp) complex was recently expressed and purified, enabling biochemical studies with the relevant triphosphate (TP) form of remdesivir and its presumptive target.
+In this study, we confirmed that remdesivir-TP is able to compete for incorporation with adenosine triphosphate (ATP).
+Enzyme kinetics revealed that EBOV RdRp and respiratory syncytial virus (RSV) RdRp incorporate ATP and remdesivir-TP with similar efficiencies.
+The selectivity of ATP against remdesivir-TP is ~4 for EBOV RdRp and ~3 for RSV RdRp.
+In contrast, purified human mitochondrial RNA polymerase (h-mtRNAP) effectively discriminates against remdesivir-TP with a selectivity value of ~500-fold.
+For EBOV RdRp, the incorporated inhibitor at position i does not affect the ensuing nucleotide incorporation event at position i+1.
+For RSV RdRp, we measured a ~6-fold inhibition at position i+1 although RNA synthesis was not terminated.
+While 2′-C-methyl-ATP is not incorporated, ara-ATP acts as a non-obligate chain terminator and prevents nucleotide incorporation at position i+1.
+Taken together, our biochemical data indicate that the major contribution to EBOV RNA synthesis inhibition by remdesivir can be ascribed to delayed chain termination.
+The long distance of five residues between the incorporated nucleotide analogue and its inhibitory effect warrant further investigation.
+Chikungunya virus (CHIKV) has caused extensive outbreaks in several countries within the Americas, Asia, Oceanic/Pacific Islands, and Europe.
+In humans, CHIKV infections cause a debilitating disease with acute febrile illness and long-term polyarthralgia.
+Acute and chronic symptoms impose a major economic burden to health systems and contribute to poverty in affected countries.
+An efficacious vaccine would be an important step towards decreasing the disease burden caused by CHIKV infection.
+Despite no licensed vaccine is yet available for CHIKV, there is strong evidence of effective asymptomatic viral clearance due to neutralising antibodies against the viral structural proteins.
+We have designed viral-vectored vaccines to express the structural proteins of CHIKV, using the replication-deficient chimpanzee adenoviral platform, ChAdOx1.
+Our vaccines induce high frequencies of anti-chikungunya specific T-cell responses as well as high titres of anti-CHIKV E2 antibodies with high capacity for in vitro neutralisation.
+Our results indicate the potential for further clinical development of the ChAdOx1 vaccine platform in CHIKV vaccinology.
+BACKGROUND: Telocytes play key roles in maintenance of organ/tissue function and prevention of organ injury.
+However, there are great challenges to investigate telocytes functions using primary telocytes, due to the difficulties of isolation, identification, and stability.
+The present study aims at constructing continuous cell strain of mouse lung telocyte cell line with stable characters by gene modification and investigating biological behaviors and responses of gene-modified telocytes to inflammation.
+METHODS: Mouse primary lung telocytes were isolated and identified using immune-labeling markers and immunoelectron microscopy.
+Primary telocytes were transformed with Simian vacuolating virus 40 small and large T antigen (SV40).
+Biological characters, behaviors morphology, and proliferation of those gene-modified telocytes were defined and monitored dynamically for 50 generations, as compared with primary lung telocytes.
+Cell cycle of mouse primary lung telocytes or gene-modified telocytes was detected by flow cytometry.
+RESULTS: Gene modified telocytes of generations 5, 10, 30 and 50 were observed with telopodes and also showed CD34 and ckit positive.
+Multiple cellular morphology were also observed on telocyte cell-line under monitor of celliq and enhanced cell proliferation were showed.
+SV40 transduction was also reduced apoptosis and increased the ratio of S and G2 phases in telocyte cell-line.
+CONCLUSION: We successfully constructed mouse lung telocyte cell-line which maintained the biological properties and behaviors as primary telocytes and could responses to inflammation induced by LPS.
+Thus, gene-modified lung telocytes, Telocyte Line, would provide a cell tool for researchers exploring the roles and applications of telocytes involved in physiological and pathological states in future.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12967-019-1870-y) contains supplementary material, which is available to authorized users.
+As the major viral proteins present on the surface of virions, viral envelope proteins are a prominent target of the host immune system in preventing and ultimately eliminating viral infection.
+In addition to the well-appreciated adaptive immunity that produces envelope protein-specific antibodies and T cell responses, recent studies have begun to unveil a rich layer of host innate immune mechanisms restricting viral entry.
+This review focuses on the exciting progress that has been made in this new direction of research, by discussing various known examples of host restriction of viral entry, and diverse viral countering strategies, in particular, the emerging role of viral envelope proteins in evading host innate immune suppression.
+We will also highlight the effective cooperation between innate and adaptive immunity to achieve the synergistic control of viral infection by targeting viral envelope protein and checking viral escape.
+Given that many of the related findings were made with HIV-1, we will use HIV-1 as the model virus to illustrate the basic principles and molecular mechanisms on host restriction targeting HIV-1 envelope protein.
+To review information on the epidemiology and disease burden of neonatal pertussis in South and Southeast Asian countries, a systematic literature review of three bibliographic databases was undertaken.
+Peer-reviewed original studies on neonatal pertussis epidemiology and burden published since 2000, with a geographical scope limited to South and Southeast Asian countries, were included.
+An increase in the number of pertussis cases has been noted since early 2000, ranging from 61 to 92.9% in infants 0–3 months old.
+The most common symptoms an infant is likely to present with are cough with or without paroxysms, cyanosis, apnea, tachypnea, difficulty in breathing and leukocytosis.
+In addition, it can lead to hospitalization (length of stay: 5–7 days), complications (e.g., pneumonia, seizures) and mortality ranging from 5.6 to 14.7%.
+Specifically, for obstetricians and gynecologists, the information available for making informed decisions on the prevention of neonatal pertussis is unreliable.
+Maternal immunization against pertussis during late stages of pregnancy has proven to be efficacious and well tolerated.
+A high burden of neonatal pertussis, as well as its complications, is observed in South and Southeast Asian countries.
+There is a need to intensify efforts to protect this vulnerable population with maternal vaccination.
+Hepatitis C virus (HCV) infection is the main cause of chronic hepatitis, affecting an estimated 150 million people worldwide.
+Initial exposure to HCV is most often followed by chronic hepatitis, with only a minority of individuals spontaneously clearing the virus.
+The induction of sustained and broadly directed HCV-specific CD4(+) and CD8(+) T cell responses, together with neutralizing antibodies (nAb), and specific genetic polymorphism have been associated with spontaneous resolution of the infection.
+However, due to its high variability, HCV is able to overwhelm the host immune response through the rapid acquisition of mutations in the epitopes targeted by T cells and neutralizing antibodies.
+This review summarizes the data on HCV diversity and the current state of knowledge about the contributions of antibodies, T cells, and host genetic polymorphism in driving HCV evolution in vivo.
+Transforming growth factor-β receptor II (TGFBR2), the type II receptor of the TGF-β/SMA- and MAD-related protein (SMAD) signaling pathway, plays a crucial role in TGF-β signal transduction and is regulated by multiple factors.
+Nevertheless, the modulation of the non-coding RNA involved in the process of TGFBR2 expression in ovaries is not well studied.
+In our study, we isolated and characterized the 3′-untranslated region (UTR) of the porcine TGFBR2 gene and microRNA-1306 (miR-1306) was identified as the functional miRNA that targets TGFBR2 in porcine granulosa cells (GCs).
+Functional analysis showed that miR-1306 promotes apoptosis of GCs as well as attenuating the TGF-β/SMAD signaling pathway targeting and impairing TGFBR2 in GCs.
+Luciferase and chromatin immunoprecipitation (ChIP) assays revealed that the transcription factor SMAD4 directly binds to the miR-1306 core promoter and inhibits its transcriptional activity.
+Furthermore, the TGF-β/SMAD signaling pathway is modulated by SMAD4 positive feedback via inhibition of miR-1306 expression in GCs.
+Collectively, our findings provide evidence of an epigenetic mechanism that modulates as well as mediates the feedback regulation of the classical TGF-β/SMAD signaling pathway in GCs from porcine ovaries.
+Investigating adaptive potential and understanding the relative roles of selection and genetic drift in populations of endangered species are essential in conservation.
+Major histocompatibility complex (MHC) genes characterized by spectacular polymorphism and fitness association have become valuable adaptive markers.
+Herein we investigate the variation of all MHC class I and II genes across seven populations of an endangered bird, the crested ibis, of which all current individuals are offspring of only two pairs.
+We inferred seven multilocus haplotypes from linked alleles in the Core Region and revealed structural variation of the class II region that probably evolved through unequal crossing over.
+Based on the low polymorphism, structural variation, strong linkage, and extensive shared alleles, we applied the MHC haplotypes in population analysis.
+The genetic variation and population structure at MHC haplotypes are generally concordant with those expected from microsatellites, underlining the predominant role of genetic drift in shaping MHC variation in the bottlenecked populations.
+The seven populations were significantly differentiated into three groups and some groups exhibited genetic monomorphism, which can be attributed to founder effects.
+The effect of specific anti‐diarrheal probiotic pastes (ADPPs) in the management of acute, uncomplicated diarrhea in dogs is unknown.
+HYPOTHESIS: Administration of an ADPP containing Enterococcus faecium 4b1707 will improve the clinical outcome of acute, uncomplicated diarrhea in dogs compared to placebo.
+METHODS: Double‐blinded, placebo‐controlled, randomized, blocked, multicenter clinical field study conducted at 14 primary care veterinary practices in the United Kingdom and Ireland.
+RESULTS: The ADPP was associated with better clinical outcome compared to placebo in dogs with acute, uncomplicated diarrhea.
+Dogs in the ADPP group had a significantly shorter duration of diarrhea (ADPP: median, 32 hours; 95% confidence interval [CI], 2‐118; n = 51; Placebo: median, 47 hours; 95% CI, 4‐167; n = 58; P = .008) and the rate of resolution of diarrhea was 1.60 times faster in the ADPP group than in the Placebo group (ratio, 1.60; 95% CI, 1.08‐2.44; P = .02).
+Fewer dogs required additional medical intervention (AMI) for non‐improvement or worsening in the ADPP group compared to the Placebo group (3.5% of dogs and 14.8% of dogs, respectively), with a relative risk of 0.88 (P = .04; AMI, ADPP, 3.5%, 2/57 dogs; Placebo, 14.8%, 9/61 dogs; relative risk, 0.88; 95% CI, 0.77‐0.99).
+CONCLUSION AND CLINICAL IMPORTANCE: The ADPP may accelerate resolution of acute diarrhea in dogs and decrease the requirement for AMI.
+The development of a safe and effective tetravalent dengue vaccine that elicits protection against all dengue virus (DENV) serotypes is urgently needed.
+The consensus sequence of the ectodomain of envelope (E) protein of DENV (cE80) has been examined as an immunogen previously.
+In the current study, a cE80 DNA (D) vaccine was constructed and evaluated in conjunction with the cE80 protein (P) vaccine to examine whether both vaccines used together can further improve the immune responses.
+The cE80 DNA vaccine was administrated using either a homologous (DNA alone, DDD) or heterologous (DNA prime-protein boost: DDP or DPP) regimen, and evaluated for immunogenicity and protective efficacy in mice.
+Among the three DNA-based immunization regimens tested, DDP immunization is the optimal immunization regimen that elicited the greatest systemic immune response and conferred protection against all four DENV serotypes.
+This work provides innovative ideas for the development of consensus E-based dengue vaccines and the testing of optimal immunization regimens.
+In ostriches, the population densities resulting from intensive rearing increases susceptibility to pathogens such as mycoplasmas.
+In addition to good management practices, vaccination offers an attractive alternative for controlling mycoplasma infections in food animals, instead of using antibiotics, which often leave unacceptable residues.
+The use of live attenuated vaccines, however, carry the concern of reversion to virulence or genetic recombination with field strains.
+Currently there are no commercially available vaccines against ostrich-infecting mycoplasmas and this study therefore set out to develop and evaluate the use of a DNA vaccine against mycoplasma infections in ostriches using an OppA protein as antigen.
+Ms03 was cloned into two DNA vaccine expression vectors after codon correction by site-directed mutagenesis.
+Three-months-old ostriches were then vaccinated intramuscularly at different doses followed by a booster vaccination after 6 weeks.
+The ability of the DNA vaccines to elicit an anti-OppA antibody response was evaluated by ELISA using the recombinant OppA protein of Ms03 as coating antigen.
+A statistically significant anti-OppA antibody response could be detected after administration of a booster vaccination indicating that the OppA protein was successfully immunogenic.
+In conclusion, the DNA vaccines were able to elicit an immune response in ostriches and can therefore be viewed as an option for the development of vaccines against mycoplasma infections.
+INTRODUCTION: Better characterisation of the epidemiological data on respiratory viral infections among people with acute respiratory tract infection (ARTI) can help to implement efficient strategies to curb the burden of ARTI in Africa.
+We will conduct a systematic review and meta-analysis to determine the prevalence and factors associated with respiratory viral infection in people of all ages with ARTI residing in Africa.
+METHODS: This work will include cross-sectional studies published between January 1, 2000 and December 31, 2017, without any language restriction, on populations residing in African countries.
+We will consider studies that reported the prevalence of respiratory viruses in people with ARTI confirmed by a polymerase chain reaction technique.
+We will be searching PubMed, Embase, African Journals Online, Web of Science, and Global Index Medicus.
+The selection of relevant studies, extraction of data, and evaluation of the quality of the articles will be carried out independently by two review authors, and the discrepancies will be resolved by consensus or intervention of a third author.
+The heterogeneity of the studies will be assessed using the χ(2) test on Cochrane’s Q statistic.
+Using meta-regression models, we will identify factors associated with viral infections in people with ARTI.
+DISCUSSION: This systematic review and meta-analysis is based on published data and therefore does not require ethical approval.
+This work will serve as a basis for the development of strategies for prevention and control ARTI in Africa and will also serve to identify data gaps and guide future investigations.
+The final report will be published in peer-reviewed journals as a scientific article and presented in workshops, conferences, and scientific conferences.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13643-019-1037-1) contains supplementary material, which is available to authorized users.
+However, as the epidemic spread of influenza occurs sporadically and rapidly, it is not easy to estimate the future variance of influenza virus infection.
+Furthermore, accumulating influenza related data is not easy, because the type of data that is associated with influenza is very limited.
+For these reasons, identifying useful data and building a prediction model with these data are necessary steps toward predicting if the number of patients will increase or decrease.
+On the Internet, numerous press releases are published every day that reflect currently pending issues.
+RESULTS: In this research, we collected Internet articles related to infectious diseases from the Centre for Health Protection (CHP), which is maintained the by Hong Kong Department of Health, to see if news text data could be used to predict the spread of influenza.
+In total, 7769 articles related to infectious diseases published from 2004 January to 2018 January were collected.
+We evaluated the predictive ability of article text data from the period of 2013–2018 for each of the weekly time horizons.
+The support vector machine (SVM) model was used for prediction in order to examine the use of information embedded in the web articles and detect the pattern of influenza spread variance.
+The prediction result using news text data with SVM exhibited a mean accuracy of 86.7 % on predicting whether weekly ILI patient ratio would increase or decrease, and a root mean square error of 0.611 on estimating the weekly ILI patient ratio.
+CONCLUSIONS: In order to remedy the problems of conventional data, using news articles can be a suitable choice, because they can help estimate if ILI patient ratio will increase or decrease as well as how many patients will be affected, as shown in the result of research.
+Thus, advancements in research on using news articles for influenza prediction should continue to be pursed, as the result showed acceptable performance as compared to existing influenza prediction researches.
+Porcine reproductive and respiratory syndrome virus (PRRSV) causes immune dysregulation during the Critical Window of Immunological Development.
+We hypothesize that thymocyte development is altered by infected thymic antigen presenting cells (TAPCs) in the fetal/neonatal thymus that interact with double-positive thymocytes causing an acute deficiency of T cells that produces “holes” in the T cell repertoire allowing for poor recognition of PRRSV and other neonatal pathogens.
+The deficiency may be the result of random elimination of PRRSV-specific T cells or the generation of T cells that accept PRRSV epitopes as self-antigens.
+Loss of helper T cells for virus neutralizing (VN) epitopes can result in the failure of selection for B cells in lymph node germinal centers capable of producing high affinity VN antibodies.
+Similar to infections with LDV, LCMV, MCMV, HIV-1 and trypanosomes, the host responds to the deficiency of pathogen-specific T cells and perhaps regulatory T cells, by “last ditch” polyclonal B cell activation.
+In colostrum-deprived PRRSV-infected isolator piglets, this results in hypergammaglobulinemia, which we believe to be a “red herring” that detracts attention from the thymic atrophy story, but leads to our second independent hypothesis.
+Since hypergammaglobulinemia has not been reported in PRRSV-infected conventionally-reared piglets, we hypothesize that this is due to the down-regulatory effect of passive maternal IgG and cytokines in porcine colostrum, especially TGFβ which stimulates development of regulatory T cells (Tregs).
+Pathogen detection, identification, and tracking is shifting from non-molecular methods, DNA fingerprinting methods, and single gene methods to methods relying on whole genomes.
+Viral Ebola and influenza genome data are being used for real-time tracking, while food-borne bacterial pathogen outbreaks and hospital outbreaks are investigated using whole genomes in the UK, Canada, the USA and the other countries.
+Also, plant pathogen genomes are starting to be used to investigate plant disease epidemics such as the wheat blast outbreak in Bangladesh.
+While these genome-based approaches provide never-seen advantages over all previous approaches with regard to public health and biosecurity, they also come with new vulnerabilities and risks with regard to cybersecurity.
+The more we rely on genome databases, the more likely these databases will become targets for cyber-attacks to interfere with public health and biosecurity systems by compromising their integrity, taking them hostage, or manipulating the data they contain.
+Also, while there is the potential to collect pathogen genomic data from infected individuals or agricultural and food products during disease outbreaks to improve disease modeling and forecast, how to protect the privacy of individuals, growers, and retailers is another major cyberbiosecurity challenge.
+As data become linkable to other data sources, individuals and groups become identifiable and potential malicious activities targeting those identified become feasible.
+Here, we define a number of potential cybersecurity weaknesses in today's pathogen genome databases to raise awareness, and we provide potential solutions to strengthen cyberbiosecurity during the development of the next generation of pathogen genome databases.
+Viral defense at mucosal sites depends on interferons (IFN) and IFN stimulated genes (ISGs), either of which may be constitutively expressed to maintain an “antiviral state” (AVS).
+Using a BEAS-2B respiratory epithelial cell line deficient in IRF1, we demonstrate higher susceptibility to infection with vesicular stomatitis virus (VSV) and influenza virus.
+IRF1-mediated restriction of VSV is IFN-independent, as blockade of types I and III IFNs and JAK-STAT signaling before infection did not affect VSV infection of either parent or IRF1 KO cells.
+Transcriptome analysis revealed that IRF1 regulates constitutive expression of ~300 genes, including antiviral ISGs: OAS2, BST2, and RNASEL and knockdown of any of these IRF1-dependent genes increased VSV infection.
+Additionally, IRF1 enhances rapid expression of IFNβ and IFNλ after stimulation with poly I:C and also regulates ISG expression.
+Mechanistically, IRF1 enhances recruitment of BRD4 to promotor-enhancer regions of ISGs for rapid expression and maintains levels of histone H3K4me1 for optimal constitutive expression.
+Finally, IRF1 also regulates constitutive expression of TLR2 and TLR3 and promotes signaling through these pattern recognition receptors (PRR).
+These data reveal multiple roles for IRF1 toward effective anti-viral responses by maintaining IFN-independent constitutive expression of anti-viral ISGs and supporting early IFN-dependent responses to PRR stimulation.
+Adoptive transfer of regulatory T cells (FOXP3(+) Tregs) has been developed as a potential curative immune therapy to prevent and treat autoimmune and graft-versus-host diseases (GVHD).
+A major limitation that has hindered the use of Treg immunotherapy in humans is the difficulty of consistently isolating and obtaining highly purified Tregs after ex vivo expansion.
+Methods: We isolated bona fide Tregs from expansion cultures based on their selective surface expression of latency-associated peptide (LAP).
+The TCR Vβ diversity and intracellular cytokine production of Tregs were determined by flow cytometer.
+Their in vitro and in vivo potency was confirmed with suppression assay and humanized xenogeneic GVHD (xGVHD) murine model, respectively.
+Results: LAP(+) repurification results in >90% LAP(+)FOXP3(+) Tregs, leaving behind FOXP3(-) and FOXP3(+) nonTregs within the LAP(-) population.
+After 4-week expansion, the LAP(+) Tregs were >1 billion cells, highly suppressive and anergic in vitro, >90% demethylated in the TSDR and able to maintain TCR Vβ diversity.
+In the xGVHD model, exogenous CD25(-)PBMC administered alone results in a median survival of 32 days.
+The co-transfer of LAP(+) Tregs increased median survival to 47 days, while the LAP parent (CD25(+)) and LAP(-) nonTregs had median survival of 39 and 31 days, respectively.
+Conclusions: These preclinical data together provide evidence that LAP(+) Tregs are highly purified with fully suppressive function for cell therapy.
+This population results in a more effective and safer product for immunotherapy to treat GVHD and provides the necessary preclinical data for transition into a clinical trial with LAP(+) Tregs to prevent or treat GVHD and other autoimmune diseases.
+The biology of autophagy in health and disease conditions has been intensively analyzed for decades.
+Several potential interventions can induce autophagy in preclinical research; however, none of these interventions are ready for translation to clinical practice yet.
+The topic of the current review is the molecular regulation of autophagy by glucagon, glucagon-like peptide (GLP)-1 and the GLP-1-degrading enzyme dipeptidyl peptidase-4 (DPP-4).
+In contrast, GLP-1 has been shown to inhibit glucagon secretion; GLP-1 also has been related to the induction of autophagy.
+DPP-4 inhibitors can induce autophagy in a GLP-1–dependent manner, but other diverse effects could be relevant.
+Here, we analyze the distinct molecular regulation of autophagy by glucagon, GLP-1, and DPP-4 inhibitors.
+Additionally, the potential contribution to autophagy by glucagon and GLP-1 after bariatric surgery is discussed.
+Disturbed balance between microbiota, epithelial cells, and resident immune cells within the intestine contributes to inflammatory bowel disease (IBD) pathogenesis.
+This model allows the analysis of host responses to enteric bacteria and facilitates improved understanding of the potential mechanisms of IBD pathogenesis.
+The current study evaluated the effects of dietary 30 mg/kg quercetin supplementation on C. rodentium-induced experimental colitis in C57BL/6 mice.
+Following dietary quercetin supplementation, the mice were infected with 5 × 10(8) CFU C. rodentium, and the pathological effects of C. rodentium were measured.
+The results showed that quercetin alleviated the effects of C. rodentium-induced colitis, suppressed the production of pro-inflammatory cytokines, such as interleukin (IL)-17, tumor necrosis factor alpha, and IL-6 (p < 0.05), and promoted the production of IL-10 in the colon tissues (p < 0.05).
+Quercetin supplementation also enhanced the populations of Bacteroides, Bifidobacterium, Lactobacillus, and Clostridia and significantly reduced those of Fusobacterium and Enterococcus (p < 0.05).
+These findings indicate that dietary quercetin exerts therapeutic effects on C. rodentium-induced colitis, probably due to quercetin’s ability to suppress pro-inflammatory cytokines and/or modify gut microbiota.
+BACKGROUND: Leishmaniasis is a parasitic disease caused by a protozoan of the Leishmania genus, and is considered a neglected tropical disease.
+It still remains a main public health concern at global level and in Arab world mainly in low-income countries.
+Therefore, this study was designed to evaluate the Arab world’s growing contribution to global leishmaniasis research.
+METHODS: This study describes a bibliometric review of all leishmaniasis research publications published between January 1998 and December 2017 indexed on the Scopus database.
+RESULTS: The total number of publications published at global level was 17,570 papers, which achieves an average annual productivity of 878.50 papers publications.
+Brazil was responsible for the greatest output with the total number of publications of 3865 followed by the Unites States (n = 2729), India (n = 2119), the United Kingdom (n = 1363), and Spain (n = 1274).
+By limiting the analysis to the publications that have been published by Arab world, the research productivity was 993 papers, which represents 5.65% of total research output at global level in research regarding leishmaniasis.
+Tunisia was responsible for the greatest output from Arab world with the total number of publications of 297 followed by Sudan (n = 192), Saudi Arabia (n = 131), Morocco (n = 119) and Egypt (n = 67).
+Since 1998, the growth of publications on leishmaniasis fluctuates, overall showing a rising trend in both global and Arab world.
+There is a highly significant correlation between publication productivity related to leishmaniasis at global level and the Arab world (r = 0.936; p-value< 0.001).
+Leishmaniasis treatment, intracellular mechanism of infection, and lifecycle of leishmania are the major current hot topics for the research in this subject at global level and the Arab world.
+CONCLUSIONS: The current study presents a novel review of the current Arab leishmaniasis-related research, and how these results are related to worldwide output.
+The data presented in the current study by this innovative approach may serve relevant researchers to direct the global leishmaniasis research to Arab counties in which leishmaniasis is endemic.
+Epitope-targeted HIV vaccine design seeks to focus antibody responses to broadly neutralizing antibody (bnAb) sites by sequential immunization.
+A chimpanzee simian immunodeficiency virus (SIV) envelope (Env) shares a single bnAb site, the variable loop 2 (V2)-apex, with HIV, suggesting its possible utility in an HIV immunization strategy.
+Here, we generate a chimpanzee SIV Env trimer, MT145K, which displays selective binding to HIV V2-apex bnAbs and precursor versions, but no binding to other HIV specificities.
+We determine the structure of the MT145K trimer by cryo-EM and show that its architecture is remarkably similar to HIV Env.
+Immunization of an HIV V2-apex bnAb precursor Ab-expressing knockin mouse with the chimpanzee MT145K trimer induces HIV V2-specific neutralizing responses.
+Overall, the chimpanzee MT145K trimer behaves as expected from design both in vitro and in vivo and is an attractive potential component of a sequential immunization regimen to induce V2-apex bnAbs.
+Crimean-Congo hemorrhagic fever virus (CCHFV), a tick-borne bunyavirus, can cause a life-threatening hemorrhagic syndrome in humans but not in its animal host.
+Recombinant vesicular stomatitis viruses (rVSV) expressing foreign glycoproteins (GP) have shown promise as experimental vaccines for several viral hemorrhagic fevers.
+Here, we developed and assessed a replication competent rVSV vector expressing the CCHFV glycoprotein precursor (GPC), which encodes CCHFV structural glycoproteins.
+The vector was tolerated and 100% efficacious against challenge from a clinical strain of CCHFV.
+This study demonstrates that a rVSV expressing only the CCHFV-GP has the potential to serve as a replication competent vaccine platform against CCHF infections.
+It is well established that chronic heavy alcohol drinking (CHD) results in significant organ damage, increased susceptibility to infections, and poor outcomes following injury.
+In contrast, chronic moderate drinking (CMD) has been associated with improved cardiovascular health and immunity.
+These differential outcomes have been linked to alterations in both innate and adaptive branches of the immune system; however, the mechanisms remain poorly understood.
+To address this question, we determined the impact of chronic drinking on the transcriptional and functional responses of peripheral blood mononuclear cells (PBMC) collected from male rhesus macaques classified as CMD or CHD after 12 months of voluntary ethanol self-administration.
+Our analysis suggests that chronic alcohol drinking, regardless of dose alters resting transcriptomes of PBMC, with the largest impact seen in innate immune cells.
+Additionally, chronic alcohol drinking is associated with a dose dependent heightened inflammatory profiled at resting and following LPS stimulation.
+These findings may explain the dichotomy in clinical and immunological outcomes observed with moderate versus heavy alcohol drinking.
+PURPOSE: Irreversible electroporation (IRE) has been demonstrated to be a safe and effective method for locally advanced pancreatic cancer (LAPC).
+The aim of this study was to evaluate the immunomodulatory effect after IRE and to evaluate the prognostic value of variations of the immune parameters in LAPC patients after IRE.
+METHODS: Peripheral blood samples of 34 patients were obtained preoperatively and on the third day (D3) and seventh day (D7) after IRE, respectively.
+The phenotypes of lymphocytes were analyzed by flow cytometry, and dynamic changes of serum levels of cytokines, complement, and immunoglobulin were assayed by enzyme-linked immunosorbent assay.
+Receiver operating characteristic (ROC) curve and concordance index (C-index) were used to compare the survival predictive ability.
+RESULTS: There was a transitory decrease followed by a steady increase for CD4(+) T cell, CD8(+) T cell, NK cell, IL-2, C3, C4, and IgG while a reverse trend was detected for Treg cell, IL-6, and IL10 after IRE.
+The alteration of CD8(+) T cell between D3 and D7 was identified as a prognostic factor for both overall survival (OS) and progression-free survival (PFS).
+The values of ROC curve (AUC) and C-indexes of the alteration of CD8(+) T cell for OS and PFS were 0.816 and 0.773 and 0.816 and 0.639, respectively, which were larger than those of other immune or inflammation-based indexes.
+The alteration of CD8(+) T cell between D3 and D7 showed relatively good performance and could be used as an effective tool for prognostic evaluation for LAPC patients after IRE.
+The main goal of aging research is to find therapies that attenuate aging and alleviate aging-related diseases.
+In this study, we screened a natural product library for geroprotective compounds using Werner syndrome (WS) human mesenchymal stem cells (hMSCs), a premature aging model that we recently established.
+Ten candidate compounds were identified and quercetin was investigated in detail due to its leading effects.
+Mechanistic studies revealed that quercetin alleviated senescence via the enhancement of cell proliferation and restoration of heterochromatin architecture in WS hMSCs.
+RNA-sequencing analysis revealed the transcriptional commonalities and differences in the geroprotective effects by quercetin and Vitamin C. Besides WS hMSCs, quercetin also attenuated cellular senescence in Hutchinson-Gilford progeria syndrome (HGPS) and physiological-aging hMSCs.
+Taken together, our study identifies quercetin as a geroprotective agent against accelerated and natural aging in hMSCs, providing a potential therapeutic intervention for treating age-associated disorders.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13238-018-0567-y) contains supplementary material, which is available to authorized users.
+Knowledge of etiology causes of diarrheal illness is essential for development and implementation of public health measures to prevent and control this disease syndrome.
+agents in stool samples from 155 child diarrheal cases enrolled between March and August 2017, in a hospital-based cross-sectional study in Thi-Qar, southeastern Iraq.
+Using molecular techniques and sequence-based characterization, adenovirus was the most frequently detected enteropathogen (53/155 (34.2%)), followed by Salmonella spp.
+was evident, and the same was revealed between various enteric viruses, particularly adenovirus and norovirus.
+The most frequent co-infection pattern was between adenovirus and Campylobacter spp., in seven cases (7/155 (4.5%)).
+Whole-genome sequencing-derived typing data for Salmonella isolates (n = 23) revealed that sequence type 49 was the most prevalent in this sample set (15/23 (65.2%)).
+To the best of our knowledge, this study provides the first report on detection and identification of floR, bla(CARB-2), and mphA antimicrobial resistance genes in Salmonella isolated from children in the Middle East region.
+Logistic regression analysis pointed to few enteropathogen-specific correlations between child age, household water source, and breastfeeding patterns in relation to the outcome of detection of individual enteropathogens.
+This study presents the first published molecular investigation of multiple enteropathogens among children <5 years of age in Iraq.
+It is important to build on this study and develop future longitudinal case-control research in order to elaborate the epidemiology of enteropathogens in childhood diarrhea in Iraq.
+AIM: Bile salt export pump (BSEP) have been confirmed to play an important role for bile acid canalicular export in the treatment of cholestasis.
+In this study, we investigated the stimulatory effect of emodin on BSEP signaling pathway in cholestasis.
+The BSEP upstream molecule farnesoid X receptor was down-regulated by small interfering RNA (siRNA) technology or guggulsterones and up-regulated by lentivirus or GW4064.
+Real-time PCR and Western blotting was employed to detect the mRNA and protein levels of BSEP in LO2 cell, rat primary hepatocytes and liver tissue.
+Rat liver function and pathological changes of liver tissue were performed by biochemical test and hematoxylin and eosin (HE) staining.
+When down-regulating farnesoid X receptor expression with the siRNA or inhibitor guggulsterones, and up-regulating farnesoid X receptor expression with the lentivirus or agonist GW4064, emodin could increase the mRNA level of BSEP and FXR and the protein level of BSEP, FXR1, and FXR2.
+Emodin also had a notable effect on rat primary hepatocytes experiment, rat pathological manifestation, BSEP, FXR1, and FXR2 positive staining in liver tissues and the test of liver function.
+CONCLUSION: Emodin has a protective effect and a rescue activity on cholestasis via stimulating FXR/BSEP pathways in promoting the canalicular export of accumulated bile.
+Bovine leukemia virus (BLV) causes enzootic bovine leukosis (EBL), a condition that threatens the sustainability of the livestock industry.
+A fluorescent loop-mediated isothermal amplification (fLAMP) assay targeting BLV env sequences was developed and used to evaluate 100 bovine blood samples.
+Compared with a conventional real-time PCR (rPCR) assay, the fLAMP assay achieved 87.3% (62/71) sensitivity and 100% (29/29) specificity.
+The rPCR assay took 65 min, while the fLAMP assay took 8 min to 30 min from the beginning of DNA amplification to final judgement with a comparable limit of detection.
+The fLAMP is a potential tool for the rapid and simple diagnosis of BLV infection to supplement ELISA testing and can be used by local laboratories and slaughterhouses without special equipment.
+In 2010, Yemen started the surveillance for severe acute respiratory infections (SARIs) by establishing 2 sentinel sites in Sana’a and Aden city.
+This study aims to determine the proportions of influenza and noninfluenza viruses among SARI patients and to determine the severity of SARI and its associated factors.
+The data of SARI patients who were admitted to SARI surveillance sites at Al Johory hospital in Sana’a and Al Wahdah hospital in Aden city during the period 2011-2016 were analyzed.
+The proportions of positive influenza viruses (type A, B) and noninfluenza viruses (respiratory syncytial, adenovirus, human parainfluenza, and human metapneumovirus), intensive care unit (ICU) admission rate, and fatality rate among SARI patients were calculated.
+A total of 89 (5%) patients had influenza viruses and 655 (36%) had noninfluenza viruses.
+Infection by influenza type (A, B) and mixed (adenovirus, human parainfluenza) was significantly associated with lower ICU admission.
+Age <15 years old, infection with influenza B, pre-existence of chronic diseases, and admission to Aden site were significantly associated with higher fatality rate among patients.
+Influenza type B, chronic diseases, and admission to Aden site are associated with higher fatality rate.
+Expanding surveillance sites and panel of laboratory tests to involve other pathogens will help to provide accurate diagnosis for SARI etiology and give more comprehensive picture.
+We recently demonstrated human exposure to PRV in Singapore, which together with previous reports from Malaysia and Vietnam suggest that human infection of PRV may occur periodically in the region.
+In this study, we screened 517 cynomolgus macaques caught in Singapore for evidence of exposure to PRV3M (also known as Melaka virus), which was first isolated from human patients in Melaka, Malaysia.
+We found that 67 serum samples were PRV3M positive by ELISA and 34 were also positive by virus neutralization assay.
+To investigate whether monkeys could act as hosts for PRV transmission, we experimentally infected cynomolgus macaques with PRV3M and housed these animals with uninfected monkeys.
+Although no clinical signs of infection were observed in infected animals, viral RNA was detected in nasal and rectal swabs and all infected macaques seroconverted.
+We provide evidence that PRV exposure in the macaque population in Singapore occurs at a relatively high prevalence and this study suggests that cynomolgus macaques may be an intermediate or reservoir host for PRVs.
+BACKGROUND: Trauma leads to a complex inflammatory cascade that induces both immune activation and a refractory immune state in parallel.
+Although both components are deemed necessary for recovery, the balance is tight and easily lost.
+Losing the balance can lead to life-threatening infectious complications as well as long-term immunosuppression with recurrent infections.
+Therefore, this review focuses on neutrophil characteristics and function after trauma and how these features can be used to identify trauma patients at risk for infectious complications.
+RESULTS: Distinct neutrophil subtypes exist that play their own role in the recovery and/or development of infectious complications after trauma.
+These findings change the initial concepts of the immune response after trauma and give rise to new biomarkers for monitoring and predicting inflammatory complications in severely injured patients.
+Several neutrophil biomarkers show promising results and analysis of these markers has become accessible to such extent that they can be used for point-of-care decision making after trauma.
+Modified vaccinia virus Ankara (MVA) is the leading poxvirus vector for development of vaccines against diverse infectious diseases.
+This distinction is based on high expression of proteins and good immunogenicity despite an inability to assemble infectious progeny in human cells, which together promote efficacy and safety.
+Nevertheless, the basis for the host-range restriction is unknown despite past systematic attempts to identify the relevant missing viral gene(s).
+The search for host-range factors is exacerbated by the large number of deletions, truncations and mutations that occurred during the long passage history of MVA in chicken embryo fibroblasts.
+By whole genome sequencing of a panel of recombinant host-range extended (HRE) MVAs generated by marker rescue with 40 kbp segments of vaccinia virus DNA, we identified serine protease inhibitor 1 (SPI-1) as one of several candidate host-range factors present in those viruses that gained the ability to replicate in human cells.
+Electron microscopy revealed that the interruption of morphogenesis in human cells infected with MVA occurred at a similar stage as that of a vaccinia virus strain WR SPI-1 deletion mutant.
+Moreover, the introduction of the SPI-1 gene into the MVA genome led to more than a 2-log enhancement of virus spread in human diploid MRC-5 cells, whereas deletion of the gene diminished the spread of HRE viruses by similar extents.
+A role for additional host range genes was suggested by the restoration of MVA replication to a lower level relative to HRE viruses, particularly in other human cell lines.
+Although multiple sequence alignments revealed genetic changes in addition to SPI-1 common to the HRE MVAs, no evidence for their host-range function was found by analysis thus far.
+Our finding that SPI-1 is host range factor for MVA should simplify use of high throughput RNAi or CRISPR/Cas single gene methods to identify additional viral and human restriction elements.
+Antimicrobial resistance (AMR) is one of the latest issues to galvanise political and financial investment as an emerging global health threat.
+This paper explores the construction of AMR as a problem, following three lines of analysis.
+First, an examination of some of the ways in which AMR has become an object for action—through defining, counting and projecting it.
+Following Lakoff’s work on emerging infectious diseases, the paper illustrates that while an ‘actuarial’ approach to AMR may be challenging to stabilise due to definitional and logistical issues, it has been successfully stabilised through a ‘sentinel’ approach that emphasises the threat of AMR.
+Second, the paper draws out a contrast between the way AMR is formulated in terms of a problem of connectedness—a ‘One Health’ issue—and the frequent solutions to AMR being focused on individual behaviour.
+The paper suggests that AMR presents an opportunity to take seriously connections, scale and systems but that this effort is undermined by the prevailing tendency to reduce health issues to matters for individual responsibility.
+Third, the paper takes AMR as a moment of infrastructural inversion (Bowker and Star) when antimicrobials and the work they do are rendered more visible.
+This leads to the proposal of antibiotics as infrastructure—part of the woodwork that we take for granted, and entangled with our ways of doing life, in particular modern life.
+These explorations render visible the ways social, economic and political frames continue to define AMR and how it may be acted upon, which opens up possibilities for reconfiguring AMR research and action.
+The aim of this study was to decipher clinical and laboratory characteristics of hemophagocytic lymphohistiocytosis after definite diagnosis of liver failure and to provide clues for early diagnosis and treatment of HLH in patients with liver failure.
+All patients presented with jaundice, persistent high-grade fever, pancytopenia, splenomegaly, evidence of hemophagocytes in the bone marrow and laboratory abnormalities indicating HLH.
+The average interval from the earliest diagnosis of liver failure to a definitive diagnosis of HLH was 17.27 days.
+For patients with liver failure after admission and subsequently definitively diagnosed with HLH, bilirubin and INR were significantly decreased.
+HLH is definitely diagnosed at an intermediate or late stage when patients have already suffered from liver failure.
+The initial dose of glucocorticoid (methylprednisolone) was decreased to 1–1.5 mg/kg/d and gradually reduced thereafter.
+In conclusion, for patients with liver failure, HLH should be screened as early as possible upon persistent fever, splenomegaly and unexplained pancytopenia.
+For patients with liver failure and HLH, the dosage of glucocorticoid should be reduced to avoid serious side effects.
+A hallmark of translation in human immunodeficiency virus type 1 (HIV-1) is a –1 programmed ribosome frameshifting event that produces the Gag-Pol fusion polyprotein.
+Here we show that the frameshifting efficiency is modulated by Leu-tRNA(Leu) that reads the UUA codon at the mRNA slippery site.
+This tRNA(Leu) isoacceptor is particularly rare in human cell lines derived from T-lymphocytes, the cells that are targeted by HIV-1.
+When UUA decoding is delayed, the frameshifting follows an alternative route, which maintains the Gag to Gag-Pol ratio constant.
+A second potential slippery site downstream of the first one is normally inefficient but can also support –1-frameshifting when altered by a compensatory resistance mutation in response to current antiviral drug therapy.
+Together these different regimes allow the virus to maintain a constant –1-frameshifting efficiency to ensure successful virus propagation.
+BACKGROUND: Idiopathic pulmonary fibrosis is characterized by loss of lung epithelial cells and inexorable progression of fibrosis with no effective and approved treatments.
+The distal airway stem/progenitor cells (DASCs) have been shown to have potent regenerative capacity after lung injury.
+In this work, we aimed to define the role of mouse DASCs (mDASCs) in response to bleomycin-induced lung fibrosis in mice.
+METHODS: The mDASCs were isolated, expanded in vitro, and labeled with GFP by lentiviral infection.
+Pathological change, collagen content, α-SMA expression, lung function, and mortality rate were assessed at 7, 14, and 21 days after bleomycin administration.
+Tissue section and direct fluorescence staining was used to show the distribution and differentiation of mDASCs in lung.
+RESULTS: The transplanted mDASCs could incorporate, proliferate, and differentiate into type I pneumocytes in bleomycin-injured lung.
+CONCLUSIONS: The data strongly suggest that mDASCs could ameliorate bleomycin-induced pulmonary fibrosis by promotion of lung regeneration and inhibition of lung fibrogenesis.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13287-019-1257-2) contains supplementary material, which is available to authorized users.
+INTRODUCTION: The earthquake is one of the most natural catastrophic crises that can cause a lot of casualties.
+Considering an earthquake-prone country, Iran is ranked as one of the world's most dangerous countries OBJECTIVE: In this article, we describe the actions taken by emergency medical service (EMS) after the earthquake in Kermanshah, Varzaghan, and Bam and compared the strengths and weaknesses of the emergency response program and the limitations and challenges of this system in dealing with these major crises.
+METHOD: This study is a cross-sectional study that compares some of the information and findings related to three earthquakes that occurred in Iran, including Bam, Varzaghan and Sarpol-e-Zahab earthquakes.
+The data reported in the present article is descriptive and is based on various independent sources such as National Emergency Operation Center, Local Emergency Operations Center (EOC), the EMS of the country, the World Health Organization, the United Nations, the statistics website, the Forensic Data website, the International Institute of Seismology and Earthquake Engineering, conferences and personal interviews.
+To ensure the credibility of the information, the authors reported data that had been verified by two or more sources.
+Post-earthquake response activities were described in details in subheadings including rapid warning and response, surge capacity plan, rapid response teams, emergency medical teams, increasing the capacity of health facilities, increasing transfer capacity, and handling, transportation and distribution of injuries.
+CONCLUSION: In the recent earthquake, had been occurred in Sarpol-e-Zahab, the health response of the country was largely satisfactory.
+The existence of structures such as EOC at various levels, the unified incident command system, emergency operations plan, and Medical Care Monitoring Center are among the most important reasons for satisfactory performance.
+The term “acute phase response” (APR) is referred to a nonspecific and complex reaction of an organism that occurs shortly after any tissue damage, such as infection, trauma, neoplasia, inflammation, and stress.
+The APR can be identified and monitored with some laboratory tests, such as the concentration of several plasma proteins, the acute phase proteins (APPs).
+The APPs are components of the non-specific innate immune response, and their plasma concentration is proportional to the severity and/or the extent of tissue damage.
+The evaluation of health status of marine mammals is difficult because the classical clinical signs of illness used for human and domestic animals are difficult to recognize and understand.
+For this reason, in the past years, several efforts were done to identify laboratory markers of disease in these animals.
+The APPs have demonstrated their role as early markers of inflammation in veterinary medicine, thus several APPs were tested in marine mammals, such as C-reactive protein (CRP), serum amyloid-A (SAA), and Haptoglobin (Hp).
+However, the difficulty to extrapolate the knowledge about APPs in one species to another, the lack of specie-specific reagents, the absence of data about negative APPs have hampered their extent use in marine mammals.
+Herein, the state of art of APPs in marine mammals is reviewed, with particular attention to pre-analytical and analytical factors that should be taken into account in validation and interpretation of APPs assays.
+Moreover, the current application, potential utility and the future developments of APPs in marine mammals is highlighted and discussed.
+The key to better understanding the mechanisms that control this process is to identify the specific substrates that each protease targets.
+To address this, we have developed iProt-Sub, a powerful bioinformatics tool for the accurate prediction of protease-specific substrates and their cleavage sites.
+It provides optimized cleavage site prediction models with better prediction performance and coverage for more species-specific proteases (4 major protease families and 38 different proteases).
+iProt-Sub integrates heterogeneous sequence and structural features and uses a two-step feature selection procedure to further remove redundant and irrelevant features in an effort to improve the cleavage site prediction accuracy.
+Features used by iProt-Sub are encoded by 11 different sequence encoding schemes, including local amino acid sequence profile, secondary structure, solvent accessibility and native disorder, which will allow a more accurate representation of the protease specificity of approximately 38 proteases and training of the prediction models.
+Benchmarking experiments using cross-validation and independent tests showed that iProt-Sub is able to achieve a better performance than several existing generic tools.
+We anticipate that iProt-Sub will be a powerful tool for proteome-wide prediction of protease-specific substrates and their cleavage sites, and will facilitate hypothesis-driven functional interrogation of protease-specific substrate cleavage and proteolytic events.
+Health planners use forecasts of key metrics associated with influenza-like illness (ILI); near-term weekly incidence, week of season onset, week of peak, and intensity of peak.
+Here, we describe our participation in a weekly prospective ILI forecasting challenge for the United States for the 2016-17 season and subsequent evaluation of our performance.
+Variants differed from each other in their assumptions about: the force-of-infection (FOI); use of uninformative priors; the use of discounted historical data for not-yet-observed time points; and the treatment of regions as either independent or coupled.
+Individual model variants were chosen subjectively as the basis for our weekly forecasts; however, a subset of coupled models were only available part way through the season.
+Most frequently, during the 2016-17 season, we chose; FOI variants with both school vacations and humidity terms; uninformative priors; the inclusion of discounted historical data for not-yet-observed time points; and coupled regions (when available).
+Our near-term weekly forecasts substantially over-estimated incidence early in the season when coupled models were not available.
+However, our forecast accuracy improved in absolute terms and relative to other teams once coupled solutions were available.
+In retrospective analysis, we found that the 2016-17 season was not typical: on average, coupled models performed better when fit without historically augmented data.
+Also, we tested a simple ensemble model for the 2016-17 season and found that it underperformed our subjective choice for all forecast targets.
+In this study, we were able to improve accuracy during a prospective forecasting exercise by coupling dynamics between regions.
+Although reduction of forecast subjectivity should be a long-term goal, some degree of human intervention is likely to improve forecast accuracy in the medium-term in parallel with the systematic consideration of more sophisticated ensemble approaches.
+After HPV binding to cell surface receptors, a cascade of molecular interactions mediates the infectious cellular internalization of virus particles.
+Aside from the virus itself, important molecular players involved in virus entry include the tetraspanin CD151 and the epidermal growth factor receptor (EGFR).
+Here, we studied plasma membrane dynamics of CD151 and EGFR and the HPV16 capsid during the early phase of infection.
+We find that the proteinase ADAM17 activates the extracellular signal-regulated kinases (ERK1/2) pathway by the shedding of growth factors which triggers the formation of an endocytic entry platform.
+Infectious endocytic entry platforms carrying virus particles consist of two-fold larger CD151 domains containing the EGFR.
+Our finding clearly dissects initial virus binding from ADAM17-dependent assembly of a HPV/CD151/EGFR entry platform.
+Amoebiasis is a parasitic disease that causes thousands of deaths every year, its adverse effects and resistance to conventional treatments have led to the search of new treatment options, as well as the development of novel screening methods.
+In this work, we implemented a 3D model of intestine and liver slices from hamsters that were infected ex vivo with virulent E. histolytica trophozoites.
+Results show preserved histology in both uninfected tissues as well as ulcerations, destruction of the epithelial cells, and inflammatory reaction in intestine slices and formation of micro abscesses, and the presence of amoebae in the sinusoidal spaces and in the interior of central veins in liver slices.
+The three chemically synthetized compounds T-001, T-011, and T-016, which act as amoebicides in vitro, were active in both infected tissues, as they decreased the number of trophozoites, and provoked death by disintegration of the amoeba, similar to metronidazole.
+Our results suggest that ex vivo cultures of precision-cut intestinal and liver slices represent a reliable 3D approach to evaluate novel amoebicidal compounds, and to simultaneously detect their toxicity, while reducing the number of experimental animals commonly required by other model systems.
+Animal experiments are widely used in preclinical medical research with the goal of disease modeling and exploration of novel therapeutic approaches.
+In the context of sepsis and septic shock, the translation into clinical practice has been disappointing.
+Classical animal models of septic shock usually involve one-sex-one-age animal models, mostly in mice or rats, contrasting with the heterogeneous population of septic shock patients.
+Many other factors limit the reliability of preclinical models and may contribute to preclinical research failure in critical care, including the host specificity of several pathogens, the fact that laboratory animals are raised in pathogen-free facilities and that organ support techniques are either absent or minimal.
+Advanced animal models have been developed with the aim of improving the clinical translatability of experimental findings.
+So-called animal ICUs refer to the preclinical investigation of adult or even aged animals of either sex, using—in case of rats and mice—miniaturized equipment allowing for reproducing an ICU environment at a small animal scale and integrating chronic comorbidities to more closely reflect the clinical conditions studied.
+Strength and limitations of preclinical animal models designed to decipher the mechanisms involved in septic cardiomyopathy are discussed.
+This article reviews the current status and the challenges of setting up an animal ICU.
+Targeted therapy is currently limited for patients with hepatocellular carcinoma (HCC) due to the lack of suitable targets.
+Kinases play pivotal roles in many cellular biological processes, whereas dysregulation of kinases may lead to various diseases, particularly cancer.
+In this study, we employed a kinome small interfering RNA (siRNA) library, comprising 710 kinase-related genes, to screen whether any kinases were essential for cell proliferation in various HCC cell lines.
+Through a kinome siRNA library screening, we found that MAP3K7 was a crucial gene for HCC cell proliferation.
+Pharmacological or genetic ablation of MAP3K7 diminished the growth, migration, and invasion of HCC cells, including primary HCC cells.
+Stable knockdown of MAP3K7 attenuated tumor formation in a spheroid cell culture model and tumor xenograft mouse model.
+In addition, silencing MAP3K7 reduced the phosphorylation and expression of mammalian target of rapamycin (mTOR) in HCC cells.
+Taken together, our results revealed that the MAP3K7-mTOR axis might promote tumorigenesis and malignancy, which provides a potential marker or therapeutic target for HCC patients.
+Harnessing the power of the immune system to recognize and eliminate cancer cells is a longtime exploration.
+In the past decade, monoclonal antibody (mAb)-based immune checkpoint blockade (ICB) and chimeric antigen receptor T (CAR-T) cell therapy have proven to be safe and effective in hematologic malignancies.
+Despite the unprecedented success of ICB and CAR-T therapy, only a subset of patients can benefit partially due to immune dysfunction and lack of appropriate targets.
+Here, we review the preclinical and clinical advances of CTLA-4 and PD-L1/PD-1-based ICB and CD19-specific CAR-T cell therapy in hematologic malignancies.
+We also discuss the basic research and ongoing clinical trials on emerging immune checkpoints (Galectin-9/Tim-3, CD70/CD27, LAG-3, and LILRBs) and on new targets for CAR-T cell therapy (CD22, CD33, CD123, BCMA, CD38, and CD138) for the treatment of hematologic malignancies.
+Commercial poultry are continually exposed to, frequently pathogenic, microorganisms, usually via mucosal surfaces such as the intestinal mucosa.
+Many of these microorganisms may have no or limited contact with the host, while most of those interacting more meaningfully with the host will be dealt with by the innate immune response.
+Fundamentally, poultry have evolved to have immune responses that are generally appropriate and adequate for their acquired microbiomes, although this is challenged by commercial production practices.
+Innate immune cells and their functions, encompassing inflammatory responses, create the context for neutralising the stimulus and initiating resolution.
+Dysregulated inflammatory responses can be detrimental but, being a highly conserved biological process, inflammation is critical for host defence.
+Heterogeneity and functional plasticity of innate immune cells is underappreciated and offers the potential for (gut) health interventions, perhaps including exogenous opportunities to influence immune cell metabolism and thus function.
+New approaches could focus on identifying and enhancing decisive but less harmful immune processes, improving the efficiency of innate immune cells (e.g., targeted, efficient microbial killing) and promoting phenotypes that drive resolution of inflammation.
+Breeding strategies and suitable exogenous interventions offer potential solutions to enhance poultry gut health, performance and welfare.
+Three methods to quantify chloroquine and its metabolite in blood matrices were developed and validated.
+METHODOLOGY & RESULTS: Different high-throughput extraction techniques were used to recover the drugs from whole blood (50 μl), plasma (100 μl) and dried blood spots (15 μl as punched discs) followed by quantification with LC–MS/MS.
+All methods were reliable with robust performance and demonstrated to be suitable to implement into high-throughput routine analysis of clinical pharmacokinetic samples.
+Human norovirus (HuNoV) is responsible for more than 95% of outbreaks of acute nonbacterial gastroenteritis worldwide.
+Chicken immunoglobulin Y (IgY)-based passive immunization has been shown to be an effective strategy to prevent and treat many enteric viral diseases.
+Here, we developed a highly efficient bioreactor to generate high titers of HuNoV-specific IgY in chicken yolks using a recombinant vesicular stomatitis virus expressing HuNoV capsid protein (rVSV-VP1) as an antigen.
+We first demonstrated that HuNoV VP1 protein was highly expressed in chicken cells infected by rVSV-VP1.
+Subsequently, we found that White Leghorn hens immunized intramuscularly with rVSV-VP1 triggered a high level of HuNoV-specific yolk IgY antibodies.
+Importantly, HuNoV-specific IgY efficiently blocked the binding of HuNoV VLPs to all three types (A, B, and O) of histo-blood group antigens (HBGAs), the attachment factors for HuNoV.
+In addition, the receptor blocking activity of IgY remained stable at temperature below 70 °C and at pH ranging from 4 to 9.
+Thus, immunization of hens with VSV-VP1 could be a cost-effective and practical strategy for large-scale production of anti-HuNoV IgY antibodies for potential use as prophylactic and therapeutic treatment against HuNoV infection.
+Ebola virus (EBOV) disease can result in a range of symptoms anywhere from virtually asymptomatic to severe hemorrhagic fever during acute infection.
+Additionally, spans of asymptomatic persistence in recovering survivors is possible, during which transmission of the virus may occur.
+In acute infection, substantial cytokine storm and bystander lymphocyte apoptosis take place, resulting in uncontrolled, systemic inflammation in affected individuals.
+Recently, studies have demonstrated the presence of EBOV proteins VP40, glycoprotein (GP), and nucleoprotein (NP) packaged into extracellular vesicles (EVs) during infection.
+EVs containing EBOV proteins have been shown to induce apoptosis in recipient immune cells, as well as contain pro-inflammatory cytokines.
+In this manuscript, we review the current field of knowledge on EBOV EVs including the mechanisms of their biogenesis, their cargo and their effects in recipient cells.
+Furthermore, we discuss some of the effects that may be induced by EBOV EVs that have not yet been characterized and highlight the remaining questions and future directions.
+The increasing norovirus diversity is currently categorized into at least 10 genogroups which are further classified into more than 40 genotypes.
+In addition to humans, norovirus can infect a broad range of hosts including livestock, pets, and wild animals, e.g., marine mammals and bats.
+Little is known about norovirus infections in most non-human hosts, but the close genetic relatedness between some animal and human noroviruses coupled with lack of understanding where newly appearing human norovirus genotypes and variants are emerging from has led to the hypothesis that norovirus may not be host restricted and might be able to jump the species barrier.
+We have systematically reviewed the literature to describe the diversity, prevalence, and geographic distribution of noroviruses found in animals, and the pathology associated with infection.
+We further discuss the evidence that exists for or against interspecies transmission including surveillance data and data from in vitro and in vivo experiments.
+Polyamines are small positively-charged molecules abundant in eukaryotic cells that are crucial to RNA virus replication.
+In eukaryotic cells, polyamines facilitate processes such as transcription, translation, and DNA replication, and viruses similarly rely on polyamines to facilitate transcription and translation.
+Picornaviruses, including Coxsackievirus B3 (CVB3), are sensitive to polyamine depletion both in vitro and in vivo; however, precisely how polyamine function in picornavirus infection has not been described.
+We observe mutations in the 2A and 3C proteases, and we find that these mutant proteases confer resistance to polyamine depletion.
+Using a split luciferase reporter system to measure protease activity, we determined that polyamines facilitate viral protease activity.
+We further observe that the 2A and 3C protease mutations enhance reporter protease activity in polyamine-depleted conditions.
+Finally, we find that these mutations promote cleavage of cellular eIF4G during infection of polyamine-depleted cells.
+In sum, our results suggest that polyamines are crucial to protease function during picornavirus infection.
+Further, these data highlight viral proteases as potential antiviral targets and highlight how CVB3 may overcome polyamine-depleting antiviral therapies.
+Annual seasonal influenza epidemics of variable severity result in significant morbidity and mortality in the United States (U.S.) and worldwide.
+Annual influenza vaccination is recommended for all persons in the U.S. aged 6 months and older, and among those at increased risk for influenza-related complications in other parts of the world (e.g.
+Observational studies have reported effectiveness of influenza vaccination to reduce the risks of severe disease requiring hospitalization, intensive care unit admission, and death.
+A diagnosis of influenza should be considered in critically ill patients admitted with complications such as exacerbation of underlying chronic comorbidities, community-acquired pneumonia, and respiratory failure during influenza season.
+Antigen detection assays are not recommended in critically ill patients because of lower sensitivity; negative results of these tests should not be used to make clinical decisions, and respiratory specimens should be tested for influenza by molecular assays.
+Because critically ill patients with lower respiratory tract disease may have cleared influenza virus in the upper respiratory tract, but have prolonged influenza viral replication in the lower respiratory tract, an endotracheal aspirate (preferentially) or bronchoalveolar lavage fluid specimen (if collected for other diagnostic purposes) should be tested by molecular assay for detection of influenza viruses.
+Observational studies have reported that antiviral treatment of critically ill adult influenza patients with a neuraminidase inhibitor is associated with survival benefit.
+Since earlier initiation of antiviral treatment is associated with the greatest clinical benefit, standard-dose oseltamivir (75 mg twice daily in adults) for enteric administration is recommended as soon as possible as it is well absorbed in critically ill patients.
+Based upon observational data that suggest harms, adjunctive corticosteroid treatment is currently not recommended for children or adults hospitalized with influenza, including critically ill patients, unless clinically indicated for another reason, such as treatment of asthma or COPD exacerbation, or septic shock.
+A magnesium complex (1) featuring a bidentate aminopyridinato ligand is a remarkably selective catalyst for the dehydrocoupling of amine‐boranes.
+This reaction proceeds to completion with low catalyst loadings (1 mol %) under mild conditions (60 °C), exceeding previously reported s‐block systems in terms of selectivity, rate, and turnover number (TON).
+Mechanistic studies by in situ NMR analysis reveals the reaction to be first order in both catalyst and substrate.
+A reaction mechanism is proposed to account for these findings, with the high TON of the catalyst attributed to the bidentate nature of the ligand, which allows for reversible deprotonation of the substrate and regeneration of 1 as a stable resting state.
+We are constantly exposed to infectious diseases, and they cause millions of deaths per year.
+The World Health Organization (WHO) estimates that antibiotic resistance could cause 10 million deaths per year by 2050.
+Multidrug-resistant bacteria are the cause of infection in at least one in three people suffering from septicemia.
+While antibiotics are powerful agents against infectious diseases, the alarming increase in antibiotic resistance is of great concern.
+Alternatives are desperately needed, and nanotechnology provides a great opportunity to develop novel approaches for the treatment of infectious diseases.
+One of the most important factors in the prognosis of an infection caused by an antibiotic resistant bacteria is an early and rigorous diagnosis, jointly with the use of novel therapeutic systems that can specifically target the pathogen and limit the selection of resistant strains.
+Nanodiamonds can be used as antimicrobial agents due to some of their properties including size, shape, and biocompatibility, which make them highly suitable for the development of efficient and tailored nanotherapies, including vaccines or drug delivery systems.
+In this review, we discuss the beneficial findings made in the nanodiamonds field, focusing on diagnosis and treatment of infectious diseases.
+We also highlight the innovative platform that nanodiamonds confer for vaccine improvement, drug delivery, and shuttle systems, as well as their role in the generation of faster and more sensitive clinical diagnosis.
+BACKGROUND: Nematodes are among the most diverse and abundant metazoans on Earth, but research on them has been biased toward parasitic taxa and model organisms.
+Free-living nematodes, particularly from the clades Enoplia and Dorylaimia, have been underrepresented in genome-scale phylogenetic analyses to date, leading to poor resolution of deep relationships within the phylum.
+RESULTS: We supplemented publicly available data by sequencing transcriptomes of nine free-living nematodes and two important outgroups and conducted a phylum-wide phylogenomic analysis including a total of 108 nematodes.
+Analysis of a dataset generated using a conservative orthology inference strategy resulted in a matrix with a high proportion of missing data and moderate to weak support for branching within and placement of Enoplia.
+A less conservative orthology inference approach recovered more genes and resulted in higher support for the deepest splits within Nematoda, recovering Enoplia as the sister taxon to the rest of Nematoda.
+Relationships within major clades were similar to those found in previously published studies based on 18S rDNA.
+CONCLUSIONS: Expanded transcriptome sequencing of free-living nematodes has contributed to better resolution among deep nematode lineages, though the dataset is still strongly biased toward parasites.
+Inclusion of more free-living nematodes in future phylogenomic analyses will allow a clearer understanding of many interesting aspects of nematode evolution, such as morphological and molecular adaptations to parasitism and whether nematodes originated in a marine or terrestrial environment.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12862-019-1444-x) contains supplementary material, which is available to authorized users.
+Maintenance of epigenetic modifiers is of utmost importance to preserve the epigenome and consequently appropriate cellular functioning.
+Here, we analyzed Polycomb group protein (PcG) complex integrity in response to heat shock (HS).
+Upon HS, various Polycomb Repressive Complex (PRC)1 and PRC2 subunits, including CBX proteins, but also other chromatin regulators, are found to accumulate in the nucleolus.
+In parallel, binding of PRC1/2 to target genes is strongly reduced, coinciding with a dramatic loss of H2AK119ub and H3K27me3 marks.
+Nucleolar-accumulated CBX proteins are immobile, but remarkably both CBX protein accumulation and loss of PRC1/2 epigenetic marks are reversible.
+This post-heat shock recovery of pan-nuclear CBX protein localization and reinstallation of epigenetic marks is HSP70 dependent.
+Our findings demonstrate that the nucleolus is an essential protein quality control center, which is indispensable for recovery of epigenetic regulators and maintenance of the epigenome after heat shock.
+BACKGROUND: For many survivors of acute respiratory distress syndrome (ARDS), the process from discharge from intensive care unit (ICU) to recovery is long and difficult.
+This study sets out to investigate the extent of ambulatory and stationary healthcare use among survivors of ARDS in Germany (multicenter DACAPO cohort) and to analyze predictors of stationary healthcare use.
+RESULTS: A total of 396 survivors of ARDS provided data at 1 year after discharge from ICU.
+Fifty percent of 1-year survivors were hospitalized for 48 days or longer after discharge from ICU, with 10% spending more than six out of 12 months in stationary care.
+All participants reported at least one outpatient visit (including visits to general practitioners), and 50% contacted four or more different medical specialties within the first year after discharge from ICU.
+CONCLUSIONS: For most of the patients, the first year after ARDS is characterized by an extensive amount of healthcare utilization, especially with regard to stationary health care.
+These findings shed light on the substantial morbidity of patients after ARDS and contribute to a better understanding of the situation of patients following discharge from ICU.
+Many emerging arboviruses are not transmitted by traditional mosquito vectors, but by lesser-studied arthropods such as ticks, midges, and sand flies.
+Small RNA (sRNA) silencing pathways are the main antiviral defence mechanism for arthropods, which lack adaptive immunity.
+Non-retroviral integrated RNA virus sequences (NIRVS) are one potential source of sRNAs which comprise these pathways.
+NIRVS are remnants of past germline RNA viral infections, where viral cDNA integrates into the host genome and is vertically transmitted.
+These are hypothesised to target incoming viral transcripts to modulate viral titre, perhaps rendering the organism a more efficient arbovirus vector.
+To explore the NIRVS landscape in alternative arbovirus vectors, we validated the NIRVS landscape in Aedes spp.
+and then identified novel NIRVS in six medically relevant arthropods and also in Drosophila melanogaster.
+We identified novel NIRVS in Phlebotomus papatasi, Culicoides sonorensis, Rhipicephalus microplus, Anopheles gambiae, Culex quinquefasciatus, and Ixodes scapularis.
+Due to their unexpected abundance, we further characterised NIRVS in the blacklegged tick I. scapularis (n = 143).
+Interestingly, NIRVS are not enriched in R. microplus, another hard tick, suggesting this is an Ixodes-specific adaptation.
+I. scapularis NIRVS are enriched in bunya- and orthomyxo-like sequences, reflecting that ticks are a dominant host for these virus groups.
+Unlike in mosquitoes, I. scapularis NIRVS are more commonly derived from the non-structural region (replicase) of negative-sense viruses, as opposed to structural regions (e.g.
+Like other arthropods, I. scapularis NIRVS preferentially integrate into genomic piRNA clusters, and serve as a template for primary piRNA production in the commonly used embryonic I. scapularis ISE6 cell line.
+Interestingly, we identified a two-fold enrichment of non-long terminal repeat (non-LTR) retrotransposons, in genomic proximity to NIRVS, contrasting with studeis in Ae.
+We characterised NIRVS phylogeny and integration patterns in the important vector, I. scapularis, revealing they are distinct from those in Aedes spp.
+Future studies will explore the possible antiviral mechanism conferred by NIRVS to I. scapularis,which may help the transmission of pathogenic arboviruses.
+Aim of this multicenter retrospective observational study was to evaluate whether poractant alfa use in pediatric ARDS might improve gas exchange in children less than 2 years old, according to a shared protocol.
+METHODS: The study was carried out in fourteen Italian PICUs after dissemination of a standardized protocol for surfactant administration within the Italian PICU network.
+The protocol provides the administration of surfactant (50 mg/kg) divided in two doses: the first dose is used as a bronchoalveolar lavage while the second as supplementation.
+RESULTS: Sixty-nine children, age 0–24 months, affected by Acute Respiratory Distress Syndrome treated with exogenous porcine surfactant were enrolled.
+The most frequent reasons for PICU admission were acute respiratory failure, mainly bronchiolitis and pneumonia, and septic shock.
+Fifty-four children (78.3%) had severe ARDS (define by oxygen arterial pressure and inspired oxygen fraction ratio (P/F) < 100), 15 (21.7%) had moderate ARDS (100 < P/F < 200).
+PO(2), P/F, Oxygenation Index (OI) and pH showed a significant improvement after surfactant use with respect to baseline (p < 0.001 at each included time-point for each parameter).
+No significant difference in blood gas variations were observed among four different subgroups of diseases (bronchiolitis, pneumonia, septic shock and others).
+CONCLUSION: The use of porcine Surfactant improves oxygenation, P/F ratio, OI and pH in a population of children with moderate or severe pARDS caused by multiple diseases.
+A shared protocol seems to be a good option to obtain the same criteria of enrollment among different PICUs and define a unique way of use and administration of the drug for future studies.
+Producing rhinovirus (RV) inocula from nasal secretions has required prolonged observation of the virus donor to exclude extraneous pathogens.
+We produced a RV-A16 inoculum using reverse genetics and determined the dose necessary to cause moderate colds in seronegative volunteers.
+METHODS: The consensus sequence of RV-A16 from a previous inoculum was cloned, and inoculum virus was produced using reverse genetics techniques.
+After safety testing, volunteers were inoculated with either RV-A16 (n = 26) or placebo (n = 10), Jackson cold scores were recorded, and nasal secretions were tested for shedding of RV-A16 ribonucleic acid.
+RESULTS: The reverse genetics process produced infectious virus that was neutralized by specific antisera and had a mutation rate similar to conventional virus growth techniques.
+The 1000 median tissue culture infectious dose (TCID(50)) dose produced moderate colds in most individuals with effects similar to that of a previously tested conventional RV-A16 inoculum.
+CONCLUSIONS: Reverse genetics techniques produced a RV-A16 inoculum that can cause clinical colds in seronegative volunteers, and they also serve as a stable source of virus for laboratory use.
+The recombinant production procedures eliminate the need to derive seed virus from nasal secretions, thus precluding introduction of extraneous pathogens through this route.
+ADP-ribosylation is a reversible chemical modification catalysed by ADP-ribosyltransferases such as PARPs that utilize nicotinamide adenine dinucleotide (NAD(+)) as a cofactor to transfer monomer or polymers of ADP-ribose nucleotide onto macromolecular targets such as proteins and DNA.
+ADP-ribosylation plays an important role in several biological processes such as DNA repair, transcription, chromatin remodelling, host-virus interactions, cellular stress response and many more.
+We demonstrate that the human PARPs - PARP10, PARP11 and PARP15 as well as a highly diverged PARP homologue TRPT1, ADP-ribosylate phosphorylated ends of RNA.
+We further reveal that ADP-ribosylation of RNA mediated by PARP10 and TRPT1 can be efficiently reversed by several cellular ADP-ribosylhydrolases (PARG, TARG1, MACROD1, MACROD2 and ARH3), as well as by MACROD-like hydrolases from VEEV and SARS viruses.
+Finally, we show that TRPT1 and MACROD homologues in bacteria possess activities equivalent to the human proteins.
+Our data suggest that RNA ADP-ribosylation may represent a widespread and physiologically relevant form of reversible ADP-ribosylation signalling.
+Autophagy, a highly regulated degradative process that promotes cellular homeostasis, is increasingly recognised as a fundamental component of the cellular response against viral infection.
+In this study, we investigated the role of autophagy during Junín virus (JUNV) multiplication using human A549 cells.
+We found that JUNV infection induces an increment of the LC3-II/LC3-I ratio, an accumulation of punctate pattern in RFP-LC3-transfected cells and the colocalisation of viral nucleoprotein and LC3 protein, suggesting autophagosome formation.
+JUNV infection also induced the degradation of the autophagy receptor p62, suggesting that complete autophagic flux was triggered.
+In addition, we showed that inhibition of autophagy with bafilomycin A1 or 3-methyladenine significantly reduces viral multiplication.
+Furthermore, JUNV infection induced the colocalisation of p62, ATG16, RAB5, RAB7A and LAMP1 with the autophagosomal LC3 protein.
+Finally, we demonstrated that siRNA experiments targeting essential autophagy genes (ATG5, ATG7 and Beclin 1) reduce viral protein synthesis and viral yield.
+PURPOSE: In Kawasaki disease (KD) patients, coronary artery complications, incomplete and refractory types occur more frequently in patients with streptococcal or other bacterial/viral infections.
+Recently, we observed a higher incidence of coronary lesions in KD patients with high anti-streptolysin O (ASO) titer.
+Therefore, we hypothesized that KD patients diagnosed with concurrent streptococcal infection have poor prognoses, with respect to treatment response and development of coronary artery lesions.
+METHODS: A retrospective review was performed in 723 patients with KD who were admitted to 2 major hospitals between June 2010 and September 2017.
+RESULTS: Among 723 patients with KD, 11 initially showed an elevated ASO titer (>320 IU/mL) or elevated follow-up ASO titer after treatment.
+Of these patients, 5 showed no response to the first intravenous immunoglobulin treatment, 3 had abnormalities of the coronary arteries.
+This is a significantly higher proportion of patients with a high ASO titer (n=3, 27.3%) than those with a normal ASO titer (n=53 [7.4%], P=0.047).
+A severe clinical course was seen in 81.8% of patients in the high ASO group versus 14.5% of patients in the normal ASO group.
+CONCLUSION: It is not certain whether acute streptococcal infection may cause KD, but this study revealed that KD with high ASO titers showed higher rates of severe clinical course.
+It may be helpful to analyze concurrent streptococcal infection in patients with a severe clinical course.
+The use of chemicals around the globe in different industries has increased tremendously, affecting the health of people.
+The modern world intends to replace these noxious chemicals with environmental friendly products for the betterment of life on the planet.
+Establishing enzymatic processes in spite of chemical processes has been a prime objective of scientists.
+Various enzymes, specifically microbial proteases, are the most essentially used in different corporate sectors, such as textile, detergent, leather, feed, waste, and others.
+As they are performing synthetic and degradative functions, proteases are found ubiquitously, such as in plants, animals, and microbes.
+Proteases are successfully considered as an alternative to chemicals and an eco-friendly indicator for nature or the surroundings.
+The evolutionary relationship among acidic, neutral, and alkaline proteases has been analyzed based on their protein sequences, but there remains a lack of information that regulates the diversity in their specificity.
+Researchers are looking for microbial proteases as they can tolerate harsh conditions, ways to prevent autoproteolytic activity, stability in optimum pH, and substrate specificity.
+The current review focuses on the comparison among different proteases and the current problems faced during production and application at the industrial level.
+Deciphering these issues would enable us to promote microbial proteases economically and commercially around the world.
+Recently, it has come to light that when these people infect others, the new infection is typically established by only one or a small number of virions from within this complex viral swarm.
+An important goal is to characterize the biological properties of HIV-1 virions that seed and exist early in new human infections because these are potentially the only viruses against which a prophylactic HIV-1 vaccine would need to elicit protection.
+This includes understanding how the Envelope (Env) protein of these virions interacts with the T-cell receptor CD4, which supports attachment and entry of HIV-1 into target cells.
+We examined early HIV-1 isolates for their ability to infect cells via the CD4 receptor of 15 different primate species.
+Primates were the original source of HIV-1 and now serve as valuable animal models for studying HIV-1.
+We find that most primary isolates of HIV-1 from the blood, including early isolates, are highly selective and enter cells through some primate CD4 receptor orthologs but not others.
+This phenotype is remarkably consistent, regardless of route of transmission, viral subtype, or time of isolation post infection.
+We show that the weak CD4 binding affinity of blood-derived HIV-1 isolates is what makes them sensitive to the small sequence differences in CD4 from one primate species to the next.
+To substantiate this, we engineered an early HIV-1 Env to have high, medium, or low binding affinity to CD4, and we show that it loses the ability to enter cells via the CD4 receptor of many primate species as the binding affinity gets weaker.
+Based on the phenotype of selective use of primate CD4, we find that weak CD4 binding appears to be a nearly universal property of HIV-1 circulating in the bloodstream.
+Therefore, weak binding to CD4 must be a selected and important property in the biology of HIV-1 in the body.
+We identify six primate species that encode CD4 receptors that fully support the entry of early HIV-1 isolates despite their low binding affinity for CD4.
+These findings will help inform long-standing efforts to model HIV-1 transmission and early disease in primates.
+Streptococcus agalactiae (Group B Streptococcus, GBS) normally colonizes healthy adults but can cause invasive disease, such as meningitis, in the newborn.
+To gain access to the central nervous system, GBS must interact with and penetrate brain or meningeal blood vessels; however, the exact mechanisms are still being elucidated.
+Here, we investigate the contribution of BspC, an antigen I/II family adhesin, to the pathogenesis of GBS meningitis.
+Disruption of the bspC gene reduced GBS adherence to human cerebral microvascular endothelial cells (hCMEC), while heterologous expression of BspC in non-adherent Lactococcus lactis conferred bacterial attachment.
+In a murine model of hematogenous meningitis, mice infected with ΔbspC mutants exhibited lower mortality as well as decreased brain bacterial counts and inflammatory infiltrate compared to mice infected with WT GBS strains.
+We determined that BspC interacts with the host cytoskeleton component vimentin and confirmed this interaction using a bacterial two-hybrid assay, microscale thermophoresis, immunofluorescent staining, and imaging flow cytometry.
+Vimentin null mice were protected from WT GBS infection and also exhibited less inflammatory cytokine production in brain tissue.
+These results suggest that BspC and the vimentin interaction is critical for the pathogenesis of GBS meningitis.
+Plasmodium vivax parasites preferentially invade reticulocyte cells in a multistep process that is still poorly understood.
+In this study, we used ex vivo invasion assays and population genetic analyses to investigate the involvement of complement receptor 1 (CR1) in P. vivax invasion.
+First, we observed that P. vivax invasion of reticulocytes was consistently reduced when CR1 surface expression was reduced through enzymatic cleavage, in the presence of naturally low-CR1-expressing cells compared with high-CR1-expressing cells, and with the addition of soluble CR1, a known inhibitor of P. falciparum invasion.
+In addition, analysis of CR1 genetic data for worldwide human populations with different exposure to malaria parasites show significantly higher frequency of CR1 alleles associated with low receptor expression on the surface of RBCs and higher linkage disequilibrium in human populations exposed to P. vivax malaria compared with unexposed populations.
+Collectively, our findings demonstrate that CR1 availability on the surface of RBCs modulates P. vivax invasion.
+The identification of new molecular interactions is crucial to guiding the rational development of new therapeutic interventions against vivax malaria.
+BACKGROUND: In summer 2014, an autochthonous outbreak of dengue occurred in Tokyo, Japan, in which Yoyogi Park acted as the focal area of transmission.
+Recognizing the outbreak, concerted efforts were made to control viral spread, which included mosquito control, public announcement of the outbreak, and a total ban on entering the park.
+Using dates of exposure and illness onset, we categorized cases into three groups according to the availability of these datasets.
+The infection process was parametrically modeled by generation, and convolution of the infection process and the incubation period was fitted to the data.
+By estimating the effective reproduction number, we determined that the effect of dengue risk communication together with mosquito control from 28 August 2014 was insufficiently large to lower the reproduction number to below 1.
+However, once Yoyogi Park was closed on 4 September, the value of the effective reproduction number began to fall below 1, and the associated relative reduction in the effective reproduction number was estimated to be 20%–60%.
+CONCLUSIONS/SIGNIFICANCE: Regardless of the assumed number of generations of cases, the combined effect of mosquito control, risk communication, and park closure appeared to be successful in interrupting the chain of dengue transmission in Tokyo.
+The Golgi apparatus is a membrane-bound organelle that serves as the center for trafficking and processing of proteins and lipids.
+To perform these functions, the Golgi forms a multilayer stacked structure held by GRASP55 and GRASP65 trans-oligomers and perhaps their binding partners.
+Depletion of GRASP proteins disrupts Golgi stack formation and impairs critical functions of the Golgi, such as accurate protein glycosylation and sorting.
+Interestingly, GRASP depletion reduces the protein level of α5β1 integrin, the major cell adhesion molecule at the surface of HeLa and MDA-MB-231 cells, due to decreased integrin protein synthesis.
+These new findings enrich our understanding on the role of the Golgi in cell physiology and provide a potential target for treating protein-trafficking disorders.
+The H9N2 subtype of avian influenza A viruses (AIV) has spread among domestic poultry and wild birds worldwide.
+A total of 42 laboratory‐confirmed cases of non‐fatal human infection with the Eurasian Y280 and G1 lineages have been reported in China, Hong Kong, Bangladesh and Egypt since 1997.
+H9N2 AIV infections in poultry have become endemic in Asia and the Middle East and are a major source of viral internal genes for other AIV subtypes, such that continuous monitoring of H9N2 AIV is recommended.
+In this study, a new, one‐step, real‐time RT‐PCR assay was developed to detect two major Eurasian H9 lineages of AIV capable of causing human infection.
+The sensitivity of this assay was determined using in vitro‐transcribed RNA, and the detection limit was approximately 3 copies/reaction.
+In this assay, no cross‐reactivity was observed against RNA from H1–15 subtypes of influenza A viruses, influenza B viruses and other viral respiratory pathogens.
+In addition, this assay could detect the H9 hemagglutinin (HA) gene from artificially reconstituted clinical samples spiked with H9N2 virus without any non‐specific reactions.
+The assay is useful both for diagnostic purposes in cases of suspected human infection with influenza H9N2 viruses and for the surveillance of both avian and human influenza viruses.
+Although F. tularensis is considered to be a potential biological weapon due to its high infectivity and mortality rate, no vaccine has been currently licensed.
+Recently, we reported that F. tularensis SCHU P9 derived ΔpdpC strain lacking the pathogenicity determinant protein C gene conferred stable and good protection in a mouse lethal model.
+In this study, the protective effect of ΔpdpC was evaluated using a monkey lethal model.
+Two cynomolgus macaques (Macaca fascicularis) intratracheally challenged with the virulent strain SCHU P9 were euthanized on 7 and 11 days post-challenge after the development of severe clinical signs.
+The bacterial replication in alveolar macrophages and type II epithelial cells in the lungs would cause severe pneumonia accompanied by necrosis.
+Though one of the two animals developed mild symptoms of tularemia, bacterial replication was limited in the respiratory organs, which may be due to a high level of humoral and cellular immune responses against F. tularensis.
+These results suggest that the ΔpdpC mutant would be a safe and promising candidate as a live attenuated tularemia vaccine.
+At the outset, mass-gathering events provide challenging settings to plan a suitable emergency public health response.
+Published studies basically talk about retrospective reviews, case studies of the public health preparedness, or health care provided at individual events.
+Developing an understanding of the variables associated with MGs is the first step for public health managers.
+Risk assessment (RA) is a crucial part of pre-event planning as it helps foresee potential risks.
+Based on RA, one can develop preventive measures and ensure that the infrastructure to control the potential problems is in place.
+This study is an attempt to systemize RA process during MG events in a country that is culturally rich but with poor resources to handle such events.
+A RA tool will be developed for planning and management of religious MG events of India.
+Extensive review of literature clubbed with key informant interviews will be done in order to identify the risk variables and decide the domains and items of the tool.
+The feasibility of the mobile-based RA tool will be tested in real-time MG event in one part of the country.
+Concurrently in the same event, a community survey of residents and visitors will be done in order to assess public perceptions of public health and environmental risks associated with MG events.
+DISCUSSION: The findings of this study will provide insights into the public health and environmental concerns that need to be considered if preventive strategies and intervention programs are to be designed for MG events.
+A “RA Tool,” which can be used in the planning and management of MG events by the public health managers will strengthen the existing health systems preparedness plans for MGs.
+Recently identified broadly neutralizing antibodies (bnAbs) show great potential for clinical interventions against HIV-1 infection.
+Here, we report on the identification and characterization of a panel of HIV-1 strains with broad and potent resistance against a large number of bnAbs, particularly those targeting the CD4-binding site (CD4bs).
+Site-directed mutagenesis revealed that several key epitope mutations facilitate resistance and are located in the inner domain, loop D, and β23/loop V5/β24 of HIV-1 gp120.
+The resistance is largely correlated with binding affinity of antibodies to the envelope trimers expressed on the cell surface.
+Our results therefore demonstrate the existence of broadly resistant HIV-1 strains against CD4bs neutralizing antibodies.
+Treatment strategies based on the CD4bs bnAbs must overcome such resistance to achieve optimal clinical outcomes.
+Pemphigus vulgaris (PV) is an autoimmune bullous disease of the skin and mucous membranes characterized by the presence of circulating and tissue-bound autoantibodies against keratinocyte cell surface antigens, specifically desmoglein (Dsg) 1 and 3.
+The pathogenic role of anti-Dsg antibodies is well-established, while the mechanism of blister formation is only partly defined.
+We have applied a previously developed method for the efficient immortalization of IgG+ memory B cells to identify novel target antigens in PV.
+Immunoprecipitation and immunoblotting studies with keratinocyte extracts indicated α-catenin as the putative antigen, then confirmed by immunoblotting on the recombinant protein.
+Although the isolated human monoclonal antibody was per se unable to dissociate keratinocyte monolayers and also to synergize with a pathogenic antibody in vitro, further studies are warranted to assess its possible in vivo contribution in the multifactorial pathogenesis and heterogeneous manifestations of PV disease.
+In addition, bats have a low incidence of cancer, but the mechanisms underlying this phenomenon remain elusive.
+Here we discovered that bat cells are more resistant than human and mouse cells to DNA damage induced by genotoxic drugs.
+We found that bat cells accumulate less chemical than human and mouse cells, and efficient drug efflux mediated by the ABC transporter ABCB1 underlies this improved response to genotoxic reagents.
+ABCB1 is expressed at higher levels in several cell lines and tissues derived from bats compared to humans.
+Furthermore, increased drug efflux and high expression of ABCB1 are conserved across multiple bat species.
+Our findings suggest that enhanced efflux protects bat cells from DNA damage induced by genotoxic compounds, which may contribute to their low cancer incidence.
+INTRODUCTION: Bovine parainfluenza virus-3 (BPIV3) and bovine respiratory syncytial virus (BRSV) are the cause of respiratory disease in cattle worldwide.
+The aim of the study was the detection and molecular characterisation of BPIV3 and BRSV from nasal swabs and lung samples of cows in and around the Erzurum region of eastern Turkey.
+The age of the animals was between 9 months and 5 years, mean 1.4 years.
+Most males were in the fattening period and being raised in open sheds; females were in the lactating period and kept in free stall barns.
+Gene-specific primers in a molecular method (RT-PCR) identified BRSV (fusion gene) and BPIV3 (matrix gene) strains at the genus level.
+RESULTS: RNA from BRSV and BPIV3 was detected in two (1.29%) and three (1.93%) samples, respectively, one of each of which was sequenced and the sequences were aligned with reference virus strains.
+CONCLUSION: The results indicate that BRSV and BPIV3 contribute to bovine respiratory disease cases in Turkey.
+This is the first report on their detection and molecular characterisation in ruminants in Turkey.
+Infections with immunosuppressive pigeon circovirus (PiCV) pose the most severe health problem to the global pigeon breeding.
+The vaccination with immunogenic PiCV recombinant capsid protein (PiCV rCP) is a potential tool for disease control.
+Because of the high prevalence of PiCV asymptomatic infections, the subclinically infected pigeons will be vaccinated in practice.
+The aim of this study was to answer a question if vaccination of asymptomatic, infected with PiCV pigeons induces a similar immune response to PiCV rCP as in uninfected birds.
+One hundred and twenty 6-week-old carrier pigeons were divided into 4 groups (2 groups of naturally infected and uninfected with PiCV individuals).
+Birds from groups V and V1 were vaccinated twice with PiCV rCP mixed with an adjuvant, whereas pigeons from groups C and C1 were immunized with an adjuvant only.
+The expression of genes encoding IFN-γ, CD4, and CD8 T lymphocyte receptors; the number of anti-PiCV rCP IgY-secreting B cells (SBC) and anti-PiCV rCP IgY were evaluated 2, 21, 39 and 46 days post vaccination (dpv).
+Study results showed that the expression of CD8 and IFN-γ genes was higher in both groups of infected pigeons than in the uninfected birds, irrespective of vaccination.
+In the uninfected birds, the expression of these genes was insignificantly higher in the vaccinated pigeons.
+The anti-PiCV rCP IgY-SBC were detected on 2 and 23 dpv and seroconversion was noted on 23 and 39 dpv in V and V1 groups, respectively.
+In the light of the results obtained, it could be concluded that pigeon circovirus recombinant capsid protein elicits the immune response in both naturally infected and uninfected pigeons, but its rate varies depending on PiCV infectious status.
+The infection with PiCV masks the potential cellular immune response to the vaccination with PiCV rCP and leads to the suppression of humoral immunity.
+To probe the effect of 3′,8″-dimerization on antioxidant flavonoids, acacetin and its 3′,8″-dimer isoginkgetin were comparatively analyzed using three antioxidant assays, namely, the ·O(2)(−) scavenging assay, the Cu(2+) reducing assay, and the 2,2′-azino bis(3-ethylbenzothiazolin-6-sulfonic acid) radical scavenging assay.
+Subsequently, the acacetin was incubated with 4-methoxy-2,2,6,6-tetramethylpiperidine-1-oxy radicals (4-methoxy-TEMPO) and then analyzed by ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry (UHPLC−ESI−Q−TOF−MS) technology.
+The results of the UHPLC−ESI−Q−TOF−MS analysis suggested the presence of a dimer with m/z 565, 550, 413, 389, 374, 345, 330, and 283 peaks.
+By comparison, standard isoginkgetin yielded peaks at m/z 565, 533, 518, 489, 401, 389, 374, and 151 in the mass spectra.
+Based on these experimental data, MS interpretation, and the relevant literature, we concluded that isoginkgetin had higher electron transfer potential than its monomer because of the 3′,8″-dimerization.
+Additionally, acacetin can produce a dimer during its antioxidant process; however, the dimer is not isoginkgetin.
+Chronic hepatitis B virus (HBV) infection represents a worldwide public health concern with approximately 250 million people chronically infected and at risk of developing liver cirrhosis and hepatocellular carcinoma.
+Nucleos(t)ide analogues (NUC) are the most widely used therapies for HBV infection, but they often require long-lasting administration to avoid the risk of HBV reactivation at withdrawal.
+Therefore, there is an urgent need to develop novel treatments to shorten the duration of NUC therapy by accelerating virus control, and to complement the effect of available anti-viral therapies.
+In chronic HBV infection, virus-specific T cells are functionally defective, and this exhaustion state is a key determinant of virus persistence.
+Reconstitution of an efficient anti-viral T cell response may thus represent a rational strategy to treat chronic HBV patients.
+In this perspective, the enhancement of adaptive immune responses by a checkpoint inhibitor blockade, specific T cell vaccines, lymphocyte metabolism targeting, and autologous T cell engineering, including chimeric antigen receptor (CAR) and TCR-redirected T cells, constitutes a promising immune modulatory approach for a therapeutic restoration of protective immunity.
+The advances of the emerging immune-based therapies in the setting of the HBV research field will be outlined.
+In the USA and other western nations, respiratory syncytial virus is one of the most commonly encountered respiratory viruses among patients who have been diagnosed with a hematologic malignancy or who have undergone a stem cell transplant.
+Multiple studies have been performed to evaluate the complications associated with respiratory syncytial virus infections.
+Other studies have evaluated therapeutic agents and strategies in which these agents can be used.
+There have also been numerous reports of outbreaks in bone marrow transplant units and oncology wards, where infection control measures have been invaluable in controlling the spread of disease.
+However, despite these novel approaches, respiratory syncytial virus continues to be potentially fatal in immunocompromised populations.
+In this review, we discuss the incidence of respiratory syncytial viral infections, risk factors associated with progression from upper respiratory tract infection to lower respiratory tract infection, other complications and outcomes (including mortality), management strategies, and prevention strategies in patients with a hematologic malignancy and in hematopoietic cell transplant recipients.
+Households are natural targets for control interventions, but quantification of the contribution of household transmission to overall spread is needed to guide policy.
+We developed a modeling framework to evaluate this contribution and key epidemic features of the ZIKV epidemic in Martinique in 2015–2016 from the joint analysis of a household transmission study (n = 68 households), a study among symptomatic pregnant women (n = 281), and seroprevalence surveys of blood donors (n = 457).
+We estimated that the probability of mosquito-mediated within-household transmission (from an infected member to a susceptible one) was 21% (95% credible interval (CrI): 5, 51), and the overall probability of infection from outside the household (i.e., in the community) was 39% (95% CrI: 27, 50).
+Overall, 50% (95% CrI: 43, 58) of the population was infected, with 22% (95% CrI: 5, 46) of infections acquired in households and 40% (95% CrI: 23, 56) being asymptomatic.
+The probability of presenting with Zika-like symptoms due to another cause was 16% (95% CrI: 10, 23).
+This study characterized the contribution of household transmission in ZIKV epidemics, demonstrating the benefits of integrating multiple data sets to gain more insight into epidemic dynamics.
+Innate immune interferons (IFNs), particularly type I IFNs, are primary mediators regulating animal antiviral, antitumor, and cell-proliferative activity.
+These antiviral cytokines have evolved remarkable molecular and functional diversity to confront ever-evolving viral threats and physiological regulation.
+We have annotated IFN gene families across 110 animal genomes, and showed that IFN genes, after originating in jawed fishes, had several significant evolutionary surges in vertebrate species of amphibians, bats and ungulates, particularly pigs and cattle.
+For example, pigs have the largest but still expanding type I IFN family consisting of nearly 60 IFN-coding genes that encode seven IFN subtypes including multigene subtypes of IFN-α, -δ, and -ω.
+Whereas, subtypes such as IFN-α and -β have been widely studied in many species, the unconventional subtypes such as IFN-ω have barely been investigated.
+We have cross-species defined the IFN evolution, and shown that unconventional IFN subtypes particularly the IFN-ω subtype have evolved several novel features including: (1) being a signature multi-gene subtype expanding primarily in mammals such as bats and ungulates, (2) emerging isoforms that have superior antiviral potency than typical IFN-α, (3) highly cross-species antiviral (but little anti-proliferative) activity exerted in cells of humans and other mammalian species, and (4) demonstrating potential novel molecular and functional properties.
+This study focused on IFN-ω to investigate the immunogenetic evolution and functional diversity of unconventional IFN subtypes, which may further IFN-based novel antiviral design pertinent to their cross-species high antiviral and novel activities.
+Metagenomics is helping to expand the known diversity of viruses, especially of those with poorly studied hosts in remote areas.
+The Neotropical region harbors a considerable diversity of avian species that may play a role as both host and short-distance vectors of unknown viruses.
+Viral metagenomics of cloacal swabs from 50 Neotropical birds collected in French Guiana revealed the presence of four complete astrovirus genomes.
+They constitute an early diverging novel monophyletic clade within the Avastrovirus phylogeny, representing a putative new astrovirus species (provisionally designated as Avastrovirus 5) according to the International Committee on Taxonomy of Viruses (ICTV) classification criteria.
+The pan-astrovirus RT-PCR analysis of the cloacal samples of 406 wild Neotropical birds showed a community-level prevalence of 4.9% (5.1% in passerines, the highest described so far in this order of birds).
+By screening birds of a remote region, we expanded the known host range of astroviruses to the avian families Cardinalidae, Conopophagidae, Furnariidae, Thamnophilidae, Turdidae and Tyrannidae.
+Our results provide important first insights into the unexplored viral communities, the ecology, epidemiology and features of host-pathogen interactions that shape the evolution of avastroviruses in a remote Neotropical rainforest.
+The repair of white matter damage is of paramount importance for functional recovery after brain injuries.
+IL-4 receptor expression was detected in a variety of glial cells after ischemic brain injury, including oligodendrocyte lineage cells.
+IL-4 deficiency in knockout mice resulted in greater deterioration of white matter over 14 d after stroke.
+Consistent with these findings, intranasal delivery of IL-4 nanoparticles after stroke improved white matter integrity and attenuated long-term sensorimotor and cognitive deficits in wild-type mice, as revealed by histological immunostaining, electron microscopy, diffusion tensor imaging, and electrophysiology.
+The selective effect of IL-4 on remyelination was verified in an ex vivo organotypic model of demyelination.
+By leveraging primary oligodendrocyte progenitor cells (OPCs), microglia-depleted mice, and conditional OPC-specific peroxisome proliferator-activated receptor gamma (PPARγ) knockout mice, we discovered a direct salutary effect of IL-4 on oligodendrocyte differentiation that was mediated by the PPARγ axis.
+Our findings reveal a new regenerative role of IL-4 in the central nervous system (CNS), which lies beyond its known immunoregulatory functions on microglia/macrophages or peripheral lymphocytes.
+Therefore, intranasal IL-4 delivery may represent a novel therapeutic strategy to improve white matter integrity in stroke and other brain injuries.
+Senescence is a cellular phenotype present in health and disease, characterized by a stable cell-cycle arrest and an inflammatory response called senescence-associated secretory phenotype (SASP).
+The SASP is important in influencing the behavior of neighboring cells and altering the microenvironment; yet, this role has been mainly attributed to soluble factors.
+Here, we show that both the soluble factors and small extracellular vesicles (sEVs) are capable of transmitting paracrine senescence to nearby cells.
+Analysis of individual cells internalizing sEVs, using a Cre-reporter system, show a positive correlation between sEV uptake and senescence activation.
+sEV protein characterization by mass spectrometry (MS) followed by a functional siRNA screen identify interferon-induced transmembrane protein 3 (IFITM3) as being partially responsible for transmitting senescence to normal cells.
+Sepsis involves a disordered host response to systemic infection leading to high morbidity and mortality.
+The cornerstone of sepsis research is the development of animal models to mimic human bacterial infections and test novel pharmacologic targets.
+Nonhuman primates (NHPs) have served as an attractive, but expensive, animal to model human bacterial infections due to their nearly identical cardiopulmonary anatomy and physiology, as well as host response to infection.
+Several NHP species have provided substantial insight into sepsis-mediated inflammation, endothelial dysfunction, acute lung injury, and multi-organ failure.
+The use of NHPs has usually focused on translating therapies from early preclinical models to human clinical trials.
+However, despite successful sepsis interventions in NHP models, there are still no FDA-approved sepsis therapies.
+This review highlights major NHP models of bacterial sepsis and their relevance to clinical medicine.
+African swine fever virus (ASFV) is a complex, cytoplasmic double-stranded DNA (dsDNA) virus that is currently expanding throughout the world.
+Currently, circulating virulent genotype II Armenia/07-like viruses cause fatal disease in pigs and wild boar, whereas attenuated strains induce infections with various levels of chronic illness.
+Sensing cytosolic dsDNA, mainly by the key DNA sensor cyclic GMP-AMP synthase (cGAS), leads to the synthesis of type I interferon and involves signaling through STING, TBK1, and IRF3.
+After phosphorylation, STING translocates from the endoplasmic reticulum to the Golgi compartment and to the perinuclear region, acting as an indispensable adaptor connecting the cytosolic detection of DNA to the TBK1-IRF3 signaling pathway.
+We demonstrate here that attenuated NH/P68, but not virulent Armenia/07, activates the cGAS-STING-IRF3 cascade very early during infection, inducing STING phosphorylation and trafficking through a mechanism involving cGAMP.
+Both TBK1 and IRF3 are subsequently activated and, in response to this, a high level of beta interferon (IFN-β) was produced during NH/P68 infection; in contrast, Armenia/07 infection generated IFN-β levels below those of uninfected cells.
+Our results show that virulent Armenia/07 ASFV controls the cGAS-STING pathway, but these mechanisms are not at play when porcine macrophages are infected with attenuated NH/P68 ASFV.
+These findings show for the first time the involvement of the cGAS-STING-IRF3 route in ASFV infection, where IFN-β production or inhibition was found after infection by attenuated or virulent ASFV strains, respectively, thus reinforcing the idea that ASFV virulence versus attenuation may be a phenomenon grounded in ASFV-mediated innate immune modulation where the cGAS-STING pathway might play an important role.
+IMPORTANCE African swine fever, a devastating disease for domestic pigs and wild boar, is currently spreading in Europe, Russia, and China, becoming a global threat with huge economic and ecological consequences.
+One interesting aspect of ASFV biology is the molecular mechanism leading to high virulence of some strains compared to more attenuated strains, which produce subclinical infections.
+In this work, we show that the presently circulating virulent Armenia/07 virus blocks the synthesis of IFN-β, a key mediator between the innate and adaptive immune response.
+In contrast, the cGAS-STING pathway is efficiently activated during NH/P68 attenuated strain infection, leading to the production of large amounts of IFN-β.
+Our results show for the first time the relationship between the cGAS-STING pathway and ASFV virulence, contributing to uncover the molecular mechanisms of ASFV virulence and to the rational development of ASFV vaccines.
+In Sinorhizobium meliloti, the tryptophan (Trp) biosynthesis genes are organized into three operons, trpE(G), ppiD-trpDC-moaC-moeA, and trpFBA-accD-folC, of which only the first one, trpE(G), contains a short ORF (trpL) in the 5′-UTR and is regulated by transcription attenuation.
+Under conditions of Trp sufficiency, transcription is terminated between trpL and trpE(G), and a small attenuator RNA, rnTrpL, is produced.
+Here, we show that rnTrpL base-pairs with trpD and destabilizes the polycistronic trpDC mRNA, indicating rnTrpL-mediated downregulation of the trpDC operon in trans.
+Although all three trp operons are regulated in response to Trp availability, only in the two operons trpE(G) and trpDC the Trp-mediated regulation is controlled by rnTrpL.
+Together, our data show that the trp attenuator coordinates trpE(G) and trpDC expression posttranscriptionally by two fundamentally different mechanisms: ribosome-mediated transcription attenuation in cis and base-pairing in trans.
+Also, we present evidence that rnTrpL-mediated regulation of trpDC genes expression in trans is conserved in Agrobacterium and Bradyrhizobium, suggesting that the small attenuator RNAs may have additional conserved functions in the control of bacterial gene expression.
+BACKGROUND: Avian infectious bronchitis virus (IBV) is a major respiratory disease-causing agent in birds that leads to significant losses.
+Dendritic cells (DCs) are specialised cells responsible for sampling antigens and presenting them to T cells, which also play an essential role in recognising and neutralising viruses.
+Expression of host non-coding RNAs changes markedly during infectious bronchitis virus infection, but their role in regulating host immune function has not been explored.
+Here, microarrays of mRNAs, miRNAs, and lncRNAs were globally performed to analyse how avian DCs respond to IBV.
+RESULTS: First, we found that IBV stimulation did not enhance the maturation ability of avian DCs.
+Interestingly, inactivated IBV was better able than IBV to induce DC maturation and activate lymphocytes.
+Gene Ontology analysis suggested that cellular macromolecule and protein location (GO-BP) and transcription factor binding (GO-MF) were abundant in IBV-stimulated avian DCs.
+Meanwhile, pathway analysis indicated that the oxidative phosphorylation and leukocyte transendothelial migration signalling pathways might be activated in the IBV group.
+Moreover, alteration of microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) was detected in IBV-stimulated avian DCs.
+In total, 19 significantly altered (7 up and 12 down) miRNAs and 101 (75 up and 26 down) lncRNAs were identified in the IBV-treated group.
+Further analysis showed that the actin cytoskeleton and MAPK signal pathway were related to the target genes of IBV-stimulated miRNAs.
+Finally, our study identified 2 TF-microRNA and 53 TF–microRNA–mRNA interactions involving 1 TF, 2 miRNAs, and 53 mRNAs in IBV-stimulated avian DCs.
+CONCLUSIONS: Our research suggests a new mechanism to explain why IBV actively blocks innate responses needed for inducing immune gene expression and also provides insight into the pathogenic mechanisms of avian IBV.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12864-019-5940-6) contains supplementary material, which is available to authorized users.
+BACKGROUND: T cell immunoglobulin mucin domain-1 (TIM-1) is a phosphatidylserine (PS) receptor, mediating filovirus entry into cells through interactions with PS on virions.
+TIM-1 expression has been implicated in Ebola virus (EBOV) pathogenesis; however, it remains unclear whether this is due to TIM-1 serving as a filovirus receptor in vivo or, as others have suggested, TIM-1 induces a cytokine storm elicited by T cell/virion interactions.
+Here, we use a BSL2 model virus that expresses EBOV glycoprotein to demonstrate the importance of TIM-1 as a virus receptor late during in vivo infection.
+METHODOLOGY/PRINCIPAL FINDINGS: Infectious, GFP-expressing recombinant vesicular stomatitis virus encoding either full length EBOV glycoprotein (EBOV GP/rVSV) or mucin domain deleted EBOV glycoprotein (EBOV GPΔO/rVSV) was used to assess the role of TIM-1 during in vivo infection.
+While G/rVSV caused profound morbidity and mortality in both mouse strains, TIM-1-deficient mice had significantly better survival than TIM-1-expressing mice following EBOV GP/rVSV or EBOV GPΔO/rVSV challenge.
+EBOV GP/rVSV or EBOV GPΔO/rVSV in spleen of infected animals was high and unaffected by expression of TIM-1.
+However, infectious virus in serum, liver, kidney and adrenal gland was reduced late in infection in the TIM-1-deficient mice, suggesting that virus entry via this receptor contributes to virus load.
+Consistent with higher virus loads, proinflammatory chemokines trended higher in organs from infected TIM-1-sufficient mice compared to the TIM-1-deficient mice, but proinflammatory cytokines were more modestly affected.
+To assess the role of T cells in EBOV GP/rVSV pathogenesis, T cells were depleted in TIM-1-sufficient and -deficient mice and the mice were challenged with virus.
+CONCLUSIONS: Our studies provide evidence that at late times during EBOV GP/rVSV infection, TIM-1 increased virus load and associated mortality, consistent with an important role of this receptor in virus entry.
+This work suggests that inhibitors which block TIM-1/virus interaction may serve as effective antivirals, reducing virus load at late times during EBOV infection.
+Sport training leads to adaptation to physical effort that is reflected by the changes in blood parameters.
+In equine endurance athletes, blood testing is accepted as a support in training, however, only the changes before versus after exercise in creatine phosphokinase activity (CPK) and basic blood parameters are usually measured.
+This study is the first longitudinal investigation of the changes in routinely measured blood parameters and, additionally, serum amyloid A (SAA), during seven months, in Arabian horses introduced to endurance training and competing in events for young horses.
+It has been determined that CPK, aspartate aminotransferase (AST), packed cell volume (PCV), hemoglobin concentration, red blood cell count (RBC), and concentration of total serum protein (TSP) slightly increased after training sessions and competitions in similar manner.
+The increase in white blood cell (WBC) count was higher after competitions and SAA increased only after competitions.
+Total protein concentration was the only parameter that increased with training during a 7-month program.
+SAA indicated only in the case of heavy effort, and, it thus may be helpful in the monitoring of training in young horses.
+In an optimal program, its concentration should not increase after a training session but only after heavy effort, which should not be repeated too often.
+Differences among hosts, resulting from genetic variation in the immune system or heterogeneity in drug treatment, can impact within-host pathogen evolution.
+However, extensive and correlated genetic population structure in hosts and pathogens presents a substantial risk of confounding analyses.
+We present a Bayesian approach for detecting host influences on pathogen evolution that exploits vast existing data sets of pathogen diversity to improve power and control for stratification.
+The approach models key processes, including recombination and selection, and identifies regions of the pathogen genome affected by host factors.
+Our simulations and empirical analysis of drug-induced selection on the HIV-1 genome show that the method recovers known associations and has superior precision-recall characteristics compared to other approaches.
+We build a high-resolution map of HLA-induced selection in the HIV-1 genome, identifying novel epitope-allele combinations.
+BACKGROUND: Vernal keratoconjunctivitis (VKC) is a common eye disease and can result in permanent decrease or loss of vision.
+Herein, we described a proposed systemic review and meta-analysis to evaluate the clinical efficacy of HED for the treatment of VKC.
+METHODS: Six electronic databases (Medline, Embase, the Cochrane database, Chinese National Knowledge Infrastructure, Wanfang database, and Chinese Biology and Medicine database) will be searched for randomized controlled trials (RCTs) which evaluating the clinical efficacy of HED for the treatment of VKC.
+Data of the included studies will be extracted and the quality will also be evaluated.
+RESULTS: This study will provide high-quality systemic review and synthesis of RCTs on efficacy of HED for the treatment of VKC.
+CONCLUSION: This systemic review and meta-analysis will conclude the efficacy of HED for the treatment of VKC.
+BACKGROUND: Garcinia species contain bioactive compounds such as flavonoids, xanthones, triterpernoids, and benzophenones with antibacterial, antifungal, anti-inflammatory, and antioxidant activities.
+In addition, many of these compounds show interesting biological properties such as anti-human immunodeficiency virus activity.
+METHODS: This study was conducted to determine the effects of ethyl acetate (45 L Ea), ethanol (45 L Et), and hexane (45 L H) leaf extracts of G. parvifolia on the infectivity of pseudorabies virus (PrV) in Vero cells.
+The antiviral effects of the extracts were determined by cytopathic effect (CPE), inhibition, attachment, and virucidal assays.
+RESULTS: The 50% cytotoxicity concentration (CC(50)) values obtained were 237.5, 555.0, and < 1.25 μg/mL for 45 L Ea, 45 L Et, and 45 L H, respectively.
+The 45 L Ea showed the greatest viral inhibition potency of 75% at 125 μg/mL.
+Both 45 L Ea and 45 l Et caused 100% residual viral inhibition at 250 μg/mL.
+The selectivity index values for 45 L Ea, 45 L Et, and 45 L H were 2.65, 1.75, and 0.10 showing that 45 L Ea had the greatest antiviral activity among the three extracts.
+CONCLUSION: This study showed that ethyl acetate is the best solvent to be used to obtain extract from G. parvifolia leaves with potent antiviral activities.
+BACKGROUND: The major infectious diseases of hepatitis B has constituted an acute public health challenge in China.
+A national project of Community-based Collaborative Innovation HBV (CCI-HBV) demonstration areas has optimized the existing community healthcare resources and obtained initial results in HBV control.
+METHODS: Based on the existing community healthcare network, CCI-HBV project combined the community health management and health contract signing service for long-staying residents in hepatitis B screening.
+After screening, patients with seropositive results were enrolled in corresponding cohorts and received treatment at an early stage.
+And the uninfected people received medical supports including health education through new media, behavior intervention and HBV vaccinations.
+In this process, a cloud-based National Information Platform (NIP) was established to collect and store residents’ epidemiological data.
+RESULTS: After two rounds of screening, HBsAg positive rate dropped from 5.05% (with 5,173,003 people screened) to 4.57% (with 3,819,675 people screened), while the rate of new HBV infections was 0.28 per 100 person-years in the fixed cohorts of 2,584,322 people.
+The quality control team completed PPS sampling simultaneously and established the serum sample database with 2,800,000 serum samples for unified testing.
+CONCLUSIONS: CCI-HBV project has established a large-scale field research to conduct whole-population screening and intervention.
+We analyzed the HBsAg prevalence and new infection rate of HBV in the fixed population for the epidemic trend and intervention effect.
+The purpose of CCI-HBV project is to establish and evaluate a practical model of grid management and field strategy, to realize the new goal to control hepatitis B in China.
+TRIAL REGISTRATION: The project was funded by the Major Projects of Science Research for the 11th and 12th five-year plans of China, entitled “The prevention and control of AIDS, viral hepatitis and other major infectious diseases”, Grant Nos.
+Tyrosinase inhibitors improve skin whitening by inhibiting the formation of melanin precursors in the skin.
+The inhibitory activity of seven phlorotannins (1–7), triphlorethol A (1), eckol (2), 2-phloroeckol (3), phlorofucofuroeckol A (4), 2-O-(2,4,6-trihydroxyphenyl)-6,6′-bieckol (5), 6,8′-bieckol (6), and 8,8′-bieckol (7), from Ecklonia cava was tested against tyrosinase, which converts tyrosine into dihydroxyphenylalanine.
+Compounds 3 and 5 had IC(50) values of 7.0 ± 0.2 and 8.8 ± 0.1 μM, respectively, in competitive mode, with K(i) values of 8.2 ± 1.1 and 5.8 ± 0.8 μM.
+Both compounds showed the characteristics of slow-binding inhibitors over the time course of the enzyme reaction.
+With stable AutoDock scores of −6.59 and −6.68 kcal/mol, respectively, compounds 3 and 5 both interacted with His85 and Asn260 at the active site.
+The enzyme kynurenine aminotransferase (KAT) catalyses the conversion of kynurenine (KYN) to kynurenic acid (KYNA).
+Although the isozymes KAT1–4 have been identified, KYNA is mainly produced by KAT2 in brain tissues.
+KNYA is an antagonist of N-methyl-D-aspartate and α-7-nicotinic acetylcholine receptors, and accumulation of KYNA in the brain has been associated with the pathology of schizophrenia.
+Although currently available KAT2 inhibitors irreversibly bind to pyridoxal 5′-phosphate (PLP), inhibition via this mechanism may cause adverse side effects because of the presence of other PLP-dependent enzymes.
+Among these, glycyrrhizic acid (GL) and its analogues, glycyrrhetinic acid (GA) and carbenoxolone (CBX), were identified as KAT2 inhibitors.
+These compounds were highly selective for KAT2 and competed with its substrate KYN, but had no effects on the other 3 KAT isozymes.
+Furthermore, we demonstrated that in complex structures that were predicted in docking calculations, GL, GA and CBX were located on the same surface as the aromatic ring of KYN.
+These results indicate that GL and its analogues are highly selective and competitive inhibitors of KAT2.
+Bats, unique among mammals with powered flight, have many species with the longest size-proportionate lifespan of all mammals.
+Heat shock protein (HSP), highly conserved master regulators of cell stress, expression was examined across tissues and various cell lines in bats.
+Basal expression level of major HSPs (HSP70 and HSP90) is significantly higher in two different bat species compared to other mammals.
+This HSP expression could be a bat-unique, key factor to modulate cellular stress and death.
+Consequently, bat cells survive prolonged heat treatment, along with other stress stimuli, in a HSP-dependent manner, whereas other mammalian cells succumbed.
+This suggests HSP expression in bats could be an important adaption to intrinsic metabolic stresses like flight and therefore an important model to study stress resilience and longevity in general.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12192-019-01013-y) contains supplementary material, which is available to authorized users.
+The initial step of retrovirus entry—the interaction between the virus envelope glycoprotein trimer and a cellular receptor—is complex, involving multiple, noncontiguous determinants in both proteins that specify receptor choice, binding affinity and the ability to trigger conformational changes in the viral glycoproteins.
+Despite the complexity of this interaction, retroviruses have the ability to evolve the structure of their envelope glycoproteins to use a different cellular protein as receptors.
+The highly homologous subgroup A to E Avian Sarcoma and Leukosis Virus (ASLV) glycoproteins belong to the group of class 1 viral fusion proteins with a two-step triggering mechanism that allows experimental access to intermediate structures during the fusion process.
+We and others have taken advantage of replication-competent ASLVs and exploited genetic selection strategies to force the ASLVs to naturally evolve and acquire envelope glycoprotein mutations to escape the pressure on virus entry and still yield a functional replicating virus.
+This approach allows for the simultaneous selection of multiple mutations in multiple functional domains of the envelope glycoprotein that may be required to yield a functional virus.
+Here, we review the ASLV family and experimental system and the reverse engineering approaches used to understand the evolution of ASLV receptor usage.
+Background: Nebulised medical aerosols are designed to deliver drugs to the lungs to aid in the treatment of respiratory diseases.
+However, an unintended consequence is the potential for fugitive emissions during patient treatment, which may pose a risk factor in both clinical and homecare settings.
+Methods: The current study examined the potential for fugitive emissions, using albuterol sulphate as a tracer aerosol during high-flow therapy.
+A nasal cannula was connected to a head model or alternatively, a interface was connected to a tracheostomy tube in combination with a simulated adult and paediatric breathing profile.
+Two aerodynamic particle sizers (APS) recorded time-series aerosol concentrations and size distributions at two different distances relative to the simulated patient.
+Results: The results showed that the quantity and characteristics of the fugitive emissions were influenced by the interface type, patient type and supplemental gas-flow rate.
+There was a trend in the adult scenarios; as the flow rate increased, the fugitive emissions and the mass median aerodynamic diameter (MMAD) of the aerosol both decreased.
+The fugitive emissions were comparable when using the adult breathing profiles for the nasal cannula and tracheostomy interfaces; however, there was a noticeable distinction between the two interfaces when compared for the paediatric breathing profiles.
+The highest recorded aerosol concentration was 0.370 ± 0.046 mg m(−3) from the tracheostomy interface during simulated paediatric breathing with a gas-flow rate of 20 L/min.
+The averaged MMAD across all combinations ranged from 1.248 to 1.793 µm by the APS at a distance of 0.8 m away from the patient interface.
+Conclusions: Overall, the results highlight the potential for secondary inhalation of fugitive emissions released during simulated aerosol treatment with concurrent high-flow therapy.
+The findings will help in developing policy and best practice for risk mitigation from fugitive emissions.
+The clinical manifestations of infections are often mild, but infections may also lead to respiratory symptoms, gastroenteritis, myocarditis, meningitis, hepatitis, and poliomyelitis, with serious impacts on human health and economic losses in animal husbandry.
+Thus far, research on picornaviruses has mainly focused on structural proteins such as VP1, whereas the non-structural protein 2B, which plays vital roles in the life cycle of the viruses and exhibits a viroporin or viroporin-like activity, has been overlooked.
+Viroporins are viral proteins containing at least one amphipathic α-helical structure, which oligomerizes to form transmembrane hydrophilic pores.
+In this review, we mainly summarize recent research data on the viroporin or viroporin-like activity of 2B proteins, which affects the biological function of the membrane, regulates cell death, and affects the host immune response.
+Considering these mechanisms, the potential application of the 2B protein as a candidate target for antiviral drug development is discussed, along with research challenges and prospects toward realizing a novel treatment strategy for picornavirus infections.
+Adenovirus vectored vaccines are a highly effective strategy to induce cellular immune responses which are particularly effective against intracellular pathogens.
+Recombinant simian adenovirus vectors were developed to circumvent the limitations imposed by the use of human adenoviruses due to widespread seroprevalence of neutralising antibodies.
+We have constructed a replication deficient simian adenovirus-vectored vaccine (ChAdOx2) expressing 4 genes from the Mycobacterium avium subspecies paratuberculosis (AhpC, Gsd, p12 and mpa).
+Safety and T-cell immunogenicity results of the first clinical use of the ChAdOx2 vector are presented here.
+DNA vaccines present one of the most cost-effective platforms to develop global vaccines, which have been tested for nearly three decades in preclinical and clinical settings with some success in the clinic.
+However, one of the major challenges for the development of DNA vaccines is their poor immunogenicity in humans, which has led to refinements in DNA delivery, dosage in prime/boost regimens and the inclusion of adjuvants to enhance their immunogenicity.
+In this review, we focus on adjuvants that can enhance the immunogenicity of DNA encoded antigens and highlight the development of a novel cytolytic DNA platform encoding a truncated mouse perforin.
+The application of this innovative DNA technology has considerable potential in the development of effective vaccines.
+Seoul virus (SEOV) is a zoonotic orthohantavirus carried by black and brown rats, and can cause hemorrhagic fever with renal syndrome in humans.
+Human cases of SEOV virus infection have most recently been reported in the USA, United Kingdom, France and the Netherlands and were primarily associated with contact with pet rats and feeder rats.
+Little is known about the cell tropism of SEOV in its reservoir and most available data is based on experimental infection studies in which rats were inoculated via a route which does not recapitulate virus transmission in nature.
+Here we report the histopathological analysis of SEOV cell tropism in key target organs following natural infection of a cohort of feeder rats, comprising 19 adults and 11 juveniles.
+All adult rats in this study were positive for SEOV specific antibodies and viral RNA in their tissues.
+Of the 19 adult rats of which subsequently additional organs were tested, SEOV RNA was detected in all lungs, followed by kidney (79%) and liver (74%).
+Histopathologic changes associated with SEOV infection were primarily found in the liver, consistent with a pathological diagnosis of a mild hepatitis.
+In conclusion, natural SEOV infection results in mild inflammation of the liver in the absence of clinical disease.
+However, conventional vaccines are only effective for a short period of time due to the propensity of influenza viruses to undergo antigenic drift and antigenic shift.
+The efficacy of these vaccines is uncertain from year-to-year due to potential mismatch between the circulating viruses and vaccine strains, and mutations arising due to egg adaptation.
+Subsequently, the inability to store these vaccines long-term and vaccine shortages are challenges that need to be overcome.
+Conventional vaccines also have variable efficacies for certain populations, including the young, old, and immunocompromised.
+As opposed to active immunization platforms (requiring the use of whole or portions of pathogens as vaccines), the rapidly developing passive immunization involves administration of either pathogen-specific or broadly acting antibodies against a kind or class of pathogens as a treatment to corresponding acute infection.
+Several antibodies with broadly acting capacities have been discovered that may serve as means to suppress influenza viral infection and allow the process of natural immunity to engage opsonized pathogens whilst boosting immune system by antibody-dependent mechanisms that bridge the innate and adaptive arms.
+By that; passive immunotherapeutics approach assumes a robust tool that could aid control of influenza viruses.
+In this review, we comment on some improvements in influenza management and promising vaccine development platforms with an emphasis on the protective capacity of passive immunotherapeutics especially when coupled with the use of antivirals in the management of influenza infection.
+Less attention is given to why and how virus fitness results from the success of virus transmission.
+Virus transmission reflects the infection-shedding-transmission dynamics, and with it, the organ system involvement and other, macroscopic dimensions of the host environment.
+This study describes the transmission ecology of the world main livestock viruses, 36 in total, a mix of RNA, DNA and retroviruses.
+Following an iterative process, the viruses are virtually ranked in an outer- to inner-body fashion, by organ system, on ecological grounds.
+The synthesis of the findings reveals a predictive virus evolution framework, based on the outer- to inner-body changes in the interplay of host environment-transmission modes-organ system involvement-host cell infection cycle-virus genome.
+For example, respiratory and enteric viruses tend to be associated with poultry and pig mass rearing.
+Ruminant and equine viruses tend to be more deep-rooted and host-specific, and also establish themselves in the vital inner-body systems.
+It is concluded that the framework may assist the study of new emerging viruses and pandemic risks.
+The traditional design of effective vaccines for rapidly-evolving pathogens, such as influenza A virus, has failed to provide broad spectrum and long-lasting protection.
+With low cost whole genome sequencing technology and powerful computing capabilities, novel computational approaches have demonstrated the potential to facilitate the design of a universal influenza vaccine.
+However, few studies have integrated computational optimization in the design and discovery of new vaccines.
+Understanding the potential of computational vaccine design is necessary before these approaches can be implemented on a broad scale.
+This review summarizes some promising computational approaches under current development, including computationally optimized broadly reactive antigens with consensus sequences, phylogenetic model-based ancestral sequence reconstruction, and immunomics to compute conserved cross-reactive T-cell epitopes.
+We propose that with the development of novel technologies that allow the integration of data sources such as protein structural modeling, host antibody repertoire analysis and advanced phylodynamic modeling, computational approaches will be crucial for the development of a long-lasting universal influenza vaccine.
+Taken together, computational approaches are powerful and promising tools for the development of a universal influenza vaccine with durable and broad protection.
+In this study, among 576 respiratory specimens from 476 mammals and 100 chickens, genogroup I PBVs were detected in three cattle and three monkeys, and a genogroup II PBV-positive sample was collected from one cattle specimen.
+More than one PBV sequence type was observed in two and one genogroup I PBV-positive samples from cattle and monkeys, respectively.
+Twenty-four complete/near-complete segments 2 (nine from respiratory and 15 from alimentary samples) from the cattle and monkey genogroup I PBVs and one complete segment 2 from the cattle genogroup II PBV were sequenced.
+In contrast, the monkey PBVs observed in this study were clustered into three distinct clades.
+This unique phenomenon is probably due to the fact that monkeys in our locality reside in separated troops with minimal inter-troop contact.
+This review provides a comparison of the theoretical issues and experimental findings for plasmid DNA and mRNA vaccine technologies.
+While both have been under development since the 1990s, in recent years, significant excitement has turned to mRNA despite the licensure of several veterinary DNA vaccines.
+Both have required efforts to increase their potency either via manipulating the plasmid DNA and the mRNA directly or through the addition of adjuvants or immunomodulators as well as delivery systems and formulations.
+The greater inherent inflammatory nature of the mRNA vaccines is discussed for both its potential immunological utility for vaccines and for the potential toxicity.
+The status of the clinical trials of mRNA vaccines is described along with a comparison to DNA vaccines, specifically the immunogenicity of both licensed veterinary DNA vaccines and select DNA vaccine candidates in human clinical trials.
+Recently, droplet-based microfluidic systems have been widely used in various biochemical and molecular biological assays.
+Since this platform technique allows manipulation of large amounts of data and also provides absolute accuracy in comparison to conventional bioanalytical approaches, over the last decade a range of basic biochemical and molecular biological operations have been transferred to drop-based microfluidic formats.
+In this review, we introduce recent advances and examples of droplet-based microfluidic techniques that have been applied in biochemistry and molecular biology research including genomics, proteomics and cellomics.
+The purpose of this review is to provide a new point of view and current status in droplet-based microfluidics to biochemists and molecular biologists.
+We hope that this review will accelerate communications between researchers who are working in droplet-based microfluidics, biochemistry and molecular biology.
+Interferon-induced transmembrane proteins (IFITMs) have been shown to strongly affect influenza A virus (IAV) infectivity in tissue culture.
+Moreover, polymorphisms in IFITM3 have been associated with the severity of the disease in humans.
+IFITM3 appears to act early in the infection, but its mechanism of action and potential interactions with incoming IAV structures are not yet defined.
+Here, we visualized endogenous IFITM3 interactions with IAV in the human lung epithelial cell line A549 and in primary human airway epithelial cells employing stimulated emission depletion super-resolution microscopy.
+By applying an iterative approach for the cluster definition and computational cluster analysis, we found that IFITM3 reorganizes into clusters as IAV infection progresses.
+IFITM3 cluster formation started at 2-3 h post infection and increased over time to finally coat IAV-containing endosomal vesicles.
+This IAV-induced phenotype was due to the endosomal recruitment of IFITM3 rather than to an overall increase in the IFITM3 abundance.
+While the IAV-induced IFITM3 clustering and localization to endosomal vesicles was comparable in primary human airway epithelial cells and the human lung epithelial cell line A549, the endogenous IFITM3 signal was higher in primary cells.
+Consisting of nearly 60 functional genes, porcine interferon (IFN)-complex represents an evolutionary surge of IFN evolution in domestic ungulate species.
+To compare with humans and mice, each of these species contains about 20 IFN functional genes, which are better characterized using the conventional IFN-α/β subtypes as examples.
+Porcine IFN-complex thus represents an optimal model for studying IFN evolution that resulted from increasing viral pressure during domestication and industrialization.
+We hypothesize and justify that porcine IFN-complex may extend its functionality in antiviral and immunomodulatory activity due to its superior molecular diversity.
+Furthermore, these unconventional IFNs could even confer some functional and signaling novelty beyond that of the well-studied IFN-α/β subtypes.
+Investigations into porcine IFN-complex will further our understanding of IFN biology and promote IFN-based therapeutic designs to confront swine viral diseases.
+Although the role of exogenous small interfering RNA (siRNA) and P-element induced wimpy testis (PIWI)-interacting RNA (piRNA) pathways in mosquito antiviral immunity is increasingly better understood, there is still little knowledge regarding the role of mosquito cellular microRNA (miRNA).
+Identifying direct interactions between the mosquito miRNAs and the RNA genome of arboviruses and choosing the relevant miRNA candidates to explore resulting antiviral mechanisms are critical.
+Here, we carried out genomic analyses to identify Aedes aegypti miRNAs that potentially interact with various lineages and genotypes of chikungunya, dengue, and Zika viruses.
+By using prediction tools with distinct algorithms, several miRNA binding sites were commonly found within different genotypes/and or lineages of each arbovirus.
+We further analyzed those miRNAs that could target more than one arbovirus, required a low energy threshold to form miRNA-viralRNA (vRNA) complexes, and predicted potential RNA structures using RNAhybrid software.
+Even without any experimental validation, which should be done as a next step, this study can shed further light on the role of miRNA in mosquito innate immunity and targets for future studies.
+Interest in bat-related viruses has increased considerably during the last decade, leading to the discovery of a rising number of new viruses in several bat species.
+Poxviridae are a large, diverse family of DNA viruses that can infect a wide range of vertebrates and invertebrates.
+To date, only a few documented detections of poxviruses have been described in bat populations on three different continents (America, Africa, and Australia).
+Herein, we report the isolation, nearly complete genome sequencing, and annotation of a novel poxvirus detected from an insectivorous bat (Hypsugo savii) in Northern Italy.
+The virus is tentatively named Hypsugopoxvirus (HYPV) after the bat species from which it was isolated.
+Genome analyses suggest that HYPV belongs to the Chordopoxvirinae subfamily, with the highest nucleotide identity (85%) to Eptesipoxvirus (EPTV) detected from a microbat Eptesicus fuscus in WA, USA, in 2011.
+To date, HYPV represents the first poxvirus detected in bats in Europe; thus, its viral ecology and disease associations should be investigated further.
+Among them, Epstein–Barr virus (EBV) is an oncogenic herpesvirus that chronically infects over 90% of the adult population, with over 200,000 cases of cancer and 150,000 cancer-related deaths attributed to it yearly.
+Acute EBV infection can present as infectious mononucleosis, and lead to the future onset of multiple cancers, including Burkitt lymphoma, Hodgkin lymphoma, nasopharyngeal carcinoma, and gastric carcinoma.
+Many of these cancers express latent viral genes, including Epstein–Barr virus nuclear antigen 1 (EBNA1) and latent membrane proteins 1 and 2 (LMP1 and LMP2).
+Previous attempts to create potent immunogens against EBV have been reported but generated mixed success.
+We designed novel Synthetic Consensus (SynCon) DNA vaccines against EBNA1, LMP1 and LMP2 to improve on the immune potency targeting important antigens expressed in latently infected cells.
+These EBV tumor antigens are hypothesized to be useful targets for potential immunotherapy of EBV-driven cancers.
+We optimized the genetic sequences for these three antigens, studied them for expression, and examined their immune profiles in vivo.
+We observed that these immunogens generated unique profiles based on which antigen was delivered as the vaccine target.
+Interestingly, LMP1vax was a very weak immunogen, generating very low levels of CD8 T cell immunity both as a standalone vaccine and as part of a trivalent vaccine cocktail.
+These studies suggest that engineered EBV latent protein vaccines deserve additional study as potential agents for immunotherapy of EBV-driven cancers.
+Symbiotic microbes impact the function and development of the central nervous system (CNS); however, little is known about the contribution of the microbiota during viral-induced neurologic damage.
+We identify that commensals aid in host defense following infection with a neurotropic virus through enhancing microglia function.
+Germfree mice or animals that receive antibiotics are unable to control viral replication within the brain leading to increased paralysis.
+Microglia derived from germfree or antibiotic-treated animals cannot stimulate viral-specific immunity and microglia depletion leads to worsened demyelination.
+Oral administration of toll-like receptor (TLR) ligands to virally infected germfree mice limits neurologic damage.
+Homeostatic activation of microglia is dependent on intrinsic signaling through TLR4, as disruption of TLR4 within microglia, but not the entire CNS (excluding microglia), leads to increased viral-induced clinical disease.
+This work demonstrates that gut immune-stimulatory products can influence microglia function to prevent CNS damage following viral infection.
+The hypogravity motor syndrome (HMS) is one of the deleterious impacts of weightlessness on the human body in orbital space missions.
+There is a hypothesis that disorders of musculoskeletal system as part of HMS arise in consequence of changes in spinal motor neurons.
+The study was aimed at bioinformatic analysis of transcriptome changes in lumbar spinal cords of mice after a 30-day spaceflight aboard biosatellite Bion-M1 (space group, S) and subsequent 7-day readaptation to the Earth’s gravity (recovery group, R) when compared with control mice (C group) housed in simulated biosatellite conditions on the Earth.
+Gene ontology and human phenotype ontology databases were used to detect biological processes, molecular functions, cellular components, and human phenotypes associated with HMS.
+Our results suggest resemblance of molecular changes developing in space orbit and during the postflight recovery to terrestrial neuromuscular disorders.
+Remarkably, more prominent transcriptome changes were revealed in R vs. S and R vs. C comparisons that are possibly related to the 7-day recovery period in the Earth’s gravity condition.
+These data may assist with establishment of HMS pathogenesis and proposing effective preventive and therapeutic options.
+A key step in the Ebola virus (EBOV) replication cycle involves conformational changes in viral glycoprotein 2 (GP2) which facilitate host-viral membrane fusion and subsequent release of the viral genome.
+Ebola GP2 plays a critical role in virus entry and has similarities in mechanism and structure to the HIV gp41 protein for which inhibitors have been successfully developed.
+In this work, a putative binding pocket for the C-terminal heptad repeat in the N-terminal heptad repeat trimer was targeted for identification of small molecules that arrest EBOV-host membrane fusion.
+Two computational structure-based virtual screens of ∼1.7 M compounds were performed (DOCK program) against a GP2 five-helix bundle, resulting in 165 commercially available compounds purchased for experimental testing.
+Based on assessment of inhibitory activity, cytotoxicity, and target specificity, four promising candidates emerged with 50% inhibitory concentration values in the 3 to 26 μM range.
+Molecular dynamics simulations of the two most potent candidates in their DOCK-predicted binding poses indicate that the majority of favorable interactions involve seven highly conserved residues that can be used to guide further inhibitor development and refinement targeting EBOV.
+IMPORTANCE The most recent Ebola virus disease outbreak, from 2014 to 2016, resulted in approximately 28,000 individuals becoming infected, which led to over 12,000 causalities worldwide.
+The particularly high pathogenicity of the virus makes paramount the identification and development of promising lead compounds to serve as inhibitors of Ebola infection.
+To limit viral load, the virus-host membrane fusion event can be targeted through the inhibition of the class I fusion glycoprotein of Ebolavirus.
+In the current work, several promising small-molecule inhibitors that target the glycoprotein GP2 were identified through systematic application of structure-based computational and experimental drug design procedures.
+The use of Internet-based systems for infectious disease surveillance has been increasingly explored in recent years.
+However, few studies have used Internet search query or social media data to monitor spatial and temporal trends of avian influenza in China.
+This study investigated the potential of using search query and social media data in detecting and monitoring avian influenza A (H7N9) cases in humans in China.
+We collected weekly data on laboratory-confirmed H7N9 cases in humans, as well as H7N9-related Baidu Search Index (BSI) and Weibo Posting Index (WPI) data in China from 2013 to 2017, to explore the spatial and temporal trends of H7N9 cases and H7N9-related Internet search queries.
+Our findings showed a positive relationship of H7N9 cases with BSI and WPI search queries spatially and temporally.
+The outbreak threshold time and peak time of H7N9-related BSI and WPI searches preceded H7N9 cases in most years.
+Seasonal autoregressive integrated moving average (SARIMA) models with BSI (β = 0.008, p < 0.001) and WPI (β = 0.002, p = 0.036) were used to predict the number of H7N9 cases.
+Regression tree model analysis showed that the average H7N9 cases increased by over 2.4-fold (26.8/11) when BSI for H7N9 was > = 11524.
+Both BSI and WPI data could be used as indicators to develop an early warning system for H7N9 outbreaks in the future.
+BACKGROUND: Angiotensin‐converting enzyme 2 (ACE2) is a homologue of angiotensin‐converting enzyme (ACE) and produces angiotensin peptides (APs), such as angiotensin 1‐9 and 1‐7 that are vasodilatory and natriuretic, and act to counterbalance angiotensin II.
+Equilibrium concentrations of renin angiotensin aldosterone system (RAAS) APs differ in dogs with heart disease compared to healthy dogs and recombinant human ACE2 (rhACE2) alters relative concentrations of APs.
+METHODS: Immunohistochemistry and assays for tissue and plasma ACE2 activity and equilibrium concentrations of plasma RAAS APs were performed.
+Median plasma ACE2 activity was significantly increased in dogs with congestive heart failure (CHF; 6.9 mU/mg; interquartile range [IQR], 5.1‐12.1) as compared to control (2.2 mU/mg; IQR, 1.8‐3.0; P = .0003).
+Plasma equilibrium analysis of RAAS APs identified significant increases in the median concentrations of beneficial APs, such as angiotensin 1‐7, in dogs with CHF (486.7 pg/mL; IQR, 214.2‐1168) as compared to those with preclinical disease (41.0 pg/mL; IQR, 27.4‐45.1; P < .0001) or control (11.4 pg/mL; IQR, 7.1‐25.3; P = .01).
+Incubation of plasma samples from dogs with CHF with rhACE2 increased beneficial APs, such as angiotensin 1‐9 (preincubation, 10.3 pg/mL; IQR, 4.4‐37.2; postincubation, 2431 pg/mL; IQR, 1355‐3037; P = .02), while simultaneously decreasing maladaptive APs, such as angiotensin II (preincubation, 53.4 pg/mL; IQR, 28.6‐226.4; postincubation, 2.4 pg/mL; IQR, 0.50‐5.8; P = .02).
+CONCLUSIONS AND CLINICAL IMPORTANCE: Recognition of the ACE2 system expands the conventional view of the RAAS in the dog and represents an important potential therapeutic target.
+BACKGROUND: Salmonellosis is a major cause of morbidity and mortality in neonatal calves, often occurring before preventative vaccines can be administered.
+HYPOTHESIS/OBJECTIVE: To evaluate the protective effect on calves of colostrum from cows vaccinated with a commercially available Salmonella Newport bacterin against a Salmonella Typhimurium challenge.
+METHODS: Nonrandomized placebo‐controlled trial in which colostrum was harvested from 30 cows that received 2 doses of either Salmonella bacterin or saline before calving.
+Colostrum collected from each group was pooled and fed to 2 groups of 10 calves at birth.
+RESULTS: No differences in mortality, clinical findings, hematology results, blood and fecal cultures, or necropsy findings between the 2 groups were observed.
+Vaccinated cows had higher colostral titers, and calves fed this colostrum had higher serum titers (mean difference, 0.429; mean [SE], 0.852 [0.02] for vaccinated versus 0.423 [0.02] for control calves).
+CONCLUSIONS AND CLINICAL IMPORTANCE: Transfer of colostral immunoglobulins from Salmonella enterica serotype Newport bacterin to neonatal calves was not sufficient to decrease mortality, clinical signs, sepsis, intestinal damage, or fecal shedding when exposed to a highly pathogenic Salmonella isolate.
+A large‐scale randomized controlled clinical trial is needed to evaluate the efficacy of this bacterin when administered in the dry period for prevention of salmonellosis in neonatal calves.
+They are categorized into three classes; IFN1 and IFN3 are the primary antiviral cytokine lineages, while IFN2 responds to a broader variety of pathogens.
+Here, we reassess interferon evolution, considering key phylogenetic pitfalls including taxon sampling, alignment quality, model adequacy, and outgroup choice.
+We reveal that cartilaginous fishes, and hence the jawed vertebrate ancestor, possess(ed) orthologs of all three interferon classes.
+We show that IFN3 groups sister to IFN1, resolve the origins of the human IFN3 lineages, and find that intronless IFN3s emerged at least three times.
+IFN2 genes are highly conserved, except for IFN-γ-rel, which we confirm resulted from a teleost-specific duplication.
+By accounting for this, we describe a new backbone IFN1 phylogeny that implies several IFN1 genes existed in the jawed vertebrate ancestor.
+One of these is represented by the intronless IFN1s of tetrapods, including mammalian-like repertoires of reptile IFN1s and a subset of amphibian IFN1s, in addition to newly-identified intron-containing shark IFN1 genes.
+IFN-f, previously only found in teleosts, likely represents another ancestral jawed vertebrate IFN1 family member, suggesting the current classification of fish IFN1s into two groups based on the number of cysteines may need revision.
+The providence of the remaining fish IFN1s and the coelacanth IFN1s proved difficult to resolve, but they may also be ancestral jawed vertebrate IFN1 lineages.
+Finally, a large group of amphibian-specific IFN1s falls sister to all other IFN1s and was likely also present in the jawed vertebrate ancestor.
+Our results verify that intronless IFN1s have evolved multiple times in amphibians and indicate that no one-to-one orthology exists between mammal and reptile IFN1s.
+Our data also imply that diversification of the multiple IFN1s present in the jawed vertebrate ancestor has occurred through a rapid birth-death process, consistent with functional maintenance over a 450-million-year host-pathogen arms race.
+In summary, this study reveals a new model of interferon evolution important to our understanding of jawed vertebrate antiviral immunity.
+Sepsis is a life-threatening condition caused by an immune response triggered by infection, and highly elevated cytokine/chemokine levels in the blood play crucial roles in the progression of sepsis.
+Serum exosomes are nanovesicles that have multiple biological functions, playing roles in antigen presentation, intercellular signal communication, inflammatory response and immune surveillance.
+In this study, we investigated the profiles of cytokines/chemokines harbored in the exosomes of septic mice and explored the mechanisms of immunomodulation on T cells treated with exosomes harvested from septic mice.
+Blood cytokines/chemokines existed in both the soluble form and in the insoluble exosomal form; the profiles of the cytokines/chemokines in these two forms displayed different dynamics in the blood of mice challenged with LPS.
+Exosomes from septic mice induced the differentiation of Th1/Th2 cells, which was blocked by specific antibodies targeting IL-12 and IL-4.
+Furthermore, preadministration of exosomes by intravenous injection restrained the inflammatory response, attenuated lung and liver tissue damage, and prolonged the survival of cecal ligation and puncture (CLP) mice.
+Our results indicate that exosomes enriched with cytokines/chemokines play critical roles in T cell differentiation, proliferation and chemotaxis during the sepsis process and have a protective effect on cecal ligation and puncture (CLP) mice.
+Thus, these findings not only strengthen our understanding of the role of sepsis via exosomes but also provide potential targets for therapeutic applications.
+Duchenne muscular dystrophy (DMD) is an X-linked disorder characterized by progressive muscle degeneration, caused by the absence of dystrophin.
+Exon skipping by antisense oligonucleotides (ASOs) has recently gained recognition as therapeutic approach in DMD.
+Conjugation of a peptide to the phosphorodiamidate morpholino backbone (PMO) of ASOs generated the peptide-conjugated PMOs (PPMOs) that exhibit a dramatically improved pharmacokinetic profile.
+When tested in animal models, PPMOs demonstrate effective exon skipping in target muscles and prolonged duration of dystrophin restoration after a treatment regime.
+Herein we summarize the main pathophysiological features of DMD and the emergence of PPMOs as promising exon skipping agents aiming to rescue defective gene expression in DMD and other neuromuscular diseases.
+The listed PPMO laboratory findings correspond to latest trends in the field and highlight the obstacles that must be overcome prior to translating the animal-based research into clinical trials tailored to the needs of patients suffering from neuromuscular diseases.
+[Image: see text] Ecofriendly N-heterocyclic carbene (NHC) organocatalysis can control the N(1)-functionalization (aza-Michael addition) and C(3)-functionalization (Morita–Baylis–Hillman reaction, MBH) of isatins in the absence of (1) a protecting group, (2) a stoichiometric reagent, and (3) heat energy.
+The challengeable N(1)-functionalization of N-unsubstituted isatins into N-substituted (NS) isatins was realized through 10 mol % NHC and 10 mol % 1,8-diazabicyclo[5.4.0]undec-7-ene catalysts within 10 min with up to 98% isolation yield.
+The subsequent MBH adducts of as-synthesized NS-isatins (N(1)/C(3)-functionalization) was perfectly acquired in 10 mol % NHC and 10 mol % 1,4-diazabicyclo[2.2.2]octane catalysis within 30 min with superiority to C(3)/N(1)-functionalization (MBH/aza-Michael).
+For guiding the application to a versatile druggable isatin library, the NHC catalysis was compared with reported functionalization of isatins in view of green chemistry principles including solvent scoring of ACS GCI pharmaceutical roundtable, E-factor, atom economy, and so on.
+Viral pathogens account for a significant proportion of the burden of emerging infectious diseases in humans.
+The Wellcome Trust-Vietnamese Initiative on Zoonotic Infections (WT-VIZIONS) is aiming to understand the circulation of viral zoonotic pathogens in animals that pose a potential risk to human health.
+Evidence suggests that human exposure and infections with hepatitis E virus (HEV) genotypes (GT) 3 and 4 results from zoonotic transmission.
+Hypothesising that HEV GT3 and GT4 are circulating in the Vietnamese pig population and can be transmitted to humans, we aimed to estimate the seroprevalence of HEV exposure in a population of farmers and the general population.
+We additionally performed sequence analysis of HEV in pig populations in the same region to address knowledge gaps regarding HEV circulation and to evaluate if pigs were a potential source of HEV exposure.
+We found a high prevalence of HEV GT3 viral RNA in pigs (19.1% in faecal samples and 8.2% in rectal swabs) and a high HEV seroprevalence in pig farmers (16.0%) and a hospital-attending population (31.7%) in southern Vietnam.
+The hospital population was recruited as a general-population proxy even though this particular population subgroup may introduce bias.
+The detection of HEV RNA in pigs indicates that HEV may be a zoonotic disease risk in this location, although a larger sample size is required to infer an association between HEV positivity in pigs and seroprevalence in humans.
+We present our experience in haploidentical stem cell transplantation (haplo SCT) in children with benign disorders.
+We performed a retrospective study where children aged up to 18 years diagnosed to have benign disorders and underwent haplo SCT from 2002 to September 2017 were included.
+Of the 54 children, the most common indications were Fanconi anaemia 12 (22%), severe aplastic anaemia 8 (14%) and primary immune deficiency disorders (PID) 25 (46%).
+Post-transplant cyclophosphamide (PTCy) was used in 41 (75.9%) and ex vivo T depletion in 13 (24.1%).
+Engraftment rates were 70% with acute graft versus host disease in 36% and cytomegalovirus reactivation in 55% children.
+There was a statistically significant difference found between survival with siblings as donors as compared to parents (p value 0.018).
+Overall survival was 60% which is the 1-year survival, with 68% survival among those with PIDs.
+Cytokine release syndrome was noted in 12/41 (29%) of children who received T replete graft and PTCy.
+In children over 6 months of age, PTCy at a cost of INR 1200 provides cost effective T cell depletion comparable with TCR α/β depletion priced at INR 1200,000.
+Activated Rac serves various cellular functions including the reorganization of the actin cytoskeleton in lymphocytes and neutrophils and production of reactive oxygen species in neutrophils.
+Since 2015, six unrelated patients with combined immunodeficiency and early-onset severe viral infections caused by bi-allelic loss-of-function mutations in DOCK2 have been described.
+Until now, the function of phagocytes, specifically neutrophils, has not been assessed in human DOCK2 deficiency.
+Here, we describe a new kindred with four affected siblings harboring a homozygous splice-site mutation (c.2704-2 A > C) in DOCK2.
+The novel mutation affects EBV-B cell migration and results in NK cell dysfunction similar to previous observations.
+Moreover, both cytoskeletal rearrangement and reactive oxygen species production are partially impaired in DOCK2-deficient neutrophils.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10875-019-00603-w) contains supplementary material, which is available to authorized users.
+ABSTRACT: Excessive activities of cysteinyl cathepsins (CysCts) contribute to the progress of many diseases; however, therapeutic inhibition has been problematic.
+Here, it is discussed that phenformin (phenylethyl biguanide) is a model for recruitment of endogenous Zn(2+) to inhibit CysHis/CysHis(X) peptidolysis.
+Benzoyl-l-arginine amide (BAA) is a classical substrate of papain-like proteases; the amide bond is scissile.
+In this review, the structures of BAA and the phenformin-Zn(2+) complex were compared in silico.
+Their chemistry and dimensions are discussed in light of the active sites of papain-like proteases.
+The phenyl moieties of both structures bind to the “S2” substrate-binding site that is typical of many proteases.
+When the phenyl moiety of BAA binds to S2, then the scissile amide bond is directed to the position of the thiolate-imidazolium ion pair, and is then hydrolyzed.
+However, when the phenyl moiety of phenformin binds to S2, then the coordinated Zn(2+) is directed to the identical position; and catalysis is inhibited.
+Hundreds of biguanide derivatives have been synthesized at the 1 and 5 nitrogen positions; many more are conceivable.
+Various substituent moieties can register with various arrays of substrate-binding sites so as to align coordinated Zn(2+) with catalytic partners of diverse proteases.
+Biguanide is identified here as a modifiable pharmacophore for synthesis of therapeutic CysCt inhibitors with a wide range of potencies and specificities.
+Established methods in biomolecule structure determination typically require purification, crystallization, or modification of target molecules, which limits their applications for analyzing trace amounts of biomolecules in complex matrices.
+Here, we developed instruments and methods of mobility capillary electrophoresis (MCE) and its coupling with MS for the 3D structural analysis of biomolecules in the liquid phase.
+The effective radius and the aspect ratio of each separated biomolecule were simultaneously determined through the separation by MCE, which were then used as restraints in determining biomolecule conformations through modeling.
+Feasibility of this method was verified by analyzing a mixture of somatostatin and bradykinin, two peptides with known liquid-phase structures.
+MCE and MCE–MS would allow us to analyze trace amounts of biomolecules in complex matrices, which has the potential to be an alternative and powerful biomolecule structure analysis technique.
+We characterized natural vertical transmission of Zika virus in pools of Aedes aegypti larvae hatched from eggs collected in Jojutla, Morelos, Mexico.
+Of the 151 pools analyzed, 17 tested positive for Zika virus RNA; infectious Zika virus was successfully isolated from 1 of the larvae pools (31N) in C6/36 cells.
+Real-time quantitative PCR and indirect immunofluorescence assays confirmed the identity of the isolate, named Zika virus isolate 31N; plaque assays in Vero cells demonstrated the isolate’s infectivity in a mammalian cell line.
+We obtained the complete genome of Zika virus isolate 31N by next-generation sequencing and identified 3 single-nucleotide variants specific to Zika virus isolate 31N using the meta-CATS tool.
+These results demonstrate the occurrence of natural vertical transmission of Zika virus in wild Ae.
+aegypti mosquitoes and suggest that this transmission mode could aid in the spread and maintenance of Zika virus in nature.
+Climate change and anthropogenic activity are currently driving large changes in nutritional availability across ecosystems, with consequences for infectious disease.
+An increase in host nutrition could lead to more resources for hosts to expend on the immune system or for pathogens to exploit.
+In this paper, we report a meta-analysis of studies on host–pathogen systems across the tree of life, to examine the impact of host nutritional quality and quantity on pathogen virulence.
+We did not find broad support across studies for a one-way effect of nutrient availability on pathogen virulence.
+We thus discuss a hypothesis that there is a balance between the effect of host nutrition on the immune system and on pathogen resources, with the pivot point of the balance differing for vertebrate and invertebrate hosts.
+Our results suggest that variation in nutrition, caused by natural or anthropogenic factors, can have diverse effects on infectious disease outcomes across species.
+Guanine (G)-quadruplexes (G4s) are unique nucleic acid structures that are formed by stacked G-tetrads in G-rich DNA or RNA sequences.
+G4s have been reported to play significant roles in various cellular events in both macro- and micro-organisms.
+The identification and characterization of G4s can help to understand their different biological roles and potential applications in diagnosis and therapy.
+In addition to biophysical and biochemical methods to interrogate G4 formation, G4 fluorescent turn-on ligands can be used to target and visualize G4 formation both in vitro and in cells.
+Here, we review several representative classes of G4 fluorescent turn-on ligands in terms of their interaction mechanism and application perspectives.
+Interestingly, G4 structures are commonly identified in DNA and RNA aptamers against targets that include proteins and small molecules, which can be utilized as G4 tools for diverse applications.
+We therefore also summarize the recent development of G4-containing aptamers and highlight their applications in biosensing, bioimaging, and therapy.
+Moreover, we discuss the current challenges and future perspectives of G4 fluorescent turn-on ligands and G4-containing aptamers.
+Longstanding discordances and enigmas persist as to the specificities and other properties of antibodies (Abs) most effective in preventing or limiting many viral infections in mammals; in turn, failure to decipher key complexities has added to headwinds for both Ab-based therapeutic approaches and rational vaccine design.
+More recently, experimental approaches have emerged—and continue to emerge—for discerning the functional role of Ab structure, especially the Fc portion of antibody, in combating viral infections in vivo.
+A wide range of in vitro measures of antibody activity, from neutralization to antibody-dependent cell mediated cytotoxicity (ADCC)—each of these terms representing only an operational notion defined by the particulars of a given assay—are poised for assignment of both relevance and reliability in forecasting outcomes of infection.
+To illustrate some of the opportunities with either zoonotic (emerging, spillover) or ancient human-adapted viruses, we draw examples from a wide range of viruses that affect humans.
+Manipulating cell cycle is one of the common strategies used by viruses to generate favorable cellular environment to facilitate viral replication.
+Coxsackievirus B (CVB) is one of the major viral pathogens of human myocarditis and cardiomyopathy.
+However, how the structural and non-structural components of CVB would manipulate cell cycle is not clearly understood.
+In this study, we demonstrated that the capsid protein VP1 of CVB type 3 (CVB3) induced cell cycle arrest at G1 phase.
+G1 arrest was the result of the decrease level of cyclin E and the accumulation of p27(Kip1).
+Study on the gene expression profile of the cells expressing VP1 showed that the expression of both heat shock protein 70-1 (Hsp70-1) and Hsp70-2 was significantly up-regulated.
+Knockdown of Hsp70 resulted in the increased level of cyclin E and the reduction of p27(Kip1).
+We further demonstrated that the phosphorylation of the heat shock factor 1, which directly promotes the expression of Hsp70, was also increased in the cell expressing VP1.
+Moreover, we show that CVB3 infection also induced G1 arrest, likely due to dysregulating Hsp70, cyclin E, and p27, while knockdown of Hsp70 dramatically inhibited viral replication.
+Cell cycle arrest at G1 phase facilitated CVB3 infection, since viral replication in the cells synchronized at G1 phase dramatically increased.
+Taken together, this study demonstrates that the VP1 of CVB3 induces cell cycle arrest at G1 phase through up-regulating Hsp70.
+Our findings suggest that the capsid protein VP1 of CVB is capable of manipulating cellular activities during viral infection.
+Extracellular vesicles (EVs) are thought to be important in cell-cell communication and have elicited extraordinary interest as potential biomarkers of disease.
+Here, we describe a cell-based assay for monitoring EV release using the EV-enriched tetraspanin CD63 fused to the small, ATP-independent reporter enzyme, Nanoluciferase.
+Release of CD63-containing EVs from stably expressing cell lines was monitored by comparing luciferase activity in culture media to that remaining in cells.
+HEK293, U2OS, U87 and SKMel28 cells released 0.3%-0.6% of total cellular CD63 in the form of EVs over 5 hrs, varying by cell line.
+To identify cellular machinery important for secretion of CD63-containing EVs, we performed a screen of biologically active chemicals in HEK293 cells.
+While a majority of compounds did not significantly affect EV release, treating cells with the plecomacrolides bafilomycin or concanamycin, known to inhibit the V-ATPase, dramatically increased EV release.
+Interestingly, alkalization of the endosomal lumen using weak bases had no effect, suggesting a pH-independent enhancement of EV release by V-ATPase inhibitors.
+The ability to quantify EVs in small samples will enable future detailed studies of release kinetics as well as further chemical and genetic screening to define pathways involved in EV secretion.
+BACKGROUND: Information on the clinical, epidemiological and molecular characterization of human metapneumovirus in critically ill adult patients with severe community-acquired pneumonia (CAP) and the role of biomarkers identifying bacterial coinfection is scarce.
+METHODS: This is a retrospective epidemiological study of adult patients with hMPV severe CAP admitted to ICU during a ten-year period with admission PSI score ≥ 3.
+RESULTS: The 92.8% of the 28 patients with severe CAP due to human metapneumovirus were detected during the first half of the year.
+Plasma levels of procalcitonin were higher in patients with bacterial coinfection (18.2 vs 0.54; p < 0.05).
+CONCLUSION: Human metapneumovirus was associated with severe CAP requiring ICU admission among elderly patients or patients with comorbidities, but also in healthy young subjects.
+While one out of four patients showed pneumococcal coinfection, plasma procalcitonin helped to implement antimicrobial stewardship.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13613-019-0559-y) contains supplementary material, which is available to authorized users.
+In order to manage and maintain stable productivity, it is important to establish policies for biosecurity.
+Avian influenza and Newcastle disease have been reported in Myanmar, but no scientific information is available for other respiratory pathogens, such as mycoplasmas and infectious bronchitis virus (IBV).
+In this study, we detected Mycoplasma gallisepticum (MG), M. synoviae (MS), and IBV in several poultry farms in Myanmar.
+RESULTS: Samples were collected from 20 farms in three major poultry farming areas in Myanmar, and MG, MS, and IBV were detected on two, four, and eight farms, respectively, by polymerase chain reaction.
+Phylogenetic analysis revealed that the observed MG and MS isolates were not identical to vaccine strains.
+Periodic surveillance is required to establish the distribution of each pathogen, and to institute better vaccine protocols.
+BACKGROUND: Acute respiratory distress syndrome (ARDS) is a common acute and severe disease in clinic.
+Recent studies indicated that Cxc chemokine ligand 5 (CXCL5), an inflammatory chemokine, was associated with tumorigenesis.
+The present study investigated the role of the CXCL5/Cxc chemokine receptor 2 (CXCR2) bio-axis in ARDS, and explored the underlying molecular mechanism.
+MATERIAL/METHODS: The pathological morphology of lung tissue and degree of pulmonary edema were assessed by hematoxylin-eosin staining and pulmonary edema score, respectively.
+Real-time PCR and Western blot analysis were performed to detect the expression levels of CXCL5, CXCR2, Matrix metalloproteinases 2 (MMP2), and Matrix metalloproteinases 9 (MMP9) in lung tissues.
+Enzyme-linked immunosorbent assay (ELISA) was performed to determine the expression levels of CXCL5 and inflammatory factors (IL-1β, IL-6, TNF-α, and IL-10) in serum.
+RESULTS: The results demonstrated that diffuse alveolar damage and pulmonary edema appeared in lipopolysaccharide (LPS)-induced ARDS and were positively correlated with the severity of ARDS.
+In addition, CXCL5 and its receptor CXCR2 were overexpressed by upregulation of MMP2 and MMP9 in lung tissues of ARDS.
+In addition, CXCL5 neutralizing antibody effectively alleviated inflammatory response, diffuse alveolar damage, and pulmonary edema, and decreased the expression levels of MMP2 and MMP9 compared to LPS-induced ARDS.
+CONCLUSIONS: We found that CXCL5/CXCR2 accelerated the progression of ARDS, partly by upregulation of MMP2 and MMP9 in lung tissues with the release of inflammatory factors.
+Human leukocyte antigen (HLA) alleles have a high degree of polymorphism, which determines their peptide-binding motifs and subsequent T-cell receptor recognition.
+The simplest way to understand the cross-presentation of peptides by different alleles is to classify these alleles into supertypes.
+However, direct structural and functional evidence for peptide presentation features of key alleles (e.g., HLA-A(*)30:01 and -A(*)30:03) are lacking.
+Herein, the molecular basis of peptide presentation of HLA-A(*)30:01 and -A(*)30:03 was demonstrated by crystal structure determination and thermostability measurements of complexes with T-cell epitopes from influenza virus (NP44), human immunodeficiency virus (RT313), and Mycobacterium tuberculosis (MTB).
+When binding to the HIV peptide, RT313, the PΩ-Lys anchoring modes of HLA-A(*)30:01, and -A(*)30:03 were similar to those of HLA-A(*)11:01 in the A3 supertype.
+However, HLA-A(*)30:03, but not -A(*)30:01, also showed binding with the HLA(*)01:01-favored peptide, NP44, but with a specific structural conformation.
+Thus, different from our previous understanding, HLA-A(*)30:01 and -A(*)30:03 have specific peptide-binding characteristics that may lead to their distinct supertype-featured binding peptide motifs.
+Moreover, we also found that residue 77 in the F pocket was one of the key residues for the divergent peptide presentation characteristics of HLA-A(*)30:01 and -A(*)30:03.
+Our results provide important recommendations for screening virus and tumor-specific peptides among the population with prevalent HLA supertypes for vaccine development and immune interventions.
+BACKGROUD: Organizing pneumonia (OP) is a rare complication of influenza infection that has substantial morbidity.
+We report the first case of OP associated with avian influenza H7N9 infection that had significant improvement with corticosteroid treatment.
+After initial clinical improvement supported by extracorporeal membrane oxygenation (ECMO), the patient’s condition worsened with persistent fever, refractory hypoxemia.
+Although OP was suspected and 1 mg/kg methylprednisolone was used, the patient’s condition didn’t improved considerably.
+An open lung biopsy was performed, and histopathological examination of the specimen was compatible with OP.
+ECMO was weaned on day 15, and he was discharged on day 71 with good lung recovery.
+CONCLUSIONS: To the best of our knowledge, this was the first case of successful management of refractory severe respiratory failure caused by avian influenza H7N9 infection complicated with OP.
+Refractory hypoxia with clinical manifestation and radiological findings compatible with OP, a differential diagnosis should be considered among patients at the second or third week of influenza H7N9 infection, especially in patients with clinical condition deteriorated after the primary influenza pneumonia was controlled.
+And a steroid dose of methylprednisolone 1.5 mg/kg may be suggested for treatment of OP associated with avian influenza H7N9 infection.
+BACKGROUND: A severe seasonal influenza epidemic was observed during 2017–2018 in China, prompting questions on clinical characteristics and outcomes of severe cases with influenza.
+METHODS: We retrospectively collected clinical data and outcomes of laboratory-confirmed hospitalized patients (severe to critical) during Jan-2011 to Feb-2018 from five hospitals, followed by a systematic analysis of cases from 2017 to 2018 (n = 289) and all previous epidemics during 2011–2017 (n = 169).
+RESULTS: In-hospital fatality was over 5-folds higher during the 2017–2018 (p < 0.01) in which 19 patients died (6.6%), whereas only 2 mortalities (1.2%) were observed during 2011–2017.
+Of the 289 hospitalized in 2017–2018, 153 were confirmed with influenza B virus, 110 with A/H1N1pdm09, and 26 A/H3N2, whereas A/H1N1pdm09 was the predominant cause of hospitalization in previous seasons combined (45%).
+Our results show that a significant lower proportion of patients aged 14 or greater were treated with oseltamivir, during the 2017–2018 epidemic, and exhibited higher levels of clinical severity.
+A sufficient supply of oseltamivir and antiviral therapy within 48 h from onset could reduce fatality rates.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12879-019-4181-2) contains supplementary material, which is available to authorized users.
+Antibodies against foreign antigens are a critical component of the overall immune response and can facilitate pathogen clearance during a primary infection and also protect against subsequent infections.
+Dysregulation of the antibody response can lead to an autoimmune disease, malignancy, or enhanced infection.
+Since the experimental delineation of a distinct B cell lineage in 1965, various methods have been developed to understand antigen-specific B cell responses in the context of autoimmune diseases, primary immunodeficiencies, infection, and vaccination.
+In this review, we summarize the established techniques and discuss new and emerging technologies for probing the B cell response in vitro and in vivo by taking advantage of the specificity of B cell receptor (BCR)-associated and secreted antibodies.
+These include ELISPOT, flow cytometry, mass cytometry, and fluorescence microscopy to identify and/or isolate primary antigen-specific B cells.
+We also present our approach to identify rare antigen-specific B cells using magnetic enrichment followed by flow cytometry.
+Once these cells are isolated, in vitro proliferation assays and adoptive transfer experiments in mice can be used to further characterize antigen-specific B cell activation, function, and fate.
+Transgenic mouse models of B cells targeting model antigens and of B cell signaling have also significantly advanced our understanding of antigen-specific B cell responses in vivo.
+Replicating recombinant vector vaccines consist of a fully competent viral vector backbone engineered to express an antigen from a foreign transgene.
+From the perspective of viral replication, the transgene is not only dispensable but may even be detrimental.
+Thus vaccine revertants that delete or inactivate the transgene may evolve to dominate the vaccine virus population both during the process of manufacture of the vaccine as well as during the course of host infection.
+A particular concern is that this vaccine evolution could reduce its antigenicity—the immunity elicited to the transgene.
+These models include evolution arising during the process of manufacture, the dynamics of vaccine and revertant growth, plus innate and adaptive immunity elicited during the course of infection.
+Although the selective basis of vaccine evolution is easy to comprehend, the immunological consequences are not.
+One complication is that the opportunity for vaccine evolution is limited by the short period of within-host growth before the viral population is cleared.
+Even less obvious, revertant growth may only weakly interfere with vaccine growth in the host and thus have a limited effect on immunity to vaccine.
+Overall, we find that within-host vaccine evolution can sometimes compromise vaccine immunity, but only when the extent of evolution during vaccine manufacture is severe, and this evolution can be easily avoided or mitigated.
+Ranavirus cross-species infections have been documented, but the viral proteins involved in the interaction with cell receptors have not yet been identified.
+Here, viral cell-binding proteins and their cognate cellular receptors were investigated using two ranaviruses, Andrias davidianus ranavirus (ADRV) and Rana grylio virus (RGV), and two different cell lines, Chinese giant salamander thymus cells (GSTC) and Epithelioma papulosum cyprinid (EPC) cells.
+The heparan sulfate (HS) analog heparin inhibited plaque formation of ADRV and RGV in the two cell lines by more than 80% at a concentration of 5 μg/mL.
+In addition, enzymatic removal of cell surface HS by heparinase I markedly reduced plaque formation by both viruses and competition with heparin reduced virus-cell binding.
+These results indicate that cell surface HS is involved in ADRV and RGV cell binding and infection.
+Furthermore, recombinant viral envelope proteins ADRV-58L and RGV-53R bound heparin-Sepharose beads implying the potential that cell surface HS is involved in the initial interaction between ranaviruses and susceptible host cells.
+To our knowledge, this is the first report identifying cell surface HS as ranavirus binding factor and furthers understanding of interactions between ranaviruses and host cells.
+Heparan sulfate proteoglycans (HSPG) are composed of unbranched, negatively charged heparan sulfate (HS) polysaccharides attached to a variety of cell surface or extracellular matrix proteins.
+Widely expressed, they mediate many biological activities, including angiogenesis, blood coagulation, developmental processes, and cell homeostasis.
+HSPG are highly sulfated and broadly used by a range of pathogens, especially viruses, to attach to the cell surface.
+In this review, we summarize the current knowledge on HSPG–virus interactions and distinguish viruses with established HS binding, viruses that bind HS only after intra-host or cell culture adaptation, and finally, viruses whose dependence on HS for infection is debated.
+We also provide an overview of the antiviral compounds designed to interfere with HS binding.
+Many questions remain about the true importance of these receptors in vivo, knowledge that is critical for the design of future antiviral therapies.
+Infectious laryngotracheitis (ILT) is an acute respiratory disease of poultry caused by infectious laryngotracheitis virus (ILTV).
+Control of the disease with live attenuated vaccines administered via eye drop build upon immune responses generated by the eye-associated lymphoid tissues.
+The aim of this study was to assess cytokine and lymphocyte changes in the conjunctiva-associated lymphoid tissues (CALT) and Harderian gland (HG) stimulated by the ocular inoculation of the ILTV chicken embryo origin (CEO) vaccine strain and virulent strain 63140.
+This study offers strong evidence to support the roles that the CALT and HG play in the development of protective ILTV immune responses.
+It supports the premise that ILTV-mediated immunomodulation favors the B cell response over those of T cells.
+Further, it provides evidence that expansions of CD8α(+) cells, with the concomitant expression of the Granzyme A gene, are key to reducing viral genomes in the CALT and halting ILTV cytolytic replication in the conjunctiva.
+Ultimately, this study revealed that the early upregulation of interleukin (IL)-12p40 and Interferon (IFN)-γ cytokine genes, which shape the antigen-specific cell-mediated immune responses, retarded the decline of virus replication, and enhanced the development of lesions in the conjunctiva epithelium.
+The herbs Plantago asiatica and Clerodendrum trichotomum have been commonly used for centuries in indigenous and folk medicine in tropical and subtropical regions of the world.
+In this study, we show that extracts from these herbs have antiviral effects against the respiratory syncytial virus (RSV) in vitro cell cultures and an in vivo mouse model.
+Treatment of HEp2 cells and A549 cells with a non-cytotoxic concentration of Plantago asiatica or Clerodendrum trichotomum extract significantly reduced RSV replication, RSV-induced cell death, RSV gene transcription, RSV protein synthesis, and also blocked syncytia formation.
+Interestingly, oral inoculation with each herb extract significantly improved viral clearance in the lungs of BALB/c mice.
+Based on reported information and a high-performance liquid chromatography (HPLC) analysis, the phenolic glycoside acteoside was identified as an active chemical component of both herb extracts.
+An effective dose of acteoside exhibited similar antiviral effects as each herb extract against RSV in vitro and in vivo.
+Collectively, these results suggest that extracts of Plantago asiatica and Clerodendrum trichotomum could provide a potent natural source of an antiviral drug candidate against RSV infection.
+The −2/−1 programmed ribosomal frameshifting (−2/−1 PRF) mechanism in porcine reproductive and respiratory syndrome virus (PRRSV) leads to the translation of two additional viral proteins, nonstructural protein 2TF (nsp2TF) and nsp2N.
+This −2/−1 PRF mechanism is transactivated by a viral protein, nsp1β, and cellular poly(rC) binding proteins (PCBPs).
+Critical elements for −2/−1 PRF, including a slippery sequence and a downstream C-rich motif, were also identified in 11 simarteriviruses.
+However, the slippery sequences (XXXUCUCU instead of XXXUUUUU) in seven simarteriviruses can only facilitate −2 PRF to generate nsp2TF.
+The nsp1β of simian hemorrhagic fever virus (SHFV) was identified as a key factor that transactivates both −2 and −1 PRF, and the universally conserved Tyr111 and Arg114 in nsp1β are essential for this activity.
+Using SHFV reverse genetics, we confirmed critical roles of nsp1β, slippery sequence, and C-rich motif in −2/−1 PRF in SHFV-infected cells.
+Attenuated virus growth ability was observed in SHFV mutants with impaired expression of nsp2TF and nsp2N.
+Comparative genomic sequence analysis showed that key elements of −2/−1 PRF are highly conserved in all known arteriviruses except equine arteritis virus (EAV) and wobbly possum disease virus (WPDV).
+Furthermore, −2/−1 PRF with SHFV PRF signal RNA can be stimulated by heterotypic nsp1βs of all non-EAV arteriviruses tested.
+Taken together, these data suggest that −2/−1 PRF is an evolutionarily conserved mechanism employed in non-EAV/-WPDV arteriviruses for the expression of additional viral proteins that are important for viral replication.
+IMPORTANCE Simarteriviruses are a group of arteriviruses infecting nonhuman primates, and a number of new species have been established in recent years.
+Although these arteriviruses are widely distributed among African nonhuman primates of different species, and some of them cause lethal hemorrhagic fever disease, this group of viruses has been undercharacterized.
+Since wild nonhuman primates are historically important sources or reservoirs of human pathogens, there is concern that simarteriviruses may be preemergent zoonotic pathogens.
+In this study, we demonstrated that an evolutionarily conserved ribosomal frameshifting mechanism is used by simarteriviruses and other distantly related arteriviruses for the expression of additional viral proteins.
+Given the crucial role of ribosome function in all living systems, the potential impact of the in-depth characterization of this novel mechanism reaches beyond the field of virology.
+Four influenza virus types have been identified to date: A, B, C and D, with only A–C known to infect humans.
+Influenza A and B viruses are responsible for seasonal influenza epidemics in humans and are responsible for up to a billion flu infections annually.
+The M2 protein is present in all influenza types and belongs to the class of viroporins, i.e., small proteins that form ion channels that increase membrane permeability in virus-infected cells.
+In influenza A and B, AM2 and BM2 are predominantly proton channels, although they also show some permeability to monovalent cations.
+By contrast, M2 proteins in influenza C and D, CM2 and DM2, appear to be especially selective for chloride ions, with possibly some permeability to protons.
+These differences point to different biological roles for M2 in types A and B versus C and D, which is also reflected in their sequences.
+AM2 is by far the best characterized viroporin, where mechanistic details and rationale of its acid activation, proton selectivity, unidirectionality, and relative low conductance are beginning to be understood.
+The present review summarizes the biochemical and structural aspects of influenza viroporins and discusses the most relevant aspects of function, inhibition, and interaction with the host.
+BACKGROUND: More than 90% of all infections in the head and neck region can be traced back to an odontogenic origin.
+In rare cases they can lead to sepsis, which may pose a vital threat to the patient.
+The purpose of this study was to analyse characteristics concerning etiology and progress of severe odontogenic infections with a fulminant development.
+METHODS: All patients with odontogenic infections requiring hospital admission were included in a retrospective analysis conducted from 02/2012 to 09/2017.
+Of 483 patients 16 patients (13 male, 3 female) showed severe exacerbation with septic progress.
+All patients underwent at least one surgical procedure that involved an extraoral incision and drainage as well as high volume irrigation intraoperatively.
+Three patients showed an exceedingly severe disease progression with multiorgan dysfunction syndrome (MODS) and circulatory arrest.
+RESULTS: Sixteen patients showed odontogenic infections that spread over multiple maxillo-facial and cervical regions accompanied by septic laboratory signs.
+In 16 cases risk factors for the development of odontogenic abscesses like diabetes mellitus, obesity, chronic alcohol and nicotine abuse, rheumatism and poor oral hygiene were present.
+Intraoperative swabs showed a typical polymicrobial aerobic and anaerobic spectrum of oral bacteria, especially anaerobes and streptococci, mainly Streptocococcus viridans.
+CONCLUSION: Odontogenic infections with fulminant progression should be treated based on clinical and imaging data with immediate surgical incision and drainage including elimination of odontogenic foci as well as intensified intra- and postoperative irrigation.
+A combination of tazobactam and piperacillin has proven to be a good first choice and can be recommended for abscesses that spread over multiple levels with initial signs of severe infections.
+Astroviruses (AstV) are single-stranded, positive-sense RNA viruses, best known for causing diarrhea in humans and are also found in many other mammals; in those, the relevance in gastroenteritis remains unclear.
+Recently described neurotropic AstV showed associations with encephalitis in humans as well as in other mammals.
+In Switzerland, two different neurotropic AstV were identified in cattle, as well as one in a sheep.
+The high genetic similarity between the ovine and one of the bovine AstV strengthens the hypothesis of an interspecies transmission.
+In humans, AstV associated with encephalitis were found also in human stool samples, suggesting that in these patients the infection spreads from the gastrointestinal tract to the brain under certain conditions, such as immunosuppression.
+The aims of this study were (1) the investigation of the potential occurrence of neurotropic AstV in feces samples, (2) the discovery and analysis of so far unknown AstV in small ruminants and other ruminant species’ fecal samples and (3) the examination of a potential interspecies transmission of AstV.
+To achieve these aims, RNA extraction out of 164 fecal samples from different ruminant species was performed and all samples were screened for known neurotropic AstV occurring in Switzerland, as well as for various AstV using RT-PCR.
+The generated sequences were compared to nucleotide- and amino acid databases, virus properties were identified, and phylogenetic analyses as well as recombination analysis were performed.
+The excretion of neurotropic AstV in small ruminants’ feces could not be demonstrated, but this work suggests the first identification of AstV in goats as well as the discovery of multiple and highly diverse new genetic variants in small ruminants, which lead to a classification into novel genotype-species.
+Additionally, the prediction of multiple recombination events in four of five newly discovered full or almost full-length genome sequences suggests a plausible interspecies transmission.
+The findings point out the occurrence and fecal shedding of previously unknown AstV in sheep and goats and pave the way towards a better understanding of the diversity and transmission of AstV in small ruminants.
+A growing body of information clearly indicates that excess ROS/RNS production and oxidative stress are major detrimental consequences of the most common commercial stressors in poultry production.
+During evolution, antioxidant defence systems were developed in poultry to survive in an oxygenated atmosphere.
+They include a complex network of internally synthesised (e.g., antioxidant enzymes, (glutathione) GSH, (coenzyme Q) CoQ) and externally supplied (vitamin E, carotenoids, etc.)
+In fact, all antioxidants in the body work cooperatively as a team to maintain optimal redox balance in the cell/body.
+This balance is a key element in providing the necessary conditions for cell signalling, a vital process for regulation of the expression of various genes, stress adaptation and homeostasis maintenance in the body.
+Since ROS/RNS are considered to be important signalling molecules, their concentration is strictly regulated by the antioxidant defence network in conjunction with various transcription factors and vitagenes.
+In fact, activation of vitagenes via such transcription factors as Nrf2 leads to an additional synthesis of an array of protective molecules which can deal with increased ROS/RNS production.
+Therefore, it is a challenging task to develop a system of optimal antioxidant supplementation to help growing/productive birds maintain effective antioxidant defences and redox balance in the body.
+On the one hand, antioxidants, such as vitamin E, or minerals (e.g., Se, Mn, Cu and Zn) are a compulsory part of the commercial pre-mixes for poultry, and, in most cases, are adequate to meet the physiological requirements in these elements.
+On the other hand, due to the aforementioned commercially relevant stressors, there is a need for additional support for the antioxidant system in poultry.
+This new direction in improving antioxidant defences for poultry in stress conditions is related to an opportunity to activate a range of vitagenes (via Nrf2-related mechanisms: superoxide dismutase, SOD; heme oxygenase-1, HO-1; GSH and thioredoxin, or other mechanisms: Heat shock protein (HSP)/heat shock factor (HSP), sirtuins, etc.)
+Therefore, the development of vitagene-regulating nutritional supplements is on the agenda of many commercial companies worldwide.
+One key player is the ubiquitously expressed serine protease furin, which cleaves a plethora of proteins at polybasic recognition motifs.
+Thus, it is not surprising that aberrant furin activity is associated with a variety of disorders including cancer.
+Furthermore, the enzymatic activity of furin is exploited by numerous viral and bacterial pathogens, thereby enhancing their virulence and spread.
+In this review, we describe the physiological and pathophysiological substrates of furin and discuss how dysregulation of a simple proteolytic cleavage event may promote infectious diseases and cancer.
+We also outline cellular mechanisms regulating the expression and activation of furin and summarise current approaches that target this protease for therapeutic intervention.
+Fulminant viral hepatitis (FVH) is a devastating and unexplained condition that strikes otherwise healthy individuals during primary infection with common liver-tropic viruses.
+We report a child who died of FVH upon infection with hepatitis A virus (HAV) at age 11 yr and who was homozygous for a private 40-nucleotide deletion in IL18BP, which encodes the IL-18 binding protein (IL-18BP).
+This mutation is loss-of-function, unlike the variants found in a homozygous state in public databases.
+We show that human IL-18 and IL-18BP are both secreted mostly by hepatocytes and macrophages in the liver.
+Moreover, in the absence of IL-18BP, excessive NK cell activation by IL-18 results in uncontrolled killing of human hepatocytes in vitro.
+These findings provide proof-of-principle that FVH can be caused by single-gene inborn errors that selectively disrupt liver-specific immunity.
+They also show that human IL-18 is toxic to the liver and that IL-18BP is its antidote.
+BACKGROUND: Researchers increasingly use social contact data to inform models for infectious disease spread with the aim of guiding effective policies about disease prevention and control.
+In this article, we undertake a systematic review of the study design, statistical analyses, and outcomes of the many social contact surveys that have been published.
+METHODS: We systematically searched PubMed and Web of Science for articles regarding social contact surveys.
+We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines as closely as possible.
+RESULTS: In total, we identified 64 social contact surveys, with more than 80% of the surveys conducted in high-income countries.
+Study settings included general population (58%), schools or universities (37%), and health care/conference/research institutes (5%).
+The largest number of studies did not focus on a specific age group (38%), whereas others focused on adults (32%) or children (19%).
+Retrospective (45%) and prospective (41%) designs were used most often with 6% using both for comparison purposes.
+The definition of a contact varied among surveys, e.g., a nonphysical contact may require conversation, close proximity, or both.
+We identified age, time schedule (e.g., weekday/weekend), and household size as relevant determinants of contact patterns across a large number of studies.
+CONCLUSIONS: We found that the overall features of the contact patterns were remarkably robust across several countries, and irrespective of the study details.
+By considering the most common approach in each aspect of design (e.g., sampling schemes, data collection, definition of contact), we could identify recommendations for future contact data surveys that may be used to facilitate comparison between studies.
+Viral infections cause substantial human morbidity and mortality, and are a significant health burden worldwide.
+Following a viral infection, the host may initiate complex antiviral immune responses to antagonize viral invasion and replication.
+However, proinflammatory antiviral immune responses pose a great threat to the host if not properly held in check.
+Interleukin (IL)-17 is a pleiotropic cytokine participating in a variety of physiological and pathophysiological conditions, including tissue integrity maintenance, cancer progression, autoimmune disease development and, more intriguingly, infectious diseases.
+Abundant evidence suggests that while IL-17 plays a crucial role in enhancing effective antiviral immune responses, it may also promote and exacerbate virus-induced illnesses.
+Accumulated experimental and clinical evidence has broadened our understanding of the seemingly paradoxical role of IL-17 in viral infections and suggests that IL-17-targeted immunotherapy may be a promising therapeutic option.
+Herein, we summarize current knowledge regarding the protective and pathogenic roles of IL-17 in viral infections, with emphasis on underlying mechanisms.
+The various and critical roles of IL-17 in viral infections necessitate the development of therapeutic strategies that are uniquely tailored to both the infectious agent and the infection environment.
+We hypothesized that fever in children with viral bronchiolitis indicates the need for consideration of superimposed bacterial pneumonia.
+We conducted a retrospective study of 349 children aged 2 years and younger with diagnoses of respiratory syncytial virus (RSV) and viral upper respiratory infection.
+Febrile children with RSV were over twice as likely to be diagnosed with bacterial pneumonia as those who were afebrile (60% vs 27%, P < .001).
+In the 171 children who had bronchiolitis caused by a virus other than RSV, 51% were afebrile.
+These children were 8 times more likely to be diagnosed with pneumonia than those who were afebrile (65% vs 8%, P < .001).
+Evaluation of febrile children with viral bronchiolitis may allow early diagnosis and treatment of secondary bacterial pneumonia.
+Persistent central nervous system (CNS) inflammation, as seen in chronic infections or inflammatory demyelinating diseases such as Multiple Sclerosis (MS), results in the accumulation of various B cell subsets in the CNS, including naïve, activated, memory B cells (Bmem), and antibody secreting cells (ASC).
+However, factors driving heterogeneous B cell subset accumulation and antibody (Ab) production in the CNS compartment, including the contribution of ectopic lymphoid follicles (ELF), during chronic CNS inflammation remain unclear and is a major gap in our understanding of neuroinflammation.
+We sought to address this gap using the Theiler's murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD) model of progressive MS.
+In this model, injection of the virus into susceptible mouse strains results in a persistent infection associated with demyelination and progressive disability.
+During chronic infection, the predominant B cell phenotypes accumulating in the CNS were isotype-switched B cells, including Bmem and ASC with naïve/early activated and transitional B cells present at low frequencies.
+B cell accumulation in the CNS during chronic TMEV-IDD coincided with intrathecal Ab synthesis in the cerebrospinal fluid (CSF).
+Mature and isotype-switched B cells predominately localized to the meninges and perivascular space, with IgG isotype-switched B cells frequently accumulating in the parenchymal space.
+Both mature and isotype-switched B cells and T cells occupied meningeal and perivascular spaces, with minimal evidence for spatial organization typical of ELF mimicking secondary lymphoid organs (SLO).
+Moreover, immunohistological analysis of immune cell aggregates revealed a lack of SLO-like ELF features, such as cell proliferation, cell death, and germinal center B cell markers.
+Nonetheless, flow cytometric assessment of B cells within the CNS showed enhanced expression of activation markers, including moderate upregulation of GL7 and expression of the costimulatory molecule CD80.
+B cell-related chemokines and trophic factors, including APRIL, BAFF, CXCL9, CXCL10, CCL19, and CXCL13, were elevated in the CNS.
+These results indicate that localization of heterogeneous B cell populations, including activated and isotype-switched B cell phenotypes, to the CNS and intrathecal Ab (ItAb) synthesis can occur independently of SLO-like follicles during chronic inflammatory demyelinating disease.
+Here, specific chicken bone marrow DC-binding peptides were selected using a phage display peptide library and confirmed through ELISA, flow cytometry, fluorescence microscopy, and laser confocal microscopy.
+The peptide candidate SPHLHTSSPWER, named SP, was fused to the infectious bursal disease virus (IBDV) structural protein and protective antigen VP2.
+In vitro, the expression of DC markers (CD80, CD83, CD86, DEC205, and MHCII) and some cytokines (IFN-γ, IL-12, TNF-α, IL-1β, IL-6, and CXCLi1) by VP2-SP-stimulated DCs was significantly higher than that by DCs treated with the VP2-control peptide at 4 h (p < 0.001).
+In addition, an oral vaccine targeting DCs was generated using chicken-borne Lactobacillus saerimneri M11 (L. sae M11) to deliver VP2 fused with SP.
+Anti-IBDV mucosal and humoral immune responses were induced efficiently via oral administration, resulting in higher protective efficacy in the VP2-SP group than the VP2 group.
+Therefore, chicken DC targeting of IBDV protective antigen VP2 delivered by L. sae provides effective immune protection in chicken.
+Our study may promote research on the DC-targeting strategy to enhance the effectiveness of chicken vaccines.
+The goals of our study were to compare the immune response to different killed and modified live vaccines against PRRS virus and to monitor the antibody production and the cell mediated immunity both at the systemic and local level.
+In the experiment, we immunized four groups of piglets with two commercial inactivated (A1—Progressis, A2—Suivac) and two modified live vaccines (B3—Amervac, B4—Porcilis).
+Twenty-one days after the final vaccination, all piglets, including the control non-immunized group (C5), were i.n., infected with the Lelystad strain of PRRS virus.
+The serum antibody response (IgM and IgG) was the strongest in group A1 followed by two MLV (B3 and B4) groups.
+Locally, we demonstrated the highest level of IgG antibodies in bronchoalveolar lavages (BALF), and saliva in group A1, whereas low IgA antibody responses in BALF and feces were detected in all groups.
+We have found virus neutralization antibody at DPV 21 (days post vaccination) and higher levels in all groups including the control at DPI 21 (days post infection).
+Positive antigen specific cell-mediated response in lymphocyte transformation test (LTT) was observed in groups B3 and B4 at DPV 7 and in group B4 at DPV 21 and in all intervals after infection.
+The IFN-γ producing lymphocytes after antigen stimulation were found in CD4(−)CD8(+) and CD4(+)CD8(+) subsets of all immunized groups 7 days after infection.
+The virus was detected in all groups of piglets in serum, saliva, and occasionally in feces at DPI 3.
+It can be concluded that antibodies after immunization and infection, and the virus after infection can be detected in all the compartments monitored.
+Immunization with inactivated vaccine A1—Progressis induces high levels of antibodies produced both systemically and locally.
+After infection virus secretion gradually decreases in group B3, indicating tendency to induce sterile immunity.
+OBJECTIVE: Tumor-treating fields are currently used to successfully treat various cancers; however, the specific pathways associated with its efficacy remain unknown in the immune responses.
+MATERIALS AND METHODS: We subjected RAW 264.7 mouse macrophages to clinically relevant levels of tumor-treating fields (0.9 V/cm, 150 kHz) and evaluated alterations in cytokine expression and release, as well as cell viability.
+Additionally, we investigated the status of immunomodulatory pathways to determine their roles in tumor-treating fields–mediated immune activation.
+RESULTS AND DISCUSSION: Our results indicated that tumor-treating fields treatment at 0.9 V/cm decreased cell viability and increased cytokine messenger RNA/protein levels, as well as levels of nitric oxide and reactive oxygen species, relative to controls.
+The levels of tumor necrosis factor α, interleukin 1β, and interleukin 6 were markedly increased in tumor-treating fields–treated RAW 264.7 cells cocultured with 4T1 murine mammary carcinoma cells compared with those in 4T1 or RAW 264.7 cells with or without tumor-treating fields treatment.
+Moreover, the viability of 4T1 cells treated with the conditioned medium of tumor-treating fields–stimulated RAW 264.7 cells decreased, indicating that macrophage activation by tumor-treating fields effectively killed the tumor cells.
+Moreover, tumor-treating fields treatment activated the nuclear factor κB and mitogen-activated protein kinase pathways involved in immunomodulatory signaling.
+CONCLUSION: These results provide critical insights into the mechanisms through which tumor-treating fields affect macrophage-specific immune responses and the efficacy of this method for cancer treatment.
+Disease-modifying treatments (including immunosuppressive treatments) have shown positive effects on the disease course, but are associated with systemic consequences on the immune system and may increase the risk of infections and alter vaccine efficiency.
+Over the last years, vaccine hesitancy has steadily grown especially in Western countries, partly due to fear of sequelae arising from vaccination, especially neurological disorders.
+In this review, we highlight the immunology of vaccination, provide a review of literature and discuss the clinical consideration of MS, vaccination and immunosuppression.
+In conclusion, there is consensus that MS cannot be caused by vaccines, neither by inactivated nor by live vaccines.
+However, particular attention should be paid to two aspects: First, in immunocompromised patients, live vaccines may lead to a stronger immune reaction with signs of the disease against which the patients have been vaccinated, albeit in weakened form.
+Second, protection provided by vaccination should be controlled in patients who have been vaccinated while receiving immunomodulatory or immunosuppressive treatment.
+In conclusion, there is evidence that systemic infections can worsen MS, thus vaccination will lower the risk of relapses by reducing the risk of infections.
+We selected the vacuolar proton ATPase inhibitor bafilomycin A1 for analysis because of its well-known antiautophagy property of impeding acidification during the late stage of autophagic flux.
+We documented that bafilomycin treatment from 48 to 72 h postinfection lowered VZV titers substantially (P ≤ 0.008).
+Because we were unable to define the site of the block in the infectious cycle by confocal microscopy, we turned to electron microscopy.
+Capsids were observed in the nucleus, in the perinuclear space, and in the cytoplasm adjacent to Golgi apparatus vesicles.
+Many of the capsids had an aberrant appearance, as has been observed previously in infections not treated with bafilomycin.
+In contrast to prior untreated infections, however, secondary envelopment of capsids was not seen in the trans-Golgi network, nor were prototypical enveloped particles with capsids (virions) seen in cytoplasmic vesicles after bafilomycin treatment.
+Instead, multiple particles with varying diameters without capsids (light particles) were seen in large virus assembly compartments near the disorganized Golgi apparatus.
+Bafilomycin treatment also led to increased numbers of multivesicular bodies in the cytoplasm, some of which contained remnants of the Golgi apparatus.
+In summary, we have defined a previously unrecognized property of bafilomycin whereby it disrupted the site of secondary envelopment of VZV capsids by altering the pH of the trans-Golgi network and thereby preventing the correct formation of virus assembly compartments.
+IMPORTANCE This study of VZV assembly in the presence of bafilomycin A1 emphasizes the importance of the Golgi apparatus/trans-Golgi network as a platform in the alphaherpesvirus life cycle.
+We have previously shown that VZV induces levels of autophagy far above the basal levels of autophagy in human skin, a major site of VZV assembly.
+The current study documented that bafilomycin treatment led to impaired assembly of VZV capsids after primary envelopment/de-envelopment but before secondary reenvelopment.
+This VZV study also complemented prior herpes simplex virus 1 and pseudorabies virus studies investigating two other inhibitors of endoplasmic reticulum (ER)/Golgi apparatus function: brefeldin A and monensin.
+Studies with porcine herpesvirus demonstrated that primary enveloped particles accumulated in the perinuclear space in the presence of brefeldin A, while studies with herpes simplex virus 1 documented an impaired secondary assembly of enveloped viral particles in the presence of monensin.
+BACKGROUND: As of February 25, 2019, 875 cases of Ebola virus disease (EVD) were reported in North Kivu and Ituri Provinces, Democratic Republic of Congo.
+Since the beginning of October 2018, the outbreak has largely shifted into regions in which active armed conflict has occurred, and in which EVD cases and their contacts have been difficult for health workers to reach.
+We used available data on the current outbreak, with case-count time series from prior outbreaks, to project the short-term and long-term course of the outbreak.
+METHODS: For short- and long-term projections, we modeled Ebola virus transmission using a stochastic branching process that assumes gradually quenching transmission rates estimated from past EVD outbreaks, with outbreak trajectories conditioned on agreement with the course of the current outbreak, and with multiple levels of vaccination coverage.
+We then constructed an ensemble of forecasts to be compared and recorded for future evaluation against final outcomes.
+From August 20, 2018 to February 25, 2019, short-term model projections were validated against known case counts.
+RESULTS: During validation of short-term projections, from one week to four weeks, we found models consistently scored higher on shorter-term forecasts.
+Based on case counts as of February 25, the stochastic model projected a median case count of 933 cases by February 18 (95% prediction interval: 872–1054) and 955 cases by March 4 (95% prediction interval: 874–1105), while the auto-regression model projects median case counts of 889 (95% prediction interval: 876–933) and 898 (95% prediction interval: 877–983) cases for those dates, respectively.
+Although the outbreak is already larger than all past Ebola outbreaks other than the 2013–2016 outbreak of over 26,000 cases, our models do not project that it is likely to grow to that scale.
+The stochastic model estimates that vaccination coverage in this outbreak is lower than reported in its trial setting in Sierra Leone.
+CONCLUSIONS: Our projections are concentrated in a range up to about 300 cases beyond those already reported.
+While a catastrophic outbreak is not projected, it is not ruled out, and prevention and vigilance are warranted.
+Prospective validation of our models in real time allowed us to generate more accurate short-term forecasts, and this process may prove useful for future real-time short-term forecasting.
+We estimate that transmission rates are higher than would be seen under target levels of 62% coverage due to contact tracing and vaccination, and this model estimate may offer a surrogate indicator for the outbreak response challenges.
+BACKGROUND: Strong laboratory capacity is essential for detecting and responding to emerging and re-emerging global health threats.
+We conducted a quantitative laboratory assessment during 2014–2015 in two resource-limited provinces in southern China, Guangxi and Guizhou in order to guide strategies for strengthening core capacities as required by the International Health Regulations (IHR 2005).
+METHODS: We selected 28 public health and clinical laboratories from the provincial, prefecture and county levels through a quasi-random sampling approach.
+The 11-module World Health Organization (WHO) laboratory assessment tool was adapted to the local context in China.
+At each laboratory, modules were scored 0–100% through a combination of paper surveys, in-person interviews, and visual inspections.
+We defined module scores as strong (> = 85%), good (70–84%), weak (50–69%), and very weak (< 50%).
+We estimated overall capacity and compared module scores across the provincial, prefecture, and county levels.
+RESULTS: Overall, laboratories in both provinces received strong or good scores for 10 of the 11 modules.
+These findings were primarily driven by strong and good scores from the two provincial level laboratories; prefecture and county laboratories were strong or good for only 8 and 6 modules, respectively.
+The module, ‘Public Health Functions’ (e.g., surveillance and reporting practices) lagged far behind all other modules (mean score = 46%) across all three administrative levels.
+CONCLUSIONS: Laboratories in Guangxi and Guizhou are generally performing well in laboratory capacity as required by IHR.
+However, we recommend targeted interventions particularly for county-level laboratories, where we identified a number of gaps.
+Given the importance of surveillance and reporting, addressing gaps in public health functions is likely to have the greatest positive impact for IHR requirements.
+The quantitative WHO laboratory assessment tool was useful in identifying both comparative strengths and weaknesses.
+However, prior to future assessments, the tool may need to be aligned with the new WHO IHR monitoring and evaluation framework.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12889-019-6777-2) contains supplementary material, which is available to authorized users.
+BACKGROUND: Altered coagulation and alveolar injury are the hallmarks of acute respiratory distress syndrome (ARDS).
+However, whether the biomarkers that reflect pathophysiology differ depending on the etiology of ARDS has not been examined.
+This study aimed to investigate the biomarker profiles of coagulopathy and alveolar epithelial injury in two subtypes of ARDS: patients with direct common risk factors (dARDS) and those with idiopathic or immune-related diseases (iARDS), which are classified as “ARDS without common risk factors” based on the Berlin definition.
+METHODS: This retrospective, observational study included adult patients who were admitted to the intensive care unit (ICU) at a university hospital with a diagnosis of ARDS with no indirect risk factors.
+Plasma biomarkers (thrombin–antithrombin complex [TAT], plasminogen activator inhibitor [PAI]-1, protein C [PC] activity, procalcitonin [PCT], surfactant protein [SP]-D, and KL-6) were routinely measured during the first 5 days of the patient’s ICU stay.
+RESULTS: Among 138 eligible patients with ARDS, 51 were excluded based on the exclusion criteria (n = 41) or other causes of ARDS (n = 10).
+Of the remaining 87 patients, 56 were identified as having dARDS and 31 as having iARDS.
+Among the iARDS patients, TAT (marker of thrombin generation) and PAI-1 (marker of inhibited fibrinolysis) were increased, and PC activity was above normal.
+In contrast, PC activity was significantly decreased, and TAT or PAI-1 was present at much higher levels in dARDS compared with iARDS patients.
+Significant differences were also observed in PCT, SP-D, and KL-6 between patients with dARDS and iARDS.
+The receiver operating characteristic (ROC) analysis showed that areas under the ROC curve for PC activity, PAI-1, PCT, SP-D, and KL-6 were similarly high for distinguishing between dARDS and iARDS (PC 0.86, P = 0.33; PAI-1 0.89, P = 0.95; PCT 0.89, P = 0.66; and SP-D 0.88, P = 0.16 vs. KL-6 0.90, respectively).
+CONCLUSIONS: Coagulopathy and alveolar epithelial injury were observed in both patients with dARDS and with iARDS.
+The different patterns of PAI-1, PC activity, SP-D, and KL-6 may help in differentiating between these ARDS subtypes.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13054-019-2559-6) contains supplementary material, which is available to authorized users.
+BACKGROUND: Zika virus (ZIKV) infections reported in recent epidemics have been linked to clinical complications that had never been associated with ZIKV before.
+Adaptive mutations could have contributed to the successful emergence of ZIKV as a global health threat to a nonimmune population.
+However, the causal relationships between the ZIKV genetic determinants, the pathogenesis and the rapid spread in Latin America and in the Caribbean remain widely unknown.
+OBJECTIVES: The aim of this study was to characterise three ZIKV isolates obtained from patient samples during the 2015/2016 Brazilian epidemics.
+METHODS: The ZIKV genomes of these strains were completely sequenced and in vitro infection kinetics experiments were carried out in cell lines and human primary cells.
+FINDINGS: Eight nonsynonymous substitutions throughout the viral genome of the three Brazilian isolates were identified.
+Infection kinetics experiments were carried out with mammalian cell lines A549, Huh7.5, Vero E6 and human monocyte-derived dendritic cells (mdDCs) and insect cells (Aag2, C6/36 and AP61) and suggest that some of these mutations might be associated with distinct viral fitness.
+The clinical isolates also presented differences in their infectivity rates when compared to the well-established ZIKV strains (MR766 and PE243), especially in their abilities to infect mammalian cells.
+MAIN CONCLUSIONS: Genomic analysis of three recent ZIKV isolates revealed some nonsynonymous substitutions, which could have an impact on the viral fitness in mammalian and insect cells.
+BACKGROUND: The complexity of diagnosis for critically ill dyspnea presentations in the emergency department remains a challenge.
+Point-of-care ultrasound (POCUS) has been shown to impact the diagnosis of dyspnea presentations in resource-rich settings, and may be of greater diagnostic benefit in resource-limited settings.
+METHODS: We prospectively enrolled a convenience sample of 100 patients presenting with dyspnea in the Emergency Department at University Teaching Hospital of Kigali (UTH-K) in Rwanda.
+After a traditional history and physical exam, the primary treating team listed their 3 main diagnoses and ranked their confidence accuracy in the leading diagnosis on a Likert scale (1–5).
+Multi-organ ultrasound scans performed by a separate physician sonographer assessed the heart, lungs, inferior vena cava, and evaluated for lower extremity deep vein thrombosis or features of disseminated tuberculosis.
+The sonographer reviewed the findings with the treating team, who then listed 3 diagnoses post-ultrasound and ranked their confidence accuracy in the leading diagnosis on a Likert scale (1–5).
+The hospital diagnosis at discharge was used as the standard in determining the accuracy of the pre- and post-ultrasound diagnoses.
+RESULTS: Of the 99 patients included in analysis, 57.6% (n = 57) were male, with a mean age of 45 years.
+Most of them had high-level acuity (54.5%), the dyspnea was of acute onset (45.5%) and they came from district hospitals (50.5%).
+The most frequent discharge diagnoses were acute decompensated heart failure (ADHF) (26.3%) and pneumonia (21.2%).
+The diagnostic accuracy for ADHF increased from 53.8 to 100% (p = 0.0004), from 38 to 85.7% for pneumonia (p = 0.0015), from 14.2 to 85.7% for extrapulmonary tuberculosis (p = 0.0075), respectively, pre and post-ultrasound.
+The clinician confidence in the leading diagnosis changed from a mean of 3.5 to a mean of 4.7 (Likert scale 0–5) (p < 0.001).
+CONCLUSIONS: In dyspneic patients presenting to this Emergency Department, ultrasound frequently changed the leading diagnosis, significantly increased clinicians’ confidence in the leading diagnoses, and improved diagnostic accuracy.
+Despite the significant progress in the recent efforts toward developing an effective vaccine against toxoplasmosis, the search for new protective vaccination strategy still remains a challenge and elusive goal because it becomes the appropriate way to prevent the disease.
+Various experimental approaches in the past few years showed that developing a potential vaccine against the disease can be achievable.
+The combination of multi-epitopes expressing different stages of the parasite life cycle has become an optimal strategy for acquiring a potent, safe, and effective vaccine.
+Epitope-based vaccines have gained attention as alternative vaccine candidates due to their ability of inducing protective immune responses.
+This mini-review highlights the current status and the prospects of Toxoplasma gondii vaccine development along with the application of epitope-based vaccine in the future parasite immunization as a novel under development and evaluation strategy.
+OBJECTIVE: Parasitic infestation is a major cause of losses in livestock production in tropical regions.
+A cross-sectional study was conducted to determine the prevalence of Gastro-intestinal (GI) parasites of dromedary camel (Camelus dromedarius) and fat-tailed sheep (dhumba), and the prevalence of hemoparasites in camel from Dhaka, Bangladesh.
+MATERIALS AND METHODS: A total of 87 fecal samples (32 dhumba and 55 camel) and 55 camel blood samples were collected during September–October 2015.
+Fecal samples were examined by direct smear, sedimentation method, flotation technique, and McMaster technique for GI parasite.
+RESULTS: 62% camel (n = 34; 95% confidence interval (CI): 47.7–74.6) were infected with at least one genus of parasite.
+(n = 16; 29%; 95% CI: 17.6–42.9), Balantidium coli (n = 12; 22%; 95% CI: 11.8–35.0), Trichostrongylus spp.
+Total 59.4% dhumba (n = 19; 95% CI: 41–76) were positive for GI parasite, including Trichostrongylus spp.
+(n = 9; 28%; 95% CI: 13.8–46.8), B. coli (n = 5; 15.6%; 95% CI: 5.3–32.8), and Trichuris spp.
+CONCLUSIONS: High percentage of parasitic infestation in camel and dhumba in the present study refers to the necessity of use of anthelmintic for health and production improvement and to prevent zoonotic parasite transmission to animal handler and workers.
+Over the last 15 years, the number of its recognized species has grown from 77 to 106, but knowledge of their interrelationships has not kept pace.
+Species limits and phylogenetic relationships of this morphologically conservative group remain problematic due both to poor sampling across the Afrotropics and to repeated instances of mitochondrial-nuclear discordance.
+Recent intensive surveys in East Africa and neighboring regions, coupled with parallel studies by others in West Africa and in Southern Africa, offer a new basis for understanding its evolutionary history.
+RESULTS: We investigated phylogenetic relationships and intraspecific genetic variation in the Afro-Palearctic clade of Rhinolophidae using broad sampling.
+We sequenced mitochondrial cytochrome-b (1140 bp) and four independent and informative nuclear introns (2611 bp) for 213 individuals and incorporated sequence data from 210 additional individuals on GenBank that together represent 24 of the 33 currently recognized Afrotropical Rhinolophus species.
+We addressed the widespread occurrence of mito-nuclear discordance in Rhinolophus by inferring concatenated and species tree phylogenies using only the nuclear data.
+Well resolved mitochondrial, concatenated nuclear, and species trees revealed phylogenetic relationships and population structure of the Afrotropical species and species groups.
+CONCLUSIONS: Multiple well-supported and deeply divergent lineages were resolved in each of the six African Rhinolophus species groups analyzed, suggesting as many as 12 undescribed cryptic species; these include several instances of sympatry among close relatives.
+Coalescent lineage delimitation offered support for new undescribed lineages in four of the six African groups in this study.
+On the other hand, two to five currently recognized species may be invalid based on combined mitochondrial and/or nuclear phylogenetic analyses.
+Validation of these cryptic lineages as species and formal relegation of current names to synonymy will require integrative taxonomic assessments involving morphology, ecology, acoustics, distribution, and behavior.
+The resulting phylogenetic framework offers a powerful basis for addressing questions regarding their ecology and evolution.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12862-019-1485-1) contains supplementary material, which is available to authorized users.
+BACKGROUND: Porcine circovirus type 3 (PCV3) is an emerging circovirus species, that has been reported in major pig-raising countries including the United States, China, South Korea, Brazil, Spain, and Poland.
+RESULTS: A real-time loop-mediated isothermal amplification (LAMP) assay was developed for rapid detection of porcine circovirus 3 (PCV3).
+The method had a detection limit of 1 × 10(1) copies/μL with no cross-reactions with classical swine fever virus (CSFV) C strain, foot-and-mouth disease virus (FMDV), porcine circovirus 2 (PCV2) LG vaccine strain, porcine epidemic diarrhoea virus (PEDV), porcine respiratory and reproductive syndrome virus (PRRSV), or pseudorabies virus (PRV).
+The PCV3 positive detection rate of 203 clinical samples for the real-time LAMP assay was 89.66% (182/203).
+CONCLUSIONS: The real-time LAMP assay is highly sensitive, and specific for use in epidemiological investigations of PCV3.
+Porcine reproductive and respiratory syndrome virus (PRRSV) is a positive-stranded RNA virus that grows in macrophages and causes acute pneumonia in pigs.
+However, due to its high antigenic variability and poorly understood immunopathogenesis, there is currently no effective vaccine or treatment to control PRRSV infection.
+The common occurrence of PRRSV infection with bacterial infections as well as its inflammatory-driven pathobiology raises the question of the value of antibiotics with immunomodulating properties for the treatment of the disease it causes.
+The macrolide antibiotic Tulathromycin (TUL) has been found to exhibit potent anti-inflammatory and immunomodulating properties in cattle and pigs.
+The aim of this study was to characterize the anti-viral and immunomodulating properties of TUL in PRRSV-infected porcine macrophages.
+Our findings indicate that blood monocyte-derived macrophages are readily infected by PRRSV and can be used as an effective cellular model to study PRRSV pathogenesis.
+TUL did not change intracellular or extracellular viral titers, not did it alter viral receptors (CD163 and CD169) expression on porcine macrophages.
+In contrast, TUL exhibited potent immunomodulating properties, which therefore occurred in the absence of any direct antiviral effects against PRRSV.
+TUL had an additive effect with PRRSV on the induction of macrophage apoptosis, and inhibited virus-induced necrosis.
+TUL significantly attenuated PRRSV-induced macrophage pro-inflammatory signaling (CXCL-8 and mitochondrial ROS production) and prevented PRRSV inhibition of non-opsonized and opsonized phagocytic function.
+Together, these data demonstrate that TUL inhibits PRRSV-induced inflammatory responses in porcine macrophages and protects against the phagocytic impairment caused by the virus.
+Research in live pigs is warranted to assess the potential clinical benefits of this antibiotic in the context of virally induced inflammation and tissue injury.
+Microbial life permeates Earth's critical zone and has likely inhabited nearly all our planet's surface and near subsurface since before the beginning of the sedimentary rock record.
+Given the vast time that Earth has been teeming with life, do astrobiologists truly understand what geological features untouched by biological processes would look like?
+In the search for extraterrestrial life in the Universe, it is critical to determine what constitutes a biosignature across multiple scales, and how this compares with “abiosignatures” formed by nonliving processes.
+Developing standards for abiotic and biotic characteristics would provide quantitative metrics for comparison across different data types and observational time frames.
+Transmissible vaccines offer a revolutionary approach for controlling infectious disease and may provide one of the few feasible methods for eliminating pathogens from inaccessible wildlife populations.
+Current efforts to develop transmissible vaccines use recombinant vector technology whereby pathogen antigens are engineered to be expressed from innocuous infectious viral vectors.
+The resulting vaccines can transmit from host to host, amplifying the number of vaccine‐protected individuals beyond those initially vaccinated directly through parenteral inoculation.
+One main engineering challenge is the potential for natural selection to favor vaccine mutants that eliminate or reduce expression of antigenic inserts, resulting in immunogenic decay of the vaccine over time.
+Here, we study a mathematical model of vector mutation whereby continuous elimination of the antigenic insert results in reversion of the vaccine back into the insert‐free vector.
+We use this model to quantify the maximum allowable rate of reversion that can be tolerated for a transmissible vaccine to maintain a critical threshold level of immunogenicity against a target pathogen.
+Our results demonstrate that even for transmissible vaccines where reversion is frequent, performance will often substantially exceed that of conventional, directly administered vaccines.
+Further, our results demonstrate the feasibility of designing transmissible vaccines that yield desired levels of immunogenicity, yet degrade at a rate sufficient for persistence of the recombinant vaccine within the environment to be minimized.
+Building sustainable national health laboratory systems requires laboratory leaders who can address complex and changing demands for services and build strong collaborative networks.
+Global consensus on laboratory leadership competencies is critically important to ensure the harmonization of learning approaches for curriculum development across relevant health sectors.
+The World Health Organization (WHO), the Food and Agriculture Organization of the United Nations (FAO), the World Organisation for Animal Health (OIE), the European Centre for Disease Prevention and Control (ECDC), the U.S. Centers for Disease Control and Prevention (CDC), and the Association of Public Health Laboratories (APHL) have partnered to develop a Laboratory Leadership Competency Framework (CF) that provides a foundation for the Global Laboratory Leadership Programme (GLLP).
+The CF represents the first global consensus from multiple disciplines on laboratory leadership competencies and provides structure for the development of laboratory leaders with the knowledge, skills and abilities to build bridges, enhance communication, foster collaboration and develop an understanding of existing synergies between the human, animal, environmental, and other relevant health sectors.
+The hydroalcoholic extract and ethyl acetate fraction of Punica granatum leaves have been known to exhibit anti-inflammatory activities.
+In this study, we investigated the therapeutic effects of galloyl-hexahydroxydiphenoyl (HHDP)-glucose isolated from pomegranate leaves on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice.
+Male BALB/c mice were treated with different doses of galloyl-HHDP-glucose (5, 50, and 100 mg/Kg) or dexamethasone at 5 mg/Kg (per os) 6 h after intra-tracheal instillation of LPS.
+Twenty-four hours after LPS challenge, bronchoalveolar lavage fluid (BALF), and lung samples were collected for analyses.
+They were evaluated by monitoring the expression of NF-κB, JNK, and cytokine genes and proteins, as well as cell migration and lung function.
+Likewise, the galloyl-HHDP-glucose-treated animals presented reduced expression of the TNF-α, IL-6, and IL-1β genes in the lungs and reduced TNF-α, IL-6, IL-1β, and IL-8 protein levels when compared with the vehicle-treated LPS-challenged mice.
+In addition, the ALI mice treated with galloyl-HHDP-glucose also presented reduced lung inflammatory cell accumulation, especially that of neutrophils, in their BALF and lungs.
+In addition, galloyl-HHDP-glucose treatment markedly ameliorated the LPS-induced pulmonary mechanism complications and attenuated weight loss.
+Overall, we showed for the first time that galloyl-HHDP-glucose protects against ALI, and may be useful for treating ALI and other inflammatory disorders.
+This study reveals that cellular stress leads to the incorporation of the adaptor protein SINTBAD (TBKBP1) into membraneless, cytosolic speckles.
+Determination of the interactome identified >100 proteins forming constitutive and stress-inducible members of an MLO that we termed SINT-speckles.
+SINT-speckles partially colocalize with activated TBK1, and deletion of SINTBAD and the SINT-speckle component AZI2 leads to impaired TBK1 phosphorylation.
+Dynamic formation of SINT-speckles is positively controlled by the acetyltransferase KAT2A (GCN5) and antagonized by heat shock protein-mediated chaperone activity.
+SINT-speckle formation is also inhibited by the autophagy-initiating kinases ULK1/2, and knockdown of these kinases prevented focal TBK1 phosphorylation in a pathway-specific manner.
+The phlebovirus-encoded non-structural protein S enhances ULK1-mediated TBK1 phosphorylation and shows a stress-induced translocation to SINT-speckles, raising the possibility that viruses can also target this signaling hub to manipulate host cell functions.
+INTRODUCTION: The implementation of evidence-based clinical practice guidelines is one of the most effective interventions for improving quality of care.
+A gap between guidelines and clinical practice often exists, which may result in patients not receiving appropriate care.
+METHOD: The records of patients with lung cancer were evaluated for adherence to guidelines by using an auditing tool that was developed to capture pertinent information.
+The study team collected data about the following variables: compliance with documentation of pathological diagnosis, documentation of disease stage prior to treatment initiation, presentation at thoracic tumour board within 30 days of diagnosis, management course, and management of end of life in terms of early ‘no code’ initiation, stopping chemotherapy and referral to palliative care prior to 2 weeks of death.
+Education and discussion with team members to address the deviations were the main interventions to improve adherence.
+Testing for epidermal growth factor receptor mutation for non-squamous cell lung cancer improved from 77% to 100%.
+CONCLUSION: Running audits to monitor adherence to guidelines and discussions with the team have a positive effect on providing consistent evidence-based care for patients with lung cancer.
+Objective: Whether lncRNA maternally expressed gene 3 (MEG3) attended to morphine-mediated autophagy of mouse hippocampal neuronal HT22 cells was probed.
+Materials and methods: HT22 cells were subjected to 10 µM morphine for 24 h. Cell autophagy was assessed by measuring LC3-II/LC3-I and Beclin-1 expression.
+Results: Morphine elevated OX1R (2.92 times), c-fos (2.06 times), p/t-ERK (2.04 times) and p/t-PKC (2.4 times), Beclin-1 (3.2 times) and LC3-II/LC3-I (3.96 times) expression in HT22 cells.
+Moreover, followed by morphine exposure, the MEG3 expression was also elevated in HT22 cells (3.03 times).
+The silence of MEG3 lowered the Beclin-1 (1.85 times), LC3-II/LC3-I (2.12 times), c-fos (1.39 times) and p/t-ERK (1.44 times) expressions in morphine-treated HT22 cells.
+Inhibitor of ERK pathway SCH772984 further promoted the influence of MEG3 silence on morphine-caused Beclin-1 (1.97 times) and LC3-II/LC3-I (1.92 times) expressions decreases.
+Conclusions: Up-regulation of MEG3 attended to the morphine-caused autophagy of HT22 cells might be through elevating c-fos expression and promoting ERK pathway activation.
+More experiments are also needed in the future to analyse the influence of other lncRNAs in drug addiction.
+BACKGROUND: The pathways and mechanism by which associations between the gut microbiome and the brain, termed the microbiome-gut-brain axis (MGBA), are manifest but remain to be fully elucidated.
+This study aims to use bibliometric analysis to estimate the global activity within this rapidly developing field and to identify particular areas of focus that are of current relevance to the MGBA during the last decade (2009–2018).
+We used the key terms “microbiome-gut-brain axis” and its synonyms because we are concerned with MGBA per se as a new concept in research rather than related topics.
+A VOSviewer version 1.6.11 was used to visualize collaboration pattern between countries and authors, and evolving research topics by analysis of the term co-occurrence in the title and abstract of publications.
+RESULTS: Between 2009 and 2018, there were 51,504 published documents related to the microbiome, including 1713 articles related to the MGBA: 829 (48.4%) original articles, 658(38.4%) reviews, and 226 (13.2%) other articles such as notes, editorials or letters.
+The USA took the first place with 385 appearances, followed by Ireland (n = 161), China (n = 155), and Canada (n = 144).The overall citation h-index was 106, and the countries with the highest h-index values were the USA (69), Ireland (58), and Canada (43).
+The cluster analysis demonstrated that the dominant fields of the MGBA include four clusters with four research directions: “modeling MGBA in animal systems”, “interplay between the gut microbiota and the immune system”, “irritable bowel syndrome related to gut microbiota”, and “neurodegenerative diseases related to gut microbiota”.
+CONCLUSIONS: This study demonstrates that the research on the MGBA has been becoming progressively more extensive at global level over the past 10 years.
+Overall, our study found that a large amount of work on MGBA focused on immunomodulation, irritable bowel syndrome, and neurodevelopmental disorders.
+Despite considerable progress illustrating the communication between the gut microbiome and the brain over the past 10 years, many issues remain about their relevance for therapeutic intervention of many diseases.
+PURPOSE: Sexually transmitted infections (STIs), representing a major global health problem, are caused by different microbes, including bacteria, viruses, and protozoa.
+Unfortunately, infections of different sexually transmitted pathogens often present similar clinical symptoms, so it is almost impossible to distinguish them clinically.
+Therefore, the aim of the current study was to develop a sensitive, multitarget, and high-throughput method that can detect various agents responsible for STIs.
+METHODS: We developed and tested a 23-plex PCR coupled with matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry (MS) assay (sexually transmitted infection-mass spectrometry, STI-MS) that simultaneously targets 11 different agents, including 8 most common clinical pathogens related to STIs (HSV-1, HSV-2, Neisseria gonorrhoeae, Chlamydia trachomatis, Treponema pallidum, Trichomonas vaginalis, Mycoplasma genitalium, and Haemophilus ducreyi) and 3 controversial microorganisms as pathogens (Mycoplasma hominis, Ureaplasma urealyticum, and Ureaplasma parvum).
+RESULTS: The results showed that the STI-MS approach can accurately detect the expected agents, without cross-reaction with other organisms.
+The limit of detection of each STI-MS assay was ranged from 1.739 to 10.009 copies/reaction, using probit analyses.
+The verification rate for each target organism of the STI-MS ranged from a minimum of 89.3% to a maximum of 100%, using conventional assays and ultrasensitive digital PCR to confirm the STI-MS-positive results.
+To further evaluate the clinical performance of this assay, 241 clinical specimens (124 urethral/cervical swabs and 117 urine) were tested in parallel using the STI-MS assay and monoplex real-time PCR for each agent.
+The overall validation parameters of STI-MS were extremely high including sensitivity (from 85.7% to 100%), specificity (from 92.3% to 100%), PPV (from 50% to 100%), and NPV (from 99.1% to 100%) for each target.
+CONCLUSION: STI-MS is a useful high-throughput screening tool for detecting mixed infections of STIs and has great potential for application in large-scale epidemiological programs for specific microorganisms of STI.
+SIMPLE SUMMARY: In this study, the effects of Saccharomyces boulardii (SB) supplement on the performance and physiological traits of Holstein calves under heat stress were investigated using a climatic chamber.
+We revealed that supplementation with SB incorporated into milk replacer can ameliorate the negative impact of heat stress on Holstein dairy calves by increasing dry matter intake (DMI), reducing rectal temperature and heart rate, and alleviating diarrhea via modulating pathogenic bacteria in the digestive tract.
+The results showed that SB can be used as an alternative anti-stressor in the diet of young dairy calves under heat stress (HS).
+ABSTRACT: The objective of this study was to determine the effects of Saccharomyces boulardii CNCM I-1079 (SB) as a feed additive on performance, diarrhea frequency, rectal temperature, heart rate, water consumption, cortisol level, and fecal bacteria population in Holstein calves (28 ± 1.6 days of age, body weight of 45.6 ± 1.44 kg, n = 16) under thermal neutral (TN) and heat stress (HS) conditions.
+During the TN period for 21 days (d 1 to 21), calves receiving SB showed quadratic or linear effects compared to the control group, showing higher dry matter intake (DMI, p = 0.002), and water consumption (p = 0.007) but lower frequency of fecal diarrhea (p = 0.008), rectal temperature (p < 0.001), heart rate (p < 0.001), and fecal microbiota at 21 day (Escherichia coli, p = 0.025; Enterobacteriaceae, p = 0.041).
+Meanwhile, calves exposed to HS for 7 days (d 22 to 28) receiving SB showed quadratic or linear effects compared to the control group, showing higher DMI (p = 0.002) but lower water consumption (p = 0.023), rectal temperature (p = 0.026), and cortisol level (p = 0.014).
+Our results suggest that live SB is useful in the livestock industry as an alternative to conventional medication (especially in times of suspected health problems) that can be added to milk replacer for young dairy calves experiencing HS.
+There is a paucity of observational data from schools and households, particularly in developing countries.
+Portable wireless sensors can record unbiased proximity events between individuals facing each other, shedding light on pathways of infection transmission.
+Design and methods: The aim is to characterize face-to-face contact patterns that may shape the transmission of respiratory infections in schools and households in Kilifi, Kenya.
+From each school, 350 students will be randomly selected proportional to class size and gender to participate.
+Nine index students from each school will be randomly selected and followed-up to their households.
+A further 3-5 neighbouring households will also be recruited to give a maximum of 350 participants per household setting.
+The sample size per site is limited by the number of sensors available for data collection.
+Each participant will wear a wireless proximity sensor lying on their chest area for 7 consecutive days.
+Data on proximal dyadic interactions will be collected automatically by the sensors only for participants who are face-to-face.
+Key characteristics of interest include the distribution of degree and the frequency and duration of contacts and their variation in rural and urban areas.
+Expected results: Resultant data will inform on social contact patterns in rural and urban areas of a previously unstudied population.
+Ensuing data will be used to parameterize mathematical simulation models of transmission of a range of respiratory viruses, including respiratory syncytial virus, and used to explore the impact of intervention measures such as vaccination and social distancing.
+Acute respiratory tract infections are a major cause of respiratory morbidity and mortality in pediatric patients worldwide.
+However, accurate viral and immunologic markers to predict clinical outcomes of this patient population are still lacking.
+Droplet digital PCR assays for influenza and respiratory syncytial virus (RSV) were designed and performed in 64 respiratory samples from 23 patients with influenza virus infection and 73 samples from 19 patients with RSV infection.
+Samples from patients with fever or respiratory symptoms had a significantly higher viral loads than those from asymptomatic patients.
+Samples from patients with influenza virus and RSV infection collected at presentation had significantly higher viral loads than those collected from patients after completing a course of oseltamivir or ribavirin, respectively.
+RSV loads correlated positively with clinical symptoms in patients ≤5 years of age, whereas influenza viral loads were associated with clinical symptoms, irrespective of age.
+Patients receiving antivirals for influenza and RSV had a significant reduction in viral loads after completing therapy.
+Digital PCR offers an effective method to monitor the efficacy of antiviral treatment for respiratory tract infections in immunocompromised hosts.
+Pneumonitis is the leading cause of death associated with the use of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (EGFR-TKIs) against non-small cell lung cancer (NSCLC).
+Hence, we aimed to test the hypothesis that EGFR tyrosine kinase activity regulates TNF-mediated bronchial epithelial cell survival, and that inhibition of EGFR activity increases TNF-induced lung epithelial cell apoptosis.
+We used surfactant protein C (SPC)-TNF transgenic (tg) mice which overexpress TNF in the lungs.
+In this model, gefitinib, an EGFR-TKI, enhanced lung epithelial cell apoptosis and lymphocytic inflammation, indicating that EGFR tyrosine kinase prevents TNF-induced lung injury.
+Furthermore, IL-17A was significantly upregulated by gefitinib in SPC-TNF tg mice and p38MAPK activation was observed, indicative of a pathway involved in lung epithelial cell apoptosis.
+Moreover, in lung epithelial cells, BEAS-2B, TNF stimulated EGFR transactivation via the TNF-α-converting enzyme in a manner that requires heparin binding (HB)-EGF and transforming growth factor (TGF)-α.
+These novel findings have significant implications in understanding the role of EGFR in maintaining human bronchial epithelial cell homeostasis and in NSCLC treatment.
+In China, eight IIDs are listed as notifiable infectious diseases, including cholera, poliomyelitis, dysentery, typhoid and paratyphoid (TAP), viral Hepatitis A, viral Hepatitis E, hand-foot-mouth disease (HFMD) and other infectious diarrhoeal diseases (OIDDs).
+The aim of the study is to analyse the spatio-temporal distribution of IIDs from 2006 to 2016.
+METHODS: Data on the incidence of IIDs from 2006 to 2016 were collected from the public health science data centre issued by the Chinese Center for Disease Control and Prevention.
+RESULTS: Regarding temporal analysis, the incidence of HFMD and Hepatitis E showed a distinct increasing trend, while the incidence of TAP, dysentery, and Hepatitis A presented decreasing trends over the last decade.
+Regarding the spatial distribution, approximately all p values for the global Moran’s I from 2006 to 2016 were less than 0.05, indicating that the incidences of the epidemics were unevenly distributed throughout the country.
+The high-risk areas for HFMD and OIDD were located in the Beijing-Tianjin-Tangshan (BTT) region and south China.
+A higher incidence rates for dysentery and Hepatitis A were observed in the BTT region and some west provincial units.
+The high-risk areas for Hepatitis E were the BTT region and the Yangtze River Delta area.
+CONCLUSIONS: Based on our temporal and spatial analysis of IIDs, we identified the high-risk periods and clusters of regions for the diseases.
+HFMD and OIDD exhibited high incidence rates, which reflected the negligence of Class C diseases by the government.
+The authorities should pay more attention to Class C diseases and Hepatitis E. Regardless of the various distribution patterns of IIDs, disease-specific, location-specific, and disease-combined interventions should be established.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12879-019-4400-x) contains supplementary material, which is available to authorized users.
+Once thought a mere ribosome factory, the nucleolus has been viewed in recent years as an extremely sensitive gauge of diverse cellular stresses.
+Emerging concepts in nucleolar biology include the nucleolar stress response (NSR), whereby a series of cell insults have a special impact on the nucleolus.
+While these stresses might influence nucleolar biology directly or indirectly, other perturbances whose origin resides in the nucleolar biology also trigger nucleolar and systemic stress responses.
+Among the latter, we find mutations in nucleolar and ribosomal proteins, ribosomal RNA (rRNA) processing inhibitors and ribosomal DNA (rDNA) transcription inhibition.
+The p53 protein also mediates NSR, leading ultimately to cell cycle arrest, apoptosis, senescence or differentiation.
+The nucleolar size and ribosome biogenesis, and how they connect with the Target of Rapamycin (TOR) signalling pathway, are also becoming important in the biology of aging and cancer.
+Simple model organisms like the budding yeast Saccharomyces cerevisiae, easy to manipulate genetically, are useful in order to study nucleolar and rDNA structure and their relationship with stress.
+Tripartite motif containing-21 (TRIM21) is a cytosolic ubiquitin ligase and antibody receptor that provides a last line of defense against invading viruses.
+It does so by acting as a sensor that intercepts antibody-coated viruses that have evaded extracellular neutralization and breached the cell membrane.
+Upon engagement of the Fc of antibodies bound to viruses, TRIM21 triggers a coordinated effector and signaling response that prevents viral replication while at the same time inducing an anti-viral cellular state.
+Therapeutically, TRIM21 has been shown to be detrimental in adenovirus based gene therapy, while it may be favorably utilized to prevent tau aggregation in neurodegenerative disorders.
+In addition, TRIM21 may synergize with the complement system to block viral replication as well as transgene expression.
+TRIM21 can also be utilized as a research tool to deplete specific proteins in cells and zebrafish embryos.
+Here, we review our current biological understanding of TRIM21 in light of its versatile functions.
+Filovirus serological diagnosis and epidemiological investigations are hampered due to the unavailability of validated immunoassays.
+Diagnostic performance of three indirect enzyme-linked immunosorbent assays (I-ELISA) was evaluated for the detection of IgG antibody to Ebola virus (EBOV) in human sera.
+One I-ELISA was based on a whole EBOV antigen (WAg) and two utilized recombinant nucleocapsid (NP) and glycoproteins (GP), respectively.
+Validation data sets derived from individual sera collected in South Africa (SA), representing an EBOV non-endemic country, and from sera collected during an Ebola disease (EBOD) outbreak in Sierra Leone (SL), were categorized according to the compounded results of the three I-ELISAs and real time reverse-transcription polymerase chain reaction (RT-PCR).
+At the cut-off values selected at 95% accuracy level by the two-graph receiver operating characteristic analysis, specificity in the SA EBOV negative serum panel (n = 273) ranged from 98.17% (GP ELISA) to 99.27% (WAg ELISA).
+Diagnostic specificity in the SL EBOV negative panel (n = 676) was 100% by the three ELISAs.
+The diagnostic sensitivity in 423 RT-PCR confirmed EBOD patients was dependent on the time when the serum was collected after onset of disease.
+It significantly increased 2 weeks post-onset, reaching 100% sensitivity by WAg and NP and 98.1% by GP I-ELISA.
+Application of highly active antiretroviral drugs (ARDs) effectively reduces morbidity and mortality in HIV-infected individuals.
+However, the emergence of multiple drug-resistant strains has led to the increased failure of ARDs, thus calling for the development of anti-HIV drugs with targets or mechanisms of action different from those of the current ARDs.
+The first peptide-based HIV entry inhibitor, enfuvirtide, was approved by the U.S. FDA in 2003 for treatment of HIV/AIDS patients who have failed to respond to the current ARDs, which has stimulated the development of several series of protein- and peptide-based HIV entry inhibitors in preclinical and clinical studies.
+In this review, we highlighted the properties and mechanisms of action for those promising protein- and peptide-based HIV entry inhibitors targeting the HIV-1 gp120 or gp41 and discussed their advantages and disadvantages, compared with the current ARDs.
+Viruses are known to have some of the highest and most diverse mutation rates found in any biological replicator, with single-stranded (ss) RNA viruses evolving the fastest, and double-stranded (ds) DNA viruses having rates approaching those of bacteria.
+As mutation rates are tightly and negatively correlated with genome size, selection is a clear driver of viral evolution.
+To understand how these two processes affect the long-term evolution of viruses infecting humans, we comprehensively analyzed ssRNA, ssDNA, dsRNA, and dsDNA viruses, to find which virus types and which functions show evidence for episodic diversifying selection and correlated evolution.
+We show that selection mostly affects single stranded viruses, that correlated evolution is more prevalent in DNA viruses, and that both processes, taken independently, mostly affect viral replication.
+However, the genes that are jointly affected by both processes are involved in key aspects of their life cycle, favoring viral stability over proliferation.
+We further show that both evolutionary processes are intimately linked at the amino acid level, which suggests that it is the joint action of selection and correlated evolution, and not just selection, that shapes the evolutionary trajectories of viruses—and possibly of their epidemiological potential.
+Diagnosis usually relies on antibody screening by point-of-care tests (POCT), e.g., by enzyme-linked immunosorbent assays (ELISA), and confirmation using Western blot (WB).
+We increasingly observed ELISA-negative, WB-positive samples and aimed to substantiate these observations using 1194 serum/plasma samples collected from 1998 to 2019 primarily from FIV-suspect cats.
+While 441 samples tested positive and 375 tested negative by ELISA and WB, 81 samples had discordant results: 70 were false ELISA-negative (WB-positive) and 11 were false ELISA-positive (WB-negative); 297 ambiguous results were not analyzed further.
+The diagnostic sensitivity and specificity of the ELISA (82% and 91%, respectively) were lower than those reported in 1995 (98% and 97%, respectively).
+FIV RT-PCR was positive for two of these samples and was weakly positive for two ELISA- and POCT-negative samples.
+Our results suggest that FIV diagnosis has become more challenging, probably due to increasing travel by cats and the introduction of new FIV isolates not recognized by screening assays.
+For a long time, viruses have been shown to modify the clinical picture of several autoimmune diseases, including type 1 diabetes (T1D), systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), Sjögren’s syndrome (SS), herpetic stromal keratitis (HSK), celiac disease (CD), and multiple sclerosis (MS).
+Best examples of viral infections that have been proposed to modulate the induction and development of autoimmune diseases are the infections with enteric viruses such as Coxsackie B virus (CVB) and rotavirus, as well as influenza A viruses (IAV), and herpesviruses.
+Epidemiological studies in humans and experimental studies in animal have shown that viral infections can induce or protect from autoimmunopathologies depending on several factors including genetic background, host-elicited immune responses, type of virus strain, viral load, and the onset time of infection.
+Still, data delineating the clear mechanistic interaction between the virus and the immune system to induce autoreactivity are scarce.
+Available data indicate that viral-induced autoimmunity can be activated through multiple mechanisms including molecular mimicry, epitope spreading, bystander activation, and immortalization of infected B cells.
+Contrarily, the protective effects can be achieved via regulatory immune responses which lead to the suppression of autoimmune phenomena.
+Here we provide an overview of the current understanding of viral-induced autoimmunity and the mechanisms that are associated with this phenomenon.
+To date, a number of mannose-specific lectins have been isolated and characterized from seaweeds, especially from red algae.
+In fact, man-specific seaweed lectins consist of different structural scaffolds harboring a single or a few carbohydrate-binding sites which specifically recognize mannose-containing glycans.
+Depending on the structural scaffold, man-specific seaweed lectins belong to five distinct structurally-related lectin families, namely (1) the griffithsin lectin family (β-prism I scaffold); (2) the Oscillatoria agardhii agglutinin homolog (OAAH) lectin family (β-barrel scaffold); (3) the legume lectin-like lectin family (β-sandwich scaffold); (4) the Galanthus nivalis agglutinin (GNA)-like lectin family (β-prism II scaffold); and, (5) the MFP2-like lectin family (MFP2-like scaffold).
+Another algal lectin from Ulva pertusa, has been inferred to the methanol dehydrogenase related lectin family, because it displays a rather different GlcNAc-specificity.
+In spite of these structural discrepancies, all members from the five lectin families share a common ability to specifically recognize man-containing glycans and, especially, high-mannose type glycans.
+Because of their mannose-binding specificity, these lectins have been used as valuable tools for deciphering and characterizing the complex mannose-containing glycans from the glycocalyx covering both normal and transformed cells, and as diagnostic tools and therapeutic drugs that specifically recognize the altered high-mannose N-glycans occurring at the surface of various cancer cells.
+In addition to these anti-cancer properties, man-specific seaweed lectins have been widely used as potent human immunodeficiency virus (HIV-1)-inactivating proteins, due to their capacity to specifically interact with the envelope glycoprotein gp120 and prevent the virion infectivity of HIV-1 towards the host CD4+ T-lymphocyte cells in vitro.
+Canine parvovirus (CPV) is a common etiological agent of acute enteritis, which occurs globally in domestic and wild carnivores.
+Despite the widespread use of inactivated or live attenuated vaccines, the emergence of antigenic variants and the influence of maternal antibodies have raised some concerns regarding the efficacy of commercial vaccines.
+While no specific antiviral therapy for CPV infection exists, the only treatment option for the infection is supportive therapy based on symptoms.
+Thus, there is an urgent medical need to develop antiviral therapeutic options to reduce the burden of CPV-related disease.
+In this study, a cytopathic effect (CPE)-based high-throughput screening assay was used to screen CPV inhibitors from a Food and Drug Administration (FDA)-approved drug library.
+After two rounds of screening, seven out of 1430 screened drugs were found to have >50% CPE inhibition.
+Three drugs—Nitazoxanide, Closantel Sodium, and Closantel—with higher anti-CPV effects were further evaluated in F81 cells by absolute PCR quantification and indirect immunofluorescence assay (IFA).
+Time of addition assay indicated that the drugs inhibited the early processes of the CPV replication cycle, and the inhibition effects were relatively high within 2 h postinfection.
+Western blot assay also showed that the three drugs had broad-spectrum antiviral activity against different subspecies of three CPV variants.
+In addition, antiapoptotic effects were observed within 12 h in Nitazoxanide-treated F81 cells regardless of CPV infection, while Closantel Sodium- or Closantel-treated cells had no pro- or antiapoptotic effects.
+Since the safety profiles of FDA-approved drugs have already been extensively studied, these three drugs can potentially become specific and effective anti-CPV drugs.
+Febrile neutropenia (FN) is an inflammatory response causing fever that may develop during cancer therapy-induced neutropenia.
+Patients presenting with FN are routinely subjected to careful history taking and physical examination including X-rays and microbiological evaluations.
+Nevertheless, an infection is documented clinically in only 20–30% of cases, whereas a causative microbial pathogen is not identified in over 70% of FN cases.
+Although it is recognized that ulcerative oral mucositis may be involved in the development of FN, the contribution of infections of the periodontium, the dentition, and salivary glands may be underestimated.
+These infections can be easily overlooked, as symptoms and signs of inflammation may be limited or absent during neutropenia.
+This narrative review is aimed to inform the clinician on the potential role of the oral cavity as a potential source in the development of FN.
+RATIONALE: Our pilot study suggested that noninvasive ventilation (NIV) reduced the need for intubation compared with conventional administration of oxygen on patients with “early” stage of mild acute respiratory distress syndrome (ARDS, PaO(2)/FIO(2) between 200 and 300).
+OBJECTIVES: To evaluate whether early NIV can reduce the need for invasive ventilation in patients with pneumonia-induced early mild ARDS.
+METHODS: Prospective, multicenter, randomized controlled trial (RCT) of NIV compared with conventional administration of oxygen through a Venturi mask.
+RESULTS: Two hundred subjects were randomized to NIV (n = 102) or control (n = 98) groups from 21 centers.
+In the NIV group, PaO(2)/FIO(2) became significantly higher than in the control group at 2 h after randomization and remained stable for the first 72 h. NIV did not decrease the proportion of patients requiring intubation than in the control group (11/102 vs. 9/98, 10.8% vs. 9.2%, p = 0.706).
+The ICU mortality was similar in the two groups (7/102 vs. 7/98, 4.9% vs. 3.1%, p = 0.721).
+Multivariate analysis showed minute ventilation greater than 11 L/min at 48 h was the independent risk factor for NIV failure (OR, 1.176 [95% CI, 1.005–1.379], p = 0.043).
+CONCLUSIONS: Treatment with NIV did not reduce the need for intubation among patients with pneumonia-induced early mild ARDS, despite the improved PaO(2)/FIO(2) observed with NIV compared with standard oxygen therapy.
+Registered 19 April 2012 ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13054-019-2575-6) contains supplementary material, which is available to authorized users.
+The first consensus report of the working party of the Asian Pacific Association for the Study of the Liver (APASL) set up in 2004 on acute-on-chronic liver failure (ACLF) was published in 2009.
+With international groups volunteering to join, the “APASL ACLF Research Consortium (AARC)” was formed in 2012, which continued to collect prospective ACLF patient data.
+Based on the prospective data analysis of nearly 1400 patients, the AARC consensus was published in 2014.
+In the past nearly four-and-a-half years, the AARC database has been enriched to about 5200 cases by major hepatology centers across Asia.
+The data published during the interim period were carefully analyzed and areas of contention and new developments in the field of ACLF were prioritized in a systematic manner.
+The AARC database was also approached for answering some of the issues where published data were limited, such as liver failure grading, its impact on the ‘Golden Therapeutic Window’, extrahepatic organ dysfunction and failure, development of sepsis, distinctive features of acute decompensation from ACLF and pediatric ACLF and the issues were analyzed.
+These initiatives concluded in a two-day meeting in October 2018 at New Delhi with finalization of the new AARC consensus.
+Only those statements, which were based on evidence using the Grade System and were unanimously recommended, were accepted.
+Finalized statements were again circulated to all the experts and subsequently presented at the AARC investigators meeting at the AASLD in November 2018.
+After detailed deliberations and data analysis, the original definition of ACLF was found to withstand the test of time and be able to identify a homogenous group of patients presenting with liver failure.
+New management options including the algorithms for the management of coagulation disorders, renal replacement therapy, sepsis, variceal bleed, antivirals and criteria for liver transplantation for ACLF patients were proposed.
+The final consensus statements along with the relevant background information and areas requiring future studies are presented here.
+BACKGROUND: Reverse genetics systems enable the manipulation of viral genomes and therefore serve as robust reverse genetic tools to study RNA viruses.
+A DNA-launched rescue system initiates the transcription of viral genomic cDNA from eukaryotic promoter in transfected cells, generating homogenous RNA transcripts in vitro and thus enhancing virus rescue efficiency.
+As one of the hazardous pathogens to ducklings, the current knowledge of the pathogenesis of duck astrovirus type 1 (DAstV-1) is limited.
+The construction of a DNA-launched rescue system can help to accelerate the study of the virus pathogenesis.
+METHODS: In this study, a DNA-launched infectious clone of DAstV-1 was constructed from a cDNA plasmid, which contains a viral cDNA sequence flanked by hammerhead ribozyme (HamRz) and a hepatitis delta virus ribozyme (HdvRz) sequence at both terminals of the viral genome.
+A silent nucleotide mutation creating a Bgl II site in the ORF2 gene was made to distinguish the rescued virus (rDAstV-1) from the parental virus (pDAstV-1).
+Immunofluorescence assay (IFA) and western blot were conducted for rescued virus identification in duck embryo fibroblast (DEF) cells pre-treated with trypsin.
+The growth characteristics of rDAstV-1 and pDAstV-1 in DEF cells and the tissue tropism in 2-day-old ducklings of rDAstV-1 and pDAstV-1 were determined.
+RESULTS: The infectious DAstV-1 was successfully rescued from baby hamster kidney (BHK-21) cells and could propagate in DEF cells pre-treated with 1 μg/ml trypsin.
+Upon infection of DEF cells pre-treated with trypsin, DAstV-1 mRNA copies were identified after serial passaging, and the result showed that rDAstV-1 and pDAstV-1 shared similar replication kinetics.
+Animal experiment showed that the rDAstV-1 had an extensive tissue tropism, and the virus was capable of invading both the central and the peripheral immune organs in infected ducklings.
+We believe this valuable experimental system will contribute to the further study of DAstV-1 genome function and pathogenesis.
+Some of this extremely broad variation in susceptibility is explained by the size of the initial inoculum or the influenza exposure history of the individual; some is explained by generic host factors, such as frailty, that decrease resilience following any systemic insult.
+Some demographic factors (pregnancy, obesity, and advanced age) appear to confer a more specific susceptibility to severe illness following infection with influenza viruses.
+As with other infectious diseases, a substantial component of susceptibility is determined by host genetics.
+GLDC, IRF7/9 variants), or defects in cell-mediated immunity with increased baseline levels of systemic inflammation (obesity, pregnancy, advanced age).
+These mechanisms may explain the prolonged viral replication reported in critically ill patients with influenza: patients with life-threatening disease are, by definition, abnormal hosts.
+Understanding these molecular mechanisms of susceptibility may in the future enable the design of host-directed therapies to promote resilience.
+Elephant endotheliotropic herpesvirus-hemorrhagic disease (EEHV-HD) is the primary cause of acute, highly fatal, hemorrhagic diseases in young Asian elephants.
+Although monocytopenia is frequently observed in EEHV-HD cases, the role monocytes play in EEHV-disease pathogenesis is unknown.
+Samples of blood, frozen tissues, and formalin-fixed, paraffin-embedded (FFPE) tissues from EEHV1A-HD, EEHV4-HD, co-infected EEHV1A and 4-HD, and EEHV-negative calves were analyzed.
+Peripheral blood mononuclear cells (PBMCs) from the persistent EEHV4-infected and EEHV-negative calves were also studied.
+The results showed increased infiltration of Iba-1-positive macrophages in the inflamed tissues of the internal organs of elephant calves with EEHV-HD.
+In addition, cellular apoptosis also increased in the tissues of elephants with EEHV-HD, especially in the PBMCs, compared to the EEHV-negative control.
+In the PBMCs of persistent EEHV4-infected elephants, cytokine mRNA expression was high, particularly up-regulation of TNF-α and IFN-γ.
+Our study demonstrated for the first time that apoptosis of the PBMCs increased in cases of EEHV-HD.
+Furthermore, this study showed that monocytes may serve as a vehicle for viral dissemination during EEHV infection in Asian elephants.
+Nanocarrier drug delivery systems (NDDS) have been paid more attention over conventional drug delivery system for cancer therapy.
+However, the efficacy is hampered by the fast clearance of activated macrophage from the blood circulation system.
+In this study, glycyrrhizin (GL) was introduced into alginate (ALG) nanogel particles (NGPs) to construct multifunctional delivery vehicle to decrease the fast clearance of activated macrophage and enhance the anticancer efficacy with the combination therapy of GL and doxorubicin (DOX).
+Methods: We firstly synthesized the GL-ALG NGPs with intermolecular hydrogen bond and ionic bond as the multifunctional delivery vehicle.
+The immune response and phagocytosis of macrophage on GL-ALG NGPs were investigated on RAW 264.7 macrophages.
+The active targeting effects of GL-ALG NGPs were further studied on hepatocellular carcinoma cell (HepG2) and H22 tumor-bearing mice.
+Moreover, the anticancer molecular mechanism of DOX/GL-ALG NGPs was investigated on HepG2 cells in vitro and tumor-bearing mice in vivo.
+Results: GL-ALG NGPs could not only avoid triggering the immuno-inflammatory responses of macrophages but also decreasing the phagocytosis of macrophage.
+The bioavailability of DOX was increased about 13.2 times by DOX/GL-ALG NGPs than free DOX in blood.
+The mice with normal immune functions used in constructing the tumor-bearing mice instead of the nude mouse also indicated the good biocompatibility of NGPs.
+The results suggested that the anticancer molecular mechanism of the combination therapy of glycyrrhizin and doxorubicin in ALG NGPs was performed via regulating apoptosis pathway of Bax/Bcl-2 ratio and caspase-3 activity, which was also verified in H22 tumor-bearing mice.
+Conclusion: DOX/GL-ALG NGPs could attenuate the activation of macrophage and enhance the therapeutic efficacy for hepatocellular carcinoma.
+Our results suggest that the combination therapy would provide a new strategy for liver cancer treatment.
+High-throughput sequencing (HTS) enables most pathogens in a clinical sample to be detected from a single analysis, thereby providing novel opportunities for diagnosis, surveillance, and epidemiology.
+However, this powerful technology is difficult to apply in diagnostic laboratories because of its computational and bioinformatic demands.
+We have developed DisCVR, which detects known human viruses in clinical samples by matching sample k-mers (twenty-two nucleotide sequences) to k-mers from taxonomically labeled viral genomes.
+DisCVR was validated using published HTS data for eighty-nine clinical samples from adults with upper respiratory tract infections.
+These samples had been tested for viruses metagenomically and also by real-time polymerase chain reaction assay, which is the standard diagnostic method.
+DisCVR detected human viruses with high sensitivity (79%) and specificity (100%), and was able to detect mixed infections.
+Moreover, it produced results comparable to those in a published metagenomic analysis of 177 blood samples from patients in Nigeria.
+DisCVR has been designed as a user-friendly tool for detecting human viruses from HTS data using computers with limited RAM and processing power, and includes a graphical user interface to help users interpret and validate the output.
+Herpes simplex virus type 1 (HSV-1), an enveloped DNA virus, plays a key role in varieties of diseases including recurrent cold sores, keratoconjunctivitis, genital herpes and encephalitis in humans.
+Great efforts have been made in developing more effective and less side-effects anti-herpes simplex virus agents, including traditional Chinese herbal medicines.
+In the present study, we evaluated the antiviral efficacy of Rheum tanguticum nanoparticles against HSV-1 in vitro and in vivo.
+R. tanguticum nanoparticles could inactivate the HSV-1 virions and block the viral attachment and entry into cells.
+Time-of-addition assay indicated that R. tanguticum nanoparticles could interfere with the entire phase of viral replication.
+Besides, R. tanguticum nanoparticles showed the ability to inhibit the mRNA expression of HSV-1 immediate early gene ICP4 and early gene ICP8 as well as the expression of viral protein ICP4 and ICP8.
+Moreover, R. tanguticum nanoparticles have been proved to protect mice against HSV-1 induced lethality by decreasing the viral load and alleviated pathological changes in brain tissues.
+In conclusion, we demonstrated that R. tanguticum nanoparticles could inhibit HSV-1 infection through multiple mechanisms.
+These results suggest that R. tanguticum nanoparticles may have novel roles in the treatment of HSV-1 infection.
+BACKGROUND: Epstein–Barr virus (EBV) is a highly prevalent human herpesvirus capable of infecting the central nervous system and establishing persistent infection.
+METHODS: We employed solid phase immunoassay techniques to measure immunoglobulin G (IgG) class antibodies to EBV virions and defined proteins in 432 individuals with schizophrenia and 311 individuals without a history of a psychiatric disorder.
+Levels of antibodies between the groups were compared by multivariate analyses incorporating clinical, genetic, and demographic measures.
+RESULTS: Individuals with schizophrenia had marked elevations in the levels of antibodies to EBV virions as compared to the control population.
+Further analyses indicated increased levels of reactivity to EBV-viral capsid antibody (VCA) but not to EBV nuclear antigen-1 (EBNA-1) or to other human herpesviruses.
+Western blot analysis confirmed increased reactivity to VCA proteins in the group of individuals with schizophrenia and documented a lack of increased levels of antibodies to EBNA-1.
+Genetic analyses indicated an additive effect of increased levels of antibodies to EBV virions and genetic susceptibility to schizophrenia, with individuals with elevated levels of both type of markers having a greater than 8.5-fold odds of a schizophrenia diagnosis.
+CONCLUSIONS: Individuals with schizophrenia have increased levels of antibodies to some but not all EBV proteins indicating an aberrant response to EBV infection.
+OBJECTIVES: Feline immunodeficiency virus (FIV) and feline leukaemia virus (FeLV) are immunosuppressive viruses in cats that increase their susceptibility to zoonotic pathogens.
+This study aimed to determine the occurrence of one or both viruses, the risk factors associated with infection, and to develop further recommendations.
+METHODS: This was a cross-sectional study conducted at the Veterinary Faculty of Eduardo Mondlane University, Mozambique, between March and December 2017, in 145 cats.
+From each of 145 cats, we took 1.5 ml of blood by jugular puncture for detection of antibodies to FIV and FeLV antigens in whole blood using a commercial test kit, DFV Test FeLV/FIV.
+RESULTS: We found an overall prevalence of 11.0% and 14.5% for FIV antibodies and FeLV antigens, respectively, with four (2.8%) cats coinfected by both pathogens.
+Male cats were more likely to be infected with FIV (odds ratio [OR] 1.1, 95% confidence interval [CI] 0.3–4.0) compared with female cats.
+Clinically ill cats were more likely to have a positive result for FeLV antigen infection (OR 18.8, 95% CI 5.2–68.3).
+Moreover, cats living in suburban areas have a greater chance of a positive result for FeLV infection (OR 3.7, 95% CI 1.4–9.6) compared with cats living in urban areas.
+CONCLUSIONS AND RELEVANCE: FIV and FeLV occur in cats from Maputo and possibly all over the country.
+Further studies should be conducted in Mozambique and other African countries to define the burden of both pathogens in cats, coinfection with other zoonotic pathogens and the possible role played by the cats on the transmission of zoonotic and opportunistic diseases to humans.
+BACKGROUND: Invasive mold infections in children with hematological malignancies are associated with high mortality rates.
+The use of combination antifungal therapy in cases with a severe clinical course is increasing, although information on the efficacy and safety of this approach is limited.
+METHODS: We present a case series of 13 children affected by hemato-oncological disorders who received combination antifungal therapy for invasive mold infections at our center (Pediatric Hematology, San Gerardo Hospital, Monza, Italy) from 2011 to 2016, with the aim of describing their clinical characteristics, types of infections, treatment regimens, clinical outcomes, and treatment safety.
+RESULTS: Combination antifungal therapy included liposomal amphotericin associated with caspofungin (5/13, 38.4%), voriconazole (5/13, 38.4%), or posaconazole (3/13, 23.1%).
+The 12-week treatment response rate was 69.2% (6/13 patients showed complete response, 3/13 partial response).
+The crude mortality was 30.7% (4/13): half was related to invasive mold infections (2/13, 15.38%) and half to disease progression (2/13, 15.38%).
+Overall, treatment was well tolerated, and we did not observe any permanent discontinuation of antifungals due to related side effects.
+CONCLUSIONS: In our experience, combination antifungal therapy seems to be a safe option in immunocompromised children with invasive mold infections.
+Well-designed studies are needed to confirm the safety of this approach and to better understand its efficacy in the pediatric setting.
+BACKGROUND: Personal protective equipment (PPE) helps protect healthcare workers (HCWs) from pathogens and prevents cross-contamination.
+METHODS: Thirty participants at a Midwestern academic hospital were recruited and assigned to 1 of 3 doffing simulation scenarios: 3 mask designs (n = 10), 2 gown designs (n = 10), or 2 glove designs (n = 10).
+Semistructured interviews about their doffing approaches were conducted and audio-recorded, then transcribed and thematically analyzed.
+RESULTS: Three overarching themes were identified in interviews: doffing strategies, cognitive processes, and barriers and facilitators.
+Cognitive processes during doffing largely pertained to tracking contaminated PPE surfaces, examining PPE design cues (eg, straps), or improvising based on prior experience from training or similar PPE designs.
+Doffing barriers and facilitators typically related to PPE design, such as PPE fit (or lack of it) and fastener type.
+Some participants also described personal barriers (eg, glasses, long hair); however, some PPE designs helped mitigate these barriers.
+CONCLUSIONS: Efforts to improve HCWs’ doffing performance need to address HCWs’ preferences for both safety and expediency when using PPE, which has implications for PPE design, training approaches, and hospital policies and procedures.
+BACKGROUND: The CDC hosts monthly panel presentations titled ‘Public Health Grand Rounds’ and publishes monthly reports known as Vital Signs.
+OBJECTIVES: This study quantified the effect of hashtag count, mention count, and URL count and attaching visual cues to #CDCGrandRounds or #VitalSigns tweets on their retweet frequency.
+METHODS: Through Twitter Search Application Programming Interface, original tweets containing the hashtag #CDCGrandRounds (n = 6,966; April 21, 2011–October 25, 2016) and the hashtag #VitalSigns (n = 15,015; March 19, 2013–October 31, 2016) were retrieved respectively.
+Negative binomial regression models were applied to each corpus to estimate the associations between retweet frequency and three predictors (hashtag count, mention count, and URL link count).
+We manually coded the 30 tweets with the highest number of retweets for each cycle, whether it contained visual cues (images or videos).
+Univariable negative binomial regression models were applied to compute the prevalence ratio (PR) of retweet frequency for each cycle, between tweets with and without visual cues.
+FINDINGS: URL links increased retweet frequency in both corpora; effects of hashtag count and mention count differed between the two corpora.
+Of the 58 #CDCGrandRounds cycles, 29 were found to have statistically significantly different retweet frequencies between tweets with and without visual cues.
+Of these 29 cycles, one had a PR estimate < 1; twenty-four, PR > 1 but < 3; and four, PR > 3.
+Of these 19 cycles, six were PR > 1 and < 3; and thirteen, PR > 3.
+CONCLUSIONS: The increase of retweet frequency through attaching visual cues varied across cycles for original tweets with #CDCGrandRounds and #VitalSigns.
+Future research is needed to determine the optimal choice of visual cues to maximize the influence of public health tweets.
+High-throughput multi-omics studies and corresponding network analyses of multi-omic data have rapidly expanded their impact over the last 10 years.
+transcripts, proteins, metabolites) interact within cellular systems, the greatest amount of knowledge can be gained from networks that incorporate multiple types of -omic data.
+However, biological and technical sources of variation diminish the ability to detect cross-type associations, yielding networks dominated by communities comprised of nodes of the same type.
+We describe here network building methods that can maximize edges between nodes of different data types leading to integrated networks, networks that have a large number of edges that link nodes of different–omic types (transcripts, proteins, lipids etc).
+We systematically rank several network inference methods and demonstrate that, in many cases, using a random forest method, GENIE3, produces the most integrated networks.
+This increase in integration does not come at the cost of accuracy as GENIE3 produces networks of approximately the same quality as the other network inference methods tested here.
+Using GENIE3, we also infer networks representing antibody-mediated Dengue virus cell invasion and receptor-mediated Dengue virus invasion.
+A number of functional pathways showed centrality differences between the two networks including genes responding to both GM-CSF and IL-4, which had a higher centrality value in an antibody-mediated vs. receptor-mediated Dengue network.
+Because a biological system involves the interplay of many different types of molecules, incorporating multiple data types into networks will improve their use as models of biological systems.
+The methods explored here are some of the first to specifically highlight and address the challenges associated with how such multi-omic networks can be assembled and how the greatest number of interactions can be inferred from different data types.
+The resulting networks can lead to the discovery of new host response patterns and interactions during viral infection, generate new hypotheses of pathogenic mechanisms and confirm mechanisms of disease.
+Widespread geographic movement and extensive comingling of exhibition swine facilitates the spread and transmission of infectious pathogens.
+Nasal samples were collected from 2862 pigs at 102 exhibitions and tested for five pathogens.
+Influenza A virus remains a top threat to animal and human health, but other pathogens may be disseminated through the exhibition swine population.
+Upon initiation at a start codon, the ribosome must maintain the correct reading frame for hundreds of codons in order to produce functional proteins.
+While some sequence elements are able to trigger programmed ribosomal frameshifting (PRF), very little is known about how the ribosome normally prevents spontaneous frameshift errors that can have dire consequences if uncorrected.
+Using high resolution ribosome profiling data sets, we discovered that the translating ribosome uses the 3′ end of 18S rRNA to scan the AUG-like codons after the decoding process.
+The postdecoding mRNA:rRNA interaction not only contributes to predominant translational pausing, but also provides a retrospective mechanism to safeguard the ribosome in the correct reading frame.
+Partially eliminating the AUG-like “sticky” codons in the reporter message leads to increased +1 frameshift errors.
+Remarkably, mutating the highly conserved CAU triplet of 18S rRNA globally changes the codon “stickiness”.
+Further supporting the role of “sticky” sequences in reading frame maintenance, the codon composition of open reading frames is highly optimized across eukaryotic genomes.
+These results suggest an important layer of information embedded within the protein-coding sequences that instructs the ribosome to ensure reading frame fidelity during translation.
+Both antiseptic hand rubbing (AHR) using ethanol-based disinfectants (EBDs) and antiseptic hand washing (AHW) are important means of infection control to prevent seasonal influenza A virus (IAV) outbreaks.
+We aimed to elucidate the situations and mechanisms underlying the reduced efficacy of EBDs against IAV in infectious mucus.
+Additionally, AHR and AHW effectiveness against infectious mucus adhering to the hands and fingers was evaluated in 10 volunteers.
+Our clinical study showed that EBD effectiveness against IAV in mucus was extremely reduced compared to IAV in saline.
+IAV in mucus remained active despite 120 s of AHR; however, IAV in saline was completely inactivated within 30 s. Due to the low rate of diffusion/convection because of the physical properties of mucus as a hydrogel, the time required for the ethanol concentration to reach an IAV inactivation level and thus for EBDs to completely inactivate IAV was approximately eight times longer in mucus than in saline.
+On the other hand, AHR inactivated IAV in mucus within 30 s when the mucus dried completely because the hydrogel characteristics were lost.
+Until infectious mucus has completely dried, infectious IAV can remain on the hands and fingers, even after appropriate AHR using EBD, thereby increasing the risk of IAV transmission.
+IMPORTANCE Antiseptic hand rubbing (AHR) and antiseptic hand washing (AHW) are important to prevent the spread of influenza A virus (IAV).
+This study elucidated the situations/mechanisms underlying the reduced efficacy of AHR against infectious mucus derived from IAV-infected individuals and indicated the weaknesses of the current hand hygiene regimens.
+Due to the low rate of diffusion/convection because of the physical properties of mucus as a hydrogel, the efficacy of AHR using ethanol-based disinfectant against mucus is greatly reduced until infectious mucus adhering to the hands/fingers has completely dried.
+If there is insufficient time before treating the next patient (i.e., if the infectious mucus is not completely dry), medical staff should be aware that effectiveness of AHR is reduced.
+Since AHW is effective against both dry and nondry infectious mucus, AHW should be adopted to compensate for these weaknesses of AHR.
+Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infections and hospital visits during infancy and childhood.
+Although risk factors for RSV infection have been identified, the role of microbial species in the respiratory tract is only partially known.
+We aimed to understand the impact of interactions between the nasal microbiome and host transcriptome on the severity and clinical outcomes of RSV infection.
+We used 16 S rRNA sequencing to characterize the nasal microbiome of infants with RSV infection.
+We used RNA sequencing to interrogate the transcriptome of CD4(+) T cells obtained from the same set of infants.
+After dimension reduction through principal component (PC) analysis, we performed an integrative analysis to identify significant co-variation between microbial clade and gene expression PCs.
+We then employed LIONESS (Linear Interpolation to Obtain Network Estimates for Single Samples) to estimate the clade-gene association patterns for each infant.
+Our network-based integrative analysis identified several clade-gene associations significantly related to the severity of RSV infection.
+The microbial taxa with the highest loadings in the implicated clade PCs included Moraxella, Corynebacterium, Streptococcus, Haemophilus influenzae, and Staphylococcus.
+Interestingly, many of the genes with the highest loadings in the implicated gene PCs are encoded in mitochondrial DNA, while others are involved in the host immune response.
+This study on microbiome-transcriptome interactions provides insights into how the host immune system mounts a response against RSV and specific infectious agents in nasal microbiota.
+Our objective was to determine if lipid profiles of vaginal swabs were different between postnatal gilts suckled by sow or fed milk replacer the first 48 h after birth, with or without a lard-based fat supplement.
+Gilts (>1.3 kg) were selected at birth across 8 litters and assigned to one of four treatments: 1) suckled by sow (S, n = 8); 2) suckled by sow plus administration of a fat supplement (SF, n = 5); 3) bottle-fed solely milk replacer (B, n = 8); or 4) bottle-fed solely milk replacer plus administration of a fat supplement (BF, n = 7).
+At 48 h postnatal, vaginal swabs of gilts were taken with a cytology brush, and lipids were extracted for analysis using multiple reaction monitoring (MRM)-profiling.
+Lipids extracted from serum collected at 48 h from gilts, milk collected at 24 h from sows, and milk replacer were also analyzed with MRM-profiling.
+Receiver operating characteristic curve analysis found 18 lipids recovered from vaginal swabs that highly distinguished between S and B gilts [area-under-the-curve (AUC) > 0.9], including phosphatidylethanolamine with 34 carbons and four unsaturations in the fatty acyl residues [PE (34:4)].
+Twelve lipids from vaginal swabs highly correlated (r > 0.6; p < 0.01) with nutrition source.
+For example, mean intensity of PE (34:4) was 149-fold higher in milk replacer than colostrum.
+Consequently, PE (34:4) was found to have 1.6- and 2.12-fold higher levels in serum and vaginal swab samples (p < 0.001), respectively, of B gilts as compared to S gilts.
+Findings support that vaginal swabs can be used to noninvasively study effects of perinatal nutrition on tissue composition.
+Commonly used exoskeletons have a left-right pair, but when only one leg of the wearer is uncomfortable, it is effective to wear the exoskeleton on only the uncomfortable leg.
+The designed exoskeleton uses a lightweight material and uses a wire-driven actuator, which reduces the weight of the driving section that is attached on the knee directly.
+In addition, the lower frame length of the exoskeleton can be changed to align with the complex movement of the knee.
+Furthermore, the length between the knee center of rotation and the ankle (LBKA) is measured by using this structure, and the LBKA values are used as the data for intention detection.
+These value helps to detect the intention because it changes faster than a motor encoder value.
+Neural network detects the intention of three motions (stair ascending, stair descending, and walking), Training results showed that intention detection was good in various environments.
+HIV-related stigma has been associated with worse health-related quality of life (HRQoL) among people living with HIV (PLWH).
+Little is known about how different types of HIV-related stigma (i.e., anticipatory, internalized, or enacted HIV-related stigma) influence HRQoL and whether these relationships differ by gender.
+The sample included 912 PLWH aged 18 years or older enrolling in HIV care at four health facilities in Tanzania.
+HRQoL was assessed with the life satisfaction and overall function subscales of the HIV/AIDS-Targeted Quality of Life (HAT-QoL) instrument.
+Sex-stratified multivariable logistic regression modeled the association of anticipatory, internalized, and enacted HIV-related stigma on poor HRQoL.
+Across all participants, the mean life satisfaction score was 63.4 (IQR: 43.8, 81.3) and the mean overall function score was 72.0 (IQR: 58.3, 91.7).
+Mean HRQoL scores were significantly higher for women compared to men for overall function (5.1 points higher) and life satisfaction (4.3 points higher).
+Fourteen percent of respondents reported recent enacted HIV-related stigma and 13% reported recent medium or high levels of internalized stigma.
+In multivariable models, high internalized and high anticipatory stigma were significantly associated with higher odds of poor life satisfaction and poor overall function in both men and women.
+Psychosocial interventions to prevent or reduce the impact of internalized and anticipatory stigma may improve HRQoL among persons in HIV care.
+Future research should longitudinally examine mechanisms between HIV-related stigma, poor HRQoL, and HIV care outcomes.
+Long-read sequencing (LRS) has become increasingly important in RNA research due to its strength in resolving complex transcriptomic architectures.
+In this regard, currently two LRS platforms have demonstrated adequate performance: the Single Molecule Real-Time Sequencing by Pacific Biosciences (PacBio) and the nanopore sequencing by Oxford Nanopore Technologies (ONT).
+Even though these techniques produce lower coverage and are more error prone than short-read sequencing, they continue to be more successful in identifying polycistronic RNAs, transcript isoforms including splice and transcript end variants, as well as transcript overlaps.
+Recent reports have successfully applied LRS for the investigation of the transcriptome of viruses belonging to various families.
+In this work, we used the Sequel and MinION technique from PacBio and ONT, respectively, to characterize the lytic transcriptome of the herpes simplex virus type 1 (HSV-1).
+In most samples, we analyzed the poly(A) fraction of the transcriptome, but we also performed random oligonucleotide-based sequencing.
+Our investigations identified more than 2,300 previously undetected transcripts, including coding, and non-coding RNAs, multi-splice transcripts, as well as polycistronic and complex transcripts.
+Random-primed sequencing revealed that each convergent gene pair produces non-polyadenylated read-through RNAs overlapping the partner genes.
+Furthermore, we identified novel replication-associated transcripts overlapping the HSV-1 replication origins, and novel LAT variants with very long 5’ regions, which are co-terminal with the LAT-0.7kb transcript.
+Overall, our results demonstrated that the HSV-1 transcripts form an extremely complex pattern of overlaps, and that entire viral genome is transcriptionally active.
+Efficiency and fidelity of protein secretion are achieved thanks to the presence of different steps, located sequentially in time and space along the secretory compartment, controlling protein folding and maturation.
+After entering into the endoplasmic reticulum (ER), secretory proteins attain their native structure thanks to specific chaperones and enzymes.
+Only correctly folded molecules are allowed by quality control (QC) mechanisms to leave the ER and proceed to downstream compartments.
+Proteins that cannot fold properly are instead retained in the ER to be finally destined to proteasomal degradation.
+Exiting from the ER requires, in most cases, the use of coated vesicles, departing at the ER exit sites, which will fuse with the Golgi compartment, thus releasing their cargoes.
+Protein accumulation in the ER can be caused by a too stringent QC or by ineffective transport: these situations could be deleterious for the organism, due to the loss of the secreted protein, and to the cell itself, because of abnormal increase of protein concentration in the ER.
+In this review, we will describe the pathophysiology of protein folding and transport between the ER and the Golgi compartment.
+The human nasal epithelium is the primary site of exposure to influenza virus, the initiator of host responses to influenza and the resultant pathologies.
+Influenza virus may cause serious respiratory infection resulting in major complications, as well as severe impairment of the airways.
+Here, we elucidated the global transcriptomic changes during H3N2 infection of human nasal epithelial cells from multiple individuals.
+Using RNA sequencing, we characterized the differentially-expressed genes and pathways associated with changes occurring at the nasal epithelium following infection.
+We used in vitro differentiated human nasal epithelial cell culture model derived from seven different donors who had no concurrent history of viral infections.
+Statistical analysis highlighted strong transcriptomic signatures significantly associated with 24 and 48 h after infection, but not at the earlier 8-h time point.
+In particular, we found that the influenza infection induced in the nasal epithelium early and altered responses in interferon gamma signaling, B-cell signaling, apoptosis, necrosis, smooth muscle proliferation, and metabolic alterations.
+These molecular events initiated at the infected nasal epithelium may potentially adversely impact the airway, and thus the genes we identified could serve as potential diagnostic biomarkers or therapeutic targets for influenza infection and associated disease management.
+SIMPLE SUMMARY: Porcine epidemic diarrhea is one of the major problems in current swine husbandry worldwide, and effective measures for prevention and treatment are scarce.
+We found that high dose 25-hydroxyvitamin D(3) supplementation could ease intestinal injury and inhibit intestinal immune response induced by porcine epidemic diarrhea virus (PEDV), suggesting that feeding a high dose of 25-hydroxyvitamin D(3) could be used as an approach against PEDV infection.
+ABSTRACT: We conducted this experiment to determine if feeding 25-hydroxyvitamin D(3) (25(OH)D(3)) to weaned pigs would alleviate porcine epidemic diarrhea virus (PEDV) infection and immune response.
+Forty-two weaned pigs were allotted to 1 of 6 dietary 25(OH)D(3) treatments (5.5, 5.5, 43.0, 80.5, 118.0, 155.5 μg 25(OH)D(3)/kg diet) for 26 days.
+On day 22 of the trial, all the treatments were orally administrated with PEDV except for one of the 5.5 μg 25(OH)D(3)/kg treatments, which was challenged with the same volume of sterile saline and served as control.
+PEDV administration also induced severe diarrhea (p < 0.05), reduction of villous height and the ratio of villous height to crypt depth, and increase of crypt depth and serum diamine oxidase activity (p < 0.05).
+Furthermore, 155.5 μg 25(OH)D(3)/kg supplementation downregulated the mRNA abundance of inflammatory cytokines and interferon signal pathway-related genes (p < 0.05) compared with CON-PEDV.
+These results suggested that dietary supplementation of 155.5 μg 25(OH)D(3)/kg could alleviate intestinal damage and protect against PEDV-induced inflammatory status.
+Marek’s disease (MD) is a T cell lymphoma disease induced by Marek’s disease virus (MDV), a highly oncogenic α herpesvirus primarily affecting chickens.
+In this study, to identify high-confidence candidate genes of MD genetic resistance, high throughput sequencing (RNA-seq) was used to obtain transcriptomic data of CD4(+) T cells isolated from MDV-infected and non-infected groups of two reciprocal crosses of individuals mating by two highly inbred chicken lines (6(3) MD-resistant and 7(2) MD-susceptible).
+After RNA-seq analysis with two biological replicates in each group, we identified 61 and 123 single nucleotide polymorphisms (SNPs) (false discovery rate (FDR) < 0.05) annotated in 39 and 132 genes in intercrosses 6(3) × 7(2) and 7(2) × 6(3), respectively, which exhibited allele-specific expression (ASE) in response to MDV infection.
+Similarly, we identified 62 and 79 SNPs annotated in 66 and 96 genes in infected and non-infected groups, respectively.
+We identified 534 and 1543 differentially expressed genes (DEGs) (FDR < 0.05) related to MDV infection in intercrosses 6(3) × 7(2) and 7(2) × 6(3), respectively.
+The qRT-PCR of 11 important ASE genes was performed for gene functional validation in CD4(+) T cells and tumors.
+Combining the analyses, six genes (MCL1, SLC43A2, PDE3B, ADAM33, BLB1, and DMB2), especially MCL1, were highlighted as the candidate genes with the potential to be involved in MDV infection.
+Gene-set enrichment analysis revealed that many ASE genes are linked to T cell activation, T cell receptor (TCR), B cell receptor (BCR), ERK/MAPK, and PI3K/AKT-mTOR signaling pathways, which play potentially important roles in MDV infection.
+Our approach underlines the importance of comprehensive functional studies for gaining valuable biological insight into the genetic factors behind MD and other complex traits, and our findings provide additional insights into the mechanisms of MD and disease resistance breeding in poultry.
+Some proteins are expressed as a result of a ribosome frameshifting event that is facilitated by a slippery site and downstream secondary structure elements in the mRNA.
+This review summarizes recent progress in understanding mechanisms of –1 frameshifting in several viral genes, including IBV 1a/1b, HIV‐1 gag‐pol, and SFV 6K, and in Escherichia coli dnaX.
+The exact frameshifting route depends on the availability of aminoacyl‐tRNAs: the ribosome normally slips into the –1‐frame during tRNA translocation, but can also frameshift during decoding at condition when aminoacyl‐tRNA is in limited supply.
+Different frameshifting routes and additional slippery sites allow viruses to maintain a constant production of their key proteins.
+The emerging idea that tRNA pools are important for frameshifting provides new direction for developing antiviral therapies.
+Despite the availability of an effective prophylactic vaccine leading to sterilizing immunity, hepatitis B virus (HBV) is responsible for chronic liver disease in more than 250 million individuals, potentially leading to cirrhosis and hepatocellular carcinoma.
+Antiviral drugs able to completely suppress virus replication are indeed available but they are, by and large, unable to eradicate the virus.
+Several alternative new treatment approaches are currently being developed but none have so far captured the interest of clinicians for possible clinical development.
+A constant feature of chronic HBV infection is T-cell exhaustion resulting from persistent exposure to high antigen concentrations as shown by the high expression of programmed cell death protein 1 (PD-1) by HBV-specific CD8 T cells.
+One way of tackling this problem is to develop HBV-specific neutralizing antibodies that would clear excess envelope proteins from the circulation, allowing for nucleos(t)ide analogs or other antiviral drugs now in preclinical and early clinical development to take advantage of a reconstituted adaptive immunity.
+Several fully human monoclonal antibodies (mAb) have been developed from HBV-vaccinated and subjects convalescent from acute hepatitis B that show different properties and specificities.
+It is envisaged that such neutralizing mAb may be used as adjuvant treatment to reduce viral protein load, thus rescuing adaptive immunity in an effort to optimize the effect of antiviral drugs.
+1,4‐Triazolyl combretacoumarins have been prepared by linking the trimethoxyarene unit of combretastatin A4 with coumarins, via a 1,2,3‐triazole.
+For this, 4‐azidocoumarins were accessed by a sequential two‐step, one‐pot reaction of 4‐hydroxycoumarins with (benzotriazol‐1‐yloxy)tris(dimethylamino)phosphonium hexafluorophosphate (BOP), followed by reaction with NaN(3).
+In the reaction with BOP, a coumarin‐derived phosphonium ion intermediate seems to form, leading to an O (4)‐(benzotriazolyl)coumarin derivative.
+For the CuAAC reaction of azidocoumarins with 5‐ethynyl‐1,2,3‐trimethoxybenzene, catalytic [(MeCN)(4)Cu]PF(6) in CH(2)Cl(2)/MeOH with 2,6‐lutidine, at 50 (o)C, was suitable.
+The 4‐azidocoumarins were less reactive as compared to PhN(3) and the NBO coefficients of the azido groups were compared by DFT analysis.
+On the basis of the biological and solubility data of one 1,4‐triazolyl combretacoumarin, four analogs lacking one or two methoxy groups were synthesized.
+Reactivity differences among the phenylacetylenes were noted and the NBO coefficients of the alkynes were compared by DFT analysis.
+The desmethoxy 6‐bromo‐4‐(4‐(4‐methoxyphenyl)‐1H‐1,2,3‐triazol‐1‐yl)‐2H‐chromen‐2‐one also showed cytotoxicity against the two cell lines, but this did not appear to be consistent with apoptosis.
+We describe rapid, label-free detection of Influenza A viruses using the first radial mode of oscillations of lead zirconate titanate (PZT) piezoelectric discs with a 2 mm radius and 100 µm thickness fabricated from a piezoelectric membrane.
+The discs are modified with a synthetic sialylglycopolymer receptor layer, and the coated discs are inserted in a flowing virus suspension.
+Label-free detection of the virus is achieved by monitoring the disc radial mode resonance frequency shift.
+Piezo transducers with sialylglycopolymer sensor layers exhibited a long lifetime, a high sensitivity and the possibility of regeneration.
+We demonstrate positive, label-free detection of Influenza A viruses at concentrations below 10(5) virus particles per millilitre.
+We show that label-free, selective, sensitive detection of influenza viruses by home appliances is possible in principle.
+The aim of this study was to investigate the experiences of medical transportation of Korean travelers who suffered accidents abroad and then transferred home by our aeromedical team.
+We collected demographic and clinical data on patients injured while traveling abroad from January 2013 to July 2017.
+Descriptive analyses based on 4 different transportation methods and transport time since hospitalization were performed.
+Of these, 28 (84.8%) were trauma cases with pedestrian injuries being the most common (11 cases; 39.3%).
+Twenty patients were repatriated by flight-stretchers, 6 by flight-prestige, 2 by ship, and 5 by air ambulance.
+The air ambulance was the most expensive (average 61,124 US Dollars) mode of transportation (P = .001) and the ship took the longest time (14 hours) to transport patients back to Korea from regions with similar distance (P = .0023).
+Transfer time should be an important considering factor and directly contacting and communicating with the specialized staff of foreign hospitals could also be very important to reduce unnecessary overseas hospital stay and cost incidence.
+Acute lung injury (ALI), developing as a component of the systemic inflammatory response syndrome (SIRS), leads to significant morbidity and mortality.
+Reactive oxygen species (ROS), produced in part by the neutrophil NADPH oxidase 2 (Nox2), have been implicated in the pathogenesis of ALI.
+Previous studies in our laboratory demonstrated the development of pulmonary inflammation in Nox2-deficient (gp91(phox-/y)) mice that was absent in WT mice in a murine model of SIRS.
+Given this finding, we hypothesized that Nox2 in a resident cell in the lung, specifically the alveolar macrophage, has an essential anti-inflammatory role.
+Using a murine model of SIRS, we examined whole-lung digests and bronchoalveolar lavage fluid (BALf) from WT and gp91(phox-/y) mice.
+Both genotypes demonstrated neutrophil sequestration in the lung during SIRS, but neutrophil migration into the alveolar space was only present in the gp91(phox-/y) mice.
+Macrophage inflammatory protein (MIP)-1α gene expression and protein secretion were higher in whole-lung digest from uninjected gp91(phox-/y) mice compared to the WT mice.
+Gene expression of MIP-1α, MCP-1, and MIP-2 was upregulated in alveolar macrophages obtained from gp91(phox-/y) mice at baseline compared with WT mice.
+Further, ex vivo analysis of alveolar macrophages, but not bone marrow-derived macrophages or peritoneal macrophages, demonstrated higher gene expression of MIP-1α and MIP-2.
+Moreover, isolated lung polymorphonuclear neutrophils migrate to BALf obtained from gp91(phox-/y) mice, further providing evidence of a cell-specific anti-inflammatory role for Nox2 in alveolar macrophages.
+We speculate that Nox2 represses the development of inflammatory lung injury by modulating chemokine expression by the alveolar macrophage.
+Human norovirus (HuNoV) GII.P17-GII.17 (Kawasaki2014 variant) reportedly emerged in 2014 and caused gastroenteritis outbreaks worldwide.
+To clarify the evolution of both VP1 and RNA-dependent RNA polymerase (RdRp) regions of GII.P17-GII.17, we analyzed both global and novel Japanese strains detected during 2013–2017.
+Time-scaled phylogenetic trees revealed that the ancestral GII.17 VP1 region diverged around 1949, while the ancestral GII.P17 RdRp region diverged around 2010.
+The evolutionary rates of the VP1 and RdRp regions were estimated at ~2.7 × 10(−3) and ~2.3 × 10(−3) substitutions/site/year, respectively.
+The phylogenetic distances of the VP1 region exhibited no overlaps between intra-cluster and inter-cluster peaks in the GII.17 strains, whereas those of the RdRp region exhibited a unimodal distribution in the GII.P17 strains.
+Conformational epitope positions in the VP1 protein of the GII.P17-GII.17 strains were similar, although some substitutions, insertions and deletions had occurred.
+Strains belonging to the same cluster also harbored substitutions around the binding sites for the histo-blood group antigens of the VP1 protein.
+Moreover, some amino acid substitutions were estimated to be near the interface between monomers and the active site of the RdRp protein.
+These results suggest that the GII.P17-GII.17 virus has produced variants with the potential to alter viral antigenicity, host-binding capability, and replication property over the past 10 years.
+When confronted with a globally spreading epidemic, we seek efficient strategies for drug dissemination, creating a competition between supply and demand at a global scale.
+Propagating along similar networks, e.g., air-transportation, the spreading dynamics of the supply vs. the demand are, however, fundamentally different, with the pathogens driven by contagion dynamics, and the drugs by commodity flow.
+We show that these different dynamics lead to intrinsically distinct spreading patterns: while viruses spread homogeneously across all destinations, creating a concurrent global demand, commodity flow unavoidably leads to a highly uneven spread, in which selected nodes are rapidly supplied, while the majority remains deprived.
+Consequently, even under ideal conditions of extreme production and shipping capacities, due to the inherent heterogeneity of network-based commodity flow, efficient mitigation becomes practically unattainable, as homogeneous demand is met by highly heterogeneous supply.
+Therefore, we propose here a decentralized mitigation strategy, based on local production and dissemination of therapeutics, that, in effect, bypasses the existing distribution networks.
+Such decentralization is enabled thanks to the recent development of digitizable therapeutics, based on, e.g., short DNA sequences or printable chemical compounds, that can be distributed as digital sequence files and synthesized on location via DNA/3D printing technology.
+We test our decentralized mitigation under extremely challenging conditions, such as suppressed local production rates or low therapeutic efficacy, and find that thanks to its homogeneous nature, it consistently outperforms the centralized alternative, saving many more lives with significantly less resources.
+Background and objectives: The use of antagonistic probiotic microorganisms and their byproducts represents a promising approach for the treatment of viral diseases.
+In the current work, the effect of exopolysaccharides (EPSs) produced by lactic acid bacteria from different genera on the structural and functional characteristics of cells and the development of adenoviral infection in vitro was studied.
+Materials and Methods: Cytotoxicity of six EPSs of lactic acid bacteria of the genera Lactobacillus, Leuconostoc and Pediococcus was determined by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay.
+The influence of the EPSs on the infectivity of human adenovirus type 5 (HAdV-5) and on the cell cycle under a condition of adenovirus infection was studied using plaque reduction assay and flow cytometric analysis, respectively.
+Results: It was shown that exopolysaccharides were non-toxic to Madin-Darby bovine kidney cells (MDBK) as they reduced their viability by 3–17%.
+A change in the distribution of the cell cycle phases in the non-infected cell population treated with EPSs was observed.
+The analysis demonstrated an increase in the number of cells in the S phase by 47% when using EPSs 15a and a decrease in the number of cells in the G1 phase by 20–27% when treated with the EPSs 15a, 33a, and 19s.
+The use of EPSs did not led to the normalization of the life cycle of HAdV-5 infected cells to the level of non-infected cells.
+Among the studied exopolysaccharides, anti-adenovirus activity was found for EPS 26a that is produced by Lactobacillus spp.
+The treatment of cells with the EPS following virus adsorption completely (100%) suppressed the formation and release of HAdV-5 infectious.
+Conclusions: EPS 26a possessed distinct anti-HAdV-5 activity and the obtained data demonstrate the potential of using exopolysaccharides as anti-adenoviral agents.
+Infectious diseases have a huge impact on animal health, production and welfare, and human health.
+Understanding the role of host genetics in disease spread is important for developing disease control strategies that efficiently reduce infection incidence and risk of epidemics.
+While heritable variation in disease susceptibility has been targeted in livestock breeding, emerging evidence suggests that there is additional genetic variation in host infectivity, but the potential benefits of including infectivity into selection schemes are currently unknown.
+A Susceptible-Infected-Recovered epidemiological model incorporating polygenic genetic variation in both susceptibility and infectivity was combined with quantitative genetics selection theory to assess the non-linear impact of genetic selection on field measures of epidemic risk and severity.
+Response to 20 generations of selection was calculated in large simulated populations, exploring schemes differing in accuracy and intensity.
+Assuming moderate genetic variation in both traits, 50% selection on susceptibility required seven generations to reduce the basic reproductive number R(0) from 7.64 to the critical threshold of <1, below which epidemics die out.
+Adding infectivity in the selection objective accelerated the decline towards R(0) < 1, to 3 generations.
+Our results show that although genetic selection on susceptibility reduces disease risk and prevalence, the additional gain from selection on infectivity accelerates disease eradication and reduces more efficiently the risk of new outbreaks, while it alleviates delays generated by unfavourable correlations.
+In conclusion, host infectivity was found to be an important trait to target in future genetic studies and breeding schemes, to help reducing the occurrence and impact of epidemics.
+Although some adjuvants have been approved for commercial use in human vaccines (e.g., Alum, MF59, and AS03), they might elicit adverse side effects, such as autoimmune diseases.
+Recently, we developed a novel single-stranded RNA (ssRNA) nano-structure adjuvant, which can stimulate both Th1 and Th2 responses.
+In this study, we evaluated the safety and toxicological profiles of this ssRNA nano-structure adjuvant in vitro and in vivo.
+Mice were intramuscularly immunized with the ssRNA nano-structure adjuvant three times, once every 2 weeks.
+The results indicate no significant differences in hematological and serum biochemistry parameters between the ssRNA-treated groups and the control group.
+The levels of IgE and anti-nuclear antibodies, which are markers of autoimmune disease, were not different between the ssRNA-treated groups and the control group.
+The findings of this study suggest that the ssRNA nano-structure can be used as a safe adjuvant to increase vaccine efficacies.
+In this study, a novel oral vaccine of recombinant Lactobacillus plantarum (L. plantarum) containing the gp85 protein was explored, and the effects of this vaccine on the prevention of subgroup J Avian Leukosis Virus (ALV-J) infection were assessed.
+In the current study, the gp85 protein of ALV-J was expressed on the surface of L. plantarum with the surface-display motif, pgsA, by constructing a shuttle vector pMG36e:pgsA:gp85.
+Subsequently, Specific Pathogen Free Hy-Line Brown layer chickens were orally vaccinated with the recombinant L. plantarum and presented with high levels of serum immunoglobulin G (IgG) and secretory immunoglobulin A (sIgA) titers in bile and duodenal-mucosal fluid.
+After challenged with ALV-J of a 3 × 10(3) 50% tissue culture infective dose (TCID50), serum samples of the chickens were collected and viremia was analyzed.
+Results showed that, compared to the L. plantarum and PBS control group, the recombinant L. plantarum group showed a significant rise in antibody levels after inoculation, and provide improved protection against ALV-J according to viremia detection.
+These results indicate that oral immunization with the recombinant L. plantarum provided an effective means for eliciting protective immune response against early ALV-J infection.
+The success of oral infection by viruses depends on their capacity to overcome the gut epithelial barrier of their host to crossing over apical, mucous extracellular matrices.
+As orally transmitted viruses, densoviruses, are also challenged by the complexity of the insect gut barriers, more specifically by the chitinous peritrophic matrix, that lines and protects the midgut epithelium; how capsids stick to and cross these barriers to reach their final cell destination where replication goes has been poorly studied in insects.
+Here, we analyzed the early interaction of the Junonia coenia densovirus (JcDV) with the midgut barriers of caterpillars from the pest Spodoptera frugiperda.
+Using combination of imaging, biochemical, proteomic and transcriptomic analyses, we examined in vitro, ex vivo and in vivo the early interaction of the capsids with the peritrophic matrix and the consequence of early oral infection on the overall gut function.
+We show that the JcDV particle rapidly adheres to the peritrophic matrix through interaction with different glycans including chitin and glycoproteins, and that these interactions are necessary for oral infection.
+Proteomic analyses of JcDV binding proteins of the peritrophic matrix revealed mucins and non-mucins proteins including enzymes already known to act as receptors for several insect pathogens.
+In addition, we show that JcDV early infection results in an arrest of N-Acetylglucosamine secretion and a disruption in the integrity of the peritrophic matrix, which may help viral particles to pass through.
+Finally, JcDV early infection induces changes in midgut genes expression favoring an increased metabolism including an increased translational activity.
+These dysregulations probably participate to the overall dysfunction of the gut barrier in the early steps of viral pathogenesis.
+A better understanding of early steps of densovirus infection process is crucial to build biocontrol strategies against major insect pests.
+The clinical application of HIV fusion inhibitor, enfuvirtide (T20), was limited mainly because of its short half-life.
+Here we designed and synthesized two PEGylated C34 peptides, PEG2kC34 and PEG5kC34, with the PEG chain length of 2 and 5 kDa, respectively, and evaluated their anti-HIV-1 activity and mechanisms of action.
+We found that these two PEGylated peptides could bind to the HIV-1 peptide N36 to form high affinity complexes with high α-helicity.
+The peptides PEG2kC34 and PEG5kC34 effectively inhibited HIV-1 Env-mediated cell–cell fusion with an effective concentration for 50% inhibition (EC(50)) of about 36 nM.
+They also inhibited infection of the laboratory-adapted HIV-1 strain NL4-3 with EC(50) of about 4–5 nM, and against 47 HIV-1 clinical isolates circulating in China with mean EC(50) of PEG2kC34 and PEG5kC34 of about 26 nM and 32 nM, respectively.
+The plasma half-life (t(1/2)) of PEG2kC34 and PEG5kC34 was 2.6 h and 5.1 h, respectively, and the t(1/2) of PEGylated C34 was about 2.4-fold and 4.6-fold longer than C34 (~1.1 h), respectively.
+These findings suggest that PEGylated C34 with broad-spectrum anti-HIV-1 activity and prolonged half-life can be further developed as a peptide fusion inhibitor-based long-acting anti-HIV drug for clinical use to treat HIV-infected patients who have failed to respond to current anti-retrovirus drugs.
+Filoviruses have become a worldwide public health concern, especially during the 2013–2016 Western Africa Ebola virus disease (EVD) outbreak—the largest outbreak, both by number of cases and geographical extension, recorded so far in medical history.
+During the 2013–2016 Western Africa outbreak, Ebola virus (EBOV) was detected in the lung of infected patients suggesting a role in lung pathogenesis.
+However, little is known about lung pathogenesis and the controversial issue of aerosol transmission in EVD.
+This review highlights the pulmonary involvement in EVD, with a special focus on the new data emerging from the 2013–2016 Ebola outbreak.
+Tick-borne encephalitis virus (TBEV), a member of the genus Flavivirus (Flaviviridae), is a causative agent of a severe neuroinfection.
+In order to determine whether TBEV interacts with this host process in its natural target cells, we analysed de novo protein synthesis in a human cell line derived from cerebellar medulloblastoma (DAOY HTB-186).
+We observed a significant decrease in the rate of host protein synthesis, including the housekeeping genes HPRT1 and GAPDH and the known interferon-stimulated gene viperin.
+In addition, TBEV infection resulted in a specific decrease of RNA polymerase I (POLR1) transcripts, 18S and 28S rRNAs and their precursor, 45-47S pre-rRNA, but had no effect on the POLR3 transcribed 5S rRNA levels.
+To our knowledge, this is the first report of flavivirus-induced decrease of specifically POLR1 rRNA transcripts accompanied by host translational shut-off.
+The aim of this study of serpentovirus infection in captive snakes was to assess the susceptibility of different types of snakes to infection and disease, to survey viral genetic diversity, and to evaluate management practices that may limit infection and disease.
+Antemortem oral swabs were collected from 639 snakes from 12 US collections, including 62 species, 28 genera, and 6 families: Pythonidae (N = 414 snakes; pythons were overrepresented in the sample population), Boidae (79), Colubridae (116), Lamprophiidae (4), Elapidae (12), and Viperidae (14).
+Infection was more common in pythons (38%; 95% CI: 33.1–42.4%), and in boas (10%; 95% CI: 5.2–18.7%) than in colubrids (0.9%, 95% CI: <0.01–4.7%); infection was not detected in other snake families (lamprophiids 0/4, 95% CI: 0–49%; elapids 0/12, 95% CI: 0–24.2%; and vipers 0/14, 95% CI: 0–21.5%), but more of these snakes need to be tested to confirm these findings.
+Respiratory signs were only observed in 1 of 8 infected boas and were absent in the single infected colubrid.
+Divergent serpentoviruses were detected in pythons, boas, and colubrids, suggesting that different serpentoviruses might vary in their ability to infect snakes of different families.
+Older snakes were more likely to be infected than younger snakes (p-value < 0.001) but males and females were equally likely to be infected (female prevalence: 23.4%, 95% CI 18.7–28.9%; male prevalence: 23.5%, 95% CI 18–30.1%; p-value = 0.144).
+Neither age (p-value = 0.32) nor sex (p-value = 0.06) was statistically associated with disease severity.
+Longitudinal sampling of pythons in a single collection over 28 months revealed serpentovirus infection is persistent, and viral clearance was not observed.
+In this collection, infection was associated with significantly increased rates of mortality (p-value = 0.001) with death of 75% of infected pythons and no uninfected pythons over this period.
+Offspring of infected parents were followed: vertical transmission either does not occur or occurs with a much lower efficiency than horizontal transmission.
+Overall, these findings confirm that serpentoviruses pose a significant threat to the health of captive python populations and can cause infection in boa and colubrid species.
+BACKGROUND: Worldwide, the number of emerging and re-emerging infectious diseases is increasing, highlighting the importance of global disease pathogen surveillance.
+Traditional population-based methods may fail to capture important events, particularly in settings with limited access to health care, such as urban informal settlements.
+In such environments, a mixture of surface water runoff and human feces containing pathogenic microorganisms could be used as a surveillance surrogate.
+METHOD: We conducted a temporal metagenomic analysis of urban sewage from Kibera, an urban informal settlement in Nairobi, Kenya, to detect and quantify bacterial and associated antimicrobial resistance (AMR) determinants, viral and parasitic pathogens.
+RESULTS: A large variation of read abundances related to bacteria, viruses, and parasites of medical importance, as well as bacterial associated antimicrobial resistance genes over time were detected.
+Significant increased abundances were observed for a number of bacterial pathogens coinciding with higher abundances of AMR genes.
+Vibrio cholerae as well as rotavirus A, among other virus peaked in several weeks during the study period whereas Cryptosporidium spp.
+CONCLUSION: The metagenomic surveillance approach for monitoring circulating pathogens in sewage was able to detect putative pathogen and resistance loads in an urban informal settlement.
+Thus, valuable if generated in real time to serve as a comprehensive infectious disease agent surveillance system with the potential to guide disease prevention and treatment.
+The approach may lead to a paradigm shift in conducting real-time global genomics-based surveillance in settings with limited access to health care.
+PURPOSE OF REVIEW: Hepatic ischemia-reperfusion injury (IRI), an inevitable event during liver transplantation, represents a major risk factor for the primary graft dysfunction as well as the development of acute and chronic rejection.
+Neutrophils, along macrophages, are pivotal in the innate immune-driven liver IRI, whereas the effective neutrophil-targeting therapies remain to be established.
+In this review, we summarize progress in our appreciation of the neutrophil biology and discuss neutrophil-based therapeutic perspectives.
+RECENT FINDINGS: New technological advances enable to accurately track neutrophil movements and help to understand molecular mechanisms in neutrophil function, such as selective recruitment to IR-stressed tissue, formation of neutrophil extracellular traps, or reverse migration into circulation.
+In addition to pro-inflammatory and tissue-destructive functions, immune regulatory and tissue-repairing phenotype associated with distinct neutrophil subsets have been identified.
+SUMMARY: Newly recognized and therapeutically attractive neutrophil characteristics warrant comprehensive preclinical and clinical attention to target IRI in transplant recipients.
+mRNA contexts containing a ‘slippery’ sequence and a downstream secondary structure element stall the progression of the ribosome along the mRNA and induce its movement into the −1 reading frame.
+In this study we build a thermodynamic model based on Bayesian statistics to explain how −1 programmed ribosome frameshifting can work.
+As training sets for the model, we measured frameshifting efficiencies on 64 dnaX mRNA sequence variants in vitro and also used 21 published in vivo efficiencies.
+With the obtained free-energy difference between mRNA-tRNA base pairs in the 0 and −1 frames, the frameshifting efficiency of a given sequence can be reproduced and predicted from the tRNA−mRNA base pairing in the two frames.
+Our results further explain how modifications in the tRNA anticodon modulate frameshifting and show how the ribosome tunes the strength of the base-pair interactions.
+Tumor-associated macrophages (TAMs) promote tumor progression and inhibit anti-tumor immune response by producing various mediators and preferentially express CD163, CD204, and CD206.
+However, the role of these TAM subsets in oral squamous cell carcinoma (OSCC) remains unclear.
+Here we investigated the expression and function of TAM subsets in OSCC, especially in cancer cell proliferation.
+Biopsy sample from 44 patients with OSCC were examined for the expression of TAM markers and EGF by immunohistochemistry.
+We also examined the effect of conditioned medium from TAM subsets on the proliferation of OSCC cells.
+CD163(+) cells were detected diffusely all over the tumor and connective tissue area, while CD204(+) and CD206(+) cells were mainly detected in/around the tumors.
+Flow cytometric analysis found that CD206(+) TAMs strongly produced EGF compared with CD163(+) and CD204(+) TAMs.
+Cell proliferation and invasion of OSCC cells cultured with conditioned medium of CD206(+) TAMs were strongly enhanced and inhibited by anti-EGFR.
+CD206(+) TAMs might play a critical role in the proliferation of OSCC via EGF production.
+Point-of-care tests are needed for the screening of head and neck squamous cell carcinoma (HNSCC) and other malignancies.
+Luciferase immunoprecipitation systems (LIPS), employing light-emitting proteins, were used to examine serum antibodies against several cancer-associated targets in blood donor controls and subjects with colon cancer (CC) and HNSCC.
+The assessment of antibodies against the wild type p53 tumor antigen showed that approximately 25% of the CC and 20% of the HNSCC patients were seropositive.
+In addition, humoral responses against two p53 mutants, p53-R175H and p53-R273H, generally tracked the antibody responses seen against wild type p53.
+Analysis of antibodies against highly specific biomarkers of HPV-16-associated malignancy, E2, E6, and E7 oncoproteins, revealed no seropositivity in blood donors and CC patients.
+However, 45% (9/20) of the HNSCC patients showed E6 seropositivity, which overlapped all the detectable E2 (40%; 8/20) and E7 seropositive subjects (35%; 7/20).
+Using neodymium magnets, ultrarapid LIPSTICKS testing of HPV-16 E6 antibodies in <60 s per HNSCC sample demonstrated almost the same diagnostic performance (40% sensitivity and 100% specificity) as LIPS testing in 2.5 h. While additional improvements and standardization are needed, these results highlight the possibility of using these approaches for the diagnosis of HPV-16-associated HNSCC.
+Interplay between Cymbidium mosaic virus (CymMV)/Odontoglossum ringspot virus (ORSV) and its host plant Phalaenopsis equestris remain largely unknown, which led to deficiency of effective measures to control disease of P. equestris caused by infecting viruses.
+In this study, for the first time, we characterized viral small interfering RNAs (vsiRNAs) profiles in P. equestris co-infected with CymMV and ORSV through small RNA sequencing technology.
+vsiRNAs, with A/U bias at the first nucleotide, were predominantly 21-nt long and they were derived predominantly (90%) from viral positive-strand RNA.
+21-nt siRNA duplexes with 0-nt overhangs were the most abundant 21-nt duplexes, followed by 2-nt overhangs and then 1-nt overhangs 21-nt duplexes in infected P. equestris.
+Continuous but heterogeneous distribution and secondary structures prediction implied that vsiRNAs originate predominantly by direct Dicer-like enzymes cleavage of imperfect duplexes in the most folded regions of the positive strand of both viruses RNA molecular.
+Furthermore, we totally predicted 54 target genes by vsiRNAs with psRNATarget server, including disease/stress response–related genes, RNA interference core components, cytoskeleton-related genes, photosynthesis or energy supply related genes.
+Gene Ontology classification showed that a majority of the predicted targets were related to cellular components and cellular processes and performed a certain function.
+All target genes were down-regulated with different degree by vsiRNAs as shown by real-time reverse transcription polymerase chain reaction.
+Taken together, CymMV and ORSV siRNAs played important roles in interplay with P. equestris by down modulating the expression levels of endogenous genes in host plant.
+Even though transitivity is a central structural feature of social networks, its influence on epidemic spread on coevolving networks has remained relatively unexplored.
+Here we introduce and study an adaptive susceptible-infected-susceptible (SIS) epidemic model wherein the infection and network coevolve with nontrivial probability to close triangles during edge rewiring, leading to substantial reinforcement of network transitivity.
+This model provides an opportunity to study the role of transitivity in altering the SIS dynamics on a coevolving network.
+Using numerical simulations and approximate master equations (AMEs), we identify and examine a rich set of dynamical features in the model.
+In many cases, AMEs including transitivity reinforcement provide accurate predictions of stationary-state disease prevalence and network degree distributions.
+Furthermore, for some parameter settings, the AMEs accurately trace the temporal evolution of the system.
+We show that higher transitivity reinforcement in the model leads to lower levels of infective individuals in the population, when closing a triangle is the dominant rewiring mechanism.
+These methods and results may be useful in developing ideas and modeling strategies for controlling SIS-type epidemics.
+OBJECTIVES: There are numerous point‐of‐care tests (POCTs) available on the market, but many of these are not used.
+This study reviewed literature pertaining to the evaluation/usage of POCTs in primary care, to investigate whether outcomes being reported reflect aspects previously demonstrated to be important for general practitioners (GPs) in the decision to implement a POCT in practice.
+METHODS: Scopus and Medline were searched to identify studies that evaluated a POCT in primary care.
+We identified abstracts and full‐texts consisting of applied studies (eg trials, simulations, observational studies) and qualitative studies (eg interviews, surveys).
+Data were extracted from the included studies, such as the type of study, the extent to which manufacturers were involved in the study, and the biomarker/assay measured by the test(s).
+Studies were evaluated to summarise the extent to which they reported on, amongst others, clinical utility, user‐friendliness, turnaround‐time and technical performance (aspects previously identified as important).
+RESULTS: The initial search resulted in 1398 publications, of which 125 met the inclusion criteria.
+From these studies, 83 POCTs across several disease areas (including cardiovascular disease, venous thromboembolism and respiratory‐tract‐infections) were identified.
+There was an inconsistency between what is reported in the studies and what GPs consider important.
+GPs perceive clinical utility as the most important aspect, yet this was rarely included explicitly in test evaluations in the literature, with only 8% of evaluations incorporating it in their analysis/discussion.
+CONCLUSIONS: This review showed that, despite the growing market and development of new POCTs, studies evaluating such tests fail to report on aspects that GPs find important.
+To ensure that an evaluation of a POCT is useful to primary care clinicians, future evaluations should not only focus on the technical performance aspects of a test, but also report on the aspects relating to the clinical utility and risks.
+Guertu virus (GTV) is a tick-borne phleboviruses (TBPVs) which belongs to the genus Banyangvirus in the family of Phenuiviridae.
+In vitro and in vivo studies of GTV demonstrated that it was able to infect animal and human cell lines and could cause pathological lesions in mice.
+Glycoproteins (GP, including Gn and Gc) on the surface of Guertu virus (GTV) could bind to receptors on host cells and induce protective immunity in the host, but knowledge is now lacking on the information of B cell epitopes (BCEs) present on GTV-GP protein.
+The aim of this study was to identify all BCEs on Gn of the GTV DXM strain using rabbit pAbs against GTV-Gn.
+Seven fine BCEs and two antigenic peptides (APs) from nine reactive 16mer-peptides were identified, which are E(Gn)1 ((2)PIICEGLTHS(11)), E(Gn)2 ((135)CSQDSGT(141)), E(Gn)3 ((165)IP EDVF(170)), E(Gn)4 ((169)VFQEL K(174)), E(Gn)5 ((187)IDGILFN(193)), E(Gn)6 ((223)QTKWIQ(228)), E(Gn)7 ((237)CHKDGIGPC(245)), AP-8 ((299)GVRVRPKCYGFSRMMA(314)) and AP-9 ((355)CASH FCSSAESGKKNT(370)), of which six of mapped BCEs were recognized by the IgG-positive sheep serum obtained from sheep GTV-infected naturally.
+Multiple sequence alignments (MSA) based on each mapped BCE motif identified that the most of identified BCEs and APs are highly conserved among 10 SFTSV strains from different countries and lineages that share relatively close evolutionary relationships with GTV.
+The fine epitope mapping of the GTV-Gn would provide basic data with which to explore the GTV-Gn antigen structure and pathogenic mechanisms, and it could lay the foundation for the design and development of a GTV multi-epitope peptide vaccine and detection antigen.
+Clinical signs occurred shortly after birth or started at an age of under 4 weeks and included apathy, dysphoric vocalization, hypermetric ataxia, intension tremor, head tilt, circling, proprioceptive deficits, seizures and ventral strabismus consistent with a diffuse intracranial lesion.
+Histopathologically, a severe multifocal reduction of myelin formation and moderate diffuse edema without inflammation was detected leading to the diagnosis of leukodystrophy.
+Combined linkage analysis and homozygosity mapping in two related families delineated critical intervals of approximately 29 Mb.
+The comparison of whole genome sequence data of one affected Standard Schnauzer to 221 control genomes revealed a single private homozygous protein changing variant in the critical intervals, TSEN54:c.371G>A or p.(Gly124Asp).
+In humans, several variants in TSEN54 were reported to cause different types of pontocerebellar hypoplasia.
+The genotypes at the c.371G>A variant were perfectly associated with the leukodystrophy phenotype in 12 affected Standard Schnauzers and almost 1000 control dogs from different breeds.
+The identification of a candidate causative variant enables genetic testing so that the unintentional breeding of affected Standard Schnauzers can be avoided in the future.
+BACKGROUND: Respiratory viral (RV) outbreaks in rehabilitation facilities can jeopardise patient safety, interfere with patient rehabilitation goals and cause unit closures that impede patient flow in referring facilities.
+PROBLEM: Despite education about infection prevention practices, frequent RV outbreaks were declared each year at our rehabilitation facility.
+The primary outcome was the number of bed closure days due to outbreak per overall bed days.
+Process measures included delays in initiation of transmission-based precautions, RV testing and reporting of staff to occupational health and safety (OHS).
+INTERVENTIONS: Based on comprehensive analysis of prior outbreaks, the following changes were implemented: (1) clear criteria for initiation of transmission-based precautions, (2) communication to visitors to avoid visitation if infectious symptoms were present, (3) exemption of staff absences if documented due to infectious illness, (4) development of an electronic programme providing guidance to staff about whether they should be excluded from work due to infectious illness.
+RESULTS: The number of bed closure days due to outbreak per overall bed days dropped from 2.8% to 0.5% during the intervention season and sustained at 0.6% during the postintervention season (p<0.001).
+There were fewer delays in initiation of droplet and contact precautions (28.8% to 15.5%, p=0.005) and collection of RV testing (42.9% to 20.3%, p<0.001), better reporting to OHS (9 vs 28.8 reports per 100 employees; p<0.001) and fewer isolation days (7.8% vs 7.3%; p=0.02) without a significant increase in missed work hours per 100 hours worked (4.0 vs 3.9; p=0.12).
+CONCLUSION: This Quality Improvement study highlights the process changes that can prevent respiratory outbreaks in the rehabilitation setting.
+As a response to a diverse array of external stimuli, early growth response protein 1 (Egr-1) plays important roles in the transcriptional regulation of inflammation and the cellular immune response.
+However, a number of intracellular pathogens colonize immune cells and the implication of Egr-1 in the host-pathogen interplay has remained elusive.
+Here, we have characterized the Egr-1 responses of primary murine and human dendritic cells (DCs) upon challenge with the obligate intracellular parasite Toxoplasma gondii.
+We report that live intracellular parasites induce a sustained high expression of Egr-1 in DCs, different from the immediate-early Egr-1 response to parasite lysates, inactivated parasites or LPS.
+Moreover, a distinct nuclear localization of elevated amounts of Egr-1 protein was detected in infected DCs, but not in by-stander DCs.
+The ERK1/2 MAPK signaling pathway mediated the canonical immediate-early Egr-1 response to soluble antigens in a MyD88/TLR-dependent fashion.
+In contrast, a non-canonical extended Egr-1 response that relied primarily on p38 MAPK signaling was induced by intracellular parasites and was exhibited similarly by MyD88-deficient and wildtype DCs.
+The extended phase Egr-1 response was dramatically reduced upon challenge of DCs with T. gondii parasites deficient in GRA24, a secreted p38-interacting protein.
+Importantly, Egr-1 silencing led to elevated expression of co-stimulatory molecules (CD40, CD80) in Toxoplasma-infected DCs and in LPS-challenged immature DCs, indicating that Egr-1 responses suppressed maturation of DCs.
+Moreover, the IL-12 and IL-2 responses of Toxoplasma-challenged DCs were modulated in a GRA24-dependent fashion.
+Jointly, the data show that the Egr-1 responses of DCs to microbial external stimuli and intracellular stimuli can be selectively mediated by ERK1/2 or p38 MAPK signaling, and that Egr-1 can act as an intrinsic negative modulator of maturation in primary DCs.
+BACKGROUND: Arbaeenia mass gathering (MG) in Karbala, Iraq, is becoming one of the largest MGs in the world.
+The health care infrastructure in Iraq is inadequately prepared to serve the health needs of the millions of pilgrims.
+OBJECTIVE: This study aimed to describe the temporary health care facilities installed and run by the local community to provide health care services to Arbaeenia pilgrims in Karbala, Iraq.
+METHODS: A survey was conducted in all community-based health care facilities located along part of Najaf to Karbala road within Karbala governorate.
+Data were collected on staff profile, type of services provided, use of basic infection control measures, medical equipment, drugs and supplies, and the most commonly encountered medical problems.
+Only 18 (15.0%, 18/120) facilities were licensed, and 44.1% (53/120) of the workers were health professionals.
+The health care workers provided different services including dispensing drugs (370/1692, 21.87%), measuring blood pressure and blood sugar (350/1692, 20.69%), and caring for wounds and injuries (319/1692, 18.85%).
+Around 97% (116/120) health facilities provided services for musculoskeletal disorders and only 16.7% (20/120) provided services for injuries.
+The drugs available in the clinic were analgesics, drugs for gastrointestinal and respiratory diseases, and antibiotics, with an availability range of 13.3% to 100.0%.
+Infection control practices for individual protection, environmental sanitation, and medical waste disposal were available in a range of 18.1% to 100.0%.
+CONCLUSIONS: Community-based health care facilities experienced a profound shortage of trained human resources and medical supplies.
+They can significantly contribute to health services if they are adequately equipped and follow standardized operation procedures.
+Among the various nano/biomaterials used in cancer treatment, the beauty and benefits of DNA nanocomposites are outstanding.
+The specificity and programmability of the base pairing of DNA strands, together with their ability to conjugate with different types of functionalities have realized unsurpassed potential for the production of two- and three-dimensional nano-sized structures in any shape, size, surface chemistry and functionality.
+This review aims to provide an insight into the diversity of static DNA nanodevices, including DNA origami, DNA polyhedra, DNA origami arrays and bioreactors, DNA nanoswitch, DNA nanoflower, hydrogel and dendrimer as young but promising platforms for cancer theranostics.
+The utility and potential of the individual formats in biomedical science and especially in cancer therapy will be discussed.
+Rift Valley fever virus (RVFV) is a zoonotic mosquito-borne virus that was first discovered in Kenya in 1930 and has since spread to become endemic in much of Africa and the Arabian Peninsula.
+Rift Valley fever (RVF) causes recurrent outbreaks of febrile illness associated with high levels of mortality and poor outcomes during pregnancy—including foetal malformations, spontaneous abortion and stillbirths—in livestock, and associated with miscarriage in humans.
+No vaccines are available for human use and those licensed for veterinary use have potential drawbacks, including residual virulence that may contraindicate their use in pregnancy.
+To address this gap, we previously developed a simian adenovirus vectored vaccine, ChAdOx1 RVF, that encodes RVFV envelope glycoproteins.
+ChAdOx1 RVF is fully protective against RVF in non-pregnant livestock and is also under development for human use.
+Here, we now demonstrate that when administered to pregnant sheep and goats, ChAdOx1 RVF is safe, elicits high titre RVFV neutralizing antibody, and provides protection against viraemia and foetal loss, although this protection is not as robust for the goats.
+In addition, we provide a description of RVFV challenge in pregnant goats and contrast this to the pathology observed in pregnant sheep.
+Together, our data further support the ongoing development of ChAdOx1 RVF vaccine for use in livestock and humans.
+RESULTS: Incidences of 5 chicken respiratory viruses: avian influenza virus (AIV), Newcastle disease virus (NDV/AAVV-1), infectious bronchitis virus (IBV), avian metapneumovirus (aMPV) and infectious laryngotracheitis virus (ILTV) were assessed on commercial Pakistani farms with respiratory problems from 2014 through to 2016.
+While AIV and AAVV-1 were frequently detected (16 to 17% of farms), IBV and aMPV were rarely detected (in 3 to 5% of farms) and ILTV was not detected.
+We characterized H9 AIV of the G1 lineage, genotype VII AAVV-1, GI-13 IBV, and type B aMPV strains with very little genetic variability in the 2-year study period.
+Co-infections with AIV and AAVV-1 were common and wild type AAVV-1 was detected despite the use of vaccines.
+CONCLUSIONS: Our data shows that AIV (H9), AAVV-1, IBV and aMPV are prevalent in commercial poultry in Pakistan.
+Further studies are necessary to assess circulating strains, economic losses caused by infections and coinfections of these pathogens, and the costs and benefits of countermeasures.
+Furthermore, veterinarians and farmers should be informed of the pathogens circulating in the field and hence advised on the use of vaccines.
+INTRODUCTION: Epidemic forecasting and prediction tools have the potential to provide actionable information in the midst of emerging epidemics.
+While numerous predictive studies were published during the 2016–2017 Zika Virus (ZIKV) pandemic, it remains unknown how timely, reproducible, and actionable the information produced by these studies was.
+METHODS: To improve the functional use of mathematical modeling in support of future infectious disease outbreaks, we conducted a systematic review of all ZIKV prediction studies published during the recent ZIKV pandemic using the PRISMA guidelines.
+Using MEDLINE, EMBASE, and grey literature review, we identified studies that forecasted, predicted, or simulated ecological or epidemiological phenomena related to the Zika pandemic that were published as of March 01, 2017.
+Eligible studies underwent evaluation of objectives, data sources, methods, timeliness, reproducibility, accessibility, and clarity by independent reviewers.
+Spatial spread, R(0) (basic reproductive number), and epidemic dynamics were most commonly predicted, with few studies predicting Guillain-Barré Syndrome burden (4%), sexual transmission risk (4%), and intervention impact (4%).
+Case count (67%), vector (41%), and demographic data (37%) were the most common data sources.
+Real-time internet data and pathogen genomic information were used in 7% and 0% of studies, respectively, and social science and behavioral data were typically absent in modeling efforts.
+Forty percent of studies made model data entirely available, 29% provided all relevant model code, 43% presented uncertainty in all predictions, and 54% provided sufficient methodological detail to allow complete reproducibility.
+While the use of preprints improved the accessibility of ZIKV predictions by a median of 119 days sooner than journal publication dates, they were used in only 30% of studies.
+The accessibility, reproducibility, timeliness, and incorporation of uncertainty in these published predictions varied and indicates there is substantial room for improvement.
+To enhance the utility of analytical tools for outbreak response it is essential to improve the sharing of model data, code, and preprints for future outbreaks, epidemics, and pandemics.
+Respiratory syncytial virus (RSV) infection is a leading cause of severe acute lower respiratory tract infection in infants and children worldwide.
+Vitamin A deficiency (VAD) is one of the most prevalent nutrition-related health problems in the world and is a significant risk factor in the development of severe respiratory infections in infants and young children.
+Bovine RSV (BRSV) is a primary cause of lower respiratory tract disease in young cattle.
+The calf model of BRSV infection is useful to understand the immune response to human RSV infection.
+We have previously developed an amphiphilic polyanhydride nanoparticle (NP)-based vaccine (i.e., nanovaccine) encapsulating the fusion and attachment proteins from BRSV (BRSV-NP).
+Calves receiving a single, intranasal dose of the BRSV-NP vaccine are partially protected from BRSV challenge.
+Here, we evaluated the impact of VAD on the immune response to the BRSV-NP vaccine and subsequent challenge with BRSV.
+Our results show that VAD calves are unable to respond to the mucosal BRSV-NP vaccine, are afforded no protection from BRSV challenge and have significant abnormalities in the inflammatory response in the infected lung.
+We further show that acute BRSV infection negatively impacts serum and liver retinol, rendering even well-nourished individuals susceptible to VAD.
+Our results support the use of the calf model for elucidating the impact of nutritional status on mucosal immunity and respiratory viral infection in infants and underline the importance of VA in regulating immunity in the respiratory mucosa.
+METHODS: We compared the results of a liquid bead array xTAG Respiratory Virus Panel (RVP; (Luminex Corporation, Toronto, Canada) and a solid microarray Verigene Respiratory Virus Plus (RV+; Nanosphere, Northbrook, IL) for the detection of influenza A virus (INF A), influenza B virus (INF B), and respiratory syncytial virus (RSV) in 170 respiratory specimens from hospitalized patients.
+RESULTS: Overall, xTAG RVP demonstrated sensitivities and specificities of 97.6 and 100% for INF A, 100 and 99.4% for INF B, and 100 and 100% for RSV, while the Verigene RV+ test sensitivities and specificities were 95.1 and 98.5%, 100.0 and 99.4%, and 97.1 and 100%, respectively.
+There were no significant differences in the area under the curves between the two assays for each virus (P = 0.364 for INF A, P = 1.000 for INF B, P = 0.317 for RSV).
+Comparing the results of two assays, discordant results were present mostly due to subtype assignments and identification of coinfections.
+The detection of viruses was not significantly different (P = 1.000) and the virus/subtype assignment showed good agreement with kappa coefficients of 0.908.
+CONCLUSION: The xTAG RVP and Verigene RV+ showed high sensitivities and specificities, and good overall agreement in detection and identification of INF and RSV.
+These assays can be used in clinical settings for a reliable detection of respiratory viruses found commonly in hospitalized patients.
+BACKGROUND: The Eastern Mediterranean Public Health Network, supported by the Biosecurity Engagement Program, contributed significantly to strengthening the preparedness and response to the emerging and re-emerging infections in the region.
+OBJECTIVE: This study aimed to determine the gaps, challenges, and priorities for preventing the emerging and re-emerging infections, with a focus on biosafety and biosecurity in four countries of the region, namely, Egypt, Iraq, Jordan, and Morocco.
+METHODS: A total of two different methods were used to determine the gaps and priorities for preventing the emerging and re-emerging infections.
+The first method was a rapid assessment for the preparedness and response to the emerging and re-emerging infections in four countries of the region, with a focus on biosafety and biosecurity.
+The second method was a face-to-face round table meeting of the participating teams for two days, where the teams from all countries presented their countries’ profiles, findings, priorities, and gaps based on the countries’ assessments.
+RESULTS: The assessment and meeting resulted in several priorities and recommendations for each of the countries in the areas of legislation and coordination, biosafety and biosecurity, surveillance and human resources, case management and response, infection control and prevention, and risk communication and laboratory capacity.
+CONCLUSIONS: Many recommendations were relatively consistent throughout, including improving communication or building collaborations to improve the overall health of the country.
+We investigated factors structuring the helminth and protozoan infections of wolves (Canis lupus) by using coprological analyses.
+Faecal samples (n = 342) were analysed from 11 wolf packs belonging to three different geographical and ecological settings in Italy (Abruzzo, Lazio e Molise National Park, PNALM: 4 packs, 88 samples), in France (Mercantour National Park, PNM: 4 packs, 68 samples) and in the U.S.A. (Yellowstone National Park, YNP: 3 packs, 186 samples).
+Parasites were found in 29.4%–88.6% of the samples and parasite taxa ranged from four to ten in each study area.
+and Toxascaris leonina were most common in faecal samples from YNP, whereas Capillaria spp., Taeniidae and Uncinaria stenocephala were predominant in PNALM.
+We used generalised linear mixed models to assess the relationship between parasite infection or the number of parasite taxa and selected ecological drivers across study areas.
+Significant effects illustrated the importance of the ecological factors such as occurrence of free-ranging dogs, diet composition and wolf density, as well as the ancestry of the wolf populations, in shaping parasite-wolf communities.
+Additional investigations are needed to elucidate the impact of parasitic infections on wolf populations, as well as the role of anthropogenic factors in facilitating parasitic diffusion to apex predators.
+BACKGROUND AND AIM: Determining reference values for hematological and biochemical parameters of Asian house shrew (Suncus murinus) is important for wildlife research to protect human health in surrounding communities.
+This study aimed to establish the reference values for selected hematology and serum clinical chemistry analyses that may contribute to research on shrew in future.
+MATERIALS AND METHODS: Blood samples (n=51) were collected from shrews between July and December 2015, Bangladesh, to estimate the levels of hemoglobin (Hb), packed cell volume (PCV), total leukocyte count (TLC), total erythrocyte count (TEC), lymphocyte, monocyte, neutrophil, eosinophil, basophil, calcium, phosphorus (P), sodium (Na), chloride (Cl), urea, glucose, total protein (TP), creatinine, and alanine transaminase (ALT).
+RESULTS: Although the values did not differ significantly among sexes, age was found to be a significant factor.
+Hb, PCV, TEC, glucose, and P were higher in males; eosinophil, Na, Cl, TP, and ALT were higher among females.
+Adults had significantly greater urea and glucose (p<0.05) while juveniles had insignificantly higher values for TLC, PCV, neutrophil, P, and TP.
+CONCLUSION: This study provides the first reference values for this species in Bangladesh and can be used to guide wildlife research studies.
+The lung plays a vital role in maintaining homeostasis, as it is responsible for the exchange of oxygen and carbon dioxide.
+Pulmonary homeostasis is maintained by a network of tissue-resident cells, including epithelial cells, endothelial cells and leukocytes.
+Myeloid cells of the innate immune system and epithelial cells form a critical barrier in the lung.
+Recently developed unbiased next generation sequencing (NGS) has revealed cell heterogeneity in the lung with respect to physiology and pathology and has reshaped our knowledge.
+New phenotypes and distinct gene signatures have been identified, and these new findings enhance the diagnosis and treatment of lung diseases.
+Here, we present a review of the new NGS findings on myeloid cells in lung development, homeostasis, and lung diseases, including acute lung injury (ALI), lung fibrosis, chronic obstructive pulmonary disease (COPD), and lung cancer.
+Based on this technology, we synthesized DNA templates, which were transcribed into sgRNA in vitro, and further detected their efficiency of purified sgRNAs with Cas9 nuclease.
+The sgRNAs synthesized by this approach can effectively cleave the DNA fragments of interest in vitro and in vivo.
+Compared with the conventional method for generating sgRNA, it does not require construction of recombinant plasmids and design of primers to amplify sgRNA core fragment.
+Only several short primers with overlapped sequences are needed to assemble a DNA fragment as the template of sgRNA.
+The delivery of biologic cargoes to airway epithelial cells is challenging due to the formidable barriers imposed by its specialized and differentiated cells.
+Among cargoes, recombinant proteins offer therapeutic promise but the lack of effective delivery methods limits their development.
+Here, we achieve protein and SpCas9 or AsCas12a ribonucleoprotein (RNP) delivery to cultured human well-differentiated airway epithelial cells and mouse lungs with engineered amphiphilic peptides.
+These shuttle peptides, non-covalently combined with GFP protein or CRISPR-associated nuclease (Cas) RNP, allow rapid entry into cultured human ciliated and non-ciliated epithelial cells and mouse airway epithelia.
+Instillation of shuttle peptides combined with SpCas9 or AsCas12a RNP achieves editing of loxP sites in airway epithelia of ROSA(mT/mG) mice.
+We observe no evidence of short-term toxicity with a widespread distribution restricted to the respiratory tract.
+This peptide-based technology advances potential therapeutic avenues for protein and Cas RNP delivery to refractory airway epithelial cells.
+As one of many nonstructural proteins of porcine reproductive and respiratory syndrome virus (PRRSV), nonstructural protein 12 (Nsp12) has received relatively little attention, and its role in virus replication, if any, is essentially unknown.
+By the application of reverse genetic manipulation of an infectious PRRSV clone, the current study is the first to demonstrate that Nsp12 is a key component of PRRSV replication.
+In addition, the biochemical properties of Nsp12 were evaluated, revealing that Nsp12 forms dimers when exposed to oxidative conditions.
+Furthermore, we systemically analyzed the function of Nsp12 in PRRSV RNA synthesis using a strand-specific PCR method.
+To our surprise, Nsp12 was not found to be involved in minus-strand genomic RNA (-gRNA) synthesis; importantly, our results indicate that Nsp12 is involved in the synthesis of both plus- and minus-strand subgenomic mRNAs (+sgmRNA and -sgmRNA).
+Finally, we found that the combination of cysteine 35 and cysteine 79 in Nsp12 is required for sgmRNA synthesis.
+To our knowledge, we are the first to report the biological role of Nsp12 in the PRRSV lifecycle, and we conclude that Nsp12 is involved in the synthesis of both + sgRNA and -sgRNA.
+Peptides are secreted by different cell types and are trendy therapeutic agents that have attracted attention for the treatment of several diseases such as infections.
+Antimicrobial peptides exert various mechanisms such as changing cell membrane permeability which leads to inhibition or death of bacterial cells.
+mesenchymal stem cells (MSCs) are key to produce antimicrobial peptides and to inhibit the growth of pathogens.
+These cells have been shown to be capable of producing antimicrobial peptides upon exposure to different bacteria.
+As a result, antimicrobial peptides can be considered as novel agents for the treatment of infectious diseases.
+The purpose of this review was to investigate the targets and mechanisms of antimicrobial peptides secreted by MSCs.
+Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine that increasingly is being studied in cancers and inflammatory diseases.
+Though murine models have been instrumental in understanding the functional role of MIF in different pathological conditions, the information obtained from these models is biased towards a specific species.
+In experimental science, results obtained from multiple clinically relevant animal models always provide convincing data that might recapitulate in humans.
+Syrian golden hamster (Mesocricetus auratus), is a clinically relevant animal model for multiple human diseases.
+Hence, the major objectives of this study were to characterize the structure and function of Mesocricetus auratus MIF (MaMIF) and finally evaluate its effect on pancreatic tumor growth in vivo.
+The MaMIF primary sequence, biochemical properties, and crystal structure analysis showed greater similarity with human MIF.
+The crystal structure of MaMIF illustrates that it forms a homotrimer as known in human and mouse.
+The in vitro functional studies show that MaMIF has tautomerase activity and enhances activation and migration of hamster peripheral blood mononuclear cells (PBMCs).
+Interestingly, injection of MaMIF into HapT1 pancreatic tumor-bearing hamsters significantly enhanced the tumor growth and tumor-associated angiogenesis.
+Together, the current study shows a structural and functional similarity between the hamster and human MIF.
+Moreover, it has demonstrated that a high level of circulating MIF originating from non-tumor cells might also promote pancreatic tumor growth in vivo.
+BACKGROUND: Pertussis causes severe disease in young unvaccinated infants, with preterms potentially at highest risk.
+We studied pertussis in hospitalized infants as related to gestational age (GA) and vaccination history.
+METHODS: Medical record data of 0-2y old patients hospitalized for pertussis during 2005–2014 were linked to vaccination data.
+Multivariable logistic regression was used to study the association between GA and vaccination history on the clinical disease course.
+We compared vaccine effectiveness (VE) against hospitalization for pertussis between term and preterm infants (i.e., <37w GA) using the screening method as developed by Farrington.
+Median age at admission was 3 m for preterms and 2 m for terms (p < 0.001).
+Preterms more often had received pertussis vaccination (62% vs 44%; p = 0.01) and more often had coinfections (37% vs 21%; p = 0.01).
+Preterms tended more often to have complications, to require artificial respiration or to need admittance to the intensive care unit (ICU).
+Vaccinated preterms and terms had a lower median length of hospital stay and lower crude risks of apneas and the need for artificial respiration, additional oxygen, and ICU admittance than those not vaccinated.
+After adjustment for presence of coinfections and age at admittance, these differences were not significant, except the lower need of oxygen treatment in vaccinated terms.
+Effectiveness of the first vaccination against pertussis hospitalizations was 95% (95% CI 93–96%) and 73% (95% CI 20–91%) in terms and preterms, respectively.
+Effectiveness of the second dose of the primary vaccination series was comparable in both groups (86 and 99%, respectively).
+Preterms were overrepresented, with higher need for intensive treatment and less VE of first vaccination.
+These findings stress the need for alternative prevention, in particular prenatal vaccination of mothers, to reduce pertussis in both groups.
+Non-structural protein 1 (NS1) of influenza virus has been shown to inhibit the innate immune response by blocking the induction of interferon (IFN).
+In this study, we isolated two single-stranded RNA aptamers specific to NS1 with K(d) values of 1.62 ± 0.30 nM and 1.97 ± 0.27 nM, respectively, using a systematic evolution of ligand by exponential enrichment (SELEX) procedure.
+The selected aptamers were able to inhibit the interaction of NS1 with tripartite motif-containing protein 25 (TRIM25), and suppression of NS1 enabled retinoic acid inducible gene I (RIG-I) to be ubiquitinated regularly by TRIM25.
+Additional luciferase reporter assay and quantitative real-time PCR (RT-PCR) experiments demonstrated that suppression of NS1 by the selected aptamers induced IFN production.
+It is noted that viral replication was also inhibited through IFN induction in the presence of the selected aptamers.
+These results suggest that the isolated aptamers are strongly expected to be new therapeutic agents against influenza infection.
+[Image: see text] Nucleoside analogues are among the most common medications given for the treatment of viral infections and cancers.
+The ProTide approach was developed using a phosphorylated nucleoside that is masked by esterification with an amino acid and phenol forming a chiral phosphorus center.
+The biological activity of the ProTides depends, in part, on the stereochemistry at phosphorus, and thus, it is imperative that efficient methods be developed for the chemical synthesis and isolation of diastereomerically pure ProTides.
+Chiral ProTides are often synthesized by direct displacement of a labile phenol (p-nitrophenol or pentafluorophenol) from a chiral phosphoramidate precursor with the appropriate nucleoside analogue.
+The ability to produce these chiral products is dictated by the synthesis of the chiral phosphoramidate precursors.
+The enzyme phosphotriesterase (PTE) from Pseudomonas diminuta is well-known for its high stereoselectivity and broad substrate profile.
+Screening PTE variants from enzyme evolution libraries enabled the identification of variants of PTE that can stereoselectively hydrolyze the chiral phosphoramidate precursors.
+The variant G60A-PTE exhibits a 165-fold preference for hydrolysis of the R(P) isomer, while the variant In1W-PTE has a 1400-fold preference for hydrolysis of the S(P) isomer.
+Using these mutants of PTE, the S(P) and R(P) isomers were isolated on a preparative scale with no detectable contamination of the opposite isomer.
+Combining the simplicity of the enzymatic resolution of the precursor with the latest synthetic strategy will facilitate the production of diastereometrically pure nucleotide phosphoramidate prodrugs.
+BACKGROUND: Interleukin-35 (IL-35) is a recently discovered cytokine that plays a role in immune suppression and has therefore been the subject of a great deal of research.
+OBJECTIVES: The aim of this research was to assess the international scientific output of IL-35 research and explore its hotspots and frontiers from 2009 to 2018 by bibliometric analysis.
+METHODS: Publications about IL-35 research from 2009 to 2018 were retrieved from the Web of Science Core Collection (WoSCC).
+Citespace V was used to analyze years, journals, countries, research institutions, areas of exploration, research hotspots, and trends of publication.
+RESULTS: We retrieved a total of 416 publications and observed a trend of publications increasing over the past decade.
+The largest number of publications belonging to one country and one institution, respectively, was China (202) and Tianjin Medical University (17).
+Trending keywords may indicate frontier topics, including “infectious tolerance,” “autoimmune,” and “central nervous system.” CONCLUSION: This study provides valuable information on the study of IL-35 so that researchers may identify new research fields.
+AIM: Newcastle disease virus (NDV) is a member of genus Avulavirus within the family Paramyxoviridae.
+Interest of using NDV as an anticancer agent has arisen from its ability to kill tumor cells with limited toxicity to normal cells.
+METHODS: In this investigation, the proliferation of brain tumor cell line, glioblastoma multiform (DBTRG.05MG) induced by NDV strain AF2240 was evaluated in-vitro, by using MTT proliferation assay.
+Furthermore, Cytological observations were studied using fluorescence microscopy and transmission electron microscopy, DNA laddering in agarose gel electrophoresis assay used to detect the mode of cell death and analysis of the cellular DNA content by flowcytometery.
+RESULTS: MTT proliferation assay, Cytological observations using fluorescence microscopy and transmission electron microscopy show the anti-proliferation effect and apoptogenic features of NDV on DBTRG.05MG.
+Furthermore, analysis of the cellular DNA content showed that there was a loss of treated cells in all cell cycle phases (G1, S and G2/M) accompanied with increasing in sub-G1 region (apoptosis peak).
+CONCLUSION: It could be concluded that NDV strain AF2240 is a potent antitumor agent that induce apoptosis and its cytotoxicity increasing while increasing of time and virus titer.
+OBJECTIVE: Spontaneous intracerebral hemorrhage (ICH) is caused by the rupture of small blood vessels and other health problems.
+We analyzed the risk factors for hematoma expansion in ICH patients and compared the predictability of hematoma expansion in ICH patients with the use of tranexamic acid.
+METHODS: We performed retrospective analysis of ICH patients who underwent follow-up computed tomography scans from October 2008 to October 2018.
+Of the 329 included patients, 67 who received tranexamic acid and 262 who did not receive tranexamic acid were compared.
+We also analyzed the risk factors of 45 and 284 patients who did and did not experience hematoma expansion, respectively.
+RESULTS: Hematoma expansion was observed in 7 (10.4%) of 67 patients in the tranexamic acid group and 38 (14.5%) of the 262 patients who did not receive tranexamic acid.
+There was no statistically significant difference between patients who did and did not received tranexamic acid (p=0.389).
+In the multivariate logistic regression analysis of risk factors for hematoma expansion, spot sign and a maximal diameter of 40 mm were identified as risk factors.
+CONCLUSION: We could not confirm the effect of tranexamic acid on hematoma expansion in ICH patients.
+Spot sign and the maximal diameter of hematomas were confirmed as risk factors of hematoma expansion.
+If the maximal diameter is greater than 40 mm, the hematoma should be closely monitored.
+SIMPLE SUMMARY: Recent research has debated the effects of milk and forage feeding regimes in the first weeks of life on the future performance of dairy calves.
+However, little is known about how feeding regime can affect behavioural and physiological responses, which have the potential to impact on calf health and well-being.
+Traditional methods of assessing calf health and welfare such as behavioural observations and blood sampling can be time consuming and impractical for producers and invasive for animals involved.
+Developments in technology have increased the availability of on-farm non-invasive devices which allow automatic and remote collection of behavioural and physiological data linked to animal health and welfare.
+This study aimed to use devices to measure lying behaviour, heart rate, heart rate variability and infrared temperature of calves offered high or low levels of milk replacer and different types of forage throughout the first ten weeks of life.
+Calves displayed changes in lying behaviour and heart rate variability as a result of changes in milk replacer feeding frequency.
+Additionally, infrared temperature changes were detected during periods of vaccination which corresponded with a rise in core body temperature.
+Results have highlighted that these sensors can provide important and useable data regarding overall calf well-being on commercial farms.
+ABSTRACT: This study aimed to examine the use of non-invasive monitoring technologies as a means of capturing behavioural, physiological and health responses of calves allocated to different nutritional regimes.
+Seventy-four Holstein Friesian calves were individually penned and allocated to receive either high (HML) or conventional (CML) milk replacer (MR) levels between 5–70 days of age.
+Additionally calves were allocated to one of four forage treatments: (i) chopped straw offered between 14–70 days of age (CS14), (ii) chopped straw offered between 56–70 days of age (CS56), (iii) grass silage offered between 56–70 days of age (GS56), and (iv) no forage in the pre-wean period (NF).
+A representative sample of calves from each treatment were fitted with activity sensors and heart rate monitors throughout the experimental period to examine lying behaviour and heart rate variability, respectively.
+Thermal images of the eye and rectal area of each calf were taken 5 days/week between 5–77 days of age.
+Faecal and respiratory scoring of each individual calf was carried out on a daily basis throughout the experimental period.
+Milk replacer feeding level had limited effects on measures of calf health, although HML calves tended to have an increased likelihood for receiving treatment for scour than CML calves.
+Daily lying time (min/d) was lower in HML calves following reduction in MR feeding frequency at 43 days of age and weaning at 71 days of age when compared with CML calves.
+Additionally, HML calves displayed a lower heart rate variability following weaning, this suggestive of increased stress load.
+There were limited effects of forage treatment, however, CS14 calves displayed a greater daily lying time following MR step-down at 68 days of age, this potentially indicating increased rumination.
+Results of the present study highlight the benefits of using remote monitoring technologies as a means of detecting behavioural and physiological changes as a result of nutritional management strategy in individually housed dairy calves.
+The experimental infection of rhesus macaques (rh) with simian immunodeficiency virus (SIV) is an important model for human immunodeficiency virus (HIV) infection of humans.
+The interferon-induced transmembrane protein 3 (IFITM3) inhibits HIV and SIV infection at the stage of host cell entry.
+However, it is still unclear to what extent the antiviral activity of IFITM3 observed in cell culture translates into inhibition of HIV/SIV spread in the infected host.
+We have shown previously that although rhIFITM3 inhibits SIV entry into cultured cells, polymorphisms in the rhIFITM3 gene are not strongly associated with viral load or disease progression in SIV infected macaques.
+Here, we examined whether rhIFITM3(2), which is closely related to rhIFITM3 at the sequence level, exerts antiviral activity and whether polymorphisms in the rhIFITM3(2) gene impact the course of SIV infection.
+We show that expression of rhIFITM3(2) is interferon-inducible and inhibits SIV entry into cells, although with reduced efficiency as compared to rhIFITM3.
+However, analysis of a well characterized cohort of SIV infected macaques revealed that none of the polymorphisms had a significant impact upon the course of SIV infection.
+These results and our previous work suggest that polymorphisms in the rhIFITM3 and rhIFITM3(2) genes do not strongly modulate the course of SIV infection in macaques.
+We prospectively analyzed outcomes of haploidentical hematopoietic stem cell transplantation using αβ(+) T-cell receptor/CD19(+) depleted grafts.
+Twenty-eight patients were diagnosed with acute lymphoblastic leukemia (ALL), 27 patients were diagnosed with acute myelogenous leukemia, and in eight other hematological malignancies were diagnosed.
+Twenty-three were in first complete remission (CR), 20 in second CR, 20 beyond second CR.
+Median time to neutrophil and platelet recovery was 14 (range 9–25) and 10 days (range 7–30), respectively.
+The probability of non-relapse mortality (NRM) by day +100 after transplantation was 10 ± 4%.
+With a median follow-up of 28 months, the probability of relapse was 32 ± 6% and disease-free survival was 52 ± 6%.
+As such, a high CD56(dim/)CD56(bright) NK cell ratio early after transplantation was associated with better disease-free survival (DFS) (≥3.5; 77 ± 8% vs. <3.5; 28 ± 5%; p = 0.001) due to lower relapse incidence (≥3.5; 15 ± 7% vs. <3.5; 37 ± 9%; p = 0.04).
+Viral reactivation/disease and presence of venooclusive disease of liver in the non-caucasian population had a significant impact on NRM.
+αβ(+) T-cell receptor/CD19(+) cell-depleted haploidentical transplant is associated with good outcomes especially in patients in early phase of disease.
+A rapid expansion of “mature” natural killer cells early after transplantation resulted on lower probability of relapse, suggesting a graft vs. leukemia effect independent from graft-vs.-host reactions.
+Here, we show that the US Food and Drug Administration-approved oral drug nitazoxanide (NTZ) broadly amplifies the host innate immune response to viruses and inhibits Ebola virus (EBOV) replication.
+We find that NTZ enhances retinoic-acid-inducible protein I (RIG-I)-like-receptor, mitochondrial antiviral signaling protein, interferon regulatory factor 3, and interferon activities and induces transcription of the antiviral phosphatase GADD34.
+NTZ significantly inhibits EBOV replication in human cells through its effects on RIG-I and protein kinase R (PKR), suggesting that it counteracts EBOV VP35 protein's ability to block RIG-I and PKR sensing of EBOV.
+NTZ also inhibits a second negative-strand RNA virus, vesicular stomatitis virus (VSV), through RIG-I and GADD34, but not PKR, consistent with VSV's distinct host innate immune evasion mechanisms.
+Thus, NTZ counteracts varied virus-specific immune evasion strategies by generally enhancing the RNA sensing and interferon axis that is triggered by foreign cytoplasmic RNA exposure, and holds promise as an oral therapy against EBOV.
+Recent studies indicate that HEV exists in two forms: naked, nonenveloped virions that are shed into feces to mediate inter-host transmission, and membrane-cloaked, quasienveloped virions that circulate in the bloodstream to mediate virus spread within a host.
+Elucidating the entry mechanism for both virion types is essential to understand HEV biology and pathogenesis, and is relevant to the development of treatments and preventions for HEV.
+This review summarizes the current understanding of the cell entry mechanism for these two HEV virion types.
+The papain-like cysteine protease 2 (PLP2) within the N-terminus of the porcine reproductive and respiratory syndrome virus (PRRSV) nsp2 replicase protein specifies a deubiquitinating enzyme (DUB), but its biochemical properties and the role in infection have remained poorly defined.
+By using in vitro assays, we found that the purified PLP2 could efficiently cleave K63 and K48 linked polyubiquitin chains Ub3-7 in vitro although displaying a differential activity in converting the respective ubiquitin dimers to monomer.
+The subsequent mutagenesis analyses revealed that the requirement for PLP2 DUB activity surprisingly resembled that for cis-cleavage activity, as several mutations (e.g., D91R, D85R, etc.)
+that largely ablated the DUB function also blocked the cis- but not trans-proteolytic cleavage of nsp2/3 polyprotein.
+Moreover, the analyses identified key mutations that could differentiate DUB from PLP2 cis- and trans-cleavage activities.
+Further reverse genetics analyses revealed the following findings: (i) mutations that largely blocked the DUB activity were all lethal to the virus, (ii) a point mutation T88G that selectively blocked the cis-cleavage activity of PLP2 did not affect viral viability in cell culture, and (iii) an E90Q mutation that did not affect either of the PLP2 activities led to rescue of WT-like virus but displayed significantly reduced ability to induce TNF-α production.
+Our findings support the possibility that the PLP2 DUB activity, but not cis-cleavage activity, is essential for PRRSV replication.
+The data also establish a strong link of nsp2 to pro-inflammatory cytokine induction during infection that operates in a manner independent of PLP2 DUB activity.
+The present study aimed to evaluate the mechanisms of inhibiting lipid accumulation in free fatty acid (FFA)-treated HepG2 cells caused by bark and fruit extracts of Toona sinensis (TSB and TSF).
+TSB and/or TSF promoted phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-coA carboxylase and peroxisome proliferator-activated receptor alpha upregulation.
+Furthermore, TSB and TSF suppressed FFA-induced liver X receptor, sterol regulatory element-binding transcription protein 1, fatty acid synthase, and stearoyl-CoA desaturase 1 protein expression.
+Moreover, TSB and/or TSF induced phosphorylation of Unc-51 like autophagy-activating kinase and microtubule-associated protein 1A/1B-light chain 3 expressions.
+Therefore, TSB and TSF relieve lipid accumulation by attenuating lipogenic protein expression, activating the AMPK pathway, and upregulating the autophagic flux to enhance lipid metabolism.
+Moreover, TSB and TSF reduced TG contents, implying the therapeutic use of TSB and TSF in NAFLD.
+In recent years, affective computing has been actively researched to provide a higher level of emotion-awareness.
+Among a myriad of target emotions, boredom, in particular, has been suggested to cause not only medical issues but also challenges in various facets of daily life.
+However, to the best of our knowledge, no previous studies have used electroencephalography (EEG) and galvanic skin response (GSR) together for boredom classification, although these data have potential features for emotion classification.
+To investigate the combined effect of these features on boredom classification, we collected EEG and GSR data from 28 participants using off-the-shelf sensors.
+During data acquisition, we used a set of stimuli comprising a video clip designed to elicit boredom and two other video clips of entertaining content.
+The collected samples were labeled based on the participants’ questionnaire-based testimonies on experienced boredom levels.
+Using the collected data, we initially trained 30 models with 19 machine learning algorithms and selected the top three candidate classifiers.
+After tuning the hyperparameters, we validated the final models through 1000 iterations of 10-fold cross validation to increase the robustness of the test results.
+Our results indicated that a Multilayer Perceptron model performed the best with a mean accuracy of 79.98% (AUC: 0.781).
+It also revealed the correlation between boredom and the combined features of EEG and GSR.
+These results can be useful for building accurate affective computing systems and understanding the physiological properties of boredom.
+This syndrome is well documented and characterized by attenuated function of innate and adaptive immune cells.
+Several pharmacological interventions aimed to restore the immune response are emerging of which interferon-gamma (IFNγ) is one.
+It is of paramount relevance to obtain clinical information on optimal timing of the IFNγ-treatment, −tolerance, −effectiveness and outcome before performing a RCT.
+We describe the effects of IFNγ in a cohort of 18 adult and 2 pediatric sepsis patients.
+METHODS: In this open-label prospective multi-center case-series, IFNγ treatment was initiated in patients selected on clinical and immunological criteria early (< 4 days) or late (> 7 days) following the onset of sepsis.
+The data collected in 18 adults and 2 liver transplanted pediatric patients were: clinical scores, monocyte expression of HLA-DR (flow cytometry), lymphocyte immune-phenotyping (flow cytometry), IL-6 and IL-10 plasma levels (ELISA), bacterial cultures, disease severity, and mortality.
+RESULTS: In 15 out of 18 patients IFNγ treatment was associated with an increase of median HLA-DR expression from 2666 [IQ 1547; 4991] to 12,451 [IQ 4166; 19,707], while the absolute number of lymphocyte subpopulations were not affected, except for the decrease number of NK cells 94.5 [23; 136] to 32.5 [13; 90.8] (0.0625)].
+Plasma levels of IL-6 464 [201–770] to 108 (89–140) ng/mL (p = 0.04) and IL-10 from IL-10 from 29 [12–59] to 9 [1–15] pg/mL decreased significantly.
+The other patients had a rapid clinical improvement assessed by the SOFA score and bacterial cultures that were repeatedly positive became negative.
+CONCLUSION: Guided by clinical and immunological monitoring, adjunctive immunotherapy with IFNγ appears well-tolerated in our cases and improves immune host defense in sepsis induced immuno suppression.
+Metabolomics aims to measure and characterise the complex composition of metabolites in a biological system.
+Metabolomics studies involve sophisticated analytical techniques such as mass spectrometry and nuclear magnetic resonance spectroscopy, and generate large amounts of high-dimensional and complex experimental data.
+Open source processing and analysis tools are of major interest in light of innovative, open and reproducible science.
+The scientific community has developed a wide range of open source software, providing freely available advanced processing and analysis approaches.
+The programming and statistics environment R has emerged as one of the most popular environments to process and analyse Metabolomics datasets.
+A major benefit of such an environment is the possibility of connecting different tools into more complex workflows.
+Combining reusable data processing R scripts with the experimental data thus allows for open, reproducible research.
+This review provides an extensive overview of existing packages in R for different steps in a typical computational metabolomics workflow, including data processing, biostatistics, metabolite annotation and identification, and biochemical network and pathway analysis.
+In total, this review summarises more than two hundred metabolomics specific packages primarily available on CRAN, Bioconductor and GitHub.
+Cynomolgus macaques (Macaca fascicularis, Mafa) have been used as important experimental animal models for carrying out biomedical researches.
+The results of biomedical experiments strongly depend on the immunogenetic background of animals, especially on the diversity of major histocompatibility complex (MHC) alleles.
+However, there is much less information available on the polymorphism of MHC class I genes in cynomolgus macaques, than is currently available for humans.
+In this study, we have identified 40 Mafa-A and 60 Mafa-B exons 2 and 3 sequences from 30 unrelated cynomolgus macaques of Vietnamese origin.
+As for the remaining 72 known alleles, 15 alleles are shared with other cynomolgus macaque populations and 32 are identical to alleles previously reported in other macaque species.
+In addition, the Mafa-A1 genes were found to be more diverse than human HLA-A and the functional residues for peptide binding sites (PBS) or TCR binding sites (TBS) in Mafa-A1 have greater variability than that for non-PBS or non-TBS regions.
+Overall, this study provides important information on the diversity of Mafa-A and Mafa-B alleles from Vietnamese origin, which may help researchers to choose the most appropriate animals for their studies.
+BACKGROUND: The Hindu Kush and Karakoram mountain ranges in Pakistan’s northern areas are a natural habitat of the snow leopard (Panthera uncia syn.
+Uncia uncia) but the ecological studies on this animal are scarce since it is human shy by nature and lives in difficult mountainous tracts.
+The pilot study is conducted to exploit the genetic diversity and population structure of the snow leopard in this selected natural habitat of the member of the wildcat family in Pakistan.
+METHOD: About 50 putative scat samples of snow leopard from five localities of Gilgit-Baltistan (Pakistan) along with a control sample of zoo maintained male snow leopard were collected for comparison.
+Significant quality and quantity of genomic DNA was extracted from scat samples using combined Zhang–phenol–chloroform method and successful amplification of cytochrome c oxidase I gene (190 bp) using mini-barcode primers, seven simple sequence repeats (SSR) markers and Y-linked AMELY gene (200 bp) was done.
+RESULTS: Cytochrome c oxidase I gene sequencing suggested that 33/50 (66%) scat samples were of snow leopard.
+AMELY primer suggested that out of 33 amplified samples, 21 (63.63%) scats were from male and 12 (36.36%) from female leopards.
+Through successful amplification of DNA of 25 out of 33 (75.75%) scat samples using SSR markers, a total of 68 alleles on seven SSR loci were identified, showing low heterozygosity, while high gene flow between population.
+DISCUSSION: The low gene flow rate among the population results in low genetic diversity causing decreased diversification.
+This affects the adaptability to climatic changes, thus ultimately resulting in decreased population size of the species.
+Lower respiratory tract infections (LRTIs) refer to the inflammation of the trachea, bronchi, bronchioles, and lung tissue.
+The prevalence of LRTIs in the elderly population is not only related to underlying diseases and aging itself, but also to a variety of clinical issues, such as history of hospitalization, previous antibacterial therapy, mechanical ventilation, antibiotic resistance.
+These factors mentioned above have led to an increase in the prevalence and mortality of LRTIs in the elderly, and new medical strategies targeting LRTIs in this population are urgently needed.
+After a systematic review of the current randomized controlled trials and related studies, we recommend novel pharmacotherapies that demonstrate advantages for the management of LRTIs in people over the age of 65.
+Strengths and limitations of these drugs were evaluated based on whether they have novelty of mechanism, favorable pharmacokinetic/pharmacodynamic profiles, avoidance of interactions and intolerance, simplicity of dosing, and their ability to cope with challenges which was mainly evaluated by the primary and secondary endpoints.
+The purpose of this review is to recommend the most promising antibiotics for treatment of LRTIs in the elderly (both in hospital and in the outpatient setting) based on the existing results of clinical studies with the novel antibiotics, and to briefly review current medications for respiratory communicable diseases in the elderly, aiming to a better management of LRTIs in clinical practice.
+Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) is the most important endemic pathogen in the U.S. swine industry.
+Despite control efforts involving improved biosecurity and different vaccination protocols, the virus continues to circulate and evolve.
+One of the foremost challenges in its control is high levels of genetic and antigenic diversity.
+Here, we quantify the co-circulation, emergence and sequential turnover of multiple PRRSV lineages in a single swine-producing region in the United States over a span of 9 years (2009–2017).
+By classifying over 4,000 PRRSV sequences (open-reading frame 5) into phylogenetic lineages and sub-lineages, we document the ongoing diversification and temporal dynamics of the PRRSV population, including the rapid emergence of a novel sub-lineage that appeared to be absent globally pre-2008.
+In addition, lineage 9 was the most prevalent lineage from 2009 to 2010, but its occurrence fell to 0.5% of all sequences identified per year after 2014, coinciding with the emergence or re-emergence of lineage 1 as the dominant lineage.
+The sequential dominance of different lineages, as well as three different sub-lineages within lineage 1, is consistent with the immune-mediated selection hypothesis for the sequential turnover in the dominant lineage.
+As host populations build immunity through natural infection or vaccination toward the most common variant, this dominant (sub-) lineage may be replaced by an emerging variant to which the population is more susceptible.
+An analysis of patterns of non- synonymous and synonymous mutations revealed evidence of positive selection on immunologically important regions of the genome, further supporting the potential that immune-mediated selection shapes the evolutionary and epidemiological dynamics for this virus.
+This has important implications for patterns of emergence and re-emergence of genetic variants of PRRSV that have negative impacts on the swine industry.
+Constant surveillance on PRRSV occurrence is crucial to a better understanding of the epidemiological and evolutionary dynamics of co-circulating viral lineages.
+Further studies utilizing whole genome sequencing and exploring the extent of cross-immunity between heterologous PRRS viruses could shed further light on PRRSV immunological response and aid in developing strategies that might be able to diminish disease impact.
+Background: The genus Orthobornavirus comprises non-segmented, negative-stranded RNA viruses able to infect humans, mammals, reptiles and various birds.
+Parrot bornavirus 1 to 8 (PaBV-1 to 8) causes neurological and/or gastrointestinal syndromes and death on psittacines.
+We aimed to identify and to produce epidemiologic knowledge about the etiologic agent associated with a death of two female Psittacus erithacus (grey parrot).
+The N and X proteins of PaBV-4 were more related to avian bornaviruses, while phosphoprotein was more related to variegated squirrel bornavirus 1 (VSBV-1).
+Within the P gene/phosphoprotein a highly conserved region between and within bornavirus species was found.
+Broad screening studies are required to help understanding the role of wild birds in the emergence and spread of pathogenic bornaviruses.
+PaBV-4 phosphoprotein is closer to VSBV-1 associated with lethal encephalitis in humans than with some of the avian bornaviruses.
+BACKGROUND: Infection by multidrug-resistant (MDR) pathogens leads to poor patient outcomes in intensive care units (ICUs).
+We studied the effects of ICU relocation on MDR respiratory pathogen detection rates and patient outcomes.
+Baseline patient characteristics, types of respiratory pathogens detected, antibiotics used, and patient outcomes were measured.
+RESULTS: A total of 463 adult patients admitted to the ICU, 4 months before and after the relocation, were included.
+Baseline characteristics, including age, sex, and underlying comorbidities, did not differ between the two groups.
+After the relocation, the incidence rate of MDR respiratory pathogen detection decreased from 90.0 to 68.8 cases per 1,000 patient-days, but that difference was statistically insignificant.
+The use of colistin was significantly reduced from 53.5 days (95% confidence interval [CI], 20.3 to 86.7 days) to 18.7 days (95% CI, 5.6 to 31.7 days).
+Furthermore, the duration of hospital stay was significantly reduced from a median of 29 days (interquartile range [IQR], 14 to 50 days) to 21 days (IQR, 11 to 39 days).
+CONCLUSIONS: Incidence rates of MDR respiratory pathogen detection were not significantly different before and after ICU relocation.
+However, ICU relocation could be helpful in reducing the use of antibiotics against MDR pathogens and improving patient outcomes.
+AIM: Evaluation of the thermal and physical conditions for inactivation of adenovirus (AdV), porcine sapelovirus 1 (PSV1) and the economically important viruses porcine epidemic diarrhoea virus (PEDV) and porcine circovirus 2 (PCV2) in the production of spray‐dried porcine plasma (SDPP).
+METHODS AND RESULTS: Citrate‐treated porcine plasma of pH 7·5, 9·8 and 10·2 (8·5% dry‐matter) was spiked with PEDV, PSV1, PCV2 and AdV and incubated at 3°C for maximum 24 h, and at 44 or 48°C for maximum 10 min (Experiment 1).
+Spiked citrate‐treated concentrated plasma of pH 7·5 and 9·8 (24% dry‐matter) was spray dried in a laboratory scale apparatus (Experiment 2).
+Aliquots of SDPP were stored over a period of 0–10 weeks at 11 and 20°C (Experiment 3).
+Reverse transcription(RT)‐quantitative PCR detected no notable reduction in viral genomes in treated plasma and SDPP samples.
+At pH 10·2 and 3°C, infectivity of PEDV in plasma was reduced with a reduction factor of 4·2 log 10 (LRF) at 10 h contact time, whereas heating to 44°C for at least 1 min at alkali pH was needed to achieve a LRF of 4·2 for AdV.
+Spray drying at an outlet temperature of 80°C reduced AdV infectivity effectively (LRF = 5·2) and PEDV infectivity for 95% (LRF = 1·4).
+After storage at 20°C for 2 weeks no infectious PEDV was re‐isolated from SDPP anymore (LRF ≥4·0).
+Due to growth of antibiotic‐resistant bacteria from plasma in cell cultures used for PCV2 isolation, no data regarding inactivation of PCV2 were obtained.
+Spray drying in combination with storage for ≥2 weeks at 20°C eliminated infectivity of PEDV effectively.
+SIGNIFICANCE AND IMPACT OF THE STUDY: The conditions for inactivation of virus in plasma and SDPP determined are important for producers to inactivate PEDV during production of SDPP.
+For more than 50 years there has been an ongoing effort to combat transfusion‐transmitted infections and provide patients with the safest possible blood.
+Initial methods included screening donors for travel histories to banned areas and for high‐risk behaviors, but pathogen‐specific assays performed at the collection and manufacturing sites also have become key factors in assuring blood safety.
+Many of these have focused on donor and laboratory‐based screening for transfusion‐transmitted diseases, as evidenced by the hepatitis and human immunodeficiency virus screening in the 1970s, 1980s, and 1990s.
+More recently, this effort has expanded to develop donor screening assays to identify other blood‐borne pathogens, such as Zika and West Nile viruses and Babesia.
+In recent years, the Food and Drug Administration has approved rapid tests to identify bacterially contaminated PLT units in the blood bank before transfusion.
+Other supplemental methods have been developed, however, that aim to inactivate blood‐borne pathogen(s) present in the blood product, rather than to rely on our ability to identify and interdict contaminated and infected components.
+Pathogen reduction technology, as this is referred to, provides a proactive way to further reduce the risk posed by transfusion‐transmitted infections.
+In this work, we study the environmental and operational factors that influence airborne transmission of nosocomial infections.
+We link a deterministic zonal ventilation model for the airborne distribution of infectious material in a hospital ward, with a Markovian multicompartment SIS model for the infection of individuals within this ward, in order to conduct a parametric study on ventilation rates and their effect on the epidemic dynamics.
+Our stochastic model includes arrival and discharge of patients, as well as the detection of the outbreak by screening events or due to symptoms being shown by infective patients.
+For each ventilation setting, we measure the infectious potential of a nosocomial outbreak in the hospital ward by means of a summary statistic: the number of infections occurred within the hospital ward until end or declaration of the outbreak.
+We analytically compute the distribution of this summary statistic, and carry out local and global sensitivity analysis in order to identify the particular characteristics of each ventilation regime with the largest impact on the epidemic spread.
+Our results show that ward ventilation can have a significant impact on the infection spread, especially under slow detection scenarios or in overoccupied wards, and that decreasing the infection risk for the whole hospital ward might increase the risk in specific areas of the health‐care facility.
+Moreover, the location of the initial infective individual and the protocol in place for outbreak declaration both form an interplay with ventilation of the ward.
+Transmissible gastroenteritis (TGE), caused by transmissible gastroenteritis virus (TGEV), is one many gastrointestinal inflections in piglets, characterized by diarrhea, and high mortality.
+Probiotics are ubiquitous bacteria in animal intestines, which have many functions, such as promoting intestinal peristalsis and maintaining the intestinal balance.
+We found that the supernatant of the Lp-1 strain of Lactobacillus plantarum, isolated in our laboratory, and named Lp-1s had marked anti-TGEV effect on IPEC-J2 cells.
+Lp-1s could induce large amounts of interferon-β in IPEC-J2 cells in the early stage (6 h) of infection with TGEV, and increased the level of phosphorylated signal transducer and activator of transcription and its nuclear translocation in the late stage (24–48 h) of infection.
+This resulted in upregulated expression of interferon-stimulated genes, and increased the transcription and protein expression of antiviral proteins, resulting in an anti-TGEV effect.
+STUDY DESIGN: We collected a NP swab on children aged 2–12 years with acute sinusitis and processed it for bacterial culture, viruses, cytokine expression, and 16S ribosomal RNA gene sequencing analysis.
+During the course of the study, we expand the scope of evaluation to include RNA sequencing, which we accomplished by cutting the tip of the swab.
+RESULTS: Of the 174 children enrolled, 126 (72.4%) had a positive bacterial culture and 121(69.5%) tested positive for a virus.
+Cytokine measurement, as judged by the adequate levels of a housekeeping enzyme (GAPDH), appeared successful.
+From the samples used for 16S ribosomal sequencing we recovered, on average, 16,000 sequences per sample, accounting for a total of 2,646 operational taxonomic units across all samples sequenced.
+Cutting the tip of the swab did not affect the recovery yield for viruses or bacteria, nor did it affect species richness in microbiome analysis.
+CONCLUSION: We describe a minimally invasive sample collection protocol that allows for multiple diagnostic and research investigations in young children.
+Glucose-6-phosphate dehydrogenase (G6PD) is the rate-limiting enzyme of the pentose phosphate pathway that modulates cellular redox homeostasis via the regeneration of NADPH.
+G6PD-deficient cells have a reduced ability to induce the innate immune response, thus increasing host susceptibility to pathogen infections.
+G6PD-deficient peripheral blood mononuclear cells (PBMCs) from patients and human monocytic (THP-1) cells were used as models to investigate whether G6PD modulates inflammasome activation.
+A decreased expression of IL-1β was observed in both G6PD-deficient PBMCs and PMA-primed G6PD-knockdown (G6PD-kd) THP-1 cells upon lipopolysaccharide (LPS)/adenosine triphosphate (ATP) or LPS/nigericin stimulation.
+The pro-IL-1β expression of THP-1 cells was decreased by G6PD knockdown at the transcriptional and translational levels in an investigation of the expression of the inflammasome subunits.
+The phosphorylation of p38 MAPK and downstream c-Fos expression were decreased upon G6PD knockdown, accompanied by decreased AP-1 translocation into the nucleus.
+Impaired inflammasome activation in G6PD-kd THP-1 cells was mediated by a decrease in the production of reactive oxygen species (ROS) by NOX signaling, while treatment with hydrogen peroxide (H(2)O(2)) enhanced inflammasome activation in G6PD-kd THP-1 cells.
+G6PD knockdown decreased Staphylococcus aureus and Escherichia coli clearance in G6PD-kd THP-1 cells and G6PD-deficient PBMCs following inflammasome activation.
+These findings support the notion that enhanced pathogen susceptibility in G6PD deficiency is, in part, due to an altered redox signaling, which adversely affects inflammasome activation and the bactericidal response.
+The glycoprotein (GP) of LASV mediates viral entry into host cells, and correct processing and modification of GP by host factors is a prerequisite for virus replication.
+Here, using an affinity purification-coupled mass spectrometry (AP-MS) strategy, 591 host proteins were identified as interactors of LASV GP.
+Gene ontology analysis was performed to functionally annotate these proteins, and the oligosaccharyltransferase (OST) complex was highly enriched.
+Functional studies conducted by using CRISPR-Cas9-mediated knockouts showed that STT3A and STT3B, the two catalytically active isoforms of the OST complex, are essential for the propagation of the recombinant arenavirus rLCMV/LASV glycoprotein precursor, mainly via affecting virus infectivity.
+Knockout of STT3B, but not STT3A, caused hypoglycosylation of LASV GP, indicating a preferential requirement of LASV for the STT3B-OST isoform.
+Furthermore, double knockout of magnesium transporter 1 (MAGT1) and tumor suppressor candidate 3 (TUSC3), two specific subunits of STT3B-OST, also caused hypoglycosylation of LASV GP and affected virus propagation.
+Site-directed mutagenesis analysis revealed that the oxidoreductase CXXC active-site motif of MAGT1 or TUSC3 is essential for the glycosylation of LASV GP.
+The STT3B-dependent N-glycosylation of GP is conserved among other arenaviruses, including both the Old World and New World groups.
+Our study provided a systematic view of LASV GP-host interactions and revealed the preferential requirement of STT3B for LASV GP N-glycosylation.
+IMPORTANCE Glycoproteins play vital roles in the arenavirus life cycle by facilitating virus entry and participating in the virus budding process.
+N-glycosylation of GPs is responsible for their proper functioning; however, little is known about the host factors on which the virus depends for this process.
+In this study, a comprehensive LASV GP interactome was characterized, and further study revealed that STT3B-dependent N-glycosylation was preferentially required by arenavirus GPs and critical for virus infectivity.
+The two specific thioredoxin subunits of STT3B-OST MAGT1 and TUSC3 were found to be essential for the N-glycosylation of viral GP.
+Our study provides new insights into LASV GP-host interactions and extends the potential targets for the development of novel therapeutics against Lassa fever in the future.
+Zika virus (ZIKV) infection during human pregnancy may lead to severe fetal pathology and debilitating impairments in offspring.
+Inoculation resulted in trans-fetal virus spread and persistent infection in the placenta and fetal membranes for two months.
+Offspring did not show congenital Zika syndrome (e.g., microcephaly, brain calcifications, congenital clubfoot, arthrogryposis, seizures) or other visible birth defects.
+However, a month after birth, a portion of offspring exhibited excessive interferon alpha (IFN-α) levels in blood plasma in a regular environment.
+Most affected offspring also showed dramatic IFN-α shutdown during social stress providing the first evidence for the cumulative impact of prenatal ZIKV exposure and postnatal environmental insult.
+Other eleven cytokines tested before and after stress were not altered suggesting the specific IFN-α pathology.
+While brains from offspring did not have histopathology, lesions, and ZIKV, the whole genome expression analysis of the prefrontal cortex revealed profound sex-specific transcriptional changes that most probably was the result of subclinical in utero infection.
+RNA-seq analysis in the placenta persistently infected with ZIKV provided independent support for the sex-specific pattern of in utero-acquired transcriptional responses.
+Collectively, our results provide strong evidence that two hallmarks of fetal ZIKV infection, altered type I IFN response and molecular brain pathology can persist after birth in offspring in the absence of congenital Zika syndrome.
+Since the progression of cirrhosis is accelerated each time a complication recurs, the management and treatment of the complication is critical in enhancement of the quality of life and expectation of life in patients.
+The use of model for end-stage liver disease with incorporation of serum-sodium (MELD-Na) with physiological indicators can be used to assess severity and differentiate therapeutic interventions.
+This study is aimed to determine the mean survival period and cumulative survival rate by classifying patients into high-risk and low-risk groups based on MELD-Na, a predictor of mortality in liver disease, and to investigate the mortality prognostic factors.
+263 patients who were diagnosed with liver cirrhosis complications for the first time and hospitalized were selected as the subjects of this study.
+The collected data were analyzed based on the survival package provided by the statistical program R version 3.4.2.
+Subjects were classified into high-risk and low-risk groups using MELD-Na 14 points where sensitivity and specificity crossed the cut-off point.
+Gender, age, and primary caregiver were significant variables in the mortality high-risk group, and AST, albumin, and primary caregiver were significant variables in the mortality low-risk group.
+Based on these mortality prognostic factors, it is possible to present the factors affecting mortality in patients who were diagnosed with liver cirrhosis complications for the first time.
+The classification of patients by risk level could be the foundation to provide accurate guidelines for management and it is necessary to modify prognostic factors and apply nursing interventions to manage complications.
+Wounded skin is one of the preferred niches for Pseudomonas aeruginosa, which has developed diverse strategies to impair tissue repair processes and promote infection.
+Here, we analyse the effect of the P. aeruginosa fucose-binding lectin LecB on human keratinocytes and demonstrate that it triggers events in the host, upon binding to fucosylated residues on cell membrane receptors, which extend beyond its role as an adhesion molecule.
+We found that LecB associates with insulin-like growth factor-1 receptor and dampens its signalling, leading to the arrest of cell cycle.
+In addition, we describe a novel LecB-triggered mechanism to down-regulate host cell receptors by showing that LecB leads to insulin-like growth factor-1 receptor internalisation and subsequent missorting towards intracellular endosomal compartments, without receptor activation.
+Overall, these data highlight that LecB is a multitask virulence factor that, through subversion of several host pathways, has a profound impact on keratinocyte proliferation and survival.
+PURPOSE: This study evaluated the specificity of different avian secondary antibodies used in Western blot and dot-blot ELISA to detect avian bornavirus antibodies in bird plasma.
+METHODS: Plasma samples were collected from: two Blue and gold macaws, one positive and one negative for avian bornavirus by RT-PCR; a Cockatiel and a Monk parakeet prior to and following experimental infection; and, two Mallards, one positive and one negative for avian bornavirus by RT-PCR Samples were analyzed by Western blot and dot-blot ELISA that incorporated recombinant avian bornavirus nucleoprotein as the target analyte.
+Four species-specific anti-IgY secondary antibodies were used in the assays: goat anti-macaw IgY, goat anti-bird IgY, goat anti-duck IgY, and rabbit anti-chicken IgY.
+RESULTS: In the Western blot, anti-macaw IgY secondary antibody produced strong signals with Blue and gold macaw and Cockatiel positive plasma, but no signal with Mallard positive plasma.
+Anti-bird IgY secondary antibody produced strong signals with Blue and gold macaw, Cockatiel, and Mallard positive plasma.
+Anti-duck and anti-chicken IgY secondary antibody produced a strong and moderate signal, respectively, only with Mallard positive plasma.
+In the dot-blot ELISA, there was a distinct and significant difference (P<0.05) in the signal intensity between the different secondary antibodies within a bird species.
+Anti-macaw IgY secondary antibody produced significantly (P<0.05) stronger signals than the other secondary antibodies in Blue and gold macaw, Cockatiel, and Monk parakeet positive plasma, while anti-duck IgY secondary antibody produced significantly (P<0.05) stronger signals than the other secondary antibodies in Mallard positive plasma.
+CONCLUSION: In testing psittacines with immunoassays, and especially in assays that incorporate short incubation reaction times such as a dot-blot ELISA, species-specific anti-IgY secondary antibodies provided more accurate results.
+Viral encephalitis is a rare but clinically serious consequence of viral invasion of the brain and insight into its pathogenesis is urgently needed.
+Important research questions concern the involvement of the host innate immune response in pathogenesis, key to which is the role played by microglia, resident macrophages of the brain parenchyma.
+Do microglia have a protective function, by coordinating the innate immune response to viral infection, or do they drive pathogenic neuroinflammation?
+Here we synthesize recent data from mouse models of acute viral encephalitis, which reveal an unambiguously protective role for microglia.
+Depletion of microglia, via blockade of colony-stimulating factor 1 receptor (CSF1R) signaling, led to increased viral replication accompanied by more severe neurological disease and heightened mortality.
+Whilst the underlying mechanism(s) remain to be defined, microglial interactions with T cells and phagocytosis of infected neurones appear to play a role.
+Paradoxically, the production of inflammatory cytokines was increased in several instances following viral infection in microglia-depleted brains, suggesting that: (i) cells other than microglia mediate inflammatory responses and/or (ii) microglia may exert a regulatory function.
+Under certain circumstances the microglial antiviral response might contribute negatively to longer-term neurological sequelae, although fewer studies have focused on this aspect in encephalitis models.
+Understanding regulation of the microglial response, and how it contributes to disease is therefore a priority for future studies.
+Collectively, these findings demonstrate the central role of microglia in pathogenesis, suggesting the exciting possibility that defects of microglial function might contribute to encephalitis susceptibility and/or outcome in humans.
+Artificial blood is an innovative concept of transfusion medicine where specifically designed compounds perform the task of transport and delivery of oxygen in the body to replace this function of allogenic human blood transfusion.
+Several molecules have been developed in the past few decades to achieve this objective and continous refinements are being continuously made in the quest of the ideal blood substitute.
+Currently, available technology manufactures artificial blood from haemoglobin obtained from outdated human/bovine blood (Haemoglobin Based Oxygen Carriers) or utilizing Perfluorocarbons.
+These synthetic blood substitutes are advantageous in that they do not require compatibility testing, are free from blood borne infections, have prolonged shelf life and do not require refrigeration.
+Artificial blood is projected to have a significant impact on the development of medical care in the future.
+It can complement the current blood products for transfusion and create a stable supply of safe and effective products.
+It is likely to reduce the requirements of blood transfusions drastically especially in settings of trauma and surgery thereby reducing the reliance on banked donated blood.
+IMPORTANCE: Measles cases and outbreaks continue to occur in the United States after the introduction of measles from endemic settings.
+OBJECTIVE: To discern the factors associated with measles transmission in the United States after measles had been eliminated.
+DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study was conducted from January 1, 2001, to December 31, 2017, in the United States among US residents and international visitors with confirmed measles.
+A maximum likelihood algorithm that uses the observed dates of rash onset and the known distribution of the serial interval (time between symptom onset in related consecutive cases) was applied to outbreak notification data to estimate the effective reproduction number (R), or the mean number of new infections generated per case.
+Transmissibility was assessed by comparing R based on the characteristics of primary and secondary cases of measles.
+MAIN OUTCOMES AND MEASURES: Effective reproduction number (R), or the mean number of successful transmission events per case of measles (ie, the mean number of persons to whom each patient with measles spreads measles).
+RESULTS: A total of 2218 individuals with confirmed measles cases (1025 female, 1176 male, and 17 sex not reported; median age, 15 years [range, 0-89 years]) reported from 2001 to 2017 were evaluated.
+Among patients who received no doses of measles vaccine, R was 0.76 (95% CI, 0.71-0.81); among patients who received 1 dose of measles vaccine, R was 0.17 (95% CI, 0.11-0.26); among patients who received 2 doses or more of measles vaccine, R was 0.27 (95% CI, 0.17-0.39); and among patients with unknown vaccination status, R was 0.52 (95% CI, 0.44-0.60).
+Among patients born before 1957, R was 0.35 (95% CI, 0.20-0.58), and among those born on or after 1957, R was 0.64 (95% CI, 0.61-0.68).
+R was higher when primary and secondary cases of measles were patients aged 5 to 17 years (0.36 [95% CI, 0.31-0.42]) compared with assortative transmission in other age groups (<1 year, 0.14 [95% CI, 0.10-0.20]; 1-4 years, 0.25 [95% CI, 0.20-0.30]; 18-29 years, 0.19 [95% CI, 0.15-0.24]; 30-49 years, 0.15 [95% CI, 0.11-0.20]; ≥50 years, 0.04 [95% CI, 0.01-0.10]).
+CONCLUSIONS AND RELEVANCE: The findings of this study support having high targets for 2-dose measles vaccine coverage, particularly among school-aged children in the United States.
+Human viral hepatitis, a major cause of morbidity and mortality worldwide, is caused by highly diverse viruses with different genetic, ecological, and pathogenetic features.
+Technological advances that allow throughput sequencing of viral genomes, as well as the development of computational tools to analyze such genome data, have largely expanded our knowledge on the host range and evolutionary history of human hepatitis viruses.
+Thus, with the exclusion of hepatitis D virus, close or distant relatives of these human pathogens were identified in a number of domestic and wild mammals.
+Also, sequences of human viral strains isolated from different geographic locations and over different time-spans have allowed the application of phylogeographic and molecular dating approaches to large viral phylogenies.
+In this review, we summarize the most recent insights into our understanding of the evolutionary events and ecological contexts that determined the origin and spread of human hepatitis viruses.
+Therefore, the aim of this study is to evaluate the global scientific output of research of aflatoxin by using bibliometric techniques.
+METHODS: This bibliometric study was conducted using Scopus database and classified the retrieved publications were classified from different aspects, including the countries/region of focus, journals, authors, institutes, citations, and content analysis to discover any hot and emerging topics.
+In addition, the bibliometric analysis of the international collaborative network and hot research topics were generated by VOSviewer© software version 1.6.10.
+RESULTS: The search engine of the Scopus database found 9845 documents published in the field of aflatoxin.
+The USA is the top publishing source in the world (22.85%), followed by China (11.85%), India (9.32%), and Italy (5.25%).
+In earlier years, researchers focused on terms related to the topics of “sources and biosynthesis of aflatoxin”, “health effects by aflatoxin”, and “detoxification and treatment of aflatoxin”.
+However, in recent years, researchers pay more attention to the topic of detection and quantification of aflatoxin.
+CONCLUSIONS: The quantity of research in global aflatoxin has substantially increased over the past two decades.
+The evaluation of the historical status and development trend in aflatoxin scientific research can guide future research, and ultimately provide the basis for improving management procedures for governmental decisions, healthcare, industries, and educational institutions.
+BACKGROUND: There is little descriptive data on Stenotrophomonas maltophilia hospital-acquired pneumonia (HAP) in critically ill patients.
+Our objective was to describe the epidemiology and prognostic factors associated with S. maltophilia pneumonia, focusing on antimicrobial therapy.
+METHODS: This nationwide retrospective study included all patients admitted to 25 French mixed intensive care units between 2012 and 2017 with hospital-acquired S. maltophilia HAP during intensive care unit stay.
+Secondary endpoints included microbiologic effectiveness and antimicrobial therapeutic modalities such as delay to appropriate antimicrobial treatment, mono versus combination therapy, and duration of antimicrobial therapy.
+RESULTS: Of the 282 patients included, 84% were intubated at S. maltophilia HAP diagnosis for duration of 11 [5–18] days.
+The Simplified Acute Physiology Score II was 47 [36–63], and the in-hospital mortality was 49.7%.
+Empirical antimicrobial therapy was considered effective on S. maltophilia according to susceptibility patterns in only 30% of cases.
+Survival analysis did not show any benefit from combination antimicrobial therapy (HR = 1.27, 95%CI [0.88; 1.83], p = 0.20) or prolonged antimicrobial therapy for more than 7 days (HR = 1.06, 95%CI [0.6; 1.86], p = 0.84).
+No differences were noted in in-hospital death irrespective of an appropriate and timely empiric antimicrobial therapy between mono- versus polymicrobial S. maltophilia HAP (p = 0.273).
+The duration of ventilation prior to S. maltophilia HAP diagnosis and ICU length of stay were shorter in patients with monomicrobial S. maltophilia HAP (p = 0.031 and p = 0.034 respectively).
+CONCLUSIONS: S. maltophilia HAP occurred in severe, long-stay intensive care patients who mainly required prolonged invasive ventilation.
+Empirical antimicrobial therapy was barely effective while antimicrobial treatment modalities had no significant impact on hospital survival.
+Viral late domains are used by many viruses to recruit the cellular endosomal sorting complex required for transport (ESCRT) to mediate membrane scission during viral budding.
+Unlike the P(S/T)AP and YPX((1–3))L late domains, which interact directly with the ESCRT proteins Tsg101 and ALIX, the molecular linkage connecting the PPXY late domain to ESCRT proteins is unclear.
+The mammarenavirus lymphocytic choriomeningitis virus (LCMV) matrix protein, Z, contains only one late domain, PPXY.
+We previously found that this domain in LCMV Z, as well as the ESCRT pathway, are required for the release of defective interfering (DI) particles but not infectious virus.
+To better understand the molecular mechanism of ESCRT recruitment by the PPXY late domain, affinity purification-mass spectrometry was used to identify host proteins that interact with the Z proteins of the Old World mammarenaviruses LCMV and Lassa virus.
+Several Nedd4 family E3 ubiquitin ligases interact with these matrix proteins and in the case of LCMV Z, the interaction was PPXY-dependent.
+We demonstrated that these ligases directly ubiquitinate LCMV Z and mapped the specific lysine residues modified.
+A recombinant LCMV containing a Z that cannot be ubiquitinated maintained its ability to produce both infectious virus and DI particles, suggesting that direct ubiquitination of LCMV Z alone is insufficient for recruiting ESCRT proteins to mediate virus release.
+However, Nedd4 ligases appear to be important for DI particle release suggesting that ubiquitination of targets other than the Z protein itself is required for efficient viral ESCRT recruitment.
+The correlation between charting statistics or regions could be considerably important in monitoring the states of multiple outcomes or regions.
+In this paper, we propose a new nonparametric strategy for multivariate process monitoring when the distribution of a process variable is unknown.
+We discuss the EWMA control chart based on rank methods for a multivariate process, and the approach is completely nonparametric.
+A simulation study demonstrates that the proposed method is efficient in detecting shifts for multivariate processes.
+A real Japanese influenza data example is given to illustrate the performance of the proposed method.
+Newcastle disease virus (NDV) causes severe infectious disease in poultry and selectively kills tumor cells, by inducing apoptosis and cytokines secretion.
+In this report, we study the mechanisms underlying NDV-induced apoptosis by investigating the unfolded protein response (UPR).
+We found that NDV infection activated all three branches of the UPR signaling (PERK-eIF2α, ATF6, and IRE1α) and triggered apoptosis, in avian cells (DF-1 and CEF) and in various human cancer cell types (HeLa, Cal27, HN13, A549, H1299, Huh7, and HepG2).
+Further study revealed that activation of PERK-eIF2α induced the expression of transcription factor CHOP, which subsequently promoted apoptosis by downregulating BCL-2/MCL-1, promoting JNK signaling and suppressing AKT signaling.
+In parallel, IRE1α mediated the splicing of XBP1 mRNA and resulted in the translation and nuclear translocation of XBP1s, thereby promoting the transcription of ER chaperones and components of ER-associated degradation (ERAD).
+Knock down and overexpression studies showed that CHOP, IRE1α, XBP1, and JNK supported efficient virus proliferation.
+Our study demonstrates that the induction of eIF2α-CHOP-BCL-2/JNK and IRE1α-XBP1/JNK signaling cascades promote apoptosis and cytokines secretion, and these signaling cascades support NDV proliferation.
+Here, we map the endogenous in vivo ISGylome in the liver following Listeria monocytogenes infection by combining murine models of reduced or enhanced ISGylation with quantitative proteomics.
+Our method identifies 930 ISG15 sites in 434 proteins and also detects changes in the host ubiquitylome.
+The ISGylated targets are enriched in proteins which alter cellular metabolic processes, including upstream modulators of the catabolic and antibacterial pathway of autophagy.
+Computational analysis of substrate structures reveals that a number of ISG15 modifications occur at catalytic sites or dimerization interfaces of enzymes.
+Finally, we demonstrate that animals and cells with enhanced ISGylation have increased basal and infection-induced autophagy through the modification of mTOR, WIPI2, AMBRA1, and RAB7.
+Taken together, these findings ascribe a role of ISGylation to temporally reprogram organismal metabolism following infection through direct modification of a subset of enzymes in the liver.
+Socio-economic factors are widely believed to have been an important driver of the transmission of Ebola Virus Disease (EVD) during the West African outbreak of 2014–16, however, studies that have investigated the relationship between socio-economic status (SES) and EVD have found inconsistent results.
+Using nationally representative household survey data on whether respondents knew a close friend or family member with Ebola, we explore the SES determinants of EVD exposure along individual, household, and community lines in Liberia and Sierra Leone.
+While we find no overall association between household wealth and EVD exposure, we find that pooled data mask important differences observed within countries with higher wealth households more likely to have been exposed to EVD in Sierra Leone and the opposite relationship in Liberia.
+Finally, we also generally find a positive association between education and EVD exposure both at the individual and the community levels in the full sample.
+There is an urgent need to better understand these relationships to examine both why the outbreak spread and to help prepare for future outbreaks.
+BACKGROUND: Pneumocystis jirovecii pneumonia (PJP) remains a severe disease associated with high rates of invasive mechanical ventilation (MV) and mortality.
+The objectives of this study were to assess early risk factors for severe PJP and 90-day mortality, including the broncho-alveolar lavage fluid cytology profiles at diagnosis.
+METHODS: We prospectively enrolled all patients meeting pre-defined diagnostic criteria for PJP admitted at Nantes university hospital, France, from January 2012 to January 2017.
+Diagnostic criteria for PJP were typical clinical features with microbiological confirmation of P. jirovecii cysts by direct examination or a positive specific quantitative real-time polymerase chain reaction (PCR) assay.
+Severe PJP was defined as hypoxemic acute respiratory failure requiring high-flow nasal oxygen with at least 50% FiO(2), non-invasive ventilation, or MV.
+RESULTS: Of 2446 respiratory samples investigated during the study period, 514 from 430 patients were positive for P. jirovecii.
+Of these 430 patients, 107 met criteria for PJP and were included in the study, 53 (49.5%) patients had severe PJP, including 30 who required MV.
+All patients were immunocompromised with haematological malignancy ranking first (n = 37, 35%), followed by solid organ transplantation (n = 27, 25%), HIV-infection (n = 21, 20%), systemic diseases (n = 13, 12%), solid tumors (n = 12, 11%) and primary immunodeficiency (n = 6, 8%).
+By multivariate analysis, factors independently associated with severity were older age (OR, 3.36; 95% CI 1.4–8.5; p < 0.05), a P. jirovecii microscopy-positive result from bronchoalveolar lavage (BAL) (OR, 1.3; 95% CI 1.54–9.3; p < 0.05); and absence of a BAL fluid alveolitis profile (OR, 3.2; 95% CI 1.27–8.8; p < 0.04).
+Factors independently associated with 90-day mortality were worse SOFA score on day 1 (OR, 1.05; 95% CI 1.02–1.09; p < 0.001) whereas alveolitis at BAL was protective (OR, 0.79; 95% CI 0.65–0.96; p < 0.05).
+In the subgroup of HIV-negative patients, similar findings were obtained, then viral co-infection were independently associated with higher 90-day mortality (OR, 1.25; 95% CI 1.02–1.55; p < 0.05).
+CONCLUSIONS: Older age and P. jirovecii oocysts at microscopic examination of BAL were independently associated with severe PJP.
+Both initial PJP severity as evaluated by the SOFA score and viral co-infection predicted 90-day mortality.
+[Image: see text] Recombinase polymerase amplification (RPA) is an isothermal DNA amplification method with broad applications as a point-of-care test and in molecular biology techniques.
+Because RPA has the advantage of amplifying DNA under isothermal conditions, we utilized RPA as a DNA library amplification tool.
+In this study, we used a sheared genomic DNA library and an oligonucleotide (oligo) library for the comparison of polymerase chain reaction and RPA.
+Thus, to amplify the size-variable DNA library uniformly, we introduced a linear amplification strategy with RPA and successfully improved the uniformity.
+On the other hand, using the same-sized oligo library, we confirmed that RPA amplified this library uniformly without modification of the protocol.
+These results demonstrate that RPA can be applied not only to amplify a specific target as previously demonstrated but also to amplify a complex DNA library composed of a large number of different DNA molecules.
+However, there is no clear evident on the effect of the regulation of ER stress and mitochondrial function by Angiotensin-converting enzyme 2 (ACE2) on the prevention of intramuscular fat metabolism.
+We investigated the effects of ACE2 on ER stress and mitochondrial function in skeletal muscle lipid metabolism.
+METHODS: The triglyceride (TG) content in skeletal muscle of ACE2 knockout mice and Ad-ACE2-treated db/db mice were detected by assay kits.
+Meanwhile, the expression of lipogenic genes (ACCα, SREBP-1c, LXRα, CPT-1α, PGC-1α and PPARα), ER stress and mitochondrial function related genes (GRP78, eIF2α, ATF4, BCL-2, and SDH6) were analyzed by RT-PCR.
+Lipid metabolism, ER stress and mitochondrial function related genes were analyzed by RT-PCR in ACE2-overexpression C2C12 cell.
+Moreover, the IKKβ/NFκB/IRS-1 pathway was determined using lysate sample from skeletal muscle of ACE2 knockout mice.
+The ACE2 knockout mice displayed an elevated level of ER stress and mitochondrial dysfunctions in skeletal muscle.
+In contrast, activation of ACE2 can ameliorate ER stress and mitochondrial function, which slightly accompanied by reduced TG content and down-regulated the expression of skeletal muscle lipogenic proteins in the db/db mice.
+Additionally, ACE2 improved skeletal muscle lipid metabolism and ER stress genes in the C2C12 cells.
+CONCLUSIONS: ACE2 was first reported to play a notable role on intramuscular fat regulation by improving endoplasmic reticulum and mitochondrial function.
+Host immune response may be involved in the pathogenesis of children Mycoplasma pneumoniae pneumonia (MPP).
+In the current study, we investigated the alterations of cytokines levels among control, mild MPP and severe MPP children to determine whether cytokine signatures associate with MPP and correlate with disease severity.
+We measured 13 cytokines in bronchoalveolar lavage fluid (BALF) of 88 children with MPP and 26 children with foreign body aspiration (FB) using a Luminex system.
+Linear discriminant analyses were performed to develop predictive models of mild MPP and severe MPP on these children.
+We observed nearly complete separations of severe MPP group, mild MPP group and control group in linear discriminant analyses.
+Eleven cytokines significantly increased in children with MPP, and seven cytokines had statistically significant upward linear trends correlated with MPP severity.
+In addition, compared to control group, both IFNγ/IL4 ratio and IFNγ/IL13 ratio increased in mild MPP and severe MPP groups.
+Our results suggest that children MPP can alter BALF cytokines signatures which associate with disease severity and can be characterized by a distinct airway molecular phenotype that has elevated Th1/Th2 ratios.
+Lack of disease surveillance in small companion animals worldwide has contributed to a deficit in our ability to detect and respond to outbreaks.
+In this paper we describe the first real-time syndromic surveillance system that conducts integrated spatio-temporal analysis of data from a national network of veterinary premises for the early detection of disease outbreaks in small animals.
+We illustrate the system’s performance using data relating to gastrointestinal disease in dogs and cats.
+The data consist of approximately one million electronic health records for dogs and cats, collected from 458 UK veterinary premises between March 2014 and 2016.
+For this illustration, the system predicts the relative reporting rate of gastrointestinal disease amongst all presentations, and updates its predictions as new data accrue.
+The system was able to detect simulated outbreaks of varying spatial geometry, extent and severity.
+The system is flexible: it generates outcomes that are easily interpretable; the user can set their own outbreak detection thresholds.
+The system provides the foundation for prompt detection and control of health threats in companion animals.
+The 2019 hepatitis A outbreak has become increasingly prevalent among adults in Korea and is the largest outbreak since that in 2009-2010.
+The incidence in the current outbreak is highest among adults aged 35-44 years, corresponding to the peak incidence among those aged 25-34 years 10 years ago.
+Causes of these repeated outbreaks of hepatitis A in Korea are low level of immunity among adults, Korean food culture that consumes raw seafood such as salted clam and inadequate public health system.
+Among countermeasures, along with general infectious disease control measures including control of the infectious agent, infection spread, and host, urgent actions are needed to review the vaccination policy and establish an adequate public health system.
+The large economic impact of PED on the swine industry worldwide has made the development of an effective PED vaccine a necessity.
+S0, a truncated region of the porcine epidemic diarrhea virus (PEDV) spike protein, has been suggested as a candidate antigen for PED subunit vaccines; however, poor solubility problems when the protein is expressed in Escherichia coli, and the inherent problems of subunit vaccines, such as low immunogenicity, remain.
+Flagellin has been widely used as a fusion partner to enhance the immunogenicity and solubility of many difficult-to-express proteins; however, the conjugation effect of flagellin varies depending on the target antigen or the position of the fusion placement.
+Here, we conjugated flagellin, Vibrio vulnificus FlaB, to the N- and C-termini of S0 and evaluated the ability of the fusion to enhance the solubility and immunogenicity of S0.
+Flagellin conjugation in the presence of the trigger factor chaperone tig greatly improved the solubility of the fusion protein (up to 99%) regardless of its conjugation position.
+Of importance, flagellin conjugated to the N-terminus of S0 significantly enhanced S0-specific humoral immune responses compared to other recombinant antigens in Balb/c mice.
+These findings provide important information for the development of a novel PED vaccine and flagellin-based immunotherapeutics.
+Pet owners frequently administer antimicrobials to their pets and therefore have an important role to play in promoting antimicrobial stewardship in veterinary medicine.
+However, best methods of educating pet owners about antimicrobial stewardship have yet to be defined.
+While visual materials such as brochures and posters are often used in health promotion campaigns, their effectiveness in veterinary medicine is unknown.
+The objective of this study was to determine whether pet owners noticed and retained the message of a poster with an antimicrobial stewardship message placed in veterinary clinic exam rooms.
+A total of 111 pet owners from five veterinary clinics (three general practices, two low-cost clinics) in the greater Philadelphia area participated in the study.
+Participants completed a survey asking whether they noticed the poster and if they could paraphrase its message.
+In a follow-up survey, an antibiotic knowledge score was calculated from answers to questions assessing their knowledge of the poster message.
+At the end of the study, veterinarians at participating clinics were interviewed about their experiences with the poster.
+Only 51 (46.4%) participants noticed the poster, and only 11 (9.9%) could partially or completely reproduce its message.
+No demographic or clinic-level factors were significantly associated with noticing the poster or recalling its message.
+Antibiotic knowledge scores were highly correlated (ρ = 0.87, p < 0.001) with baseline knowledge and not affected by viewing the poster (p = 0.955).
+Veterinarians expressed skepticism that the poster was effective in conveying a message of judicious antibiotic use to clients and noted no difference in the frequency with which they discussed antibiotic resistance or felt pressured to prescribe antibiotics by their clients.
+Posters alone will likely have limited impact in conveying a message of judicious antibiotic use to pet owners.
+However, they might be useful as part of an active, multi-modal education strategy, especially if complemented by veterinarian actions.
+BACKGROUND: Since the Sepsis-3 criteria, change in Sequential Organ Failure Assessment (SOFA) score has become a key component of sepsis identification.
+Thus, it could be argued that reversal of this change (Δ(SOFA)) may reflect sepsis response and could be used as measure of efficacy in interventional trials.
+METHODS: Data from two previously published randomized controlled trials were studied: the first reporting on patients with severe Gram-negative infections as a derivation cohort and the second reporting on patients with ventilator-associated pneumonia as a validation cohort.
+RESULTS: We included 448 patients within the derivation cohort and 199 within the validation cohort.
+Mean SOFA scores on day 1 were 6.06 ± 4.07 and 7.84 ± 3.39, and 28 day mortality 22.8% and 29.6%, respectively.
+In the derivation cohort, the earliest time point where Δ(SOFA) score predicted mortality was day 7 (AUROC (95% CI) 0.84 (0.80–0.89); p < 0.001).
+The best tradeoff for prediction was found with 25% changes (78% sensitivity, 80% specificity); less than 25% decrease of admission SOFA was associated with increased mortality (odds ratio for death 14.87).
+CONCLUSIONS: Δ(SOFA) on day 7 is a useful early prognostic marker of 28-day mortality and could serve as an endpoint in future sepsis trials alongside mortality.
+Resident memory T cells (T(RM) cells) are an important first-line defense against respiratory pathogens, but the unique contributions of lung T(RM) cell populations to protective immunity and the factors that govern their localization to different compartments of the lung are not well understood.
+Here, we show that airway and interstitial T(RM) cells have distinct effector functions and that CXCR6 controls the partitioning of T(RM) cells within the lung by recruiting CD8 T(RM) cells to the airways.
+The absence of CXCR6 significantly decreases airway CD8 T(RM) cells due to altered trafficking of CXCR6(−/−) cells within the lung, and not decreased survival in the airways.
+CXCL16, the ligand for CXCR6, is localized primarily at the respiratory epithelium, and mice lacking CXCL16 also had decreased CD8 T(RM) cells in the airways.
+Thus, the CXCR6/CXCL16 signaling axis controls the localization of T(RM) cells to different compartments of the lung and maintains airway T(RM) cells.
+Severe influenza infections are often associated with the excessive induction of pro-inflammatory cytokines, which is also referred to as “cytokine storms”.
+Several studies have shown that cytokine storms are directly associated with influenza-induced fatal acute lung injury and acute respiratory distress syndrome.
+The efforts to use immunomodulatory agents alone or in combination with antiviral agents in the treatment of influenza in animal models have resulted in the achievement of protective effects accompanied with reduced cytokine production.
+Animal models, despite being ideal to study the anti-inflammatory responses to influenza virus infection, are very costly and time-consuming.
+Therefore, there is an urgent need to establish fast and economical screening methods using cell-based models to screen and develop novel immunomodulatory agents.
+In this study, we screened seven human cell lines and found that the human monocytic cell U937 supports the replication of different subtypes of influenza viruses as well as the production of the important pro-inflammatory cytokines and was selected to develop the cell-based model.
+The U937 cell model was validated by testing a panel of known antiviral and immunomodulatory agents and screening a drug library consisting of 1280 compounds comprised mostly of FDA-approved drugs.
+We demonstrated that the U937 cell model is robust and suitable for the high-throughput screening of immunomodulators and antivirals against influenza infection.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12250-019-00145-w) contains supplementary material, which is available to authorized users.
+The aim of the present study was to screen the anti-dengue potential of crude leaf extracts of two plants from Pavetta tomentosa and Tarenna asiatica.
+For larvicidal assay, the acetone extract of both plants showed maximum effects, with the least LC(50) and LC(90) values (P. tomentosa (5.968 and 7.493 μg/ml) and T. asiatica (1.288 and 1.992 μg/ml)) and the same extract of both plants exhibited better pupicidal potency.
+The adulticidal activity of both plants (0–60 min interval periods) recorded best results in acetone extracts and the LC(50) and LC(90) values were recorded as P. tomentosa (32.105 and 41.001 μg/ml) and T. asiatica (09.012 and 11.854 μg/ml).
+Among the two plants P. tomentosa acetone leaf extract have good antiviral property against Dengue viral cell line.
+In addition, the phytochemical nature of the plant reveals the presence of saponins, flavonoids and alkaloids in all the tested extracts of both plants.
+GC-MS analysis revealed Hexanedioic acid, Bis(2-Ethylhexyl) Ester (22.54) and 2,6,10,14,18,22- Tetracosahexane, 2,6,10, 15, 19,15,19,23- Hexamethyl-(ALL-E)- (25.33) identified as two major phytoconstitutents in P. tomentosa and Tetracontane (23.580) is a major compound identified from T. asiatica acetone extracts.
+The functional groups of chemical compounds (aromatis, alkanes, alkyls and carboxylic acids) from P. tomentosa and T. asiatica were analyzed by FT-IR spectrum.
+As infectious disease outbreaks emerge, public health agencies often enact vaccination and social distancing measures to slow transmission.
+Individual willingness to take precautions may be influenced by global factors, such as news media, or local factors, such as infected family members or friends.
+Here, we compare three modes of epidemiological decision-making in the midst of a growing outbreak using network-based mathematical models that capture plausible heterogeneity in human contact patterns.
+Individuals decide whether to adopt a recommended intervention based on overall disease prevalence, the proportion of social contacts infected, or the number of social contacts infected.
+While all strategies can substantially mitigate transmission, vaccinating (or self isolating) based on the number of infected acquaintances is expected to prevent the most infections while requiring the fewest intervention resources.
+Unlike the other strategies, it has a substantial herd effect, providing indirect protection to a large fraction of the population.
+We estimated the potential impact of trends in diabetes prevalence upon mortality and the future burden of dementia and disability in England and Wales.
+METHODS: We used a probabilistic multi-state, open cohort Markov model to integrate observed trends in diabetes, cardiovascular disease and dementia to forecast the occurrence of disability and dementia up to the year 2060.
+Model input data were taken from the English Longitudinal Study of Ageing, Office for National Statistics vital data and published effect estimates for health-state transition probabilities.
+The baseline scenario corresponded to recent trends in obesity: a 26% increase in the number of people with diabetes by 2060.
+This scenario was evaluated against three alternative projected trends in diabetes: increases of 49%, 20% and 7%.
+RESULTS: Our results suggest that changes in the trend in diabetes prevalence will lead to changes in mortality and incidence of dementia and disability, which will become visible after 10–15 years.
+If the relative prevalence of diabetes increases 49% by 2060, expected additional deaths would be approximately 255,000 (95% uncertainty interval [UI] 236,000–272,200), with 85,900 (71,500–101,600) cumulative additional cases of dementia and 104,900 (85,900–125,400) additional cases of disability.
+With a smaller relative increase in diabetes prevalence (7% increase by 2060), we estimated 222,200 (205,700–237,300) fewer deaths, and 77,000 (64,300–90,800) and 93,300 (76,700–111,400) fewer additional cases of dementia and disability, respectively, than the baseline case of a 26% increase in diabetes.
+CONCLUSIONS/INTERPRETATION: Reducing the burden of diabetes could result in substantial reductions in the incidence of dementia and disability over the medium to long term.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00125-019-05015-4) contains peer-reviewed but unedited supplementary supplementary material, which is available to authorised users.
+This work presents a simple one-pot protocol to achieve core-doped shell nanohybrids comprising silver nanoparticles, curcumin and thermoresponsive polymeric shell taking advantage of the reducing properties of phenolic curcumin substance and its ability to decorate metallic surfaces.
+Silver nanoparticles were synthesized, via sodium citrate and silver nitrate addition into a boiling aqueous solution of curcumin, monomers and surfactant.
+These curcumin-capped AgNPs enabled, after adding the radical polymerization initiator, the assembling of the growing polymer chains around the hydrophobic AgNP surface.
+The resultant core-doped shell nanohybrids exhibit plasmonic, luminescent and volume thermoresponsive properties, with improved possibilities to be used as successful therapeutic platforms.
+In fact, the possibility to nanoconfine the synergistic antioxidant, antiviral, antibacterial features of silver and curcumin in one bioavailable hybrid paves the way to promising applications in the biomedical field.
+Advocates for a One Health approach recognize that global health challenges require multidisciplinary collaborative efforts.
+While past publications have looked at interdisciplinary competency training for collaboration, few have identified the factors and conditions that enable operational One Health.
+Through a scoping review of the literature, a multidisciplinary team of researchers analyzed peer-reviewed publications describing multisectoral collaborations around infectious disease-related health events.
+The review identified 12 factors that support successful One Health collaborations and a coordinated response to health events across three levels: two individual factors (education & training and prior experience & existing relationships), four organizational factors (organizational structures, culture, human resources and, communication), and six network factors (network structures, relationships, leadership, management, available & accessible resources, political environment).
+The researchers also identified the stage of collaboration during which these factors were most critical, further organizing into starting condition or process-based factors.
+The research found that publications on multisectoral collaboration for health events do not uniformly report on successes or challenges of collaboration and rarely identify outputs or outcomes of the collaborative process.
+This paper proposes a common language and framework to enable more uniform reporting, implementation, and evaluation of future One Health collaborations.
+Influenza A viruses (IAVs) are important animal and human emerging and re-emerging pathogens that are responsible for yearly seasonal epidemics and sporadic pandemics.
+IAVs cause a wide range of clinical illnesses, from relatively mild infections by seasonal strains, to acute respiratory distress during infections with highly pathogenic avian IAVs (HPAI).
+For this study, we infected A549 human lung cells with lab prototype A/PR/8/34 (H1N1) (PR8), a seasonal H1N1 (RV733), the 2009 pandemic H1N1 (pdm09), or with two avian strains, an H5N1 HPAI strain or an H7N9 strain that has low pathogenicity in birds but high pathogenicity in humans.
+We used a newly-developed aptamer-based multiplexed technique (SOMAscan(®)) to examine >1300 human lung cell proteins affected by the different IAV strains, and identified more than 500 significantly dysregulated cellular proteins.
+Our analyses indicated that the avian strains induced more profound changes in the A549 global proteome compared to all tested low-pathogenicity H1N1 strains.
+The PR8 strain induced a general activation, primarily by upregulating many immune molecules, the seasonal RV733 and pdm09 strains had minimal effect upon assayed molecules, and the avian strains induced significant downregulation, primarily in antimicrobial response, cardiovascular and post-translational modification systems.
+Background: Rhinovirus C is an important pathogen of asthmatic and non-asthmatic children hospitalised with episodic wheeze.
+Previous studies on other respiratory viruses have shown that several host cytokines correlate with duration of hospitalisation, but this has yet to be investigated in children with RV-C infection.
+We determined the nasal cytokine profiles of these children and investigated their relationship with RV-C load and clinical outcome.
+Flocked nasal swabs were collected from children aged 24–72 months presenting to the Emergency Department at Princess Margaret Hospital with a clinical diagnosis of acute wheeze and an acute upper respiratory tract viral infection.
+RV-C load was determined by quantitative RT-PCR and cytokine profiles were characterised by a commercial human cytokine 34-plex panel.
+RV-C was the most commonly detected virus in pre-school-aged children hospitalised with an episodic wheeze.
+However, Th17 response cytokines IL-17 and IL-1β were only elevated in RV-C-infected children with pre-existing asthma.
+Medically attended RV-C-induced wheeze is characterised by a Th2 inflammatory pattern, independent of viral load.
+Zika virus (ZIKV) infection during pregnancy leads to severe congenital Zika syndrome, which includes microcephaly and other neurological malformations.
+No therapeutic agents have, so far, been approved for the treatment of ZIKV infection in humans; as such, there is a need for a continuous effort to develop effective and safe antiviral drugs to treat ZIKV-caused diseases.
+After screening a natural product library, we have herein identified four natural products with anti-ZIKV activity in Vero E6 cells, including gossypol, curcumin, digitonin, and conessine.
+Except for curcumin, the other three natural products have not been reported before to have anti-ZIKV activity.
+Among them, gossypol exhibited the strongest inhibitory activity against almost all 10 ZIKV strains tested, including six recent epidemic human strains.
+The mechanistic study indicated that gossypol could neutralize ZIKV infection by targeting the envelope protein domain III (EDIII) of ZIKV.
+In contrast, the other natural products inhibited ZIKV infection by targeting the host cell or cell-associated entry and replication stages of ZIKV.
+A combination of gossypol with any of the three natural products identified in this study, as well as with bortezomib, a previously reported anti-ZIKV compound, exhibited significant combinatorial inhibitory effects against three ZIKV human strains tested.
+Importantly, gossypol also demonstrated marked potency against all four serotypes of dengue virus (DENV) human strains in vitro.
+Taken together, this study indicates the potential for further development of these natural products, particularly gossypol, as the lead compound or broad-spectrum inhibitors against ZIKV and other flaviviruses, such as DENV.
+Human immunodeficiency virus (HIV) is a global health concern affecting millions of individuals with a wide variety of currently circulating subtypes affecting various regions of the globe.
+HIV relies on multiple regulatory proteins to modify the host cell to promote replication in infected T cells, and these regulatory proteins can have subtle phenotypic differences between subtypes.
+One of these proteins, HIV-1 Trans-Activator of Transcription (Tat), is capable of RNA interference (RNAi) Silencing Suppressor (RSS) activity and induction of cell death in T cells.
+We investigated the ability of Tat subtypes and variants to induce RSS activity and cell death.
+TatB, from HIV-1 subtype B, was found to be a potent RSS activator by 40% whereas TatC, from HIV-1 subtype C, showed 15% RSS activity while subtype TatC variants exhibited varying levels.
+A high level of cell death (50–53%) was induced by subtype TatB when compared to subtype TatC (25–28%) and varying levels were observed with subtype TatC variants.
+These observations further our understanding of subtype-specific augmentation of Tat in HIV-1 replication and pathogenesis.
+Zika virus (ZIKV) is transmitted by Aedes mosquitoes and exhibits genetic variation with African and Asian lineages.
+ZIKV Natal RGN strain, an Asian-lineage virus, has been identified in brain tissues from fetal autopsy cases with microcephaly and is suggested to be a neurotropic variant.
+However, ZIKV Natal RGN strain has not been isolated; its biological features are not yet illustrated.
+This study rescued and characterized recombinant, single-round infectious particles (SRIPs) of the ZIKV Natal RGN strain using reverse genetic and synthetic biology techniques.
+The DNA-launched replicon of ZIKV Natal RGN was constructed and contains the EGFP reporter, lacks prM-E genes, and replicates under CMV promoter control.
+The peak in the ZIKV Natal RGN SRIP titer reached 6.25 × 10(6) TCID50/mL in the supernatant of prM-E-expressing packaging cells 72 h post-transfection with a ZIKV Natal RGN replicon.
+The infectivity of ZIKV Natal RGN SRIPs has been demonstrated to correlate with the green florescence intensity of the EGFP reporter, the SRIP-induced cytopathic effect, and ZIKV’s non-structural protein expression.
+Moreover, ZIKV Natal RGN SRIPs effectively self-replicated in rhabdomyosarcoma/muscle, glioblastoma/astrocytoma, and retinal pigmented epithelial cells, displaying unique cell susceptibility with differential attachment activity.
+Therefore, the recombinant ZIKV Natal RGN strain was rescued as SRIPs that could be used to elucidate the biological features of a neurotropic strain regarding cell tropism and pathogenic components, apply for antiviral agent screening, and develop vaccine candidates.
+Feline leukaemia virus (FeLV) is a retrovirus associated with fatal disease in progressively infected cats.
+While testing/removal and vaccination led to a decreased prevalence of FeLV, recently, this decrease has reportedly stagnated in some countries.
+This study aimed to prospectively determine the prevalence of FeLV viraemia in cats taken to veterinary facilities in 32 European countries.
+FeLV viral RNA was semiquantitatively detected in saliva, using RT-qPCR as a measure of viraemia.
+Risk and protective factors were assessed using an online questionnaire to report geographic, demographic, husbandry, FeLV vaccination, and clinical data.
+The overall prevalence of FeLV viraemia in cats visiting a veterinary facility, of which 10.4% were shelter and rescue cats, was 2.3% (141/6005; 95% CI: 2.0%–2.8%) with the highest prevalences in Portugal, Hungary, and Italy/Malta (5.7%–8.8%).
+Using multivariate analysis, seven risk factors (Southern Europe, male intact, 1–6 years of age, indoor and outdoor or outdoor-only living, living in a group of ≥5 cats, illness), and three protective factors (Northern Europe, Western Europe, pedigree cats) were identified.
+Using classification and regression tree (CART) analysis, the origin of cats in Europe, pedigree, and access to outdoors were important predictors of FeLV status.
+FeLV-infected sick cats shed more viral RNA than FeLV-infected healthy cats, and they suffered more frequently from anaemia, anorexia, and gingivitis/stomatitis than uninfected sick cats.
+Most cats had never been FeLV-vaccinated; vaccination rates were indirectly associated with the gross domestic product (GDP) per capita.
+In conclusion, we identified countries where FeLV was undetectable, demonstrating that the infection can be eradicated and highlighting those regions where awareness and prevention should be increased.
+The unavailability of a specific antiviral drug against the chikungunya virus (CHIKV) disease has created an alarming situation to identify or develop potent chemical molecules for remedial management of CHIKV.
+In the present investigation, in silico studies of dihydrorugosaflavonoid derivatives (5a–f) with non-structural protein-3 (nsP3) were carried out.
+nsP3 replication protein has recently been considered as a possible antiviral target in which crucial inhibitors fit into the adenosine-binding pocket of the macrodomain.
+The 4′-halogenated dihydrorugosaflavonoids displayed intrinsic binding with the nsp3 macrodomain (PDB ID: 3GPO) of CHIKV.
+The non-cytotoxic dose was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and was found to be <100 μM.
+The compounds 5c and 5d showed their inhibitory potential for CHIKV, which was determined through cytopathic effect assay and plaque reduction assay, which show inhibition up to 95 and 92% for 70 μM concentration of the compounds, respectively.
+The quantitative real-time polymerase chain reaction assay result confirmed the ability of 5c and 5d to reduce the viral RNA level at 70 μM concentration of compounds to nearly 95 and 93% concentration, respectively, in cells with CHIKV infection.
+The executed work will be meaningful for the future research of studied dihydrorugosaflavonoids against prime antiviral entrants, leading to remedial management to preclude CHIKV infection.
+Predicting disease emergence and outbreak events is a critical task for public health professionals and epidemiologists.
+Advances in global disease surveillance are increasingly generating datasets that are worth more than their component parts for prediction-oriented work.
+Here, we use a trait-free approach which leverages information on the global community of human infectious diseases to predict the biogeography of pathogens through time.
+Our approach takes pairwise dissimilarities between countries’ pathogen communities and pathogens’ geographical distributions and uses these to predict country–pathogen associations.
+We compare the success rates of our model for predicting pathogen outbreak, emergence and re-emergence potential as a function of time (e.g.
+With only these simple predictors, our model successfully predicts basic network structure up to a decade into the future.
+We find that while outbreak and re-emergence potential are especially well captured by our simple model, prediction of emergence events remains more elusive, and sudden global emergences like an influenza pandemic are beyond the predictive capacity of the model.
+Together, our model is able to use the information on the existing country–pathogen network to predict pathogen outbreaks fairly well, suggesting the importance in considering information on co-occurring pathogens in a more global view even to estimate outbreak events in a single location or for a single pathogen.
+BACKGROUND: Clinical and epidemiological differences between acute respiratory distress syndrome (ARDS) that presents at the initiation of mechanical ventilation [MV] (ARDS at MV onset) and that which develops during the course of MV (ARDS after MV onset) are not well understood.
+We conducted an observational study in five Peruvian ICUs to characterize differences between ARDS at MV onset and after MV onset and identify risk factors for the development of ARDS after MV onset.
+METHODS: We consecutively enrolled critically ill patients with acute respiratory failure requiring at least 24 h of mechanical ventilation and followed them prospectively during the first 28 days and compared baseline characteristics and clinical outcomes by ARDS status.
+RESULTS: We enrolled 1657 participants on MV (mean age 60.0 years, 55% males) of whom 334 (20.2%) had ARDS at MV onset and 180 (10.9%) developed ARDS after MV onset.
+Average tidal volume at the initiation of MV was 8.7 mL/kg of predicted body weight (PBW) for participants with ARDS at MV onset, 8.6 mL/kg PBW for those who developed ARDS after MV onset, and 8.5 mL/kg PBW for those who never developed ARDS (p = 0.23).
+Overall, 90-day mortality was 56% and 55% for ARDS after MV onset and ARDS at MV onset, respectively, as compared to 46% among those who never developed ARDS (p < 0.01).
+Adults with ARDS had a higher body mass index (BMI) than those without ARDS (27.3 vs 26.5 kg/m(2), p < 0.01).
+Higher peak pressure (adjusted interquartile OR = 1.51, 95% CI 1.21–1.88), higher mean airway pressure (adjusted interquartile OR = 1.41, 95% CI 1.13–1.76), and higher positive end-expiratory pressure (adjusted interquartile OR = 1.29, 95% CI 1.10–1.50) at MV onset were associated with a higher odds of developing ARDS after MV onset.
+CONCLUSIONS: In this study of mechanically ventilated patients, 31% of study participants had ARDS at some point during their ICU stay.
+Patients with ARDS after MV onset had a similar 90-day mortality as those with ARDS at MV onset.
+Higher airway pressures at MV onset, higher PEEP, and higher BMI were associated with the development of ARDS after MV onset.
+BACKGROUND: Increasing numbers of aging individuals with chronic co-morbidities travel to regions where falciparum malaria is endemic.
+Thus, the influence of chronic diseases on the outcome of falciparum malaria is an issue of major importance.
+Aim of the present study was to assess whether non-communicable diseases increase the risk for severe imported falciparum malaria.
+METHODS: A retrospective observational study of all adult cases with imported falciparum malaria hospitalized between 2001 and 2015 in the tertiary care Charité University Hospital, Berlin, was performed.
+RESULTS: A total of 536 adult patients (median age 37 years; 31.3% female) were enrolled.
+With older age, lack of previous malaria episodes, being a tourist, and delayed presentation, well-characterized risk factors were associated with severe malaria in univariate analysis.
+After adjustment for these potential confounders hypertension (adjusted odds ratio aOR, 3.06 95% confidence interval, CI 1.34–7.02), cardiovascular diseases (aOR, 8.20 95% CI 2.30–29.22), and dyslipidaemia (aOR, 6.08 95% CI 1.13–32.88) were individual diseases associated with severe disease in multivariable logistic regression.
+Hypertension proved an independent risk factor among individuals of endemic (aOR, 4.83, 95% CI 1.44–16.22) as well as of non-endemic origin (aOR, 3.60 95% CI 1.05–12.35).
+CONCLUSIONS: In imported falciparum malaria hypertension and its related diseases are risk factors for severe disease.
+Dysregulated leukocyte responses underlie the pathobiology of sepsis, which is a leading cause of death.
+Here we report the development and testing of an inertial microfluidic system for the label-free isolation and downstream functional assessment of leukocytes from 50 μl of peripheral blood.
+We used the system to assess leukocyte phenotype and function in serial samples from 18 hospitalized patients with sepsis and 10 healthy subjects.
+The sepsis samples had significantly higher levels of CD16(dim) and CD16(−) neutrophils and CD16(+) ‘intermediate’ monocytes, as well as significantly lower levels of neutrophil-elastase release, O(2)(−) production and phagolysosome formation.
+Repeated sampling of sepsis patients over 7 days showed that leukocyte activation (measured by isodielectric separation) and leukocyte phenotype and function were significantly more predictive of the clinical course than complete-blood-count parameters.
+We conclude that the serial assessment of leukocyte function in microlitre blood volumes is feasible and that it provides significantly more prognostic information than leukocyte counting.
+Old World camels have served humans in cross‐continental caravans, transporting people and goods, connecting different cultures and providing milk, meat, wool and draught since their domestication around 3000–6000 years ago.
+In a world of modern transport and fast connectivity, these beasts of burden seem to be out‐dated.
+However, a growing demand for sustainable milk and meat production, especially in countries affected by climate change and increasing desertification, brings dromedaries (Camelus dromedarius) and Bactrian camels (Camelus bactrianus) back onstage and into the focus of animal breeders and scientists.
+In this review on the molecular genetics of these economically important species we give an overview about the evolutionary history, domestication and dispersal of Old World camels, whereas highlighting the need for conservation of wild two‐humped camels (Camelus ferus) as an evolutionarily unique and highly endangered species.
+We cannot emphasise enough the importance of balancing the need for improving camel production traits with maintaining the genetic diversity in two domestic species with specific physiological adaptation to a desert environment.
+Ribonucleases (RNases) are a large number of enzymes gathered into different bacterial or eukaryotic superfamilies.
+Bovine pancreatic RNase A, bovine seminal BS-RNase, human pancreatic RNase 1, angiogenin (RNase 5), and amphibian onconase belong to the pancreatic type superfamily, while binase and barnase are in the bacterial RNase N1/T1 family.
+In physiological conditions, most RNases secreted in the extracellular space counteract the undesired effects of extracellular RNAs and become protective against infections.
+Instead, if they enter the cell, RNases can digest intracellular RNAs, becoming cytotoxic and having advantageous effects against malignant cells.
+Their biological activities have been investigated either in vitro, toward a number of different cancer cell lines, or in some cases in vivo to test their potential therapeutic use.
+Nevertheless, the use of RNases in therapy remains an appealing strategy against some still incurable tumors, such as mesothelioma, melanoma, or pancreatic cancer.
+The RNase inhibitor (RI) present inside almost all cells is the most efficacious sentry to counteract the ribonucleolytic action against intracellular RNAs because it forms a tight, irreversible and enzymatically inactive complex with many monomeric RNases.
+Therefore, dimerization or multimerization could represent a useful strategy for RNases to exert a remarkable cytotoxic activity by evading the interaction with RI by steric hindrance.
+Indeed, the majority of the mentioned RNases can hetero-dimerize with antibody derivatives, or even homo-dimerize or multimerize, spontaneously or artificially.
+Immuno-RNases, in particular, are fusion proteins representing promising drugs by combining high target specificity with easy delivery in tumors.
+The results concerning the biological features of many RNases reported in the literature are described and discussed in this review.
+Furthermore, the activities displayed by some RNases forming oligomeric complexes, the mechanisms driving toward these supramolecular structures, and the biological rebounds connected are analyzed.
+These aspects are offered with the perspective to suggest possible efficacious therapeutic applications for RNases oligomeric derivatives that could contemporarily lack, or strongly reduce, immunogenicity and other undesired side-effects.
+BACKGROUND: There is a marked paucity of data concerning AKI in Sub-Saharan Africa, where there is a substantial burden of trauma and HIV.
+METHODS: Prospective data was collected on all patients admitted to a multi-disciplinary ICU in South Africa during 2017.
+Development of AKI (before or during ICU admission) was recorded and renal recovery 90 days after ICU discharge was determined.
+RESULTS: Of 849 admissions, the mean age was 42.5 years and mean SAPS 3 score was 48.1.
+Male gender, illness severity, length of stay, vasopressor drugs and sepsis were independently associated with AKI.
+AKI was associated with a higher in-hospital mortality rate of 31.8% vs 7.23% in those without AKI.
+Age, active tuberculosis, higher SAPS 3 score, mechanical ventilation, vasopressor support and sepsis were associated with an increased adjusted odds ratio for death.
+CKD developed in 14 of 110 (12.7%) patients with stage 3 AKI; none were dialysis-dependent.
+CONCLUSIONS: In this large prospective multidisciplinary ICU cohort of younger patients, AKI was common, often associated with trauma in addition to traditional risk factors and was associated with good functional renal recovery at 90 days in most survivors.
+Although the HIV prevalence was high and associated with higher mortality, this was related to the severity of illness and not to HIV status per se.
+BACKGROUND: The use of extracorporeal membrane oxygenation (ECMO) in awake, spontaneously breathing and non-intubated patients (awake ECMO) may be a novel therapeutic strategy for severe acute respiratory distress syndrome (ARDS) patients.
+The purpose of this study is to assess the feasibility and safety of awake ECMO in severe ARDS patients receiving prolonged ECMO (> 14 days).
+METHODS: We describe our experience with 12 consecutive severe ARDS patients (age, 39.1 ± 16.4 years) supported with awake ECMO to wait for native lung recovery during prolonged ECMO treatment from July 2013 to January 2018.
+Outcomes are reported including the hospital mortality, ECMO-related complications and physiological data on weaning from invasive ventilation.
+RESULTS: The patients received median 26.0 (15.5, 64.8) days of total ECMO duration in the cohort.
+The total invasive ventilation duration, lengths of stay in the ICU and hospital in the cohort were 14.0(12.0, 37.3) days, 33.0(22.3, 56.5) days and 46.5(27.3, 84.8) days, respectively.
+Survivors had more stable respiratory rate and heart rate after extubation when compared to the non-survivors.
+CONCLUSIONS: With carefully selected patients, awake ECMO is a feasible and safe strategy for severe pulmonary ARDS patients receiving prolonged ECMO support to wait for native lung recovery.
+OBJECTIVES: Feline immunodeficiency virus (FIV) and feline leukaemia virus (FeLV) are retroviruses affecting cats worldwide.
+The objectives of the study were to estimate the prevalence of these retroviruses in domestic cats in Hungary and to characterise the phylogenetic relationships of FIV strains.
+METHODS: A total of 335 anticoagulated whole-blood samples obtained from both a healthy and ill cat population were examined for the presence of FIV and FeLV with two methods: ELISA and PCR.
+Sequencing and phylogenetic analysis of partial polymerase (pol) gene sequences was performed to describe circulating FIV subtypes.
+RESULTS: Statistical analysis showed 11.8% and 9.9% true prevalence of FeLV and FIV, respectively, with ELISA.
+The apparent prevalence calculated from the PCR results were 17.3% for FeLV and 13.1% for FIV.
+Phylogenetic analysis of partial pol gene sequences obtained from 22 FIV strains showed that all observed Hungarian strains belonged to FIV subtype B.
+The strains were grouped into several monophyletic subgroups reflecting the geographic locations of the origin of the samples.
+CONCLUSIONS AND RELEVANCE: We report the first thorough overview of the prevalence of FeLV and FIV in Hungary, which is relatively high, and give insight into the genetic diversity of Hungarian strains of FIV.
+No therapeutics or vaccines are currently licensed; however, a vaccine has shown promise in clinical trials.
+A critical step towards development of effective therapeutics is a better understanding of factors that govern host susceptibility to this pathogen.
+As macrophages are an important cell population targeted during virus replication, we explore the effect of cytokine polarization on macrophage infection.
+METHODS/MAIN FINDINGS: We utilized a BSL2 EBOV model virus, infectious, recombinant vesicular stomatitis virus encoding EBOV glycoprotein (GP) (rVSV/EBOV GP) in place of its native glycoprotein.
+Macrophages polarized towards a M2-like anti-inflammatory state by combined IL-4 and IL-13 treatment were more susceptible to rVSV/EBOV GP, but not to wild-type VSV (rVSV/G), suggesting that EBOV GP-dependent entry events were enhanced by these cytokines.
+Examination of RNA expression of known surface receptors that bind and internalize filoviruses demonstrated that IL-4/IL-13 stimulated expression of the C-type lectin receptor DC-SIGN in human macrophages and addition of the competitive inhibitor mannan abrogated IL-4/IL-13 enhanced infection.
+Two murine DC-SIGN-like family members, SIGNR3 and SIGNR5, were upregulated by IL-4/IL-13 in murine macrophages, but only SIGNR3 enhanced virus infection in a mannan-inhibited manner, suggesting that murine SIGNR3 plays a similar role to human DC-SIGN.
+In vivo IL-4/IL-13 administration significantly increased virus-mediated mortality in a mouse model and transfer of ex vivo IL-4/IL-13-treated murine peritoneal macrophages into the peritoneal cavity of mice enhanced pathogenesis.
+SIGNIFICANCE: These studies highlight the ability of macrophage polarization to influence EBOV GP-dependent virus replication in vivo and ex vivo, with M2a polarization upregulating cell surface receptor expression and thereby enhancing virus replication.
+Our findings provide an increased understanding of the host factors in macrophages governing susceptibility to filoviruses and identify novel murine receptors mediating EBOV entry.
+The majority of these are in non-coding regions, and are commonly assigned to the nearest gene along the genome.
+However, this approach neglects the three-dimensional organisation of the genome, and the fact that the genome contains arrays of extremely conserved non-coding elements termed genomic regulatory blocks (GRBs), which can be utilized to detect genes under long-range developmental regulation.
+Here we review a GRB-based approach to assign loci in non-coding regions to potential target genes, and apply it to reanalyse the results of one of the largest schizophrenia GWAS (SWG PGC, 2014).
+We further apply this approach to GWAS data from two related neuropsychiatric disorders—autism spectrum disorder and bipolar disorder—to show that it is applicable to developmental disorders in general.
+We find that disease-associated SNPs are overrepresented in GRBs and that the GRB model is a powerful tool for linking these SNPs to their correct target genes under long-range regulation.
+Our analysis identifies novel genes not previously implicated in schizophrenia and corroborates a number of predicted targets from the original study.
+The results are available as an online resource in which the genomic context and the strength of enhancer–promoter associations can be browsed for each schizophrenia-associated SNP.
+Children are more vulnerable to the risks of air pollution, including susceptibility to acquiring chronic diseases in their developing lungs.
+Despite these, there are no specific masks designed for and tested in children that are available to protect our young from the common particulate air pollutants today.
+We evaluated safety, fit and comfort of a specially designed paediatric N95 mask with an optional micro ventilator (micro fan, MF) in healthy children aged 7–14 years, in a randomized, two-period crossover design.
+The subjects’ cardiorespiratory physiological measurements were assessed in different states of physical activity under different interventions (mask without and with MF).
+The use of the mask without MF increased the End-Tidal CO(2) (ETCO(2)) and Fractional concentration of Inspired CO(2) (FICO(2)) at rest and on mild exertion, as expected.
+The use of the mask with MF brought FICO(2) levels comparably closer to baseline levels without the mask for both activities.
+The mask, with or without the MF, was found to be well fitting, comfortable and safe for use in children at rest and on mild exertion.
+The N95 mask tested offers a promising start for more studies in the paediatric population.
+BACKGROUND: Pristine carbon dots (CDs) derived from citric acid pyrolysis are used in a variety of biomedical research such as imaging and drug delivery.
+To address this need, we studied toxicity of the CDs to breast cancer cells using MTT and LDH assays.
+In addition, we investigated photo-induced cytotoxicity of the synthesized CDs in a wide concentration range under white light.
+RESULTS: Our results suggest little cytotoxicity of the CDs after 24 h exposure of cells.
+Only the high quantum yield CDs caused a significant toxicity to cells at the highest concentrations of 2.0 and 1.5 mg/ml compared to other CDs at similar concentrations.
+CONCLUSION: The optimization of synthesis conditions from this study may help develop safe and efficient CDs for imaging and drug delivery.
+Very few case reports in the literature have described a relationship between Graves disease and thrombotic thrombocytopenic purpura.
+We present a case of a patient with Graves disease who was found to be biochemically and clinically hyperthyroid with concurrent thrombotic thrombocytopenic purpura.
+CASE PRESENTATION: Our patient was a 30-year-old African American woman with a history of hypertension and a family history of Graves disease who had recently been diagnosed with hyperthyroidism and placed on methimazole.
+She presented to our hospital with the complaints of progressive shortness of breath and dizziness.
+On further evaluation, she was diagnosed with thrombotic thrombocytopenic purpura, depending on clinical and laboratory results, and also was found to have highly elevated free T4 and suppressed thyroid-stimulating hormone.
+The patient ultimately had a cardiac arrest with pulseless electrical activity and died despite multiple attempts at cardiopulmonary resuscitation.
+CONCLUSION: Graves disease is an uncommon trigger for the development of thrombotic thrombocytopenic purpura, and very few cases have been reported thus far.
+Therefore, clinicians should be aware of this association in the appropriate clinical context to comprehensively monitor hyperthyroid patients during treatment.
+The purpose of this study was to develop a tool for community-based health organisations (CBHOs) to evaluate the preparedness in biohazards concerning epidemics or bioterrorism.
+We searched concepts on partnerships of CBHOs with health systems in guidelines of the Centers for Disease Control and Prevention and literature.
+Then, we validated the researcher-made tool by face validity, content validity, exploratory factor analysis (EFA), confirmatory factor analysis (CFA) and criterion validity.
+Data were collected by sending the tool to 620 CBHOs serving under supervision of Iran’s ministry of health.
+Opinions of health professionals and stakeholders in CBHOs were used to assess face and content validity.
+After conducting face validity and calculating content validity ratio and content validity index, we reached 54 items in the field of planning, training and infrastructure.
+Three items exchanged between the fields according to factor loads in EFA, and CFA verified the model fit as Comparative Fit Index, Tucker-Lewis index and root mean square error of approximation were 0.921, 0918 and 0.052, respectively.
+Planning, training and infrastructure fields are the most important aspects of preparedness in health-based CBHOs.
+Applying the new assessment tool in future studies will show the weaknesses and capabilities of health-based CBHOs in biohazard and clear necessary intervention actions for health authorities.
+Despite the global zoonotic disease burden, the underlying exposures that drive zoonotic disease emergence are not understood.
+Here, we aimed to assess exposures to potential sources of zoonotic disease and investigate the demographics, attitudes, and behavior of individuals with sustained occupational animal contact in Vietnam.
+We recruited 581 animal workers (animal-raising farmers, slaughterers, animal health workers, and rat traders) and their families in southern and central Vietnam into a cohort.
+Cohort members were followed for 3 years and interviewed annually regarding (1) demography and attitudes regarding zoonotic disease, (2) medical history, (3) specific exposures to potential zoonotic infection sources, and (4) socioeconomic status.
+Of the 297 cohort members interviewed, the majority (79.8%; 237/297) reported raising livestock; almost all (99.6%; 236/237) reported being routinely exposed to domestic animals, and more than a quarter (28.7%; 68/237) were exposed to exotic animals.
+Overall, 70% (208/297) reported slaughtering exotic animals; almost all (99.5%; 207/208) reported consuming such animals.
+The consumption of raw blood and meat was common (24.6%; 73/297 and 37%; 110/297, respectively).
+Over half (58.6%; 174/297) reported recent occupational animal-induced injuries that caused bleeding; the use of personal protective equipment (PPE) was limited.
+Our work demonstrates that individuals working with animals in Vietnam are exposed to a wide range of species, and there are limited procedures for reducing potential zoonotic disease exposures.
+We advocate better education, improved animal security, and enforced legislation of PPE for those with occupational animal exposure in Vietnam.
+Npl4 is likely to be the most upstream factor recognizing Lys48-linked polyubiquitylated substrates in the proteasomal degradation pathway in yeast.
+Along with Ufd1, Npl4 forms a heterodimer (UN), and functions as a cofactor for the Cdc48 ATPase.
+Here, we report the crystal structures of yeast Npl4 in complex with Lys48-linked diubiquitin and with the Npl4-binding motif of Ufd1.
+The distal and proximal ubiquitin moieties of Lys48-linked diubiquitin primarily interact with the C-terminal helix and N-terminal loop of the Npl4 C-terminal domain (CTD), respectively.
+Mutational analysis suggests that the CTD contributes to linkage selectivity and initial binding of ubiquitin chains.
+Ufd1 occupies a hydrophobic groove of the Mpr1/Pad1 N-terminal (MPN) domain of Npl4, which corresponds to the catalytic groove of the MPN domain of JAB1/MPN/Mov34 metalloenzyme (JAMM)-family deubiquitylating enzyme.
+This study provides important structural insights into the polyubiquitin chain recognition by the Cdc48–UN complex and its assembly.
+During RV infection, NSP5 undergoes hyperphosphorylation, which is primed by the phosphorylation of a single serine residue.
+The role of this posttranslational modification in the formation of viroplasms and its impact on virus replication remain obscure.
+Here, we investigated the role of NSP5 during RV infection by taking advantage of a modified fully tractable reverse-genetics system.
+A trans-complementing cell line stably producing NSP5 was used to generate and characterize several recombinant rotaviruses (rRVs) with mutations in NSP5.
+We demonstrate that an rRV lacking NSP5 was completely unable to assemble viroplasms and to replicate, confirming its pivotal role in rotavirus replication.
+A number of mutants with impaired NSP5 phosphorylation were generated to further interrogate the function of this posttranslational modification in the assembly of replication-competent viroplasms.
+We showed that the rRV mutant strains exhibited impaired viral replication and the ability to assemble round-shaped viroplasms in MA104 cells.
+Furthermore, we investigated the mechanism of NSP5 hyperphosphorylation during RV infection using NSP5 phosphorylation-negative rRV strains, as well as MA104-derived stable transfectant cell lines expressing either wild-type NSP5 or selected NSP5 deletion mutants.
+Our results indicate that NSP5 hyperphosphorylation is a crucial step for the assembly of round-shaped viroplasms, highlighting the key role of the C-terminal tail of NSP5 in the formation of replication-competent viral factories.
+Such a complex NSP5 phosphorylation cascade may serve as a paradigm for the assembly of functional viral factories in other RNA viruses.
+IMPORTANCE The rotavirus (RV) double-stranded RNA genome is replicated and packaged into virus progeny in cytoplasmic structures termed viroplasms.
+The nonstructural protein NSP5, which undergoes a complex hyperphosphorylation process during RV infection, is required for the formation of these virus-induced organelles.
+However, its roles in viroplasm formation and RV replication have never been directly assessed due to the lack of a fully tractable reverse-genetics (RG) system for rotaviruses.
+Here, we show a novel application of a recently developed RG system by establishing a stable trans-complementing NSP5-producing cell line required to rescue rotaviruses with mutations in NSP5.
+This approach allowed us to provide the first direct evidence of the pivotal role of this protein during RV replication.
+Furthermore, using recombinant RV mutants, we shed light on the molecular mechanism of NSP5 hyperphosphorylation during infection and its involvement in the assembly and maturation of replication-competent viroplasms.
+Acute respiratory distress syndrome (ARDS) is a devastating hypoxemic respiratory failure, characterized by disruption of the alveolar-capillary membrane barrier.
+Mesenchymal stem cells (MSCs) have emerged as a potentially attractive candidate for the management of ARDS through facilitating lung tissue regeneration and repair by releasing paracrine soluble factors.
+Among these, the strategy using genetically modified MSCs has received increased attention recently due to its distinct advantage, in conferring incremental migratory capacity and, enhancing the anti-inflammatory, immunomodulatory, angiogenic, and antifibrotic effects of these cells in numerous preclinical ARDS models, which may in turn provide additional benefits in the management of ARDS.
+Here, we provide an overview of recent studies testing the efficacy of genetically modified MSCs using preclinical models of ARDS.
+The mortality rate of hemorrhagic African swine fever (ASF), which targets domestic pigs and wild boars is caused by African swine fever virus (ASFV), can reach 100%.
+Since the first confirmed ASF outbreak in China on 3 August 2018, 156 ASF outbreaks were detected in 32 provinces.
+There is no effective treatment or vaccine for it and the present molecular diagnosis technologies have trade-offs in sensitivity, specificity, cost and speed, and none of them cater perfectly to ASF control.
+Thus, a technology that overcomes the need for laboratory facilities, is relatively low cost, and rapidly and sensitively detects ASFV would be highly valuable.
+Here, we describe an RAA-Cas12a-based system that combines recombinase aided amplification (RAA) and CRISPR/Cas12a for ASFV detection.
+The fluorescence intensity readout of this system detected ASFV p72 gene levels as low as 10 aM.
+For on-site ASFV detection, lateral-flow strip readout was introduced for the first time in the RAA-Cas12a based system (named CORDS, Cas12a-based On-site and Rapid Detection System).
+We used CORDS to detect target DNA highly specifically using the lateral-flow strip readout and the assay displayed no cross-reactivity to other 13 swine viruses including classical swine fever (CSF).
+CORDS could identify the ASFV DNA target at femtomolar sensitivity in an hour at 37°C, and only requires an incubator.
+For ease of use, the reagents of CORDS were lyophilized to three tubes and remained the same sensitivity when stored at 4°C for at least 7 days.
+The generation of tissue-resident memory T cells (T(RM)) is an essential aspect of immunity at mucosal surfaces, and it has been suggested that preferential generation of T(RM) is one of the principal advantages of mucosally administered vaccines.
+We have previously shown that antigen-specific, IL-17-producing CD4(+) T cells can provide capsular antibody-independent protection against nasal carriage of Streptococcus pneumoniae; but whether pneumococcus-responsive T(RM) are localized within the nasal mucosa and are sufficient for protection from carriage has not been determined.
+Here we show that intranasal administration of live or killed pneumococci to mice generates pneumococcus-responsive IL-17A-producing CD4(+) mucosal T(RM).
+Furthermore, we show that these cells are sufficient to mediate long-lived, neutrophil-dependent protection against subsequent pneumococcal nasal challenge.
+Unexpectedly, and in contrast with the prevailing paradigm, we found that parenteral administration of killed pneumococci also generates protective IL-17A(+)CD4(+) T(RM) in the nasal mucosa.
+These results demonstrate a critical and sufficient role of T(RM) in prevention of pneumococcal colonization, and further that these cells can be generated by parenteral immunization.
+Our findings therefore have important implications regarding the generation of immune protection at mucosal surfaces by vaccination.
+The seasonal burden of influenza coupled with the pandemic outbreaks of more pathogenic strains underscore a critical need to understand the pathophysiology of influenza injury in the lung.
+Interleukin-22 (IL-22) is a promising cytokine that is critical in protecting the lung during infection.
+This cytokine is strongly regulated by the soluble receptor IL-22-binding protein (IL-22BP), which is constitutively expressed in the lungs where it inhibits IL-22 activity.
+However, the importance of this axis is not understood during an infection such as influenza.
+Here we demonstrate through the use of IL-22BP-knockout mice (il-22ra2(−/−)) that a pro-IL-22 environment reduces pulmonary inflammation during H1N1 (PR8/34 H1N1) infection and protects the lung by promoting tight junction formation.
+We confirmed these results in normal human bronchial epithelial cells in vitro demonstrating improved membrane resistance and induction of the tight junction proteins Cldn4, Tjp1, and Tjp2.
+Importantly, we show that administering recombinant IL-22 in vivo reduces inflammation and fluid leak into the lung.
+Taken together, our results demonstrate the IL-22/IL-22BP axis is a potential targetable pathway for reducing influenza-induced pneumonia.
+Illuminating the role of specific gene duplications within the human lineage can provide insights into human-specific adaptations.
+The so-called human core duplicon gene families have received particular attention in this respect, due to special features, such as expansion along single chromosomes, newly acquired protein domains and signatures of positive selection.
+Here, we summarize the data available for 10 such families and include some new analyses.
+A picture emerges that suggests broad functions for these protein families, possibly through modification of core cellular pathways.
+Still, more dedicated studies are required to elucidate the function of core-duplicons gene families and how they have shaped adaptations and evolution of humans.
+OBJECTIVE: To determine costs of hospitalization associated with bronchopulmonary dysplasia (BPD) during the first year in very low birth weight infants.
+STUDY DESIGN: Retrospective cohort study of California births from 2008–2011 linking birth certificate, discharge records, and clinical data from California Perinatal Quality Care Collaborative.
+Inclusion: birthweight 401–1500 grams, gestational age <30 weeks, inborn or transferred within 2 days, alive at 36 weeks corrected, and without major congenital anomalies.
+Median hospitalization cost in the first year was $377,871 per infant with BPD compared to $175,836 per infant without BPD (adjusted cost ratio 1.54, 95% confidence interval 1.49–1.59).
+Infants with BPD also had longer length of stay and a higher likelihood of rehospitalization.
+For a long time, this virus was mostly unnoticed due to its mild symptoms and low fatality rates.
+However, during the 2015–2016 epidemic in Central and South America, when millions of people were infected, it was discovered that ZIKV causes microcephaly in the babies of mothers infected during pregnancy.
+An examination of the M and C proteins of the ZIKV shell using the disorder predictor PONDR VLXT revealed that the M protein contains relatively high disorder levels comparable only to those of the yellow fever virus (YFV).
+On the other hand, the disorder levels in the C protein are relatively low, which can account for the low case fatality rate (CFR) of this virus in contrast to the more virulent YFV, which is characterized by high disorder in its C protein.
+A larger variation was found in the percentage of intrinsic disorder (PID) in the C protein of various ZIKV strains.
+Using both in vivo and in vitro experiments, laboratories have also previously shown that strains of African origin have a greater potential to inflict higher fetal morbidity than do strains of Asian lineage, with dengue-2 virus (DENV-2) having the least potential.
+Strong correlations were found between the potential to inflict fetal morbidity and shell disorder in ZIKV (r(2) = 0.9) and DENV-2 (DENV-2 + ZIKV, r(2) = 0.8).
+A strong correlation between CFR and PID was also observed when ZIKV was included in an analysis of sets of shell proteins from a variety of flaviviruses (r(2) = 0.8).
+These observations have potential implications for antiviral vaccine development and for the design of cancer therapeutics in terms of developing therapeutic viruses that penetrate hard-to-reach organs.
+BACKGROUND AND AIM: Bovine respiratory syncytial virus (BRSV) is one of the main causes of severe pneumonia, interstitial edema, and emphysema in cattle.
+The current study investigated the prevalence and risk factors of BRSV in cattle in the Nineveh Province, Iraq.
+MATERIALS AND METHODS: Between September 2017 and September 2018, 450 serum samples were collected from non-vaccinated cattle of different ages and breeds for BRSV testing.
+RESULTS: The prevalence of BRSV was 83.11%, and it was significantly (p<0.05) higher in cattle aged greater than 7 months-1.5 years than in older animals; in imported cattle than in Native animals; and in animals originating from large herds (100 animals) than in those from smaller herds (40 animals).
+When samples from different regions of the Nineveh Governorate were compared, the northern region was associated with the highest prevalence of the disease.
+Samples harvested in the winter displayed the highest BRSV titer, compared to those collected during the other seasons.
+Risk factors such as animal age, origin, herd size, and the herd’s geographical location are associated with an increased prevalence of the disease in this region.
+DNA, when folded into nanostructures with a specific shape, is capable of spacing and arranging binding sites into a complex geometric pattern with nanometre precision.
+Here we demonstrate a designer DNA nanostructure that can act as a template to display multiple binding motifs with precise spatial pattern-recognition properties, and that this approach can confer exceptional sensing and potent viral inhibitory capabilities.
+A star-shaped DNA architecture, carrying five molecular beacon-like motifs, was constructed to display ten dengue envelope protein domain III (ED3)-targeting aptamers into a two-dimensional pattern precisely matching the spatial arrangement of ED3 clusters on the dengue (DENV) viral surface.
+We show that this structure is a potent viral inhibitor and that it can act as a sensor by including a fluorescent output to report binding.
+Our molecular-platform design strategy could be adapted to detect and combat other disease-causing pathogens by generating the requisite ligand patterns on customized DNA nanoarchitectures.
+The common route of A. phagocytophilum transmission is through a tick bite, the main vector in Europe being Ixodes ricinus.
+Despite the apparently ubiquitous presence of the pathogen A. phagocytophilum in ticks and various wild and domestic animals from Europe, up to date published clinical cases of human granulocytic anaplasmosis (HGA) remain rare compared to the worldwide status.
+It is unclear if this reflects the epidemiological dynamics of the human infection in Europe or if the disease is underdiagnosed or underreported.
+Epidemiologic studies in Europe have suggested an increased occupational risk of infection for forestry workers, hunters, veterinarians, and farmers with a tick-bite history and living in endemic areas.
+Although the overall genetic diversity of A. phagocytophilum in Europe is higher than in the USA, the strains responsible for the human infections are related on both continents.
+However, the study of the genetic variability and assessment of the difference of pathogenicity and infectivity between strains to various hosts has been insufficiently explored to date.
+Most of the European HGA cases presented as a mild infection, common clinical signs being pyrexia, headache, myalgia and arthralgia.
+The diagnosis of HGA in the USA was recommended to be based on clinical signs and the patient’s history and later confirmed using specialized laboratory tests.
+However, in Europe since the majority of cases are presenting as mild infection, laboratory tests may be performed before the treatment in order to avoid antibiotic overuse.
+The drug of choice for HGA is doxycycline and because of potential for serious complication the treatment should be instituted on clinical suspicion alone.
+Tick-borne nairoviruses (order Bunyavirales) encode an ovarian tumor domain protease (OTU) that suppresses the innate immune response by reversing the post-translational modification of proteins by ubiquitin (Ub) and interferon-stimulated gene product 15 (ISG15).
+Ub is highly conserved across eukaryotes, whereas ISG15 is only present in vertebrates and shows substantial sequence diversity.
+Prior attempts to address the effect of ISG15 diversity on viral protein-ISG15 interactions have focused on only a single species’ ISG15 or a limited selection of nairovirus OTUs.
+To gain a more complete perspective of OTU-ISG15 interactions, we biochemically assessed the relative activities of 14 diverse nairovirus OTUs for 12 species’ ISG15 and found that ISG15 activity is predominantly restricted to particular nairovirus lineages reflecting, in general, known virus-host associations.
+To uncover the underlying molecular factors driving OTUs affinity for ISG15, X-ray crystal structures of Kupe virus and Ganjam virus OTUs bound to sheep ISG15 were solved and compared to complexes of Crimean-Congo hemorrhagic fever virus and Erve virus OTUs bound to human and mouse ISG15, respectively.
+Through mutational and structural analysis seven residues in ISG15 were identified that predominantly influence ISG15 species specificity among nairovirus OTUs.
+Additionally, OTU residues were identified that influence ISG15 preference, suggesting the potential for viral OTUs to adapt to different host ISG15s.
+These findings provide a foundation to further develop research methods to trace nairovirus-host relationships and delineate the full impact of ISG15 diversity on nairovirus infection.
+Failure to reproduce results from some scientific studies has raised awareness of the critical need for reproducibility in translational studies.
+Macroscopic and microscopic examination is a common approach to determine changes in tissues, but text descriptions and visual images have limitations for group comparisons.
+Semiquantitative scoring is a way of transforming qualitative tissue data into numerical data that allow more robust group comparisons.
+Semiquantitative scoring has broad uses in preclinical and clinical studies for evaluation of tissue lesions.
+Reproducibility can be improved by constraining bias through appropriate experimental design, randomization of tissues, effective use of multidisciplinary collaborations, and valid masking procedures.
+Scoring can be applied to tissue lesions (eg, size, distribution, characteristics) and also to tissues through evaluation of staining distribution and intensity.
+Semiquantitative scores should be validated to demonstrate relevance to biological data and to demonstrate observer reproducibility.
+Statistical analysis should make use of appropriate tests to give robust confidence in the results and interpretations.
+Following key principles of semiquantitative scoring will not only enhance descriptive tissue evaluation but also improve quality, reproducibility, and rigor of tissue studies.
+BACKGROUND: Herpesviridae reactivation among non-immunocompromised critically ill patients is associated with impaired prognosis, especially during acute respiratory distress syndrome (ARDS).
+However, little is known about herpes simplex virus (HSV) and Cytomegalovirus (CMV) reactivation occurring in patients with severe ARDS under veno-venous extracorporeal membrane oxygenation (ECMO).
+We tried to determine the frequency of Herpesviridae reactivation and its impact on patients’ prognosis during ECMO for severe ARDS.
+RESULTS: During a 5-year period, 123 non-immunocompromised patients with a severe ARDS requiring a veno-venous ECMO were included.
+Sixty-seven patients (54%) experienced HSV and/or CMV reactivation during ECMO course (20 viral co-infection, 40 HSV alone, and 7 CMV alone).
+HSV reactivation occurred earlier than CMV after the beginning of MV [(6–15) vs. 19 (13–29) days; p < 0.01] and after ECMO implementation [(2–8) vs. 14 (10–20) days; p < 0.01].
+In univariate analysis, HSV/CMV reactivation was associated with a longer duration of mechanical ventilation [(22–52.5) vs. 17.5 (9–28) days; p < 0.01], a longer duration of ECMO [15 (10–22.5) vs. 9 (5–14) days; p < 0.01], and a prolonged ICU [29 (19.5–47.5) vs. 16 (9–30) days; p < 0.01] and hospital stay [44 (29–63.5) vs. 24 (11–43) days; p < 0.01] as compared to non-reactivated patients.
+When considered separately, both HSV and CMV reactivation were associated with a longer duration of MV as compared to non-reactivation patients [29 (19.5–41) and 28 (20.5–37), respectively, vs. 17.5 (9–28) days; p < 0.05].
+Co-reactivation patients had a longer duration of MV [58.5 (38–72.3); p < 0.05] and ICU stay [51.5 (32.5–69) vs. 27.5 (17.75–35.5) and 29 (20–30.5), respectively] as compared to patients with HSV or CMV reactivation alone.
+In multivariate analysis, HSV reactivation remained independently associated with a longer duration of MV and hospital length of stay.
+CONCLUSIONS: Herpesviridae reactivation is frequent among patients with severe ARDS under veno-venous ECMO and is associated with a longer duration of mechanical ventilation.
+The direct causative link between HSV and CMV reactivation and respiratory function worsening under ECMO remains to be confirmed.
+Influenza is a major cause of morbidity and mortality worldwide, as well as in China.
+Knowledge of the spatial and temporal characteristics of influenza is important in evaluating and developing disease control programs.
+This study aims to describe an accurate spatiotemporal pattern of influenza at the prefecture level and explore the risk factors associated with influenza incidence risk in mainland China from 2005 to 2018.
+The incidence data of influenza were obtained from the Chinese Notifiable Infectious Disease Reporting System (CNIDRS).
+The Besag York Mollié (BYM) model was extended to include temporal and space-time interaction terms.
+The parameters for this extended Bayesian spatiotemporal model were estimated through integrated nested Laplace approximations (INLA) using the package R-INLA in R. A total of 702,226 influenza cases were reported in mainland China in CNIDRS from 2005–2018.
+The yearly reported incidence rate of influenza increased 15.6 times over the study period, from 3.51 in 2005 to 55.09 in 2008 per 100,000 populations.
+The temporal term in the spatiotemporal model showed that much of the increase occurred during the last 3 years of the study period.
+The risk factor analysis showed that the decreased number of influenza vaccines for sale, the new update of the influenza surveillance protocol, the increase in the rate of influenza A (H1N1)pdm09 among all processed specimens from influenza-like illness (ILI) patients, and the increase in the latitude and longitude of geographic location were associated with an increase in the influenza incidence risk.
+After the adjusting for fixed covariate effects and time random effects, the map of the spatial structured term shows that high-risk areas clustered in the central part of China and the lowest-risk areas in the east and west.
+The insufficient flu vaccine supplements, the newly emerging influenza A (H1N1)pdm09 and expansion of influenza surveillance efforts might be the major causes of the dramatic changes in outbreak and spatio-temporal epidemic patterns.
+Clusters of prefectures with high relative risks of influenza were identified in the central part of China.
+Future research with more risk factors at both national and local levels is necessary to explain the changing spatiotemporal patterns of influenza in China.
+Porcine epidemic diarrhea virus (PEDV) infection can induce intestinal dysfunction, resulting in severe diarrhea and even death, but the mode of action underlying these viral effects remains unclear.
+This study determined the effects of PEDV infection on intestinal absorption and the expression of genes for nutrient transporters via biochemical tests and microarray analysis.
+Sixteen 7-day-old healthy piglets fed a milk replacer were randomly allocated to one of two groups.
+After 5-day adaption, piglets (n = 8/group) were orally administrated with either sterile saline or PEDV (the strain from Yunnan province) at 10(4.5) TCID(50) (50% tissue culture infectious dose) per pig.
+All pigs were orally infused D-xylose (0.1 g/kg BW) on day 5 post PEDV or saline administration.
+One hour later, jugular vein blood samples as well as intestinal samples were collected for further analysis.
+In comparison with the control group, PEDV infection increased diarrhea incidence, blood diamine oxidase activity, and iFABP level, while reducing growth and plasma D-xylose concentration in piglets.
+However, PEDV administration increased mRNA levels for phosphoenolpyruvate carboxykinase 1, argininosuccinate synthase 1, sodium/glucose co-transporter-1, and cystic fibrosis transmembrane conductance regulator in the jejunum.
+Collectively, these comprehensive results indicate that PEDV infection induces intestinal injury and inhibits the expression of genes encoding for nutrient transporters.
+Chronic kidney disease is an epidemiologically identified risk factor for development of severe dengue in dengue-affected patients.
+However, available data on the immune pathogenesis in end stage renal disease (ESRD) patients affected by dengue is insufficient.
+We performed an in vitro study to evaluate the sequential immunological reactions and viral load in dengue virus type 2-infected mononuclear cells of patients with ESRD (n = 34) and in healthy controls (n = 30).
+The concentrations of interleukins (IL)-1 receptor antagonist (Ra), IL-2, IL-6, IL-8, IL-10, IL-12p40, granulocyte-macrophage colony-stimulating factor (GM-CSF), monocyte chemotactic protein-1 (MCP-1), macrophage inflammatory protein-1b (MIP-1b), vascular endothelial growth factor (VEGF), tumor necrosis factor (TNF)-α and viral load cycle threshold (Ct) were measured in the dengue virus type 2-infected mononuclear cells at 6 h, 24 h, 48 h, and 72 h post-infection.
+We found in the ESRD group significantly higher GM-CSF and IL-2 levels at 6 h post-infection.
+However, IL-8, IL-10, IL-12p40, TNF-α, MCP-1, and MIP-1b levels were found significantly lower than in the control group.
+At 24 h, 48 h, and 72 h post-infection, significantly lower levels of IL-1Ra, IL-6, IL-8, IL-10, IL-12p40, TNF-α, MCP-1, and MIP-1b were detected in ESRD group.
+Concentration of VEGF at 24 h and 48 h, and of GM-CSF at 48 h and 72 h were also found to be lower in ESRD group than in control group.
+Compared with controls, the viral load Ct values were significantly lower in ESRD group at 6 h and 24 h post-infection No significant difference in viral load Ct values between two groups was found at 48 h and 72 h post-infection.
+Our study discloses that the expression of immune mediators of dengue-infected mononuclear cells is impaired in ESRD patients.
+PURPOSE: To compare early changes in autonomic nervous system (ANS) tone between newborns with complex congenital heart disease (CHD) and newborns without CHD.
+METHODS: We performed a case–control study of heart rate variability (HRV) in newborns with complex CHD [transposition of the great arteries (TGA) or hypoplastic left heart syndrome (HLHS)] and low-risk control newborns without CHD.
+Cases with CHD were admitted following birth to a pediatric cardiac intensive care unit and had archived continuous ECG data.
+ECG data in cases and controls were analyzed for HRV in the time and frequency domains at 24 h of age.
+We analyzed the following HRV metrics: alpha short (α(s)), alpha long (α(L)), root mean square short and long (RMS(s) and RMS(L)), low-frequency (LF) power, normalized LF (nLF), high-frequency (HF) power, and normalized HF (nHF).
+We used ANOVA to compare HRV metrics between groups and to control for medication exposures.
+RESULTS: HRV data from 57 infants with CHD (TGA, n = 33 and HLHS, n = 24) and from 29 controls were analyzed.
+The HRV metrics α(S), RMS(L), LF, and nLF were significantly lower in infants with CHD than in the controls.
+Due to the effect of normalization, nHF was higher in CHD infants (P < 0.0001), although absolute HF was lower (P = 0.0461).
+After adjusting for medications, α(S) and nLF remained lower and nHF higher in newborns with CHD (P < 0.0005).
+CONCLUSIONS: Infants with complex CHD have depressed autonomic balance in the early postnatal period, which may complicate the fetal–neonatal transition.
+Aminopeptidase M (AMP) inhibition is of interest for several diseases, such as highly vascularized cancer types.
+Porcine AMP inhibition—a model for human AMP—activity was spectrophotometrically measured by the formation of p-nitroanilide from L-leucine-p-nitroanilide substrate by AMP.
+AMP inhibition by MG770 exhibited comparable inhibition levels to amastatin (IC(50) values: 1.20 ± 0.1 μM and 0.98 ± 0.1 μM, respectively), while MG756 was slightly less potent (with IC(50) values of 3.26 ± 0.5 μM).
+Molecular modelling suggests a potential binding mode, based on the interaction with the Zn(2+) cofactor, where MG770′s extra methyl group contributes to the disturbance of the Zn(2+) cofactor complex and highlights the importance of hydrophobicity for the site.
+Although random matching can improve the number of base pairs, these non-consecutive base pairs cannot make contributions to reduce the free energy.
+RESULT: In order to improve the efficiency of searching procedure, our algorithm take consecutive base pairs as the basic components.
+Firstly, our algorithm calculates and archive all the consecutive base pairs in triplet data structure, if the number of consecutive base pairs is greater than given minimum stem length.
+Secondly, the annealing schedule is adapted to select the optimal solution that has minimum free energy.
+CONCLUSION: The experimental results have been demonstrated to provide a competitive and oftentimes better performance when compared against some chosen state-of-the-art RNA structure prediction algorithms.
+BACKGROUND: Telocytes (TCs) are newly identified interstitial cells that participate in tissue protection and repair.
+The present study investigated the mechanisms underlying the protective effect of TCs in a mouse model of respiratory distress.
+METHODS: The mouse model of acute respiratory distress syndrome (ARDS) was established by intratracheal instillation of lipopolysaccharide (LPS).
+After instillation of TCs culture medium, lung injury was assessed, and angiogenesis markers, including CD31 and endothelial nitric oxide synthase (eNOS), were detected by immunofluorescence.
+Bioinformatics analysis was used to screen significantly differentially expressed microRNAs (miRNAs) in cultured TCs stimulated with LPS, and the regulation of downstream angiogenesis genes by these miRNAs was analysed and verified.
+PI3K subunits and pathways were evaluated by using a PI3K p110α inhibitor to study the involved mechanisms.
+RESULTS: In ARDS mice, instillation of TCs culture medium ameliorated LPS-induced inflammation and lung injury and increased the protein levels of CD31 and eNOS in the injured lungs.
+A total of 7 miRNAs and 1899 mRNAs were differentially regulated in TCs stimulated with LPS.
+Functional prediction analysis showed that the differentially expressed mRNAs were enriched in angiogenesis-related processes, which were highly correlated with miR-21a-3p.
+Culture medium from TCs with miR-21a-3p inhibition failed to promote angiogenesis in mouse models of LPS-induced ARDS.
+In cultured TCs, LPS stimulation upregulated the expression of miR-21a-3p, which further targeted the transcription factor E2F8 and decreased Notch2 protein expression.
+TCs culture medium enhanced hemangioendothelioma endothelial cells (EOMA cells) proliferation, which was blocked by the miR-21a-3p inhibitor.
+The PI3K p110α inhibitor decreased vascular endothelial growth factor levels in LPS-stimulated TCs and reversed the enhancing effect of TCs culture medium on EOMA cells proliferation.
+We monitored the survival of human pathogenic bacteria [Escherichia coli (ATCC), extended-spectrum β-lactamase-producing E. coli (Clinical isolate), New Delhi metallo-β-lactamase-producing E. coli (clinical isolate), Staphylococcus aureus (ATCC)] on dry materials (vinyl chloride, aluminum, plastic, stainless steel) at distinct temperatures (room temperature or 15°C–37°C).
+These bacteria favored a lower temperature for their prolonged survival on the dry fomites, regardless of the material type.
+Interestingly, when mixed with S. aureus, E. coli survived for a longer time at a lower temperature.
+Cardiolipin, which can promote the survival of S. aureus in harsh environments, had no effect on maintaining the survival of E. coli.
+Although the trends remained unchanged, adjusting the humidity from 40% to 60% affected the survival of bacteria on dry surfaces.
+Scanning electron microscopic analysis revealed no morphological differences in these bacteria immediately before or after one day of dry conditions.
+In addition, ATP assessment, a method used to visualize high-touch surfaces in hospitals, was not effective at monitoring bacterial dynamics.
+A specialized handrail device fitted with a heater, which was maintained at normal human body core temperature, successfully prohibited the prolonged survival of bacteria [Enterococcus faecalis (ATCC), E. coli (ATCC), Pseudomonas aeruginosa (ATCC), S. aureus (ATCC), Acinetobacter baumannii (clinical isolate), and Serratia marcescens (clinical isolate)], with the exception of spore-forming Bacillus subtilis (from our laboratory collection) and the yeast-like fungus Candida albicans (from our laboratory collection)] on dry surfaces.
+Taken together, we concluded that the tested bacteria favor lower temperatures for their survival in dry environments.
+Therefore, the thermal control of dry fomites has the potential to control bacterial survival on high-touch surfaces in hospitals.
+During the Ebola virus disease (EVD) epidemic in Western Africa (2013‒2016), antimalarial treatment was administered to EVD patients due to the high coexisting malaria burden in accordance with World Health Organization guidelines.
+In an Ebola treatment center in Liberia, EVD patients receiving the combination antimalarial artesunate-amodiaquine had a lower risk of death compared to those treated with artemether-lumefantrine.
+As artemether and artesunate are derivatives of artemisinin, the beneficial anti-Ebola virus (EBOV) effect observed could possibly be attributed to the change from lumefantrine to amodiaquine.
+Amodiaquine is a widely used antimalarial in the countries that experience outbreaks of EVD and, therefore, holds promise as an approved drug that could be repurposed for treating EBOV infections.
+We investigated the potential anti-EBOV effect of amodiaquine in a well-characterized nonhuman primate model of EVD.
+Using a similar 3-day antimalarial dosing strategy as for human patients, plasma concentrations of amodiaquine in healthy animals were similar to those found in humans.
+However, the treatment regimen did not result in a survival benefit or decrease of disease signs in EBOV-infected animals.
+While amodiaquine on its own failed to demonstrate efficacy, we cannot exclude potential therapeutic value of amodiaquine when used in combination with artesunate or another antiviral.
+Zika virus (ZIKV) infection is currently one of the major concerns in human public health due to its association with neurological disorders.
+Intensive effort has been implemented for the treatment of ZIKV, however there are not currently approved vaccines or antivirals available to combat ZIKV infection.
+In this sense, the identification of virulence factors associated with changes in ZIKV virulence could help to develop safe and effective countermeasures to treat ZIKV or to prevent future outbreaks.
+Here, we have compared the virulence of two related ZIKV strains from the recent outbreak in Brazil (2015), Rio Grande do Norte Natal (RGN) and Paraiba.
+In spite of both viruses being identified in the same period of time and region, significant differences in virulence and replication were observed using a validated mouse model of ZIKV infection.
+While ZIKV-RGN has a 50% mouse lethal dose (MLD(50)) of ~10(5) focus forming units (FFUs), ZIKV-Paraiba infection resulted in 100% of lethality with less than 10 FFUs.
+Combining deep-sequencing analysis and our previously described infectious ZIKV-RGN cDNA clone, we identified a natural polymorphism in the non-structural protein 2 A (NS2A) that increase the virulence of ZIKV.
+Moreover, results demonstrate that the single amino acid alanine to valine substitution at position 117 (A117V) in the NS2A was sufficient to convert the attenuated rZIKV-RGN in a virulent Paraiba-like virus (MLD(50) < 10 FFU).
+The mechanism of action was also evaluated and data indicate that substitution A117V in ZIKV NS2A protein reduces host innate immune responses and viral-induced apoptosis in vitro.
+Therefore, amino acid substitution A117V in ZIKV NS2A could be used as a genetic risk-assessment marker for future ZIKV outbreaks.
+BACKGROUND: Telocytes (TCs) have the capacity of cell–cell communication with adjacent cells within the tissue, contributing to tissue repair and recovery from injury.
+The present study aims at investigating the molecular mechanisms by which the TGFβ1-ITGB1-PI3K signal pathways regulate TC cycle and proliferation.
+METHODS: Gene expression of integrin (ITG) family were measured in mouse primary TCs to compare with other cells.
+TC proliferation, movement, cell cycle, and PI3K isoform protein genes were assayed in ITGB1-negative or positive mouse lung TCs treated with the inhibition of PI3Kp110α, PI3Kα/δ, PKCβ, or GSK3, followed by TGFβ1 treatment.
+RESULTS: We found the characters and interactions of ITG or PKC family member networks in primary mouse lung TCs, different from other cells in the lung tissue.
+The deletion of ITGB1 changed TCs sensitivity to treatment with multifunctional cytokines or signal pathway inhibitors.
+The compensatory mechanisms occur among TGFβ1-induced PI3Kp110α, PI3Kα/δ, PKCβ, or GSK3 when ITGB1 gene was deleted, leading to alterations of TC cell cycle and proliferation.
+Of those PI3K isoform protein genes, mRNA expression of PIK3CG altered with ITGB1-negative TC cycle and proliferation.
+CONCLUSION: TCs have strong capacity of proliferation through the compensatory signaling mechanisms and contribute to the development of drug resistance due to alterations of TC sensitivity.
+Pre-emptive vaccination is regarded as one of the most protective measures to control influenza outbreak.
+There are mainly two types of influenza viruses—influenza A and B with several subtypes—that are commonly found to circulate among humans.
+The traditional trivalent (TIV) flu vaccine targets two strains of influenza A and one strain of influenza B.
+The quadrivalent (QIV) vaccine targets one extra B virus strain that ensures better protection against influenza; however, the use of QIV vaccine can be costly, hence impose an extra financial burden to society.
+This article endeavours to explain such a dilemma through the framework of a vaccination game, where individuals can opt for one of the three options: choose either of QIV or TIV vaccine or none.
+Our approach presumes a mean-field framework of a vaccination game in an infinite and well-mixed population, entangling the disease spreading process of influenza with the coevolution of two types of vaccination decision-making processes taking place before an epidemic season.
+The dynamics of a spreadable disease are largely governed by four factors: proactive vaccination, retroactive treatment, individual decisions, and the prescribing behaviour of physicians.
+Under the imposed vaccination policy and antiviral treatment in society, complex factors (costs and expected effects of the vaccines and treatments, and fear of being infected) trigger an emulous situation in which individuals avoid infection by the pre-emptive or ex post provision.
+Aside from the established voluntary vaccination game, we propose a treatment game model associated with the resistance evolution of antiviral/antibiotic overuse.
+Moreover, the imperfectness of vaccinations has inevitably led to anti-vaccine behaviour, necessitating a proactive treatment policy.
+However, under the excessively heavy implementation of treatments such as antiviral medicine, resistant strains emerge.
+The model explicitly exhibits a dual social dilemma situation, in which the treatment behaviour changes on a local time scale, and the vaccination uptake later evolves on a global time scale.
+The impact of resistance evolution and the coexistence of dual dilemmas are investigated by the control reproduction number and the social efficiency deficit, respectively.
+Our investigation might elucidate the substantial impacts of both vaccination and treatment in the framework of epidemic dynamics, and hence suggest the appropriate use of antiviral treatment.
+In a recent randomized controlled trial (Dexmedetomidine for Sepsis in Intensive Care Unit (ICU) Randomized Evolution [DESIRE]), we demonstrated that dexmedetomidine was associated with reduced mortality risk among patients with severe sepsis.
+We performed this exploratory sub-analysis to examine the mechanism underlying improved survival in patients sedated with dexmedetomidine.
+METHODS: The DESIRE trial compared a sedation strategy with and without dexmedetomidine among 201 mechanically ventilated adult patients with sepsis across eight ICUs in Japan.
+In the present study, we included 104 patients with Acute Physiology and Chronic Health Evaluation II (APACHE II) scores of ≥ 23 (54 in the dexmedetomidine [DEX] group and 50 in the non-dexmedetomidine [non-DEX] group).
+Initially, we compared the changes in the sequential organ failure assessment (SOFA) scores from the baseline within 6 days after randomization between groups.
+Subsequently, we evaluated the variables comprising the organ component of the SOFA score that showed relevant improvement in the initial comparison.
+There was no difference in the median APACHE II score between the two groups (29 [interquartile range (IQR), 25–31] vs. 30 [IQR, 25–33]; p = 0.35).
+The median SOFA score at the baseline was lower in the DEX group (9 [IQR, 7–11] vs. 11 [IQR, 9–13]; p = 0.01).
+While the renal SOFA subscore at the baseline was similar for both groups, it significantly decreased in the DEX group on day 4 (p = 0.02).
+During the first 6 days, the urinary output was not significantly different (p = 0.09), but serum creatinine levels were significantly lower (p = 0.04) in the DEX group.
+The 28-day and in-hospital mortality rates were significantly lower in the DEX group (22% vs. 42%; p = 0.03, 28% vs. 52%; p = 0.01, respectively).
+CONCLUSION: A sedation strategy with dexmedetomidine is associated with improved renal function and decrease mortality rates among patients with severe sepsis.
+BACKGROUND: Global end-diastolic volume (GEDV) measured by transpulmonary thermodilution is regarded as indicator of cardiac preload.
+A bolus of cold saline injected in a central vein travels through the heart and lung, but also the aorta until detection in a femoral artery.
+While it is well accepted that injection in the inferior vena cava results in higher values, the impact of the aortic volume on GEDV is unknown.
+In this study, we hypothesized that a larger aortic volume directly translates to a numerically higher GEDV measurement.
+METHODS: We retrospectively analyzed data from 88 critically ill patients with thermodilution monitoring and who did require a contrast-enhanced thoraco-abdominal computed tomography scan.
+Per milliliter increase of the aortic volume, we found a GEDV increase by 3.0 ml (95% CI 2.0 to 4.1 ml, p < 0.001).
+In case a femoral central venous line was used for saline bolus injection, GEDV raised additionally by 2.1 ml (95% CI 0.5 to 3.7 ml, p = 0.01) per ml volume of the vena cava inferior.
+When aortic volume was included in multivariate regression, GEDV variance was unaffected by sex, age, body height, and weight.
+CONCLUSIONS: Our results suggest that the aortic volume is a substantial confounding variable for GEDV measurements performed with transpulmonary thermodilution.
+As the aorta is anatomically located after the heart, GEDV should not be considered to reflect cardiac preload.
+BACKGROUND: Human metapneumovirus (HMPV) is an important cause of acute respiratory illness in young children.
+Whole genome sequencing enables better identification of transmission events and outbreaks, which is not always possible with sub-genomic sequences.
+RESULTS: We report a 2-reaction amplicon-based next generation sequencing method to determine the complete genome sequences of five HMPV strains, representing three subgroups (A2, B1 and B2), directly from clinical samples.
+In addition to reporting five novel HMPV genomes from Africa we examined genetic diversity and sequence patterns of publicly available HMPV genomes.
+We found that the overall nucleotide sequence identity was 71.3 and 80% for HMPV group A and B, respectively, the diversity between HMPV groups was greater at amino acid level for SH and G surface protein genes, and multiple subgroups co-circulated in various countries.
+Comparison of sequences between HMPV groups revealed variability in G protein length (219 to 241 amino acids) due to changes in the stop codon position.
+Genome-wide phylogenetic analysis showed congruence with the individual gene sequence sets except for F and M2 genes.
+BACKGROUND: Antimicrobial resistance (AMR) compromises the treatment of patients with serious infections in intensive care units (ICUs), and intensive care physicians are increasingly facing patients with bacterial infections with limited or no adequate therapeutic options.
+A survey was conducted to assess the intensive care physicians’ perception of the AMR situation in the European Union/European Economic Area (EU/EEA).
+METHODS: Between May and July 2017, physicians working in European ICUs were invited to complete an online questionnaire hosted by the European Society of Intensive Care Medicine.
+The survey included 20 questions on hospital and ICU characteristics, frequency of infections with multidrug-resistant (MDR) bacteria and relevance of AMR in the respondent’s ICU, management of antimicrobial treatment as well as the use of last-line antibiotics in the six months preceding the survey.
+For the analysis of regional differences, EU/EEA countries were grouped into the four sub-regions of Eastern, Northern, Southern and Western Europe.
+Infections with MDR bacteria in their ICU were rated as a major problem by 257 (24.2%), moderate problem by 360 (33.9%) and minor problem by 391 (36.8%) respondents.
+Third-generation cephalosporin-resistant Enterobacteriaceae were the most frequently encountered MDR bacteria followed by, in order of decreasing frequency, meticillin-resistant Staphylococcus aureus, carbapenem-resistant Enterobacteriaceae, carbapenem-resistant Pseudomonas aeruginosa and vancomycin-resistant enterococci.
+Perception of the relevance of the AMR problem and the frequency of specific MDR bacteria varied by European sub-region.
+Bacteria resistant to all or almost all available antibiotics were encountered by 132 (12.4%) respondents.
+CONCLUSIONS: The percentage of European ICU physicians perceiving AMR as a substantial problem in their ICU is high with variation by sub-region in line with epidemiological studies.
+The reports of bacteria resistant to almost all available antibiotics and the limited availability of last-line antibiotics in ICUs in the EU/EEA are of concern.
+Glycoconjugate vaccines based on bacterial capsular polysaccharides (CPS) have been extremely successful in preventing bacterial infections.
+The glycan antigens for the preparation of CPS based glycoconjugate vaccines are mainly obtained from bacterial fermentation, the quality and length of glycans are always inconsistent.
+Such kind of situation make the CMC of glycoconjugate vaccines are difficult to well control.
+The well controlled glycan antigens are more easily to obtain, and them are conjugated to carrier protein to from the so-call homogeneous fully synthetic glycoconjugate vaccines.
+Several fully glycoconjugate vaccines are in different phases of clinical trial for bacteria or cancers.
+BACKGROUND: Acute kidney injury (AKI) is a common complication in burn patients admitted to the intensive care unit (ICU) associated with increased morbidity and mortality.
+Our primary aim was to review incidence, risk factors, and outcomes of AKI in burn patients admitted to the ICU.
+Secondary aims were to review the use of renal replacement therapy (RRT) and impact on health care costs.
+METHODS: We conducted a systematic search in PubMed, UpToDate, and NICE through 3 December 2018.
+All reviews in Cochrane Database of Systematic Reviews except protocols were added to the PubMed search.
+We searched for studies on AKI according to Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease (RIFLE); Acute Kidney Injury Network (AKIN); and/or Kidney Disease: Improving Global Outcomes (KDIGO) criteria in burn patients admitted to the ICU.
+We collected data on AKI incidence, risk factors, use of RRT, renal recovery, length of stay (LOS), mortality, and health care costs.
+Random effect model meta-analysis revealed that the incidence of AKI among burn patients in the ICU was 38 (30–46) %.
+Patients with AKI were almost evenly distributed in the mild, moderate, and severe AKI subgroups.
+Risk factors for AKI were high age, chronic hypertension, diabetes mellitus, high Total Body Surface Area percent burnt, high Abbreviated Burn Severity Index score, inhalation injury, rhabdomyolysis, surgery, high Acute Physiology and Chronic Health Evaluation II score, high Sequential Organ Failure Assessment score, sepsis, and mechanical ventilation.
+AKI patients had 8.6 (4.0–13.2) days longer ICU LOS and higher mortality than non-AKI patients, OR 11.3 (7.3–17.4).
+CONCLUSIONS: AKI occurred in 38% of burn patients admitted to the ICU, and 12% of all patients received RRT.
+Protective vaccines require the induction of antigen-specific CD4(+) T cells via mycobacterial peptides presented by MHC class-II in infected macrophages.
+In order to identify mycobacterial antigens bound to MHC, we have immunoprecipitated MHC class-I and class-II complexes from THP-1 macrophages infected with BCG, purified MHC class-I and MHC class-II peptides and analysed them by liquid chromatography tandem mass spectrometry.
+We have successfully identified 94 mycobacterial peptides presented by MHC-II and 43 presented by MHC-I, from 76 and 41 antigens, respectively.
+Gene ontology analysis suggests most of these antigens are associated with membranes and involved in lipid biosynthesis and transport.
+The sequences of selected peptides were confirmed by spectral match validation and immunogenicity evaluated by IFN-gamma ELISpot against peripheral blood mononuclear cell from volunteers vaccinated with BCG, M.tb latently infected subjects or patients with tuberculosis disease.
+Three antigens were expressed in viral vectors, and evaluated as vaccine candidates alone or in combination in a murine aerosol M.tb challenge model.
+When delivered in combination, the three candidate vaccines conferred significant protection in the lungs and spleen compared with BCG alone, demonstrating proof-of-concept for this unbiased approach to identifying new candidate antigens.
+A wide range of cancer immunotherapy approaches has been developed including non-specific immune-stimulants such as cytokines, cancer vaccines, immune checkpoint inhibitors (ICIs), and adoptive T cell therapy.
+Since 2011, these drugs have received marketing authorisation for melanoma, lung, bladder, renal, and head and neck cancers, with remarkable and long-lasting treatment response in some patients.
+The novel mechanism of action of ICIs, with immune and T cell activation, leads to unusual patterns of response on imaging, with the advent of so-called pseudoprogression being more pronounced and frequently observed when compared to other anticancer therapies.
+Pseudoprogression, described in about 2–10% of patients treated with ICIs, corresponds to an increase of tumour burden and/or the appearance of new lesions due to infiltration by activated T cells before the disease responds to therapy.
+To overcome the limitation of response evaluation criteria in solid tumors (RECIST) to assess these specific changes, new imaging criteria—so-called immune-related response criteria and then immune-related RECIST (irRECIST)—were proposed.
+The major modification involved the inclusion of the measurements of new target lesions into disease assessments and the need for a 4-week re-assessment to confirm or not confirm progression.
+This paper reviews current immunotherapeutic approaches and summarises radiologic criteria to evaluate new patterns of response to immunotherapy.
+Furthermore, imaging features of immunotherapy-related adverse events and available predictive biomarkers of response are presented.
+BACKGROUND: An efficient surface cleaning strategy would first target cleaning to surfaces that make large contributions to the risk of infections.
+METHODS: In this study, we used data from the literature about methicillin-resistant Staphylococcus aureus (MRSA) and developed an ordinary differential equations based mathematical model to quantify the impact of contact heterogeneity on MRSA transmission in a hypothetical 6-bed intensive care unit (ICU).
+The susceptible patients are divided into two types, these who are cared by the same nurse as the MRSA infected patient (Type 1) and these who are not (Type 2).
+RESULTS: The results showed that the mean MRSA concentration on three kinds of susceptible patient nearby surfaces was significantly linearly associated with the hand-touch frequency (p < 0.05).
+The noncompliance of daily cleaning on patient nearby high-touch surfaces (HTSs) had the most impact on MRSA transmission.
+If the HTSs were not cleaned, the MRSA exposure to Type 1 and 2 susceptible patients would increase 118.4% (standard deviation (SD): 33.0%) and 115.4% (SD: 30.5%) respectively.
+The communal surfaces (CSs) had the least impact, if CSs were not cleaned, the MRSA exposure to Type 1 susceptible patient would only increase 1.7% (SD: 1.3).
+If the CE was not cleaned, the exposure to Type 1 patients would only increase 8.4% (SD: 3.0%), while for Type 2 patients, it can increase 70.4% (SD: 25.4%).
+CONCLUSIONS: This study provided a framework to study the pathogen concentration dynamics on environmental surfaces and quantitatively showed the importance of cleaning patient nearby HTSs on controlling the nosocomial infection transmission via contact route.
+BACKGROUND: General self-efficacy is considered one of the most influential parameters affecting the quality of clinical practice and nurses’ perceived professional benefits (NPPB).
+Perceived organizational support (POS) is regarded as being central in understanding job-related attitudes, and it is important to enhance POS for nurses to maintain their current employment.
+Many studies have explored the relationships among general self-efficacy, POS, nursing practice environment (NPE) and NPPB.
+However, a moderating effect of NPE has not been fully explored in nurses, especially among paediatric nurses.
+METHODS: A descriptive cross-sectional study was conducted from July to October 2018 with 300 paediatric nurses from 3 Class A tertiary hospitals in Jilin Province.
+The respondents completed the General Self-Efficacy Scale, Perceived Organizational Support Scale, Practice Environment Scale and Nurses’ Perceived Professional Benefits Scale.
+RESULTS: General self-efficacy and POS were significantly positively associated with NPPB, which showed that the model had a good fit to the data.
+NPE was found to play a partial mediating role between POS and NPPB and also had a complete mediating role between general self-efficacy and NPPB.
+CONCLUSIONS: The results suggest that general self-efficacy indirectly influences NPPB, and POS directly and indirectly influences NPPB by NPE.
+Effective measures should be taken to improve nurses’ practice environment in hospitals to raise nurses’ enthusiasm and confidence in their work.
+BACKGROUND: We aimed to compare the clinical characteristics of patients with community-acquired pneumonia (CAP), healthcare-associated pneumonia (HCAP), and hospital-acquired pneumonia (HAP) caused by Klebsiella pneumoniae and analyze the antimicrobial resistance and proportion of hypervirluent strains of the microbial isolates.
+METHODS: We conducted a retrospective study on patients with pneumonia caused by K. pneumoniae at the Taipei Veterans General Hospital in Taiwan between January 2014 and December 2016.
+To analyze the clinical characteristics of these patients, data was extracted from their medical records.
+K. pneumoniae strains were subjected to antimicrobial susceptibility testing, capsular genotyping and detection of the rmpA and rmpA2 genes to identify hypervirulent strains.
+RESULTS: We identified 276 patients with pneumonia caused by K. pneumoniae, of which 68 (24.6%), 74 (26.8%), and 134 (48.6%) presented with CAP, HCAP, and HAP, respectively.
+The 28-day mortality was highest in the HAP group (39.6%), followed by the HCAP (29.7%) and CAP (27.9%) groups.
+The HAP group also featured the highest proportion of multi-drug resistant strains (49.3%), followed by the HCAP (36.5%) and CAP groups (10.3%), while the CAP group had the highest proportion of hypervirulent strains (79.4%), followed by the HCAP (55.4%) and HAP groups (41.0%).
+Hypervirulent strains were prevalent in all 3 groups of pneumonia patients, even in those with HAP.
+OBJECTIVE: To describe the epidemiology of carbapenem-resistant Enterobacteriaceae (CRE) healthcare-associated infections (HAI) in Egyptian hospitals reporting to the national HAI surveillance system.
+METHODS: Design: Descriptive analysis of CRE HAIs and retrospective observational cohort study using national HAI surveillance data.
+The patient population included patients admitted to the intensive care unit (ICU) in participating hospitals.
+Enterobacteriaceae HAI cases were Klebsiella, Escherichia coli, and Enterobacter isolates from blood, urine, wound or respiratory specimen collected on or after day 3 of ICU admission.
+For CRE HAI cases reported during 2011–2017, a hospital-level and patient-level analysis were conducted using only the first CRE isolate by pathogen and specimen type for each patient.
+For facility, microbiology, and clinical characteristics, frequencies and means were calculated among CRE HAI cases and compared with carbapenem-susceptible Enterobacteriaceae HAI cases through univariate and multivariate logistic regression using STATA 13.
+The multivariate regression analysis demonstrated that carbapenem resistance was associated with specimen type, pathogen, location prior to admission, and length of ICU stay.
+Between 2011 and 2017, there was an increase in the proportion of Enterobacteriaceae HAI cases due to CRE (p-value = 0.003) and the incidence of CRE HAIs (p-value = 0.09).
+CONCLUSIONS: This analysis demonstrated a high and increasing burden of CRE in Egyptian hospitals, highlighting the importance of enhancing infection prevention and control (IPC) programs and antimicrobial stewardship activities and guiding the implementation of targeted IPC measures to contain CRE in Egyptian ICU’s .
+BACKGROUND: Although the prediction of renal prognosis in patients with IgA vasculitis with nephritis (IgAVN) is important, the association between gastrointestinal bleeding (GIB) and its renal prognosis is unknown.
+This study investigated the effect of GIB on the progression to end‐stage kidney disease (ESKD) in patients with IgAVN.
+METHODS: We compared the clinicopathological findings at diagnosis, therapy, and clinical outcomes between 10 patients with GIB and 20 patients without GIB in 30 patients with IgAVN aged ≥18 years at the renal biopsy.
+The outcomes and factors affecting the progression to ESKD were evaluated using the Kaplan‐Meier method with log‐rank test and Cox proportional hazards models.
+RESULTS: End‐stage kidney disease, clinical remission, and deaths from any related cause occurred in 6, 17, and 2 patients, respectively.
+In Kaplan‐Meier analyses, the GIB group showed a higher incidence of ESKD (50% vs 5%, P = .003) and a lower incidence of clinical remission (20% vs 75%, P = .003).
+Although the numbers were not statistically significant, this group tended to have a greater number of deaths than the non‐GIB group (7% vs 0%, P = .07).
+In a multivariable Cox model adjusted for hypertension and urinary proteinuria, GIB could not demonstrate a significant association with ESKD (hazard ratio, 4.51; 95% confidence interval, 0.39‐52.7; P = .23).
+CONCLUSION: IgAVN with GIB has worse renal outcome, but GIB does not have a statistically significant association with progression to ESKD.
+Viruses have been infecting their host cells since the dawn of life, and this extremely long-term coevolution gave rise to some surprising consequences for the entire tree of life.
+It is hypothesised that viruses might have contributed to the formation of the first cellular life form, or that even the eukaryotic cell nucleus originates from an infection by a coated virus.
+The continuous struggle between viruses and their hosts to maintain at least a constant fitness level led to the development of an unceasing arms race, where weapons are often shuttled between the participants.
+In this literature review we try to give a short insight into some general consequences or traits of virus–host coevolution, and after this we zoom in to the viral clades of adenoviruses, herpesviruses, nucleo-cytoplasmic large DNA viruses, polyomaviruses and, finally, circoviruses.
+Mammalian asparagine endopeptidase (AEP) is a cysteine protease that cleaves its protein substrates on the C-terminal side of asparagine residues.
+Converging lines of evidence indicate that AEP may be involved in the pathogenesis of several neurological diseases, including Alzheimer’s disease, Parkinson’s disease, and frontotemporal dementia.
+AEP is activated in the aging brain, cleaves amyloid precursor protein (APP) and promotes the production of amyloid-β (Aβ).
+We renamed AEP to δ-secretase to emphasize its role in APP fragmentation and Aβ production.
+AEP also cleaves other substrates, such as tau, α-synuclein, SET, and TAR DNA-binding protein 43, generating neurotoxic fragments and disturbing their physiological functions.
+Here, we review the recent advances in the role of δ-secretase in neurodegenerative diseases, with a focus on its biochemical properties and the transcriptional and posttranslational regulation of its activity, and discuss the clinical implications of δ-secretase as a diagnostic biomarker and therapeutic target for neurodegenerative diseases.
+Among eight viral RNA segments, the multiple functions of nucleoprotein (NP) play important roles in viral replication and transcription.
+METHODS: To understand how NP contributes to the virus evolution, we analyzed the NP gene of H3N2 viruses in Taiwan and 14,220 NP sequences collected from Influenza Research Database.
+The identified genetic variations were further analyzed by mini-genome assay, virus growth assay, viral RNA and protein expression as well as ferret model to analyze their impacts on viral replication properties.
+RESULTS: The NP genetic analysis by Taiwan and global sequences showed similar evolution pattern that the NP backbones changed through time accompanied with specific residue substitutions from 1999 to 2018.
+Other than the conserved residues, fifteen sporadic substitutions were observed in which the 31R, 377G and 450S showed higher frequency.
+We found 31R and 450S decreased polymerase activity while the dominant residues (31 K and 450G) had higher activity.
+The 31 K and 450G showed better viral translation and replication in vitro and in vivo.
+CONCLUSIONS: These findings indicated variations identified in evolution have roles in modulating viral replication in vitro and in vivo.
+This study demonstrates that the interaction between variations of NP during virus evolution deserves future attention.
+BACKGROUND: Heart failure (HF) has been recognized as a global pandemic with a high rate of hospitalization, morbidity, and mortality.
+Although numerous advances have been made, its representative molecular signatures remain largely unknown, especially the role of genes in HF progression.
+The aim of the present prospective follow-up study was to reveal potential biomarkers associated with the progression of heart failure.
+METHODS: We generated multi-level transcriptomic data from a cohort of left ventricular heart tissue collected from 21 HF patients and 9 healthy donors.
+By using Masson staining to calculate the fibrosis percentage for each sample, we applied lasso regression model to identify the genes associated with fibrosis as well as progression.
+The genes were further validated by immunohistochemistry (IHC) staining in the same cohort and qRT-PCR using another independent cohort (20 HF and 9 healthy donors).
+Enzyme-linked immunosorbent assay (ELISA) was used to measure the plasma level in a validation cohort (139 HF patients) for predicting HF progression.
+RESULTS: Based on the multi-level transcriptomic data, we examined differentially expressed genes [mRNAs, microRNAs, and long non-coding RNAs (lncRNAs)] in the study cohort.
+The follow-up functional annotation and regulatory network analyses revealed their potential roles in regulating extracellular matrix.
+By using the survival time before transplantation, COL1A1 was identified as a potential biomarker for HF progression and its upregulation was confirmed by both IHC and qRT-PCR.
+Furthermore, COL1A1 content ≥ 256.5 ng/ml in plasma was found to be associated with poor survival within 1 year of heart transplantation from heart failure [hazard ratio (HR) 7.4, 95% confidence interval (CI) 3.5 to 15.8, Log-rank p value < 1.0 × 10(− 4)].
+CONCLUSIONS: Our results suggested that COL1A1 might be a plasma biomarker of HF and associated with HF progression, especially to predict the 1-year survival from HF onset to transplantation.
+Modern societies are exposed to a myriad of risks ranging from disease to natural hazards and technological disruptions.
+Exploring how the awareness of risk spreads and how it triggers a diffusion of coping strategies is prominent in the research agenda of various domains.
+It requires a deep understanding of how individuals perceive risks and communicate about the effectiveness of protective measures, highlighting learning and social interaction as the core mechanisms driving such processes.
+Methodological approaches that range from purely physics-based diffusion models to data-driven environmental methods rely on agent-based modeling to accommodate context-dependent learning and social interactions in a diffusion process.
+However, little attention has been paid to the role of intelligent learning in risk appraisal and protective decisions, whether used in an individual or a collective process.
+The differences between collective learning and individual learning have not been sufficiently explored in diffusion modeling in general and in agent-based models of socio-environmental systems in particular.
+To address this research gap, we explored the implications of intelligent learning on the gradient from individual to collective learning, using an agent-based model enhanced by machine learning.
+Our simulation experiments showed that individual intelligent judgement about risks and the selection of coping strategies by groups with majority votes were outperformed by leader-based groups and even individuals deciding alone.
+The choice of how to represent social learning in an agent-based model could be driven by existing cultural and social norms prevalent in a modeled society.
+However, improperly set mechanical ventilation can further increase the risk of death in patients with ARDS.
+Recent studies suggest that ventilation-induced lung injury (VILI) is caused by exaggerated regional lung strain, particularly in areas of alveolar instability subject to tidal recruitment/derecruitment and stress-multiplication.
+Thus, it is reasonable to expect that if a ventilation strategy can maintain stable lung inflation and homogeneity, regional dynamic strain would be reduced and VILI attenuated.
+A time-controlled adaptive ventilation (TCAV) method was developed to minimize dynamic alveolar strain by adjusting the delivered breath according to the mechanical characteristics of the lung.
+The goal of this review is to describe how the TCAV method impacts pathophysiology and protects lungs with, or at high risk of, acute lung injury.
+We present work from our group and others that identifies novel mechanisms of VILI in the alveolar microenvironment and demonstrates that the TCAV method can reduce VILI in translational animal ARDS models and mortality in surgical/trauma patients.
+Our TCAV method utilizes the airway pressure release ventilation (APRV) mode and is based on opening and collapsing time constants, which reflect the viscoelastic properties of the terminal airspaces.
+Time-controlled adaptive ventilation uses inspiratory and expiratory time to (1) gradually “nudge” alveoli and alveolar ducts open with an extended inspiratory duration and (2) prevent alveolar collapse using a brief (sub-second) expiratory duration that does not allow time for alveolar collapse.
+The new paradigm in TCAV is configuring each breath guided by the previous one, which achieves real-time titration of ventilator settings and minimizes instability induced tissue damage.
+This novel methodology changes the current approach to mechanical ventilation, from arbitrary to personalized and adaptive.
+The outcome of this approach is an open and stable lung with reduced regional strain and greater lung protection.
+BACKGROUND: There have been no systematic studies of microbiological differences before and after antibiotics treatment.
+The aim of this study was to evaluate the effect of prior receipt of antibiotics on the microorganism distribution.
+METHODS: A retrospective, observational cohort study was conducted in a 3200-bed tertiary, referral, teaching hospital in eastern China.
+During a 2-year period, all hospitalized patients treated with antimicrobial agents were enrolled in this study.
+Among 48,692 patients evaluated, the 27,792 (57.1%) who were sampled within 2 days before or after administration of the first dose of antimicrobial agents were included.
+Distribution of clinical specimens and the microorganism were compared between before and after antibiotic drug treatment groups.
+RESULTS: Compared to specimens taken after antibiotics exposure, specimens taken before antibiotics exposure had a higher proportion of blood and urine specimens and a higher culture positive rate (all P < 0.001).
+Higher percentages of Staphylococcus aureus (9.9% vs. 8.5%, P = 0.041), non-fermenting bacteria (27.7% vs. 19.9%, P < 0.001), and fungi (8.4% vs. 4.0%, P < 0.001) were isolated from the group after antibiotics exposure, while the percentages of Streptococcus spp.
+(4.8% vs. 2.7%, P < 0.001), Haemophilus influenzae (2.3% vs. 0.8%, P < 0.001), and Moraxella catarrhalis (0.7% vs. 0.1%, P < 0.001) were higher in the group before antibiotics exposure.
+Further analysis found significant differences of microbes derived from respiratory secretions, blood or urine samples.
+We found, after antibiotics exposure, the separation rate of non-fermenting bacteria was significantly increased (all P < 0.05), and the separation rate of Candida spp.
+was higher, with statistical significance in airway secretion and urine samples (both P < 0.05), but the separation rate of Staphylococcus aureus among the three groups was not affected by antibiotics.
+Interestingly, no statistical difference was found for microbes isolated from body fluid specimens between the two groups.
+CONCLUSIONS: The outcome revealed that antibiotic-insensitive organisms such as non-fermentative bacteria and fungi were more frequently isolated after antibiotics exposure.
+However, this trend might be specimen dependent and was not obvious in body fluid specimens.
+BACKGROUND: In pediatric cardiac anesthesiology, there is increased focus on minimizing morbidity, ensuring optimal functional status, and using health care resources sparingly.
+One aspect of care that has potential to affect all of the above is postoperative mechanical ventilation.
+Ironically, it is recognized that mechanical ventilation may increase risk of adverse outcomes in the postoperative period.
+Hence, many institutions have advocated for immediate extubation or early extubation after many congenital heart surgeries which was first reported decades ago.
+METHODS: 637 consecutive patient charts were reviewed for pediatric patients undergoing cardiac surgery with cardiopulmonary bypass.
+Those that were extubated in the operating room (OR) at the conclusion of surgery (Immediate Extubation or IE), those that were extubated within six hours of admission to the ICU (Early Extubation or EE) and those that were extubated sometime after six hours (Delayed Extubation or DE).
+Multiple variables were then recorded to see which factors correlated with successful Immediate or Early Extubation.
+RESULTS: Overall, 338 patients (53.1%) had IE), 273 (42.8%) had DE while only 26 patients (4.1%) had EE.
+The median age was 1174 days for the IE patients, 39 days for the DE patients, whereas 194 days for EE patients (p < 0.001).
+Weight and length were also significantly different in at least one extubation group from the other two (p < 0.001).
+The median ICU LOS was 3 and 4 days for IE and EE patients respectively, whereas it was 9.5 days for DE patients (p < 0.001).
+DE group had a significant longer median anesthesia time and cardiopulmonary bypass time than the other two extubation groups (p > 63,826.88 < 0.001).
+Regional low flow perfusion, deep hypothermia, deep hypothermic circulatory arrest, redo sternotomy, use of other sedatives, furosemide, epinephrine, vasopressin, open chest, cardiopulmonary support, pulmonary edema, syndrome, as well as difficult intubation were significantly associated with delayed extubation (IE, EE or DE).
+CONCLUSIONS: Immediate and early extubation was significantly associated with several factors, including patient age and size, duration of CPB, use of certain anesthetic drugs, and the amount of blood loss and blood replacement.
+IE can be successfully accomplished in a majority of pediatric patients undergoing surgery for congenital heart disease, including in a minority of infants.
+BACKGROUND: Vaccines are the most reliable alternative to elicit sterile immunity against malaria but their development has been hindered by polymorphisms and strain-specificity in previously studied antigens.
+Highly conserved Plasmodium falciparum reticulocyte-binding protein homologue-5 (PfRH5) has been identified as a potential candidate for anti-disease vaccine development.
+However, there is paucity of data on the extent of genetic variations on PfRH5 in field isolates of Plasmodium falciparum.
+This study described genetic polymorphisms at the high affinity binding polypeptides (HABPs) 36718, 36727, 36728 of PfRH5 in Nigerian isolates of P. falciparum.
+This study tested the hypothesis that only specific conserved B and T cell epitopes on PfRH5 HABPs are crucial for vaccine development.
+METHODS: One hundred and ninety-five microscopically confirmed P. falciparum samples collected in a prospective cross-sectional study of three different populations in Lagos, Nigeria.
+Tajima’s D and the ratio of nonsynonymous vs synonymous mutations were utilized to estimate the extent of balancing and directional selection in the pfrh5 gene.
+RESULTS: Sequence analysis revealed three haplotypes of PfRH5 with negative Tajima’s D and dN/dS value of − 1.717 and 0.011 ± 0.020, respectively.
+A single nucleotide polymorphism, SNP (G → A) at position 608 was observed, which resulted in a change of the amino acid cysteine at position 203 to tyrosine.
+Haplotype and nucleotide diversities were 0.318 ± 0.016 and 0.0046 ± 0.0001 while inter-population genetic differentiation ranged from 0.007 to 0.037.
+Five polypeptide variants were identified, the most frequent being KTKYH with a frequency of 51.3%.
+One B-cell epitope, 151 major histocompatibility complex (MHC) class II T-cell epitopes, four intrinsically unstructured regions (IURs) and six MHC class I T-cell epitopes were observed in the study.
+Phylogenetic analysis of the sequences showed clustering and evidence of evolutionary relationship with 3D7, PAS-2 and FCB-2 RH5 sequences.
+CONCLUSIONS: This study has revealed low level of genetic polymorphisms in PfRH5 antigen with B- and T-cell epitopes in intrinsically unstructured regions along the PfRH5 gene in Lagos, Nigeria.
+A broader investigation is however required in other parts of the country to support the possible inclusion of PfRH5 in a cross-protective multi-component vaccine.
+The brainstem conveys sensory and motor inputs between the spinal cord and the brain, and contains nuclei of the cranial nerves.
+It controls the sleep-wake cycle and vital functions via the ascending reticular activating system and the autonomic nuclei, respectively.
+Brainstem dysfunction may lead to sensory and motor deficits, cranial nerve palsies, impairment of consciousness, dysautonomia, and respiratory failure.
+The brainstem is prone to various primary and secondary insults, resulting in acute or chronic dysfunction.
+Of particular importance for characterizing brainstem dysfunction and identifying the underlying etiology are a detailed clinical examination, MRI, neurophysiologic tests such as brainstem auditory evoked potentials, and an analysis of the cerebrospinal fluid.
+Detection of brainstem dysfunction is challenging but of utmost importance in comatose and deeply sedated patients both to guide therapy and to support outcome prediction.
+In the present review, we summarize the neuroanatomy, clinical syndromes, and diagnostic techniques of critical illness-associated brainstem dysfunction for the critical care setting.
+This study was conducted to investigate the role of GHITM gene in the apoptosis and growth of the golden apple snail Pomacea canaliculate.
+RESULTS: The complete cDNA of this gene was cloned using the rapid amplification of cDNA ends (RACE) method and subjected to bioinformatics analysis.
+The full-length cDNA was 2242 bp, including an open reading frame of 1021 bp that encoded a protein of 342 amino acid residues.
+The mRNA expression profiles of GHITM gene in different tissues (liver, kidney, gonad and foot) and different growth phases (6-months old and 2-years old) showed that it was expressed in various tissues and different growth phases.
+Silencing of the GHITM gene by RNAi (RNA interference) experiments revealed that the GHITM gene possibly plays a role in inhibiting apoptosis through detecting the Caspase (Cysteine-requiring Aspartate Protease)-3 activity.
+In addition, the aperture width and body whorl length of the snail was significantly affected by RNAi, suggesting that this gene plays a significant role in promoting the growth of the organism.
+CONCLUSIONS: These results demonstrated that the GHITM gene was involved in apoptosis and growth in golden apple snail.
+OBJECTIVE: To examine the extent to which acute care hospitals in the Netherlands have adopted recommended practices to prevent catheter-associated urinary tract infection (CAUTI), central line-associated bloodstream infection (CLABSI), ventilator-associated pneumonia (VAP), and Clostridioides difficile infection (CDI).
+METHODS: Between 18 July 2017 and 31 October 2017, we surveyed the infection prevention teams of all acute care hospitals in the Netherlands.
+The survey instrument was based on the ‘Translating Healthcare-Associated Infection Prevention Research into Practice’ (TRIP) questionnaire and adapted to the Dutch context.
+Descriptive statistics were used to examine the reported regular use of CAUTI, CLABSI, VAP, and CDI prevention practices as well as the hospital characteristics.
+Surveillance systems for monitoring CAUTI, CLABSI, VAP, and CDI were present in 17.8, 95.4, 26.2, and 77.3% of hospitals, respectively.
+For CAUTI, the majority of hospitals regularly used aseptic technique during catheter insertion (95%) and portable bladder ultrasound scanners (86.1%).
+For CLABSI, all hospitals regularly used maximum sterile barrier precautions and chlorhexidine gluconate for insertion site antisepsis.
+Avoidance of the femoral site for central line insertions was regularly used by 65.9% of hospitals.
+With the exception of disposable thermometers (31.8%), all prevention practices to prevent CDI were regularly used by more than 80% of hospitals.
+CONCLUSIONS: Most Dutch hospitals report regular use of recommended practices for preventing CLABSI and CDI.
+Several specific practices to prevent CAUTI and VAP were less frequently used, however, providing an opportunity for improvement.
+In a recent study, we proposed a novel method to evaluate hypoxic ischemic encephalopathy (HIE) by assessing propofol-induced changes in the 19-channel electroencephalogram (EEG).
+The study suggested that patients with HIE are unable to generate EEG slow waves during propofol anesthesia 48 h after cardiac arrest (CA).
+Since a low number of electrodes would make the method clinically more practical, we now investigated whether our results received with a full EEG cap could be reproduced using only forehead electrodes.
+EEG was recorded approximately 48 h after CA using 19-channel EEG cap during a controlled propofol exposure.
+The slow wave activity was calculated separately for all electrodes and four forehead electrodes (Fp1, Fp2, F7, and F8) by determining the low-frequency (< 1 Hz) power of the EEG.
+In patients without HIE (N = 6), propofol substantially increased (244 ± 91%, mean ± SD) the slow wave activity in forehead electrodes, whereas the patients with HIE (N = 4) were unable to produce such activity.
+The results received with forehead electrodes were similar to those of the full EEG cap.
+With the experimental pilot study data, the forehead electrodes were as capable as the full EEG cap in capturing the effect of HIE on propofol-induced slow wave activity.
+The finding offers potential in developing a clinically practical method for the early detection of HIE.
+The study described poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) accumulation in Bacillus aryabhattai PHB10 for the first time and evaluated the polymer induced cytotoxicity in-vitro with PHBV/poly(ethylene glycol) (PEG) blends.
+The B. aryabhattai strain produced 2.8 g/L PHBV, equivalent to 71.15% of cell dry mass in a medium supplemented with propionic acid, after 48 h incubation.
+The optimum temperature and pH for the copolymer accumulation was 31 °C and 7, respectively.
+The gas chromatography–mass spectrometry and nuclear magnetic resonance analyses confirmed the polymer obtained as PHBV.
+The differential scanning calorimetry analysis revealed that the melting point of the material as 90 °C and its thermal stability up to 220 °C.
+The average molecular weight (Mn) and polydispersity index of the sample was estimated by gel permeation chromatography analysis and observed as 128.508 kDa and 2.82, respectively.
+The PHBV and their blends with PEG were tested for cytotoxicity on human keratinocytes (HaCaT cells) and the cells incubated with PHBV/PEG2kDa blends were 99% viable, whereas with the PHBV alone showed comparatively higher cytotoxicity.
+The significant improvement in the cell viability of PHBV/PEG2kDa blends indicates its potential as a candidate for skin graft applications.
+To achieve high-level expression of recombinant PCV3 Cap in Escherichia coli (E. coli), the gene of wild-type entire Cap (wt-eCap) was amplified from clinical samples, and three optimized entire Cap (opti-eCap) and one optimized Cap deleted nuclear location signal (NLS) (opti-dCap) gene fragments encoding the same amino acid sequence with wt-eCap were synthesized based on the codon bias of E. coli.
+One recombinant strain with the highest expressed soluble eCap from four entire Cap (one wt-eCap and three opti-eCap) and one recombinant strain expressed opti-dCap were selected for further purification.
+The purified eCap and dCap were identified by transmission electron microscopy (TEM), a large number of round hollow particles with a diameter of 10 nm virus-like particles (VLPs) were observed in eCap, whereas irregular aggregation of proteins observed in dCap.
+After formation the VLPs were applied as a coating antigen to establish an indirect ELISA (I-ELISA) for detection of PCV3-specific antibody in swine serum.
+373 clinical swine serum samples from China collected in 2019 were tested utilizing the VLP-based I-ELISA method under optimized conditions.
+To the best of our knowledge, this is the first report of self-assembly into VLPs of PCV3 recombinant Cap.
+Our results demonstrated that the VLP-based I-ELISA will be a valuable tool for detecting the presence of PCV3 antibodies in serum samples and will facilitate screening of large numbers of swine serum for clinical purposes.
+BACKGROUND AND AIMS: Nonalcoholic steatohepatitis (NASH) is a common inflammatory liver condition that may lead to cirrhosis and hepatocellular carcinoma (HCC).
+Risk factors for NASH include a saturated fat diet, altered lipid metabolism, and genetic and epigenetic factors, including microRNAs.
+Serum levels of cholecystokinin (CCK) are elevated in mice and humans that consume a high-saturated fat diet.
+CCK receptors (CCK-Rs) have been reported on fibroblasts which when activated can induce fibrosis; however, their role in hepatic fibrosis remains unknown.
+We hypothesized that elevated levels of CCK acting on the CCK-Rs play a role in the development of NASH and in NASH-associated HCC.
+METHODS: We performed a NASH Prevention study and Reversal study in mice fed a saturated fat 75% choline-deficient–ethionine-supplemented (CDE) diet for 12 or 18 weeks.
+In each study, half of the mice received untreated drinking water, while the other half received water supplemented with the CCK-R antagonist proglumide.
+RESULTS: CCK receptor antagonist treatment not only prevented NASH but also reversed hepatic inflammation, fibrosis, and steatosis and normalized hepatic transaminases after NASH was established.
+Thirty-five percent of the mice on the CDE diet developed HCC compared with none in the proglumide-treated group.
+We found that CCK-BR expression was markedly upregulated in mouse CDE liver and HCC cells compared with normal hepatic parenchymal cells, and this expression was epigenetically regulated by microRNA-148a.
+CONCLUSION: These results support the novel role of CCK receptors in the pathogenesis of NASH and HCC.
+Using the RNA-dependent RNA polymerase (RdRp) from poliovirus (PV) as our model system, we have shown that Lys-359 in motif-D functions as a general acid in the mechanism of nucleotidyl transfer.
+In the context of the KH virus, RdRp-coding sequence evolves, selecting for the following substitutions: I331F (IF, motif-C) and P356S (PS, motif-D).
+Each exhibits a unique recombination phenotype, with IF-KH being competent for copy-choice recombination and PS-KH being competent for forced-copy-choice recombination.
+Although the IF-PS-KH RdRp exhibits biochemical properties within twofold of wild type, the virus is impaired substantially for recombination in cells.
+We conclude that there are biochemical properties of the RdRp in addition to speed and fidelity that determine the mechanism and efficiency of recombination.
+The interwoven nature of speed, fidelity, the undefined property suggested here, and recombination makes it impossible to attribute a single property of the RdRp to fitness.
+However, the derivatives described here may permit elucidation of the importance of recombination on the fitness of the viral population in a background of constant polymerase speed and fidelity.
+Objective: The goal was to develop a pediatric airway stent for treating tracheobronchomalacia that could be used as an alternative to positive pressure ventilation.
+The design goals were for the stent to allow mucus flow and to resist migration inside the airways, while also enabling easy insertion and removal.
+A mechanics model of stent compression is derived to assist in selecting stent design parameters (pitch and wire diameter) that provide the desired amount of tracheal support, while introducing the minimal amount of foreign material into the airway.
+Worst-case airway area reduction with stent support is investigated experimentally using a pressurized tracheal phantom matched to porcine tracheal tissue properties.
+Since the helical design covers only a small portion of the epithelium, mucus transport through the stented region was minimally impeded.
+Furthermore, the screw-like stent resisted migration, while also providing for atraumatic removal through the use of an unscrewing motion during removal.
+Conclusion: The proposed stent design and tools represent a promising approach to prevent airway collapse in children with tracheobronchomalacia.
+Significance: The proposed technology overcomes the limitations of existing airway stents and may provide an alternative to maintaining children on a ventilator.
+BACKGROUND: Randomised controlled trials (RCTs) provide the most reliable information to inform clinical practice and patient care.
+We aimed to map global clinical research publication activity through RCT-related articles in high-impact-factor medical journals over the past five decades.
+METHODS: We conducted a cross-sectional analysis of articles published in the highest ranked medical journals with an impact factor > 10 (according to Journal Citation Reports published in 2017).
+A process of standardization was conducted to unify the different terms and grammatical variants and to remove typographical, transcription and/or indexing errors.
+Descriptive analyses were conducted (including the number of articles, citations, most prolific authors, countries, journals, funding sources and keywords).
+The Lancet (n = 3593; 9.1%), the Journal of Clinical Oncology (n = 3343; 8.5%) and The New England Journal of Medicine (n = 3275 articles; 8.3%) published the largest number of RCTs.
+The global productivity ranking was led by the United States (n = 18,393 articles), followed by the United Kingdom (n = 8028 articles), Canada (n = 4548 articles) and Germany (n = 4415 articles).
+Seventeen authors who had published 100 or more articles were identified; the most prolific authors were affiliated with Duke University (United States), Harvard University (United States) and McMaster University (Canada).
+The main funding institutions were the National Institutes of Health (United States), Hoffmann-La Roche (Switzerland), Pfizer (United States), Merck Sharp & Dohme (United States) and Novartis (Switzerland).
+The 100 most cited RCTs were published in nine journals, led by The New England Journal of Medicine (n = 78 articles), The Lancet (n = 9 articles) and JAMA (n = 7 articles).
+diabetes control, hormone replacement therapy in postmenopausal women, multiple therapies for diverse cancers, cardiovascular therapies such as lipid-lowering statins, antihypertensive medications, and antiplatelet and antithrombotic therapy).
+CONCLUSIONS: Our analysis identified authors, countries, funding institutions, landmark contributions and high-impact-factor medical journals publishing RCTs.
+Over the last 50 years, publication production in leading medical journals has increased, with Western countries leading in research but with low- and middle-income countries showing very limited representation.
+BACKGROUND: Professional caregivers working in child and youth welfare institutions are frequently faced with the complex mental health issues, emotional needs and challenging coping strategies of clients with cumulated traumatic experiences, leaving them prone to developing high levels of stress, burn-out and compassion fatigue.
+Trauma-informed care (TIC) is a milieu-therapeutic approach that aims to promote the self-efficacy and self-care of youth welfare staff by guiding them to a better understanding of their own and their clients’ stress symptoms and countertransference.
+Despite increasing efforts to implement TIC practices, and more widespread recognition of their value in youth welfare systems, there is a lack of studies evaluating the effectiveness of this approach.
+The aim of this study was to assess the effects of TIC practices in youth welfare institutions on both the physiological stress of staff members and clients’ physical aggression towards their caregivers.
+METHODS: Data was obtained from a longitudinal study investigating the effectiveness of TIC in 14 residential youth welfare institutions.
+Our sample consisted of 47 youth welfare employees (66.0% female) aged from 23 to 60 years (M = 37.4, SD = 10.4 years).
+Hair cortisol concentration (HCC) and occurrences of client physical aggression were assessed at four annual measurement time points (T1 to T4).
+RESULTS: Participants in five institutions employing TIC practices (intervention group) showed significantly lower HCC at T4 than staff members from institutions who did not receive training in TIC (control group), indicating reduced physiological stress levels.
+CONCLUSIONS: TIC might be a promising approach for reducing the emotional burden of employees and institutions should invest in training their staff in TIC practices.
+More research is necessary, to investigate the benefits and efficacy of TIC, both to youths and staff members, and to foster a better understanding of which specific factors may contribute to stress reduction.
+BACKGROUND: Catheter-related bloodstream infections (CR-BSI) cause high neonatal mortality and are related to inadequate aseptic technique during the care and maintenance of a catheter.
+The incidence of CR-BSI among neonates in Hung Vuong Hospital was higher than that of other neonatal care centres in Vietnam.
+METHODS: An 18-month pre- and post-intervention study was conducted over three 6-month periods to evaluate the effectiveness of the intervention for CR-BSI and to identify risk factors associated with CR-BSI.
+During the intervention period, we trained all nurses in the Department of Neonatology on BSI preventive practices, provided auditing and feedback about aseptic technique during catheter care and maintenance, and reorganised preparation of total parenteral nutrition.
+All neonates with intravenous catheter insertion ≥48 h in the pre- and post-intervention period were enrolled.
+We used Poisson regression to calculate rate ratio (RR) and 95% confidence interval (CI) for CR-BSI incidence rates and logistic regression to identify risk factors associated with CR-BSI.
+RESULTS: Of 2225 neonates enrolled, 1027 were enrolled in the pre-intervention period, of which 53 CR-BSI cases occurred in 8399 catheter-days, and 1198 were enrolled in the post-intervention period, of which 32 CR-BSI cases occurred in 8324 catheter-days.
+Incidence rates of CR-BSI significantly decreased after the intervention (RR = 0.61, 95% CI 0.39–0.94).
+Days of hospitalisation, episodes of non-catheter–related hospital-acquired infections, and the proportion of deaths significantly decreased after the intervention (p < 0.01).
+The CR-BSI was associated with days of intravenous catheter (odds ratio [OR] = 1.05, 95% CI 1.03–1.08), use of endotracheal intubation (OR = 2.27, 95% CI 1.27–4.06), and intravenous injection (OR = 8.50, 95% CI 1.14–63.4).
+Regular refresher training and auditing and feedback about aseptic technique during care and maintenance of catheters are critical to reducing CR-BSI.
+BACKGROUND: Pneumonia is a frequent complication in patients undergoing heart transplantation (HTx) that increases morbidity and mortality in this population.
+The aim of this study was to investigate the predictive risk factors for POP in HTx recipients.
+METHODS: In this retrospective study, all patients undergoing HTx between January 2014 and December 2015 were included.
+RESULTS: A total of 175 patients were included without any patients being lost to follow-up, and 89 instances of POP were diagnosed in 59 (34%) patients.
+In the multivariate analysis, the risk factors were preoperative mechanical ventilation (OR 1.42 [1.12–1.80], P < 0.01) and perioperative blood transfusion (OR 1.42 [95% CI: 1.20–1.70], P < 0.01).
+POP significantly impacted mortality at 30 days (OR: 4 [1.3–12.4], P = 0.01) and 1 year (OR: 6.8 [2.5–8.4], P < 0.01) and was associated with a longer duration of mechanical ventilation, time to weaning from venoarterial extracorporeal membrane oxygenation and stay in an intensive care unit.
+CONCLUSION: After HTx, preoperative mechanical ventilation and blood transfusion were risk factors for POP and were associated with increased mortality.
+BACKGROUND: Immunization with attenuated malaria sporozoites protects humans from experimental malaria challenge by mosquito bite.
+Protection in humans is strongly correlated with the production of T cells targeting a heterogeneous population of pre-erythrocyte antigen proteoforms, including liver stage antigens.
+Currently, few T cell epitopes derived from Plasmodium falciparum, the major aetiologic agent of malaria in humans are known.
+METHODS: In this study both in vitro and in vivo malaria liver stage models were used to sequence host and pathogen proteoforms.
+Proteoforms from these diverse models were subjected to mild acid elution (of soluble forms), multi-dimensional fractionation, tandem mass spectrometry, and top-down bioinformatics analysis to identify proteoforms in their intact state.
+RESULTS: These results identify a group of host and malaria liver stage proteoforms that meet a 5% false discovery rate threshold.
+CONCLUSIONS: This work provides proof-of-concept for the validity of this mass spectrometry/bioinformatic approach for future studies seeking to reveal malaria liver stage antigens towards vaccine development.
+BACKGROUND: Toxocariasis is a worldwide zoonotic parasitic disease caused by species of Toxocara and Toxascaris, common in dogs and cats.
+Herein, a meta-analysis was contrived to assess the prevalence of Toxocara/Toxascaris in carnivore and human hosts in different regions of Iran from April 1969 to June 2019.
+METHODS: The available online articles of English (PubMed, Science Direct, Scopus, and Ovid) and Persian (SID, Iran Medex, Magiran, and Iran Doc) databases and also the articles that presented in held parasitology congresses of Iran were involved.
+RESULTS: The weighted prevalence of Toxocara/Toxascaris in dogs (Canis familiaris) and cats (Felis catus) was 24.2% (95% CI: 18.0–31.0%) and 32.6% (95% CI: 22.6–43.4%), respectively.
+Also, pooled prevalence in jackal (Canis aureus) and red fox (Vulpes vulpes) was 23.3% (95% CI: 7.7–43.2%) and 69.4% (95% CI: 60.3–77.8%), correspondingly.
+Weighted mean prevalence of human cases with overall 28 records was 9.3% (95% CI: 6.3–13.1%).
+The weighted prevalence of Toxocara canis, Toxocara cati, and Toxascaris leonina was represented as 13.8% (95% CI: 9.8–18.3%), 28.5% (95% CI: 20–37.7%) and 14.3% (95% CI: 8.1–22.0%), respectively.
+CONCLUSION: Our meta-analysis results illustrate a considerable prevalence rate of Toxocara/Toxascaris, particularly in cats and dogs of northern parts of Iran.
+The presence of suitable animal hosts, optimum climate and close contact of humans and animals would have been the reason for higher seroprevalence rates of human cases in our region.
+Despite the availability of highly effective direct-acting antiviral (DAA) regimens for the treatment of hepatitis C virus (HCV) infections, sustained viral response (SVR) rates remain suboptimal for difficult-to-treat patient populations such as those with HCV genotype 3, cirrhosis or prior treatment experience, warranting development of more potent HCV replication antivirals.
+AT-527 is the hemi-sulfate salt of AT-511, a novel phosphoramidate prodrug of 2’-fluoro-2’-C-methylguanosine-5'-monophosphate that has potent in vitro activity against HCV.
+The EC(50) of AT-511, determined using HCV laboratory strains and clinical isolates with genotypes 1–5, ranged from 5–28 nM.
+AT-511 did not inhibit the replication of other selected RNA or DNA viruses in vitro.
+AT-511 was approximately 10-fold more active than sofosbuvir (SOF) against a panel of laboratory strains and clinical isolates of HCV genotypes 1–5 and remained fully active against S282T resistance-associated variants, with up to 58-fold more potency than SOF.
+In vitro, AT-511 did not inhibit human DNA polymerases or elicit cytotoxicity or mitochondrial toxicity at concentrations up to 100 μM.
+Unlike the other potent guanosine analogs PSI-938 and PSI-661, no mutagenic O(6)-alkylguanine bases were formed when incubated with cytochrome P450 (CYP) 3A4, and AT-511 had IC(50) values ≥25 μM against a panel of CYP enzymes.
+In hepatocytes from multiple species, the active triphosphate was the predominant metabolite produced from the prodrug, with a half-life of 10 h in human hepatocytes.
+When given orally to rats and monkeys, AT-527 preferentially delivered high levels of AT-9010 in the liver in vivo.
+These favorable preclinical attributes support the ongoing clinical development of AT-527 and suggest that, when used in combination with an HCV DAA from a different class, AT-527 may increase SVR rates, especially for difficult-to-treat patient populations, and could potentially shorten treatment duration for all patients.
+This retrospective cohort study investigated the association between in-hospital survival and two-dimensional (2D) echocardiography within 24 hours after the return of spontaneous circulation (ROSC) in patients who underwent in-hospital cardiopulmonary resuscitation (ICPR) after in-hospital cardiopulmonary arrest (IHCA).
+The 2D-echo and non-2D-echo groups comprised eligible patients who underwent transthoracic 2D echocardiography performed by the cardiology team within 24 hours after ROSC and those who did not, respectively.
+After propensity score (PS) matching, 142 and 284 patients in the 2D-echo and non-2D-echo groups, respectively, were included.
+A logistic regression analysis showed that the likelihood of in-hospital survival was 2.35-fold higher in the 2D-echo group than in the non-2D-echo group (P < 0.001).
+Regarding IHCA aetiology, in-hospital survival after cardiac arrest of a cardiac cause was 2.51-fold more likely in the 2D-echo group than in the non-2D-echo group (P < 0.001), with no significant inter-group difference in survival after cardiac arrest of a non-cardiac cause (P = 0.120).
+In this study, 2D echocardiography performed within 24 hours after ROSC was associated with better in-hospital survival outcomes for patients who underwent ICPR for IHCA with a cardiac aetiology.
+Thus, 2D echocardiography may be performed within 24 hours after ROSC in patients experiencing IHCA to enable better treatment.
+Porcine circovirus type 3 (PCV3) contains two major open reading frames (ORFs) and the ORF2 gene encodes the major structural capsid protein.
+In this study, nuclear localization of ORF2 was demonstrated by fluorescence observation and subcellular fractionation assays in ORF2-transfected PK-15 cells.
+The subcellular localization of truncated ORF2 indicated that the 38 N-terminal amino acids were responsible for the nuclear localization of ORF2.
+The truncated and site-directed mutagenesis of this domain were constructed, and the results demonstrated that the basic amino acid residues at positions 8–32 were essential for the strict nuclear localization.
+The basic motifs (8)RRR-R-RRR(16) and (16)RRRHRRR(22) were further shown to be the key functional nucleolar localization signals that guide PCV3 ORF2 into nucleoli.
+Furthermore, sequence analysis showed that the amino acids of PCV3 nuclear localization signals were highly conserved.
+Overall, this study provides insight into the biological and functional characteristics of the PCV3 ORF2 protein.
+The QX-type avian infectious bronchitis virus (IBV) is still a prevalent genotype in Southwestern China.
+To analyze the antigenicity and pathogenicity characteristics of the dominant genotype strains (QX-type), S1 gene sequence analysis, virus cross-neutralization tests, and pathogenicity test of eight QX-type IBV isolates were conducted.
+Sequence analysis showed that the nucleotide homology between the eight strains was high, but distantly related to H120 and 4/91 vaccine strains.
+Cross-neutralization tests showed that all eight strains isolated from 2015 and 2017 belonged to the same serotype, but exhibited antigenic variations over time.
+The pathogenicity test of the five QX-type IBV isolates showed that only three strains, CK/CH/SC/DYW/16, CK/CH/SC/MS/17, and CK/CH/SC/GH/15, had a high mortality rate with strong respiratory and renal pathogenicity, whereas CK/CH/SC/PZ/17 and CK/CH/SC/DYYJ/17 caused only mild clinical symptoms and tissue lesions.
+These findings may provide reference for research on the evolution of IBV and vaccine preparation of infectious bronchitis (IB).
+Nevertheless, their biological role in these early-branching parasites and their role in host-parasite interaction are not well elucidated.
+Prostaglandin F(2α) synthase (PGF2S) has been observed in the Leishmania braziliensis secreted proteome and in L. donovani extracellular vesicles.
+Furthermore, we previously reported a positive correlation between L. braziliensis PGF2S (LbrPGF2S) expression and pathogenicity in mice.
+METHODS: LbrPGF2S gene expression and PGF2α synthesis in promastigotes were detected and quantified by western blotting and EIA assay kit, respectively.
+To investigate LbrPGF2S localization in amastigotes during bone marrow-derived macrophage infection, parasites expressing mCherry-LbrPGF2S were generated and followed by time-lapse imaging for 48 h post-infection.
+PGF2S homolog sequences from Leishmania and humans were analyzed in silico using ClustalW on Geneious v6 and EMBOSS Needle.
+RESULTS: Leishmania braziliensis promastigotes synthesize prostaglandin F(2α) in the presence of arachidonic acid, with peak production in the stationary growth phase under heat stress.
+LbrPGF2S is a cytoplasmic protein enriched in the secretory site of the parasite cell body, the flagellar pocket.
+It is an enzyme constitutively expressed throughout promastigote development, but overexpression of LbrPGF2S leads to an increase of infectivity in vitro.
+The data suggest that LbrPGF2S may be released from intracellular amastigotes into the cytoplasm of bone marrow-derived macrophages over a 48-hour infection period, using time-lapse microscopy and mCherry-PGF2S (mChPGF2S)-expressing parasites.
+The putative transfer of this enzyme, involved in pro-inflammatory lipid mediator synthesis, to the host cell suggests a potential role in host-parasite interaction and may partially explain the increased pathogenicity associated with overexpression of LbrPGF2S in L. braziliensis.
+Our data provide valuable insights to help understand the importance of parasite-derived lipid mediators in pathogenesis.
+BACKGROUND: Plasmodium falciparum (Pf) whole-organism sporozoite vaccines have been shown to provide significant protection against controlled human malaria infection (CHMI) in clinical trials.
+Initial CHMI studies showed significantly higher durable protection against homologous than heterologous strains, suggesting the presence of strain-specific vaccine-induced protection.
+However, interpretation of these results and understanding of their relevance to vaccine efficacy have been hampered by the lack of knowledge on genetic differences between vaccine and CHMI strains, and how these strains are related to parasites in malaria endemic regions.
+METHODS: Whole genome sequencing using long-read (Pacific Biosciences) and short-read (Illumina) sequencing platforms was conducted to generate de novo genome assemblies for the vaccine strain, NF54, and for strains used in heterologous CHMI (7G8 from Brazil, NF166.C8 from Guinea, and NF135.C10 from Cambodia).
+The assemblies were used to characterize sequences in each strain relative to the reference 3D7 (a clone of NF54) genome.
+Strains were compared to each other and to a collection of clinical isolates (sequenced as part of this study or from public repositories) from South America, sub-Saharan Africa, and Southeast Asia.
+RESULTS: While few variants were detected between 3D7 and NF54, we identified tens of thousands of variants between NF54 and the three heterologous strains.
+These variants include SNPs, indels, and small structural variants that fall in regulatory and immunologically important regions, including transcription factors (such as PfAP2-L and PfAP2-G) and pre-erythrocytic antigens that may be key for sporozoite vaccine-induced protection.
+Additionally, these variants directly contributed to diversity in immunologically important regions of the genomes as detected through in silico CD8(+) T cell epitope predictions.
+Of all heterologous strains, NF135.C10 had the highest number of unique predicted epitope sequences when compared to NF54.
+Comparison to global clinical isolates revealed that these four strains are representative of their geographic origin despite long-term culture adaptation; of note, NF135.C10 is from an admixed population, and not part of recently formed subpopulations resistant to artemisinin-based therapies present in the Greater Mekong Sub-region.
+CONCLUSIONS: These results will assist in the interpretation of vaccine efficacy of whole-organism vaccines against homologous and heterologous CHMI.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13073-019-0708-9) contains supplementary material, which is available to authorized users.
+BACKGROUND: Knowledge about parasitic infections is crucial information for animal health, particularly of free-ranging species that might come into contact with livestock and humans.
+METHODS: We investigated the seroprevalence of three tissue-cyst-forming apicomplexan parasites (Toxoplasma gondii, Neospora caninum and Besnoitia besnoiti) in 506 individuals of 12 wildlife species in Namibia using in-house enzyme linked immunosorbent assays (indirect ELISAs applying purified antigens) for screening and immunoblots as confirmatory tests.
+We included six species of the suborder Feliformia, four species of the suborder Caniformia and two species of the suborder Ruminantia.
+cheetahs (Acinonyx jubatus, n = 250) and leopards (Panthera pardus, n = 58), we investigated T. gondii seroprevalence in relation to age class, sex, sociality (solitary, mother-offspring group, independent sibling group, coalition group) and site (natural habitat vs farmland).
+RESULTS: All but one carnivore species (bat-eared fox Otocyon megalotis, n = 4) were seropositive to T. gondii, with a seroprevalence ranging from 52.4% (131/250) in cheetahs to 93.2% (55/59) in African lions (Panthera leo).
+We also detected antibodies to T. gondii in 10.0% (2/20) of blue wildebeest (Connochaetes taurinus).
+Adult cheetahs and leopards were more likely to be seropositive to T. gondii than subadult conspecifics, whereas seroprevalence did not vary with sex, sociality and site.
+Furthermore, we measured antibodies to N. caninum in 15.4% (2/13) of brown hyenas (Hyaena brunnea) and 2.6% (1/39) of black-backed jackals (Canis mesomelas).
+Antibodies to B. besnoiti were detected in 3.4% (2/59) of African lions and 20.0% (4/20) of blue wildebeest.
+CONCLUSIONS: Our results demonstrate that Namibian wildlife species were exposed to apicomplexan parasites at different prevalences, depending on parasite and host species.
+In addition to serological work, molecular work is also needed to better understand the sylvatic cycle and the clear role of wildlife in the epidemiology of these parasites in southern Africa.
+The simultaneous electrochemical determination of myricetin and rutin remains a challenge due to their indistinguishable potentials.
+To solve this problem, we constructed a ternary platinum nanoparticle, reduced graphene oxide, multi-walled carbon nanotubes (Pt@r-GO@MWCNTs) nanocomposite via a facile one-pot synthetic method.
+Under the optimized conditions, the ternary Pt@r-GO@MWCNTs nanocomposite exhibited good electrocatalytic activity toward myricetin and rutin via solid phase extraction and excellent performance for the simultaneous determination of myricetin and rutin.
+The oxidation peak current of myricetin was proportional to its concentrations in the range of 0.05–50 μM with a detection limit of 0.01 μM (S/N = 3).
+The linear range for rutin was 0.05–50 μM with a detection limit of 0.005 μM (S/N = 3).
+The ternary nanocomposite sensor also exhibited good reproducibility and stability, and was successfully used for the simultaneous determination of myricetin and rutin in real orange juice samples with recoveries ranging between 100.57% and 108.46%.
+Plasmacytoid dendritic cells (pDCs) are sensor cells with diverse immune functions, from type I interferon (IFN-I) production to antigen presentation, T cell activation, and tolerance.
+Regulation of these functions remains poorly understood but could be mediated by functionally specialized pDC subpopulations.
+Our analysis uncovers a murine pDC-like population that specializes in antigen presentation with limited capacity for IFN-I production.
+Using a multifaceted cross-species comparison, we show that this pDC-like population is the definitive murine equivalent of the recently described human AXL(+) DCs, which we unify under the name transitional DCs (tDCs) given their continuum of pDC and cDC2 characteristics.
+Altogether, we provide a framework for deciphering the function of pDCs and tDCs during diseases, which has the potential to open new avenues for therapeutic design.
+During HIV infection, cell-to-cell transmission results in endosomal uptake of the virus by target CD4+ T cells and potential exposure of the viral ssRNA genome to endosomal Toll-like receptors (TLRs).
+TLRs are instrumental in activating inflammatory responses in innate immune cells, but their function in adaptive immune cells is less well understood.
+Here we show that synthetic ligands of TLR8 boosted T cell receptor signaling, resulting in increased cytokine production and upregulation of surface activation markers.
+Adjuvant TLR8 stimulation, but not TLR7 or TLR9, further promoted T helper cell differentiation towards Th1 and Th17.
+In addition, we found that endosomal HIV induced cytokine secretion from CD4+ T cells in a TLR8-specific manner.
+TLR8 engagement also enhanced HIV-1 replication and potentiated the reversal of latency in patient-derived T cells.
+The adjuvant TLR8 activity in T cells can contribute to viral dissemination in the lymph node and low-grade inflammation in HIV patients.
+The role of laparoscopic surgery for left-sided colon cancer has been supported by the results of randomized controlled trials.
+However, its benefits and disadvantages in the real world setting should be further assessed with population-based studies.The hospitalization data of patients undergoing open or laparoscopic surgery for left-sided colon cancer were sourced from the Taiwan National Health Insurance Research Database.
+Patient and hospital characteristics and perioperative outcomes including length of hospital stay, operation time, opioid use, blood transfusion, intensive care unit (ICU) admission, and use of mechanical ventilation were compared.
+Patients undergoing laparoscopic surgery had shorter hospital stay (p < 0.0001) and less demand for opioid analgesia (p = 0.0005).
+Further logistic regression revealed that patients undergoing open surgery were 1.70, 2.89, and 3.00 times more likely to have blood transfusion, to be admitted to ICU, and to use mechanical ventilation than patients undergoing laparoscopic surgery.
+The overall survival was comparable between the 2 groups.With adequate hospital quality and volume, laparoscopic surgery for left-sided colon cancer was associated with improved perioperative outcomes.
+Out of these four high morbidity diseases, venereal syphilis is mediated by sexual contact; the other three diseases are transmitted by close personal contact.
+The global distribution of syphilis is alarming and there is an increasing need of proper treatment and preventive measures.
+RESULTS: Here, the genome sequences of 53 T. pallidum strains isolated from different parts of the world and a diverse range of hosts were comparatively analysed using pan-genomic strategy.
+Phylogenomic, pan-genomic, core genomic and singleton analysis disclosed the close connection among all strains of the pathogen T. pallidum, its clonal behaviour and showed increases in the sizes of the pan-genome.
+Based on the genome plasticity analysis of the subsets containing the subspecies T pallidum subsp.
+pertenue, we found differences in the presence/absence of pathogenicity islands (PAIs) and genomic islands (GIs) on subsp.-based study.
+CONCLUSIONS: In summary, we identified four pathogenicity islands (PAIs), eight genomic islands (GIs) in subsp.
+Concerning the presence of genes in PAIs and GIs, we found some genes related to lipid and amino acid biosynthesis that were only present in the subsp.
+BACKGROUND: Epidemiologic studies show that cocaine- and amphetamine-regulated transcript prepropeptide (CARTPT) gene polymorphism modifies diet-obesity relationships.
+However, the interaction between CARTPT gene polymorphism and diet quality indices have not been investigated yet.
+The current study was aimed to evaluate the interaction between major dietary indices including Diet Quality Index-International (DQI-I) and Healthy Eating Index (HEI)-2015 and CARTPT gene rs2239670 variants among apparently healthy obese Iranians.
+METHODS: This cross-sectional study was carried out by employing 288 apparently healthy obese adults aged 20–50 years with a BMI of 30–40 kg/m(2).
+Diet quality was evaluated by Diet Quality Index-International (DQI-I) and Healthy Eating Index-2015 (HEI-2015) using a 132-items semi-quantitative validated food frequency questionnaire.
+The CARTPT gene rs2239670 polymorphism was genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR–RFLP) technique.
+Blood concentrations of glycemic markers, lipid profile, α-melanocyte stimulating hormone (MSH) and agouti-related peptide (AgRP) were also measured.
+RESULTS: The significant interactions were identified between CARTPT gene polymorphism and HEI, affecting BMR (P(Interaction) = 0.003), serum glucose (P(Interaction) = 0.009) and high density lipoprotein cholesterol HDL concentrations (P(Interaction) = 0.03) after adjusting for the effects of sex and age.
+Also we found gene-diet interaction between CARTPT genotypes and DQI-I in terms of fat mass (FM; P(Interaction) = 0.02), waist circumference (WC; P(Interaction) < 0.001), body mass index (BMI; P(Interaction) < 0.001), basal metabolic rate (BMR, P(Interaction) < 0.001), serum fasting glucose (P(Interaction) < 0.01) and AgRP (P(Interaction) = 0.05) in individuals even after adjusting for potential confounders.
+CONCLUSION: Current study showed the effects of interaction between CARTPT genotype with adherence to HEI and DQI-I scores on obesity-related anthropometric and metabolic risk-factors.
+The avian influenza virus outbreak in 1997 highlighted the potential of the highly pathogenic H5N1 virus to cause severe disease in humans.
+Therefore, effective vaccines against H5N1 viruses are needed to counter the potential threat of a global pandemic.
+We have previously developed a fast-acting and efficacious vaccine against Ebola virus (EBOV) using the vesicular stomatitis virus (VSV) platform.
+In this study, we generated recombinant VSV-based H5N1 influenza virus vectors to demonstrate the feasibility of this platform for a fast-acting pan-H5 influenza virus vaccine.
+We chose multiple approaches regarding antigen design and genome location to define a more optimized vaccine approach.
+After the VSV-based H5N1 influenza virus constructs were recovered and characterized in vitro, mice were vaccinated by a single dose or prime/boost regimen followed by challenge with a lethal dose of the homologous H5 clade 1 virus.
+We found that a single dose of VSV vectors expressing full-length hemagglutinin (HAfl) were sufficient to provide 100% protection.
+The vaccine vectors were fast-acting as demonstrated by uniform protection when administered 3 days prior to lethal challenge.
+Moreover, single vaccination induced cross-protective H5-specific antibodies and protected mice against lethal challenge with various H5 clade 2 viruses, highlighting the potential of the VSV-based HAfl as a pan-H5 influenza virus emergency vaccine.
+BACKGROUND: Optimal anti-bacterial activity of meropenem requires maintenance of its plasma concentration (Cp) above the minimum inhibitory concentration (MIC) of the pathogen for at least 40% of the dosing interval (fT > MIC > 40).
+We aimed to determine whether a 3-h extended infusion (EI) of meropenem achieves fT > MIC > 40 on the first and third days of therapy in patients with severe sepsis or septic shock.
+We also simulated the performance of the EI with respect to other pharmacokinetic (PK) targets such as fT > 4 × MIC > 40, fT > MIC = 100, and fT > 4 × MIC = 100.
+METHODS: Arterial blood samples of 25 adults with severe sepsis or septic shock receiving meropenem 1000 mg as a 3-h EI eight hourly (Q8H) were obtained at various intervals during and after the first and seventh doses.
+Plasma meropenem concentrations were determined using a reverse-phase high-performance liquid chromatography assay, followed by modeling and simulation of PK data.
+European Committee on Antimicrobial Susceptibility Testing (EUCAST) definitions of MIC breakpoints for sensitive and resistant Gram-negative bacteria were used.
+RESULTS: A 3-h EI of meropenem 1000 mg Q8H achieved fT > 2 µg/mL > 40 on the first and third days, providing activity against sensitive strains of Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter baumannii.
+However, it failed to achieve fT > 4 µg/mL > 40 to provide activity against strains susceptible to increased exposure in 33.3 and 39.1% patients on the first and the third days, respectively.
+Modeling and simulation showed that a bolus dose of 500 mg followed by 3-h EI of meropenem 1500 mg Q8H will achieve this target.
+A bolus of 500 mg followed by an infusion of 2000 mg would be required to achieve fT > 8 µg > 40.
+Targets of fT > 4 µg/mL = 100 and fT > 8 µg/mL = 100 may be achievable in two-thirds of patients by increasing the frequency of dosing to six hourly (Q6H).
+CONCLUSIONS: In patients with severe sepsis or septic shock, EI of 1000 mg of meropenem over 3 h administered Q8H is inadequate to provide activity (fT > 4 µg/mL > 40) against strains susceptible to increased exposure, which requires a bolus of 500 mg followed by EI of 1500 mg Q8H.
+While fT > 8 µg/mL > 40 require escalation of EI dose, fT > 4 µg/mL = 100 and fT > 8 µg/mL = 100 require escalation of both EI dose and frequency.
+BACKGROUND: Herpes simplex virus (HSV) replication can be detected in the respiratory secretions of a high proportion of ventilated intensive care unit (ICU) patients.
+We investigated whether patients with ventilator-associated pneumonia not responding to antibiotics and in whom high levels of HSV could be detected in respiratory secretions benefit from acyclovir treatment.
+METHODS: Respiratory secretions (bronchoalveolar lavage fluid or tracheal aspirates) were tested for HSV replication by quantitative real-time PCR.
+ICU survival times, clinical parameters, and radiographic findings were retrospectively compared between untreated and acyclovir treated patients with high (> 10(5) HSV copies/mL) and low (10(3)–10(5) HSV copies/mL) viral load.
+Fewer patients with high viral load responded to antibiotic treatment (12% compared to 40% of low load patients, p = 0.001).
+Acyclovir improved median ICU survival (8 vs 22 days, p = 0.014) and was associated with a significantly reduced hazard ratio for ICU death (HR = 0.31, 95% CI 0.11–0.92, p = 0.035) in high load patients only.
+Moreover, circulatory and pulmonary oxygenation function of high load patients improved significantly over the course of acyclovir treatment: mean norepinephrine doses decreased from 0.05 to 0.02 μg/kg body weight/min between days 0 and 6 of treatment (p = 0.049), and median PaO(2)/FiO(2) ratio increased from 187 to 241 between day 3 and day 7 of treatment (p = 0.02).
+CONCLUSIONS: In patients with ventilator-associated pneumonia, antibiotic treatment failure, and high levels of HSV replication, acyclovir treatment was associated with a significantly longer time to death in the ICU and improved circulatory and pulmonary function.
+BACKGROUND: Predisposing conditions and risk modifiers instead of causes and risk factors have recently been used as alternatives to identify patients at a risk of acute respiratory distress syndrome (ARDS).
+METHODS: We conducted a secondary analysis of the multicenter, prospective, Focused Outcomes Research in Emergency Care in Acute Respiratory Distress Syndrome, Sepsis and Trauma (FORECAST) cohort study that was conducted in 59 intensive care units (ICUs) in Japan during January 2016–March 2017.
+Adult patients with severe sepsis caused by non-pulmonary infection were included, and the primary outcome was having ARDS, defined as meeting the Berlin definition on the first or fourth day of screening.
+Multivariate logistic regression modeling was used to identify risk modifiers associated with ARDS, and odds ratios (ORs) and their 95% confidence intervals were reported.
+The following explanatory variables were then assessed: age, sex, admission source, body mass index, smoking status, congestive heart failure, chronic obstructive pulmonary disease, diabetes mellitus, steroid use, statin use, infection site, septic shock, and acute physiology and chronic health evaluation (APACHE) II score.
+RESULTS: After applying inclusion and exclusion criteria, 594 patients with non-pulmonary sepsis were enrolled, among whom 85 (14.3%) had ARDS.
+Septic shock was diagnosed in 80% of patients with ARDS and 66% of those without ARDS (p = 0.01).
+APACHE II scores were higher in patients with ARDS [26 (22–33)] than in those without ARDS [21 (16–28), p < 0.01].
+In the multivariate logistic regression model, the following were independently associated with ARDS: ICU admission source [OR, 1.89 (1.06–3.40) for emergency department compared with hospital wards], smoking status [OR, 0.18 (0.06–0.59) for current smoking compared with never smoked], infection site [OR, 2.39 (1.04–5.40) for soft tissue infection compared with abdominal infection], and APACHE II score [OR, 1.08 (1.05–1.12) for higher compared with lower score].
+CONCLUSIONS: Soft tissue infection, ICU admission from an emergency department, and a higher APACHE II score appear to be the risk modifiers of ARDS in patients with non-pulmonary sepsis.
+BACKGROUND: Vietnam is shifting toward integrating HIV services into the public health system using social health insurance (SHI), and the HIV service delivery system is becoming decentralized.
+The study aim was to investigate current SHI coverage and patients’ perspectives on this transition.
+METHODS: A survey of 1348 HIV-positive patients on antiretroviral therapy (aged ≥18 years) was conducted at an HIV outpatient clinic at a central-level hospital in Hanoi, Vietnam, in October and November 2018.
+Insurance coverage, reasons for not having a SHI card, perceived concerns about receiving HIV services in SHI-registered local health facilities, and willingness to continue regularly visiting the current hospital were self-reported.
+Logistic regression analyses were performed to analyze factors associated with not having a SHI card and having concerns about receiving HIV services in SHI-registered hospitals/clinics.
+The most frequently reported reason for not having a SHI card was that obtaining one was burdensome, followed by lack of information on how to obtain a card, and financial problems.
+Most patients (86.6%) had concerns about receiving HIV services at SHI-registered local health facilities, and disclosure of HIV status to neighbors and low quality of HIV services were the main concerns reported.
+Participants aged < 40 years old and unmarried were more likely to report lack of SHI cards, and women and those aged ≥40 years were more likely to have concerns.
+CONCLUSIONS: Although SHI coverage has been rapidly improving among HIV patients, most participants had concerns about the current system transition in Vietnam.
+In response to their voiced concerns, strengthening the link between higher-level and lower-level facilities may help to ensure good quality HIV services at all levels while mitigating patients’ worries and anxieties.
+Innate lymphoid cells (ILCs) are defined as lymphocytes that lack RAG recombinase and do not express diverse antigen receptors; however, recent studies have revealed the adaptive features of ILCs.
+Mouse cytomegalovirus (MCMV)- and cytokine-induced memory natural killer (NK) cells circulate in the blood and are referred to as conventional memory NK cells.
+In contrast, virus- and hapten-induced memory NK cells, hapten-induced memory ILC1s, and cytokine-induced memory-like ILC2s exhibit long-term residency in the liver or lung, and are referred to as tissue-resident memory ILCs.
+Considering their similar migration patterns and memory potential, tissue-resident memory ILCs could be regarded as innate counterparts of resident memory T (T(RM)) cells.
+Both tissue-resident memory ILCs and T(RM) cells share common characteristics in terms of dynamics, phenotype, and molecular regulation.
+The emergence of ILC memory expands the basic biology of ILCs and prompts us to re-examine their functions in disease progression.
+This review discusses the evidence supporting tissue-resident memory NK cells and other memory ILC subsets, compares them with T(RM) cells, and highlights key unsolved questions in this emerging field.
+METHOD: A cross-sectional questionnaire study was conducted among the staff nurses of the multi-specialty Gokul Newtech Hospital, Jamnagar, Gujarat.
+RESULT: There was no statistically significant difference between the mean knowledge score concerning the study participant’s age, work experience, and education.
+According to the survey, a majority of the nurses either did not know the answer or answered incorrectly.
+CONCLUSION: It can be concluded that there is a requirement of new guidelines and recommendations in the existing teaching and training modules being followed by the nursing schools across the country.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12663-019-01240-x) contains supplementary material, which is available to authorized users.
+Advances in nucleic acid amplification technologies have revolutionized diagnostics for systemic, inherited, and infectious diseases.
+Current assays and platforms, however, often require lengthy experimental procedures and multiple instruments to remove contaminants and inhibitors from clinically-relevant, complex samples.
+This requirement of sample preparation has been a bottleneck for using nucleic acid amplification tests (NAATs) at the point of care (POC), though advances in “lab-on-chip” platforms that integrate sample preparation and NAATs have made great strides in this space.
+Alternatively, direct NAATs—techniques that minimize or even bypass sample preparation—present promising strategies for developing POC diagnostic tools for analyzing real-world samples.
+Specifically, we surveyed potential testing systems published from 1989 to 2017, and analyzed their performances in terms of robustness, sensitivity, clinical relevance, and suitability for POC diagnostics.
+We introduce bubble plots to facilitate our analysis, as bubble plots enable effective visualization of the performances of these direct NAATs.
+Through our review, we hope to initiate an in-depth examination of direct NAATs and their potential for realizing POC diagnostics, and ultimately transformative technologies that can further enhance healthcare.
+BACKGROUND: Acute diarrhoea is a common cause of illness and death among children in low- to middle-income settings.
+World Health Organization guidelines for the clinical management of acute watery diarrhoea in children focus on oral rehydration, supplemental zinc and feeding advice.
+Routine use of antibiotics is not recommended except when diarrhoea is bloody or cholera is suspected.
+Young children who are undernourished or have a dehydrating diarrhoea are more susceptible to death at 90 days after onset of diarrhoea.
+Given the mortality risk associated with diarrhoea in children with malnutrition or dehydrating diarrhoea, expanding the use of antibiotics for this subset of children could be an important intervention to reduce diarrhoea-associated mortality and morbidity.
+METHODS: ABCD is a double-blind, randomised trial recruiting 11,500 children aged 2–23 months presenting with acute non-bloody diarrhoea who are dehydrated and/or undernourished (i.e.
+Enrolled children in Bangladesh, India, Kenya, Malawi, Mali, Pakistan and Tanzania are randomised (1:1) to oral azithromycin 10 mg/kg or placebo once daily for 3 days and followed-up for 180 days.
+Primary efficacy endpoints are all-cause mortality during the 180 days post-enrolment and change in linear growth 90 days post-enrolment.
+DISCUSSION: Expanding the treatment of acute watery diarrhoea in high-risk children to include an antibiotic may offer an opportunity to reduce deaths.
+These benefits may result from direct antimicrobial effects on pathogens or other incompletely understood mechanisms including improved nutrition, alterations in immune responsiveness or improved enteric function.
+The expansion of indications for antibiotic use raises concerns about the emergence of antimicrobial resistance both within treated children and the communities in which they live.
+If the trial shows significant benefits of azithromycin use, this may provide evidence to support reconsideration of antibiotic indications in the present World Health Organization diarrhoea management guidelines.
+Conversely, if there is no evidence of benefit, these results will support the current avoidance of antibiotics except in dysentery or cholera, thereby avoiding inappropriate use of antibiotics and reaffirming the current guidelines.
+BACKGROUND: Retrograde type A aortic dissection (RTAD) is a fatal aortic disease secondary to descending aortic dissection, and might be misdiagnosed due to its atypical symptoms lead to catastrophic outcomes.
+CASE PRESENTATION: We herein reported a case of a 40-year old Chinese non-comorbid man who received conservative treatment for acute type B aortic dissection and progressed to RTAD in a painless manner in a week.
+After open surgical aortic repair with stented elephant truck technique, the patient survived without obvious complication and cured with a satisfactory outcome in a half-year follow-up.
+CONCLUSION: This case indicates that RTAD may present without typical symptoms, early diagnosis and open surgical procedure are imperative for treating RTAD.
+Foot-and-mouth disease is endemic in livestock in large parts of Africa and Asia, where it is an important driver of food insecurity and a major obstacle to agricultural development and the international trade in animal products.
+Virtually all commercially available vaccines are inactivated whole-virus vaccines produced in cell culture, but the adaptation of a field isolate of the virus to growth in culture is laborious and time-consuming.
+This is of particular concern for the development of vaccines to newly emerging virus lineages, where long lead times from virus isolate to vaccine can delay the implementation of effective control programs.
+High antigen yields in production cells are also necessary to make vaccines affordable for less developed countries in endemic areas.
+Therefore, a rational approach to cell culture adaptation that combines prior knowledge of common adaptive mutations and reverse genetics techniques is urgently required.
+This review provides an overview of amino acid exchanges in the viral capsid proteins in the context of adaptation to cell culture.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11262-019-01714-7) contains supplementary material, which is available to authorized users.
+In this paper we introduce a single serotype transmission model, including an age-dependent mosquito biting rate, to find the optimal vaccination age against dengue in Brazil with Dengvaxia.
+The optimal vaccination age and minimal lifetime expected risk of hospitalisation are found by adapting a method due to Hethcote (Math Biosci 89:29–52).
+The effects of antibody-dependent enhancement (ADE) and permanent cross-immunity after two heterologous infections are studied.
+ADE is assumed to imply risk-free primary infections, while permanent cross-immunity implies risk-free tertiary and quaternary infections.
+Data from trials of Dengvaxia indicate vaccine efficacy to be age and serostatus dependent and vaccination of seronegative individuals to induce an increased risk of hospitalisation.
+The optimal vaccination age is compared to that achievable under the current age restriction of the vaccine.
+The assumption of ADE generally leads to a higher optimal vaccination age in this case.
+If vaccination induces a risk, the optimal vaccination ages are much higher, particularly for permanent cross-immunity.
+ADE has no effect on the optimal vaccination age when permanent cross-immunity is considered; otherwise, it leads to a slight increase in optimal vaccination age.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11538-019-00690-1) contains supplementary material, which is available to authorized users.
+BACKGROUND: The aim of this study was to investigate the concordance between ventilator-associated events (VAE) and ventilator-associated lower respiratory tract infections (VA-LRTI), and their impact on outcome.
+METHODS: This retrospective study was performed in five 10-bed ICUs of a teaching hospital, during a 2-year period.
+Ventilator-associated lower respiratory tract infections (VA-LRTI), including ventilator-associated tracheobronchitis (VAT) and ventilator-associated pneumonia (VAP) were prospectively diagnosed.
+268 VAP (17.8 per 1000 ventilator-days), 127 VAT (8.5 per 1000 ventilator-days) and 262 VAE (17.4 per 1000 ventilator-days) were diagnosed.
+There was no agreement between VAT and VAE, and the agreement was poor between VAP and VAE (k = 0.12, 95% CI 0.03–0.20).
+VAE and VA-LRTI were associated with significantly longer duration of mechanical ventilation, ICU and hospital length of stay.
+VAE episodes were significantly associated with longer duration of mechanical ventilation and length of stay, but not with ICU mortality.
+BACKGROUND: Compassion is intrinsically situated within particular contexts and how these contexts can shape compassion has not been well-described.
+OBJECTIVE: The purpose of the study was to describe how individual and contextual challenges can impact compassion within critical care and palliative care settings.
+DESIGN: This qualitative study adopted phenomenology and autoethnography to inform data collection, and principles of activity theory and realist inquiry for data interpretation.
+PARTICIPANTS: Five clinicians who work in critical care (n = 3) and palliative care (n = 3) participated in the study.
+Participants observed and recorded field notes (n = 53) on instances of suffering and compassion in their workplace settings.
+At the end of the study period, they participated in a focus group or individual interview to reflect on their experiences.
+Data was analyzed using constructivist grounded theory techniques and iteratively synthesized through group discussion and model building.
+KEY RESULTS: The findings reflected four phenomena associated with compassion in context: individual gaps and lapses in compassion, relational challenges, contextual constraints on compassion, and distributed compassion.
+Individual gaps and lapses in compassion involved inattention, intention vs. perception, personal capacity, and personal toll.
+Contextual constraints consisted of situational pressures, the clinical environment, gaps in education, and organizational culture.
+The distribution of compassion within teams and how teams adapt their behaviors in response to perceived needs for greater compassion modulated these challenges.
+CONCLUSIONS: The study illustrates the many ways in which compassion can be shaped by context and highlights the role of teamwork in identifying gaps and lapses in compassion and responding in a way that supports patients, families, and colleagues.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11606-019-05467-9) contains supplementary material, which is available to authorized users.
+Sepsis is typically triggered by an overwhelming systemic inflammatory response to pathogens, and may lead to severe organ dysfunction and/or death.
+Sepsis consequently has a high mortality rate and a high rate of complications for survivors, despite modern medical advances.
+Therefore, drug identification and validation for the treatment of sepsis is of the utmost importance.
+As a selective phosphodiesterase-4 inhibitor, rolipram also exhibits the abilities of inhibiting multiple pro-inflammatory cytokines production in macrophages and toxin-induced inflammation in mice.
+We found that rolipram significantly improves survival in mice challenged with gram-negative bacterium E. coli, CLP, or E. coli derived lipopolysaccharide.
+We have also found that rolipram inhibits organ damage, pro-inflammatory cytokine production, and intracellular migration of early-stage inflammatory elements.
+The protective effects of rolipram on septic mice may result from inhibition of the MAP kinase and NF-κB signaling pathways.
+Rolipram may therefore be a potential novel sepsis treatment, one that would bypass the time-consuming and costly drug-discovery process.
+Kazakhstan and the United States have partnered since 2003 to counter the proliferation of weapons of mass destruction.
+The US Department of Defense (US DoD) has funded threat reduction programs to eliminate biological weapons, secure material in repositories that could be targeted for theft, and enhance surveillance systems to monitor infectious disease outbreaks that would affect national security.
+The cooperative biological research (CBR) program of the US DoD’s Biological Threat Reduction Program has provided financing, mentorship, infrastructure, and biologic research support to Kazakhstani scientists and research institutes since 2005.
+The objective of this paper is to provide a historical perspective for the CBR involvement in Kazakhstan, including project chronology, successes and challenges to allow lessons learned to be applied to future CBR endeavors.
+A project compendium from open source data and interviews with partner country Kazakhstani participants, project collaborators, and stakeholders was developed utilizing studies from 2004 to the present.
+An earlier project map was used as a basis to determine project linkages and continuations during the evolution of the CBR program.
+It was determined that consistent and effective networking increases the chances to collaborate especially for competitive funding opportunities.
+Overall, the CBR program has increased scientific capabilities in Kazakhstan while reducing their risk of biological threats.
+However, there is still need for increased scientific transparency and an overall strategy to develop a capability-based model to better enhance and sustain future research.
+Finally, we offer a living perspective that can be applied to further link related studies especially those related to One Health and zoonoses and the assessment of similar capability-building programs.
+Ninety years after the discovery of the virus causing the influenza disease, this malady remains one of the biggest public health threats to mankind.
+Some of the reasons for this disturbing situation stem from the sophistication of the viral machinery, but another reason is the lack of a complete understanding of the molecular and physiological basis of viral infections and host–pathogen interactions.
+Even the functions of the influenza proteins, their mechanisms of action and interaction with host proteins have not been fully revealed.
+These questions have traditionally been studied in mammalian animal models, mainly ferrets and mice (as well as pigs and non-human primates) and in cell lines.
+Although obviously relevant as models to humans, these experimental systems are very complex and are not conveniently accessible to various genetic, molecular and biochemical approaches.
+The fact that influenza remains an unsolved problem, in combination with the limitations of the conventional experimental models, motivated increasing attempts to use the power of other models, such as low eukaryotes, including invertebrate, and primary cell cultures.
+In this review, we summarized the efforts to study influenza in yeast, Drosophila, zebrafish and primary human tissue cultures and the major contributions these studies have made toward a better understanding of the disease.
+We feel that these models are still under-utilized and we highlight the unique potential each model has for better comprehending virus–host interactions and viral protein function.
+Background: Major intercontinental outbreaks of invasive meningococcal disease associated with the Hajj occurred in 1987, 2000, and 2001.
+Mandatory meningococcal vaccination for all pilgrims against serogroups A and C and, subsequently, A, C, W, and Y controlled the epidemics.
+Overseas pilgrims show excellent adherence to the policy; however, vaccine uptake among domestic pilgrims is suboptimal.
+This survey aimed to evaluate meningococcal vaccine uptake among Hajj pilgrims and to identify key factors affecting this.
+Methods: An anonymous cross-sectional survey was conducted among pilgrims in Greater Makkah during the Hajj in 2017–2018.
+Data on socio-demographic characteristics, vaccination status, cost of vaccination, and reasons behind non-receipt of the vaccine were collected.
+Results: A total of 509 respondents aged 13 to 82 (median 33.8) years participated in the survey: 86% male, 85% domestic pilgrims.
+Only 389/476 (81.7%) confirmed their meningococcal vaccination status; 64 individuals (13.4%), all domestic pilgrims, did not receive the vaccine, and 23 (4.8%) were unsure.
+Among overseas pilgrims, 93.5% certainly received the vaccine (6.5% were unsure) compared to 80.9% of domestic pilgrims (p < 0.01).
+Being employed and having a tertiary qualification were significant predictors of vaccination adherence (odds ratio (OR) = 2.2, 95% confidence interval (CI) = 1.3–3.8, p < 0.01; and OR = 1.7, CI = 1–2.5, p < 0.05, respectively).
+Those who obtained pre-Hajj health advice were more than three times as likely to be vaccinated than those who did not (OR = 3.3, CI = 1.9–5.9, p < 0.001).
+Lack of awareness (63.2%, 36/57) and lack of time (15.8%, 9/57) were the most common reasons reported for non-receipt of vaccine.
+Conclusion: Many domestic pilgrims missed the compulsory meningococcal vaccine; in this regard, lack of awareness is a key barrier.
+Being an overseas pilgrim (or living at a distance from Makkah), receipt of pre-Hajj health advice, and employment were predictors of greater compliance with the vaccination policy.
+BACKGROUND: Streptococcus agalctiae (Group B Streptococcus, GBS) is a perinatal pathogen and a leading cause of neonatal infections worldwide.
+Serotype, sequence type, clonality, antibiotic resistance genes and surface protein profiles of GBS are scarce in Ethiopia, a reason that this study was planned to investigate.
+METHODS: Sixteen colonizing GBS isolates obtained from recto-vaginal swabs of pregnant women and body surfaces of newborns were further analyzed.
+Minimum inhibitory concentration (MIC) test, and whole genome sequence (WGS) methods were done for antibiotic susceptibility test, and molecular characterization of the isolates.
+RESULTS: All the GBS isolates analyzed were belonged to four capsular serotypes: II, 11/16(68.8%), V, 3/16(18.8%), Ia and VI each with 1/16(6.3%) and five sequence type (ST-2, ST-10, ST-14, ST-569 and ST-933).
+The five STs were grouped into the four clonal complexes (CC - 1, CC-10, CC-19, and CC-23).
+Different surface proteins and pili families such as ALP1, ALPHA, ALP23, PI-1 / PI-2A1, PI-1 / PI-2B, and Srr1 were detected from WGS data.
+All isolates were found to be susceptible to the tested antibiotics except for tetracycline in MIC and WGS test methods used.
+CONCLUSION: Further studies on serotype and molecular epidemiology will provide a comprehensive data of the GBS capsular serotype and clones available in Ethiopia.
+BACKGROUND: The use of extracorporeal membrane oxygenation (ECMO) as a bridge to lung transplantation has greatly increased.
+The objective of this multicenter prospective observational cohort study was to evaluate lung transplantation outcomes in Korean Organ Transplantation Registry (KOTRY) patients for whom ECMO was used as a bridge to transplantation.
+METHODS: Between March 2015 and December 2017, a total of 112 patients received lung transplantation and were registered in the KOTRY, which is a prospective, multicenter cohort registry.
+The entire cohort was divided into two groups: the control group (n = 85, 75.9%) and bridge-ECMO group (n = 27, 24.1%).
+RESULTS: There were no significant differences in pre-transplant and intraoperative characteristics except for poorer oxygenation, more ventilator use, and longer operation time in the bridge-ECMO group.
+The prevalence of primary graft dysfunction at 0, 24, 48, and 72 h after transplantation did not differ between the two groups.
+Although postoperative hospital stays were longer in the bridge-ECMO group than in the control group, hospital mortality did not differ between the two groups (25.9% vs. 13.3%, P = 0.212).
+The majority of patients (70.4% of the bridge-ECMO group and 77.6% of the control group) were discharged directly to their homes.
+Finally, the use of ECMO as a bridge to lung transplantation did not significantly affect overall survival and graft function.
+CONCLUSIONS: Short- and long-term post-transplant outcomes of bridge-ECMO patients were comparable to recipients who did not receive ECMO.
+Furthermore, little is known regarding the association between NOAF and resource use or hospital costs.
+METHODS: Retrospective analysis (2011–2016) of a prospectively collected registry from two Canadian hospitals of consecutive ICU patients aged ≥ 18 years.
+The primary outcome was hospital mortality, and we used multivariable logistic regression to adjust for confounders.
+While NOAF was not associated with increased odds of hospital death among the entire cohort (adjusted odds ratio [aOR] 1.02 [95% confidence interval [CI] 0.97–1.08]), an interaction was noted between NOAF and sepsis, and the presence of both was associated with higher odds of hospital mortality (aOR 1.28 [95% CI 1.09–1.36]) than either alone.
+Among patients with NOAF, treatment with a rhythm-control strategy was associated with higher costs (CR 1.24 [95% CI 1.07–1.40]).
+CONCLUSIONS: While NOAF was not associated with death or requiring discharge to long-term care among critically ill patients, it was associated with increased length of stay in ICU and increased total costs.
+BACKGROUND: The present study aims to assess the cost-effectiveness of an influenza vaccination program for children in the Netherlands.
+This requires an evaluation of the long-term impact of such a program on the burden of influenza across all age groups, using a transmission model that accounts for the seasonal variability in vaccine effectiveness and the shorter duration of protection following vaccination as compared to natural infection.
+METHODS: We performed a cost-effectiveness analysis based on a stochastic dynamic transmission model that has been calibrated to reported GP visits with influenza-like illness in the Netherlands over 11 seasons (2003/2004 to 2014/2015).
+We analyzed the costs and effects of extending the current program with vaccination of children aged 2–16 years at 50% coverage over 20 consecutive seasons.
+RESULTS: The childhood vaccination program is estimated to have an average incremental cost-effectiveness ratio (ICER) of €3944 per QALY gained and is cost-effective in the general population (across 1000 simulations; conventional Dutch threshold of €20,000 per QALY gained).
+The childhood vaccination program is not estimated to be cost-effective for the target-group itself with an average ICER of €57,054 per QALY gained.
+Even though introduction of a childhood vaccination program decreases the number of infections, it tends to lead to larger epidemics: in 23.3% of 1000 simulations, the childhood vaccination program results in an increase in seasons with a symptomatic attack rate larger than 5%, which is expected to cause serious strain on the health care system.
+In 6.4% of 1000 simulations, the childhood vaccination program leads to a net loss of QALYs.
+However, childhood influenza vaccination is not cost-effective when only outcomes for the children themselves are considered.
+In approximately a quarter of the simulations, the introduction of a childhood vaccination program increases the frequency of seasons with a symptomatic attack rate larger than 5%.
+BACKGROUNDS: The aim of this study is investigating the benefits and harms of neuromuscular blocking agents (NMBAs) in patients with acute respiratory distress syndrome (ARDS).
+METHODS: We comprehensively searched PubMed, EMBASE, and Cochrane library for randomized controlled trials comparing NMBAs to any other comparator.
+We pooled data using relative risk (RR) for dichotomous outcomes and weighted mean difference (WMD) for continuous outcomes, with 95% confidence intervals.
+We assessed the quality of included studies using the Cochrane tool and levels of evidence using the GRADE method.
+The results showed NMBAs use was not associated with reduced 28 days mortality (RR 0.78; 95% CI, 0.58 to 1.06; P = 0.11), 90 days mortality (RR, 0.92; 95% CI, 0.81 to 1.04; P = 0.16), and intensive care unit (ICU) mortality (RR, 0.90; 95% CI, 0.79 to 1.03; P = 0.13) in patients with ARDS.
+However, 21–28 days mortality was slightly lower in patients received NMBAs (RR 0.73; 95% CI, 0.54 to 0.99; P = 0.04; I(2) = 53%).
+Finally, NMBAs use was associated with a lower risk of barotrauma (RR, 0.55; 95% CI, 0.35 to 0.85; P = 0.007).
+CONCLUSION: In patients with respiratory distress syndrome, NMBAs may be beneficial in reverse refractory hypoxemia and may be associated with reduced short-term mortality and incidence of barotrauma.
+However, there is no significant effects of NMBAs on mid-term and long-term mortality, and further studies are required.
+The central role that erythrocyte invasion plays in Plasmodium falciparum survival and reproduction makes this process an attractive target for therapeutic or vaccine development.
+However, multiple invasion-related genes with complementary and overlapping functions afford the parasite the plasticity to vary ligands used for invasion, leading to phenotypic variation and immune evasion.
+Overcoming the challenge posed by redundant ligands requires a deeper understanding of conditions that select for variant phenotypes and the molecular mediators.
+While host factors including receptor heterogeneity and acquired immune responses may drive parasite phenotypic variation, we have previously shown that host-independent changes in invasion phenotype can be achieved by continuous culturing of the W2mef and Dd2 P. falciparum strains in moving suspension as opposed to static conditions.
+Here, we have used a highly biologically replicated whole transcriptome sequencing approach to identify the molecular signatures of variation associated with the phenotype switch.
+The data show increased expression of particular invasion-related genes in switched parasites, as well as a large number of genes encoding proteins that are either exported or form part of the export machinery.
+The genes with most markedly increased expression included members of the erythrocyte binding antigens (EBA), reticulocyte binding homologues (RH), surface associated interspersed proteins (SURFIN), exported protein family 1 (EPF1) and Plasmodium Helical Interspersed Sub-Telomeric (PHIST) gene families.
+The data indicate changes in expression of a repertoire of genes not previously associated with erythrocyte invasion phenotypes, suggesting the possibility that moving suspension culture may also select for other traits.
+To investigate CTL epitope applications in swine, SLA-1(*)1502-restricted peptide epitopes matching porcine reproductive and respiratory syndrome virus (PRRSV) strains were explored by crystallography, biochemistry, and the specific pathogen-free (SPF) swine experiments.
+First, nine predicted PRRSV peptides were tested by assembly of the peptide-SLA-1(*)1502 (pSLA-1(*)1502) complexes, and the crystal structure of the SLA-1(*)1502 complex with one peptide (NSP9-TMP9) was determined.
+The NSP9-TMP9 peptide conformation presented by pSLA-1(*)1502 is different from that of the peptides presented by the known pSLA-1(*)0401 and pSLA-3(*)hs0202 complexes.
+Two consecutive Pro residues make the turn between P3 and P4 of NSP9-TMP9 much sharper.
+Next, the potential SLA-1(*)1502-restricted peptide epitopes matching four typical genetic PRRSV strains were identified based on the peptide-binding motif of SLA-1(*)1502 determined by structural analysis and alanine scanning of the NSP9-TMP9 peptide.
+Finally, taking NSP9-TMP9 as an example, the CTL immunogenicity of the identified PRRSV peptide epitope was evaluated.
+The SPF swine expressing the SLA-1(*)1502 alleles were divided into three groups: modified live vaccine (MLV), MLV+NSP9-TMP9, and the blank control group.
+NSP9-TMP9 was determined as a PRRSV CTL epitope with strong immunogenicity by flow cytometry and IFN-γ expression.
+Our study developed an integrated approach to identify SLA-I-restricted CTL epitopes from various important viruses and is helpful in designing and applying effective peptide-based vaccines for swine.
+BACKGROUND: A substantial proportion of breast cancer patients develop metastatic disease, with over 450,000 deaths globally per year.
+Bone is the most common first site of metastatic disease accounting for 40% of all first recurrence and 70% of patients with advanced disease develop skeletal involvement.
+Treatment of bone metastases currently focusses on symptom relief and prevention and treatment of skeletal complications.
+Combining systemic therapy with a bone-targeted agent, such as radium-223, may provide an effective treatment with minimal additional side effects.
+METHODS/DESIGN: CARBON is a UK-based, open-label, multi-centre study which comprises an initial safety phase to establish the feasibility and safety of combining radium-223 given on a 6-weekly schedule in combination with orally administered capecitabine followed by a randomised extension phase to further characterise the safety profile and provide preliminary estimation of efficacy.
+DISCUSSION: The CARBON study is important as the results will be the first to assess radium-223 with chemotherapy in advanced breast cancer.
+If the results find acceptable rates of toxicity with a decrease in bone turnover markers, further work will be necessary in a phase II/III setting to assess the efficacy and clinical benefit.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13063-019-3643-6) contains supplementary material, which is available to authorized users.
+INTRODUCTION: Annual influenza vaccination is recommended for older adults, but evidence regarding the impact of repeated vaccination has been inconclusive.
+AIM: We investigated vaccine effectiveness (VE) against laboratory-confirmed influenza and the impact of repeated vaccination over 10 previous seasons on current season VE among older adults.
+METHODS: We conducted an observational test-negative study in community-dwelling adults aged > 65 years in Ontario, Canada for the 2010/11 to 2015/16 seasons by linking laboratory and health administrative data.
+RESULTS: We included 58,304 testing episodes for respiratory viruses, with 11,496 (20%) testing positive for influenza and 31,004 (53%) vaccinated.
+Adjusted VE against laboratory-confirmed influenza for the six seasons combined was 21% (95% confidence interval (CI): 18 to 24%).
+Patients who were vaccinated in the current season, but had received no vaccinations in the previous 10 seasons, had higher current season VE (34%; 95%CI: 9 to 52%) than patients who had received 1–3 (26%; 95%CI: 13 to 37%), 4–6 (24%; 95%CI: 15 to 33%), 7–8 (13%; 95%CI: 2 to 22%), or 9–10 (7%; 95%CI: −4 to 16%) vaccinations (trend test p = 0.001).
+For patients who were not vaccinated in the current season, residual protection rose significantly with increasing numbers of vaccinations received previously.
+CONCLUSIONS: Although VE appeared to decrease with increasing numbers of previous vaccinations, current season vaccination likely provides some protection against influenza regardless of the number of vaccinations received over the previous 10 influenza seasons.
+Mechanical ventilation induces lung injury by damaging alveolar epithelial cells (AECs), but the pathogenesis remains unknown.
+Focal adhesion kinase (FAK) is a cytoplasmic protein tyrosine kinase that is involved in cell growth and intracellular signal transduction pathways.
+This study explored the potential role of FAK in AECs during lung injury induced by mechanical ventilation.
+High-volume mechanical ventilation (HMV) was used to create a mouse lung injury model, which was validated by analysis of lung weight, bronchoalveolar lavage fluid and histological investigation.
+In addition, recombinant FAK was administered to mice via the tail vein, and then the extent of lung injury was assessed.
+Mouse AECs were cultured in vitro, and FAK expression in cells under stretch was investigated.
+The results showed that HMV decreased FAK expression in AECs of mice, while FAK supplementation attenuated lung injury, reduced protein levels/cell counts in the bronchoalveolar lavage fluid and decreased histological lung injury and oedema.
+The protective effect of FAK promoted AEC proliferation and migration and prevented cells from undergoing apoptosis, which restored the integrity of the alveoli through Akt pathway.
+Therefore, the decrease in FAK expression by HMV is essential for injury to epithelial cells and the disruption of alveolar integrity.
+We have previously demonstrated that a recombinant Listeria ivanovii (LI) strain expressing the ESAT-6 or Ag85C protein of Mycobacterium tuberculosis (Mtb) as a tuberculosis (TB) vaccine candidates induced antigen-specific cellular immune responses after intravenous immunization of mice.
+However, whether such recombinant strains could induce desired immune responses in the lung, where TB infection occurs, is not clear.
+In this paper, C57BL/6 J mice were intranasally vaccinated with attenuated LIΔactAplcB-Rv3875 (Δ refers to gene deletion in the bacterial genome) or LIΔactAplcB-Rv0129c, the two vaccine candidates that utilize LI as an antigen delivery vector.
+Bacterial load in the target organs, histological changes in the infected organs, the percentage of specific cytokine-secreting T cells in the lung and spleen, IgG levels in the serum and secretory IgA (SIgA) levles in bronchoalveolar lavage (BAL) fluid were determined at specific days post inoculation (dpi).
+The results showed that both strains were mainly confined to the lung and were eliminated at 10 dpi.
+The histological damage caused by the infection in the lung was slight and recovered by day 5.
+Intranasal vaccination of the mice twice at an interval of 4 weeks notably elicited TB antigen-specific CD4(+) and CD8(+) T cell responses in the lung and SIgA secretion in the pulmonary mucosa, and significantly enhanced the percentage of double-functional CD8(+) T cells (IFN-γ(+) TNF-α(+) CD8(+)).
+To our knowledge, this is the first report regarding the used of LI vector vaccines to induce promising lung-localized cellular and humoral immune responses by intranasal vaccination.
+These data suggest that LI could be a novel and promising live vector to construct an intranasal vaccine against respiratory diseases.
+The Plasmodium falciparum gametocyte surface protein, Pfs48/45, is a potential target for malaria transmission-blocking vaccines.
+However, due to its size and complexity, expression of the full-length protein has been difficult, leading to focus on the C-terminal six cysteine domain (6C) with the use of fusion proteins to facilitate expression and folding.
+In this study, we utilized the baculovirus system to evaluate the expression of three Pfs48/45 proteins including the full-length protein, the 6C domain fragment and the 6C domain mutant to prevent glycosylation.
+Expression of the recombinant Pfs48/45 proteins was conducted in super Sf9 cells combined with the use of tunicamycin to prevent N-glycosylation.
+The proteins were then evaluated as immunogens in mice to demonstrate the induction of functionally active polyclonal antibody responses as measured in the standard membrane feeding assay (SMFA).
+Further characterization of the biologically active 6C protein demonstrated it was homogeneous in terms of size, charge, conformation, absence of glycosylation, and containing proper disulfide bond pairings.
+This study presents an alternative expression system, without the need of a fusion protein partner, for the Pfs48/45 6C protein fragment including further evaluation as a potential transmission-blocking vaccine candidate.
+In the neonatal intensive care unit (NICU), heart rate, respiratory rate, and oxygen saturation are vital signs (VS) that are continuously monitored in infants, while blood pressure is often monitored continuously immediately after birth, or during critical illness.
+Although changes in VS can reflect infant physiology or circadian rhythms, persistent deviations in absolute values or complex changes in variability, can indicate acute or chronic pathology.
+Recent studies demonstrate that analysis of continuous VS trends can predict sepsis, necrotizing enterocolitis, brain injury, bronchopulmonary dysplasia, cardiorespiratory decompensation, and mortality.
+Subtle changes in continuous VS patterns may not be discerned even by experienced clinicians reviewing spot VS data or VS trends captured in the monitor.
+In contrast, objective analysis of continuous VS data can improve neonatal outcomes by allowing heightened vigilance or preemptive interventions.
+In this review, we provide an overview of the studies that have used continuous analysis of single or multiple VS, their interactions, and combined VS and clinical analytic tools, to predict or detect neonatal pathophysiology.
+We make the case that big-data analytics are promising, and with continued improvements, can become a powerful tool to mitigate neonatal diseases in the 21(st) century.
+Patients with frequent exacerbations represent a chronic obstructive pulmonary disease (COPD) subgroup requiring better treatment options.
+The aim of this study was to determine the innate immune mechanisms that underlie susceptibility to frequent exacerbations in COPD.
+We measured sputum expression of immune mediators and bacterial loads in samples from patients with COPD at stable state and during virus-associated exacerbations.
+In vitro immune responses to rhinovirus infection in differentiated primary bronchial epithelial cells (BECs) sampled from patients with COPD were additionally evaluated.
+Patients were stratified as frequent exacerbators (≥2 exacerbations in the preceding year) or infrequent exacerbators (<2 exacerbations in the preceding year) with comparisons made between these groups.
+Frequent exacerbators had reduced sputum cell mRNA expression of the antiviral immune mediators type I and III interferons and reduced interferon-stimulated gene (ISG) expression when clinically stable and during virus-associated exacerbation.
+A role for epithelial cell-intrinsic innate immune dysregulation was identified: induction of interferons and ISGs during in vitro rhinovirus (RV) infection was also impaired in differentiated BECs from frequent exacerbators.
+Frequent exacerbators additionally had increased sputum bacterial loads at 2 wk following virus-associated exacerbation onset.
+These data implicate deficient airway innate immunity involving epithelial cells in the increased propensity to exacerbations observed in some patients with COPD.
+Therapeutic approaches to boost innate antimicrobial immunity in the lung could be a viable strategy for prevention and treatment of frequent exacerbations.
+Upon infection, chikungunya fever (CHIKF) can result in long-term joint pain and arthritis, and despite intense research, no licensed vaccine for CHIKV is available.
+We have developed two recombinant chimpanzee adenovirus-vectored vaccines (ChAdOx1) that induce swift and robust anti-CHIKV immune responses with a single dose, without the need for adjuvants or booster vaccines.
+Here, we report the vaccines’ protective efficacies against CHIKV infection in a lethal A129 mouse model.
+Our results indicate that a single, un-adjuvanted ChAdOx1 Chik or ChAdOx1 Chik ΔCap dose provided complete protection against a lethal virus challenge and prevented CHIKV-associated severe inflammation.
+These candidate vaccines supported survival equal to the attenuated 181/25 CHIKV reference vaccine but without the vaccine-related side effects, such as weight loss.
+Vaccination with either ChAdOx1 Chik or ChAdOx1 Chik ΔCap resulted in high titers of neutralizing antibodies that are associated with protection, indicating that the presence of the capsid within the vaccine construct may not be essential to afford protection under the conditions tested.
+We conclude that both replication-deficient ChAdOx1 Chik vaccines are safe even when used in A129 mice and afford complete protection from a lethal challenge.
+RHD, characterized by hemorrhaging, liver necrosis, and high morbidity and mortality in rabbits and hares, causes severe economic losses in the rabbit industry worldwide.
+Due to the lack of an efficient in-vitro propagation system for RHDV, the current vaccine is produced via chemical inactivation of crude RHDV preparation derived from the livers of infected rabbits.
+Inactivated vaccines are effective for controlling RHD, but the potential problems of biosafety and animal welfare have negative effects on the application of inactivated vaccines.
+In this study, an oral Lactobacillus casei (L. casei) vaccine was used as an antigen delivery system to express RHDV capsid protein VP60(VP1)-eGFP fusion protein.
+Our results indicate that oral administration of this probiotic vaccine can stimulate secretory immunoglobulin A (SIgA)-based mucosal and IgG-based humoral immune responses in rabbits.
+Our findings indicate that the L. casei expression system is a new strategy for the development of a safe and efficient vaccine against RHDV.
+Pseudorabies virus (PRV), a member of the Herpesviridae, is the causative agent of an acute infectious disease in a variety of animals.
+The emergence of a novel variant strain brought huge economic losses to the pig industry since classical vaccine strains were not completely effective against variant strains.
+Therefore, the development of new anti-pseudorabies virus drugs and vaccines is of great significance for the treatment and prevention of pseudorabies.
+In this study, we found that germacrone, one of the major components of the essential oils extracted from Rhizoma Curcuma, was able to effectively inhibit PRV replication in a dose-dependent manner in vitro.
+Germacrone showed antiviral activity against PRV in the early phase of the viral replication cycle.
+Moreover, we found that germacrone does not directly kill the virus, nor does it affect the expression of the PRV receptor protein nectin-1, nectin-2, and CD155.
+Our results suggest germacrone could be used as an efficient microbicide or immunomodulatory agent in the control of the emerging variant PRV.
+Acute respiratory infections (ARIs) are extremely common in children, especially those under 5 years old.
+They can lead to complications, super-infection, respiratory failure, and even compromised respiratory function in adulthood.
+This review reports current issues about vaccines against the main respiratory pathogens to highlight the available strategies to reduce the burden of paediatric respiratory disease.
+The optimal use of influenza, pneumococcal, pertussis and measles vaccines is required in order to reduce ARI burden.
+Recently, advances in the knowledge of respiratory syncytial virus structural biology and immunology as well as the development of new techniques to generate vaccine candidates have increased the number of promising vaccines even against this harmful pathogen.
+Antimicrobial stewardship program (ASP) is one of the most important strategies for managing infectious disease treatment and preventing antimicrobial resistance.
+We evaluated perceptions of current ASP, potential setbacks of ASP implementation, and future demands on ASP services among physicians and pharmacists in the CHS.
+The qualitative research was conducted through in-depth individual interviews and focus group discussions with 11 physicians and 11 pharmacists.
+In addition, a quantitative gap analysis was conducted to assess the different awareness and demands on services of ASP and preferred antimicrobial-related problems (ARP).
+The identified setbacks were unorganized institutional leadership, the undefined roles of healthcare professionals, a lack of reimbursement, the hierarchical structure of the health system, and the labor-intensive working environment of pharmacy services.
+Although demands for ASP improvement were similar among professionals, they had different preferences in prioritizing each service item of ASP/ARP development and the profession responsible for each service.
+Continuous administrative and financial investments, understanding ASP contents, ASP-specific information technology, and interdisciplinary collaboration with good communication among healthcare professions are needed to continue the progression of ASP.
+Zika virus (ZIKV) is an emerging mosquito-borne flavivirus that has spread to more than 70 countries worldwide since 2015.
+We have previously reported the development of various adenoviral vectored vaccine candidates (ChAdOx1 ZIKV) with the ability to stimulate effective immunity in mice and provide protection upon a ZIKV challenge model, using a non-adjuvanted single vaccination approach.
+In this study, we constructed various modified vaccinia Ankara (MVA) viruses to express the ZIKV Envelope (E) with modifications on the precursor membrane (prM) or on the C-terminus envelope transmembrane domain (TM), similar to our ChAdOx1 vaccine candidates.
+MVA-ZIKV vaccine candidates were evaluated as a non-adjuvanted single vaccination regimen against a ZIKV Brazilian isolate, using viraemia as the correlate of protection.
+Here, we report the induction of a modest level of anti-ZIKV E antibodies by all MVA vectored vaccines and sub-optimal efficacy in a ZIKV challenge model.
+Our results indicate the requirement of additional strategies when using MVA-ZIKV vaccines to afford sterile protection upon a non-adjuvanted and single vaccination regime.
+BACKGROUND: Acinetobacter baumannii is a Gram-negative opportunistic pathogen with a notorious reputation of being resistant to antimicrobial agents.
+The capability of A. baumannii to persist and disseminate between healthcare settings has raised a major concern worldwide.
+METHODS: Our study investigated the antibiotic resistance features and molecular epidemiology of 52 clinical isolates of A. baumannii collected in Pakistan between 2013 and 2015.
+Comparative sequence analyses of the ampC and bla(OXA-51-like) alleles were used to assign the isolates into clusters.
+Free online applications were used to determine the phylogeny of genomic sequences, retrieve the multilocus sequence types (ST), and detect acquired antimicrobial resistance genes.
+The largest cluster, Ab-Pak-cluster-1 (bla(OXA-66) and ISAba1-ampC-19) included 24 isolates, belonged to ST2 and International clone (IC) II, and was distributed between two geographical far-off cities, Lahore and Peshawar.
+Ab-Pak-clusters-2 (bla(OXA-66), ISAba1-ampC-2), and -3 (bla(OXA-66), ISAba1-ampC-20) and the individual isolate Ab-Pak-Lah-01 (ISAba1-bla(OXA-66), ISAba1-ampC-2) were also assigned to ST2 and IC II.
+On the other hand, Ab-Pak-clusters-4 (bla(OXA-69), ampC-1), -5 (bla(OXA-69), ISAba1-ampC-78), and -6A (bla(OXA-371), ISAba1-ampC-3) belonged to ST1, while Ab-Pak-cluster-6B (bla(OXA-371), ISAba1-ampC-8) belonged to ST1106, with both ST1 and ST1106 being members of IC I.
+This cluster corresponded to ST158, showed a well-delineated position on the genomic phylogenetic tree, and was equipped with several antimicrobial resistance genes including bla(OXA-23) and bla(GES-11).
+Altogether, 6/7 of the clusters and 45/52 (86.5%) of the isolates belonged to IC I (n = 9) or II (n = 36), making Pakistan no exception to the global domination of these two clones.
+The onset of ST158 in Pakistan marked a geographical dispersal of this clone beyond the Middle East and brought up the need for a detailed characterization.
+BACKGROUND: In endemic areas, pregnant women are highly susceptible to Plasmodium falciparum malaria characterized by the accumulation of parasitized red blood cells (pRBC) in the placenta.
+In subsequent pregnancies, women develop protective immunity to pregnancy-associated malaria and this has been hypothesized to be due to the acquisition of antibodies to the parasite variant surface antigen VAR2CSA.
+In this systematic review we provide the first synthesis of the association between antibodies to pregnancy-specific P. falciparum antigens and pregnancy and birth outcomes.
+METHODS: We conducted a systematic review and meta-analysis of population-based studies (published up to 07 June 2019) of pregnant women living in P. falciparum endemic areas that examined antibody responses to pregnancy-specific P. falciparum antigens and outcomes including placental malaria, low birthweight, preterm birth, peripheral parasitaemia, maternal anaemia, and severe malaria.
+RESULTS: We searched 6 databases and identified 33 studies (30 from Africa) that met predetermined inclusion and quality criteria: 16 studies contributed estimates in a format enabling inclusion in meta-analysis and 17 were included in narrative form only.
+Estimates were mostly from cross-sectional data (10 studies) and were heterogeneous in terms of magnitude and direction of effect.
+Included studies varied in terms of antigens tested, methodology used to measure antibody responses, and epidemiological setting.
+Antibody responses to pregnancy-specific pRBC and VAR2CSA antigens, measured at delivery, were associated with placental malaria (9 studies) and may therefore represent markers of infection, rather than correlates of protection.
+Antibody responses to pregnancy-specific pRBC, but not recombinant VAR2CSA antigens, were associated with trends towards protection from low birthweight (5 studies).
+CONCLUSIONS: Whilst antibody responses to several antigens were positively associated with the presence of placental and peripheral infections, this review did not identify evidence that any specific antibody response is associated with protection from pregnancy-associated malaria across multiple populations.
+Further prospective cohort studies using standardized laboratory methods to examine responses to a broad range of antigens in different epidemiological settings and throughout the gestational period, will be necessary to identify and prioritize pregnancy-specific P. falciparum antigens to advance the development of vaccines and serosurveillance tools targeting pregnant women.
+The Bacteremia Antibiotic Length Actually Needed for Clinical Effectiveness (BALANCE) pilot randomized clinical trial (RCT) determined that it was feasible to enroll and randomize intensive care unit (ICU) patients with bloodstream infection to 7 versus 14 days of treatment, and served as the vanguard for the ongoing BALANCE main RCT.
+We performed this BALANCE-Ward pilot RCT to examine the feasibility and impact of potentially extending the BALANCE main RCT to include patients hospitalized on non-ICU wards.
+METHODS: We conducted an open pilot RCT among a subset of six sites participating in the ongoing BALANCE RCT, randomizing patients with positive non-Staphylococcus aureus blood cultures on non-ICU wards to 7 versus 14 days of antibiotic treatment.
+We compared feasibility outcomes, patient/pathogen characteristics, and overall outcomes among those enrolled in this BALANCE-Ward and prior BALANCE-ICU pilot RCTs.
+We estimated the sample size and non-inferiority margin impacts of expanding the BALANCE main RCT to include non-ICU patients.
+RESULTS: A total of 134 patients were recruited over 47 site-months (mean 2.9 patients/site-month, median 1.0, range 0.1–4.4 patients/site-month).
+The overall recruitment rate exceeded the BALANCE-ICU pilot RCT (mean 1.10 patients/site-month, p < 0.0001).
+Overall protocol adherence also exceeded the adherence in the BALANCE-ICU pilot RCT (125/134, 93% vs 89/115, 77%, p = 0.0003).
+BALANCE-Ward patients were older, with lower Sequential Organ Failure Assessment scores, and higher proportions of infections caused by Escherichia coli and genito-urinary sources of bloodstream infection.
+The BALANCE-Ward pilot RCT patients had an overall 90-day mortality rate of 17/133 (12.8%), which was comparable to the 90-day mortality rate in the ICU pilot RCT (17/115, 14.8%) (p = 0.65).
+Simulation models indicated there would be minimal sample size and non-inferiority margin implications of expanding enrolment to increasing proportions of non-ICU versus ICU patients.
+CONCLUSION: It is feasible to enroll non-ICU patients in a trial of 7 versus 14 days of antibiotics for bloodstream infection, and expanding the BALANCE RCT hospital-wide has the potential to improve the timeliness and generalizability of trial results.
+Standard inactivated influenza vaccines are poorly immunogenic in immunologically naive healthy young children, who are particularly vulnerable to complications from influenza.
+Here, we meta-analyze randomized controlled trials with efficacy data (3 trials, n = 15,310) and immunogenicity data (17 trials, n = 9062).
+Compared with non-adjuvanted counterparts, adjuvanted influenza vaccines provide a significantly better protection (weighted estimate for risk ratio of RT-PCR-confirmed influenza: 0.26) and are significantly more immunogenic (weighted estimates for seroprotection rate ratio: 4.6 to 7.9) in healthy immunologically naive young children.
+Nevertheless, in immunologically non-naive children, adjuvanted and non-adjuvanted vaccines provide similar protection and are similarly immunogenic.
+These results indicate that oil-in-water emulsion adjuvant improves the efficacy of inactivated influenza vaccines in healthy young children at the first-time seasonal influenza vaccination.
+Clot formation might be associated with this complication, but the precise mechanism of an abnormal elevation in pressure has not been identified.
+We investigated sufficient conditions for in-circuit elevation in pressure using an ex vivo re-circulation circuit with porcine blood.
+Specifically, we investigated the effect of blood conditions, the type of anticoagulation, and pro-inflammatory stimulation on in-circuit pressure.
+We also examined the cause of an abnormal elevation of in-circuit pressure by specifically degrading DNA, RNA, or protein components of an obstructed filter and by using immunofluorescent techniques.
+Neither a change in temperature nor change in pH in the blood increased in-circuit pressure.
+In contrast, long-term storage of blood, pro-inflammatory stimulation by phorbol myristate acetate, and heparin administration significantly increased in-circuit pressure.
+Abnormal in-circuit elevation in pressure was associated with deposition of extracellular DNA on the outlet surface of the filter.
+In an ex vivo re-circulation circuit system, extracellular DNA deposition on the filter is responsible for an abnormal in-circuit elevation in pressure.
+To prevent the occurrence of medication errors in clinical practice, safety concerns may be included in the risk management plan and subsequently be addressed with routine and/or additional risk minimisation measures.
+OBJECTIVE: This study aims to describe safety concerns around medication errors and the risk minimisation measures for centrally authorised products in the European Union.
+METHODS: All safety concerns included in the risk management plans of originator centrally authorised products, authorised between 1 January, 2010 and 31 December, 2017, were collected from the European Public Assessment Report registry.
+Medication error safety concerns were categorised by Anatomical Therapeutic Classification code, year of authorisation, type of medication error and type of risk minimisation measure.
+RESULTS: During the study period, 311 centrally authorised products were approved, of which 84 had at least one medication error safety concern.
+The proportion of centrally authorised products with medication error safety concerns showed variation between 2010 and 2017 ranging from 15.2% to 36.4%.
+The type of medication error was highly variable, drug administration error was listed most frequently (n = 17).
+For 27 out of 95 medication error safety concerns, corresponding to 23 centrally authorised products, additional risk minimisation measures were required.
+All additional risk minimisation measures consisted of educational material targeted at healthcare professionals (85.2%) and/or patients (51.9%).
+For 78.3% of centrally authorised products with additional risk minimisation measures for medication errors, studies to evaluate the effectiveness of the additional risk minimisation measures were agreed upon.
+CONCLUSIONS: Medication error safety concerns were listed for almost a quarter of centrally authorised products approved during the study period.
+Further research is needed to evaluate the effectiveness and continued need for additional risk minimisation measures for medication errors.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s40264-019-00874-7) contains supplementary material, which is available to authorized users.
+To investigate the evolution of lung function in preterm infants with and without bronchopulmonary dysplasia (BPD) and to determine the perinatal characteristics associated with indexes of lung function in later infancy.
+Longitudinal lung function assessments were performed at approximately 6, 12, 18, and 24 months of corrected age in preterm infants.
+Although all preterm infants (n = 121; 61 without BPD and 60 with BPD) exhibited decreased lung function in early infancy (6 months of age), after body length was adjusted for, only infants with BPD exhibited poor performance.
+Furthermore, the lung function of infants with mild to moderate BPD caught up gradually, but the generally poor lung function performance of infants with severe BPD, especially in forced expiratory flow, persisted until later age (24 months).
+Regarding perinatal characteristics, the z-score of body length at the time of examination and total number of days on positive-pressure ventilation are the major determinants of lung function in later infancy.
+Zika virus (ZIKV) is a mosquito-borne member of the Flaviviridae family that has been known to circulate for decades causing mild febrile illness.
+The more recent ZIKV outbreaks in the Americas and the Caribbean associated with congenital malformations and Guillain-Barré syndrome in adults have placed public health officials in high alert and highlight the significant impact of ZIKV on human health.
+New technologies to study the biology of ZIKV and to develop more effective prevention options are highly desired.
+In this study we demonstrate that direct delivery in mice of an infectious ZIKV cDNA clone allows the rescue of recombinant (r)ZIKV in vivo.
+A bacterial artificial chromosome containing the sequence of ZIKV strain Paraiba/2015 under the control of the cytomegalovirus promoter was complexed with a commercial transfection reagent and administrated using different routes in type-I interferon receptor deficient A129 mice.
+The rZIKV recovered from these mice remained fully virulent in a second passage in mice.
+Interestingly, infectious rZIKV was also recovered after intraperitoneal inoculation of the rZIKV cDNA in the absence of transfection reagent.
+Further expanding these studies, we demonstrate that a single intraperitoneal inoculation of a cDNA clone encoding an attenuated rZIKV was safe, highly immunogenic, and provided full protection against lethal ZIKV challenge.
+This novel in vivo reverse genetics method is a potentially suitable delivery platform for the study of wild-type and live-attenuated ZIKV devoid of confounding factors typical associated with in vitro systems.
+Moreover, our results open the possibility of employing similar in vivo reverse genetic approaches for the generation of other viruses and, therefore, change the way we will use reverse genetics in the future.
+A fast Endospore Germinability Assay (EGA) was validated with traditional plate counts to enumerate single endospore germination events for monitoring surface sterilization.
+The assay is based on a time-gated luminescence microscopy technique enabling visualization and enumeration of individual germinating endospores.
+Germinating endospores release calcium dipicolinate to form highly luminescent terbium dipicolinate complexes surrounding each germinating endospore.
+EGA and heterotrophic plate counting (HPC) were used to evaluate the swab/rinse recovery efficiency of endospores from stainless steel surfaces.
+EGA and HPC results were highly correlated for endospore recovery from stainless steel coupons inoculated with range of 1,000 endospores per coupon down to sterility.
+Dosage-dependent decrease of surface endospore germinability were observed in dry heat, UV irradiation, oxygen plasma and vaporized hydrogen peroxide treatments, measured with EGA and HPC.
+EGA is a fast and complementary method to traditional HPC for quantitative sterility assurance testing of surfaces.
+This work introduces and validates a 15-minute or faster assay for germinable endospores to complement the conventional lengthy, culture-based surface sterility validation, which is critical in hospitals, food and pharmaceutical industries to help minimize nosocomial infection, food spoilage, and pharmaceutical contamination.
+BACKGROUND: Despite increasing use of the flipped classroom (FC) technique in undergraduate medical education, the benefit in learning outcomes over lectures is inconsistent.
+Best practices in preclass video design principles are rarely used, and it is unclear if videos can replace lectures in contemporary medical education.
+METHODS: We conducted a prospective quasi‐experimental controlled educational study comparing theory‐based videos to traditional lectures in a medical student curriculum.
+Medical students enrolled in an emergency medicine clerkship were randomly assigned to either a lecture group (LG) or a video group (VG).
+The slide content was identical, and the videos aligned with cognitive load theory‐based multimedia design principles.
+Students underwent baseline (pretest), week 1 (posttest), and end‐of‐rotation (retention) written knowledge tests and an observed structured clinical examination (OSCE) assessment.
+We compared scores between both groups and surveyed student attitudes and satisfaction with respect to the two learning methods.
+RESULTS: There were 104 students who participated in OSCE assessments (49 LG, 55 VG) and 101 students who participated in knowledge tests (48 LG, 53 VG).
+The difference in OSCE scores was statistically significant 1.29 (95% confidence interval = 0.23 to 2.35, t(102) = 2.43, p = 0.017), but the actual score difference was small from an educational standpoint (12.61 for LG, 11.32 for VG).
+CONCLUSIONS: Videos based on cognitive load theory produced similar results and could replace traditional lectures for medical students.
+Educators contemplating a FC approach should devote their valuable classroom time to active learning methods.
+The regulation of ubiquitination status in the cell is controlled by ubiquitin ligases acting in tandem with deubiquitinating enzymes.
+Ubiquitination controls many key processes in the cell from division to death making its tight regulation key to optimal cell function.
+Activity based protein profiling has emerged as a powerful technique to study these important enzymes.
+With around 100 deubiquitinating enzymes and 600 ubiquitin ligases in the human genome targeting a subclass of these enzymes or even a single enzyme is a compelling strategy to unpick this complex system.
+In this review we will discuss different approaches adopted, including activity-based probes centered around ubiquitin-protein, ubiquitin-peptide and mutated ubiquitin scaffolds.
+We examine challenges faced and opportunities presented to increase specificity in activity-based protein profiling of the ubiquitin conjugation/deconjugation machinery.
+BACKGROUND: Young women in sub-Saharan Africa remain at the epicentre of the HIV epidemic, with surveillance data indicating persistent high levels of HIV incidence.
+In South Africa, adolescent girls and young women (AGYW) account for a quarter of all new HIV infections.
+Determined, Resilient, Empowered, AIDS-free, Mentored and Safe (DREAMS) is a strategy introduced by the United States President’s Emergency Plan for AIDS Relief (PEPFAR) aimed at reducing HIV incidence among AGYW in 10 countries in sub-Saharan Africa by 25% in the programme’s first year, and by 40% in the second year.
+This study will assess the change in HIV incidence and reduction in risk associated behaviours that can be attributed to the DREAMS initiative in South Africa, using a population-based cross-sectional survey.
+METHODS: Data will be collected from a household-based representative sample of AGYW (between the ages 12–24 years) in four high prevalence districts (more than 10% of the population have HIV in these districts) in South Africa in which DREAMS has been implemented.
+A stratified cluster-based sampling approach will be used to select eligible participants for a cross-sectional survey with 18,500, to be conducted over 2017/2018.
+A questionnaire will be administered containing questions on sexual risk behaviour, selected academic and developmental milestones, prevalence of gender based violence, whilst examining exposure to DREAMS programmes.
+Biological samples, including two micro-containers of blood and self-collected vulvovaginal swab samples, are collected in each survey to test for HIV infection, HIV incidence, sexually transmitted infections (STIs) and pregnancy.
+This study will measure trends in population level HIV incidence using the Limiting antigen (LAg) Avidity Enzyme Immuno-Assay (EIA) and monitor changes in HIV incidence.
+DISCUSSION: Ending the HIV/AIDS pandemic by 2030 requires the continual monitoring and evaluation of prevention programmes, with the aim of optimising efforts and ensuring the achievement of epidemic control.
+This study will determine the impact DREAMS interventions have had on HIV incidence among AGYW in a ‘real world, non-trial setting’.
+Strains producing extended-spectrum beta-lactamases (ESBLs) or carbapenemases are considered global priority pathogens for which new treatment and prevention strategies are urgently required, due to severely limited therapeutic options.
+South and Southeast Asia are major hubs for antimicrobial-resistant (AMR) K. pneumoniae and also for the characteristically antimicrobial-sensitive, community-acquired “hypervirulent” strains.
+The emergence of hypervirulent AMR strains and lack of data on exopolysaccharide diversity pose a challenge for K. pneumoniae BSI control strategies worldwide.
+METHODS: We conducted a retrospective genomic epidemiology study of 365 BSI K. pneumoniae from seven major healthcare facilities across South and Southeast Asia, extracting clinically relevant information (AMR, virulence, K and O antigen loci) using Kleborate, a K. pneumoniae-specific genomic typing tool.
+RESULTS: K. pneumoniae BSI isolates were highly diverse, comprising 120 multi-locus sequence types (STs) and 63 K-loci.
+The latter represent genotypic AMR-virulence convergence, which is generally considered a rare phenomenon but was particularly common among South Asian BSI (17%).
+Of greatest concern, we identified seven novel plasmids carrying both iuc and AMR genes, raising the prospect of co-transfer of these phenotypes among K. pneumoniae.
+CONCLUSIONS: K. pneumoniae BSI in South and Southeast Asia are caused by different STs from those predominating in other regions, and with higher frequency of acquired virulence determinants.
+K. pneumoniae carrying both iuc and AMR genes were also detected at higher rates than have been reported elsewhere.
+The study demonstrates how genomics-based surveillance—reporting full molecular profiles including STs, AMR, virulence and serotype locus information—can help standardise comparisons between sites and identify regional differences in pathogen populations.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13073-019-0706-y) contains supplementary material, which is available to authorized users.
+We conducted a three-phase study using human factors engineering (HFE) approach to enhance environmental cleanliness.
+METHODS: This study was conducted using a prospective interventional trial, and 28 (33.3%) of 84 wards in a medical center were sampled.
+The three-phases included pre-intervention analysis (Phase 1), implementing interventions by HFE principles (Phase 2), and programmatic analysis (Phase 3).
+The evaluations of terminal cleaning and disinfection were performed using the fluorescent marker, the adenosine triphosphate bioluminescence assay, and the aerobic colony count method simultaneously in all phases.
+Effective terminal cleaning and disinfection was qualified with the aggregate outcome of the same 10 high-touch surfaces per room.
+A score for each high-touch surface was recorded, with 0 denoting a fail and 10 denoting a pass by the benchmark of the evaluation method, and the total terminal cleaning and disinfection score (TCD score) was a score out of 100.
+RESULTS: In each phase, 840 high-touch surfaces were collected from 84 rooms after terminal cleaning and disinfection.
+After the interventions, the TCD score by the three evaluation methods all showed significant improved.
+The carriage incidence of multidrug-resistant organism (MDRO) decreased significantly from 4.1 per 1000 patient-days to 3.6 per 1000 patient-days (P = .03).
+CONCLUSION: The HFE approach can improve the thoroughness and the effectiveness of terminal cleaning and disinfection, and resulted in a reduction of patient carriage of MDRO at hospitals.
+Larger studies are necessary to establish whether such efforts of cleanliness can reduce the incidence of healthcare-associated infection.
+The bacterium primarily infects the throat and upper airways and the produced diphtheria toxin (DT), which binds to the elongation factor 2 and blocks protein synthesis, can spread through the bloodstream and affect organs, such as the heart and kidneys.
+For more than 125 years, the therapy against diphtheria has been based on polyclonal horse sera directed against DT (diphtheria antitoxin; DAT).
+Animal sera have many disadvantages including serum sickness, batch-to-batch variation in quality and the use of animals for production.
+In this work, 400 human recombinant antibodies were generated against DT from two different phage display panning strategies using a human immune library.
+A panning in microtiter plates resulted in 22 unique in vitro neutralizing antibodies and a panning in solution combined with a functional neutralization screening resulted in 268 in vitro neutralizing antibodies.
+61 unique antibodies were further characterized as scFv-Fc with 35 produced as fully human IgG1.
+The best in vitro neutralizing antibody showed an estimated relative potency of 454 IU/mg and minimal effective dose 50% (MED50%) of 3.0 pM at a constant amount of DT (4x minimal cytopathic dose) in the IgG format.
+The targeted domains of the 35 antibodies were analyzed by immunoblot and by epitope mapping using phage display.
+All three DT domains (enzymatic domain, translocation domain and receptor binding domain) are targets for neutralizing antibodies.
+When toxin neutralization assays were performed at higher toxin dose levels, the neutralizing capacity of individual antibodies was markedly reduced but this was largely compensated for by using two or more antibodies in combination, resulting in a potency of 79.4 IU/mg in the in vivo intradermal challenge assay.
+These recombinant antibody combinations are candidates for further clinical and regulatory development to replace equine DAT.
+Streptococcus agalactiae is a causative agent of streptococcosis disease in various fish species, including Nile tilapia (Oreochromis niloticus Linn.).
+Vaccination is an effective disease prevention and control method, but limitations remain for protecting against catastrophic mortality of fish infected with different strains of streptococci.
+Immunoproteomics analysis of S. agalactiae was used to identify antigenic proteins and construct a chimeric multiepitope vaccine.
+Epitopes from five antigenic proteins were shuffled in five helices of a flavodoxin backbone, and in silico analysis predicted a suitable RNA and protein structure for protein expression.
+Overexpressed proteins were determined to be 30 kDa and 25 kDa in the E. coli and TK1 systems, respectively.
+The efficacy of the chimeric multiepitope construct as a recombinant protein vaccine and DNA vaccine was evaluated in Nile tilapia, followed by S. agalactiae challenge at 1 × 10(7) CFU/mL.
+Relative percentage survival (RPS) and cumulative mortality were recorded at approximately 57–76% and 17–30%, respectively.
+These chimeric multiepitope vaccines should be applied in streptococcosis disease control and developed into a multivalent vaccine to control multiple diseases.
+Atrial fibrillation (AF) is a progressive arrhythmia with underlying mechanisms that are not fully elucidated, partially due to lack of reliable and affordable animal models.
+Here, we introduce a system for long-term assessment of AF susceptibility (substrate) in ambulatory rats implanted with miniature electrodes on the atrium.
+AF substrate was tested two- and four-weeks post implantation and was also compared with implanted rats early post-implantation (Base).
+In the MI group only, AF duration was correlated with the level of atrial fibrosis and was inversely correlated with systolic function.
+Further studies indicated that serum inflammatory markers (IL-6, TNF-alpha) were not elevated in the shams.
+Finally, enhanced biocompatibility of the atrial electrode did not inhibit the gradual development of AF substrate over a testing period of up to 8 weeks.
+Overall, we successfully validated the first system for long-term AF substrate testing in ambulatory rats.
+BACKGROUND: Critically ill patients undergo extensive physiological alterations that will have impact on antibiotic pharmacokinetics.
+Up to 60% of intensive care unit (ICU) patients meet the pharmacodynamic targets of beta-lactam antibiotics, with only 30% in fluoroquinolones.
+Not reaching these targets might increase the chance of therapeutic failure, resulting in increased mortality and morbidity, and antibiotic resistance.
+The DOLPHIN trial was designed to demonstrate the added value of therapeutic drug monitoring (TDM) of beta-lactam and fluoroquinolones in critically ill patients in the ICU.
+METHODS: A multi-centre, randomised controlled trial (RCT) was designed to assess the efficacy and cost-effectiveness of model-based TDM of beta-lactam and fluoroquinolones.
+Eligible patients will be randomly allocated to either study group: the intervention group (active TDM) or the control group (non-TDM).
+In the intervention group dose adjustment of the study antibiotics (cefotaxime, ceftazidime, ceftriaxone, cefuroxime, amoxicillin, amoxicillin with clavulanic acid, flucloxacillin, piperacillin with tazobactam, meropenem, and ciprofloxacin) on day 1, 3, and 5 is performed based upon TDM with a Bayesian model.
+Other outcomes amongst all survival, disease severity, safety, quality of life after ICU discharge, and cost effectiveness will be included.
+DISCUSSION: No trial has investigated the effect of early TDM of beta-lactam and fluoroquinolones on clinical outcome in critically ill patients.
+The findings from the DOLPHIN trial will possibly lead to new insights in clinical management of critically ill patients receiving antibiotics.
+Recently we have identified that the peptide PH((1–110)) from polyhedrin self-aggregates and incorporates foreign proteins to form particles.
+We have proposed that this peptide can be used as an antigen carrying system for vaccines.
+However, the immune response generated by the antigen fused to the peptide has not been fully characterized.
+RESULTS: In the present study we demonstrate the use of a system developed to generate nano and microparticles carrying as a fusion protein peptides or proteins of interest to be used as vaccines.
+Immunization of animals with the particles in the absence of adjuvant result in a robust and long-lasting immune response.
+Proteins contained inside the particles are maintained for over 1 year at ambient temperature, preserving their immunological properties.
+CONCLUSION: The rapid and efficient production of the particles in addition to the robust immune response they generate position this system as an excellent method for the rapid response against emerging diseases.
+The thermostability conferred by the particle system facilitates the distribution of the vaccines in developing countries or areas with no electricity.
+BACKGROUND: This study aims to evaluate the gap between countries’ self-evaluation and external evaluation regarding core capacity of infectious disease control required by International Health Regulations and the influence factors of the gap.
+METHODS: We collected countries’ self-evaluated scores (International Health Regulations Monitoring tool, IHRMT) of 2016 and 2017, and external evaluation scores (Joint External Evaluation, JEE) from WHO website on 4rd and 27rd November, 2018.
+There were 127 and 163 countries with IHRMT scores in 2016 and in 2017, and 74 countries with JEE scores included in the analysis.
+The gap between countries’ self-evaluation and external evaluation was represented by the difference between condensed IHR scores and JEE.
+The Human Development Index (HDI) and data indicating the density of physicians and nurses (HWD) were collected to reflect countries’ development and health workforce statuses.
+Then, chi-square test and logistic regression were performed to determine the correlation between the gap of IHRMT and JEE, and civil liberties, human development, and health workforce status.
+There were significantly more countries with high HDI status, high CL status and high HWD status in groups with bigger gap between IHRMT and JEE.
+And countries with higher HDI status presented a higher risk of having bigger gap between countries’ self and external scores (OR = 3.181).
+CONCLUSION: Our study result indicated that countries’ transparency represented by CL status do play a role in the gap between IHR and JEE scores.
+The main reason for the gap in the current world is the different interpretation of evaluation of high HDI countries, though low CL countries tended to over-scored their capacity.
+BACKGROUND: As patients with left ventricular assist device (LVAD) have long expected survival, the incidence of noncardiac surgery in this patient population is increasing.
+Here, we present the anesthetic management of a patient with a continuous-flow LVAD who underwent video-assisted thoracic surgery (VATS).
+CASE PRESENTATION: A 37-year-old man with LVAD was scheduled to undergo VATS because of repeated spontaneous pneumothorax.
+Generally, patients with these devices have marginal right heart function; therefore, it is important to avoid factors that worsen pulmonary vascular resistance (PVR).
+However, VATS requires one-lung ventilation (OLV) and it tends to cause increase in PVR, leading to right heart failure.
+In the present case, when the patient was set in a lateral decubitus position and progressive hypoxia was observed during OLV, transesophageal echocardiography demonstrated a dilated right ventricle and a temporally flattened interventricular septum, and the central venous pressure increased to approximately 20 mmHg.
+Because we anticipated deterioration of right heart function, dobutamine and milrinone were administered and/or respirator settings were changed to decrease PVR for maintaining LVAD performance.
+Finally, resection of a bulla was completed, and the patient was discharged in stable condition on postoperative day 37.
+CONCLUSIONS: The anesthetic management of a patient with LVAD during VATS is challenging because the possible hemodynamic changes induced by hypoxia associated with OLV affect LVAD performance and right heart function.
+In our experience, VATS that requires OLV will be well tolerated in a patient with LVAD with preserved right heart function, and a multidisciplinary approach to maintain right heart function will be needed.
+OBJECTIVES: Information provided by news media during an infectious disease outbreak can affect the actions taken to safeguard public health.
+There has been little evaluation of how the content of news published during an outbreak varies by location of the news outlet.
+This study analyzes coverage of the 2014 Ebola outbreak by one news outlet operating within a country affected by the outbreak and one country not directly affected.
+METHODS: A qualitative content analysis was conducted of articles published in two national news outlets, The Globe and Mail (Canada) and the Vanguard (Nigeria), between January 1 and December 31, 2014.
+Articles available through LexisNexis Academic were sorted by date and sampled using a stratified sampling method (The Globe and Mail n = 100; Vanguard n = 105).
+A coding scheme was developed and modified to incorporate emerging themes until saturation was achieved.
+RESULTS: There were substantial differences in outbreak coverage in terms of the topic and content of the articles, as well as the sources consulted.
+The Globe and Mail framed the outbreak in terms of national security and national interests, as well as presenting it as an international humanitarian crisis.
+CONCLUSION: Our findings highlight how different geographic contexts can shape reporting on the same event.
+Further research is required to investigate how the political, social or economic situations of a country shape its news media, potentially influencing actions taken to control disease outbreaks.
+Compared with conventional procedures, the uniportal video-assisted thoracoscopic surgery (UniVATS) rises in popularity in thoracic surgery because of less pain and faster recovery.
+Between October 2013 and March 2018, eight scoliotic patients with extremely large Cobb angle and profoundly limited flexibility underwent UniVATS for anterior release, followed by posterior instrumentation and fusion.
+The mean age at the time of surgery was 14.8 ± 2.4 years and the mean follow-up was 2.2 ± 1.3 years.
+The average levels of anterior thoracic discectomy and posterior fusion were 3.6 ± 0.7 and 11.5 ± 1.2, respectively.
+The mean coronal and sagittal correction rates were 70 ± 19% and 71 ± 23%, respectively.
+UniVATS contributed to minor access trauma (3-cm incision) with minimal blood loss, shorter operation time (75 ± 13 mins), less requirement of stay in the intensive care unit (0.3 ± 0.5 day) or chest tube placement (0.3 ± 0.7 day), speedier and narcotic-free recovery, and earlier ambulation within one day.
+This is the first study to assess the safety and efficacy of UniVATS in the treatment of severely stiff thoracic scoliosis, providing comparable surgical outcomes, less pain, faster recovery and superior cosmetic results without significant complications.
+This 2020 installment of the annual ‘Antibodies to Watch’ series documents the antibody therapeutics approved in 2019 and in regulatory review in the United States or European Union, as well as those in late-stage clinical studies, as of November 2019*.
+At this time, a total of 5 novel antibody therapeutics (romosozumab, risankizumab, polatuzumab vedotin, brolucizumab, and crizanlizumab) had been granted a first approval in either the US or EU, and marketing applications for 13 novel antibody therapeutics (eptinezumab, teprotumumab, enfortumab vedotin, isatuximab, [fam-]trastuzumab deruxtecan, inebilizumab, leronlimab, sacituzumab govitecan, satralizumab, narsoplimab, tafasitamab, REGNEB3 and naxituximab) were undergoing review in these regions, which represent the major markets for antibody therapeutics.
+Also as of November 2019, 79 novel antibodies were undergoing evaluation in late-stage clinical studies.
+Of the 79 antibodies, 39 were undergoing evaluation in late-stage studies for non-cancer indications, with 2 of these (ublituximab, pamrevlumab) also in late-stage studies for cancer indications.
+Companies developing 7 (tanezumab, aducanumab, evinacumab, etrolizumab, sutimlimab, anifrolumab, and teplizumab) of the 39 drugs have indicated that they may submit a marketing application in either the US or EU in 2020.
+Of the 79 antibodies in late-stage studies, 40 were undergoing evaluation as treatments for cancer, and potentially 9 of these (belantamab mafodotin, oportuzumab monatox, margetuximab, dostarlimab, spartalizumab, 131I-omburtamab, loncastuximab tesirine, balstilimab, and zalifrelimab) may enter regulatory review in late 2019 or in 2020.
+Overall, the biopharmaceutical industry’s clinical pipeline of antibody therapeutics is robust, and should provide a continuous supply of innovative products for patients in the future.
+OBJECTIVES: The A/H1N1 mass vaccination program in Canada garnered considerable attention from the media, including extensive newspaper coverage.
+Media reports have been shown to influence the public’s health care decisions, including vaccination choices.
+We analyzed Canadian newspapers’ portrayal of the A/H1N1 vaccine including mention of risks and benefits of the vaccine and whether the article supported, questioned or was neutral about the vaccine.
+METHODS: We compiled a data set of Canadian newspaper articles (N=234) and conducted a frequency content analysis to examine discussion and/or mention of evidence concerning vaccination, risks of the A/H1N1 virus and the vaccine, and tone of article in regards to the vaccination program in Canada.
+RESULTS: Reasons for getting vaccinated appeared in 71.8% of the articles, whereas only 18.4% provided reasons against getting vaccinated.
+Discussion of evidence to support claims for or against getting vaccinated appeared in only 27.8% and 6.8% of the articles, respectively.
+Risks associated with contracting the A/H1N1 virus were discussed in 49.6% of the articles and risks of the A/H1N1 vaccine were discussed in 12.4% of the articles.
+However, serious risks associated with contracting the A/H1N1 virus were also frequently discussed in the print media.
+The news articles rarely presented direct evidence to support statements that the vaccine was safe, effective and properly tested.
+Known risks (such as potential allergic reactions and flu-like side effects) of the vaccine were rarely reported.
+Objectives: Anticipating increases in hospital emergency department (ED) visits for respiratory illness could help time interventions such as opening flu clinics to reduce surges in ED visits.
+Five different methods for estimating ED visits for respiratory illness from Telehealth Ontario calls are compared, including two non-linear modeling methods.
+Daily visit estimates up to 14 days in advance were made at the health unit level for all 36 Ontario health units.
+Estimates generated by regression, Exponentially Weighted Moving Average (EWMA), Numerical Methods for Subspace State Space Identification (N4SID), Fast Orthogonal Search (FOS), and Parallel Cascade Identification (PCI) were compared to the actual number of ED visits for respiratory illness identified from the National Ambulatory Care Reporting System (NACRS) database.
+Models were fit using the first 304 days of data and prediction accuracy was measured over the remaining 348 days.
+Results: Forecast accuracy was significantly better (p<0.0001) for the 12 Ontario health units with a population over 400,000 (75% of the Ontario population) than for smaller health units.
+Compared to regression, FOS produced better estimates (p=0.03) while there was no significant improvement for PCI-based estimates.
+FOS, PCI, EWMA and N4SID performed worse than regression over the remaining smaller health units.
+Conclusion: Telehealth can be used to estimate ED visits for respiratory illness at the health unit level.
+OBJECTIVES: Recent experiences have demonstrated that restrictive measures remain a useful public health tool during infectious disease outbreaks.
+However, the use of restrictive measures is not without controversy, as there is no agreed-upon threshold for when and how to invoke restrictive measures.
+The objectives of this study are to solicit perspectives from Canadians on the ethical considerations of using restrictive measures in response to influenza pandemics, and in turn, to use public views to contribute to a better understanding of what is considered to be the justifiable use of restrictive measures.
+METHODS: A series of town hall focus groups with Canadian residents from June 2008 to May 2009, in three Canadian regions, in order to achieve broad public engagement (n=3 focus groups with a total of 17 participants).
+RESULTS: Two key themes emerged from all town hall focus groups: 1) create an environment for compliance through communication rather than enforcement, and 2) establish the delineation between individual rights, community values, and the greater good.
+CONCLUSION: While there is a need for a decision-making authority and even a mechanism for enforcement, our data suggest that a more tractable approach to restrictive measures is one that enables individuals to voluntarily comply by creating an environment to compel compliance based on communication.
+This approach requires restrictive measures to be a) proportional to the threat, b) implemented along with reciprocal arrangements provided to those affected, and c) accompanied by open and transparent communication throughout all stages so that citizens can both understand and participate in decision-making.
+BACKGROUND: The aim of our study was to analyze the risk factors of nosocomial infection after cardiac surgery in children with congenital heart disease (CHD).
+METHODS: We performed a retrospective cohort study, and children with CHD who underwent open-heart surgeries at Shanghai Children’s Medical Center from January 1, 2012 to December 31, 2018 were included.
+The baseline characteristics of these patients of different ages, including neonates (0–1 months old), infants (1–12 months old) and children (1–10 years old), were analyzed, and the association of risk factors with postoperative nosocomial infection were assessed.
+Nosocomial infection rates in neonates, infants, and children with congenital heart disease were 32.9, 15.4, and 5.2%, respectively.
+After adjusted for confounding factors, we found STS risk grade (OR 1.38, 95%CI: 1.167–1.633; P < 0.001), BMI < 5th percentile (OR 1.934, 95%CI: 1.377–2.715; P < 0.001), CPB time (OR 1.018, 95%CI: 1.015–1.022; P < 0.001), lymphocyte/WBC ratio<cut off value (OR 3.818, 95%CI: 1.529–9.533; P = 0.004) and AST>cut off value (OR 1.546, 95%CI: 1.119–2.136; P = 0.008) were significantly associated with nosocomial infection in CHD children.
+CONCLUSION: Our study suggested STS risk grade, BMI, CPB duration, low lymphocyte/WBC or high neutrophil/WBC ratio were independently associated with nosocomial infection in CHD infant and children after cardiac surgery.
+BACKGROUND: Timely infant testing for HIV is critical to ensure optimal treatment outcomes among exposed infants.
+While world health organization recommends HIV exposed infants to be tested between 4 to 6 weeks of age, in developing countries like Ethiopia, access to timely infant testing is still very limited.
+The study is intended to assess timely infant testing, testing for HIV at the 18th month, test results and factors influencing HIV positivity among infants born to HIV positive mothers in public hospitals of Mekelle, Ethiopia.
+METHODS: A cross-sectional study design was employed on 558 HIV exposed infants, using consecutive sampling technique.
+A checklist was used to extract 4 years (January 2014–December 2017) secondary data, collected from January–April 2018.
+Data were analyzed using SPSS version 20, and binary logistic regression model was used to examine the association of independent variables with the outcome variables.
+Mothers who attended antenatal care (AOR: 2.77; 95% CI: 1.17, 6.55) and who were counselled on feeding options (AOR: 2.01; 95% CI: 1.11, 3.65) were strongly associated with timely infant testing.
+Poor maternal adherence status was associated with infants’ HIV positivity at the 18th month of antibody test (AOR: 15.93; 95% CI: 2.21, 94.66).
+Being rural resident (AOR: 4.0; 95% CI: 1.23, 13.04), being low birth weight (AOR: 5.64; 95% CI: 2.00, 16.71) and not receiving ARV prophylaxis (AOR: 4.70; 95% CI: 1.15, 19.11) were positively associated with the overall HIV positivity.
+Mother’s poor adherence status was associated with infant’s HIV positivity at the 18th month of antibody testing.
+Being rural resident, being low birth weight, and not receiving ARV prophylaxis were the factors that enhance the overall HIV positivity.
+Timely infant testing, counselling on feeding options and adherence should be intensified, and prevention of mother-to-child transmission program in rural settings need to be strengthened.
+Released from the post-pituitary gland, vasopressin induces vasoconstriction through the activation of V1a receptors located on vascular smooth muscle cells.
+Due to its non-selective receptor affinity arginine–vasopressin also activates V2 (located on renal tubular cells of collecting ducts) and V1b (located in the anterior pituitary and in the pancreas) receptors, thereby potentially promoting undesired side effects such as anti-diuresis, procoagulant properties due to release of the von Willebrand’s factor and platelet activation.
+During septic shock, vasopressin plasma levels were reported to be lower than expected, and a hypersensitivity to its vasopressor effect is reported in such situation.
+Terlipressin and selepressin are synthetic vasopressin analogues with a higher affinity for the V1 receptor, and, hence, potentially less side effects.
+In this narrative review, we present the current knowledge of the rationale, benefits and risks of vasopressin use in the setting of septic shock and vasoplegic shock following cardiac surgery.
+Clearly, vasopressin administration allows reducing norepinephrine requirements, but so far, no improvement of survival was reported and side effects are frequent, particularly ischaemic events.
+Finally, we will discuss the current indications for vasopressin and its agonists in the setting of septic shock, and the remaining unresolved questions.
+The rapid spread of avian influenza H5N1 in Asia in late 2003 has moved the world to a new state of pandemic alert.
+The risk of further human cases will persist, as will opportunities for a pandemic virus to emerge.
+Coordination has been fostered through the development of a national pandemic preparedness plan and ongoing development of systems and processes for national health emergency management.
+Specific areas of advancement include: enhancement of rapid surveillance and communication capacity, the pandemic vaccine strategy, acquisition of an antiviral stockpile, research prioritization, international collaboration, and an international meeting of Ministers of Health (October 2005) to enhance global cooperation and coordination in advance of a possible influenza pandemic.
+Key next steps include: publication of the 2005 edition of the Canadian Pandemic Influenza Plan; conducting emergency exercises to help strengthen planning at all levels and across health care, emergency management and NGO sectors; developing H5N1 vaccine and clinical trials; evaluating the need to supplement national antiviral stockpile; and undertaking public and key stakeholder consultations to provide further input into planning strategies and activities.
+Youth violence is a significant issue for public health because of the potential for longterm impacts on individuals, families and communities.
+However, there is limited understanding of violence from a public health perspective within rural communities.
+Rural refers to those communities with a population less than 10,000 outside the main commuting zone of a large urban area.
+Population health approaches, including the social determinants of health, are well supported by public health officials.
+Generating information about rural youth violence from a Canadian perspective would add to our understanding of these social determinants while providing guidance for policy and program development.
+An ongoing two-phase Canadian study on rural youth violence included qualitative interviews with 52 youth and the completion of a questionnaire that had been developed from the qualitative responses.
+The findings generated from this ongoing study will be useful in linking violence with social factors that impact health and thereby guide population health programs and policies.
+In this way, the role of public health to develop policies and implement programs will be directly influenced by evidence while addressing an ongoing public health concern.
+In public health, however, decisions about who will approve, pay for, and deliver services are often accompanied by decisions on when and how to compel individual behaviour.
+Policy becomes complex because different stakeholders interpret evidence differently: stakeholders may assign different weights to policy goals and may even define the same goals differently.
+In the debate over mandatory annual influenza vaccination for health care workers, for example, proponents as well as opponents of mandatory vaccination may convey arguments in security terms.
+Those in favour of mandatory vaccination emphasize subclinical infections and duty of care (public security) while those opposed emphasize risk of adverse events (personal security).
+Proponents assert less worker absenteeism (efficiency) while opponents stress coercion and alternate personal infection control measures (liberty and individual rights/responsibilities).
+Determining the place of mandatory influenza vaccination for health care workers thus demands reconciling policy trade-offs and clarifying the underlying disputes hidden in the language of the policy debate.
+BACKGROUND: CDH UK is a registered charity governed by a volunteer committee and providing informal support to patients, families and healthcare workers affected directly or indirectly with congenital diaphragmatic hernia (CDH) internationally.
+This is the first patient-led survey undertaken by CDH UK aiming for highlighting the feeding problems and their impact on the daily life of CDH survivors.
+METHODS: Answers from CDH survivors were collected through an online questionnaire (SurveyMonkey(®)) undertaken by CDH UK.
+The questionnaire contained questions about their feeding problems and support they were receiving for it.
+MAIN RESULTS: Overall, 151 patients answered some parts of the survey and 102 patients completed the questionnaire.
+Gastric acid reflux (GER) and growth retardation were the commonest symptoms experienced by 97 (91.5%) and 72 (62.2%) responders, respectively.
+Only 18 (17.0%) responders have received any written information on feeding or details of patient/parent support.
+Eighty (75.5%) responders are satisfied with the level of support they are receiving, but 78 (76.4%) answered that the whole experience associated with the disease has been very or extremely stressful.
+CONCLUSIONS: CDH survivors frequently have various issues with feeding, which may not be adequately supported or discussed clinically.
+It is desirable to assist the patients to reliable resources of long-term support, including multidisciplinary team (MDT) approach.
+Hypoxemic respiratory failure is usually accompanied with a certain extent of consolidation and alveolar derecruitment, which may still be present even after the patients have achieved the status of readiness to extubate.
+This study aimed to evaluate whether pre-extubation FRC is associated with the risk of extubation failure in patients with hypoxemic respiratory failure.
+We used a technique based on a nitrogen multiple breath washout method to measure FRC before the planned extubation.
+The median FRC before extubation was 25 mL/kg (Interquartile range, 20–32 mL/Kg) per predicted body weight (pBW).
+The median FRC was higher in the extubation success group than in the extubation failure group (27 versus 21 mL/Kg, p < 0.001).
+Reduced FRC was associated with higher risk of extubation failure (odds ratio, 1.14 per each decreased of 1 mL/Kg of FRC/pBW, 95% CI, 1.05–1.23, p = 0.002).
+Reduced FRC may be incorporated into the traditional risk factors to identify patients at high risk for extubation failure.
+BACKGROUND: Reproductive failure in sow herds due to infection with influenza A viruses has been described in the literature, but only a few studies have focused on the pathogenesis and the clinical signs of the infection.
+Case reports indicate an association between infections with influenza A viruses and reduced reproductive performance, although it has been difficult to experimentally reproduce the clinical outcome of poor reproductive performance.
+The aim of the present longitudinal field study was to compare the reproductive performance parameters before and after the implementation of vaccination against the influenza A (H1N1)pdm09 virus in sow herds infected with pandemic influenza A virus.
+Therefore, farm-specific data of 137 sow herds in Germany, including 60,153 sows, as well as the clinical presentation of the infection were surveyed via questionnaire.
+Furthermore, average performance parameters (return to oestrus rate, abortion rate, stillbirth rate, number of piglets born alive per litter, preweaning mortality rate and number of piglets weaned per sow per year) were recorded for 6 months before vaccination and 6 months after completion of primary vaccination.
+RESULTS: In 79.8% of the farms, the clinical presentation of the infection was characterised by a reduced reproductive performance.
+These findings were confirmed by analysis of the performance parameters, which revealed a significant decline in the return to oestrus rate (p < 0.001), abortion rate (p < 0.001) and preweaning mortality rate (p = 0.023) and a significant increase of the number in piglets born alive (p = 0.001) and piglets weaned per sow per year (p < 0.001) after immunisation.
+CONCLUSION: The present study represents the first attempt to demonstrate the association of influenza A virus infection, vaccination and the alteration in reproductive performance parameters, investigating a large number of cases.
+The results show that by vaccinating against the influenza A (H1N1)pdm09 virus, an improvement in reproductive performance can be achieved in sow herds infected with pandemic influenza A virus.
+Additionally, the large number of herds that were affected by poor reproductive performance after infection with the aforementioned virus confirms the assumption of an association between pandemic influenza A virus and reproductive losses.
+BACKGROUND: We have previously shown that HCC patients and healthy subjects are equally responsive to a RNAdjuvant(®), a novel TLR-7/8/RIG-I agonist based on noncoding RNA developed by CureVac, by an ex vivo evaluation.
+However, the immunological effect of adjuvants on immune cells from cancer patients undergoing chemotherapy remains to be demonstrated.
+Different adjuvants currently used in cancer vaccine clinical trials were evaluated in the present study on immune cells from cancer patients before and after chemotherapy in an ex vivo setting.
+METHODS: PBMCs were obtained from 4 healthy volunteers and 23 patients affected by either colon (OMA) or lung cancer (OT).
+The effect of CpG, Poly I:C, Imiquimod and RNA-based adjuvant (RNAdjuvant(®)) was assessed using a multiparametric approach to analyze network dynamics of early immune responses.
+Evaluation of CD80, CD86 and HLA-DR expression as well as the downstream effect on CD4(+) T cell phenotyping was performed by flow cytometry; cytokine and chemokine production was evaluated by Bio-Plex ProTM.
+RESULTS: Treatment with RNAdjuvant(®) induced the strongest response in cancer patients in terms of activation of innate and adoptive immunity.
+Indeed, CD80, CD86 and HLA-DR expression was found upregulated in circulating dendritic cells, which promoted a CD4(+) T cell differentiation towards an effector phenotype.
+RNAdjuvant(®) was the only one to induce most of the cytokines/chemokines tested with a pronounced Th1 cytokine pattern.
+According to the different parameters evaluated in the study, no clear cut difference in immune response to adjuvants was observed between healthy subjects and cancer patients.
+Moreover, in the latter group, the chemotherapy treatment did not consistently correlate to a significant altered response in the different parameters.
+CONCLUSIONS: The present study is the first analysis of immunological effects induced by adjuvants in cancer patients who undergo chemotherapy, who are enrolled in the currently ongoing cancer vaccine clinical trials.
+The results show that the RNAdjuvant(®) is a potent and Th1 driving adjuvant, compared to those tested in the present study.
+Most importantly, it is demonstrated that chemotherapy does not significantly impair the immune system, implying that cancer patients are likely to respond to a cancer vaccine even after a chemotherapy treatment.
+Schistosomiasis causes significant levels of morbidity and mortality in many geographical regions of the world.
+The control of schistosomiasis over the last several decades has been centered on the mass drug administration (MDA) of praziquantel (PZQ), which is the only drug currently available for treatment.
+Despite the concerted efforts of MDA programs, the prevalence and transmission of schistosomiasis has remained largely unchecked due to the fact that PZQ is ineffective against juvenile schistosomes, does not prevent re-infection and the emergence of PZQ-resistant parasites.
+In addition, other measures such as the water, sanitation and hygiene programs and snail intermediate hosts control have had little to no impact.
+These drawbacks indicate that the current control strategies are severely inadequate at interrupting transmission and therefore, implementation of other control strategies are required.
+Ideally, an efficient vaccine is what is needed for long term protection thereby eliminating the current efforts of repeated mass drug administration.
+However, the general consensus in the field is that the integration of a viable vaccine with MDA and other control measures offer the best chance of achieving the goal of schistosomiasis elimination.
+This review focuses on the present status of schistosomiasis vaccine candidates in different phases of human clinical trials and provide some insight into future vaccine discovery and design.
+Rift Valley Fever (RVF) is an emerging zoonotic arbovirus with a complex cycle of transmission that makes difficult the prediction of its expansion.
+Recent outbreaks outside Africa have led to rediscover the human disease but it remains poorly known.
+The wide spectrum of acute and delayed manifestations with potential unfavorable outcome much complicate the management of suspected cases and prediction of morbidity and mortality during an outbreak.
+We identified gaps in the field and provided a practical algorithm to assist clinicians in the cases assessment, determination of setting of care and prolonged follow-up.
+BACKGROUND: Postoperative hypoxemia in acute type A aortic dissection (AADA) is a common complication and is associated with negative outcomes.
+This study aimed to analyze the efficacy of low-dose (5–10 ppm) inhaled nitric oxide (iNO) in the management of hypoxemia after AADA surgery.
+METHODS: In this retrospective observational study, Medical records of patients who underwent AADA surgery at two institutions between January 2015 and January 2018 were collected.
+RESULTS: Among 436 patients who underwent surgical repair, 187 (42.9%) had hypoxemia and 43 were treated with low-dose iNO.
+After PSM, patients were included in the iNO treatment (n = 40) and PSM control (n = 94) groups in a 1:3 ratio.
+iNO ameliorated hypoxemia at 6, 24, 48, and 72 h after initiation, and shortened the durations of ventilator support (39.0 h (31.3–47.8) vs. 69.0 h (47.8–110.3), p < 0.001) and ICU stay (122.0 h (80.8–155.0) vs 179.5 h (114.0–258.0), p < 0.001).
+CONCLUSIONS: In this study, we found that low-dose iNO improved oxygenation in patients with hypoxemia after AADA surgery and shortened the durations of mechanical ventilation and ICU stay.
+No significant side effects or increase in postoperative mortality or morbidities were observed with iNO treatment.
+These findings warrant a randomized multicenter controlled trial to assess the exact efficiency of iNO for hypoxemia after AADA.
+We used pre- and post-vaccination sera and peripheral blood mononuclear cells from a flagellin adjuvanted F1/V vaccine trial to evaluate for protective markers.
+Here, we report for the first time in humans that inverse caspase-3 levels, which are measures of protective antibody, significantly increased by 29% and 75% on days 14 and 28 post-second vaccination, respectively.
+The strongest positive and negative correlations between protective antibody levels and gene expression signatures were identified for IFNG and ENSG00000225107 genes, respectively.
+Several genes associated with these responses were identified that could serve as potential correlates of protection.
+Moral bioenhancement, nudge-designed environments, and ambient persuasive technologies may help people behave more consistently with their deeply held moral convictions.
+Alternatively, they may aid people in overcoming cognitive and affective limitations that prevent them from appreciating a situation’s moral dimensions.
+Or they may simply make it easier for them to make the morally right choice by helping them to overcome sources of weakness of will.
+Second, such technologies will actually help people get morality right and behave more consistently with whatever the ‘real’ right thing to do turns out to be.
+The paper then considers whether or not humanity loses anything valuable, particularly opportunities for moral progress, when being moral is made much easier by eliminating difficult moral deliberation and internal moral struggle.
+Ultimately, the worry that moral struggle has value as a catalyst for moral progress is rejected.
+Moral progress is understood here as the discovery and application of new values or sensitization to new sources of harm.
+Invasive candidiasis (IC) is the most common nosocomial infection and a leading cause of mycoses-related deaths.
+High-systemic toxicity and emergence of antifungal-resistant species warrant the development of newer preventive approaches against IC.
+Here, we have adopted an immunotherapeutic peptide vaccine-based approach, to enhance the body’s immune response against invasive candida infections.
+Using computational tools, we screened the entire candida proteome (6030 proteins) and identified the most immunodominant HLA class I, HLA class II and B- cell epitopes.
+By further immunoinformatic analyses for enhanced vaccine efficacy, we selected the 18- most promising epitopes, which were joined together using molecular linkers to create a multivalent recombinant protein against Candida albicans (mvPC).
+The selected mvPC epitopes are homologous against all currently available annotated reference sequences of 22 C. albicans strains, thus offering a higher coverage and greater protective response.
+A major advantage of the current vaccine approach is mvPC’s multivalent nature (recognizing multiple-epitopes), which is likely to provide enhanced protection against complex candida antigens.
+BACKGROUND: Influenza reassortment, a mechanism where influenza viruses exchange their RNA segments by co-infecting a single cell, has been implicated in several major pandemics since 19th century.
+Owing to the significant impact on public health and social stability, great attention has been received on the identification of influenza reassortment.
+METHODS: We proposed a novel computational method named HopPER (Host-prediction-based Probability Estimation of Reassortment), that sturdily estimates reassortment probabilities through host tropism prediction using 147 new features generated from seven physicochemical properties of amino acids.
+We conducted the experiments on a range of real and synthetic datasets and compared HopPER with several state-of-the-art methods.
+RESULTS: It is shown that 280 out of 318 candidate reassortants have been successfully identified.
+Additionally, not only can HopPER be applied to complete genomes but its effectiveness on incomplete genomes is also demonstrated.
+The analysis of evolutionary success of avian, human and swine viruses generated through reassortment across different years using HopPER further revealed the reassortment history of the influenza viruses.
+We hope this method could facilitate rapid reassortment detection and provide novel insights into the evolutionary patterns of influenza viruses.
+Avian pathogenic Escherichia coli (APEC), a pathotype of extraintestinal pathogenic E. coli, causes one of the most serious infectious diseases of poultry and shares some common virulence genes with neonatal meningitis-associated E. coli.
+TonB-dependent receptors (TBDRs) are ubiquitous outer membrane β-barrel proteins; they play an important role in the recognition of siderophores during iron uptake.
+Here, in the APEC strain DE205B, we investigated the role of four putative TBDRs—ireA, 0007, 0008, and 2235—in iron uptake.
+Glutathione-S-transferase pulldown assays indicated that the proteins encoded by these genes directly interact with TonB.
+Moreover, the expression levels of all four genes were significantly upregulated under iron-depleted conditions compared with iron-rich conditions.
+The expression levels of several iron uptake-related genes were significantly increased in the ireA, 0007, 0008, and 2235 deletion strains, with the upregulation being the most prominent in the ireA deletion mutant.
+Furthermore, iron uptake by the ireA deletion strain was significantly increased compared to that by the wild-type strain.
+Moreover, a tonB mutant strain was constructed to study the effect of tonB deletion on the TBDRs.
+We found that regardless of the presence of tonB, the expression levels of the genes encoding the four TBDRs were regulated by fur.
+In conclusion, our findings indicated that ireA, 0007, 0008, and 2235 indeed encode TBDRs, with ireA having the most important role in iron uptake.
+These results should help future studies explore the mechanisms underlying the TonB-dependent iron uptake pathway.
+Here we describe the in-country establishment and quality control (QC) of a multiplex bead assay (MBA) for three sero-surveys in Haiti.
+Titration curves of hyperimmune sera were included on assay plates, assay signals underwent 5-parameter regression, and inspection of the median and interquartile range (IQR) for the y-inflection point was used to determine assay precision.
+The medians and IQRs were similar for Surveys 1 and 2 for most antigens, while the IQRs increased for some antigens in Survey 3.
+Levey-Jennings charts for selected antigens provided a pass/fail criterion for each assay plate and, of 387 assay plates, 13 (3.4%) were repeated.
+Individual samples failed if IgG binding to the generic glutathione-S-transferase protein was observed, with 659 (2.0%) samples failing.
+The final dataset included 609,438 anti-malaria IgG data points from 32,099 participants; 96.6% of all potential data points if no QC failures had occurred.
+The MBA can be deployed with high-throughput data collection and low inter-plate variability while ensuring data quality.
+The humanization of animal model immune systems by genetic engineering has shown great promise for antibody discovery, tolerance studies and for the evaluation of vaccines.
+Assessment of the baseline antibody repertoires of unimmunized model animals will be useful as a benchmark for future immunization experiments.
+We characterized the heavy chain and kappa light chain antibody repertoires of a model animal, the OmniRat, by high throughput antibody sequencing and made use of two novel datasets for comparison to human repertoires.
+Intra-animal and inter-animal repertoire comparisons reveal a high level of conservation in antibody diversity between the lymph node and spleen and between members of the species.
+Multiple differences were found in both the heavy and kappa chain repertoires between OmniRats and humans including gene segment usage, CDR3 length distributions, class switch recombination, somatic hypermutation levels and in features of V(D)J recombination.
+The Inference and Generation of Repertoires (IGoR) software tool was used to model recombination in VH regions which allowed for the quantification of some of these differences.
+Diversity estimates of the OmniRat heavy chain repertoires almost reached that of humans, around two orders of magnitude less.
+Despite variation between the species repertoires, a high frequency of OmniRat clonotypes were also found in the human repertoire.
+These data give insights into the development and selection of humanized animal antibodies and provide actionable information for use in vaccine studies.
+Obesity is a multifaceted pathophysiological condition that has been associated with lipid accumulation, adipocyte dysfunction, impaired mitochondrial biogenesis and an altered metabolic profile.
+Redox imbalance and excessive release of inflammatory mediators have been intricately linked in obesity-associated phenotypes.
+Hence, understanding the mechanisms of redox signaling pathways and molecular targets exacerbating oxidative stress is crucial in improving health outcomes.
+The activation of Na/K-ATPase/Src signaling, and its downstream pathways, by reactive oxygen species (ROS) has been recently implicated in obesity and subsequent nonalcoholic steatohepatitis (NASH), which causes further production of ROS creating an oxidant amplification loop.
+Apart from that, numerous studies have also characterized antioxidant properties of heme oxygenase 1 (HO-1), which is suppressed in an obese state.
+The induction of HO-1 restores cellular redox processes, which contributes to inhibition of the toxic milieu.
+The novelty of these independent mechanisms presents a unique opportunity to unravel their potential as molecular targets for redox regulation in obesity and NASH.
+The attenuation of oxidative stress, by understanding the underlying molecular mechanisms and associated mediators, with a targeted treatment modality may provide for improved therapeutic options to combat clinical disorders.
+In late 2012 it was evidenced that most of the human genome is transcribed but only a small percentage of the transcripts are translated.
+This observation supported the importance of non-coding RNAs and it was confirmed in several organisms.
+To understand the function of lncRNAs, it is fundamental to investigate in which cells they are preferentially expressed and to detect their subcellular localization.
+Recent improvements of techniques that localize single RNA molecules in tissues like single-cell RNA sequencing and fluorescence amplification methods have given a considerable boost in the knowledge of the lncRNA functions.
+In recent years, single-cell transcription variability was associated with non-coding RNA expression, revealing this class of RNAs as important transcripts in the cell lineage specification.
+The purpose of this review is to collect updated information about lncRNA classification and new findings on their function derived from single-cell analysis.
+We also retained useful for all researchers to describe the methods available for single-cell analysis and the databases collecting single-cell and lncRNA data.
+We conducted a systematic review to identify the knowledge gaps around childhood pneumonia in Bhutan.
+METHODS: We searched PubMed, ScienceDirect and Google scholar from conception to 3rd December 2018, World Health Organization, UNICEF, Bhutan’s Ministry of Health and other local databases for relevant reports.
+We included any report describing pneumonia in Bhutanese children with regards to the burden of the disease, aetiology, related risk factors, clinical and prognostic characteristics, surveillance systems and national preventive strategies.
+Although with notable decreasing trends, pneumonia is still accountable for a high burden and mortality rate in Bhutanese children.
+The national surveillance system focuses mainly on influenza identification but has recently introduced other viral aetiology to monitor.
+We found very scarce or no data with regard to the bacterial aetiology, related risk factors and clinico-radiological and prognostic characteristics.
+CONCLUSION: There is a dearth of data regarding the epidemiological, microbiological, clinical and radiological characteristics of pneumonia in children in Bhutan, leading to challenges while implementing evidence-based management and effective national preventive strategies.
+RNA-protein interactions (RPIs) play a very important role in a wide range of post-transcriptional regulations, and identifying whether a given RNA-protein pair can form interactions or not is a vital prerequisite for dissecting the regulatory mechanisms of functional RNAs.
+Currently, expensive and time-consuming biological assays can only determine a very small portion of all RPIs, which calls for computational approaches to help biologists efficiently and correctly find candidate RPIs.
+Here, we integrated a successful computing algorithm, conjoint triad feature (CTF), and another method, chaos game representation (CGR), for representing RNA-protein pairs and by doing so developed a prediction model based on these representations and random forest (RF) classifiers.
+When testing two benchmark datasets, RPI369 and RPI2241, the combined method (CTF+CGR) showed some superiority compared with four existing tools.
+Especially on RPI2241, the CTF+CGR method improved prediction accuracy (ACC) from 0.91 (the best record of all published works) to 0.95.
+When independently testing a newly constructed dataset, RPI1449, which only contained experimentally validated RPIs released between 2014 and 2016, our method still showed some generalization capability with an ACC of 0.75.
+Accordingly, we believe that our hybrid CTF+CGR method will be an important tool for predicting RPIs in the future.
+Simple laboratory culture conditions and a wide range of genetic tools have made it a model organism for studying haloarchaeal cell biology.
+Halophilic enzymes of potential interest to biotechnology have opened up the application of this organism in biocatalysis, bioremediation, nanobiotechnology, bioplastics and the biofuel industry.
+Functionally active halophilic proteins can be easily expressed in a halophilic environment, and an extensive genetic toolkit with options for regulated protein overexpression has allowed the purification of biotechnologically important enzymes from different halophiles in H. volcanii.
+However, corrosion mediated damage caused to stainless-steel bioreactors by high salt concentrations and a tendency to form biofilms when cultured in high volume are some of the challenges of applying H. volcanii in biotechnology.
+The ability to employ expressed active proteins in immobilized cells within a porous biocompatible matrix offers new avenues for exploiting H. volcanii in biotechnology.
+This review critically evaluates the various application potentials, challenges and toolkits available for using this extreme halophilic organism in biotechnology.
+This high-risk group of infection was previously identified by conducting large-scale visits/interviews, or manually screening among tons of recorded surveillance videos.
+Both are time-intensive and most likely to delay the control of communicable diseases like influenza.
+In this paper, we address this challenge by solving a multi-tasking problem from the captured surveillance videos.
+This multi-tasking framework aims to model the principle of Close Proximity Interaction and thus infer the infection risk of individuals.
+The complete workflow includes three essential sub-tasks: (1) person re-identification (REID), to identify the diagnosed patient and infected individuals across different cameras, (2) depth estimation, to provide a spatial knowledge of the captured environment, (3) pose estimation, to evaluate the distance between the diagnosed and potentially-infected subjects.
+Our method is expected to be effective in accelerating the process of identifying the potentially infected group and ultimately contribute to the well-being of public health.
+The pulmonary stem/progenitor cells, which could be differentiated into downstream cells to repair tissue damage caused by influenza A virus, have also been shown to be the target cells of influenza virus infection.
+In this study, mouse pulmonary stem/progenitor cells (mPSCs) with capability to differentiate into type I or type II alveolar cells were used as an in vitro cell model to characterize replication and pathogenic effects of influenza viruses in PSCs.
+First, mPSCs and its immortalized cell line mPSCs(Oct4+) were shown to be susceptible to PR8, seasonal H1N1, 2009 pandemic H1N1, and H7N9 influenza viruses and can generate infectious virus particles, although with a lower virus titer, which could be attributed by the reduced vRNA replication and nucleoprotein (NP) aggregation in the cytoplasm.
+Nevertheless, a significant increase of interleukin (IL)-6 and interferon (IFN)-γ at 12 h and IFN-β at 24 h post infection in mPSCs implicates that mPSCs might function as a sensor to modulate immune responses to influenza virus infection.
+In summary, our results demonstrated mPSCs, as one of the target cells for influenza A viruses, could modulate early proinflammatory responses to influenza virus infection.
+N(4)-Hydroxycytidine (NHC) is an antiviral ribonucleoside analog that acts as a competitive alternative substrate for virally encoded RNA-dependent RNA polymerases.
+It exhibits measurable levels of cytotoxicity, with 50% cytotoxic concentration values ranging from 7.5 μM in CEM cells and up to >100 μM in other cell lines.
+The mitochondrial DNA-dependent RNA polymerase (POLRMT) has been shown to incorporate some nucleotide analogs into mitochondrial RNAs, resulting in substantial mitochondrial toxicity.
+NHC was tested in multiple assays intended to determine its potential to cause mitochondrial toxicity.
+NHC showed similar cytotoxicity in HepG2 cells incubated in a glucose-free and glucose-containing media, suggesting that NHC does not impair mitochondrial function in this cell line based on the Crabtree effect.
+We demonstrate that the 5′-triphosphate of NHC can be used by POLRMT for incorporation into nascent RNA chain but does not cause immediate chain termination.
+In PC-3 cells treated with NHC, the 50% inhibitory concentrations of mitochondrial protein expression inhibition were 2.7-fold lower than those for nuclear-encoded protein expression, but this effect did not result in selective mitochondrial toxicity.
+A 14-day incubation of HepG2 cells with NHC had no effect on mitochondrial DNA copy number or extracellular lactate levels.
+In CEM cells treated with NHC at 10 μM, a slight decrease (by ∼20%) in mitochondrial DNA copy number and a corresponding slight increase in extracellular lactate levels were detected, but these effects were not enhanced by an increase in NHC treatment concentration.
+In summary, the results indicate that mitochondrial impairment by NHC is not the main contributor to the compound’s observed cytotoxicity in these cell lines.
+RATIONALE: There remains significant controversy regarding the optimal approach to fluid resuscitation for patients in shock.
+The magnitude of care variability in shock resuscitation, the confounding effects of disease severity and comorbidity, and the relative impact on sepsis survival are poorly understood.
+OBJECTIVE: To evaluate usual care variability and determine the differential effect of observed and predicted fluid resuscitation volumes on risk-adjusted hospital mortality for mechanically ventilated patients in shock.
+METHODS: We performed a retrospective outcome analysis of mechanically ventilated patients admitted to intensive care units using the 2013 Premier Hospital Database (Premier, Inc.).
+Observed and predicted hospital mortality were evaluated by observed and predicted day 1 fluid administration, using the difference in predicted and observed outcomes to adjust for disease severity between groups.
+Both predictive models were validated using a second large administrative database (Truven Health Analytics Inc.).
+Secondary outcomes included duration of mechanical ventilation, hospital and ICU length of stay, and cost.
+RESULTS: Among 33,831 patients, observed hospital mortality was incrementally higher than predicted for each additional liter of day 1 fluid beginning at 7 L (40.9% vs. 37.2%, p = 0.008).
+Compared to patients that received expected (± 1.5 L predicted) day 1 fluid volumes, greater-than-expected fluid resuscitation was associated with increased risk-adjusted hospital mortality (52.3% vs. 45.0%, p < 0.0001) among all patients with shock and among a subgroup of shock patients with comorbid conditions predictive of lower fluid volume administration (47.1% vs. 41.5%, p < 0.0001).
+However, in patients with shock but without such conditions, both greater-than-expected (57.5% vs. 49.2%, p < 0.0001) and less-than-expected (52.1% vs. 49.2%, p = 0.037) day 1 fluid resuscitation were associated with increased risk-adjusted hospital mortality.
+CONCLUSIONS: Highly variable day 1 fluid resuscitation was associated with a non-uniform impact on risk-adjusted hospital mortality among distinct subgroups of mechanically ventilated patients with shock.
+These findings support closer evaluation of fluid resuscitation strategies that include broadly applied fluid volume targets in the early phase of shock resuscitation.
+BACKGROUND: Neuromuscular blocking agent (NMBA) has been proposed by medical guidelines for early severe acute respiratory distress syndrome (ARDS) because of its survival benefits.
+METHOD: A search was performed of the Pubmed, Scopus, Clinicaltrials.gov, and Virtual Health Library databases for randomized controlled trials (RCT) evaluating 28-day mortality in ARDS patients treated with NMBA within 48 h. An English language restriction was applied.
+Relevant data were extracted and pooled into risk ratios (RR), mean differences (MD), and corresponding 95% confidence intervals (CI) using random-effect model.
+RESULTS: From 2675 studies, we included five RCTs in the analysis, for a total of 1461 patients with a mean PaO(2)/FIO(2) of 104 ± 35 mmHg.
+The cisatracurium group had the same risk of death at 28 days (RR, 0.90; 95% CI, 0.78–1.03; I(2) = 50%, p = 0.12) and 90 days (RR, 0.81; 95% CI, 0.62–1.06; I(2) = 56%, p = 0.06) as the control group (no cisatracurium).
+The secondary outcomes of mechanical ventilation duration and ventilator-free days were not different between the two groups.
+Cisatracurium had a significantly lower risk of barotrauma than the control group with no difference in intensive care unit (ICU)–induced weakness.
+The PaO(2)/FIO(2) ratio was higher in the cisatracurium group but not until 48 h. Meta-regression analysis of the baseline PaO(2)/FIO(2) ratio, positive end-expiratory pressure (PEEP) revealed no heterogeneity.
+Subgroup analysis excluding the trial using high PEEP and light sedation strategy yielded an improvement in all mortality outcomes.
+CONCLUSION: NMBA improves oxygenation only after 48 h in moderate, severe ARDS patients and has a lower barotrauma risk without affecting ICU weakness.
+However, NMBA does not reduce ventilator-free days, duration of mechanical ventilation or, most importantly, the mortality risk regardless of the severity of ARDS.
+Health care-associated infections such as Pseudomonas aeruginosa bacteremia pose a major clinical risk for hospitalized patients.
+However, these systemic infections are presumed to be a “dead-end” for P. aeruginosa and to have no impact on transmission.
+Here, we use a mouse infection model to show that P. aeruginosa can spread from the bloodstream to the gallbladder, where it replicates to extremely high numbers.
+Bacteria in the gallbladder can then seed the intestines and feces, leading to transmission to uninfected cage-mate mice.
+Our work shows that the gallbladder is crucial for spread of P. aeruginosa from the bloodstream to the feces during bacteremia, a process that promotes transmission in this experimental system.
+Further research is needed to test to what extent these findings are relevant to infections in patients.
+Peste des petits ruminants virus causes a highly contagious disease, which poses enormous economic losses in domestic animals and threatens the conservation of wild herbivores.
+Diagnosis remains a cornerstone to the Peste des petits ruminants Global Control and Eradication Strategy, an initiative of the World Organisation for Animal Health and the Food and Agriculture Organisation.
+The present review presents the peste des petits ruminants diagnostic landscape, including the practicality of commercially available diagnostic tools, prototype tests and opportunities for new technologies.
+The most common peste des petits ruminants diagnostic tools include; agar gel immunodiffusion, counter-immunoelectrophoresis, enzyme-linked immunosorbent assays, reverse transcription polymerase chain reaction either gel-based or real-time, reverse transcription loop-mediated isothermal amplification, reverse transcription recombinase polymerase amplification assays, immunochromatographic lateral flow devices, luciferase immunoprecipitation system and pseudotype-based assays.
+These tests vary in their technical demands, but all require a laboratory with exception of immunochromatographic lateral flow and possibly reverse transcription loop-mediated isothermal amplification and reverse transcription recombinase polymerase amplification assays.
+Thus, we are proposing an efficient integration of diagnostic tests for rapid and correct identification of peste des petits ruminants in endemic zones and to rapidly confirm outbreaks.
+Deployment of pen-side tests will improve diagnostic capacity in extremely remote settings and susceptible wildlife ecosystems, where transportation of clinical samples in the optimum cold chain is unreliable.
+BACKGROUND: No-touch environmental disinfection using ultraviolet devices has been highlighted in the past several years to control the transmission of multidrug-resistant organisms (MDROs).
+This study aimed to evaluate the effectiveness of disinfection by portable pulsed xenon ultraviolet (PX-UV) devices in controlling transmission of MDROs in a non-US healthcare setting.
+METHODS: All patients admitted in the intensive care unit in a 629-bed tertiary referral hospital in Japan from August 2016 to February 2019 were enrolled.
+During the study period, PX-UV disinfection was added to manual terminal cleaning after every patient transfer/discharge.
+For microbiological evaluation, surfaces were selected for sampling by contact plates before/after manual cleaning and after PX-UV.
+RESULTS: The incidence of newly acquired methicillin-resistant Staphylococcus aureus (MRSA) declined significantly (13.8 to 9.9 per 10,000 patient days, incidence rate ratio 0.71, p = 0.002), as well as that of newly acquired drug-resistant Acinetobacter (48.5 to 18.1, 0.37, p < 0.001).
+The percent reduction of the microbiological burden by manual cleaning was 81%, but a further 59% reduction was achieved by PX-UV.
+CONCLUSIONS: PX-UV is effective in further reducing the microbial burden and controlling MDROs in a non-US healthcare setting.
+BACKGROUND: In addition to outbreaks of nosocomial influenza, sporadic nosocomial influenza infections also occur but are generally not reported in the literature.
+This study aimed to determine the epidemiologic characteristics of cases of nosocomial influenza compared with the remaining severe cases of severe influenza in acute hospitals in Catalonia (Spain) which were identified by surveillance.
+METHODS: An observational case-case epidemiological study was carried out in patients aged ≥18 years from Catalan 12 hospitals between 2010 and 2016.
+For each laboratory-confirmed influenza case (nosocomial or not) we collected demographic, virological and clinical characteristics.
+We defined patients with nosocomial influenza as those admitted to a hospital for a reason other than acute respiratory infection in whom ILI symptoms developed ≥48 h after admission and influenza virus infection was confirmed using RT-PCR.
+RESULTS: One thousand seven hundred twenty-two hospitalized patients with severe laboratory-confirmed influenza virus infection were included: 96 (5.6%) were classified as nosocomial influenza and more frequently had > 14 days of hospital stay (42.7% vs. 27.7%, P < .001) and higher mortality (18.8% vs. 12.6%, P < .02).
+The variables associated with nosocomial influenza cases in acute-care hospital settings were chronic renal disease (aOR 2.44 95% CI 1.44–4.15) and immunodeficiency (aOR 1.79 95% CI 1.04–3.06).
+CONCLUSIONS: Nosocomial infections are a recurring problem associated with high rates of chronic diseases and death.
+Rickettsia are obligate intracellular bacteria that evade antimicrobial autophagy in the host cell cytosol by unknown mechanisms.
+Other cytosolic pathogens block different steps of autophagy targeting, including the initial step of polyubiquitin coat formation.
+Here, we show that actin mobilization is insufficient to block autophagy recognition of the pathogen Rickettsia parkeri.
+Instead, R. parkeri employs outer membrane protein B (OmpB) to block ubiquitylation of bacterial surface proteins, including OmpA, and subsequent recognition by autophagy receptors.
+Although OmpB is dispensable for bacterial growth in endothelial cells, it is essential for R. parkeri to block autophagy in macrophages and to colonize mice because of its ability to promote autophagy evasion in immune cells.
+Our results indicate that OmpB acts as a protective shield to obstruct autophagy recognition, revealing a distinctive bacterial mechanism to evade antimicrobial autophagy.
+Objectives: (a) To understand how to integrate geospatial concepts when implementing point-of-care testing (POCT); (b) to facilitate emergency, outbreak, and disaster preparedness and emergency management in healthcare small-world networks; (c) to enhance community resilience by using POCT in tandem with geographic information systems (GISs) and other geospatial tools; and (d) to advance crisis standards of care at points of need, adaptable and scalable for public health practice in limited-resource countries and other global settings.
+Value: Small-world networks and their connectivity facilitate efficient and effective placement of POCT for optimal response, rescue, diagnosis, and treatment.
+Spatial care paths™ speed transport from primary encounters to referral centers bypassing topographic bottlenecks, process gaps, and time-consuming interruptions.
+Regional GISs position POCT close to where patients live to facilitate rapid triage, decrease therapeutic turnaround time, and conserve economic resources.
+Isolation laboratories equipped with POCT help stop outbreaks and safely support critically ill patients with highly infectious diseases.
+POCT-enabled spatial grids can map sentinel cases and establish geographic limits of epidemics for ring vaccination.
+Impact: Geospatial solutions generate inherently optimal and logical placement of POCT conceptually, physically, and temporally as a means to improve crisis response and spatial resilience.
+If public health professionals, geospatial scientists, and POCT specialists join forces, new collaborative teamwork can create faster response and higher impact during disasters, complex crises, outbreaks, and epidemics, as well as more efficient primary, urgent, and emergency community care.
+Network properties govern the rate and extent of various spreading processes, from simple contagions to complex cascades.
+Recently, the analysis of spreading processes has been extended from static networks to temporal networks, where nodes and links appear and disappear.
+We focus on the effects of accessibility, whether there is a temporally consistent path from one node to another, and reachability, the density of the corresponding accessibility graph representation of the temporal network.
+The level of reachability thus inherently limits the possible extent of any spreading process on the temporal network.
+We study reachability in terms of the overall levels of temporal concurrency between edges and the structural cohesion of the network agglomerating over all edges.
+We use simulation results and develop heterogeneous mean-field model predictions for random networks to better quantify how the properties of the underlying temporal network regulate reachability.
+Drug-resistant Mycobacterium tuberculosis (M. tuberculosis) has become an increasingly serious public health problem and has complicated tuberculosis (TB) treatment.
+However, the detailed molecular mechanisms of LOF-resistant M. tuberculosis in TB treatment have not been revealed.
+Our study performed transcriptome and methylome sequencing to investigate the potential biological characteristics of LOF resistance in M. tuberculosis H37Rv.
+In the transcriptome analysis, 953 differentially expressed genes (DEGs) were identified; 514 and 439 DEGs were significantly downregulated and upregulated in the LOF-resistant group and control group, respectively.
+In the methylome analysis, 239 differentially methylated genes (DMGs) were identified; 150 and 89 DMGs were hypomethylated and hypermethylated in the LOF-resistant group and control group, respectively.
+It was notable that nine genes expressed downregulated mRNA and upregulated methylated levels, including pgi, fadE4, php, cyp132, pckA, rpmB1, pfkB, acg, and ctpF, especially cyp132, pckA, and pfkB, which were vital in LOF-resistant M. tuberculosis H37Rv.
+The overlapping genes between transcriptome and methylome could be essential for studying the molecular mechanisms of LOF-resistant M. tuberculosis H37Rv.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00239-019-09926-z) contains supplementary material, which is available to authorized users.
+BACKGROUND: Gastrointestinal (GI) cytomegaloviral (CMV) infection is common among patients with immunocompromised status; however, data specific to GI-CMV infection in immunocompetent patients are comparatively limited.
+METHODS: This retrospective study included patients diagnosed with GI-CMV infection at Siriraj Hospital (Bangkok, Thailand) during 2008–2017.
+Baseline characteristics, presentations, comorbid conditions, endoscopic findings, treatments, and outcomes were compared between immunocompetent and immunocompromised.
+Immunocompetent patients were significantly older than immunocompromised patients (73 vs. 48.6 years, p < 0.0001).
+Significantly more immunocompetent patients were in the ICU at the time of diagnosis (21.0% vs. 8.6%, p = 0.024).
+GI bleeding was the leading presentation in immunocompetent, while diarrhea and abdominal pain were more common in immunocompromised.
+Blood CMV viral load was negative in significantly more immunocompetent than immunocompromised (40.7% vs. 12.9%, p = 0.002).
+Significantly more immunocompetent than immunocompromised did not receive any specific therapy (25.5% vs. 4.4%, p ≤ 0.01).
+CONCLUSION: GI-CMV infection was frequently observed among immunocompetent elderly patients with comorbidities or severe concomitant illnesses.
+Significantly higher mortality was observed in immunocompetent than in immunocompromised patients, but this could be due to more severe concomitant illnesses in the immunocompetent group.
+Intracellular vesicle fusion is mediated by soluble N-ethylmaleimide sensitive factor attachment protein receptors (SNAREs) and Sec1/Munc18 (SM) proteins.
+It is generally accepted that membrane fusion occurs when the vesicle and target membranes are brought into close proximity by SNAREs and SM proteins.
+In this work, we demonstrate that, for fusion to occur, membrane bilayers must be destabilized by a conserved membrane-embedded motif located at the juxtamembrane region of the vesicle-anchored v-SNARE.
+Comprised of basic and hydrophobic residues, the juxtamembrane motif perturbs the lipid bilayer structure and promotes SNARE-SM-mediated membrane fusion.
+The juxtamembrane motif can be functionally substituted with an unrelated membrane-disrupting peptide in the membrane fusion reaction.
+In the past two decades there has been a significant expansion in the number of new therapeutic monoclonal antibodies (mAbs) that are approved by regulators.
+The discovery of these new medicines has been driven primarily by new approaches in inflammatory diseases and oncology, especially in immuno-oncology.
+The perception of very high costs associated with mAbs has led to the assumption that they play no role in prophylaxis for diseases of poverty.
+However, improvements in antibody-expression yields and manufacturing processes indicate this is a cost-effective option for providing protection from many types of infection that should be revisited.
+Recent technology developments also indicate that several months of protection could be achieved with a single dose.
+Moreover, new methods in B cell sorting now enable the systematic identification of high-quality antibodies from humanized mice, or patients.
+This Review discusses the potential for passive immunization against schistosomiasis, fungal infections, dengue, and other neglected diseases.
+This study was conducted to measure the inactivation characteristics of UVs and TiO(2) against Salmonella.
+Among various sterilization conditions, the largest number of pathogen in black pepper powder was inactivated by UV-A and UV-C combined with TiO(2) coating.
+The microbial count of black pepper powder treated simultaneously with UV-A and UV-C was less than that of black pepper powder treated with alone.
+In this study, it was indicated that the combined treatment of UV-C, UV-A and TiO(2) coating was effective for reducing S. Typhimurium and E. coli O157:H7 on black pepper powder.
+BACKGROUND: Outbreaks of acute undifferentiated febrile illness (AUFI) are common in Nepal, but the exact etiology or risk factors for them often go unrecognized.
+A proper epidemiological and clinical characterization of such outbreaks is important for appropriate treatment and control efforts.
+METHODS: An investigation was initiated as a response to increased presentation of patients at Patan Hospital from Chalnakhel locality in Dakchinkali municipality, Kathmandu with AUFI from June 10 to July 1, 2016.
+Focused group discussion with local inhabitants and the epidemiological curve of febrile patients at local primary health care centre confirmed the outbreak.
+The household-survey was conducted in the area with questionnaire administered on patients to characterize their illnesses and their medical records were reviewed.
+A different set of questionnaire was administered on the patients and controls to investigate the association with common risk factors.
+RESULTS: Eighty one patients from 137 households suffered from febrile illness within 6 weeks window before the investigation.
+All the 67 sampled patients with acute fever had a generalized illness without a discernible focus of infection.
+Only 38% of the patients had received a clinical diagnosis while the rest were treated empirically without a diagnosis.
+Forty-two (63%) patients had been administered antibiotics, most commonly, ofloxacin, cefixime or azithromycin with a mean fever clearance time of 4 days.
+CONCLUSION: Based on the pattern of illness, this outbreak was most likely a mixture of self-limiting viral infections and enteric fever.
+This study shows that even in the absence of a confirmed diagnosis, a detailed characterization of the illness at presentation and the recovery course can suggest the diagnosis and help in formulating appropriate recommendation for treatment and control.
+The current prophylaxis and therapeutic interventions for IAV requires frequent changes due to the continuous antigenic drift and antigenic shift of IAV.
+Emerging evidence indicates that the host microRNAs (miRNAs) play critical roles in intricate host-pathogen interaction networks.
+Cellular miRNAs may directly target virus to inhibit its infection and be developed as potential anti-virus drugs.
+METHODS: In this study, we established a broad-spectrum anti-IAV miRNA screening method using miRanda software.
+The screened miRNAs were further verified by luciferase assay, viral protein expression assay and virus replication assay.
+RESULTS: Five cellular miRNAs (miR-188-3p, miR-345-5p, miR-3183, miR-15-3p and miR-769-3p), targeting 99.96, 95.31, 92.9, 94.58 and 97.24% of human IAV strains recorded in NCBI, respectively, were chosen for further experimental verification.
+Finally, we found that miR-188-3p downregulated PB2 expression at both mRNA and protein levels by directly targeted the predicted sites on PB2 and effectively inhibited the replication of IAV (H1N1, H5N6 and H7N9) in A549 cells.
+BACKGROUND: Multi-drug resistant (MDR) Acinetobacter baumannii and Pseudomonas aeruginosa are major causes of nosocomial infections globally.
+They are the current World Health Organization critical priority pathogens for resistance, Antimicrobial resistance (AMR) surveillance and discovery of new antibiotics.
+However, there is paucity of data on nosocomial infections (NIs) caused by such superbugs in Ethiopia.
+Therefore, this study determined the magnitude and profile of nosocomial MDR A. baumannii and P. aeruginosa infections among patients hospitalized at Felegehiwot referral hospital, Northwest Ethiopia.
+METHODS: A cross-sectional study was conducted at Felegehiwot referral hospital from April 1 to July 31, 2018.
+A total of 238 patients with blood stream, urinary tract and surgical site NIs were enrolled conveniently.
+Either blood, urine and wound swab specimens were collected and processed using standard bacteriological procedures.
+A. baumannii and P. aeruginosa isolates were identified using standard bacteriological techniques and confirmed by automated Vitek2 Compact.
+The results were interpreted as per the standard zone sizes of Clinical and Laboratory Standards Institute.Chi-square test was done to determine associations among variables.
+The proportion of nosocomial MDR blood stream, urinary tract and surgical site infections were 13(8.9%), 5(8.3%) and 2 (6.3%), respectively.
+The frequency of NI was 9(3.8%) for MDR A. baumannii and 11(4.6%) for MDR P.aeruginosa.
+All isolates of A. baumannii and P. aeruginosa were 100% resistant to ampicillin and piperacillin.A.
+baumannii isolates were 33.3 and 44.5% resistance against meropenem and ciprofloxacin, respectively while P.aeruginosa isolates revealed 36.4 and 45.5% resistance against ciprofloxacin and meropenem, respectively.
+CONCLUSIONS: Health care associated infections of MDR A.baumannii and P. aeruginosa are critical problems in the study area.
+Treatment of NIs for patients on health care should be guided by antimicrobial susceptibility testing.
+BACKGROUND: Previous studies suggest that prone positioning (PP) can increase PaO(2)/FiO(2) and reduce mortality in moderate to severe acute respiratory distress syndrome (ARDS).
+The aim of our study was to determine whether the early use of PP combined with non-invasive ventilation (NIV) or high-flow nasal cannula (HFNC) can avoid the need for intubation in moderate to severe ARDS patients.
+Non-intubated moderate to severe ARDS patients were included and were placed in PP with NIV or with HFNC.
+The efficacy in improving oxygenation with four support methods—HFNC, HFNC+PP, NIV, NIV+PP—were evaluated by blood gas analysis.
+The main causes of ARDS were pneumonia due to influenza (9 cases, 45%) and other viruses (2 cases, 10%).
+PaO(2)/FiO(2) in HFNC+PP were significantly higher in the success group than in the failure group (125 ± 41 mmHg vs 119 ± 19 mmHg, P = 0.043).
+PaO(2)/FiO(2) demonstrated an upward trend in patients with all four support strategies: HFNC < HFNC+PP ≤ NIV < NIV+PP.
+CONCLUSIONS: Early application of PP with HFNC, especially in patients with moderate ARDS and baseline SpO(2) > 95%, may help avoid intubation.
+The PP was well tolerated, and the efficacy on PaO(2)/FiO(2) of the four support strategies was HFNC < HFNC+PP ≤ NIV < NIV+PP.
+The significance of the integral membrane protein Niemann-Pick C1 (NPC1) in the ebolavirus entry process has been determined using various cell lines derived from humans, non-human primates and fruit bats.
+Fruit bats have long been purported as the potential reservoir host for ebolaviruses, however several studies provide evidence that Mops condylurus, an insectivorous microbat, is also an ebolavirus reservoir.
+In order to study Ebola virus (EBOV) cellular entry and replication in M. condylurus, we derived primary and immortalized cell cultures from 12 different organs.
+The NPC1 receptor expression was characterized by confocal microscopy and flow cytometry comparing the expression levels of M. condylurus primary and immortalized cells, HeLa cells, human embryonic kidney cells and cells from a European microbat species.
+The aim was to elucidate the suitability of primary and immortalized cells from different tissues for studying NPC1 receptor expression levels and their potential influence on EBOV replication.
+The NPC1 receptor expression level in M. condylurus primary cells differed depending on the organ they were derived from and was for most cell types significantly lower than in human cell lines.
+Immortalized cells showed for most cell types higher expression levels than their corresponding primary cells.
+Concluding from our infection experiments with EBOV we suggest a potential correlation between NPC1 receptor expression level and virus replication rate in vitro.
+Life chaos, the perceived inability to plan for and anticipate the future, may be a barrier to the HIV care continuum for people living with HIV who experience incarceration.
+Between December 2012 and June 2015, we interviewed 356 adult cisgender men and transgender women living with HIV in Los Angeles County Jail.
+We assessed life chaos using the Confusion, Hubbub, and Order Scale (CHAOS) and conducted regression analyses to estimate the association between life chaos and care continuum.
+Forty-eight percent were diagnosed with HIV while incarcerated, 14% were engaged in care 12 months prior to incarceration, mean antiretroviral adherence was 65%, and 68% were virologically suppressed.
+Adjusting for sociodemographics, HIV-related stigma, and social support, higher life chaos was associated with greater likelihood of diagnosis while incarcerated, lower likelihood of engagement in care, and lower adherence.
+Identifying life chaos in criminal-justice involved populations and intervening on it may improve continuum outcomes.
+AIMS AND OBJECTIVES: Oral health deteriorates following hospitalisation in critical care units (CCU) but there are no validated measures to assess effects on oral health-related quality of life (OHQoL).
+The objectives of this study were (i) to develop a tool (CCU-OHQoL) to assess OHQoL amongst patients admitted to CCU, (ii) to collect data to analyse the validity, reliability and acceptability of the CCU-OHQoL tool and (iii) to investigate patient-reported outcome measures of OHQoL in patients hospitalised in a CCU.
+METHODS: The project included three phases: (1) the development of an initial questionnaire informed by a literature review and expert panel, (2) testing of the tool in CCU (n = 18) followed by semi-structured interviews to assess acceptability, face and content validity and (3) final tool modification and testing of CCU-OHQoL questionnaire to assess validity and reliability.
+For construct validity, the CCU-OHQoL was strongly and significantly correlated (correlation coefficients 0.71, 0.62 and 0.77, p < 0.01) with global OHQoL items.
+In the validation study, 37.8% of the participants reported a deterioration in self-reported oral health after CCU admission.
+Finally, 26.9% and 31% of the participants reported considerable negative impacts of oral health in their life overall and quality of life, respectively.
+CONCLUSIONS: The new CCU-OHQoL tool may be of use in the assessment of oral health-related quality of life in CCU patients.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11136-019-02335-1) contains supplementary material, which is available to authorised users.
+The Plasmodium falciparum (Pf) cysteine-rich protective antigen (PfCyRPA) has emerged as a promising blood-stage candidate antigen for inclusion into a broadly cross-reactive malaria vaccine.
+This highly conserved protein among various geographical strains plays a key role in the red blood cell invasion process by P. falciparum merozoites, and antibodies against PfCyRPA can efficiently prevent the entry of the malaria parasites into red blood cells.
+The aim of the present study was to develop a human-compatible formulation of the PfCyRPA vaccine candidate and confirming its activity in preclinical studies.
+Recombinant PfCyRPA expressed in HEK 293 cells was chemically coupled to phosphoethanolamine and then incorporated into the membrane of unadjuvanted influenza virosomes approved as antigen delivery system for humans.
+Laboratory animals were immunised with the virosome-based PfCyRPA vaccine to determine its immunogenic properties and in particular, its capacity to elicit parasite binding and growth-inhibitory antibodies.
+The vaccine elicited in mice and rabbits high titers of PfCyRPA-specific antibodies that bound to the blood-stage parasites.
+At a concentration of 10 mg/mL, purified total serum IgG from immunised rabbits inhibited parasite growth in vitro by about 80%.
+Furthermore, in a P. falciparum infection mouse model, passive transfer of 10 mg of purified total IgG from PfCyRPA vaccinated rabbits reduced the in vivo parasite load by 77%.
+Influenza virosomes thus represent a suitable antigen delivery system for the induction of protective antibodies against the recombinant PfCyRPA, designating it as a highly suitable component for inclusion into a multivalent and multi-stage virosomal malaria vaccine.
+BACKGROUND: Compared to continuous vibrating mesh nebulizer (VMN), inspiration synchronized VMN has shown increased inhaled dose during noninvasive ventilation; however, its use during aerosol delivery via high-flow nasal cannula (HFNC) is still unknown.
+METHODS: An adult manikin was connected to a dual-chamber model lung, which was driven by a critical care ventilator to simulate spontaneous breathing.
+A HFNC system was utilized with temperature at 37 ° C while gas flow at 5, 10, 20, 40, and 60 L/min.
+Inspiration synchronized and continuous aerosol generation were compared at different positions (at the inlet of humidifier vs close to patient).
+RESULTS: When nebulizer was placed close to patient, inhaled dose was higher with inspiration synchronized than continuous aerosol generation at all gas flows (p = 0.05) except at 5 L/min.
+When placed at the inlet of humidifier, compared to continuous, inspiration synchronized aerosol generated higher inhaled dose with gas flow set below 50% of patient inspiratory flow [23.9 (20.6, 28.3)% vs 18.1 (16.7, 19.6)%, p < 0.001], but lower inhaled dose with gas flow set above 50% of patient inspiratory flow [3.5 (2.2, 9.3)% vs 9.9 (8.2, 16.4)%, p = 0.001].
+Regardless of breathing pattern, continuous aerosol delivered greater inhaled dose with nebulizer placed at humidifier than close to patient at all gas flows except at 5 L/min.
+CONCLUSION: When the HFNC gas flow was set higher than 50% of patient inspiratory flow, no significant advantage was found in inspiration synchronized over continuous aerosol.
+However, inspiration synchronized aerosol generated 30% more inhaled dose than continuous with gas flow set below 50% of patient inspiratory flow, regardless of nebulizer placement.
+BACKGROUND: High-frequency oscillatory ventilation (HFOV) use was associated with greater mortality in adult acute respiratory distress syndrome (ARDS).
+Nevertheless, HFOV is still frequently used as rescue therapy in paediatric acute respiratory distress syndrome (PARDS).
+In view of the limited evidence for HFOV in PARDS and evidence demonstrating harm in adult patients with ARDS, we hypothesized that HFOV use compared to other modes of mechanical ventilation is associated with increased mortality in PARDS.
+METHODS: Patients with PARDS from 10 paediatric intensive care units across Asia from 2009 to 2015 were identified.
+The primary outcome was 28-day mortality and secondary outcomes were 28-day ventilator- (VFD) and intensive care unit- (IFD) free days.
+Genetic matching (GM) method was used to analyse the association between HFOV treatment with the primary outcome.
+Additionally, we performed a sensitivity analysis, including propensity score (PS) matching, inverse probability of treatment weighting (IPTW) and marginal structural modelling (MSM) to estimate the treatment effect.
+There were significant differences in baseline oxygenation index (OI) between the HFOV and non-HFOV groups (18.8 [12.0, 30.2] vs. 7.7 [5.1, 13.1] respectively; p < 0.001).
+A total of 118 pairs were matched in the GM method which found a significant association between HFOV with 28-day mortality in PARDS [odds ratio 2.3, 95% confidence interval (CI) 1.3, 4.4, p value 0.01].
+VFD was indifferent between the HFOV and non-HFOV group [mean difference − 1.3 (95%CI − 3.4, 0.9); p = 0.29] but IFD was significantly lower in the HFOV group [− 2.5 (95%CI − 4.9, − 0.5); p = 0.03].
+From the sensitivity analysis, PS matching, IPTW and MSM all showed consistent direction of HFOV treatment effect in PARDS.
+This study suggests caution but does not eliminate equivocality and a randomized controlled trial is justified to examine the true association.
+ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13054-020-2741-x) contains supplementary material, which is available to authorized users.
+Attempts to target the kidney Renin Angiotensin System using native ACE2 to treat kidney disease are hampered by its large molecular size, 100 kDa, which precludes its glomerular filtration and subsequent tubular uptake.
+Here, we show that both urine and kidney lysates are capable of digesting native ACE2 into shorter proteins of ~60–75 kDa and then demonstrate that they are enzymatically very active.
+We then truncated the native ACE2 by design from the C-terminus to generate two short recombinant (r)ACE2 variants (1-605 and 1-619AA).
+These two truncates have a molecular size of ~70 kDa, as expected from the amino acid sequence and as shown by Western blot.
+ACE2 enzyme activity, measured using a specific substrate, was higher than that of the native rACE2 (1-740 AA).
+injection of 1-619 resulted in detectable ACE2 activity in urine, whereas infusion of the native ACE2 did not.
+Moreover, ACE2 activity was recovered in harvested kidneys from ACE2-deficient mice infused with 1-619, but not in controls (23.1 ± 4.3 RFU/µg creatinine/h and 1.96 ± 0.73 RFU/µg protein/hr, respectively).
+In addition, the kidneys of ACE2-null mice infused with 1-619 studied ex vivo formed more Ang (1–7) from exogenous Ang II than those infused with vehicle (AUC 8555 ± 1933 vs. 3439 ± 753 ng/mL, respectively, p < 0.05) further demonstrating the functional effect of increasing kidney ACE2 activity after the infusion of our short ACE2 1-619 variant.
+We conclude that our novel short recombinant ACE2 variants undergo glomerular filtration, which is associated with kidney uptake of enzymatically active proteins that can enhance the formation of Ang (1–7) from Ang II.
+These small ACE2 variants may offer a potentially useful approach to target kidney RAS overactivity to combat kidney injury.
+In order to understand the possible mechanisms influencing clinical presentation of hepatitis E in pregnant women, we explored a system biology approach.
+These included non-pregnant (NPR, acute and convalescent phases) and pregnant (PR, 2(nd) and 3(rd) trimesters, acute phase and subclinical HEV infections) patients and corresponding healthy controls.
+In contrast to exclusive up-regulation of nonspecific, early immune response transcripts in the NPR patients, the PR patients exhibited broader and heightened expression of genes associated with innate as well as adaptive T and B cell responses.
+The study identified for the first time (1) inverse relationship of immunoglobulin (Ig) genes overexpression and (2) association of differential expression of S100 series genes with disease presentation.
+The data suggests possible involvement of TLR4 and NOD1 in pregnant patients and alpha defensins in all patient categories suggesting a role in protection.
+Association of response to vitamin D, transcripts related to NK/NKT and regulatory T cells during subclinical infection are noteworthy.
+The data obtained here could be correlated with several studies reported earlier in hepatitis E patients suggesting utility of PBMCs as an alternate specimen.
+The extensive, informative data provided here for the first time should form basis for future studies that will help in understanding pathogenesis of fulminant hepatitis E.
+BACKGROUND: Prone positioning (PP) during veno-venous ECMO is feasible, but its physiological effects have never been thoroughly evaluated.
+Our objectives were to describe, through electrical impedance tomography (EIT), the impact of PP on global and regional ventilation, and optimal PEEP level.
+METHODS: A monocentric study conducted on ECMO-supported severe ARDS patients, ventilated in pressure-controlled mode, with 14-cmH(2)O driving pressure and EIT-based “optimal PEEP”.
+Before, during and after a 16-h PP session, EIT-based distribution and variation of tidal impedance, VT(dorsal)/VT(global) ratio, end-expiratory lung impedance (EELI) and static compliance were collected.
+Subgroup analyses were performed in patients who increased their static compliance by ≥ 3 mL/cmH(2)O after 16 h of PP.
+RESULTS: For all patients (n = 21), tidal volume and EELI were redistributed from ventral to dorsal regions during PP.
+Median (IQR) optimal PEEP decreased from 14 (12–16) to 10 (8–14) cmH(2)O. Thirteen (62%) patients increased their static compliance by ≥ 3 mL/cmH(2)O after PP on ECMO.
+This subgroup had higher body mass index, more frequent viral pneumonia, shorter ECMO duration, and lower baseline VT(dorsal)/VT(global) ratio than patients with compliance ≤ 3 mL/cmH(2)O (P < 0.01).
+CONCLUSION: Although baseline tidal volume distribution on EIT may predict static compliance improvement after PP on ECMO, our results support physiological benefits of PP in all ECMO patients, by modifying lung mechanics and potentially reducing VILI.
+Further studies, including a randomized–controlled trial, are now warranted to confirm potential PP benefits during ECMO.
+BACKGROUND: Both overfeeding and underfeeding of intensive care unit (ICU) patients are associated with worse outcomes.
+A reliable estimation of the energy expenditure (EE) of ICU patients may help to avoid these phenomena.
+However, the effect of neuromuscular blocking agents on EE, which conceptually would lower EE, has not been extensively investigated.
+METHODS: We studied a cohort of adult critically ill patients requiring invasive mechanical ventilation and treatment with continuous infusion of cisatracurium for at least 12 h. The study aimed to quantify the effect of cisatracurium infusion on EE (primary endpoint).
+Multivariable analysis showed a significantly lower EE after cisatracurium infusion (MD − 132.0 kcal (95% CI − 212.0 to − 52.0; p = 0.001) in all patients.
+This difference was statistically significant in both sepsis and non-sepsis patients (p = 0.036 and p = 0.011).
+Non-sepsis patients had lower EE than sepsis patients (MD − 120.6 kcal; 95% CI − 200.5 to − 40.8, p = 0.003).
+CONCLUSIONS: Our data suggest that continuous infusion of cisatracurium in mechanically ventilated ICU patients is associated with a significant reduction in EE, although the magnitude of the effect is small.
+Cisatracurium infusion is associated with overfeeding in only a minority of patients and therefore, in most patients, no reductions in caloric prescription are necessary.
+BACKGROUND: As more and more diagnostic and interventional options are becoming available for use in pediatric patients, techniques of procedural sedation analgesia (PSA) are being administered in considerably growing numbers as well.
+AIMS: The objective of this research effort was to conduct the first countrywide survey on the status quo of sedation analgesia as delivered to children and adolescents in Germany.
+METHODS: We dispatched letters to all pediatric hospital settings in Germany (n = 305), including a questionnaire that had been developed with existing guidelines taken into account.
+Its items were designed to elucidate the current practice of PSA throughout these pediatric centers regarding (a) organizational structures and (b) standards of medication and staffing.
+RESULTS: A total of 138 centers returned the questionnaire, hence the response rate was 45.2%.
+Deficits were nevertheless identified, most notably in terms of on-location equipment and staff provided to deliver sedations.
+Adequate staffing was not provided in up to 44.2% of centers, depending on the diagnostic or interventional procedures for which the PSA was delivered.
+CONCLUSIONS: Adequate care structures for the management of procedural sedation analgesia have been implemented by many pediatric centers in Germany.
+On the downside, these findings also reveal deficits that will take efforts to be eliminated.
+BACKGROUND: The epidemiological control of malaria has been hampered by the appearance of parasite resistance to anti-malarial drugs and by the resistance of mosquito vectors to control measures.
+This has also been associated with weak transmission control, mostly due to poor control of asymptomatic patients associated with host-vector transmission.
+This highlights the importance of studying the parasite’s sexual forms (gametocytes) which are involved in this phase of the parasite’s life-cycle.
+Some African and Asian strains of Plasmodium falciparum have been fully characterized regarding sexual forms’ production; however, few Latin-American strains have been so characterized.
+This study was aimed at characterizing the Colombian FCB2 strain as a gametocyte producer able to infect mosquitoes.
+METHODS: Gametocyte production was induced in in vitro cultured P. falciparum FCB2 and 3D7 strains.
+In vitro zygote formation from FCB2 gametocytes was induced by incubating a gametocyte culture sample at 27 °C for 20 min.
+A controlled Anopheles albimanus infection was made using an artificial feed system with cultured FCB2 gametocytes (14–15 days old).
+RESULTS: The FCB2 strain expressed Pfap2g, Pfs16, Pfg27/25 and Pfs25 sexual differentiation-related genes after in vitro sexual differentiation induction, producing gametocytes that conserved the expected morphological features.
+FCB2 gametocytes were differentiated into zygotes and ookinetes after an in vitro low-temperature stimulus and infected An.
+CONCLUSIONS: Even with the history of long-term FCB2 strain in vitro culture maintenance, it has retained its sexual differentiation ability.
+albimanus infection capability, thus enabling its use as a tool for studying sexual form biology, An.
+BACKGROUND: Haemonchus contortus (H. contortus) is one of the most important parasites that cause huge economic losses to small ruminant industry worldwide.
+To date, no widely-approved methods for the identification of prepatent H. contortus infection are available to identify prepatent H. contortus infection properly.
+The aim of this study was to evaluate the diagnostic potential of recombinant cold shock H. contortus protein (rHc-CS) during early and late infections of H. contortus in goat.
+H. contortus eggs were not detected by fecal egg count technique from feces collected at 0 to 14 days post infection (D.P.I).
+Hence, results of immunoblotting assay showed specific anti rHc-CS antibody detection in all goat sera collected at early stage (14 D.P.I) and late stage (21–103 D.P.I) of H. contortus infection.
+Furthermore, no cross reactivity was observed against Trichinella spiralis, Fasciola hepatica and Toxoplasma gondii or uninfected goats.
+Among several evaluated rHc-CS indirect-ELISA format variables, favorable antigen coating concentration was found 0.28 μg/well at 37 °C 1 h and overnight at 4 °C.
+Moreover, optimum dilution ratio of serum and rabbit anti-goat IgG was recorded as 1:100 and 1:4000, respectively.
+The best blocking buffer was 5% Bovine Serum Albumin (BSA) while the best time for blocking, serum incubation and TMB reaction were recorded as 60, 120 and 10 min, respectively.
+CONCLUSION: These results validated that rHc-CS is a potential immunodiagnostic antigen to detect the specific antibodies during early and late H. contortus infections in goat.
+BACKGROUND: Muscle weakness following critical illness is the consequence of loss of muscle mass and alteration of muscle quality.
+Ultrasonography is a reliable tool to quantify muscle mass, but studies that evaluate muscle quality at the critically ill bedside are lacking.
+Shear wave ultrasound elastography (SWE) provides spatial representation of soft tissue stiffness and measures of muscle quality.
+METHODS: Two operators tested in healthy controls and in critically ill patients the intra- and inter-operator reliability of the SWE using transversal and longitudinal views of the diaphragm and limb muscles.
+Reliability was calculated using the intra-class correlation coefficient and a bootstrap sampling method assessed their consistency.
+Longitudinal views of the diaphragm (ICC 0.83 [0.50–0.94]), the biceps brachii (ICC 0.88 [0.67–0.96]) and the rectus femoris (ICC 0.76 [0.34–0.91]) were the most reliable views in a training set of healthy controls.
+Intra-class correlation coefficient for inter-operator reproducibility and intra-operator reliability was above 0.9 for all muscles in a validation set of healthy controls.
+In critically ill patients, inter-operator reproducibility and intra-operator 1 and 2 reliability ICCs were respectively 0.92 [0.71–0.98], 0.93 [0.82–0.98] and 0.92 [0.81–0.98] for the diaphragm; 0.96 [0.86–0.99], 0.98 [0.94–0.99] and 0.99 [0.96–1] for the biceps brachii and 0.91 [0.51–0.98], 0.97 [0.93–0.99] and 0.99 [0.97–1] for the rectus femoris.
+The probability to reach intra-class correlation coefficient greater than 0.8 in a 10,000 bootstrap sampling for inter-operator reproducibility was respectively 81%, 84% and 78% for the diaphragm, the biceps brachii and the rectus femoris respectively.
+CONCLUSIONS: SWE is a reliable technique to evaluate limb muscles and the diaphragm in both healthy controls and in critically ill patients.
+BACKGROUND: As demonstrated during the global Ebola crisis of 2014–2016, healthcare institutions in high resource settings need support concerning preparedness during threats of infectious disease outbreaks.
+This study aimed to exploratively develop a standardized preparedness system to use during unfolding threats of severe infectious diseases.
+First, interviews (n = 5) were conducted to identify which factors trigger preparedness activities during an unfolding threat.
+Second, these triggers informed the design of a phased preparedness system which was tested in a focus group discussion (n = 5) were conducted to identify which factors trigger preparedness activities during an unfolding threat.
+Second, these triggers informed the design of a phased preparedness system which was tested in a focus group discussion (n = 5) were conducted to identify which factors trigger preparedness activities during an unfolding threat.
+Second, these triggers informed the design of a phased preparedness system which was tested in a focus group discussion ( RESULTS: Four preparedness phases were identified: preparedness phase green is a situation without the presence of the infectious disease threat that requires centralized care, anywhere in the world.
+Phase orange is a realistic chance of an unexpected case within the country, or unrest developing among population or staff; phase red is cases admitted to hospitals in the country, potentially causing a shortage of resources.
+Consensus was reached on the need for the development of a preparedness system and national coordination during threats.
+CONCLUSIONS: In this study, we developed a standardized system to support institutional preparedness during an increasing threat.
+Use of this system by both curative healthcare institutions and the (municipal) public health service, could help to effectively communicate and align preparedness activities during future threats of severe infectious diseases.
+BACKGROUND: With the fast-paced aging and increasing digitalization of society, there has been a growing interest in the effect of mobile device use on cognitive function and depression in older adults.
+However, research examining this issue among older adults in residential care homes (RCHs) is scant.
+Therefore, this study aimed to examine the impact of mobile device use on the cognitive function and depressive symptoms of older adults living in RCHs.
+METHODS: A cross-sectional survey was conducted using a sociodemographic questionnaire, the Montreal Cognitive Assessment (MoCA) and the 15-item Geriatric Depression Scale (GDS-15).
+RESULTS: A total of 235 senior residents (aged 82.58 ± 5.54) in four RCHs were surveyed.
+Users of mobile devices had a significantly higher total MoCA score (25.02 ± 4.14) and a significantly lower GDS-15 score (3.28 ± 2.74) than non-users (MoCA: 19.34 ± 5.21, GDS-15: 4.69 ± 2.90).
+Multivariate linear regression indicate that mobile device use is significantly associated with total MoCA score, six of the seven sub-scores (visuospatial abilities and execution functions, attention, language, abstraction, delayed recall, and orientation)(P < 0.05).
+Logistic regression showed that mobile device use was significantly associated with the level of depressive symptoms (OR = 0.458, 95%CI = 0.249–0.845).
+CONCLUSIONS: Use of mobile devices has a significant association with the cognitive function and depressive symptoms of older adults living in RCHs, and thus should be encouraged as a measure to maintain and improve cognition and prevent depression.
+Worldwide strategies between 2010 and 2017 aimed at controlling malarial parasites (mainly Plasmodium falciparum) led to a reduction of just 18% regarding disease incidence rates.
+Many biologically-derived anti-malarial vaccine candidates have been developed to date; this has involved using many experimental animals, an immense amount of work and the investment of millions of dollars.
+This review provides an overview of the current state and the main results of clinical trials for sporozoite-targeting vaccines (i.e.
+the parasite stage infecting the liver) carried out by research groups in areas having variable malaria transmission rates.
+However, none has led to promising results regarding the effective control of the disease, thereby making it necessary to complement such efforts at finding/introducing new vaccine candidates by adopting a multi-epitope, multi-stage approach, based on minimal subunits of the main sporozoite proteins involved in the invasion of the liver.
+Protective ventilation is the cornerstone of treatment of patients with the acute respiratory distress syndrome (ARDS); however, no studies have yet established the best ventilatory strategy to adopt when patients with acute exacerbation of interstitial lung disease (AE-ILD) are admitted to the intensive care unit.
+Due to the severe impairment of the respiratory mechanics, the fibrotic lung is at high risk of developing ventilator-induced lung injury, regardless of the lung fibrosis etiology.
+The purpose of this review is to analyze the effects of mechanical ventilation in AE-ILD and to increase the knowledge on the characteristics of fibrotic lung during artificial ventilation, introducing the concept of “squishy ball lung”.
+The role of positive end-expiratory pressure is discussed, proposing a “lung resting strategy” as opposed to the “open lung approach”.
+Despite all the research done on the first Zika virus (ZIKV) epidemics, it was only after the Brazilian epidemic that the Congenital Zika Syndrome was described.
+This was made possible due to the large number of babies born with microcephaly in the Northeast region (NE) in a narrow time.
+We hypothesize that the fivefold difference in the rate of microcephalic neonates between the NE and other regions is partially an effect of the population prior immunity against Dengue viruses (DENV), that cross-react with ZIKV.
+In this ecological study, we analysed the interaction between dengue fever epidemics from 2001 to 2014 and the 2015/2016 microcephaly epidemic in 400 microregions in Brazil using random-effects models under a Bayesian approach.
+The estimated effect of the time lag between the most recent large dengue epidemic (>400/100,000 inhabitants) and the microcephaly epidemic ranged from protection (up to 6 years prior) to an increased risk (from 7 to 12 years).
+This sustained window of protection, larger than described in previous longitudinal studies, is possibly an effect of herd immunity and of multiple exposures to DENV that could boost immunity.
+mRNA technologies have the potential to transform areas of medicine, including the prophylaxis of infectious diseases.
+The advantages for vaccines range from the acceleration of immunogen discovery to rapid response and multiple disease target manufacturing.
+A greater understanding of quality attributes that dictate translation efficiency, as well as a comprehensive appreciation of the importance of mRNA delivery, are influencing a new era of investment in development activities.
+The application of translational sciences and growing early-phase clinical experience continue to inform candidate vaccine selection.
+Here we review the state of the art for the prevention of infectious diseases by using mRNA and pertinent topics to the biotechnology and pharmaceutical industries.
+BACKGROUND: Various transcription factors are involved in the process of mutually exclusive expression and clonal variation of the Plasmodium multigene (var) family.
+Recent studies revealed that a P. falciparum SWI/SNF-related matrix-associated actin-dependent regulator of chromatin (PfSWIB) might trigger stage-specific programmed cell death (PCD), and was not only crucial for the survival and development of parasite, but also had profound effects on the parasite by interacting with other unknown proteins.
+However, it remains unclear whether PfSIWB is involved in transcriptional regulation of this virulence gene and its functional properties.
+METHODS: A conditional knockdown system “PfSWIB-FKBP-LID” was introduced to the parasite clone 3D7, and an integrated parasite line “PfSWIB-HA-FKBP-LID” was obtained by drug cycling and clone screening.
+Growth curve analysis (GCA) was performed to investigate the growth and development of different parasite lines during 96 h in vitro culturing, by assessing parasitemia.
+Finally, we performed qPCR assays to detect var gene expression profiling in various comparison groups, as well as the mutually exclusive expression pattern of the var genes within a single 48 h life-cycle of P. falciparum in different parasite lines.
+RESULTS: GCA revealed that conditional knockdown of PfSWIB could interfere with the growth and development of P. falciparum.
+The parasitemia of PfSWIB∆ showed a significant decline at 96 h during in vitro culture compared with the PfSWIB and 3D7 lines (P < 0.0001).
+qPCR and RNA-seq analysis confirmed that depletion of PfSWIB not only silences upsA, upsC and partial upsB var genes, as well as removes the silencing of partial upsB var genes at the ring stage in PfSWIB∆ line, but also leads to aberrant expression of upsA and partial upsB/upsC var genes at the mature stage of P. falciparum, during a single 48-h life-cycle.
+CONCLUSIONS: We demonstrated that PfSWIB was involved in the process of clonal variation in var gene expression, and crucial for the survival and development of Plasmodium parasite.
+These findings could provide better understanding of the mechanism and function of PfSWIB contributing to the pathogenesis in malaria parasites.
+BACKGROUND: Obesity is a global epidemic, and it is widely known that increased Body mass index (BMI) is associated with alterations in respiratory mechanics.
+OBJECTIVE: To assess the safety and effectiveness of different ventilation strategies in obese patients undergoing bariatric surgery.
+METHODS: A systematic review of randomized clinical trials aimed at evaluating ventilation strategies for obese patients was carried out.
+CONCLUSION: There is some evidence that the alveolar recruitment maneuvers associated with PEEP lead to better oxygenation and higher compliance.
+There is no evidence of differences between pressure control ventilation (PCV) and Volume control ventilation (VCV).
+The International Symposium on Pneumococci and Pneumococcal Diseases (ISPPD) is the premier global scientific symposium dedicated to the exchange, advancement and dissemination of the latest research on the pneumococcus, one of the world’s deadliest bacterial pathogens.
+Since the first ISPPD was held in 1998, substantial progress has been made to control pneumococcal disease, for instance, more than half of surviving infants (78.6 million) from 143 countries now have access to the life-saving pneumococcal conjugate vaccine (PCV).
+The 11th ISPPD (ISPPD-11) was held in Melbourne, Australia in April 2018 and the proceedings of the symposium are captured in this report.
+Twenty years on from the first ISPPD, there remain many challenges and unanswered questions such as the continued disparity in disease incidence in Indigenous populations, the slow roll-out of PCV in some regions such as Asia, the persisting burden of disease in adults, serotype replacement and diagnosis of pneumococcal pneumonia.
+ISPPD-11 also put the spotlight on cutting-edge science including metagenomic, transcriptomic, microscopy, medical imaging and mathematical modelling approaches.
+ISPPD-11 was highly diverse, bringing together 1184 delegates from 86 countries, representing various fields including academia, primary healthcare, pharmaceuticals, biotechnology, policymakers and public health.
+In the era of the “sickest first” policy, patients with very high model for end-stage liver disease (MELD) scores have been increasingly admitted to the intensive care unit with the expectation that they will receive a liver transplant (LT) in the absence of improvement on supportive therapies.
+Such patients are often admitted in a context of acute-on-chronic liver failure with extrahepatic failures.
+Sequential assessment of scores or classification based on organ failures within the first days after admission help to stratify the risk of mortality in this population.
+Although the prognosis of severely ill cirrhotic patients has recently improved, transplant-free mortality remains high.
+Yet, the increased relative scarcity of graft resource must be considered alongside the increased risk of losing a graft in the initial postoperative period when performing LT in “too sick to transplant” patients.
+Consideration of a patient’s comorbidities and frailty is an appealing predictive approach in this population that has proven of great value in many other diseases.
+Using this expertise, data are accumulating on favourable post-LT outcomes in very high MELD populations, particularly when LT is performed in a situation of stabilization/improvement of organ failures in selected candidates.
+The absence of “definitive” contraindications and the control of “dynamic” contraindications allow a “transplantation window” to be defined.
+This window must be identified swiftly after admission given the poor short-term survival of patients with very high MELD scores.
+In the absence of any prospect of LT, withdrawal of care could be discussed to ensure respect of patient life, dignity and wishes.
+Hantaviruses (HVs) are rodent-transmitted viruses that can cause hantavirus cardiopulmonary syndrome (HCPS) in the Americas and hemorrhagic fever with renal syndrome (HFRS) in Eurasia.
+Together, these viruses have annually caused approximately 200,000 human infections worldwide in recent years, with a case fatality rate of 5–15% for HFRS and up to 40% for HCPS.
+Only whole virus inactivated vaccines against HTNV or SEOV are licensed for use in the Republic of Korea and China, but the protective efficacies of these vaccines are uncertain.
+In this review, we summarized the epidemiology, virology, and pathogenesis of four HFRS-causing viruses, HTNV, SEOV, PUUV, and DOBV, and two HCPS-causing viruses, ANDV and SNV, and then discussed the existing knowledge on vaccines and therapeutics against these diseases.
+We think that this information will shed light on the rational development of new vaccines and treatments.
+Given the magnitude of the school-aged child population, a sizeable proportion of influenza virus transmission events are expected to occur within school settings.
+However, influenza virus activity in schools is not well-understood, likely due to our limited ability to accurately monitor for respiratory viruses without disrupting the school environment.
+In this study, we evaluated the use of a bioaerosol sampling method to noninvasively detect and quantify airborne influenza A virus (IAV) densities in a public elementary school.
+Air samples were collected from multiple locations in the school, two days per week, throughout an eight-week sampling period during influenza season.
+Real-time RT-PCR targeting the IAV M gene revealed detectable IAV on five occasions in densities ranging from 2.0 × 10(−1) to 1.9 × 10(4).
+The majority of IAV-associated particles were ≤4 μm in diameter, and theoretical calculations indicate infectious thresholds after minutes of exposure.
+Our study represents the first identification and quantification of airborne influenza virus in an elementary school, and the results suggest that airborne IAV has the potential to circulate in schools during influenza season, in large enough doses known to cause infection.
+BACKGROUND: Human mesenchymal stem/stromal cells (hMSCs) represent a promising therapeutic strategy for ventilator-induced lung injury (VILI) and acute respiratory distress syndrome.
+Translational challenges include restoring hMSC efficacy following cryopreservation, developing effective xenogeneic-free (XF) hMSCs and establishing true therapeutic potential at a clinically relevant time point of administration.
+We wished to determine whether cytokine pre-activation of cryopreserved, bone marrow-derived XF-hMSCs would enhance their capacity to facilitate injury resolution following VILI and elucidate mechanisms of action.
+METHODS: Initially, in vitro studies examined the potential for the secretome from cytokine pre-activated XF-hMSCs to attenuate pulmonary epithelial injury induced by cyclic mechanical stretch.
+Later, anaesthetised rats underwent VILI and, 6 h following injury, were randomized to receive 1 × 10(7) XF-hMSC/kg that were (i) naive fresh, (ii) naive cryopreserved, (iii) cytokine pre-activated fresh or (iv) cytokine pre-activated cryopreserved, while control animals received (v) vehicle.
+Finally, the role of keratinocyte growth factor (KGF) in mediating the effect of pre-activated XF-hMSCs was determined in a pulmonary epithelial wound repair model.
+RESULTS: Pre-activation enhanced the capacity of the XF-hMSC secretome to decrease stretch-induced pulmonary epithelial inflammation and injury.
+Both pre-activated fresh and cryopreserved XF-hMSCs enhanced resolution of injury following VILI, restoring oxygenation, improving lung compliance, reducing lung leak and improving resolution of lung structural injury.
+Finally, the secretome of pre-activated XF-hMSCs enhanced epithelial wound repair, in part via a KGF-dependent mechanism.
+CONCLUSIONS: Cytokine pre-activation enhanced the capacity of cryopreserved, XF-hMSCs to promote injury resolution following VILI, potentially via a KGF-dependent mechanism.
+The Madin-Darby Canine Kidney (MDCK) cell line is widely used as epithelial cell model in studies ranging from viral infection to environmental pollutants, and vaccines production.
+However, little is known about basal expression of genes involved in innate immunity, and the ability to respond to infectious and non-infectious stressors.
+Therefore, the aims of our study were to evaluate the basal level of expression of pivotal genes in the innate immune response and cell cycle regulation, as well as to evaluate the ability of this cell line to respond to infectious or non-infectious stressors.
+As surmised in our working hypothesis, we demonstrated the constitutive expression of genes involved in the innate immune response and cell defense alike, including TLRs, Interleukins, Myd88, p65/NF-kB and p53.
+Moreover, we described the ability of this cell line to respond to LPS and cadmium (Cd2+) in terms of gene expression and cytokine release.
+These data confirm the possibility of using this cell line as a model in studies of host/pathogen interaction and response to non-infectious stressors.
+Deep learning (DL) is a subset of artificial intelligence (AI), which uses multilayer neural networks modelled after the mammalian visual cortex capable of synthesizing images in ways that will transform the field of glaucoma.
+Autonomous DL algorithms are capable of maximizing information embedded in digital fundus photographs and ocular coherence tomographs to outperform ophthalmologists in disease detection.
+Other unsupervised algorithms such as principal component analysis (axis learning) and archetypal analysis (corner learning) facilitate visual field interpretation and show great promise to detect functional glaucoma progression and differentiate it from non-glaucomatous changes when compared with conventional software packages.
+Forecasting tools such as the Kalman filter may revolutionize glaucoma management by accounting for a host of factors to set target intraocular pressure goals that preserve vision.
+Activation maps generated from DL algorithms that process glaucoma data have the potential to efficiently direct our attention to critical data elements embedded in high throughput data and enhance our understanding of the glaucomatous process.
+It is hoped that AI will realize more accurate assessment of the copious data encountered in glaucoma management, improving our understanding of the disease, preserving vision, and serving to enhance the deep bonds that patients develop with their treating physicians.
+Deliberate infection, however, creates challenging questions, particularly in low and middle-income countries (LMICs) where HIS are new and ethical challenges may be heightened.
+We examined stakeholder perceptions about the acceptability and ethics of HIS in Malawi, to inform decisions about planned pneumococcal challenge research and wider understanding of HIS ethics in LMICs.
+METHODS: We conducted 6 deliberative focus groups and 15 follow-up interviews with research staff, medical students, and community representatives from rural and urban Blantyre.
+We also conducted 5 key informant interviews with clinicians, ethics committee members, and district health government officials.
+RESULTS: Stakeholders perceived HIS research to have potential population health benefits, but they also had concerns, particularly related to the safety of volunteers and negative community reactions.
+Acceptability depended on a range of conditions related to procedures for voluntary and informed consent, inclusion criteria, medical care or support, compensation, regulation, and robust community engagement.
+These conditions largely mirror those in existing guidelines for HIS and biomedical research in LMICs.
+Stakeholder perceptions pointed to potential tensions, for example, balancing equity, safety, and relevance in inclusion criteria.
+CONCLUSIONS: Our findings suggest HIS research could be acceptable in Malawi, provided certain conditions are in place.
+Ongoing assessment of participant experiences and stakeholder perceptions will be required to strengthen HIS research during development and roll-out.
+The 2014–2015 highly pathogenic avian influenza (HPAI) H5NX outbreak represents the largest and most expensive HPAI outbreak in the United States to date.
+Despite extensive traditional and molecular epidemiological studies, factors associated with the spread of HPAI among midwestern poultry premises remain unclear.
+To better understand the dynamics of this outbreak, 182 full genome HPAI H5N2 sequences isolated from commercial layer chicken and turkey production premises were analyzed using evolutionary models able to accommodate epidemiological and geographic information.
+Epidemiological compartmental models embedded in a phylogenetic framework provided evidence that poultry type acted as a barrier to the transmission of virus among midwestern poultry farms.
+Furthermore, after initial introduction, the propagation of HPAI cases was self-sustainable within the commercial poultry industries.
+Discrete trait diffusion models indicated that within state viral transitions occurred more frequently than inter-state transitions.
+Distance and sample size were very strongly supported as associated with viral transition between county groups (Bayes Factor > 30.0).
+Together these findings indicate that the different types of midwestern poultry industries were not a single homogenous population, but rather, the outbreak was shaped by poultry industries and geographic factors.
+The purpose of this investigation was to identify the prevalence of hypoalbuminemia and obesity in orthopaedic trauma patients with high-energy injuries and to investigate their impact on the incidence of surgical site complications.
+Patients 18 years of age and older undergoing intramedullary nail fixation of their femoral shaft fractures at a university-based level-1 trauma centre were assessed.
+Malnutrition was measured using serum markers (albumin <3.5 g/dL) as well as body mass index (BMI) as a marker of obesity (BMI > 30 kg/m(2)).
+The overall incidence of wound complications in our study population was 9.65% (n = 25/259).
+A logistic regression model showed that non-obese patients (BMI < 30 kg/m(2)) were at significantly reduced risk for perioperative wound complications (Odds Ratio 0.400 [95% confidence interval 0.168, 0.954], p = 0.039).
+This study demonstrated a substantial prevalence of hypoalbuminemia and obesity among orthopaedic trauma patients with high-energy injuries.
+Future studies are required to further define malnutrition and its correlation with surgical site complications in orthopaedic trauma patients.
+Viral samples from 68 participants from 2016 through 2017 were sequenced and paired with epidemiological data.
+Phylogenetic and network inferences, drug resistant mutations (DRMs), subtypes and HIV-1 diversity estimations were completed.
+was seen in men who have sex with men, heterosexual, and male participants in DC.
+NGS allowed us to characterize the local phylodynamics of HIV-1 in DC more broadly and accurately, given a better representation of its diversity and dynamics.
+Reconstructed haplotypes provided novel and deeper phylodynamic insights, which led to networks linking a higher number of participants.
+Our understanding of the HIV-1 epidemic was expanded with the powerful coupling of HIV-1 NGS data with epidemiological data.
+The endoplasmic reticulum (ER) is the major organelle in the cell for protein folding and plays an important role in cellular functions.
+The unfolded protein response (UPR) is activated in response to misfolded or unfolded protein accumulation in the ER.
+In this review, we summarize the contribution of ER stress to the innate immune response to invading microorganisms and its role in the pathogenesis of infectious diseases.
+Since cancer stem cells (CSCs) were first identified in leukemia in 1994, they have been considered promising therapeutic targets for cancer therapy.
+These cells have self-renewal capacity and differentiation potential and contribute to multiple tumor malignancies, such as recurrence, metastasis, heterogeneity, multidrug resistance, and radiation resistance.
+The biological activities of CSCs are regulated by several pluripotent transcription factors, such as OCT4, Sox2, Nanog, KLF4, and MYC.
+In addition, many intracellular signaling pathways, such as Wnt, NF-κB (nuclear factor-κB), Notch, Hedgehog, JAK-STAT (Janus kinase/signal transducers and activators of transcription), PI3K/AKT/mTOR (phosphoinositide 3-kinase/AKT/mammalian target of rapamycin), TGF (transforming growth factor)/SMAD, and PPAR (peroxisome proliferator-activated receptor), as well as extracellular factors, such as vascular niches, hypoxia, tumor-associated macrophages, cancer-associated fibroblasts, cancer-associated mesenchymal stem cells, extracellular matrix, and exosomes, have been shown to be very important regulators of CSCs.
+Molecules, vaccines, antibodies, and CAR-T (chimeric antigen receptor T cell) cells have been developed to specifically target CSCs, and some of these factors are already undergoing clinical trials.
+This review summarizes the characterization and identification of CSCs, depicts major factors and pathways that regulate CSC development, and discusses potential targeted therapy for CSCs.
+OBJECTIVES: According to the World Health Organization, there have been frequent reports of Ebola virus disease (EVD) since the 2014 EVD pandemic in West Africa.
+We aim to estimate the outbreak scale when an EVD infected person arrives in Korea.
+METHODS: Western Africa EVD epidemic mathematical model SEIJR or SEIJQR was modified to create a Korean EVD outbreak model.
+The expected number of EVD patients and outbreak duration were calculated by stochastic simulation under the scenarios of Best case, Diagnosis delay, and Case missing.
+RESULTS: The 2,000 trials of stochastic simulation for each scenario demonstrated the following results: The possible median number of patients is 2 and the estimated maximum number is 11 when the government intervention is proceeded immediately right after the first EVD case is confirmed.
+With a 6-day delay in diagnosis of the first case, the median number of patients becomes 7, and the maximum, 20.
+If the first case is missed and the government intervention is not activated until 2 cases of secondary infection occur, the median number of patients is estimated at 15, and the maximum, at 35.
+CONCLUSIONS: Timely and rigorous diagnosis is important to reduce the spreading scale of infection when a new communicable disease is inflowed into Korea.
+Moreover, it is imperative to strengthen the local surveillance system and diagnostic protocols to avoid missing cases of secondary infection.
+About 30% of patients with impaired cardiac function have ventricular dyssynchrony and seek cardiac resynchronization therapy (CRT).
+In this study, we demonstrate synchronized biventricular (BiV) pacing in a leadless fashion by implementing miniaturized and wirelessly powered pacemakers.
+With their flexible form factors, two pacemakers were implanted epicardially on the right and left ventricles of a porcine model and were inductively powered at 13.56 MHz and 40.68 MHz industrial, scientific, and medical (ISM) bands, respectively.
+The power consumption of these pacemakers is reduced to µW-level by a novel integrated circuit design, which considerably extends the maximum operating distance.
+Leadless BiV pacing is demonstrated for the first time in both open-chest and closed-chest porcine settings.
+The clinical outcomes associated with different interventricular delays are verified through electrophysiologic and hemodynamic responses.
+The closed-chest pacing only requires the external source power of 0.3 W and 0.8 W at 13.56 MHz and 40.68 MHz, respectively, which leads to specific absorption rates (SARs) 2–3 orders of magnitude lower than the safety regulation limit.
+This work serves as a basis for future wirelessly powered leadless pacemakers that address various cardiac resynchronization challenges.
+Human influenza A viruses are known to be transmitted via the air from person to person.
+It is unknown from which anatomical site of the respiratory tract influenza A virus transmission occurs.
+Here, pairs of genetically tagged and untagged influenza A/H1N1, A/H3N2 and A/H5N1 viruses that are transmissible via the air are used to co-infect donor ferrets via the intranasal and intratracheal routes to cause an upper and lower respiratory tract infection, respectively.
+In all transmission cases, we observe that the viruses in the recipient ferrets are of the same genotype as the viruses inoculated intranasally, demonstrating that they are expelled from the upper respiratory tract of ferrets rather than from trachea or the lower airways.
+Moreover, influenza A viruses that are transmissible via the air preferentially infect ferret and human nasal respiratory epithelium.
+These results indicate that virus replication in the upper respiratory tract, the nasal respiratory epithelium in particular, of donors is a driver for transmission of influenza A viruses via the air.
+Bacterial infections continue to threaten humankind and the rapid spread of antibiotic resistant bacteria is alarming.
+Current antibiotics target essential bacterial processes and thereby apply a strong selective pressure on pathogenic and non-pathogenic bacteria alike.
+One alternative strategy is to block bacterial virulence systems that are essential for the ability to cause disease but not for general bacterial viability.
+We have previously show that the plant natural product (-)-hopeaphenol blocks the type III secretion system (T3SS) in the Gram-negative pathogens Yersinia pseudotuberculosis and Pseudomonas aeruginosa.
+(-)-Hopeaphenol is a resveratrol tetramer and in the present study we explore various resveratrol dimers, including partial structures of (-)-hopeaphenol, as T3SS inhibitors.
+To allow rapid and efficient assessment of T3SS inhibition in P. aeruginosa, we developed a new screening method by using a green fluorescent protein reporter under the control of the ExoS promoter.
+Using a panel of assays we showed that compounds with a benzofuran core structure i.e.
+viniferifuran, dehydroampelopsin B, anigopreissin A, dehydro-δ-viniferin and resveratrol-piceatannol hybrid displayed significant to moderate activities towards the T3SS in Y. pseudotuberculosis and P. aeruginosa.
+Influenza A group 1 HA stem-nanoparticles have been demonstrated to confer heterosubtypic protection in animals; however, the protection does not extend to group 2 viruses, due in part to differences in glycosylation between group 1 and 2 stems.
+Here, we show that introducing the group 2 glycan at Asn38(HA1) to a group 1 stem-nanoparticle (gN38 variant) based on A/New Caledonia/20/99 (H1N1) broadens antibody responses to cross-react with group 2 HAs.
+Immunoglobulins elicited by the gN38 variant provide complete protection against group 2 H7N9 virus infection, while the variant loses protection against a group 1 H5N1 virus.
+The N38(HA1) glycan thus is pivotal in directing antibody responses by controlling access to group-determining stem epitopes.
+Precise targeting of stem-directed antibody responses to the site of vulnerability by glycan repositioning may be a step towards achieving cross-group influenza protection.
+BACKGROUND: Ventilator-associated pneumonia (VAP) is a significant cause of mortality in the intensive care unit.
+The invention of electronic sensors has been applied to analyze the volatile organic compounds in breath to detect VAP using a machine learning technique.
+However, the process of building an algorithm is usually unclear and prevents physicians from applying the artificial intelligence technique in clinical practice.
+The objective of this study was to develop a breath test for VAP with a standardized protocol for a machine learning technique.
+This study enrolled subjects in an intensive care unit of a hospital in southern Taiwan from February 2017 to June 2019.
+We recruited patients with VAP as the case group and ventilated patients without pneumonia as the control group.
+We collected exhaled breath and analyzed the electric resistance changes of 32 sensor arrays of an electronic nose.
+We split the data into a set for training algorithms and a set for testing.
+We applied eight machine learning algorithms to build prediction models, improving model performance and providing an estimated diagnostic accuracy.
+RESULTS: A total of 33 cases and 26 controls were used in the final analysis.
+Using eight machine learning algorithms, the mean accuracy in the testing set was 0.81 ± 0.04, the sensitivity was 0.79 ± 0.08, the specificity was 0.83 ± 0.00, the positive predictive value was 0.85 ± 0.02, the negative predictive value was 0.77 ± 0.06, and the area under the receiver operator characteristic curves was 0.85 ± 0.04.
+The mean kappa value in the testing set was 0.62 ± 0.08, which suggested good agreement.
+CONCLUSIONS: There was good accuracy in detecting VAP by sensor array and machine learning techniques.
+BACKGROUND: Our recent meta-analysis indicated that vitamin C may shorten the length of ICU stay and the duration of mechanical ventilation.
+Here we analyze modification of the vitamin C effect on ventilation time, by the control group ventilation time (which we used as a proxy for severity of disease in the patients of each trial).
+METHODS: We searched MEDLINE, Scopus, and the Cochrane Central Register of Controlled Trials and reference lists of relevant publications.
+We included controlled trials in which the administration of vitamin C was the only difference between the study groups.
+We did not limit our search to randomized trials and did not require placebo control.
+One author extracted study characteristics and outcomes from the trial reports and entered the data in a spreadsheet.
+We used meta-regression to examine whether the vitamin C effect on ventilation time depends on the duration of ventilation in the control group.
+RESULTS: We identified nine potentially eligible trials, eight of which were included in the meta-analysis.
+We pooled the results of the eight trials, including 685 patients in total, and found that vitamin C shortened the length of mechanical ventilation on average by 14% (P = 0.00001).
+Vitamin C was most beneficial for patients with the longest ventilation, corresponding to the most severely ill patients.
+In five trials including 471 patients requiring ventilation for over 10 h, a dosage of 1–6 g/day of vitamin C shortened ventilation time on average by 25% (P < 0.0001).
+CONCLUSIONS: We found strong evidence that vitamin C shortens the duration of mechanical ventilation, but the magnitude of the effect seems to depend on the duration of ventilation in the untreated control group.
+BACKGROUND: Previous scoring models such as the Acute Physiologic Assessment and Chronic Health Evaluation II (APACHE II) and the Sequential Organ Failure Assessment (SOFA) scoring systems do not adequately predict mortality of patients undergoing continuous renal replacement therapy (CRRT) for severe acute kidney injury.
+Accordingly, the present study applies machine learning algorithms to improve prediction accuracy for this patient subset.
+METHODS: We randomly divided a total of 1571 adult patients who started CRRT for acute kidney injury into training (70%, n = 1094) and test (30%, n = 477) sets.
+The primary output consisted of the probability of mortality during admission to the intensive care unit (ICU) or hospital.
+We compared the area under the receiver operating characteristic curves (AUCs) of several machine learning algorithms with that of the APACHE II, SOFA, and the new abbreviated mortality scoring system for acute kidney injury with CRRT (MOSAIC model) results.
+RESULTS: For the ICU mortality, the random forest model showed the highest AUC (0.784 [0.744–0.825]), and the artificial neural network and extreme gradient boost models demonstrated the next best results (0.776 [0.735–0.818]).
+The AUC of the random forest model was higher than 0.611 (0.583–0.640), 0.677 (0.651–0.703), and 0.722 (0.677–0.767), as achieved by APACHE II, SOFA, and MOSAIC, respectively.
+The machine learning models also predicted in-hospital mortality better than APACHE II, SOFA, and MOSAIC.
+CONCLUSION: Machine learning algorithms increase the accuracy of mortality prediction for patients undergoing CRRT for acute kidney injury compared with previous scoring models.
+BACKGROUND: High glycemic variability (GV) is common in critically ill patients; however, the prevalence and mortality association with early GV in patients with sepsis remains unclear.
+METHODS: This retrospective cohort study was conducted in a medical intensive care unit (ICU) in central Taiwan.
+Patients in the ICU with sepsis between January 2014 and December 2015 were included for analysis.
+All of these patients received protocol-based management, including blood sugar monitoring every 2 h for the first 24 h of ICU admission.
+Mean amplitude of glycemic excursions (MAGE) and coefficient of variation (CoV) were used to assess GV.
+RESULTS: A total of 452 patients (mean age 71.4 ± 14.7 years; 76.7% men) were enrolled for analysis.
+They were divided into high GV (43.4%, 196/452) and low GV (56.6%, 256/512) groups using MAGE 65 mg/dL as the cut-off point.
+Patients with high GV tended to have higher HbA1c (6.7 ± 1.8% vs. 5.9 ± 0.9%, p < 0.01) and were more likely to have diabetes mellitus (DM) (50.0% vs. 23.4%, p < 0.01) compared with those in the low GV group.
+Kaplan–Meier analysis showed that a high GV was associated with increased 30-day mortality (log-rank test, p = 0.018).
+The association remained strong in the non-DM (log-rank test, p = 0.035), but not in the DM (log-rank test, p = 0.254) group.
+Multivariate Cox proportional hazard regression analysis identified that high APACHE II score (adjusted hazard ratio (aHR) 1.045, 95% confidence interval (CI) 1.013–1.078), high serum lactate level at 0 h (aHR 1.009, 95% CI 1.003–1.014), having chronic airway disease (aHR 0.478, 95% CI 0.302–0.756), high mean day 1 glucose (aHR 1.008, 95% CI 1.000–1.016), and high MAGE (aHR 1.607, 95% CI 1.008–2.563) were independently associated with increased 30-day mortality.
+CONCLUSIONS: We found that approximately 40% of the septic patients had a high early GV, defined as MAGE > 65 mg/dL.
+Higher GV within 24 h of ICU admission was independently associated with increased 30-day mortality.
+These findings highlight the need to monitor GV in septic patients early during an ICU admission.
+BACKGROUND: The risk factors for multi-drug resistant infection (MDRI) in the pediatric intensive care unit (PICU) remain unclear.
+It’s necessary to evaluate the epidemiological characteristics and risk factors for MDRI in PICU, to provide insights into the prophylaxis of MDRI clinically.
+METHODS: Clinical data of 79 PICU children with MDRI were identified, and 80 children in PICU without MDRI in the same period were selected as control group.
+The related children’s characteristics, clinical care, microbiologic data, treatments provided, and outcomes of the patients with were reviewed and collected.
+Univariate and multivariate logistic regression analyses were performed to identify the potential risks of MDRI in PICU.
+RESULTS: Of the diagnosed 79 cases of MDRI, there were28 cases of CR-AB, 24 cases of MRSA, 22 cases of PDR-PA,3 cases of VRE and 2 cases of CRE respectively.
+Univariate analyses indicated that the length of PICU stay, the duration of mechanical ventilation > 5 days, parenteral nutrition, coma, urinary catheter indwelling, invasive operation, 2 or more antibiotics use were associated with MDRIs (all p < 0.05); The logistic multiple regression analyses indicated that coma, parenteral nutrition, 2 or more antibiotics use and the duration of mechanical ventilation > 5 days were independent risk factors associated with MDRI (all p < 0.05).
+CONCLUSIONS: This present study has identified several potentially modifiable risk factors for MDRI in PICU, it’s conducive to take appropriate measures targeting risk factors of MDRI for health care providers to reduce MDRI.
+Ricin toxin is a plant‐derived, ribosome‐inactivating protein that is rapidly cleared from circulation by Kupffer cells (KCs) and liver sinusoidal endothelial cells (LSECs)—with fatal consequences.
+Rather than being inactivated, ricin evades normal degradative pathways and kills both KCs and LSECs with remarkable efficiency.
+Uptake of ricin by these 2 specialized cell types in the liver occurs by 2 parallel routes: a “lactose‐sensitive” pathway mediated by ricin's galactose/N‐acetylgalactosamine‐specific lectin subunit (RTB), and a “mannose‐sensitive” pathway mediated by the mannose receptor (MR; CD206) or other C‐type lectins capable of recognizing the mannose‐side chains displayed on ricin's A (RTA) and B subunits.
+In this report, we investigated the capacity of a collection of ricin‐specific mouse MAb and camelid single‐domain (V(H)H) antibodies to protect KCs and LSECs from ricin‐induced killing.
+In the case of KCs, individual MAbs against RTA or RTB afforded near complete protection against ricin in ex vivo and in vivo challenge studies.
+In contrast, individual MAbs or V(H)Hs afforded little (<40%) or even no protection to LSECs against ricin‐induced death.
+Complete protection of LSECs was only achieved with MAb or V(H)H cocktails, with the most effective mixtures targeting RTA and RTB simultaneously.
+Although the exact mechanisms of protection of LSECs remain unknown, evidence indicates that the Ab cocktails exert their effects on the mannose‐sensitive uptake pathway without the need for Fcγ receptor involvement.
+In addition to advancing our understanding of how toxins and small immune complexes are processed by KCs and LSECs, our study has important implications for the development of Ab‐based therapies designed to prevent or treat ricin exposure should the toxin be weaponized.
+The ability to preserve metabolically active livers ex vivo for 1 week or more could allow repair of poor-quality livers that would otherwise be declined for transplantation.
+Current approaches for normothermic perfusion can preserve human livers for only 24 h. Here we report a liver perfusion machine that integrates multiple core physiological functions, including automated management of glucose levels and oxygenation, waste-product removal and hematocrit control.
+Study of multiple ex vivo parameters and early phase reperfusion in vivo demonstrated the viability of pig livers perfused for 1 week without the need for additional blood products or perfusate exchange.
+We tested the approach on ten injured human livers that had been declined for transplantation by all European centers.
+After a 7-d perfusion, six of the human livers showed preserved function as indicated by bile production, synthesis of coagulation factors, maintained cellular energy (ATP) and intact liver structure.
+Studies reporting chest images of respiratory syncytial virus (RSV)-induced lower respiratory tract infection (LRTI) in an outbreak setting and their relationship to the clinical manifestation are limited.
+During a genetically confirmed RSV outbreak, eight patients underwent both chest X-ray and computed tomography (CT).
+Among these, 5 cases had newly appearing abnormalities on CT, although chest X-ray was able to detect abnormalities in only 2 cases (40%).
+Although bronchial wall thickening was common, other findings and their distribution were variable, even in an outbreak setting.
+All patients with both a history of anticancer chemotherapy against hematological cancer and lower respiratory symptoms, such as wheezing, sputum, and hypoxemia, had abnormalities on CT, suggesting that these two factors might be important for predicting the existence of LRTI in RSV-infected patients.
+Although combination antiretroviral therapy (cART) has improved the health of millions of those living with HIV-1 (Human Immunodeficiency Virus, Type 1), the penetration into the central nervous system (CNS) of many such therapies is limited, thereby resulting in residual neurocognitive impairment commonly referred to as NeuroHIV.
+Additionally, while cART has successfully suppressed peripheral viremia, cytotoxicity associated with the presence of viral Transactivator of transcription (Tat) protein in tissues such as the brain, remains a significant concern.
+Our previous study has demonstrated that both HIV-1 Tat as well as opiates such as morphine, can directly induce synaptic alterations via independent pathways.
+Herein, we demonstrate that exposure of astrocytes to HIV-1 protein Tat mediates the induction and release of extracellular vesicle (EV) microRNA-7 (miR-7) that is taken up by neurons, leading in turn, to downregulation of neuronal neuroligin 2 (NLGN2) and ultimately to synaptic alterations.
+More importantly, we report that these impairments could be reversed by pretreatment of neurons with a neurotrophic factor platelet-derived growth factor-CC (PDGF-CC).
+Pharyngitis is usually caused by a viral infection for which antibiotics are often unnecessarily prescribed, adding to the burden of antimicrobial resistance.
+Identifying who needs antibiotics is challenging; microbiological confirmation and clinical scores are used but have limitations.
+In a cross-sectional study nested within a randomized controlled trial, we estimated the prevalence and antibiotic susceptibility profiles of group A Streptococcus (GAS) in patients presenting to primary care with a sore throat and fever in northern Thailand.
+We then evaluated the use of C-reactive protein (CRP) and clinical scores (Centor and FeverPAIN) to identify the presence of GAS.
+One hundred sixty-nine patients were enrolled, of whom 35 (20.7%) had β-hemolytic Streptococci (BHS) isolated from throat swab culture, and 11 (6.5%) had GAS.
+All GAS isolates were sensitive to penicillin G. The median CRP of those without BHS isolation was 10 mg/L (interquartile range [IQR] ≤ 8–18), compared with 18 mg/L (IQR 9–71, P = 0.0302) for those with GAS and 14 mg/L (IQR ≤ 8–38, P = 0.0516) for those with any BHS isolated.
+However, there were no significant relationships between CRP > 8 mg/L (P = 0.112), Centor ≥ 3 (P = 0.212), and FeverPAIN ≥ 4 (P = 1.000), and the diagnosis of GAS compared with no BHS isolation.
+Targeted CRP testing through clinical scoring may be the most cost-effective approach to ruling out GAS infection.
+The activation of somatic mutations conferring sensitivity to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors has been widely used in the development of advanced or metastatic primary lung cancer therapy.
+In the present study, a loop-mediated isothermal amplification (LAMP) method was used to identify EGFR mutations, and its efficiency was compared with the Therascreen quantitative PCR assay.
+Using LAMP and Therascreen to analyze surgically resected tissue samples from patients with pulmonary adenocarcinoma, EGFR mutations were observed in 32/59 tumor samples (LAMP) and 33/59 tumor samples (Therascreen).
+Notably, the LAMP assay identified one tumor as wild-type, which had previously been identified as a deletion mutation in exon 19 via the Therascreen assay (Case X).
+However, the direct sequencing to confirm the EGFR status of the Case X adhered to the results of the LAMP assay.
+Further experiments using Case X DNA identified this exon 19 deletion mutation using both methods.
+Overall, the present study shows that the LAMP method may serve as a valuable alternative for the identification oncogene mutations.
+Gene transcription profiles across tissues are largely defined by the activity of regulatory elements, most of which correspond to regions of accessible chromatin.
+Regulatory element activity is in turn modulated by genetic variation, resulting in variable transcription rates across individuals.
+Here we characterize expression and chromatin state dynamics across three tissues—liver, lung, and kidney—in 47 strains of the Collaborative Cross (CC) mouse population, examining the regulation of these dynamics by expression quantitative trait loci (eQTL) and chromatin QTL (cQTL).
+QTL whose allelic effects were consistent across tissues were detected for 1,101 genes and 133 chromatin regions.
+Also detected were eQTL and cQTL whose allelic effects differed across tissues, including local-eQTL for Pik3c2g detected in all three tissues but with distinct allelic effects.
+Leveraging overlapping measurements of gene expression and chromatin accessibility on the same mice from multiple tissues, we used mediation analysis to identify chromatin and gene expression intermediates of eQTL effects.
+Based on QTL and mediation analyses over multiple tissues, we propose a causal model for the distal genetic regulation of Akr1e1, a gene involved in glycogen metabolism, through the zinc finger transcription factor Zfp985 and chromatin intermediates.
+This analysis demonstrates the complexity of transcriptional and chromatin dynamics and their regulation over multiple tissues, as well as the value of the CC and related genetic resource populations for identifying specific regulatory mechanisms within cells and tissues.
+Temperate phages are considered as natural vectors for gene transmission among bacteria due to the ability to integrate their genomes into a host chromosome, therefore, affect the fitness and phenotype of host bacteria.
+Many virulence genes of pathogenic bacteria were identified in temperate phage genomes, supporting the concept that temperate phages play important roles in increasing the bacterial pathogenicity through delivery of the virulence genes.
+However, little is known about the roles of temperate phages in attenuation of bacterial virulence.
+Here, we report a novel Bordetella bronchiseptica temperate phage, vB_BbrS_PHB09 (PHB09), which has a 42,129-bp dsDNA genome with a G+C content of 62.8%.
+Phylogenetic analysis based on large terminase subunit indicated that phage PHB09 represented a new member of the family Siphoviridae.
+The integration site of PHB09 is specifically located within a pilin gene of B. bronchiseptica.
+Importantly, we found that the integration of phage PHB09 significantly decreased the virulence of parental strain B. bronchiseptica Bb01 in mice, most likely through disruption the expression of pilin gene.
+Moreover, a single shot of the prophage bearing B. bronchiseptica strain completely protected mice against lethal challenge with wild-type virulent B. bronchiseptica, indicating the vaccine potential of lysogenized strain.
+Our findings not only indicate the complicated roles of temperate phages in bacterial virulence other than simple delivery of virulent genes but also provide a potential strategy for developing bacterial vaccines.
+Down syndrome (DS) is frequently comorbid with congenital heart disease and has recently been shown to reduce the sedative effect of benzodiazepine (BDZ)-class anesthesia but this effect in a clinical setting has not been studied.
+We retrospectively reviewed patient records in our pediatric intensive care unit (PICU) of pediatric cardiovascular operations between March 2015 and March 2018.
+DS patients had a high probability of receiving a higher midazolam dosage and dexmedetomidine dosage over the study period (probability = 0.99, probability = 0.97) while depth of sedation was not different in DS patients (probability = 0.35).
+Multi regression modeling included severity scores and demographic data showed DS decreases midazolam sedation compared with controls (posterior OR = 1.32, 95% CrI = 1.01–1.75).
+In conclusion, midazolam dosages should be carefully adjusted as DS significantly decreases midazolam sedative effect in pediatric heart surgery patients.
+recombination
+E-value
+522
+power of 2
+March 11, 2009
+polio incidence
+188
+community information
+Forty-three
+Supplementary File 1
+additional analyses
+DI-R reverse primer
+Animal Center of Guangzhou Medical University
+EBER2
+modern mass spectrometry
+protein expression
+Mucins
+MMLV reverse transcriptase enzyme
+15
+nuclear export of unspliced and partially spliced mRNAs
+PBMC
+fever
+Data points representing non-symptomatic animals
+2.0
+TNF-α
+Swab sampling and experiments
+IFN-β promoter activation
+RSM
+1, 6, 10 and 14 weeks
+labeled cell bodies
+Modification indices
+7.6%
+align nucleotide sequences exclusively
+0.9% NaCl
+y
+changes in γ
+Weiskopf et al.
+Agilent SurePrint
+SDS-PAGE
+QI
+76%
+2006
+Constitutive immune processes
+2
+multiple cardiovascular diseases
+airway
+Balkan endemic nephropathy
+169
+fever, respiratory distress and neurological disorders
+reactive oxygen species
+EBV transformation
+between 6 weeks to 2 months
+Thermo Scientific Multiscan EX
+vaccine developments
+hsa-miR-106b and miR-93 108
+29
+HP-PRRSV and PRRSV
+a designed change of the potential NXS/T motif
+regression analysis
+annotated red boxes or ellipses
+α1 CD2 domain
+Bikaner
+4uC
+pMK117
+NS5B
+No obvious cytotoxicity
+80 mM dynasore
+38
+constrains the walk path
+Liver cirrhosis
+ssDNA PI
+Bats
+Cerebral malaria
+30
+5 × 10 4 per well
+Epidemiological
+Fast Start Universal SYBR Green Master
+C. pneumoniae
+Peptide-coated, mature DCs
+4.67 pmol mL −1
+new and re-emerging viruses
+needle exchange services
+digestive enzymes
+properly addressed proteins to cell compartments
+anticodon
+decision-making
+suilysin
+Twenty-seven
+both sense and respond to the volume of proteins trafficking through the system
+ImageJ
+age, gender, risk factors, and secondary infection
+move
+Tcf4
+cooperation between TLR2 and TRIF
+human monoclonal antibodies
+resident memory T cells
+11-month
+1 week
+E3
+multiple cross-species transmissions from sooty mangabeys
+inhibitory cellular responses
+Bright red
+inhibits
+5780 cells/μL
+a contact is considered broken
+when it adsorbs to a host cell
+delivery of Cas RNP
+binding sites
+18
+NLRP3 inflammasome activation
+6
+realist reviews
+23 602
+RLU values
+Elevation
+cleaning behavior
+V2-apex
+28
+adjuvants
+genomic RNA hetero-and homo-dimers
+automated geocoding software packages
+Small red squares
+bacterial enteritis
+67%
+the least stable genes
+33
+0.95
+genes for glycoside hydrolase and PTS
+42
+Pisum
+non-survivors
+AMA1-specific and/or non-AMA1 IgGs
+RNA sequencing
+Isotype antibodies
+aseptic techniques
+SR
+Oral informed consent
+inhibits translation
+Countries' population, gross domestic product and income
+3D
+8
+rifampicin
+reticuloendothelial cells
+systemic heme metabolism
+Three
+Hispanic
+GFP-L
+immunodominant
+Gag processing
+Student's t-test
+dysregulation of immunity
+changes in phase
+GenePix Pro 7.2
+20 min
+57.9 years
+Fisher exact tests
+ZEN
+slowing of the normal fork speed
+graphML
+2009
+New York
+three
+Mantel-Cox test
+16 h
+Deprotonation of the His37 tetrad
+SIgA
+the secondary structure of neither the 3 0 nor the 5 0 DB
+five
+treatment and prevention failures
+Large numbers of persons who are not at-risk but who are concerned
+Environmental samples
+A random forest
+IgA2
+Proteomes
+limitations of the methods used
+44 × 42 × 40 mm
+antiviral
+Oct-4 siRNAtreated LC-CD133 +
+Phellodendron phosphor
+0.1-0.3 lM
+further studies
+20
+influenza
+VRC 500
+CD4 + T cells
+Environmental effects
+unmodified uridine
+geographical
+Twenty-eight days
+Lactoperoxidase
+21/3/2020
+neutrophil oxidative burst capacity
+non-parametric
+a non corneal pathogen
+an age-structured population and multiple strains with cross-immunity
+2.2 kJ/mol
+engineered
+Twentyfour hours
+Victoria
+RNeasy Mini Kit
+T-cellmediated adaptive immune responses
+bone marrow neutrophil stimulation and mobilization pathways
+acidification
+2 or 7 days
+35 min
+Frequent control
+between 1 and 7 days
+13AE3%
+BW
+IL-22
+120 hours
+immunosuppression
+57
+formalin inactivation step
+10%
+STAT3
+suspended replicates which were not sequenced
+haemagglutinin and the neuraminidase
+7-8 ml/kg
+dopamine theory
+FDR of 0.1
+Syncytium formation
+TNF protein
+Enolase
+severe outcome
+protein transport
+ECL Western Blotting Detection Reagents
+atelectasis, pleural effusion or acute pulmonary embolism
+∩ ξ P S
+three
+endotheliochorial
+control RNA molecule
+ChAdOx1 Zika
+100%
+30%-65%
+3/9 bats
+DF-1 cell line
+rRNA
+closely-related viruses
+multiple-host FMDV
+Stem 1
+N = 12
+inflammasomes
+renal function test, urinary output or vasoactive drugs requirements
+genetic diversity
+coma
+80%
+VaxiJen V2.0 server
+handwashing
+295
+Modification indices
+tubulin polymerization and stabilization
+Fuhyohigai
+A threshold of 13 %
+a 9mer peptide-epitope
+244
+autophagic death
+4
+Γ νβ
+pediatric
+During the day
+22 days
+reduced
+liposome co-floatation assay
+3 days
+rituximab
+prokaryotes
+21
+Obtaining singlespecies genomes from culture
+1 ml of each reaction
+1 × 10 6 cells
+Autophagy
+persistent infections
+21 days
+0.4μg/kg/min
+chemical kindling
+an MOI of 1
+automated sequencing machines
+contacts with adults who are too sick to attend such mass gathering events
+10-fold
+amino acid composition
+IFITM1, 2 and 3
+Bryopsis plumosa and Caulerpa prolifera
+30 %
+significant associations at P < 0.05
+A, B and C
+point-of-care
+t 0
+the results with and without ChaseABC
+Seven weeks
+E. coli strain SM10 λpir
+9 cm H 2 O
+revert the up-regulation of PD-L1 by BCG
+monocytes
+mental health material
+David Delo Research Grant
+QGR and QGG
+Supplementary Data
+SARS-CoV
+continuous variables that followed a normal distribution
+three
+75
+essential
+traditional cardiovascular risk factors or the male-related phenotypes
+dehydration or catabolism of muscle protein
+fulminant
+proinflammatory
+phylodynamic modeling
+blast injury
+20
+30%
+inevitable
+Twenty
+conserved regulators related to high and low viral pathogenicity
+viral DNA content
+lack of financial means
+four
+10.1186/s12985-015-0439-5
+AlamarBlue reagent
+autophagosome
+Plasma BUN and Cre
+60 mbar
+haemagglutination
+more than 3
+IL-10-like
+BAL fluid
+E
+4,885
+encephalomyocarditis virus
+RSV-specific qPCR assay
+Translabel metabolic reagent
+peptide hits
+intentions
+GATA2-mediated relative luciferase activity
+MRPL19
+National interest
+7
+maxillofacial
+36%
+Siderophores
+1 week
+L. calcarifer
+major histocompatibility complex
+10-20%
+maximizing the number of mixed
+Eleven
+C57BL/6
+491
+Student t test
+p-198A
+meeting IHR obligations with regard to points of entry
+Cryptosporidiosis
+just over one third
+80
+two-fold
+22.7%
+catabolism pathway
+expensive equipments, considerable skills and high costs
+surviving
+antidepressants
+open doors, open windows and AC systems
+influenzal infection in ferrets
+5 min
+gel loading dye
+carrageenan and Zanamivir
+ribosome
+U18666A
+Novel influenza vaccine designs
+10% PBS-buffered formalin
+Vif-SIVsmE041 degradation
+Th2 cytokine production
+Figure 3
+1 hour
+~200,000
+OATP1B3 surface protein levels
+whether the identified organisms belonged
+p * class of models
+Thailand
+The current management and treatment of COPD exacerbations
+closed communities
+HAART
+four
+IFRD1
+BHK cells
+The development of antibodies
+supernatant and cellular lysates
+Collagen remodeling
+American Thoracic Society
+pre-epidemic warnings
+healthcare-related costs
+0.037
+Fig 6
+fragility
+The PM
+three
+deformation of the cell from cell-substrate and cell-cell interactions
+enhancement
+other provinces of China
+49
+Nested logistic regression models or ROC curves
+longer
+abuse and violence
+amplifying a fragment of 1,740 bp
+TNF-α
+novel mechanisms of APC assembly and regulation
+IL-6
+Staufen1
+Four
+Pseudotype or recombinant VSV
+Ebola virus
+1811
+APACHE II
+purely expressive
+communicable diseases
+2 minutes
+195
+canonical
+α=0.05
+confirmed bacterial, viral or probable bacterial or viral
+RanBP10
+severe hypoxemia burden
+ROS
+to ensure reproducibility
+IBV
+Derek Wanless
+naturally processed foreign peptides
+the cell body
+Spring Festival migration
+elastase
+FRBs
+duration of mechanical ventilation
+vancomycin and daptomycin
+Monoclonal antibody 4G2
+4
+miRBase
+elevated levels of DNA synthesis
+allergic models and Th 2 cytokine models
+HA challenged cells
+serum antibody response
+7 days
+eft-2
+Fifty-two
+Logistic regression models
+32%
+29
+300 µl of receptor-destroying enzyme
+30% to 37%
+38%
+20.2 kg/m 2
+50%
+LIGPLOT
+10d
+mortality
+8 hours or longer
+8.5-10 million
+expression of various ISGs
+recombination
+template switching
+R i
+personal hygiene practices and health behaviors
+10
+ICD taxonomy does not adequately incorporate phenotype similarity knowledge into disease category structures
+protection against ocular inflammation
+518,313
+lower than limits
+the translocon
+influenza virus NP
+MEM inoculated tissue or cells
+40
+Two weeks
+six
+Protein phylogeny
+SHH
+Pathogen Associated Molecular Patterns
+macrophages
+Allergic symptoms
+June
+The identification of putative LIR motifs
+Bootstrap values
+reactions become unreliable
+general mental health or psychological distress
+Adjusting N c for background nucleotide composition
+atypical
+3A5
+39,642
+NS1-1, -32 and -34
+vegetation related land cover
+Frameshifting
+increased
+5 days
+endosomes
+FIND
+TCR γδ and NKG2D
+Heat and dehydration
+internal mismatches or on unique stretches of nucleotides
+centrifugation
+previous reports
+six
+multiple bilateral lobar or segment consolidation
+1.89
+25
+empty-vector DNA transfected into the effector cells
+protective antibodies
+TNF-α KO mice
+Variola major virus
+keyword searching
+mutations in additional p53 exons
+RNA integrity
+Viral production of all of the mutant versions
+motor strength and control
+Assay standardization commitments
+KUNJ, DENV and TAQ
+between individual vesicles
+4,000
+variable ventilation
+defensive microbes
+24-hour
+Vehicles for ocular gene therapy
+better chance of HCV clearance
+age
+HEM-primed PMNs
+EW 9
+more explicit control over the demographic processes regulating birth and death rates
+Interaction surface area
+five
+depopulation
+being a member of a household with a confirmed case
+21%
+Annexin A2
+100%
+10
+means to those ends
+improve nurses' job satisfaction and nursing service quality
+lower fusogenicity and decreased F activation
+117
+Initial bacterial inoculum
+RT-qPCR and ELISA
+Denaturing PAGE
+electron microscope
+virus dissemination
+implicit solvent model
+Individual variation in host infectivity
+methicillin
+Asterisks
+0.025%
+antiviral and hospitalization administration
+cc-by
+functional IFN-c polymorphisms
+gRSV-FR-GC>Us
+19
+p239
+overall protein content
+0.039 ng/mL
+Valent et al.
+five
+5%
+Correlates
+5 minutes
+intravenous immune globulins
+the previously published literature
+21
+Markovian models
+2005
+just before and 1 h post immunization
+preventing AEs
+Western blot analysis
+four
+twice weekly
+RV
+diaminobenzidine
+neurodegenerative
+IFN-α
+Flock house virus
+encoding the specific tumor antigen
+RNA6
+Ct9
+three
+Me2NH·BH3
+PPARα
+oseltamivirresistance
+Gaolan
+rupintrivir and pleconaril
+transmission uncertainty would be even more extreme
+weekly
+acidic organelles
+A 1 and A 2
+PMO production
+mice
+47
+50%
+15,014
+5 days
+Five
+Data
+continued viral growth and potentially persistent infection in mosquito cells
+fluorescence
+root mean square deviation
+19
+28 years
+the gene TSS
+USP7
+obtaining specimens prior to the administration of antimicrobials
+BB-N and S1-N
+100 weeks
+five
+emergency verbal assent
+A f i
+Identify, develop and evaluate effective behavioral interventions and strategies
+Increased mobility
+C. difficile Spo0A
+Smith-Waterman alignment scores
+all life stages of the virus
+30
+C9
+African A and O surface proteins
+viscoelastic properties
+One hundred twenty-five
+enhanced viral burden and cytokine expression
+10%
+regression and stochastic
+24 h
+small blood vessels
+classification models
+multidrugresistant tuberculosis
+polyProArg, polyGlyPro and polyProAla
+10 9 copies to 1 copy of plasmidswasused
+viral RNAs
+cell line-dependent
+specific for the transmembrane region of the envelope gene
+larger validation studies
+peptidylprolyl isomerase B mRNA
+hyper-phosphorylation of Rb
+ELISA
+5 min
+several billion
+severe thrombocytopaenia
+Zeiss Axio Imager A1 fluorescence microscopy
+thrombin and strep-His8
+BST2
+Polymerase chain reaction
+Throat-swab specimens
+their sequences hold the target molecular address
+positive for H1N1 influenza infection
+bluetongue virus
+SNP at position +166
+immortalization
+TRAF3
+good correlativity with the HI test
+cardiovascular and renal functions
+five
+n MS
+IAV
+a larger stockpile
+genes
+SA linkages and their respective distribution in the human airways
+how to balance openness and avoiding concern
+SNARES
+furin/PCSK3
+RNA
+1.8 µH
+80
+36 hours
+SVV infection
+uncontrolled DENV replication
+pCAGGS vector
+Five
+extracellular stimuli
+PTSD
+protective
+HBV persistence
+34
+RNases
+pcDNA3.1-ROP18-flag
+real media coverage data
+confirm the diagnosis
+PCR product
+PTC-124
+fingolimod and cladribine
+chemiluminescence
+mouse phenotypes
+three
+Inhibition of Pol I transcription
+Differences in abundances
+Xrn1p
+HBV cccDNA
+patient-reported outcomes
+disulfide
+A plasmid containing the cDNA of an HCV consensus clone
+seven
+36 h
+cause-of-death modelling
+Five
+All fitting and model comparison scripts
+whether an outbreak is 1-wave or multi-wave in nature
+site-specific Ca 2+ binding properties
+1.5 × 10 4 /well
+>25 000
+virologic factors
+DIG High Prime DNA Labeling and Detection Starter Kit II
+heavy rainfall and periods of sustained low rainfall
+Superdex 200
+Supporting hospitals
+c-Myc protein
+1,209,602 Da
+zebrafish and medaka
+TDP-43 aggregates
+greatly exaggerated
+exposed to non-selective solvent attraction or hydrophobic exclusion
+Mappable Interactome
+209
+infection
+day 42 sera
+six months
+H1N1v
+individuals will underweigh the true cost of illness avoidance
+G+C content
+Distinctions
+132
+false-negative results may occur due to sequence variation in primer and probe targets
+gene expression studies of sALS
+0.6-0.8 mg/ kg/day
+recognition of shared goals
+endemic or emerging
+angiotensin-converting enzyme
+5.83%
+Pfizer Inc
+six
+divergence
+400-fold
+Probit regression analysis
+Transmission reduction
+MG
+12
+avian influenza virus, Newcastle disease virus and IBV
+viral multiplication
+animal models
+55 min
+75 months
+ARDS and VILI
+twice
+PD-L1 status
+1 ll
+every 3 days
+Ribavirin
+no lower toxicity
+21 days
+40 ml
+Oleic and palmitic acids
+Resveratrol
+Rhinovirus
+sgRNA
+AS-IV
+RNA pseudoknots
+goblet cells
+elucidated
+fewer than 10
+Linear regression
+RNA-dependent RNA polymerase
+Biotin
+HBoV
+LTβR-mediated signaling
+MPC
+accumulation of NSs
+a uniform and symmetric relevance measure
+selective
+low-viral loads
+Nodal
+relevant B cell, CD4 T cell and CD8 T cell epitopes
+Full set
+increases phosphorylation
+protein synthesis
+16
+dendritic
+Tens of thousands
+THP-1 cells
+American Medical Association
+44
+RNA polymerase I
+remission
+nonpermissive environmental cues
+Bayes factor tests
+homologous recombination
+EBOV -pseudotyped virus entry into 293T cells
+14 weeks
+nine
+safety data from special populations
+Three
+two
+256
+50 ng
+large variations
+all the presumptively FIV-positive cats
+CD8 T cells
+key gaps in preparedness
+cut-off scores
+the compound myricitrin
+filovirus
+fibrotic genes
+three
+7500
+hydrophobic
+why sodium sulfite treatment would affect the virus-plant interactome
+receptor, regulator and cytokines
+selective decontamination of the digestive tract
+Nuclear import of vector DNA
+higher vapor pressure
+expected natural infections
+HA and NA sequences
+7%
+4
+GAPDH
+multi-step protection/deprotection procedures
+Chemokine and cytokine responses
+T cells
+28 days
+logistical capacity
+allograft fibrosis
+Notch
+CCR7
+kinetics
+hepatocytes
+chymotrypsin
+AtRNA/His6-MS2
+STAT6
+1 mM phosphoramidon
+hand washing
+TAR DNA-binding protein 43
+patient survival
+mAb
+virus, ferret housing condition, and exhaled aerosol sample size
+facilitated viral accumulation
+FMDV replication
+neuronal homeostasis
+11
+oncogenes and tumor suppressor genes
+external events
+chronic hypoxic diseases
+twice a week
+Macromolecular crowding
+Peter Guthrie Tait
+Further information on research design
+Liver, spleen, and kidneys
+widespread nuclear abnormalities
+murine CEACAM1
+an acute infection can have dangerous sequelae
+hMPV or parainfluenza infections
+similar objects are more likely to be related to some other objects
+Pneumonia
+pentamidine
+50%
+dwarfism, poor development, diarrhea, and mortality
+Pili
+2087
+surface residues
+further research
+The coupling of MD simulations with MCE experiments
+subclinical and asymptomatic cases
+October 4, 2009
+Cumulative evidence that might be biased
+1=p
+complementary
+Dr. M. Zerial
+21
+low-dose Ang II infusion
+mortality
+45%
+differences
+Dismal prognosis
+Co-infection of leptospirosis and dengue
+standard procedures
+8-20 s
+Seventy percent
+Forty-two
+recurrent
+Gallid herpesvirus 2
+17.4-31.7%
+5%
+four
+MDRIs
+two
+knowledge
+translation
+70%
+28.610
+three
+the existence of each protein and the S-palmitoylation
+localization and protein function
+Western blot analysis
+20
+BSC-1 cells
+1500
+soluble proteins
+regression curves
+60 days
+splicing of MIE transcripts
+iProt-Sub
+titer
+238
+cc-by
+accessibility index
+y
+a signaling cascade producing multiple biological active intermediates
+14
+the liver
+Amico Ultra 15 mL centrifugal filter
+Breseq
+55%
+doubly acylated
+pentobarbital
+three days
+Well-designed clinical trials
+500-fold
+An alternative pathway
+migratory
+His126
+IRF3/7
+35.5%
+70,000/60,000 at 200 m/z
+Thirty years
+chalcones
+community structure
+183-H12-5C
+lipopolysaccharide
+the connection between extracellular matrix and cytoskeletal muscle fibers
+multiple indistinct contact points
+0.25
+JFRL
+IAPs
+versus host disease
+75 M
+hospital mortality
+7.02-fold
+elevation
+Ras/Raf/MEK/ERK signaling
+Early identification and effective management
+HIV-negative
+Kozak consensus sequence
+80%
+Acquired immune deficiency syndrome
+cosmopolitanism literature
+non-human primate models
+Ded1p
+monomorphic
+BSA-coated beads or blank beads
+lipid peroxidation
+10%
+the latent period, the infectious period, and the detection time distribution
+EBV transformation
+factorial validity
+spatially coupled models
+k-Nearest Neighbor classifier
+Lungs
+multiple translation termination codons
+failure to adequately integrate and apply a thorough understanding of policy analysis theory
+G. Barton
+facilitates proper histone transcript processing and trafficking
+Branch lengths
+δ-Secretase
+Antibody-virus mixtures
+Ebola
+purinergic
+Room Temperature Dehydrated
+improved treatment response
+local clinics
+centromeric
+16
+a protease specific for this most conserved eukaryotic protein
+A-particle
+neuron
+ImageJ
+NS1-GFP
+rapamycin
+NF-kB/MAPK
+tropical, subtropical and temperate
+cell growth, proliferation and survival
+CAR and DAF
+mice
+influenza A virus
+ID cows
+impose few restrictions on the evolution of θ
+fetal brain
+pro-inflammatory cytokines
+Paramyxoviridae
+acute neurological impairment and mental deterioration
+81.8%
+low
+Indirect
+anti-viral immunity
+Griess-Assay
+HBV
+60
+parameters were varied
+three
+4%
+Γ
+pre-warmed media containing 4SU
+C-terminus of hsβADR1
+Karber method
+20.3%
+25%
+by monitoring the disc radial mode resonance frequency shift
+admission to an ICU, in-hospital death and length of hospital stay
+EBOV
+partner with peer navigators or community health workers
+Stimune
+LQUV
+TasA
+platelet aggregation
+four
+Far-western blotting analysis
+IL-12p70
+FLUAV
+co-evolutionary
+200 µL of chloroform
+Clusters
+Humans
+RNA viruses
+3.5pg
+by heat map analysis
+human disease
+selection for drug resistance
+163
+neighbor-net method
+Access to diagnostic tests
+anti-mouse IgA
+orbital puncture
+SOFA and CURB-65
+Influenza antiviral therapy
+miR-1306 may participate in apoptosis
+carbonic
+microglia
+pattern recognition receptors
+influenza vaccination policies
+IL-15
+HBV, HCV and HIV
+symptom scoring system
+Olig2 stained cells
+two-stage sampling
+Peak fractions
+MenW CPS
+p53
+The amount of residual soluble protein
+standardized promiscuity values
+six or more hours
+World Health Organization
+FACS-caliber
+1 µl
+druggability scores
+nasopharyngeal colonization
+binding pockets
+SA-17
+LT1 DNA
+Virus escape mutants
+enhanced RSV clearance
+very small
+Coleman et al.
+the actual needs of users
+circumcision
+hMPV progeny virus production
+type I interferon signaling
+antibiotics
+heliox improved CO 2 removal
+HI antibody parameters
+progression to LRTI
+private behavior
+feline URI
+Six
+0.5%
+H1/H5derived
+Luminescence
+Approximately twenty
+innate and adaptive immune responses
+almost 5 days
+in the producer cell
+febrile days
+streptavidin-Cy3
+IRF1
+discrete packets of information that travel as units along linear pathways
+three
+sialic acid residues
+weight
+mechanisms of virus and Ab transmission from mother to fetus
+sensitivity and specificity
+human transmission and infections from the reservoir
+162
+non-replicating PV constructs
+conformance, completeness and plausibility
+escape mutations
+Cell-free BAL and tissue samples of lavaged right lungs
+75%
+gene order
+linear models
+tryptic autolytic peaks
+NI-NTA
+3
+the cell cycle
+marker proteins
+a constitutively expressed cytosolic chaperone
+Bilateral ground-glass opacities and pulmonary lesions
+antibody-coupled beads
+stimulates FcγR2B transcriptional response and receptor expression
+Full length protein
+DENV2
+host gene expression
+NHP study
+Proliferation, clonal expansion, and cytokine secretion
+41%
+critical health literacy
+modified nucleosides
+Acetone Bisacetone derivative
+59 to 39
+FLAG-tagged OATP1B1 and 1B3
+supernatants
+0.141
+10%
+reassuring
+STAT1, ISG15, MX and PKR protein expression
+three
+SEIR model
+relationships between variables
+4%
+Coriell Institute for Medical Research
+HLA-A2 and A3-restricted tumor-associated peptides
+NPC1 + endolysosomes
+organ injury
+cellular and humoral responses
+reduced cytokine expression
+fluorescent marker and the ATP assay
+10 min
+cholesterol transporter and re-distribution to cellular membranes
+thrombocytopenia and shock
+at the time of diagnosis
+Excess 293T cells
+CD8 + T
+0.5%
+109
+effective reproduction number
+RT-qPCR quantification method
+Western Blot
+1.1 to 5.5
+ITPR1
+Total protein
+influenzainduced death
+three
+CCL2 and CXCL10
+CLEC9A or DNGR1
+real-time PCR and semi-quantitative PCR
+EV-71 infection
+defense against MDV infection
+associated parameters
+viral target cells
+SOFA score
+methyltransferases
+unpaired t test
+the last previous valid data point
+universal primer sequences
+loss of antibody surface expression
+emodin, UDCA or DXM
+vital
+future strategies
+42 V and 275uC
+hypoxic
+Pneumonia and bronchitis
+tetrasaccharide 30
+biased T-cell cross-reactivities
+Handwashing
+25%
+The evolution of MHC-CNV
+NF-B expression
+Mutations to both canonical and noncanonical sequences
+3.09 × 10 −17 μM
+polyfunctional
+lung injury
+1 h
+Mermithida
+cell cycle arrest
+mesenchymal layer
+IFN-γ
+Four
+Autophagy
+dimerization
+CedPV antigen
+glycosylation
+50%
+30 million
+10,000
+344
+1 to 16 g/mL
+antiviral
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+Abcam
+DEFA1B, DEFA3 and DEFA4
+tropical-subtropical
+destroyed
+IgG1
+Spotted fever
+5 ml TE buffer
+children under age
+187
+host immune responses
+Singapore, Mexico, and Venezuela
+eight
+gene lists
+5%
+HEPES buffer with 5% DMSO
+virus replication or virus production
+cIFN-a
+Eight
+Cumulative windows
+HIV-negative
+all available randomized controlled trials
+234.2 seconds
+Endotoxin-free plasmid DNA purification kit
+SPSS 20
+20%
+pro-inflammatory
+A3-specific
+major pH-dependent conformational changes
+proteins
+TGF-β-induced EMT
+−0.0742
+66%
+severe and multiple Opportunistic Infections and tumors occurrence
+those obtained by the CSFV generic qRT-PCR
+an HPV infection
+at least 10 years
+partial pressure of arterial oxygen
+antimicrobial catheters
+43.5%
+Data
+three
+acetylcholinesterase-2
+vaccine delivery protocols and public messaging
+Primary signal intensity
+diminished
+Additional engineering
+Resveratrol and polydatin
+50 mm/min
+Phe60, Arg55 and Lys125
+cytotoxicity detection kit
+chromosome Xp22
+gondii
+a conserved sequence within the reverse transcriptase gene
+The Gene Ontology
+RAGE
+0.03 mN/m
+APP processing and Aβ levels
+no amplicons
+age
+helpful assistance
+suicidal behaviour
+surgery, chemotherapy or radiotherapy
+1995
+Eight
+two
+proinflammatory cytokines and chemokines
+viral plaque formation
+sufficient antibody responses against different viruses
+T regulatory cells
+local staff
+6.4 log copies/mL
+British and American medical journals
+Starvation
+309
+Liver lobes
+Statistical differences
+median survival
+Extracted nucleic acid
+WNV infections
+15.1 nm
+dsRNA
+1 H-NMR
+relative risk
+three
+activated
+gene expansion of IFITM10
+Meningiomas
+Ten
+10%
+70,000/60,000 at 200 m/z
+six
+modify and adapt
+antiviral
+threading of the unfolded Ub moiety
+routine viral load monitoring
+data acquisition
+specific information within mRNAs
+p-nitrophenyl phosphate
+pseudoknot induced frameshifting efficiency
+assay performance
+the chaff
+demographic differences
+12 hrs
+replication of murine noroviruses
+host immune responses
+IL-2, IL-10 and TGF-b
+germline-encoded
+a fraction of greatly varying size
+grade 3
+differences in binding efficiency to the host receptor
+severe hypoxemia
+AxyPrep Multisource Genomic DNA Miniprep Kit
+Dr. Mikhail Balayan
+DCs
+additions and subtractions
+imported cases
+Th2
+infection by some viruses
+intellectual
+eIF4G and PABP
+conformational and linear epitopes
+three
+Seventeen
+translation through a region near the 3 0 end of the polyprotein ORF
+10 g
+furin and plasmin
+the number of edges incident to a node
+Angiotensin II type 1
+12 days
+MBL2
+0.6 kcal/mol
+P. perniciosus
+keratanase
+increased levels of anxiety and distress
+mouse cTnT plasma concentrations
+t 1/2
+> 5%
+linear interpolation and extrapolation
+16E6
+resistance to BmNPV infection
+Five
+satellite imaging
+Random Forests
+table 3
+hydrophobic interactions
+CXCL9
+24 h
+SINT-speckle formation
+No difference in food intake
+leprosy
+APCs
+adaptive immune cells
+20 min
+metabolic functions
+2003
+Src
+hand-washing facilities, showers and toilets
+inhibit the virus
+10
+influenza
+Bioneer
+Thr160Ala
+anti-apoptotic effects
+IL10-R2
+lectures on health education
+total specificity
+NIH Office of Human Subjects Research
+Myc, Myb, ErbB2, Ras, and Raf
+pPG-COE-DCpep/L393
+L2 translocation
+vaccinia
+T3
+innate immune responses
+3 to 8
+TBEV
+C gives a strong binding energy
+OS9 and XTP3-B
+Numbers of antibiotic usages
+an extended C-terminal α-helix
+43,771
+expenditure on prevention of obesity
+cDNA from infected cells
+adaptation requires indirect paths
+fudging the immune response
+meningococcus
+mitochondrial gene sequences
+w k
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+high sample throughput
+autocrine growth factors
+Cyclooxygenase-2
+PostgreSQL
+low viral loads
+RNA interference
+7 days
+Q226L/I and G228S substitutions in the HA protein
+15 min
+Propidium iodide
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+Bone substitutes
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+Eighteen
+DNA immunization technique
+Protein A-10 nm gold conjugate
+Pneumocystis carinii and bacterial pneumonia
+differential subcellular trafficking and cytosolic partitioning
+bivariate X 2 tests of independence
+wild-type cells
+total RNA
+44
+Covaris S220 focused ultrasonicator
+transmissible spongiform encephalopathies
+evaluate the contribution of each single variable to classification
+all-cause mortality
+marine mammals
+PMScoremin
+Cinanserin
+unbiased, simultaneous profiles of gene expression
+the complete inventory of genes found in any member of the species
+Koch's postulates or other assessments of direct viral injury
+7%
+QIAmp viral RNA Mini kit
+modify the nasopharyngeal microbiota of farmers
+pandemic
+C s
+Acinetobacter Baumannii
+exhaust security
+r
+bacterial meningitis
+coding RNAs
+CDS and mature peptides
+CD225 domain
+TADR
+SPSS
+Confocal microscopy
+fasting serum glucose and Ag-RP levels
+22
+100 to 3,000
+particle size
+current ILI case data
+influenza therapy
+Three
+20
+lipid oxidation
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+summer
+1167
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+groups
+12 person-years
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+F-XMRV-F
+Bretschneider cardioplegic solution
+proteins
+reverse intersubunit rotation
+to ensure adequate power to detect a pre--specified effect size
+citizens either infected or treated
+ARVectoNBV
+by their origin, morphology, gene expression pattern, and function
+cleaves prM
+poultry sales
+Duolink In Situ mounting medium with DAPI
+interactions with the ion centers of iron or other transition metals
+Illness consultations
+epitope tags
+nonenveloped viruses
+Protein G column chromatography
+cc-by
+Env incorporation
+constant influx of incomers
+one
+2004
+9.3
+R231A
+most points are near or under the theoretical curve
+Products of the GII.4 and MNV RdRps
+infection
+2-CTC resin
+Shuttle peptide-protein formulations
+SKD and KCA
+external rates of infection
+trauma, infection, and neo plasm
+antigenic variations
+infection or an adverse reaction to the blood components
+general practitioner
+TGEV infected pFcRn mRNA levels
+Regulation of alternative splicing of the MIE transcripts
+two
+regulatory patterns of the cell that are unique to either proteins or transcripts
+external
+Virus replication and viral infectivity
+Ͼ32
+resistance to disinfectants or biocides
+tropical underdeveloped countries
+Egypt
+10%
+median clan sizes
+Fifteen
+100 mg/ml fetuin
+contact with the febrile person
+membrane-tethering activity
+HPLC and mass spectrometry
+sera Lectins
+polysome profiling
+rVSV/EBOV GP entry
+truncated NS1
+HEX and FAM fluorescence dyes
+generally broader ranges of acceptable parameter values
+18th
+additional purposes
+80%
+ATP
+NOX-1
+mixed taxa
+Sperm
+macrophages and dendritic cells
+Wilcoxon rank sum test
+IL-4, IL-13 and IL-10
+epithelial disrepair
+Variation in coat colour
+50-fold
+attending physician or intensivist
+optimal intervention
+other type of abnormality patterns
+T. b. rhodesiense
+β-secretase specific fluorogenic substrate
+p S and p P
+LncRNAs
+reduced
+viral entry
+growth curves
+Detection of ALT in serum
+flow cytometry
+serum samples
+nystatin
+NK cells
+viral fusion
+a seasonal influenza
+STATA
+detection mechanisms that use probabilistic analysis
+acyclovir
+populations are independent
+hormone-sensitive lipase
+EMAN
+failure to mount full Th1 cell immunity to viral infection
+V'max FRC
+Formal criteria
+90%
+performance outcomes
+Model 2
+CD122
+Three
+Target concentrations as low as 0.14 ng/mL of HBsAg
+SSTR2
+1957
+since ancient times
+Graphpad Prism 5.0
+symptomatic
+scientific explanation and guidance on some psychological phenomena
+prevents the spread of virus from infected cells
+ELISA plates
+13
+haemagglutinin
+appropriate stability of the instrument
+cell surface
+statistical analysis
+CDK2
+The time course of the reproduction number
+SV40
+national ethics committees
+Five
+sympathetic
+22
+SuperScript III One-Step Platinum@ Taq
+LE/L cholesterol accumulation
+they are of biological significance
+5 min
+1.5 ml
+pigs
+3,099
+when both antigens were combined
+how members of the general public respond to pandemic influenza
+intracellular protein turnover
+compliance
+26
+bias and unavoidable stochastic randomness
+BALB/c mice and Hartley guinea pigs
+Relative expression level
+Lasso
+cloacal and tracheal excretion of LPAI
+Sequences of codon-optimized prME genes
+100
+pseudo
+cross-reactive cytotoxic T lymphocytes
+1918
+Spatial heterogeneity
+personal protective equipment
+Doxorubicin
+6
+the proliferation of lymphocytes
+a unique receptor
+SuperScript II RNase H-Reverse Transcriptase
+13%
+100%
+11
+peripheral blood and marrow
+19
+Hidex Sense Microplate Reader
+blindness, chronic bronchitis, and cancers of the respiratory tract
+Leica Microdissection System
+Sheep and goats
+Dbp5p
+variability of its measurements
+T helper 1
+forbs and grasses
+proteolytic degradation in serum
+World Health Organization
+high
+epidemiological
+Influenza Virus
+Invitrogen
+AaHig
+protein residues with the ligand molecules
+weakly active
+$20 g
+live attenuated vaccines
+92%
+monomeric RNA:protein complexes
+neuron cells
+neutrophil elastase
+oxygen requirement
+Repeated therapeutic lavages
+creating a safer global blood supply
+Metabolic acidosis and hyperlactataemia
+an RNA chaperone
+pro-survival effects
+Epithelial differentiation
+Lv2 restriction
+30-40%
+depression
+Rutin
+RPMI 1640 medium containing 10% fetal bovine serum
+week 6
+The first chain cDNA
+PRRSV replication
+Frameshifting
+immunomodulatory
+zero
+Aedes albopictus
+multifactor complexes
+One microgram of RNA
+24 hours
+29.8%
+ARIs
+pandemic category 1
+27 yr
+parasite metabolic processes and host immune modulation
+Anxiety and Depression Scale
+UBA domain
+distributions of plausible values
+ELISPOT assay
+SBV, BQCV and ABPV
+atypicality of a region in terms of oligonucleotide usage
+moderate cerebral edema
+0.60
+TRIzol
+inconsistent test performance
+78
+EC apoptosis
+Leucine enkephalin amide acetate
+compounds with bacteriostatic effect
+a prey library of human kidney cDNA
+favorable outcome
+56.4%
+Skog et al 50
+HMGB1
+women
+Molecular knockout studies
+Conformational epitopes mapping
+One-hundred
+random-effect meta-regression
+More work
+DVG-324NC
+phenix.sculptor
+interstitial pneumonia with consolidation and hemorrhage
+data
+5 min
+whether motif D is in an open or closed conformation
+moDC
+Cardiac myofibroblasts
+p63 pos LNEPs
+myxothiazol
+Eight
+Nucleofector6 electroporation protocol
+5-10 genome copies/PCR reaction
+a lentiviral gene-therapy vector
+6 weeks
+more intensive production systems and more rigorous biosecurity measures
+using the same tissue sections
+t-test analysis
+two
+CDC
+eIF4G-depleted RRL
+Three matching trimers
+gene expression patterns and kinetics are different between these tissues
+Eigenvector centrality of a vertex
+lipid-based nanocarriers
+Br-ApoE -PMO
+Diffuse alveolar damage
+High-quality sequence reads
+796
+20
+700,000
+active mucocutaneous PV
+care facilities, the military and the cruise industry
+hygromycin B
+non-intuitive
+Light of Friendship Association of Taiwan
+respiratory epithelial cells
+53
+four
+IL-6
+three
+0.05
+CTFFIND3
+0.1% of Triton X-100
+NYMV and MIDWV
+50 mg/ml
+public health policy as well as health care delivery
+743,599
+increases
+Lentiviral shRNA vectors
+random mixing by degree
+13
+Cell count
+7-day
+normal function or minimal disability
+that in other places
+A. caninum
+Seventy-four
+apoptotic death
+Three weeks
+routinely-used laboratory methods
+Saudi
+IL-4
+June-July
+evolution of nanomedicine
+UV spectrophotometer
+the factor of the distance between the candidate and the diagnosed patient
+Analytical sensitivity
+S-foci
+modulation of the host response
+PCR
+endothelial cell inflammation
+to assess cell autophagy
+26
+tropical
+48 hours
+3,5-DCQA
+SDS 1.3
+Tyr397 phosphorylation of FAK
+rapid development of varices and bleeding
+NTZ's ability to suppress replication of PKR-sensitive viruses
+antiviral
+regulating antiapoptotic genes
+Pictet-Spengler cyclomethylenation
+20
+SPAM1, CRISP1, and IZUMO
+100
+ACBD3
+target-decoy based strategy
+less than 20 min
+Spontaneous immortalization
+a lobby at the lift
+PltA and PT-S1
+to increase the chance of finding any endogenous MS2 RNA in the stools
+HPIV3
+protein or RNA structure prediction approaches
+an optimal panel of synthetic polyomavirus antigens
+recombination
+retinal ganglion cells
+3
+crossover recombination
+7 days
+Institutional Animal Care Committee
+Poly-dimethylsiloxane
+HSV entry
+50%
+to reduce the risk of smallpox
+Group1
+qRT-PCR
+probes to detect SGs in the training set of images
+antibiotic
+NS3
+staggering levels of complexity
+RNAhybrid tools
+default parameters
+Anigen rapid CPV/CCV Ag Test kit
+multiple sclerosis
+new interfaces involved in protein-protein interactions between host and pathogen factors
+Table A1
+Removing the other branch lengths
+Substantial genetic diversity
+renal replacement therapy
+Four
+minimum clinical standard
+binds to PKR and inhibits PKR activation
+M2
+Mx1-Cre transgenic mice
+lectins
+what elements of the feature were the main determinants of the difference
+20%
+PDE4
+rapid sampling and sequencing of the Western Africa's 2013-15 outbreak sequences
+390 million
+polyprotein
+unmodified siRNA molecules
+Microbial translocation
+The manuscript
+random forest
+Microglial numbers
+X-ray
+minimize animals' suffering
+bf
+viral infections
+spoIIAA, spoIIE, and spoIIGA
+endogenous lamin A and C
+Three
+immunohistochemical staining
+once, twice or three times
+three
+Microbiological samples
+correctly detecting an epidemic of influenza
+Timeliness
+value was assigned the highest concentration of inhibitor tested
+Fronhoffs
+Structure-guided biochemical
+bacterial ribosomal RNA
+2009
+Natural killer cells
+Kenya
+TLR5 and NLRC4/NAIP5
+5 min
+Graph-Pad Prism
+two
+maximum temperature and specific humidity
+PERCH integrated analysis
+CellSens Dimensions
+Genes
+CARPA
+73
+active site
+permanent cross-immunity
+throat swab
+two related strains of E. coli
+standard deviation
+a face-toface interaction
+Effective control of circulating influenza viruses in swine populations
+182
+Mutational pressure and natural selection
+P<0.05
+less structured
+1 : 1
+furin cleavage site
+diabetes
+Comparative
+luciferase activity
+20
+Pig contagious pleuropneumonia
+investigating the localization and distribution of the proteins in infected living cells
+5-20 days
+corticosteroid
+sliced likelihood
+Kenya
+day zero
+mice lacking caspase-1 or ASC
+human rabies
+dichloromethane
+Heartland virus
+positional variations in physicochemical properties and surface characteristics
+OsSGT1
+microvillar
+allows remission of the lesions
+Figure 7
+Borna disease virus
+viral titers
+Xbp1 signaling
+to remain consistent with other quantitative studies measuring airborne IAV densities
+Stigma
+IFN-γ
+Written informed consent
+30 minutes
+ONFH and non-ONFH patients
+12:1
+adaptive immunity
+illness
+stable isotope labeled peptides
+β s and β r
+Univariate
+soil and water
+human-adaptation
+the most conserved amino acids
+class or family
+CD8 T cells
+MaxQuant
+Ninety-five percent confidence interval of means
+one-third
+CBF1
+three
+glutathione S-transferase 2
+after bathroom use
+accelerated structural determination
+2 hours
+buying live poultry
+rhesus monkey
+VP1, VP2, VP3, and VP4
+2 days
+pulmonary viral load
+virus that lacked DVGs
+The presence or absence of O chains
+increase
+primary cultures of human respiratory tract epithelial cells
+time consuming
+resveratrol
+six
+UFS
+mPSCs
+Unpaired two-tailed student's t test
+2 definitions
+13,000
+unpredictable
+an AUC score of 0.879
+degenerative
+we cannot detect HLA-associated selection to the consensus
+chemical modifications
+Bovine respiratory disease
+increase target nucleic acid concentration
+200 nM
+5|21z20z14~139
+molecular parameters of the identified solutes
+Seventy-four
+binding of the viral RNA to RIG-I
+prevention
+VSV-846
+North American biodefense priorities
+MN titer
+oncolytic
+difficulties in analyzing the mitochondrial genomes
+10 min
+50-100 million
+inhibitory
+Aspartic proteases
+50 million
+GSH synthesis
+250 mL and 1 mL of TRIzol
+Protein Data Bank
+three
+biological membranes
+fractured condyle
+17 nm
+tanshinone IIA
+six
+cell surface proteoglycans
+acidic vaginal secretions
+a serial
+348
+32 model-runs
+niche conservatism
+35.3 kDa
+µ-oxo dimer
+Gram-negative and Gram-positive
+The transcripts of EGR1 and viral RNA
+CENPO
+disease phenotypes
+A1 and A2
+fomite-targeted
+10
+AMPK
+Tscm cells
+cytosol
+changes in fecal microbes
+Monensin sodium salt
+postoperative brain infection
+variability
+an optimal time for initiation of ART
+host cells
+19%
+IFNβ-mediated communication with other leukocytes
+natural
+amplification of the PRV gB gene
+GRB2
+neighbor-joining method
+hypoxia and high SAPS score
+939
+300
+29,182
+19
+limiting the role of government
+waste from the agriculture industry
+proinflammatory
+Orient Bio
+3-5 days
+NS3/4A
+mortality
+effector T cells
+a disease transmissibility value, an incubation period and infectious period distribution
+increases
+b age
+10 1
+phylogenetic
+types I and III IFNs
+homologous or cross-reacting determinants
+2003
+parvins and filamins
+30 min
+production capacity
+Survival, body weight, and viral titers
+Lean lines
+veno-venous
+All packing diagrams
+100%
+excess PMN-derived proteases
+urbanicity
+more sophisticated tools
+15%
+over the lung areas
+5%
+absorption spectra
+CMV, RSV, and PIV
+500 000
+Kruskal-Wallis test
+executes membrane fusion
+Porod-Debye
+1 million
+four
+chest x-ray
+Vietnam
+more detailed insights into the epidemic dynamics
+sites of transposon insertions
+fresh medium
+2683
+Purified human tracheal Siglec-8 ligand
+viral load
+24%
+subclinical or non-severe symptoms
+E. coli enzyme leader peptidase
+maximal
+18.8%
+no gaps were introduced
+39.3%
+191
+three
+rapid progress
+mAbs that bind to the glycan cap
+Glycerol
+two days
+53
+transformed cells
+inhibitory
+high enantiomeric excess
+B reg cells
+protocols for data or information sharing among levels of government
+10.4 percent to 42.2 percent
+Charles Rice
+hundreds or thousands
+polyethelyene
+mean ± 95% confidence interval
+A subsequent graft from a deceased donor
+time-varying covariates
+rats
+QIAamp Viral RNA Mini Kit
+2-3 minutes
+83
+flavivirus CFR
+Wild type Nef myristoylation
+octuplicates
+0.5%
+GE Healthcare and IBA
+Four
+Eight
+leafhopper
+3aminobenzamide, PJ34, or INO-1001
+VelvetOptimiser 46
+2A and 3C
+18
+phase Ib
+54 to 56 kDa
+6.32
+26,675
+FolE, QueC, QueD, QueE, and QueF
+cancer types
+PPV
+157
+clearance functions of the macrophages of the liver
+actin cytoskeleton reorganization
+575 nm
+clarification
+5-20%
+half
+different T helper responses
+twice
+a non-cognate interaction
+Pneumococcal Polysaccharide Vaccine
+papillar carcinomas
+in vitro frameshifting efficiency
+Table 1
+Superscript II and amino-allyl dUTP
+Site of infection
+Protein A/G
+a superior nasal step
+bovine viral diarrhea persistent infection
+design primers
+433.2 pg/mL
+Figure 7
+More than 180
+prolong the life span
+VHL
+logistic regression analysis
+eyes and brain
+infection status of the individuals
+Accurate predictions about the magnitude and timing of peak incidence
+7
+pigs
+toxicity testing
+encephalopathy or encephalitis
+Hspa1a and KFL4/KFL9
+Four
+Two-thirds
+Ab-Pak-cluster-1
+removal of partial haplotype observations
+eudemonistic
+Influenza A virus
+immunogenicity
+Respiratory infection
+Sun Hur
+6
+previous observations
+flexibility and adaptability
+Peru
+30 in the dark
+storage below -45ºC
+receptor recycling
+different groups world-wide
+1 h
+PD-1
+EMSA
+active
+DMSO
+one month
+Real-time PCR
+1918
+24 h
+pathogen spatio-temporal dynamics
+insect, nematode, or fungal vectors
+a comparison between observed and modeled data
+hematoxylin
+Further study
+Genetic variation in IGEs
+day 8
+alcohol-based
+Immunodeficiency, asplenia, and older age
+accelerate FIV transcription
+18%
+human immunodeficiency virus type 1
+yUfd1 NBM
+kidney, liver, and pancreas
+LDS buffer
+least infringement
+posttranscriptional
+four
+A and B
+model selection framework
+17,489
+via the PAF receptor on A549 cells
+12/61
+9
+MARV GP-MR78
+Vaccination
+25%
+changes in the H-2K b /peptide complex
+30 minutes
+IL-1b
+host factors
+6-8 days
+the choice of target
+drier
+CD4
+MAFFT
+RdRp template switch
+More thorough filtering
+TLR4
+public health policy evaluation and planning
+loss of the killer phenotype
+89
+liner epitope and conformational epitope
+extended periods of time
+community preparedness
+chemical
+bacterial and viral infections, connective tissue diseases and sepsis
+28 days
+ICU-acquired pneumonia
+application of antiviral drugs
+lung ANG2 upregulation
+Ceacam1-Tg T cells
+16%
+hMPV
+ischemic
+slight fluctuation
+11%
+July 2016 to November 2017
+NPEPPS/PSA
+anti-HA IgG production
+FPV
+consistent
+splicing
+PerkinElmer Lambda 40 spectrophotometer
+missing classifier
+Dropouts account and intention to treat analysis
+mitochondrial transfer
+IL-10
+502
+40%
+committee members
+over 93%
+c-Myc and cyclin D1
+increasing scientific understanding and in progressing promising therapeutics through development
+RNA-dependent RNA polymerase
+73%
+E. chaffeensis
+Puerto Rico's cool and wet mountainous area
+Syntenic maps
+9
+0.04%
+St. Jude institutional review board
+pool of host factors
+no external fund
+18
+GRASP-mediated unconventional vesicles
+α-catenin
+Three weeks
+virus inocula
+Nicotine Replacement
+HA1-HA2 dissociation
+The tool
+human AFP
+Thrombocytopaenia
+proteases
+trypan blue exclusion method
+autophagy
+neurodegenerative
+ten
+Thirty
+potent
+strongly positively correlated
+three
+lower delivery of the segment by infecting virions
+careful review and approval
+IV-injected RBCs to massively accumulate
+perforin-dependent
+52%
+acquired or congenital
+increase or decrease
+Laemmli polyacrylamide gel technique
+cellular stress response
+2343
+10-15 min
+Community education
+cross-border, legal and illegal migrants seeking work
+Mitochondrial N-formyl peptides
+three independent experiments
+influenza A virus
+airway occlusion technique
+TG-ROC
+Epitopes showing high levels of amino acid similarity to each other
+four
+Reproducibility of the levels of gene expression
+Overreliance on genomic studies
+78%
+bilateral crepitation and wheezing
+Synthesis of anti-genomes
+CVB3 2A and 3C
+inhibition of Ras signaling
+1X Washing Buffer
+nonfucosylated glycans
+Data on contacts between individuals in specific settings or in the general population
+×100
+31
+10,324
+dynamical networks
+Vasculotide
+limited radial growth
+moist
+4
+10%
+flow cytometric
+10.91
+Dscam
+More than 1,000
+noroviruses and influenza viruses
+drill down into subregions and neighborhoods that are affected by epidemics
+mutations in the donor
+$1%
+point mutations, insertions, deletions, and other sequence variations
+macrophage-protective
+GFP + effector T cells
+five
+large doses of ionizing irradiation
+a series of evidence-based interventions
+Hydrogen
+processing in the nucleus
+genes not addressed in the text
+77%
+Spatial Time Series Regression Spatial time series regression
+murine noroviruses
+64.3
+LPS
+predicted PBs and RSS
+Human immunodeficiency virus type 1
+a single, mutually exclusive value
+K48 chains
+biosafety level 2 containment facilities
+amplicon-specific 2GO probe fluorescence
+periodate
+g 2
+cationic amphiphilic drugs
+Bridge host
+reactive oxygen species induction
+inhibitor quality
+Abcam
+neurotoxic
+CHIPS and CUSP
+tertiary prevention
+0.5
+pinocytosis
+1
+cell type-specific
+trace plots
+clients who are distinct from those they meet in their routine hospital work
+receptor sorting into ECVs/MVBs
+70 μL Tris
+an arrow
+Compartmental modeling
+respiratory
+EFNA4
+8 h
+epithelia, endothelia and leukocytes
+Human peripheral blood
+replication/transcription levels of the RNA replicon
+>90%
+DMVD cleavage site
+statistical models
+Non-transfected cell lysate
+The sequence signature
+23%
+78
+1918—1919
+317
+GenePix Pro 6.0 software
+dsRNA
+Ten
+psychological
+viral fitness
+a main interview, a self-report questionnaire and a medical interview
+proteins involved in the pathogenicity and virulence of K. pneumoniae
+zero
+a dual effector response
+decreased
+VC and CC cells
+independent
+computational predictions of previously described gene boundaries
+Yeasts
+CMI
+PARP-1
+VLPs
+26%
+time post-infection
+2009
+Affymetrix Genechip technology
+diatomic composition
+vcRNAs primed with RT primer L 126+
+Fifty
+Anthrax
+extracellular domain
+4%
+ethical and moral
+3
+90%
+92
+Interleukin-10
+understanding the mechanisms of viral persistence
+1.4 years
+efficacy and safety
+antagonistic activity
+nasopharyngeal swabs
+single-molecule
+lower respiratory infections
+all the participants
+Meta-analysis
+selective pressure
+Standard solutions of small molecules with different concentrations
+94.3%
+EDTA vaccutainers
+thrombocytopaenia
+mRCAs and C3
+raw reads
+Bacillus subtilis
+confocal
+proteolytically cleaved
+personal protective equipment
+two
+three
+A consistent and comparative description of the burden of diseases and injuries
+20 min
+Osteopontin
+NS1 protein
+epitope-binding promiscuity
+no significant differences
+3,137
+H5-HA1 and GST
+antisense oligonucleotide -mediated splice correction
+290 nm
+respiratory diseases
+adequate fit indices
+16
+cell viability
+external peer review
+siNTC-treated and nontreated cells
+Microbiological
+27
+SDHA
+serum creatinine
+RNeasy Extraction Kit
+Five
+Principal component analysis of polymorphism at bi-allelic sites
+circulating platelets
+duration of fever and viral shedding
+a silent killer
+lab-confirmed and syndromic
+Leaf samples and wood samples from the stem
+0.01%
+public and private partnerships
+Chemokines
+Cotton swabs
+24-h
+a biomarker
+SDS-PAGE
+Nosocomial infection
+RNA knots
+two thirds
+Western blot
+Contact with bodily fluids from EVD patients
+the hybridization process
+signal intensities
+2017-2018
+intraepithelial lymphocytes
+morbidity and weight loss
+Caveolins
+HAdV
+open source software tools
+Hy's law
+Stress-mediated activation of key viral promoters
+TamifluH
+20%
+different methods of sample collection and variation of calculation methods
+5-10 days
+k-means clustering
+severe organ impairment
+health staff
+cytoplasmic
+26 hrs
+S + 1
+Example 1
+spectrophotometer
+1 of 2000
+AP2 clade genes
+assumes that household agents were isolated when performing risk perception and coping appraisals
+Lysate
+low signal to noise ratio
+50%
+the underlying sugar chain
+polyvalent IgGs
+fucose-moiety
+right-sided heart failure
+post-operative management of malignant melanoma patients
+TEA or paxilline
+case isolation and quarantine
+pathogen load
+47.33
+shedding
+10%
+a set of statistical replicate inferences
+CP culling
+6
+higher-level constraints
+rapid upregulation of type I interferon
+exclusion of patients within the highest CRB 65 categories
+F. tularensis
+increased mean survival drastically
+September 30, 2014
+pRL-TK
+18s
+adverse side effects
+TCID 50
+PRINCE
+The ubiquitin gene
+T-Coffee and LocaRNA
+80S ribosome
+social norms
+HMGB1
+parasite uptake
+200
+alamarBlue reagent
+high variability
+high-order oligomers
+4
+Alpherpesvirus
+virus replication of both human and avian influenza viruses
+higher frequencies of TLA-responding CD4 + T cells
+fatigue and pruritus
+two
+30
+48 hours
+10%
+an immunoreceptor tyrosine-based switch motif
+PI3K/Akt, Src, and STAT3
+reported vaccination uptake
+RNA polymerase I transcription activity
+parameter samples
+effector or memory cells
+increased amounts of state intervention
+12 months
+phGag-Pol
+a prior exclusion of an ongoing VZV infection
+University of Alberta Animal Care and Use Committee
+sophisticated computational tools
+suppression by the pDC IFN response
+β-glucuronidase
+36
+Marburg virus and Ebola virus
+LPS
+GraphPad Prism 5.0
+NP1
+S498R
+serum or mucosal antibodies
+VP3
+progranulin
+Foot-and-mouth disease virus
+decreasing mortality of host cells
+AS03-adjuvant
+Stability analysis for seasonal systems
+cholesterol
+oral
+MATLAB 6.5
+injury progression
+Basic reproduction number
+one-way
+dying cells
+one
+T83 and I113
+H16
+Severe clinical conditions
+lung mechanics and anatomic dead space
+Virus stocks
+homo-or heterodimers
+1918
+RNA recombination
+quantification of an apparent dissociation constant
+GST pull-down assays
+Multiple test results for a single specimen
+KCTF
+step-wise
+42
+cc-by
+4
+shared antagonism
+Samples
+Tetramer Technique
+reduced viral loads in the blood
+2.48
+Five
+library preparation
+a known peptide/MHC complex structure
+71%
+443
+60
+Three
+laboratory to "wild" rodents
+SNAP amplitudes
+A model without seasonal terms
+2020
+9 m 3 /min
+33
+Glycine-Arginine Rich region
+6
+mature
+2.87 million
+72%
+85%
+fusion
+Heme staining
+6 mM
+12
+0.62 ± 0.08
+Exon 9
+Toll-like receptors
+hepatitis A virus
+0.677
+FlowJo
+Pasteurella multocida
+adhesion molecules
+co-expression of LAG3 and CD49b
+PA gene
+MIA
+42
+Emile Littré
+1 in 500
+liver graft-versus-host-disease
+they might confound the analyses
+$27 mg/mL
+kidney damage
+indirectly increases ACE2 expression
+benzofuran and pyrrolyridine
+U27C mutation in SF220
+NucleoBond® Xtra
+aggravated
+acute respiratory distress syndrome
+Transcriptome
+an ''open'' Env structure
+an addition risk of infection
+dephosphorylation of oligo
+significantly higher
+neo-minophagen C and glycyron tablets
+normal cell line
+63/2010/EU
+A pool of candidate structures
+fever
+V3 loop mimetics
+interdisciplinary collaboration
+clear learning goals and the correct level of complexity and organization
+48 h
+Amyloid depositions and neurofibrillary tangles
+sulfuric acid
+Db data
+6 h
+Vaccination
+73%
+the PACF
+apoptosis induction by reovirus
+A workshop
+air desiccation
+25%
+human
+JAK1, TYK2
+lower than that of P-site tRNA Phe slippage
+trained nurses
+0.85km
+tertiary lymphoid follicles
+Creative Commons Attribution 4.0 International License
+vascular
+15
+NK cells
+Ongoing evolution of viral pathogens
+Further isomerisation in the ER
+losses of hybridization signal
+256
+15 minutes
+ILI
+pmf
+DFA
+50
+60%
+HBeAg
+yeast cytosol to vacuole targeting pathway
+phosphatidic acids
+25%
+metagenomics
+PRRSV genome
+BHK-21 cells
+non-significance
+interesting aspects of large ribonucleoprotein assemblies
+IL-17A
+Brucella abortus sequence
+21
+27%
+cytokine production
+Green fluorescence and DAPI
+proinflammatory
+renin
+broiler chick liver
+neutropenic
+LR Clonase II
+cell apoptosis
+a knowledge gap in the host-pathogen interactome
+disaster preparedness, emergency management, and public health response
+just as likely
+fragment ions
+transient decreases in some of the parameters
+Viral genetic data
+biosafety considerations
+sophisticated computer algorithms
+7
+negative neutralizing activity
+Genetic polymorphism
+15% and 38%
+IL-4 expression
+subject-specific lists of proteins
+indicating β-strands formed over NS2B
+European Collection of Cell Cultures, UK
+retention of lymphocytes
+holistic
+GR-SU
+42
+The choice of model viruses
+WT and SPC-TNF tg mice
+increases
+goggles and earplugs
+1 day
+2.0-4.3
+36
+edges
+without significant sorting
+4Á5 days
+0.40, 0.39, and 0.35
+33%
+2009
+computationally predicted base-paired stems
+whether it contributes to the evolution of the virus
+Malaria anaemia
+when richer call data are available
+the intergenic promoter
+pRB
+body weight
+spectrophotometrer NanoDrop ND-1000
+angiogenic
+Pseudoknots
+intrahepatic
+whiskers
+proliferation
+10
+Ethnicity
+comparative Ct method
+HHV-5 DNAemia
+Lineweaver-Burk plots
+12, 14 and 20
+kDa
+twice
+Vaccination
+PSL
+IL-7
+compound #8
+global
+Biolayer interferometry
+Equation
+serum-free DMEM
+Viral peptides
+four
+u v and u m
+zanamivir
+stem-specific antibodies
+vesicles
+under the View menu
+very different underlying processes and conditions
+deep-learning
+MgCl 2 concentration and annealing temperature selection criteria
+23.6%
+Replicon particles
+70S initiation complexes
+complexity of geospatial patterning
+5-7 days
+mesial temporal lobe epilepsy
+peribronchiolar inflammatory cells
+93.4%
+FDA/CBER analytical plasma panels
+reverse vaccinology
+Reflexivity
+Medication errors
+synthesis of the encoded protein
+1524
+PTX3
+homologous
+CCL2, CCL8, and CXCL10
+a smaller reduction in Rt
+eGFP fluorescence
+Viral family and genus richness
+immunomodulators, induced interferon, or recruitment of immune cells
+Dengue
+the health status of their baby
+1970s
+up to the administration of cycle 2 day 1
+retroaortic
+end point ELISA
+83-89%
+significant increase of abundance in the protein complex
+115
+hypoxemic respiratory failure and hypercapnic respiratory failure
+mRNA
+coagulation necrosis
+786-O
+11
+adverse clinical outcome
+ATCC
+5%
+fibrotic
+a rate limiting non-erythroid enzyme
+infectives
+deficiencies
+percolation theory
+higher concentrations
+p38 MAPK phosphorylation
+50%
+Profile Hidden Markov Models
+cellular internalization
+All SAEs
+104,000
+71%
+Lagerstroemin
+large numbers of potential interactions can be sampled at relatively low cost
+six hours
+The efficacy of the formulations
+Influenza
+80 lg/ml
+100%
+36%
+1=l
+inhibiting
+aminopeptidase N
+disease reproduction number and the serial interval
+kDa protein
+1289
+anti-cancer drug
+strong upregulation of FOXP3
+positive-strand
+nonmammalian
+Zip-tip C18
+silica gel-protected aluminum sheets
+cytokine receptors
+Viral RNA
+health care providers
+30 min
+neutrophil granulocytes
+Treponema denticola leucine-rich repeat protein
+62%
+K d
+2Â RNA loading dye
+accelerates
+decreased cell migration and invasion
+CBR
+STAT-6 protein
+239 kcal/mol
+Genomic DNA Mini Kit
+anti-hybrids antibodies
+10 minute
+mutant VP5 sequences
+DNAse I
+Prevention of pediatric HIV
+templates for RT-qPCR reactions
+Three
+16.7159
+25%
+β = 0.20
+a curated set of 25 000 viral protein families
+immunofluorescence
+51.08 years
+Inflammation
+recombinant capsid proteins
+SARAMIS
+Microglia
+under 6 years
+Nanoparticles
+systolic BP
+GAPDH
+1
+V Q
+a significant finding
+Rigaku R-Axis Spider diffractometer
+Lagrangian
+mutational pressure
+infections with certain herpesviruses
+Additional evidence
+70-90%
+changes in behavior
+diagnosis confirmation by PCR
+virus-induced apoptosis and CNS injury
+D2 and D3 flagellin domains
+Solvent molecules
+a forecasting method
+interstitial and alveolar oedema
+two
+HIV/AIDS, lower respiratory infections and diarrhoeal disease
+at the optimum temperature
+n=3
+axial coding
+seven
+every 3 or 5 years
+20
+Autophagy
+severe thrombocytopenia
+PHYLIP
+siRNAs
+frameshifting efficacy
+TDP-43 and FUS
+paracellular gaps
+pneumonia, sepsis and bleeding
+whenever a certain epidemiological quantity is less than unity
+icosahedral
+TLR5
+One
+A limited reduction of movement
+23 amino acid from the human tyrosinase signal peptide
+sensitivity analyses
+avian influenza virus infection
+cells
+IgG
+inflammation and hepatocyte injury
+intrathymic precursor
+DP
+inference on the posterior distribution of the root and internal node states
+Lys57
+another level of stringency
+H. Sweiti
+four SELDI peaks
+twisted conformations
+biotinylated BSA
+Serious Adverse Event
+Backward bifurcations
+indigenous case
+incorporation of miR-192 target sites
+Hong Kong
+higher
+Elevations in IL-6 and TNF-α levels in BAL fluid
+50%
+novel delivery system
+bandage
+HTT events
+host cellular machinery
+1 µg 7SK-as RNA
+other respiratory viruses
+decrease
+airway infection
+communicable disease control
+primates
+T. whipplei
+IBB-2
+2
+protein dynamics
+PB1 translation
+lymphocyte count
+Affymetrix Mouse Gene 2.0 ST Array
+Five
+experienced enacted stigma
+increased phosphorylation of JNK
+ELISA-based
+cognitive, motor, sensory and behavioral functions
+9
+carbohydrate binding
+8-and 10-fold higher
+Biosafety Level 3
+binding of GFP to 3A
+Sequence bias for HSV IRV formation
+DAP12 upregulation
+90%
+2.2%
+Sore throat
+cc-by
+561
+2,600 IU/mg
+>42.84 mmol/l
+Elaspol, CG inhibitor and AEBSF
+synthetic and biological
+VFA
+195
+Z-FA-FMK and E64d
+The remaining blood
+257
+random primers
+P04851
+Rhabdoviridae
+children
+0.8848
+20%
+432
+30 minutes
+a regulator of immune responses
+36
+antiviral drugs and testkits
+improve lung compliance and antiinflammatory capacity
+24-hour
+it also shares characteristics of macropinocytosis
+25
+In vitro biophysical and biochemical approaches
+0.8%
+native epitopes
+a committed Treg lineage
+Direct-zol RNA Miniprep Plus Kit
+IMPH2
+overseas contract workers
+particle size
+serum NGAL
+14
+2.5 × 10 5 cells per well
+de novo initiated RNA
+metabolic process
+GRASP
+NLRP3 and NLRP6
+PB2-Q591K and D701N
+cirrhosis, chronic heart failure and cancer
+induction of metal sequestration
+all of the NSCLC cell lines
+fever
+cleavage of prM
+activation of the Cdc42/p38MAPK pathway
+10%
+Bacillus subtilis
+vasoprotective/antiproliferative
+total duration of within-and between-group contacts
+green and yellow nodes
+5%
+Four
+2009
+H155T and Q156H
+MON601
+1-O-acylceramide
+metals, ceramics, polymers, and composite materials
+IL-10 expression
+salp chain
+PIV-associated LRI
+serum albumin
+20 minutes
+twice
+AD-4-and AD-5-specific mabs
+Staurosporine
+Two
+Kogan
+classify a range of different viruses
+crossreactive immune responses
+2 days
+196
+the number of indels
+Pneumonia
+Ten-fold
+dsUAR
+S. maltophilia
+mathematical modeling
+Cldn2
+the timeline would be shortened
+Antigen sparing
+1:10
+inhaled
+156
+The Journal of Infectious Diseases
+20 min
+LTBI
+action of molecules with known bioactivities
+mycoplasma
+81,000 to 138,000
+Interleukin-6
+Baloxavir marboxil
+Kuan-tzu
+between October 9 and October 21, 2011
+if all the following conditions were satisfied
+L pro catalytic activity
+c A and c S
+inverted membrane curvature
+peak protective function of antibodies
+enhances cell growth and tumor progression
+control for input virus carry-over
+oxygenation
+Cytokines
+high amount of contact between the disinfectant and virus particles
+aging, cancer and disease
+cardiothoracic ratio
+narrow-spectrum penicillin
+Site-specific cancer incidence and mortality estimates
+bioassays
+The acquaintancies
+increased almost twice
+a potential antigen based immunodiagnostic assay
+SWB and physiological health
+SilSOS Femme
+thirteen
+12
+NASA
+Excel
+Acinetobacter baumannii
+rVSIVs expressing tibrovirus G glycoproteins
+supernatants
+TLR4
+Phe
+Leica Bond RXM
+Antimicrobials
+GII.4
+6 days of infectiousness
+cleavage of trans peptide by chymotrypsin
+Epidemiology
+a third
+Metal binding to the engineered protein
+sepsis
+diffuse and bilateral ground glass opacities
+Efforts to improve nowcasts and short-term predictions of influenza activity
+Glycerolyte 57
+3x10 7 plaque forming units per ml of media
+a pair of fluorescent probes placed in close proximity
+Neuroimaging
+To clarify the cellular localization
+Indexed samples
+viral and cellular
+Parameters
+over 200 arthropod associated viruses, microbes, and metazoans
+SPARK and SYP
+nine
+2.2 log 10 copies per millilitre per day
+University of Utah DNA/Peptide Core Facility
+H7N9
+140
+HTs
+Transcriptor First Strand cDNA synthesis kit
+metagenomics
+GC12
+adequate porosity and pore size
+oncogenic
+ABCA1-mediated sterol efflux
+Tanzania's South-Central region
+2013
+3,651
+3 years
+respiratory infections
+fibromyalgia and osteoporosis
+85%
+2009-2010
+dual coding with error mitigation
+high molecular mass and low chemical stability
+Affymetrix
+37 °C
+distinct resting cytokine profiles
+non-AMA1 IgG
+SPSS software 13.0
+Silybum marianum
+HSF1
+442
+Disability weights for alcohol use disorders
+44
+2x10 4 MDCK cells/well
+twenty-five
+total incidence data
+Three
+dendritic cells
+Private possession
+Fig. 6
+AmBisome and Abelcet
+antibacterial prophylaxis
+20 to 61
+ADMA9
+Quantification standards
+higher
+Random fragments with 39 A tails
+1h
+Phagocytic
+below 10
+More than 2 million
+onechild policy
+virus isolation, electron-microscopic observation and serological tests
+progressive disease
+Information regarding the origin of poultry
+Toll-like receptor 4
+FRC
+90%
+Hepatocellular carcinoma
+64.9%
+further investigations
+AlexaFluor-594 secondary antibody
+disruption of the PS
+lung innate immunity
+5.6%
+proteomics studies
+H-7100 transmission electron microscope
+GRASP
+February 2009
+circulating monocytes
+phage-display experiments
+five
+access to patient clinical data
+23,000
+VAP
+40μL of CellTiter-Glo 2.0
+macroaggregate filter
+Niemann-Pick C1
+ImageJ
+ATCC
+1%
+4.5 mM
+100%
+36,073 bp
+labor-intensive methods of production and limited manufacturing capacity
+An enhancer
+reduced exhaustion of the stimulated T cells
+Purified MT145K sample
+17 s
+5%
+aminoacyl-tRNAs
+Genomic DNA
+6916 ± 8934 IU/ml
+population density
+1.6% to 2.4%
+Visual cues
+cleavage with factor Xa restriction
+a laboratory professional
+TSB and TSF extracts
+5% below the non-NPI period mean
+GFP localization
+expression of the mouse IFN-l receptor
+10.3 per 1,000
+IIV and LAIV
+Campylobacter jejuni and Salmonella enterica
+solubility
+100%
+the environment
+physicochemical
+NaBH 3 CN
+when failure to ventilation strategy occurs
+Murine leukemia virus
+morbidity
+HeV-specific sera
+Degenerative
+several origins
+Proteoform intensity
+MDCK cells
+rotavirus
+GMP
+isotocin
+AM2
+28%
+8
+Roma Today
+TRIM56
+IL-35
+A four-fold rise in MAT titer
+more FcRn-dependent transcytosis
+E2-A162 residue
+biologging devices
+minimum CI
+prediction of future disease severity
+ARV
+Subversion
+MG planning and/or operational processes
+laminal secretion of peptides and amines
+peptide library phosphorylation data
+15N and 46R
+NS3/NS3a
+published data sources on pathogens, their hosts and geographic ranges
+pCI-neo and pmCherry-C1
+Innate lymphoid cells
+telephone help lines
+pigs
+27%
+Inspect3D
+dephosphorylation
+ten
+detachment
+indirect
+bystander damage
+ligands and receptors
+using willingness circled on a 6-point scale
+47
+five
+a known contact between a first case in a family and a previous case
+ARDS
+Three
+20µW@8Hz
+glycyrrhizin
+cross-protection to heterologous infections
+41%
+Hantaan
+I. scapularis
+every 2-3 days
+53
+Pandemic Hospital Based Surveillance
+50%
+IL-1β and IL-6
+sumoylation and phosphorylation
+7-and 14-day-old
+the protection of pathogens against alcohol-based disinfectants
+bacteria
+SuperScript III Reverse Transcriptase
+I 3
+immunologic escape
+1 μM
+three
+2009
+Codon adaptation index values
+HSB colorimetric space
+non-severe pneumonia
+intracellular pool of protein
+recombinant BmNPV
+futility
+the error increases in proportion to the magnitude of the initial statistic
+Monoclonal antibodies 6D11 and M2188
+Instant Blue Coomassie-based solution
+Student's t test
+2016
+Enlarged image of yellow box area
+79%
+one RFID tag
+12.5%
+amplification product sizes
+a GCN4
+direct infection of oligodendrocytes
+SpO2 analytics
+lipid rafts
+moderate
+neuronal survival
+extract from total lung
+controlling the assembly of regular-shaped viroplasms
+a protective phenotype
+Single-particle analysis
+specific symptoms and symptom-onset
+600 to 15,000
+nicked DNA and nuclear chromatin condensation
+cc-by
+proinflammatory
+742
+active-site glutamic acid
+Review level evidence
+122 665
+IRF2
+hepatoma cells
+hepatocytes and bile duct epithelial cells
+VeriKine TM Mouse Interferon-β ELISA kit
+Altered protein turnover
+~2000
+K48-linked polyubiquitin
+Strand-specific PCR
+symptomatic relapse of a prior infection and infections first appearing on ART
+FR
+truncated
+IL-6
+five
+suicidal ideation
+CD11b, TLR2 and TLR4
+LDL
+2 days
+reduced duration of mechanical ventilation and stay in the ICU
+urea powder
+pH-assay
+3000 × g
+H9N2-subtype
+barrier procedures
+single cell suspensions of lung and spleen tissue
+Cervical tissue
+Strain-specific real-time RT-PCR assays
+examining a range of scenarios ahead of time
+sterile immunity
+LELs
+native-like Env trimers
+Kevin T
+54
+pattern of mutation
+QPCR
+CEACAM1-S
+one
+300
+fusion of the autophagosome with the lysosome
+lysosomotropic alkalizing agent
+Astacin metalloproteases
+an amyloid coat
+decreased
+higher NC uptake
+Autoregressive models
+porcupine bile
+EBOV antiviral therapy
+P gene
+epidemic extinction
+λ i
+whether the respective approach was evaluated in this paper
+developing the data collection infrastructure
+arginine
+Basic Local Alignment Search Tool
+AR expression
+T7 RNA polymerase
+psychological distress
+DC-SIGN and L-SIGN
+52.0, 108.3 and 194.7
+contact with pilgrims
+1994-2004
+one point
+NK cells
+30% to 60%
+7.4%
+over 90 million
+cold stress
+13%
+systematic multisite clinical studies
+A/H3N2
+drug delivery assessment and analysis
+live poultry
+social distancing behaviour
+runny nose, sore throat and cough
+101
+30 mg
+1.5 weeks
+Reagent-based contamination
+Necrosis
+glycoproteins
+10,000
+28
+associations between specific genetic variants of the Y chromosome and hypertension
+contacts between individuals or computers
+memory T cells
+RHDV
+9%
+HCC recurrence
+exenatide
+r
+viruslike particle production
+MALDI-TOF mass spectrometry
+5-7 days
+LPS-induced ALI
+1:1
+important clues to the identity of the differentially expressed gene
+bacteriocins and hydrogen peroxide
+preclinical and clinical studies
+NOXoriginated DCFH
+J. L. R.
+it demonstrated the lowest level of bacterial removal
+senescence
+TLE6 mutation
+FD Rapid GolgiStain Kit
+Extensive wash
+enzyme-linked immunosorbent assay
+MOV10
+a depression of the AKT/mTOR pathway
+all known and putative sialocatabolic functions
+host factors
+Chinese and Korean
+six
+the National Health Commission
+The fluid chart
+Th1-mediated
+15%
+IL-1 receptor-like-1
+rapid fluorescent focus inhibition test
+data-driven methods
+GraphPad Prism
+33%
+AgaS
+three
+information service hotline
+IL-1 receptor type 1
+earlier stages
+$200
+mechanisms
+roots
+severe osteopenia
+gallic acid
+T. gondii rhoptries
+2000
+fever
+religiosity and political extremism
+Guangdong
+IAV replication
+Information
+Ozonation
+three days
+the slope of the curve in its linear portion
+piglets
+ewe372-H1-W and ewe375-D4
+187
+Model-based statistical methods
+250 ng/l
+two
+Protein misfolding cyclic amplification
+SL1-5
+Southern Medical University Ethics Committee
+SUMO peptidases
+67.6 years
+hypoferremia
+index hospitalization events and post-discharge events
+an approach
+viral vaccines
+Human MIF
+A588V
+translational recoding
+25%
+electronegative
+group G rotavirus
+protein and Env
+12 h
+Exposure dependent weights
+10%
+FOXO3A
+388
+viruses
+30-50%
+respiratory health of farmers
+CD40Lmediated apoptosis
+stromal cell-derived factor-1
+Cellular immunity
+Waterfowl parvovirus
+methionine or cysteine
+abrogate functional regions and cell signaling pathways
+some level of population structure occurs locally in the genome
+over 300
+PCR on the 16S rRNA
+ATP
+airway epithelium
+Bulgaria and Serbia
+fluorescence microscopy
+þ1 frameshifting
+Twelve
+many participants
+5
+severe disease
+ACAM2000
+560/mm 3
+acyclic analogue of guanosine
+granzymes and perforin
+b-protobacteria
+class D oxacillinases
+introns 5 and 7
+χ 2 test
+false positives
+A thorough analysis of HLA-type
+49 kDa
+Tween 80
+LPS-induced macrophage activation
+one or more tagged CTB subunits
+$2.7 billion
+immunocompromised patients
+69
+herbal
+624,472
+bias
+5%
+amino acid substitutions
+cyclin d1
+Lymphocytic Choriomeningitis Virus
+West Nile virus and Dengue virus
+220
+HCV core protein levels
+imidazole
+P. falciparum 3D7 parasites
+5.73
+λ max
+Utah State University Laboratory Animal Research Center
+by adding more edges over time
+summary
+Jack-knife
+two hours
+Sindbis
+Salicylaldehyde
+intestine and lung epithelial cells
+ECMO
+ORF50/RTA
+Aldosterone
+Lactobacillus
+training
+53
+LigT
+eIF6
+Origin
+Prevnar13®
+overcoming IFITM3
+80%
+Haptoglobin
+cytopathic
+genetic exchange communities
+retrospective analysis of the data
+biosynthetic process
+Costar half-area high binding assay plates
+Colorimetric
+indicator chemicals
+epidemiological
+30%
+timely infant testing
+diametrically opposed
+13
+Porcine epidemic diarrhea
+a demand expressed by commentators in debate surrounding GOFR
+Wild-type mice
+in-house in sterilized cages
+Preferential mixing
+direct effects of radiation on pathogen survival
+GP
+intravenous peramivir
+Hendra virus and Nipah virus
+Microscale thermophoresis
+a vibrant and well-prepared health system
+dropped temporarily
+flow cytometry analysis
+intrathecal production
+Hydrophobic interaction chromatography
+innate immune system
+viruses belonging to GI and GII
+Two
+keeping the force needed to unwind the type 1 rod within a narrow range
+Q162R-S170T
+robust cellular immune responses
+multiple PrfA-dependent promoters
+lethal disease
+clinical
+ring-like
+15
+embryonic development
+decreased signal-to-noise ratio and dynamic range of the assay
+combustion of organic materials
+autoimmunity
+Maintaining the structures of D and E domains
+BeWo cells
+standard deviations
+seven days
+multidrug resistant
+Phe388 at the coil and Tyr398 at the helix
+Data
+AEC 1340 and 1390
+depletion of CD103 + DCs
+40 min
+more than 100
+new agents
+11,661
+DV1 E glycoprotein
+5% BSA
+development and maturation of the ovary
+two
+inhibits DDX58 signaling
+Threeto six-day-old emerged female mosquitoes
+berberine and palmatine
+antiviral host defense
+2CLP and SO rats
+adaptation to the human immune system
+increases
+Thirty-six
+IRF3
+vesicular stomatitis virus glycoprotein expression plasmids
+FIV
+HIV-1 Assay
+laminin derived peptide
+Seventeen
+240 million
+27
+IFN-ω
+Screening and recruitment
+2-3 weeks
+Brefeldin A
+14 and 60 D.P.I
+0.50, 0.98 and 0.66
+F80L
+four
+interstitial lung space
+Tat and oligoarginine peptides
+E. ovinoidalis
+TBSV accumulation
+overlapping ORFs that are larger than expected by random chance
+293T cells
+Patients with pneumonia
+stacked and partially helical
+ethical dilemmas
+R A and R P
+250,000 to 500,000
+three
+enhanced susceptibility toward infection
+suitable search terms
+biomarker profiles
+scrambled or MINK siRNA
+absence of marker-QTL association
+5%
+a reference set of CDSs
+hydrophobic
+arginine and lysine
+dated samples
+2000
+Sialyl-Tn
+hospital staff and general practitioners
+48,000
+Sapovirus
+4 • C
+Major histocompatibility complex class I molecules
+ViralORFeome
+Marrow
+NS3 protease
+standard methods
+hepatitis A
+42
+minus-strand
+220C
+a robust immune response
+US11
+residual inflammation
+HIV, SIV, and MoMLV
+greater generic conspiracist ideation
+95%
+83
+GlcNAc
+sedative
+helicase activity
+PCR
+Newcastle disease virus strain NA-1
+autoimmune diseases
+50μM
+2
+Speed-fidelity trade-off Trade-offs
+Cotia virus
+one
+Residue-and surface-based tools
+100 mg/kg
+10
+PureLink PCR Purification Kit
+Zeptometrix Corporation and SeraCare Life Sciences
+silent rDNA repeats
+development of antibioticresistant bacteria
+cells
+three
+The funders
+a scaffolding structure
+5
+rodents
+transmission rates and population densities
+individuals
+11,000,000
+mutation bias
+10.3%
+heterosubtypic
+0.05
+supernatant
+infarct volume
+robust
+Odyssey Infrared Imaging System
+HBoV1
+Seven
+78.3%
+measurement of CLABSI
+TMEV-infected mice
+10%
+30 min
+neurons
+5 µM
+pET-28a-NDM-1
+two
+95%
+DPPC
+Four weeks
+intraspecific
+CycleQ30%
+T20-resistant
+lumens
+mechanical ventilation
+30.2%
+Total limb paralysis
+0.788
+0.704
+Mfold program
+Aviparvovirus
+complex
+30
+dementia and musculoskeletal disease
+14p1
+predisposition from environmental stressors
+a huge repertoire of targets
+6
+two
+directly acting on viral proteins
+REV
+single-gene assays
+antioxidant, anti-inflammatory and anticancer
+medical and nursing
+106
+true concentration
+similar expression profiles
+reinitiation after termination at the end of sORF2
+6 hr
+chimeric MNs
+rAAV9
+ectomycorrhizal
+hydrodynamic transfection
+chemiluminescent drug screen assay
+Cells
+Pulse oximeter
+antiviral
+November 2004
+welltolerated
+a hygromycin-thymidine kinase fusion gene
+30 min
+movement restriction
+influenza-induced lethality
+k i
+MOPV infectious particle production
+display of folded proteins on hybrid phage
+290
+functional groups of various amino acids
+between 2009 and 2010
+97.2%
+2017-04-13
+Traumatic hemorrhage
+1-5%
+ephemeral local secondary structures
+,20-fold
+5%
+P<0.05
+100% confluent BSR cells
+~50-60 kD
+fungal
+discrete-time and continuoustime models
+F-α, IL-1β, and IL-6
+Viral oncolysis
+three
+toxicity
+stimulating the growth
+High binding affinity and stable binding of peptides to MHC in vitro
+60 years and older
+55% and 64%
+ARIMA model
+Basic Local Alignment Search Tool
+Genetic diversity
+RNA stability selection
+within 10% of the true value
+remdesivir and chloroquine phosphate
+Input module
+ImageJ
+the range of the CBI
+Web of Science
+UV spectrophotometry
+HeLa cells
+Confusing word choice on when a person with EVD is contagious
+100 mM EDTA
+encoding both VP1 and VP2
+Type IIB von Willebrand disease
+phylogenetic
+human and animal funding sources
+its incorporation into virions
+transitivity
+school curriculum
+BPD
+HSES
+0.83
+133
+2-5 days
+PaLung cells
+40%
+Surface plasma resonance
+the nucleus
+sulfuric acid
+twice per day
+Contaminating RPL2
+Five
+10
+Contrast levels
+7 days
+bird, equipment or people movement
+homogeneous monomeric and stable particles
+pigs
+Cancer metastasis
+Five million
+pandemic
+jawed vertebrates
+visual inspection
+working adults
+Favipiravir and 2'-Cmethyl-cytidine
+Dualmembrane kit3
+entomopathogenic
+PBS
+10 mg of monomethoxypoly glycol
+bolus
+twice
+Deacetylation by SIRT7
+HHV-6 activity
+PEG-it Virus Precipitation Solution
+85˚C
+Blood samples
+field-based epidemiological investigations
+VV-Gag
+MiRNA
+Hepatitis C Virus
+Fourier transition method
+Disease-related proteolysis
+general
+coevolve
+population health
+Ten
+variable region
+HA-mediated membrane fusion
+50%
+biomarkers
+Table 2
+120 min post-feeding
+rare
+poor results
+three
+short term transfers in culture
+27
+Vero cells
+insurance cover
+39%
+microglial-derived proteases
+Antioquia, Colombia
+PAN packaging into virions
+gamma, lognormal and Weibull
+embryonic development and metabolism
+actin polymerization
+Transcriptome
+density gradient centrifugation
+8-10%
+RNA bases
+Third party
+RIPA Buffer
+production of mitochondrial reactive oxygen species
+CsCl gradients
+naturally occurring hepadnaviral infection
+ORF3
+10 min
+neurogenesis
+four times per day
+Blood samples
+0.999
+cytokine responses
+mortality, myocardial injury and renal injury
+Crohn disease and other intestinal disorders
+Public surfaces
+PKA
+septic shock
+health workers
+avoid treatment and testing
+Ficoll-Paque density gradient
+multiple logistic regression
+Excel
+Biomek FX
+membrane permeability of the cytotoxin
+virological synapse
+1-3
+between 4 and 6 h
+Mann-Whitney U test
+broad fitness costs
+A73
+44/12
+Marked CpG deficiency
+effort
+environmental cues
+21
+Smad6
+Nup98, Nup153 and Nup62
+Strain IC6010
+Firmicutes
+ENC
+beta cells
+PKC activation
+60-70%
+normal lung cells
+RNA structures typical of À1 PRF stimulatory elements
+infected hepatocytes
+individual, host species, virus biotype, dose and route of infection
+total cellular RNA
+Macrophages
+Infection Section
+simple stochastic models
+dendroscope
+Parainfluenza virus type 3
+howler monkeys
+Leishmania infantum
+increases
+Phase III
+Ten
+physical splines and virtual connectivity
+IRF7, IRF9, and ISG15 mRNAs
+real-time PCR
+T reg proliferation
+5 days
+four
+helpful
+≥60 days
+NH/P68
+phenol/chloroform
+MTCP1
+linear
+DENV
+Specificity
+contact with infected respiratory secretions
+statistical analysis
+trnK gene sequences
+National Healthcare Group Domain Specific Review Board
+18.3 μM
+immature virus particles
+they cannot correspond to the number of genes
+self-protection with protective gear
+B cell clone
+88%
+External elastic lamina area and lumen area
+Plaques
+Indirect ELISA
+3421
+30 min
+CAA severity
+1000 simulated series of 20 consecutive seasons
+Two
+decreases
+92.6%
+Endosomal
+general oral examination
+Inhibitor-B kinase ε
+Oral administration
+Zymo Viral RNA kit
+Quantity one v4.4
+did not affect NMD-resistance
+the toxin
+oseltamivir phosphate
+DNA methylation
+plateau pressures or driving pressures at the initiation of mechanical ventilation
+graphs proteins
+Enrichments at specific chromatin loci
+13 years
+decreased
+stereotypical changes in gene expression
+apoptosis
+anti-inflammatory effects
+Hepatotoxicity
+33 mM of the b-gal substrate C12FDG
+Table S2
+disease severity
+1282
+temperature, humidity, and atmospheric pressure
+Herpesviridae
+higher
+silicon, inorganic glass, and ceramic
+elevated exposure to carcinogens or infectious agents
+963
+flies
+40
+Quanta
+25
+cerebral infection or septicemia
+three
+One hundred microliters of PBS
+IPO-Me-Glc
+lyophilized aliquots
+M3
+1062
+metabolic
+Multivariate logistic-regression models
+Synplot2
+breeding conditions in lab facilities or interactions in an ecosystem
+cough, coryza, or conjunctivitis
+3D
+a viral recognition module
+R 0 = 1
+80%
+disruption of viral membrane
+Met and Thr
+significantly increased
+80%
+when free isolation units become available
+nanodrop measurements
+Cu 2+ antioxidant enzymes
+cell metabolic profile
+binding of an 83 kD form of PA to specific cell surface receptors
+1 hour
+more collaborative research efforts
+TLR2 and TLR4
+48 h
+GA-mediated
+Human rhinoviruses
+1%
+diffracting
+2 weeks
+recurrent hepatitis
+Vaccines
+daily
+100%
+chest computed tomography or bronchoscopy
+peptides
+Communal surfaces
+21%
+phosphopeptide meta-analysis, correlation network analysis, and literature mining
+respiratory failure
+2 min
+389
+two
+close monitoring and fluid management
+MDCK cells
+Corticospongious
+Primers specific for each of the ISGs
+DNA damage
+cross-species transmission
+no methylation
+high attack rates, several waves of infection and high mortality in young adults
+over 100
+To replicate in the cytoplasm
+Miltenyi gentleMACS™ Dissociator
+HotKnots V2.0
+Inositolrequiring enzyme 1
+7 days
+Delivery to the lungs
+19
+OVA-specific plasma IgE and IgG1
+large-scale production of IgY in chickens
+interference of the space structure
+Mitophagy
+Mean dot signal intensity
+spermatogonia and Sertoli cells
+CXCL5
+14
+confocal microscopy
+similar redistributions of LysoTrackerpositive endosomes
+1 ng/ml
+9%
+host protein synthesis
+IFN-γ
+2570
+mutation pressure
+Type I rat tail collagen
+ELISA configuration employed
+9 May 2009
+CCHFv expression
+Spearman rank correlation analysis
+Three
+PR8
+FBSM
+three
+Epithelial cells, macrophages, DCs and neutrophils
+Dr. Bin Wang
+CCHFV OTU
+NS5
+2 h
+contact tracing, ring vaccination and quarantine
+1000-fold
+Balifase
+Twenty six
+6
+7 days and 11 days
+neutrophils
+tRNA levels
+AusAID
+4%
+NS1
+cap 0
+An identification of commonly regulated proteins in tumour and sera
+angiotensin receptor blocker
+eLife
+VN and local IgA antibody responses
+cross-protection to heterologous infections
+QuantityOne
+Purified GST and Nus
+few strains are concurrent in time
+The knot
+4,570
+67%
+eIF4A
+thirteen
+comparative study
+research on regular and random networks
+adipose-derived stem cells
+5%
+One hundred and forty
+unbiased measurements of intra-network gene expression and fold-change ranked segmentation
+circulating IgM
+mediation analysis
+antibodies to viral protein PEDV-N and actin
+Influenza virus A/Anhui/1/2013
+a ring of perithecia
+Buffer-based eluants
+24 h
+Influenza A H1N1 infection
+the planning process
+avian influenza
+increases
+an N-terminal six-histidine tag
+UV-responsive
+regulatory molecules
+Immunoreactive proteins
+individuals with schizophrenia
+EMCV and picornaviral IRES
+MassTag PCR
+spatial heterogeneity
+herbal medicine
+Short chain fatty acids, propionate, butyrate and acetate
+45uC
+Culture-based assays
+ABCE1 and ATP
+the period of febrile, hypotensive and oliguric phases
+vasodilation, antigrowth, proapoptotic
+signalling
+frequency doubling
+3.5 h
+lack of specific data
+12
+nanS
+Six
+60%
+NFE2L2
+the approach taken herein
+six
+Caspase-Glo 3/7 Assay System
+mouse anti-Flag Mab or rabbit anti-MYC Mab
+RNA hairpin not capable of stimulating À1 PRF
+purple formazan crystals
+HAV-infected cells
+threenucleotide ID
+t* = 50
+four
+MAVS
+HSV-1
+six
+À8.16 kcal/mol
+multiple viral infections
+Laboratory data
+11
+day 0 and day 42
+urban centers
+zero
+nine
+multicollinearity
+controlling the movement of both live poultry and avian products
+Influenza vaccination
+86%
+chromosome 7
+15 min
+pore cut offs of 35 nm
+10 to 7 days
+Chinese journals
+MAGT1 and TUSC3
+high probability
+The CSN
+differences in the genetic background of the host and parasites, and transmission rate
+AT1 and AT2 cells
+45.8 T 14.1%
+1437
+CT or TT IFN-λ3
+statistical analyses
+0.052
+17
+their subsequent evolutionary course
+P2RY12 expression
+diseases from breaking out
+RIG-I agonists
+filovirus IgG indirect ELISA system
+MTT
+expansion of tick populations
+ethnic heterogeneity
+codonW program
+3 H-thymidine
+TNFα promoter
+3k sequences in D
+694
+W10 and W35
+bilirubin and coagulopathy
+reactive antibodies
+Mawell
+UV-Vis Spectrophotometer
+63%
+microenvironment
+LN CD4 + T cells
+Airway hemorrhage
+evolvability
+prevalence
+JEM-1230 electron microscope
+three
+decentralized
+30 pmol
+480-490 nm
+Tfrc
+1 hour
+ECM genes and their miRNA and lncRNA regulators
+subcellular proteomics
+individual written consent
+Modifications
+egg yolk immunoglobulin
+pulling speed
+promiscuity level
+S 2
+Shapiro-Wilk test
+typical dinoflagellates
+Colubridae
+ub j and lb j
+r s ≡
+Rectal temperatures
+The FAMlabeled unselected ssDNA library
+blood
+Hepatitis B virus and hepatitis C virus
+90%
+fingerprint-and histogram-based methods
+7 groups
+binds and sequesters ISGylated viral proteins
+Equation
+Serum
+Immunofluorescence
+antithrombotic
+bone marrow of pigs
+putative chIFITM1
+95% confidence intervals for predicted arrival date
+Four
+H5N1
+Live poultry markets
+make
+bird
+30 minutes
+stem pocket-directed BnAbs
+Cellular and humoral
+IL-7
+targeting HSV-1
+50-100 million
+36-84%
+benign situation-related seizures
+2 h
+Special interest groups
+CD11b expression on the neutrophils
+GHx 9-11 CxCGx 2 GxE
+two
+security and law enforcement
+taking pharmaceutical antiviral medications and seeking medical help
+50 μL of Dual-Glo Luciferase reagent-1
+a reservoir of influenza
+PRRSV nsp2
+HIV-1 entry and replication
+alternative and complementary
+29%-78%
+Beckman AMPure solid phase reversible immobilisation technique
+1,759 bp
+15 min
+insight and to work effectively
+132
+pBS/U6-IL8
+MSFsc
+21
+luciferase assay
+vaccines
+Universal Probe Library
+AMPKα1/SIRT1
+PK-15 cells
+120/100,000
+two
+T-cell-secreted cytokines
+NAbs
+GC content
+image J
+12
+wet lab validation
+Irgm1, Usp18, Trim21 and Trim30
+PEG conjugation
+Activation
+the first variable
+P. aeruginosa and Burkholderia cepacia
+200 cells/microL
+virus dose and vitality
+Fifty percent
+spatial homogeneity coefficient
+HDV
+23
+Warburg effect
+antiviral efficacy
+QIAamp viral RNA mini kit
+Administration of blood products and fluids
+mining of cryptocurrency
+48 h post shRNA transfection
+30%
+conformation dependent
+60-90 mg frozen lung tissue
+ELISA
+IFN-β
+Operon Biotechnologies
+the period used for fitting the exponential curve
+metagenomic analysis
+plasma biomarkers
+BTV
+Diapause
+945 nt
+tracing of contacts of contacts
+signaling pathways involved in lung development and/or maintenance of adult epithelial cells
+Ten
+host cell caspase activity
+1-7 114
+late-stage
+Seven days
+Candida Genome
+2 2DDCT method
+Twenty-four hours
+Three
+three
+ActA
+higher
+Nanolight Technology
+-AA mutants
+the protease and the active sites
+inter-individual variability
+purchasing power parity
+oxidative stress in hepatocytes
+Baculovirus
+six
+proximal
+agar diffusion method
+Ebola
+flow cytometry
+structure
+1%
+b-Hairpin mimetics
+when running the eight models
+1 year
+G1 generation
+proteins
+three
+2006
+50
+Monitoring HCWs' health
+Macrophages
+Waterbirds and granivorous passerines
+A score ≥ 2
+beta-galactosidase expression
+Chinese or herb* or traditional or plant or medic*.
+direct contact with contaminated respiratory, digestive, and urinary secretions
+143
+triggers of physiological processes
+72%
+seven
+anti-malarial vaccine
+dose 2
+high loading capacity
+tetherin antagonism
+ER stress
+three
+manmade
+noise
+antigenic drift
+end-expiratory
+half
+4,710
+Lack of 2=-O methylation of the cap structure
+purified virus stock
+National governments
+Epichloë
+404
+the next step of Illumina HTS
+heme
+Parameter sets having higher or lower values of AR or SAR
+Airway driving pressure
+NHPs
+MAGT1 and TUSC3
+liveattenuated influenza vaccines
+10%
+The DDR pathway
+Parameters of hemodynamics, blood gases and lung mechanics
+αβ + T-cells
+9.8%
+Fluview
+India
+feral colonies
+I
+migrated faster
+>1 billion
+log dilutions of ZIKV
+studies of human infectious diseases
+accuracy
+see doctors
+contacts with bird secretions or droppings
+rA2-GC4
+88
+carbon and nitrogen
+research strategies
+ATG5
+viral invagination
+Ingenuity Pathway Analysis
+40%
+FIV replication
+Epidemic forecasting and prediction tools
+42
+yellow fever and dengue
+NF-κB and AP-1
+154
+10
+polymers
+inhibitors in the extracted DNA templates
+smoking and alcohol consumption
+Mobile phases A
+100 mM fusion inhibitory peptide
+369
+2001
+Escherichia coli DH5a
+Crohn's disease and ulcerative colitis
+Sequence Read Archive
+social contacts
+Knockdown of Sec16B and core COPII components
+72 hours
+a decrease in enthalpy
+viral sequences of genotype S6/L3,18
+dynamic light scattering
+4uC
+by counting fluorescent cells
+FAT10
+variability
+Guangzhou Municipal Exit-Entry Administration Office
+Mutschler and colleagues
+256
+subnetwork analysis
+nearly 7000
+50-60%
+1%
+5
+0.2 to 7 g
+Dinucleotide SSRs
+viral antigens
+cell morphology
+Mastitis
+to block the EDIII-mAb binding
+immunostaining for surface HA protein
+Sapienza University
+secondary infections
+850 cm 2
+229
+the solution to the Euler -Lotka equation
+Fourier transform infrared
+miR-208a potential in contrasting DOX cardiotoxicity
+four
+A reliable risk model
+early aggressive therapy
+time to resolution of cough
+autophagy flux
+how many individuals are infected
+high scoring hits
+92%
+10,049
+35%
+minor residual catalytic activity
+24 h
+isolation history
+SIRT7-mediated deacetylation
+11 months
+moral
+evolutionary dimension
+2390
+increases both the number of cases within each country and the respective outbreak probability
+114/60 mmHg
+PhyloD
+1,200,000
+lungs
+Mx3005P or ABI7900 thermal cyclers
+calculation time
+92.3%
+MjsvCL
+predicted infections
+parasite
+95%
+over 40
+1811
+29%
+decreased cell viability
+SD rat
+Hepcidin
+patterns of substitutions between species
+regulatory circuits which mediate metabolic responses
+hyaluronidase
+avian-like swine
+nine
+A transition
+three
+positive selection
+H7N9
+ImageJ
+Methods
+CICs
+QIAmp virus RNA mini kit
+National Institutes of Health Rocky Mountain Laboratories Animal Care and Use Committee
+mechanical ventilatory support
+standard descriptive statistics
+siRNA screening
+high OPV-DNA loads
+ARDS Network low tidal volume protocol
+the corresponding author
+165
+adjuvant
+Insertional mutagenesis
+IL-6 −/− lung fibroblasts
+rs1130866
+flow cytometry
+non-nucleolar
+driving pressure
+lack of a suitable receptor
+acidification of the cytosol
+location for activities
+H. volcanii strain
+rosuvastatin
+1946
+TLR3 and TLR4 mediated signaling
+all base-pair combinations
+TCA
+Poractant alfa
+unique serial numbers
+demographic information as well as distance typically travelled to school or work
+bacterial
+Dichotomin A
+a shot of a defensin expression construct
+Cxcl5
+interaction of GP with the endosomal receptor NPC1
+seven
+Platelet aggregation
+metabolic endotoxemia
+four
+knockout and wild-type mice
+Human influenza hemagglutinin
+Larger clinical trials
+trafficking of EBOV particles to NPC1 + endolysosomes
+Reed-Muench
+Tasly Pharmaceutical
+four
+inability to confidently ascertain admission dates from outside hospitals
+rabbit anti-pigeon IgG
+a pNA-attached trypsin substrate
+Five
+Bregs
+age and gender
+217 nm
+vSS1, vSS2, and vCC1
+myelin proteolipid protein
+11
+public schools
+Statistical Package for Social Sciences software
+B. thailandensis
+coal burning
+11 years
+three
+ESC self-renewal
+lack of clear sequence similarity
+more than a century
+16
+differ
+splenocytes
+increases resistance of macrophages to HIV-1 infection
+HCAP
+Gender
+MS² spectra
+vascular endothelial growth factor
+germinal center B-cells
+general transcription
+Claudin-1 and occludin
+2 h and 15 min
+numbers per 1,000 patient-days with 95% confidence intervals
+Decoration of the nanoparticles surface with targeting molecules
+novel strategies that are independent of host immunity
+Cervix cancer
+66 and 32
+Ubiquitination
+25
+human immunodeficiency virus
+130-170 million
+severity and mortality
+optimization of megapeptide design
+IL-10
+any other possible pattern
+The first two
+metabolic, hormonal and immunological
+1 week
+high functional avidity
+Inflammatory
+134
+40
+the sequence search space
+HBoV
+GTW15 and GTW16
+25˚C
+DNA vaccines
+unwinding duplex viral DNA at replication forks
+RdRp inhibitors
+liposomal aerosol
+One hundred fourteen
+one of the first furin inhibitors
+half-life
+inhibitory metal
+30%
+2.0
+room temperature
+expression of LPL pre-peak
+FcɛRIγ/FCE1A
+1 hour
+digestive
+331
+S. typhimurium ST49
+trained interviewers
+58 kDa
+13/3/2020
+Birds
+Kenya
+positive selection
+weather
+the nearest infected city
+cell surface HS
+seven
+improving national managerial capacity and human resource capacity building
+membrane and α-helices
+Hydrophobic interaction chromatography
+IRF3
+positive
+Pip2a and Pip2b
+Suqian, Nantong and Zhenjiang
+domains or individual positions critical to protein function
+disodium hydrogen phosphate
+P < 0.05
+regression of tumor at distant sites
+atypical PKC isoforms
+assessing the correlates of protection
+-slow and -gamma
+two
+3
+grey
+4.9 ng/ml
+three
+Exacerbations
+significantly
+0.5%
+Spinal motor neurons
+50
+positive feedback for RIG-I signaling
+The level of IgG or IgA
+serum triglycerides and PERC and TCA AUCs
+matrix metalloproteinases
+insomnia, depression, and anxiety
+2430 to 2454 nucleotides
+3 months
+2.84 g/mL
+indirect healthcare costs
+44
+duration of treatment of opportunistic infections
+Mammalian S-lectins
+The industrial environment
+fungi
+single nucleotide substitutions
+elevated FFAs level
+normality
+proteins
+negative
+65 μL/min
+Subtypes that can be neutralized by PN-SIA49
+the ER
+MAVS
+mink astroviruses
+stratified
+Amiya K. Banerjee
+Models
+apoptosis
+Leverage of a query chemical
+1.7 million
+determinations of biomarkers in clinically accessible fluid compartments
+virus replication
+inhibits viral translation
+b k
+CE
+Amino acid exchanges
+Meta-Morph
+5 min
+1950s
+Intraperitoneal injection
+Hong Kong
+plerixafor
+45 min
+three
+elevation of in-circuit pressure
+urokinase
+mortality six months post-ICU discharge
+differences between the reference genome and sequences in the viral sample
+SIR model
+how much stool sample should be added into our assay
+Santa Cruz Biotechnology
+Norway
+six
+vaccinations
+10
+respect for the government
+Multiple models
+Amato et al.
+PGN N-deacetylation
+HBoV-1, 2 and 3-specific primer pair and probes
+iterative process
+experimental method
+AlphaLISA assay
+Coinfection
+nomenclature
+3%
+DENV2
+reciprocal
+ATCC
+A scoring system
+acute respiratory distress syndrome
+close to the value observed in the commuting flows
+20%-30%
+Calabrese and colleagues
+31 -80.5%
+fear of side effects and questions about its efficacy
+perfect complementarity between the miRNA seed region and the target
+Antiviral treatment
+statistical analyses
+0.85%
+peripheral blood mononuclear cells
+mTORC2
+630,000
+Tracheal organ culture
+mAbs
+cesium chloride density gradient ultracentrifugation
+moderate
+Dong Thap HRSC
+LDS buffer
+23-24uC
+Graphs
+5 days
+longitudinal
+Phenomenological models
+OR
+gammaherpesvirus-encoded lncRNAs
+pulmonary intravascular macrophages
+alleviating the pulmonary inflammatory reaction and increasing survival rates
+disease spread
+RSV
+influenza vaccination
+methods, models and biomarkers
+Virus-infected or mock-treated mice
+SYPRO Orange
+STING
+30%
+ECG
+9
+pknotsRG
+Being young and leading a healthy lifestyle
+Medical Research Council Guidelines of Good Clinical Practice
+targeting myeloid cells
+Clear and countable virus plaques
+exogenous MaMIF treatment
+drive the maturation
+decreases HIV-1 infection
+coordinated actin rearrangement
+larger sample sizes
+53
+viral fusion
+liver, spleen, lymph node and bone marrow
+chloramphenicol, ampicillin and kanamycin resistance
+Leica SP2 Confocal Scanning Laser Microscope
+individual patient identifiers
+BMP4
+canonical CDR H3
+Validated TaqMan assays
+Comets
+2 O 2 -induced degradation products
+#Gi
+ACE2
+Twelve
+Malondialdehyde
+2-4 h
+5 -end truncated and full-length U6 snRNAs
+98.4%
+Reduced gross and histopathological lesions
+supernatant
+immunocompromised
+farming
+patient presentation with acute, subacute, or recurrent DAH
+activating cytotoxic T-cells
+Plasminogen activator inhibitor-1
+Africa
+increased binding to liver tissue and/or increased dissemination to the liver
+Twenty-five
+swine
+immunity
+5 min
+elevated viral titers
+they can come for service
+hepcidin
+1.7 × 0.9 cm
+Common contaminants
+795
+Refractory hypoxemia
+a basic human right
+1971
+cholesterol and sphingolipids
+resistance against anti-retroviral therapy
+5'-RCGTG-3'
+E. coli derived K5 polysaccharides
+very high
+Cleavage of prM
+stability and reproducibility
+RNA viruses
+Table 1
+Cell Viability Assay Kit
+up to several tens of microns
+a unified and powerful management organization
+31 months
+Phylogenetic analyses based on env and gag nucleotide sequences
+newborn hamsters
+Pinellia ternata agglutinin
+mitochondria
+Mouse-passaged PVM
+severe brain pathology
+Diarylheptanoids
+ribosome density
+maintenance of high R t values
+mass and routine
+calibrated model
+destroy
+MBL
+a significantly decreased function
+JNK1/2
+hamsters
+NCK-8
+dephosphorylates pNPP
+passenger data
+lung injury
+gamma-tubulin
+Ab-Pak-Lah-01
+anthropometric
+ultracentrifugation
+IRF3/7 and NFkB
+1 mg/ml
+generalized linear model likelihood ratio test
+greater than 95% protection
+mortality
+2,2%
+accelerated mortality
+20
+pU/pLA
+49
+q n
+higher-order
+one
+1 × 10 7 cells/mL
+annual outbreaks
+virus infection
+they were few
+therapy
+PHYLIP
+membranes of damaged lysosomes
+DNeasy Genomic DNA Extraction Kit
+age, sex and severity of hepatitis
+10%
+intervention measures
+differences in perceptions of severity and susceptibility of diseases and vaccines
+Cell invasion through the extracellular matrix
+50.3%
+amplify a 340-bp amplicon
+x i
+liquid chromatographytandem MS
+three
+26
+Rottlerin
+models
+7.0
+Memorial Sloan Kettering Cancer Center
+six
+two
+Defective interfering genomic segments
+ssc-miR-30d_R-1
+100U MspI
+which variables related to COPD exacerbations should be investigated
+Vaccines
+Novel automated genomics and proteomics analyses
+lung epithelial cells
+viral reactivation
+immunofluorescence
+Supporting Information
+5 %
+cell surface HS
+Crossing the endoplasmic reticulum membrane
+9
+TRIzol
+a dietary flavonoid compound
+Coinfection with different HBV genotype strains
+Ciclesonide
+Processing bodies
+Ca 2+
+400 to 500 nm
+Protein kinase C
+Those publications which provided information on the numbers of cases, deaths or attack rates
+Poisson ratio of m ¼ 0.4
+July 2009
+geographically and culturally limited
+QuickChange Lightning Site-Directed Mutagenesis Kit
+cytopenias and infusion reactions
+two
+pre-processing, annotation, statistical analysis and data visualisation
+LptD or other important membrane proteins in other Gram-negative human pathogens
+a list of proteins for each gel band
+homogenous borders
+protective
+1 tachyzoite in PBS
+20 mL of 1610 8 cell/mL suspension
+HVR1
+ZIKV prME
+low-dose Ang II infusion
+200
+enhanced migration to draining LNs or apoptosis
+ISRE activity-luciferase reporter assay
+phosphotyrosine
+NMA, MD simulation, and NMR
+71.1%
+CypA
+11
+Type I
+Quantification of the current scale or nature of the AMR problem
+Inability to early identify patients who will fail NPPV
+36.7%
+SP-D levels
+total anti-virus Ig antibodies
+population size
+an early transient response
+Neprilysin
+anti-tumor activity
+geometry and surface charge of the structure
+antigen presentation to T cells is preserved
+hunting
+genome-integrated sequences
+24
+Hepadnaviridae
+airway antimicrobial immunity
+polyA-tails
+Student's t test
+11
+Flouroshield mounting media with DAPI
+Ammonia
+cotransfection
+PRO
+high specificity
+plasmid pYM-14
+ARDS
+the pathogen receptor
+100
+CD8 T cells
+Negeri Sembilan and Selangor
+USP7
+0.24 Å and 0.26 Å
+local community organizations
+food and water quality
+fibrosis development
+Ulceroglandular
+restricted CD4 and CD8 T cell epitopes
+biomass accumulation
+AIV and IBV
+protein-coding IFnL4 mrnA
+P < 0.0005
+Ded1p
+Four
+24 h
+phylogenetic
+Immunoblot
+SGW X-4 micro-melting point apparatus
+clinical samples
+Vaccination
+HBV-17 and HBV-19
+Phylogenetic relationships of the IBDV strains
+GP 1,2
+immunoblotting
+TNF-induced apoptosis
+Autophagy
+heart-lung machines
+sucrose gradient ultracentrigugation
+HIV and malaria
+Drug-target interactions
+Kenya
+mating and the production of spores versus yeast
+GraphPad Prism
+ATG12
+IRF9
+Cell counting kit-8 Dojindo Molecular Technologies
+EM Data Bank
+viral preintegration complexes containing HIV-1 Integrase
+1.6 million
+ESR1
+1.59%
+hyena food items
+Gram positive
+Living Image 4.5
+NDV
+Nicholas Evans
+three times higher
+passenger antigens
+six
+Adenovirus
+5%
+fiber damage
+Clustering
+RAD51
+influenza B
+red stars
+guinea pigs and ferrets
+SAXSquant 3.5
+self-report based
+PCR amplification of target genes
+16.2 and 18.3
+fetal lung inflammation, increased airway surfactants, and increased lung volumes
+NanoDrop 1000 spectrophotometer
+almost no reduction
+ddPCR
+0.13
+host cytoplasm
+lung tissue
+100fold
+antibiotics
+porcine
+aquaporin 5
+HIV/AIDS
+bioinformatic
+hVivo Services Limited
+K +
+Remote ischemic post conditioning
+antibody production
+mutation pressure
+8%
+serum
+72 h
+how to ensure that breathing is effective
+when the desired temperature is furthest from ambient
+404
+39
+HFMD transmission
+QuikChange Site-Directed Mutagenesis Kit
+GraphPad Prism V.5
+3 days
+controls
+age, sex, medical comorbidities, and obesity
+tick-borne and mosquito-borne agents
+update
+NADPH oxidases in phagocytes
+sACE2
+antiinflammatory
+bacterial binding affinity
+delayed patient care, patient safety concerns, and delayed system implementation
+most common
+497 to 1140
+6 months
+100%
+10
+Glycyrrhizin
+Pneumonia
+rapid tumor formation
+7 days
+leukemia inhibitory factor and retinoic acid
+16 mg/mL
+lymph nodes
+53 kDa
+Lung ultrasonography
+several
+SYBR Green
+Administrative and billing data
+0.15
+Mice, ferrets, and nonhuman primates
+general prognosis and current resource limitations
+Caspase-11 gene expression
+free FITC
+33 million
+13-fold
+allostery
+K 2
+InfluSim
+more than one hundred
+active invasion
+periodic
+30 min
+PrimeScript RT reagent Kit
+TET-21C
+LSV2
+5 days
+individual-based epidemiology models
+0.01
+five
+incomplete or inadequate vaccination
+Laundry
+high information about the virus-host interaction
+five
+MDRTB and HIV infection
+Cells
+8 hours
+10 mins
+Bronchiec tases
+training years
+polymorphism
+western blot
+the number of nodes
+I N
+lower stress levels and greater individual well-being
+automatic
+positive end-expiratory pressure
+confounding by surgically-linked blood transfusion
+every two years
+Fragmentation of chromosomal DNA
+0.3158
+Population doubling
+NF-kappaB and MAPK
+lamivudine
+Gehan-Breslow-Wilcoxon Test
+twice
+global pollination
+T66N Rab34
+HA, NP, and NA
+Five
+isolation and characterization of these cells at the single-cell level
+extends
+rapid contact tracing
+three days
+PSI-BLAST
+three
+highly positively
+mild mutations
+122
+all mental health workers
+influenza
+cell survival
+immunocompromised conditions
+influenza
+copper sulfate
+GAPDH
+induces close to the largest possible change in RNA structure
+abnormalities of the GM-CSF signal transduction pathway
+final proof
+control
+Toxoplasmosis
+Seven
+five
+1918
+West Africa
+10%-16%
+Diarrhea
+acute inflammatory reactions
+σ ∆l i
+Ub
+7.64
+phospho-Csk antibody
+The N-terminus of IPO
+mimotopes
+2 μg purified RNA
+6 months
+increased transmissibility in ferrets
+PA, PB1, PB2 and NP
+Transducers
+1999/2000
+60-100 nm
+Vivo-Morpholinos
+STart4
+Eleven
+a single basic amino acid
+T7 RNA polymerase
+vagal tone
+randomized clinical trials
+0.18
+polyprotein expression strategy
+Hombikat UV100
+11
+dominant
+100 mM RGD peptide
+third microdomain
+the proliferation of Caco-2 cells
+transient inflammation and compensatory remyelination
+Acute myocardial infarction
+a nuclease-resistant DNA hairpin
+partial pressure of carbon dioxide
+25 000
+co-infected reservoirs
+80
+CL-QJ 274218 partial sequences
+specialized
+IFNγ
+circRNA_finder
+Fecal samples
+Cyanobacteria
+pain and hypotension
+Mitochondrial impairment or dysfunction
+80 to 90%
+lower urban development
+2004
+10
+CS-formed nanoparticles
+March to May
+Compound II
+the estimator of R 0
+two bsheets that cross over each other
+intracellular endosomes
+cellular stress or the innate immune response
+coping appraisal
+Equal numbers of the vectors
+human tissue cDNA arrays
+Lectins, TIM-1, and TAM kinase Axl
+cell proliferation
+dye bias
+FK506-binding protein family
+Zinc deficiency
+papain
+Akaike
+documents issued by supranational institutions
+0 and 1
+EBV-related
+puncta that represents a single mRNA transcript
+distance
+HIV infection
+40 s
+patients visiting the hospital for treatment
+Breathspec GC-IMS
+RECIST
+four
+Ebola virus glycoprotein
+Applied Biosystems Sequence Detection Systems Version 2.4 software
+Hepatitis C
+immunomodulatory
+79.29 to 83.27%
+social distancing
+fluorescent
+industrial
+Hospitals
+The assay described in Fig 5
+40.7%
+one-way analysis of variance on ranks
+slightly above 10%
+development of colitis
+cost
+15 ml spin concentrators
+grow rapidly
+interpreting the large volume of available information
+CD4 T cells
+Drugs
+GeoChip 4.0
+increased access to the HR-1 region
+microglia
+PFU/mL
+VP40, GP and NP
+mutagenicity and carcinogenicity
+RC
+Cerebral malaria
+FLX800
+SOFA
+CD40, CD74, CD86 and CCR7
+to find a compound with no cytotoxicity
+cc0
+worsening
+G±U base pairs
+psychological inflexibility
+NucleoSpin Gel and PCR Clean-up system
+8
+lethargy, anorexia, weight loss and immunosuppression
+99% per amino acid
+higher sensitivity and smaller sample volume requirements
+35
+21st of November 2014
+axis
+Nuclear extracts
+one-third
+M1 macrophages/microglia
+x i
+cryo-EM
+China
+JD and SB
+160.25 ± 9.47 mg/dL
+twice
+Finding a live virus in a healthy bat specimen
+education
+ifn-α
+progressive multifocal encephalopathy
+hypotension
+stage 5 and stage 2
+31% efficacy against HIV-1 acquisition
+severe
+QIAamp RNA Mini Kit
+no significant association
+More than 180,000
+rennin-angiotensin-aldosterone
+malaria
+F2
+SplitsTree
+response plans
+60-90 mg frozen lung tissue
+hospital demographics
+viral infectivity and titers
+IgM, IgG, and IgA
+air transport
+eight
+template switching
+2014
+12%
+SAS-9.3
+socio-economic indicators
+culture positive rate
+tabulated data
+more than 500
+Supernatants
+cytokine production
+The nuclear pore and the cellular process of nuclear trafficking
+severe hand, foot and mouth disease
+type I diabetic
+histopathological evaluation
+cholesterol moiety
+44.2%
+two
+11
+LAMP
+Erdos-Rényi models
+human macrophages
+measles
+100%
+tetracycline or fluoroquinolones
+type I IFN
+Class 2
+1332
+inhibit
+62
+10%
+endoplasmic reticulum
+Two microlitre of the FPM
+adults
+measuring to what degree heroin is generating psychoactive effects in an animal
+a separate model
+the time staring from May 1, 2009 to May 23, 2010
+21
+MEDI-565
+gastrointestinal tract
+increased hepatocyte USP18
+risky primary infections
+cynomolgus macaques
+eukaryotic
+Eukaryotic expression vector P4
+samples
+DNA
+factors other than co-infection with CxFV
+delayed cytopathic effect development
+generation time
+binding to the chromatography column
+37
+Greater than 60%
+mixing acetic acid, phosphoric acid, and boric acid
+XOD
+immunofluorescence
+128
+6
+Chemical differences between MG770 and MG756
+coumarins
+feasibility of both the intervention and the RCT processes
+excitotoxicity and oxidative toxicity
+genetically tractable
+Sepsis, ARDS, traumatic head injury, and HIV/AIDS
+ultrasound evaluation of dorsal diaphragmatic movement
+active targeted drug delivery combined nano-technological carrier platforms
+Bwa mem
+population doubling time
+binding of neutralizing antibodies
+Creative Commons Attribution Non-Commercial License
+76.5%-78.7%
+Gram-positive
+1.82:1
+155
+resistance of respiratory system
+HCs
+16
+Neutrophil Elastase
+Pro-caspase 8
+SDF Etajima Hospital
+Prone position ventilation
+38.35%
+33.4%
+14/3/2020
+Similar
+normal
+147
+low mortality rates and yet high fetal morbidity rates
+CM2
+train and evaluate CNNs
+2%
+N
+six to nine hours
+each model's uncertainty
+30 days
+Zaire Ebola virus
+Flavonoids
+100 nM range
+study participants
+mean EGFP intensities
+1-3%
+an empty vector
+DENV viral proteins
+2007
+Central and East Jakarta
+null
+hemolysis
+entropy
+magnetic beads
+Tlr4
+cisplatin
+one week
+mammals
+non-negligible
+reporter luciferase
+cc-by
+International Circumpolar Surveillance Climate Change and Infectious Disease Group
+uncoupled variants
+p19
+Hepatocarcinogenesis
+Small sample sizes
+free radicals
+RC
+Normal mouse serum
+intermediate syncytiogenic activities
+Beckman Biomek FX 96-channel robot
+69%
+Dr James Cantlie
+Mapping
+G1252
+geographic correlation studies
+pair-wisely base-to-base comparison and visualization
+fewer available sequences
+improve population health
+26
+therapeutic
+0.1%
+5
+Gaussian graphical models
+Vaccination
+caspase-dependent
+SPSS 17.0
+three
+Chameleon Vision II Ti:Sapphire laser
+one
+females
+Imaging system
+H7N9
+blood-stage infections
+NIV
+four
+NPC1 receptor
+every 4 to 8 hours
+I49
+9−10 nucleotides
+RT-PCR
+articles
+too brief
+positions 78/ 79 of STING
+two
+Targeting control efforts on individuals with highest potential to spread disease
+24 h
+impediments of bacterial identification and research
+booster injections
+gPC8 and gPC12
+some fractions of within-host viral populations may be lost
+Drug Design, Development and Therapy
+Two
+CCSP
+autophagy
+log-rank test
+oligonucleotide primers
+binding site druggability
+633
+71%
+1:500
+60%
+pyroptosis
+berberine and emodin
+31
+GM3
+Nine
+Th2
+alanine or valine
+receptor retention, receptor release, and F retention by peptides
+SGTA client proteins
+The number of newly imported cases on day t
+Brainstem
+A control group
+life
+several-fold
+host pressure
+isolating focus individuals
+lithify
+SRC
+replication of human immunodeficiency virus
+assessing virus-host interactions
+degradation of the ECM
+respiratory viruses
+iProt-Sub
+target, signal or probe amplification
+dynamic exclusion of 60 s
+exponential growth
+40
+95%
+escape
+NEPV, Gumbo Limbo
+a protective effect against SONFH
+a peak representing the extended extension primer appeared at the expected mass
+SARS MA15
+a BHLF1 homolog
+noddies
+3
+BUN and Cre
+eliminate infectivity without affecting receptor binding
+1%
+Data recorders
+anti-CEACAM1 mAb
+lack of comparability in terms of age or antiviral therapy between study groups
+resource limitation
+28,333 Da
+15.9 %
+stability of the heterohexameric AB 5 holotoxins
+7 month-old
+aae-miR-11-5p
+mass spectrometry
+galactosyl residues of glycoproteins
+α-2,3 linked SA
+70
+more epitopes detected from the C-terminal ends
+epidemiological history
+Respiratory infections
+Leven
+some clusters
+leukocyte squeezing motion
+Due attention to the soft periphery
+Phylogenetic
+quarantine
+visualization tools
+high-throughput approach
+viral heterotrimeric polymerase
+infection of EV71
+48%
+pseudogenes
+simulations
+IP-10 and I-TAC
+fluorescence
+R06E-J cells
+Pair-based
+HCV-associated, hand-annotated genetic data
+HI antibody
+Let-7f and miR-24
+host cell factors and physiological processes
+rate of convergence
+95%
+Influenza A/H1N1
+4%
+high-throughput
+Kir2.1 folding defects
+P2X7R
+seven
+commodity flow algorithms
+95%
+Nairobi
+dispase-treated tracheas
+Age-related macular degeneration
+Flow cytometric
+false positive rates
+MBHE system
+PKC
+media
+Germany
+382
+rotavirus and astrovirus
+Increased activity of the Atg1/ULK kinase
+immune response against a broader range of pathogens
+intracellular and extracellular reporters
+severe respiratory failure
+plasma membrane
+PP2A, GAPDH and UBC
+2,646
+late endosomes
+differential viral infectivity
+dimers and monomer
+56
+4
+LPS-activated
+The region of intersection
+Definitions and categorization methods of operation volumes, and correct identification of SSIs
+LPS
+three
+6-fold
+20%-30%
+a searching method
+a significant interaction between valence and component
+clinical, microbiological and radiological
+Java 2 Enterprise Edition Software Toolkit
+reverse vaccinology
+assembly of Vpu-WT
+dinoflagellates
+low and medium risk
+Our results
+reachability
+positive selection
+up to 2 months
+Non-stretched cells
+NGS
+enhanced
+a placebo with blinding
+SA and SL EBOV IgG negative serum panels
+a good prognostic
+43.4 years
+generalized
+CBF1
+the C-domain of GST-σ
+2003
+2014
+ESBL-producing organisms
+118
+Zwitterionic polysaccharides
+reovirus-infected cells
+Minimum start and maximum end loci of each cluster
+pro-inflammatory cytokines
+ISG15
+Regions Of Interest
+Homologous sequences
+the one of our present objective
+Various housekeeping genes, ribosomal RNA and total RNA
+Chinese herbal medicines
+5
+mathematical models
+$6
+TLR-mediated
+subtype B
+Foot-and-mouth disease
+cellular ACE2 levels
+post-research access to a broader population
+12%
+CD57+
+costimulatory
+1915
+adenovirus
+chisquare test or Fisher's exact test
+extracorporeal membrane oxygenation
+Agar
+Drs. M. Peeples and P. Collins
+sequence variation on the surface of vaccine candidate proteins
+viruses, systemic conditions, drugs, or toxins
+2 to 141
+Brazil
+Five
+Phlebotomy
+8%
+1 hour
+placentation
+5%
+reduced viral titres
+Thomas Bollyky
+PKR, OAS/RNase L or Mx
+severe outcomes of the diseases
+binding to cell receptors
+IAV infection
+greater than two-fold
+CpG
+G6PD
+The interface between public health and health care
+1997
+acute respiratory distress syndrome
+16
+ten
+40
+secretory genes
+antiinfluenza
+higher conformational dynamics
+50,000
+113
+individuals
+explore the challenges posed by an Earth System
+small analytes
+RT-PCR and agarose gel electrophoresis
+contradictions in the language used
+classical hexanucleotide polyadenylation
+reports on outcome
+63 tagged extenders
+reagent and manufacturing variability
+MHC-I and II
+Pseudogymnoascus destructans
+RNeasy Mini Kit
+specificity, selectivity, and rapidity
+viral antigens
+higher
+H
+RSV
+enhanced inflammatory indices
+HIV-1 RNA
+Outbreak duration
+21%
+target exon number and oligomer annealing coordinates
+to create a standard curve
+bronchitis
+a sequence containing a BirA enzymatic biotinylation site
+waders
+percutaneous
+Linear regression
+Retroviral pseudoparticles
+reactive oxygen species and haemoglobin
+NO and IFN-γ
+attenuate −1 PRF
+disruption of nucleolus structure
+nanomolar
+PVDF
+Multiple sequence alignments
+phase angle difference
+1.10 Ϯ 0.99 M
+maintenance medium
+touching, handling, living close to, and consuming animal products
+serum-free media
+Biobanks/Biorepositories
+M-MLV Reverse Transcriptase and random hexamer primer
+acute lung injury and ARDS
+GoogLeNet-TL
+interleukin-4 and IL-21
+1975
+TBSV RNA synthesis
+poor prognosis
+phosphorylation
+Creb3L1 mRNA
+antiviral drugs
+1 h
+serum creatine kinase level
+the earliest systemic host antiviral response activated following infection
+adjuvants
+calmodulin and α-catenin
+MED1
+further development
+Arterial pH
+local levels of angiotensin peptides
+luciferase activity
+significant
+C3-fragment C3d
+Dolly the sheep
+57.4%
+Newcastle disease virus
+Two
+to design a drug able to destroy HIF-1-expressing cells
+Avidity
+enzymatically active protein
+Two-sample Kolmogorov-Smirnov tests
+amplify the region between positions 130 and 201
+Atg20, Atg21, and Atg24
+an activated ACE/Ang II pathway
+non-neutrophilic
+14%
+Escalation
+virulence factor
+Twenty-six
+Ebola virus and Marburg virus NPs
+purine metabolic pathway
+1.02
+MDEO-12
+1/m
+relative fluorescence units
+near the entry channel of the ribosome
+Santa Cruz Biotechnology
+SCARB2
+silver nitrate
+an expedited psychiatric evaluation
+10.1371/journal.pone.0048608
+concentration and extraction methods
+80%
+Mutations
+allergic asthma
+antimicrobial defense
+Arrows
+heroes
+host cell translation machinery
+complicated disease
+0.8%
+364
+LAMP amplicon loop sequences
+influenza virus-induced inflammation in the lung
+144
+Bartonella
+to measure exposure to environmental tobacco smoke
+experimental testing
+pulmonary hemorrhage
+Insertion of the HA epitope
+HCV
+two
+those who received interventions might be more likely to be enrolled in the surveys
+initiation
+Fixed and permeabilized islets cells
+5-month
+at home
+IFN-stimulated gene factor 3
+DNA sequencing
+three
+blue
+MBP-and MOG-specific response
+C and V
+two
+consistent patterns and similar risk estimates
+lower limits of the active and inactive pairs
+more than half
+programmed cell death
+12
+Serial deletion of 75 bp
+Michael V
+to lock P-site ligand in a suboptimal conformation
+Hitting
+RAS
+lytic
+10 12
+MHC class II antigen presentation pathway
+non-trivial
+apo-enzyme
+ESCRT proteins
+DAPI
+parents of children who were asked to go into quarantine
+SVM classifier
+Peptide-MHC structure determination
+different NTFs play specific roles in HCV life cycle
+peak viraemia
+18
+SH-UF
+KL~P i P log P Q
+Future trials
+disaster preparedness and public health
+two degrees of prolonged hemorrhagic shock
+Emilia-Romagna
+a-helical structure
+Community-acquired respiratory viruses
+underlying molecular mechanisms of inflammatory response
+retention of ACE2 on the cell membrane
+DENV
+IEDB population coverage tool
+sex, geographical distribution and/or host group size
+Duration of respiratory support
+NMS-873
+fluorescent antibodies
+1.75
+hematoxylin and eosin
+Waterfowl
+type A
+4 million
+caspase-11-dependent
+hypoxemic
+The consequences of the absence of selective pressure
+amiRNA #1-mediated effect
+spatial autocorrelation
+eIF4F
+50%
+on dry ice
+Codon-optimized cre recombinase
+Figure 3
+two-step PCR
+1180
+Cortex Magnoliae Officinalis
+Fig. 2
+optical microscopic examination
+30
+Digital PCR
+A2 and A3
+Ubiquitin
+resistance patterns, and human exposure pathways
+Two
+batch-to-batch
+Parker hydrophilicity scale method 38
+recoding cassettes
+tight and intricate interactions
+via the airborne route
+Sex
+master regulator
+exosomes
+Ͼ99%
+ethanol
+our study design
+GraphPad Prism 4.0
+58.3%
+therapeutic
+selection of resistant mutants
+Retinoic acid
+Population genetics
+Full-length genome sequencing
+respiratory syncytial virus
+Total cell nucleic acid
+three
+Sequence numbering
+genes
+force, duration, and velocity
+Serum and urine
+115.0 Ϯ 92.4%
+increased levels of IL4
+a p-value between 0.008 and 0.001
+changes in pseudotyping efficiency
+A preconceived and tested questionnaire
+Gobierno de Espana
+5′ 3D7 and 3′ FCR3
+neurological
+passive immunization with SHIVIG
+35
+842 ml to 2,189 ml
+The relationship between staff and parents
+severe disease
+expression of specific influenza viral genes
+S
+text
+24 h
+over-fitting
+PfSWIB
+four
+apoptosis
+10218
+cantilevertype sensors and MSS
+2017
+FACSAria
+hostpathogen interactions
+an advantage in some experimental settings
+Aspergillus fumigatus
+6 hours
+symptomatic malaria
+60.7 and 6.9
+251
+9.4-23%
+120
+tens of thousands
+Tsan Xiao and David Garboczi
+intestinal
+PEEP
+The group with corticosteroids
+Fifteen
+innate immune response
+influenza A viral strains
+Coronavirus
+activates NF-NB-dependent transcription
+lung tissue
+2 days
+significant changes in the hematological parameters
+computed tomography pulmonary angiography
+five
+the viral lipid coat
+Streptavidin-coated magnetic beads
+3 turning points
+gRNA translation
+viral immune evasion
+virus-based vectors
+The methodology for reverting back to germline
+24
+reduced mRNA expression
+virus-induced complement dysregulation
+attachment to a target cell
+Employment status
+temperature-and drug-specific growth phenotypes
+antigen-directed immunity
+500
+74
+11 bp in stem 1
+abdominal cramping
+tryptase + mast cells and CD207+ Langerhans cells
+HCV-infected
+35-fold
+10%
+90 %
+environmental and trend analysis
+receptor density and identity
+Cluster V.2 and V.4
+p38 MAPK and its associated MAPK kinase
+March 31 of 2013
+ten
+inhibiting autophagosome maturation
+levels and enzyme activities
+respiratory function
+nine
+pleural pressure
+40
+lipofectamine
+VZV antibodies in the normal range
+Codon optimization fat1
+early autophagosome formation
+protective
+135,000
+enhances sumoylation
+C-type
+Titres
+Influenza A viruses
+Quantitative resistance predictions
+enhances frameshifting 10-fold
+17
+Illumina HiSeq2500
+0 -300 ms
+HRV-C026
+an evidence based clinical decision tool
+core components
+3 to 5 million
+Gene transduction through viral vector delivery
+Eq.
+China
+eight
+IAV
+Virulent IBDV
+assays without any templates
+one year
+four
+24,790
+heart rate
+25 l
+RNA sequencing
+seasonality
+Pileup format
+hrMCP-1
+passage 8
+bortezomib
+local laboratories
+2011-11-01
+altered genetic codes
+immobility, ruffled hair, and labored breathing
+AKT and JNK
+TLR9 /TLR21
+Richard Shope
+protective responses
+similar rates of dead cells
+age, environment and milk
+twice
+70,061
+hydrological processes
+genetic predisposition, viral mimicry, vitamin and mineral deficiency, geographical location
+3.0 silk suture
+40.3uC
+10 µg/ml and threefold serial dilutions
+Code reuse and object inheritance
+rapid phagosome acidification for lysosomal protein activation
+accelerate viral FH pathogenesis
+detailed
+6 ml/kg
+intracranial inoculation
+M k
+50 to 75%
+strong expression
+to effectively control each flavivirus
+461
+2009
+IRF7
+41
+seven
+interesting biological mechanisms
+transmission electron microscopy studies
+template switching as the primary mechanism of poly polymerase activity
+flattening
+Lipofectamine 2000
+Toll-like receptor-3 agonist poly I:C
+acetic acid
+phylogenetic
+Microfire 24-bit CCD camera
+12.5%
+NK cells
+Plasma proteome profiling
+infectious viruses
+binding site similarities
+signs of ill health and distress
+first strand cDNA
+A, A and B
+Cabal et al.
+realtime experiments
+viral clearance and vertical transmission
+glial fibrillary acidic protein
+20
+host miR-NAs
+40 cycles of denaturation
+1949
+functional
+antiviral activity
+written informed consent
+computational
+Respiratory syncytial virus
+host specificity
+trends in diabetes prevalence
+host cell binding and membrane fusion
+IL-12
+the evolutionary changes occurring within parasite or host lineages
+eqTHN_del_GPI
+SIRT1
+Cinanserin and losartan
+107
+descent
+452
+Impaired vRNA replication and NP aggregation in cytosol
+Huoxiang Zhengqi capsules
+2013 to 2016
+The giant component
+below the identity line
+chloroform
+known quantities of a synthetic calibrant RNA template
+excessive RNA polymerase activity in mammalian myeloid cells
+positive
+The scenario
+Bradford method
+Globalization and Health
+serial platelet counts
+Anti-HAV IgM
+Western blotting and negative-staining electromicroscopy
+four
+three
+0.8 s
+ten
+clean and high-resolution EM maps
+47
+Table 1
+secreted cAMP
+cartilage, bone, muscle and fat
+emergency mental health care
+seabird migrations
+Tony Epstein and Yvonne Barr
+CD81 and CD9
+validated clinical scores
+Multivariate statistical analysis
+University of Oxford Animal Care and Ethical Review Committee
+daily
+~4 million
+400 per 100,000 live births
+viral infectionassociated illnesses
+DGEA
+E2F7/8
+37
+loading control
+RNeasy mini kit
+100%
+The number of confirmed cases
+high level of illness severity and high mortality rate
+sFat1
+200,000
+Products containing triclosan
+an outbreak threshold
+standard 10-fold dilution spot assays
+resistance to phagocytosis and complement-mediated killing
+90 days
+SAS Enterprise Guide 7.1
+70 chaperones
+distinguishing introgression from incomplete lineage sorting
+#pragma omp parallel
+STAT1 and STAT2
+10 min
+Five
+Maintenance therapies
+benzylpiperazine adamantane
+Multiple hypothesis testing
+mean ± SE
+accurate quantification
+13 per cent
+multiple
+257
+24 hours
+Dog serum
+two
+constitutive immune assumptions
+AP2 and TOE3
+five
+NK-cellmediated antibody-dependent cellular cytotoxicity
+The number of locations in location group LH
+24 h
+actively cycling cells
+25
+LPS
+3D
+surface
+HIV-1 infection
+June 2002
+IL-10
+geographic heterogeneity has not been explicitly represented
+potentially crucial objects
+1 mm pieces
+9
+66
+MGs
+a counterion
+R 0 = 1.8
+metabolic protein dynamics
+DendoU
+To study viral effects of specific mutations
+twice
+Danishefsky and Livingston'
+Hepadnaviridae
+Clinical trials
+4.97 mg/ml
+effector memory or central memory subsets
+sCHIKV plasmid
+western blot analysis
+whole-genome shotgun method
+three
+genomic
+Bronchial epithelial cells
+increased transiently
+places from where the next important emerging pathogen is least likely to originate
+CD4-induced epitopes
+The amount of encapsulated b-galactosidase
+age, gender, birthplace, educational level, occupation, and socioeconomic status
+Uganda
+initiating and regulating viral translation
+The observed distances
+Intensive care unit length of stay
+survival rates
+Social power
+lentiviral assay inhibition
+Glial cells
+10%
+SHELXS-97
+Branche et al
+Transforming growth factor beta
+Astrocytes
+recombination
+liberal antiviral distribution for prophylaxis
+Freshwater fish
+Tree shapes
+adhesion molecules
+C-type
+virus stock
+300 kb
+PK5510
+macrophage inflammatory activities
+50%
+seven
+SNA and MAA
+whether the confounding factors taken into account were listed
+least-squares fitting
+Co-infection of the same cell
+pol N,1
+western blotting
+consistent activity level, temperament, and food intake
+antiviral effects of defensins
+Quantitative EM
+Zika virus
+T-705 and ribavirin
+108
+3,39diaminobenzidine
+MAXIscript
+CSLM
+over 100,000
+four
+EDII 101/106/107 epitope
+central nervous system
+72 h
+PCR products
+5500 V
+H5Cam
+policy recommendations
+BIRB 796
+Forty
+GFP fluorescence
+an NdeI and an XhoI cleavage site
+Blood
+11
+1093
+New York City
+suppressed NSs-induced PKR downregulation
+consumer behavior change
+IFN signaling
+ripping of the S1-L1 hairpin
+RNAi Designer
+the capacity and contact frequency of environment
+develop various lines of defense
+infectious diseases
+51.1%
+putative initiation codons
+sputum and endotracheal aspirates
+Northern and Central Italy
+Roche/454 titanium-based adaptors
+Csk
+positive
+data
+MEGA version 4
+Upon infection with MHV3
+further experimental verification
+conservation at the codon
+mosquito vectors
+3.7%
+Ad vectors
+MCPyV
+SPIO
+Additional staff
+Seven
+Ascites/HE/AVB
+ISG15 conjugates
+Total RNA
+survivors and non-survivors
+chemotherapy
+155
+Feedback from service users
+thermal denaturation
+APC Calibration
+CD4 + and CD8 + T cell populations
+Niemann-Pick C1
+cell culture medium of CHO-K1 cells
+confocal
+817
+66.9%
+Ten
+supernatants
+The structures of target or homologous proteins
+One unit of N-acetyl-Lglutamate kinase
+IAV fusion
+worsening oxidative stress
+11%
+hippocampal neurons
+December 2013
+Non-ST-elevation myocardial infarction
+ubiquitin-deconjugating USPs
+serum-free DMEM medium
+USP18
+safe and immunogenic
+language barriers and other factors
+dry ice
+−63 to −75
+progeny virions
+hydrophobicity
+2 1 -dAMP
+more than 20
+sylvatic
+S. aureus and S. pyogenes
+Percentage of specimen tested positive
+CD8 + memory T cells
+phosphoinositide 3-kinase
+MCMC 70
+L1
+heterodimer
+rate matrix L
+R551S
+Three
+69
+176,200
+Demographic inference
+3.3
+HCVpp
+HCV NS3 protein
+titration
+159
+reaction kinetics
+parasympathetic outflow
+146
+oxidative stress
+neural tube defects
+less than 10 fold
+proinflammatory and CD4 + mediated inflammatory response
+Dr Carmen Garrido
+200
+s IB→I 2
+lactase-phlorizin hydrolase
+maintenance of the cell productivity
+Efforts
+splicing-specific
+healthy adult mice and a DMD disease mouse model with leaky muscles
+weekdays
+Spatial structure
+13.968.5 years
+φ
+291,000-646,000
+Greater Difference in Absolute Value
+83%
+18.1%
+hairpin-type stem-loop
+Acinetobacter Baumannii
+IAV-induction of type I IFNs
+RNA binding motifs
+periodic and spline
+V2 loop antibody
+protecting 99% of the population
+C3, fH, and fB
+121 million
+27
+Osteoclasts
+model M
+Acriflavine
+4%
+Amplification of community DNA
+AUCs
+16%
+D,L-diaminopimelic acid
+adjuvanted influenza vaccines
+acute demyelination
+category B agents
+MESOMARK
+S. aureus
+Nikon Diaphot inverted microscope
+0.9993
+virus-encoded RNA-dependent RNA polymerases
+Background Genotype
+PSCC cell metastasis
+β-actin
+The common snipe
+lung epithelial damage
+polyhydroxy-alkanoates
+Full review
+HA
+Ebola virus
+45
+sterile distilled water
+increased secretion of CPYinveratase fusion protein
+cardiovascular disease
+serious brain injury
+bacilliform shape
+IDRISI
+Puerto Rico and Saint Martin
+anti-inflammatory effects
+bootstrap arrival times
+distinct physiological responses
+Further research and discussion
+ethanol sensitive
+variation
+five
+December 2019
+thousands
+Molecular
+dark-matter structures
+9
+84%
+ricin
+samples
+cc-by
+ART
+1
+delivery into transplanted organs
+Non-influenza virus infections
+infantile colic, functional constipation, irritable bowel syndrome
+colorectal
+BS-C-1 cells
+interstitial and alveolar
+DNA vaccine
+biochemical
+retrieval information from relevant documents
+NK cells and T cells
+Synthesis of several pro-inflammatory or Type 1 cytokines
+cc-by
+ball and stick with a transparent van der Waals surface
+Prof. Zhizhong Cui
+Ostriches with more than two missing sampling points
+H5N1
+killed
+infection cluster
+99
+Namibian National Herbarium
+an instrument-free, electricity-free nucleic-acid amplification test
+theoretically
+CS
+Pain
+89
+5-24-year
+five
+two
+Detection of single cells
+a prior suicide attempt
+INSR
+The cell-cell fusion infection pathway
+selection for their resistance to intrinsic antiviral restriction mechanisms
+antiviral
+restriction-induced travel delays
+0
+43
+Proportion of county designated as an important bird area
+intra-arterial RH
+Dashed lines
+residue 77
+Primer Express
+one
+the estimated parameters are expected to be robust
+10%
+ILI
+10.1371/journal.pone.0069982
+39
+185
+MiRNA-200a-3p
+EGFRvIII
+antibody positive
+single amino acid mutations
+neurogenic
+an assembling retrovirus particle
+Stichting HIV Monitoring
+NaOH
+HMPV positive clinical samples
+18
+20 h
+very short
+access log time series
+histological biopsy
+Processivity
+smart phone camera
+activity determined via high-content image system
+Statistical
+transcription by the RNA polymerase II
+27
+Foxp3 production
+Australia
+FMDV RNA in serum
+electrophoretically homogeneous csf-IgG mix
+independent
+Evo-devo
+20%
+our research was too applied to merit space on their campus
+the nucleus
+32
+the risks associated with ARF and ARF/SS
+apnea
+mevalonate
+early mild ARDS
+the initial date selected for the simulation
+between 35 and 50 minutes
+E2
+61 ml/kg
+N36 trimer
+conductive and respiratory sections
+Gleason pattern 3
+aquatic shorebirds
+a TA cloning vector
+disease spread
+rA2-GC4
+Trizol
+through orofecal routes
+CD14 polymorphisms
+viral RNA-induced oligomerization of influenza A NP
+treatment duration and outcome criteria
+security, self-efficacy and stress reduction of the staff
+March 2007
+TFIIH p44
+15 minutes
+culture samples
+CHIKV-mediated MCP-1 production
+Written informed consent
+GAPDH and ACT
+O15 E-GRASP
+70%
+30°C
+18 hours
+sepsis
+Figures 2A and 2B
+1647
+surfactant contained cells
+Type II
+payment
+every other day
+20-80%
+Fc-FgR interaction-dependent effector functions
+empirical in vitro MHC binding data
+50%
+infant death
+the binding of the two substrates
+Data S1 and S2
+laryngeal chondritis
+Wide distribution
+magnetic streptavidin beads
+1019
+varies widely
+29
+exopolysaccharides
+three
+Regulated gene expression
+Pichia pastoris
+ancestral
+variola virus
+jackknife test
+a bumble bee pathogen
+Our analyses
+6%
+activation of cell signaling networks at immune cell contacts
+one
+SARS, HIV and Ebola viruses
+increased early viral replication and reduced viral titers over time
+SAS
+Public health
+on the surface of mature dendritic cells
+SRP104704
+gender and exposure
+regulating
+seasonal influenza vaccination
+research
+four
+IFNs
+innate natural killer cells and the adaptive CD8 T cells
+60%
+Primates
+63%
+streptavidin-biotin
+CTL epitopes
+adenoviral vectors and adeno-associated virus vectors
+RNase L
+Many characteristics of the DNA, RNA and protein sequences
+10%
+endocrine, genital, lymphoreticular organs
+immune-modulatory
+89
+reducing epidemic severity
+92%
+selection bias
+Twelve
+Coagulation
+β R0
+expression of proinflammatory cytokines
+additional variables
+Group 6
+8-years
+IRENE
+influenza and respiratory syncytial virus
+Roche
+live attenuated influenza vaccines
+three
+cell cycle progression
+Eagle's minimal essential medium
+Natural selection
+unicellular
+hybridize to each positive-strand viral genome
+320-400 nm
+an inactivated virus
+myc-His tag
+Zika one
+CHIKF
+Graphpad Prism 5.03
+Mitigation resources
+7 mmoi
+the FS
+traditional phylogeny
+231
+evaluation of these responses from baseline to the last study visit
+TLR7 and TLR3
+V and W
+a publicly accessible online service
+minimal MW differences
+31%
+specific structural features of adenoviruses
+lung inflammation and immunopathology
+>3 g/d
+GCMS and FTIR
+five
+48 h
+individuals in that category interviewed
+2 x 10 6 RLU or greater
+77%
+transmission parameter b and infectious period parameter c
+Two
+transferred helper cells
+Aquaporin 4
+cDNA
+multivariable
+oseltamivir
+325,922
+community-based providers and organizations that are familiar with vulnerable groups
+different definitions of the time post infections
+Every effort
+female-biased immunopathology
+evolutionary
+ABPP-SILAC
+inserts which did not contain cells
+cap-dependent
+HSPs
+70 mm
+VEGFC and PGF
+reduced starter feed intake
+unwinding
+unwanted cells are programmed to be cleared
+1 mL of cold 2 x BHI
+host immune responses
+Recombination
+Age
+P25 TiO 2 NPs
+33 weeks
+pandemic influenza threat perceptions
+further studies
+rational
+approximation
+RTI
+metabolic
+17.65%
+transcription factors
+Substitution T160A
+median and 95% upper limit of the CI of Culicoides captures
+high risk groups
+Peptides and proteins
+144
+22.4
+binds PLP irreversibly
+cytokines
+1813
+La Reunion Island
+chronic cell-mediated
+Three
+TA98 and TA100
+MZ, CD, and SX
+N1
+protein A
+pEASY-B-D
+recovery
+20
+cc-by
+positive
+thymine nucleotide
+Ni-NTA affinity resin and MagneHis Niparticles
+neutralization activity testing
+The Investigator
+five-fold
+R e,C 1 = 2.01
+ISRE promoter activation
+between 8 and 10 amino acids
+calcu-
+Minimal stimulation of IL-10
+10 days
+acetone extract
+kidney Ang II concentration and AT1R expression
+neonatal bile acids pneumonia
+e
+R 0
+articles published in non-Scopus database
+RSV
+ThermoFisher
+capture efficiency
+KCD code of the NHIS-NSC
+TNFα
+Verso cDNA Synthesis Kit
+p40%
+cooperative unfolding in FECs
+90%
+polyA-tailed DNA
+lipid degradation
+136
+proportion of cases vaccinated
+CD4 + T helper 1 cells and natural killer T cells
+real-time polymerase chain reaction
+12-hour
+IFN-δ
+FGL2 expression
+DETA NONOate or insulin
+infection
+Lactate dehydrogenase level
+minor-groove base triples
+marked follicular and paracortical hypertrophy
+31 ng/l
+2524
+E-CO and airway eosinophil counts decreased
+5 min
+Camp Zachary Taylor
+systemic complement activation
+Mab 4A1
+MyD88-mediated pathway
+phylogenetic
+10
+downregulating
+HRP-conjugated anti-mouse IgG
+Cell-mechanics
+susceptibility
+mannose
+cDNAs
+intracellular pathogen diversity
+72 hpi
+safety
+24 hours
+where public health ends and clinical practice begins
+10 min
+Four
+individual
+activate senescence
+60-65%
+public, commercial, or not-for-profit
+juxtamembrane motif
+Exhausted viral-specific T cells
+TNF-α and IL-6
+predicting the peak time
+communication
+-7-oxozeaenol
+degradation and inactivation of the pIFN-γ protein
+GAPDH and HPRT1
+archeological sequence data
+61
+1993
+RIG-I and MDA5
+85%
+neonatal death, stillbirth, and preterm birth
+lifetime expected risk E
+to induce ribosomal frameshifting
+0.6
+hematophagous
+8.5 ± 0.09 minutes
+once a week
+Voluntary reporting
+rapidly decreased
+eIF5
+rehabilitation instructions
+up-and down-regulated genes interactions
+avian
+PB1-F2
+reduction in opportunities for within-host
+SPA
+HCV
+four
+amino acid substitutions
+ω
+30.8 hours
+TwistAmp™ exo kit
+SIRT7
+health care information
+unhappiness and stress
+methionine
+Analysis of GP CL -bearing VSVs
+infectivity
+to focus on the potential for revival of long-dormant microbial pathogens
+radium-223 and capecitabine
+mixing vessels
+Murine leukemia virus
+11
+44
+crows
+outside the PBG
+CHIKV
+lower temperatures
+tumor necrosis
+differences in microorganisms
+attributable fraction
+1.5%
+mean ± SD
+human influenza viruses
+56
+WuXi AppTec
+Translational shut-off
+665nm and 620nm
+Idealized networks
+changes through the seasons
+75.2%
+Congestive heart failure
+Genetic heterogeneity
+7
+One hundred
+seven
+50%
+conduction velocity
+non-linear regression analysis
+ulcers, schistosomiasis, liver disease and tuberculosis
+after passage through cell culture
+densitometric
+simplistic classifications
+39
+red
+page 10
+25%
+NMR analysis
+IL-6, IL-8, and IL-9
+$40%
+three
+Greater retention in treatment
+14.8%
+40%
+five
+TAAR2
+strongly induced
+monovalent
+European diving beetles
+Antigen
+infection control
+JEV serogroup viruses
+reversed
+four
+Sigma-Aldrich
+five
+static imaging
+1500
+Begg's and Egger's tests
+wild-type, S528A and W529A mutants
+characteristic
+0.842
+data
+$543.3 billion
+γ h
+functional considerations
+1.3 million
+the CT region
+rDNA
+pathogenic
+The weeks of peak activity
+viral loads in the upper and lower respiratory tracts
+NS
+P max
+human AT-II cells
+agenda-setting theory
+GOLD guidelines
+multicomponent
+cross-neutralization studies and phylogenetic relationships
+improving and targeting prevention efforts and planning for health care delivery needs
+GM-CSF signaling
+Buenos Aires
+Compound Topographical Index
+reagents
+adverse health effects and increases the mortality rate
+2 days
+153
+virus establish infection across genital tract or intestinal tissue
+US
+IBD
+The antiviral function of 90K
+1918
+disinfectants
+type I interferon signaling
+weak interactions
+HUVEC and THP-1 cells
+10-fold serial dilutions
+an interaction between GA and BPD
+311
+Respiratory syncytial virus
+fundamentally different
+6 weeks of age
+RNA splicing, transport, turnover and translation
+phylogenetic trees
+transcription factors
+six
+60 %
+Tomato bushy stunt virus
+the specific origin
+K151A/E153L/R157L
+3 days
+IAV
+less than twofold differences in gene copy number
+equal amount of samples had been transferred
+essential considerations
+PubMed Central
+according to clinical judgment
+The number of accessible direct paths from WT to the quadruple mutant
+normality of distribution and equality of variance
+20
+The CTD
+chemical and biological
+R170H
+Histopathologic examination
+midbrain, pons, and medulla oblongata
+p-values
+interference efficacy
+rounded cells in the alveolar corners
+99%
+180 million
+Nine
+requested cumulative ILI reporting
+Mabs 3F4 and 5D6
+cyst area
+Clinical trials
+Listeria monocytogenes
+the maturation or processing of the receptor protein
+purification
+>90%
+adenoviruses
+significantly correlated
+reproducibility of RNA-seq results
+FUT2
+Eleven
+World Health Organisation
+RPI2662
+very few
+residues 69 to 119
+Clinical data, diagnosis, treatment modalities, and blood samples
+E. coli
+influenza surveillance
+twice
+shedding of BoDV-1
+virus titres
+Supernatant harvested 6 dpi
+Tconv and CD8 T cells
+ACEI or ARB use
+Gp160 processing
+proteolytic digestion and proteasomal degradation
+15 to 62%
+London
+39
+help prioritize social media-related psychology research
+Section 2
+F12K
+treatment response
+1.7
+5-10 minutes
+η and η
+any extra dimension that is not offered but self-generated
+dysentery
+FSC-H
+the epithelial layer
+production of early neutralizing antibodies
+10%
+hypergammaglobulinemia
+20 μL
+Simulated temperature
+59 and 39 untranslated regions or genes with a high mutation rate
+Maxwell-Garnett model
+Diagnostic testing
+Lack of wobble uridine modification
+opioid-neutralizing antibodies
+73%
+a better picture of local dynamics
+bilateral alveolar infiltrates and bilateral pleural effusion
+97.37%
+10%
+ISGs
+immunofluorescence and reverse transcriptase polymerase chain reaction
+NS5B
+steric pressure among crowded disordered domains
+ρ
+Acanthocheilonema spirocauda
+Astroviridae
+Respiratory syncytial virus
+formulation
+attenuates the virus in vitro and in vivo
+virus production
+framing theory
+liver
+it does not formally require different data streams to be independent
+p53
+Over half
+mass-spectrometry and RNA-seq
+Five to six percent
+two
+17
+lncRNAs
+irreversible metabolic damages
+Cases in which death occurred before ESKD incidence
+TNBC
+eight
+antiviral and immune-modulatory
+Italy
+Poisson regression models
+inhibitory
+AppDapxIDapxIIC
+2 ml of DpnI
+S25
+CNN
+mutations in NA
+5 minutes
+full protection from infection
+three
+NGAL and ROS levels
+V. cholerae
+CD8 + T cell expansions
+Two-percent
+neutrophil apoptosis
+Metabolic labelling
+28%
+granulocyte colony-stimulating factor
+IgA
+infection of subsequent rounds
+SIVcpz
+primary human hepatocytes
+Two-way ANOVA
+15
+inhibits ferroptosis
+>70%
+ultraviolet B
+Dinucleotide frequency analysis
+SNPs in LD
+cystatin C
+specific structures, processes and/or components of the brain and nervous system
+tick-borne encephalitis virus
+Surface plasmon resonance
+keyword searching
+they are not targeted at household transmission
+Severe sepsis and septic shock
+4%
+Western blot analyses
+The supernatant
+azide-fluorochrome
+four
+48 h
+intramuscular immunization
+high diapause rate
+NT$1792
+1960
+gene expression changes during specific phases of epileptogenesis
+Cholic acid
+HIV-1 specific primers
+iodine
+CD147
+splice correcting agents
+daily
+GFP + cells
+13
+11,315
+Homologies with well characterized sequences
+Trehalose
+8 days
+52
+53%
+lipid modification
+in vitro replication assay and in vivo plaque assay
+25
+JEV
+genes
+analytical techniques
+Rising temperatures and changing rainfall patterns
+FeLV
+Lv3
+previously reported data
+Nikon type A immersion oil
+ondansetron
+antiosteosarcoma effect
+thirty-one
+Lee Foshay
+towards the 59 boundary of the TURBS
+extrapolation from model membranes
+Rabbit anti-HBZ serum
+autophagy
+chloride channel 1
+host cell receptors
+Small differences in distance
+VSV-based
+MCMV Smith strain
+ampicillin/sulbactam
+repeat laboratory testing
+permeability
+Hand Washing Method
+intention stability
+cGAS activity
+NIBSC
+Economic development
+Hyperuricemia
+substitution rates
+proinflammatory cytokine secretion
+NEBNext Poly mRNA Magnetic Isolation Module
+CCR4-specific
+endosomal escape
+65%
+R 0
+scaffold, solution, and gas
+rVSV vectors
+ARV
+HIV, HCV and HSV
+IC 50
+play a key role in regulating inflammatory processes
+particle infectivity
+filoviruses
+newly developed technologies to excite or detect emission
+peak height
+0.926
+three
+Immunofluorescence
+soluble CD4
+catalyst
+activated NK cells
+aseptic collection
+71.34 percentage points
+one
+acute respiratory failure
+robust pro-inflammatory responses
+DRMs
+P. aeruginosa and Burkholderia cepacian
+24
+NucleoSpin RNA II
+between the 25 th of June and the 4 th of July
+moral enhancement
+fluorescence spectroscopy and RT-PCR
+19.6%
+ρ 0
+EVD transmission
+outbreaks of HFMD
+localization and orientation
+17%
+IAV NP
+viral gene sequencing
+prME-opt gene
+nosocomial and imported infections
+PBC and self-efficacy
+rule of five
+ATP bioluminescence
+polycarvenoside A
+PP2C
+10% higher
+10.4cm
+575
+oxidative stress, inflammation and autophagy
+targets
+implicit content
+interesting
+48 hr
+cytotoxicity test
+hematology, clinical chemistry, urine analysis and parasitology
+nickel
+CD8 + T cell responses
+improved protective efficacy
+Bio-Rad Life Sciences
+1 h
+2 million
+Fujian H5N1
+Theiler´s murine encephalomyelitis virus -infection
+degenerate sequences
+reduced +1 frameshifting at the CAG codon
+HSPGs
+227
+personal risk
+alpha-toxin
+cluster size and locations
+Gln-89
+0 to 10
+≈4.1 million
+Functional analysis of this genomic region in non-human primates
+Iridoviridae family members
+Magnetic nanoparticles
+three million
+bone marrow
+metabolic byproducts of intestinal bacteria
+RAxML Blackbox webserver and MrBayes 3.1
+SEM
+410-08
+20
+almost 300
+clinical signs index
+bacterial NA
+Student-Newman-Keuls test
+PMN apoptosis
+Potato virus X
+surveillance and epidemiological investigation
+Katherine Richards
+protein adhesion
+DENV infection
+Rac1 and Rho
+two
+A129 mice
+neutrophils
+kidney ACE2
+TBM, bacterial meningitis, and sepsis
+321
+uninfected group and infected group
+1 mg/ml FITCdextran
+non-homologous recombination
+cyclohexaleucine peptide 9
+recognize conserved epitopes in the HA stalk domain
+40
+twice daily
+vital
+Medium-chain acyl-CoA dehydrogenase deficiency
+hepatoprotective
+2001
+QIAquick Purification Kit
+geNorm and deltaCt
+The role of VPg in RNA packaging
+Kinases activated in response to infection
+interval I
+a receptor-destroying enzyme treatment step
+11,552
+RSV F glycoprotein
+very similar viral growth
+30
+200
+C
+3,791
+plum-colored
+γδ T cells
+1 week
+Student's t test
+131
+11
+geNorm
+NFkB activation
+acute exacerbations
+.5 fold
+50%
+31.6%
+receptor NTCP binding
+at the level of CFTR inclusion into COPII vesicles
+82.91%
+World Organization for animal health
+p53 for degradation
+immunity and development
+molecular specificity and network modularity
+Plantar fasciitis
+polysaccharide capsule
+up to eight months
+Amiodarone, dronedarone, and verapamil
+2003-2006
+serum amyloid A
+area under the curve
+DDD, DDP, and DPP
+twice weekly
+lower Vt and higher plateau pressures
+Mac2 positive cells
+facilitation or reduction
+long TSS isoforms
+Corbett CAS1200 robotics
+TREM-1
+ρ
+two
+FHA's research office
+short-and medium-term predictions of influenza activity
+cross-reactivity model
+European Early Warning and Response System
+seasonal signal
+Cell type and cell state
+Denmark
+plasmid pMD19-T-TK DNA
+Dr. Boping Zhou
+15
+Ultra-early stage
+326 Å
+63 amino acids
+adapter contamination
+CD8 T cell response
+Robust analytical frameworks
+66,602, 168,964, and 68,863 particles
+error
+R 0 cases
+prior viral sequence knowledge
+Adeno-X Adenoviral System 3
+the need to predict which bacterial species are likely to be relevant
+Japan
+further supply of N proteins
+10%
+respiratory epithelial cells
+RRT
+ORF
+6.9-17.1 weeks
+4 h
+GA combined with matrine
+idarubicin
+90%
+85%
+Istanbul, Turkey
+computational methods
+the mean Cq of all samples of the genes
+6
+device utilization
+higher mobility
+One hundred and ninety-two
+Compassion
+5%
+class II and extended class II regions
+Ni-NTA resin
+SIR model
+RNase A and DNase I
+oil spill and oil-free ocean surface pixels
+the corresponding author
+MSF Belgium volunteers
+L-CR1
+PRJNA318707
+highly oedematous and extensively exudative
+IAV
+16.5%
+society-based risk assessment and direct commitment
+five
+more effective biomarkers
+2 days
+seven
+pro-inflammatory responses of DCs
+K1
+percentage of labelled cells
+more than 890
+LAL assay
+six
+Expression and activation of caspase-11
+multiple regression models
+VZV pneumonia
+early January and late March
+correlation statistics and multivariable regression models
+2010
+26 229
+Polybeads and Protein
+n
+15
+70%
+viral RNA accumulation
+Atg8
+5.1 per day
+peak MDA and peak lactate levels
+2008
+FAK
+GlcNAc
+quasispecies
+alternative
+cold Triton-X 100
+ribosomes in the cytoplasm
+github. com/jemmageoghegan
+A3G incorporation into virions
+no emission to communal surfaces
+Real-time PCR
+Microsoft Excel or GraphPad Prism
+VP2 protein
+antibiotic
+PCBP2
+dehydratation, hypoactivity and marked liquid feces
+direct cell-to-cell spread
+72.76%
+1392
+Super-oxide dismutase-1
+June 2019
+80%
+2
+labour-intensive
+western blotting
+decreased infectious virus release
+IgM antibodies
+translation inhibition and concomitant SG formation
+Pipetting speed
+four
+6765 g/dL
+patterns
+90.2%
+primers
+increase in circulating half-life
+acute EBOV infections
+Acinetobacter baumannii
+larger variability and less curve fitting
+viruses and host nodes dichotomy
+more resistant
+any inference on both network and infectious disease models
+the serial interval
+marginal
+Handwashing
+Pandemic management strategies
+distilled water
+influenza
+GAD65
+ApoE fragments
+purification of the virions
+JAGS code
+Figure 1B and C
+Riyadh Regional Laboratory
+16
+8
+pneumonia prevention
+15%
+lavage samples
+translation inhibition
+Demeler's algorithm may not give correct results
+drug discovery of anti-inflammatory and antiviral agents against influenza
+hCT
+CPXV
+Spectral counts
+mucosal blood flow
+an epidemic
+anti-HCV activity
+101
+prevention
+confocal
+Worry and Susceptibility
+VE-cadherin
+downsides
+host susceptibility and virulence of influenza strains
+15,029
+À14.1
+208
+H7N9
+abnormally high phosphorylation state
+20.0 %
+54
+unique ear tag identifiers
+negatively regulates neuron formation
+D7 from enrollment
+2.9 deaths/10 000 population
+vaccines and antiviral agents
+Seasonal influenza vaccination
+137
+demyelination
+0.62
+nucleolus
+frameshifting efficiency
+potassium influx
+KOBAS 2.0 software
+Acute pulmonary responses
+2020
+to monitor the duration of asymptomatic shedding
+381
+a double strand RNA binding protein
+Intracellular delta antigen
+π ij
+Guangxi and Guizhou Provinces
+clinical correlations between defensin abundance and viral transmission or disease
+SeV copy-back DVGs
+quantitatively different gene expression responses
+15 min
+93
+insulin receptor substrates
+60%
+RPL11 and RPL5
+NR1H3
+collectins
+codon distributions
+7 reads per base
+universal transport medium
+mixed effects model
+alterations in the receptor binding
+clinically relevant conditions
+83% mortality
+glucose oxidase
+mutagenic
+Phase I/II
+double stranded DNA or singlestranded DNA
+TNFa, IL-1b and IFN-b
+2 kb
+repeated sampling
+lack of adequate information on lung geometry during growth
+siRNAs targeting VDAC3
+Saudi Arabia
+May 2016
+0.05
+Epitopes
+Ginsenoside Rb1
+Henry Grosjean
+EBV
+NF-кB
+2,000
+kD
+ABS 2 and 3
+no quality costs
+inhalational anthrax
+a very different mechanism
+55.3%
+The formation of contact between astrocytes and neural synapses
+Perkinsus SL RNAs
+breeding failure
+reliability of data collected
+one
+Mann-Whitney U-test
+parenchymal area
+Use of summary statistics
+M4 Parameter a
+Four
+bacterial co-infection
+ELISpot reader
+Western blot
+maturation
+P-site tRNA
+PF573228
+Illumina CASAVA pipeline
+Bayluscide
+alters the permeability
+Purified native rACE2 1-740
+qualitative estimates
+17
+matrix metalloproteinase-3
+Four
+PR8-mCherry
+BER
+RVA
+decrease the rate of endosomal release of PMO
+malaria, tuberculosis and HIV
+3-4 days
+May 18
+Antimicrobial resistance
+25
+α5-and β1-integrin degradation
+over 300 GB
+CC 50
+17
+Awake ECMO
+increased TIP production
+57.4
+personal information
+10.6%
+one month
+no longer expressed TcdC
+250 ms
+18%
+B2
+cytotoxicity
+specific venues and other sub-populations
+BMV RNA replication
+Figure 2
+Real-time PCR
+LAMP reactions
+effective sample size
+Over 80%
+62
+11,325
+positive signaling
+GDC
+Genes, automation and brickdust
+Presence of bone marrow hemophagocytosis
+214
+The advent of antiretroviral therapies
+Exposure impacts and their consequences
+humans
+GraphPad Prism
+Forty-nine
+80/40 mm Hg
+24 h
+enhanced responses to LPS
+cytokine "death" receptors
+cyclic dinucleotides
+RMassScreening
+36
+Purposive sampling
+biological
+IL-17A/F
+9 years old
+few
+T-cell exhaustion
+charge-charge interaction
+New technologies
+a new framework
+Renilla luciferase
+DCs
+viruses
+98.2%
+gRNA
+44
+assembles
+longer length of stay and prolonged ventilatory support
+Computational and bioinformatics
+566
+GCF 000001405.26 GRCh38
+mildly reactive
+a method that predicts only pseudoknots
+20 min
+Boltzmann constant
+postmortem immersion
+H5N1
+Virus titers
+six
+Axenfeld-Rieger syndrome
+significant correlations
+Σn
+Pharyngitis
+.
+340
+hsa04912
+E. faecium
+type II
+80%
+species-specific
+balancing invasiveness against the potential for obtaining adequate and sufficient tissue for diagnosis
+The size of the transmission bottleneck
+18
+Eritoran
+Ripley's L function
+disease phase-dependent
+hepatic lesions and concurrent areas of leukocyte infiltration
+K154E
+>80%
+Table S1
+Generalized Born solvation model
+HMW neddylated proteins
+84%
+maintaining the chain of infection as the pathogen spreads
+6620
+10
+1280
+virus binding to target cells
+2006
+Probiotics and prebiotics
+5 min
+neither mfold 1 nor mfold 2 represent the sole active confirmation
+Increased production of IFN-gamma
+ASP-trained clinical pharmacists and medical microbiologists
+artificial Beijing
+reduced
+persistent infection with pancreatropic enteroviruses
+4 Å
+preventing/ reducing lung injury
+Liberia
+binding to the IFN promoter
+CRT-mediated PrCR
+BSL2
+3,153
+ade4
+Multivariate analysis
+one metal binding site per SsTroA monomer
+Georgia
+fluorescence microscopy and indirect immunofluorescence assay
+11
+S rib
+Evolution
+3
+raising awareness and education
+stalk-specific antibodies
+14
+E1 protein
+serine
+Corticosteroids
+conformational epitopes
+Poisson Inverse-Gaussian regression model
+The samples collected without the exhaled breath from human subjects
+treatment for a bacterial pneumonia
+$10
+Apdm09
+cholesterol, sphingomyelin, ceramide, and PS
+RNA binding, PB2 binding, oligomerization and NLS
+47%
+retention of antigen expression
+NFKB1a, IKBKB
+7%
+Bethyl Laboratories
+> 95%
+fuzziness within the fingerprints
+HVR1
+gymnosis
+hypocoagulable profiles
+Analysis and interpretation of data
+Questions or messages regarding errors
+life span
+53%
+higher
+decrease
+31 months
+Genepix 6
+emphysema and osteoporosis
+host factors
+Leptospira
+cases that cannot be confirmed
+NLRP3 inflammasome
+NetCTLv1.2
+>95%
+The GP spike
+Lowry assay
+binds to HRV capsids
+2010
+5 min
+erroneous scienti fi c conclusions
+young children, impaired older adults or patients with underlying airway disease
+structural
+seven
+10 µL
+six
+virus-like particles
+IL-6
+166
+Nucleic acid
+PA replication
+pipo-site deletions
+January 15, 2020
+particular clinical features and severe illness
+clinical symptoms, history of potential exposure, and serologic studies
+Variable Wavelength Detector
+spectrophotometry
+admission route, severity, and infection site
+AaWRKY1
+a genuine GI disease outbreak
+expression intensity
+34.5 ms
+released-active
+to maintain themselves within populations
+IL-6
+cell lysates
+key cytokine
+replication-dependent Luc expression
+any estimate of peak
+Ampure beads
+27.5%
+serological classification
+VEGFA
+four
+more cases
+watershed transform algorithm
+a subset S
+Smo-Gli-1 signaling
+denaturing PAGE
+apoptotic cells
+30 min
+all neonates with intravenous catheters in DON
+32
+mycetoma
+Six to eight days
+fluorescence
+Ixodes
+25-75 nM
+male
+PNGase
+12
+contact between infected and susceptible populations
+15 min
+ER-Golgi
+TNF
+gender, age, and socioeconomic status
+type II pneumocytes
+TM homo-oligomer formation
+foreign travel
+direct evidence
+X k
+QuantiTect Probe RT-PCR Kit
+Axl receptor tyrosine kinase
+Professor Y. Bu
+all-year round vehicle washing
+apoptotic cell population
+minor
+Lack of management and conflicts within the team
+2-5A
+validated laboratory methods
+H5
+1 h
+High-frequency oscillatory ventilation
+quasispecies
+testing healthy animals
+negative
+phylodynamic model
+0.1 mg/ml
+confocal microscope
+655,000
+Bird droppings
+syndromic surveillance
+monocytes
+the tools' overall performance
+rhesus monkeys
+1.6
+zebrafish
+SARS
+comorbidity
+Forty
+Chinese scholarly journals
+interest
+immunoblot analysis
+five
+D-dimer
+neocortex and hippocampus
+three
+humans' alteration of the planet
+virological clearance or clinical outcome
+D SA
+clinod
+stakeholders
+10 mm
+1.85
+unbound virus
+PRRSV
+subsampling error
+correlation tendency
+Massachusetts
+MyD88 and IRAK1
+tracheal swab samples
+agent-based model
+Influenza vaccination
+academic performance by subject areas
+rs4430796
+gene fusion
+mixing up with each other
+cryoEM
+10 2 copies/reaction
+Circulating tumour cells
+rat anti-mouse CD16/CD32 monoclonal antibody
+n-BuLi
+The area of accessible diversified surface
+a core committee
+The loop composition
+TGF-β
+cellular ROS and cardiotonic steroids
+TPV of 0.860
+Apoptosis
+11
+the larger amino acid sequence
+Triterpenic
+emerging infectious diseases and public health threats
+disease pathology
+SSP
+recovering the relevant codes from the text
+phosphate centres
+RNeasy mini kit
+17.2 g/m 3
+GBS
+HSF3
+membrane fusion
+Cell surface cAMP receptors
+mosquito-borne
+20%
+post-capillary venules
+Hedgehog
+92%
+IL-12
+the presence of a wildtype spo0F allele
+CldU labeling of restarted forks
+Further studies
+spectrophotometer
+197.7 days
+adenoviral genome
+neuronal
+real time RT-PCR
+65 Caspase activity
+1%
+HIV-1 Transmission Dynamics
+23 days
+40
+advance knowledge of the behaviour of b t along the whole course of the epidemic
+4 1C
+SpiB
+puromycin-resistance
+4% paraformaldehyde
+public health recommendations
+significant relationships between microbial taxa and clinical outcome
+HBsAg protein
+SCORTEN
+Selenium
+serum amyloid A and haptoglobin
+20% piperidine
+52
+horizontally transmitting respiratory and enteric viruses
+over 1300
+diverse essential physiological pathways
+Transfection efficiencies
+≈0.43
+CD3
+outer and inner nuclear membranes
+over-the-counter
+Blood samples
+benztropine
+55
+The horizontal axis
+Average signal probe intensities
+adequate
+The structure of contact networks
+The mapping process
+The largest within-cluster SD
+TNT-mediated
+Expertise and motivation
+DURC
+Identification of drug-target interactions
+Differential degradation ρ > 1
+Software Vector NTI
+E MM
+simple random, systematic or stratified sampling methods
+Inverse probability of treatment weighting
+caspase-independent
+double-loop learning
+key residues
+knowledge of dominant organisms
+body weight and BP
+3 mM of MPA
+recombinant or recombinantlike
+F-measure
+60S ribosomal
+cell proliferation
+HLA promiscuity level
+over 65
+AIDS
+trachea and lung transcriptomes
+0.5 µM:0.1 µM
+FRET-based probe
+geriatrics
+plaque assay or a 50% tissue culture infective dose assay
+none
+bridging interactions
+12.36%
+cancer
+intra-arterial injection of S. aureus
+oxygen
+specific cell-mediated immunity
+most of group B taxa are earlier viruses
+a polymorphic site
+JLV
+177
+Astroviridae Study Group
+every four months
+10 nM
+weekly
+1.04-1.27
+recent
+MIDGE vectors
+fossil life
+matrix protein M1
+Taeniidae and, Sarcocystis spp.
+fungistatic effect of IASOS
+December through April
+transparency
+risk factors
+HIV/AIDS
+Eight
+graph invariants
+vomiting, fever, and diarrhea
+heroism
+Suicide by jumping
+13
+disappearance of all target lesions
+spleen and lymph nodes
+problems of very different character
+infectious lifespan
+Fmoc-L-azido-ornithine
+further optimization
+macrophages
+Merianieae species
+Plantar fascia
+-α and IL-1β
+5
+0.2% porcine gelatine
+5%
+40 min
+diversity
+Mafft-einsi
+human-adaptation
+KP t,m
+IFNL4
+steps 3 and 4
+1918
+ampicillin
+terms at low order in the normal form transform
+interferon-stimulated gene factor 3
+IB-RA and SB-RA
+5%
+aberrant TAAR1 regulation and function
+18
+93%
+specimens are sent to distant reference laboratories
+CSPG induced axonal dieback and degeneration
+30 µL of CellTiter-Glo®
+disease onset date
+Figure 2
+16 h
+Escherichia coli multidomain protein SufI
+1.4 times
+USPIO
+The primary sequence of the RNAs
+Mass and Conn
+overexpression of IL-1β
+NKG2D-mediated
+Representatives from the Funder and Sponsor
+increased considerably
+5%
+three
+ethanol-induced loss in oxidative phosphorylation system proteins
+Ang 1-7
+Tissues
+ER stress
+Malaysia
+0.9-2.1
+probabilistic model
+OPD
+TMAG
+genes upregulated by IL-4
+antigen-presenting
+The probability of emergence
+Estimates
+Further studies
+Dengue
+-80°C
+severe
+3-4 days
+a causative action
+virus-induced secondary bacterial infection
+Purified NB
+5,500 nt
+the raw p-value
+preclinical
+knives
+6 days
+steroids
+91%
+six
+PSI-938
+neuronal population and morphology remained largely unaffected
+HI titers
+monoclonal microbead
+parameter combinations for which the vaccine is self-extinguishing
+μM
+the host
+IL-6, TNF-α and COX2
+RPiRLS
+1,482
+mechanistic
+2009
+Single crystal X-ray diffraction data
+travel to China
+generation of cross reactive antibodies
+perceived personal probability of becoming infected while using public transportation
+primary or adjunctive herbal treatment
+VAP
+Data mining techniques
+Viral DNA
+Type I
+0.01
+78
+2955
+Nixon and Giedroc
+Basic clinical
+years of age
+1000
+LvATF4
+2
+the gene TSS
+naturally between two successive indices
+RNA viruses
+catalytic, immunomodulatory and antitumor properties
+NF-κB-SEAP expression
+a sub-network
+MN401425-MN401446
+three
+eight
+Phylogenies
+no difference between LAIV and inactivated influenza vaccine
+mutational pressure and translational selection
+1 hour
+negate the need for a pretreatment step
+GL receptor
+3.38%
+conserved viral proteins
+low CVP
+Anti-CHIKV polyclonal rabbit
+More than 10 %
+one-way ANOVA
+94 million
+three times to that
+10
+physiologic levels
+October 2007-March 2008
+the maximum concentration
+further transformation of VSMCs
+higher viral titers
+Internet-based
+High-Pure Viral Nucleic Acid KitR
+December 31, 2014
+4.3
+APOC1
+4.8 µL
+survive with bias over other individuals
+-hydroxyl
+sharp discharges from the frontotemporal area
+paracellular cation permeability
+10%
+chronic low-grade inflammatory disease
+Gbp2, Gbp5, and Gbp7 mRNA
+vitamin D
+Dixon method
+minor to more serious
+24 weeks
+cholera
+oligosaccharide deacetylation
+electrographic status epilepticus
+16
+Image-Pro Plus 6.0 software
+a general marker of infection
+ZDOCK
+UV
+Fibrin
+decrease
+replication
+three
+eight
+cryptochromes
+getting infected
+a distinct feature
+PvPep95 and PvPep96.03
+Over 10
+decreased NK cell frequencies/function and serum IL-12 levels
+3100
+Log ACE2 activity
+their importance
+case-based rapid risk assessment
+Living Image 4.0
+3= proximal
+Pneumonia
+codon-anticodon interaction
+increases
+5 to 20 mg of total RNA from uninfected control and infected samples
+purple formazan crystals
+Avian diseases
+IL-1Ra production
+hyperthermic temperatures
+finding possible functional targeting strategies to control inflammation in patients who are susceptible to infections
+Carole Baskin
+tail-hair samples
+interferon signaling
+new pathogenic and zoonotic bornavirus species
+90%
+acute exacerbations of chronic airway inflammatory diseases
+MS
+adenovirus-induced changes on nucleolar composition
+numerator/denominator bias
+chronic obstruction of airway flow
+Policy briefs and presentations at national meetings
+B t
+1 µl of each cDNA
+C.zeylanoides
+Co-infection with porcine parvovirus
+70%
+Prediction tools or 3D-structural analyses
+enzymatic protection
+two
+high production and inventory costs
+oxidant stress-dependent
+2 days
+12
+Saxony and New Brandenburg
+#pragma omp parallel
+lung length
+Brighton Red
+DC-SIGN
+limits
+Mycoplasma pneumoniae
+western blot analysis
+latent infection period
+3.5 mm
+five
+Qinghailike viruses
+110,465
+1:2
+9.1
+The distance of joints in the 3D world
+UNC93B1
+RLuc
+Pain
+VLP vaccines
+ssRNA association
+Continuous variables with normal distribution
+if non-severe illness is more common than detected
+degraded
+their ability to identify adequately and exactly the individuals to be targeted by a programme
+Vary Insulin protocols
+Nucleospin RNA Plus Kit
+oxidative stress
+~50%
+twice
+higher P max
+80%
+42%
+gallic acid
+outcome
+generalization capability
+① to ⑬
+Ambros et al.
+20% polyacrylamide, 7 M urea gel
+50 and 100 nM of TFO1
+phylogeographic substitution model
+negative costimulatory
+mock controls
+influenza A
+genetic and environmental factors
+R g
+C2-G18 base pair
+activity in vivo
+median and interquartile range
+biodegradable PLGA microspheres
+non-specific NP interactions
+IFNAR2 and IFNGR2
+glycyrrhizic acid monoammonium salt
+Comprehensive Antibody Vaccine Immune Monitoring Consortium
+Nikon Eclipse TE2000-U fluorescence microscope
+10 years
+kennel cough
+Cardinal and Cadenza
+Two
+Streptococcus pneumoniae
+PARF
+9
+Restricted classes of pseudoknots
+Next-generation sequencing analysis of a variety of gene panels
+user-friendly
+T reg s
+PCV2 and some of the avian circoviruses
+Combining debulking surgery with radiotherapy
+SNF7
+neonatal infection
+CD163
+IBV
+a single large wave
+elevation of in-circuit pressure
+cellular targets
+viral RNA
+0.3 × 10 6 cells/mL
+P-values below 0.05
+200
+adhesion proteins
+virus-induced encephalitis
+oxidative burst activity
+drugs
+Avian influenza
+A549, 16HBE, and HEK-293
+Nanobodies
+51%
+ML29 down-regulation of IFI44
+metabolites
+YFV-17D infection
+Rolling window size
+separately
+CNPase
+Hepatitis C
+humoral immune response
+excessive apoptotic alterations
+atrial signal detection and analysis
+counterimmunoelectrophoresis
+Mice
+Significant nucleic acid sequence variation
+Zetasizer
+W
+31 to 42%
+elongated structures
+30,088
+significant moderated effect on the mediation relationship
+HCV
+Dr. D. Corti
+plant genomic DNA kit
+publication of this article
+5 μg/ml
+Taylor-linearized
+ABI 7300 SDS software v.1.3
+anti-inflammatory cytokines
+2003
+76
+virulent
+294G
+14
+complementation
+generation of alveolar epithelial cells
+systemic inflammatory response
+Atelidae
+length time-effect bias
+The interferon system
+−80 • C
+γ δ T cells
+terminal regions
+26%
+fluorochrome-conjugated mAbs
+ASP
+1978
+15%
+paraspeckles
+23
+24.0%
+syber green master mix
+Histological scores
+14.3%
+RVA
+Traditional Chinese conservatism
+Antibody-mediated neutralization
+20%-50%
+1257
+corrected p
+pH1N1
+Network metrics
+cell-surface expression
+2.1
+CD3 + T cells
+DOCK3.7
+cloacal and oropharyngeal
+three
+Kaplan-Meier curves
+IL-1β or IL-6
+population health
+platelet counts under 150,000/μL
+two
+48%
+regulatory sequences or regulatory factor binding sites
+immune
+100 ml ATBS substrate
+four
+Ly49H-mediated NK cell activation
+monthly
+field epidemiological studies or clinical studies
+V9 and LOB7
+6
+inducing inflammation around blood vessels and rupturing atherosclerotic plaques
+1976
+conventional parenteral immunization
+quarantine
+Saudi Arabia
+KKL
+one-way ANOVA
+obstetricians and gynecologists and public health physicians
+mutagenicity and carcinogenicity of a compound
+A. baumannii and P. aeruginosa
+a homotetramer
+tandem multiplex PCR
+an exacerbation event
+presence of consensus amino acid residues substituted during conservancy analysis
+22.52 ± 0.18 µM
+PCR products
+Results
+quantitative structure-toxicity
+how often individuals recognize a given peptide from a pathogen
+primary translation of input viral RNA
+483
+À1 RF
+neurobiological
+PLY and caspase-1
+.10 TCID 50
+an injection site
+ClpP and FtsH
+1-2%
+reverse transcription polymerase chain reaction
+drying and staining
+anti-P2RY12
+.90%
+relative fitness
+autophagy induction
+indoleamine 2,3-dioxygenase
+Survival to 28 days
+regulatory network sparsity
+Obesity
+estimated vector density
+Thirteen
+age, race and geographic localization
+four times daily
+CXCL10
+number of peptides sampled per randomization
+internally consistent and distinct from existing relevant measures
+NCBI GenBank database
+6-10
+five
+novel gene responses against influenza in the future
+1%
+regular expression based matching
+18.5 months
+38
+4.8%
+ImageJ64
+liver
+targeted quarantine/vaccination
+Supplemental Table 1
+4176
+over 50 proteins
+UCKL1
+LMP2A
+Parent-Teacher Association
+DEP techniques
+MHC class II
+carnitine palmitoil transferase 1
+EF-2 function
+charge repulsion from the anionic dextran-sulfate
+Anti-drug education
+Three
+Virus stocks
+neighbourhood hybridization intensity profile analysis and nucleotide substitution bias analysis
+protects mice against ZIKV infection
+SVQYHPLA
+Quality indicators
+RANDOX
+585
+nuclear calcium signals
+280˚C
+University of Florida
+alveolo-arterial oxygen gradient
+diamidines
+via the IM or IN route
+ubiquitin-dependent proteasome degradation
+Mersenne Twister
+IL-13, IL-10 and IL-17A mRNA relative levels
+linear regression or multiple linear regression
+secondary attack rates
+75%
+1121
+tetherin
+2009
+infection status and presence of viral RNA
+six
+analysis of transcriptomes of non-model species
+The ompA::tn mutant lacked full-length OmpA
+0.203 ± 0.112
+cytokines
+1.30
+The multifunctional factor NS5
+macropinocytosis
+HIV-1 viral titers and replication
+Bayesian hierarchical modelling framework
+IFN-I signaling
+supernatants
+the standard deviation of the mean
+soluble receptors
+microfluidic
+3 and 2
+LC3-II
+non-painful chronic pancreatitis
+three
+2009-2010
+codon usage bias
+three
+Data obtained from the experiments
+University of Ottawa
+benztropine
+743
+Manton and Stallard
+the correct fragment length
+entropy and relative entropy
+direct
+inspiration synchronized VMN
+fusion
+Spectral analysis
+negligible
+statistical significance
+39
+pre-transmission interval
+vr3
+respiratory and renal
+white blood cell count, PCV, hemoglobin concentration, and RBC
+viral replication
+essential
+Type VII
+Each result
+damage
+two
+Toll-like receptor 9 agonists
+O 2 and H 2 O 2
+PRRSV infectivity
+EpiInfo7
+the virus
+c n ∼ 0.2
+PD-L1
+compositional constraints
+autophagy elongation complex proteins
+vaccinia
+US$2500
+fifteen
+81.8%
+66%
+mRNA
+Trypsin
+HIV RT
+Malaysia
+ipg
+15%
+hemagglutinin
+MRM analysis
+six
+APOBEC3 proteins
+four
+Influenza NA
+loss of stem-cell maintenance
+accuracy and sharpness
+higher NC uptake
+Interactions with probability above an upper threshold
+the m36 epitope
+30 days
+mononuclear cell
+antiretroviral therapy
+control efforts that superimpose on any climate effects
+symptoms or diagnoses of patients from ED and/or physician office visits
+the position of the first residue from the peptide mapped onto the protein sequence
+over 2314 exabytes
+three
+diffuse alveolar damage
+regional circulating strains
+translation initiation and polypeptide chain elongation
+viral RNA transcription
+drug concentrations
+Severe hemodilutional anemia
+follicle cell type
+PPARα and PPARγ
+five random fields per well
+18S and 28S
+elevation of in-circuit pressure
+weekly
+siRNA duplexes
+Ace-2
+100 mM of amiloride
+binds to HMGB1 and inactivates its biological activities
+quantity of interest
+catalyst 1 and trimethoxybenzene in C6D6
+poor prognosis
+CD8 T RM cells
+initiating
+0.1%
+cytokines
+MS Excel software
+efficient VLP release
+population-based national data
+conventional entropic measures
+memory demands
+PanAd3-NPM1
+COX-2 and VEGF
+Two
+four
+cytoplasmic
+rapid
+weekend
+MA
+mRNA 2° structures
+disease selfmanagement of a patient
+membranous web regions / DMVs
+Western blot analysis
+SSEA-1
+48 hpi
+euarchontoglires
+P70S
+nuclear localization of B1
+45
+procedures
+skipping of one or more exons
+Circadian disruptions
+pVSVΔG-CCHFV-GPC
+R 0
+Modulation of MCP-1 levels
+C2 endo
+lack of clinical sign data
+immediate high sensitivity POC molecular diagnostic testing
+paraffin
+gradient elutions
+35% to 70%
+clinical
+PIMs activation
+histopathological
+17 h
+the highest attainable standard of health
+O. ostertagi nASP
+RNA ADP-ribosylation
+IRAS protein
+sero-neutralization and protection assays
+BACE-1
+lepidopterans
+a 30 gauge needle
+Ambient particulate matter
+malignant tumors with an aggressive behavior
+diversification of parasites and potentially speciation
+alters nuclear transport pathways
+PCNA, BMP2, and IL-6
+concentrators
+EBV and CpG
+their respective data
+48
+51
+IL-15
+similar results
+Universality
+twenty-four
+PottersWheel Toolbox
+320,448
+univariate boxplots and cumulative distribution function plots
+interleukin 4, IL-5, and IL-13
+C2
+1022
+blocking of sea or land transport
+HIV transmission
+spherical
+13
+livers 1 to 6
+myeloid
+vaccination
+Sepsis
+7.4
+20 mm
+initiate antimicrobial responses
+close agreement between the KDE and actual spatial probability
+non-neutralizing
+intraocular route
+independence
+Eight
+H1N1-related search queries
+latex
+viral promoter
+S > 0
+induce the removal of infected cells before progeny virus budding and spread
+protection from disease
+a series of receptors and their associated signaling molecules
+6 months
+A unique infrastructure and search strategy system
+PLANET
+bioinformatics
+Cost and complexity
+gradient descent
+CHEMGRID
+ompB STOP ::tn bacteria
+28%
+Nuclear factor-kB
+AZD9668
+95% ethanol
+Assays
+the window with lowest -LogP value
+Soap align 2.21
+mammal specific IgG antibodies
+Phenformin
+Hantaan virus
+fluorescent
+A single early switch point
+1 to 5 days
+16 hours
+English
+LipidTOX green stain
+4 weeks
+participating in everyday activities
+damp out in time
+spo0A
+lower
+ribosomal machinery
+0.44 to 0.56
+Synergy 2 microplate luminometer
+evaluating the quality of observation studies
+Type II
+CCL3L1
+2,500 to 4,000 mm
+eukaryotic cell line
+anti-CD3 monoclonal antibody
+requiring varying degrees of attention, concentration, and effort
+The supernatant
+Normal
+Microglial processes
+Between 23 and 31%
+16 h
+Vero and Vero-derived cell lines
+91%
+lack of SP-D expression
+reverse read-direction ORFs
+Strategic planning and adequate protections
+DNA Lad-der™
+murine leukemia virus
+biologically vital proteins
+Helium-neon
+DNA
+increase in expiratory resistance
+tumor progression
+to conduct large HIV treatment trials
+biomarkers
+IGF-1R
+opposed
+T cells
+E. necator
+protease sensitivity
+4283
+January 2018
+Diffuse alveolar haemorrhage
+177
+sGPEdit+GP 1,2 Edit antiserum
+70%
+60 min
+LacZ
+reliable longitudinal administrative data
+RNA
+virus from the spleen
+antisense oligonucleotides
+370
+GADD34 induction by poly I:C
+Elevated body temperature
+Pattern recognition receptors
+CliRes
+Analyze Dataset
+$50,000
+host Src
+microbial concentration
+different outcomes
+our mid-term strategic decisions
+gene expression similarities estimated by generalized linear regression models
+Hepatitis C Virus
+geographic location and travel
+IFNL4-TT
+second residue
+key orchestrators of the immune response
+protein sequences
+epochal evolution model
+hyaline
+CD8 + T cells
+transparent, fair, replicable and coordinated processes and tools
+tissue injury
+data on genetic diversity and their clinical association among pediatric populations
+3-4 weeks
+novel diagnostic technologies
+tighter CD4 binding
+128
+The blue arrow
+GeneClean Spin Kit
+Standard PCR
+15 min
+ORF50 transcription and virion production
+Viruses
+Nine
+differentially expressed
+their location within the central nervous system
+Central nodes
+seroprotection rate ratio
+Astragali radix
+10 000
+human pathology
+Tandemly arrayed duplicated genes
+TGFB1
+strongly reduced DAI/Zbp1 expression
+quasispecies
+field case tracing
+10%
+24 h
+activated macropinocytic pathway
+low MV
+p53REs
+windows
+MRSA
+infection
+Verbal consent
+Purifying selection
+188.5 pg/mL
+Recording exposure procedures within farms
+MARDS
+4% paraformaldehyde or with methanol:acetone
+Anatoxin A
+glutathione
+VP4 and VP7
+B90%
+10
+dose-response
+worse
+Turnaround
+Global budgeting
+unexpected
+≈1 year
+amplification bias
+vital signs
+445
+Six
+24
+Pro-inflammatory
+WHO
+search circles
+target cell limited model
+99.9%
+proper evaluation of multiple RGs
+42
+electroporation
+HT22
+2.7 days
+Two
+Primer pair P2/P3
+preexisting mental health concerns
+individual variation in infectiousness
+1%
+0.5 µg
+26%
+hexanoic acid
+bad breath and toothbrushing frequency
+basic virus transmissibility
+Tetherin
+bronchial wall thickenings
+NK cells
+genetic drift
+hydrophobicity
+Guava Cell Cycle solution
+microscopic findings
+the capsid protein precursors
+splenocytes
+habitat hotspots
+θ
+Adherent cells
+8
+4°C
+Calbiochem
+5
+mutSL-based
+GENSTYLE
+University of Cambridge
+Tp2-class C9 protein
+genetic determinants of the HDL proteome and lipidome
+1 year
+~50
+cytopathic effect protection assay
+0.015
+A corona wire
+antiviral
+ΔpbrB mutants
+8-12 weeks
+An N c plot
+24 h
+50%
+16-18 million
+NF-κ B, AP-1 and IRF3
+induction and inhibition in the signaling network
+mAb114
+very low doses of protein were needed
+480 bp
+10 μM Picolyl biotin azide
+Germany and Great Britain
+pathogenetic
+fitness
+reduce the shedding of pathogens to wildlife disease vectors or into the environment
+sympathetic outflow
+LBM size and city
+Proteomics and expression profiling
+235
+>10 4 colony-forming units per milliliter
+laboratory data and culture results
+mechanical
+IFN synthesis
+Pruritus UDCA
+cytomegalovirus and herpes simplex virus
+1700
+paired-end information
+subunits
+6,42
+Toll like receptor 3 and TLR7
+the exact structure of 2
+type I immune responses
+loop size and tertiary interactions
+zoonotic
+Summary statistics
+18 days
+more experiments
+miRNA expression profiles
+P value for each comparison o0.0001
+3-35 d
+11
+1 versus 4, and 2 versus 2
+enhanced stability
+DENV-2 infection in the brain
+35
+stochastic center manifold reduction
+Respiratory droplet transmission
+27
+August to November
+43
+Virus Varroosis
+Network entropy
+Total protein
+ML and neighbor-net
+pro-inflammatory
+deep learning
+coagulasenegative Staphylococci
+LC Packings C18 PepMap 100
+by retaining edges present in all the individual graphs
+IL-10
+inhibition
+viral epitopes
+immunofluorescence
+bacterial pathogens
+bistability and hysteresis bifurcation
+bridge hosts
+≥4-fold increase in HI or NI titer
+an edge
+protection and in viral clearance
+50,000
+95%
+recombination and reassortment in RNA viruses
+three
+SK1
+cell-penetrating homing peptides
+E. coli DH10Bac cells
+SAMD9
+Intermittent hemodialysis
+112
+Mab 5D6
+I. scapularis
+epochal evolution model
+saving money and time
+A complex
+right-skewed
+excessive cardiac fibrosis
+microchannel
+the manufacturer
+1 day
+6 to 6.5
+three million
+cumulative operation volumes
+93
+reduce the number of allogeneic RBCs transfused
+a heavily reduced cellular genome
+TRIM25
+traditional medicine
+40 min
+458
+adults hospitalized with influenza with and without pneumonia
+midazolam
+30 %
+Nuclear blebbing
+production of Brucella specific IgG
+catalytic subunits
+Isolate HA16-5
+trypan blue exclusion
+OmpB
+Bats
+SREBP-regulated gene
+all potentially relevant biomarkers
+epigenetic changes
+BB0069
+reporter gene expression
+proteins that accumulate with the viral genomes
+acute haemorrhagic fever
+Berlin
+RNA
+severe lung damage
+real-time reverse-transcription polymerase chain reaction assays
+Poisson likelihood
+2.0%
+AP2s
+PGD2
+SPPV-063
+personal protective devices
+neighbouring countries
+low resolution grids
+proportional to ):
+HOCl-induced modifications
+eight
+Mice
+biosecurity factors
+increased
+Ectomycorrhizal
+40
+Cuba
+Adamantine, rimantadine and alkylated imino sugars
+4
+,3-fold
+failure to target other components of the immune system
+clearing viral infection
+Lys or Arg
+2009
+Ifitm3 -/- mice
+97
+under inverted microscope
+tr-eVLPs
+high rates of contamination
+secretory granule packaging machinery
+rate constant
+docking of the liposomes
+single-stranded spacers
+4%
+muramyl dipeptide
+fresh medium
+Mild exertion
+Long-term follow-up data
+preparations and considerations
+>62 and <188
+repeated measures regression model
+Global budgeting
+HCV E2 construct
+Phylogenetic
+Gammaproteobacteria
+TSG101
+GFP + cells
+individual LCMV replicative RNA species
+protein C system
+lack of tissue-specific developmentally regulated control mechanisms
+BV2 and HEK293T cell lines
+Autophagy
+low codon bias
+papain-like cysteine proteases
+Figure 3
+back-pocket
+SCHU S4
+transplantation
+MHV
+641
+individual strains
+10%
+nucleoprotein genes
+12 h
+5
+ablates the synthesis of the SH and G glycoproteins
+antigenic
+methionine
+shRNA
+Ethical
+enzyme linked immunosorbent assay
+thousands
+12
+2%
+1 μ M thapsigargin
+>28%
+1975
+underexplored
+Microfluidic channels
+Primary ciliary dyskinesia
+important
+One microgram of total RNA
+L-A-encoded proteins
+Eq.
+60%
+bacterial infection
+antioxidant
+protein degradation
+viral nucleic acid
+poliovirus
+C-terminal fusions to the thioredoxin tag
+mass-scale vaccinations
+Serologic testing
+mice
+templates
+2%
+experts
+ADAM17
+tissue culture supernatants
+Biolayout Express 3D
+Time to hypoxaemia resolution
+depression of host cellular immunity
+PCR
+CHIKV RNA and infectious virus levels
+copies
+antigenic mimics of the native parasite protein
+VF development
+lipid rafts
+partial inhibition
+Firmicutes and Bacteriotedes
+TNF-a
+MSDN
+eukaryotic translation elongation factor 1B complex
+724
+27
+recognizes sialic acid on the host surface glycan
+intrinsic enzymatic activity
+Quantification of GAPDH gene
+3.6%
+Novel approaches for rational design in the genomic era
+yellow green
+between 4 to 10 days
+sPLA2
+International Journal of Food Microbiology
+adenovirus and 2009 H1N1
+tenfold cross-validation
+CD55
+intensive care units
+Nidoviralies
+three
+Soluble GP1-Fc
+~30 kDa
+VP3-E76G
+Invitrogen
+Sen-siFAST Probe Lo-ROX One-Step Kit
+R1597W
+homogeneous mixing among individuals
+intrahepatic NK cells
+delayed chain termination
+MAPKs
+Plastic Maxisorb microwells
+9
+overproduction of free radicals
+PCC t
+exportin-5
+SP-D expression
+4 h
+1 g of RNA
+Mitochondria dynamics
+co-inhibitory pathways
+0.58
+Pneumocystis jiroveci pneumonia
+multiple representations of the primary protein sequence
+forward stepwise variable-selection strategy
+multivariate
+Insurance package
+1715
+a glycopeptide antibiotic
+picornaviruses
+decreases
+metagenomic sequencing of urban sewage
+Angiotensin II
+3.7%
+demographic and clinical variables between SARI and ILI patients
+180 min
+EMBOSS transeq
+55
+natural killer cell
+18
+238
+β-actin
+Transport of animals to market
+three
+Mutant R411A
+highest hybridization signal
+by using their specific compound characteristics
+O-antigen
+codon usage pattern
+Three millilitres of blood
+75%
+Bliss independence model
+RIG-I signaling
+favorable conditions for smallpox transmission
+peak levels of sXBP1 transcripts
+21 days
+models for estimating CV risk
+antioxidant
+clustering of related results
+Samples incubated with only the secondary antibodies
+genotypic information
+environmental, occupational, and metabolic risks
+100 μg/mL PA
+UPR
+97%
+Ad early E1A
+26
+H5/H7
+Conidial suspensions of transformants and the G526 strain
+ermC
+anomalous
+Viral RNA extracted from SARS-CoV
+54
+30,000
+B cells and MNV specific antibody
+malnutrition
+Sankoff approach
+mass spectrometry
+epidermal growth factor receptor
+Y613A and Y624A
+The PIC window
+ssc-miR-30d_R-1
+sufficient pathogen reduction and acceptable product quality
+Passive immunization
+polymerase chain reaction
+nine
+reduced inflammatory responses
+its origin
+Primary antibody
+Proteolysis of the particle preparation
+free gp120
+homogeneous
+bio-active specialized plant metabolites
+six
+12
+seven
+18%
+Information about the ventilation system settings and restaurant size
+107,100
+ZIKV-prME
+anticipation effects
+cytotoxicity
+Marshall E. Kadin
+Linear correlation analysis
+β2M and RPS15
+7.09x10 -4 substitutions/site/year
+Conformational flexibility
+dissemination methods
+twice
+0.4 -0.9
+reduced pharmacodynamics of the drug
+cross-referenced the data with the text of each publication
+steroid dose
+pain, fatigue and organ dysfunction
+6
+superscript III
+apoptosis
+10
+Hoechst dye
+winter school vacation
+1649
+genetic background and environmental stress factors
+western blotting
+22
+anti-apoptotic
+nonsticky proteinaceous compounds
+eight
+IBMX
+80%
+2001
+P
+City Health Department
+plasma FAA
+huge
+A flaviviral E protein 4G2 monoclonal antibody
+rural youth violence
+ruminating
+EXPO32
+maximum likelihood method
+Lower respiratory infections
+fast phase
+TBP
+HA
+IL-10-secreting CD8 neg cells
+Confusion, Hubbub, and Order Scale
+Induction of viperin mRNA expression
+M. pneumoniae
+preonset of psychosis
+Hitachi F-3000 spectrofluorometer
+a causative organism
+how evaluations are conceived and conducted
+2%
+Major histocompatibility complex I restricted cytotoxic T lymphocytes
+Depletion of ULK1/2
+14 dpc
+Seventeen
+transformation with adenovirus
+disease
+681
+effective mucociliary clearance
+alternative formulations of the underlying optimization problem
+CD62L
+increased fluorescence signal
+humoral
+29.3%
+viral clearance
+HTNV antigen levels and RNA loads
+modular assays attached to smartphones
+30% ± 14.93%
+1513
+H3K79 methylation
+clinical drug development platforms
+mES/ MCDB201
+collagen production
+The PrP genotype
+CEACAM18
+MHC class I peptide presentation
+Energy minimization
+IFNAR −/− A129 immunodeficient mice
+alignment-free methodology
+4
+60 ± 5%
+Receiver operating characteristic curves
+46%
+Microorganism infection and tissue injuries
+IgY-VLP solutions
+Vietnam
+spliceosomes
+egret, heron and pond heron species
+six
+anti-FLAG and antihuman Fc
+The founding sponsors
+Undifferentiated epithelial cell culture model
+copy number differences
+470
+10 µM
+small study effects
+two
+Helios protein and neuropilin-1
+predictive mode
+confocal
+sequence data
+efficient
+changes in overall physiology
+infection
+formic acid
+$60%
+HIV1 Nef protein
+glycoprotein degradation
+protein
+obesity, steatosis, and type 2 diabetes
+24
+isolation and contact tracing
+cholesterol
+72 hours
+aminopeptidase M
+around three weeks post-infection
+15 ml of RT buffer containing RNasin inhibitor and cycloheximide
+twice per day
+inflammatory
+R 0 and R t
+Low-dose SC
+FRET state of ∼0.3
+bootstrap confidence intervals
+improve cell viability
+GISs
+citrate buffer
+independently encapsidated separate segments
+oligonucleotides
+time series
+pneumococcus and viral pathogens
+CTF + CGR
+MEV NS1 mRNA coding region
+78%
+lectins
+Gln288
+α-catenin
+fever, fatigue, dry cough, sore throat and headache
+2398
+gene segments
+DEN-4
+immobilization control
+basic
+Powered airpurifying respirators
+neutrophil biomarkers
+62
+pathogen's dynamics
+iron colorimetric assay kit
+nanogels
+Five
+DAKO Liquid DAB Substrate Chromogen System
+A better understanding of the disease pathology
+NaN 3 and 18crown-6
+89%
+Hantavirus
+Mastomys natalensis
+infection with the homologous virus
+L118A/I119A
+p-values
+plasmacytoid dendritic cells
+epithelial-mesenchymal transition signaling
+phosphoramidon
+MNV-1 permissive BV-2 cells
+Neuroinflammation secondary to TBI
+100%
+A virus stock of Langat virus strain TP21
+patient safety
+speci-fication
+the type of ventilator
+Pneumonia
+co-engagement of different immune receptors
+80%
+differences in IAV-interference with host genes expression
+Bid
+in vitro neutralization
+m 7 G 46
+blood samples
+IL-15
+2 mg of total RNA
+extremely high
+renal blood flow and urinary output
+granulocyte-macrophage colony-stimulating factor
+Dysentery and TAP
+10
+85
+Hb digestion
+40S ribosomal
+total protein ubiquitination and ISG15ylation
+endoplasmic reticulum
+Escherichia coli
+OCTA
+H3N2 HA1
+normal form coordinate transform method
+Inhibition of aminopeptidases
+immaturity
+significant protection
+flow cytometer
+bleeding
+proportionate mixing
+a duplex formed by complementary antisense oligonucleotides
+effective solutions
+HN and HC
+Redesigning primers
+Non-specific amplification
+apoptotic or necrotic
+Graph
+two
+ADE and cross immunity
+Pileup
+R 0 = exp
+N-acetylglucosamine
+Rotaflow Maquet Centrifugal Pump
+viral transmission
+disorders of the airways largely related to the presence of persistent inflammation
+cellular response
+CyDs
+Stromatolite structures
+46%
+7.0
+Staphylococci
+JE progression
+Chikungunya or dengue
+-20uC
+gene dosage and phenotypic character
+cysteine-rich
+Sunlight and ultraviolet rays
+ferrets
+7
+7,800
+strength and toughness
+Xenopus and Drosophila
+Pulmonary complications including atelectasis, pneumonia, and acute respiratory failure
+production of neuropeptides
+10-fold
+balanced immune responses
+cross-reaction
+InlB
+Foxp3-EGFP
+LAS AF Lite software
+NK cells
+transport of G to the plasma membrane
+hospital mortality
+C-type
+thoracoscopy
+endothelial cells
+G33
+short substrate/inhibitor segments of protein loops or strands
+IL-27
+Fourteen
+lung IFN-γ mRNA
+105
+230
+PANTHER database
+five
+Fifty four
+sialic acid clustering
+sympathetic
+fungi and oomycetes
+temporal signal
+to minimize the costs associated with performing chart review
+Japanese encephalitis virus 4
+13,753
+2.5%
+H1N1
+PD-1-positive cells
+18.4%
+Three
+Fractions of 0.5 ml
+Mouse PSCs and mPSCs Oct4+
+Insertion of tail-anchored proteins into the ER membrane
+Mas
+investigations into identifying alternative methods
+17%
+APACHE-II scoring system
+59
+fold differences and statistical tests
+cell surface receptor-mediated endocytosis and sorting
+6.6610
+specific interventions
+the value of the residual sum of squares
+44
+371
+QDD 1.3
+Twenty-four hours
+lowest inhibitor concentration
+FISH
+Xicheng District
+four
+Chemical off-gassing
+5 mm
+two-tailed t test
+Evolutionary distances
+protein immobilization
+human nucleolus-associated chromatin domains
+4,017 amino acids
+versatile plasticity
+enzyme-linked immunosorbent assay kit
+H5N1 HPAI reservoirs
+seven
+LAMP reactions
+121
+fluorescent infected cells expressing GFP
+bulky phenyl group
+three days
+CD9 and CD81
+occult metastases
+116
+nine
+Environmental surveillance
+flow cytometry
+CpG dinucleotide
+use of ACE inhibitor and/or angiotensin receptor blockers
+continuous assessment
+Diarrhea
+mice
+JX036326-JX036359
+mRNA degradation by RNA silencing
+Toronto, Canada
+positive and negative controls
+socio-economic groups
+98.9%
+>12,000
+cell necrosis
+closed-loop microfluidics platform
+Ancestral knowledge
+children between the ages of 6-24 months
+African countries
+N-terminus
+higher copies of virion produced
+Dicer
+mineral-oil-spread
+IP-10 and RANTES
+time, place, and genetic information
+working-age adults
+Whatman No. 1 filter paper
+conserved
+thousands
+HAdV-C strains
+lower levels of tracing success
+ImageJ
+NFkB activity
+periods of influenza activity in Georgia
+30 minutes
+transcription/replication complex
+LPS
+GeneChip Operating System v 1.2
+RT-LAMP reaction
+Circoviridae
+GC residues
+viral replication
+enhances the p65 protein in gastric CSCs
+pDC loss
+14 dpi
+hyaluronidase
+Nrf2
+1x RBC lysis buffer
+MDDCs
+longitude and latitude data
+malarial drugs
+BCA assay
+no measurable cell death
+two
+500,000
+lethal H5N1 infection
+monocytes
+save the life of patients in the late period
+Viremia
+neity
+23 to 44%
+TI cell TNF-a production
+PRV
+Pulmonary fibrosis
+doxycycline
+financial limitations
+confirmatory diagnosis and epidemiological surveys
+Ectropis obliqua picorna-like virus
+cldn3, 4 and 18
+WT and lpr mice
+45%
+Kaempferol
+Regional persistence of polio
+23
+non-allergic rhinitis and influenza like-illness
+quantum mechanical polarizable force
+B cells
+perfluorocarbon
+44
+GLMM and BRT
+Lp-1s
+neighboring relationships
+2%
+media
+enhanced
+fever triage, identifying suspected cases, and transferring to the local IDH
+Poisson's Law
+cancer development and prognosis
+EIciRNAs
+Hemorrhagic fever with renal syndrome
+a bipartisan parliamentary group
+RNeasy
+2H5-A14
+biological
+mucous membranes
+hexon
+mitotic spindle
+completely elucidated
+Enhanced surveillance
+thin-layer
+tetraspanin membrane protein family
+SYFPEITHI
+bronchiolitis and severe neonatal infections
+stabilisation
+3
+lower HTNV RNA loads
+PTM of STATs
+true/false
+Hitachi H-7100 electron microscope
+mild, moderate, severe and dead
+2 weeks
+Sustainability, Sovereignty and Solidarity and bio-Security
+Human endogenous retrovirus
+PyMOL and UCSF Chimera
+WildNet
+luciferase
+all
+six
+Discharge codes
+maternal antibodies
+absorbance measured at 280 nm
+potential homologues
+Administrative data
+positive
+mitochondria compartment
+Mitochondria
+Capacity problems
+heat shock
+Early detection of fibrosis progression and the development of portal hypertension
+HEp-2 cells
+its ER localization
+Rodentassociated viruses
+hemagglutinin and neuraminidase
+significant hurdles
+ATPase, helicase, endonuclease and ATP binding activities
+codon model
+to escape the disaster
+OrgMassSpecR
+macrophage-infiltration
+11
+sticky
+pre NDV challenge growth rate
+down-regulation of mir-21
+Geir Gunnlaugsson
+The variance of daily temperature
+turned up
+toxicity
+generate long-lasting memory CTLs
+neutrophil elastase
+Student's t-test
+HBs-humAbs
+Models based on ordinary differential equations
+molecular and phenotypic characterizations of AIVs
+primates and ungulates
+higher tidal volume
+angiotensin converting enzymes
+ethidium bromide
+Multiple factors
+40 amino acid domain region
+Student's t test
+generalized linear regression model
+Wide use of Big Data
+HPV capsid disassembly
+Ga-citrate and donepezil
+increases
+Descriptive statistics
+FTLSV strains isolated from Japan
+Serum samples
+19,461
+three
+Sixty milliliter ice-cold saline
+unusual and very unfortunate
+Avastrovirus 5
+Forty-one
+Sixty-one
+serological data and hospitalization data
+0.08
+tumour progression
+simulations of metapopulation models
+Met 706
+Fidelity adjustment mutagenesis based live attenuated vaccine design
+SAP-SII and SOFA score
+10%
+malaria-negative children with infectious diseases
+Myodes glareolus
+P. jiroveci
+Forty-one percent
+Norway, Sweden, Germany, Belgium, Poland and Switzerland
+toxicity of the ssRNA nano-structure adjuvant
+Th17 differentiation
+mutational bias
+55
+DcR3
+RIDD
+≥30 bp
+61
+54 %
+standard error of the mean
+lung mechanics
+translation
+Onco-inflammation
+Mandatory notification and laboratory surveillance
+N-glycans
+neuraminidase inhibitor
+Healthy, unstressed cells
+priority setting
+herpesviruses
+tropocollagen
+sensitivity
+regular and repeating
+a Shh agonist
+CypA
+Fractions
+routine public health settings
+Maxima H Minus First Strand cDNA Synthesis Kit
+Chloroform
+RMSD
+ðâ max Þ
+immunoblot
+37
+30%
+0.1%
+May
+4 weeks
+sheep
+grassroots networks
+leaky scanning
+Glyceraldehyde-3-phosphate dehydrogenase
+genetic
+Ceacam1 À / À mice
+65.7%
+stimulates Ubp9 and Ubp13 catalytic activity
+GR and HE
+Hashida and colleagues
+H3N2
+p53, ROS, and autophagy molecules
+H5N1
+polymerase chain reaction
+cap-dependent
+protostomes and deuterostomes
+translational elongation rate
+57.7%
+airway epithelial cells
+PBMCs
+IL-XPCI
+transducing
+subtle, unrecognized differences in nutritional and health management
+K d
+urine
+liver and pancreas
+foscarnet
+200
+2.3%
+Web Figure 2
+Ni-NTA column
+IL-6 and IL-17
+fixed
+4-7 fold
+small molecule efflux
+Val-X-Ala site
+Rabies, brucellosis, and anthrax
+pleiotropic
+lecithin
+U 1 2 A 3 A 4 C 5 6
+295
+378
+air-filled pulmonary alveoli
+c.208 A>T
+high specificity
+changes in compliance of the respiratory system
+10%
+SSTR2
+mRNA technology
+2 hours
+412-423
+pneumotropic
+larger case numbers further away from the upper credible bound
+Palmitoylation by membrane-bound DHHC proteins
+three weeks
+DCs in PPs
+C5a
+a helicase
+3968
+Ionocytes
+protective efficacy in nonhuman primates
+Osteonecrosis of the femoral head
+stretch of adenylates
+Kozak consensus sequences for the macaque ISGs
+C1
+45%
+22 876
+resistant
+an equimolar mixture of G and C
+Integrins
+host immune response
+kDa
+viral
+4.3 to 7.2
+they may not be contacted by members of the community or whānau
+Ege University Ethical and Research Project Committee
+three
+situational pressures, the clinical environment, gaps in education, and organizational culture
+inability to identify the cell type responsible for the change in gene expression
+toll-like
+G101T
+53.4%
+Influenza
+innate immunity
+cell membranes and perinuclear autophagic vesicles
+fights cancer
+local Southern partners
+Thirtyone
+lipodystrophy
+how RNA substructures may interact during DENV replication
+cytoplasmic extract
+Division of Global Migration and Quarantine
+Fifteen
+500,000
+sequencing of the cDNA amplicons
+56
+Hispanic/Latino
+High-quality reBmBac DNA
+dead cells
+cytoplasmic granules
+Illustra GFX PCR DNA and Gel Band Purification Kit
+Measles, mumps and rubella
+paying for the vaccine
+upregulation of type I IFN
+culture-based diagnostic tests
+bacterial coinfection
+to explore people's perceptions of the swine flu vaccine
+one-half to two-thirds
+Tospovirus
+31 per cent
+TLR4
+The stairs feature
+innate immune cells
+infectious disease transmission
+species recovery following wildfire
+Hepatitis E virus
+GpSGHV pathogenesis
+S2
+28
+peripheral blood lymphocytes
+macropinosomes
+impairments of lung function and quality of health and life
+290,000 to 650,000
+increment in some subtypes
+ELISA
+trypsin
+2,3
+SAA
+rare variants
+3 dpi
+21
+EMMIE
+lazarettos
+Interferon inducible transmembrane proteins
+Invitrogen
+1981 and 1984
+convalescent bovine
+w
+chromosome 5 position 33
+MoMLV
+10 min
+Lipid mixing
+RTA
+15 minutes
+South Sudan
+Beijing
+RAND Corporation
+63%
+RNA
+intraclass correlation coefficients
+a compensatory mechanism
+selects the city which contributed with the largest number
+two different pathogen inputs
+101
+six
+matrix-assisted
+Lassa-exposed cells
+quantitative cICAT analysis
+JUNV RNA synthesis
+palmitate
+type I interferon system
+immunofluorescence
+eigenvalues and cumulative contribution rate
+muscle aches, headache, and fatigue
+transcription readthrough
+crown-of-thorns starfish
+41.7%
+Supplementary material
+cellular membranes that are remodeled and expanded with newly synthesized lipids
+comprehensive
+Alteration of the normal pH
+28
+152
+16
+65%
+10 kg
+BMS-986094
+cell survival
+paralysis, seizures and deafness
+cerium precipitation method
+Risk of publication bias
+FASTA
+the pooled set of overlapping genes
+Creative Comm ons Attribution 4.0 International License
+versatile
+host cell vATPases
+ELISA
+440
+58
+Shaanxi, China
+effective training and supervision of MHCI workers
+TRAP activity
+once
+the drug's clinical benefit
+Children younger than 15 years
+simulated scenarios
+Protein-A/G
+C-mannosylation
+The Nrf2 pathway
+data
+NKG2Cþ NK cells
+cc-by
+Bronchiolitis
+900,000
+2 h
+RFP
+semi-quantitative indicators
+Background-adjustment, quantile normalization and log 2 transformation
+risk factors
+apoptotic cell death
+Subtype U
+obesity
+Compounds 1, 3, 4, 6, 10, and 11
+acute respiratory distress syndrome
+600
+10%
+HMGB1 protein
+2-6 day
+asymptomatic
+Hyperparasitaemia
+ATCC Cat No CCL-185
+Colocalization
+80%
+drops in egg production and induce respiratory disease
+SKP2
+2 h
+the active site of the envelope glycoprotein
+CEACAMs and KIRs
+a boost
+nc P1127T
+two
+harmful
+Individual datasets for the date of exposure and illness onset
+JEV antigen
+clones with multiple substitutions in one or more contact regions
+dengue fever
+improve fish fitness and immune defences
+In vitro infection of endothelial cells by influenza virus
+87%
+X-ray
+CCAA
+less than 10%
+GSK-3b-mediated
+parasite GSTs
+protein levels in pg/ml
+twice a day
+hepatoma cell lines
+PPIA and B2M
+the ID with the largest interquartile range of expression value
+significantly slows wound healing
+cause-specific
+cell viability
+Logistic regression
+9
+personal Vulnerability to infection
+finding conserved primers
+Mitochondrial dysfunction
+MetaCore software
+electrophoresis
+an explanation for these findings
+80%
+IP-10 and I-TAC
+infection
+5-30%
+HFIP/DCM
+binding
+IL-10 and Vb8 + CD8 + T cells
+the formation and accelerates the decay of C3 and C5 convertases
+integrin activity
+exon skipping and viral gene therapy
+IFIM4P
+quarantine and voluntary home withdrawal
+four
+cell death
+Clean nitrogen
+SAFV-3
+anti-tubercular drugs
+methanol
+statistical maximum-likelihood estimation
+any event of potential international public health concern to be declared
+repair
+general community
+VirHostNet
+ROS production
+1957
+PTV-A NSs
+Antibody titers and specificity
+community-onset pyogenic infections
+Country-level influenza disease estimates
+naked HAV
+toll-like receptors
+140
+16 546
+multiple flu seasons each year
+proximal conducting/convective airways
+Breast cancer
+Almost 80%
+necrotic enteritis toxins and/or enzymes
+Department of Tuberculosis Intensive Care Unit
+ACE2 or cathepsin A
+100%
+type-1 diabetes and multiple sclerosis
+post-PCR dissociation curve analysis
+generation time
+rehydration therapy
+TLR7 ligands
+loss of CD8 + T cell function
+LaSota
+receiver operating characteristics curves
+ill-defined symptoms, signs, or conditions
+COA
+400
+Minimum free folding energy
+three
+CD4
+60%
+40%
+multiple-alignment
+L gene
+29%
+equity
+different measures of error
+valuable insights
+a complete absence of cross-immunity
+EndoFree Plasmid Mega Kit
+a nucleotide polymorphism exceeding 50% of the isolate virus population
+Interactions with pets, insects and wild animals
+a score of one
+CRISPR-Cas9
+21
+FKC and pcDNA3.1
+method 1 and method 2
+whether the codon biases of genes are influenced by mutation
+Nurse Practitioner
+20 hours
+plasmablast
+SM934 Collagen-induced arthritis
+Phylogenetic
+u and v
+IL-13 + cells/HPF
+three
+20%
+Viral complementary DNA
+Underlying co-morbidities
+the BCTI
+mirVana isolation kit
+MMPs
+21
+PCR
+Fourteen microliters of EDTA
+pressure
+TF TCF4
+pBB2.2
+The vertical axis
+GitHub
+10 min
+Soluble NP
+Protein A agarose Fast Flow 50%
+odds ratio
+TARG1
+MVA-infected epithelial cells
+decreased cell surface CD62L
+Five
+serine or argenine
+200 mL of BMG
+H7N9-symptom-onset data
+1 μg/ml
+chi-square goodness of fit test
+azithromycin or placebo
+particular conditions of the organism
+ER stress
+average tidal volumes
+increased hemorrhage and edema
+α5β1-integrin protein level
+cytoplasm
+The ERK pathway
+Serfling-based Poisson model
+deviations from the predicted three copies of each gene
+diabetic retinopathy resistance
+few
+antibiotic treatment
+Two
+90%
+Isotype
+monocytes
+150 μM
+manidipine
+calreticulin/CD91 receptor complex
+full-dose IM delivery
+Elem1
+2009
+LBP-1 and sCD14
+exosome production
+CDK1-cyclin B
+more relevant and persuasive
+means ± standard error of the mean
+20%
+simple and quick AHR
+104
+international data
+Percoll concentration
+2%
+Aliquots of viral stock
+Requirements to identify dual-use concerns
+TGEV-N
+the difference between target gene and the average of reference genes
+26
+Capillary zone electrophoresis
+1970s
+middle-lower fields
+crucial
+upregulation of TAAR1
+slower
+IPTG
+in vitro resistance to neuraminidase inhibitors
+Israel meningo-encephalitis turkey virus
+protect chickens from infection
+choriocarcinoma
+gene expression stability analysis
+EGFRvIII mRNA
+A long reverse-direction ORF
+Kanehisa Laboratories
+memory T lymphocytes
+multi-alignment of orthologous proteins
+specific compounds
+Ego depletion
+2 h
+NSG mice
+what participants thought about or paid attention to
+7 min
+failed to induce apoptosis or activate NF-κB production
+lymphocyte counts
+all-trans-retinoic acid
+69
+Streptococcus pneumoniae
+Over 350 million
+QIamp Viral RNA mini kit
+68
+damaged molecule repair
+EV-miR-7-mediated synaptic injury
+Trypsin-EDTA
+Microsoft Visual Basic 6, Microsoft Access Database 2007, and Universal Library components
+Plasmid DNA
+IBV-specific T cells
+protected mice against lethal carcinoma cell challenge
+aerobic
+biomarkers
+seven
+significantly enhanced autophagic flux
+lack of vitality and social function
+important
+dynamics in the intermediate host population
+an in-frame construct
+no data found in the study
+IL-6/STAT3-dependent interstitial fibrosis
+30.8 hours
+The total RNA of cultured cells and lung tissue
+DNA
+alveolar pneumocytes
+RPMI1640 media
+20
+three
+Competency questions
+mechanism mediating this enhancement
+3A and PI4KB
+S15a
+The voice of local stakeholders
+Western blot
+4-5 days
+65%
+Signature peptides
+virus survival studies
+cholera
+fluorescent color-coded Luminex®beads
+four
+Dogubeyazit State Hospital
+ELISA reader
+Changes in biotic and abiotic conditions
+phosphatase
+whether burial is safe and appropriate, or whether the bodies should be cremated
+dynamic exclusion
+atypical
+Tables 1 and 2
+pseudoviral infection
+delayed response
+Purified splenic
+serum levels and/or functions of MBL
+cross-scale
+Significance
+Host population density
+peptide chain release factor 2
+four
+28 days
+30 cycles
+RT-PCR
+three
+angiotensin I-converting enzyme -inhibitory activity
+HLA-A*0201 positive
+an increase of H7 reactivity
+septic patients with overall decreasing Th2/Th1
+CK1.2
+PacI and NdeI or EcoRI
+IPC, antimicrobial stewardship, and CRE surveillance
+Eight
+pain
+Cell media or membrane fractions
+728
+ligand and receptor
+Multivariate stepwise logistic regression
+RT p66 and p55
+Sera
+by using MUSCLE with a maximum of 64 iterations
+45 min
+naïve
+anti-Toxocara IgG 4
+recombinant XendoU B
+21
+host responses to sepsis
+P/F and oxygenation index
+serum or mucosal antibodies
+466,815
+both strains
+large vesicles
+HIV-mediated syncytium formation
+loop 2 sequence and length
+live-attenuated influenza viruses
+post-transcriptional tailing of native rRNA
+daily
+2-8%
+14
+FACSDiva
+black bar
+Willmore energy-based features
+Partial least squares
+acute respiratory distress syndrome
+2005
+four
+IBs
+HeLa cells
+serological evidence of prior BVDV-1 exposure/infection
+Differential miRNA expression
+114
+two
+the presence of a furin cleavage site
+CD4 + T cells
+road crashes
+retinal regeneration
+45,804
+our knowledge
+14
+challenging logistics
+specificity and cellular toxicity
+erythrocyte membranes
+interacting
+detrimental
+cell signaling receptor and cell proliferation markers
+60%
+50 million
+EBOV GP-pseudotyped VSV encoding the Luc gene
+α-MMC and MAP30
+access to Internet, multimedia and multi-task processing
+76.1%
+Pseudoknots
+higher EHV-1 DNA levels
+RNeasy Mini Kit
+1,300
+stress
+Bunyaviruses
+five
+Cell viability
+the origins of replications
+Fiji
+observation time
+H1-subtype
+primary airway epithelial cells
+infected cells treated with a positive anti-influenza compound
+10%
+a lysine
+poor illumination and camera viewpoint
+cell death
+age
+improving patient safety and quality of care
+9
+0.011 ± 0.008 mg m −3
+systemic antibodies
+somite-specific and stagedependent
+2
+12
+caspase-11-dependent
+Taiwan National Health Insurance
+Takeda
+pseudotyped
+severe disease states
+Log2 Expression Ratios
+enhanced clinical and laboratory surveillance capacity
+microbial sequence similarity
+Antibody levels in serum and BAL
+73.9%
+Urinary, renal and plasma ACE2 activity
+patients with an extra-pulmonary infectious disease
+six
+b-actin
+selective reaction monitoring mass spectrometry
+NIH-AIDS Research and Reference Reagent Program
+sodium-N-lauroylsarcosine
+mild fever
+New York, NY
+50 million
+56
+Macrophages
+informatics savvy workforce
+positive and effective nursing
+loss of NEO resistance
+Gn protein
+increasing by 24% and 28%
+decreased survival of spinal motor neurons
+selection
+Quidel Sofia POC test
+ECL reagent
+CO2 asphyxiation
+continuing medical education
+Active smoking
+C. difficile Spo0A
+rainfall and flooding
+9
+Cu 2+ reducing assay
+chromosome 12
+relative abundance of AMR genes
+Pearson product-moment correlation coefficient
+nearly 20
+Salmonella and viral vectors such as Ad
+CEACAM1
+Ly-6G+
+necroinflammation
+NK cells
+17.5uC
+Malignant pleural mesothelioma
+17
+leucocyte transendothelial migration signalling pathways
+1 h
+decapitation
+four
+Anti-MPER humoral
+MagMAX Viral RNA Isolation Kit
+morbidity and clinical signs of infection
+DNA damage response
+APC-conjugated antibodies
+school-aged children and adolescents
+Selectable markers
+peer counselors
+reporter system
+eight
+cc-by
+transcription of the corresponding plasmid clone using T7 RNA polymerase
+bacterial
+14
+asparagine-linked glycosylation
+Taffeta scripts
+10 ng/ml
+1.5-2.5
+100 nL of 3 × 10 10 ffu/mL rVSV
+conserving the genetic integrity, diversity and traditional management of the species
+carry out similar assessments
+an appropriate animal model of inflammatory bronchiolitis
+direct numerical integration
+18.35 %
+congestive to necrotic-ulcerative enterocolitis
+impaired pulmonary function, neuromuscular weakness, and neuropsychiatric
+AS1411 aptamer
+H rot
+mouse MIF crystal structure
+Polymerase chain reaction
+motorized pullback device
+UDP-Glc
+end-tidal PCO 2
+nucleotide content at codon positions 1 and 2
+capture antibodies
+Selection during transmission
+HCMV
+cc0
+18,389
+central
+Old guidelines for airway flow
+95% credible interval
+PPI networks
+30
+phage display technology
+National Health Insurance Administration and National Health Research Institutes
+5 μl RNA
+Free floating 3D-NS
+12 days
+xx
+bicistronic
+Avogadro constant
+stair ascending
+bootstrapped coefficients
+Multiple-organ dysfunction syndrome
+application length, treatment intervals and route of delivery
+anxiety
+2013-15
+EB66
+crosstalks between MAPKs
+proteasomal degradation of RIG-I
+Ca 2 + -calmodulin
+decreased
+loglinear models
+0.107
+represent complex anatomical structures in lungs
+other factors
+16.9%
+organized and sustained
+lethal
+Node color gradient
+VOSviewer
+peptide binding ability to HLA-A*0201 molecules
+intramuscularly into the deltoid
+herd protection
+noise
+The assumption on case-hospitalization risk
+Two
+more than 40 years ago
+1967
+apoptosis
+Positive and negative controls
+0.6 to 3.2 mM
+microarray hybridization technique
+212 million
+MinION
+Real-time PCR
+Probiotics
+Four
+four
+Modulating the immunogenicity of subdominant CTL determinants
+Purified protein concentrations
+10,000 individuals
+CC 50
+FALPA
+Inhibition of pol I transcription by ActD
+cap-dependent
+24 h
+IL-4 and IFN-γ
+a gene or a term
+PBS pH 7.2
+3-Iodothyronamine
+advanced virus infection
+permeability, affinity, and selectivity
+0.99
+p
+clock genes
+The vector backbone
+Perkinsus marinus
+Positive
+ER-to-nucleus
+>5300
+myelodysplastic syndrome
+Collecting and annotating
+via a diacylglyceryl anchor
+17
+Bacterial pathogens
+148
+Water w1
+Laser confocal
+Ca 2+ concentration
+recombination between strains from distinct clusters
+inhibition of cell proliferation and increased apoptosis
+Phylogenetic
+Two
+10-fold
+Induction of neutralizing antibody response
+cancer, metabolic and hormonal disorders
+quantitative
+outside of Africa
+LigPlot
+iProt-Sub
+electroporation
+T lymphocytes
+H&E stained sections
+low
+mast cells
+ethics
+C3a receptor and C5a receptor
+novel moieties from a screening library
+1002
+our results
+pro-inflammatory
+Cvl-NI-2
+FlowJo
+dihydroberberine and sunitinib
+CD or Trp
+autocorrelation value
+2.5-log copies/mL
+cellular immune responses
+phosphatase
+1.3 to 2.7
+Infection of animal cells with FMDV
+systemic inflammation and risk of bacteremia
+Image-Pro Plus 6.0
+inhibited CSFV replication in PAMs
+sgRNAs
+sodium pentobarbital/ketamine
+downregulation of IFN-β and IL-6 expression
+evaluate the scores and tissues
+13
+network dilution via
+tolerogen
+two
+1 h
+0.005
+external infection
+Native agarose gel electrophoresis
+ADIPOQ, ACE2, APOE and CETP
+Dendritic cells
+ClustalW
+E. coli BL21 Star cells
+the bone bank administrator
+Fig. 1
+intramuscular cedilanid
+36
+assays
+SA expression
+CypA and TBP
+antibody production and antibody half-life
+thirty six
+Replica exchange molecular dynamics with solute tempering
+non-pharmaceu-tical measures
+prehistoric times
+250,000
+Multi-Task Group LASSO
+lower
+high amounts of sugars
+37%
+Students-Newman-Keuls post hoc test
+62%
+translation of the RVFV lacking the NSs gene
+Quantitect RT
+Brain lesion volume
+exocrine, endocrine, hematopoietic and neuronal cells
+mumps virus
+the one which had not been adequately studied explicitly in previously published risk models
+two representative inflammatory cytokines
+general intellectual status
+DENV-1, -2, -3, and -4
+conventional medication
+200
+the formation of nucleoli
+diluted HCl
+complement protein C1
+enhances resistance to IAV infection
+20 million copies/ml
+DDCt method
+cytokine-induced neutrophil chemoattractant-1
+infection, peritonitis, and social variations
+right censoring
+Group I peptide
+Accutase cell detachment solution
+15 min
+Kernel-based metapopulation models
+23
+A window into the natural conditions for commensal and pathogenic organisms
+IgG Antibodies
+5%
+heterogeneous sub-populations of viral variants
+86 viral genes
+1:1
+37%
+antifungal
+oral histories
+DuoSet ELISA kits
+Anti-CD4 mAb
+5% b-mercaptoethanol
+severe allergic inflammation and an asthmatic syndrome
+HeLa cells
+2012-15-2934-00123
+mesenchymal stem cells
+high phagocytic indeces
+10,685
+chimpanzees
+lack of specificity
+67
+to rank genes on the basis of their stability
+450
+artificial acquired immune response simulator
+various responses
+one third
+dispanin family
+Thirty-three
+Dot Blot assays
+high titers against the H5N1 subtype
+Cry1 and Cry2
+crazypaving
+entry of BTV-1 into BHK cells
+specific needs and adaptations
+Genome Institute of Singapore
+35-fold
+Nedd8 and ubiquitin
+siExplorer and RFRCDB -siRNA
+Materials and Methods
+ongoing engagement
+a sample of at least 500
+Lung function
+Cross-reactivity with host antigens
+λ
+anti-inflammatory and anti-apoptotic
+DENV2
+R I 0
+FRBs
+Routes of exposure
+60,153
+postoperative mechanical ventilation
+134
+longitudinal studies and/or less restrictive eligibility criteria
+100 ng/ml of LPS
+mast cells
+reverse genetics
+macrophage-derived inflammation
+Mann-Whitney analysis
+decrease
+Fourteen
+five
+A better understanding of family experiences
+Cytoplasmic vacuolation of respiratory epithelial cells
+25
+poorer NA activity
+SM d34:1 and PE 18:1p/ 20:4
+Institutional Animal Care and Use Committee
+Three
+NZ existing wool quality traits programme
+CPE
+peptidic C3
+growing
+core lists
+diverse
+10 min
+cell-mediated
+200 μg of anti-IFN-γ or anti-TNF antibody
+active
+128
+data directed analysis
+ELISA
+Increase in heart rate and vasoconstriction
+inhibited IRF3 activation and IFN induction
+vimentin
+six groups
+additional visits
+productivity and wider societal costs
+R n and R n,0
+3.0%
+coronary artery disease
+HBV envelope protein
+six
+protein-level selection on the second amino acid
+L1 and IAP retrotransposition
+simplistic linear model
+depression
+0.030
+Toronto, Canada
+fusion triggering and membrane fusion
+Six
+environmental conditions or developmental periods
+Binding responses from duplicate injections of each concentration of ClfA
+2~2.5
+mannose type oligosaccharides
+UCSF Chimera
+IFN-γ
+viral gene expression regions
+more confidently predict the future
+serum viral loads
+surgical resection
+3
+95%
+εW
+Isothermal amplification
+100%
+frequency
+≥90%
+peptic ulcer disease
+10 μmol/L
+mice
+DNA minor grove binders
++17
+12
+Thirty-four
+12% SDS-PAGE
+PfMYST
+empirical
+38%
+The CRE
+π
+Descriptive codes
+important
+12
+246
+Candida albicans
+cytochrome P450 3A4
+Sera of unimmunized mice and irrelevant antibody
+a community
+Isothermal amplification
+in response to oncogenic or DNA damaging stresses
+NDDS
+fractional TMT signals
+antigenic determinants
+Custom python scripts and bash scripts
+TgROP18
+6-week
+the diversity of viruses reported for feces
+endothelial and epithelial cell junctions
+respiratory infection or even life-threatening infection in children
+Oct4, Sox2, Nanog and Lin28
+73.0%
+less desirable characteristics
+17
+PPAR Transcription Factor Assay Kit
+cells where N but not PreGn was detected
+IL-1b
+cytokines, chemokines, proteases, and growth factors
+rapid atrial fibrillation
+AZ1A, AZ1B and AZ1C
+H9N2 avian strain
+Listeria monocytogenes
+viral load
+Eq.
+DNA unwinding and origin of replication processes
+drug resistance
+Input parameters
+entry
+class II
+1943
+a-fibrinogen
+TS
+the same genomic position
+the total number of contact persons reported by a participant
+in replicates
+massive remodelling
+16-0136
+IFNL4-∆G
+Rhesus macaque
+virus genes
+GPD2
+three
+sucrose phosphorylase
+IBV-infected DCs
+malaria, HIV, childhood vaccination, and maternity services
+separation membrane capacity
+Microspheres
+autonomic system activity and blood pressure
+100,000
+in vivo stability
+recent analyses in national burden of disease studies
+21
+NOA36
+24 hours
+1 month
+0.1% FA
+cytosolic
+self-reported diaries
+SGs and PBs
++39
+100%
+30°C
+competent DH5a cells
+residue 294G
+1
+staff turnover
+PCR
+MFI
+1:15,000
+fidelity-variant or WT CHIKV
+HeLa cells
+94-250 ng ml −1
+justifiable reason
+20
+11 to 34%
+24hrs
+modifies splicing events
+West Nile virus
+Three
+IAV in infectious mucus
+PEG/NaCl
+electrochemiluminescence immunoassay system
+sixteen
+viral transduction
+Pseudoknot detection
+signal transduction of uninfected bystander cells
+The liver, spleen and lung
+rather small
+avalanche photodiode
+Pathogen-associated molecular patterns
+Phase I clinical trials
+Faxitron MX-20-DC12
+competitive dominance
+three
+T-cell cross-reactivity
+Role 4 facilities
+Canadian Institutes of Health Research grant
+Systemic
+human class I molecules
+Further investigation
+0.2 M EDTA
+1.5 hr
+ABI PRISM SNaPshot Multiplex Kit
+hazardous waste
+short time-to-result period
+intestinal epithelium
+IL-1β
+Drak2 -/-T cells
+social status
+Rubisco
+Three
+comorbidity
+Further work
+numerous papers
+292
+trustworthiness
+recombinant pegylated IFN-alpha 2
+Figs. 3 and 4
+use of adjunctive therapies
+cleave Gag
+Epitope immunogenicity
+mechanistic visualization
+Cathepsin K
+any of these diseases
+nine
+logistic regression analysis
+sequence optimization algorithm
+AD3BF2D ligand
+CD1d
+influenza virus
+six
+upregulation of Jak1/STAT3 signalling
+IFNL4-TT/TT
+1,570,733 read pairs
+16 dpi
+Inflammatory
+higher codon usage bias
+E. coli derived K5 polysaccharides
+Gag
+local climatic conditions
+individualized
+propidium iodide exclusion dye assay
+stable cell lines expressing CD63 fused to a nanoluciferase reporter
+twice
+twenty-first century
+ITGA3
+relevant email contacts
+3.77 e 6 bits
+Smartphone applications
+OABSS
+gossypol
+NASH
+13,095
+ten
+cardiologists, academicians, and industry
+biotic and abiotic
+Σ Zi = λ/Σ
+Human CD4 + T cells
+GPVI activation
+cervical
+nucleic acid sequences
+50%
+obesity epidemic
+World Health Organization
+C6
+generation of an antigenome of positive polarity
+H 2 O 2 and menadione
+38.5 • C
+977
+a series of group discussions
+host translation
+C4
+Pdca1
+substantial and dose-dependent GIA activities
+three
+lowest
+2006
+Space-Time permutation
+120 days
+Behavioural
+decreased
+intravenous palivizumab
+r and θ become irrelevant
+28.6%
+naked DNA or DNA complexing NC
+PFS
+laboratory confirmatory tests
+the exosome
+severe imported falciparum malaria
+simulation experiments
+the Golgi
+up-regulation of MIE gene expression and subsequent reactivation
+0.1%
+12 h
+South China Agriculture University Institutional Animal Care and Use Committee
+IL-22
+over 50%
+tRNA Gln
+new analytic methods
+239
+CD4 + and CD8 + T cells
+lipidation of protein
+More than 320
+Protein-protein interaction networks
+12 hours
+three
+80-kV transmission electron microscope
+kappa, iota and lambda
+emit the fluorescent signal
+2000µg/L
+isolate
+Liposomal doxorubicin and vinorelbine
+gas chromatography/mass spectrometry
+Ensembl and NCBI databases
+Four days
+EIF2 and FBLN7
+R0 = 2.5
+One month
+2014-01-11
+1/8 day
+L2 ORFs
+120 min
+regularly
+Nurses
+odds ratio confidence intervals
+quasineutral
+The serial interval mean
+54,156,824
+translation of RNA and DNA repair
+DAVID
+nested models
+Nasopharyngeal samples
+2.07 Å
+R 0 > 1
+overexpression of S125A-B23
+spo0A
+one
+50 μl peripheral venous blood
+PHI and GHI
+ten
+clinical
+the very same factors
+less respiration
+December 2019
+26
+urochordates
+VLPs
+digoxigenin-UTP
+0.9%
+CT
+anti-rabbit HRP and anti mouse HRP
+Adequate geographic distribution of existing and stockpiled ventilators
+seven
+five
+lower airway symptoms
+8,746
+reachability versus concurrency
+impaired MCMV defense
+nested qRT-PCR assays
+64.5%
+five
+acute gastroenteritis
+60%
+cap-dependent translation
+angiotensin-converting enzyme homologue
+The resources and ingenuity of researchers and clinicians
+hematoxylin and eosin
+Dedicator of cytokinesis 2
+3 to 10%
+24 hours
+John Sheehan
+302
+on the tip of the HA molecule
+Integrins
+antigenic changes
+total immune cells
+Roche Real Time Ready RNA Virus Master Kit
+metagenomics analysis
+8098
+5%
+20%
+they play a role in AMD
+Betulinic acid
+ABCB1
+Drosophila
+STING
+prevent pathogenic influenza virus infection
+The doctor/nurse
+Modification patterns
+500
+mediates interaction with several PCSKs
+transforms into antigen-specific memory T cells
+EMBOSS CHIPS
+80%
+2 h
+17
+drug repositioning or repurposing
+CloneManager5
+backbone mass
+ampicillin resistance gene
+human herpesvirus 6
+eight
+High host density
+7
+72 hpi
+optimal
+SRI-7968
+mediating divergent effects
+50%
+Zeiss Axiovert 200M fluorescence microscope
+Herd immunity
+domains
+orthology
+young adults
+a forum for countries to communicate and work to protect
+mechanistic and proof of concept studies
+atypical pneumonia
+degradation of the RNA sample
+how many people, on average, an infected person passes the virus on to
+ad libitum
+88
+reliability thresholds
+metalloproteins
+200 µL ethanol
+crucial
+Eq.
+6 ng/µl
+C. fastigiata
+A
+33%
+,1 mM dominant-negative eIFA
+Thirty-three
+vinca alkaloid
+30 min
+a thousand random seroprevalence datasets
+the infectives
+western blot analysis
+219 million
+miR-181b
+Microsoft Excel
+haemagglutinin and neuraminidase activities
+avian ILT herpesvirus
+Protein or peptide drugs
+in vivo
+glycosylation
+Immunofluorescence assay
+8
+Cervical Cancer Screening Course
+Delphi
+7
+three
+Two
+higher +1 PRF
+vessel numbers
+as a discrete number and unit of measurement
+73%
+reasonable
+Optimal RSV-specific antibody levels
+Glomerular mesangial matrix expansion, renal fibrosis, and inflammation
+72 hours
+VP1 and VP3/4
+f >= 1.0
+13
+Adding a temporal element to the clustering process
+PBS
+110
+Schiphol Airport
+microcephaly
+NGO0451
+TM-align
+Dun and Bradstreet's Strategic Database
+AUROC
+day 11
+Access to the means of suicide
+HCMV gB
+preaxial polydactyly
+active relaxation
+12 hours
+influenza A and respiratory syncytial virus
+glycyrrhizin therapy
+Actinobacteria
+exclusion rules
+The extension of peptides
+positive correlation between the oligomer stability and acyl transfer rates
+similarity matrix
+1 µL of 3 × 10 10 ffu/mL rVSV
+increased mortality
+Stereolithography and Selective Laser Sintering
+98
+inhibited
+Irf7
+between 60 and 90%
+Accipitriformes and Anseriformes
+373
+37
+ALP
+carbapenem resistance
+À0.7 to À3.5 kcal/mol
+2.5% colloidal carbon
+CD3 + T cells
+SPSS
+on the day of ICU admission
+Sequence logo
+nonspecific early punctate hyperfluorescent lesions
+narrative
+7 mL per kg of body mass
+Nosocomial outbreaks
+50 nm
+B
+Recruitment maneuvers
+115
+Plasmodium falciparum
+S. aureus strains
+hematopoietic
+global poverty relief
+N-acetylcysteine
+IL-8
+methicillin-sensitive
+propagation of the cAMP pulse throughout the cell population
+antigenic distance hypothesis
+32 pg/mL
+Bcl2
+uncoating and maturation of the virus
+Faecal microbiota transplantation
+15
+MN assay
+Different bacterial species
+780
+antibody-decorated AdV
+position 33
+guinea pigs
+FA mice
+BALB/c mice
+optimal cut-off
+a filovirus antibody fingerprint
+Hong Kong
+vulnerabilities in the host system or database interpreter
+CC 50
+shuttle peptide-mediated protein delivery
+LC3
+Primordial follicles
+Guillain-Barre Syndrome
+genes up-regulated
+Over curve
+Liberia
+97.3%
+trace and monoamine levels
+second strand synthesis and clean-up
+2009
+Fifteen
+fpPSK2 and 5
+ALI
+~8%
+their prevalence in the population
+interest
+dependent variables
+ω or dN/dS values
+CD80
+2-3 days
+C62S substitution
+mouse and human
+Polymerase chain reaction
+treatment and prevention keywords
+Cyclic GMP-AMP synthase
+mass spectrometry
+34%
+catalytic Tyr residue
+4 weeks
+temperature
+HCV RNA replication
+Age and related changes in bone density
+L. lactis
+cyclic multimeric
+ATF4 2/2 MEFs
+67%
+Increased data sharing
+54
+Ab concentration and/or serum avidity
+Viral infection
+Pip6a-PMO
+full-length wild type and mutants HAs cloned
+MRC-5 and VeroE6
+Adolescent girls and young women
+Feeding of pets with raw food diets
+memory cells
+CHIKV DNA plasmid libraries
+time-place-type
+low expression and inherent instability
+H5N1
+repressive
+2, 3, or 7 days post-infection
+tables
+influenza A viruses
+interactive
+activated effector T cells
+17.5%
+simulated data and the number of daily reported cases
+DNA-Free™ kit
+twice
+Substantial human, economic, and social losses
+0.1C
+The Nomenclature of Territorial Units for Statistics
+ROM
+g
+529
+photoreceptor function
+stop codons
+30%
+Detection of single cells
+Permutation p values for overlap
+Thrombocytopenia
+EQ tandem repeats
+Additional studies
+Two months
+30%
+HKL2000
+9.6 and 12.5 fold
+none
+93
+sudden death, vomiting, diarrhea, lethargy or inappetence
+middle cerebral artery occlusion
+phosphatebuffered saline
+etiology
+267
+460 nm
+0.7
+1:2
+saliva
+ethyl acetate
+an asterisk
+four
+protected mice against H5N1 challenge
+Sel-Plex
+34%
+ORF1 of CBPV RNA1
+22.1%
+Absorbance
+control
+infectious
+51
+Nairobi
+Novel K-loci
+P t
+twice
+AtPSK4-myc
+lower socioeconomic classes
+raw data
+the dimer
+MicroRNA-driven RNA interference
+ProPred1
+7-14 days
+CVTree
+selection through non-synonymous nucleotide changes
+Site-specific
+fractional years
+Switzerland
+increasing the sample size
+August 2015
+mosquito analyte with LAMP primers
+bed occupancy
+dual-luciferase reporter assay
+Fever data from the ED
+hotspot
+Minimal
+2-10%
+0.1% of the population
+estimate
+PLC-γ1
+destructive sequential methods
+Apoptosis and necrosis
+q g
+1890s
+NS5
+Fluorescence
+between 1982 and 2014
+LMP1
+inadequately sensitive typing methods
+95% CI
+partial
+transcriptional slippage
+sensing of IFN before infection
+1918
+four
+a fall in blood pressure
+TNF-␣
+98.04%
+5.0
+no obvious clinical symptoms
+chemically modified nucleosides
+disease burden
+10%
+three
+R 0,N becomes a progressively higher surd
+biological
+Binding to BPTI
+selectivity helix
+cytotoxicity, photo-induced toxicity, and cellular uptake
+ethical
+Percutaneous and transjugular
+para substituted diamidines
+0.8766
+one way
+real-time forecasting
+Rhinovirus
+regular refresher courses
+Single-nucleotide polymorphisms
+shed gp120
+patents
+viral effects
+RPA primers and probes carrying 5-9 base pair mismatches
+generation time distribution
+Chinese microblogs
+infected cells
+Five
+R443I
+Culture supernatants
+59
+stable 6-HB
+.
+Bioqual, MD, USA
+Positive hybridoma cells
+intratracheally delivered
+PaO2/FiO2
+combination of a prionlike domain and a RRM
+invest in new players and models
+cases 2, 4, 7 and 8
+information on age, gender and region
+Nodavirales
+100%
+available datasets
+AKT, MAPK1, and IKK
+BDR
+qRT-PCR
+IL-10-deficient
+Recombinant vector vaccines
+21,334
+protection
+antiviral activity
+23 March 2020
+host cellular machinery
+the legislature
+grouped according to geographic location
+2009
+increased the infection of both viruses
+GC content
+Eligibility
+enhances TCR signaling
+6
+TCID 50
+FACS
+The virosphere
+20%
+26
+MALDI-TOF mass spectrometry
+over 200
+4-week
+90%
+Pregnancy
+becomes tight
+slightly elevated
+three
+overcoming four free energy
+weighted least squares
+intervention-related lost productivity
+Models' performance on short-term projections
+1 mM
+singletons
+Confidence in Concept Scheme
+shorter
+one realisation of the epidemic process
+TNF-a, IL-6 or IL-1b
+Sensitivity
+RoNi/7.1
+49.3%
+44 cfu/m 3
+NF-B luciferase
+lack of availability, high cost, and side effects
+maternally acquired passive immunity
+cost
+molecular binding events
+The length of an influenza season
+> =5 days
+to determine changes in filter airflow resistance
+24%
+pneumotachometer
+high-mannose glycan forms
+infectious diseases
+a list of positive and negative new peptide sequences
+Compound SYL1712
+Xia's test
+130
+HBP1
+Annexin V-FITC/PI double staining
+low
+2L q 2 /Lt *
+RNAi-resistant
+HSV reactivation
+dyn2/Eps15 endocytic pathway
+viral dissemination, differences in tissue tropism and host response
+retinoic acid signaling
+Cochrane Risk of Bias Tool
+CAU20140305-2
+expand into different lineages
+ELISpot wells
+an upward curvature
+WT1 126
+Immediate measures
+RSME
+four
+FBS
+Son et al
+auto-agglutination
+leader±body TRS duplex formation
+paradoxical activation of both BRAF and CRAF
+Parsonnet Lab
+2-6
+serum-free DMEM
+18 h
+DNA dendrimers
+GAPDH
+IL-4
+TREx BCBL1-RTA cells
+Brazil and India
+loss of epithelial barrier
+Clustering
+QuikChange II Site-Directed Mutagenesis Kit
+to prevent the possible reassortment of the hemagglutinin segment
+immunohistochemical
+six
+80-100
+quantitative
+the same value
+FoxP3 buffer
+2-5A
+pcDNA3/Myc-RSAD2
+every 3 days
+fibrinopurulent
+Angiotensin converting enzyme
+England
+9.6 kb
+Complete data analysis
+Far-UV CD
+Federal Privacy Act
+78%
+Feline upper respiratory infection
+Clinical and radiological
+two-pore channel 2
+89%
+tumor angiogenesis
+GentleMACS machine
+proinflammatory
+53
+CellQuest
+18 hours
+crown dependencies
+presence or absence of virus
+Eastern equine encephalitis virus
+six simulation scenarios
+The specificity of the PEDV RT-PSR assay
+Bartlett test
+a T at position 17 and a G
+pain
+Five
+11
+η = 0 ]
+stress conditions
+eculizumab
+food
+hairpin
+10
+false-positive results
+rat specific markers NeuN and nestin
+Five
+544
+Equine arteritis virus
+Hsp70
+0.2 µL
+neuroinflammation
+SPSS
+Strand Bias
+treatment conditions
+two hours
+community leaders
+Sedative drug use per ventilated hour
+Non-invasive ventilatory support
+PcrV
+0.1%
+PCK1 and ASS1
+whether they fit a 1-phase or 2phase model
+13
+structural proteins
+assessments of forced flows and volumes in infancy
+challenges
+Viral fitness, virulence, and pathogenesis
+simulated data
+Hypofibrinogenemia
+Monoclonal
+episomal and integrated form
+channels proteins down more favorable folding pathways
+thrombocytopenia
+regulating CSNK1E mRNA levels
+Revisiting the pandemic plans
+one-factor models
+Three
+NQ 4
+Linux
+stimulates HCV replication
+49
+ImageJ
+five
+to understand why there are some viruses which strongly avoid disorder
+hematoxylin and eosin
+myristylation
+ultrasonic aerosol inhalation
+the role, if any, of vertical transmission in dISF persistence
+five
+Hemagglutinating allantoic fluid
+2.5-fold
+PPE
+$40 kDa ORF1p
+11p15.5
+ventricular tachycardia and atrial ventricular block
+Proteins identified that could distinguish MPP from HC and IDC
+normal epidemiologic investigative procedures
+GAPDH
+25%
+regular meetings, formalized MoUs, and data sharing
+human-to-human
+laboratory proficiency
+Passive lysis buffer
+trypan blue dye exclusion test
+acute respiratory distress syndrome
+adjusted and unadjusted odd ratios
+Ilm1p
+D
+Hexahydrohippurate
+effective and non-toxic protein
+shuttles
+100%
+HBGAs
+attending physicians
+Antimicrobial Agents and Chemotherapy
+supplies from stockpiles
+RAB GTPases
+Treatment of rapamycin
+CFTR modulating and correcting drugs
+occurrence of ancillary causes of selection
+recombinatorial cloning
+80
+double replicative form DNA
+unknown
+EIT
+0.75 mg/kg/day
+Heilongjiang Baizhou Bio-engineering Co., Ltd
+estimated model
+35 to 40 nm
+liner epitope
+200
+p35
+Communicable Disease Control Medical Network
+Forty-seven
+flag epitope
+G3BP1
+positive end-expiratory pressure
+slight upregulation of DDIT-3/CHOP
+Yangtze River Delta
+64%
+residue changes and geometric deviations
+ILI-score
+Nucleospin Plasmid QuickPure kit
+pre-travel health consultations
+The transfer rate between hands and various surfaces
+Portland Group FORTRAN compiler
+superbugs
+the repeat length
+LPS
+The dynamics of the processing nucleolar proteins
+186
+M. bovis BCG Pasteur strain
+alignments to their maximal length
+A 0 and A
+454
+Lassa virus
+ELISA
+SpectroDESIGNER
+E. sinensis
+those with the greatest bronchial hypersensitivity to histamine
+providing optimal protection against infection
+3
+three
+upon request from the first author
+Metagenomic viral contigs
+vaccination uniformly at random
+a
+to identify risk factors for the susceptibility to RTIs
+IFN-a
+degradative endolysosomal compartments
+cytoskeletal proteins
+the number of proteins
+Sanger sequencing
+5,459
+3
+serotype III
+at the cell surface
+RNA genetic diversity
+RNAse One digestion
+122
+Dt
+cystathionine
+Blast2GO software
+Hfl1
+PC2
+plasmacytoid DCs and myeloid DCs
+Guangzhou
+seven
+4.8 days
+Four
+very low
+the folding of tRNA
+Duck and geese densities
+TLR signaling
+ECL
+inappropriately normal or mildly elevated levels of parathyroid hormone
+Duplicate articles
+37 • C
+ethical
+ten
+the time post-infection
+29
+FcgR-expressing macrophages or other meloid cells
+BALB/c macrophages
+reduced by 40%
+6 h
+EVD
+Table 1
+international travel
+decreased
+public health
+fluid flow
+2013-02-07
+NanoDrop
+Southeast Asia
+GFP
+rescues the gB 3A virus small-plaque phenotype
+hkiz1.7
+animal vaccination and climate
+9.1
+Photocatalyst-mediated
+nine
+Transferrin
+targeted layered containment strategies
+South Korea
+City of Hope Comprehensive Cancer Center
+visualization and monitoring of G4s structures
+1 µL of 3 × 10 10 ffu/mL rVSV
+infectious and traumatic
+transfected DNA and RNA
+IFNL SNPs
+Molecular biology aspects of insecticide resistance
+Epstein-Barr virus
+pulmonary permeability
+various cut points
+defined optical parameters
+Bovine respiratory syncytial virus
+Lyon, France
+the intensity of a given mass over time
+stealth
+Plasmodium falciparum
+spring-summer of 2009
+6.3%
+g S i,1
+RNA
+43
+cytotoxicity
+14
+SuperScript III First-Strand Synthesis System
+48-hour
+Farm-type specific movement parameters and contact rates
+Binding assays
+significant differences
+The funders
+43.9 kcal/mol
+ARDS
+infected donor cells
+capsid protein
+15
+the regulation of the innate host response
+decrease stimulation
+governmental charge officer
+MinKNOW control software
+mid-1990s
+public health
+multiple host cell factors
+more than 3 millions
+T cells
+0 and 1
+JEV
+Biomarker Wizard Software
+mental health
+Sporulation
+56.41%˘4.6%
+HLA-08:01
+42%
+chronic organ dysfunctions
+intranasal
+three gRNA molecules
+2%
+cDNA
+3
+LiftOver resource
+Bacilli
+Institutional Animal Care and Use Committee
+73
+NucleoSpin®Gel and PCR Clean-up kit
+inhibits
+Wilcoxon and Kruskal Wallis tests
+5 × 10 5 cells/mL
+NSP1
+type II pneumocytes
+gaps in identifying and addressing emerging and re-emerging infections
+TGFBR2
+over half a century
+complement and coagulation
+one-way
+delay in generating an alarm
+Gpd2p and Lys21p
+mathematical and computational models
+templates for primary transcription
+percent cell viability versus compound concentration
+3
+interstitial
+Clone Manager Professional ver 9.11
+CD11b magnetic beads
+mutational pressure
+8.14 and 12.77 hours
+nonlipidated, ATG8/LC3-positive vesicles
+explanations
+prevent infection of the recipient
+Malignant
+Four
+COPD disease severity
+PSI-BLAST pre-profile processing
+spring from 2015 to 2018
+71
+E90R
+cerebral herniation
+40%
+Ankyrin G
+heteroduplex rejection
+Pharmacokinetic properties
+617-bp
+2 hr
+infection
+the same statistic
+transport medium
+a recombination event
+Bacterial sialidases
+Filamentous growth
+Contract poultry
+three
+2
+The majority
+4000
+distancing
+zetasizer
+American Type Culture Collection
+4 days
+antibody
+MicroRNA sequences
+amei
+age, gender and relationship
+active and inactive pairs
+47
+fresh frozen plasma
+11%
+20%
+viral gene expression
+silent rDNA repeats
+three
+Barriers to signal
+One or two
+Nucleotide coordinates
+virion associated host shuttoff
+A sill
+nine
+72 h
+694
+Table 4
+2-5 weeks after school reopened
+reaching an effective intracellular concentration
+4 °C
+plaque assay
+retinopathy of prematurity
+diagnosis of ARDS
+telazol/xylazine
+WHO, SPC, and the US Centers for Disease Control and Prevention
+outgrowth of a single bacterial lineage
+Blood samples
+CEACAM1
+Diagram
+three days
+active severe sepsis
+M1 58-66 CTL epitop
+1 mM to 30 M
+28
+Differing approaches
+pEGFP-N2
+between days 9-12
+6HB
+their meetings
+10 s
+Cyclic GMP
+multivariable-adjusted logistic regression
+replication of HCV
+multiple promoters
+time after trauma
+50%
+life-style factors
+60
+tracheal ring disruption
+protein synthesis and cell viability
+A Hopf bifurcation
+6
+monoculture
+reptilian
+0-4 and 5-14
+CVB3 infection
+infectious disease
+corticosteroid therapy
+chimeric
+F a = 14%
+four
+epidemics
+Supplementary Table 10
+1 μg/ml trypsin
+Seventy-four
+11,323
+Vectashield with DAPI
+mice infected with H1N1 pdm virus
+branching process theory
+12 weeks
+Corynebacteriaceae
+39
+PD-1positive cells
+o50%
+B cells
+auxin
+Prophylactic
+pessimism subscale
+autophagosome-independent LC3 organelles
+6
+firewall, database, Web server, a geographic information system server, and computation
+pulmonary damage and neutrophilic response
+general translation
+four
+62%
+incompetently managed allocation
+Incidence periodicity of the model
+F2, F3, F4, and F6
+L2 protrusion
+rAMPV-4/Fc BC
+symptom onset
+More complicated and realistic models
+M.tb disease
+one
+Amino acid conservation plots
+Spatial monitoring of health-facility data
+alanine
+northern blotting
+Individual susceptibility and infectivity
+Extracellular vesicles
+RL to be a potential safe and effective anti-RA agent
+while the patient is being mechanically ventilated
+VAP
+Apdm09
+sip53 and sip16
+1:20
+Influenza NS1
+characteristic neurological symptoms
+densitometric
+statistically insignificant
+8
+Transcriptional
+IL-2-secreting cells
+3D/4 cells
+discontinuous gradient of sucrose
+informed consent
+High transition probabilities
+Docking of the de novo compounds back to the receptor
+personal information
+oxygen inhalation and tranquilizers
+SELDI-TOF-MS
+GenBank
+p35S-TuMVCPGFP
+FAK-deficient cells
+abolishes its reactivity toward UbVME and ISG15VS
+Canada
+antiviral
+Acute respiratory distress syndrome
+vitamin D-binding protein
+9.4
+rating an overall body of evidence by the GRADE approach
+steatosis
+DNA tetrahedron structures
+50%
+Neisseria meningitidis
+vaccination, antiviral and social distancing
+CD86
+MKP-1 expression
+traditional phylogenetic methods
+To drastically reduce contaminants
+Minimizing the delay between admission and beginning antimicrobial treatment
+single cell FACS technique
+protein G Sepharose
+Histone fractions
+higher mortality rates
+cycloaddition reaction
+L points
+healthcare workers' confidence and commitment to professionalism
+2 or 3 d
+longer
+76%
+transmission between ferrets
+prevention and treatment of infectious diseases
+t ij
+FoldX
+different viruses
+CSF1R
+The apo c-Myc 370-409
+prevents cleavage of viral proteins required for replication
+memory T cells
+Pneumonia
+viruses
+complex pathology
+observational
+NKG2A
+Peaks
+metatranscriptomics
+Eight weeks
+15
+1X binding buffer
+between 15,000-11,000 years ago
+Excessive reactive oxygen species
+IRE1a
+15
+ketamine and xylazine
+biological concepts with bioinformatic analyses
+A virus in swine
+vault RNA
+analytical performance
+significant effect
+78%
+spatial resolution
+390 million
+natural selection
+IFN production
+Nine
+hemorrhagic fevers
+budgets
+Chromeo TM
+TB
+Instant Clue
+TR1.3
+Sydney
+Flow cytometry and cell sorting technologies
+PLA
+cloacal shedding
+microbial infections
+Supernatants
+CBER core facility
+mosquito brain cells
+pharmacophore
+significant
+Algorithms
+Culex flavivirus
+Nm and typable Hi
+IPAC
+10%
+Methods
+amino-ionized
+100 µL per well
+8 M urea denaturation
+lower
+seed
+sodium borohydride/chloranil-based assay
+Cirrhosis
+actindependent
+cysteine analyte
+The abundance of alpha helices
+protease inhibitors
+strains
+room temperature
+hepatitis C
+pneumonia
+98%
+a trusting relationship with the local providers
+39
+to replace their names
+GO and REACTOME
+Infection of hamsters and mice
+the required tertiary structure
+eight segments of single-stranded RNA
+PCR
+type 1 inflammatory responses
+disruption of the VP24-NP interaction
+rosiglitazone
+NetMHCIIpan 3.1 server 40
+32
+IEM
+Type II secretory phospholipases A2
+Image Lab 5.2.1
+adequate psychometric properties
+the SEM for duplicate PCRs
+Infection
+species-specific lentiviral restriction factors
+infected cells secreting Gluc
+six
+negligible
+both the N-and C-terminus
+Staphylococci and streptococci
+HIV-specific influenza incidence rates
+5
+780
+26
+less well defined
+Avian pathogenic Escherichia coli
+Angiosperms
+6
+DNase-/RNase-free water
+Trace Amine Associated Receptor 1
+connector loop
+M1 expression
+type I-IFN signaling
+a peptide segment of HCK
+Georgia
+19
+immuno-electron
+standardizing results
+precursor cleavage and the detection of the processed GP2 subunit
+tumor
+N termini of the peptides
+Ingenuity Pathways Analysis
+Table 4
+CVB3 receptor expression
+low immunogenicity of cancer antigens
+12%
+cell number
+PB1 T123A
+Dr. Paul Ehrlich
+Phylogenetic analysis
+50 μl
+5
+132
+26.2
+One-quarter
+five
+staff shortages
+DC-SIGNR int2-180A variant
+one year
+plasmids for DI-244 production
+retinoic acid receptor responder protein TIG1
+3% H 2 O 2 in methanol
+860
+SCSDVs
+diffuse densities
+an interview guide
+MDA5
+May through July
+oxidative
+altered CSNK1E mRNA levels
+20%
+sIgA
+two asterisks
+3.7%
+15
+inguinal LN
+Nested PCR methods
+false-negative results
+mild
+environmental measures
+Supernatants
+100,000
+GEM particles
+genetic algorithm
+Fluo-3 AM
+target antibiotics
+Eupatorium adenophorum
+an RNA ligase
+monoclonal B cells
+93
+four
+Mortality
+Nigeria 75/1
+staging workup
+Further investigation
+CCL2
+mid-April
+6 h
+0.5-1.5 mm
+48
+EVs
+126
+lumbar
+1.7.1
+Renal replacement therapy
+MHV-3
+virus particles with immature genomes
+Western blotting
+rural
+68
+Second-messenger-regulated kinases
+100%
+outcome misclassification
+aged mice
+1-81
+greater than 2
+six
+Parvoviruses
+Bioworks 3.3
+the number of publications
+embryonic stem cells
+NBT/BCIP system
+2000
+Grade B
+HuSkMc
+delayed administration of oseltamivir prophylaxis
+Gaithersburg, MD
+FACS Aria Ill Cell Sorter
+EFV
+677
+Favipiravir
+B iliary atresia
+Mating-compatible strains
+microglia
+4%
+Private data
+SeqPrep
+1.4%
+T cells
+31 out of 38
+34/94
+TRAF, BTrCP, JAK3 and TRADD proteins
+serum free growth medium
+CAP proteins
+Targeting papain family cysteine proteases
+peptide's flexibility
+Respiratory infections
+patients and GPs
+human health resources
+Creative Commons Attribution License
+10%
+sialic acid receptors
+54%
+2011
+Case fatality rate
+Neuro Probe ChemoTx W Disposable Chemotaxis system
+NO
+influenza virus-mediated cytopathic effects
+endodomain
+Michael Weekes
+78.3%
+Meyer's hematoxylin
+glucosylceramide
+randomly
+dynein and kinesin motors
+47
+tunnel-like
+chronic obstructive pulmonary disease
+synthesize
+increased
+intraspecies
+Blood samples
+the appropriate halide
+the brain
+Lymphocytes
+2622
+IL8 and TNF
+isoxazolidines trans-11/cis-11
+epithelial cells of various human organs
+Hep2 cells or gradient purified RSV particles
+contamination of tissue specimens and experimental tools
+agents share information about risks and potential protective actions
+R 0
+coactivators
+1% agarose gels
+25-50%
+in vitro digestion of target genes
+570
+the backbones differ
+effective vaccine peptides
+pig density and climate
+Ͼ10%
+peritoneal cavity
+human travelling behaviour
+41
+ligase enzymatic activity
+Homotypic fusion of ER tubules
+MS B cells
+Appropriate nutrition delivery
+250,000-500,000
+capsid
+subarachnoidal hemorrhage
+13.4%
+6 ml/kg
+flexibility
+SPIDER software
+singlet oxygen and hydrogen peroxide
+Docking analysis
+the GC
+R 0
+25
+virus-infected
+MF
+Haemophilus influenzae
+nine
+periodic confinement
+Five
+pUC19 vector
+disease severity
+complex health challenges
+TALON affinity resin
+crAssphage
+350
+bivalves
+bias
+real-time quantitative polymerase chain-reaction
+constructive
+All authors
+living related liver transplant recipients
+mediates the membrane fusion reaction
+Variable regions and stalk of E2
+two
+100
+antiviral efficacy, social distancing conformance, and CDC response delay
+Lse
+11
+33%
+Standard deviations
+2% PTA
+50 copies/μL
+efficacy of these antisense molecules
+IRF7 deficiency and GATA2 deficiency
+UV spectroscopy
+promoter activity
+Idu-Flight
+Antibody-based pharmaceuticals
+Canada, Saudi Arabia, Mexico, Argentina Australia/ New Zealand
+Statistical
+18%
+Symptomatic controls
+2004
+poor prognosis
+23%
+The exposed period
+recombinant CNPV
+6 months
+80%
+Bigman
+Influenza
+resistance-associated polymorphisms
+cDNA
+MEDI8852
+limited
+H7 or H10N7
+hydrogen peroxide/methanol
+two
+Mann-Whitney U test
+9.5%
+quantifiable
+0.6 mM spermidine
+TBP, PPIA, and B2M
+6 days
+deciduous
+FACS was used to sort the monoclonal beads
+numerical integrator
+1AE1 to 3AE3
+serum ACE2 activities
+retroviral infections
+M2 agarose
+7.29
+Thrombocytopenia
+suspension viscosity
+a functional ESCRT pathway
+Heather Höpfl
+Mahidol University
+1918
+five
+Zhang Zhongjing
+24 h
+dynamic programming
+different community resources
+MEDLINE and LILACS
+2
+consumer health vocabulary
+BioEdit
+QIAGEN RNeasy Mini Kit
+4000 L/h
+Coxsackie virus 3C protease
+transmission capacity
+viability
+Infectious Disease Act
+cold-blood
+mannose-binding CLRs
+Asia
+tRNA scaffold-encoding region
+Dimethyl pimelimidate
+distance metric
+Validation of repeatability
+hydrophobic cleft
+the endothelium
+AirPath
+non-transformed
+Pearson correlation coefficient
+brain lysates
+increased levels of IFN1 and cytokines
+capability
+acute and chronic events
+pulmonary mechanics variables
+the antisense sequence
+Known antigenic proteins
+Self-Assembling Protein Nanoparticles
+88.3%
+existing ORFs
+6 × lysis buffer
+hard-shell clams and eastern oysters
+80 nm
+in vitro or in vivo
+0.026
+Soricomorpha hosts
+20%
+two
+R 0
+20%
+human well being, liberty, equality, and our democratic way of life
+200 µl/well casein buffer
+intact nucleoli
+Protein Preparation Wizard
+cell debris
+organisations faced unique ethical challenges when dealing with a public health crisis
+a panel of PA-oligosaccharides
+RF model
+C34
+2 µl
+7.36
+spermatogonia
+corrupt
+Criticism
+Statistical
+Appropriate vaccination programs
+adipose-derived stem cells
+The pool of internal β1 integrins
+Molecular Imager FX and Quantity One software
+MM
+tubular epithelial cells
+bleach and PX-UV disinfection
+169
+Non-recommended behavior
+Phi29 DNA polymerase
+antigen receptors and MHC molecules of all vertebrate species
+Protective flow redistribution and hypersecretion of mucus
+PaCO 2
+fungal and viral agents
+maternal H1N1 influenza immunization
+Fig 3K
+intramolecular
+previously published studies
+CD4 and CD8
+SHAKE
+12.66%
+no further enhancement
+Fluorescence imaging
+5400
+many other molecular biology data repositories
+protective
+caspase-1 activation
+C-type
+August
+90-98%
+diminished transmission
+DD > 0°C and clusters
+LRGVAPL
+24 h
+12
+pro-inflammatory cytokines
+dsRNA
+neurogenesis, cancer and c-secretase biology
+75
+RdRp
+unique substitution
+25 mM
+δ-crystallin
+the substituents of the molecule
+pH
+restricts HPV transcription and vDNA replication
+live pneumococcus
+antigen specific B cells
+Shannon's information entropy
+MZP
+chi-square or Fisher's exact test
+Label free proteomics
+uncomplicated sequence typing schemes
+GenBank
+PD-1 blockade
+donor splice site
+0.4 to 64 years
+Determining the appropriate taxonomic level
+4%
+supplementary material
+enzymatic degradation
+school closure policy
+49
+35%
+1.61
+ADAM17-dependent spatial proximity
+guinea pigs
+7.06 billion
+MVA-GP
+defective endosomal escape
+swine
+Wnt/β-catenin
+HGF/c-Met signaling
+WorldPop-InternalMigration-v1 code 74
+Annexin V-PE/7-AAD dual staining
+Guangdong
+Toll-like receptor 7 and retinoic acid inducible gene 1
+treatment
+Neutrophil infiltration to the alveolar space
+10.3390/ijms15034915
+BBP
+quality control take-over
+1212
+it was most effective in vitro
+two
+IRF8 expression
+Kaplan-Meier curve
+Control of pandemic influenza
+cGAMP
+Length of initial hospital stay
+6
+20 min
+Geographical variation
+sequence homology
+automorphism-driven lumping
+25 min
+MSCs
+B-cell proliferation
+15 to 60 years
+Computer Aided Similarity Evaluation System software
+lack of adequately trained human resources
+96%
+Six
+1940s
+unmet medical needs
+cigarette smoke
+the authors
+further research
+The run
+Compartmentalization
+reducing uncertainty through research
+neurotropic flavivirus
+V
+rodents and mosquitoes
+Simvastatin
+spots containing low signal or poor signal uniformity
+16
+1021
+search engine data
+cytokines and chemokines
+12 628
+normal mRNA homeostasis
+7
+30 min
+maximum likelihood phylogenetic trees
+Raw data of fastq format
+40 mM citrate buffer
+Junta de Andalucía
+five
+10 6 and 10 5
+BioProject/BioSample/Short Read Archive
+negative
+mKate2 expression
+3D
+123
+antibiotic resistance
+diagnostic costs
+1 h
+500mg/ml G418 and 1 mg/ml puromycin
+Viruses
+University of Bologna and the Centre Hospitalier Universitaire
+2.6 × 10 5 cells
+process medication preparation and dispensing
+acute respiratory diseases
+RNeasy kit
+Macrophages
+Benjamini-Hochberg Multiple Testing correction
+Anopheles mosquito
+pre-weaning development stages
+United States Health and Human Services
+Blood samples
+2019-10-14
+mutation pressure
+August 2002
+0.00678
+19
+potential outbreaks
+SYBR Safe and Coomassie Brilliant Blue
+43
+maternal tetanus vaccination
+Estimating the time lag between environmental/climatic variables and infections
+A/PR8 influenza virus or lentivirus
+57˚C
+four
+FasL
+Pepinfo
+four
+FimA
+24 h
+higher-order epistasis
+MSP-1
+twice a day
+T-cell
+Dr. Maurizio Crestani
+virus not detected
+Vietnam
+98,500
+secretory pathway components
+an increase in antibody levels
+dozens of hours
+short
+viral contents
+Further information on research design
+MKP-1 expression
+cleavage
+Seven
+eight
+CD4 binding site antibodies
+Abundant
+Ab studies
+reduced viral replication, spreading, and pathogenesis
+Veno-venous extracorporeal membrane oxygenation
+10%
+enhance the B-and T-cell responses
+significant
+CIITA
+the front end, the turning point, and the back end
+Canada
+malarial
+Seropositivity
+3 to 7%
+chest X-rays or CT
+steroid pulse therapy
+9
+DDX3 and Rev
+ecological impacts
+2008
+release of TNF-α
+discretization and solver properties
+BLAST-P and OrthoMCL
+10,616
+α2-3-linked
+an AG bulge
+13
+BCR signalling
+90%
+A location
+IP-10 and MCP-1
+BCA method
+crystallography
+hematoxylin and eosin
+Fundamental changes to the drug development pipeline
+Brazil
+12
+40 min at 32uC
+Fluoromount-G ®
+~48hrs
+Minipreps
+99-09
+flow cytometry
+Convergence at most or all K-values
+CDV-F protein
+study sample size
+Three weeks
+ImageJ
+cold temperatures and low relative humidity
+inducible proteasome genes
+47S rRNA
+sorting and packaging signals
+0.99
+almost a century
+aa substitutions per site
+Cell debris
+PARP inhibitor
+energy dissipation
+G astroenteritis
+Nikon TE-2000 inverted microscope
+MDA5
+the corresponding author
+kinase
+chloroquine dose
+gender
+Ethical Review Committee of Aga Khan University Hospital
+16 months
+analytical results on the efficacy of isolation and quarantine
+144 months
+isotope-labelling
+different analytical approaches
+JC
+Multi-item measures
+proliferation of OPC
+interactions between primers, template and polymerase
+binds to the stalk region of the HA molecule identifying epitope-1
+Lower airway disease
+Pseudomonas aeruginosa
+antifibrogenetic
+monoclonal antibodies
+mRNA thermal stability
+2011
+edges
+reptiles, amphibians, and fish
+chewing problems
+biotinylated goat-anti-rabbit IgG
+THF
+Four
+Group 3
+a reverse Watson-Crick geometry or a trans arrangement
+5% to 10%
+inhibition of Ras signaling
+epidemic vector mosquitoes
+98%
+V1a receptors
+adequate hospital quality and volume
+continuous quality improvement interventions
+Hydrogen peroxide
+perceived good health status
+Peristaltic pump
+Pegylated interferon-alpha 2a
+phagosome maturation
+transmission and recovery rate uncertainties
+promiscuous
+cell counts
+when at least 5 % of reads displayed a mutation for that nucleotide
+pentamidine-related analogues
+8.5%
+secreted proteins
+Dravet syndrome
+4 h
+between nine and 42 deaths per million HCP
+HPVs
+1974
+SSIs control
+the pseudoknot
+UXT, RPS23, RPL4 and RPS9
+3-fold
+higher
+immunosuppressed
+48-hour
+15
+60%
+CXCL11
+two
+GENIE3
+flock-level mortality data and statistical back-calculation methods
+monosaccharide fucose
+RNAse/DNAse-free water
+data from other farms and systems
+phylogenetic implications and interpretations
+accurate diagnosis
+191
+DC-SIGN/R-mediated
+Carter
+Targeting of myeloid cells
+miRNAs
+TMEM119
+clumping of human and rabbit platelets
+NLR and PLR
+Three
+raising the ratio of CD4 + /CD8 + T cells
+pneumonia
+Google
+50
+epidermal and dermal cells
+Jagged1
+2 weeks
+60 kDa
+U.S. Defense Advanced Research Projects Agency
+peridomestic settings
+handwashing behaviors
+FucA1
+public health interventions
+weighted histogram analysis method 49
+ROCT
+political pressure
+reproduction numbers
+gene knockouts and developmental models
+flow cytometry
+antibodyrelated auto-immune reactions
+fibrogenic
+Table A2
+GraphPad Prism
+1 ml of Cal/07 inoculum
+CTLs
+Short Oligonucleotide Analysis Package
+The angle of beating
+1.33
+specificity and consistent amplification of the target region
+1,2166178 or 1,364636 sfc/ million
+Antipsychotics
+channels proteins down more favorable folding pathways
+190 to 260 nm
+allele effects plots
+exposure to traumatic events
+ensuring interoperability
+Error bars and statistics
+decomposition method
+competition under elevated mutation rates
+enhances growth of cells of other animal species
+Nonspecific binding
+18
+NeuNAc
+sequence specific capture of coding RNA
+recombination events
+pGEX-4t-1
+Hong Kong
+55%
+lung mRNA silencing
+LC3-II/GAPDH ratio
+Newcastle disease
+optimal pH and optimal temperature
+Th ese limitations
+one average impact of disasters on school functioning
+RIG-I
+Brefeldin A
+critical
+Image J Software
+news articles related to infectious diseases
+risk assessments and treatments
+Ribo-zero ™ rRNA Removal Kit
+HSV-1
+1.6 to 77.4%
+Identification of the bioactive conformation
+following a chemokine gradient
+IPC
+diagnostic decisions
+C39endo
+Cell^D imaging software
+500
+CC
+clays and carbonate
+monoclonal B cells
+DMOG
+the authors
+Eugene Koonin
+6.7%
+purposive quota sampling
+C. l. familiaris
+social life
+proteomics
+four
+a return
+zymosan fluorescent beads
+90%
+21.47
+pSORTb v 3.0
+miR-124-1
+Genewix
+southern Brazil
+IFN signaling and stress granules
+host jumping
+1.41-fold
+50-100 million
+improved editing
+aggression
+catalytic redox factor
+feature learning and classification
+BLAST
+IL-4 and TGF-β
+five
+520
+double-stranded viral RNA
+hematoxylin-eosin
+episome replication, segregation and persistence of viral genome
+4',6diamidino-2-phenylindole
+7820 pg/ml
+12 years
+15 to 20
+NS3 viral proteins
+Dr. Manuel Varas-Godoy
+Parasite biomass
+documenting each part of the pathogen's niche
+cross-correlation between points from different grids
+SOFA score and non-HIV patients
+strongyloidiasis
+relevant capacities
+Exosomes
+development and differentiation
+57%
+vitamin D 3
+Phred/Phrap/Consed software
+PP2A's scaffolding B subunit
+months
+related functioning changes
+Google Scholar
+ISG15
+loci
+25-µl aliquots of thawed cell lysate
+4000 L/h
+enabling discussion with family
+sucrose banding
+counselling
+immunoblotting assay
+oNP-β-Gal
+ORF29a and ORF65
+statistical differences in fold changes among groups
+Early growth response gene-1
+fibro
+b-tubulin + cells
+20.5%
+increased hybridization above the 23S RNA band
+CD154
+50
+biogenesis
+the tide of decolonisation
+Partial least squares
+hypoxia
+poly or poly
+general practitioners or medical laboratories
+reliability of parameter estimates
+CD4BS, V2 glycans and V3 glycan
+acrosomal region
+messenger RNA
+PNA/PMO internalization peptides
+Personal Arrayer 16
+34
+metalloproteases
+Movement restriction policies
+biological functions
+PKR
+Beclin-1
+six months
+soluble expression
+18 m time-point
+phylogeographic
+D'Agostino and Pearson omnibus normality test
+three
+Ab binding sites
+an MOI of 33
+iterative
+two
+Cauliflower mosaic virus
+augmented host response
+CAM
+days 3 and 5 postinfection
+current models of co-translational protein folding
+Fzd receptors and LRP coreceptors
+methyl 4,5-DCQA
+translation
+excessive or inappropriate inflammation
+commercialized
+KB
+56
+5
+evaluating intrahost CHIKV evolution
+rescued the reduced cell adhesion and migration phenotype
+harmful and fatal
+right upper limb
+US$1 billion
+CPE
+predictors of in-hospital mortality
+GLMM and BRT
+Lys-and Gln-tRNAs
+the role of NETs and extracellular DNA in disease
+PSG enrichments
+peptide crossreactivity
+Biocompatibility
+s.d. from 3 independent experiments
+sarcopenia
+MEGA 2.1
+Chymotrypsin
+XAMPP
+Blot
+the pseudoknot
+9
+Germany
+156
+expression patterns of genes
+upregulation of ISG expression
+2 x 10 8 cells of H37Ra
+nonanchor residues
+LIVE/DEAD Aqua Dead Cell Stain Kit
+detection of circulation
+antibody selection
+VP40 expression
+NORSE
+Elevation
+three
+increased viral burden
+1997
+0.5%
+Toxicity
+thirteen years
+formaldehyde
+Coalition for Epidemic Preparedness Innovations
+Flag-Mage-g1
+monocyte-derived DCs
+ADAM10
+PD-1 + NK and T cells
+10 μl of streptavidin beads
+Information on the general HIS approach
+naïve T cells
+2009
+CC IFN-l3
+infectious and inflammatory agents or host-derived factors
+Kibale red colobus
+101
+TRAF2
+Zinc-finger antiviral protein
+four
+astrogenesis
+four
+PfCSP
+the model's goodness-of-fit
+one of the above-mentioned operations
+dye uptake assay
+Flow cytometric
+Global Change Newsletter
+reverse genetics
+−100 V
+viral cores
+synchronized intermittent mandatory ventilation
+heat-based pretreatment
+MGH
+week 39
+communication and synchronization overheads
+Viruses
+Flies
+NP-450G
+VP1
+66
+an S-shaped melting curve
+FHV
+a gene involved in immune responses
+VR2332
+nonneutralizable viruses
+ignoring contact structure
+47
+similar results
+Aminoacylated
+0.0480
+0.447
+PLGA
+cancer, lung cancer therapy and the presence of comorbid disease
+A specific immune response
+inhibitory
+un-infected cells
+dramatic
+pandemic influenza A virus
+4 weeks
+Rab6
+60S
+500 µL of 10% Acetic acid
+CAI
+ubiquitination
+to give early visibility of the article
+69%
+the lowest sum of collapse and overdistension percentages
+NS1
+quality-control
+Bayesian formalism
+mAb 447-52D
+the FDA
+no more than four naturally occurring bases in a row
+Table 1
+D
+regulation of TGF-β1 expression
+two
+one week
+Understanding the impact of transmission intensity on acquired immunity
+SFTPA and AQP5
+individual mandatory tests and the herd screening tests
+dependent variable
+some cut-off value
+4846
+The elicitation and regulation of molecular events
+in situ evolution
+HNE
+LACV tissue tropism
+glycosilation
+627,000
+viral mRNA
+hematoxylin and eosin
+DNA double-strand breaks
+high-risk clusters
+follow-up and assessment of all influenza cases who applied to health care centers
+L
+PMN activation
+licorice
+x i
+10
+all highrisk and intermediate-risk patients
+10%
+drug development
+diffuse lung disease
+60
+HRP-conjugated streptavidin
+Me2NH·BH3 and 1
+ET antioxidant capacity
+drug binding pocket
+Vpu 1-52
+70%
+50 µg/mL
+discernible inhibition or spurious actuation
+Amplification curves and good linear relationship
+metronidazole
+22.3 mcg/l
+receptor-mediated
+HHV-4 infection
+linear regression
+by issuing a private simulation identifier key upon submission
+identification errors
+Sequence information
+the best and most upto-date tools
+Checklists
+investigation of why infectious pathogens are omitted from disease surveillance and impact quantification work
+enterovirus 71 viral particle assembly
+glycinin promoter primer
+20%
+colchicine
+higher
+sex and LOS variables
+processing of viral mRNAs
+4 L/min
+Bronchopneumonia patterns
+we did not assess stroke outcome in the long term
+293T cells
+eight hours
+nonsense-mediated decay
+16
+lobar consolidation of the lower lobes and evidence of fibrosis
+ΔΔC T method
+gonorrhea
+enhances HIV-1 replication
+X-deficient pHBV1.3D
+0.01%
+14 days
+Walker A and Walker B motifs
+1235
+tetherin
+viral infection
+Seroconversion in animals
+highly specific target recognition and great deal of target binding affinity
+adenogenesis
+0.05% Triton X-100
+different host susceptibility
+contralateral
+Accuracy of SP-D measurements
+red
+susceptibility to PRRSV infection
+10 %
+6.2 months
+25%
+60
+1092
+positively charged
+sputum homogenization before nucleic acid extraction
+Inequality A1-2
+regulation of Akr1e1 expression
+B cell receptor
+A set of proteins or specific self-assembled chemical cells
+120-aa peptide product
+transnational
+1574
+a genetic variant that introduces a premature stop codon
+Primer for renalase gene
+secondary bacterial pneumonia
+TRIM-Away
+viral persistence
+compromise of various structures ranging from the cornea to the occipital cortex
+Ginseng and Salviae
+Linear Mixed Model
+panhandle structure
+all the components in the microenvironment of LAPC after IRE therapy
+The neutrality plot
+Accuracy
+B cells
+Primers and probes
+great changes in the demographic composition of the Chinese population
+LSV2
+74%
+Total RNA
+Saccharomyces cerevisiae Ski2
+very young and elderly
+r B m
+PMA-mediated PKR degradation
+nucleotide insertion differences between SVCV strains
+light microscopy
+Specific target amplification
+non-conservative amino acid mutations
+ACE inhibitors and ANG II receptor blockers
+days to weaning from admission to the intensive care unit
+PK15 porcine
+carbohydrate epitopes
+an investigation of ECoV in Ireland
+Western blot
+peripheral, multifocal, and diff use
+GSE115571
+YWHAZ and GAPDH
+5%
+viral polymerase
+in response to current events
+Maxim RT premix kit
+the outcome of the MRP changes significantly
+XD
+Sandia Biotech
+5 hours
+Written informed consent
+7 days
+request
+AlkB vs. RdRp
+five
+hemagglutinin
+recombination
+6-8 h post infection
+0.13 to 16
+mycobacterial lysis
+one week
+HIV-1 envelope protein
+mean internal over external branch lengths
+Nigeria 75/ 1
+TNFSF10, HDAC4 and HDAC5
+81.2%
+inaccurate
+bootstrap values
+immunochemical nephelometry
+12%
+treatment with the Mirasol System
+Genotypes at every variant within the IFITM3 gene
+36%
+75 mg
+definitive radiographic evidence of vascular ischemic pathology
+Cesium chloride density gradient ultracentrifugation
+human receptor crystallographic data
+IL-6
+Fluid balance
+Ͻ0.05
+Communication
+Arteriography
+control
+disulfide oxidoreductase activity of Shigella flexneri
+four
+D233
+swine and avian species
+30-60 minutes
+FKBP-LID tag
+three
+7 d
+wild species
+inflammatory cytokines
+analyze more closely their origin and biochemical properties
+Stamen Design
+elastase
+anticancer
+one
+Traf1
+14/3/2020
+six
+IFITM3
+MRT-PCR assay
+zero
+type I and type II cells
+Pyrazoles
+cc-by
+eighteen
+cyclooxygenase-1
+identification of appropriate vaccines
+one aliquot
+quinoline antimalarials
+Protein size, nature of the SP and presence of a propeptide
+1984
+selective constraint
+TMV RNA
+three
+between outbreaks
+20
+SOCS-3 mRNA
+NS1 protein
+Uniformly modified ASOs
+RV-C
+cell proliferation
+Fever
+adequate to keep blood pressure stable
+identification of oncogenic mutations in lung cancer
+recognize
+pig density and climate seasonality
+The integrity of the described constructs
+25
+intervals of time after each study injection
+95 %N MP with 5% aqueous oxalic acid
+Plastic-shafted polyester-tipped swabs
+miR-181b mimics and inhibitors
+further population structuring
+62.4%
+Table 5
+Eleven
+eM2 peptide
+Bovine respiratory syncytial virus
+Twenty-five
+through a time-varying contact parameter
+Gastrointestinal symptoms
+two
+28 ± 8 nM
+all the national immunization scheduled vaccines
+ONC
+Resources and infrastructure
+by email
+interneuronal transport
+using the codons with the highest codon decoding rates
+The Simplified Acute Physiology Score 3
+one
+round
+6 days
+crucial
+174
+ssc-miR-30d_R-1 expression
+NIRVS formation
+elucidated
+15-19 months
+103.7 Ϯ 21.2%
+0.1
+cervical cancer and anogenital, head and neck tumors
+negative reaction mixture
+ethnic minorities
+89%
+X
+testes, thalamus, thyroids and parathyroids
+pulmonary hypertension and persistent digital ischemia
+bifurcation of an ancestral sequence
+breathing is continuous
+its carrier protein
+EC 50
+similar objects are more likely to be related to some other objects
+filling a 4-by-N table of optimal scores
+2003
+R ExtraNos j
+dynamitin
+small horizontal lines
+delayed public health response
+False discovery rate
+more than twice as long
+TCM theory
+The probability of a type 1 error
+ABI Prism 7500 sequence detection system
+spore quantities
+4 weeks postimmunization
+unrestricted use, distribution, and reproduction in any medium
+PKA activity
+3-4 ml/cm H 2 O
+sRNAs
+Crisis capacity
+provided patients with study information materials
+RNA recruitment assay
+GLP-2-immunoreactive L cells
+spline correlogram estimation
+legislation
+S57 in AP1/AP2/AP3
+3
+empty particles
+Calcium
+mercurial insensitive water channel
+FIO 2
+NK cells
+Nucleomegaly
+cDNA synthesis
+anti-inflammatory
+10 µm
+9 amino acids long
+Phylogenetic
+Multiple clones
+depression and anxiety
+Plus-strand RNA viruses
+neutrophil microbial killing ability
+the supernatant
+Vaccines
+Subclinical infections
+Nearly all
+Lys48-linkage specificity of yNpl4
+six
+synchronized intermittent mandatory ventilation
+Albany model
+Spleens, mesenteric lymph nodes, and Peyer's patches
+RBV
+CDC
+4,797
+antitrypanocidal drugs
+Spontaneous breathing
+Nonspecific rabbit polyclonal antibody
+Hyperphage
+2004
+4% paraformaldehyde or formaldehyde
+LAIV
+intravenously deliver DC in vivo
+Purified GG-modified peptides
+Data Safety Monitoring Board / Safety Monitoring Committee
+DNA vaccines
+86%
+SJS/TEN
+Early and rapid reduction of HBV DNA
+between 24 and 36 hours of age
+53.5%
+biologic
+Computer-aided analyses
+high viral burden
+10% SDS-polyacrylamide gels
+The timing of exon skipping treatment
+three
+epidemiology, diagnosis and, mainly, infection control of VAP
+22%
+virus immune evasion of a Th2 and humoral response
+QIAampMinElute Virus Spin kit
+codon usage variation and nucleotide composition
+isolates
+cell proliferation and gene expression
+25%
+designing and analyzing polymerase chain reaction primers
+Cell type, assay endpoint, and the virus input
+Coronaviridae
+during cap-mediated translation inhibition
+malaria drug development
+T20
+7.41
+440 amino acids long
+10%
+The investigator
+T 0
+infected hosts
+two
+CHIKV-LR
+mosaicity
+Washington, DC
+national security
+individual based model
+VM patients
+Henk Buck
+IL-10
+Culicoides
+Attachment of polyethylene glycol polymer
+infection
+0.8 mL/min
+oxidative stress
+I nterferon
+eEF1A
+gluconeogenesis and glycolysis I
+mammals, arthropods, birds, and the environment
+protease degradation
+Forty-five
+Cellular mRNA
+Liver failure
+three
+social amoebas
+cell fate and proliferation
+four
+two
+concentration
+Thematic
+Cxcl5
+Two
+Adobe Photoshop
+detecting pollutants in our daily lives
+12
+filtration performance
+Post-therapeutics or drugs
+case reports, serological surveys or genetic studies
+daily
+very high-dimensional epidemic models
+impairments to physiological functioning
+24 November 2013
+15%
+EDII-104, -329, -331, and -389
+bat longevity
+ezrin and MARCKS protein
+1:5
+Krugar Park
+sixteen
+4%
+20 min
+luciferase activity
+acquired depth information
+hOgg1-6pcDNA3.1
+32%
+maximize its power to detect variants
+human and bovine noroviruses
+T7 RNA polymerase
+inhibitory activity
+11
+searching for disease-specific search queries
+ventilation had improved
+HCV transmission
+Loss-of-function mutations in BTK
+IFNreceptors
+The size of the amplicon
+RPTPσ
+extreme care
+ASH, RON, EVS, HYL and DJ
+Synergy or additive effects
+continuous administration of drugs
+50
+2009
+winter
+monobasic
+CD13 KO
+unacceptable
+90 min
+LRTs
+HDI status
+self from non-self molecules
+GM-CSF
+astrocytes
+two-fold
+sinus tachycardia with no significant ST/T wave changes
+25
+Streptococcus pyogenes
+1918
+Further studies
+0.941
+peritoneal cavity
+infectious agents
+inflammatory
+de-identified form
+IFN-λ4 protein
+Cryoelectron
+16
+TRIZOL
+13 cups
+EV protein release
+chi-square or Fisher exact test
+CARTPT
+70-100%
+site-specific inference of positive selection
+10% formalin
+suicidal behaviours
+0.46 times lower
+a partial Z region and 2 predicted IGR hairpins
+biological
+IRES
+circulating influenza strains
+voltage-activated chloride ion channel
+Between 3-5 million
+The patients' clinical and demographic data
+CC IFN-l3
+PEMV-2
+600,000
+46 dpv
+positive-sense
+IL-22
+peracetic acid
+inflammatory cell infiltration and haemorrhage
+S-palmitoylated
+viral polymerase NS5B
+MLD 50 values
+LPS-dependent lung injury and inflammation
+31
+activation of the proteins involved in LD formation
+divergent pathways
+supernatants
+FhGST-S1
+tryptophan
+Protein lysates
+The funder
+predictive validity
+convalescence
+moist and sunny
+central conserved domain
+13/47
+contact network patterns
+toltrazuril
+EPCR and thrombomodulin expression
+daily
+mechanistic
+70%
+addressing the unmet need for a human RVF vaccine
+G418
+126
+covariates
+GlaxoSmithKline Biologicals SA
+.2
+SCR3/4 with the virus surface
+eNOS and Ras
+novel approaches
+ferrostatin-1
+Zidovudine
+MacMahon
+Plasmodium ovale mono-infection of a human subject
+76
+500 to 21 bp
+it should be less sensitive to the mutations that cause resistance to protease inhibitors
+NPC1 overexpression
+Raina MacIntyre
+206
+Nanopore MinION R9
+increased NSE and reduced GFAP expression
+adenoassociated virus
+TNF-a responses
+endoytosis
+Prostaglandin F 2α
+Separate logistic regression models
+Human infection with H7N9
+Directionality theory
+13
+calreticulin, HSP and high mobility group box-1
+48
+Streptococcus aureus and Candida albicans
+NKT cells
+Saccharomyces cerevisiae strain BY4741
+RNAlater
+80
+western blotting
+action
+>25%
+CTLA4
+Aliquots
+95%
+R 0
+H5N1
+b
+R5
+a negative regulator
+one of the long noncoding RNAs
+outbreak and epidemic information
+thirteen
+length of stay <8 days
+diversity in parasite lineages
+Forty-nine
+environmental contamination
+intranasal challenge
+70%-90%
+IEX-1L
+transcriptional
+Urticaria
+19
+on hospital admission
+drugs or fusion proteins
+glioma cell surface receptor alpha 6 beta 1 integrin
+7.30 to 7.45
+gene expression analysis
+lipopeptide
+Proteins with glycosaminoglycan side chains
+endosomes 4 GIM4
+communities taken during a shift from sulfate to Fe-reducing conditions
+24 hours
+a transport mechanism for effective movement of messages
+a modifed morphology
+robust
+immobilization with correct orientation of biological material
+N-linked sugar
+5%
+modern standard education model
+decreased viral loads
+Immunophilins
+15%
+Peking University Ethnics Committee
+annually
+15%
+flaviviruses, influenza, and BYDV
+CMV-negative or autologous units
+Viral DNA Extraction Kit
+ZIKV replication
+>24,000
+four
+5 and 10
+inflammatory response and deregulated cytokine production
+10 mL
+common tests
+to capture the actual transmission of influenza
+24
+Recombinant human PDGF-CC Protein
+0.5%
+Programmed Death receptor
+nine
+smallpox
+N-Octadecyl-D-mannosylamine
+C ancer
+4.7-fold higher
+suppress the host immune responses
+IL-33
+ISG15
+61%
+aptamer-based
+cytolytic
+1-3 week
+Neuraminidase activity
+density gradient
+stimulated with the two peptides
+23 weeks
+generalized-growth model
+D C
+aligning the peptide substrate
+Tissue Lyser
+20
+viral mRNA transcription
+structural plasticity
+40%
+anti-paramyxovirus activity
+0.05-0.20 mM
+relation to each other
+nephropathogenic strain of infectious bronchitis virus
+Torque teno virus
+TDP-43 or FUS
+Pathogens
+Staphylococcus aureus
+LLPS
+I=76,512 bits
+infectivity
+Oligoadenylate synthetases
+gemcitabine
+51
+Ten
+Each incubation sample and the corresponding control
+a different HCV protein
+specific primers
+hyaluronic acid capsule
+Azadirachtin
+The specificity of the~65-kDa band
+iNOS
+ectopic c-Fos
+PSI
+20%
+Secondary genome sequence comparisons and phylogenetic analyses
+fever and myalgia
+livers and spleens
+passive
+simulation optimization problem
+PowerPoint
+once the exogenous gene can be successfully transferred to the embryos
+MG-C and PB
+sACE2 activity
+1,231
+antiviral
+Information about the ventilation system settings and restaurant size
+cutaneous reactions
+pPBAC plasmid
+lower respiratory tract symptoms and possibly diarrhea
+Cistanche deserticola Y. C. Ma
+11
+Proposition A2
+two positive control samples
+6 h
+2014
+Identification of drug-target interactions
+15
+QuantityOne
+CD8 T cells
+14%
+zoonoses
+204
+selective
+Chi-square test
+FRC
+Bacterial and viral infections
+24
+latent infection
+the root mean square deviation between residues that are structurally aligned
+glycoprotein
+extracellular
+bacterial and viral infections
+seven
+autoimmune T cells
+Multivariable logistic regression
+UniGene
+Centre for the Integrated Health of Women, Adolescents and Children
+two
+1:16,127 and 1:25,600
+tomographic slices
+18 h
+crosstalk between pathways
+0.5 mL1M NaOH
+65 C for 45 min followed by 80 C for 5 min
+splenocytes
+HATU and DIPEA in NMP
+Acinetobacter
+13
+Cisatracurium bolus and infusion
+Oregonin and hirsutanonol
+enhanced
+Titre of the rMVA-GFP stock
+suppression of proliferation and elevation of apoptosis
+Jier Biological
+critical aspects of influenza infection and immunity
+put in place control measures
+initiation complex
+pedigree of the study animals
+42%
+Reed-Muench method
+30%
+40
+Four
+SPSS 20.0
+five
+attachment and internalization of EBOV
+epidermal growth factor receptor variant III
+5,000
+MMLV reverse transcriptase
+Hydrogen bonds
+Plasmid DNA
+6%
+TLR4 and TLR2
+97.1%
+condensation of a part of the rDNA copies into heterochromatin
+LDVL
+monoclonal
+degenerative
+edges
+10,000
+0.05
+eight
+900 μl
+Illegal gutter oils
+Institutional support for funded studies and interventions
+anti-inflammatory
+1,425,981
+A. testudinarium
+six
+NF-κB activity
+9.8%
+Big Data
+Membrane fusogenicity
+three times
+questions intended to collect data on suicide attempts
+IFN-λ4
+2.20 Å
+Curing HBV
+polymer-solvent
+SEM
+every three days
+host taxonomic order
+transient infection
+74.9%
+variant analysis
+94-100%
+highest
+Riken Bioresource Center
+unstimulated
+6 weeks
+five
+inhibits mitochondrial DNA replication
+LC/MS peptide mapping
+HeLa cells
+phylogenetic resolution
+DRAG mice
+Gene C
+Kombucha
+similar symptoms
+173 and 180
+neonatal
+Administration of LFK
+gachhi
+Time delay
+111
+improve the health of the entire population
+other viruses
+Linear RPA
+privately and anonymously
+5,806,237
+TRIzol reagent
+90%
+SpAtg8
+Huntington's disease, and Parkinson's disease
+159S and 162A
+pembrolizumab and nivolumab
+Generalitat Valenciana
+every 6 months
+permutations of the repeated measurements
+immune competence
+Egr-1
+G-protein coupled receptor superfamily
+AaHig
+$8.5-fold
+CHIKV and SFV replication
+482
+Th2-biased and weak IFN-γ response
+it would be too late to seriously impair the T cell repertoire
+on the basis of the gene data bank and protein knowledgebase bank annotations
+kinase-inactive K46I mutant
+weight loss and survival rate
+W-type
+endolysosomal membrane injury
+acidic endosomes
+FcγRIIB receptors
+mortality
+Blood samples
+cattle and pigs
+Dicer protein
+90
+high levels of oral and nasal viral shedding
+2%
+platelet activation and reduced platelet count
+5 to 6 weeks
+1937
+Target molecules
+Seasonal infl uenza A
+XCalibur data system
+7.6 months
+1918
+chemically stable and inert material
+HEV71 and coxsackievirus A16
+one week
+ADVIA 2400 Instrument
+bacterial scavenging
+Cancer
+Syndecans and glypicans
+the viral part of the environmental sample
+Wt and IFN-abR 2/2 mice
+100-450 ng of extracted raw RNA
+tend to the sick
+Drosophila
+Histagged recombinant Hsp90
+co-divergence
+pathway
+greater-or less-thanexpected DOF volumes
+sentinel
+Image J
+tertiary hospitals
+2.5 hours
+ESRD
+four
+388.2
+Binding susceptible host cells
+the pendulum
+viral replication
+0.92
+RBCs
+translation of T7p-derived mRNAs
+an upper threshold of 255
+More than two hundred
+90%
+proteasome or autophagy
+PopART
+TLR4 -/animals
+P-site
+the same, or neighbouring, homesteads
+7-AAD + CD3
+fluorescent signal
+luminal and membrane substrates
+182
+IPC activities
+G
+age and underlying medical conditions of the patients
+Dengvaxia
+CGR
+undeniable
+10 µM Y27632
+suitable ancestors
+Future reports from large, prospective observational cohorts
+M NaOH
+doses of vectors
+embryonic precursors
+mass
+coiled-coil structure
+3.45, 4.25, and 4.5 min
+wheren iÀ 1
+37°C for 1 h
+age and experience of participants
+Charcot
+RACE PCR products
+proHNP1A
+IFN1 and IFN3
+PTEX150
+gross pathology
+4
+R&D systems and Sigma-Aldrich
+pUC-attR1-CmR
+fragments upstream of the lplA gene and the ssuA gene
+HIV/AIDS
+2AE9 days
+influenza virus A
+Innate IFNs
+CV = × 100
+children
+sensitivity analyses across a wide range of influenza parameters
+High levels of frameshifting
+PTX3
+gRNA abundance
+SIRbased perceptual-influenza model
+sodium taurocholate cotransporting polypeptide
+very fast
+36.8%
+Swiss-PBD Viewer 4.10 software
+24 h
+pneumonia
+103
+please fill all the destinations in the blank
+key elements underlying an environmentally modified, potential effect of human genes
+increased co-morbidity
+Bergnia ciliata
+LNA2
+Recombinant acetylated cyclophilin
+adults
+Coca Cola
+automated GRB target gene prediction
+18 h
+N-glycolylneuraminic acid
+TIGR4 or other wild type streptococcal strains
+Oral inquiry for financial interests of relevant personal
+Prone positioning
+pro-inflammatory
+bta-miR-455-3p
+AP2-R2
+descriptive statistics
+extreme levels of inequality
+to emulate the libraries sequenced on the HiSeq
+29
+CNS infiltration by CD11b + Ly-6C hi monocytes
+unclear
+six
+a reporter virus
+15 Days to Slow the Spread
+two
+HIS mouse BM and spleens
+Etoposide
+a single open reading frame
+30 min
+Logistic regression
+PDR001
+PfSWIB knockdown
+15
+First-strand cDNA
+angiotensinogen
+Upper respiratory tract infection
+synchrotron radiation
+MTT assay
+CEACAM1-L
+the amino group of G15
+empirical studies
+inducible NOS
+AP-2
+administration of a single dose of polarizing stimuli
+culture and individual anxiety
+Quality of life
+100:1
+Rift Valley fever virus
+Clinical Significance
+SPSS 16.0 software
+at least 20 passages
+Infectious disease outbreaks
+Rayleigh light scattering
+All the staff in all the participating sites
+shared genes
+virus replication and release of progeny virus particles
+Screening for allele-specific expression
+frameshift-inducing activity
+pandemic
+Social distancing
+morbilliviruses
+980
+Biolise 2.0
+parents, as well as CCC staff
+group III
+110
+bacterial pneumonia
+median values and interquartile ranges
+medical centers
+methionine 40 is essential for PB1 function
+thin layers
+10 ng/mL
+195
+DTU Food
+S 1 1
+Secretory IgA
+four
+23
+32%
+ADRV and RGV binding
+different kinds of influenza are analysed together
+GalT
+NotI and SnaBI of pPIC9K
+labeled cell bodies
+7.13 s
+DENV-infected WT and SK1 -/mice
+rare
+ImageMaster 2D Platinum 7.0 software
+1 h
+proinflammatory
+this study
+tRNA splicing
+Na + and Cl 2 counter ions
+4 months
+Four million
+Fear and stress
+300
+DNA purifications
+ClassyFire
+viral fitness and host cell tropism
+a-1 antitrypsin
+non-immune cells
+Herpesviruses
+primary bovine thyroid cells
+Viremia
+400 to 500 nm
+22,365
+Biomarker pattern based on CART analysis
+polycarbonate restraint tube
+70
+global and local resource allocation
+1.2%
+Student's t test
+disorder
+7
+103kDa
+a natural cell protectant
+written informed consent
+Detection software
+metaregression
+untreated hBEC
+to protect against viruses, bacteria and non-self antigens
+gentamicin
+tubules
+D. melanogaster and A. mellifera
+Allogeneic hematopoietic cell transplantation
+high
+8 h after LPS/GalN-treatment
+α
+cellular slime molds
+host nutrition, fat storage and the metabolism of vitamins and minerals
+Scottish Enhanced Respiratory Virus Infection Surveillance system
+phylogenetic
+sciIAVs
+transmission electron microscopy
+a prehairpin intermediate
+YTHDF2
+Tumor necrosis factor-α
+lysosomes
+bile acid uptake
+prior knowledge of the target sequence
+immediate treatment and management
+Otunba Tunwase Children's Emergency Ward
+a surrogate Vac-HCV infection model
+PhyloPart 2.0
+Dysbiosis of intestinal microbiota
+30 mg L -1
+Ala138 and Leu142
+Euthanasia criteria
+germacrone
+integrins
+proteolytic processing of AMA1
+delay and dispersion
+pharmacological
+types of land cover and agriculture
+University of New South Wales Ethics Committee
+intestinal failure-associated
+n/3
+reproducibility rule
+2006
+90%
+Se bioaccumulation
+docking and simulations
+cell pellets
+up to 9 h
+moderate cleavage
+l. 96-97 and l. 110-11
+Twelve
+Vaccination
+mRNA-microRNA networks
+punctate accumulation
+17
+CXCR4
+host defense mechanisms
+Formulation 6
+water droplets
+Lys48-linked diubiquitin
+antioxidant
+60%
+sfRNA
+3 ×10 5 -6 × 10 5 cells/cm 2
+diarrhea
+Epidermal growth factor protein
+94.74%
+EZ T7 High Yield In Vitro Transcription Kit
+TNF-α and IL-1β
+0.83
+603
+12
+baseline values
+Triton X-100
+any virus
+natural selection by the host
+1 lg/ml LPS
+H3K4me4 transferase
+HFMD cases
+38 to 80 mm
+comparing MDS HCT outcomes between matched sibling and double UCB donors
+Airway mucosal immunity and mucociliary clearance
+cytotoxic
+21%
+polar amino acids
+foam cells
+Tumor matrix
+20
+their experiences during the Ebola outbreak
+2003
+preimmune rabbit sera
+the luminal epithelium
+impulse control impairments following injury
+2,969
+First Strand cDNA synthesis Kit
+no epitope residues
+H7N9
+actin binding
+TKM-130803
+medical institutions around the world
+4
+Clinical care
+inhibition of different hematopoietic growth factors
+CD8 T cells
+one
+60 min
+segment 2
+getting exposed to the infections
+PBDK peptide
+wild and managed animals
+1090
+ten
+assuming roles and responsibilities
+respiratory transmission
+energies
+Ion mobility separation
+Colitis
+hydrophilic
+no software or computational tools are necessarily needed
+Asian PUUV-like species
+twelve
+low
+26.6%
+necrotic neutrophils
+immunoregulatory cytokines and the allergyassociated cytokines
+white 96-well plates
+KNIME
+pentapeptide sharing
+the potential of globally coordinated collective action
+pseudoknot structure
+Sixty-eight
+Wikipedia
+complicated
+paeonol
+temperate salamanders
+V2-apex bnAbs
+a pellet
+antibody binding-enzyme-linked
+abolishes DC-induced IFN-g secretion by NK cells
+Five
+mouse model
+70%
+accumulate in the reaction
+MCMC
+mimic the respective HFV infections
+Tibroviruses
+MediaWiki
+endosomal escape
+significant cell perturbations
+87
+change antigenically
+new variant IBVs
+imaging, molecular and histopathological techniques, and grain culture
+deep mutational scanning
+N and NSs genes
+members of the general public
+RNAprotect Bacteria Reagent
+Avian leucosis virus subgroup J
+GP1 and GP2 monomers
+Breeden and Nasmyth
+fungal species
+SP5-2-LD
+in adequate ethanol
+Download selection
+non-uniform
+hMPV M2-2
+bacteriophages and porcine viruses
+protein content
+0.2 mol%
+deleterious
+mass spectrometry
+The nucleolus
+Karyopherin-α1
+$2 per extraction
+memory B cells
+activity
+Cardiovascular disease
+viral infection
+δ 13 C
+Trimmomatic 0.35
+The Ethics Committee of the Oswaldo Cruz Foundation
+seven
+rs524
+Dunnett's post-hoc test
+Lung sections
+6.64 ± 0.10 log CFU/g
+efficacy
+i
+23 or 24 years
+Japan
+spatial structures
+pathogens that cause pneumonia but were not tested for
+specific programs
+The nuclei
+symptom prevalence
+microplate reader
+proteins
+4174±636
+invasive grass/fire cycle
+6
+linear interpolation
+Eleven
+14
+97%
+American Tissue Culture Collection
+HEK-Blue LPS Detection kit 2
+Two
+Potential frameshifting sites
+Sensitive genomics tools
+6 and 12 hours
+3 or more
+15
+49,6-diamidino-2phenylindole
+NIMHANS Central animal research facility
+628
+SSRP1 and SUPT16H
+highthroughput
+TIMP-1 secretion and oxidative stress
+NTI Advance 10
+bat paramyxovirus B16-40
+differences between breed groups
+10%
+43
+eyes and testis
+73
+Reactivity to the HA-conserved pool and NP/M1 pool
+1 min
+early viremia and generalization of infection
+parameterization choices
+GFP marker
+p3Flag-V
+outcrossing and transgene silencing
+small
+252
+28,283,587
+One hundred
+trnS-trnG and trnH-psbA
+AAV vectors
+A self-administered questionnaire
+oligodendrocytes
+15 minutes
+Treatment with antivirals and hospitalization
+less
+the C-terminal domain
+data from individual mice
+Matrix protein
+Previous influenza infection
+ACE and ACE2
+ANOVA
+586
+770
+The impact of testkits
+blood, urine, stool, sputum, and CSF
+−1 PRS
+5.7 days
+double-membrane vesicles
+fluorescent
+Prism 5
+348
+54
+WP Diseased
+Loring Miner
+diabetes
+rnTrpL
+what range of scenarios are consistent with the initial data
+1 %
+AXL, Tyro3, TIM-1, and DC-SIGN
+cellular invasion
+one or two
+p7 from subtypes GT4 and GT5
+three
+23%, 60%, and 69%
+24 hrs
+twenty-fold
+86%
+AKT
+50%
+amygdalin
+nearly half
+intercalation of the detergent
+bacterial
+a more conservative estimate of C
+CDE-fed
+most native to least native
+understudied questions
+immunogenicity of DNA priming
+GF Rimmelzwaan
+Amso et al.
+20.12 to +0.57
+twelve
+PSV1 and PCV2
+dcf
+reflectivity experiments
+SOFA, ECMOnet and PRESERVE
+enterovirus RNA-dependent RNA polymerase
+fulminant
+type of species, size of flocks, and extent of commercialization
+very rarely
+apoptosis
+25 and 6 nucleotides/second
+physiological immune responses to ingested food antigens
+public hospitals
+14 months
+Flow cytometric
+37%
+0.007% -0.048%
+wt mice
+Clinical specimens
+barriers
+100
+The PNA strand
+mycophenolic acid
+the ACF of the residuals
+1962
+flow cytometry
+3 weeks
+developing guidelines for the management of poisoning and chemical and radionuclear events
+10% of China population
+EBOV
+dsRNA-79
+Fibroblast motility
+gene knockout technology
+47,540,000 and 35,080,000
+January to May 2010
+24 h
+p k
+two
+Herpes simplex
+two-by-two
+FXII-deficient
+generalized-growth model
+more than one week
+five interaction motifs
+51.5%
+study staff
+the general public
+Porcine alveolar macrophages
+CMV promoter
+Angiotensin II
+14.5%
+product-marker configurations
+2009
+HRV
+percolation-based methods
+Supplementary Table 5
+12
+GSK Vaccines Animal Research Center
+Infected control
+the two terms
+French Polynesia and Colombia
+FlowJo
+Vectastin ABC kit and DAB HRP substrate
+independence
+TFP846 protein
+epidemiology models
+12 h
+Signal-to-noise ratios
+Phagocytosis
+12
+falciparum malaria
+1700 rpm
+2 μg/mL
+GADD34 and the dephosphorylation of eIF2α
+3500 rpm
+rgH9N2
+cGAS
+Flavivirus NS2A protein
+oligonucleotide primers
+adamantanes and the neuraminidase inhibitors
+Hypomorphic mutations
+between 21 st July and 8 th September 2007
+Five
+modifying the stereochemistry of Arg
+Bid
+filter paper
+3 h
+Six
+EBOV infection
+degrades
+lower airway symptoms
+ATG5-ATG12
+North American H7 lineage
+travel time
+human influenza A viruses
+Antithymocyte Globulin and Cyclosporine
+Resistance to antibiotics
+population dissemination rates
+human norovirus strains
+BVDV infection
+Kaposi's sarcoma-associated herpesvirus
+Six
+Culicoides imicola
+the drug binding site
+Endogenous housekeeping genes
+Antibodies
+24 h
+SVEC4-10 cells
+Mouse and rats
+Habit
+MAT
+6 00
+ZIKV E protein
+lack of culturally appropriate resources
+6-8
+six
+linkage
+the IND Sponsor
+their experiences
+histopathological and immunohistochemical
+shock of unknown origin
+545,227
+HNP1
+once every month
+Hashtag count
+impaired SG disassembly
+vehicle control
+Lelystad virus
+sialylation and glycosulphation
+cell fusion and the endocytic pathway
+2014
+Flow cytometry
+multimodal
+balancing selection
+TMPRSS2 and HAT
+Demographic and Health Questionnaire
+much time thinking through the issue
+electrostatic attraction, hydrogen bonding, and hydrophobic interaction
+H5, H7, or H1 HA
+50 million
+10%
+94.73%
+twice weekly
+respiratory syncytial virus
+severe encephalitis
+avoiding blood clotting
+Betaplate liquid scintillation counter
+changed dramatically
+190, 226 and 228
+aggrephagy, mitophagy, lipophagy
+myelin
+Human non-tumor lung tissue samples
+NN rule
+Three
+four
+TLRs
+five
+Point mutations
+virus inhibition
+Western blotting
+vascular-endothelial cadherin
+R program and STATA
+porcine AMac
+Simple representations of protein functional and structural domains
+The samples having similar fusion transcript variants
+statistical significance
+6.9%
+long-lived mammals
+Akaike weights
+continuous turnover of locally established viral populations
+β-glucuronidase
+virulence gene expression
+polyketide synthase
+antiviral
+reconstructing a large number of closely related quasispecies sequences
+12
+Ded1p helicase
+74.8%
+2003
+malaria
+fourth-order Runge-Kutta method
+seasonal influenza vaccines
+Three
+hydrocarbons
+European Convention on Human Rights
+35
+particle bombardment
+0.91
+mYFP-SpAtg8
+INHAND system
+a sustained shortfall in body size
+group E pigeons
+three
+112
+θ 2
+its catalytic domain binds Ub
+Mechanisms
+Arterial PCO 2
+3,819,675
+Tubulin
+amide
+length of the probe
+50%
+174
+privacy approaches
+PS
+45
+WT-LASV
+UTX
+727
+250,000
+brain-and/or neuron-specific functions
+48 h
+similar but not identical
+coinfection with other genotypes
+health
+4.1
+eIF4E
+Individ sources for the research
+risk
+early disease screening and diagnosis
+deteriorated bilateral pulmonary infiltrations
+informal social distancing measures
+IL-10
+37%
+Basic Local Alignment Search Tool
+case definitions
+molecular diagnosis based on oral swabs
+6
+Nine
+Vsig4 −/−
+cycloheptane
+UCLA
+Canadian Tire
+human IgG1 isotype
+more
+Sensitivity analysis
+NK cells
+the lungs
+two
+the MHC region
+Nucleic acid
+PyMOL
+SaB
+H e
+Depletion of T cells
+Acute respiratory distress syndrome
+lack of individual benefit
+K237A
+schistosomiasis
+explant and intravital
+tumor necrosis factor receptors
+normalized matrix factor
+Affymetrix GeneChip Command Console
+nonautonomous elements
+virion release and dissemination
+cell damage and cytokines production
+the role of mixed heterogeneities
+1 month
+IA/B and IC
+BIPA-P AP group
+Urechis unicinctus
+hepatitis, water-borne diseases
+personal
+30 minutes
+BBG
+Histomorphometric
+56,600
+grey
+hemagglutinin and neuraminidase
+peak viraemia
+rovalpituzumab tesirine
+ribosome biogenesis, cell signaling, and stress response
+95%
+PHGDH and HMOX2
+Penicillin and streptomycin
+Recombinant HA
+Ifitm3
+Magazines
+clinical outcome
+UniProtKB, PeptideAtlas, Pfam and STRING
+soft-clipping
+OATP1B1
+k max
+reverse transcription realtime PCR
+accuracy
+3,198
+RTIs
+HIV-1 5 0 UTR IRES activity
+Kupffer cells
+H7N9
+exosomes
+a phylogenetic clade
+multi-stakeholder
+the PM
+x100
+X-MLV
+92%
+parameter estimation
+74%
+prescription patterns and counts of close connections between formulas and herbs
+supramolecular layers
+Coincidence filtering
+PiCV
+Job security and income replacement
+transmissibility and reproduction numbers
+13
+5-fluorouracil
+autoimmunity
+providing explanations and informing the public
+unstable asthma, COPD, and infectious lung disease
+>95%
+Live vaccines
+448
+Acclimation
+over 30
+DV
+Bradford method
+60 minutes
+1986
+JFH1
+Isoflurane
+Two
+all of its neighbors become infected
+mass mobile vaccination campaigns
+Support Vector Machine and Quantitative Matrix based algorithm
+human challenge
+99% per amino acid
+β
+nine
+four
+human rights and distributive/egalitarian concerns
+Pythagorean theory of numbers
+pig cells
+mutation of the juxtamembrane motif
+damages
+alcohol abuse and depression
+12-18 h
+66 Å
+PRSS3-activating
+China
+Kruskal-Wallis test
+10 5 cfu/ml
+ignoring the underlying mechanisms driving those patterns
+pop-attack
+transneuronal
+three strands running back and forth
+1977
+documentation
+translational studies
+Phylogenetic
+Viral DNA
+0.46%
+IP-10
+bronchovascular mark-ings
+diagnostic approach D1
+other essential parameters
+bacteremia
+amplifies the drugs antitumor effect
+nine
+polymorphic
+alcohol use
+matrix layout
+mental health care
+15
+MOI 10
+reproduction number
+smaller signal overlap and increased disease ratio
+in vitro and in vivo models
+acid stability
+55.8%
+sialidase
+b-actin staining
+Annexin V
+July 2015
+2 hours
+several indices
+n z
+52%
+jackknife cross-validation
+Promoters and terminators
+distributions
+destructive exon skipping
+144,133
+neurologic
+West China Hospital
+susceptibles
+primary
+Infection with influenza B
+Bobvious^trade-off
+The UniProt website
+Low-Interrupted and High-Stable
+analysing clinical sample
+RIG-I, PKR, and GADD34
+30 nM
+45 min
+USA, Hong Kong, Australia, and China
+Proteasome inhibition
+positive
+1945
+The effective number of codons
+in vitro evaluation
+spherical
+PaO 2 /FiO 2
+GenBank
+yet to be determined
+oxygen rich environment
+354
+prevent or minimize the impact of RSV infection
+24
+E62H
+five
+monosaccharide composition and linkage patterns
+human patterns of light to moderate drinking
+protection against CAP
+LightCycler96 qPCR machine
+17%
+action, and perceived benefits
+receptor binding affinity and receptor usage
+two
+0.5
+TLR9
+mortality
+probable" cases
+MBL2 variants
+low constraints imposed by fewer interacting protein partners
+1 to 6 km
+MALDI-ToF
+Impaired
+specimen taken after antibiotic therapy
+intensity-based absolute quantification
+2000
+Hamamatsu ORCA CCD Camera
+immunosuppressive
+2%
+lipid-based
+GB virus C
+frameshifting
+a Gabonese world-renowned scientific research center
+health ministries
+1 hour
+HIV-1-infected HBMECs
+stronger
+dose-dependent
+11
+FAPs
+hemophagocytic cells
+20 concurrent cases
+Makona EBOV
+seven
+1.3%
+a new sample
+repeated immunization with the same vaccine and dose
+Fifteen
+a versatile biotechnology tool
+Dubowitz
+H. influenzae and S. pneumoniae
+intranasal papain administration
+Flow cytometric
+Hokkaido Prefecture
+trypanorhynch tapeworms
+Table S1
+ER transformation
+MHV induced
+Spearman correlation analysis
+600 µL of lysate
+August 2006
+Coiled-coil domains
+generalized linear binary regression model
+DC-SIGN rs2287886
+34.3 kDa
+1000
+Uniprot database
+migration staggers over several months
+6%
+dN to dS
+CD4-independent infection
+19
+Sepsis
+Blood gas
+to avoid interference from maternal antibodies
+90 min
+nsp2 mutants or parental virus
+34
+impairment in CD95 activation
+greater
+benefits
+34 years
+Hoechst 33342
+Western blotting
+Chinese yellow chicken NLRP3
+125 million
+ROS
+substrate prefer-ence in OTU enzymes
+increased viscosity
+Passive properties of the cell, membrane and series resistance and capacitance
+antimicrobial resistance
+competing interests
+practical consequence
+CD80, CD86 and CD40
+Asn67-to-Asp deamidation
+Boc chemistry
+SLAM
+its own proscript
+22
+mass spectrometry with a surface enhanced biochip
+E18
+5-15%
+data reduction, data display and data conclusion-drawing/verifying
+UbiSite
+Cardiac angiotensinogen
+CD4 + T cells
+NSP2
+biomedical research
+vRNA levels
+dividing the number of infected cells with that of uninfected cells
+Australia, Germany and Sudan
+the 5' IRES
+6
+TRAFtransgenic mouse models
+IRF7
+VarScan
+cytoplasm
+shorter duration of hospitalization
+A/ H3N2 and B strains
+eIF5 GTPase activity
+Seventeen
+scientific self-control
+virus induced IFN-ab
+Immunopathology
+the probability that any case will be detected by routine surveillance measures
+DAVID
+85
+HouseBrackmann score
+macropinosome maturation beyond the Rab5 positive stages was not necessary
+IgM and IgG ELISAs
+certain samples obtained from patients
+Herons and egrets
+detection of variants in viral genome
+the growth of the ARs
+36 hr
+Cells
+Quercetin and resveratrol
+50%
+Enteroviruses
+Table S1
+two-sided Z tests
+4
+5000
+Mathematical models
+Restricting access to the means of suicide
+Impact factor
+annually
+10
+RMS S
+China
+pigs
+32
+the outbreak threshold
+chickens
+10 min 15 sec
+philosophical
+1-month
+ubiquitination of IFNAR1
+AnyBody Modeling System
+The courtroom
+pneumonia
+safety and the right to withdraw
+2005
+by study design
+Bank voles
+detection of the adsorbed sTfR fused with His-tag
+One-way hierarchical
+60% probability cut-off
+DENV1, 2, 3, and 4
+Humanized mice
+InfluSim
+oseltamivir phosphate
+54
+H7N3
+activity monitors
+Sixty-eight weeks
+alter viral virulence
+BCA Protein Assay kit
+Recombination of sub-genomic fragments
+IPTG
+~25.2±2.8%
+golden hamster, rat, and mouse
+febrile
+Allen group
+glycan shields
+evolvability of phage 6 populations
+12
+IFN-γ
+infectious virus
+imidazoline receptor antisera-selected protein
+cytopathic effect
+Cancer
+sensitivity to TKI therapy
+by alteration between mosquitoes and human host
+overlapping genes
+endangered species
+Aspo0F
+Particulate matter
+Dulbecco's modified Eagle's medium
+two
+histological and imaging
+Seal/H10N7
+2012
+dashed red curve
+Adipose tissue
+GP stability
+DNA
+TiO 2
+pulmonary inflammation and neutrophils infiltration
+how accurately the ribosome is positioned when a particular codon is encountered
+antagonizing IFN induction and action
+GFP-PTPN23 and HA-ABIN2
+stirrers
+GENIE3
+jk
+Neutralizing monoclonal antibodies
+Entamoeba spp. and Giardia spp
+nasal swabs or bronchoalveolar lavage
+six
+TNF-α
+Cell type and cell state
+ISKDC classification and crescentic lesions
+particle counts
+A variogram
+30X coverage
+16 days
+Stepwise and backward procedures
+0.54-1.29%
+immune dysregulations
+140 nm
+recombinant human ACE2
+179 bp and 155 bp
+NKYVET 2015-0066
+receptor recognition and viral fusion
+Southern blot analysis
+S. pneumoniae
+polyethylenimine
+GMT ratios
+Rpl19
+memory
+TLR3
+poly-Ub specific vOTUs
+B1 mRNA
+luciferase expression
+40%
+2
+target gene expression
+3%
+Maela Temporary Shelter
+existing therapies
+3.5 million
+comparable expression of pro-inflammatory
+viral particles of IBV
+fluorescence requires excitation light to travel to the location of the fluorescent probe
+5 ± 1 d
+seven
+Vaccination
+NLS
+heart and diaphragm
+four
+15 weeks
+3
+Ebola virus glycoprotein
+HAGMA refractory to conventional therapy
+influenza Apdm09
+Foci of mineralization
+HRP-conjugated goat anti-guinea pig IgG
+12
+nine
+90% confluence
+the droplet state
+via regular pre-paid mail
+mitochondria
+severe immunodeficiency of the T cells
+two
+population access to healthcare
+28.2%
+35
+efficient and effective longitudinal research
+VRK2
+unknown
+92.9%
+DNA and RNA
+Primary viral pneumonia
+the most severe manifestation of ulcerative colitis
+National Institutes of Health Tetramer Core Facility
+peripheral vasoconstriction
+classes that are infected with pathogen and vector
+international coordination and prolonged collaboration
+abiosignature
+its pseudoatom representation
+SDHA
+78%
+stranded cDNA
+the structure with MFE
+ELISA assay
+p k
+TJ
+Lipofectamine TM 2000
+55% viral and 5% non-infectious
+20%
+an introductory information meeting
+IFN-I production
+glycogen debranching enzyme deficiency
+ten
+IL-13
+arthropods
+The lung
+the requesting center
+ProteomeXchange Consortium
+Deproteinization
+phenotypic
+The Consortium for Functional Glycomics
+peptone water
+charged
+Five
+open and closed conformations
+Communicable Diseases Law Reform Act of Germany
+steam autoclav ing
+spiked concentrated plasma
+the daily or weekly number of incident infections
+C/EBPα
+Details of the different kind of modifications for the novel antimicrobial peptide engineering
+non-log-transformed MFI
+identification requirements and criteria for specificity testing
+402
+chromatin remodelers
+LT patients
+BioEdit Sequence Alignment Editor Software
+10 genome equivalents per reaction
+viral RNA and the replication proteins
+PRRSV replication
+different translation factors
+engineered amphiphilic peptide
+95.19%
+membrane trafficking pathway
+activates recruitment of MAVS on mitochondrion
+98%
+static imaging
+Phoenix
+GenCall was invariably superior
+confocal
+antibody-mediated tumor-protective immunity
+21-28 days
+their size
+800 ng of the labeled reaction
+~2.0Â10 9 /mL
+Disease resilience
+how do biologists make sense of it from mathematical models
+ATGGAGGAATGGTCCCTGGCTATC
+season and year of enrollment
+0.966
+Inhaled nitric oxide
+severities grades
+research design
+testing of dilutions in fivefold steps
+perlecan, agrin, and collagen XVII
+Mavericks
+2007
+a proportional reduction in the first passage time
+the most right band
+RNA templates
+Cox regression
+six hours
+Nine hundred and forty-four
+615
+three
+January 2005
+broad agreement with these findings
+Human metapneumovirus
+HS binding
+preconditioning
+liquid nitrogen
+necessary for the interaction
+Confidence intervals
+Complaint Coder
+15
+reads value of 186,363 transcripts
+pir gene
+Arthritic diseases
+8-isoprostane
+$98%
+twice per day
+MEME
+non-hematopoietic cells
+K
+Nairovirus
+Bronchiolitis
+Sigma-Aldrich Company
+cellular levels of fatty acid synthase
+separately
+Peptides lacking membrane binding domains
+~40 ml and 45-75 ml
+peptide fragments of protein antigens
+CD80 and CD86
+3 weeks
+teratologic effects
+AT 1 and AT 2
+more research
+spherical
+DNA vaccine carriers
+five
+SUMO-1
+their homes
+affinity chromatography
+rs4820294 and rs13057866
+Morelos, Puebla, México and Hidalgo
+numbered
+19
+Mexican Institute for Social Security
+Twenty-five percent
+integrin alpha 3
+Photocatalytic
+sine and cosine
+Nonspecific binding
+recombinant E protein
+asialoglycoprotein
+leukocytes
+DI particles
+extracellular matrix
+$432.54
+Ferulic acid
+Jurkat T-cells
+Lamin B1
+10 μL of eluate
+phospholipids and palmitic acid
+under the bottom of the animal excrement collection DPTE transfer container
+MMP9
+estrogen
+10 days
+Antibody responses against Gag, Env or Tax
+less than 20%
+investments in the development of innate immunity
+Detailed experimental and theoretical study
+rapid clinical diagnosis
+travel restriction and social distancing
+lung mononuclear cells
+HcRed-LC3
+anti-viral therapeutics
+A window of 90nt
+preventive measures
+its binding to the membrane
+CD123 CAR-T cells
+immunological tests
+alternative initiation mechanism
+an extended, H-type pseudoknot
+DEP current challenges and limitations
+Running water
+TNF-α
+EV71/VP1
+few
+hybridization to RNA
+20.8%
+geometric mean
+diabetes
+deprotection of G2912 and U2955
+SCXK 2015-0018
+2.0%
+four
+transcriptional coactivator
+monoclonal or polyclonal antibodies
+BFA treatment
+ProDesign
+Con A
+Multidimensional Scale of Perceived Social Support
+HLA-DQ
+epidemic duration
+23%
+cmnm 5 s 2 U
+African green monkey kidney cells
+Stc1
+NucleoSpin RNA II kit
+black dotted lines
+Lineage modifications and taxonomic revisions
+dismal
+the set of explanatory variables and θ their associated regression parameters
+2-week after the primary immunization
+Node color gradient
+SDS-PAGE
+Malvern Dispersion Software
+Wuhan
+22
+TFs
+IGV
+diarrhoea, vomiting, dehydration, and weakness of the body
+six
+IFN responses
+snoRNA and pre-mRNA levels
+unsustainable
+precursor T
+DNA replication, recombination and repair
+Stokes law
+HVR3 of the S1 gene
+programmed frameshifting
+discovered relevant subsets of mass clusters
+Gabon
+Dr Margaret Chan
+Canada
+82.0%
+17
+Atg11 and ALFY
+Recode
+binding at one or more drugvirus base pairs
+surfactant
+Human papilloma viruses
+w
+pseudorabiesvirus
+nearly equivalent
+47
+a broad range of diseases
+antigen
+Hsp90 activity
+W/D weight ratio of the lung and total protein concentration in BALF
+Sputum and urine samples
+Microglia
+copy numbers
+An estimator of body condition
+accumulation of NSs
+PRJNA300864
+antibacterial agents
+23,816
+10 minutes
+412
+whether there is a role for TURBS RNA secondary structure
+peginterferon and ribavirin
+1.015-1.106
+0.778
+cytosolic sensor
+viral recrudescence
+0.81
+microvesicles
+App's antiviral effect on PRRSV
+thrombosis and bleeding
+IRAV
+every 50 fs
+Sunrise TM plate reader
+measure, identify and quantify a large number of metabolites in a biological system
+neutrophil count
+fever, anaemia, anorexia and weight loss
+a transmission cluster
+enhanced anchorage independent growth
+properties
+pharmaceutical
+PROCR
+12
+intestinal commensal flora
+18
+H5N1and H7N7
+divergent
+Shannon entropies and minimum-free energy genome secondary structure models
+Diffraction data
+PDMP treatment
+50% inhibitory doses
+25 years
+3.3
+89
+complement-mediated protection from pathogens
+Clustering
+seven
+cost calculation
+four
+optical density
+corticosteroid
+i
+29.1%
+fundamental aspects of viral morphogenesis
+N closer to the 39 promoter
+CD8+ T cells
+TEM
+artificial insemination
+26.3%
+Eight
+2
+Ile-91
+A neutrality plot
+β-actin
+disease progression
+four
+Clinical staff
+matrix protein gene
+parsimony and fit indices
+61%
+developer A
+uncontrolled
+PLC digital output module
+self-suggestion
+a linear relationship
+cardiac MRI
+release the air sensor
+four
+bearded vultures
+Crowded living conditions and poor sanitation
+77%
+Sofosbuvir
+three
+ILI
+hematoxylin/eosin
+Written informed consent
+5
+3 days
+route of administration
+two weeks
+mononucleotide
+SDS-PAGE
+aliphatic residual apolarity
+Chronic immune activation and inflammation
+hundreds of millions
+11H10
+10 µM
+Logistic regression
+HCV RdRp and other positive-sense RNA viruses
+Lymphoplasmacytic aggregates of mild cellularity
+Germacrone
+when it transmits
+the attending physician
+young children
+The cycle threshold
+anti-β-actin antibody
+external validation of published scores
+0%, 3.0% and 24.6%
+reverse transcriptase SuperScript II
+lipopolysaccharide is intravenously administered to healthy volunteers
+TRIzol
+Preliminary trials
+SES
+one or more prior suicide attempts
+Infected cells and culture supernatants
+35, 40, 50, and 60 • C
+Several network models
+621 ± 154 nM
+cDNA synthesis
+effective construction of AMR
+Weibull distribution
+Four
+the emergency department
+four
+B cell immunodominance of the Aβ epitope
+20%
+Three
+intestinal pathogens
+LeFE random forest machine learning algorithm
+2006
+2 days
+Non-cannonical
+52,293
+63.2%
+common cold infections
+mouth guards and more protective helmets
+GI bleeding
+a collection of rights-based guidelines for humanitarian response
+the percentage of transfected cells
+accumulating a discrete time series
+HCC
+five
+30%
+Malaria Journal
+alkaline phosphatase-conjugated anti-rabbit secondary antibody
+17
+b
+2 days
+differential effects
+1900 and 1918
+adamantane derivatives
+relative band intensity
+thermodynamic cycles
+7.8 mM
+13
+ratios of pre-to mature miR-122s
+bronchopneumonia
+viral replication
+penile cancer
+single SNPs
+If more than one ORF was identified
+adenosine
+live bird markets
+C. xiaoi
+biological
+Risk communication
+indoor niches
+thioredoxines
+APC3 and APC8
+higher levels of cell fluorescence
+E.coli, Baculovirus
+decode method
+extraintestinal effects
+CCK-8
+184
+Saturation
+5-100 ng/mL
+B19
+novel prevention strategies
+14 days
+Over 99%
+dual-energy X-ray absorptiometry
+morpholine rings and phosphorodiamidate linkages
+The next-generation matrix of Large Domain
+Routine immunization
+10%
+PB2
+40
+excessive anti-inflammatory effects
+Delphi 14 method
+hepatic microsomal
+venous blood
+dual labeled probes quantitative PCR
+six
+absence of a control group
+equal access to resources
+13
+pCABSD
+cumulative incidence
+ADRV and RGV
+90.7%
+vaccine or treatment
+4,344 nt in length
+Human enterovirus 71
+Cheetahs and leopards
+14.8%
+gels
+a public health emergency
+5%
+60%
+vaccine formulations
+Quantum mechanical calculations
+by means of a statistical model
+full activity
+UCL
+ensuring an adequate blood supply to the regenerating tissues
+14 days
+highly conserved
+1.6
+AAV-5 and AVV-6
+malformed models
+LAMP
+Peptides
+87.1%-98.6%
+Image J software
+Toxic hepatitis
+ventilators
+3
+p-SMAD3
+a relevant ISO accreditation
+IFN-R-deficient
+ProSeq grouping Task
+p44, p62 and XPD
+Na + /H + exchangers
+72A1
+ELISA and WB test
+proteasome-dependant
+ORF2 VRPs
+capture ELISA
+Mcl-1
+a summary of all viruses found in diarrhea
+Chromosomal transfer
+inhibited
+Lipid metabolism
+bacterial
+alveoli
+Pseudouridine
+20%
+425
+genetic drift
+one category
+variable
+did not change the percentage of infected cells
+solvent
+epithelial cells monolayers
+with 0.5 mM EDTA
+Economic reserves
+proteolytic
+community
+ACE
+reactivation
+3+
+heat shock protein 90
+cDNA
+ensuring sufficient food
+functional
+CD4+ T cells
+natural interferon producing cells
+rapamycin complex 1
+sM2 fused with or without CTA1
+partial charge neutralization
+at the points of the star
+Other conditions
+basal TLR3 and TLR7 transcripts
+growth of subcutaneously growing B16 melanoma
+Noise
+nosocomial transmission
+natural language processing
+time and group
+Spray-dried plasma proteins
+cc-by
+a relatively slow unidirectional migration wave
+LPM
+parasite pressure
+1%
+Stress leukograms
+seven
+fever and diarrhea cases
+6,053
+directly viral molecules
+Serum total protein and calf age at first diarrhea
+saponins
+A 32-L/min air pump
+overall DNA methylation level
+Alkaline protease
+a place having a dedicated team at one location
+TRIM22 and IFITM2
+J v
+metamorphosis
+Poisson distribution
+DeltaVision Deconvolution
+four antigenic sites
+CCCP or Valinomycin
+domain 1 and 2
+to attract more cells to the site of infection
+FlyFectin
+TRIzol
+overlapping
+48 hrs
+adjuvants
+Interferon regulatory factor activation and PRR signaling
+Typhoon FLA 7000
+more than 40%
+assessment of the pathogenicity of NDV isolates
+Lou Lamoriello
+anxiety and fear
+database search
+CNS
+Crystal structures
+64% to 56%
+microbial proteolytic proteases
+Peking ducks
+in vitro
+pituitary gland
+polyethylene glycol
+nucleotide substitution
+Almost 40 %
+diagnoses on hospital discharges or on death certificates
+RNA
+antiviral
+X. tropicalis
+mutator phenotypes and altered drug sensitivity
+AP-1
+AxyPrep DNA Gel Extraction Kit
+new therapies
+Over 1400
+randomizations
+VP1 or VP4/VP2 sequence alignments
+Sufficient input HRV titre
+seven
+ArcGIS
+survival benefit
+GraphPad Prism
+9%
+hospitalized cases
+extensive pulmonary injury
+HCC aldolase
+extensive within-host genetic diversity
+respiratory
+binding and expression target analysis
+serial dilutions of viral suspension
+bone-targeted
+prohibitins on TH17 cells
+FLIP
+filament images
+leakiness
+absence of monocytes
+6 hr
+15
+critically ill
+43.1%
+glucose levels
+American Type Culture Collection
+Cryptococcus DEAD helicase
+135
+29
+H uman rhinoviruses
+Desi, Sonali, and broiler
+AI and PS scores
+Oman, Cuba, and India
+NV
+Cisatracurium
+percentage neutralization
+4
+genetically modified shrimp
+Total RNA
+historical genetic introgression
+constant epidemiological parameters
+Polymerase chain reaction
+Epithelial cell invasion and macrophage death
+the best three results
+laboratory biosafety and security
+2
+increased surfactant catabolism and CD11b expression
+ATF4
+genome wide assembly required for full chicken genome
+disease mechanism and therapy to be improved
+low
+EV-71
+sulfur rich
+simple correlation coefficients
+Synonymous triplets
+LL
+POLR1
+Zika RDT
+2-5 min
+T. sinensis
+human Fc fragment protein
+37AE2
+Uninfected ferret corneal epithelial sheets
+four
+11
+end-point consolidation
+24
+ENSEMBL database
+Table 5
+chicken embryo fibroblasts
+population health approaches
+Kadam virus
+clan CN
+controlling the pre valence of MDR pathogens
+Secondary outcomes
+24 hrs
+H3
+Stockholm
+at least
+59%
+eightfold
+low
+accuracy of disinfectant dilution and overall TCD scores
+1990
+ATCC
+adaptive host-defense genes
+drinking water
+thrice a week
+COVlD-19
+evolutionary entropy
+JMP software version 11
+digestive efficiency
+DNA
+Signal and target amplification techniques
+145,365 through 145,845
+pTRH1-Gfp
+LigT
+246.8 kDa
+hot spots
+Blister fluid
+Sensitivity analysis
+cells and the cell controls
+10
+0.534
+dogfish shark and little skate
+1610 8 /ml
+Gly297 and Phe301 of yUfd1
+Median Absolute deviation of j th column
+22/3/2020
+0.5612
+television
+food safety and security
+3%
+four
+interaction of Na/K-ATPase-mediated Src activation
+Position, velocity and acceleration
+AQP3 and Claudin 1
+4 monthly
+98%
+3
+Ecological niche models
+Africa
+SV40 capsids
+Different interventions
+arginine tag
+boredom
+Ͼ1
+increased host nutrition
+l
+3
+anti-norovirus agents
+recent alcohol intake
+a quarter
+blocking complete folding
+1 mg/kg/day
+ProteinChip Arrays
+PBL Interferon Source
+10 nm
+A pdm09
+Cholesterol
+hospitalacquired
+criterion of non-naive countries
+10
+90%
+an anti-N humoral immune response
+viral infection
+n
+innate sensing
+CD8 + and CD4 + T cell cross-recognition
+glutaredoxin-1
+Mint3 inhibition
+2x10 4 MDCK cells/well
+autoimmune liver disease and immune-mediated liver injury
+TLIKELKRLGI
+bronchoalveolar duct junction
+excess
+electrostatic interactions
+urethral synechiae
+minimization of the time patients spend at high risk
+Endothelial nitric oxide
+complex structures with cauliflower-like structures
+two
+Proteases
+100 µl cDMEM
+periodicity
+pseudogenes
+promoting focal B cell organization
+2014
+transmission prevention
+5
+118
+cosmopolitan frame
+extensive characterization
+Autophagy
+calcium-palmitate complexes
+Syria
+Three months
+American
+wild-type
+Absorbance
+GSE86449
+pRSETC-NSs
+IMG/VR
+severely ill younger case-patients without pre-existing medical conditions
+Mathematical models
+five
+growth-inhibitory
+epitopes
+biased sequence availability
+P-value
+2009
+Identifying risk factors
+69
+4 h post starvation
+RNase A
+70%
+normal expression levels of cell receptors, effective mucus production and ciliary activity
+Ad5
+ABCF1
+virusinduced COPD exacerbations
+B16-F10 target cells
+Twelve
+jModelTest 2.0
+proinflammatory
+virology
+AgaR2-recognizable palindrome
+Ebola virus and Lassa virus
+conditioning on phylogenetic summaries
+the type of tumor
+10%
+prognostic biomarkers
+spillover transmission
+971
+SHP chimeric gene
+homology-modelled
+homo-and heteromolecular recombination systems
+Western blot analysis
+manipulate
+Fluoroskan Ascent FL reader
+blue
+335
+specific molecules
+Southern blot analysis
+Nuclearencoded rpl22
+farm management
+birds
+A1
+CpG ODN
+pre-mRNA processing and selection of exon 6
+costimulatory receptors
+pneumolysin
+Viremia
+with three expression plasmids containing N, P or L gene
+synplot2
+2-5 mM
+599.83 MHz
+12.5 ± 1.4 dpi
+Cytofix/Cytoperm Plus Kits
+Controversy
+4%
+TESSy
+BRACO-19
+Bracketing
+Boonyaratanakornkit, Jim; Taylor, Justin J.
+where they traveled
+endogenous cellular À1 RF signals
+regression analysis
+influenza virus PR8 NS1
+Evan's blue assay
+Cultured
+CCL2 and CXCL10
+X-ray and ultrasonography
+Glycan patterns and topological shielding
+counter and evade the multi-layered host restriction defense system
+28%
+90%
+evolving, dynamical systems models
+Monocyte Isolation Kit
+IFN production
+Pyrogallol
+Extracorporeal membrane oxygenation
+niosomes
+five
+Four
+Endothelial cell proliferation and differentiation
+GTP cofactor
+Additional file 5
+317
+cancer virotherapy
+Thermal inactivation of biological microbes
+groups with related functions
+ELISPOT
+hypoglycemia
+protease sensitivity and CatB dependence
+10 min
+Matrigel-coated Transwell filters
+transmission potential and mitigation interventions
+Data
+three
+phenol extraction and ethanol precipitation
+1774
+Clark
+goat serum
+Mobile laboratories
+Streptococcus pneumoniae
+85
+nodes and edges
+Two micrograms of RNA
+GRF1, GRF2 and GRF3
+the JAK/STAT pathway
+exon-skipping activity
+HEV71
+production and secretion of type I IFNs
+Four
+Epstein-Barr Virus
+a larger NS1-related protein
+I LT and I TP
+Four
+interleukin-10
+Tyr74
+HT pathway microscope
+NEAT2
+tetraspannins
+Hypoxic preconditioning
+the origins of immunological novelties
+ubiquitylation of NSs
+fetal growth restriction, premature birth, or spontaneous abortion
+biosafety level 4 facilities
+Sweden
+reverse primer
+phosphoinositide 3-kinase
+lower
+Western blot analysis
+10 to 20%
+L10L and L10H
+phenanthroquinuolizidine alkaloids 16 and 17
+our results
+large-scale epidemics
+COL1A1
+ST cells and IEC cells
+Colombia
+246 to 467
+10% polyethylene glycol
+Rule 2
+cross-type edges
+1998
+phospho-Csk-S364
+astrogliosis, neutrophil infiltration, and T cell infiltration
+secreted IFNs
+freely migrate to the lung
+virus-encoded miRNAs
+15%
+M2e-specific proliferation
+190
+adaptive immune mechanisms
+steric hinderance
+women who are pregnant
+Mock-infected cells
+2.0
+brome mosaic virus
+every two days
+39
+20%
+Timeliness and sensitivity
+chromosome XII
+Spatial networks
+Sepsis
+94.83%
+mean fluorescence
+greater kudus and impalas
+MP
+tissue damage
+50%-90%
+confounding by indication
+serious
+60 nm
+fever, cough, and myalgia
+rapid DNA vaccine production
+its utility as a delivery system
+host cell transcription
+low or even absent
+phosphatase-activating domain
+200 to 10,000
+Atg5
+nonoverlapping GO terms and KEGG pathways
+testing the prediction ability of five different models
+Thailand
+Emergencies, hazard affected bodies and interventions
+hydrophobic regions
+Male felids
+Red blood cell lysis buffer
+Four
+Isolate 3.3
+a freely available online server
+A
+SOLVE 33 APBS
+two weeks
+parameter estimates and equal-tailed 95% credible intervals
+overfitting
+background clutter
+Mucin 5AC glycoprotein and cytokeratin-14
+>10 µM
+pediatric P&I-HA
+NK and NKT cells
+14
+Seven
+33%
+an envelope surrounding an isometric capsid
+A3 supertype alleles
+pancreatic islet cells
+Primer Explorer V5
+10-fold
+phylogeographic
+1 week
+10.1038/srep13028
+no lower toxicity
+Over 200
+407 viral proteins and 1012 human proteins
+peroxidase-conjugated
+$80%
+relatively little
+ATP-P2X7R axis
+H5N1-induced oxidative stress
+twice
+relationship between species
+decreased barrier function
+Oral vaccines
+3 days
+HIV infection and immune suppression
+67
+overexpression of the specific gene
+proteasome
+pathogenic capforming enzymes
+PN1
+66 ± 12 years
+macrophages
+influenza A/H7N9 specific RNA
+four
+sepsis-related organ failure assessment
+2,316
+more efficient techniques
+invasive mechanical ventilation combined with a prone position
+9.6
+East Africa refugia
+optimal parasite recovery
+Respiratory viruses
+Equal
+Three
+expression of IFN-stimulated genes
+*5-50 MB
+Polymeric
+Slices
+Each graph
+virus RNA
+plaque
+nested PCR assay
+30
+Xp
+HPAI H5N1
+JUNV yield
+12.7+/-2.2 cmH2O
+Two-hundred and fifty-four
+University of Southampton
+IFN-␥
+three
+woodchucks, chimpanzees, and humans
+natural
+Mutagenesis PCR
+ρ
+37°C
+GLG Consulting
+memory integrals
+viral replication
+$6 times
+a tree hollow
+Ber > Cop > Jat > Pal > Epi
+Student's t-test
+seasonally feeding on migrating Palearctic birds
+web sites or databases are no longer maintained
+283 nm
+the majority of major DRMs
+48 hours
+10%
+emergency boxes
+3
+nine
+462
+consequences
+ethyl acetate
+the reader
+CC and VC cells
+three weeks
+mediating paracrine senescence
+S. pneumoniae
+elevated CVP
+adaptive immunosuppressive agents
+Drift
+13%
+degradation of chromatin
+Ig class switching and somatic hypermutation
+phosphorylated
+Phosphomimetic substitution
+intein chemistry
+1,838
+all individuals are social
+An R script
+COPII assembly
+solubility
+C-terminal residues
+Pertussis
+septic shock
+IFNG
+acute exacerbations
+Antibiotic resistance
+One hundred and seventy three
+F-actin-binding protein
+tetramethylsilane
+1 week
+8.7 mL/kg PBW
+poly-ubiquitin chains
+Laredo, Texas
+electrocautery
+Stratagene Mx3000P QPCR Systems
+3,057
+indoleamine 2,3dioxygenase 1
+2.2 to 3.6
+levels
+TGF-β
+BH3 domains of various pro-apoptotic regulators
+2.9%
+ISG15
+leukocyte extravasation
+seizures in the generalized tonic-clonic form
+38
+290
+P frame
+37
+The delay of the peak increases with the proportion of detected cases
+3.2
+entry of molecules and particles into the cell
+VP1 of EV71
+homogeneous plaques of about 2 mm in size
+the average degree distribution
+within normal range
+symptomatic and asymptomatic cases
+testing of antibodies in BTM
+Liver and kidney dysfunction and necrosis
+14
+71-78
+36
+1.9 mM
+CABS-dock
+32%
+two
+N H
+cleave host capped pre-mRNAs
+reduction
+stable associations with other subunits of the OST complex
+Zika virion release
+UNMC PEN Brain Banking for Study of Neurologic Diseases
+firmly adherent
+JEOL JEM-1400 electron microscope
+western blots
+1I7G, 2PRG, and 2ZNP
+increasing severities of simulated outbreak
+HTSeq
+One percent
+financial shortcomings
+129
+Microarray data
+MegAlign
+protein function and evolution
+The nucleolus
+anti-apoptotic
+viral replication and virulence
+ROCK
+HKY model
+13 ~ 90
+Northern blot analysis
+cluster 2
+the concentration of polymerases on the promoters will decrease
+theoretical models
+effect size threshold of 2
+fever, rash, myalgia, and/or fatigue
+significance
+what people perceive as familiar or unfamiliar
+three days
+maltose
+G solv
+training in the principles and practice of POCT
+UPP1
+residues
+HTNV and SEOV
+single-donor apheresis PLT concentrates
+56.6%
+previously published data
+Berlin ARDS criteria
+PIV5 protein synthesis
+sterile and non-sterile
+medians and interquartile ranges
+NMD-resistance
+Diekmann and Heesterbeek
+Rule 48
+parasite
+PPMOs
+ELISA
+avian reovirus sA protein
+previous studies
+PTC
+M. pneumoniae
+Figure 3
+viral quasispecies theory
+Vero E6 cells
+140
+0 to 1
+lung parenchymal tissues
+outreach clinics
+40-65%
+corneal and pupillary light reflexes
+more than 300
+theory-based research
+110
+NK cells
+feature evaluation
+social interactions
+multivariate regression modeling
+misclassification of current season vaccination status
+Pathogen-specific incidence estimates
+Phylogenetic and regression analyses
+day 6
+10 min
+ROCK-dependent cytoskeletal remodeling
+3 days
+1918
+ICAM-1
+1AE22
+randomized controlled trial
+12.5%
+HNF1B
+aggression in ice hockey
+7
+urealyticum
+multimedia
+small
+a number of different pathogens
+Chromosome 10
+scientific
+monoclonal
+porcine
+24 h
+less than 1.5-fold
+S2-expressed recombinant AaHig protein
+six
+• NO
+7%
+cytoplasmic RNA
+21 × 21
+short heterologous peptides
+higher
+pathogenic viruses and bacteria
+1610 8 CFU/ml
+eight
+higher activities
+34
+SLC
+two or more isoforms
+Hue
+99.9%
+Eleven
+B cell hybridomas
+apoptosis
+multivariable logistic regression modeling
+Cross-border contact tracing
+three
+Superantigens
+Molar concentrations of salt
+four
+59-diphosphate RNA
+membrane disruption
+PKR activation
+genomic variability
+1 hour
+HIF1α
+hepatocyte-growth factor scattering of epithelial cells
+typical failure cases and limitations in our experiments
+general floods
+a RA tool
+LDH release assay
+phosphorylation of Akt and GSK3β expression
+Primary Health Care Centre
+49%
+FlowJo
+CS
+2000
+Yos9p
+interest
+acute loose motion and vomiting
+multi-protein subunit complexes
+Influenza virus
+viral replication properties
+Gag and Env
+aseptically
+18
+Reciprocal-best-BLAST-Hits
+Student's t-test
+IRIS
+eight
+Visual logistics
+65%
+between 45 and 55%
+personal protective
+Eighteen
+TN1 and TN2
+spikes in the news event stream
+1957, 1968, and 2009
+FIP200
+IL-1β
+CA and iso-CA
+Intense homologous recombination
+Maladaptive coping to the environment
+daily counts of cases
+60%
+between 45 to 90 minutes
+DEPs
+slope validation
+Two field assistants
+the values for healthy patients
+flow cytometry analysis
+heating time and temperature
+6 dpi
+western-blot signals
+neutral selection
+extracellular
+3
+Two tailed paired students t-test
+Poor resolution of interferon phylogenies
+Doubles
+trafficking of HIV particles
+Group 1
+PKR
+liver cirrhosis
+34%
+VI 882
+I O
+similar type distributions for symptomatic and asymptomatic individuals
+R. tanguticum nanoparticles
+Salmonella Newport antibody titers
+34
+File S1
+ECMO
+HIPPA
+pathogens
+private institutes and non-governmental organizations
+assembling into pseudo-particles
+early growth response protein 1
+RABV
+P jirovecii detection through BAL in ARDS patients
+573,903
+NF-κB pathway
+severe bleeding and multi-organ failure
+the most acutely ill patients
+by inspiratory pressure minus PEEP
+societal estrangement
+residues
+average annual incidence in 5-14 year olds
+Texas A&M University and the University of North Carolina
+Vif and Vpu
+target binding to the Rb1 query protein
+Z-Phe-Arg-MCA
+40
+15 h
+short investigation time
+Infection control
+independently
+Macpherson
+security, intelligence and law enforcement authorities
+Health Promotion Law
+data from contact investigations and case clusters
+non-linear mixed effect model
+sentinel clinical data
+genetic erosion and population decline
+HeLa UPRT cells
+Age
+GTP and UTP
+Identification of relevant biological processes
+Viruses from outside the tumor mass
+dendritic cells
+a limiting dilution approach
+Integrin lymphocyte function-associated antigen 1
+SOPs for isolation and quarantine
+brought it back from overseas
+autoimmune pathogenesis
+virus
+Constitutive expression of hly
+1=c~205+100 years
+expenses
+practicality of the measurement setup
+phylogenetic analysis
+CMV viremia
+space allocations
+uniform contact timing
+15
+neuronal
+Platinum Taq Hi-Fi
+ϖ and ϑ
+fully human antibodies
+a short and a long αhelix
+Vasopressin
+phagocytosis and clearance
+strain background
+44
+479
+unclear
+gene normalization between samples
+LH
+cross-species conservation information
+Written informed consent
+Site directed mutagenesis
+Quick antimicrobial response
+Trypsin in the myocardium
+quantitative real-time polymerase chain reaction
+emulsion monodispersity
+hemagglutinin
+C6
+detrimental to the overall health of the host
+neural constituents
+pretreatment with 10d
+Proteins
+SU binding and the down-modulation of receptor by virus infection
+decreased viability
+Centers for Disease Control and Prevention
+ketamine and xylazine
+Threshold IME values
+uV-exposed mice
+less
+Monoclonal anti-HAX-1 antibody
+selenocysteine
+Activation of the innate immune system
+recombinant virus receptor
+cysteine
+reactive oxygen species
+10
+An AAV expressing an HA antigen
+Bradford protein assay
+complexity
+susceptible, intermediate or resistant
+2011
+three variables and two parameters
+overexpression of hnRNP F
+autoreactive pro-inflammatory T cells
+2009-08-18
+natural infections
+oral route
+sofosbuvir
+more than 80
+12
+7.5 times higher
+substantial overlap with decompensated liver disease
+two
+seven
+assembles
+cellular and humoral responses
+Road density
+ten
+osteoblasts, chondrocytes and adipocytes
+constructs generated previously by others
+care
+recent epidemiological data
+À1 and +1 FS
+pathogenesis
+rounded refractile cells
+aggravate ARDS progression
+seizures and encephalitis
+PNGase F
+2.8 years
+clinical trial recruitment and individualised care
+two segments
+potent, cross-reactive NAbs
+Core-on cells
+virus and microbial antigens
+more stringent criteria
+bronchointerstitial pneumonia
+~10%
+eight
+flow cytometry
+PI4P
+Homoharringtonine
+10
+histones
+T cells
+24%
+Fc function
+four
+two
+TBSV repRNA synthesis
+hepatocytes canalicular membranes
+6 days
+Inflammation of different visceral organs
+multiplexed and quantitative
+December to March
+One-half
+20
+high vs low, high vs medium, and low vs high pathogenicities
+1:150
+ρ ¼ 1 1þδ
+host transience
+Google Scholar
+Chronic hepatitis C virus infection
+interests
+classical human MHC class I molecules
+ARDS
+Energy recovered from the biochar production process
+strains associated with the production of many haplotypes
+four
+Further work
+peptide
+Centers for Disease Control and Prevention
+transmission links
+IrAE drug
+12
+Bacillus anthracis
+2138.386134.08 LFU/mg
+EWMA, regression, and Autoregressive Integrated Moving Average
+Encephalitis
+120
+IBV pseudoknot
+1 week
+MAP4K6
+in vivo transgene production
+Agro-JetH
+a suitable method for the comprehensive profiling of metabolites within bovine plasma
+KB buffer
+Delay, Contain, and Protect
+Leupeptin
+R 0
+Q-fever and the 2009 flu pandemic
+274
+antigenic shift and antigenic drift
+kinase inhibitors
+graftversus-host disease
+The SGDS
+by implementing ODE models at the nodes
+relative differences in EBOVGP-specific cellular and humoral antigenicity
+A Corbett Rotorgene 3000
+Student's t test
+C48
+CSIRO animal ethics committees
+sporadically
+astrocytes
+direct ubiquitination of Z is with the indicated mutations
+four decades
+nitric oxide
+Vps3 and Vps8
+lower suicide rates
+2,166
+SHELXD
+1.7 days
+venoarterial ECMO
+attenuates growth of the virus
+Phenotypic plasticity
+R38
+lipid accumulation, ER stress and mitochondrial dysfunction
+three
+cellular
+Oesophagus
+Influenza virus
+CTL effector cells
+R 0 = 2 × 3 = 6
+1:14
+148
+improving the clinical signs and addressing the primary disease process
+Jim O'Neill
+fruit bats
+high host nucleic acid content
+binding of viral nucleic acids
+Phylogenetic
+mutual-information min-max and forward greedy wrapper
+next generation sequencing technology
+IDO expression
+generates C5a and C5b
+enhanced local HSV-2 replication
+17
+cotton rat
+carp, salmonids
+VAR2CSA
+AAA to A_AA and A_AN
+The lower left block
+6 weeks
+0.2 mL/min
+catalytic residues
+homologues
+FoxP3 Transcription Factor Fix/Perm Buffer
+nontropical
+Respiratory volume monitoring
+62.8%
+CEACAM1
+gp120
+lipid-based
+pathologists
+Melt curve
+chemiluminescence
+Bi ions
+linear
+CPV-2c
+greatly influence the statistical results
+Forced vital capacity and forced expiratory volume in 1 second
+7-45%
+using the meta package in R
+S25
+pharmacological intervention
+impairment in endothelium-dependent vascular reactivity
+Positive and negative controls
+bacterial adherence to cells
+histopathological change
+spo0F allele
+genomic
+TE671, SF268, and ARPE-19
+Confirmatory factor analysis
+outbreaks
+Viruses
+binary covariate
+BAL fluid cytology profiles
+higher reductions on R 0
+flow cytometry
+Twenty
+pH 5.0
+Human cytomegalovirus
+core promoter binding
+Dengue Virus type 2
+Lymphocyte activation gene-3
+viral membrane fusion
+arbidol hydrochloride
+HRVs
+clathrin adaptor network
+polyethyleneimine derivative transfection reagent
+300-600
+tumor maintenance and metastasis
+epitope
+activated T cells
+490
+inhibition of the T3SS
+42%
+value was assigned the highest concentration of inhibitor tested
+genotype II
+rapid response intervention
+one million
+A similar strategy
+people of a similar cultural and educational background as potential study participants
+erythrocyte-binding activity
+evasion
+100,000 MWCO PES Spin-X UF Concentrator
+hamsters and cotton rats
+hospital or laboratory data
+proteases
+one order of magnitude higher than that of CIRP
+Discs from FTA cards
+TRI reagent
+intuition, author, and journals
+enhanced binding affinity
+disordered pressure generators
+10×
+VP4 protein
+diabetes
+0.2
+endothelial dysfunc tion
+199
+8 h
+laminin and skimmed milk powder
+PHEV
+Measuring the saturated solubility in some organic solvent
+Γ
+3 to 10
+entry into human and nonhuman primate cells
+rs707922
+ddH 2 O
+genetic instability
+whether they show HAI and/or neutralizing function
+Pandemic-related excess mortality
+polyomavirus
+LILRB1
+an intact PPXY late domain
+Rotaviruses
+Wuhan hospital
+geNorm and NormFinder
+T
+peroxynitrite
+1 week
+loss of mechanical compliance
+a comprehensive review
+cystatin F
+J-AC and C-HS
+two
+sham and ZIKV group images
+host-pathogen interactions and environmental factors
+the complexity of a model
+DNA damage
+the challenge of identifying influenza-related illness
+15:1
+REOV and HIV and TERT
+males
+166,832
+10
+BiP
+report generator
+65
+autonomic nervous system
+immunofluorescence
+Clade I of H7N9 viruses
+airway antiviral defense
+mitochondrial metabolism
+120
+a modest delay in replication
+11.83%
+components of the MG plan
+March 29, 2016
+37%
+1.6-1.8
+low virus titer
+Camargue
+Asia-Pacific
+174
+2x10 7 RPs/mL
+10-15%
+an inability to find and implement alternative solutions in a crisis
+statistical significance
+5%
+New York City
+Anti-mouse CEACAM1 Ab CC1
+17
+temperature, humidity, and atmospheric pressure
+Differences in gene ranking
+20
+supercoiled DNA
+P
+viruses
+inflammation, angiogenesis, and tissue remodelling
+significantly different
+key residues that differ between different branches
+White spot syndrome
+T cells
+Scenario d
+MATLAB
+to prevent tissue damage
+criteria to decide when to conduct contact tracing
+lower tidal volumes
+T m1/2
+adult wildcaught culicine mosquitoes
+poxvirus replication and pathogenesis
+40 cm
+improved the methods section
+In-frame exonic deletions
+ES2 peptide and water-soluble mucopolysaccharide CS
+CD55
+respiratory failure
+2.48 log10
+key changes
+suboptimal primer design and imperfect cycling conditions
+seasonal influenza vaccines
+95 °C
+G3BP1
+The Cox model key assumption of proportional hazards
+8
+phage DNA
+206
+ORF
+10 mg
+detection of known and novel viruses
+phosphorylation
+90 to 97%
+102
+access to flowers
+Four weeks
+1278
+stable secondary structure
+thickened wall arteries and vessel occlusion
+Albumin serum level
+healthcare-associated infections
+public awareness index
+FigTree
+Harris hip scores
+M ventilation zones
+decreased PaO 2 /FIO 2 ratio
+BEDTools genomecov
+A polyA tail
+1976
+1:1,000
+Table 2
+Ebola-specific
+Albuquerque
+GAVVALSTTFA and GIAFGAVELFD
+diarrhea scores
+uncompromised
+host genomics
+BoAstV and OvAstV
+Fifty-six
+telomere attrition and senescence
+VAP
+Creative Commons Attribution Noncommercial License
+The STING pathway
+goat
+structural parameter non-identifiability
+AARC-ACLF model
+mutations
+50% CO 2 containing 50% O 2
+Packaging of the genomic RNA
+infrastructure
+three
+333
+definitions
+γ − 2βΦξ ≥ −2β
+1.5 kcal/mol
+15
+342
+influenza A
+62.1%
+Directed evolution approaches
+Ancient viruses
+substrate for GRK2
+Bibliometric analyses
+The appointed media relations officer
+QIAQuick Gel Extraction Kit
+ten
+0 and 84 years
+standard deviations
+lymph node swelling
+2 and 4 h
+Nuclear receptors
+objectivity and transparency
+Reads from the control cells
+American Type Culture Collection
+MALDI-TOF mass spectrometry
+4
+mutational pressure
+1976
+higher
+0.1 mg/mL
+statin treatment
+pandemic influenza
+G36-CD28z CART cells
+7
+enteric and meningitis pathogens, TB and malaria
+Dynamic disease fluctuations
+10,311
+lung tissue from control subjects
+USA and Great Britain
+New species
+0.2 mg ml −1
+179
+ERK1/2 phosphorylation
+FDA
+Two hundred twenty seven
+bedside
+84%
+iProx motif
+LCL-721.220 or CCRF-CEM
+toremifene
+Indonesian Islands
+frequent activation of broadly reactive B cells
+left papillary muscle
+GFP-expressing E. coli
+December to April
+reaction mixtures
+p#0.05
+glioma cell infiltration
+22
+RNA polymerase III
+1,584
+horses and for high-risk personnel
+CV for LS data set
+Mahoney strain of type 1 poliovirus
+Ifitm
+Figure 4A
+BCL2L11
+epoxy
+viral resistance
+activates autophagy
+σ
+,120 kDa
+10%
+12.5 9 40 cm
+VP16 and Oct1
+onset to outcome
+its anti-apoptotic and mitogenic functions
+G418
+transcription factors
+Diabetes incidence and prevalence estimates
+430
+Colloidal gold
+BMDM media
+miRNAs
+missing data points and partly unreliable results of titrations
+PmFKBP46
+Proteins
+three
+6 to 10.1 days
+755 999
+unique identification numbers
+SMA type I fibroblasts
+3 kb of sequence 5 of the holin genes
+SQLite
+number of days of rainfall in a month
+bradykinin
+GEO
+NMR spectra
+250 SFC
+150 nM
+the Bundestag and Federal Government
+publCIF
+49.4 %
+5 minutes
+northeastern and central Taiwan
+nationwide activity of laboratory-confirmed influenza
+Abdul LatifJameeI Institute for Disease and Emergency Analytics
+a toxic or radioactive 'bomb'
+95%
+14.6 years
+Kidney
+CFI75 LWD 16XW/0.8 lens
+51.14557
+three
+0.41 and 0.70
+screening or antiviral prophylaxis
+The KAAD
+protein tertiary organizations
+Patients with sepsis and septic shock
+2.1 Hz
+2.9-13.8%
+BD Biosciences
+limited resources
+LPS
+vulnerability
+vitamin C shortened the length of ventilation on average by 25%
+broad-spectrum coverage
+3 to 20 L/min
+serology
+primary infections not contributing to the risk
+1007
+3 of illness
+One hundred and ninety four
+NS5A
+Two weeks
+Ebola virus disease
+Sigma
+missionary and nonmedical service workers
+interactions between U33 and A37
+GSH and GSSG
+phages
+Real-time PCR
+to understand better their material properties
+beclin-1 gene promotor region
+commuting distance distributions
+94%
+data
+Acute encephalitis syndrome
+Pleurobranchoidea
+Guangdong
+Comparative
+target-decoy strategy
+s 2
+Phosphorylation of eIF2α
+1.5 hours
+DNA synthesis
+wash their hands
+Cytokines
+Mock-or HSV-1-infected cells
+scannable paper forms
+slightly under 2 PFU per tomato
+pulmonary and infectious diseases
+Pelvic
+lncPro
+streptavidine-PE
+GAPDH and PP2A
+DNA sequencing
+at least one patient sample
+11.9 ± 1.2
+quite reasonable and creditable
+ω > 0
+metabolism of many commonly prescribed medications
+convergent validity
+PB2
+piezoelectric immunosensor
+limitation of DNA availability and budget constraints
+observations in Dock2 −/− mice
+1,687
+50%
+hopelessness
+precision τ
+24 h
+Japan
+Using full FOV data
+A and M epitopes
+physiological
+A and C nucleotides
+The Discovery Environment of iPlant Collaborative
+25%
+death nor on myocardial infarction
+current achievements and ongoing developments in the design of optimized DNA vaccines and delivery methods
+Dr. Kelvin Kong
+PATRIC
+immigration
+Mann-Whitney U or Fisher exact tests
+population stratification analysis
+loss of innate immune function
+a screen for novel caspase cleavage events
+OmpB
+33
+123.2 nm
+A. Keller
+Nuclease-mediated editing of dystrophin gene defects
+visible
+LIBSVM package
+Anti-BAFF mAb supernatants
+nucleotides 3975 to 4046 of GenBank
+improvement in both safety and efficacy
+mouse pancreatic islets
+communicable and non-communicable diseases
+male rats
+Altitude
+1,500 cells/cm 2
+University of Pittsburgh Animal Care Facility
+Preparing for health threats and emergencies
+PI4P and cholesterol
+did not significantly block high D-glucose-induced ACE2 shedding
+30%-50%
+adenovirus
+One lady's husband
+titration method
+Tmem119
+persistence and number of viable microorganisms
+Roslin Institute
+biotrauma
+7%
+Mirasol
+non-specific viral syndrome, ocular and congenital disease
+Patient-level antibiotic treatment data
+rainy seasons or low air humidity
+NNK induced migration of normal human bronchial epithelial cells
+1.15610 26
+the apoptosis
+PPMO-Fl
+STAT1 levels
+C12L encoding SPI-1 and K1L
+a series of sensitivity experiments
+1,785
+MTT assay
+censoring of the observation period
+phylodynamics
+high resolution influenza polymerase structure
+Sec16A
+one third
+6.32
+Epistasis
+160-fold
+166,167,000
+10
+5 g l −1
+miR-20a
+PdI
+recovered more slowly
+36%
+one
+protease activity
+a lifesaver or a transmitter of disease
+doublelength particles
+H10-specific primers
+FASTA
+alumina slurry
+The whole nucleotide sequence of each mutant HHD gene
+Colors
+viral DNA release and decay by cytoplasmic DNases
+bifurcation
+symbol nomenclature
+virulence gene expression
+receiver operating characteristic
+simple synthesis and modification, design flexibility, high target specificity, and good stability
+Gene chip analysis
+59pppRNA
+0.018 U/mg
+5%
+distinguish sepsis patients at presentation from healthy donors
+12
+weight loss and survival
+The method proposed in the main text
+T. cati
+vulnerable
+two putative stems
+coordinate organization and assembly of entry receptor complexes
+H1N1
+hematoxylin-eosin
+Circular TFO1
+African lions
+2 -5 oligoadenylates
+trachea responses
+Lactate concentration
+93.8%
+greater infectivity of the transcytosed virus
+DAC-reactivation of FOXO3A
+100%
+Total RNA
+a unique identification number
+lipopolysaccharides
+CXCR3
+Inter-hrHPV conservancy
+the attending physician
+anti-inflammatory effects on influenza-induced cytokine responses
+dry weights
+tumor penetration
+DB mice
+relative humidity
+mut1 or SCARB2 3 0 UTR mut2
+porous
+simulations
+September 2009
+2.9%
+2-7%
+RNALater
+592
+pSTMV and pRP
+The observed distribution of AlkB domains
+Septic shock
+12%
+GABA
+GCA 21 codon
+Five
+cytosolic cytochrome
+existing local financial support
+Fc tag-containing proteins
+One-way
+Lactate dehydrogenase activity
+University of Wisconsin Cardiovascular Physiology Core Facility
+epigenetic control
+previous models developed for Europe
+Gaussian functions of standard deviation and amplitude 1 and using a target approximation error
+D2 and D3
+promote carcinogenesis
+Change of conformation
+1 hr
+β actin housekeeping gene
+Colorbar
+SEN2278 and SEN4030
+GPS receiver
+serial 10-fold dilutions of the RNA
+risk of infection by influenza A/H1N1 virus
+morphological changes
+RT-PCR products
+mortality at day 28
+B λ
+Cesarean delivery
+fluorescent intercalating dyes or molecular probes
+3
+mutants by AONs
+Man-Whitney U test
+nicotinic receptors a9 and a10
+jl R
+three
+host NK cells
+Lower values
+a technician
+an ethical framework for policy and planning
+26.7%
+rough estimates
+western blot analysis
+bivalves
+HAPE
+Glyceraldehyde 3-phosphate dehydrogenase
+30%
+TempEst
+70% to 100%
+illness
+3.9%
+high levels of IL-6
+linear interpolation from adjacent values
+intensivists to incorporate new interventions into their practice
+Predicting lncRNA-protein interaction networks
+retroviruses and adenoviruses
+serum ferritin
+MHC class II and co-stimulatory molecules
+two
+Filoviruses
+the number in the population of an area
+replication-competent PRV
+Composite scores
+further investigation
+yellow
+lactating cows
+necrotizing bronchiolitis and DAD
+Apoptosis
+infection in slaughter-age pigs
+Chikungunya virus
+laboratory investigation
+lower lobe
+G x
+DPOAE and ABR
+eleven
+molecular detection
+nearly 200
+Calibration
+HEK293, HeLa, and A549
+Poisson distribution method of binomial variables
+providing a broad plan
+chemo and radiotherapy
+Field studies
+1 mM IPO solution was titrated with 25 mM carbohydrate solution
+24 hr
+RPMI-1640
+Zinc
+Maricopa county
+CPR
+55
+over use of sedatives
+a base call of A, C, G, T, or N
+Co-regulation
+preferential binding to LPS and circulating lipoproteins
+Jeffrey Bergelson
+morphine
+three
+10
+solvent/detergent mixtures
+60
+subtracting the sample mean from scores
+protection may be T cell mediated
+anaphylatoxins C3a and C5a
+bedtools genomecov tool
+Housing conditions and diet
+Figs 1 and 4
+1569
+malaria control
+Reed and Muench methods
+R Software
+QuikChange Site-Directed Mutagenesis Kit
+CD8+ T cell expansion
+observable model
+Alexander von Humboldt foundation
+medium with supplements
+expansions of clonal populations
+twice
+11
+Negative correlation coefficients
+twice
+advice
+30 min
+according to their properties of action
+confocal laser scanning
+within-household transmission
+increased hand-washing
+nausea, vomiting, diarrhea, and hepatotoxicity
+529552-HK
+71
+MicroRNAs
+Domains and items
+poly-T oligo-attached magnetic beads
+5%
+Becn1 or Atg7
+Acanthamoeba polyphaga mimivirus
+24
+151
+poor transcription of the fucA1 gene
+5 min
+immunodepleting malignant CTCL cells
+from snout
+4
+Membrane filters
+daily
+three
+they are unable to move on microtubules
+Geir Gunnlaugsson
+Stress granule formation
+IL-6
+three
+TRAF6
+inhibits membrane binding
+three
+intracellular vesicle fusion
+Associations with all-cause mortality
+SINV-C482G
+mRNA degradation
+feline leukemia virus as well as feline immunodeficiency virus
+K-means
+Uninfected cells
+four
+they would be unlikely to be accepted as an organ donor
+864
+2,185
+Rhesus macaque and sooty mangabey A3G
+GBs of infected animals
+synthetic quantitative calibrators
+SSP
+caveolae-mediated
+hierarchical regression
+83%
+Orientation towards public welfare
+sampler cutoff size, jet-to-plate distance and microorganism
+MSConvert
+Graft failure
+abrogating the formation of viral ribonucleoproteins
+inflammatory chemokines
+microbial DNA and RNA
+RIG-I
+positive-strand
+three
+Lightcycler 480 SW1.5 programme
+more than 30 residues
+excess amount of progeny RNAs
+43-kDa full-length and fragmented
+tumor necrosis factor alpha -induced NF-B nuclear translocation
+200 µL
+lyase activity
+Super-spreading
+Two
+JcDV break in and transport across the epithelium
+reduces the levels of mature 28S rRNA
+2,376,021
+the up-regulation of IFN-b gene
+5 EU/kg body weight/dose
+27
+a-tubulin
+15 min
+60-70%
+VOPBA
+2
+close contacts
+frameshifting
+measured disease epidemiology
+four
+Coelenterazine
+defects in the NPC1 protein
+220
+SomaLogic panel
+GraphPad Prism 5
+HIF-1α
+community transmission
+high sequence diversity
+IFNa and IFN-c
+Two
+ATRQβ-001
+1.6 million
+tetraspanin membrane protein family
+Odjik WLC
+14 days
+therapeutic ratios
+three
+every three days
+761
+Lipofectamine 2000
+90%
+IP3
+Two
+letter codes
+static reporters
+serum or fecal material extracts
+means and SD
+Mouse ISG15 variants
+47
+flu surveillance
+at least yearly
+80%
+sites of subtype consensus differences
+perform two or three replicates
+four
+a diagnostic PCR
+FluorSave reagent
+GraphPad Prism 6.0
+7.3
+single-membrane tubular structures
+2 cm
+IRF3 activation
+Noroviruses
+Three
+U bodies
+macrophages
+TNF-α
+2
+alternative local control methods
+5 km
+maturation and secretion of DV1
+0.05
+highly immunogenic
+Antigen 5-related proteins
+IL-17
+PMN band cells
+The gel
+Increased levels of antibody
+XOD
+apoptosis
+social interactions which can lead to infection do change
+help-seeking
+Idiopathic ARDS
+50, 100 or 200 mg/L
+a core pseudoknot
+enhanced filamentation
+Titers of DENV stocks
+6 d
+Conformational changes
+229
+Activation of the NF-κB pathway
+sticks
+10-15
+HLA-A * 30:01
+location of further downstream out of frame stop codons
+5.2 months and 10.8 months
+splenectomy
+Agrobacterium culture carrying empty pGD-35S plasmid
+B and T cells
+prospective, observational
+14.0%
+total SPS scores
+reporting precision
+parvovirus B19
+H-indices
+neutralizing activity for 13.6A
+type I IFNs
+hypertension
+TLR2
+amastatin
+Various hypotheses
+scissile
+free energy values
+10 ms
+underreporting of dietary intakes in obese adults
+EMICT
+guanidium-based lysis buffer
+Colonel Samuel Bel-Nono
+hormones and gender
+1, 2, 3, and 4
+Nagelkerke Pseudo-R 2
+Procalcitonin
+MTT
+gastrointestinal
+protective
+complexity of geospatial patterning
+Hsieh & Cheng
+multiplexed
+1104
+Protein degradation rates
+electrophoresis and fluorescence analysis
+mitochondrial glycolysis pathway
+April 27, 2009
+10, 5, and 3
+embryogenesis and organogenesis
+does not produce any spores
+points and animals
+www.dovepress.com
+two
+Over 85%
+lung parenchyma
+potential intronic variations
+360
+plaque size and virulence
+seven
+herpes family viruses
+γ δ T cells
+oxidative protein unfolding
+Ct
+>7 years old
+neuroanatomical
+a safe and stable vaccine with long lasting immunity
+100
+MATLAB
+low probability of all trees
+CD4 and CD8 T cells
+5.3 cases per 100 ICU admissions
+Digested plasmids
+smoking
+abundant levels of NSs
+supplementary material
+BBP
+adipocyte phenotype alteration
+myricitrin
+viral isolation, vaccine development and production
+bigger
+review design and manuscript proof reading
+phage 6
+the means of the three independent experiments
+CEACAM1
+genotype or allele frequency
+convenience sampling
+48 hr
+Mathematical models
+false-positives
+4x10 5 cells/mL
+negative
+perforin
+statistical significance
+invade
+two
+conformational alterations
+16
+The last well
+Weighted inclusion of all elements
+severe acute respiratory syndrome
+Pneumococcal pneumonia
+protective
+219 bp
+residues
+21%
+ovine colostrum
+pulmonary Nogo-B expression
+gel electrophoresis
+Lysozyme
+Human NK cells and macrophages
+inflammatory
+Over-expression of different types of NPIPB and NPIPA genes
+Gel densitometry
+36 h
+Frameshifting
+52.2%
+763
+those alignments often do not conserve the reading frame
+interest
+inflammatory cytokine profiles
+regulatory
+Regulation 178/2002/EC
+oral immunization
+900,000
+Alum
+n
+1.02
+chemokine binding to their specific receptors and glycosaminoglycans
+PSEN1
+80%
+September 3, 2019
+many commonly used drugs
+soluble aggregates of EGFP
+enhance maturation and type I IFN production in PDCs
+anti-inflammatory
+30 days
+Oxford-Diffraction XCALIBUR E CCD diffractometer
+mRNA expression of CXCL9
+5
+increase the N F /n ratio
+990
+associate and assemble at the plasma membrane
+HHD mice
+Special care
+Shearing
+incident power
+MT
+viniferifuran
+leader± body base pairing
+Km and Kcat
+Centers for Disease Control and Prevention
+latitude, population density, and the proportion of children
+the government
+membrane proteins
+viral −1 PRF
+data
+UNDP-PCR assay
+Samples of right and left lungs
+BW25113
+Vaccination
+subsidize government sector salaries
+red blood cell
+Demetrius, Gundlach and Ochs
+Bio-Plex Manager Software
+442 nt
+13.25%
+N
+6.4-8.6 µM
+Two
+tedium
+dissociate
+12
+100
+cc-by
+CrebA
+268
+4 weeks
+operons
+MAC
+inflammatory cell recruitment into the lungs
+BIRC5
+1.8%
+24 h
+Transmission studies using reverse genetics
+less than 0.1
+50%
+circular genomes
+11.7% and 3.5%
+3
+δ-crystallin
+H5 HA
+larger funding
+pulmonary capillaries
+20
+additional cases of virus hijacking events
+specifi c therapy
+PRJEB14938
+TCM theories
+admin-istration of antibiotics
+memory cells expressing CD38 + IgD − cells
+MEK-inhibitors
+digital droplet PCR
+axonal swelling and breakdown
+individual social distancing
+group A healthy enriched B case enriched
+high price
+linearized DNA
+impaired monocyte function
+helps virion assembly
+ACE activity
+Five
+YLDSNNFPW
+to effectively provide the evolutionary benefit
+binding free energy differences
+ORR
+12-fold
+1536
+Systematic identification of potential target proteins
+Twenty eight
+epigenetic regulation
+SD
+10
+27
+therapeutic
+diabetes and multiple sclerosis
+spherical or cup-shape
+personal resources
+selection schemes
+significantly enriched
+2009
+100
+a list of query viral protein sequences
+78%
+about every ten years
+end-point titration technique
+dengue, malaria and leptospirosis
+30%
+2 : 1
+three
+Citrus psorosis ophiovirus
+taxol
+whites
+Magnetic Luminex ® Screening Assay Kit
+Antioxidant capacity
+antimicrobial activity
+end-oflife
+test-negative
+substrate DNA
+Oxidative
+7 days
+hydroperoxide
+18
+identifying ORFs larger than expected by chance alone
+RNeasy minikit
+HIV and hepatitis
+germ-free
+76
+overphosphorylation
+Glycyrrhizin
+viral replication complexes
+17%
+limited access
+heat shock
+TRX2
+inactivated virus preparations
+bacterial diversity analyses
+Economic development
+resistance to beclabuvir
+p62/sequestosome 1 TBK1
+man flu
+DCs and monocytic cells
+ML is much cheaper than HP
+17.0
+130-fold lower
+intracellular cholesterol homeostasis
+mAb 4G2
+Alveolar macrophages
+USP28
+NCCN Guidelines
+two
+cardiovascular disease
+alterations in the solubility and conformation
+demographic heterogeneity dictated by V
+photosynthesis, transcription, and translation
+gs6
+Public health decision making
+nicotinamide adenine dinucleotide
+one year per demarcation
+Mortality due to LRDs caused by CRVs
+ENaC
+IFN-κ
+iatrogenic and AIDS-related KS
+lungs
+greater-than-template-length products
+Serum from H5 HAlo infected mice
+lung tumor cell lines
+Five
+black boxes
+one reflection
+reduced MeV F CSE
+Hand washing
+A/WSN/33 virus segment 2 mutant libraries
+70
+CHOP
+Vi-cell XR
+patient-centered outcomes
+JMN3-003
+Microglia
+immune cells, astrocytes, chemokines and cytokines
+cytoplasmic fraction
+a moderately conserved SIM
+terpolymers
+Varroa mites
+quantitative data
+δ-secretase
+participation in the entire implementation process
+six
+4sU
+Sputum 2'-5=OAS
+five
+selectively binds to a specific sequence
+nine
+Erns and E2
+chest
+17
+2 hours
+four
+five
+Reed and Muench method 40
+isolation specificity filter
+R 0 = 1.8
+the slippery sequence
+axonal outgrowth
+cDNA
+50 μl of 50% V5-agarose beads
+pharmacologic inhibition of TLR signal
+amantadine and oseltamivir
+necessity
+tree
+Appendix S1 Equation
+Jackson Laboratory, USA
+StepOne TM System
+Economy Class
+Recombinant protein
+100 mm
+particle to infectivity ratios
+0.6%
+production of stable cell lines
+convergence
+sevoflurane
+Big Dye Terminator v3.1
+7
+16,723
+pancreatic lipase
+2003
+Flow Jo software
+RT-qPCR assay
+1966
+systolic volume and pulse pressure variation of 10% or above
+15 min
+7 to 37
+IFN-β
+Screening for aneuploidy
+a sufficiently sensitive cell type
+Severe
+enhanced the production of interferon-β
+proteomics
+a specific ratio of enzymes to structural proteins critical for virus infectivity
+fimC and mat
+cardiomyopathy of sepsis
+VSV*DG
+cascade reactions
+historical healthcare records
+sepsis-induced immunosuppression
+The certainty of evidence
+monoclonal anti-NDV/HN antibody
+six
+cost, complexity and local acceptance of their use
+non-adjuvanted vaccine
+nine
+Responsible and accountable focal points
+Ang II
+S-nitrosylation
+VLP mutants
+no similarity between lineages
+central or lymphoid memory cells
+a core hydrophobic sequence of 16 amino acids
+likelihood profiling
+eqTHN_del_GPI
+quercetin
+once per week
+E
+21
+58%
+cDNA clones
+bell-shaped
+placental
+Recombinase polymerase amplification
+acacetin
+inhibits the production of IFN in canonical autophagy
+Fibronectin
+T cells
+Arrows
+CTT, TAC and TTT
+Nodes and edges
+Extrapulmonary
+Adherence status of the participants
+PBS
+9 %
+26
+9.1
+word2vec
+infections, medications, vaccinations, sun exposure and stressful life events
+Contrasts
+TRIM56
+20% incorporation of whole blood in LAMP
+slightly larger
+Bacillus
+tdFLIM
+The entomological inoculation rate
+pragmatic
+COOT
+RSCU values
+AKI biomarkers
+DG init
+American Spinal Cord Injury Association
+every four months
+FlowJo software
+eQTL-associated conjugation DMEs
+thrice
+critical
+interstate arrangements
+10%
+StructMap
+3 November 2014
+67
+attenuated growth phenotype
+closer ortholog
+2-DE based proteomics
+gene reassortments
+5 days
+Venturia canescens
+445
+attachment of a protein to a surface
+phosphorylated histone H3
+regulation of gene expression and translation
+clinical data and previously identified biomarkers
+Three
+a different clinical course
+0%
+saturation
++1 frameshift
+Nova Scotia's neighboring province
+Easterners
+6.0
+light-dependent
+Two
+1997 and 1998
+filter adjustment
+viruses
+Aromatase
+impairment of the insulin signalling pathway
+de novo viral protein synthesis
+over 1 year
+Residues in antigenic epitopes
+tumor cells
+group I and group II
+39
+more attention
+177
+precautions
+TRIF
+532
+target vaccines
+Viral growth
+a linear relationship
+205
+defined T cell epitopes
+€1.05 million
+all the facts
+fatal
+normal aerobic fitness
+Effective control of all the analytical steps
+A2676-A2679
+JH6 and JH7
+protein precipitation
+48 hpi
+formal probability distributions
+Declaration of Helsinki
+selective destruction or physical separation of mismatch-containing heteroduplexes
+Influenza
+ampicillin
+improving the underlying mechanisms of the disease and exploring new therapeutic approaches
+Polyethylene glycols -siRNA conjugate
+electrical stimulation
+technical limitations of high-throughput sequencing
+2,692,325
+229
+Stealth™ RNAi Negative Control Duplex
+70%
+17
+Fop
+JEOL 1230 transmission electron microscope
+decreased cell adhesion and migration
+l-arabinose
+distal pancreatectomy
+a similar format with different attributes
+mouse mammary tumor virus
+Immunization, Antigen, and Antigen Presenting Cell
+maintain a distance to a sick acquaintance or relative
+standard curves
+more than 50
+treatment and/or reassurance
+Childhood respiratory tract infections
+vaccination
+16
+influenza
+strong pathogen-killing effects
+FluA or FluB purified protein IgG
+age
+1
+312
+2005
+Subgroup
+four
+Steffen et al.
+zoonotic spillover
+Na + /K + -ATPase ATP1A1
+absolute quantitation
+lower
+The box enclosing the dots
+Bovine viral diarrhoea/mucosal disease
+which sequences are minimally essential for function
+proviral or antiviral
+ethics approval
+reduced
+inhibition of the virus dependency factor furin
+eYFP component
+CLE model
+Six
+transport
+UTMB Institutional Animal Care and Use Committee
+vaccination
+CUUUGA
+.50%
+T-cell clonal exhaustion
+TNF-α and IL-6
+tissue damage, necrosis, apoptosis, and inflammatory cellular infiltration
+the entire liver
+production of NO
+population size
+red dot box area
+In-fusion SMARTer Directional cDNA Library Construction Kit
+colorimetric
+HIV
+5 g/L
+alveolar compartments
+Chest radiographs
+Adjusted odds ratio
+Close contact
+4132
+get serious long term effects
+Perception about a country's preparation
+2000-8000, 10,000, and 70
+an ancient coagulation factor
+IFI27L2
+15 min
+programmatic analysis and overall feedback
+apocynin
+HTSeq-count 56
+APN/CD13 molecule
+invasive
+Post hoc analysis of pairwise comparisons via Bonferroni correction
+drisapersen
+10
+DyeLight 488 labeled Streptavidin
+apoptosis
+cerebellum
+upstream ORFs
+CSU Veterinary Diagnostic Laboratory
+All Delphi discussion participants
+all patients withdrawn from the study, safety data, and deaths
+two
+TIM-4-sufficient
+prophylaxis
+10,000
+ring vaccination and space flight
+MRC Centre for Global Infectious Disease Analysis
+evaluating the disease severity and prognosis of the HFRS patients
+Contact tracing
+Tukey's Honest Significant Difference method
+caveolin-1
+hepatocarcinoma cell line
+chromatin-associated cyclin-dependent kinase 8
+A549 lung adenocarcinoma cells
+P-Selectin Glycoprotein Ligand 1
+EV production
+receptor protein folding
+contacts between apolar patches
+PIV
+Standard recombinant porcine IFN-γ
+SAROTUP and MimoDB
+point of care
+Drug resistance
+regulates differentiation
+to assure secure transactions
+both sequences supporting non-homologous crossovers
+tissue injury
+HSV-1-tk
+remarkably reduced reproductive performance
+protein levels
+fluorogenic labeling
+22%
+Two
+oval-shaped
+substrate stiffness
+Tetherin
+Further studies
+q~0:7
+Prevention
+21.8%
+CTF RNA
+2.5-3.5
+Cardiac remodelling
+Plasmodium falciparum CSP
+total cellular RNA
+genes
+Imaris software
+B lymphocytes
+Taconic Laboratories
+GPGR/Q/K sequence
+cholesterol mislocalization
+interest
+Peak VO 2
+RT-PCR
+encoded amino acids
+H7N9 virus specific antibodies
+epitopes not shared with sGP
+multiple chains of mean duration T
+Half
+HMCK
+5
+37 kDa position
+500
+plaque velocity
+SeqTrack
+Human Papillomavirus Type 16 Infection
+NG2-positive neural progenitor cells
+hubris
+3-fold higher
+inducible Treg
+Workflows and input/output data
+crucial
+48 million
+72 hours
+BAP31
+hundreds of thousands
+E. coli
+regression analysis
+HBZ
+increases in susceptibility to virus-induced cell killing and changes in global gene expression
+conidiation
+No necrosis
+17
+acute encephalitis
+phosphorylation of JAK2
+reduced
+Species identification
+effective viral clearance
+10,000
+120 DNA tetrahedra
+424
+globally compromised
+quantitative predictions
+keratinocyte growth factor
+pseudoknot structures
+hospital infection control teams
+antiviral and hospitalization
+proinflammatory
+Controlling brain edema
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+three
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+regulating IFN immune and inflammation responses
+sucrose gradient
+2000
+immunity, virulence factors, contact type and patterns, and climatic conditions
+Philippine forum
+7
+similarity
+Protein Data Bank
+Bean yellow dwarf virus
+1995
+microbiological
+BiV pacing
+CRF-AD35, B, C, and D
+peptide signature
+seabirds
+pulmonary edema
+competing interests
+e bi
+Our assay
+distinctively
+SD
+different definitions of parasites, pests and pathogens
+at least three
+heat-related illness
+grouper samples
+Charles River Laboratories, Inc
+splicing correction assay
+JAK/STAT pathways
+Five
+dimers and even polymers
+once the intervention trigger threshold was reached
+perceived fear
+Accession numbers
+8.5 days
+GRP78
+unknown
+68 %
+tracking structural integrity of the MCAD protein
+A reproducible source of considerably purified Clara cells
+Spo0A
+80-90%
+Bill and Melinda Gates Foundation
+0.18 and 0.05 μM
+metabolism, survival and innate immunity
+Quasispecies genetic complexity
+IFN induction
+experimental data
+TMS
+90%
+SEAP production
+Mer-mediated efferocytosis
+22%
+antiviral
+Data gathered from multiple sources
+Modified probes with 5-mm spheres
+RNaseL
+AT I cells
+disease prognosis
+CD4 + and CD8 + T cells
+A sepharose beads
+postal codes, counties and states
+NLRP3-mediated pyroptosis
+higher
+3,340
+the WB with the recombinant antigens
+usefulness of national or regional level trends in incidence or prevalence
+linear scanning
+protein A agarose columns
+10 210 -10 27
+6 h
+9 out of 14
+LN metastasis
+RT-PCR assays
+toxicity
+Materials & Mehtods
+57%
+Epithelix Sàrl
+inflammation
+3 h
+paclitaxel
+CTD phosphorylation
+C, U, A, G
+contigs
+leucines and isoleucines
+present in a hospital during their admission for other reasons
+1-day-old
+viral genome alterations
+transmission electron microscope
+red blood cells
+Robert Wood Johnson Foundation
+mPK −1
+three
+64
+differential access to healthcare and noninsured health coverage
+Overexpression of CXCR7 and additional CXCL12
+Huh7 xenograft model
+bipartite or multipartite
+DNA microarrays
+Five
+multi-basic cleavage site
+51 days
+contact tracing
+Strand-specific primers
+brome mosaic virus and cowpea chlorotic mottle virus
+abnormal behavior, clinical signs, or mortality
+lethal immunopathology
+SYFPEITHI and BIMAS
+paracetamol toxicity
+pIFN-γ
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+African green monkeys
+qRT-PCR and viral load
+~210 6 /mL
+apoptosis, oncogenesis, and cellular growth and proliferation
+PND4
+Yates Chi-squared
+RNA gel shift analysis
+sexual contact
+a lincosamide antibiotic
+2%
+ALI
+GuHCl
+Interevent times
+Extracting a restricted list of features
+BTV NS4 or GIV NS4
+quantifying in vivo effect on downstream transcription
+de novo cap-dependent translation initiation
+Seven days
+ImageQuant
+2D
+using ten randomly selected samples from each group
+decrease in ACE2
+neurological disorders, and cancer
+FYA/FYB
+eGFP and EBOV GP
+66 kDa
+two to three times per week
+reassortment
+228
+50-90%
+Spearman correlation coefficients
+gelindependent techniques
+neurons and glial cells
+GAPDH mRNA
+~50 μL
+Binary logistic regression model
+nsp4
+essential
+Mean relative lung weights and lung wet:dry weight ratios
+hyperglycemia
+binding of sialoadhesin
+REG3γ
+Gancao
+Atlas of Coiled Coils
+supernatant
+glucocorticoids
+non-polar, polar, and charged
+pCFG5-EGZ retroviral vector
+14
+mitigating avian influenza spread
+scientists
+amino acid sequence identity
+site-speci fi c transgenics
+HA protein
+15-20%
+94
+CD103 − T RM cells
+reviewer
+30 min
+CD133 + CSCs
+to describe the methods of public health intervention
+UK
+macrophages
+statistical
+myeloid-derived suppressor cells
+Deep vein thrombosis
+Two
+$1.1%
+0.5%
+1 day
+4%
+poly
+receptor internalisation and degradation
+gel-shift assays
+fatty acids
+proxies
+Phylogenetic bootstrap neighbour-joining trees
+Bibliometric analysis
+artificial Beijing
+human contact with infected poultry or virus-contaminated environments
+First stranded cDNA
+half an hour
+F
+BBB disruption
+TGF-β1 mRNA expression
+successful VSEL isolation
+Ai9 mice
+double deckers
+Western blot analysis
+3
+47 million
+100 000
+RNA MICROMAX TSA labeling and detection kit
+clathrin-dependent
+susceptibility
+CEACAM1
+Relapse
+~1,000ϫ coverage
+stimulates the IRE1 and the ATF6 axes
+MDR A. baumannii
+HCDR3 and LCDR1
+SMARCA2-regulated factors
+drip-flow
+35.0%
+WT mice
+other possible contributing factors
+promoter activity
+53.33%
+H4K16ac
+ignorance of the contribution of the overall peptide structure to binding
+b
+GALLEX assay
+anti-Toxoplasma
+Syncytium formation
+milled
+an exchange between a pyrimidine and a purine structure
+Two-tailed t-tests
+ANISOU entries
+rinsing cells thrice with PBS
+66.2%
+10 min
+E ≤ 1/R 0
+when the ribosome is stalled over the slippery sequence
+Flooding
+Expertise in clinical ethics
+subcutaneous tumor model mice
+desmosomal proteins at the plasma membrane
+The value of sequence data
+blood brain barrier
+continued breastfeeding
+virus load and proliferation dynamics
+toxic
+PE
+chronic
+R package PROPER
+died
+hospitals or travel clinics
+three
+10,436
+Kaplan-Meier method
+serum-free medium
+3.12 particles per µL
+dialysis-related factors
+The design
+ssRNA and DNA
+P53
+1.0 mM
+countrylevel
+sealing
+Epithelial cells
+multiplex amplicons
+cortex and striatum
+showsnps function
+supernatant
+FTY720/fingolimod
+the SCOP database
+endothelial • NO release
+exacerbations
+Leica TCS SP5 confocal microscope
+Table 1
+the absorbance after 24 hours of cell seeding
+QX-type isolates
+an aspartate
+3 nt 5 0
+four days
+bone
+Seven
+His120
+24 hours
+Macrophages
+Hourly values of temperature
+helium
+a window of length K
+Streptococcus pneumoniae
+increases
+tractable models
+2%
+Luxol fast blue
+a pattern of virus labelling
+allergic skin inflammation
+IL-1 and TNF
+615
+nine
+miRNeasy Mini kit
+increasing social distancing
+determines that the liver returns to a size that is strictly proportional to body size
+a pair of serum
+microRNA lin-4
+p-336TT
+DNA polymerase
+HLA-DR
+further validation
+Taiwan
+75%
+Adenoviruses
+antiviral agents
+phylodynamic analyses
+three to four weeks
+SARI
+influenza and chikungunya
+43 years
+silicone injections
+personal invulnerability
+shifting this servicebased approach to a patient-centric approach
+high-fidelity PCR-amplified DNA fragments
+mitochondria-associated PHB
+a weight with a value between 0 and 1
+HuNoV-specific IgY
+DNA damage
+11.2
+58
+Montanide ISA50
+control, luciferase or ADAM17 siRNA
+24 h
+specialized
+mouse
+MZ B cells
+Fifteen out of 17
+The exact role of complement in many diseases
+TLR3, TLR7/8, and TLR9
+mononuclear phagocytic system
+disorderpromoting residues
+Guidelines
+shuttles between the nucleus and the cytoplasm
+redirect those cells to the targeted cancer cell
+content and timings
+qScript XLT 1-Step RT-qPCR ToughMix
+ewe192-B5
+oxygen-dependent phagocytosis
+significantly reduced virus release
+mice
+housekeeping functions of autophagy
+SFPQ/PSF
+higher household and workplace transmission
+pitavastatin accumulation
+BCPREDS server
+66.6%
+1909 kcal
+Tetramers of p/MHC I alleles
+PPs
+Dynactin 1 and IFITM3
+17
+Pepro Tech
+redox
+Promega genomic DNA kit A1125
+SPSS statistical software
+size and, more importantly, location
+CEM and Jurkat T cells
+S-palmitoylated
+behavioural interventions
+virus binding and internalization assays
+Ovation RNA-Seq primer sequence
+Thirty-seven
+Figure S1A
+how you are feeling and if you have taken any medications
+random drift
+anti-HPV16 neutralizing antibody titers
+higher vaccination cost
+virology
+black dashed lines
+10-month
+L2
+increase bile flow and decrease bile acid concentration
+ammonium-dependent
+possible, probable, and proven
+severe eutrophication
+Transcription of IL-10
+Phylogenetic analysis
+EMBOSS antigenic
+B-1a cells
+to avoid unintentional contamination
+fungal contamination
+e β
+ALT and AST enzymes
+1068 days
+DMEM containing 2% FBS
+spatial information about mRNA molecule distribution in the cell
+HT vectors
+decreased
+monkeypox
+30%
+Escherichia coli peritonitis
+the alternative complement pathway
+6
+IFN-β promoter activity
+anti-malarial vaccine candidates
+cAMP
+magnetics, optics, and electronics
+endocytosis pathways
+13
+75,000
+variable ratios
+22
+four
+94%
+virus replication
+GLE1 and NUP214
+Acute fibrinous and organizing pneumonia
+More details regarding the epidemic model and the Stan code
+DRAK2
+Nuremberg, Germany
+recombination breakpoints
+Olympus IX70 photomicroscope
+Mycobacterium avium paratuberculosis
+I i
+Text S1
+angiogenic
+perceived protective behaviors
+Fourteen
+0.18
+1450
+patients with fungal infections
+whether they reliably identify GAS infection
+Pulse oximetry
+secretion of watery saliva
+12.5%
+11
+Enhanced regulatory oversight
+deep mutational scanning
+December 2015
+G3BP1
+reagents
+higher values of T
+real time assay
+10% mortality in compensated cirrhosis
+Formation of active replicase complex
+activation or inactivation of inflammatory peptides
+Acyclovir
+Issues/bug reports
+60
+BioStation ID system
+Mass spectra
+self-evaluation, peer review and voluntary external evaluations
+nasal DNA vaccine delivery
+oxaliplatin
+CG-atoms of different Vpu structures
+HCMC
+macrophage inflammatory protein -1α
+adenosine
+oceanic
+Classification and regression trees
+dehydroampelosin B and viniferifuran
+Large-scale virulent B. bronchiseptica cultures
+83%
+CA II
+Areas with observed bias
+three
+RNA extraction
+Bcl-x
+age, sex and residence
+High-dose infusions of Chase
+4.42
+RPL4, EEF1A1, and RPS23
+PERC
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+genealogical
+c and the offset in the power law kernel
+13 947
+Fluorescence
+higher infection rates
+12
+13,649
+429
+in accordance with predefined criteria
+10-20%
+Kuhn length
+animal deaths
+Table S2
+the pHvalue
+microglial subpopulations
+HFD-induced additional weight gain and calorie intake
+patients, families, and the team itself
+$US 2500
+CoMFA and CoMSIA descriptors
+HTLV-1-positive
+pattern recognition receptors
+make the game safer
+MyImageAnalysis
+84 months
+37
+recombinant human TGF-b 1
+Twenty-four hours
+T regulatory cells
+mRNA and protein
+field data
+mortality
+Removing the data for more viruses
+MTG-LASSO
+64.2 years
+80%
+untreated infected cells
+fixative
+two-dimensional
+156
+SO, SM, RK and GM
+data collection tool
+Influenza A of subtype H9N2
+nuclease cleavage
+molecular docking studies
+SE = ln) / 1.96
+3-valent serum
+BLASTn
+gradient centrifugation
+TNF-α and macrophage inhibitory factor
+airborne particulate matter
+concentration dependent
+ProteinChipH Data Manager Client 3.5
+by spiking in known amounts of heavy-labelled peptide analogues
+STAT-1 and IRF-7
+the body of the deceased
+severe atrophic enteritis and villous fusion
+Student's t-test and Fisher's exact test
+tFAK and β-Actin detection
+TRIzol
+n j
+APACHE
+Ang-,
+humidity
+nasal washes with high viral titers
+The proposed algorithm
+21
+a potential incident of self-contamination
+Information on the efficiency and proportion of particles that contain detectable EdC
+ambulatory follow-up
+148
+Folder Automation Software
+extraneural sites
+Br-ApoE
+endosomal membranes
+Peak oxygen uptake
+T RM cells
+caspases
+manidipine
+any improvement in respiratory system compliance
+three
+plaque burden and Aβ levels
+Chromosome 11
+five
+animal models or mere observational patient data
+Absolute extraction recovery
+our study
+Prognosis of a disease
+hepatic insufficiency and renal failures
+1
+$383 ± 93 nM
+SNPs
+Chrysin
+TLR2 and TLR4
+Multi-level repeated-measures modelling
+44%
+the same
+2-fold
+Human immune cells
+IL-4/IL-13 stimulation
+indicators of mental illness
+PLA
+bioinformation software and molecular immunology
+ECH0825
+Magnetic bead capture
+nearly 400,000
+seven
+observed SARS data from China
+dinucleotide biases
+15 min
+pivotal
+Panels
+peripheral CD4 + T cell count
+Dennis R. Burton
+extracellular and intracellular pathogen counts
+E90R and D91N
+low-income countries
+three
+small sample size
+genetic drift
+in a discontinuous gradient of sucrose
+identifying GH-dependent phosphosites
+lock files
+Oligonucleotides
+Background luminescence
+the task
+Cq values for amplification and amplicon melting temperatures
+Solvent
+PottersWheel Toolbox
+Cav-1
+LSV specific primers
+statistically significant
+extreme lack of trust
+Protein jagged-1
+350-525 nm
+40 µL of CellTiter-Glo 2.0
+regulation of autophagy
+binary logistic regression model
+10 μL of WST-8
+80 mL
+immunoregulatory
+Bacterial pellets
+645 nm
+three
+N 1 -methylguanosine
+an authentic mapping from nt 1 to 317
+MxA
+self-report data
+water collection points
+Serum
+Old World and New World
+mice
+⊆
+megapeptides
+color-coded microspheres
+tropical rain forests
+Nab resistance
+pathogenic
+NLRP3
+Kα2
+58
+Inter-rater reliability
+Lipofectamine 3000 kit
+344
+16
+M isperceptions of risk
+elevated levels of IL-10, IL-6 and IFN-g
+,10 mm
+Insect parvoviruses
+Agresti-Coull method
+wild products
+TLR4
+Immunofluorescence
+follicular germinal centres
+Exacerbated disease and mortality
+Redox imbalance
+Institutional Ethics Review Board
+spill-over infection
+Ruthenium complexes
+Hospitalbased CLs
+severe hypoxia
+80%
+AM22 and D25
+three
+misclassification of vaccination status
+Serological tests with IgA anti-tTG
+band of high molecular weight
+renal lesions
+GraphPad Prism
+0.05
+T. equinum is highly closely related
+Modified residues
+The S H
+miR-373
+50%
+Prevalence data
+endogenous siRNAs
+1.1%
+4-11 day old
+MagMAX™ Viral RNA Isolation Kit
+Figure 8
+lentiviral pseudotypes
+IgY anti-STAg
+supernatants
+.50%
+92%
+Twelve
+88
+testis-expressed genes
+norepinephrine and dobutamine
+get vaccinated
+Hong Kong Hospital Authority
+35.5 ears
+the mechanism of entry of other filoviruses
+ClustalW2
+combinatorial genetic analysis
+psychological
+inflammation
+personal relationships
+Protruding RNA
+real-time reverse transcription polymerase chain reaction assay
+50-90%
+Hantaan virus
+Echotoxins
+CD4 and CD8 T cells
+four
+92%
+The growth of the 1942 strain
+Forecasts
+PER1, PER2, CLOCK, and BMAL1
+amplify a 91-bp fragment specific to pAD2TE1 mRNA
+High production of both IgM and TNFα
+NH4Cl and BafA1
+Three
+Pseudoknot
+CSF1 and IL34
+HutC
+42%
+by ultrasonication
+sodium
+S r
+6
+Eight
+within normal limits
+98,200
+34%
+p values
+protein-level
+Edouard Bertrand
+Assiut University Hospitals
+coadaptation
+the activity of mTOR
+I-HC
+independent pulldown assays
+SQL server
+resistance to BmNPV infection
+pandemic H1N1 and chicken H5N1
+EMCV
+Group IV
+Figure 4
+demonstrable capacity to mitigate public health risks
+brain natriuretic peptide
+Prior infection of both cell types with PRRSV
+shorter DFS
+five
+number and percentage
+Classical SELEX
+malaria-infected
+178
+increase the virulence
+modules for plasma and serum separation
+Re]
+Standard solutions of DMF
+proxies
+Chisquare test or Fisher's exact test
+p<0.05
+0.9%
+.26
+J Christopher Farmer
+Ctenocephalides felis
+3
+ICP34.5 gene
+CD11b
+CD40L
+Maximum supplemental oxygen use per 24-hour period
+eight
+tryptophan
+ILC3 cells
+15-80%
+8% per year
+pneumoniae
+Materials and Methods
+nuclear atypia
+Dysgenesis in sex organs dependent on androgen/AR-driven development
+DENV-2 E protein
+activate distinct pathways of the cellular UPR
+SVM
+3.43
+Aquaporins
+molecular weight shift
+mycobacterial
+expired air
+1.6 million
+lungs and spleen
+carbapenems
+Aurodox
+thrombin-antithrombin III complex activity
+1,296
+Social support
+human TRIM25
+Enhanced Chemiluminescence Western Blot Detection Reagents
+atomic coordinates of the RNA backbone
+propidium iodide
+dephosphorylation of ULK1
+lateral wall scarring
+GPIs and GIPLs
+Ganglioside G M1
+GENIE3
+Theta
+One in 10
+Adlhoch
+gene transformation
+discovery of new molecular scaffolds
+state of unresponsiveness
+27
+attenuates neurovirulence
+bronchopneumonia group
+bed rest and oxygen inhalation
+Integrated DNA Technologies
+LC3-containing membranes
+ATG12
+Deng Yiqun
+protein concentration
+Neuraminidase inhibitors
+very effective
+full compliance of patients with screening recommendations
+AutoDock Vina
+Western blotting
+a weak Lewis acid
+2202
+0.05
+Core Hopping
+58%
+it is not exclusive to this subset of viruses
+a duplicated print of buffer alone
+kappa = 0.81
+DWV titers
+puerarin
+STAT-1 phosphorylation
+function
+4
+in-vivo
+Structural Equation Modeling
+retinopathy of prematurity
+NZV
+3%
+several complications of T2DM
+differentiation
+1 mL of 75% ethanol
+deterioration of CD8 + T cell functions
+Sign epistasis and reciprocal sign epistasis
+LeTx
+$3%
+1.3
+post-transcriptional modifications
+peak VO 2
+Hsp27
+mild or no histopathological changes in the brain or other major organs
+138
+mass spectrometry
+Soluble forms of EBOV GP
+partially deleted viral genomes
+0.2 mg/ml
+a stab wound
+Infection
+Sangon Biotech
+recognition and timely initiation of treatment
+Sanger sequencing
+14 days
+transient social distancing
+Exosomes
+Shandong Agriculture University Institutional Animal Care and Use Committee
+human papillomavirus and arenaviruses
+targeting the ISG15 and/or the ubiquitin system
+sensitive probes
+SARS and MERS
+conjunctival disease
+Five
+Blood pressure reading
+inadequate antigen levels
+appropriate knowledge, prevention, and treatment
+Surveillance using web-query data
+inhibitory
+pandemic influenza and the West Nile virus
+wet-weight
+NiV infection
+Smallpox
+0.20 ± 0.11
+PKCa
+any information on the flexibility of the structure
+85% ± 1.3
+an upper limit
+Salmonella protease sseL
+diazepam 8 μg/mL
+T cell
+10.7-18.6%
+Photodynamic therapy
+FluWatch
+10 6 mg of DNA per reaction
+natural killer cells
+health risk and/or protection
+789 aa-long
+baseline severity of hypoxemia
+Low-current and high-frequency electrical stunning
+Engineered
+low titer of input VZV
+lateral peptide parameters
+institutional review board approval
+Imbalance of T cell regulation
+7.3 magnitudes and a depth of 18.1 kilometers
+133.5 kbp to 135.1 kbp
+65%
+major
+Pathogen specific surveillance
+TSG-6
+1700 rpm
+hypersporulating variants
+secondary structure prediction
+25 to 60%
+140
+serum samples
+RT-qPCR
+non-covalently linked
+Travelers
+several hours
+108
+two
+carbon catabolite repression and gene expression
+enhanced redundancy
+two amino acid changes
+Centricon Plus-20
+shortened maturation cycle and desirable lead developability
+liver USP18 expression
+12% SDS-PAGE
+reviewing the subject matter as well as the existing document
+reasonable
+MVA-based A vaccines
+Taq DNA polymerase
+free-grazing ducks
+three
+tight junctional
+Hoechst 33342 and propidium iodide
+2 mM
+activation of the reporter gene
+Quantitect Reverse Transcription Kit
+in vitro MHC binding assays
+FK506 binding protein 12
+35 million
+Reverse transcription loop-mediated isothermal amplification
+AURKA
+antimicrobials
+fully developed ectopic germinal centers
+MV
+Secretory IgA
+Coinfection with AIVs and a bacterial pathogen
+what pathogens are circulating
+Wuxi Red Cross Blood center
+1 M Tris-HCl
+12.9% Gln and 27.7% Pro
+stable secondary and tertiary structures
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+PeptideAtlas
+detection by inflammasomes
+Five
+ixodid hard ticks
+phylogenies
+GPUs
+Gram-positive bacteria
+$41%
+36.4%
+any part of the genomic sequence of CEA
+1 and 100 copies/mL
+infl uenza vaccine strategies and pandemic planning
+3 days
+10%
+A14 and A17
+every third day
+IL-18
+over thousand
+14.7%
+RABV
+tetramethylbenzidine
+fluorescent fusion proteins
+privileged
+chemical and structural determinants
+a database for creating and managing viral ORF clones
+2/5
+Sixteen
+Xeno RNA Control
+scRNA-seq
+C1 and C3
+near each group of toilets and near each food service area
+epidemic decline is much more rapid
+80%
+0.86% ammonium chloride solution
+intercalation of the dye
+salvage treatment
+Doxycycline, tetracycline, and penicillin
+9.7 days
+SEC-MALS
+eight
+miR-210
+hospitalization rates, intravenous fluid requirement
+18
+non-parametric
+premature birth
+Strong laboratory capacity
+colony-forming units
+SDS
+26
+diminished thymopoiesis
+Data
+vector competence
+genomes of LPAIV, EDSV, and NDV
+mice and cotton rats
+few
+recombinant plasmids
+Pseudotype neutralization
+1.06 times greater
+enzymatic activity
+dyspnea, dehydration and diarrhea
+28.6%
+autopsy studies
+both sexes
+membranous vesicles
+255
+1.14
+miR-122
+Bioscientia reference laboratory in Germany
+infectious patients
+Data
+sodium nitrite
+20 min
+KAPA Library Quantification Kit
+15 min
+F106 and A112
+Six
+QIAshredder columns
+higher than 90 C
+BEAST
+Delays in the identification and/or reporting of HPAI infection
+CYC-D
+physicians
+Sixty-two
+meta-analysis
+innate immune response
+long-term political commitment, training and resources
+immunity
+Information
+lymphocytes and plasma cells
+optical density
+P-values 0.05
+mosquito
+how proteins are trafficked to MVBs and exosomes
+Minimum Information About a Microarray Experiment guidelines
+2250
+up to 10 years
+1 week
+military assets
+Vero cells
+The author
+transient
+Student's unpaired t-test
+our use of multiple scopes of statistical significance
+Further studies
+HT01 and an HT01/HT02 heterozygote
+cc-by
+interferons a and b
+DEAD-box helicase
+Respiratory syncytial virus
+differ
+15 Å
+15-HETE
+Partial chain termination
+EUMS
+VacA-mediated
+primed template
+TRIM56
+Demographic data
+161
+supporting predictions of elimination
+blood-brain barrier permeability
+75%
+35% glycerol
+Lymphocytes and alveolar macrophages
+virome
+Three
+39.5 ± 0.11 degrees Celsius
+oral vaccines
+China Animal Health and Epidemiology Center
+viral spillover
+N-linked glycosylation
+Estimates of resource gaps
+kinetic effects
+WGA
+two
+Table 1
+num-bers
+a value between 1 and 20
+3
+endocytic vesicles
+Targeting homeostasis and repair/inflammation
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+NS1-GFP
+5.948EϪ4 substitutions/site/year
+bioterrorist attack
+blood cultures
+17.5%
+53
+chronic inflammation, tissue damage and fibrosis
+patient identifiers
+nucleases
+Statistical significance
+ATF4
+IL-10, IL-12 and IL-23
+acute organ dysfunction
+At the edge of the FG loop
+hypertension
+disease recurrence
+zero
+Bid-regulated apoptosis
+$19.3 billion
+80%
+vasculitis, dermatomyositis, and organizing pneumonia
+President Obama
+vulnerable motor neurons
+Protein complexes
+brings the activating UCE sequence into close proximity with the core promoter element
+reverting to a more traditional lifestyle
+timing and/or site of ZIKV infection
+independent of their known relevance to infectious diseases
+artificial miRNAs
+Susceptible
+26
+multiplexed plasmids
+Ottawa Health Science Network Research Ethics Board
+two
+Feline Parvovirus
+initial pathogen invasion
+fewer intermediate nodes
+longer time effects
+inflammatory response
+246
+a second alignment and maximum likelihood phylogenetic tree
+37 • C
+Women with incomplete baseline data
+section 20
+Picornaviridae
+CD4+ T cells and STAT4/6
+single mutations in HN
+Pietermaritzburg
+The level of polymerases that scan through the whole genome
+39,305
+viral vectored gene therapy
+14
+positive
+research on microbes in the built environment
+Gram-negative
+prevention rather than treatment
+Pichia pastoris
+18 hours
+family tree
+four
+PR3 concentration
+septic shock and trauma-induced SIRS
+pMark-S
+Luohanguo
+50%
+honesty
+near or at the base of IHC sensory cells
+American Type Culture Collection
+monitoring side effects
+40%
+Fifty-and eighty percentmaximal inhibitory concentrations
+data
+fusion between viral and host-derived membranes
+lack of information
+May 2002
+2013-01-11
+occasional problems in the initial experience
+conidia
+Table 5
+conformational changes
+HCMV Merlin
+2006
+HBx and CRTC1
+Each translated pool
+2 months
+interferon activation
+bovine
+2024
+T4 ligase
+pediatric hospitals
+functionally important
+repulsive potential
+partially restored IGF-1R levels
+nitrocellulose membranes
+an artifactual degradation of L1 RNA
+lower mean cumulative number of lesions
+160 million
+replication inhibition assay
+Mg 2+
+exogenous IFN
+integration of the activities of the different systems
+High Capacity cDNA RT Kit
+reducing transmission during funerals
+gene identified from the primary screen
+data-constrained models
+TIIA
+14 days
+University of Pittsburgh Institutional Review Board
+~35,000
+acquiescence and extremity
+two
+a role of SP-D in atherogenesis
+N-terminal lectin domain
+MDA-MB-231
+Data that could not be found in individual articles
+p300
+the chain size that is considered anomalously large will rise
+performing useless and costly experiments
+H3
+14%
+20 minutes
+Differences in viral loads
+remarkably high levels of expression
+non-diseased lung tissue
+ChemoProphylaxis with Sporozoites
+wildlife officials
+smaller-sized
+twice
+Burkitt's lymphoma
+vaccines
+eIF2•GTP
+an inaccurate assessment of prognosis
+NTM co-infection
+to thwart enteric Shigella infection
+Invitrogen Superscript III cDNA synthesis kit
+a potent proatherogenic factor
+more than one antibody fragment
+fever, cough, rhinorrhoea or sore throat
+rabbit polyclonal anti-Listeria genus-specific antibody
+suppression by other MARV proteins
+Dr. R.G. Webster
+£20.4 million
+ubiquitinates lysine 18
+phages
+necropsy
+Non-parametric Kruskal-Wallis test
+19
+seven
+Chronic lymphocytic leukemia
+10 min
+poliovirus fadeout frequency
+HBV and HCV
+VSV RNA
+PARylation
+20 mg/kg
+Peking Union Medical College Hospital Institutional Review Board
+m4G2
+Poor governance
+mtROSinduced NLRP3 dependent pro-inflammatory responses
+R 2 0
+a Markov chain
+XMRV Env-mediated membrane fusion
+the following points
+flu virus neuraminidase
+reciprocal sign epistasis
+mid twentieth Century
+HAP
+microgravity-sensitive
+alveolar macrophages
+3.2
+C
+five minutes
+90,000
+high sensitivity values
+African and Portuguese
+fluorochrome conjugated monoclonal antibodies
+Social interaction
+TACE shRNA
+4-15
+RNase A and T1
+pT183 and pY185
+The death rate for all compartments
+Fcc receptor IIIA
+565
+50 mg/mL lysozyme and 0.1% Triton
+rescue experiments
+product complex
+ortho-dihydroxyphenyl group was absent
+peptidases
+A
+high bed occupancy
+Per a 2-specific IgE
+Lipid rafts
+serine hydrolases
+1 h
+96
+schizophrenia with auditory hallucination
+1 hour
+Protocol deviations
+zanamivir
+U-I/C ED group
+repressed expression
+guinea pigs
+environmental and social
+pumps
+reliable incidence rate estimate
+Anatidae
+protocolized continuous insulin infusion
+exon 12A
+His-Mermaid
+Timothy McVeigh and Terry Nichols
+Any descriptions too long for the figure legend
+asbestos-induced collagen deposition and fibrosis
+burn patients
+Pseudomonas syringae
+ENC-plot
+all relevant feedback and comments
+Flow cytometry
+longer lived residual condensed foci
+mouse bone marrow-derived macrophages
+Serum samples
+the disease caused by SARS-CoV-2
+DNeasy Blood and Tissue Kit
+Centrifuge and Kraken
+protein kinase C
+nanogel particles
+Food Industry Research and Development Institute
+RiboTag translatome profiling
+wood shavings
+four times
+surveys
+terminal sialic acids
+differences in sensitivity of proteomics methods
+57.38 g/l
+demographic functions
+methanol
+60 300
+one third
+Unlikely contact
+nonsense-mediated decay and subsequent loss of protein
+Cytokines and chemokines
+based on the formation of syncytia and nuclear aggregation
+Multidisciplinary
+two
+a i = 1
+ALI/ARDS
+18.1%
+five
+optimism
+Six
+420
+NAb
+TCs cycle and proliferation
+acceptable
+faster
+helix
+1983
+biological samples
+made dramatic statements
+RNA
+DAVID and KEGG databases
+dityrosine C-terminus
+five
+19
+92.3%
+the length and the mutation rate of the considered DNA sequence
+Table S4
+Nppa and CXCL11
+neuraminidase inhibitor
+Panels A and C
+Toll-like receptors 7 and 8
+sites of injury
+28-day mortality risk
+1700
+Ca 2+ and Ni 2+
+80%
+enhanced
+miR-146b-5p and let-7g
+Cidofovir
+to activate selected precursors
+Sixty-eight
+untagged
+Primary antibody omission
+over 25 years ago
+immune deficiency syndrome and tuberculosis
+tRNA Lys mnm5s2UUU
+Invariance of the energy under rigid motions
+Wales and Scotland
+to maintain a native-like environment and increase conformational stability
+nidus
+capillary morphogenesis
+Acclimation temperatures
+1:10
+Heteroplasmy
+150 pg/ mL to 300 ng/mL
+Expansion, enhancement, and integration of maternal and early life immunization
+the world's number-1 health threat
+plasticity
+fever
+ancient DNA
+Shino-Test Corporation
+thermalcycling
+human
+ORF1 and ORF4
+Trafficking proteins
+12%
+G6PD deficiency
+brain tissue
+three
+shorter
+theatres
+factors that govern host susceptibility to leptospiral infection
+10
+Eighty-eight percent
+Belgium
+wide spectrum antibiotics
+a representative
+DNA loads
+hyperinsulinemia
+T 3
+Thirtyfive
+functional neutralization assays
+frequent intra-segment recombination and an error-prone polymerase
+7.5%
+multiple compounds presented in the formula or complex prescription act synergistically
+four
+a property of the underlying gene sequences
+non-susceptible forms
+bioinformatics pipeline
+proline
+CRF07_BC
+20 mM
+treatment with tazobactam and piperacillin
+particle size distribution and type of atomizer
+Hospital financing arrangements
+Avian influenza
+12.5
+resilience
+high viremia titers
+vertebrate-incompetent
+30%
+mobile phones
+anti-inflammatory
+tRNA Ser CAG
+Vb8/Vb14 CD8 + T cells
+170
+survival
+to account for loop length diversity
+3 minutes
+IVCAS 1.0228
+8
+March 2014
+225
+Non-viral gene therapy
+two
+pro-coagulant and pro-inflammatory pathways
+national borders
+98%
+p38 and ERK
+sh-EK#2mediated EK knockdown
+Typhoon 9400
+S protein
+68%
+six
+serial 10 µ m brain sections
+hypergeometric tests
+floral characters
+180 kDa
+three
+hazard ratio for ICU death
+antiviral NP and anti-alpha acetylated tubulin
+relatively low RNA concentrations
+97%
+Central African Republic and Nigeria
+0.60
+Bilayer thickness
+2%
+children
+cc-by
+Optical maps
+GeneMapper 3.7
+20 months
+identical virus material from the environment
+more heterogeneous delivery of the inhaled anesthetic
+6 to 8
+cross-reactive viral antigens
+27%
+nodes and their connections
+utopian
+12 688 Da
+3-6 monthly intervals
+the globulation rate
+A sterile blade
+ELR+
+a nucleophile
+37
+Six
+p-DEP effect
+>1 bit
+National guidelines for triage
+Proteomics
+3-21 days
+Human adenoviruses
+Whole-genome comparison
+Unmethylated CpG-rich DNA
+38.3%
+H275Y
+HBV substitution rates
+Salmonellosis
+IZUMO and FLOT2
+538
+necrosis
+odds ratio and chi-square distribution
+26
+four
+three
+H x,y,z
+declined
+at least twice daily
+Avian infectious bronchitis virus
+50%
+detecting known viruses
+eight
+systemic spread of virus
+clumping and precipitation of the antigen out of solution
+HSQC
+six
+m max
+28
+the corresponding author
+Caliciviruses
+15%
+p33 or p92 replication proteins
+45%
+91,000
+viral concentration methods
+CD8+ T cells
+DNA viruses
+winter and spring
+PNGase F
+Antigen-antibody complexes
+Members of the genus Trichophyton
+Biosprint One-for-all Vet Kit
+compromised
+they represent non-coding RNAs
+Phyllanthus urinaria
+0.591
+fecal-oral route
+site I in HSA
+redox-sensitive
+2009
+resource use
+heterogeneous
+decrease
+Staphylococcal enterotoxin sensitization
+38 of 39
+9.7%
+genetic resistant
+17 days
+strong
+GIS
+linear regression models
+13%
+a library of antibodies
+virulence
+293T
+LPL, IEL, and FRT
+Definitions, basic theory and discussion of further results
+Infectious bursal disease virus
+FMOC peptide synthesis chemistry
+154 and 389
+porcine coronaviruses
+40
+immunofluorescent
+Information of crystal structures of protein-peptide complexes
+spore-forming
+the percentage of proteins annotated with each GO term
+SureSelect Human V4/V5 enrichment kit
+56
+carbohydrates such as Me-Man, Me-Glc and Me-Gal
+17,310
+responded vigorously
+individual cellular proteins
+enhanced accumulation of renal ADAM17
+76,175
+protein gel electrophoresis
+all-cause mortality
+3.42 ± 0.52 × 10 8 relative light units
+Projected chronic disease mortality rates
+plant CRY in higher plants
+immunofluorescence
+0.95
+increase of membrane fusion inhibitory activity
+37 nm
+1,022
+CD150
+Life Satisfaction scale
+30.7 ± 24.4 days
+t-test between CON and CON-PEDV
+thermal and mechanical unfolding
+HPRT, L19 and GAPDH
+progenitor
+99%
+its own translation
+more conserved epitopes
+Tet-On system
+higher risk of fetal abnormalities
+Russia
+ΔFosB
+Cumulative evidence that might be biased
+reverse transcription
+prolonged fever and severe respiratory symptoms
+Viral leader-mRNA and M protein
+two
+T-cell activation
+41.9%
+1973
+UL33
+$100 FFU
+respiratory
+possible sequencing errors
+2 mg/ml of TPCK treated trypsin
+43
+2 µg/g FW
+2%
+pathogenesis and cell tropism
+E-site juxtaposing upstream internal SD
+1
+150
+std
+DNA vectors
+written informed consent
+virus exit and spread
+satisfactory results
+21 days
+CSII-CMV-EGFP
+healthy controls
+late referral of patients to clinics
+infection
+Lung cancer
+cytokines
+parsimony
+parasite groups
+30 000
+LPS-induced endotoxic shock
+binding affinity between host and virus proteins
+1997
+COPD frequent exacerbators have innate antiviral immune dysfunction
+NT-proBNP concentration
+paracellular charge selectivity
+Virus titers in each fraction
+all-cause
+1 in 10,000
+SPE, SLE + and phospholipid removal
+GO and HPO
+Fresh samples
+Na/K-ATPase signaling
+cell lysates or pellets
+8 days
+Twenty-four hour
+Parent or guardian
+mutation rates
+SARI cases
+immunostimulatory
+Oligo 2
+V'max FRC
+design and evaluation of drug formulations
+every 4 weeks
+given or larger area under the curve value
+media
+Leave-one-out cross validation
+infect the new host and undergo further mutation
+clinically relevant information
+smartphone 19
+Four
+type IV collagen
+seven
+correct
+41%
+half
+pVIII
+microorganisms
+NS1
+cytokines
+viral flora
+two complementary approaches
+higher proviral loads and worse outcome
+network formation
+198.6 pg/mL
+HZQ and JES
+copper sulfate
+the observed total number of deaths in a given week
+abrogate
+liver transplantation
+insoluble Aβ level
+29 234
+genes for deacetylase/isomerase/aldolase
+epidermal growth factor-like domain 7
+IL-10-expressing B cells
+CD163-and CD204-positive
+32
+effect sizes
+16h
+dengue virus transmission
+mobile phones
+Infection
+computē
+Tracking frequency of URI
+10 µm
+mean ± SD relative to the 10 μl bead samples
+further studies
+2008
+six
+97.92% to 100%
+FACs Calibur
+Flanking Sequence
+27
+120 minutes
+Correspondence analysis
+moderate to severe CAA
+B cells
+FASN
+Lung involvement of P. marneffei
+tracing
+pathogen epitopes
+10%
+reduces the costs associated with being immobilized
+up-and down-regulated
+Notch-1 receptor signaling pathway
+fluorescence
+2007
+2 and 4
+-20.4 and -5.3 kcal mol -1
+Three
+3
+Two
+0.113 to 0.148
+microbial
+Sex differences in the immune responses to influenza viruses
+ξ
+CD13 KO infarcted hearts
+71
+2,4-dinitrochlorobenzene
+cc-by
+5 minutes
+CT
+seven
+High dependency and coronary care admissions
+pathological
+improved methods for template preparation, sequencing and imaging, and data analysis
+mass spectrophotometry
+June to August of 2015
+9.5 hour
+Ang-II
+Breathing difficulties
+a lipid molecule in close contact with the peptide must significantly reduce its order
+change dramatically
+riverine buffalo
+the natural route of infection
+Nasal swab specimens
+Short chain fatty acids
+81%
+E. coli cultures
+BLASTN
+2.79
+provincial level
+500 ml
+three
+34
+4 • C
+Ang II level
+The accelerating effect and aggravating effect
+Grade GRADE
+Thirty-five
+Clinical and demographic characteristics
+knockout mice
+chest CT scan
+critical
+194
+RPMI
+six to nine points
+3D
+interactions
+70%
+Immunofluorescence
+Three days
+an exchange of three Japanese sentences or a physical touch on the skin
+HCE
+deferoxamine
+recombinant OppA protein
+homologous recombination
+shrinkage
+18
+Goat anti-ZH501
+syn-plot2
+inflammatory
+His-ES24-based ELISA
+CD133, nestin, and CD44
+2'-modified
+aberrant structures resembling viroplasms
+neuroendocrine immune network
+robustness to population structure
+specific genetic subpopulations
+Clinical and microbiology data
+59-TGA GCG GAT AAC AAT TTC AC-39
+BC and GB
+proton transport models
+Viraemia
+ACE2
+Topomer CoMFA and Ellman
+100 ml/well
+between 34 and 38 weeks
+pro-inflammatory
+luciferase
+WM volume or myelinated fibre diameter
+individual pathogens
+the full length protein
+astrocytes
+Calciviridae
+b and xmid
+sustained survival
+determinant
+comparison between PBS and vaccine treated groups
+multifunctional
+0.43
+CMV promoter
+lentivirus, adenovirus and adeno-associated virus
+four
+squalene
+long term dormancy
+SALSA derivatisation
+Human fibrinogen
+RNA residence times in NP
+code or shared libraries
+LptE
+different locations
+cross-T-cell
+rhesus macaque
+immune-mediated competition
+finding who the infector was and when the case was infected
+placental tissues
+100%
+InflA probe
+T lymphocytes
+10%
+apoptosis
+positive-strand RNA viruses
+4% paraformaldehyde
+Gag
+Serum biomarkers
+10%
+flow cytometric analysis
+DSASA
+upregulated production of IFN
+three
+HBV infection
+tumor suppressor
+more complete clearance of intact virus
+2 reverse genetic protocols
+RNA-Seq
+X =
+periodic oscillations
+P11LR and P11/LRR
+become involuted
+activity and the lack of an inoculum effect
+continuous lipid and cellular membrane synthesis
+Cat-scratch disease
+DNAs
+two weeks
+Adenovirus
+HuNoV structural protein VP1
+Severe acute respiratory illness surveillance
+Virus replication and infectivity
+unbiased characterizations of autonomic tone
+anti-inflammatory
+Oropharyngeal swab specimens
+potency
+28 DPC
+Leafhoppers
+PEARL
+target organs
+Vaccinia virus
+ATP
+N wobbles
+Bottom row
+Acute DENV infection
+12
+improvement in bilateral consolidation and groundglass opacity
+single-primer linear RPA
+three
+biologically relevant data
+viral replication capability
+15 minutes
+administrative
+19
+Apoptosis
+Rabies-specific immunoglobulin
+Titration curves
+the variance predicted by the different models
+Text S2
+children and adults
+Sex
+Disordered regions
+LOS
+small molecule chemical diversity
+86%
+XML
+western lowland gorillas
+MIP-1α
+2-6%
+Charles Gerhardt
+0603-exposed mice
+semi-conservative replication
+An ROI
+mono-negative bidentate around the metal ion
+emergent strains
+polyacrylamide gel electrophoresis
+Chimera
+nonanesthetized
+RAS
+metagenomic sequencing and de novo assembly
+impaired trafficking of infiltrating myeloid populations
+individual protocols
+58
+pigs
+Duke NUS Graduate Medical School
+fever, myalgias, headache, and pleuritic chest pain
+summary errors
+CD27 and CD28
+direct co-opting of the translation machinery
+The membrane
+Penicilliosis
+352
+Philadelphia International Airport
+sulfuric acid
+Ŷ
+mortality
+as a function of time
+Statistical
+Group 1
+collision energy of 50 eV
+Triage
+genotype II
+TIM-4
+SpectraMax M5 Microplate Reader
+text messaging
+Hundred and three
+60%
+novel therapeutic agents
+Vesp-6
+Mouse IL-10 ELISA MAX TM Deluxe
+mediates the cap-independent translation of EV71 RNA
+Venn diagrams
+Univariate and multivariate Cox proportional hazards models
+five
+1 hr
+153
+7.4, 7.1, 6.8 or 6.4
+24 h
+subnuclear
+D21 IFITM3-expressing
+19 days
+Antigens
+once a week
+they are able to produce nearly all of their ATP
+0.67%
+Alage Dairy Farm
+LAS AF Lite software
+158
+AMPK activation
+real life decision-making
+IL-1α
+Immunofluorescence
+live bat experiments
+induction of neutralizing antibodies
+microenvironment
+Goal-directed resuscitation
+Table 3
+cre
+1%
+Table S3
+Western blot
+10 11 cfu/ml
+Th2 cells
+1996
+Type 1 and Type 2 pneumocytes
+cross-reaction with A/Wis/05
+12
+460
+lower
+novel hypoxia/HIF-1α-regulated targets
+Multivariable logistic regression analysis
+Creb3L1
+regression
+fluorescence
+proper protein processing, expression and function
+divergent
+1995
+H9N2/wis
+Dr. Hung-Jen Liu
+Description of all functional elements in the H. somni system
+Genotropin
+12 months
+chisquare test statistics
+STRING 9.01 Server
+serious
+FKBP11
+54
+larger
+3.0 mm polyester transwell inserts
+3,000
+a relative risk of 1.0
+HCV-infected hepatocytes
+dihydroorotate dehydrogenase
+viral replication
+human hypocretin receptor 2
+Abnormal muscle echogenicity
+negative staining
+235,000
+local health bureaus
+respiratory
+I49 and S31
+95
+269
+p ≤ 0.05
+Supernatants
+Mast cells
+most details of human mobility
+Multipartite viruses
+Understanding how viruses and their hosts co-evolve
+purifying selection and mutational saturation
+E11
+pDCs
+flavivirus
+E. coli BL21
+5.5
+45%
+0.1% crystal violet solution
+doripenem
+KPNA2
+82%
+observations, recordings and measurements
+k min
+37
+MVA
+local investigators
+PolK and the FA pathway
+UV
+total tau levels
+financial and economic impact surveys
+25
+pregnant women, the elderly, and potentially older children
+48 h
+Agnostic biosignatures
+J&K Scientific Corporation
+true knots
+Outbreak events
+60%
+France
+H5
+Gel electrophoresis
+SLEDAI
+IDO
+every day
+nocardiamides A and B
+Trx1-Prx1 disulfide-linked conjugate
+purchasing power parity
+NSCLC xenografts
+High-throughput
+Every single life lost to suicide
+$40.50 billion
+virions from supernatant of infected Vero cells
+hepatic stellate cells
+low accuracy rate
+THP1 cells
+complement evasion
+immunofluorescence
+Q411
+enhancement of inflammation
+the capsid
+FHV-1
+polymerase chain reaction-restriction fragment length polymorphism technique
+Zika virus infection
+reviews
+mechanical ventilation
+0.47 AE 0.07 g
+156 million
+traditional medicine
+reduce the production of TNF-α
+C-terminal domain
+Vibrio cholerae
+2%
+Relative lung weights
+4147
+Qiagen Gel Extraction Kit
+SRP154218
+61
+antigen presentation
+VOI
+-80°C
+2008-11-07
+new systematic review literature
+810
+SJPL cells
+Ae. aegypti and Ae. albopictus
+Pathogen-negative specimens
+Cufflinks
+Viruses
+minus-strand synthesis
+Mean Absolute Percentage Error
+9-fold
+a vaccinia virus vector
+three
+antiviral activity
+IL-17A
+Risk communication
+11 genes
+Contralateral mastectomy
+CVB3
+fl ow cytometry
+Nine RGs
+Ranaviruses
+strand synthesis
+linear quantitative similarity
+20
+inhibitors
+search engine data biases levels
+weight redistribution
+inflammasome signaling
+IFN-λ 4
+10
+Evolutionary
+DL
+analyses of standard biochemical parameters
+Thirty-three
+antiviral
+tertiary interactions
+GFP + cells
+Cystic fibrosis and COPD
+Neurotropic mouse hepatitis virus infection
+NPC1 and LAL
+Twenty-four
+ten
+IgG and IgM
+Lassa VLP egress
+routine
+EBOV-GP mediated virus entry
+79.7% of the variability in peak timing
+user bulletin no. 2 of the ABI Prism 7700 Sequence Detection System
+proportionality, reciprocity, and consideration of community goods
+3,000-49,000
+risk stratification in H1N1 pneumonia
+PLEX-ID/Flu assay
+2 weeks
+33%
+401
+twice a day
+CompuSyn
+95%
+At least two
+target cell membrane
+IFN-driven
+Left ventricular assist devices
+30 μM
+receptor signalling
+Cilnidipine
+evolution and functional differentiation
+counterproductive work behaviour
+lymphoid tissues
+BD Cytofix/Cytoperm solution
+trypsin
+high selection pressure
+tgG-RL fusion antigen
+saprophytic filamentous
+7
+Pancreatic cancer
+Cholinesterase
+nuclear factor-κB
+severe sepsis
+further evidence
+Our analysis
+5.3%
+XLStat
+Ten
+Purified DNA
+complex human behaviors
+spleen mononuclear cells
+50%
+5
+fibrosis
+CNS inflammation
+Cyp3a2 expression
+apoptotic cells with degraded DNA
+phylogenetic trees
+IFIT1
+human challenge studies
+intact
+two
+0.2%
+SGTs
+~25 ng L1/array
+go off duty
+13.6%
+Z Y V
+Mabtech
+three months
+productive RSV internalization by macropinocytosis
+cross-group bNAbs
+VSV
+stringent mitochondrial quality control mechanisms
+IL-4, IL-13 and OVA specific IgE
+pneumonia and acute respiratory distress syndrome
+respiratory syncytial virus and cholera
+An audit trail
+RNeasy
+BLAST
+exogenous protease
+high DENV-binding avidity
+acute renal failure
+covering the whole population of a country at a given point in time
+accuracy, speed, automation, and cost
+100-400 µl DAB
+Reverse genetics technology
+388
+mature naïve B cells
+I 2 statistic
+SAS 9.1.3
+suboptimal
+5 minutes
+recipient cells
+20 min
+accelerates pathways to tertiary care and intervention
+bell-like graphs
+polymerase activity
+the ability to fix complement or bind to Fc γ receptors
+Poisson regression
+our population represents a profoundly immunocompromised population
+secondary anti-mouse horse radish peroxidase conjugated antibodies
+Collagen deposition
+GeneJET RNA purification kit
+KFDV
+8.3%
+Amino acid sequence of proteins
+Twenty-two
+7%
+coexistence of monopartite and multipartite forms
+amantidine and rimantadine
+HMGB1
+disturbances
+TRIzol™ Reagent
+synthesis of the final modification mnm 5 U
+L2
+aggregated data
+CDOCKER
+26
+Angiogenesis
+membrane fluidity
+dystrophin
+Receiver Operating Characteristics curves
+zanamivir
+MgCl 2 addition
+knockdown of TSEN54
+filter paper
+63
+ACE2
+1
+airway mucosa
+E protein
+partial orthogonality
+mass accuracy
+virus production rate
+greatly
+VP60-eGFP fusion protein
+7500
+surface presentation
+43
+NF54
+chikungunya-VLPs
+TLR4 rs11536889 and CD14 rs2563298
+490,174 IEQ
+390 million
+mass spectroscopy
+trachea
+Seventeen
+pateamine A and hippuristanol
+44
+0.3%
+expression patterns similar to the other replicates
+hepatitis C virus or human immunodeficiency virus
+pseudouridine
+Ventilator-free days, length of ICU stay, and mortality
+exons 3-9
+viremic time points
+a novel cell permeable triterpenoid antioxidant
+HTT in distantly related species
+920
+100
+Thrombopoietin and neural cell adhesion molecule L1
+six
+3.00
+inducible
+95%
+Eleven
+kidney, lung and brain
+IL-10
+Zhejiang Province, China
+oligonucleotide
+HTT
+the Internet
+the ion
+DrugBank and TTD
+Logistic regression analysis
+intravenous immunoglobulins
+COVID-19
+MilkoScan FT120
+92
+A dedicated research coordinator
+significant protective effects
+gastrointestinal tract
+dermis
+MEDI-565 binding
+bats
+Immune Epitope Database
+114
+vehicle inoculated control animals
+the political calendar
+R205, K211, and R298 31
+Human antibodies of irrelevant specificity
+100 μg
+computer simulations
+Phase Five
+attenuated or inactivated whole viruses or partially purified viral proteins
+MMP2 and MMP9
+medication or humidification of air
+asthma
+86%
+Macrocystis pyrifera C. Agardh
+1 day
+Linkage disequilibrium
+drug-polymer ratio
+Pneumonia
+L1 protein expression
+Malaria
+62%
+bornavirus RNA
+multiple regression analysis
+Hepcidin
+bacterial sepsis and corticosteroids
+long-term complications and subsequent disabilities
+The Principal Investigator
+family resilience and biological resilience
+the corresponding author
+varying transmission with infectious cell density
+macrolides
+ethanol
+a constitutively expressed heat shock protein 70 family
+dwarfism and diarrhea
+PRRSV replication
+HDL-C QTL
+l p,i
+Ae. albopictus and Ochlerotatus
+necroptosis
+29%
+metagenomics
+PLP
+119
+IFITM3
+established sRNA reservoirs
+IVIg
+letting clemency prevail
+CBA assay
+genetic
+HiberixH
+abroad hospitals
+understanding the cellular metabolism, mode of infection
+protein A-sepharose Fast Flow beads
+computational
+automated DNA sequencing
+4
+tracking CDC surveillance data
+the longest ORF
+DDX1
+% of the travel costs
+upregulated
+carrier RNA
+one or two
+an overall larger source population size
+U UUAAAC slippery sequence
+cytokines
+PRRSV titers
+10%
+jargon
+± SEM
+60%
+Rc
+ACEi, ARBs, and aldosterone receptor blockers
+Arg292Lys, Asn294Ser, and His274Tyr
+10 μg recombinant hepatitis B vaccine
+correlates of infection or protection
+fully protonated or deprotonated
+peak-1: 1613.8
+Urinary vanin-1 and/or NGAL
+wild-type constraint
+-51.1%
+healers
+H7N9
+high-mannose-type
+primary fetal human hepatocytes
+Viruses
+β-defensins
+95%
+gated Cx3cr1 + Tcf4 + cells
+The cap
+diarrheal illness
+pathogen specific as well as situation specific criteria
+13-14
+dying colonies
+host body mass, and our direct measure of phylogenetic distance to humans
+minor patch releases
+genes related to innate or adaptive immune responses
+Tie2 signalling
+cellular metabolism
+eleven
+micro-RNAs
+dissimilarity matrix
+eight
+statistical
+eight
+17,187
+clade 2
+48
+Fifteen
+CD11b expression on the neutrophils
+5 days
+access to tools and knowledge
+30 min at room temperature
+Thompson Reuters
+viral diarrhea
+30 to 40 minute
+mitochondria
+5
+ribosomal frameshifting
+higher mortality, greater possibility of RRT and longer duration
+Serratia
+genomic sequences
+XLStat
+epidemiological, clinical, and virologic characteristics
+type I and type III
+length of stay and live outcomes
+abiotic and biotic
+500 nM
+virion-size particles containing electron-dense cores
+histological evaluation
+100%
+10 weeks
+restrict tissue damage and switch to recovery
+REDExtract-N-Amp Tissue PCR Kit
+fresh puromycin media
+RSI
+CD4+ T cells
+95%
+theoretical studies
+haplotype
+late summer of 2016
+apoptotic
+28.38 kcal/mol
+three
+murine AT2 cells
+augmented virus entry and replication
+Antibodies
+AT 1 receptors
+10-fold
+hundreds
+mean with positive and negative standard deviation for each diagnostic group
+Molecular mimicry
+STAT1 and STAT4 levels
+73.4% of the population
+isotopic quantification
+nine
+Z-FA-FMK and E64d
+Cattle
+50-80%
+an association between rs805297 and T2D duration
+Isotype, FMO, or another population
+seeking care for poultry
+Diseases causing hypoxemic respiratory failure
+alterations
+Echinococcus granulosus
+lipid
+streptavidin-coated magnetic beads
+Parsimony
+Selection for within-host growth
+4.0 deaths/10 000 population
+RNA binding motifs
+131
+H1N1 influenza
+21
+supernatant
+De-identified datasets
+E76G variant
+one
+The Journal of Infectious Diseases
+H5N1
+differential effect
+population density
+hope, resilience, optimism, and self-efficacy
+Heterosubtypic immunity
+Carollia perspicillata
+peripheral blood mononuclear cells
+parameter estimation
+unstable inflation
+culture
+HRV-78 of high virus titre and purity
+inhibited the translation of AaET transcripts
+millions of years
+cc-by
+Penicilin and streptomycin
+thousands
+dominant-negative function
+peacock
+RNAi
+one-way ANOVA and Fisher's least significant difference posttest
+Acute exacerbation
+single-stranded small RNAs
+40
+4
+nine
+mutational pressure
+bacterial meningitis
+required factors for parasite development
+hydrophobic residues
+cDNA
+Discovery Studio 3.5 Modeler block
+VP40 protein of EBOV
+three
+MALAT1 hairpin
+natural log transformation
+42
+sensitivity or specificity
+catalyze the hydrolysis of a variety of different RNA substrates
+Section III
+H7N9 virus specific antibodies
+misleading results
+A second alignment
+activate specific immune responses
+2.5% serum or 0.2% BSA
+one-way analysis of variance and Tukey's multiple comparisons test
+Training staff on SARI case management
+ribosome profiling
+functionally related genes
+One-way
+1.5%-19%
+Leica SP8 confocal microscope
+early clinical response
+70%
+microneutralization assay
+type II
+41 nM
+Movement proteins
+2019-05-07
+oxidative stress
+regions within a protein that lack a rigid or fixed structure
+Vero-SLAM cells
+retention of ACE2 activity
+5 days
+host behavior, survival rate, and/or fecundity
+The Global Change Master Directory
+RNase L
+0.8560.53%
+7
+24 hours
+Kvector
+EcAtg5
+HMGB1-TLR4
+Progress
+Fusogenic property of our VLPs
+Dr. Olivier
+GGT
+EGR1
+4 endosomal escape
+increased protective practices
+six
+antihypnozoite
+tissue degeneration and leukocytic infiltrates
+stimulates the activity of three DUBs
+39%
+immune deficiency syndromes and cancers
+expression data
+A nuanced understanding of the characters of inter-professional negotiations
+viruses
+ATII cells
+EAAAK, AAY, and GPGPG
+health equity
+gastroesophageal reflux and recurrent chest infections
+6
+P2, P3, and P9 residues
+Nine
+generalized immunosuppression
+5 days
+A virus
+λ
+SI, MMR, MAH, MMH, and AI
+alcoholinduced liver disease
+Direct epitope changes
+Lorenz Von Seidlein
+IFN-c
+3.168
+Department of Livestock Development
+biomedical research
+6 grades
+HCPS
+2009
+economic difficulties, improper integration with the rest of the society and family violence
+34 days
+symptomatic
+ChemStation software
+translation is arrested
+85
+effective germinal center activity
+85% of the spots on the array
+Free State Province
+therapeutic antibodies
+2
+Trimer phosphoramidite codons
+random-effects model
+22 minutes
+41%
+structure 11
+stainless wire
+Mef2c
+a relative risk of 1.0
+lymphocytes
+pleuritis
+repressing BmNPV replication in host cells
+all activity
+1 to 50 mg/L
+UDP-GlcNAc
+PCR
+survival
+1%
+Culture supernatants or mouse serum
+moment closure
+RIG-I activation
+FS values
+roles for receptor binding and low pH
+NIAID IRB
+zoonotic infectious disease emergence
+increased heart rate and lower RMSSD
+201
+mice
+functionally connected
+epidemic behavior
+1985
+liquid chromatography−tandem mass spectrometry
+mutual information, correlation, and random forest
+40%-50%
+250 nl/min
+data mining from previous epidemiological studies
+58.3%
+59.4%
+striped skunks
+potential differences in clinical and billing practices
+MHC binding or T cell restriction data and HLA gene frequencies
+Aptamers
+collections of closely related mutant spectra or mutant clouds
+Ethical
+caution
+Agglomeration
+Simeoni et al.
+Two
+interferons
+Hendra virus
+1,193
+3800
+misclassification rate
+Venovenous and venoarterial ECMO descriptions for respiratory support
+positive IEDB immunogenicity score and high degree of conservancy
+Laboratory testing to identify prognostic indicators
+delayed oseltamivir treatment
+gravity flow
+Liver disease
+nine
+virus biology
+2004
+40 hr
+Ducks and seabirds
+type 2 diabetes and extensive fatty liver disease
+QIAGEN RNeasy Kit
+9
+fast catalytic rate and high stability
+Four
+IFNL4
+2013-09-18
+RPM and qPCR
+secondary follicles
+Thermodynamic stability of the codonanticodon base-pairing interactions
+potent anti-tetherin activity
+Total viral richness
+Fisher exact test
+maximum parsimony method
+Clinical picture, laboratory detection, and epidemiological confirmation
+justRMA
+Manganese superoxide dismutase
+1.4%
+HPV PsV
+Statistical
+herd immunity generated by mass vaccination
+209
+IFN-α
+80%
+Rhinoviruses
+singular value decomposition and root-mean-square error
+M protein
+Programme EVA Centre for AIDS Reagents
+hospitals, doctors' offices, schools, airports and airplanes
+The C-terminal segment of the homomorph
+VEGF-A
+tyrosine
+acute otitis media
+10%
+bereaved by suicide
+Supplementary Table 2c
+different organs and species
+Forty
+binding conformation
+−80 • C
+mask type
+protection of the public from harm
+monocyte-to-M2
+break down plant saponins
+U modifications
+CPP-mediated siRNA delivery in vivo
+synonymous variation and variation in untranslated regions of the gene
+A-starting codons for serine and arginine
+80 to 100 percent
+Sequencing
+5.78-7.27 photons/s
+GraphPad Prism
+available pharmacokinetic data
+Social norms
+15
+Repetitive, incomplete and mixed sequences
+higher resolution and/or higher magnification images
+FACS
+a time-continuous deterministic function
+Xrn1p
+flavivirus
+NPs
+2013
+HBV
+2009
+denaturing PAGE
+IVPI
+patient stays
+ISG15
+oncolytic
+vaccination
+2.67
+eight-year
+issues linked to different layers
+The structural and dynamic properties of the ligands binding to the receptor
+80 mg/day
+a potent transcription factor
+scientific investigations of conspiracy theories
+82
+monocytes/ macrophages, memory T cells and NK cells
+reduced sensitivity to rotavirus
+fission vesicles
+electrical impulses and informative molecular signaling
+attraction and repulsion of glycolipids
+55
+immune and developmental regulation
+Coxsackievirus A6
+AMPK
+98
+diminished viral replication
+EAE
+Seven
+pressure time product *p < 0.05
+autophagy
+airborne transmission
+risk-map
+ribavirin and DMSO
+Mouse anti-IL-13 mAb clone DL11
+backwards tracing
+stress response
+30%
+215
+BIAevaluation 3.2
+demyelinization nodi
+cDNA
+four
+ScAtg8
+mortality prognostic factors
+twice
+WellRed D2 and LicorIR-800 dyes
+5.21 and 5.69
+infection-enhancement
+the femur volume
+Our ability to evaluate exercise performance
+IL-2
+abrasion or biting flies
+Plateau pressures
+monoplex PCRs
+slower replicative kinetics
+tosylsubstituted doubly activated enes
+methanol
+hydrophobicity
+21 days
+685 million
+STAT1 and STAT2
+TIM-3
+sialic acids
+131
+PNG
+random
+ARDS
+Nitrite oxide
+lethal H3N2 influenza A virus infections
+bearded vultures
+nucleotide substitutions per site reactions
+sixteen
+goblet cells
+10% SDS-PAGE
+isoliquiritigenin
+Adjustments based on population density and population in slums
+6.8, 5.7, and 5.2
+Table S2
+10%
+cancer
+Y
+high-quality
+intestinal epithelial barrier
+ELISPOT
+eIF4GI
+328
+Contact tracing
+Candidate scFv-phages particles
+4-20%
+ethidium bromide staining
+High molecular weight
+modification of U
+acute respiratory distress syndrome
+NF-κ B
+GADD34 and PKR
+GraphPad Prism 6
+QD649 quantum dots
+A surveillance system
+11 to 13 days
+Frizzled and Disheveled
+rdrr.io
+polyvinylidene difluoride membranes
+1.7
+IL-17 + γδ T cells
+increased HIV targeting and a reduction in p16 and p21 levels
+100
+Contact tracing
+Animal disease surveillance
+genome-wide mutational pressure
+Membranes with transferred proteins
+Real-time RT-PCR
+subjective judgement
+e-Myco Plus
+alveolar epithelial cells
+testosterone
+Acute kidney injury
+SNARE-SM-mediated membrane fusion
+Innaxon Biosciences
+ascending paralysis
+14
+Europeans
+viral protease enzyme activity
+best practice guidelines
+CCL2 and CXCL10
+protein misfolding and/or instability
+Public Health England
+EGP-based mitigation
+SK1
+trust and attenuates fear
+The pig
+WB analysis
+phosphorylation and glutathionylation
+viral infection
+59-deoxyribonucleotidase
+pellets
+.
+differential gene expression profile
+other passengers and traffic staff
+LGALS1
+cation adduct formation
+extreme values of costs
+PB2 residue 627
+10.3390/jcm9030623
+an important source of error
+rational and user-friendly
+domestic cattle and sheep
+suboptimal and adverse gene therapeutic responses
+TGF-β stimulation
+PBMCs
+Nextera XT
+pCAGGs-IRES-eGFP
+The metal ion
+protein propagation
+University of Peradeniya
+by mimicking sumoylation enzymes
+Cellular and viral determinants
+hepatic tolerance
+usage per 1000 codons
+Uniprot Taxonomy
+385
+appropriate curation and cross-calibration of standards
+the values determined for the 16S rRNA gene
+1%
+Low to modest neutralizing antibody titers
+2 µM 17-AAG
+θ 2
+when schools and day care centres are opened or closed
+Virions
+53
+17%
+Acute inflammation
+higher capacity of sample loading
+purified KUPEV OTU and GANV OTU
+RPL4 and RPS9
+transfection efficiency
+low
+the HA stem
+cc-by
+2 days
+identifying other coordinately regulated genes
+193
+7.8 mM
+Respiratory Multicode Assay
+EMBOSS:cons
+onestep-ahead residuals
+synovial recruitment of EPCs
+veterinarians
+worse
+Water bodies
+cancers and neurodegenerative pathologies
+TGF-β signaling
+Four
+cDNA microarray and oligonucleotide microarray analyses
+PERV transfer
+mortality in tissue culture
+J. Vieira
+Equation 3
+Spatial and temporal dynamics of RNA viruses
+Cx3cr1
+Compartmental models
+CHIKV RNA titers
+an asterisk
+SPSS 14.0
+a new method for predicting the interaction of drugs with nuclear receptors
+Stigmatising environments
+ZR viral RNA kit
+500-600
+tumor antiviral defenses
+PNM
+one-third
+2
+cryo-electron
+increasing Ag dose
+interaction of host cell and microbial components
+GAPDH mRNA
+KLW, SB and KEH
+Comparisons of TLRs
+cytotoxicity
+Oxidation of lipids and proteins
+The American Thoracic Society
+general psychological counselling
+Irreversible
+Visual inspection of the most likely chains of transmission
+24 hpi
+20
+amyloid-β A4 precursor protein-binding family A member 3
+2004
+21°C
+Marshfield Labs
+ORR
+Xigris ®
+500 ml of isopropanol
+specialized phospholipid biosynthesis
+unrestrained whole-body plethysmography
+six
+inhibition of RdRp activity
+limitations in the amount of urine available
+Doxycycline
+phagosomal escape and intracellular growth
+36%
+Statistical significance
+FlowJo 7.6.2 software
+fatty acid synthase
+face mask type
+scalloped
+three
+heat stress
+online
+sufficient medical services
+MHV infection of the spinal cord
+80%
+~73%
+CV disease and other chronic diseases related to aging
+CD4 + T Cell Enrichment Cocktail
+dihydrouridine
+viral lung titer
+week 25
+FluWatch
+Ten
+Colorado State University
+30
+Fully refined NMR structures
+viral load
+T CM and T EM phenotypes
+Mx1 ISG mRNA expression
+Odyssey Software
+comparable
+cytolytic elimination of hepatocytes that expressed HCV proteins
+ketoconazole
+moderately influenced
+6 HPI
+170
+24 hpi
+200 L of chloroform
+Atherosclerosis
+DNA vaccine
+revised and more complete datasets
+large sample cohorts and different populations
+lower
+MEGA 5.0
+UPR
+more than 600
+Algorithm 1
+.347
+evaluating which longitudinal data streams provide the most information
+pDCs
+27 years
+triplet periodicity
+Cryptosporidium infection
+chloroplasts
+2 9 500 mg
+55%-82%
+microbial variomes
+Pronase
+functional overlapping proteins
+Animal #4552
+information
+2 s
+reassortants or low pathogenic wild-type avian viruses
+ADAM17
+parallel alignment between two stems
+10%
+chimera type
+hygiene behaviors during the early phases of the influenza A 2009 pandemic
+PCR using primers for the AdE4 gene
+hydrophilic basic residues
+Adjunctive therapy with Traditional Chinese Medicine
+RT-PCR
+serological tests and PCR assays
+preterm lamb model
+High-performance thin-layer chromatography
+autoimmunity
+did not exist
+Y
+Renal damage
+pleurisy
+3,5-DCQA
+political orientation and endorsement of extraterrestrial cover-ups
+Antibodies
+elemental
+areas with analogous overlapping environmental conditions
+glioma cells
+a trait
+Nucleospin RNA II
+Dunnett's t-test
+Synergy volume
+early or late death
+oestriol
+PJ34
+24 h
+the 5 and 3 ends
+distinguishing avian, human and swine strains
+1 week
+71
+live-bird markets
+50
+pRL-SV40 Renilla luciferase vector
+work-in-progress
+cytotoxic bovine seminal RNase
+All binding of Siglec-8 to human tracheal cross sections
+glucose repression
+Inhibition zones
+antibiotic-containing plates
+The spectral radius of M
+250 ng total RNA
+5 February
+1 hour
+1/20 volume of reaction mixture
+103,962.85
+novel and known mutations
+93.8%
+3.7
+lymphoid organs
+fluorescence
+the day of VRC 308 enrollment and first injection
+n
+unrealistically optimistic
+a 45 kDa doublet
+16
+HIV-1 Nef
+212
+Additional studies
+15
+1 × 10 1 copies/μL
+Russia
+the intron
+24%
+S2
+a well-known c-secretase inhibitor
+economical development
+Licor Odyssey CLx imaging system
+Eppendorf MasterCycler ProS
+LPS ex vivo whole blood stimulation
+95%
+neuraminidase inhibitors
+mental health care
+Metropolis-Hastings Markov Chain Monte Carlo procedure
+Vaccination
+higher
+nsP2 and nsP3
+4 -PMO
+HopPER
+138
+12
+E-MTAB-2982
+analyzing and visualizing side-chain packing
+septic
+interleukin
+erythromycin and azithromycin
+when R t exceeded 1.0
+Nigericin
+ten
+ON1
+Barcodes not present in INOC30
+POLYMOD
+M81
+inability to generate products across the mutations
+inactivates pathogens
+a 2TCM
+age
+the IM
+SP-D
+Time of positivity
+One out of every ten
+isolation of V3 specific clones
+Sanofi-Pasteur
+Environmental vectors
+N1
+>10 3 NT50 titres
+c N
+autophagy
+Dynamic detection of plasma sCD138
+Three
+PANTHER-PSEP
+TFG
+N-terminal RD
+ISG20
+62
+lamin B1
+cc-by
+Light microscopy
+percentages
+IgG + PCs and plasmablasts
+virotherapy response
+independence between the samples
+NA
+deionized water
+two canine kidney tissue supernatant fluids
+leishmaniasis and dyslipidaemia research
+2 weeks
+208
+twice
+WHO
+NGD
+virus crawling and gliding
+47%
+six
+identical
+220
+skin contact or even ingestion by healthy animals
+nosocomial transmission of respiratory viruses
+760000
+transmission of sexually transmitted diseases
+87%
+rabbit reticulocyte lysates
+Adenoviruses and Betaherpes
+Tissue Differentiation-Inducing Non-Protein Coding RNA
+k 20 and k 21
+25 days
+the number of points that all hospitals claim
+B23
+the lung
+how much the segment deviates from the main orientation of the vasculature
+three
+a variety of factors
+health insurance
+red blood cells
+Morphological
+2μM
+Chi square test and Fisher exact test
+aliquots of the culture supernatants
+therapy of tinea capitis
+$30,205
+viral load in blood or disease presentation
+suppurative
+polyclonal
+Cell lysates
+22
+0.4%
+predominantly round or oval
+The oxygenator membrane
+6 h post injury
+Viruses
+MT1-MMP
+Primary endothelial cells
+mouse
+prevention
+VRC01
+MEDI3902
+detrimental
+98
+4 h
+NS4
+2007
+delayed early kinetics
+272
+5% skimmed milk
+s/p ratios
+logical extensions of classical probabilistic models
+flexibility of our approach
+acute respiratory distress syndrome
+RAGE, TLR2 and TLR4
+adult stage
+areas of Hendra replication
+RLR receptor pathway
+decreased virus titers
+hairpin-loops
+resazurin reduction assay
+eight
+Alanine transaminase
+steerable filters
+pronuclear injection
+Almost one million
+chromatin-level
+The TSC
+mass, retention time, and monosaccharide compositions
+crude DNA preparation and simple field-deployable detection devices
+Experimental validation
+SP-A and SP-D
+three
+Translocation of cytoplasmic NF-κ B to the nucleus
+R563
+205
+VV G1 protein
+Chloroquine resistance
+a mesh of proteins
+vRNA and the viral RdRps
+dimethyloxaloylglycine
+DENV1-4
+23 to 34 kcal/mol
+8
+IFN-γ
+70%
+six
+amino acid transport and protein synthesis
+sopE gene
+φ ¼ 0:0015
+Zrank
+zebularine
+Transfected
+poliovirus, coxsackievirus, and hepatitis B virus
+2 −ΔΔct method
+13.3 mg/L
+EBV-mediated B-cell transformation
+50%
+NSs-mediated
+DMF technologies
+Khanh Hoa Provincial Hospital
+three
+75%
+Pneumonia
+10.3%
+Ca 2ϩ
+Haloplex
+4697
+1.6 × 10 11 vp per mL
+<0.1
+p44K plasmid
+real time PCR
+Fifty eight
+polymyxin B columns
+natural IgG
+Long-term presence of viral nucleic acid
+34%
+ciliated cells and goblet cells
+BatchEffects
+TriZol
+respiratory illness
+SPSS V21.0
+IFITM3
+environmental
+10
+The PPI network
+optical absorbance
+optical density
+CVD and malignant invasive cancers
+equilibration
+expression of the viral structural protein prM
+neurological symptoms
+Two
+MMR, influenza, varicella and tetanus
+PCR
+how much you know to write the sequence
+Heat shock protein 90 beta
+time-series aerosol concentrations and size distributions
+400 M
+69
+measles
+Inclusion of data after day 4
+methanol
+PHA mitogen
+spectrophotometrically
+molecular
+different budding mechanisms
+Default settings
+cc-by
+three and seven days post-exposure
+binding to CAP256 UCA Ab
+undetectable
+Bursts of keywords
+20:80 CPTEG:CPH copolymer
+GFP + effector T cells
+49-74%
+refreshment and diuretic agents
+6%
+121,805
+Enterocytes
+18
+contact droplet infection of the nasopharynx
+72-83%
+dose-sparing formulations
+30-day
+The structure of the obtained CS-ES2-AF
+N-terminal 33-50 amino acid sequence
+569
+PR-mediated Gag cleavage
+Invitrogen
+didactic teaching
+loss of such waters
+36
+Overexpression of the HER-2 receptor
+1 hour
+development areas
+Oxygen
+intramolecular conformational changes
+influenza
+6Á6%
+anti-cancer
+TFA/triisopropylsilane /H2O solution
+0.00672
+SPSS
+21
+softer repulsion
+Illumina Pipeline
+inserted miRNA target sites
+54 yrs
+six
+No rectal temperature variations
+2017
+RNA
+IFN-α
+Total protein content
+Betweenness
+no comprehensive warning and response system
+antibodies directed primarily to conserved HA2 stem epitopes
+host cell receptors
+95 l of 80% ethanol
+exercise mimetics
+6-27 per 1000 children <5 years
+complementary studies
+β-actin gene expression
+Image-iT LIVE Green Reactive Oxygen Species Kit
+Caviwipes-1
+one-third
+decreased
+fifty
+Ethical
+critical policy insights
+Gene expression data
+2
+larger peptides
+1.34
+Grid values of fractional tree cover and built-up
+Infectious disease modelling
+variola major
+osteocalcin
+DIVA
+Two weeks
+0-15 years old
+Elevated Ka/Ks values
+PhyML 3.1
+whole cells
+Obtaining a good approximation of the pMHC complex geometry
+5
+real-time prediction of space-time disease spread
+filter with wavelengths 614/50 nm
+three
+CETP-mediated transfer activity
+fruits, seeds, and root vegetables
+two targets of each pathogen
+CodonW version 1.4.2
+20%
+$3,801
+cysteine protease caspase-1
+B1 and B2
+EMSA and supershift assays
+.95%
+ADE
+NCBI's Gene Expression Omnibus database
+0-50 bp
+NIH Guide for the Care and Use of Laboratory Animals
+CTG clearance
+100% GFP expression
+50%
+16%
+6.3 per 1000 patient-days
+glyceraldehyde-3-phosphate dehydrogenase
+x ij
+caramellar
+multiple comparisons
+GP structure and virion particles
+m
+twice a day
+ECs
+bluetongue virus
+Avonex
+Fiji software 64
+Twenty-two
+mutational reversions
+Recombinant wild-type EBOV expressing GFP
+24 hours
+to avoid triggering TLR9
+Perceiving the risk of an infectious disease
+no significant correlation
+information
+2400
+CCR5
+mean ± SD
+palmitoylation and myristoylation
+selective digestive
+IRE1-mediated signaling
+Increasing the vector dose or adopting a prime-boost regimen
+2 μ l of cDNA template
+quali tative tests of clot quality
+D 0
+Rh5
+downstream regions
+ALLN
+s st
+pleiotropic
+enhanced T-cell proliferation and CTL responses
+Distance
+14
+protease and phosphatase
+the quantile
+At least five
+3 of the annotated BKRF3 AUG
+therapy
+one
+increased HIV replication
+R-AFP
+advanced breast cancer
+pPAN-WT and pRTA-EGFP
+careful treatment
+3.0 × 10 3
+Proportionate amplification of differ-ent transcripts
+165
+Western blot analysis
+SNP
+S-sulfonates
+cap accessibility and 5′ leader secondary structure
+Develop healthy public policy
+GenElute mammalian total RNA
+43
+patients admitted in the NICU with cerebral haemorrhage
+4/6
+proteo-lipid mixture
+to accommodate the lack of observation of transmission events
+muscular
+flying fox
+FACSCalibur flow cytometer
+Dot coloring
+strandedness
+Carbamidomethylation
+provision of necessary background information
+multi-sectoral collaborations
+neonatal
+50%
+60 to 100 nm
+HBV and hepatitis C virus
+septic tanks
+historical and local
+International law
+mean values
+proteosomal degradation
+150 000
+NoVare
+pathogenesis
+incorporating the nucleoside analogue
+episodic memory decline
+microplate absorbance reader
+Vitrobot Mark IV
+Ifitm1
+18
+depletion
+Proteins responsible for host OST activity
+Eurasia and the Southwestern Indian Ocean
+bats might shift to other wild mammals or humans
+Eight
+pigs
+RCREVs
+0. 3
+10 µL of anti-SMAD4 antibody or rabbit IgG antibody
+triethylamine
+441
+pooled intravenous immunoglobulin
+19
+SAα2-6 Gal
+Peptides
+127
+FMDV
+any family member previously having been diagnosed with diabetes
+10
+80%
+FAB-MS +
+269
+100 ml of MEM TPCK-Trypsin
+rocaglamide
+robust biomarkers
+2012
+WHO
+All cultural
+iodine intake
+The growing problem of globally emerging infectious diseases
+13.2-51
+280 nm
+a specific drug
+inflammatory
+day 90
+10,000-15,000
+3hrs
+90-min
+Triplet loss
+Transducing the acutely injured lung
+toxic
+102 Sanger-based sequencing
+data from both genetic lines
+210
+Brazil
+SAMFIRE
+Thematic analysis
+to identify major sources of variation in synonymous codon usage
+18 h
+incongruent
+49%
+three
+half to three-quarters
+TMB substrate
+1238: 638
+pharmacological
+nontrivial
+AaHig
+IRF8 expression
+31%
+H1N1
+ATP
+Sepsis
+SWISSPROT database
+Abundant viral antigen staining
+to be inclusive
+neutrophils
+72 h of fermentation
+Mean fluorescence intensity values
+Chikungunya virus
+Lopinavir/ritonavir
+selective outcome reporting
+Katnal1 1H/1H mice
+antibody-selection pressure
+control inhibitors
+coordinate transcriptional activation of secretory component machinery
+IFNL
+qV
+Glasgow Modified Eagle's Medium
+discriminated the total cell lysate from the L1 RNP fractions
+Ca 2+ and electrolyte homeostasis
+SOLV-MAP
+LearnCoil VMF
+Breath samples
+checking for a woman's drug consumption
+epidemic threats
+keyword searching and the reference standard
+two
+liver
+142
+China
+osterix
+3.76
+severe malaria
+Quanto software
+scale images
+Disease transmission models
+Green fluorescence
+ADAM10
+35
+one-to four-week predictions
+Green Cross Veterinary Products
+Laboratory services relevant to infectious diseases and public health
+Glycoprotein B
+G4
+Vaccination against FeLV
+male
+Blood glucose levels
+25%
+immune globulins and T lymphocyte subsets
+virion internalization
+postal code of residence
+Fold change
+cryptogenic
+Total genetic variation
+Cycloheximide
+septic shock
+TTG
+the current state
+The adverse event
+18
+Mathematical models for intracellular virus growth
+Filter binding assays
+arboviral inoculum
+I PBVs
+Dissenting setting parameters of analysis 1 and 2
+lectins
+10%
+valid interactors
+B lymphocytes
+Nonalcoholic fatty liver disease
+severe line broadening
+rod-shaped
+transcription factor binding sites
+rotary
+age
+34
+oligomerization
+pVIII
+adenosine-stimulated chloride transport
+4 hours
+ELISA binding curves
+deep
+data collected
+Fermentas
+lung and stomach
+Labeling with fluorogenic probes
+~85%
+CSN subunit 8
+Valgancyclovir
+4.1
+house dust
+A AA.G and U UU
+fresh enterocytes, goblet cells, and mucus layer
+7 days
+energy-dependent
+serine moiety
+1361
+eM2
+21 days
+connectivity
+interferon γ and vitamin D
+oligomerization
+470
+93%
+over expression of blood coagulation
+contamination
+the contribution of infected cells and T cells to disease severity
+3 days
+tracheal swab samples
+5% fetal bovine serum
+Hippocrates
+green, magenta, and red
+fitted logistic regression model
+744
+100 µL of the Two-Component ABTS Peroxidase System
+k
+type I
+52%
+exposure of the virus to innate immune sensors
+Loop-mediated isothermal amplification
+protein overload in the ER
+IFN
+peak disease severity
+cellular
+viral genome
+Political and infrastructural issues
+to evade the type I IFN response
+IFN-α
+decreases the rate of CSFV proliferation
+6.0%
+SAM vaccines encoding influenza antigens
+GCs of growing follicles
+T cells
+Reed-Frost model
+N t and N 0
+First Affiliated Hospital of ZheJiang University
+four
+Nagelkerke Pseudo-R 2
+11
+subglottic aspirate sample
+daily
+antiviral, anti-tumor, and immunomodulatory
+Forty-eight hours
+antitumor
+The Future of Public Health in the 21st Century
+cytotoxicity
+380 ppm
+Global Virome Project
+our atomic model
+Confidence interval
+3 to 9 days
+increase treatment costs
+IFN-λ
+the intersection point
+the most critical mechanisms involved in innate immunity to infection
+13
+cholesterol
+supportive and rehabilitative
+qualitative information on the structure and localization of the peptide species
+Geneious 9.1.2
+C. burnetii
+RNAlaterH
+inability of TRTRVSRLY to block RRV binding
+LightCycler96 real-time PCR machine
+CD4 T cells
+immunity
+Quantitative analysis of epidemic spread within human communities
+detects the laser position and records the change of cantilever location
+E18
+In vivo metabolites
+intact -labeled siRNA molecules
+Plasmid
+100%
+DAPI
+21°C
+log-normal
+Rapid uptake of free calcium by the ER
+17
+95% confidence interval
+39 and 59 MO
+PAN RNA
+C-reactive protein level
+PrCR
+miosis
+host nuclear factors
+CD8 + T cells
+1,648
+the data give only indirect indications of the drug's action
+4.32±0.89 μM
+induction of a powerful and persisting anti-tumor immune stimulation
+70
+three
+Model-based analysis of tiling arrays
+three infected individuals
+12
+15-34 years
+DNA vaccine carriers
+PDI
+any structure on x
+nuclear export of viral intronless mRNAs
+138
+UTR
+Various elements of an mRNA molecule
+Table 2
+MARC-145 cells
+α-MEM-complete culture medium
+six
+pre-existing antibodies
+potent and novel SAIs
+Monitoring of pulmonary and vital parameters
+enzymatic removal of sialylated KS chains
+Apdm09
+E2 antigenic site 3
+PRISMA protocol
+help-seeking for suicidal behaviour
+Figure 4A
+island-to-island migrations
+sex and gender
+Fig 5
+93
+DVs and the producing cell line
+HEp-2 cells
+Papers on influenza
+IFITM3
+scientific
+alternative processes
+4-or 5-week
+Influenza A infection and immunosuppression
+≥5.6 mmol/L
+human-to-human transmission
+personal preventive measures
+foodborne illnesses
+Zika
+Eight
+Viral infection
+infection by a less virulent type of virus
+C3A hNTCP
+Descriptive statistical analyses
+prophylactic management
+low-quality reads and duplicates
+decrease diastoledependent left ventricle perfusion
+guinea pigs
+weight loss, poor productivity, and decrease in fertility
+Structural analysis
+Engineering vaccine design for manipulating antigen presentation and processing pathways
+37,930
+pro-inflammatory
+larger
+MBV and RsBV1
+Apdm09
+90/50 mmHg
+local written protocols
+GW4064
+intra-bloc trade
+low-salt buffer
+multispecies coalescent
+more research
+Arg 260 and Lys 257
+over 140
+University of Pennsylvania Institutional Animal Care and Use Committee
+WMid
+cross-species APOBEC3 expression
+more rigorous estimates of reproduction numbers
+loss of TRIM56induced monoubiquitination
+endosomal sorting of membrane proteins
+resistant phenotypes
+eight
+93,326
+Aptamers
+apoptosis
+Antigen-specific CD8 T cell-mediated
+Eighteen
+Western blotting
+plasmid DNA
+Composition
+25
+225
+immunosuppressive
+Direct RT-RPA
+4 h
+Zoletil 50
+Th17 profile
+the dosage will be increased or decreased
+four
+Replicating-competent reporter-expressing viruses
+5 μg/ml
+Foxp3 − Tr1 cells
+pCa37
+HIV-1-transfected HEK293T
+Cincinnati Children's Hospital Medical Center
+human monocytes-derived macrophages
+14 generations
+SNPs in ifitm3
+135
+431
+CD4
+liver
+IL-1b, IL-6, and RANTES levels
+affinity measurements, cell culture assays, or physicochemical properties
+AJAX
+hunting guns
+1,232
+54
+IGF-1R levels
+two signs that showed statistically significant association with risk
+Gaussian distributions
+one RFID tag
+fecal-oral route
+influenza virus
+monocytes, macrophages and DCs
+ethical
+Analyses of communication strategies with MCDA
+15
+the importance of host species for cross-infectivity
+high bacterial contamination
+30 months
+massive release of proteolytic enzymes
+our method
+unclear
+Primary influenza pneumonia
+Ca 2+ signaling
+Leukemia
+Vic-226-228HA
+saturating concentrations of substrate
+Chromosome walking
+long stretches of non-coding DNA
+Hemagglutination assays
+subtle fibrillar collagen accumulation
+Combination therapy
+Details and differences in approach
+PB2-588V
+proper PPP-RNA binding
+Table 4
+Overall survival
+Bac-to-Bac expression system
+488
+d cell
+Eighteen
+5HJ3
+normal prostate, primary prostate tumours and lymph node metastases
+doctors and nurses
+Sialic acid
+12hr
+HA, NA, and M1 genes
+Pulmonary infection
+IFITM-resistance in Env
+four
+the prodromal period
+Immunofluorescence
+months
+cDNA microarray
+viruses containing different nsP1a/4 variants
+transmembrane protein
+lungworms
+CEF
+viral camouflage patterns
+Minkowski metrics
+1774
+H7N9
+the state of chaperone association
+780
+the need for new treatments
+ouabain, bufalin, and rocaglamide
+149
+T
+ileal digestibilities of energy, protein and amino acids
+Organ-or tissue-specific patterns
+homodimeric CEACAM1 interactions
+P4, E5, and V8
+inflammation
+24 h
+P
+quality
+Viability assays
+Ten
+orthogroups
+RNAi delivery system
+Psychological support
+six
+miR-143
+OR
+7-11 days
+3 weeks
+~3.2 fold higher levels of antibodies
+fluc gene
+level of production
+multiple growth conditions
+zoonotic swine influenza viruses
+15 nt
+SSR69071
+H1
+rate of infection
+77
+SDS-PAGE
+10 thousand
+a mammalian protein
+29
+Three
+to identify the main principles by which public employees should operate
+Team-based
+escape from human MxA
+Cytochrome P450 1A proteins
+Hematologic conditions
+54%
+IFN-JAK/STAT axis antagonist genes
+co-administration with influenza vaccine
+Eight
+Information of each country's density of physicians and nurses
+20 µl
+eleven
+35
+EGFP-TARG1
+LoFi CHIKV
+cough
+systemic viral replication
+Four
+primary human dermal fibroblasts
+SYBR Green-based real-time PCR
+overinterpreting empirical results
+LN images
+cleaner living environment leads to higher incidence of autoimmune disorders
+Salmon calcitonin
+Seven
+protease
+Fourteen
+Health insurance status
+ICU mortality
+workplace
+U0126
+ID microneedle vaccination
+viruses
+Cryofibrinogenemia
+cyclosporin
+fairness and equity
+thrombin
+u
+peptide-specific spots per 10 6 cells
+300,000
+Replicates
+78%
+Category 2 and Category 3
+100
+ribozymes, catalytic RNAs closely related to viroids
+chimeric mAbs
+meninges and large blood vessels
+S-palmitoylation
+0.5-1.5 Mb
+5%
+triggers cytokine production
+heat treatment
+acyl-donor and -acceptor moieties
+HBM Basal Medium
+A hundred nanograms of diluted DNA
+community acquired pneumonia
+MobA89K
+33
+tumor weight
+disordered or displaced
+hMPV/NL/1/00
+their cellular functions
+PS
+Picornaviridae
+5 consecutive days
+Tregs
+5 μg commercially available EGF
+Pamela Martinez, Nicholas Jewel, and Stephen Kissler
+social or spatial effects on spreading patterns
+on the reverse strand
+twice
+alpha-NAGA
+2 −△△Ct method
+MAP and SS
+Influenza-specific reverse transcription PCR
+sterile
+40
+hygienic educational programs and disease prevention programs
+3 to 5 times more than baseline levels
+Charles River, Calco, Italy
+140
+monocytes
+three
+later stages
+Thermo Fisher
+attenuated and recombinant-vectored
+CD4 + and CD8 + T cells
+hypersensitive to pore-forming toxin
+an epidemic
+similar
+10 pfu
+males
+2002
+TGF-β and IL-6
+ImageJ
+English
+to reflect codon preferences of human genes and IAV
+Beijing
+AT-527
+virus spread
+Ae. albopictus
+HO-1
+H3N2 vaccine response
+antigenicity and pathogenicity
+pseudotype input
+R848
+Buffy coats
+40%
+Jean Gruenberg
+elongate the life span of SMA model mice
+reduced
+Cell-line studies
+Neutralizing antibody
+endothelial cells
+comparison of genetic similarity and differences between African and global strains
+18
+Salmonellosis and Campylobacteriosis
+14
+p38 MAPK
+ADG
+between March 2005 and December 2010
+TM
+FEELnc 45
+for some time
+online statistics regarding flu patients on a national basis every week
+PPRV virions
+13
+compartmental models or other aggregated models
+Seventy-four
+R 0
+m = S 6 i = 1 m i = 3.54
+arrests cell cycle
+Venn diagrams
+real-time quantitative PCR
+qPCR
+an acid wash
+3, 12, 18 months
+comprehensive
+Japan
+sufficient
+review board of Faculty of Medicine of University
+contact transmission
+Spectral analysis
+spreading
+assumptions about the structural characteristic of the network
+Further study
+SIVmac
+4247
+HL4029AH
+Epitope mimetics
+18
+269
+systemic oxidant stress
+viral nucleoprotein
+Substitution of amino acids in all mutant constructs
+Glycyrrhizin
+Fasteris
+subchorionic hematoma
+functional fraction of genome
+ChIP
+replication
+CsrA/ RsmA protein
+culture supernatants
+gene-specific PCR primers
+0.5
+peptide-specific CTLs
+ultraviolet spectrophotometry
+Maximum Expected Accuracy of the base pairs
+IL-17RA
+retain detectable sequence similarity over long distances
+subsystems and FIGfams
+12
+Thirty-eight
+22%
+-2
+Spain
+0.24 μ M
+ANS-DSF
+10.2-28.9%
+Uni-12 primer
+death receptor signaling
+immunoglobulinbound
+MD trajectories
+S. pneumoniae
+high-pressure nervous syndrome
+Prompt diagnostic and treatment
+THBS1
+high mutation rates, high yields, and short replication times
+Western blotting
+performance criteria for specific types of microorganisms
+Seven hundred fiftytwo
+143
+logistic equation
+233
+miPPR-21
+multiple-antibiotic-resistant strains
+which region of each oncoprotein is rich of the epitope
+inhibits the intersubunit rotations and prohibits the binding of EF-G
+we assumed that the disease is transmitted only via the airborne route
+a significant public health cost
+adenovirus infection
+damage
+Human astroviruses
+RT-PCR
+C plants
+CXCR4/7
+beta cell dysfunction
+a
+appropriate control measures
+loci-focused strain typing approaches
+a frame shift
+cDNA
+HSV
+Four
+The LINCS algorithm
+LC3-II
+enterprise risk management
+1,733
+calendar time t
+DENV and VSV infection
+low affinity and high affinity molecules
+95%
+CHO-K1 and VeroE6 cells
+N protein and L protein
+FcRn
+QIAamp DNA mini Kit
+271TP
+DI titer
+HNE activity assay
+Patients with one of the following characteristics
+local" QTL
+EC 50
+1997
+electronion interaction potential
+b d
+the Golgi compartment
+Bio-metric data systems chip
+November 2007
+Interdisciplinary cooperation
+knowledge of the observed peak
+hippocampal
+311
+48 hours
+scFv 10F
+50%
+lyssaviruses
+three
+Apoptotic
+9.5 hour
+10 S. pneumoniae GE
+Intratracheal delivery via microsprayer aerosolizer
+transmission rate
+F X 2 1
+educating the general public about the utility of NMC
+The absorbance at 450 nm
+ABI 7500 v. 2.3
+70%
+catalytic function and non-catalytic function
+VEID-based assays
+MicroRNAs
+Magnetic nanoparticles
+5000
+fall
+enhanced inflammatory reaction
+protein-suspended bead array platform multiplex kits
+15.3%
+anthelminthic
+17
+intervals
+5
+all influenza A viruses
+male sex, adulthood, and exposure to outdoors
+humoral
+Creative Commons Attribution Noncommercial License
+promotes the fusogenic activity
+the importance of improving the annotation of genetic variants in the mouse genome
+biased
+RNA affinity purification
+activated PrfA drives its own transcription
+procedure failure
+36 days
+inhibition of inflammation and homeostasis
+Cell lysates
+Six
+mice
+97%
+VV, RSV A2 and HSV-1
+distinguishing between bacterial and viral infections
+seven
+mass transfer is limited in biofilms
+infectious pulmonary tuberculosis
+heat shock response
+C-type
+inhibited in similar way PV egress
+50
+the number of infected mosquitoes
+evolution of novel reassortant variants
+30 min
+interests
+Nsp12 dimerization
+viral replication
+Phase II
+development of record-keeping systems, quality audits, and preparation of analytic datasets
+959
+neurological disorders
+spatially separated
+natural selection
+Host and infection dynamics
+Table 3
+Escherichia coli
+daily
+GAVVALSTTFA
+flow cytometry
+the possibility of a blunted illness
+readily deconjugated ISG15
+JEV infection
+33 min
+October 1st
+enhanced
+nuclear transport machinery
+acidosis
+Mx1
+a conservative test
+fingers, palm, thumb and connection
+bats and swine
+14
+travelers
+bulk modulus
+60 min
+50-60%
+6 weeks
+Me-Glc
+5 μl/min
+78%
+2,000 nM
+Oceanic
+FuzCav
+Veterinary Clinics and Hospitals
+immunofluorescence analysis
+mean values
+undetected infection
+host contamination
+higher
+endotoxin contamination
+Table 1
+UniProt 181
+1,4-butanediol
+Chinese herbal kombucha
+TMUV
+priming of RNA synthesis
+ten
+early MALS diagnosis
+statist scope thesis
+equal protein concentration
+HT7F and FLXR
+188
+dead-end
+MicroSpin G-25 columns
+shared transcriptional regulatory motifs
+5 min
+error as a risk state
+typical
+5 -UNN-3
+tumor
+more depressive symptoms are present
+fluorescent
+depression
+999
+26
+tyrosine kinase AXL
+free-to-publish
+selectively capture a variety of bioparticles at different locations in the channel
+1.8 mg/ml
+moderate BS and PP
+discordant
+how things work at a systems level
+European Center for Disease Control
+microlitre quantities of blood
+disease
+Thirty-one
+bacterial infection
+antigen-specific antibody probes
+multiple reassortments between different Eurasiatic strains
+Serum
+long-term physical and functional recovery
+Two-dimensional
+770
+Microtubule severing enzymes
+10 5Á6 EID 50 /ml
+viral replication and assembly
+DAPI
+oligomer concentrations of 50 nmol/L and higher
+instrumentation
+target variants that differ by only one or two nucleotides
+cyclopentane
+three
+0.02% butylated hydroxyanisole
+antigen plus NEI
+inflammatory cell infiltration and epidermal thickness
+AT-9010
+caveolin-1
+6
+61
+DC vaccines
+mutational pressure and translational selection
+Source data
+GAPDH
+Runx1 and Spi1
+Log-rank tests
+hemocytometer
+0.68%
+scRNA-seq
+>60%
+2004
+infants' weight and age
+An 'unusual' match
+lymphoma or leukemia
+polymerase chain reaction test
+interleukin-2
+priority lists of human and domestic animal pathogens present in Europe
+small
+Ku Shen
+Small angle X-ray scattering
+the size of the genome
+Rice
+2 days
+Creatine kinase
+52
+VEGF pathway
+HCs
+79.6%
+1993
+cholera
+rmzTab-M
+efficient epidemic mitigation
+coughing and sneezing
+5610 5 cells/well
+the nuclear transport apparatus
+biological events follow each other sequentially in a rolling fashion
+ten
+cytoplasmic membranes
+MDR-Ab
+a kozac sequence CCACCATGG
+broadly varying patterns from highly distinct peaks to poorly resolved generational clusters
+HCV core protein expression
+Δ med IDP
+Evidence of variable strength and on diverse conditions
+loose networks between ambulatory care services
+metabolic acidosis
+Geobacillus stearothermophilus
+hemagglutinin and neuraminidase
+H1N1
+0.1%
+GraphPad Prism
+blinded study personnel
+γ δ T cells
+H1-HT
+slightly biased, relatively stable and conserved ARO aromaticity
+5.6
+IL-15 and activating receptor HLA-G
+18 days
+Perkinsus olseni
+observations
+Liberia, Nigeria and Sierra Leone
+14
+2013
+user-defined
+any other pathogens
+total amounts of FAK and pY397-FAK
+mediates its binding to F-actin
+peritoneal
+equilibria
+five
+pseudogenes
+Seven
+omegaMap 0.5
+The accuracy of all constructs
+mice
+Three
+Parallel analysis
+NotI /SfiI
+study limitations
+proteins and synthetic polymers
+Manipulation of pre-mRNA splicing
+Multidimensional scaling
+background levels
+40%
+Africa
+b-actin
+diluted streptavidin-HRP conjugate solution
+Directional selection
+plaque assay
+pH-dependent conformational changes
+f~f c
+paucimannose
+Weaker effects
+4 h
+CD and SVA data
+wound healing
+a protocol
+Peacock
+pigs
+severity of the disease
+two
+positive
+molecular amplification of HSV DNA
+sepsis-related
+10 days
+twice or three times
+flow cytometry
+MatNH-and MatH-RNA3
+lytic buffer
+46%
+Waters Alliance Waters 2695 separation module and W2475 fluorescence detector
+7
+An electronic nose
+crisis client's absolute trust in MHCI workers
+GLA and SE
+R. rosea fractionation studies
+crossover region
+TruSeq HT preparation kit
+serum degradation
+750 times
+Sers nodavirus
+MM, HdP, and LF
+46%
+Shaking chills or shivering
+neutrophilic inflammation
+peptides
+Training health workers in the assessment and management of mental and substance use disorders
+A fraction
+FACS Vantage cell sorter
+an adequate database
+interdependence
+three
+cattle sample submissions
+oligonucleotides
+an LPAI progenitor
+avoidance-neutrality
+50:1
+IFNλ4p179
+one trusted official source of information
+Resonance overlap
+5%
+animal identification within a herd
+Data regarding underlying medical conditions
+share knowledge and resources
+1, 4, and 7 days
+a cascade of interactions with multiple cellular factors
+learning and teambuilding opportunities
+Donor plasma
+Multicollinearity
+technical and organizational
+NS2B-NS3 pro
+physiological functions, molecular biology, or genetic predisposition
+MT rates
+three
+smooth
+Atlastinmediated vesicle dimerization
+proteases
+increased EGFR internalization
+IL17A and IL17F
+DI water
+Ascites fluids
+Columbiformes
+four
+10%
+the classical secretion pathway
+Anterior Gradient 2 Homolog
+rapamycin complex
+four
+density-gradient centrifugation
+antibody epitopes
+1 min
+apoptosis
+changes in pH
+N-glycans
+primer dimers
+highly infectious diseases
+nystatin
+BEAS-2B
+rabies virus
+one fourth
+thin lines
+special
+regression modelling
+Stella
+pI:charge
+0.01
+infected cattle
+2009
+Six
+porcine peripheral blood mononuclear cells
+antibody responses against the target pathogen
+docking
+Detecting Mechanism of Action by Network Dysregulation
+2013
+peptide affinity
+Tarifa
+Two interacting proteins
+Gratuitous violence
+The flows W
+Bdetergent isolation
+Leghorns
+The % of blood tolerated in a reaction
+Dispositional pessimism
+GeneArt
+two
+Environmental sampling
+higher
+the explicit formal specifications
+splenic CD8+ T cells
+HLA type
+CFlow plus
+LSV2
+1 µM
+UVGI, EtO, and VHP
+characterization of entire proteomes
+R563 and K565
+APOBEC3G
+293
+sepsis-induced immunosuppression
+subclinical stages of JD
+nucleotide polymorphisms
+2018-02-20
+a proximally truncated SL6-like structure
+CTL019
+Cronbachs's alpha
+sequence similarities
+Sepsis
+virus-induced cytotoxicity
+ATG7
+antiviral activity
+nasopharyngeal and sinus infections
+ASL
+45
+risk of regional disease progression in experimental injury
+100 V
+2020
+hox
+TREM TREM
+50-90%
+size exclusion chromatography
+ELR1-IN
+CD209
+Crimean-Congo haemorrhagic fever
+formalin
+via email
+Nigeracin
+PR8
+covalently bound complexes
+Creatinine clearance
+serious adverse events
+week
+ICD code and Diagnostic and Statistical Manual of Mental Disorders
+proximal polyadenylation site
+acute weight loss
+High levels of sequence divergence and disparate interaction specificities
+Site-Align
+MYC deregulation
+auditory neuropathy spectrum disorders
+weight forms of GP
+gB
+14 out of 32
+two
+mdx mice
+epithelial migration, proliferation, and apoptosis
+Dramatic
+doxycycline
+hypophysitis and adrenal insufficiency
+control mice
+two
+NAFLD
+influenza infection
+IL-1Ra
+a collection of compounds derived from plasma or serum
+August, September and October
+winter
+flu-like
+Inflammation
+structural determination
+Sweden
+cross-immunity
+June, July, and August
+quantitative internal calibration
+248
+Oligonucleotide usage
+5
+cardiorespiratory symptoms
+solution space
+decreased significantly
+11%
+10%
+alternative substances
+HEK293T pLenti-mock cells
+via a break in the skin or inhalation of wind-blown cysts
+ACLF
+p.Tyr67His and p.Lys329Glu
+disease diagnosis, drug discovery, and vaccine development
+cellular detachment
+FBS
+heparan sulfate and chondroitin sulfate
+type I and type II
+Precision
+posttranslational modifications
+Spore concentrations
+IFI202b
+workforce reduction
+Genes with intron retentions
+200 kV
+the attending physician
+mucosal immune responses
+two
+cross-presentation mechanisms
+significantly higher
+a thorough search algorithm
+60%
+apoptosis of DC
+Bundesministerium
+rAdglob
+ES2
+condensed
+10
+TCM practitioners
+prespecified
+Total RNA
+pandemic and other emergencies
+sodium pentobarbital anaesthesia
+Mean synonymous site variability
+oxygen-tolerant
+Antisense RNAs
+U_UUU_UUA
+SGK1
+Five
+IL-10
+A small soluble delta peptide
+Ion trap instruments
+DNA methylation, histone modifications, and miRNA interference
+Bronchial epithelial cells
+public health intervention
+1 h
+p62
+six minutes
+G proteins
+Functional health
+low cytosolic amino acid concentrations
+diffusion
+D0
+increased toxin production
+64.5 kDa
+Scanning Electron Microscopy
+the template of sgRNA
+Charles River
+0.61
+ELISpot
+GQRSRI
+linear mixed models
+a human hepatoma cell line
+heat shock proteins or chaperone proteins
+Lassa virus
+positive
+3
+two
+quiescent intervals between them
+HUVECs and Jurkat cells
+eleven
+Inhibition of these early steps on the plasma membrane
+International Chemical Workers Union
+polydatin or resveratrol
+co-treated cells
+it can only allow monitoring of G4s in fixed cells
+two-thirds
+inflammatory-like
+test
+respiratory syncytial virus
+LB agar and broth
+no significant correlations between GC 3 and GC 12
+five
+rescue growth
+28S rRNA
+EBERs
+IFN-αω
+natural log-transformed concentrations in picograms per milliliter
+23,646
+Cot-1 DNA
+Gelatin
+consumers
+Evidence to support one or another evolutionary pathway
+UC Davis DNA Technologies Core
+three
+GAM
+1%
+Pfaffl formula
+four
+The New World temperate zone
+MS2 coat protein
+standard deviations
+Fold change
+Surfactant protein D
+septic shock
+severe ARDS
+91%
+4F/4R and 5F/5R
+Thailand
+Matrix metalloproteinases
+database curation
+knowledge score
+multiple gene products
+FilmArray Respiratory Panel
+QiAamp DNA Mini Kit
+yellow fever virus
+thorn prick
+raltegravir
+Streptococcus agalactiae
+24
+gp41 NHR and CHR
+functional HIV products
+67%
+dimensionality
+m
+Cells
+multiple biological functions
+8-12 weeks of age
+uncertain
+Ingenuity Pathway Analysis or MetaCore
+58%
+Entebbe, Uganda
+polygonal shapes
+two
+Ten
+the benefit of NIV versus oxygen in pneumonia-induced early mild ARDS
+de novo Ig synthesis
+reaction time threshold values
+PCR primer pairs
+sodium periodate
+10 mm
+CD8 T cells
+six
+NUP133
+apoptosis
+IHR and JEE core capacity scores
+social desirability bias
+antiviral treatment
+R 73 script
+permanent neurologic damage and psychiatric disorders
+Absolutely RNA miniprep kit
+Corrected parental information
+three
+every four hours
+lateral
+up to 7 days
+Transmissibility and severity
+40%
+one
+Kaplan-Meier
+UV transilluminator
+fatty acid synthase
+smoke inhalation-induced acute lung injury
+ethylene glycol bis-succinimidylsuccinate
+28
+actively induce autophagic flux
+life chaos
+potential confounding effect
+reverse genetics
+27
+recently
+7.7fold to 41.1-fold higher
+70 mg/kg
+viremia
+13
+supernatant of cells
+slow bonding
+future research directions
+global end-diastolic volume
+viral infectivity
+compartmental-based coalescent models
+discriminant measures
+3 to 5 weeks
+C-terminal
+saturation
+70 to 80%
+agarose gel electrophoresis
+second and third trimesters
+zero
+spatial maps of the infectious pressure
+their theoretical I
+49
+ECs
+lipopolysaccharide and other bacteria cell wall components
+American Type Culture Collection
+enhanced rVSV/EBOV GP infection
+Multiple-step contact tracing
+humoral immune responses
+Pulmonary hypertension
+excessive salt intake
+250,000 to 500,000
+Kinase prediction algorithms
+RpLP0
+Respiratory viruses
+dietary
+178
+vaccination
+to minimize animal experimentation
+promoter
+Sequence alignments of coding sequences containing RT stop codons
+routine screening of Herpesviridae
+peak inspiratory pressure
+2 months
+buffers
+transfection efficiency and pharmacokinetics of pDNA
+Electrode geometry
+nsP2 G641D and nsP4 C483Y
+increasing the match goal
+RC i
+RT-PCR
+Electrostatic interactions between host and phage proteins
+conjugative mating experiments
+the original input virus
+Th17
+The activity of the protease
+activated LNEPs
+Human Respiratory Syncytial Virus
+the modeller
+Chaos game representation
+unclear
+Biostim pulse generator
+GSH
+Ubiquitination
+secondary lymphoid tissue
+Sex, obesity and LVH
+VHTYG
+10.1002/cti2.1115
+3
+abnormalities of grey and white matter
+ULTRASCAN II version 9.9
+IAPV
+FGF
+Myotis mystacinus
+medians and interquartile ranges
+Three
+Leaf and root samples
+Total RNA
+Influenza A
+nM
+Influenza
+RSV subtypes
+The corresponding authors
+IRF7
+die
+37.4 and ∼100 kDa
+Landsberg erecta ecotype
+28
+ambiguity of codons and sequences
+mice
+15% to 35%
+Age and sex
+Statistical
+K310 and E311
+X k
+circulating monocytes
+wild ducks
+NS3/ 4A complex and NS5A protein
+48 hpi
+Electron
+day 0
+Thirteen
+over 50%
+H7N9
+eIF5B-dependent activation of IRESmediated XIAP mRNA translation
+OligoWalk
+NucZip model
+Acini count fold changes
+Risk assessment
+Chemical siRNA Modification
+serotype 1
+gH protein
+oxygen-free radicals
+Three
+Clean-Trace Luminometer
+Competitive ELISA
+Type I
+high altitude, low temperature and low oxygen tension
+serial dilution
+TGF-β
+Cys
+chloroform
+406
+internal genes
+8.43%
+Cap-independent
+different levels of exhaled methyl thiocyanate
+Intravenous blood
+RQ1 DNase
+SPSS 16.0 software
+19
+RLS
+Laboratory testing
+sensors of changing environments
+1%
+all variables
+age and gender
+24
+winter
+Influenza A virus
+similar distributions of distances between random structures
+A database
+61
+1.5
+172-198
+by binning into days
+de-identified data
+deposited calcium
+recreational and equestrian
+MassTag PCR
+16
+excellent separation
+Mycobacterium tuberculosis
+Cathelicidin
+polyester sheets
+cytosolic chaperonin
+relevant criteria
+negative binomial transmission function
+G-quadruplex
+genotyping studies of viruses
+confirmation of etiology by laboratory testing
+avoiding any type of vaccination
+life-threatening lung injury and respiratory distress syndrome
+7 d
+proportional
+mAb MR78
+on the top of the capsid proximal to the HBGA binding pocket
+transgene expression
+195-fold higher
+shrinkage
+increased demyelination
+anti-CD3ε
+N and NSs genes
+S. flexneri
+elevated cell proliferation and reduced migration
+over 90%
+pEGFP-C3
+24 hours
+All the professionals
+infection with S. pneumoniae
+Tim Berners-Lee
+20%
+ADAR
+PCA
+Listeria monocytogenes
+The occurrence and degree of autophagy
+4%
+studies on respiratory pathogens and clinical diagnostics
+112
+different outcomes of infection
+572
+four
+prophylaxis
+wafer masks
+an imputed value of 5
+manually or semi-manually
+20%
+4°C
+codon usage bias patterns
+herbs and nutritional substances
+cells lacking such signaling
+Anatinae
+general function prediction
+different values for the number of simulated chains
+Supplementary Table 1
+cytoplasm
+those from the hospital
+FCR3 and NF54
+Occupants
+50-219 nm
+2,025
+nucleolar localization
+antitoxins
+pseudoknots
+expand reverse transcriptase and oligo-dT primer
+TfR1
+Patient 3
+four
+ER
+ESCRT proteins
+H5N1 HPAI
+flies and mice
+4uC
+molecular targets causal for human disease
+50%
+Pegivirus, Pestivirus and Flavivirus
+aromatic and hydrophilic residues
+biomolecules
+increased affinity for heparin
+Recombination
+SnPP or ZnPP
+wt mice
+FASN
+resistance
+2
+a H-type pseudoknot or a series of hairpins
+Yca1 and Aif1
+Vps3 and Vps8
+Influenza type A
+affinity purification-mass spectrometry
+tetramer positive
+add in markers
+Influenza
+lack of appropriate posttranslational modification mechanisms
+The predicted localization
+higher CD4 + CD8 + T cell percentages
+63%
+increases
+Control and Prevention
+at least 4
+MetaGeneMark
+RV3
+SP-D
+tissue damage
+PLEX and immunosuppressive therapy
+inflammatory cell adhesion
+cationic
+Fecal samples
+Liprin-α4
+Interleukin-1b
+41
+villous immaturity and stromal changes
+IFIT1
+Collaborations
+evolutionary
+molecular diagnostics
+shifting between membrane bound and unbound conformations
+Dr. John Rose
+Phe420Ser
+55.5±2.33
+the proportion of infected individuals in a population
+12
+best tissue quality and high virus concentration
+BALB/c
+a delivery system
+IL-6 and IL-10
+Host ER stress and UPR
+every two weeks
+A1
+Eight
+siRNA, plasmid DNA, ASOs, and small drug molecules
+29 days of age
+a7 GFP expression
+Astrovirus, rotavirus, and caliciviruses
+metal-on-metal
+CcBV genome
+RSL3 and FIN56
+Pten overexpression lentivirus
+Localization probabilities and posttranslational modification scores
+95%
+inhibited viral replication
+PLA 2 s
+six
+monoclonal antibody therapy
+5 min
+correct
+12h
+enhances the efficiency of anti-PDL1 checkpoint blockade inhibitors
+SCHEMA
+Two third
+300,000-500,000
+chronic inflammatory processes during persistent infection or demyelinating diseases
+Culicinae
+Sialic acid
+VAP
+Fifteen
+U1D
+breeding or engineering resistant birds
+BLOSUM62
+Cide B
+D 95
+Respiratory dead space
+tissues and organs of the body
+Eight weeks
+7 days
+differences
+10%
+36%
+lack of PBD
+Gao, George Fu; Wu, Ying
+PCR
+K-string
+XmAb14045 and MGD006
+expression
+3
+The coiled-coil domain containing 137 gene
+orange
+similar levels of mean 16 s rRNA amplicon quantities
+insufficient resource preparation
+three
+The non-synonymous/synonymous rate ratio
+P. aeruginosa and E. coli
+replication
+1,114
+significantly reduced virus production
+ALI/ARDS
+3
+glucose and human chorionic gonadotrophin
+I log N
+intrinsic and extrinsic
+rBVs
+Heat-shock proteins
+5 days
+Ebola infection
+a novel broadly neutralizing epitope on HA stem region
+global surveillance
+endogenous NTCP
+cryostabilizing solution
+Thai
+18%
+10.1371/journal.pone.0048702
+15 nM
+Ontario Ministry of Health and Long Term Care
+dopamine D2 receptor
+Supportive therapy
+15%
+random variation
+February 2016
+Wikipedia
+three
+translation
+MHV-3
+a year
+Patients who required admission
+0.002% to 0.02%
+IFN molecular evolution
+bacterial
+280 days
+Systemic reactogenicity
+isolate 16681
+daily
+Knock down of PHBs expression
+Exendin-4
+Pneumonia
+ACE2
+DNeasy Blood & Tissue Kit
+more than 100 years
+Apoptosis
+specific degradation of complementary mRNA
+conserve energy
+microarrays or mass-sequencing methods
+6 to 15 days
+antigens
+SHC1, PI3K, and PLC-γ-1
+uORFs
+site entropy
+activation of immune cells
+severe lymphopenia, gastrointestinal symptoms, and liver and renal dysfunction
+AQP3 expression
+Lassa virus
+Primer-BLAST software
+AgeI and EcoRI restriction sites
+secretory
+aluminum
+a polyprotein
+Viable influenza A virus
+N150 days
+ImageJ/FIJI
+2 hours less
+47%
+41
+oral administration
+V2C cells
+sterile filtered PBS
+refolds into the highly stable postfusion structure
+political
+IRs
+RIG-I and TRAF6
+38%
+Two
+372
+Prevention Keywords
+34
+cc-by
+7 days
+multimerization
+STAT1 shRNA-transduced cells
+APMV-1
+TLR4
+bioluminescent and fluorescent RVFV
+host defense against certain pathogens and tissue inflammation
+77%
+Sp-cAMPS
+2017-12-21
+overestimated
+nsP2 G641D substitution
+Statistical Analysis System
+transacylation
+Hepatocyte proliferation
+20
+Exosomes
+mitotic figures
+low
+8.3 nM
+helical AIMs
+The ostrich
+Ϫ2FS product
+Two hundred and seventy-six
+A549
+1.0
+Cu 2
+acute, acute plus persistent, and persistent infections
+accuracy
+myosin II along with actin bundles
+cytochrome c ions
+lectins and other surface receptors
+Institut Pasteur
+R 0
+more resistant
+PBS-P
+random initialized and freshly trained
+Annett Kannegießer
+neuraminidase inhibitor antiviral drugs
+a patient
+The Application of Clinical Genetics
+tropical
+octameric
+electrochemiluminescence
+rz scores
+Super-Script III first strand synthesis kit
+cell cycle
+mediating entry and fusion of the virus into the hosts
+346
+ferrets
+Bag5
+R30K change
+Shaanxi, China
+G. Stark
+apoptotic stimuli
+Profiling table at genus level
+One
+Toyokuni et al.
+Microtiter plates
+binds a fluorogenic ligand and activates its fluorescence
+multiple interactions
+Csl4-NT
+mass dispensing
+Not all oligomers excise a targeted exon with equal efficiency
+four
+five
+behavior similar to the data
+6 days
+Constant EIT monitoring
+proviral
+presence of a species
+six well supported lineages of avian astroviruses
+Anti-tumor
+length of stay
+5016
+6 l/min
+Human ERManI
+building an evidence base
+between 6 and 8 days
+three standard deviation values above mean negative control serum
+high relapse rate of UC
+MSC-EVs
+mesenchymal stem cells
+cytokines and growth factors
+Two hundred forty-eight
+useful knowledge
+broad spectrum
+21
+discordant
+hormone responsive element
+metabolic
+rearrangement
+ten
+cellular Ca 2+ -regulated proteins or pathways
+PrimeScript RT-PCR Kit
+High resolution models
+4.2
+Feline upper respiratory infection
+GeneArt Technology
+monolayers with CPE
+43
+fibrotic
+Met, Y and PCP domains
+RAxML 88
+the number of the initially responding B cells
+Testing models of pathogenesis
+10%
+statistically significant
+467.3 g/mol
+decrease in plasticity
+other acute-care facilities
+a protein whose mRNA expression was altered by ILTV infection
+influenza
+secretion of intracellular proteins
+Gag and Env
+Emotional labour
+N. apis
+48
+a normal distribution
+stratum pyramidale
+ILTV replication
+13.8±0.9 hours
+extreme values of u
+Ala50, Tyr137 and Gln200
+anoikis
+swine
+gDNA from the parent strain 3D7
+C11R
+3
+prevention and vigilance
+game birds
+Tamura-Nei method 59 using Megalign Pro
+supportive care
+0.003 cm
+20
+enhances the type I interferon expression
+International Protein Index database
+Vertical transmission
+High throughput antibody sequencing
+delays in response efforts
+5.4%
+five
+viral
+low
+Stacked base interactions
+vacuolar proton ATPase inhibitor BAF
+The core sequence
+Stop-codon readthrough
+length and structure
+acute respiratory distress syndrome fusion circRNA
+Image-J plug-in
+Gene Ontology
+3
+Gating strategy
+BALB/c mice
+25
+5 days
+CCS-UFPE Ethical Committee
+washings
+BCM and GL
+viral replication
+productive infection of DCs and storage of viral progeny
+BLASTP and TBLASTN
+10%
+histologic progression to liver cirrhosis
+species-specific differences
+ZUFSP
+contacts of long duration
+TLR7
+lipid metabolism-related categories
+499 cells/mm 3
+SPSS 13.0
+dilated cardiomyopathy and chronic heart failure
+LD scans
+calibrated quality values
+9
+215,000
+20 h
+Type I interferons
+mRNA
+transmembrane
+silver
+between 19 and ~140,000
+MAS-1 R oncogene Gprotein coupled receptor
+lower respiratory tract infections
+1-way analysis of variance
+four years
+97% pair-wise identity
+DNA sequencing
+RSV-A ON1
+30
+computed tomography
+0.8610 LOOCV-AUC
+24 h
+Resource limitation
+310
+where the protease cleavage has occurred
+Dr. P. Gissen
+glycoprotein
+7/13
+MAR
+holidays
+large-scale tools
+1741
+challenge with divergent influenza subtypes
+ALI culture
+viruses of the Bunyamwera serogroup
+apoptosis
+Microtubule severing enzymes
+standardised HMDB IDs
+investigators at the Johns Hopkins Center for Public Health Preparedness
+low
+8 November 2011
+pseudotyping lentiviruses with RABV-G
+proteasomes
+Acute lung injury
+20%
+70-80%
+plasma
+intrinsic
+Ebola
+hemagglutinin and neuraminidase
+784
+virus transmission strictly based on epithelial modes
+2009
+epidemic modelling of data from 19th Century European smallpox outbreaks
+300
+cost
+endothelial cells
+depression and feelings of loneliness and despair
+4
+Beijing Vital River Laboratory Animal Co., Ltd.
+between 2 and 20
+logistic regression
+Smartphone camera
+Secondpapillomavirinae
+EVOC systems
+a resident physician
+fuse with lysosomes
+TLR15
+JetPRIME
+Actinomycin D
+more detailed analysis
+TLR4
+host entry factor CD81
+the correction factor n
+long poly DNA tracts
+17%
+molecular mimicry
+confocal microscopy
+two-sample proportion tests
+ARDS
+6
+The UFS
+eGFP pos
+Cap-independent translation
+Rabbits and cattle
+false-negative findings
+elevated ACE2 activity
+200
+Each study participant
+in the presence of rFGL2
+Quanti-tyOne
+GDI2
+149
+Malaysia
+50-60%
+6
+inhibiting the infiltration of immune cells
+GXXXT/S for myristylation
+12
+sub-micromolar inhibitory activities
+nine
+six
+12
+Group I conditions
+viral proteins
+Consistency
+pulmonary embolism and acute myocardial infarction
+novel, sensitive and specific biological markers
+their geographic location
+smokers and non-smokers
+three
+Pulsoximetry
+glycoprotein precursor processing
+level of gene expression
+S, E, I, and R
+Phylogenetic diversity of pathogens
+Nichirei-Histofine Simple Stain Mouse MAX PO
+a consecutive complementary base pair set
+virus particle and infectious virus release
+plaque assay
+filter degeneracy
+25%
+TRIAD microplate reader
+PEI-based
+random-effects model
+PB2, PB1, and PA
+Significant upregulation of eotaxin-2
+the individual with risk perceptual status
+isolation and air travel restrictions
+toothpaste
+China
+one-third
+EBV
+pigs
+cough, wheeze, bronchitis, or pneumonia
+meaningful comparison
+cc-by
+Six
+EBOV infection
+Sialic acid O-acetylation
+number of hosts in queue for location
+Z and h
+Mass-spectrometry
+A549 and H441
+disease and control parameters
+polarity in the lacZ gene
+Prof. Susan Zolla Pazner
+f i
+mutant
+our choice of prior distribution
+Two
+an unsaturated trihydroxy C18 fatty acid
+an equal portion of each patient's SIL spiked NPL sample
+uncertainty caused by the possibility of false negatives
+quarantine
+cardiovascular instability
+20 breaths min −1
+17
+Viral factories
+HMPV
+The specificity of PCR products
+the need for certain knowledge and skills
+Wild-type adult BALB/c mice
+Phylogenetic
+Activated protein C
+15 residues long
+DMC analyses
+F protein
+Northeast and Southeast China
+adenovirus replication-permissive animal models
+phylogenetic
+15-24 years
+blood sugar
+Vesicular stomatitis virus
+Leopards Hill virus
+low-glucose
+chest CTs
+replicative
+trachea
+ACE inhibitors and ARB
+30 minutes
+2 days
+regulates the function
+1963
+cortisol concentration
+Vaccine efficacy trials
+CLEC4C DTR mice
+epidemiology
+14
+the complete influenza incidence
+Elasmobranchs
+a pathogenic role for cytokine autoantibodies
+bacterial infection
+142
+three
+via intercalation into the pocket between two G-quartet units
+haphazard
+cervical, axillary, and inguinal lymph nodes
+Force
+adult-specific vaccination programs
+their perfect complements encoded on color-addressed microspheres
+Michel Camplo and Olivier Siri
+activates multiple immune pathways
+controversial
+Three
+Reverse database hits
+40
+active SJIA
+ORP analysis
+Monte-Carlo Markov chain samplings
+interfacility transfer
+Actin
+Highly Pathogenic Avian Influenza
+2.19-2.48
+Dyspnoea and cyanosis
+CL1-5 cells and NPC-TW01 cells
+continuous tissue oxygenation
+stakeholders
+C1 inhibitor
+15
+more extreme
+livestock movements
+PROSPERO
+Botanical drugs
+mice, ferrets and non-human primates
+One hundred
+12
+CRF07_BC
+decreased neuraminidase activity
+More than half
+35 kGy
+Nucleolar integrity
+IL-27R expression
+heteropentameric chloride channel receptors
+deficiency of SP-A and SP-D
+LF/HF ratio
+100 times higher
+One quarter
+demographics as well as the region of the household
+1998
+antibody-based methods
+HLA genes in humans are extremely polymorphic
+Cultivation
+Eight
+two
+protein-based
+clusters 1 and 2
+95%
+454
+HRP-conjugated mouse anti-human IgG Fc antibody
+nuclear transport machinery
+110
+Hjelle, Brian; Torres-Pérez, Fernando
+cell-free supernatant
+IgG
+human immunodeficiency virus
+clinical assessments
+Endosymbiogenesis
+Complex mechanistic models
+11 6 2 min
+every 3 years
+all of the anti-H9 sera
+Blood samples
+5%
+HAdV-E4
+SHFV
+cat G
+51
+Informed and voluntary consent
+TLR-induced
+flow cytometry
+flexibility
+65.6%
+IRF1
+H1-subtype IAVs
+106
+Wild-type missense levels
+pHOx Plus Blood Gas Analyzer
+June or July
+Surveillance data
+DMEM medium
+AMPKα1 phosphorylation and SIRT1 expression
+AP-1 DNA-binding activity
+HBZ
+mast cells
+a color
+Myc-tagged WT and mutant RNase L cDNAs
+B. subtilis OhrA
+large-scale animal movements
+2008
+different combinations of drugs and therapies
+pipeline v1.8.1
+GenBank
+IP-10, RANTES and IL-6
+2-10%
+histopathologic
+how the characteristics of the field change over time
+three days
+indirect cell membrane immunofluorescence
+Glomus cells
+25
+Menisdaurin
+GFP levels
+adaptive antiviral strategy
+Stanford University School of Medicine
+1959
+ribosome biogenesis
+Disseminated disease
+being female
+the bird age
+by regulating p21
+genetic similarity
+Mca-APK-Dnp substrate
+1 day
+translation, RNA metabolism, protein modifications and intracellular transport or membrane modifications
+XendoU
+PCR amplification
+380 nm
+endogenous levels of ACE2 protein
+L118A/I119A
+the sequential aggregate of the eight assigned gene segment lineages
+pneumonia
+Three weeks
+CPB
+11.5
+Phylogenetic algorithms
+50%
+Y-scores
+17%
+translational activity
+Chittagong Veterinary and Animal Sciences University
+PCR
+DN57opt, DN80opt and DN81opt
+dystrophin protein
+three
+35,114
+E2F8
+disease
+deterministic compartmental model
+polyadenylation
+82 years old
+50 mM mannose and 5 mM EDTA
+254 ± 12 pA and 622 ± 13 pA
+microvascular abnormalities
+IL4pred and IFNepitope
+encephalitis
+Twenty-four hours
+antibody produced from a single antigen-specific B cell
+ATPase Na/K transporting subunit alpha 1 and prohibitin
+The final logistic model
+injurious ventilation
+Gluc-expressing viruses
+IREI, ATF6, and PERK
+Molecular chaperones
+cytolytic
+dynamic transmission model
+Dr. Yanjin Zhang
+LLPS of the polySH3-polyPRM system
+Descriptive statistics
+The Global Fund to Fight AIDS, Malaria and TB
+amphiregulin/EGFR
+interleukin
+HLATyphon
+inflammatory
+severe parenchymal inflammation with no obvious airspaces
+the bacteria
+Cucumber mosaic virus and Plum pox virus
+impaired formation and deposition of immune complexes
+MPP software
+7
+ProteinChipH Fractionation Kit
+Angiotensin II
+48,692
+cell-free supernatant
+two
+cmnm 5 s 2 U
+all affected individuals, their family members and medical staff
+105
+12
+LAG3/CD49b double positive
+IgG antibody conjugating colloidal gold
+Levenshtein distance
+An improved blocking procedure
+protection against bacterial infections
+disruption of the genetic material
+nasopharyngeal colonization with respiratory bacteria
+800
+ferrets
+ΔPARF
+any time
+1.0 and 2.0
+26.7%
+T cells
+M. domestica spp.
+1963
+11
+green fluorescent protein
+specific features
+marginal
+MEWDS is underdiagnosed
+mobile POCT and properly trained, certified, and annually validated personnel
+4 th May 2015
+crowded conditions created by synthetic particles with narrow size distribution
+folding of siRNAs
+Higher
+body temperature
+Acute respiratory distress syndrome
+GS De Novo Assembler
+H7N9
+ssDNA TM
+Routine disease surveillance and the prompt identification and isolation of clinically ill animals
+pathophysiology of lung injury
+HRV-A infections
+HI and MN
+PID values
+change
+Matrix-assisted laser desorption/ionization-time of flight analysis
+70% to 30%
+mid-1970s
+sj/bTREC ratio
+TL1 and TL2
+69.48%
+CD11b
+Spheroid culture
+FADDL
+68%
+5.6 Â 10 6 /mol
+90%
+MS-based
+Quality control and deviations from HWE
+Two
+sugar RDCs or sugar conformation
+all of the eight-point dose response curves
+SVM
+3 h
+55.4 ± 5.0951 μM
+pcDNA3.1
+30 min
+ITS2 and psbA-trnH
+Five
+2015-01-15
+LeFE random forest machine learning algorithm
+Atg16l1
+α-Tubulin levels
+Further research
+helix F
+shRNA
+more than one genotype/lineage of each virus species
+11 fibronectin structures
+four
+Protein concentration of lysates
+NK cells
+Krt5 pos cells
+IFN induction and action in infected cells
+RNase A
+163.com
+relaxes the constraints on internationalization
+leopard
+spikes
+an APMV
+Embryonic day 0
+sequencing reads generated from the genomes of a large number of species
+McNemar's test for matched pairs
+CFSE lo alloactivated T cells
+2 h
+twice
+F i and A i
+Ni-affinity chromatography
+k nearest neighbor algorithm
+parasite granulomas
+viral RNA synthesis
+immune responses
+depression and alcohol use disorders
+RNA sequencing
+activation or cytokines
+Khyber Pakhtunkhwa Wildlife Department
+hippocampal T cells
+hydrolases
+escape mutations
+10%
+lymphoid tissue damage
+80%
+263
+Molecular diagnostics
+Autophagy
+300
+Influenza A virus X31 and Phil82X
+context-specific
+ELISA
+sialic acid
+81 %
+monitoring virus evolution
+16 mg/ mL
+increased expression of ACE2 and MAS-1 R proteins
+valid
+jpHMM scal
+CD40L-mediated apoptosis
+Glu
+Control samples
+Ifn-α
+FastQC v0.11.5
+3-5 days
+Critical illness
+27
+Sex and genus
+CD4 cell count
+antibody-dependent enhancement
+Hirt DNA
+23,000
+50-60kDa
+Comprehensive English and Spanish language literature reviews
+Tat protein expression
+ACE2 activity assessed against an artificial substrate
+quadruplet codons
+CD46
+endocrine disruptor
+vitamin D deficiency
+329
+proliferate
+glycoproteinspecific T cell responses
+UAF1
+therapeutic interventions
+4/11
+1.81 and 1.86
+Oligonucleotide site-directed mutagenesis
+100%
+extracellular
+69,5 %
+When the daily vaccination rate is fixed
+mannan
+Aminopeptidase N/CD13
+three
+p24 levels
+monobenzone-induced memory CD49b + cNK cells
+social marketing strategies
+1 hour
+secondary progressive MS post-mortem brain tissue
+IASOS
+t*
+Biphasic unfolding transitions
+length
+culling of unsold birds
+IFIT5
+confirmation of pandemic H1N1 influenza A infection
+bacterial toxins
+differentiating local transmission from a new focus
+Fruit bats
+protease sensitivity
+phage output titer
+PREP
+delayed oseltamivir therapy
+pathogens not tested for and thus with no data
+80%
+mice and humans
+the prediction of disease spread and the establishment of effective control measures will be hampered
+0.79
+21
+Phytohemagglutinin
+enzymatic
+thermodynamic parameters
+PFT
+LOS and NEC
+Education regarding the cognitive sequelae of critical illness
+growth-promoting signals
+WNV
+nsP3
+IL-10
+mutation of the other six residues
+26%
+G6PD-knockdown cells
+an underestimation of the population bottleneck
+operates other motion
+1976-2001
+IL-1β-induced inflammation
+receptor attachment
+16
+5-10 min
+Relative synonymous codon counts
+Method 1
+Hsp90
+Akaike Information Criterion
+Autodock 4.2
+2010
+Blood, duodenum, ileum, and spleen tissues
+37-40 mg/mL
+functionally influence digestive system function
+a binary judgment of having or not having a disease
+up-regulation of mTOR activities enhancing cell proliferation
+Phase 6
+CDR'
+chloride ion secretion
+24
+24 h
+three
+NS3pro
+mSAMD9L
+viral replication
+Pathogen-informative
+the protective effect of DIZE
+eight
+search behaviors related to HFMD vary throughout the province
+on the CRF and on the concomitant medication form
+spatial and temporal variability in the case-reproduction ratio
+SERCA
+UVimaging
+SaCyp
+socioeconomic, environmental, and ecological
+~2 μg/ml
+Tumors
+Twenty-seven
+reproducibility
+Lactobacillaceae
+secondary structure
+72 hr
+NLS-2
+Israel meningoencephalitis turkey virus
+Professor David Blackbourn
+Spiegelman's Monster
+patient records
+TLR4-dependent signaling
+School closure
+inflammatory cell recruitment and cytokine release
+circulating IgM
+low pH
+disease-free survival
+different types of regulators
+co-infection
+50 nt
+to guarantee safe and long lasting effects
+Virus distribution
+miPepBase
+PERCH
+Propensity scores
+between November and April
+1259.7 Da
+high-risk targets identified by security organizations
+single-stranded DNA binding protein
+ACE2
+MHC class II compartment
+several interesting candidates
+RotaShield TM
+Normal levels of complement system's proteins and plasma protein electrophoresis
+Hepatitis B
+30 °C
+49%
+hospital-associated
+0.2%
+people who live in urbanized areas
+erm
+counted
+206 nm
+V2
+in their soluble forms
+Microglial activation and increased proinflammatory cytokine production
+epitope identification
+CPU-and memorydemanding
+ω
+ACE2/Ang-
+0.5 M sodium bicarbonate
+High level of variability in BKV
+El Niño/Southern oscillation
+regulates ABCA1 expression
+VIRIP
+Concurrent bacteremia
+normal translation resumes
+an aMDA-5 autoantibody
+mouse
+In vitro trials
+mortality
+3.666 × 10 6 uL
+100%
+R 0 and ⁎ R
+The shortness of MLE of serial interval
+Penn State College of Medicine Flow Cytometry Core Facility
+3 days
+SFPQ
+DAPI
+four
+Superscript IV Reverse Transcriptase
+stress intensity
+IAV-bacterial co-infections
+RNA architecture
+ImageJ
+PE anti-Tim-3 antibody
+interactions between core proteins
+Disruption of CNS homeostasis, neuronal deterioration and inflammation
+class or family
+patients with both acute and chronic infection
+the unobserved component
+3 perl scripts
+four
+4
+C 15 H 10 O 5
+oseltamivir
+Western Lightning Plus ECL detection reagent
+12,000
+phylogenetic order
+pneumococcus
+30 s
+separate episodes
+whole blood
+cholesterol intracellular storage in host LDs
+erastin-mediated ferroptosis
+Tubulin
+88%
+114
+coupled and uncoupled
+2500 nt
+public reaction to a disease is frequently disproportionate to the number of cases
+rapid weight loss
+24-h
+structure-assisted design of small molecules
+23
+Weibo
+infection of PTH
+quantitative estimations of sequence similarities and dissimilarities
+108
+a past primary DENV2 infection
+1978
+CIS and VHL
+fluorescence activated cell sorting
+nonspecific symptoms
+antiviral drugs, ventilators, and general hospital care
+regulators of the protein-coding sequences
+Amazon Web Services Marketplace
+superior cost and resource effectiveness
+explore the public's views on the pandemic influenza vaccination
+cells in different cell cycle phases
+set new values in the input fields or move sliders
+2 weeks
+TBC2target
+individuals with chronic, underlying medical conditions
+UPR-induced NF-kappaB activation and ROS generation
+high
+1:10,000
+DCs
+t R
+receipt of any of six intervention components
+double positive cells
+contact duration
+Sera
+acid conditions
+antiviral
+ocular adverse reaction and serious derangements of electrolytes
+14
+RPL4
+150
+mitotic microtubule dynamics
+defense response to viruses
+text
+regulatory sequences or Transcription Factor binding sites
+S-palmitoylation
+HepaRG
+Figure 2
+infectious agents
+10% 8 M urea acrylamide gels
+R 3 and R 4
+cervical cancer cells
+53
+pig, sheep, and bovines
+GraphPad Prism 6
+cellular oxidative stress
+niclosamide
+10.3390/v2122559
+37%
+91%
+Doripenem
+3 weeks
+near the outer edge of the template tunnel
+CRP and PCT
+Acinetobacter baumannii
+Hominoid Old World primates
+ECG
+38%
+165
+endothelial cell pyroptosis
+Athens
+10
+means and standard deviations
+Drug treatment
+higher concentrations
+sharper slopes
+IS2404 PCR
+HindIII and EcoRI
+artiodactyls
+hemocytometer
+positively charged residues
+whenever
+1.76
+sites of MCMV antigen expression
+2.27/1,000 person-year
+400 ng of total RNA
+20
+Confocal
+muSOX-induced
+genotypic
+HNF-1 alpha mutations
+mucosally delivered subunit-vaccines
+concentrated
+15
+a lock and key
+Guangdong
+n > 400 vesicles
+host-related factors and environmental factors
+HIFs
+Five
+rhinovirus, coronavirus, influenza
+45 minutes
+clinical benefit
+PT cells
+random
+>95%
+56°C
+pharmacological agents
+FPIX in the DV
+statistical package
+11
+w52%
+type II pneumocytes
+poor prognosis
+high-affinity binding
+Fifty-two
+Table 2
+HIV-1
+84%-87%
+The ligation reaction of fragments 1 and 2
+2009
+pathway and network centric
+pooling samples
+functional incompetence
+alteration of the disulfide bond pattern
+CU-CPT9b
+log-rank test
+lung epithelium
+11%
+acid solution
+epithelial and endothelial cells
+Fisher's combined probability test
+73%
+6 months
+Alexa Fluor 594-labeled donkey anti-mouse IgG
+regulatory reasons
+VP88GFP-expressing cells
+Total eIF4E activity
+involve people in the decision making process
+IFN-α
+0.8 mg/kg
+carbohydrate
+antibodydependent
+multiple organ failure and death
+a trained nurse
+polarized and nonpolarized
+45.5%
+poor
+Figure 8B
+Titers
+lysine 2066
+Concomitant
+20%
+repeat dosing
+enterovirus 71
+Purified pDCs
+more severe leukemoid reaction, plasma leakage and coagulation disorders
+Troponin T
+PTX blocks T cell motion
+DC-derived IL-2
+PCR
+Comprehensive medical screening
+C23
+95
+the trimerization of independently folded monomers
+the nuclear membrane
+the best fit of the model to the data
+MGs
+cell-apoptosis induction
+guanylate-binding proteins 2 and 5
+Dengue fever
+Virus binding to host cell surface receptors
+Akaike Information Criterion
+Molecular chaperones
+vRNA
+protein quality control
+Epi Info 6
+AMCase
+ERK, p38 and Akt
+leukoencephalitis
+up to eight
+80.5%
+F-7000 fluorescence spectrophotometer
+Staphylococcus aureus
+0.68
+E10
+65
+∼14 days
+M-CSF-treated cells
+three
+4%
+particle formation
+12%
+405
+ΔP
+90
+56
+15
+whole genome short-read sequencing data
+re-infection of individuals or loss of immunity
+Marik and Corwin
+geographic isolation, population demography and vaccine coverage
+three
+450,480
+13%
+transmembrane Toll-like receptors
+two months
+significant
+methylated
+CC 50
+28
+the mechanism of frameshifting
+two
+Macrophages or the closely related myeloid suppressor cells
+Tocris
+Enhanced
+CXCL16
+five
+17.4%
+P1, 1B, 1C and 1D
+two-way repeated measures analysis of variance
+anti-vector blocking responses
+inflammatory
+MLKL
+age, sex, occupational status or family history
+black
+water fowl
+systematic and concrete planning
+PDI-dependent DT toxicity
+translation-level regulators
+Standard deviation for each mean
+worsening sepsis severity
+vaccine growth
+ACE1/ANG II/AT1R axis
+1040
+30 nm
+442
+329
+200 μL and 100 μL
+21%
+six
+Susceptible-Infectious-Recovered model
+all three structures
+15 min
+21,087.1 billion RMB
+plasmid A
+25 µL of antigen
+Figure 3
+six
+H5N1
+IP inoculation
+S. aureus Newman WT
+10%
+susceptibility to rupintrivir
+phosphadtidyl serine or other ubiquitous cell surface receptors
+POCT
+How G6PD is involved in the activation of the inflammasome
+person-centric model
+WATERGATE 3-9-19 pulse
+synthetic oligonucleotide
+a single introduction of infection
+C
+Charles M. Rice
+Microglia and macrophages
+eIF4E
+Sexrelated
+reacting to diagnostic needs in epidemic events
+one week
+Dell Precision TM T5500
+Arginine stereochemistry
+disease status
+Five
+similar results
+pain sensation
+a new family of viruses
+Affymetrix GeneChip Mouse Array
+Bovine serum albumin
+43.26 μg/ml
+Power calculation
+PEI/Luc NPs
+two
+into a parallel homodimer
+symptomatic disease
+Globalization
+spring and winter
+VIDISCR
+60,000
+0.1-0.5 µg/mL
+microfilariae
+None
+second-generation sequencing
+reBmBac
+primary cells
+Libraries
+ALI
+low
+heat-related illnesses and trauma-related injuries
+immunomics
+mitotic, meiotic, and postmeiotic
+vesicle swabs
+1 − θ = k 2 /
+240,000
+Nrf2
+diseases
+genome stability
+amino acid changes
+Baroreflex
+15 min
+27
+initiating on the wrong reading frame
+6.0%
+CVB3
+Caspase activity
+Kidney cortex
+stress fibers
+capsular types
+myeloma
+367
+Bronchial smooth muscles cells
+9 generations
+the Ministry of Health
+IL-10
+Figure 4d
+eleven
+Twenty-five
+high-touch surfaces
+Gene regulation
+to counteract enhanced muscle protein breakdown
+Isoelectric point
+R 11
+apoptotic
+Vaccinations
+digestive efficiency
+endemicity
+amorphous
+orthopaedic
+FCV and FHV-1
+hydrogen bondforming moieties
+H78-C10.0
+cDNA preparation
+LSECtin
+two different chromosomal fragments
+viral particles
+passive
+mean expression of all genes in each module
+Hrk and Bid
+13 March 2020
+Apdm09 activity
+10.1371/journal.pone.0002432
+55 C
+LMICs
+Public security
+autoimmune diseases
+nan
+40
+Sixty-one
+non-parametric 2-tailed Student t-test
+suspected
+hypoxia
+adaptation
+23
+Mimivirus
+Eleven
+elevates
+NHP endotoxemia
+Bio-Rad MyCycler thermal cycler
+five
+stringently controlled, definitive intervention trials
+four
+Foxp3
+Intravenous injection of immune globulin
+glycoarray
+stay in the office
+2009
+all links that ever appear available between nodes i and j
+bronchitis
+supersonic waves
+WHO 2009
+C22
+not all patients were managed with all four support strategies
+30.1 and 14.3 fold
+protocol standardisation
+NHP models
+to study emerging infectious diseases
+9256543256
+a quantifier and a qualifier transition
+sialic acids
+24 h
+recombinant proHNP1
+PCV
+Hepatocellular carcinoma
+formation of the cystine loop
+Red
+during the analysis of two closely related litters with four affected puppies
+>86%
+N-terminally truncated LASV rNP
+ten
+54
+genomic plasmids
+MLKL
+transitivity
+Sepsis
+Node coloring
+compensation for a temporary hypercoagulatory state of the body
+GSE103207
+modulators of the immune system or virulence factors
+syndromic
+Innate immune responses
+metaplasia of squamous epithelial cells
+mouse KAT2
+Twenty-one
+non-specific
+reactions
+Golgicide A
+T cells and dendritic cells
+cytopathic effects of poliovirus
+s
+hydrophobic degeneration
+Synonymous codon usage
+94%
+larvicide spraying
+the manufacturer
+festina lente
+HBoV 1/2/3
+t i
+respiratory epithelial cells
+Microsatellite instability
+0.132
+GENIE3
+56
+WBC counts, CRP, and PCT levels
+cryptic
+protein transduction domains
+end point RT-PCR
+turning points
+flow cytometry
+Gene Expression Omnibus database 1
+3 to 36 days
+18S
+population ageing
+more than 4000
+severe adverse reactions
+A450
+Xtract with identical parameters
+oral administration
+four
+CD81
+HPV infection
+high
+Newcastle disease virus
+four
+TBSV -strand RNA synthesis
+Particle mesh Ewald method method 15
+Comprehensive reviews on molecular actions of UDCA
+PCR
+to provide a searchable virtual library on the web
+Ribosomal protein S7 mRNA levels
+alphavirus
+Biosafety Level 3
+five
+synthetic influenza incidence data
+R 0
+20
+Logistic regression analysis
+social contact behavior
+100 million
+predicted DOF model
+BAC cDNA clones
+ISG-encoding lentiviral vectors
+symptom onset date
+parameter number
+RH
+cell lines
+12 hours
+50 to 70 % of injected embryos
+severe immunosuppression
+domestic livestock and/or farmed wildlife populations
+291
+a snowball approach
+individual-based models
+6 November 2013
+risk averseness
+CD8 T lymphocytes
+Quadratic discriminant analysis
+a review of a clearly formulated question
+EpiData
+tumor necrosis factor alpha
+linear trend
+78%
+light sensing
+MSP ox 1-4
+SUMO-1
+hexahistidine
+increased pulmonary inflammation
+extracellular matrix and regulation of blood pressure
+SnapGene
+January 2009
+IFITMs
+phylodynamic models
+TUB
+autophagy stimulation
+HRV specific semi-nested PCR
+CIAP
+wounding-healing
+27%
+6 weeks
+homodimer
+24 h
+idiosyncratic
+One million
+a washing step
+pcDNA3.1-Myc-PKR296R
+6 days
+All authors
+standard RT-PCR
+QIAmp DNA mini kit
+Drs. Richards, Pepine, Raizada, and Kim
+Spike-in controls
+Prediction and pre-warning
+Poisson distribution
+feedback of the results to HCWs
+high MOI or longer time points
+GUIs
+permutation test
+two-way
+12 weeks
+rhinovirus
+The possibility for such harms
+data from additional settings and years
+Gel filtration chromatography
+59.3% to 96.4%
+PCV-2 and PRRSV
+2 12.3
+TRACER v1.6
+MagExtractor-PCR & Gel Clean up kit
+71
+PureLink TM Viral RNA/ DNA Kit
+50%
+further investigation
+three
+regulating CII-induced differentiation of Th17 cells
+81%
+lysosomal cathepsin B
+Chest
+influenza viruses
+18%
+to reproduce the data on the age-dependent daily contact numbers
+21 days
+artificial protease substrates
+1.2-1.7
+10.5%
+Ebolaviruses
+nosocomial infections
+antibiotic-associated diarrhea
+HT and PLT
+inflammatory bowel disease
+hemodynamically
+p19 protein
+One hundred nanometer polystyrene nanostandard particles
+a set of parameter values ν
+Sepsis-3
+Genecore Corporation
+pCAGG-NP
+Fever
+Internal standards
+ethyl-substituted ThT
+LPS
+14
+PrtP
+1,028,840
+Antiviral chemoprophylaxis
+11 million
+an IFN-inducible protein
+critically ill patients with acute respiratory distress syndrome
+Gamma-secretase inhibitors
+rs117648444-C/T
+pAC-A
+mimivirus
+δ
+0.0012%
+lung
+calcium chloride method
+private clinics, psychiatric hospitals or nursing homes
+CD4 cell count and time since HIV diagnosis
+direct-acting antiviral agents
+inflammatory response
+elevated pH cyt
+Lassa hemorrhagic fever
+the managers of DAH grants
+DHFR mutant strain
+novel and longer CDR3 regions
+Single round selection
+82
+indirect calorimetry
+firebrick
+FUJIFILM Wako Pure Chemical, Ltd
+l tr
+three different matrix metalloproteases
+deoxypodophyllotoxin
+Respiratory syncytial virus
+Genomic DNA
+nonmonotonic
+Drug-induced acute fatal liver injury
+Cortex Magnoliae Officinalis
+0 to 1
+volatile metabolites in exhaled breath
+pBR322
+0.02 mg protein/ml
+courage
+56%
+proteomic approaches
+host-species specific defect
+oncogenic retroviruses
+population sensitivity and false positive rate
+apparent reduction of product level
+1
+Viral RNA
+313 nM
+clathrin-mediated endocytosis
+pDest14/N TAILHN
+Alignment of different mammalian ABCB1 protein sequences
+diarrheic calves
+cytoskeletal rearrangements and shape change
+dsRNA
+Visual Analog Scale
+Viral RNAs
+rabbit anti-human HSP90β mAb
+selective inhibitors
+exercise training
+14/3/2020
+black
+Surgical exploration
+ACE and KDR
+cytoplasmic LD abundance
+68.0 cases
+classic medulloblastoma
+21 days
+epitope-based
+38
+2.3 µm min −1
+14-day
+IL-12p35
+Viruses
+during the late stages of infection
+days during which supplemental oxygen was required
+VP24
+Miranda software
+95,000
+ISG15
+Respiratory epithelial cells and macrophages
+key mediator
+6 months
+16 of 18
+GLIDA
+Globalization and Health
+clinical trials
+545
+Syrian hamster transcriptome
+cc-by
+increased TTV burden
+Levinthal's paradox
+Vacuolating cytotoxin
+GS
+Study of the link between taxonomic proximity and genomic signature proximity
+vRNP export
+ORF as well as UTR sequences
+GHITM
+2 mg of total RNA
+E. festucae codon usage
+Two weeks
+Viral RNA
+90%
+public ground transport
+the same sample
+absolute quantification of transcript levels in single cells
+least-squares fitting
+serum sample
+onset of symptoms and outcome
+Microneedles
+haplotypes
+two large fragments
+7 head-to-tail β-strands
+TBI in sport
+30 min
+supernatants
+Sequences from different parts of the world
+λ = 280 nm
+60%
+HisPur™ Ni-NTA Resin
+Caffeic acid
+an integer between 0 and 15
+21
+Two out of four
+tet40
+DC-SIGN
+Gremlin-1 staining
+significantly increased
+suppressing
+Meningococcal
+Three
+three different replication mechanisms
+eight
+rabbit antihuman CD3
+amino acid R443
+113,228 compounds
+a regular stem
+log 10 /ml
+Supplementary Information Table S3
+Cufflink
+AT-9010
+RNA viral protein interactions with host proteins
+16
+PCR artifacts
+subclinically infected with PiCV pigeons
+8.5 ± 2.2 mL/kg
+missing value imputation, outlier removal and data normalisation
+Predicted xis and integrase genes
+transducing CD133-positive cells
+Japan
+further resolution of antibody epitopes
+P
+immunochemistry tests, cytogenetic studies, and molecular techniques
+the nature of the state
+changes in R 0 when R 0 > 1
+Eighty-nine
+MeOH extract
+1702 cell eq./m 3
+diagnosing, treating and preventing oral disease
+25%
+PYD
+F110_9318
+selective
+NCT01317745
+to identify LRDs caused by CRVs
+one
+5%
+sinapinic acid
+complement-dependent
+endocrine disruptors to radiation
+41.8%
+TRIF
+Smad4
+permanent
+HETATM record names
+RSV-GFP virus
+an outbreak
+antibiotic regimen
+fine particle aerosols
+quantitative attenuation and an endpoint of stable, permanent attenuation
+glycoprotein cleavage by the proprotein convertase furin
+the virus is able to cross the blood-brain barrier and stimulate inflammation
+200 μm
+demographic, geographic, and socioeconomic
+HBTU:HOBt
+scoring model
+0.2%
+total cell lysate
+Pane C
+global significance
+desiRm
+28%
+Skin cancer
+an M protein with a lower PID
+monophyletic
+ACJ
+Logistic regression
+87.6%
+the most elaborate and diverse clusters on the antigen surface
+essential associated proteins
+SR and KH
+C-terminal tails
+long carbon chain
+Alveolar macrophages
+March 2017
+goat anti-mouse IgG 10 nm gold conjugate
+71.8%
+lethal
+NUTS 0
+mice and in chickens
+sacral function
+GP2 residues
+synthesis of the NS3 viral protein
+NFKB1 and REL
+Written informed consent
+read counting, normalization and calculations of fold changes
+Discriminant analysis and principal component analysis
+calling attention clearly to a common or significant particular risk
+Los Alamos HIV sequence database
+1 month
+The area under a random curve
+intracellular transport and organisation of the genome
+148
+basement membrane component laminin
+Theiler's murine encephalomyelitis virus
+real-time PCR
+Allele frequencies
+Shannon Evenness Index
+Rapid pressure changes and the exhaust system
+primary particle size
+nurses
+Notch1
+63
+23 million
+38%
+any references to things that were deleted and definitions that are impossible
+Nikon NIS Element Software
+transcription of IFNα and IFNβ
+safety issues
+PTH
+100%
+4 hr
+SOD
+modulation of PAMPinduced immune responses
+1.1 mg
+vision impairment and floaters
+1179
+CCHF
+2008
+disperse
+increases the neuronal firing rates
+physiology
+Proadrenomedullin
+281
+lower
+thyroid function
+A/H1N1
+50
+adult haemoglobin
+deleting MEs
+27%
+NucleoSpin Extract II Kit
+Structural data
+graphs
+Baidu
+HEK293
+base-pairing required for RNA folding
+0.04 ± 0.02 Pa·s
+30
+inflammatory cytokine and chemokine production
+Institute of Tropical Medicine
+44%
+upon a HS
+the size of the protein coding area in the genome
+cytokine/chemokine levels
+Methodical analysis of the structure of DCIR
+1.6
+pro-and anti-inflammatory
+group E pigeons
+human and zoonotic
+immune response
+histopathological changes
+104 pg/ml
+renin-angiotensin system
+10-kDa
+the "mouth" of the F pocket
+unsuitability
+41
+differentiation of neural stem cells into astrocytes
+regulation of C3 function
+low quality sequence regions
+Telomere attrition
+Mycobacterium tuberculosis DarG-macro
+3.8
+Wageningen Bioveterinary Research
+bovine fetal fibroblast cells
+exacerbation severity
+reduced entry-enhancing activity
+GC B cell reactions
+moderate elevation of maturation markers
+SPI1 and SP2
+acute renal failure
+anchorage independent growth
+four iterative stages
+Over a million
+vaccine efficacy
+FACS
+2-3-week
+Forty-six
+disease severity
+Immunohistochemistry and PCR
+rhesus macaques
+de novo assays
+unparalleled information
+personal protective equipment
+guinea pig
+porcine Oct4 + Ccsp + colony cells
+IL-1β and TNF-α
+CD20
+GeoChip 2.0
+Viral proteins
+substrate proteolysis
+Euphorinae
+to optimize the system for endpoint measurements of enzymatic hydrolysis reactions
+reasonable
+HIV-1
+Cellfree supernatants
+RRV 31,32
+1%
+T-bet
+10 μg/mL oseltamivir phosphate
+HFMD transmissibility
+14 days
+Lyme disease
+inserting additional probes
+viral E proteins
+568 days
+to avoid underestimation of the number of CEA genes
+0 frame translation
+causal relationships between single predictors and outcome
+more than 40%
+S. agalactiae serotype III
+PCR and sequencing
+adult vaccines
+0.3%
+Eight
+5%
+46 years
+NS1 sequences of SA14-14-2 strain
+TLR3
+SOD and GSH-Px
+crossreactive
+Fifteen
+frequency-dependent relationship
+QSAR
+MHC class I
+Ub
+regulate motor deficits and neuroinflammation
+50%
+HBV, HCV, HIV, and West Nile virus
+Taconic Farms
+a rapid reversible head domain movement
+secondary over primary infection
+capacity building for improved infrastructure and administration
+Due attention to the soft periphery
+24%
+45 to 56%
+endo-lysosomal compartments
+H1N1
+transport medium
+mRNA variants
+wane
+56
+2 weeks
+CD274
+high similarity
+wild-type and TMPRSS2 KO mice
+relieved
+hamster
+Disease severity scores
+wobble uridine modification
+it can survive in host tissues for several days
+FITC-conjugated secondary antibodies
+PET, AFLP, and cardiomyopathy
+sepsis-associated AKI
+All data
+chromatin accessibility
+avoidable mortality rates
+to stringently evaluate the efficacy of tolerance induction protocols
+UV melting experiments
+Peptide-MHC class I binding
+nuclear targeting sequence
+ATRQβ-001 vaccination
+3 days later
+age, gender, risk factors, and secondary infection
+grew at an increasingly exponential rate
+RPMI
+health and maternal antibody status
+acute inflammation
+U6
+BGLAP
+hydrophobicity
+Full atom type and bond information
+Up to 50,000
+established exposure control guidelines
+Dating recombination events
+xtract
+live and inactivated
+independent reproduction numbers
+433
+GCrich ssDNA
+to com-
+show-tiling program
+Nature Research Reporting Summary
+Each death record
+Zoster neuralgia
+Hong Kong HA and NA sequences
+Open and transparent communication
+phylogenetics
+clustering
+IFN-c SNPs
+Virus stock
+IL-4
+lymphoid
+cellular proteostasis
+language
+Capacity building
+VSV
+GCSF
+pH1N1
+the effect of distance decay in the search scope
+82%
+CR1 SNP data
+lysenin
+2019-09-24
+mortality by suicide
+limitless
+acute diarrhea, vomiting, dehydration and high mortality in neonatal piglets
+Four
+Blastocystis spp.
+unbiased deep sequencing
+wild orangutans
+Combined GC content
+Activation and degranulation of polymorphonuclear neutrophils
+Paris, France
+epitope mapping
+four
+22
+neuroprotective
+heterogeneity
+over 1 billion
+74.8%
+anti-inflammatory
+probabilities
+RT-qPCR assay
+about 1 week
+Demyelination of the central nervous system
+CVA16
+interleukin-STAT3
+Nucleoside ms 2 i 6 A
+between 1 and 3
+62%
+VAS visualization
+324
+crowding
+H275Y
+poly I:C
+The nucleolus
+Asp406
+IFITM3
+Detailed field studies
+HA-activity
+RNA aptamer
+human
+Nucleic acid quality
+high fat diet mice
+TCBZ response in phase III sequestration based detoxification
+the analytic method and key themes
+asthma and COPD
+General linear models
+host cell cycle
+CRI SPR-Cas9 genome editing system
+cell cytotoxicity
+Aconitine
+12 and 6 pmol/25
+Qiagan Blood DNA Midi Kit
+endothelial cells
+protein
+10%
+UV light
+cold PBS
+Molecular Devices Spectramax 384 Plus spectrophotometer
+future studies
+by severity and relationship to treatment
+Ubc9 and PIASy
+White-tailed deer
+sensitivity analysis
+3 to 4 on the 5-point scale
+N. meningitidis and S. pyogenes
+virus-induced apoptosis of lung epithelial cells
+there were no significant differences between any of the time points
+single cell suspension
+2004
+m
+Healthcare utilization surveys
+aee-miR-11-5p
+host chaperone
+any known medical history
+Balamuthia mandrillaris
+Spearman's linear regression analysis
+renal dysfunction and failure
+85%
+HBP1 and fgl2
+body weight gain
+Tetramethylbenzidine
+similarities between poorly sequence-conserved proteins
+microbiome-derived epitopes
+BALB/c and C3H
+clinical
+Caudovirales
+airway surface liquid
+The determined current state
+HTSeq
+HPVs
+gemcitabine
+facilitating the assembly of the viral replicase complex
+flavivirus
+Out-ofphase regions
+5 and 24 hours
+PCR genotyping assays from tail biopsies
+SpectraMax M2 microplate reader
+twice
+bone marrow chimera
+AIV
+hierarchical
+Olympus IX-70
+C. burnetii
+difficulty accessing or affording food
+a realistic description of the epidemic
+DENV
+GCBS
+18
+depression
+Group 2d-1
+solubility
+no or little effects on cell permeabilization
+Further analysis
+beclin-1
+protective
+50
+anti-HA antibodies
+genetic instability
+6 hours
+Foxp3 − Tr1 cells
+73%
+three
+Patients ventilated with higher P max
+preexisting immunity
+C. burnetii
+24 h
+Restriction digest using BclI
+39,539
+innate immune cell types
+PhosphorImager
+50%
+THK
+small chromatic spots
+likelihood function
+Goat anti-mouse HRP-conjugated secondary antibody
+twice
+2 days
+ζ_i
+2012
+macrolide resistance
+mRNA depletion and PABPC relocalization
+LPA
+maximize the patient's quality of life
+HI and MN tests
+Definite Focus
+mAb
+activated germinal center centrocytes
+eleven
+The partition coefficient
+S4 Table
+318
+Activity budgets
+25,683
+three
+four
+hypertrophy of the myometrium
+de novo sphingolipid biosynthesis
+SEM
+contact tracing
+clinical decision making
+virological data
+whether our work can meet the expectations
+LC-MS/MS matrix effects
+common changes associated with lymphocyte activation and cell proliferation
+more than 25
+tapir
+quarantine or screening programs
+Large, multiplexed proteins
+SupTOC-Pam3CSK4-48h
+FISHView Version 5.5
+IL-1β
+Eli Lilly and Company
+Unpaired t-tests
+pools of peptides assigned to HIV-1 Env regions
+polyadenylated
+the extent to which nodes in a network tend to cluster
+the reciprocal values of the last serum dilution that completely inhibited
+chronic respiratory abnormalities, cardiac disease, immunodeficiency, and pregnancy
+Nigerian tobacco mosaic virus
+5 days
+medical authority
+1976
+MEF2C
+binding the IFN-␤ promoter
+Newcastle disease virus
+decreased FAP
+finding host-oriented drug targets
+5919
+10 ll
+Microglia
+r i 2
+three
+nitrocellulose membranes
+pfmdr1
+0.02 ng
+IFITM
+LysoTracker Red DND-99
+machine learning
+DMEM
+chemotactic
+k-means algorithm
+mortality
+linear regression models
+amplify most of the known mouse antibody sequences
+exploration of the basic interaction between the ventilation and the outbreak
+multiple residues/regions of the envelope glycoprotein
+phylogenetic trees
+druggability
+ATP hydrolysis
+higher incidence of waterborne infectious diseases
+alkylated RNA
+epifluorescence
+21 • C
+Non-LTR retrotransposons
+RNeasy Mini Kit
+greater access in the workplace
+neutral
+Genetic bottlenecks
+viral attenuation
+Research Electronic Data Capture software
+PRRS in pigs
+48
+confirmation of the serological relationship between these two types
+hydrolysable
+synergistic
+263
+P 0
+BD CBA Software
+Mechanical stretch during breathing
+unaltered
+Glycan Atlas
+Fourteen
+XendoU
+72
+HIV-2, hepatitis C and dengue viruses
+%ES
+Computerized
+R. tanguticum nanoparticles
+numerical stability
+physicochemical properties and formulation
+weekly
+15 min
+PyMOL™ software
+two groups in the biomarker study
+57%
+Cell lines stably expressing the or dual-luciferase HIV reporter
+an increase in the expression of VEGFA
+HYPV
+changes in the characteristics of cell metastasis-associated behavior
+four
+6MWT test and timed function tests
+72%
+100
+sequence alignments of selected flavivirus clades
+polarization of low-and high-avidity responses
+12%
+zero
+high
+HIV-1 entry
+IL-4 and IL-13
+Further examination of this phenomenon using historical ILI data
+hDC-SIGN and SIGNR1
+shrimp immunity against the virus
+mixed infection
+RTA transcripts level
+42 kDa
+Pertussis
+Leishmania infantum
+Yca1-dependent
+356
+CT
+Current protocols
+Six
+great advantages
+weekly
+IL-21
+Dr. Minetta Gardinier
+The importance of local circumstances and their possible impact on liability
+seven
+Research into the mechanisms of henipavirus pathogenesis
+zPicture
+317
+PaKiT01 cells
+culture
+dental records
+syndromic
+three
+InfluSim
+bspC gene deletions
+nasal turbinates
+The genetic information of flaviviruses
+10 2 copies
+Adenovirus type 14
+splicing
+a better model
+between September 2017 and September 2018
+θ r
+RNA interference
+SuperSignal West Pico Chemiluminescent Substrate
+Barabási-Albért model
+nucleic acid amplification tests
+thrombotic occlusions of medium and small vessels
+response in severe cases
+Isotype-matching coated beads
+Ministries of health and national policy-makers
+PhusionH high-fidelity polymerase
+acute fulminant hepatitis
+NaHCO 3
+Table 1
+10 minutes
+IELAGTLTLT
+C57BL/6J mice
+coherence
+risk assessment in air
+Means and standard errors of the mean
+Lr/100
+p6 pol -retaining PR
+TET-21 cells
+Twenty-two
+H5, H7, H9, N1 and N7
+woodchuck PBMCs and splenocytes
+Influenzalike-illness data
+discriminating positions within a set of highly similar sequences
+ontology
+259
+oligonucleosomal fragments
+338
+three
+population contact rates, travel patterns, climatic conditions, and geography
+8 of 13
+diff erent viral vectors
+QIAamp viral RNA kit
+suckling mice
+75,100%
+Symptomatic, potentially infectious and/or contaminated victims
+> 50%
+1838
+61 years
+ectopically expressed fusion protein
+6.25 g/mL
+Type II HSR
+liposomes and nanogels
+4 Ig domains and the long cytoplasmic domain
+three
+inverse dilutions
+mitigation measures
+Gene therapy
+Carbonate apatite
+reference database
+A pause of about three seconds for the first ribosome
+24 h
+a unique point
+More than 800
+4 to 8
+CXCL10
+5x loading buffer
+spray drying
+RNA cleavage and release from membranes
+63.9%
+deficiencies in mononuclear cells
+bovine submaxillary gland mucin
+11
+one
+pMKvector
+activate IFN-β production
+Transparency and honest communication
+anti-inflammatory
+30%
+ATP8B1
+Nextera XT DNA Sample Preparation kit
+NP evolution history
+Turner energy model
+Sep 2010
+24 h
+HeV Viral Antigen and Lesions in the Brain
+anti-Gag, anti-Env and anti-Tax
+lungs
+1335
+Novosphingobium aromaticivorans
+90%
+15
+inconsiderably higher
+The focus on influenza
+spo0A and sigH
+three times
+Respiratory syncytial virus
+negative baseline HAI responses
+Detailed binding between the protein and all nucleotides
+New York City
+subcortical
+less side effect
+Mfold v.3.4
+collagenase
+2,925
+frameshifting
+13
+958
+enveloped positivesense single-stranded RNA viruses
+protectin D1 levels
+4 hours
+miR-10a content
+A gradient from water and acetonitrile
+P. falciparum CSP
+vaccination of healthcare workers
+RNA polymerase
+Infrequent sneezing
+10
+covariates
+8,466
+Dectin-2
+19, 20, 24, 48
+foot-and-mouth disease
+2714
+seven
+cell membrane fractions
+Professor Padraic Fallon
+type I interferon production
+R software version 2.11.1
+1 μl
+Crystallography
+amphotericin B deoxycholate and flucytosine
+Virus group and independent virus-specific models
+Specimen rotator
+human exacerbations
+host species, cell type and virus type
+29
+zero
+host antiviral responses
+prM and E
+pH1N1 infection
+1:64
+presence of isoforms
+extremely hydrophobic
+PI3K isoform proteins
+cyclic diadenosine monophosphate
+isolated cases
+severe dehydration and diarrhea
+Survival analysis
+Eleven
+osteopontin
+VLPs containing recombinantly expressed VP1 capsid proteins
+EEA1
+113
+LTi cells
+three weeks
+twice daily
+acceptance and mindfulness
+Mammary secretions
+branch length
+back-splicing
+20 min
+2 days
+red
+20
+HIV screening and monitoring of IDUs
+Two
+Conditioning regimens
+PR3
+three
+viremia
+molecular
+0.001 TCID 50 /ml
+Phyllanthus urinaria
+MetaHitassembly
+94.6 per cent and 100 per cent
+Cytokines
+previous primary DENV2 and DENV3 infections
+a AMR gene
+1 hour
+HA of Aichi H3N2
+noninvasive assessment of severity of a broad range of pulmonary conditions
+1 km
+two
+ConSortß
+Research Electronic Data Capture system
+Induction of SOCS-3 expression
+asymptomatic
+novel viral lineages
+67
+Thermal stability of the nsP2 protease
+multivariate associations
+inducing antigen-specific antibody and T-cell responses
+169,000 years
+Arboviruses
+Dual luciferase activity
+treatment
+malonaldehyde
+B cells
+anhydrous acetic anhydride
+higher
+North Dakota Electronic Animal health Surveillance System
+enzymatic activity
+Enzymatic capping
+3%
+importance or essentiality
+BioPulverizer
+MAGE-G1
+entry to their borders
+6 months
+USKD
+HAV sequence alignment
+miRNA 21 and miRNA 128
+channel exchangers
+medium without or with increasing concentrations of EdC
+PRRSV replication
+to fulfill functions in the remodeling of ribonucleoprotein complexes
+prophylactic antibody therapies
+the outbreak threshold
+A random peptide library
+9
+The final height
+Phusion polymerase kit
+cc-by
+O. caudatum
+R 0
+antiviral treatment of influenza in hospitalized patients
+3.4 Kb long
+MEGA5
+59
+DNA methylation and histone methylation
+5 min
+influenza A viral infection
+58.3%
+Reporter HIV-1 particles
+Sendai virus
+The specificity of the reactions
+single stranded monoclonal beads
+risk communication
+written informed consent
+Histopathological
+long read lengths
+>98%
+one or two
+over 100 years
+Song and colleagues
+12%
+the inflamed CNS
+as percentage of total 100 platelets counted
+Plasmids containing various Rluc reporters
+standard TAT-5000 models
+Mean fluorescence intensity
+MTT solution
+cleavage
+Poisson distribution
+lyophilized LAMP assay mixes
+diagnostically-useful peptides
+synonymous sites
+ring-shaped distributions
+10 s
+TOM1
+human plasmacytoïd dendritic cells
+human mobility
+laboratory mice
+recruitment of individuals
+11
+modeling of sequencing errors
+133,469
+three
+change
+CXCL-8
+keratanase I
+5.3 mM Tris phosphine hydrochloride
+21 days
+positions 186, 226 and 196
+8559
+anti-GFP and anti-Flag
+CPV and VP2
+paper-based extraction and in situ amplification with lateral flow
+miRNAmediated antiviral effects
+platelet aggregation
+NF-B signaling
+epitope-specific response
+35-40%
+6.6 log 10 PFU/mL
+accumulation of phosphorylated eIF2a
+how the control group therapy compares with the treatment group
+compensatory anti-inflammatory response syndrome
+PEDV phylogenetic and phylogeographic data analyses
+2.5 mL
+More than 99%
+dual power supplies and dual network cards
+divergent transitions
+negative-sense
+flow cytometry
+confocal microscope
+BS
+A. C. G. T
+eight
+the first conserved a-helical segment of the LHR
+AT1 stimulation
+Aurora B protein
+immunogenicity studies
+Ruben Donis
+Purified RNA samples from HEK293 cells
+bowtie2
+early 2000s
+alveolar
+less than 10%
+April 2013
+rodents
+pHrodo red E. coli bioparticles conjugate
+parasitized red blood cells
+Our book chapter
+TARG1
+non-polyposis colorectal cancers
+1348
+based on the signal level degradation
+26
+Oral disease
+8%
+488
+4-fold antibody increase
+viral quasispecies heterogeneity
+cytokine assessment culture supernatants
+1 mL of 1% crystal violet in methanol
+increased risk of death or worsening disease
+Rosetta software
+Staphylococcus aureus
+0.5 g
+indicator diseases
+HBoV1 prevalence
+S. pneumoniae
+1000 simulated datasets
+OXA-23
+Uninfected cells
+confirmed H7N9 patients
+84.2%
+Infectious disease outbreaks
+to increase DO 2
+arterial
+differences in endosomal escape
+68 an ontology
+lower
+20%
+reduced body size
+16S rRNA gene highthroughput sequencing
+Amplified DNA
+EGD-e loci names
+Hemagglutination of RBCs
+between 4 pm and 8 am
+simian retrovirus 1 -related sequences
+control reactions
+changes in termination codon recognition
+viral replication
+DF1 cells
+genetic engineering
+MINK
+0.793
+Mitophagy
+GI-16
+Unspecific binding and cross-reactivity
+three
+oligosaccharides
+U5
+R a
+Zhoushan Archipelago of Zhejiang Province of China
+Anti-c-myc agarose conjugate
+more intact
+kg/day
+79
+Supernatant
+confocal microscopy
+10 days
+phylogenetic analyses
+2 h
+potential foci of infection
+35%
+liver
+HIV inactivation
+significantly greater
+mutation pressure is the only factor influencing evolution
+rabbit anti-ERp57 antibody and mouse anti-PreGn
+12 days
+Mn 2+
+importins
+PH
+CD8 + T cells
+AM
+hamster
+cis-regulatory
+Further information on research design
+Reaction mixture
+National Centre for Cell Sciences, Pune, India
+XF-hMSCs
+homo-tyrosine
+younger
+protein that contacts the hairpin of the MNV subgenomic promoter
+Site-directed mutagenesis
+Keyboards, headphones, desktops, mice and mobile phones
+Five
+ISG15
+mandatory
+heteroduplex mobility ratio
+41.2%
+morbidity and mortality
+ethanol-induced hepatocytes oxidative damage
+bacterial infections
+giant-cell syncytia
+MMTV and New World arenaviruses
+MN025547-MN026153
+ARDS and capillary leak syndrome
+6
+fiscal resource allocation decisions and poverty reduction
+kidney-lung cross-talk
+pink
+Seven hundred and sixty-three
+discovery
+lower
+Photoshop CS2
+three
+if viruses passaged through closely related hosts showed evidence of parallel genetic changes
+68 of 118
+PEDV infection
+100%
+Alcohol
+80 mL/kg/min
+more recent selective events within a species
+0.2% trypan blue dye exclusion
+35%
+persons >75 years
+NGO1634
+yeast and Drosophila
+51%
+bacterial genomic DNA
+FP-01.1, Flu-v and Multimeric-001
+The slow exchange of the imino N 1 with water
+its new tropism
+expression of wildtype EBNA1
+Italy
+pharyngeal viral load
+elevated mortality
+RT-PCR
+7.6%
+how they were treated and the advice which they were given
+tuber samples
+half-siblings
+100%
+The DL2000 marker and the protein low weight marker
+Afrotropics and Eastern Eurasia
+irrational use
+Unwanted emotional tension
+Bangladesh, the United States, and Canada
+2 to 5 hours
+5.2 × 10 9 PFU/mL
+luminescent signal
+Canu
+predictive performance
+cell-cell contact dependent mechanism
+endothelial cells and arterial smooth muscle cells
+8.5 and 9.5 min
+Visual maps for the spatial distributions of diarrhoea incidence and annual amplitude
+11.5
+reverses both attenuation in virulence and the enhanced frequency of infected cells
+potential circumstances under which an extra conceptual development is necessary
+1956
+groundwater involved in cementation
+$166.3
+Three
+Testing EEG reactivity
+two are known to transmit disease in humans
+sterile PBS
+r j
+raminidase
+daidzein
+phenotype
+Viral dsRNAs
+sinusitis, respiratory muscle weakness, and ventilator-associated pneumonia
+48 h
+network structures
+subnormal magnetic moment
+6 days
+2015
+IPS-1, Cardif, and VISA
+72
+Macropinocytosis
+eukaryotic receptors
+T-cell proliferation
+Discussion B-cell memory
+spontaneous remyelination
+IgG titer
+bluetongue virus
+Lung tissue sections
+Five
+improved performance
+cooperative unfolding of H4b and H5
+aquaporins
+histone acetyltransferase p300
+four
+during mitosis
+four
+binding
+autophagy/mitophagy and mitochondrial biogenesis
+5%
+RSV, rhinoviruses and influenzaviruses
+codon optimization
+RNA 2
+VP40 positivity
+Thioflavin-T fluorescence based assay
+49
+536
+decreased cell-cell and virus-cell fusion
+selecting effective features or feature combination
+whether any of the residues were non-essential
+20 μl MTT solution
+cell-free
+Training in new skills and competencies
+60-80%
+7 hours
+multi-phase Richards model
+Env
+dermis and oropharyngeal mucosa
+automated gel documentation system
+18
+chromosomal DNA
+by releasing a subset of different GFs
+BSA-colloidal gold suspension
+SNARE-Munc18-1-mediated membrane fusion
+autumn and winter
+glycoprotein-1
+10 min
+20 nM
+mouse plasma and breast milk
+60%
+chest
+Wilson and Reeder
+heterotaxy and various genetic syndromes
+placental mammals
+Flaviviruses
+Vascular endothelial growth factor
+Nitazoxanide
+ONPRC Institutional Animal Care and Use Committee
+mechanistic model
+TAF11
+different patterns of variation in the reproduction number
+illness
+500
+free Gln and Glu
+Jagged-1
+Hydralazine and labetalol
+cyp1a1 and cyp2j3
+10 min
+10,000
+translational bias
+infectious pathogens
+David Barker
+5.6.2
+second messengers
+AIDS
+Day 4 or Day 5 safety measure testing
+three
+UFS switching
+comparative Ct method
+30 minutes
+barrier-like
+Amyloid precursor protein
+aggression
+Descriptive
+42.9%
+41%
+Two
+MedCalc
+a mask
+innate immunity
+.
+Permitting greater flexibility in the form of the possible intervention
+many variant types
+those observed in viral genomes
+the corresponding authors
+total, soluble, and insoluble fractions
+qPCR
+pVax1
+proteolytic
+2 x 2 cm
+infectious
+notifiable infectious disease system
+SeaPorter TLR5
+2
+137
+pro-inflammatory factors
+27 μg/ml
+Foxp3 + IL-10 + CD4 + T cells
+additional sites
+GFP
+three
+380
+Nasal oxygen
+how many people were diagnosed with or dying from swine flu
+cynomolgus macaques
+the total number of ILI cases
+28
+core 1 and core 3 synthases
+twice
+AAV2-sFLT01
+live traps
+blood urea nitrogen
+2.64
+Restriction enzyme recognition sites
+61
+four
+tumor cell migration and invasion and macrophage infiltration
+cytoplasmic activity
+agitation, conjunctival hemorrhage, and coma
+Urine
+m-63
+2000 yuan
+RNA molecule
+Frequencies and basic descriptive statistics
+K E~B K b H
+plasma IL-4, IL-10 and INF-γ
+obtaining high-quality actionable data about suicidal behaviour
+single base pairs
+post-operative
+α synuclein proteinopathy
+prompt reporting of exposures and the symptoms of illness
+V
+inappropriate use of antimicrobials
+L:H ratios
+different gene constellations
+viral load
+τ a and τ b
+mouse
+eHEV infectivity
+300
+19
+dispersion
+Peroxisome proliferator activated receptor gamma
+outbreaks of disease
+minimal
+reduced tumor burden
+paddy straw and water
+HepG2 and Huh7 cells
+stability
+binds to and inhibits the Cdh1 activator protein
+Plasmids containing only the GFP or HA gene fragment
+reliable cellular function, individual development, and offspring reproduction
+geographic locality
+H5N1 HA DNA vaccines
+temporal change in gene expression
+reticulate
+SPSS 14.0
+Bovine coronavirus
+Macroevolution
+conserved primers
+proteins involved in the regulation of apoptosis
+Myeloid-derived suppressor cells
+substantial changes in the NMR spectrum
+December 2013
+Arg168
+MicroCal Origin software
+non-pH1N1 febrile illness
+co-infections with other enteric viruses, microbiota and management factors
+RNA-seq dataset
+Protein Data Bank
+EcoRI and PstI
+to balance specificity and sensitivity
+952
+Life Satisfaction Scale
+viral attenuation
+57
+Formal ethical approval from a medical ethical committee
+X-ray crystallography or NMR
+severe septic patients
+viral proteins
+Five
+PAO1
+100
+Infectious bronchitis
+a single virus particle
+Enhanced cmRNA Stability and ACE2 Protein Translation
+blocks
+calcein acetoxymethyl ester
+10 ml of a sonicated media containing 14 C-stearic acid
+recall decay
+6 g
+reverse transcriptase and PCR amplified
+females
+pulmonary
+household size
+further spread of the influenza virus
+2003
+t Ã
+days before and after treatment by INFγ
+anti-GP 1,2 antibodies
+Four
+four
+-578125.270 kj/mol
+to avoid saturation of the mass spectrometer detector
+larval Ae. albopictus
+rCyp
+401
+anti-FLAG M1 agarose affinity gel
+Bias
+upper respiratory infections
+IL-8
+CD11b + CD45 int cells
+protecting endangered animals
+300
+Bi anomalous signal
+vesicular compartments
+galactose
+Diagnosis and treatment of secondary bacterial infections
+observational studies
+increase risk of suicidal behavior
+IIV
+personal, religious or ethical beliefs
+6-8 mL/kg of ideal body weight
+three
+sixfold
+Four
+distance restriction
+O-acetylated sialic acids
+colony forming units
+malaria
+IFNλ4 isoforms
+Age related macular degeneration
+modest increases in sulfur amino acid source
+Room pressurization
+A new sachet
+coenzyme A
+41,947
+30 minutes
+mid-April 2009
+Philip Lambach
+stabilized matrix base method
+anti-acetyl-lysine antibody
+FAS
+phosphatidylinositol 3-kinase
+target cells
+2014
+clearance of RSV from the lungs
+Infection of the mouse thymus by highly virulent influenza
+CCK-BR
+differential
+China
+dominance
+MLV infectivity
+firefly luciferase
+English
+within a half hour
+H1N1, H7N9
+TNFa, COX-2 and NF-kB
+BiNGO
+donors of the Chongqing Eye Bank
+complete loss of lung aeration
+24, 28 and 32h
+new populations
+predictive factors of hospital mortality
+47
+affinity chromatography
+Prospective randomized trials
+retropepsin
+washing buffer
+five
+masking
+computer-actuated solenoid-valves
+The ribs and clavicle
+leukomyeloencephalopathy
+over 50 years ago
+community awareness and understanding of benefits of preventive health
+45-days
+selective
+Myeloperoxidase content
+>11,000
+IL-6 and IL-10
+GDT data
+40%
+according to the above-mentioned categories
+better therapies
+Anti-CEA radio-immunoconjugate anti-bodies
+four
+depressive symptoms
+virus-specific and cell-specific differences in antagonist functions
+influenza development
+Horizontal black lines
+eight
+drug-binding sites, structural components and mutation hotspots
+36 hours
+details
+4.90%
+100 μ l of BriteLite substrate
+greater generic conspiracist ideation
+2016-03-11
+10%
+chronic non-communicable diseases
+PXD015646
+growth inhibition test
+Oseltamivir
+26
+a stop codon
+1.82%
+allergic reaction
+enhanced inflammation
+cell ovarian, uterine and prostate cancers
+low oxygen levels
+unsupervised
+other cellular or viral proteins
+pathogenassociated molecular patterns
+amiloride
+Data-File S2
+Production of IFNa
+36,954
+late 1990s
+doffing practices
+immunosuppressive
+dementia and disability
+ITAF
+2-3 weeks
+Table S1
+59
+93.20%
+total RNA
+Viral RNA
+inhibited or enhanced the replication of one or more viruses
+ICH patients
+Plasmapheresis
+the GPs
+WHO
+The real CPI networks
+Consolidation
+TLR7
+58 %
+computer simulations
+ATF6α and ATF6β
+Inflammation
+cleaves
+Positive end expiratory pressure
+Per2
+Yersinia pestis
+Node color gradient
+a membrane-bound receptor, JAKs, and STATs
+FlowJo
+50.4%
+health workers
+16 minutes
+Chi-square test
+1995
+five
+RPMI
+BmBac
+50%
+interference by the contaminated proteins
+Surfactant Protein C
+Eleven
+integrin-focal ad- hesion signal transduction
+Relative gene expression
+lung function
+four
+germline heterozygous mutation of the GATA2 gene
+Ice-cold HSV-1 strain KOS
+cytolytic activity
+Additive manufacturing
+Dashed lines
+increased production of Th1 cytokines
+collectin
+well-shaped nanoparticles
+histopathological
+likelihood of receiving treatment for scour
+Technical thesauri
+600 days
+prevent a proper immune response
+Cox proportional hazards regression model
+every ten minutes
+rVSV vectors
+12 hrs
+40%
+Stem cells
+protective
+1
+Codon usage bias
+selection of siRNA-resistant viruses
+Burroughs Wellcome Fund
+AM strain
+late spring 1891
+more than 60
+biology/medicine
+desialylation of chicken erythrocytes
+Gene expression
+7.3%
+Bivalent-Analyte model
+TMV RNA
+important for tRNA to translate the genetic code
+H5N1
+Serial dilutions
+group 3 species D. minutum
+modified mRNAs
+Classical and neo-classical economics
+constitutional levels of circulating SP-D
+One hundred and seventy
+Alveolar macrophages
+virus genome replication
+ER-association for an mRNA
+identifying critical residues in escape mutants and crystal structures
+1985
+dimers
+Extracted nucleic acid
+three
+contrasting
+separate
+P
+Patients with non-recovery of Th2/Th1
+Photoactivatable Rac1
+Cox regression
+virology
+T
+Methylene blue
+development of ruminal acidosis
+recombinations and transpositions
+a standard curve of a serial dilution of virus
+semi-artificial and real-world HIV-1 Group M sequences
+reversed
+synthetic TLR ligands
+voluntary or involuntary displacement, and immediate or delayed displacement
+preset variables
+WT
+three
+2009
+naive plasma
+Six
+patient-reported outcomes
+three
+Acute respiratory illnesses
+The immune system
+sequence-specific and sequence-independent
+collaborative
+SRD-12B cells
+diminished expression and secretion of immunoglobulins
+PKR
+active/inactive
+8-hour
+the location of the deletion mutants
+Disassembly of the viral capsid
+rapamycin treatment
+fold back on itself
+cAMP
+fulminant hepatitis
+CBPV
+Histograms of the RF indexes
+15 days
+antimicrobial effects
+a true field test for nucleic acids
+Toll-like receptors
+eco-friendlier
+viral induced cancer development
+the environment
+30 min
+decreasing mitochondrial oxidation
+mice challenged with LPS 4 days after influenza infection
+Data capture concerning bicarbonate infusion and neuromuscular blockade agents
+49.0 nm
+Creb3-Arf4 signaling
+6.5-7.5
+43
+Compound 3b
+p38
+Numbers in brackets
+oncoinflammation
+five
+OASL
+obesity
+purified IPO
+7 days
+children and younger adults
+cHL
+18
+single, double, triple and quadruple substitutions
+eight
+dendritic cells
+a new model having broken-line relationships with the predictor
+double-stranded RNA
+BRT models
+disruption of H5
+heterogeneity
+PBMCs
+L2 epitope-based protein vaccine
+the state and cosmopolitan global justice
+CV disease
+EAD
+1999
+strategy using CPa and CPb DNA and protein
+mechanically ventilated
+3%
+29
+regulation of viral RNA levels and localization
+Relative nucleolar and nuclear localization
+the protective allele
+retention of a highly ordered stair-stepped conformation
+diacylglycerol and calcium
+increased constitutive STAT1 expression and strong STAT1 phosphorylation
+Small molecules
+Ambra1
+National Institutes of Health AIDS Research and Reference Reagent Program
+Personal Digital Assistant
+Twenty-nine
+Oxytetracycline
+S
+Figure 8
+four days and 11 days
+FCGR2B 232I/I
+ultra-high coverage sequencing
+RG
+receptor for human or murine norovirus
+asymptomatic
+CARBON CTRU trial statistician
+G. vaginalis
+cutaneous and mucosal epithelium
+40
+by using a NetNGlyc 1.0 server
+68
+Strepavidin-APC or PE
+boys
+oligodT anchor primer
+Paracoccidioides brasiliensis
+CBP and p300
+15 min
+another epidemic wave
+P. jirovecii infection
+malaria antigens
+60%
+Alternate mRNA spliced variants
+vectors
+Immunohistochemical
+large prospective studies
+each other
+YA laccase
+Stanford University Non-Medical Human Subjects Institutional Review Board
+between 400 and 700 bps
+8,157
+products of the unit cost and the number of test animals
+one-way
+expression of latent genes during the latency stage
+T cells
+DENV2
+G
+40
+3
+CHMP's recommendation
+FAK
+932
+a period of acclimatisation
+four
+exceptional and transferrable immunostimulatory potential
+10 μM
+health services delivery
+mitochondrial membrane
+ambient analyte assays
+non-fermentative bacteria and fungi
+plaque reduction neutralization test
+Leica TCS SP5 confocal microscope
+mutations mapping to bD
+Twenty
+A detailed literature review of available US-specific evidence
+Genotyping of all healthy controls
+1 hour
+weekdays
+extracted RNA
+CD86
+viral culture
+1976
+Asia
+ribosome profiling
+296
+their own poison
+T1a
+Fifteen
+slight modifications
+late viral genes
+Nasal washes and fecal swabs
+NETosis
+R563A
+2017-05-25
+inter-group score
+joint safety events and total joint replacements
+HCV
+acidic
+28
+PCA
+The serial interval
+to protect their respective mature virions
+Arg130
+T17
+cc-by
+45%
+140
+p k
+2-4 h
+Ion One Touch ES
+7 days
+0.6 kcal/mol
+detrimental to antiviral activity
+future opportunities for knowledge sharing
+D
+means and SD
+Hierarchical clustering
+E1
+New HRV type names
+chloroplast translation initiation factor 1
+Mn 2+ -dependent endoribonucleases
+Barbari
+positive selection on the viral population
+Congenital malaria
+acute lung injury
+great interest
+people will invest substantial resources in disease avoidance
+H7N9 viral RNA
+autoimmune thyroid disorders and type 2 diabetes
+12 days
+Reference ranges
+introduction and dissemination of AIVs
+sexual contact patterns
+Categories
+RNA secondary structures
+IL-17
+high titre RVFV nAbs
+CRISPR/Cas
+Genomic DNA
+25 L of RNase A and 50 L of propidium iodide
+the balance between pro-and anti-inflammatory cytokines
+precachexia, cachexia, and refractory cachexia
+right-skewed
+95.38%
+Residue 260 on GP1
+prophylactic
+bulky disordered domains
+cDCs, and pDCs
+Recognition of high immunogenic CD8+ T cell epitopes
+ePCR
+those reported previously
+The US Food and Drug Administration
+GFX™ PCR DNA and Gel Band Purification Kit
+10%
+4 hours
+tumor metastasis and development
+mass vaccination, screening tests using BTM, and active surveillance for PI cattle
+live, attenuated, or inactivated
+Montanide ISA 71 VG
+Thermo-Fisher Scientific
+IL-17 antagonistic therapy
+co-infections with other parasites; and beneficial symbioses
+unpaired Student's t-test
+6.7 hours
+>95%
+Icons
+substitution/codon/year and substitution/site/year
+systematic over-prediction of the number of new cases
+165 ± 20 nm 3
+brain-derived neurotrophic factor
+Telomere shortening
+binds Ars2
+iScript™ cDNA Synthesis Kit
+13
+Olympus Provis
+age-dependent efficacy
+DNA concentration
+transmission probability
+Asp452, Asp469, and Asp489
+intrinsic disorder
+coincidental upper respiratory infections or colonization
+V I
+53
+R t values
+immunosuppressive cytokines
+bronchial epithelial cells
+pressure differential pneumotachometer
+anti-diabetic
+15%
+HeLa cells
+two
+6 dpi
+A nitrogen tank
+histones H2A and H2B
+PGF2S
+39%
+three
+MG756 and MG770
+correlate with known spillover events into and between apes
+strengthening the Th1 response
+Chemiluminescence
+Phylogeny
+Mean shortest path length
+platelet activation
+Chinese herbal medicine
+livestock culling
+declined
+Spectral matching of measured MS/MS data with spectral libraries
+primary fever, coughing, and fatigue
+thymocyte proliferation
+Truncated Tat peptide and penetratin
+FACS
+15%
+exploitation of hydrocarbon
+Epitope mapping
+Analyzed and interpreted the data
+Prf1 2/2 hosts
+PD-1 and CTLA-4
+clinical terms as well as pathogen phrases for the main pathogens of disease
+FACS
+anti-FLAG antibody
+new methods of array construction
+15 min
+semi-adherence of the S2R+ cell line
+Nine
+protein-carbohydrate interactions
+Silica Microspheres beads
+AKT
+β-DG and dystrophin
+cartilaginous fishes
+ACE2 levels
+six groups
+open-wound area
+An effective vaccine against dengue
+herpes simplex virus type 1 and adenoviruses
+taurine
+p38 MAPK
+mule deer
+late pregnancy
+Antigen-presenting cells
+S7
+2
+Four hours
+client-server code
+0
+Beijing
+antimicrobial resistance
+activates a signaling cascade
+Morbillivirus C proteins
+three
+Activated CD4 T cells
+3%
+all bases with low quality scores
+sepsis
+755,999
+50%
+58%
+Thickened ileal mucosa
+6 or 7 days
+99%
+resazurin reduction assay
+ARCA
+real-time PCR
+7.01
+intensity-based absolute quantification plots
+MSF or WHO
+EBV and KSHV
+intact mammals
+antiviral activity
+Disulfide bond exchange
+FatiGo
+antiviral drugs
+50-fold
+lower BMIs
+H
+33%
+Japan
+an isolate from the Asian lineage
+125
+rZH501-M847-G
+S. paucimobilis
+RAF B
+positional clustering
+12 h
+Mitogen-activated
+Growth of recombinant rΔM2-2 CAN97-83
+to evade the effects of interferon
+herbal medicine identification
+24 hours
+HeLa cells
+decreased activity of Cyp3a
+lower
+Classical SELEX
+Alpha-1 antitrypsin
+many preschool-aged children still attend preschools during school holidays
+Phosphorylation by MLCK
+peak viral titer
+when R 0 < 1
+Mesenteric ischemia
+0.15
+dystrophin
+72 hours
+ketamine
+domain III region
+Wild-type IAVs
+black to gray and white
+4
+Stata
+ectodomain
+Phyre2 protein structure prediction webserver
+15
+poly RNA
+Cox-regression model
+Supernatants
+GMP
+AUC and DD
+D and A
+seven
+interaction fingerprints
+24.7 ± 2.1 kg
+an early oseltamivir treatment arm
+two
+PRIDE 60
+6
+low
+Nosocomial influenza cases
+-7.3 kcal/mol
+precise identification of the culprit pathogen
+rapid turnover
+optical absorption
+USP47
+80%
+human
+cellular
+10-50%
+best local estimates
+47%
+mesangial proliferation and glomerular hypertrophy
+day 30 after the first immunization
+17.4 kDa
+osteo-tendinous
+Dot coloring
+DB and GM
+Anguillicola crassus
+unsterile
+0.8 mL of 50% PEG1450
+artificial incubation errors
+Eight
+Nonspecific inhibitor MN-1
+nuclear proteins
+Early antibiotic therapy
+Strand-specific RT-qPCR
+TMS
+two
+Sangon Biotech Co., Ltd.
+optimism/pessimism
+Africa
+top 20 enriched GO terms
+3938
+ginsenosides
+paroxetine
+Gram-negative or Gram-positive bacteria
+PDZbinding motif
+neuraminidases
+Plaque purification
+50%
+black
+P. falciparum
+dysphagia, abdominal pain, diarrhea, and upper or lower GI bleeding
+600
+29
+40%
+x 1
+four
+HERC5
+Ethidium bromide
+an ancestral sequence
+MP-12-R16H/M250K
+1,847
+Biological process annotations
+modules for quality trimming, error correction, assembly, and haplotype reconstruction
+Sequence similarity search options
+US Biomax
+retention goals
+building, storing and querying biological sequence data
+Th1 memory cells
+standard deviation
+Putative paralogs and contaminants
+133 or 202 mg/ml
+high mortality rates
+conventional PCR and Sanger sequencing
+Qiagen RNeasy Plus Mini Kit
+63
+168
+97.3-99.7%
+Enterically administered oseltamivir
+mouse cohorts
+455 and 360
+proteins
+Haemophilus parasuis
+disease dynamic model
+Mg 2+
+24
+JM, RD, JV, GG and PL
+The natural history of pneumonia
+GGT and urease
+One mL fractions
+Manson
+DNase
+723
+Positive end-expiratory pressure
+Samples
+Co-evolution
+1%
+host
+USP18
+their state in the previous time step
+High APA-CHE III scores and organ support
+variables
+CD4 T cells
+QIAEX II gel extraction kit
+cytokine gene expression
+asthma patients with naturally occurring viral infections
+Virus infection and neutralization
+3.5 to 4.5 months
+39 million
+One
+Release from the Apical surface and the Basolateral surface
+Gel-permeation chromatography
+120 h
+Hashimoto's thyroiditis
+regression
+Retrovirus particles
+alterations
+Interferon-α and IFN-β
+2,700
+Diffraction
+demonstrating accountability to funders, legislators and the general public
+with respect to an unrooted tree
+20-cm
+nasal ciliated epithelium
+pharmacologic interventions
+Kidney injury biomarkers
+14 dpi
+Protein concentration of dialyzed samples
+nasal continuous positive airway pressure
+PGRS domain-harboring cells
+156
+factor antigens
+transcription factors
+significant
+693610
+Rickettsia conorii
+42 nm
+MHV
+GenBank
+seven
+to prevent unnecessary animal discomfort
+XendoU
+AR clusters
+submaximal bench stepping
+43
+Hokkaido University Hospital
+β-chemokine
+apoptotic cell death
+FACS Calibur
+SOAPaligner
+P-values
+IFNAR1/2
+priming via viral mRNAs
+1 hr
+Alien pathogens
+Huh7 cells treated overnight with Bafilomycin A1
+a discrete time interval
+cardiolipin
+Ethical approval and patient informed consent
+7
+Bands marked by black arrows
+International Committee on Taxonomy of Viruses
+24-h scratch test and transwell migration assays
+Caspase-1
+Vesicle fusion
+10 min
+inhibition of autophagy
+Supplementary Figure S1
+susceptible population fraction
+confidentiality reasons
+1.61
+98 kD, 64 kD and 50 kD
+1461
+IFN levels in the sera
+seven
+two
+dialectical
+Acetylation of histone
+the total set of recommendations
+vaccine-induced cytokine production
+infectious HCV particles
+20 min
+survival rate
+three
+0.156 to 2.50 mM
+IL-4
+Hematoxylin and eosin staining
+Bound fluorescence
+81%
+operational Bayesian theory
+initiate infection
+2013
+differing infectivity and virulence
+iScript cDNA synthesis kit
+CHIKV-LR
+Sixteen
+DDX60
+thoraco-abdominal sonography and scanography
+2-3
+Iκ Bα
+QuikChange II site-directed mutagenesis
+high density and variety of avian hosts
+3 to 7 days
+a balanced response of both CD4 + and CD8 + T cells
+Dwt
+O i−1
+21 Days
+NSP3 segment of RVA
+Autophagy inhibitors
+field and laboratory studies on mechanical transmission of pathogens by flies
+IFN-l3
+charged residues
+99.6%
+NHIP
+HISAT2 87
+18 days
+hepatitis C virus protein production
+one year
+2-3 %
+5.3%
+ImageJ
+Sub-clinical infection
+virus infection
+18S gene
+Autophagy
+Materials and Methods
+1000mg/L
+CrebA
+Evolutionary adaptation of pathogens
+NF
+cryo-electron tomography
+axonal loss
+The increase in fluorescence
+effective delivery
+65
+143
+490 nm
+anti-inflammatory
+5-α-dihydrotestosterone
+86.9%
+Creb3L3 transcript
+hypomodification
+Institutional Animal Care and Use Committee
+Vsfold5
+159
+reverses IFITM3's inhibition of viral replication
+80 to 90%
+anchors
+standard deviation
+direct acting antivirals
+values and processes that seek to redress the power disparities within institutions
+381
+Contact tracing
+10 ng/mL
+37-mm
+data
+dextran-rich phase
+Lymphopenia
+peak lung cellularity
+CXCR4
+immature, non-infectious, and empty subviral particles
+a single species
+early brain changes
+Euclidean distance
+hypoxia
+enhance
+C. xiaoi
+human DNA
+M-MuLV Reverse Transcriptase
+fever, anorexia, lethargy and diarrhoea
+GenBank
+p ij
+regulation of angiogenesis and the Warburg effect
+VP1 RNA
+a deglycosylated form of fulllength ACE2
+porcine circovirus type 2 and PRRSV or HEV
+0.66
+2003
+42
+3D
+anti-IL8:IL8 complexes
+physical parameters
+cytomegalovirus
+low
+brown hyenas and black-backed jackals
+Cost per test
+GFAP and MHC class II
+Spatial
+Nocodazole
+arthropod borne
+Deleterious hemodynamic effects
+inflammatory
+MV
+Dr Carl P. Blobel
+AM
+cap-dependent protein translation
+total cellular protein
+Non-infectious inflammation
+dogs presenting with dyspnea and secondary pulmonary hypertension
+1148
+T-17β-G
+60 minutes
+Magnetic
+GGGAAGC
+UFS duplex structure
+three
+120
+identical
+45%
+enzyme-linked immunosorbent assay
+seven
+three
+R
+Case #1
+30,000 Da
+IL-9
+Complementary DNA aliquots
+81093
+cap-independent translation
+8.605 nM
+Cysteine carbamidomethylation
+statistically significant
+four differential equations
+two
+infl uenza A
+10
+compound 20
+Western blotting
+PLP standard
+high GC content
+50%
+the square root of the variance
+an inflammatory response
+0.98
+10%
+non-infected DF-1 cells
+non-specific electrostatic interactions
+five
+2009
+Stratagene
+rational and user-friendly
+Cel I/II and terminal deoxy-nucleotide transferase enzymes
+phylogenetic analysis
+early 1980s
+90-100%
+syncytia
+cc-by
+obesity
+increased viral pathogenicity
+more than 50 years
+Continuous variables
+the major secondary structures are conserved
+three
+Methacholine
+proteases
+follicular burnout
+2A and 3C
+chemotactic
+reporter dye 5-FAM
+I/R
+cell survival in CRC
+10%
+bushpigs
+gene expression levels of ALV-J-specific genes
+4-12%
+Kuwait and Qatar
+diaphragm
+Western blot
+4%
+skin cancer progression
+at least twice
+Tight junctions
+106
+death and dying
+at least once daily
+Pathogenic
+road crashes, fires, and general floods
+geographic relationships between patients and resources
+EPX-mAb
+univariate linear models
+2 min
+bat flies
+CTSB/L and SMN isoforms
+Four
+Hypoxia
+respiratory signs
+UPF1
+17 and 16 datasets
+variable cell number
+inflammation and oxidative stress
+HeV viral antigen
+reasonable
+Internalized HIV-related stigma
+therapeutic cancer vaccines
+16
+SVBp32
+it can only reduce, but never completely abolish, endogenous gene expression
+Densitometric
+32
+an imbalance between Doxidants and antioxidants
+outbreaks of the same disease or diseases with similar routes of transmission
+IVC
+blood and tissue cultures
+suboptimal structure detection
+bicistronic luciferase reporter construct
+E64-resistant
+March
+pGEM-3Z/H
+39
+454
+one or more viral encoded glycoproteins
+HBGAs
+retrospective descriptive studies, drug selection studies and prediction studies
+based on the type of SCI
+NMRPipe and Sparky
+Row C
+mucus secreting glands
+surface contamination model
+oral
+50 μL of reconstituted Luciferin detection reagent
+Virus and genome detection
+80%
+mean ± standard deviation
+simple exponential smoothing
+Modification of A37
+combining both groups in outcome analyses
+neutralizing the biologic activity of the cytokine
+December 2019
+Naïve RM IgG
+axon growth and plasticity within the glial scar
+four
+developing a HIV-1 inoviral vaccine
+pleiotropic
+Three
+Study-entry laboratory tests
+10 ng/mL
+low-income countries
+316 mg L −1
+every two days
+depth estimation, posture estimation, and risk evaluation
+plasmid DNA that was not formulated in transfecting agents
+JuncBASE 49
+1995
+≈2-3 weeks
+Adaptive immune cells
+10, 25, 50, 150 or 200 mg/L
+antibody-escape mutants
+UV-C
+Alternative Hypothesis
+NOXderived ROS
+R&D
+upon request
+The probability that an infectious individual infects a susceptible
+KSOS and HYA
+three days
+the means with standard errors over 50 replicates
+five
+67%
+Poverty
+social distancing
+between 45 and 60 minutes
+T3
+Obesity
+reverse-phase
+FMDV
+SL-A
+<10 ng/dL
+Lithium Lithium
+distinct pattern of refines genes discriminating between two classes of leukemia
+in vivo
+straw-coloured fruit bats
+GSE65973
+10%
+Eighty
+extrinsic
+chronic obstructive pulmonary diseases and cystic fibrosis
+Candid #1
+Simplification of the next generation matrix
+Panel C
+NDV-Gag
+Highly elevated levels of various cytokines and chemokines
+ROS production by MDMs
+2 weeks
+160
+53
+close contacts
+SPSS 21.0
+BSR-T7/5 cells
+each assay
+4
+Assessment of clinical, microbiologic, and radiologic response to treatment
+avidin-biotin-immunoperoxidase
+95 per cent
+mortality follow-up at 30-days post-bronchoscopy
+Lymphocytes
+0.2 mm
+broad spectrum antibacterial drugs and antimalarial molecules
+40%
+Indonesia
+6,857,100
+Attenuation of live virus by deletion of IFN antagonist genes
+Apoptotic signaling
+13 M
+Enterococcus and Enterobacter
+S. pneumoniae
+Liver tissue samples
+ReoPro
+cruise ships and airplanes or airports
+significant
+our patients
+framework matrices
+REGN3470, 3471, and 3479
+AKI
+triggers a nonlytic expulsion of bacteria
+q
+antiviral therapies
+WNV
+48 hours
+further investigations for the presence of as yet unidentified organisms
+1011
+phagocytosis
+vaccines
+169
+residual confounding
+acetylserine
+Serologic diagnostic testing
+20 days
+satellite cells
+gut contractility
+purification of the virions
+regulatory T cells
+the weaning process
+VP40
+three
+E. chaffeensis inclusions
+an ensemble consisting of random trees
+50,000
+FCs, DFC, GC, nucleolar vacuoles
+Wilcoxon Mann-Whitney Test
+tens to thousands
+Hundreds of ISGs
+#2031 and #2032
+liver and spleen
+To address this possibility
+Ten
+5%
+83%
+10,000
+MAP1LC3/LC3
+Botulism and atropine poisoning
+what we stated as purpose of the test sets
+0.61
+Phlebotomine sand flies
+768
+Disorder in the inner shell
+experiments
+67
+Infectious bronchitis virus
+RNA processing and degradation
+Unpaired Student's t-test
+similar levels of LC3-II/LC3-I ratio
+Italy
+1%
+Bioinformatics
+IgG3
+Infection caused by respiratory viruses
+host defense against invading pathogens
+external standard method
+Hospital registration numbers
+point of care instrument placement
+further study
+peptidome
+Cleavage of the ACE-2 FRET peptide
+recombinant
+the cut-off
+plasma viral RNA
+≥20
+control standards, standard curves, and reliability statistics
+the interaction with other risk factors and potential confounders
+study participants
+immunoediting
+eight
+pro-inflammatory signaling
+one
+detection and diagnosis of specific bacteria 2−4 and viruses
+N s
+$50% of normal
+peracute fatality
+Peacetime
+previous report
+increased activation of STAT1 and OASL2
+Atg5-mediated mechanisms
+beginning, approaching, clustering, invading, migrating, and transmigrating
+statin levels
+tyrosine kinase receptor c-kit
+antimalarial
+anticipatory stigma
+a vertex
+68
+Eighteen
+10 min
+etiology
+18-20 h
+Plasmid DNA
+15 min
+10,000
+anti-ClfA MAb 11H10 or SAR114
+0.002%
+antimicrobial
+cDNA
+Human health risk assessment
+Polyclonal AD-1-specific antibodies
+60,078 kg
+10%
+IL-18
+GL, GA and CBX
+between wtRNA1 and Mag1-RNA3
+acoustic, light, RF, and chemical signals
+five
+Florida FeLV clade
+hundreds of thousands
+significant reductions in ammonemia
+chronic
+airways infections
+Chitin recognition
+Probe pair specificity
+RSV infection severity
+interval
+Bound proteins
+gastrointestinal parasites
+$20-100 million
+DENV1-FGA/89
+homologous structural alignment
+Cellular and viral determinants
+627
+100 g/l
+four
+Microarray sequences generated from these replicate experiments
+βactin
+step-wise
+Quercetin glycosides
+UL57
+Tissue samples
+over 80%
+54.25%
+192
+glycyrrhizin
+regional compliance and resistance
+diversity of PPE
+a community of more than one host species
+neutravidin agarose resin
+42
+a binary outcome
+quantitative RT-PCR
+1.3
+generalized linear model
+Two-thirds
+Ribosomal frameshifting
+Internet searching
+10%
+when the genomic information structures of model organisms are completely clear
+VK and JK
+exercise
+Anthrax LT
+lack of consensus
+ccdB
+similarities in terms of gene lengths
+selecting the appropriate workflow
+circulation of influenza viruses globally
+prevention, detection and management of outbreaks of communicable disease
+type III IFNs
+metaMS
+RIG-I-mediated antiviral responses
+46
+AutoDock Tools suite
+4689
+intensity
+S-HBsAg and HBcAg
+ARDS
+CD spectroscopy
+alpha-2,3 sialic acids
+indirect correlation between host and pathogen genetics
+1,090
+foreign medical teams
+Carole Baskin
+hepatocytes
+accurate knowledge of the dispersion parameter
+7 days
+Fragile X syndrome
+key
+serum levels of inflammatory cytokines
+The type of domains found in each toxin
+5%
+agent-based models
+unmotivated measures
+relative luminescence units
+growth factors
+Rfam 9 SEED or FULL alignment files
+OTULIN
+their m/z and retention times within tolerance levels
+700,000
+Bayesian
+early 1970s
+p *
+rs12979860
+serum
+Riboswitches
+high positive predictive value
+coinfections
+miR-200a-3p
+data with scattered peptides
+6925
+35
+The contact network
+Empirical
+medical volunteers
+CNS injury during meningitis
+endolysosomal
+Extracted nucleic acid
+measuring the tRNA levels in different time point
+The band containing the RTP
+TAP1-knockout mice
+directs the synthesis of a de novo initiated 19-nt product
+1.7 kb
+epidemiological factors and possible interventions
+increased viral replication
+5 days
+Genome cyclization
+monosaccharide composition and partial glycosidic linkage patterns
+HP23
+Power SYBR Green PCR Master Mix kit
+individual LTZs
+Glycosulphate
+Multi-photon excitation
+SPSS 17.0
+isoproterenol and transferrin
+Monotherapy with ritonavir-boosted protease inhibitors
+Yoyogi Park
+6.25 × 10 6 TCID50/mL
+immunohistochemical
+anti-Actin and anti-Lamin A
+IRDye goat anti-mouse or anti-rabbit
+ethnic differences
+alkaloids
+20
+Breath-holding spells
+respiratory diseases
+O-Acetylation of sialic acids
+components of their cellular hosts
+p65/p50 heterodimer
+children more than 6 months old
+Serum samples
+stimulation index
+methodological issues
+the level of the luminal ER chaperone BiP
+health authorities
+two
+Kibale red colobus
+effector immunity and inflammation
+LDH
+TRAFs
+Rnase-free water
+FastPrep
+RNMT
+12%
+diffuse
+20 μL
+Early echocardiography
+vocabulary and language
+a long-established incumbent strain
+0.1% SDS solution
+moles, bats, shrews, and elephants
+263.24 mm
+40.6%
+fractional modifiers
+replication and transcription activator
+gold and silver
+Seven hundred twenty-four
+consistency of epitope prediction
+hematoxylin and eosin
+13 weeks
+data-logging thermometer
+~2 × 10 −10 cm 2 /s
+oil-free surfaces
+QuikChange Site-Directed Mutagenesis kit
+T4 polynucleotide kinase
+predefined
+rolling-circle amplification
+Vervet monkeys
+viral infection
+GRK2i and BafA1
+proton conduction
+3
+a9 nAChR
+FRET analysis
+ciliated cells, mucus-producing goblet cells and basal cells
+450 nm
+Na + and K +
+vascular permeability
+EBOV growth
+Frequency of use and Room for innovation
+Foot-and-mouth disease
+animal phyla
+30 minutes
+complement-like immune response
+π ij
+ASD patients
+V3V5
+host
+regenerative processes
+viral loads
+cHV68
+40.7%
+HuNoV capsid protein
+Immunoglobulin deficiencies
+diagnostic needs
+purified VACV virions
+dysregulated
+fluctuating glucose conditions
+discrete domains
+Decentralization
+virus-endosome fusion
+between 10 and 100 nM
+1-7%
+correlation of amplification products to the presence or absence of a specific target
+SEV-induced activation of the ISRE promoter
+six
+genetic
+50%
+Mortality
+4.4 %
+TIM-1
+hydrophobic
+E1A-F
+LacZ
+BAL fluid total WBC count $510/mL
+Spatial heterogeneity
+8
+apolipoprotein A-I and haptoglobin
+cell viability
+post-transcriptional regulatory mechanism
+orangutan, marmoset, and gorilla
+alveolar epithelial and endothelial barriers
+30%
+Larger experimental datasets
+immunoblots
+diffuse thrombotic
+every supervisor's dreams
+250
+TRIM38 and TRIM56
+different outcomes
+Tachypnea
+coagulation factors
+194
+N35 -N34 -SGGRGG-C28
+six
+1A 10 and 6A 3 to 1A
+unacceptably high sample horizons
+University of Pittsburgh Investigational Review Board
+C14B1
+one reviewer
+Cut off value
+exponential growth rate
+61
+exogenous soluble neuraminidase
+polysomal
+A hexapeptide motif MYPPPY
+Belgian isolates
+N protein levels
+Alum
+17
+de-identified serum specimens with annotated data
+neuroprotection
+0.1
+ecologic
+TopHat2
+ammonium chloride
+the meanings of Sn, Sp, Acc and MCC
+115
+Formation of atelectasis
+availability of transportation or dependency of family members
+abdominal cramps, nausea, a high prevalence of vomiting, and diarrhea
+eight
+stochastic models
+aspartate-semialdehyde dehydrogenase gene
+STAT2 KO hamster
+dense
+vimentin
+pneumonia
+Clinical
+Blood samples
+G4-ThT complex
+11.5 d
+50 µL
+network modelling
+Th2/Th1
+GRB2
+genomic manipulations
+diffusion
+Dr. Juan Gambini
+HIV and TB
+Sec23a
+strong transcriptional changes in 244 genes
+34 weeks
+an appropriate workflow
+The rate of PERV transfer
+rs12252-C
+.
+SIgA
+RNeasy Mini Kit
+Yes, No, Unclear, and Not applicable
+production of the acute phase response proteins
+PCR-based suppressive subtractive hybridization techniques
+NSP2 expression
+21%
+more research
+GFP
+T cell response
+five
+covariates with sample size less than five
+350
+30 min
+privacy
+MbCD
+92%
+SK1
+74
+deISG15ylation activity
+bind the HIV-1 FSS
+11.8%
+more than 10 weeks
+systemic tumor resistance
+DAPP1 and CARD11
+k
+cap-independent
+to analyze the impact of PB1-F2 expression on host response
+Sera from pre-immune mice
+PP2A
+Polymerase incomplete primer extension cloning
+antiviral
+Varying the force loading rate
+heritable
+75%
+generalized linear modeling
+867
+Trolox and phosphate-buffered saline solutions
+28 kDa
+Cell proliferation
+PBMCs
+B cells
+50%
+TargetSearch and SWATHtoMRM
+erroneous interpretation of the data
+foci of mineral deposits
+83 of 463
+epicardial pacing
+Hsp90
+neopterin
+a memory phenotype
+DAPI Fluoromount-G
+3.33%
+the data generated by the simulation
+potential adverse effects
+FMP-specific CTLs
+Transmission electron microscopy
+Herpesviridae
+Fas
+DEFs at 12 and 24 hpi
+ventricular arrhythmia, cardiac dilation, and cardiac collapse
+the vaccine
+microarrays
+78
+carbonic acid
+The methylation to m 1 A 9
+ectodomain shedding of membrane proteins
+descriptive statistics
+two
+HCV genotype 1a
+10 min
+Urinary
+V H 1-69
+unfeasible TEM and/or NO n measurement
+20%
+>50%
+2016
+UGGT
+nsp1b, nsp2, and nsp11
+4% nondenaturing polyacrylamide gel
+IL28R
+acute-on-chronic liver failure
+high
+absolute humidity
+cellular ROS levels
+CodMod
+4 B-cell-penetrating peptide moiety
+515 mm 3
+2-3 weeks
+exerted an efficient viral replication
+Genome cyclization
+Microscopic
+NK cells
+Highly Pathogenic Avian Influenza
+particle size
+Cytotoxic doses of LT
+95.9%
+volume-amplified magnetic nanobead detection assay
+England and Wales
+6 mg
+timely testing
+virus elimination
+MADP1
+1 January 2009 and 31 May 2016
+Antisense oligonucleotides
+Excel
+tetramethyl benzidine
+a sequence domain
+fluorescent
+luciferase assay
+1-year mortality
+Three
+epitope enhancement
+an equally rapid decline
+patient-controlled analgesia
+.80%
+SCARB2
+relative local rearrangement in the palm domain
+18.0-20.0 g
+extracellular vesicles
+between 24 and 72 hours
+fluorescent
+attenuate IIS signaling
+three
+reemergence
+Infectiousness
+systematically
+global case definitions
+normal 6-12 h
+every 2-3 dpc
+RNA-silencing complex
+low-energy accidents
+620 nm/g
+CD8+ T cells
+BLASTn
+4.1%
+mediates attachment of virions to the host receptors
+Twenty-four hours
+renal function
+PLY
+glutathione reductase
+Twenty-four hours
+1952
+Novel antisense RNAs
+VP1
+2
+chemokines
+targeted therapy with cetuximab
+plant sourced materials
+airborne bacteria
+important
+HLA-A, -B and -C
+EPIFIL
+thirty
+Western blot analysis
+liver
+cellular component, biological process and molecular function
+ABH and Lewis antigens
+GRSF-1
+distribution shapefiles
+20 min
+PPRV-F VLPs
+9.4%
+PI4KB
+histocompatibility receptors
+immature cortical pericytes
+21
+Figure 1
+antiangiogenesis agents
+IgA avidity
+251-292
+three
+Travel restrictions
+contact precautions
+mosquitoes
+Significant increases in frameshifting
+GeneSpring
+illegal poisoning
+multivariable regression models
+bioactivity
+Fibrosis scores and liver function tests
+The T7 RNA polymerase promoter
+spatial dispersal
+nosocomial urinary tract, post-operative surgical site and blood stream infection
+two weeks
+Inhibitors
+Expression of SIRT7
+unbounded secular terms
+32
+1.5 h
+reduced electrostatic screening
+26
+biosafety level -4 pathogens
+Glucagon
+multiple mechanisms against HCV infection
+Acidosis
+chemokine
+21
+118
+Transferrin receptor 1
+GraphPad Prism software
+three
+decreased worker absenteeism
+beneficial or unfavorable
+all the piglet sera
+overexpansion due to bronchiolitis
+25
+2000
+mediates bioelectric responses to NGF
+subtle glycan shifts
+unsolicited
+intermolecular
+PCR-based suppressive subtractive hybridization
+D2 and D3
+143.4 ± 29.76
+products of the expected sizes
+SAM-dependent
+Early viral proteins
+10.0
+preservation of a U-turn motif in E.coli anticodon loop
+17
+supportive care and neuraminidase inhibitors
+over 80%
+bone marrow stem cells
+The nature and quality of air exchange, circulation and filtration
+genotypic changes
+hearing
+47
+statistical
+catB activity
+positive amplification of HBV target genes
+3,000 ps
+Epitopes or antigenic determinants
+15-80%
+Terlipressin
+7-8%
+its solubility
+viral replication and pathogenicity
+Tetraspanin proteins
+SARS PLpro
+Receiver operating characteristic curves
+false positive base calls
+three
+3 H-methyl transfer
+between November and December of each year
+DVG 70-114
+17%
+5 days
+lead inhibitor K31, K34, and 103772
+TRAF6
+134
+total protein concentrations
+Molecular simulations
+15-30%
+C
+Fainting
+splenic and BM
+JNK activation
+comorbidities
+sepsis induced cardiomyopathy
+30 min
+risks to health
+physicians' duty to care
+time-series analyses
+K and G
+severe cases of acne
+RANBP2
+Influenza A viruses
+4
+culture-based method
+blue, green and red
+mucosal/respiratory system
+ABCB4
+Cas12a
+999
+Dr. John Harty
+fixatives
+flexible and single-stranded
+FV10-ASW
+Bunyamwera virus
+sources of bias and heterogeneity
+severe consequences
+10 mA
+13 days
+0.412
+shutting off host protein synthesis
+lys627 mutation
+Fiji software 64
+confocal and orthogonal arrangements
+GSK2606414
+rhMPV/ ΔM2-2 infected cells
+influenza A infection status of the flock
+Plasmid pOFX310
+151
+10 412
+Applied Biosystems 7900 and 7500 real-time PCR instruments
+719 084
+The reduction of the average duration of stay
+Four
+electrostatic
+FMD symptoms
+Six
+Four days
+The infectiousness of second and subsequent re-infections
+China, Indonesia and Ghana
+systemic
+6.0 to 8.0
+58%
+100 %
+Personnel Protection Equipment
+2.2%
+Translation initiation
+blood
+113
+200 nm-240 nm
+suppression of virus endocytosis
+Urine and serum
+Contemporary tuberculosis
+RdRp
+perceived severity of the disease
+bats
+all users' data
+Glutathione
+peptide-ELISA
+platelet desialylation
+symptom onset
+79%
+cell tropism
+weight
+cell lysates
+fibrotic ATS plaques
+reverse-phase high-performance liquid chromatography
+11.5 ± 1.4 d
+nuclear entry
+Data
+the cat owners
+back-splicing
+native-like Env trimers
+Four hundred and twenty-three
+replicate efficiently
+porcelain mortar and pestle
+commercial ELISA tests
+ERK1 and ERK2
+clinical diagnosis
+Mechanistic
+hepatocellular carcinoma
+DR examination rooms
+5
+66%
+D1 ring
+MEGAN V5.2.1 and Mothur software
+RLU readings
+improve the outcome of CAP
+DC electric current
+two
+38
+lighter shade
+Guillain-Barré syndrome
+43
+pack size and Park ID
+Phylogenetic
+highly divergent strains
+DISOPRED v3
+50 μm
+cytoplasmic
+an increased rate of transplant rejection
+Four
+node degree, assortativity, and clustering at the level of triangles
+EBV
+IFITM proteins
+Potent vaccine delivery and adjuvant systems
+470
+one minus the probability of having no outbreaks greater than y cases
+LAMP1 pathway
+co-translational translocation
+the counted number at week t
+human enteroviruses
+Cxcr3
+S. sonnei
+tests
+virus binding to alpha-2,3-sialic acid
+The NCBI Bookshelf
+microbial molecules
+IFN-γ, IL-6 and IL-10
+delay the peak
+PEDV specific
+confounding or reverse causality
+lower lung lobes
+0.25%
+Further investigation
+50%
+1-13
+Activated STAT6
+Subcutaneous
+in depth tissue penetration
+innate immune response
+a hospital admission for an elective procedure
+phylogenetic
+SAL analogues
+Tamil Nadu
+RT-PCR, immunohistochemistry, and in situ hybridization
+Sichuan Agriculture University
+Emergence of intronless interferons
+DnaG-K6AY7A
+hydroxyproline
+dry materials
+S-palmitoylation
+30 weeks
+all eigenvalues
+responsive cytokines/chemokines
+Extracorporeal Membrane Oxygenation
+χ2 test
+pathogens
+SA Biosciences
+Machine learning algorithms
+standard precautions
+complementarity
+mobile apps or online sites
+196
+1,020
+recombination events between or within species
+58%
+seven
+increasing height of the peaks
+20%
+PVL cytotoxicity
+nausea, vomiting and abdominal pain
+mesenchymal
+35.7%
+2%
+9.4
+five
+WHO
+343,5 hours
+CDK4 and hTERT
+expression of viral RNAs and proteins from the transfected plasmids
+23 June
+High-throughput deep sequencing of the HIV genome
+Viennese
+Lymphocytopenia and pleural effusion
+prevention and the treatment of chronic ulcers
+peptide bonds
+38%
+Preparedness against pandemic influenza
+5 mL
+HMBS and HPRT1
+detection of a real outbreak
+R 0
+the supernatant/lysate of transfected cells
+avian
+six
+Oneway ANOVAs
+histopathological results
+an introduction text was presented to the participants
+35%
+0.05%
+membrane-anchored complex
+ResFinder and ABRicate
+UK
+in-house
+three
+VP8
+Sixteen hours
+increasing tissue repair pathways
+β-actin
+94%
+EFSA
+all domain III-specific monoclonal antibodies
+Blood and urine cultures
+16S RNA and the internal transcribed spacer region
+100 ml of the mix antibody-virus
+research
+hospital patients
+five
+Friend virus
+ClustalW
+a detailed description of the samples and sequencing protocol
+eliminate likely pathogens from a single specimen
+Clontech
+calculating more cases than the inputted population
+Data sharing
+Parasite burden
+cytotoxic T lymphocytes
+4
+3%
+negative
+Generalist strains
+A10L and L4R
+HSPG2 and CELA1
+Friedrich Sertürner
+3
+100%
+PhastSystem
+three
+its biological significance
+pre- anti-rabbit IgG secondary antibody
+different numbers or combinations of viral taxa
+speed of evolution and the adaptive route
+Ala152
+four PasAstV
+oxidoinflammatory
+liposomal dosage
+type 2
+≈60-70%
+The level of significance for terms and groups
+human IFN-l4 detection
+after 6-11 d of illness
+αA-crystallin
+Endothelial adhesion
+negative regulators of Th1 differentiation
+2.85 days
+18.3%
+0.76
+Cambodia and Lao PDR
+beta-blockers
+NK cells
+to provide an estimate of the severity of seasonal influenza epidemics
+intoxicating host cells
+four
+Virus staining
+identification of sites of viral persistence
+lack of patient-level severity of illness scoring
+The dimer
+global cognitive decline
+liver, intestine, subcutaneous fat and testis
+sporulation
+IL-10
+HRV species C
+94%
+shorter
+35
+SG formation
+cheetahs
+minor allele frequencies or genotype prevalence
+MalE-type ABC sugar transport system periplasmic component
+Promoter activity
+ARTD1
+31
+13, 17 and 19
+inhibit the function of AC and reduce the intracellular cAMP levels
+Human RAB7
+LNs
+Decentralization
+axons
+Inflammatory bowel disease
+HA-mediated membrane fusion
+10
+203
+Mouse Enzyme-Linked Immunosorbent Assay Kit
+make a final simple conclusion or relate the results of one prototype sequence
+JAC1
+tailored pharmacological and psychological treatments
+highquality reference databases
+0.032 to 1.074 mg ml À 1
+less than 5%
+mosquitoes
+pro and anti-apoptotic
+Poor treatment adherence, inappropriate inhaler use, or depression
+Seqman program
+Japanese
+Ankfy1
+gene sequence
+substantial differences between the 2 groups in the management of dogs
+supplementary material
+glycoside
+99.9%
+3-nitrotyrosine
+Rectangle in C
+antiviral function
+four
+dATP with Go Taq enzyme
+antiviral
+C62S substitution
+Analysis of volatile organic compounds in exhaled breath
+RT-PCR testing of LRT samples
+IL-1, IL-6, and NO secretion
+Fusion of transplanted stem cells with recipient cardiomyocytes
+distinct regulatory mechanisms in different cell types
+logical consistency, subjective interpretation and adequacy
+epidemiological model
+the mass balancing carbonyl moiety is released as a neutral fragment
+extendedspectrum betalactamase producing bacteria
+DNA-dependent
+pulmonary
+two
+the set of genes elevated in all CSF1-Fctreated
+reciprocal
+three
+30 h after LCMV infection
+Three-month-old SPF chickens
+Type II
+subunit vaccines
+Nineteen
+the accumulation of viral proteins
+rosiglitazone
+ERK1/2 and p38 MAPK
+host-protective function
+Purified H5 and H7 binding to immobilized MEDI8852
+Twenty-one
+FGD4
+9A8 mAb
+a conserved sequence within the reverse transcriptase gene
+500-600/min
+coalescent
+vsfold5
+0 to 28
+cytokinesTNF-α, MIP-2, and KC
+Dual-use discourse
+bronchoalveolar lavage
+a proline
+15
+Z proteins
+kinase R
+remyelinate nude axons
+GraphPad Prism 5
+Dr. A. Rudensky
+different clade
+600
+36 hours after challenge
+4500 V
+5 Mbp
+drug availability in n
+nine
+virion release
+27
+29%
+1.8
+prevention of serine-2 RNAPII degradation and RTCs formation
+codon:anticodon pairing
+DIs
+when schools and day care centres are opened or closed
+LO28
+Future studies
+plaque reduction assay
+to better recognize their viral targets
+apoptosis
+IFN1 and IFN3
+concatenated protein trees
+nLC-MS/MS
+Sabin I
+plant survival and performance
+crossing structure elements
+a double fate
+estimates of incidence or prevalence
+Viral RNA
+intentional release
+Area under the receiver operating characteristic curve
+SYBR Green I nucleic acid gel stain
+AGN
+TLR4/RAGE
+contaminated feed or water
+SNARE-Munc18-1-mediated membrane fusion
+25.74%
+gestalt pattern matching
+Creb3L3 transcript
+Plateau pressures
+increased influenza vaccination
+130
+gBlock templates
+pressure
+statistical significance and differential expression
+a strategy
+Glaucoma
+r-gene units with nascent pre-rRNA transcripts
+an IFN inducible gene
+Peptide or protein coding genes
+prevention of the MHV-3 mediated disease severity
+viral titers
+374
+Naïve CD4 + T cells
+repress translation
+viral infection
+Virtually irreversible binding
+3
+42 HI GMT
+highlight uncertainties or to practice a transparent decision-making process
+20X SSC and 10% SDS
+Belgium
+innate immune antagonism
+human immunodeficiency virus
+A421V and A553G
+0.91%
+0.5%
+1.18
+1.5 mL PBS
+correlates of protection
+HCV NS5A and core-NPT
+genes
+immune rejection
+RBV and ETAR
+ARDS susceptibility
+14 to 37%
+Four
+Ccr4
+Sharing of phages encoding virulence or antibiotic-resistance genes
+4-6 weeks
+Apoptosis
+P
+those obtained with the DDX19B mutant protein
+TMPRSS2:ETS fusion genes
+several unidentified orthologous pairs
+6 hr
+76
+11
+producers and veterinarians
+ECFP4 fingerprints
+SARS corona virus
+satisfactory DNA yields
+take part in the ETT
+MHV spike glycoprotein
+3
+Woolf test of homogeneity
+empirical data on laboratory-confirmed seasonal influenza
+drug resistance
+AST/ALT
+virus, bacteria, mycoplasma, and environmental factors
+anti-Salmonella Typhimurium protection
+helix α5
+inflammatory/ immune responses
+Immunoreactivity of these genes
+The level of actin
+statistical
+TNFα
+6%
+31 ± 14 d
+baculovirus
+effective
+identify property-specific toxicity attributes of particles
+45
+off-target Env-specific responses
+qRT-PCR and immunohistochemical assays
+Release of newly synthesized virions
+abrogation of the function of virus-specific CD8 + T cells
+atherogenesis
+QuickExtract
+Ebola virus and Pandoraea apista to human herpesvirus 2
+CnGB1
+more reservoir species than expected by chance
+hepatic lipid metabolism and hepatic carcinogenesis
+multitype
+viral life cycle, host immunological factors, or patient clinical symptoms
+OX40, TCR, CD28, and CD137
+Varicella-zoster
+G36-CD28z CART cells
+the supernatant
+anti-renalase monoclonal antibodies
+networkfocused public management
+CTL, HTL and BCL
+Virus titer
+Dual labeling
+light microscopy
+45%
+horseradish peroxidase-conjugated streptavidin
+effects of subclinical in utero infection
+usage preferences
+Campylobacter jejuni
+cut-off scores
+9,600
+1:1000
+BPD
+The author
+ADE phenomenon
+nasal turbinates, brain, and spinal cord
+Figure 7
+158
+lipid/steroid metabolism
+Saturation effects
+Cat intake number and mixed-age housing
+Gong and Peersen
+anti-N IgG
+p62/ SQSTM1
+54%
+100%
+lateral temporal and posterior cingulate regions
+11,000
+six
+borderline-significant preference of the second hypothesis over the first
+ImageJ software
+Bright-field and direct fluorescence of the transplanted lung
+155
+1,080
+His-Ala
+Chain size thresholds
+Purposive sampling and snowballing techniques
+Curosurf surfactant
+24
+biopsy spots
+GGO with ILS thickening
+constraint
+CDC
+elevated VSV replication
+The obtained best fit
+960
+LBMs
+G_GUC_UCU
+Parvovirus VP1
+images of the deflected PMNs
+guilt
+6
+A branched 2 -Lys-NHS
+Toll-like receptors
+Particulate matter
+54.5%
+26
+differential exon usage
+fetal bovine serum
+SIV Nef antagonism
+one
+isotype control antibodies
+DNA-hydrolyzing activity
+ShelX 30
+ZH501
+Student's t test
+association between BRD and SNPs
+NP/OP colonization with pneumococcus
+lymphoid atrophy
+.
+ratios of pre-to mature miR-122s
+cyclopentane
+moderate
+coordination
+helium
+influenza NP detection
+PB1-F2 expression
+10
+80%
+low to null activity
+non-parametric repeated-measure Friedman tests
+the receptor for poliovirus entry
+0.933
+IFNc
+Quantitative real-time PCR
+tyrosine phosphatases
+antibodydependent cellular cytotoxicity
+FKPB/Rapamycinbinding domain
+glycoproteins gB, gD and gH/gL
+end-point
+template switching
+E7
+an autonomous folding unit
+lipophilic dye DiD
+cellular
+1 min
+E
+absolute agreement
+3CD
+positive serology
+chlorination of the Ahda terminal methyl group
+Over 2000
+ChopNSpice
+β-actin
+Olex2
+76
+Spherical gold NPs
+SPPV-063
+symptom relief management
+R G = 1.21
+One hundred and twenty-one
+TUNEL assay, flow cytometry, and western blot
+hardiness
+SHFV nsp2
+GenBank
+respiratory, gastrointestinal, and urogenital tracts
+120 minutes
+SalI and NotI
+Pierce C18 Tips
+90.52 percent
+co-stimulatory
+FCA
+density-dependent
+male Swiss Webster mice
+28.37%
+therapeutic antibodies
+HI assays
+Infl uenza A viruses
+2.8%
+reduction in cellular mRNA levels
+immunosuppression
+reflectivity data
+Hydrophobic interaction
+HIV-RNA and CD4 counts
+six
+390
+The global budget system
+current vaccine strategies
+0.1 kcal/mol
+urbanization and deforestation
+10 min
+special ruler
+bioinformatics software
+high levels of all immunological genes studied
+platelets and tumour cells
+97 % to 100 %
+Severe trauma
+internal standards
+4
+10,535
+long-term neuromuscular, cognitive, and psychological symptoms
+sPLA2
+7 days
+MDCK cells
+P1
+Apoptosis
+permission to withdraw
+Unphosphorylated IFN-stimulated gene factor 3
+96
+parameters
+Network type models
+interleukin
+DDCt method
+>669 kDa
+1:640
+mediate isomerization of the SU-TM disulfide bond
+cardiac involvement of leptospirosis
+tyrosine kinase AXL
+32
+vomiting, diarrhea, and abdominal pain
+slowing down the infusion rate
+GL
+A. sinensis and S. miltiorrhiza
+Vps3/8 knockdown cells
+skin infection
+14
+exclusion
+rodents
+H5-VN04
+an anti-MPER specific response
+low replicative fitness
+phenotypic
+ATCV-1
+patchouli alcohol
+optimum pH and temperature
+HCV attachment and entry/fusion into the host cells
+50%
+2.9%
+50%
+contact tracing
+at least once a week
+metabolic process
+field-laboratory-bioinformatic protocol
+water/moisture and temperature
+random Gaussian distributions
+Depression
+The PTSD Module of the CIDI
+PK Solver
+Infectious
+PD-1
+sialic acid and galactose
+Asp
+Branching reliability
+retroviral
+blocked the toxic effects of deficiency in the BDNF/ TrkB signaling pathway
+length-dependent
+0.25%
+Mutational robustness
+lower preventative sense
+pressure support
+Just Another Gibbs Sampler software
+McNemar's test
+the tradeoff between call rate and accuracy
+cross-reactivity
+IEDB web server
+the number of model parameters
+Avastrovirus 1a
+Prophylactic
+Cellular lysates
+physiological
+Massively parallel signature sequencing
+Three hours
+the discovery of new viruses
+subsistence agriculture
+immunosuppressive effects
+2-to 3-fold
+GraphPad Prism 5
+none
+Coinfections and age at admission
+>50%
+Cooperativity and positive feedback
+important
+competition
+log TCID 50 / mL
+Plague
+Toxoplasma gondii
+valine
+polyfunctional
+3,173
+MB-003
+non-medical service workers
+daily
+Herbimycin A
+pigs
+ACE2
+n B m
+short-read data
+inter-and intrapatient variability
+granuloma formation
+ZIKV transfer across the placental barrier
+five
+10%
+PCR
+cyclic dinucleotide c-di-GMP
+hematological malignancies
+transparency
+hierarchical
+2.56
+DENV-MINI RNA
+Chi square tests
+Inducible expression of IL-33
+prediction
+three
+the highest MCCs
+Akt
+transcription 1 and STAT2
+10 days
+a t test
+15%
+®rm
+six
+suicide
+to benefit the reader
+electron density
+more than 10
+superoxide anions
+33-50 of ZGP and RGP
+r A
+623
+1 week
+contact intensity
+DENV-2
+994
+three
+tertiary lymphoid organs or ectopic lymphoid follicles
+529
+infection and endocytic uptake
+PPE fit
+swine
+membrane stabilizing effect
+young pigeon disease syndrome
+miRNAs
+poor absorption, rapid metabolism, and ultimately poor oral bioavailability
+nonspecific inhibition and misidentification
+chest
+Glaxo Smith Kline
+Associated bacterial BBP
+sex differences
+5c and 5d
+mathematical models
+19 th century
+malaria
+The long term consequences
+Any medical, psychiatric, social condition, occupational reason or other responsibility
+bird migratory routes
+machine learning-based tools
+Disease taxonomy
+mouse hepatitis virus and rotavirus group A
+Recovery data
+faecal stool
+dialectical
+D-Dimers or FDP
+membrane tubules
+signal loss or an individual leaving
+CBDs
+Enhanced intracellular calcium levels
+8.8610 5 M 21 s 21
+B cell activation bias
+EnVision Multilabel Reader
+Group I causes
+virus load
+Log scale
+viral genome alteration
+The RNA secondary structure
+1.80 ± 0.37
+5 days
+Syncytin-1
+fatty acid binding protein 1
+271
+platelet antigen
+405 nm
+ten
+unfolded protein response
+Global warming
+Supernatants
+urea
+early surveillance and accurate diagnosis
+ALI-cultured primary HBTE cells
+proteinase K
+liver transplantation
+collinear variables
+inflammatory
+Tc17 cell dysfunction
+Gata3
+brucellosis
+pipo
+10.0 g/kg
+B-1a cells
+higher retweet frequency
+on-site wastewater treatment
+Real data
+multiparametric
+cell migration
+flow cytometric analysis
+gel electrophoresis
+MAVS-dependent signaling
+epidemiological
+5-14 and 15-24
+comparative study
+long-term RNAi
+intranasal
+branching in phylogenetic analyses
+Availability of the complete EU-RMP in the public domain
+increased expression of GFT3C4
+Advanced age
+TAR
+pairs
+solithromycin
+nuclear
+MiRNAs
+rapid alteration in expression pattern
+Ononin
+HIV-2 Vif and Vif-SIVstm
+HDV
+anti-GP 1,2
+RanBP10 and cytochrome P450
+early registration
+intra-animal comparisons
+excessive activation of the immune system
+ratesof-influenza-related illness
+ribavirin
+premature translation terminations
+Normal liver
+CD4 and CD8
+low pH
+CD80 and CD86
+unmanageable risks
+an appropriate response
+83%
+Thirteen
+viral protein production and cytopathic response
+anti-thyroid drugs
+135
+cross-reactivity between Group 1 and Group 2
+The clinical outcome
+bibliometric
+virus replication
+60.8%
+twice
+symptoms
+OsSGT1
+ESPs
+coronavirus
+Golgi-resident GPI-anchored protein
+402
+GAPDH primers
+late in the ICU stay
+IFNL4
+x
+the extent and duration of an antimycobacterial therapy
+six
+alcohol-based
+R 0
+RPMI 1640
+non-interventional data research
+NMR spectroscopic investigations
+anxiety, vomiting and lightheadedness
+Embryonated egg inoculation
+LPS stimulation
+black
+Neutrality
+trypsin-digestion adhesion assay
+Constitutively expressed HADs and HBDs
+adaptive immunity against PRRSV infection
+Genotype 3
+viral supernatant
+i F 0 and i U 0
+Inositolrequiring enzyme 1
+IsdB
+HPAI H5N1
+986bp
+to protect and safeguard the well-being of HCPs
+pneumonia
+five
+confusion, ataxia, and seizures
+48 h
+CHO cells
+age
+well mixed
+Bispecific antibodies
+Virus-induced autoimmunity
+mediates host cell attachment and fusion
+public ground transport
+enrich the population of cells expressing GFP
+a standard procedure
+25%
+Flaviviridae
+0.65
+376
+Five
+Acute respiratory tract infections
+1918
+482
+sampling from the LRT
+INMI
+virus-specific antiapoptosis genes
+29%
+multiple APC subunits
+Palmitoylethanomide
+area quantification tool
+a comprehensive search for clinical trials
+Partial haplotype observations
+IFNL
+1-3%
+Let-7f and miR-24
+1088 base pairs
+100
+Grantham value
+Escherichia coli
+reovirus infection
+symptom
+two
+six
+three
+autophagosomes
+vacuolar-type H + -ATPase
+NS2B-NS3 pro proteolytic activity
+nine
+three
+17
+Genome structures of vectors
+chloroquine and desethylchloroquine
+GAMs and translog functions
+LAMP-to-glucose transduction
+P max
+bacterial loads
+males
+30 min
+BL21/pET28 a prokaryotic expression system
+additional power
+ϩ T cells
+Penicillium
+RNA3
+Four
+E. coli DH5α
+14 dpi
+epithelial islands
+Pairwise
+Brazil
+26 March
+3%
+the number of available animals was limited
+P-value
+100-110 kD
+influenza virus
+clinicians within the hospitals
+activate the immune system
+Microbiota data
+alveolar hemorrhage
+309
+College of Agriculture and Life Sciences
+pentobarbital
+100 ng total RNA
+nucleation and zipping
+T cells and NK cells
+another steady state of respiration had been achieved
+fever, malaise, meningitis, and encephalitis
+mammary gland
+Japanese encephalitis virus
+Risk and disease spread
+Providing the limited healthcare worker cadre with appropriate training and personal protective equipment
+M
+germline infection leading to endogenization
+31.38 ± 0.26d
+Hepatitis B virus
+70%
+microcephaly
+detailed spatio-temporal infection surveillance data
+VII
+ApoL1
+0.55
+twice
+an evolutionarily motivated score
+Los Alamos HIV-1 sequence database
+Critical response capability
+Gene-based therapy
+epitopes
+spatial and temporal
+inflammatory
+similarity between the query and template
+CRISPR-Cas
+72°C
+fluorescence intensity
+VSV particles
+genome-wide analysis
+Salmonella enterica serovar Typhi
+Filamentous phage particles
+16%
+100-120
+Autoreactive T cells
+Necrosis and apoptosis
+sequences with no predicted NoLS
+18%
+Hari et al.
+LysM-Cre +/-IFNAR fl/fl mice
+Infectious diseases
+lack of functional open reading frames
+drier
+neutralizing antibody
+Homologous
+Dew point temperature
+full-length clones for each identified gene
+sialocatabolism
+amphiphysin
+branch pattern and branch length
+lung tissue
+K 252
+Bm lymphocytes
+NPC1
+citation links
+5%
+1,920
+HIV
+genes showing V value below the cutoff limit of 0.15
+hold his or her breath
+3-5 min
+seven
+10 mj/cm 2
+ILI-syndrome
+infectious disease detection, assessment, and response
+airborne transmission
+SPSS 17.0
+where any given study would fall on an ethical spectrum
+information about the diet of exposed human and antibiotic use
+mtREV24
+21
+functional magnetic resonance imaging
+anisotropic
+α-chymotrypsin
+a template peptide
+MELD score
+5 d
+CrebA
+HPLC
+127
+13
+absorbance
+influenza
+mixed forest
+skeletal muscle
+motor neurons
+modulators
+20
+Oct-4 expression
+MH, CLD and PJ
+618
+Position Bias
+RNA levels
+GC7
+NdeI and BamHI
+Improved stability
+the disease is so stigmatised
+HopPER
+45 days
+cell-or organ-specific delivery or the complexity of mRNA pharmacology
+donkeys
+25 and 60 kDa
+alleviate endotoxininduced mortality
+increased production of infectious particles
+swabs
+oligo-A complex
+six
+ChAT
+IRES
+the patient or guardian
+hypothalamus
+regulators of innate immunity and proteins mediating transcription
+boosts trophic factor release
+2.45 GHz
+N4
+1 hr
+residual population immunity
+complement
+50%
+three
+140
+human eIF2s subunit
+by searching for their cognate antigens presented by macrophages
+9 dpi
+dynamin
+685
+an MOI of 0.5 PFU/cell of the rescue virus
+peptide pools
+Hand-held
+reduced, but measurable IFN-b
+0.1
+Access to a private car
+normal adult mice
+MODELLER 9v11 through HHpred
+Thermodynamics of eIF4E/14 complex formation
+r
+longterm memory consolidation
+600
+CD4 + cells
+18
+1,785
+a furin site
+34
+roach-allergic asthmatic
+B cells
+Table 4
+alveolar MΦs
+Many studies
+Salmonella Typhi
+6 nM
+Swiss PDB viewer
+Unraveling the common targets of the DEGs
+Written consent
+phosphatidyl-inositol-4 kinase-IIIa
+Untreated and vehicle treated lungs
+12
+two
+the genome types of the same species
+Size-exclusion
+December 2005
+6
+identical sequences and those with undetermined bases
+Ribozymes
+understanding the biology of HCs
+autophagy
+2 ml/kg
+situational awareness purposes
+label ubiquitin conjugation machinery
+600
+280°C
+15 years
+Protein expression from GAL1 promoter
+Synergism
+cattle
+6 to 12 ACH
+movement and infection spread
+17
+methodology
+severe viral hepatitis
+reinforced measures
+Pulmonary suppression of inflammation
+N = S + E + I + R
+23
+A large inoculum
+δ im ··
+two months
+Vps3/Vps8-dependent recycling pathway
+NP-hard
+91%
+12 to 15 days
+antiviral
+blood coagulation and viral genome replication
+ex vivo 3D
+Single particle
+£1.7 billion
+overuse of antibiotics
+Blue tongue virus
+2009
+targeted exome sequencing
+Lungs
+310 to 511.7 K
+50%
+CD46
+negative
+treatment
+IFN-β
+neutralization of PanAd3
+ubiquitination of IFNAR1
+chronic refractory inflammation
+$664 million
+NF-κ B
+39%
+Tbx5
+three
+research, authorship, and/or publication
+Plasma
+90% oxygen saturation target
+ImageJ
+PDIdependent DT toxicity
+108 mg/L
+Tissue sections from uninfected mice
+Arginase-1
+N-glycosylation
+25%
+0.053 PFU
+PI506
+divergent results
+Gram-negative
+1.5 mg/dl
+mediates virus-membrane fusion
+NS3pro inhibitory activity
+1-2%
+Pseudouridine
+one detected species
+four
+correct sequence
+complementation
+nonnegativity
+gastrointestinal and neurologic
+357 ± 94 ng/ml
+geographically distinct residential areas
+Type B Caps
+DEATH domain
+Thirty
+TRS base pairing
+inserted miRNA target sites
+Ideal body weight and body mass index
+Cl-inhibitor
+interactions of proteins encoded by strongly differentially expressed genes
+310
+8 fold
+2.5%
+p#0.05
+CT scans
+heat-sensitive and coldsensitive
+five
+all base pairs of G
+1/K m
+clinical trials
+MJ and JS
+endosomal membranes
+6.7%-20.6%
+cleavable cellpenetrating peptides
+recombinant virus
+310.5 Ϯ 71.2%
+Univariate and multivariate logistic regression analyses
+systemic corticosteroid
+644
+more than half a year
+RIG-I deltaCARD
+EpiFlu
+50%
+four years
+The production of two virion types
+2.6%
+78%
+HD mice
+Figure 1
+anti-cytokine neutralization
+pulmonary epithelium, angiogenesis, and the innate immune system
+Twenty-one
+socioeconomic deprivation
+CRISPR
+86.7%
+new targets for disease intervention
+3,000
+7,000
+0
+linear epitope
+1--3-imidazopyridine
+mandatory controls
+composition of the periciliary fluid
+cell cycle arrest, cell enlargement and resistance to apoptosis
+3000 to 60,000
+earlier initiation of droplet and contact precautions
+development
+abrogated
+Sexual minorities including gay men
+a constellation of genes
+electronic
+mucosal and systemic adaptive immune responses
+up to 8 generations
+dead-space/tidal volume ratio
+worsening
+neurotropic
+membrane cholesterol, the PI3K pathway, and actin
+ILCs
+XRN1
+Statistics Package of Social Sciences
+neutrophils
+one hour
+Streptomycin sensitivity
+consistent
+Slow Loris parvovirus 1
+67
+individual mandatory test and the herd screening test
+Veritas Luminometer
+four
+IFN-γ
+Bluetongue virus
+Bacterial adhesion to the surfaces of cells
+GAPDH mRNA
+pDest14/ N TAILW518
+Table 1
+solvent accessibility and proximity to the sialic acid receptor binding site
+virulence
+cc-by
+features separately from the background and human bodies
+Normal
+4,484,000
+promoter responses to RTA
+6%
+children's health
+0.95
+SZ129
+increased neuronal cell death
+coiled-coil signatures
+bacterial phagocytosis
+Glutaraldehyde-3-phosphate-dehydrogenase
+Trolox
+two
+twelve years
+A Ni-column
+loss of normal function
+18 days
+280-290 days
+axon diameters
+fine-tuning effect
+in-hospital mortality
+26
+Ka/Ks ratios
+18,193
+Zero time samples
+Semithin sections
+polygons
+better mitigation outcomes and minimizing wastage
+50%
+virus growth
+nitrates
+87%
+π
+endoplasmic reticulum-associated degradation system
+56
+expression of the ICP4 protein levels
+Jackson ImmunoResearch Laboratories
+horse-ownership
+Aligning multiple genomic sequences
+Carnoy's fixative
+48 kDa
+nine
+stress related hormones
+weaker
+Serologic testing
+lattice diagrams
+a threshold time
+its accessibility and usefulness in monitoring several physiological and pathological conditions
+72 hr pi
+Apoptosis
+luciferase activities
+a completely novel short protein
+Hemodynamic parameter
+32%
+3
+angiotensin II
+173
+chase additional genes
+231
+therapeutic treatments
+autophagosomes
+PGN
+Microtubule severing enzymes
+substoichiometric
+number of residues
+71 on-going One Health efforts
+Pulmonary function testing techniques
+abnormal enhancement of left ventricular wall
+HTT
+Hepadnaviruses
+Bayesian formulations
+lower temperature and scarce resources
+body temperature
+serum creatinine and blood urea nitrogen levels
+twice
+the need to attenuate each serotype
+knowledge of sequences gained with microarrays
+state of platelets
+30.3 %
+rip 1*
+neuroblastoma
+all windows
+Anti-b-actin
+cDNA
+BG isolates
+Cord blood and mobilized peripheral blood stem cells
+2.4.0
+The light and heavy chains
+eight
+DC-like phenotype
+lower
+63
+gastrointestinal digestion
+between postnatal week 1 and 2
+Bio-Rad iMark™ microplate reader
+autophagy and necroptosis
+JMP 12.0.1
+tuberculosis
+viral and cellular protein synthesis
+incidence of infection
+First, second, and third
+colorimetric
+artificial airways
+hexagon-centered-staraptamer complex
+1-2 months
+>80%
+100 M
+amino acids
+faster
+63 amino acid residues
+34
+10
+Prof. Teraoka
+The binding affinity between the NAG and the receptor
+Cigarette smoking
+Six
+HIV-1 p24 Antigen Capture Assay kit
+21
+6
+70%
+ERK
+RT
+Non-stained cell suspension
+Osawa and Singh
+cc-by
+G1 and S-G2-M
+PicoLab Rodent Diet 20 ad libitum
+increase
+earlier studies
+Extracellular matrix stiffness
+modified wobble uridines
+regional patterns
+TLR4
+1 hour
+flow cytometry
+≈200 kb
+50%
+Six
+mutual
+90%
+Delphi
+10% of the population were fully immune
+effective information
+analysis and dissemination of the results
+E protein in culture supernatants
+FoldX algorithm
+>80%
+14-day
+luciferase activity
+trk receptors
+disturbance of circulating lipoprotein levels and whole-body fat distribution
+Luciferase protein expression
+Spiroplasma mirum
+4.1 mg/dL
+NO •
+early recognition of subclinical mastitis
+reactivation of latent virus
+80%
+high proliferation ability
+inflammatory
+0.9993
+GC content and the mean nucleotide distance
+IFN induction
+one of the best results
+Four
+NTPase/dATPase activity
+peptides and nucleic acids
+The pathway to licensure
+ambisense plasmids
+influenza A H3-specific hemagglutinin RNA
+blood
+microorganisms
+Bloomington Stock Center
+prior
+herpes simplex virus and mouse hepatitis virus
+12 days
+antimicrobial
+Helsinki Declaration
+rofecoxib
+PA
+-11
+HVC model
+MnmEG and MnmC activities not being kinetically tuned
+Luciferase activity of cell lysate
+young to middle-aged adults
+15 µg
+informaticsdriven vaccine design
+MBP staining intensity
+biological
+selection for beneficial traits and against harmful traits
+1184
+unaffected
+SV40
+primary and secondary objective analyses
+metalloproteases M12
+Alveolar
+heterogeneous
+β-actin
+1-3%
+pH1N1 virus
+The percentage of patients who visited a neurologist/ psychiatrist or psychotherapist
+destabilization
+yellow
+low-voltage pulses
+Ten
+25%
+IL-2 and IL-6
+wwPDB
+School activities
+several cancer-related genes as well as a set of genes
+mechanically ventilated
+endoplasmic reticulum-derived vesicles
+Mucus extracts
+anti-PDI or anti-ERp57 antibody
+human and mouse STING
+One hundred and twenty
+HBV clearance or suppression
+several hosts are needed to maintain ebolaviruses
+gp350
+DMSO
+Albany model
+macrophages
+ATG5-12
+2 mL
+confidentiality; listening skills and understanding boundaries
+cluster
+T cells
+upper arms
+PUE system
+at 1:10,000 dilution
+Helper phage
+health care providers
+PSEDOPIPE approach
+functional avidity
+Blunt-ended siRNA
+p.Arg334Lys
+persistently and transiently infected animals
+Safety
+IFI27 and IRF7
+three
+Blood samples
+91%
+CDC
+bacterial infections or sepsis
+85 ± 6.2 g/l
+RPA43
+Nuclear Extract Kit
+alternative vaccines
+3 h
+virulence
+95°C
+Protein metabolism, cytoskeleton, and apoptosis
+10%
+SAA concentration
+MetaMorph 7.5
+Eight
+RT-LAMP
+PRRSV serology or PCR status
+fewer aSMA-positive myofibroblasts
+5%
+188
+hosts of pathogen-transmitting invertebrate blood-feeders
+24
+5%
+crested ibis
+Colorectal cancer
+Pneumonia
+disaster research
+Hopf bifurcations
+sequence data
+three
+A record of GCP training
+a NR
+the profile of proteins captured by the Trx1 trapping mutant
+standard methods
+Predictor independent variables
+specific functions
+NanoDrop ® ND-1000 spectrophotometry
+OD 450 nm
+pKa's
+400,000
+BCL-2 and transferrin receptor of the F81 cells
+adjuvants
+temperature, relative humidity and air pressure
+217
+FOXP3
+light-yellow
+2.83 eV
+Foodborne and waterborne IDTEs
+DAVID
+antimalarial drug-stimulated PfMDR1 ATPase activity
+dUTP
+l i and m i
+125
+demographic factors and distance from Lima
+Vortex with NS
+epithelial destruction
+0.92
+0.1%
+bromodeoxyuridine
+standardised parameter estimates
+0.6%
+QIV
+elevation, latitude, longitude, temperature, light, rainfall
+28 min
+whether the recoding event is responsive to polyamine levels in cells
+The complex structure
+LPBE
+0-7
+her previous quality of life
+asthma and COPD
+APPs
+14
+34%
+5.6-83.3%
+1 N HCl
+$140%
+1918
+a repressor domain
+bi-monthly
+loss of +1 frame FLuc translation
+Ni-NTA spin trap columns
+decreased tube formation
+6 days
+alimentary
+Trizol
+Confocal
+failure of hybridization
+TRIM21 binding
+Serpentovirinae
+whole genome sequencing
+>40%
+to elucidate the molecular basis of TS mutations
+Ordinate
+sparse and focal cell infiltrates
+GraphPad Prism
+novel and highly divergent viruses
+TLR9
+AP-1 NFAT and NF-κB
+Blood transfusion
+synchronising the epidemic trajectories in different population groups
+intermediate
+10 -12 days
+two years
+Full heroin dose− response curves
+51 mg/L of isoquercitrin
+30,453
+178
+BandScan 5.0
+ξ-heterogenity
+hypersporulation
+direct known interactions
+multiple
+different components of the JAK/STAT pathway
+culturally specific or unique emotions
+TGEV
+real applications
+Electrical Impedance Tomography
+ATG5
+Nanotechnology
+little attention
+381
+dysfunctional adipogenesis
+SMR
+Nasal swabs
+UniProt
+100%
+macrophages
+acute fatal
+NEAT1
+SPF animals
+Cross-species testing
+MHCcluster v2.0 server
+Mouse IgG diluted in triplicate
+NetNGlyc 1.0 Server and NetOGlyc Server
+viral immunopathology
+36 days
+a family of small peptides
+HPIV3
+mid-August
+via the inter-molecule disulfide bonds
+PRRSV
+sPD-1
+simple base pair maximization
+NANODROP-8000 spectrophotometer
+⁎ R
+IRESes
+great potential
+viral antigen
+focal augmentation of stretch
+multivariate
+Increasing hydrophobicity of these regions
+proinflammatory
+3.53
+200-300
+short versions of the full-length host proteins
+hepatitis C
+a set of sorted nodes V
+fold change from pre-vaccination
+Timing of the historical influenza season
+HCV core-stimulated CD4 + and CD8 + T cells
+PbrB
+Eight
+lung abnormalities
+Six hundred and fifteen
+CLS scores
+irregularity
+one
+co-evolution between the host and the pathogen
+Real-Time PCR Assay Design Tool
+Saunders and Monet
+ORF4 and ORF5
+Albumin
+recycling endosomes
+severe enteritis, vomiting and watery diarrhea
+English
+nitrated amino acid
+Supplementary Tables S2 and S3
+deep mutational scanning
+OME
+PARP13 catalytic domain
+arboviral
+CD13
+Yellow Fluorescent Protein
+ROS-calpain-ZO-1
+right-sequenced pMD-18T vectors
+230,460
+coelenterazine analog furimazine
+black
+Olympus BX50
+screen set
+Error bars and statistics
+DDB2
+20 minutes
+NHKs
+Knowledge of the suspected pathogen
+Specific long-range interactions between proteins
+luciferase activity
+77.1%
+massive lymphoma infiltration
+4 h
+RV-B
+test paper
+HA-influenza pseudotypes
+50%
+histomorphological approaches
+108
+A mechanism that forces interference between vaccine and revertant
+three
+69 %
+separation and isolation of small particles
+36
+up to 5 days
+SARS
+2-3 weeks
+98
+green fluorescent protein
+environmental guidance cues
+publication of this article
+SsRV-L
+CPU constraints
+Box plots
+0.96
+GIS
+twice
+RefFinder
+100
+Kaposi's sarcoma
+PP1a-96A
+clinical
+one of the principal investigators of the key trial of the intervention
+Calcium influx induced by suilysin
+viral vector-based approaches
+2.6%
+intrinsic disorder
+document-level classification
+moderately
+caspase-6
+2 months
+A. fumigatus
+Hematoxylin-eosin
+Student's t test
+epidemic extinction
+worldwide
+oral immunization
+removed from useable inventory
+5%
+a single protein
+The original tube without the swab
+10 ng/mL
+Total-Gabon
+difference in pathogen load
+Complex I activity and caspase 12 activity
+Alaska One Health Group
+34
+Concentration
+antiretroviral therapy
+90 nm and 240 nm standard calibration beads
+a patient in Hamburg
+immunisation
+AIRS
+HBV surface proteins
+to describe the characteristics of patients with TB requiring intensive care
+RVA and HAstV
+Allelic Discrimination
+500
+14,000 birds/km 2
+external infections
+2
+hNECs
+an uncontrolled inflammatory reaction and an inadequate immune response
+lysosomal vacuole
+53.9%
+quality of data sets
+Hax-1
+FRPP
+new viruses
+higher activation of ERK2
+0.05
+Less than 1%
+mediastinal
+Sequences from the Los Alamos HIV Sequence Database
+71
+US$ 866 000
+Fowlpox virus
+LGP2
+Ub-based suicide probes
+k
+Vanderbilt Clinical Research Center
+Outdoor activities
+testing cross-reactivity of the peptides
+A cluster
+between 2 to 7 aminoglycoside resistance genes
+CD 134
+maternal antibodies
+23
+entry of an antibodycoated particle into the cytosol
+Picornaviruses
+23
+P protein
+Picornaviridae
+branching process
+zero
+β-casein
+flow cytometry
+facilitators
+Cerebrospinal
+Fisher's exact test
+≤16.3%
+HIV-1 Tat
+DNA vaccine safety
+10.1099/mic.0.049601-0
+cell death
+12-19-year
+valine residue
+SCARB2 3 0 UTR
+4 hr
+Adaptive homeostasis
+Sixty-eight
+marked organ dysfunction
+mutation and evolution characteristics
+STATA 11.0
+refusal at follow-up
+Malnutrition and congestive heart disease
+murine herpesvirus-68
+more than
+1-specificity
+Division of Global Health Protection
+virus-specific neutralizing antibodies
+2004
+Lipid accumulation
+that used in SPR analysis
+Mann-Whitney test
+data augmentation
+HIV/AIDS
+Environmental Systems Research Institute, Inc
+hydrological processes
+Brazilian Information System for Notifiable Diseases
+MHV-3
+Disinhibition
+2,734
+compositional limitations and mutational pressure
+their effector functions
+important characteristics of interactions between respiratory viruses and their host cells
+45 minutes
+Birds
+confocal
+35%
+1,482
+hIgG
+spatial heterogeneity at the landscape scale
+Centers for Disease Control and Prevention
+Bartonella
+40 mm Hg
+24
+Ebola virus disease
+viral RNA
+4
+linear regression analysis
+EDTA
+four
+Further study
+staining
+over 50,000
+four
+polycrystalline powders and DMSO solutions
+Pteropus vampyrus
+Hypoalbuminaemia
+A549 cells
+an inventory of fixed features
+484
+1 μg/mL/peptide
+D
+Forty
+allocation of monitoring efforts
+promotes type I IFN signaling activation and decreases virus growth
+Trypan Blue
+cell debris
+Case-based
+ADOA
+13%-59%
+113 g
+it is based on the asymptotic distribution of the LRT
+Training and education
+A second elution in 90% acetonitrile
+DMSO
+successful introduction of new vaccines
+23%
+measures of epidemic risk and severity
+western-blots
+staff from EPHI and MoLFR or other appropriate animal health agencies
+p13-CW FAP
+crossspecies comparative analyses
+37.06%
+30
+pol l-leave
+point mutant strains
+IgG ADCVI activity
+standard conditions
+C57BL/6
+80%
+10
+HP H5N1
+2.14 log 10 cgeq/ml
+exon 6 of the mouse Ifnar2 gene
+85
+The corresponding author
+Understanding and predicting the direction and velocity of an invasion wave
+aberrations in histone 3' UTR processing gene transcription
+PEG-IFN/RBV
+sequence in the virus
+N protein expression levels
+postfusion conformation
+Eighteen
+1 h
+30%
+Hepatocellular carcinoma
+GraphPad Prism
+three
+Cancer cells
+a medication to prevent blood from clotting
+features calculated from sequence information only
+↓ cleavage sites
+CD4
+critical revision
+24
+59%
+stage-specific infectivity with individual heterogeneity
+mDCs
+lower BVDV prevalence
+alcohol-based
+basophils and eosinophils
+65%
+lymphocytic pleocytosis and hyperproteinorachia
+Growth rate post-NDV challenge
+4 weeks
+18-20 hours
+0.05
+HBZ-specific CD8 + T cells
+Social distancing
+Family
+SPIO
+regulatory and clinical trial complexity
+three
+around the mid length of the style
+cell polarity markers
+CHIKV-infected cells
+slower kinetics of light production
+to determine factors affecting the measurement of SP-D by ELISA
+98%
+the National Library of Medicine's controlled vocabulary
+QIAshredder columns
+0.1%
+experimental
+functional
+virulence
+One hour
+kDN measure
+The ability to detect the presence of GMO
+purity
+Five
+5-8 weeks
+28%
+toll-like receptor 4 signaling
+lethal
+2.478 Å
+Counselling on feeding options
+experimental condition
+two
+PARP10 mediated RNA ADP-ribosylation
+36.7 million
+0.110
+mice
+5-fold, 7-fold or 10-fold cross-validation
+Clip compression
+ActD
+mathematical ecology
+LSM 510 confocal microscope
+chest CT
+60S
+Type II
+15,618
+those currently being developed
+SOFA
+log K{d KL
+Grouping pre-diagnostic data into syndromes
+RTCs
+7%
+six
+ADCC
+seasons
+24 h
+position 42 and 214
+Antibiotic resistance
+3-month
+animal host receptors
+viruses
+adipose AGT
+whole lungs
+SCAU1105
+10 to 12 h
+sets with active and inactive inequalities
+REACTOME.db pathway database
+passive reporting
+heterogeneity
+hCD45, CD3, CD8, and CD19
+15 min
+Global fits
+open/accessible chromatin structures
+Generation of ROS
+distributive and other forms of justice
+Prosaposin
+multiplex PCR arrays
+ubiquitinated α-globin
+IMB-1406
+infectious virus being present
+134
+Long probes
+TRIzol reagent
+rainfall
+33.7%
+eastern Eurasian
+aortic volume
+Nine
+30 min at 4uC
+millions
+recruitment of circulating effector T cells
+signaling properties and downstream cellular function
+Fuhrman grade system
+serological
+pCMV ∆R8.2
+four
+prohibitin
+complete protection
+NIS Elements Viewer 4.20
+13 fold
+10% FCS and 5 mg/ml puromycin
+moderate water solubility and oral absorption
+an alternate elongated structure
+75%
+Delirium
+directions from each individual's home where most of the visited places are located
+Preferred Reporting Items for Systematic Reviews and Meta-Analyses
+reduction in the non-protein sulfhydryl moiety
+SUMO binding by Ubc9
+a single arginine residue
+by washing with Ca 2+ /Mg 2+ -free PBS
+the existence of each protein and the S-palmitoylation
+109
+83%
+intravenous injection
+10
+early 1980s
+1.1Gy/min
+full mediation
+Royal Children's Hospital Ethics in Human Research Committee
+adjustment for gender and severity of expiratory airflow obstruction
+specific nucleolar reorganization and altered activities of the nucleolus
+high infection probability
+20 min at 25uC
+culture medium
+high-level soluble expression of PRRSV strain
+M-CSF
+15 ml/well of 35% ethanol
+MPG-8
+their populations varied between clusters and strata
+similar levels of cell death
+FigTree
+haemolytic
+global influenza surveillance
+IFN receptor knockout mice
+Etoposide
+other G4 ligands
+BUNV
+regulate multiple host targets
+proinflammatory
+11.6
+FlexPepDock refinement protocol
+mutation rate
+69% of the genome
+IRF1
+Peptide
+elephants
+DisProt
+strial membrane protein networks
+regenerative medicine
+a reduction in POAF
+30-50%
+42
+66.6-79.4%
+1,178
+20
+LysM positive cells
+hydrophobicity/hydrophilicity characteristics
+so that all networks of a particular letter are the same size across inference methods
+Two
+inflammation
+CCK-8
+0.01
+25%
+mucus dehydration
+40%
+Small ruminants
+Biology
+1/µ H
+59UTR sequences
+CGR-24
+Loss of BRCA2 function
+ten
+Adrenomedullin
+p values less than 0.05
+greater binding efficiency
+infected wild type and IPS-1 2/2 infected mice
+UL39
+West Nile encephalitis and acute hepatitis
+a binary variable
+bacterial, fungal, viral, and parasitic pathogens
+The Picornaviridae Study Group
+EV-D70 and the coxsackievirus A24 variant
+NLRP3 inflammasome pathway
+inflammatory
+statistical comparisons of response rate
+Nine
+antiviral interferon responses from monocytes and DCs
+Trm cells
+Fig. 6
+uncertain
+SeV copy-back DVGs
+40
+homeostatic eosinophil influx
+11,782
+long-term swallowing disorders and aspiration pneumonia
+twice
+4
+five
+60 min
+2%
+5 kHz
+intra- and inter- chain disulfide bonds
+H7N9-RNA
+chemical and genetic
+the number of isolated cases
+sensitivity of the detection methods
+whether nature or nurture were responsible for distinguishing social hierarchy between two individuals
+circularity
+World Health Organization
+GNU Parallel 79
+cysteine codon
+Helsinki ethical principles
+55% and 64%
+30 min
+controlled field experiments and human behavioural risk studies
+neuropathological
+IL-10
+observed data
+Amoy
+DS-Cav1 adjuvanted with SAS + Carbopol
+62.5%
+1971
+15
+to prevent overheating of the photocatalyst-containing solution
+global fitting
+cc-by
+1.2-2.5 million years ago
+endothelial cell viability
+Bradford method
+Glatt Kosher
+infectious diseases outbreak
+shorebirds and seabirds
+apoptosis of monocytes/macrophages
+seeding kit
+cytolytic activity
+Simes p-values
+English
+59,000
+Ten
+NDV positive serum
+high parasite loads
+Genotype
+Infectious diseases
+Expertise in experimental design and statistics
+Candidiasis
+DFC
+.
+Advanced age, increased weight, sepsis, and renal replacement therapy
+1047
+overdispersion
+type I cells
+292
+11.9-fold lower
+nucleoplasm
+cough, fatigue, fever and myalgia
+pro-inflammatory mediators and related receptors
+re-activated
+35 canine parvovirus sequences
+EV71 and coxsackievirus A16
+convergent or divergent evolution
+1 hour
+PK domain
+pleural fluid
+25.2%
+Dynamic adaptive immune status monitor
+influenza A
+CAR-T cell therapy
+OAZ1
+homo-or heterodimers
+April 15, 2013 and April 14, 2014
+less biased estimates
+environmental and asymptomatic transmissions
+Emory Group
+U. parvum
+Type I IFN
+28
+cough
+likelihoods of the three scenarios of zero, low, and high vaccination coverage
+D~6
+Contact tracing
+phosphoinositide 3-kinase-AKT pathway
+autophagy
+5
+ECDC
+Trizol
+0.2%-1.2%
+Monocytes or macrophages and dendritic cells
+Chlamydiae, Rickettsiae, and L. pneumophila
+plasma leakage
+Almost two thirds
+Maxisorb 96-well plates
+activate b1 and b3 subunit-containing integrins
+Interferon-induced transmembrane proteins
+four
+SAs
+fungal
+early detection and intervention
+reduced the viral titer and increased IFNγ expression
+100μl of the substrate solution
+50%
+His37 tetrad
+1997
+Comp#1
+total protein content
+risk perception and coping
+0.001
+chemotaxis of inflammatory cells
+102
+ELISA
+broad, high-throughput binder generation and deep sequencing
+masks
+unit variance and centered
+mechanic dispersion
+daily
+SG protein interactions
+membrane remodeling
+99% confidence intervals
+cellular protein synthesis
+English
+PAXGENE Blood RNA Isolation Kit
+directly touching an infected host or contaminated surface
+bead-based and real-time TaqMan format
+29
+co-receptor localized near the receptor
+16%
+SIRT1
+one half
+trust
+5%
+pre-analysis data
+mortality
+The pulmonary circulation
+reversed
+thermodynamics
+low-population regions in the equatorial North of Brazil
+QIAampMinElute Virus Spin kit
+antigenic drift
+inflammatory cell infiltration, arterial hypoxaemia and pulmonary oedema
+gestational age and gender
+Handwashing-with-soap campaigns
+CD11c hi DC ablation
+10 μ M
+40.2%
+Reintubation due to upper airway problems
+H. Wardemann, Berlin
+Human metapneumovirus
+detaches kinesin from its surface
+proteomics
+48 h
+H244A
+red fluorescent protein
+60.3%
+6
+TCID50
+Vegetation mapping
+an acute onset and high fever
+Seoul National University Bundang Hospital
+IFN
+ecological
+Microarray data analysis
+hypothalamus, pons, medulla oblongata and spinal cord
+comparisons between variants in different clusters
+HKEGAFFLY
+One hundred and ninety
+three
+Fisher's exact tests
+10%
+after passage
+qRT-PCR
+6.78
+microplaque assay
+controls
+TMEDA
+stress hyperglycemia
+P58 IPK
+the nose and tracheal epithelium of the upper respiratory tract
+a more differentiated cell
+DayPattern and activities
+37°C
+NCTninducible -1PRF
+Within the liver
+codons
+Lewis-type fucosylation
+H4b, H5, and H4a/É 3
+treatment failures
+FimH
+FeLV-A
+medians, 25th and 75th percentiles
+70%
+IL-2 and IL-23A
+proinflammatory
+poliovirus
+virus spread
+higher potency
+future studies investigating the pathogenesis of BV
+HIV-infected women received inadequate information about postnatal care
+0.03%
+α-2,3-Gal
+Epidemiologic contact information
+foraging areas
+comp108520_c0_seq4
+Ae. albopictus
+BLASTn and BLASTx
+Lipid raft mediated endocytosis
+potent and complete
+Power
+polymorphism ss469415590
+β
+Cox proportional hazards regression model
+Reelin
+firmly pinching skin and toes with forceps
+Usability of the system
+aggregate the microbes
+porcine specific T lymphocyte lineages
+278
+QPCR
+transfection of HBP1-SiRNA into HUVECs
+four
+Pharmacogenetics
+two
+PKR expression
+cell death
+~53
+endothelial cells
+specific concerns by various federal agencies
+16
+d
+CXCR3 −/− antigen-specific effector T cells
+methanol fixation
+Cytokines IL-10 and TGF-β
+400,000
+nearly twenty years
+Four
+its small population of only 8 children
+MEGAscript T7
+G3BP1 and HDAC6
+siRNAs
+Nasal and/or oropharyngeal swabs
+cryoelectron
+people who seek medical attention each week
+hemorrhage
+Inhibition
+increased phagosome acidification
+flow cytometry assays
+mononuclear
+12%
+four
+3 min
+18 h postinfection
+Isochorismate synthase
+I A
+spurious functional enrichments
+100 ng/mL
+glial cells
+membrane-bound ribosomes
+44
+Sooty terns
+5%
+kilometres
+Electron beam radiation
+host cell receptors
+more difficult
+glomerular capillaries
+Proliferative diabetic retinopathy
+Indonesia
+3-5 days after infiltration
+Viral RNA quantities and cytokine levels
+1,664
+biological
+Inflammation
+precipitation method
+high environmental contamination
+HIS mice
+14, 20
+rejection of the null hypothesis of neutral selection
+Interferons and IFN-inducible genes
+0.19-1.08%
+the reliability of the microarray analysis
+AKT signaling
+TNF-a
+NMIA
+interaction-based
+Inflammation
+gene expression changes of well-established biomarkers associated to cancer progression
+NSs protein
+a good correlation between infectious dose and measured values
+100%
+CD4 + T cells
+KJ722809-KJ723456
+complex regulatory networks
+lack of trust on the potential use of these samples for financial gain
+0.75 h
+medicine
+5.9-6.3
+A 24 Cruzeiro reference sequence
+safety
+participants' estimation of the actual risk for infection
+50%
+tissue damage and diabetes
+non-radioactive cytotoxicity assay
+0.1%
+5-ml
+Immunofluorescence
+ActA and the bacterial phospholipases
+viral antigenic and genetic characterization
+penetrates
+Interpol
+hypoacetylation
+visited affected communities
+SEIR-like compartmentalization
+3-6 days
+devices capable of being deployed at the point-of-care
+12,500
+The bold letter
+spinning inoculation
+PKR and MX1
+drug toxicity
+plaque assay method
+Au 544 Tiop 204
+viral replication
+metabolism
+tightness of airway epithelia
+cell movement/invasion and proliferation
+autoimmune
+S8-600K
+Proteins and urea
+Ferritin
+136
+data by pairs of participants
+Transthoracic
+spatio-temporal
+pre-processing, filtering and assembly
+IL-1β
+10.5 years
+0.24 s −1
+necessary for the interaction
+p67 phox and IFIT2
+Pi
+Immunolabeling
+cycloheximide
+$87 million-dollar
+90%
+The virus stocks
+double mutant LT
+dropped substantially
+PMS/MTT color reaction
+controls
+D
+increase
+percentage of runs when there is a match
+absence of a zone of inhibition
+data bias
+50%
+culture supernatant
+98%
+3,129
+Plasmodium ovale hypnozoites
+37 C
+nine
+SARS and H5N1
+32
+studies
+lifespan, seed size, seed dispersal, height, and leaf longevity
+between 9 -27 %
+double negative T-cells
+ε A and ε B
+Supernatant
+putative TFBSs
+serum concentrations of selected serum proteins
+high R 2 and weak signal intensity
+pressure injuries
+goat anti-mouse AF 594
+Flow cytometric analysis
+68.4 %
+Detailed primers and PCR conditions
+43%
+heart development
+six-month mortality
+high potassium foods
+increased cancer incidence
+Python
+sputum cultures
+West Nile Virus
+DMSO
+1 min
+two
+bicinchoninic acid assay kit
+optimal pH and temperature, the influence of metal ions and the kinetic constants
+rTM
+margetuximab
+Durban data set
+70%
+episodic diversifying selection
+RNA 3D structures
+Retro-orbital pain and low platelets
+unadjusted
+880
+Antibodies at optimal concentrations
+1999
+NA surface protein
+FAT10
+enhances
+six
+pigs
+NLRP3 inflammasome activation
+Carbon tetrachloride
+Λ H
+10%
+three
+prolong survival of mice
+the community clinic
+acetic acid, ageing and hyperosmotic shock
+opposition, aggression or delinquency
+qRT-PCR
+probability distributions that represent our uncertainty about their values
+25
+equine cases
+logistical
+n = k*N γ
+aerosol pollution
+high fat diet mice
+objectives and strategies
+9.7%
+innate and adaptive immunity
+ClC-2
+Inflammatory and structural changes
+quadratic
+Culture media
+V and VI
+anti-Env broadly neutralizing Abs
+20 years
+disabilities or long-term health impairment
+digitalis
+BIAcore 3000
+Parameterization and calibration
+identifying transmission clusters
+80%
+190
+lead to targeted transduction of specific cell types
+WHO and the Joint United
+spinal cord tissue
+250,000 to 500,000
+>2,500
+Matrix metalloproteinases
+acute respiratory illness
+sandwich ELISA
+31
+CellTracker Green CMFDA and Red CMTPX
+individual proteins
+drastic travel restrictions
+Pakistan
+detailed information on AIV sequences
+poor outcome
+gene regulation
+simultaneously infers structures
+2 pmol siRNA per well
+upper motor neuron disease and peripheral neuropathy
+SDS-PAGE and Western blot
+Concanamycin-A
+0%
+Fig. 6
+90%
+10-40 years
+10 7.2 TCID
+dynamical models
+SWB and physiological health
+Histone H3 acetylation at lysine 56
+registers, recall systems, and target population monitoring
+BD FACS TM Lysing Solution
+macro-and microsteatosis
+AFOP
+229
+Contact tracing
+DTNF7
+10,820
+18.1%
+vector
+2 weeks
+5%
+four
+intracellular trafficking and endosomal escape
+Sanofi Pasteur
+A00-R99
+Nairobi, Kenya
+aggression
+23
+manipulation of resources
+re-expression
+Anthrax lethal toxin
+fetal brain defect
+antibodies or neutralizing epitopes
+40 min
+90%
+nuclear, mitochondrial, and plastid
+unadjuvanted
+Dual labeling
+faster spreading
+mAb binding
+390 million
+.01 or below
+CRISPR/Cas system
+TLR3 908T/C Missense
+by using an ABI Prism
+After the first 48 h
+somewhat surprising
+Prepman Ultra
+Harvested cell extracts
+vaccine development
+Temporal and spatial dynamics of RNA viruses
+Three days
+greater PrfA abundance
+Henan and Yunnan provinces
+ORF7
+Medium containing 100 mM KCl
+proline
+rabies vaccination
+480,000
+immunoinformatics based screening of vaccine target
+unwinds
+12812
+viral copies
+R t
+societal
+FUT2
+PCR-based assays
+saltout
+lipid rafts
+Enzyme linked immunospot assay
+intravenous
+luminescence
+Wilcoxon Rank Sum test
+CEACAM1-4L
+72 h after transduction
+SDP and Illumina BovineHD BeadChip
+fungus contamination
+intra-CDS microRNA pairing
+defensins and cathelicidin
+gene expression
+JC replication
+other residues
+1645
+cGAS NTase activity
+damaged
+Table 3
+the actual rate
+SMARCA2
+human cellular and metabolic processes
+clinical and economic
+P. aeruginosa
+70 µM propidium iodide
+HHV-5
+bulbospinal and corticospinal pathways
+all aspects of the work
+Three
+six
+positive, negative, or bifunctional
+pgsA-expressing vector
+activators of ER chaperone genes
+on-line
+The switch between the two regimes
+inferences of transmission events
+TM
+selection
+fold change from pre-vaccination
+Zika virus transmission
+28%
+30
+A medical director for WYD
+CAFE with a random birth and death model
+taxonomic color-code
+RNA antisense purification
+obesity, DM, statins, glucocorticoids, and shock
+γ −1 days
+alternative activation of alveolar macrophages
+RAD tests
+IL-17 + CD4 + Th17 cells
+Bats
+single amino acid substitutions at each CDR positions
+76.4 %
+EBNA1
+2016
+Clinical and laboratory information
+Food
+Frameshifting ability
+heterodimer complex
+cholesterol
+synchronizing the accumulation of the RNA transcript with the production of the partner protein
+twice
+30 mL agar
+21%
+plasma
+124
+malaria and dengue
+the lower airway
+Qiagen plasmid Giga kit
+0.34%
+RNA
+eight
+a flanking sink
+morphological and biochemical changes
+rhinovirus
+elevated
+354
+mol2db2
+HI metrics
+geographical and genetic data
+RTA
+antiviral
+HLA-A2
+HHV-7
+0.9160.02
+Polyploidy
+Agilent oligonucleotide microarray in situ hybridization plus kit
+affect the calculations
+phosphorylation dependent dimerization
+incorrect administration of medication
+classification ability of the models
+2
+gene expression-p62
+6.50 log 10 GCN/ml
+Polio, diphtheria, tetanus and meningitis
+IAV
+p ≤ 0.05
+NFAT
+BioEdit
+10%
+aromatic organic compounds
+NVSL97-7895 and SDSU28983
+Deletion of GARP on mouse Tregs
+nucleic acid testing
+survival and reproductive success
+nonspecific signs and symptoms that overlap with other infectious diseases
+Randomized controlled trials
+Six
+a deliberate smallpox release
+1 ¡ 2%
+Differential
+0.1%
+physiological
+Phase contrast and epifluorescent images
+c-di-GMP
+two-thirds
+outdoor access and intact male sex
+total RNA
+0.2-25 mg/dL
+Peak protein fractions from C
+sub-group building names
+other species or systems
+one or two
+FDR
+principal components
+reverse-transcriptase SuperScriptII
+197
+Base triple formation
+recent human HCC genomic data sets
+under isoflurane
+57
+thin-tailed distributions
+late in the exit pathway of the virion
+mosquito-borne
+gel shift analysis
+Immunopotentiators
+9.9
+downstream
+deposited sequence data
+None
+Patchouli alcohol
+100 %
+Apoptosis
+component loadings
+microarrays
+Anti-RSV IgG
+31.7Å
+LT
+2MEM
+CD8+ and CD4+
+6,191
+ACE2 levels
+3,340
+conformational
+ENaC
+PML
+web-based
+positive selection
+insulin resistance
+a large well
+75-96
+the presence of neighbourhood hubs
+14.3%
+~20%
+18
+injection of brine with different salt content, and tumbling of the muscle
+5 days
+H7N9
+p38
+Cells or supernatant
+immunostimulant
+LC-MS
+larger bottlenecks
+their use by many distinct viruses
+80%
+severe right heart failure
+50%
+14 days
+megapeptides
+Evolution of the polymerase complex
+to investigate this association by community-based survey
+3C
+Toll-like receptors
+biased observed NC values
+NSDV or GV
+3
+health workers at all levels
+mule deer
+RNAqueous kit
+SYBR Green II
+200+ hours
+Ch+2
+Social cohesion
+late passage MEFs
+50μCi/ml
+antigen dose
+Four
+y = 2.33 + 1.37
+defining and specifying classes
+five
+Ala18, Lys19, and Lys20
+technical issues
+99%
+fTLI and fPLI
+quantitative real-time PCR
+nasal, oral and conjunctival vias
+38
+183
+Kar2/Bip
+Δ
+pi-stacking
+Initiation, optimization and discontinuation
+u G and u D
+5 hours
+bỹ
+both clear and subtle allergic asthma phenotypes
+10%
+10%
+dInosinecontaining probes
+aggressive behavior
+Research
+Caselpa
+Cytoplasmic
+specific residues in the A-Box and B-Box
+A greedy search of the parameter space
+cytotoxic
+single-molecule RNA-FISH
+DNase
+DMD exons 2, 5 and 6
+The first integral
+extremely significant
+Aquatic birds
+Dengue, Yellow fever, Zika, and Chikungunya
+high viral infection
+ACE2
+the expression of most IRG proteins
+340
+NCK-8 and D-LANA-14
+accurate IOP monitoring
+cellular signaling
+psychometrically driven, definition-driven and data-driven
+16
+mechanisms of gene expression
+sepsis and RRT
+Sendai virus
+MTS-based cell viability assay
+Patchouli alcohol
+transcriptional slippage
+shared functional processes and gene families
+UBP1B
+discontinuous minus strand extension model
+IFNAR-1 mRNA levels
+A space filling model of the pentamer
+laboratory test orders
+lower
+2.4 billion RMB
+one
+ISG
+nanometer-sized particles can be conjugated with targeting ligands
+one
+79%
+the final counts
+general body condition and survival
+extensive cell proliferation, tissue thickening and reduced elasticity
+56%
+9.4
+1
+production of IFN-c and other pro-inflammatory cytokines
+H5N1
+vif coding sequences
+reduced production of viral particles
+viral antigen
+PET-CT
+Dry Polar
+rosiglitazone
+Ventilator associated pneumonia
+interferon regulatory factor 3 and 7
+1.6
+Jordan, India, Pakistan, Somalia and Tanzania
+enclosure in purple boxes
+within-farm epidemiological dynamics
+118
+degradation
+plasmacytoid dendritic cells
+sequence differences in the CD4 molecule
+safe
+abdominal incision or laparoscopy
+nPH85
+Mastadenovirus
+z20410
+2015
+f S
+TRIzol
+Bio Med Central
+ATP assay
+sensitivity
+PMC, CST, DXC, and LFX
+SIVsm
+Vaccination
+when injected intranasally
+the basic reproductive ratio
+TNF-α
+1-367 days
+Glycyrrhizic acid and glycyrrhetinic acid
+fitness constrains
+the college animal ethics committee
+coughing, wheezing and shortness of breath
+33.5%
+TaqMan W RNA-to-Ct ™ 1-Step Kit
+one month
+CD40
+herpes viruses
+2009
+IFN-β
+dose-dependent
+Two
+KM233145-KM233150
+age
+miRNA and mRNA profiles
+Quantitative real-time RT-PCR
+Anti-Tbet and anti-Gata3
+spore concentration
+C. albicans infection
+SPC staining in airways
+research
+reactive species
+neutrophils
+less than in adults
+detrimental
+Population coverage analysis
+5 minutes
+1000
+penicillin and cephalosporin
+Eighty-four
+put new labels to a historical event
+random temporal networks
+manual
+Antigen presenting cells
+AI
+Axxora LLC
+0%
+function
+Histidine-tagged recombinant protein
+Cut-3
+pDCs, mDCs and macrophages
+zinc protoporphyrin
+NEP
+regulation of
+weak
+480%
+600,000
+cytoplasmic
+faster and more effective treatments
+Nova virus
+CRISPR/Cas9-mediated genome editing technology
+SEDFIT
+less than 0.1%
+100ng of RNA
+reducing stay-time
+pancreatitis
+50-100 million
+The attenuation of possible unspecific byproducts
+density-gradient
+0.99
+RepeatMasker
+identical
+Mesothelin
+37.8%
+bone breaker illness
+UV-fluorescent
+Shanghai Institute of Cell Biology
+MK825341-MK825344
+RIP1-dependent
+three ORFs
+aggressive or sexual contacts
+170 kDa
+SMN2
+qRT-PCR analysis
+5 minutes
+logistics
+recruit RNA exosomes
+IP-10 expression
+0.5, 1, 2, and 5 pmol
+9.4%
+Prevenar™
+Gates and Bloomberg Foundations
+mice
+high-risk behaviors
+specificity determinants
+K63
+PGF and VEGFC
+412
+nosocomial infections, viral reactivations, and sepsis
+an accurate alignment
+a large number of individuals of two main species
+77.0%
+95
+client aggression
+LDH release level
+western blot analysis
+cellular delivery, stability against nuclease degradation, and side effects
+antiviral intervention
+extreme liberty-infringing methods such as isolation and quarantine
+common sense
+interesting histopathology, gross tissue, or laboratory medicine images
+HHT
+CD11b + Ly-6C lo monocytes
+Day 1 temperatures
+cell viability dyes
+enteric flora
+Population ancestry
+expression
+means to those ends
+R06E-J cells
+two
+airborne
+infection in mothers in contact with children in the home setting
+4%
+log-normal
+high levels of toxin accumulation
+miR-1306 may participate in apoptosis
+the first wave
+crystal violet
+45%
+human respiratory syncytial virus
+A standard curve of H 2 O 2
+Berlin
+nine
+Motifs 5 and 23
+small number of cases with a definite microbiologic diagnosis
+five
+RPMI-1640
+ACE inhibitors and beta-blockers
+within the olfactory mucosa of the nasal cavity
+spatial dispersal
+TNF-a
+Uniform proposal distributions
+riverine buffaloes
+OSHA
+virus assembly and replication
+SLC27A2 and ACSL3
+genomics and proteomics
+surveillance studies
+10%
+infection or alternative diagnoses
+cell adhesion and polarity
+multiplies the likely inaccuracies
+interstitial fibroblasts
+15%
+>90%
+development and maintenance
+chemotherapeutic response
+stress levels
+up to 4 weeks
+Heterogeneity
+QIAmp
+2007
+Rotarix
+Extracts prepared from pomegranate peels and seeds
+Events in the 13 languages
+Data that proved to be positively skewed with heterogeneous variance
+inhibits
+knowledge about the efficacy of masks and hand hygiene
+evade certain plant defense mechanisms
+all types of surface waters where a large number of people are bathing
+homology-independent metrics
+JAK tyrosine kinases
+UbcH8
+10
+knowledge deficits
+dissim 2
+Bead occupancy
+HAV
+48 h
+cynomolgus monkeys
+a single initial line beginning with a greater-than symbol
+2 Å
+regulating the establishment, maintenance and reactivation of latency in HCMV
+genotype 1
+pre-induction of Ifit2 in neurons
+Transcriptor first strand cDNA synthesis kit
+lost income
+swine flu
+All authors
+T cell redirection
+469
+limb and respiratory muscle quality
+The uncovering of associations between hosts and pathogens
+BHK suspension cells
+Eight
+Ceramide
+0.1 r c /τ
+recombinase enzyme
+aberrantly active transcription factors
+Rab11
+models of good public health practice
+humidity
+a natural species
+CLAMS metabolic cages
+Motif and SVM hybrid
+Travel time calculations
+cell culture supernatants
+personal health data and symptomatic staff in the work place
+Bile production
+One flow cell lane
+Mantel-Haenszel χ 2 and Fisher exact tests
+twenty
+Eight
+surface moisture, ERMI values, and Group 1 molds
+2
+miRNAs
+Boolean
+restored susceptibility to cleavage
+70S ribosomes
+three
+designing colontargeted drug delivery devices
+binding affinity
+Germany
+Eight
+serum-free medium
+death
+inhibit two evolutionary divergent members of the PC family
+37%
+Codivergence
+Vectastain ABC kit
+more vigorous and multispecific T cell responses
+three
+99 ± 0.5%
+one-third
+cap-dependent protein translation machinery
+Fractional exhaled Nitric Oxide
+A1555-G1595
+mediates spread of viral antigen to white matter through axonal transport
+diabetic phenotypic traits
+Graph-Pad
+E 338
+Belgium
+24 hours
+ELISpot
+randomization
+Influenza virus
+12
+polymerase chain reaction with Taq polymerase
+Heidi Larson
+The presence of a foreign material
+subclinical prenatal ZIKV exposure and postnatal social stress
+10 min
+S7 Fig
+lung inflation and injury progression
+MFL, IM and SV
+increased transmission
+34
+Resistance to influenza
+NVITAL
+fitness
+12
+sequencing
+underestimation of the seroconversion rate
+it missed the strong interactions from R563
+Clearance of apoptotic cells
+IRF-1 expression
+natural infection
+small changes in filter airflow resistance
+M A and M P
+HPLC experiments
+Targeting the genome of HSV-1
+high virulence of JaTH160
+systematic reviews and meta-analyses of non-randomized studies
+Matrix protein 2
+flow switching device
+two
+proteomic fingerprinting
+liver fluke physiology
+automated instruments and robotics-based techniques
+3 weeks
+increased viral loads
+Experimental cross-protection studies
+Respiratory epithelial cells
+suicides
+lamination
+less than 10,000
+EBOV
+legal provisions
+LoFreq
+eight
+defensins
+Functional antibodies to CS2
+possible undetected imported SARS-CoV-2 cases
+30 min
+pathogenic bacteria
+pharmacists
+angstroms
+random-effects model
+BEESWARM
+Prolonged treatment of PRRSV infected cells with 3-AB
+gammaherpesvirus-encoded lncRNAs
+IFIT1, 2, 3, and 5
+2
+15.4%
+four
+vRNA terminus interactions
+formal
+20 seconds
+orbital reduction factors
+A, B, and C
+impaired branching and deficient alveolisation
+0.38
+Taenia solium
+CRS grade 1-2
+Phylogenetic inference from molecular sequences
+mouse
+2.4 Å
+nine
+wild type A3BCTD
+five
+eight
+BLASTP
+10%
+6 days
+higher serum MDA levels
+cross-reactive antibody responses produced by adjuvanted vaccine
+Jackson score
+decreased food and water intake
+3 to 5 days
+non-human primates
+milk yield, growth performance and disease resistance
+5%
+the cell receptor
+four of 194 tested samples
+reduced
+0.0029%
+SYBR Green I nucleic acid gel stain
+broad-spectrum antibiotics
+Interferon-induced proteins with tetratricopeptide repeats
+tRNA shortage
+Whole blood
+to facilitate band size estimation
+145
+33
+microbes and toxins
+metaanalyses
+Reversed-phase liquid chromatography
+bioaerosols
+BV, LH, HA, MS, and CL
+tachycardia and hypertension
+Macrophages
+GIB-V or ViPR
+43.6%
+5000
+disease spread
+disease severity
+canonical PASs, cleavage signals and GU-rich regions
+serological
+hematopoietic
+negative controls
+Greek indices
+Laor, Wolmer, and Cohen
+RBC
+18
+monovalent aptamer combinations
+G
+characteristic
+90%
+nucleocapsid stability
+R 0 for canine rabies
+higher
+fluorescence intensity
+transgenes
+90%
+extra latent subclasses within an etiologic class
+21.4%
+128
+Inhibition of DNA polymerase α activity
+IL-7Rα + ILC1s
+different strategies based on experimental techniques
+Levodopa
+Three years
+elaD
+within the early trailer sequence
+Weighted Least Square with mean-and variance-adjusted estimation
+7 DPI compared to 2 DPI
+viscoelastic behavior
+0.289
+Univariate analysis
+exon-exon junctions
+Ki-67-labeled cycling cells
+background signal
+EBV, HHV 8 or other herpes viruses
+higher level of FGL2 secretion and increased fibrinogen deposition
+adherence of the RBCs to the F-expressing cells
+ENR-BSA dissolved in 0.5 M carbonate buffer
+25
+DNA corresponding to the target peptides
+Mitigating the spread of COVID-19
+Touchdown PCR
+PRRSV
+Student t test
+95
+>11 million
+pCaMPY-3xHA
+66
+partial or total loss of sensory or motor function in all four limbs
+Sel-Plex supplementation
+WNV E protein ectodomain
+mass spectrometry
+LPS-mediated TNF-α production
+β-actin
+five
+The Tulane University Institutional Review Board and the Sierra Leone Ethics Committee
+3 days
+four types of predictions
+two stable DNA hairpins
+South Africa
+Withdrawal
+454 junior next generation sequencing
+k v
+65%
+until the termination of the experiment
+GraphPad Prism
+immunological
+63%
+variable
+Sendai virus
+immunoregulatory and repairing
+SSEA-1 positive cells
+Vero cell line
+accurate information about the novel H7N9 threat
+20
+induction of ISGs
+Acute respiratory distress syndrome
+0.01%
+Y sim and Y exp
+histological
+Compounds 3e-h
+RTA-mediated promoter transactivation and subsequent synthesis of PAN RNA
+48 hr
+low-density lipoprotein receptors
+sponge-like soft tissues
+up to four months
+NFE2L2
+1953
+21 days
+Are you a sexual partner of an individual
+species abundance
+two on the antisense strand and one on the sense strand
+0.38
+Limitations in the optimization algorithm
+flow cytometry
+IFNLR1 loss of function
+3 days
+autumn or winter
+rs1965708-C and rs1059046-A
+monocytes
+Bonferroni-corrected p-values
+HN
+GBV-C database sequences
+supportive
+7 days
+17%
+more than 30
+FALA GPC and YALL GPC samples
+AB828190
+Expression of reporter protein
+Kodak BioMax Light films
+different stages of the life cycle
+228
+mobility
+1 h
+Five hundred
+Injection of the toxin
+B i and b ij
+reducing the susceptibility of previously exposed individuals
+10 to 78 million
+8.99 pg/ml
+Overall infections
+V3
+six
+splicing of mRNA
+3-5 days
+7 %
+drug diffusion, the PLGA surface and bulk erosion or swelling
+DAPI
+PRISM version 5.02
+three
+Commuting
+5-10%
+Intersection and Union
+firearms
+antiviral plus immunomodulator
+metagenomics, transcriptomics, microscopy, medical imaging and mathematical modelling
+two weeks
+broad-spectrum antiviral agents
+MAbs
+orange
+ADCC
+fitness drop
+The concept of epidemiological confirmation
+a locus obtained by merging two SNPs in LD
+Any descriptions too long for the figure legend
+ANC follow up and feeding option counselling
+vivax
+an explicit formulation
+Adaptive immune responses
+Whole blood
+epithelial barrier damage, exaggerated innate immune response, and cytokine storm
+amyloid
+DMEM
+glycerol, graphite oxide, and citric acid
+exopeptidase dipeptidyl peptidase 4
+32
+31.03%
+CL-2 and CL-3
+PFV Env amino acid sequence
+SADABS
+consensus scores
+higher
+a form to collect online epidemiological data
+Culture supernatant
+14,191
+enhanced transcytosis of HIV-1
+35
+monitoring for signs of postvaccination TMA
+diverse and unpredictable
+activates PI3K-, AKT-and mTOR signaling
+Vero E6 cells
+The entry of viruses into cells
+more severe hepatic tissue necrosis
+Five
+The interface between subunits N 0 and N +3
+improving health care
+1000
+clear steps for mitigating the risks presented by imported wildlife
+The nucleolus
+eleven
+liver sinusoid
+A volume of 256µg mL −1
+Livzon Pharmaceutical Group
+80.3%
+RNA editing
+perturbed signalling
+strategic RA and case-based RA
+$4,804
+blood samples
+PPRV H protein
+eight
+Cell media
+IFNL responses
+6.7%
+ΔG est,i
+77%
+four
+TABA
+natural autoAbs
+VSVs bearing uncleaved EBOV GP
+sleep disturbance, sexual dysfunction, and dizziness
+IEDB prediction server
+MIV boost
+flow cytometry
+0, 1.465, and 0.414
+position 78R
+resource allocation under pandemic preparedness plans
+GraphPad Prism 4
+epidemic
+day 3 or day 6
+Northern blot
+Rounding up of nuclei
+Reverse genetics
+viral clearance
+26 hrs
+1234
+pseudoknot
+generalized immunosuppression
+Induced fit and conformational selection
+14
+host nutrition
+meat or milk, skin, and wool
+214,500
+IRF-7
+interferon regulatory
+phenol/chloroform extraction-ethanol precipitation procedure
+knowledge of r and of the distribution h
+integrin α5β1
+HP-RNase
+1 × 10 5 cells/mL
+40%
+2-fold diluted supernatants
+Public health strategies
+5 μL
+pleiotropic
+haemoglobin
+proinflammatory responses of neutrophils
+Table 2
+7%
+Twenty
+12 hours
+transmission by airborne particles
+a widely accepted score
+heuristic evolution procedures
+The reassortant virus
+three
+16
+milk
+PCR-based diagnostics
+ROC curve
+BD Pharmingen or Biolegend
+24, 48, and 72 hours
+32
+lipoxins
+three
+ISG12-2
+greatly increase FIV prevalence
+a non-ionic and copolymer stabilizer agent
+host ribosome
+scoring
+sequences covered by the identified peptides
+natural herbs
+treatment
+modest
+P.-S.Y. and A.-B.F.
+inexpensive generic drugs
+HIV-1 entry
+PCSK
+The number of sections examined
+FOXP3
+18%
+112
+19
+non-replication of the findings
+health and exposure science
+Increased vascular permeability
+inter-individual differences and increasing age of the birds
+infections
+12
+GEEs
+inadequate
+the products of the catalytic reaction
+cc-by
+81
+Fisher's exact test
+86%
+two
+Nigeria
+96
+50 mM HEPES
+Infection
+27%
+a diarrheic piglet
+passes the configuration information to the parser bean
+differs by age
+autophagy-independent
+viral protein traYc and diVusion of viral infection
+DF-1 cell monolayers
+immune transfer
+Methicillin-resistant Staphylococcus aureus
+tryptophan
+SuperScriptH III First-Strand Synthesis SuperMix
+homogeneous nanoparticles
+four
+interpretation of documentation within the medical record
+one month
+interval distribution g with density g
+HCV pseudoparticles
+T cell lines
+data pooled from three independent experiments at each protein concentration
+18
+a decrease in enthalpy
+Bid
+RIG-I, MDA5 and TLR3
+HIV-TRACE
+cardiopulmonary resuscitation
+ρ I,R
+Negative SHAPE reactivity
+two
+chemically modified antisense oligonucleotides
+very limited
+Odyssey infrared imaging system software version 3.0.25
+UPDRS, SCOPA, or the PDQ-39
+PLINK
+Self-assembly
+>80%
+FMD
+a list of multiple gene products
+targeting CNS recovery following injuries and diseases
+pressor
+P and L proteins
+Receiver-operating characteristic curve analysis
+SRR1
+healthcare delivery goals
+32
+epithelium damage
+identify a set
+IAV, PPV, FCV, and PRRSV
+naïve cells
+events
+139
+Q n
+Other viral and bacterial etiologies
+Toren Finkel
+TargetScan 7.1
+neutralization
+epithelial or endothelial subsets
+calycosin-7-β-glucoside
+microenvironment
+anionic
+NP
+cis-cleavage activity
+HMGN2
+active and inactive conformations
+Phagocytosis
+VEGF
+wild-type viruses
+qPCR
+54%
+different routes
+Application of this procedure
+Seventy-five percent
+Ebola
+HCV replication complexes
+beet western yellows virus
+Official laboratory networks and research consortia
+$25
+46% to 64%
+Demographic population, removals and additions
+1%
+Spearman rank correlation analyses
+an improvement in AHR parameters and reducing specific IgE production
+two ERAD associated genes
+HIV-associated dementia
+ethical guidance and immediate HIS study design
+GAPDH mRNA titers
+functional peptide 11-mer
+Microglia
+proteolytic
+Goat-anti-rabbit IgG Alexa Fluor 594
+5-7 days
+Surveillance programmes
+autophagosome formation
+Four
+Long-term spatial and temporal scaling patterns of human movement
+Prevention before illness
+increase public interest in, and support of, research
+proinfl ammatory
+IkB degradation
+Pharmacists
+geographical
+43
+Comparative Ct method
+Karyopherin-α1
+anatomical irregularity of the foot and environmental conditions
+World Health Organization
+5%
+toxicity and emergence of drug-resistant parasites
+NS1, NS1-70K, and NP1
+FV2 protein
+H77-S
+informed written consent
+Salmonella
+their legal provisions
+MimoDB
+235
+400
+Haemagglutinin
+kidneys and, most of all, the intestine
+Interferon alpha
+blastx
+complete coding sequences
+all tested time points
+monkeys
+transmission of higher molecular weight ions
+TIB
+X-ray crystallography
+wider clinical studies
+spinal dislocation
+59%
+lung cancer
+monocyte-derived dendritic cells
+Pooled ORs and CIs
+Invitrogen Canada or Wisent
+Table S5b
+human immunodeficiency virus
+dietary amino acid homeostasis
+anti-CD3 antibody
+X 100
+two
+ER-association for an mRNA
+85%
+EVs
+Hsp70
+0.5 mCi of 3 H-methylthymidine
+PB2-701V
+810
+Blood
+25 TCR-like antibodies
+canine plasma protein
+NS5
+streptococcal toxic shock syndrome
+increases
+62.35%
+increases production of the acute phase response proteins
+The relationship between RG and BestKeeper
+Attempts to quantify such betweenstrain variation
+negligible
+rather well characterized
+allows the secondary structure of a given protein to be predicted using only sequence information
+3 μL of oleic acid
+lower titres
+Table 1
+substantial
+Sepsis
+Pneumonia
+Pancreatic islets
+PKR-induced stress granule assembly
+17
+a novel nucleic acid isothermal amplification method
+Twelve
+epithelial cell-like
+bacteria, viruses, fungi and parasites
+seven
+3
+1:4
+twenty-four
+Platinum complexes
+Biomarker
+antimalarial
+37,38
+excluded
+500
+IBV
+two fold
+32
+flaviviruses, influenza, and barley yellow dwarf virus
+TgM83+/−
+mitochondrial production of ROS
+C a
+co-purifies RNA and DNA
+98,000
+10% normal donkey serum
+October 2006 to February 2007
+AS-136A
+Infected cells
+IL-17-targeted immunotherapies
+MHV-3-induced fulminant hepatitis
+ICIs
+2019-07-10
+70 years
+one hundred and sixty
+data from functional HA studies
+HTNV-induced IFN expression
+activates protease
+23
+DAPI
+5.1 AE 0.4%
+EDTA
+reverse genetic method
+qRT-PCR using discriminating primers
+antiviral
+More than one criterion
+Contraction-induced injury
+PELOD-2
+proinflammatory signaling
+14 days
+Two-hundred
+robust expression and antiviral activity
+biphasic curves
+carotenoid biosynthesis
+reduced
+lack of immunogenicity above that seen with the placebo
+location-dependent
+PCR purification kit
+the spread of infection
+epidemiological data
+a critical recognition element for host proteins
+a value of 1
+p300/CBP
+pneumococcal
+0.5%
+translational elongation
+Complete polyprotein open-reading frame sequences
+by increasing the inoculum size
+protective
+LIBSVM package
+mixed growth
+DSMZ
+Anti-Flag beads
+the time when the serum was taken post disease onset
+Early evolution and diversification of nematodes
+Plasmid standards
+MP-12-derived NSs mutant viruses
+protective
+separate randomisation tables
+Fixation of mutations into nucleotide substitutions
+non-survivors
+sRAGE
+palmitoylation
+DNA editing
+inactivated by 1.74 log CFU/g
+Okadaic acid
+a defined set of information on the patient history
+A study clinician
+RF
+SOCS3
+six
+how to interface with public health services and resources
+Basic examples of variation
+60 minutes
+agarose gel electrophoresis
+ACT and the AQLQ
+Jugular blood
+binding of antibodies to intracellular, membrane-associated E1E2
+specific ligands
+mRNA and protein regulators
+Glucocorticoid
+median time from data collection to data entry into central database
+1999
+Dr D Piston 46 and Dr RY Tsien 47
+2.2%
+10%
+pulmonary aspergillosis
+7.7
+GRN mRNA stabilization
+PandemrixH
+Fig. 4
+L allele
+52%
+10 3 copies/ L
+Eight
+responses
+QArray2 microarray spotter
+ColorPhylo
+Receptor-binding
+nine
+20
+four
+tissue-specific targeting
+infection
+extended and flattened
+IFNAR1 phosphorylation, ubiquitination and degradation
+fresh fecal samples
+Diagnostic tests
+Antiviral T cells
+vitamin B12 and D depletions, hypothyroidism
+12-20
+proteomics, transcriptomics and other-omics data
+HA
+HBV and HCV
+a naturally occurring product found in a variety of fruits and nuts
+VSV*DG
+one
+PyMOL
+TDL-Vent
+TLR4
+Percoll gradient
+envelope incorporation onto virions
+Parameters b 1. to b 4
+DOPAL
+occurrence
+Influenza
+inflammatory
+glucose moiety
+526
+flawed
+AcmA anchor protein
+neuraminidase-inhibitor chemoprophylaxis
+to facilitate detachment and spreading
+K685 integrity
+12 hrs
+Fecal samples
+Seven
+research materials
+Qiagen RNeasy Mini Kit
+T-705
+data-driven modeling
+four
+multiplexed
+Supernatants from infected macrophage cultures
+solvent
+regulating the cytoskeleton under oxidative stress
+Glya68
+translate specific mRNAs during exponential growth
+evaporated sample
+transmission via aerosols
+as soon as the diagnosis of pneumonia was reached in the emergency department
+47%
+Sequence analysis
+cell phone data
+knowledge
+Hand searching of online journals
+β-barrel
+antibody levels
+a sequence coding for the 24 VP5 C-terminal residues
+extremely rapid transmission
+D199N
+interferon sensitive response element responsive promoter
+2002 to 2004
+feces
+16-18 mmHg
+TRPV1
+to recover the viruses and obtain the cell pellet
+The mucosal immune system
+LAVs
+7a
+southwestern
+CHD
+Representative nanoviruses and geminiviruses
+parvifoliquinone
+U ltraviolet germicidal
+membrane fusion
+nitrocellulose membrane
+transportation routes
+IAV, RSV and HRV
+natural
+CD31positive
+a solution of L 2 H in Et2O
+a γ type RNA-directed RNA polymerase
+TGF-b 1
+1 mM IPTG
+those of the birds to IBV
+identify, consider and report cases of potential concern
+mucus
+14 days
+MG, TO and DIR
+Microbeta luminometer
+polyclonal/mAb
+Helix elongation
+13 474
+current spillover surveillance efforts
+protecting chickens from lethal challenge of HPAIV H5N1 infection
+RT 2 Profiler Array Chicken Innate and Adaptive Immune Responses
+membrane proteins and lipids
+U UUC UUA
+anti-infiammatory
+IL-6
+limited quantity of blood samples available
+143
+Bowtie
+10 %
+13.48 ± 1.93 µM
+cc-by
+SINV Toto1101
+three
+Agouti
+migration and proliferation processes
+LTZs
+C-terminus
+75 mM
+gene ontogeny
+One hundred and forty-four
+Colony Collapse Disorder
+Reed -Frost model
+disease severity
+24 hours
+impaired gas exchange
+Viridans group streptococci
+Novel protection and treatment options
+cells with fragmented DNA genome
+fLAMP
+sympathetic activity
+symptomatic infection
+30%
+The ratio of infectious/total viral particles
+the number of MG participants
+disease detection, control and prevention efforts
+cellular DNA damage
+GW409544
+uncontrolled vascular leakage
+state anxiety
+national parks
+education and information
+spotted hyenas
+four
+γ
+body sizes
+His6 tag
+age and LOS
+Dell Precision™ T5500
+IFNβ
+22
+leukopenia and marked thrombocytopenia
+cigarette smoking
+The model of the HCMV gB structure
+ACE2 enzymatic activity
+Western blotting of whole cell lysates
+simplifies preparing an R project for launching on binder
+an ecologically determined community-level robustness
+Incorporation of Env glycoproteins into virions
+liver
+how well a gene is being translated
+ZL QZ
+H9N2 avian influenza virus
+intracellular compartments
+cell surface HS
+TLR3-deficient mice
+decreased 4-fold
+dried purified product
+hierarchical
+CT
+flaviviral proteins
+Very few
+PRF activity of DU177
+Four
+worse survival
+2019
+Cytokine-induced non-specific memory cNK cells
+LC3-II formation
+five days
+Plausible mechanistic pathways
+a predicted amino acid ABC transporter permease
+autophagy proteins
+tSNPs of CLEC5A
+IL-10
+43.2%
+anti-viral properties
+Toxoplasma gondii
+Plasmids encoding various XRN1 genes
+Poor test sensitivity
+hepatic
+IRF3 phosphorylation
+44%
+4T1 cells
+66
+Wolfram Mathematica and Excel
+disease surveillance platforms
+0.6%
+MetYPCP
+chronically wounded tissue
+herpes simplex virus 1 and KSHV
+Homo sapiens actin
+E123A, K124A, and E125A
+nucleotides 10-11
+4uC
+cell localization and post-translational modifications
+Total RNA from EV71
+Luciferase Assay System
+deep image extractors
+4%
+fungal aerosols
+Cardiac glycosides
+interferon-induced proteins with tetratricopeptide repeats
+IsoMIF
+colony formation of cells derived from primary epithelium
+pleurisy
+Plaque assay
+globally compromised
+95%
+analytical or culture grade purity
+organic matter in aquatic sediment
+52Á5%
+Outbred stocks
+U6
+the average age of infection
+10%
+Infection of a novel host
+IRE1 or ERN1, PKR-like
+Posttranscriptional
+Chikungunya Virus
+four
+inclusion bodies
+American Type Culture Collection
+pre-stacking about dynamic hinges
+Dendritic cells
+,20% of the wild-type mRNA yield
+RNA polymerase errors and from the lack of proofreading
+Bullying
+7-12 years
+Allobaculum
+juveniles
+expansion, range shift and new emergence of animal, plant and human diseases
+mitogen-activated protein kinase
+beta-arrestin
+two
+actin
+donated gametes
+MR899
+L1
+Fomitopsis betulina
+5' amino -modified PEDV specific probes
+Brassicaceae
+cytotoxic
+Climate warming
+a stress response
+75%
+circulating IFN-α
+1983
+coincident
+estimating intramolecular H-bond energy
+recruitment of occludin to the TJs
+∼20 min
+Determining the relative importance of priority setting criteria
+lysosomal proteases
+mitochondrial energy production and metabolism
+anxious or depressed
+cccDNA formation
+CO
+Participants' statements on their perceptions of illness and sickness-related absence
+Liver
+A minimum size or pooled study
+temperature-sensitive
+DNA replication
+metal interactions with the SsTroA protein
+widespread infection
+VP24 and VP35
+23
+>99%
+α6
+therapeutic vaccines
+CLIF-SOFA score
+1x
+Membrane-associated poliovirus proteins
+non-synonymous changes in PB1
+preexisting respiratory or cardiovascular diseases and hypertension
+FAS
+detection of both spiked viruses
+19.5-22.9
+Neuraminidase inhibitors
+CO 2
+Twenty-one
+frameshifting measurement
+chronic pain
+GRADE
+130
+three
+T and I
+1.7%
+pEGFP-C3
+48 h
+immune response and tropism of virus
+Human rhinoviruses
+geNorm and NormFinder applets
+CD4 T cells
+five
+when acutely injured
+endotoxin -induced sepsis
+300
+Interday precision
+surface protein Lig
+FACS analysis
+HIV-1 membrane fusion inhibition and proteolytic degradation
+TLS Pols
+24 h
+the SARS virus
+Autoimmunity
+platelet trapping and consumption
+R292K variant
+Integrins
+Victorian Infectious Diseases Reference Laboratory
+membrane tubules
+saves lives and reduces medical expenses
+PSMA
+Alerting timeliness
+lack of the multifunctional pUL97 protein
+anti-B220-APC and anti-IgD-PE
+nucleotides with incorrect nucleobases
+multiple ubiquitin-binding pockets
+Hsc70
+analysis of their codon distribution
+RNase A and RNase 1
+Streptavidin-alkaline phosphatase
+households
+High viral load
+seabirds
+black
+Negative
+B cells
+103
+reductions in R L and E L
+molecular adsorbent recirculating system and plasma separation and absorption system
+elastin and collagen
+6 weeks
+Internal loop
+37%
+Analysis of variance and least significant difference values
+The knowledge of these peculiar toxicities
+Activation
+agarose gel electrophoresis
+adolescents and the elderly
+Bacterial infections
+eight
+143
+two
+Carbamidomethylation of cysteines
+entry into the mammalian host
+Marburg virus
+Nine
+follow-up testing
+Error
+complement binding and opsonisation
+maximum two days
+areas
+1000
+many output poses
+CCCA
+Nitrogen-containing
+early apoptosis
+88
+9.3
+2
+monkeys
+Zetasizer
+PCBP2 protein
+Influenza A virus
+male
+16S ribosomal RNA
+external transmission rate
+prediction of cell fate
+20μl of MTT solution
+primitive macrophages in the embryonic yolk sac
+India, Pakistan, Bangladesh, and Afghanistan
+Predictive modelling
+Mortality
+16
+5 min
+transcription factors and lncRNAs
+3.6 per million
+38
+hours post-inoculation
+autoimmune
+twice weekly
+frameshifting
+four
+real-time PCR system
+E. coli
+immune response evasion/counteractions
+PMWS
+short-term mortality
+more than 25
+PENK
+No hallmark of infection
+alters
+90
+alpha-NAGA
+superoxide dismutase
+pseudoknot
+Time to in-hospital death
+25 mM cycloheximide
+translocation and subsequent exposure of microbial antigens to lymphocyte populations
+double-stranded oligo DNA
+positive inspiratory pressure
+Macrophages and monocytes
+343
+3 min
+antiviral
+1996
+Trojan
+>−300 HU
+admission to the ICU for severe respiratory failure
+portal hypertensive cirrhosis
+field studies
+negative siRNA control
+secondary structure element and Htype pseudoknot candidate dictionaries
+360 nm
+interferon-related genes and inflammatory cytokine genes
+22
+273
+advantages
+Claudin
+who wears masks
+CD11b
+dromedary camels
+Cation-exchange chromatography
+PDI
+IL-1b
+cell surface expression of both MHC class I and the IL-2 receptor
+culturing
+cholinergic
+presentation and disease severity
+Beads with oligo
+gp350+/CD154+
+high dose of virus inoculums
+boxes-and-whiskers plots
+UXT, RPS23, RPL4, and RPS9
+recall responses
+pneumocytic
+PC1score
+One unit
+leaky scanning and ribosome frame-shifting
+Apoptosis
+30%
+Six
+Clinical endpoints
+Greater than 60%
+23%
+V920
+csk homologous kinase
+Requirement for endotracheal intubation
+preparation of microparticles
+postsegregational killing
+the transmitted field
+NPs or NPCs
+30-85%
+cDNA
+mice, rat and rabbit models
+comorbidities, organ dysfunction or organ failure
+triplicate wells
+embryonic-like
+pseudovirions
+mechanisms of interaction between allergies and hosts
+Rab and Arf GTPases
+distinct spatiotemporal patterning
+lymph nodes
+M2e epitopes
+SEM
+EH
+twice a day
+cc-by
+425-430 nm
+leukocyte count
+significantly delayed
+Hamamatsu monochrome camera
+r n
+G3BP1 −/− mice
+Two
+targeted resequencing
+GAS
+Tetherin antagonism
+51.6%
+inhibit different steps of the life cycle of several viruses
+16
+250,000
+Anti-viral
+Pseudomonas pseudomallei
+The effect of a city acting as a hub of infection
+TOR
+non-inflation of the swim bladder and expanded the gut lumen area
+1 in 750,000 recipients
+cGMP-dependent protein kinase gene
+a suspected cryptococcoma
+epidemic management
+10%
+ten
+symmetrical
+sulfuric acid
+ELISA
+0.373
+decreased levels of isoprene
+LPS-TLR4
+7
+lung damage
+IAV
+biology
+porous materials
+12
+hypertensive rats
+63%
+nanomolar
+Sigma-Aldrich
+dermatology and neurology
+Throat swab specimens
+54 years
+mechano-sensitive transient receptor potential cation channels
+supernatants
+kinetics and magnitude of replicon replication and translation
+Liaison host
+2 weeks
+Nonnormally distributed continuous variables
+10 23
+deep learning and personal and professional mastery
+60 min
+25 to 30 nm
+Human bocavirus
+Ten-fold
+personal resources
+65
+Sokoine University of Agriculture
+ubiquitinated proteins
+enhanced significantly
+helium pneumoperitoneum
+19 to 26
+50 μl of 10% L-arabinose
+mouse DSS colitis model
+0.24 μ M
+Late dumping syndrome
+Twentyfive µL of calibration standard, quality control or sample
+a fourth outcome variable
+solubility and immunogenicity
+PANTHER
+SVM regression model
+Sigma-Aldrich
+an alarm
+exclusive human receptor preference
+unchanged
+woodchucks
+immunofluorescence
+Euclidean distance
+CellTiter Glo luminescent cell viability assay kit
+T cells
+Hajj
+TRIzol
+12
+B cell activation and antibody production
+cc-by
+In Situ Cell Death Detection kit
+The orthopaedic surgeon
+hepatitis A
+Bleeding
+Bellucci et al.
+a simple protocol and buffer set
+technical
+antigen specific
+DNA
+20 µL of 2 mg/mL MTT
+standardized
+CVDs
+macrophages and PRRSV
+a transduction control
+B
+30%
+A single infection
+T HIS PAPER
+no discrepancies
+whole blood
+influenza
+the most common season of HSES -winter
+Parasite-free M199 medium
+Maps
+C. gattii
+mutations
+The ArcGIS 9.3 Geometry calculator
+dispositional optimism/pessimism
+STMV Δ 150
+19
+shared culture media
+p65/p50 heterodimer
+Flaviviruses
+myostatin
+binding globulin
+immune tolerance
+influenza virus-dependent reporter gene expression
+clinical studies in heart transplantation
+glucose and lipid metabolism
+Mean cellular fluorescence
+Toxoplasma gondii
+severe disease, severe congenital malaria and even death
+exceptionally stable
+Iterative HFold
+EGFP
+eIF4F complex
+moderate
+after the functional data were acquired
+it becomes infected
+catabolic
+visceral pain and gastrointestinal disturbance
+80%
+disease
+LVDd
+15%
+different lengths of the polymer
+5%
+Temporary tracheostomy
+45F2 and 42E2
+regulatory
+84%
+differences in hospitalization access
+very low titres of viruses
+Inducible NOS
+increased expression of inflammatory cytokines
+non-classical
+Semi-nested PCR
+PPARγ
+Maputo, Mozambique
+19
+ventilator-induced lung injury
+a plugin for detecting and clustering potentially overlapping protein complexes from PPI data
+viral template
+secreted or bound HSP70
+claudin2
+CD63
+O'nyong-nyong virus
+retention of the downstream introns
+The percentage of cells with sparse heterochromatin at nuclear periphery
+MRE11 nuclease
+viral RNA isolation kit
+three
+two
+higher levels of tracheal viral load
+Expertopinion surveys
+5%
+NeuGc
+further research
+Trp371 and Ile375
+5.3 million
+1-11 µg/g FW
+39.29 and F10 to H5-VN04
+2012
+SIVrcm
+10 min
+72 hours
+foot-and-mouth disease
+149
+plasmid vectors
+bactofection
+head-directed neutralization
+the extent or weight of the correlation in the polymer chain
+SPSS 16.0
+VDAC2
+NS5 and NS5
+hACE2 transgenic mice
+Throat swab and sputum samples
+FLAGtagged construct
+fresh medium
+P. alecto and E. spelaea
+minor variants
+56
+6,200,000
+high-mobility group box 1
+Typhoon 9210 Variable mode imager
+January 2009
+53/169
+Ebola virus glycoprotein
+HAdV-7-induced pulmonary inflammation
+non-egg-adapted
+37 to 56 and 45 to 64
+inhibition of the host IFN-I response
+Sex hormones
+0.005-0.01
+multiplex PCR-based NGS
+28 days
+Nf
+migratory capacity
+entropy
+89.7%
+80%
+Akaike Information Criterion
+diagnosis, prognosis and guidance for targeted therapy
+95%
+a regulator of blood pressure
+SU11274
+sperm signaling pathways
+hematopoietic cells
+Spatial interpolation
+4.0 Å
+Neutrophil elastase
+Peptide-MHC class II binding
+WHO's next Director-General
+resources
+157
+53
+more than a century
+Table S1
+Fifteen
+cysteines
+1.1 mg
+epithelial barrier function
+Mx1
+nonporous surfaces
+incidences
+20
+ODE-and PDE-based approaches
+individual observations at a given time wave
+therapeutic
+spirothizamenthane compound
+NSs
+CR2
+satisfaction evaluations
+species divergence
+two aliquots
+34
+0.7 cm
+platform comparisons and benchmarking
+reduced acute motor deficits and improved cognitive performance
+inflammatory
+a burst of reactive oxygen species
+structural information
+dendritic cells
+40%
+1979
+Ling Gui Shu Gan Tang
+graphs
+JAK/STAT pathway
+grape pomace
+Association for the Assessment and Accreditation of Laboratory Animal Care -certified facilities
+caspase-6
+path-based
+Adenosine triphosphate
+Miro1 expression in islets
+departments or portfolios within agencies
+fresh rat blood
+cc-by
+10%
+Oxone
+explicitly
+Targeting viral RNAs
+World Journal of Gastroenterology
+4-20%
+63
+a mixed type 1 and 2 T-cell differentiation and activation pattern
+ERBs
+HIV linked
+cat-scratch
+VD
+local changes may have gone wrong long before ICP has reached the alarming value
+MRC-5
+FLUAV-HA-mediated
+1.1479
+MolProbity
+macrophages and DCs
+to explore the relationships between variables and samples
+Retinits pigmentosa
+100%
+second half of the year
+splicing correction efficiency
+Sri Lanka
+Compensation of volunteers participating in HIS research
+Point-of-care testing
+Characterization of these porcine transcripts/proteins
+to benefit the reader
+the dystrophin reading frame
+households
+sporulation
+Steroid-associated osteonecrosis
+Site-I binding
+inflammation
+94%
+3%
+begin viral clearance in the lung
+systolic
+90%
+47.97
+Event-based
+First Strand cDNA Synthesis Kit
+temperature, relative humidity, and floor surface moisture
+2005
+annual
+GP 1,2
+six
+Pakistan
+respiratory syncytial virus
+profound damage
+clotting of the circuit
+FlowJo v7.6
+within minutes after administration
+bind Ubc9
+Four
+1413
+combining selection for susceptibility and infectivity
+31%
+codon composition
+estimating seroconversion rates
+rabbit, murine and sheep
+CQR
+36 hours
+5
+7 and 13
+JMP12
+Bactrian camels
+China
+Infection control procedures
+mycophenolic acid
+The size of the highly mobile population
+64
+ColorPhylo
+severe acute respiratory distress syndrome
+hepatocytes cell death
+VZV
+two
+the top of the isopycnic gradient
+PKV
+EISS
+enterovirus and rhinovirus
+Makkah
+to evaluate the influence of LPS modification on PTX3 release
+an outbreak
+92-95%
+wood mice
+impedes viral replication
+proteaseencoding
+terpenoid backbone biosynthesis and p53 signalling pathway
+2.5 million
+Receptor binding
+12.5 µg
+mMSCs with passage number 4-6
+Fisher's exact test
+Cap thickness
+lysis buffer
+more than seven days
+1 hour
+108 nucleotides
+RNA antisense purification
+the certainty of the ME risk
+decreased rotavirus infectivity
+66.8%
+apoptotic cells
+participants' recall
+bottleneck
+Angiotensin-converting enzyme 2
+Five
+hundreds
+eight
+65
+Four
+influenza A virus
+dIgA Abs
+larger
+$0.75%
+Multivariate logistic regression analysis
+confocal
+exogenous PAMPs and endogenous alarmins
+increased values of their associated t test
+phage or cell-surface display techniques
+5.83 m/s
+2009
+RdRp
+Atg8 and Hfl1
+a threshold value
+Guangdong
+Dot blot
+Capsid-gene
+demyelination
+protection
+red
+enhances recognition by virus-specific CD8 T cells
+153
+Sanger sequencing
+2:1
+a viral gene
+spam mails
+H7N7 and HPAI H5N1
+tonsils
+96
+20%
+E2 glycoprotein, and the Capsid protein
+Superoxide radicals
+up to 21 hours
+how upset the patient was
+86.8-93.4%
+male gender
+Pearl River Delta
+307
+6
+home ventilation
+28,184
+18.1%
+3.0 log copies/mL
+RSV
+nine
+the sequence of PCR fragments
+BamHI
+new immunogenic and speciesspecific proteins
+hypothesismodification
+genome size
+four
+region C
+ribosome biosynthesis
+more than 66 months
+0.9677 Å
+CCL2 and PECAM1
+>60%
+ImageJ
+sumoylation of the RRM2 domain of hnRNPA1
+34
+18-29%
+44
+30
+C
+inside the capsid
+CCR5
+WNV
+Locations of compounds
+Hilleman
+Changes in interactions between the P-site loop and local rRNA structures
+DT administration to SiglecH DTR/DTR mice
+acidification inhibitors
+bioactive metabolites
+125
+Total nucleic acids
+1.5
+10 4.6
+AP180 CTD
+Blood cultures
+DAPI
+signal
+Resolution and mobility
+unethical
+overfitting the models to the study population
+20%
+Animal bocaviruses
+Presence of oropharyngeal mucositis
+surface plasmon resonance
+transcriptome
+regulatory mechanism of cell survival and cell death
+Alveolar recruitment
+Tears
+100 μl RANK receptor
+the importance of keeping their children at home when ill
+5%
+46673334
+increased fungal burden
+sensitivity, and throughput
+Data from at least 50 fields per experiment
+88.9%
+lipid tubules
+28
+G4 and other nucleic acid structural motifs
+2-7 days
+binding of polyfunctionalized gold nanoparticles
+78
+a standard curve
+four
+new experimental methods
+Tumbarello and colleagues
+virus morphology
+two
+80%
+host receptors
+Fc-FcR interactions
+individual social structure and movement patterns
+deleterious
+unique counter assays
+4
+Scopus
+NSs
+q f values
+Xenobiotics Biodegradation Metabolism
+6.4%
+PAE
+ZIKV NS2A V117
+Sequencing 99 clones
+74
+two
+32.8%
+I 2
+thousands
+clinical practice
+NCBI Genome Workbench and Integrative Genomics
+LPS
+FPR2/ALX
+50
+sensitization to each linked peptide
+weight loss
+Caspase-cleaved cytokeratin-18
+residential group homes and youth welfare institutions
+The identification of conserved coding and regulatory regions
+Pichia pastoris
+Australia and Japan
+TF-gene interactions
+MC
+kill both younger and older
+> 15
+delayed response
+Constraining the diabetes epidemic
+Nox-mediated ROS generation and Gbp5
+CD8 + T cells and CD68 + macrophages
+NZ European
+Humid conditions
+1977
+ω
+50 nmol/L
+eleven
+MNV titers
+the inclusion of many outliers
+healthy donor scores
+two
+tRNAs
+thinner capillaries and more conductive solvents
+different docking protocols
+2020
+low
+domain swapping
+adenovirus
+tumor-specific IgG antibodies
+CDC
+four
+buried residues
+Two
+viremia and joint swelling
+4,000
+ethical reasons
+20 mmol/l D-mannitol
+infectious and inflammatory conditions
+duration of carriage
+Cryptococcal meningitis
+3a and 3b
+80
+acute respiratory distress syndrome
+16 cmH 2 O
+DLBCL-like
+2006
+high throughput analysis
+20%
+EPEC
+SOS Médecins
+1.49m
+DNA gel elution buffer
+contact tracing
+P875A and P881A
+human rhinovirus
+four
+Community germs
+microtubule growth
+exosomal
+ectodermal
+farm workers
+10.1371/journal.pone.0163377
+Individual-based simulations
+people with chronic cardiovascular and respiratory conditions
+antioxidant and antifibrotic
+70
+hydrophobic peptide/peptide interactions
+TFIIH
+aging
+1%
+Author co-citation analysis
+age, sex, application of mechanical ventilation, and co-morbidities
+HSES
+285
+Community-acquired pneumonia
+five
+iTRAQ
+CC10-treated
+infectious diseases
+À1 ribosomal frameshifting
+Phu Tho province
+Interferon-gamma
+negative
+Dromedary
+TaqMan microRNA reverse transcription kit
+10%
+corridors
+Pneumonia
+organism spatial structure
+91
+CD4 T cells
+kaempferol and isorhamnetin
+3A visualized by coexpression of GFP
+2005
+DDX19
+mood disorders
+>5.0
+percentages of existing data
+Data
+Expression Array Manager
+HIV-specific qPCR assay
+to statistically assess the prevalence
+translation efficiency
+six
+viral encephalitis
+MyD88-and TIRAP-dependent pathways
+Methionine
+C-C motif chemokine receptor 5
+Antisera specific to viral GP1, GP2, and NP
+flavivirus NS2A protein
+Differences in daily transmission probabilities
+PFT group
+replication in infected lung tissues
+dilution factor
+Travel bans
+GraphPad Prism 7.0
+free energy
+4 C 2 repeats
+three
+Src
+B-cell epitope
+partially truncated NSs
+HSP-70
+B. mandrillaris
+G-protein-coupled receptors
+MTT assay and In vitro Immunomodulation Determination
+a pathogenic Nocardia
+an AUC score of 0.879
+complex
+Atg8
+Forward primer OS and reverse primer IAS
+15 months
+necroptosis
+complete spore survival
+0.5 ml/min
+ArfA
+ρ i
+hemodynamic stabilization
+research risks
+HO-1
+does not induce an IFN response
+mice and humans
+stronger mRNA secondary structure and slower translational elongation
+seven
+DTZ staining
+Removal of the incorporated radioactive label of ARTD10cat
+regions R4 and R5
+a subset of IFN-induced genes was upregulated
+Sigma-Aldrich Corporation
+red
+Shannon index
+PE9/PE10
+compartmental models
+188,496
+MILLIPLEX Analysis 5.1 software
+49
+Her new baby
+85%
+emergency food
+viral particles
+furin activity
+Nitrogen
+DC-SIGN
+Germany and USA
+antibody-escape variants of seasonal or novel influenza A viruses
+25
+posttranscriptional
+Toll and JAK-STAT
+geopolitical conflict
+Y 2
+confounding by population structure
+cellular networks
+Table
+foot-and-mouth disease
+identified priority actions
+hematological
+QoL
+HCDR2
+Animal lectins
+Hemodynamic alterations, hematologic change and, immunologic response
+pp120/HA4/ecto-ATPase
+social distancing
+immunosuppressive molecules
+639
+many factors
+a number of requirements
+Monte Carlo Markov Chain simulations
+The importance of environmental contamination
+logistic regression analyses
+Figure 6
+Urinary vanin-1 and/or NGAL
+four
+cough and pathologic pulmonary sound
+MaxQuant
+most or even many ways that such an estimation protocol might be conducted
+Japan
+trace-back from data based information to hard copy
+Galactomannan
+WHO
+Protein complexes
+mobility model
+exothermic
+epithelial injury
+template size of amino acid sequences
+India
+Guangzhou
+seasonal infection networks
+more than a dozen
+abnormal trafficking
+High tidal volume and minute ventilation
+Pneumonia
+In-Cell Western analysis
+a particular confined area between the two other groups
+discomfort versus safety of risk
+Critical Community Size 26
+host-and virus-specific factors
+time from study drug initiation to time of symptom alleviation
+Antifreeze proteins
+Hypertrophy-related miRNAs
+Increased oxidative damage
+Twelve µl of extracted nucleic acid
+poor mucosal antibody responses
+HAI or RT-PCR
+Circulating levels of SP-D
+red, yellow and green
+wild mice
+Efficient cleavage by the P1 and P1a proteases
+LPS/TNFa/IL-1b-induced apoptosis
+HTLV-1 protein expression
+CD8+ T cells
+1,562
+avian influenza virus and murine norovirus
+Rapid, efficient and cost-effective protein expression and purification strategies
+lysophosphatidic acid
+VER-155008
+phenylalanine
+allergic sensitization
+RSeQC
+early PVR membranes and retinal blood vessels
+Risk perception for becoming ill
+2009
+folate receptor-α
+binds and sequesters dsRNA
+6AAF and 6AAG
+570
+Multifunctional
+HLA and CFH polymorphisms
+postoperative scores
+degenerate primers and MGB-modified probe
+A summary
+8 h
+N88 on gp120
+14 days
+organic compounds and energyrich fuels
+7120
+Twista Studio Software
+specificity of the antibody-targeted approach with bacterial luminescence
+Olig2 nuclear immunoreactivity
+Cell-Titre Blue kit
+lung dysfunction
+p3xFLAG-Myc-CMV-24 expression vector
+roads
+Diagnosis
+35 years
+electron density
+the tip of the USP Fingers subdomain
+1996
+host proteins
+alterations to gut barrier function and impairments in nutrient absorption
+the absorbance activated droplet sorter
+MP-12-R16H/M250K-infected cells
+technology assessment committees
+Infections
+FR901277
+proteostasis
+proteases
+Newcastle disease virus
+Total RNA
+negative
+trauma
+100%
+1 h at 4uC
+HTLV-1
+3.5%
+H3N2
+four
+yeast ribosomes
+non-dividing cells
+the probability of an event occurring, and the effects of that event
+PAD4
+134
+uncapped viral RNA transcripts
+critical
+enveloped
+19
+haematophagous
+rabbits and hamsters
+hypoglycosylation of LASV GP
+1:6 to 6:1
+21616 TT
+acute myocardial infarction and cerebral ischemia
+101
+UVC light is likely to be effective against all airborne microbes
+WeChat and Qzone
+enhanced chemiluminescence
+The TPR motif
+11
+sequencing bias
+autophagy
+significantly higher
+logistic regression
+3 cos 2 À1 2 D E
+changes of scores of symptoms
+Nagoya Protocol
+increased white blood cell count and an increased neutrophil count
+significant reductions in titer
+a discussion about the structural differences between the two HEV virion types
+to calibrate the selected model
+FGL2 and fibrinogen deposition
+lameness
+HCV nonstructural proteins
+64
+Hes1
+health care professionals and the general public
+County of origin
+viral swabs
+ferrets
+plaque assay and ICID 50
+rats
+inflammatory networks
+IFN-responsive
+Islamov R. and coauthors
+110
+Eight
+87.4%
+luciferase activity
+96%
+RNA concentration and purity
+mannandependent pathway
+Two
+15%
+chimeric humanized mouse livers or primary human hepatocytes
+Vratza endemic regions in Bulgaria
+Cell Signaling Technology
+no relapse occurred during tapering steroids
+2.486
+75%
+AcmA
+ImageJ
+dual-targeting drugs
+67 out of 517
+components of the human services delivery system
+Group 2
+Haplotype effects
+low
+220 nm-500 nm
+small foreign peptides
+ABPP
+functional
+QÞ
+DAPI
+JEM-2200FS transmission electron microscope
+30%
+to block non-specific protein binding
+modern advanced delivery techniques
+confidence interval calculations
+Bracorhabdovirus
+RSV infection
+Ten
+increased genetic variability
+phosphorylation and citrullination
+125
+Central/East Africa
+Three
+A serious disease or condition
+Open and closed triangles
+three
+Scatterplots
+sequencing
+20
+20 min
+MeV RdRp
+miRanda and TargetSpy
+Ligated DNA
+inactivated, subunit, and live attenuated vaccines
+ILTV persistence
+Cuffdiff
+induction of p35 mRNA
+Acytostelium
+Plasmodium falciparum
+ubiquitous or tissuespeci fi c promoters
+Figure 5A
+TuMV P, FSko and ΔGDD mutants
+plasma samples
+resting microglia
+Beclin-1
+tnf-α, il-1β and il-6
+Simian tissue-culture adapted rotaviruses
+type I and type III
+19%
+Zaire
+G418 selection
+In-tAct
+Mining activity
+Arboviruses
+71%
+oxidative stress
+over 3600
+cellular defenses against pathogens
+tissue culture plastic
+concurrently
+2.90 ± 36.3 μM
+how to evaluate One Health processes
+age and weight
+higher invasion activity
+folate receptor-α
+GRSF-1
+P. vivax
+NanoDrop ND1000 spectrophotometer
+signal
+noradrenaline
+11 477
+increased expression
+RNA oligonucleotides
+6.5 µg/ml
+36.9 million
+1978
+6C
+IL-17-producing type 17 CD8 + T cells
+binds ISG15 conjugates
+White blood cell count and differential in the lung lavage
+I-TAC and IP-10
+more accurate and timely measures of AEs
+analysis of mathematical models
+Lipinsiki's rule of five
+four
+Heat exposure
+detectable
+seven
+FGF2 expression
+24 h
+NaCl particles
+Young age
+12 to 15 months
+Mnda, Herc6 and Cd274
+principal component analysis
+protein ubiquitination
+Three days
+Total RNA
+MEWDS
+to identify an optimal decision boundary
+EEG and GSR
+M4RT medium
+exemplary care
+statistical analyses
+fever and other symptoms of SARS
+29
+transmission of directly transmitted parasites among moving hosts
+210
+a His tag
+23 %
+an internal domain
+Bell's model
+SCO6450
+viral load
+Culex pipiens
+PLA2
+6%
+17
+CTL activity
+RNase H
+between day 6 and day 8
+Complementarity
+self-renewal of ES cells
+Spearman correlation analysis
+genomewide single-nucleotide polymorphism arrays
+coinfections
+20%
+EFA
+University of Pennsylvania Institutional Animal Care and Use Committee
+eight
+Students t -test
+cavity definitions by VolSite
+11
+permeability, affinity, selectivity, and cytotoxicity
+Positive mode electrospray ionization
+Excess fixative
+three
+neurodevelopmental
+Influenza A virus hemagglutinin
+c ij
+Neutrophils
+primates
+pandemic or reducing the AR
+7
+1 %
+five
+70%
+passerines
+0.3%
+protective
+nuclear extract
+microscopy
+SAS 9.4
+Antiβ-actin mAb
+63
+Wide-ranging
+an RNA that has all the genes required for replication
+Service/ operation volumes
+27
+30 minutes
+one million
+dead cells
+Three
+Two weeks
+Percutaneous transmission with sharps contaminated with infected bodily fluids
+4.2%
+diarrhea scores and diarrhea rate
+0.687 to 0.861
+cells lose the ability to form caveolae
+post-translational
+four
+142,407
+906,600
+lipid
+aPKB
+activated partial thromboplastin time
+Polysynaptic VSV vectors
+Isobaric tag for relative and absolute quantitation
+CCHFV
+two
+population density
+suppressed
+NanoDrop 2000 spectrophotometer
+six
+acute and subclinical
+Iranian
+40% to 50%
+one-third
+erythrocytes
+Scotland
+a pandemic
+further exposure
+biological
+β-blockers
+equifinality
+comparative LOD analysis
+red and blue
+selection
+Primary endothelial cells
+inverted microscope
+intracellular
+Reed and Muench
+attenuated immune response
+Weasel w 2.5
+phylogenetic distance between pairs of DRB1 alleles
+D/N -GFP Rab5
+Ningnanmycin
+IFN-b production
+9.0
+confidence intervals
+gas-phase fractionation
+Infected cells
+better optimization of MSC-based clinical treatments for inflammatory conditions
+three
+mice
+∆∆Ct values
+immunomodulatory
+plasma samples
+statistically similar
+4.4 ± 3.08 days
+dengue infection and yellow fever vaccination
+Bioluminescent
+IFN-α induced signal transduction
+GST
+more relevant information
+maintenance of a cold chain
+CD4+ Th9 cells
+Sizes of molecular weight markers
+B lymphoid malignancies
+Glucose oxidase
+accurate mass and time
+HCV
+0.7-fold
+preventing TB
+Parasitic infestation
+NEDD4, UBE3C and HECTD1
+higher than most of the metastasis samples
+3 days
+A 1 and A 2
+Ty-1
+mosquito
+1 month
+above 97%
+>60%
+IL-10 producing T cells
+macrophage polarization progression
+factors associated with each setting
+three months
+lower
+human immunology
+95%
+RNase A
+polygonal and dendritic-like
+increase its weight
+6
+random
+emergency medicine systems
+earlier diagnosis and initiation of antibiotic therapy
+V1V2
+feedlots
+transient confinement zones
+heterodimeric
+metal-based electrodes
+Prediction of T Cell Epitope NetCTL 1.2 server
+GraphPad Prism 5
+Antigenpresenting cells
+IC50
+Statistical
+MMPs
+Tecan Infinite 200 Pro
+α
+immunofluorescence assay and viral plaque assay
+FACSCalibur
+EBV, HSV-1, CMV, and VZV
+Four
+IAV cellular entry
+26
+The Journal of Infectious Diseases
+memory B cells
+Monocytes
+statistical reasons
+IL-6
+automated instruments
+Carboxyfluorescein
+4-6 weeks
+balance community
+Plasmodium
+serious danger signals
+reduced
+Signatures identifications and isolations of bio-particles
+π
+appropriate care and treatment guidelines
+Accell Cyclophilin B siRNA rhodamine labeled
+3
+35.7%
+viral replication
+DIP, NSIP, and LIP
+RVFV NSs
+leukocytes and tumor cells
+Candida 2H system
+immunodeficient NSG mice
+CELIA
+C-type
+antidiagonal and bit-parallel algorithms
+Host-target directed antibodies
+HIV amplification
+10%
+fitness for growth in monolayer culture
+integrating information from multiple ProSeqs
+5-amino acid CDRL3s
+enterovirus replication and PI4KB recruitment
+social status
+Spo0A
+7-7.5
+Systematic review findings
+rats and mice
+Infectious Bronchitis Virus
+agarose gel electrophoresis
+Airway and interstitial T RM cells
+it becomes infected
+mechanical ventilation
+proteins and nucleic acids
+pGEX-4T1 or pDEST17
+Image-Pro
+policy decisions
+to save editorial space
+4,390
+DNAzyme sensor
+land-use diversity
+R
+189
+to elucidate mechanisms of ALI pathogenesis
+Traumatic brain injury
+USP46
+Neutrophil accumulation in the myocardium
+alveolar epithelial cell
+PKR phosphorylation
+$3.81 per pool
+2 years
+Total RNA
+EF-hand Ca 2+
+nonstructural viral proteins
+nineteen
+H1N1
+unambiguous translation to trauma
+cholesterol concentration of the endosomal bilayer
+CD47 and CD31
+lipids
+within months of measles infection or vaccination
+Hubei
+2005
+Translation from the virus-or cell-like transcript
+inhibitor I9
+93% ± 3%
+2
+lung cancer, ARDS, pulmonary hypertension, pulmonary tuberculosis and silicosis
+IFIT2
+being too busy
+three
+the wide range of competing AIV subtypes
+national income differences
+cytoplasmic tail
+Neutrophil elastase
+anti-viral
+size, density, charge
+Mouse anti-HLA-A mAb
+ATP
+H7N9 RNA
+rabbit
+poliovirus RdRp
+the antigen gene
+24hrs
+Blood banks
+bring the reproductive number reliably below 1
+dendritic cells
+three
+26
+ANN algorithms
+quick door swing
+three
+high or low affinity
+Strongyloides stercoralis
+Blood and saliva
+cc-by
+Phoenix Pharmaceuticals Inc
+45
+Initial tool development, Pilot study and Validation study
+improving the health status of Canada's indigenous populations
+172,371,088
+250,000 mL −1
+ρ * → 0
+reduced cell binding
+Supernatants
+SINV-G mutator RdRp
+Paramagnetic Relaxation Enhancement experiments
+autophagy
+38
+>97%
+46
+suddenness and unpredictability
+partial pressure of oxygen in arterial blood
+virus shape
+27 to 35%
+four
+Codon
+homologous lysine residue
+4
+infection of cells with WT LCMV
+BUNV infection
+Glycosylation of GP2a and GP4 by glycans
+inflammatory
+DAP12
+critically limited
+artificial respiratory management
+13
+human diseases
+multigroup model
+plasma membrane
+Gaussia luciferase
+FESL SPC PMR ACF ED
+six
+G GP
+tetramer
+other lung function variables
+150 mM NaCl
+d ij
+20 μl
+overall survival
+green
+dyspneic
+Reed and Muench
+aromatic substances
+The HRC index
+CD39 and CD73
+PTMScan ® Ubiquitin Remnant Motif Kit
+improved cross cultural communication and improved rapport
+Neutralizing antibodies
+Infection
+BTV1-conferred autophagy and virus replication
+cough, difficulty breathing, and cough with vomit
+interest
+MOV10
+Eight
+innate
+Bias
+specimen transport media
+exclusion of other co-morbidities
+our technological limitations
+Loop primers and stem primers
+APMV-1
+predator
+Mapping land-use classes
+independently analyze all field notes and focus group and interview transcripts
+140 min
+pig convalescent-phase antiserum LL616
+10
+Pearson's correlation coefficient
+Mouse sera
+statistically significant
+singly mutated HN molecules
+251
+antiviral efficacy factor
+1000 TCID50 of a reporter-expressing Ebola virus
+rat
+mechanically ventilated
+further studies
+N-acetylglucosamine of GP
+an estimate in an academic report
+musculoskeletal
+less than 1 year after initiation of the immunization campaign
+mocktreated 2fTGH and U3A
+Culture supernatants
+~10 -9
+Forty-two
+nanometer and microsecond resolution
+blue
+Genespring statistical tool
+Reassortments of the 6 internal gene segments
+23.4%
+positive
+Bayesian network
+150
+culicids
+scattered transmission
+Poly I:C and LY-294002
+15 amino acids long
+Female
+full compliance of patients with screening recommendations
+viral RNA-dependent RNA polymerase
+Bio-Rad Protein Assay
+0.1%
+asthma
+suboptimal
+the effect of resolution is most important
+Soluble receptors and ligands
+mutant prevention concentration
+twice
+electrostatic interactions
+A calibration standard
+LoFreq
+10
+unpaired, two-tailed Student's t tests
+Whiskers
+mean and SD
+20 µL of a 2 mg/mL MTT solution
+10,000
+E2F1 and p75NTR
+TMPRSSs and PRSSs
+Society of China University Journals in Natural Sciences
+to encourage new research
+2019-nCoV
+increased
+30 min
+negligible
+1974
+10 days
+three
+183
+Escherichia coli and Klebsiella pneumonia
+R 0
+76
+seven
+Retail live-bird markets LBMs
+molecular module similarity
+EBOV infection
+One Health collaborations
+Forty-five
+along two relatively narrow ridges
+expand somewhat more rapidly
+SO rats
+Doctors without Borders, Partners in Health and the Red Cross
+42%
+M2 82 -specific
+Proteoglycans
+2004
+several infected contacts
+EpiData software
+0.47 and 0.37
+a 4-nt step
+agarose gel electrophoresis
+slows down
+quantitative
+Health Hazards
+proteasomal degradation
+Interferon-c
+more than 30
+murine pmacs
+eight
+194
+unnatural modified nucleoside analogues
+mean accuracy
+linguistic approaches for named entity recognition and named entity disambiguation
+cellular membranes
+clinicians
+assemble with 3A and/or become fluorescent
+The Norwegian Directorate of Health
+Ubiquitin-specific proteases
+chymase
+age, SOFA and diagnosis of influenza pneumonia
+hemagglutination-inhibition assay
+three
+chloroplast genetic engineering
+Astrovirus MLB3
+ESSENCE
+Nanosep® Centrifugal Filtration Devices
+3.5-4.0 x 10 4 cells/cm 2
+RNA content
+ACTB and GAPDH
+one
+genes associated with resistance to the antibiotic
+similar seroprevalence
+Blood transfusion
+White Plymouth Rock chickens
+Two hundred
+PLGA-NP-based vaccine delivery
+cc0
+statistical significance between groups
+Hepatocytes
+bite
+EBV
+GeneJET Gel Extraction kit
+21.7%
+Black background
+Recycling of the ribosomal subunits
+Ly49H
+Application of DisProt 11
+alloactivation
+A, B, C, and D
+paraseptal or irregular emphysema
+suicide
+FLUOstar OPTIMA plate reader
+Rebecca
+PRRS
+292V/I
+18%
+4%
+hundred microliters of inactivated PPRV Nig75/1
+10-cm
+5/5 homozygous
+two
+stochastic
+bromide stained 1.5% agarose gels
+620
+d max
+12
+2008
+viral NPs
+spina bifida and anencephaly
+Critically ill
+1.62 +/-2.13 and 9.82 +/-9.88
+Allometric scaling of peak VO 2
+Amyloid-b precursor protein
+immunohistological detection of MR
+VSV and NDV
+4.9%
+Specific human pathogens and antibiotic and zinc resistance genes
+influenza
+153
+long-term functional impairment
+hydrogen bonds
+Eleven
+herbal
+France
+hydrolysis
+s-RT-MELT
+age distribution
+many orders of magnitude
+5 to 6 days
+Asiatic citrus canker
+cytotoxic
+Porcine reproductive and respiratory syndrome virus
+increased BC risk
+AS and SW
+Lineage Modification
+to use sensor array signals to diagnose VAP using the machine learning technique
+PBMCs
+6.8%
+Exosomes
+NSDV
+discovery SNP and rs4803217
+viral infection
+38, 377
+a positive mismatch situation
+Health security
+cytotoxic
+five
+infection
+Active exclusion of proteins from the MW
+Murine Ifit2 protein
+See Tree
+Supplementary Data
+draining lymph nodes
+AlamarBlue
+15
+0.9832
+39
+Adenoviral vectors
+1 h
+host selectivity
+the standard deviation of the mean
+total RNA enriched for polyadenylated RNA
+Vim KD cells
+protein thermal stability
+4
+Mechanistic models
+heteroatoms
+degenerate oligonucleotides
+Gaithersburg, MD
+1.05
+18.8 days
+unidimensional
+mean total SOFA score
+reverse transcription-quantitative PCR analysis
+P 0
+ECMO
+Risk evaluation
+bacterial vaginosis
+Leptospirosis
+comparison with related studies
+a disease with a reproductive ratio R 0 = 1.75
+delay the infection progression
+HCV replication and core protein expression
+Threonine
+a fraction
+migration/invasive and soft agar colony assay
+autonomic
+virulence
+1918
+0.4-0.5
+full epidemic model
+Wild-type VSV-M protein
+3
+side, and end-on perspectives
+165
+70%
+7-8%
+hypertension
+100%
+entry that results from fusion with the plasma membrane
+Invasive cells
+Santa Cruz Biotechnology
+LAMP technology
+cell function
+40,000x
+4.16E-4 substitutions per site per year
+CRTC1 protein is stabilized in HBV-infected cells
+Increased intracranial pressure
+two
+1,593 bp
+Kruskal-Wallis test with post hoc Dunns analysis
+lack of resources, equipment or staffing
+stratified analyses based on such clinical characteristics were not possible
+pneumonia
+over one million
+Vero cells
+infection of Y. pestis 1418
+AR50_59
+contact-related covariates
+disappears
+genomic RNA
+formal risk assessments
+potential coding sequences
+kinesin-1 motors
+F 0
+24 hours
+sterility and absence of mycoplasmas
+1.5%
+SwissProt_Human database
+Visualization of the temperature factors
+alveolar collapse
+extracellular matrix
+C i
+64%
+RT-PCR/hybridization
+Poisson offspring distribution
+Fluoview
+Mitochondria Isolation Kit for Cultured Cells
+BLASTP
+13 to 56%
+Glu92
+SIR-type compartmental models
+vitamin D-binding protein
+northern France
+0.332
+One Health
+significant differences
+four
+non-formal educators and NGOs
+PF
+virologic
+virus-like
+bidirectional
+more than 1000 miles
+independently from neutropenia
+death protein 4
+MSC-CM treatment
+Europe
+viremia
+premorbid illnesses
+nt 515-554
+60%
+adenine
+96%
+Cl13
+diseased as well as healthy cattle
+69.2%
+297
+Qualitative research
+The expression level of individual genes and transcripts
+random forest
+transforming growth factor beta 1
+HSMPD
+Annexin V or Fixable Viability Dye
+STAT2
+78.6%
+95%
+Packaged +ssRNA
+285
+strengthen the public health system
+false alarm
+attenuates the inflammatory response
+individual scientists
+x k
+China and Southeast Asia
+marmosets
+FV10-ASW
+eukaryote adhesion and proliferation
+prophylactic
+genetic instability
+phylogenetic
+Growth rates
+T6SS-5
+FRG triple knock-out mice transplanted with human hepatocytes
+5%
+GFP
+stimulated only minimal, statistically insignificant, changes in the levels of immune stimulated genes
+sodium sulfite, EDTA, and transmissibility
+managing and analyzing large amounts of gene expression and mass spectrometry data
+27
+Ascosphaera apis
+H5N1-encoded miR-HA-3p
+actin control bands and PTC
+intramuscular immunization
+integrating community healthcare centers and clinics
+trypanothione reductase
+organ failure, infection, and GVHD
+0.2 mL/min
+network structure with response logistics
+individual probabilities
+differing codon usage preferences among sequences under comparison
+pre-cooled THF
+refrigeration
+subgenomic mRNA synthesis regulation
+two
+Forty-eight hours
+1.4%
+frameshift stimulation
+100%
+Twenty-four
+E1 protein overlapping peptide library
+128
+6.5 billion US dollars
+TBK1 phosphorylation
+hydroxyl
+Local transmission and clusters
+FDR threshold of 0.1
+100% confluent BSR cells
+Qβ bacteriophage virus-like particles
+less than 20%
+covalent probes
+single stranded monoclonal beads
+forced expiratory volume and FEV 1 %
+three
+W275A
+group 2 lesions
+condensation of the rDNAs
+Live vaccines
+80
+fused LOB7
+1.5 hours
+positive hits
+ESCRT-driven
+250 000-500 000
+IFN-λs
+zinc finger nucleases and transcription activator-like effector nucleases
+virus swallowed during inoculation
+Fig. 3
+CEACAM1+CD4 T cells
+HBV infection
+SV01 and SV02
+alveolar-capillary barrier injury
+3-5
+loneliness
+2 weeks
+500
+Targeting virus molecules
+intubation rate
+two
+12 hours
+2.5
+613
+one Au and two thiolates
+stress responses and transport functions
+THP-1 cell viability
+ImageJ
+changes in amino acid residues
+substantial differences among age groups
+3 days
+Prohormone convertases
+luciferase
+flow cytometry based neutralization assay
+β-actin expression level
+morphometric analysis
+Two
+Burkholderia pseudomallei
+extremely strong selection
+Eosinophil infiltration of the skin
+30
+adaptive Treg differentiation
+3 h
+50%
+apoptosis
+approach
+ENC
+1 h
+vesicular stomatitis virus
+0 to 6
+Endotoxemia
+40S
+RPV coat protein primers
+twice
+adjuvants
+oropharyngeal lesions
+gene duplication
+10%
+52.6% to 54.9%
+number of cell divisions
+Peripheral blood mononuclear cells
+through an iodixanol gradient
+higher airway pressure levels
+1.5-11.3%
+Student unpaired t test
+G 0
+Gulls
+12 to 51 h
+6,467
+eosinophilia and neutrophilic alveolitis
+zero
+other
+CCL2 and CXCL10
+220 mg/
+confocal
+three
+E. festucae
+MERS-CoV
+Plasminogen activator urokinase and integrin beta3
+DNA
+membrane curvature
+3
+cytoplasm
+Globalization and Health's 'Open Access' policy
+seroprotective responses
+a physical barrier
+Bayesian hierarchical model
+an observed morphologic change that differs from control or normal tissue architecture
+immunity and inflammation
+early 1950s
+economic and cultural pressures
+mTOR inactivation
+Student's t test
+possible change in the case mix
+pneumococcal vaccination
+docking analysis
+Macrophages and microglia
+sexual transmission
+Labeling of olivocochlear fibers
+ethidium bromide staining
+>80%
+De-MAND and DE analysis
+20 s
+MS endothelial cells
+99%
+10%
+QIAamp Viral RNA Mini kit
+5 min
+46%
+Avian influenza virus
+31
+Five
+cough or fever
+natural disease
+tRNA identity theory
+English
+1.37%
+Water
+39
+One hour
+pulmonary fibrosis
+they can describe a wide variety of errors
+AIV and AAVV-1
+80%-90%
+growth
+9.1 ± 0.5 particles per milliliter
+outbreak detection
+Quantitative northern blot analysis
+autophagy
+CSP
+infrastructure
+a directly transmitted infection and a vector-borne infection
+0.2%
+phosphorylates ERK1/2
+three
+12
+passive
+Lowry method
+6 V/cm
+plasma proteins
+which communities will be slowest to recover
+JFW, AJZ, and KYY
+twice daily
+cc-by
+64 and 68
+leukodystrophy and hypomyelination
+40%
+45%
+35%
+cell death
+to analyze viral recombination in a live host
+HCC occurrence
+RNA-protein interactions
+4,240 pg ml −1
+Steps 3 and/or 4
+two
+radiographic
+Febrile myoclonus
+photoreactive dissolved organic matter
+Promega CellTiter luminescent cell viability assay
+Epitope accessibility
+DISC-HSV
+two
+HAdV DNA
+non-specific psychological distress
+1 h
+CFE containing WT or mutated eEF1A
+ventilation
+50 µL
+protein stability
+the most current week
+coping appraisal
+MnmC
+glycine
+Two
+disease progression
+Neutrophils
+22
+70%
+glass coverslips
+Table 1
+vector-borne infections
+Medical Research Council
+Risk assessment
+reductive activity
+4% paraformaldeyde
+rapid and reliable diagnostic tools
+E. coli, wheat germ and rabbit reticulocytes extracts
+10% heat inactivated FBS and 1% PSN
+Differential scanning fluorimetry
+10%
+Molecular mimicry
+a group of probes that are within 500 bp of each other
+regenerated
+latent
+Computed
+two serine residues and one tyrosine residue
+A better understanding of the mechanisms acting at the maternal-fetal interface
+31
+lipid accumulation
+Figure 1
+zebrafish
+cTnI
+UV spectrophotometry, TEM and fluorimetry
+unfavorable outcome
+Ninety percent
+VA RNAs
+all data sets including X-ray structures
+10 3.76 TCID 50% /mL
+c i,j
+a latent period between an individual becoming infected and being able to transmit infection
+4 weeks
+F. betulina
+20%
+model 1, model 2, model 3
+conflicting results
+four
+appropriate or inappropriate activity of immunoregulatory networks
+Efforts to improve expression
+region-specific time series
+dramatic illness and identifiable travel groups
+2 − Ct method
+15%
+Each type of repeat unit
+hybridoma technology and recombinant technology
+GADD34 expression
+one hypervariable region
+susceptibility to active TB
+Connective tissue disease-associated interstitial lung disease
+PIDD
+mannosebinding lectin
+RNAs
+Aliquots of 200 µL of supernatant
+84%
+stronger FAM signal
+binds polyUb
+RAM-11-positive areas of atherosclerotic lesions
+11
+formalin
+8 weeks
+118.53
+Patrick Sawyer
+Dengue
+0.5 kcal/Å
+66.7%
+100%
+The empirical evidence and importance of connectivity correlations
+therapeutic in vivo studies
+AT2 cells undergoing apoptosis
+measurement of antibodies in BTM
+standard recombination software
+Figure 5a
+placental infection
+Base excision repair
+CASP9
+Geminiviridae
+8h post-infection
+Lactobacillus
+four
+stop free radical chain reactions by accepting electrons
+Trypsin-mediated cleavage of VP4
+six
+48.5%
+2
+maps
+Table 1
+Honduras
+Social distancing and quarantine measures
+stress
+Levels of nod1 transcripts
+90%
+more detailed work
+structural information
+BigDye Terminator v.3.1 Cycle Sequencing kit
+higher
+orchestrating inflammatory response
+fluorescent microspheres
+purine
+Table 1
+anti-viral
+MDA-MB-231
+independent test dataset, sub-sampling test, and Jack-knife test
+BC-3 and BCBL-1 cells
+enzymatic activity
+competing virus
+Methanol
+upper and lower respiratory tract infections
+Ventana Benchmark automated staining system
+Replication-Competent ALV LTR
+gene amplification method
+78
+Hemodynamic
+m47b
+29
+Trains of action potentials
+homogenous and viable
+−80 ∘ C
+cc-by
+Two-sample Kolmogorov-Smirnov test
+IRF2
+Three
+spearman rank correlation
+A minimum number of continuous, perfectly matching stretches
+inosine-5 -monophosphate dehydrogenase
+Atg9L
+Cote d'Ivoire
+day 3
+HSV-1 17+ 17
+adequate multidisciplinary and regional representation of relevant experts
+serotine bats and Daubenton's bats
+induction of the viral lytic cycle
+dengue model
+2-h
+under $5000
+24% to 34%
+levels of Ang-
+IPP software
+Zeta potential
+February 2016
+Viral titer
+Nucleotide sugar metabolism
+p30
+40
+RNA
+Professor of Medicine at the University of East Anglia
+Rhinovirusassociated illness
+8
+10-fold
+16%
+withholding antibiotic treatment
+Eliminating the hypodermic needle from vaccination
+scientific director
+31
+rapid reassortment detection
+Toho university medical center, Sakura hospital
+Apoptosis
+decreasing inflammation and accelerating blood vessel repair
+21 days
+ELISA and Western blotting assay
+isotope coded affinity tag technology
+Cytoplasmic tail
+Gag-specific CD8 + cells
+molecular tools
+cubic spline interpolation
+Inducible Hsp70
+Supplementation of 10% allantoic fluid
+a tryptophan metabolite
+if the vaccines will work
+12.9%
+average of the three last years of data
+cytotoxicity
+Sydney Carton
+1,294,310
+pro-inflammatory
+evolutionary entropy
+Ten
+7.4%
+Compound 7e
+Eleven
+Corticosteroid-induced ONFH
+2 hrs
+Splenomegaly
+public health workers
+100%
+Host resilience
+enhanced protein ubiquitination
+2.4%
+Inertial microfluidic
+under microscope and a photograph taken
+q
+UV Stratalinker 1800
+pluripotency genes
+H + leak and somewhat nonspecific cation conductance
+inflammatory damage
+35
+coordination
+T-test
+detoxification
+Simulated data
+proteaseencoding
+WT LCMV
+Mutations in the 1762/1764 positions of the X gene
+inhibitory
+Stool samples
+1, 846
+within the next year
+six primers
+immunomodulation, irritable bowel syndrome, and neurodevelopmental disorders
+ten
+Fig. S1
+Serogroup W sequence type 11
+Cyclin G Associated Kinase
+a PS
+V 1/2
+213
+Sodium dihydrogen phosphate dihydrate
+100
+significant induction of CLDN6-specific antibodies
+log of cell numbers per g faeces
+HA, M1 and NP production
+5-9
+Daily temperature differences
+premature aging
+mental health
+Dr. Julie Overbaugh
+a lock and key
+SafeStain or Coomassie Blue R-250 stain
+prolonged recruitment period
+> 20 mmHg
+three
+contact distribution model
+synthesis of L-carnitine
+antigens
+Persons infected abroad and returning to the EU
+data/analysis
+48 h
+antibodyantigen interactions
+chemopreventive
+TGF-β
+efferent
+2012
+analyses were not trapped at local optima
+40-80%
+RIG-I
+FDG-6-phosphate
+Genbank
+6 h
+anamnestic response
+public health sector and the curative sector
+Relative expression compared to control cells
+type-I IFNs
+65
+HSV-1 infection
+GP incorporation
+63
+Xaa-Pro
+200 PFU of LCMV strain WE
+Expression of the HAV insert
+amino acids 533-578
+one
+Allantoic fluid
+209
+GenePix Pro 6.1
+cc-by
+viruses bearing a negative-sense RNA genome
+four
+age-specific infection profile
+23
+Hepatocytes
+intellectual property issues
+Ten
+casting a wider net for contact tracing
+HIF-1 active cells
+3085
+Potyvirus
+TLR-mediated and other signals
+binds sialic acid residues to facilitate infection of target epithelial cells
+contigs
+1
+Ghs6 and M15.2
+j d
+little
+zoonotic infectious disease transmission
+exited the study
+ATG machinery
+fulminant
+winter waves
+RNA4 level
+T2DM
+at 1 or 5 µmol synthesis scale
+glycosylated
+control measures parameters
+GTP depletion
+3
+Vaccines and antiviral drugs
+10 g/g
+human IFNa/b or c as well as mouse IFNb
+Spain
+four
+cellpenetrating peptides
+10,436
+Hypertension
+increases membrane permeability to Ca 2+
+70%
+SPSS 13.0
+60
+79additional reactions and 10shatter libraries
+547
+mitochondria
+cytosol
+underreporting
+74
+economics
+biochemical
+Chi-square tests or Fisher exact tests
+tissue necrosis
+transcriptional and translational levels
+population growth
+Post-translational
+processing, protein stability, CSE and fusion
+using a blank sample and subtracted from test samples
+Data related to pre-transfusion hemoglobin levels and red blood cells
+AlexNet
+DNA-polymerases
+Antibiotics for Childhood Diarrhoea trial
+gene knock out and in-vivo imaging
+Siglec-8
+developing multivalent vaccines
+$5 mm
+the union
+115
+6
+monoterpenes
+4-parameter variable slope regression fitting
+early-branching clades
+endocytosis of APP
+slow cooling
+transfection at the OP cell stage
+Biofilm formation
+IFN-λ1 protein secretion
+S. pneumoniae
+20
+clustering
+qRT-PCR
+replacement of the transmembrane domain
+82%
+Central venous
+80.6%
+Charlson Comorbidity Index
+contain specific packaging signals
+three
+Neighbor-Joining method
+clinical microbiology
+200 genomes per day
+99%
+epithelial cells
+25%
+a fusion unit
+key strains
+transportation to a feedlot
+PCR primers
+FLAG tag or GFP
+48
+three
+Animalia
+Eight
+gender differences
+the antigenic nature of selected protein sequences
+Improved vaccination and delivery approaches
+fifty per cent
+the actual amount of drugs being consumed by the contact
+urban
+c-secretase
+Aptamers
+Multivariate
+Fold-induction
+cytoplasm
+IV titratable
+0% to 10%
+larger human trials
+inflammation
+accumulation of viral RNA during infection
+Written informed consent
+high titer
+Efficient restoration of circulating blood volume
+Dong Thap
+diarrhea
+carbamoyl phosphate synthetase 1
+MiSeq Reporter Software
+mitochondria
+interactions between core proteins
+vaccine efficacy trials
+removing them from their primary work
+panel D
+host epitopes
+stem 1
+integrated stress response
+acetylation
+6 minutes
+Acinetobacter baumannii
+novel and alternative targets
+MELD-Na
+May 2012
+Selleck Chemicals
+10 ml 5% acetic acid
+Two hundred forty-seven
+>80%
+DNA and RNA
+Protein engineering
+Variable expression of Zfp985
+insulin-like growth factor -1 receptor
+male sex, adulthood and exposure to the outdoors
+22%
+RNA
+Tel-Aviv University
+Three to four
+pp-NT assay
+zero-dead volume union
+20 min
+Twenty-two
+two
+55
+10
+poxvirus infected cells in chickens
+GBV-C
+weakly positive mumps antibody
+non-influenza respiratory viruses
+fluorescence-activated cell sorting
+Monocytes
+91%
+more uniform, spherical particles
+Xrn1
+research nurses and other clinic staff
+unpleasant and sometimes life-threatening disease
+10 4 cells/well
+Two
+HK1 uninfected and EBV-infected cell lysates
+0.2 μg per reaction
+does not bind target membranes
+lung tissues
+changes in the parameters that affect NK-and T-cell dynamics
+Bias
+cellular analysis of BAL fluid
+16
+a wide phylogenetic study
+further study
+integration into a point-of-care device
+retinal pigment epithelial cells
+438,000
+TNF stimulation for 5 min
+Centers for Disease Control and Prevention
+50%
+HRP-conjugated goat anti-guinea pig IgG antibody
+dialectical
+lethality
+52%
+AxioVision 4.8.2
+217
+A step function
+54
+fever, circulatory collapse with hypotension, hemorrhage and acute kidney injury
+240
+MTX
+multicolor
+10 30
+FA
+mathematical model and simulation
+biological functions
+qRT-PCR
+euthanasia
+every 24 hours
+three
+1990
+clinically astute
+28,914
+33 × 10 9 /L
+loglikelihood model
+28 kb
+T47D human breast cancer cells
+attenuated
+March to September 2016
+Mycobacterium tuberculosis
+low incidence of pertussis
+EBV and KSHV
+Reads
+6 days
+an assignment
+50 μm
+basal expression of ISGs
+Detection platforms
+a deviation of 1-3 residues
+Viral recognition by host factors
+ARC1905
+H7N9
+general cross-reactivity of anti-prM antibodies
+acute injury to lung tissue
+EAU histological scores
+localization, tissue, and cell specificity
+four
+TGFBR2
+pulmonary hepcidin level
+2 hours
+4%
+enzyme families
+CGCTAGCTACCCATGG
+pseudotype virus
+lower
+53
+A minimum concentration of 0.4 mM dNTPs
+nuclear factor of activated T cells
+αand γ-SG and α-DG
+965
+Understanding viral transmission
+DMEM
+NS4A
+diabodies
+high cost limit
+orthohepevirus A origin
+five day
+data analysis
+small horizontal lines
+EBERs
+41-fold
+R292K and E119V
+11 L/min
+a substitution in the gene rrlE
+4 min
+10.1371/journal.pone.0019705
+Eleven
+Serum
+English
+1994
+Sequence similarity richness and evenness
+four
+10%
+10, 10, and 16
+Electrostatic repulsion with protons
+John Kash
+CARD9
+de novo phospholipid biosynthesis
+local and global signals of evolutionary selection
+fold change from pre-vaccination
+miRNA sponge
+131,761
+Dr. Chris Fraser
+The area near the door
+TLR9
+80:10:6:4
+birds
+138
+4
+Human primary monocytes
+3 M LiCl
+inhibitory antiviral effects
+12%-15%
+NGO0564
+adult learning principles
+higher
+Local undertakers
+reverse transcriptionquantitative PCR
+E. albertii
+RNeasy Mini Kit
+the time frame to test for coevolution
+1000 units per week
+ICL repair and HR
+N f
+Network plots
+electrostatically favourable
+dampen pDC cytokine production
+ORFeome
+oligonucleotide probes 70 nucleotides in length
+69700 km 2
+Supplementary Materials
+5 days incubation
+a strategy
+acting upstream of caspase-11 gene expression
+30-40%
+Respiratory syncytial virus
+The genetic background of the line used
+environmental monitoring systems
+β-actin
+viral yield
+48
+IRF4 rs872071
+IL-1β
+CD172a low
+Idiopathic pulmonary fibrosis
+an underestimate
+IAV and IBV HA proteins
+canonical proteases
+E1, E2, and the core protein capsid
+cidofovir
+matrix-degrading enzymes
+ribosome biosynthesis
+21 days
+SNPs
+Strategic management of materials and personnel
+SDS-PAGE and TEM
+δ SI
+endometrium
+FLUOstar Omega microplate reader
+RNAs transcribed by host cell RNA polymerase
+perceptual discriminative power
+large-plaque viruses
+joint knowledge of chain size and the number of generations before extinction
+prophylactic strategies
+Innate immunity
+Th17 cells
+spread of infection
+Ninety-six
+cough-associated apnea, cyanosis, PHT and encephalopathy
+hyperinflammatory
+12
+2 days
+four
+pathogenic arenaviruses
+threshold of detection
+γδ T cells
+ImageJ
+Hsp27/eIF4E interaction
+Aging
+infectious diseases
+maintaining ionic gradients and modulating neuronal excitability
+Stop codon mutations
+antimicrobials
+DiNap
+formalin
+polymerase activity
+vaccine efficacy
+HIV frameshift site
+typical trees
+The CSIRO's triple adjuvant
+L. pneumophila
+CellTiter 96 Ò AQueous One Solution Reagent
+pigs and neonatal mice
+many Asian countries
+1xPBST
+improve medical graduates' knowledge and attitude toward community health
+orphans
+support for Enoplia
+58
+Golgi
+perinatal and early life
+four
+intramuscularly
+clustering
+the log of the marker area
+mnm 5 s 2 U
+FKBP11
+the brain
+EMAN
+triplex
+stress
+NT-proBNP levels
+empirical data
+reverse transcriptase, RNase H and a DNA-dependent RNA polymerase
+None
+Advisory Committee on Immunization Practices
+30%-58%
+Challenge trial refinements
+rMP12-PTNSs
+Bexsero and Trumenba
+mitochondria
+5
+CERVUS
+read count
+humoral response
+4%
+observed data
+SIGMASTAT
+Eleven
+restrict a broad range of highly pathogenic human viruses
+R 0 < 1
+Acutely infected
+Kenya
+95%
+Demographic groups
+antigen peptides
+PFAM and GO
+Eight
+RNGTT
+Nonstructural protein L
+specific
+Michaelis-Menten plot
+every 8 to 10 days
+100%
+Norwalk
+variable 3= untranslated regions
+50%
+small molecules, proteins, DNA, and virus particles
+once daily
+15
+Isoflurane
+food-borne
+GC7-triggered NP oligomerization
+robust
+10-19 years
+ocular
+Portugal
+IL18BP
+viral attenuation
+RaxML
+Neutrophil elastase inhibitors
+data
+social group learning
+gRNAs targeting HDAC5 exon 3 and exon 4
+P < 0.05
+83%
+25%
+low-titer inoculum
+paddy straw and water
+75 to 105 min
+lysates
+24
+five
+virus binding ability
+100μg/ml cycloheximid
+epistasis between any two sites would vary across different genetic backgrounds
+Google Earth
+potent and moderate antiviral agents
+Relative translation efficiency
+infection probability
+three
+1:500
+GP CL
+anti-RSV neutralizing antibody
+C-terminal segment of the homomorph
+1476
+Virus samples
+Uric acid
+unidentified viral pneumonia
+Ulp1
+the following
+8%
+NLRP3 inflammasome activation
+ATP5B
+Large aggregates
+7.5%
+mouse hepatitis virus and rotavirus group A
+6078
+Trizol reagent
+A functioning legal system
+delivers incoming viral particles to late endosomes
+ALI
+0.91 and 0.89
+epidemiological parameters
+BTV-1
+virus infection
+91.6%
+thousand
+serum albumin levels
+.91
+increasing global attention on rabies
+cc-by
+48 h
+Ribavirin
+1.2 million
+Two and a half billion
+97.5%
+Periodic assessment and improvement of the quality of data
+benzylpenicillin benzathine 2.4 MUI
+2007
+different types of commensal bacteria
+416
+reduction in disruptive handling
+50%
+viral proteins
+endemic equilibrium
+filamin A and the Src family kinase Lck
+national security and national interests
+IL-17
+SGs
+similar anatomical structures and bone density
+a reactive group
+Transition and transversion
+differential consequence
+phenylalanine, serine, and arginine
+10 IU/L
+ILI
+PR3A5 and 6G4
+preparation of sequencing libraries
+World Health Organization
+PKR-deficient
+Ficoll-density gradient
+4
+three days
+novel targets for the development of antiviral drugs
+the number of times pair ij has been in the sample space
+63%
+four
+SPSS 17.0
+the origin of eutherians
+HIV
+10.3389/fmicb.2019.00523
+mule deer
+three
+Sagrassum weighti
+reporting and recall biases
+g 3
+appropriated antibiotics
+non-uniformly weighted
+four
+Table 3
+Apolipoproteins
+CPV
+k
+Recombination
+long-term maintenance of therapeutic levels of vector-delivered transgenes
+adjuvants
+CCR5, SPP1 and b-actin
+H9N2-GFP
+anti-EGFR
+Egypt
+the government
+National CCHF prevention and control programmes
+reactivity
+computational epidemic models
+ORF1
+2,219
+MV with heliox
+nonfermenting yeast
+varies widely
+immune responses
+size, and minimal training
+4 weeks
+positive feedback for RIG-I signaling
+10 µM
+the 5 ′ end of potyviral RNAs
+499
+application to a greater pool of patients
+96%
+CFX96 Real-time PCR detection system
+20 min
+Chemiluminescence Reagent
+blood samples
+23
+10
+13.0%
+Shelter Neuter Return
+anti-SP-D and anti-megalin antibody
+Primary gastric epithelial cells
+rainfall
+Macrolides
+1% blocking solution
+conventional pandemic vaccines
+dynamics
+confocal
+The exact range of vertebrate hosts and their disease state upon infection
+text-free
+74
+Arrows
+5,000 bp
+20 mM Tris-HCl
+21 weeks
+28 nM AE 7
+inflammatory
+80%
+intermembrane domain 1 and the intracellular loop
+24 h
+computationally efficient
+LPS or zymosan
+mutation pressure
+sampling design
+a specific band corresponding to approximately 50-kDa molecular weight
+vasoconstrictor drugs
+eIF4E
+cross-border movements of animals and animal products
+3%
+inhibitory
+predictive certainty
+Initiation
+anti-pSrc
+random priming
+a set of rigid standards fixed for all time and in all contexts
+systemic
+unacceptably high
+I nfluenza
+20%
+2008-2009
+20-100%
+pol r,n,N,1
+differences in hemodynamics or UO
+taxonomy
+an intron
+2.5%
+Euclidean distance
+CAHFS Laboratory
+Secondary structure metrics
+8,950
+impact of the Great Depression
+EBOV surrogates
+hantavirus RNA
+human contact patterns and other host heterogeneity
+Low-dose vasopressin
+2 mg midazolam
+2%
+Forty-eight hours
+HPAI H5N1
+L = −1
+monocyte-attracting chemokines
+concussions
+three times a day
+infectivity of DI-244 particles
+substantial and durable
+ethidium bromide
+Comparative threshold cycle values
+0.5 and 0.65
+glycosylated SHH
+nucleolar accumulation of Pc
+detectable replicating virus load
+57%
+Microcephaly
+more efficacious
+eight
+virus-specific IgM, IgG, and IgG subclasses
+beta-galactosidase
+12
+DNase
+three
+other proteins in available databases
+spliced transcripts
+mahogany
+interactions between primers, template and polymerase
+Escherichia coli BL21-Goldenplus
+2.34 and 7.06 log10 copies/well
+elastin
+London
+adenoviruses
+the lymph node
+Blood samples
+lymphocytes
+more than 100
+10 μM EdU
+C. mellificae
+IFN-4
+18
+0.5-1 h
+incidence rate ratio
+Two different searches
+1.5% agarose gel
+Y ij
+ENSEMBL GeneView and the NCBI MapViewer
+Mann-Whitney U test
+CD8+ T cells
+interpretation of results
+look-alike regions
+between 10 6~1 0 7 bits
+venom serine carboxypeptidase
+genomic-based diagnosis and surveillance of hantavirus-borne outbreaks
+diverse astroviruses
+One week
+8,906,866 bp
+three
+M2
+YFP C-terminal fusions
+Bleeding
+hCT
+theragnostics
+3 days
+amino acid identity
+ingestion
+Infectious
+250
+3 days
+Basal autophagy
+Wales
+a third chemical
+pseudoknot-free base pairs
+cc-by
+non-overlapping epitopes
+0.3 Å
+Jalview
+viral and bacterial respiratory tract infections
+split-GFP reporter
+24 h
+Spl574
+effector memory cells
+cysteine
+Ciliary-mediated bead clearance
+rVSV
+12
+amelioration
+TNFRSF21
+optimum antigen loading efficiency, charge, stability and size of the NP
+51
+absence of a more comprehensive evaluation background
+end-expiratory lung volume
+mice and ferrets
+zoonotic
+40%
+2005
+The skeletal muscle
+45 %
+Supplementary Data
+no significant interaction effect
+antiperoxidase and antithyroglobulin
+inverted fluorescence microscope
+3526
+both kinds of strips
+cardiogenic shock
+Fifty-four
+HCV-induced NPCs
+55-min
+concurrent bacteremia
+transport of live animals
+Dr. S. Akira
+HMG CoA reductase
+performance
+separated virus
+ALV-J immune escape
+20uC with 0.4 mM IPTG
+2,747
+40-100%
+1600 bp
+HMBS and HPRT1
+animal models
+Ampelovirus
+to prevent the dissociation of RNA-protein complexes
+Formal information and hand hygiene
+Knockdown
+crude Polygonum aviculare
+influenza, cytomegalovirus and severe acute respiratory syndrome coronavirus
+41%
+inflammatory
+higher
+9 to 31%
+Synthetic peptide and multiple antigenic peptide based antigen
+Ponceau bands
+known miRNAs
+late 1970s
+emerging zoonoses
+Clean-catch mid-stream urine
+Mouth to mouth ventilations
+B and T lymphocytes
+ligase-like
+climate change
+All other ICU episodes
+L-Alanine isopropyl ester hydrochloride
+Chest infection
+tetra-peptide neck residues
+Victor 3 V Spectrophotometer
+yellow fever virus
+14.3%
+pathogenic
+1 to 5
+cell-matrix interactions
+phenformin-Zn 21 complex
+1394
+8.5 weeks
+confirmed transmission to contact-exposed pigs
+DIII variants with two independent mutations
+0.36 kg
+Intact MS2 PLP
+steroid information cards
+Finland
+pathophysiological
+HIV
+prevention and control measures
+loss events, and/or gene conversion
+Foursquare
+intracellular transmembrane glycoproteins
+controls
+reverse transcription-PCR
+percentages
+CMV reactivation
+stimulates the expression of NLRP3 and pro-IL-1β mRNA
+25-300 nm
+15
+14 hours
+non-overlapping epitopes
+75%
+carrier RNA
+injecting drug users
+30 min
+Orientation angle of the ligand binding to the receptor
+RPL4, EEF1A1, and RPS23
+similar
+Written informed consent
+mallards
+seven
+l k
+46%
+100%
+solid organ transplant recipients' increased vulnerability to these infections
+meaningful cut-offs
+donor cells
+Biacore X100 System
+cardiovascular diseases
+Beijing Institute of Microbiology and Epidemiology
+Febrile delirium
+cPK architecture
+Forward Inner Primer
+more than twice higher
+65%-70%
+the literature
+20
+Seven
+respiratory system resistance
+small interfering RNAs
+2 −ΔCT × 10
+Predictors of disease severity
+people at risk of impaired QoL
+unstable
+DENV infected cells
+Cpf1 nuclease
+3
+PA-PB1
+HRIC
+30 minutes
+5%
+IL-4/IL-13
+56%
+Positive-sense and negative-sense viral RNA
+37uC
+Crowding
+450-550 mg/m 2
+normal distribution
+31
+Excessive infiltration of polymorphonuclear leukocytes into the lungs
+resistant to C. rodentium-induced colitis
+logistic regression models
+crucial
+A DNA array
+Dilutions of immune or non-immune mouse sera
+30%
+NT-pro-BNP and myoglobin
+one to two weeks
+14 days
+ImageJ
+goat anti-mouse Alexa 555-conjugated antibody
+immunogen
+5-9 nucleotides downstream of the slippery sequence
+Noninvasive respiratory specimens
+Aviparvovirus
+Pattern recognition receptors
+unphosphorylated STAT
+Emetine
+less efficient VCP knockdown
+The amount of iron contained in cell lysates
+group 1
+65%
+antibacterial, antiviral, and antifungal
+10%
+ATP5B
+particles and the viral protein NS1
+intracellular calcium transient amplitude
+FeLV and FIV
+over all age and risk classes
+a balanced, rational response
+forty
+NK1.1 + CD3 +
+triplicate wells
+0.095
+minimum value
+CQ-loaded PLA nanoparticles system
+CD14 microbeads
+complicated use and high cost
+Enzyme dynamics in catalysis
+cohort
+2%
+clinical significance
+IFN-l3
+a sponge
+ineffective human to human transmission
+Core-on cells
+second half of 2019
+The FPT 100 %
+lowland rainforest
+5-20%
+Standardised triage procedures
+100-fold more native S598 peptide
+airborne precautions
+radius of gyration
+newly identified alleles
+Lorries
+Type VII
+cell migration
+5 days
+Fisher's exact test
+PA-Eastern
+DREAMS
+prevalence ratios
+7 days
+The UUUUU slippery sequence and the pseudoknot
+heterologously produced and purified TcdC protein
+210
+CXCR6
+phylogenetic incongruence
+disease manifestations among smokers
+Glucose concentrations at levels encountered in diabetes
+Pearson's correlation coefficients
+IFNβ promoter stimulator 1
+Perseus software algorithm
+Anti-stem antibodies
+Relative abundance
+DAPI staining of nucleus
+independent experimental data
+buffer on dissociation constants
+The standard
+bacterial respiratory infection
+connectivity and dilution
+mitochondrial RNA transcription and protein synthesis
+monocytes, macrophages and endothelial cells
+inhibitors
+recommendations for performance of these tests
+lactate dehydrogenase
+Cubs and subadults
+Approximately two-thirds
+sympathetic
+intramembrane cleavage
+logistic regression analysis and ANOVA
+RSV-inducible
+62%
+2%
+Antigen capture ELISA kits
+30 min
+1x MIC
+Pump It™ Automatic Delivery System
+phenanthroline
+3-5 %
+axis1
+to analyze the potential of TQ to induce apoptosis in Jurkat cells
+4-12% Bis-Tris gels
+8 hours
+NCBI RefSeq strains
+cytosolic cytochrome
+ATG12-ATG5 conjugation
+two
+Brainstem injury
+182
+Sigma-Aldrich
+35 476
+THBD expression
+vaccination status is checked and vaccination is started if needed
+tighter CD4 binding
+~30% to 40%
+40
+anti-BPI3V IgG
+excessive testing in stable patients
+GENIE3
+a BioSample record
+BACE1-APP interaction
+seven
+memory CD4+
+297
+C
+RNA backbone
+antiviral antibodies
+mass spectrometry
+Appropriate reference laboratories
+Caspase-3
+pigs have a full set of innate and adaptive
+48
+phenylalanine
+Five hundred ng purified DNA
+10 pM to 100 nM
+The niche approach
+Selectively relevant features
+1904
+Index case
+HEK293T cells
+70%
+weak points
+IL-10R blocked animals
+ZMapp
+lowest
+Public health interventions and individual-level adherence decisions
+C5a
+CXCL16
+differences in GVL effects
+m/z 100-1000
+over 90%
+61
+50
+unprocessed polyproteins
+ultrasound interpretation
+expression of additional IFN-inducible effectors
+selection frequency
+distance and travel times
+enterovirus and human rhinovirus genome
+read-level analysis
+studying
+different contractile behavior
+The pharmaceutical industry, its trade and access to medicines
+positive
+Negative trial data
+mutational noise
+1-25%
+ZMapp
+acute, convalescent, and chronic
+Associations between environmental temperature range and physiological tolerances
+In vivo testing
+AP-1 signaling
+Swiss-PdbViewer 4.1
+Pulmonary endothelium
+Gabon
+lysate
+5 : 1
+Imipenem and Meropenem
+FUS
+106
+Arthur Barth
+lipopolysaccharide
+graph-based signature concept
+stay home to care for sick children
+CDK and GRK2
+cc-by
+Passive incorporation
+127
+12-12-hour
+the fraction of number of new cases per case is decreasing
+idiosyncratic hybridization barriers
+115
+160 bp
+FXR/BSEP
+HTNV clearance and prevention of HFRS development
+100%
+2 weeks
+Antimicrobials
+respiratory symptoms
+One hundred and seventy-one
+Listeria
+More than 25%
+φ L
+Education and training of health workers
+viability and cytotoxicity
+Interferons
+Transcription of Gamma-1 genes
+zebrafish
+Capto Core 700 beads
+HFFF2
+ambiguity, interpersonal conflict, safety problems, and high job demands
+variable loop 2 -apex bnAb epitope
+normal organization of the nodes of Ranvier
+gonadal hormones
+stair ascending
+Four and eight weeks
+cardiotoxicity or myelosuppressive
+type II
+Lysates
+contact history
+sample processing methods
+between 10 to 20 ng/mL
+antagonistic to mutualistic
+5% SDS
+once a week
+five
+41.5 years
+cc-by
+reporter assay
+hypoglycosylation of viral GPC
+every 2 min
+2100 Bioanalyzer
+sequence divergence and diversity
+18%
+BPD and consequent pulmonary hypertension
+GPX4
+71
+adult population size, brood production, and foraging
+Dysregulation of ACE2
+values above a 3% threshold considered positive
+Prof. T. Honjo
+3
+NXY-059
+age and sex
+nuclear translocation factors
+NanoDrop spectrophotometer
+Ellman method
+SeqTrack
+Secondary structure content
+Betapropiolactone
+severe inflammatory responses
+Glycine
+6,772
+95% detection probability
+β 1
+Additional studies
+4
+PEI/DNA
+ATP binding
+zoonotic
+changing Asp552 to an Ala
+RII-SL
+115
+Bootstrap values below 70%
+a one-ended double-strand break
+two
+Dr Dario Campana
+Dividing the whole region into LTZ groups
+TransPlex reverse transcription
+Changes in fluid balance
+Therapeutic antibodies
+immunoinformatics based research
+Liesegang phenomena
+40 hours
+122 years old
+Correlation analysis of PCV
+locked in within the host body
+historical controls
+TRIZOL
+nucleotide and amino-acid similarities
+Table 4
+one organ or tract
+Four
+26/28
+70-90%
+IRES recognition
+t-test
+DMSO-d 6
+plaque reduction neutralization testing
+1%
+influenza virus antigen
+B cells
+.98%
+Ca 2+
+667
+620
+those suffering from pandemic flu and ONILIs
+Clinical data
+16
+ground glass opacities
+70%
+DVG recognition
+humans
+Shed ACE2
+cross-sectional studies
+eight
+available data
+90-100 thousand
+clinically or laboratory confirmed
+DeepView/Swiss-Pdb Viewer v3.7
+pulmonary
+in proximal tubule, podocytes, and mesangial cells
+suicide
+high-frequency surface decontamination
+optimal shape nor optimal spacing
+exogenous Ebola GP
+the number of residues of the peptide
+bone homeostasis and remodeling
+data were not available
+flow rates
+1,075
+between 11 and 25 May
+A qualified statistician
+natural selection
+molecular docking studies and thermodynamic analysis
+intubation and mechanical ventilation
+non-specific amplification
+100%
+1:80
+b
+functionality
+Recombination
+distance as well as mutual contact between subjects
+sodium
+replication-deficient adenoviruses
+10 mM ammonium acetate buffer and acetonitrile
+0.079 nmol/ml
+quintiles
+disengagement and silence
+5%
+3
+25%
+skeletal muscle TG content
+evaluation
+two to three times daily
+Increased numbers of people seeking medical care
+WZ and ZZ
+cytopathic
+89.66%
+NF-κB
+Coxiella burnetii
+an average fragment length of 200-500 bp
+ADAMTS-4
+important
+314
+Acute respiratory distress syndrome
+16s rRNA clones
+30
+EV71 VP1
+JEV serocomplex
+naïve T cells
+five
+12
+nine open reading frames
+S. pneumoniae
+by inhibiting the Spry1 gene
+smaller
+two or three atoms
+Four
+septic shock
+one-third
+PyBOP/DiPEA
+two hours
+demetallization
+confocal
+at least 40
+23
+IndiGO 2
+Engstrom
+an expected linear relationship between V and F
+an intracellular transcription
+aberrant sustained expression of pro-inflammatory cytokines and chemokines
+567
+limited
+aggravated immune response
+Bradford method
+Aging
+25%
+paramyxovirus family-specific and genus-specific primers
+sera
+Early etiological diagnosis
+Sample size
+higher knowledge scores
+five
+36 years
+KEMRI
+they underlie the majority of current mainstream pharma
+men
+45
+Further investigation
+GHRP
+Nacher and Araki
+60
+Rhinovirus
+environmental space
+ten
+Matrix protein 2
+an active cellular antiviral response
+papain
+one
+serum bilirubin
+18%
+tenascin C, CSPG4, and CD44
+Candida
+nuclease degradation
+FlowJo 10
+an acute CMV infection
+HE staining
+Native HNP1 from human leukocytes
+75%
+limited
+educational status, perception of the world and ambitions
+medical historians and paleopathologists
+p < 0.05
+a library containing 49 structural diverse drug-like molecules
+More than 8,000
+multiple alignments and subsequent truncations of the 59and 39UTRs
+human rotavirus infection
+C3a
+IAV
+MGBNFQ
+three
+carbon-bearing minerals
+Metropolis criterion
+cytokine production
+CTNNB1, CD44, STMN1 and LPL
+Mass and Conn
+60 min
+perinucleolar
+Neuroinflammation
+TIM-3
+25-40%
+Human APO-BEC3A
+60 to 80%
+59.5%
+Biotinylated goat-anti-mouse IgG
+3 mM DTT
+Genotyping for the Sgta alleles
+50%
+3-folds
+proteases
+Q89N
+the need to use the entire pathogen
+The index corresponding to the observed epidemic
+all levels of management
+blood culture
+susceptibility to infection and infectivity are controlled by the same set of genes
+$269,004
+20Á30%
+pUL21a
+flavonoids
+EPs 7630
+intravenous patient-controlled analgesia with fentanyl
+TRAF3 and TRAF6
+Ub-binding ZNF
+CesT
+30
+six
+BSL-4
+BCL2 family
+inhibits HCV replication
+Curves
+intracellularly
+antiviral therapies directed against measles
+humans
+twice
+Western blot analysis
+45%-90%
+20
+Thirty-four
+3
+Febrile seizures
+All authors
+Supportive care with appropriate infection control
+Culture based methods
+Statistical
+once
+immunisation levels
+Sin3A and MeCP2
+Hundreds
+increase
+Dulbecco's modified minimal essential medium
+nonaromatic substitutions
+0.25%
+three
+Selective IgA deficiency
+sustained inflammation, nephropathy and tissue iron deposition
+Saponin
+49.7%
+investigation of these parts of the pathogen's ecology
+ketamine/xylazine
+T-helper 1
+Antigens for the macaque ELISA
+Five
+SC236 or vehicle control
+stable SL structures and cyclization motif
+The extended stem-loop
+CDC Influenza Virologic Surveillance
+pseudohyphae
+phenolics, terpenoids and alkaloids
+Vector doses
+Gag retention
+hospitalized patients with an acute exacerbation of COPD
+CEA splice variant
+annealing temperature
+Migratory waterfowl
+lipid mixture
+iProt-Sub website
+10 and 5
+15 cm
+4, 7, and 9
+polygons
+those sequences for which the protein identity and function have been experimentally confirmed
+t
+The current state of the art in synthetic methodology
+abasic PNA 2
+low-and middle-income countries
+underlying rules
+lymphocytes
+DNA Platinum Taq Polymerase
+publication bias
+tinea imbricata
+have good transport and communication access in case of adverse events
+ACE2, Angiotensin- ] and Mas
+Receiver Operating Characteristic curve 27
+cell surface HS
+cognitive/affective
+neutralization assays
+AIDS and Hepatitis C and B
+ApoE4
+significant increases in fever rates
+ENPEP
+unique substitution and positive selection
+capsules, tablets, and solutions
+122
+33,238
+1 s
+159/89
+15-lipoxygenase
+how quarantine and class closures may affect different types of families
+resistance to drugmediated RdRp inhibition
+restricted DENV and VSV replication
+Influenza A
+results quick enough to guide point-of-care clinical decisionmaking
+autophagy enhancers
+TNF and IL-1
+Customization of health care
+Four
+drug-drug interactions mediated by CYP enzymes
+S-I-R equations
+IL-4 deficiency
+manidipine
+fear and fear reactions
+12
+target sets
+toll-like receptor 4
+harmonic frequencies
+enzymes
+Five
+seasonality
+Vimentin
+bronchiolitis, pneumonia, bronchitis, and croup
+50%
+Z-VAD-FMK
+PAML
+firefly/Renilla signal ratios
+hematoxylin and eosin
+immune CD4 + T cells
+EC6, PO1, and poliovirus 3
+agent-based or microsimulation models
+14
+DC maturation
+XendoU
+30,000
+modesty and trustworthiness
+Brains
+human respiratory virus dataset
+Lung aeration scores
+serological and virological methods
+mixed-effects logistic regression model
+27.4%
+Nosocomial transmission of respiratory viruses
+Practitioners, midwives and nurses
+Kruskal-Wallis test
+cGAMP
+macrophage polarization
+all public events
+Deborah Diamond
+nicotinamide adenine dinucleotide
+Sinopharm Chemical Reagent Co., Ltd
+1
+Prolonged expression
+infl uenza disease development
+1 μg/ml
+regulating the APC
+Infectious bronchitis
+hibernation
+stem 1 or stem 2
+three
+PDGFR-α
+public health
+60%
+Increasingly abnormal INR
+local
+anti-B220-APC and anti-IgD-PE
+TreeAnnotator
+vital status
+13%
+60%
+Plasmalogens
+Unfolding
+immunofluorescence
+TB, malaria, HIV, biochemistry, and haematology
+IRF-3
+artificial intelligence
+75.9-77.1%
+Coptis sp. and Berberis sp.
+rhinovirus/enterovirus
+chemoattractant
+Barnase
+2009
+Serial interval distribution
+DIs
+N j
+teledermatology
+47.3%
+exclusion
+social and cultural contexts
+9 m 3 /min
+glyceraldehyde-3-phosphate dehydrogenase
+Whole transcriptome spotted MEEBO microarrays
+low
+The funding sponsors
+cryo-em reconstruction
+3
+mortality
+Streptactin sepharose beads
+VirHostNet interface
+orthologous gene clustering
+blood parasites
+PB2
+viral culture
+10
+3.4
+zebrafish and stickleback
+relatively low
+take primary responsibility to establish a global partnership for development
+Population density
+CD1c + Dendritic Cell Isolation Kit
+inflammation-induced tissue damage
+family relationship
+microarray platforms
+77
+Pure water
+Supply issues
+Nterminal domain
+Tat
+PMA and ionomycin
+TaqR mastermix
+symptoms of severe neuropathogenesis
+>512 mg/L
+49
+Information on host-pathogen interactions
+the number of input dendrites
+2:2
+multi-agent
+F = 1/2d = 0.5
+neutrophilic inflammation and the ER stress response
+six
+30.5%
+T cells and neutrophils
+telestem
+differences in storage time and temperature
+binary
+human macrophages
+ViPR
+insulin resistance
+DiOC
+Weld of the nucleolus
+HTV ventilation
+Acute renal failure
+Rvs167
+UGG>GGG>CGG>AGG
+21.2±8.7%
+male
+32
+Metatranscriptomics
+63
+minimal seroprevalence
+stochastic
+69%
+0.6
+n
+two
+32
+98%
+2, 4 and 10 mins
+single-cell topological data analysis
+p-SCN-Bn-DFO
+MHC class II synthesis and ubiquitination
+rHc-CS
+Age and minority status
+≤ 0.05
+OcUGT1-assisted aglycon exchange
+blue
+97%
+34 • C
+HaploView 4.1
+Ebola VLPs
+unspecific translation initiation
+clinical observation and monitoring of hematological and chemical parameters
+respiratory CD103 + CD11b lo cDCs
+CyDyes
+1 h
+significant cell cycle arrest
+953
+Kristina Grant and Francine Cousinery
+reduced fusion capacity
+male gender
+lysates
+Bio-Rad iScript cDNA synthesis kit
+people made judgements about both likelihood and consequences
+Serfling regression
+memory CD8 T cells
+growth and differentiation
+commercially obtained from Upstate
+1000
+lactate dehydrogenase
+5-15
+multicycle growth curves
+fecal samples
+mouse hybridoma supernatants
+Diff-Quik
+Amitriptyline, venlafaxine and Fluoxetine
+reduced barrier function
+naïve T cells
+529 ± 169X
+gas chromatographic
+chronic fatigue and comorbidities
+sepsis
+18
+A421V
+4%
+10,988 nucleotides
+Sudden fall in tidal volume
+sepsis
+610
+numbers indicated by market managers
+counters and raw data
+ALI cultures
+17
+ER transmembrane cargo receptors
+repressor element-1 silencing transcription factor
+Uncapped mRNAs
+regression parameters
+Random contact
+mutations
+infect new targets
+Variability
+Pm isolation collected samples
+two
+serine-threonine kinase Raf-1
+51,709,000
+35
+macrophage
+polymerase chain reaction
+Mechanical ventilation status
+10-100 fold
+4uC
+t E max and t I max
+astrocytes or neurons
+a subset of these probes that map to unique target regions of the selected pathogens
+Argentina
+three
+geographic distance
+efficacy
+ZEN
+decreased platelet counts
+AMPs
+the additive constant term
+six
+static distributions of SA
+P3 1 12
+Interferon IFN-β
+separate
+Inflammatory
+116
+training on Ebola
+30 µM
+Comparison of its predictive value compared with type assignments based on VP1 sequences
+dose or treatment duration
+mucosal
+the apical surface of the airway epithelium
+Likelihood Ratio
+timing and impact of influenza epidemics
+IL-12p40
+8 hours
+23
+ubiquitination of proteins
+two
+Four
+sH5 3 -specific ELISA
+Avian influenza A
+macrophages
+long-distance travel
+ClarityChrom
+IFN-γ expression
+intracellular proteolysis
+fatal pathogenesis of C. albicans infection
+Glycosylation
+C. jejuni
+vector copies/spleen
+10,345
+6
+MEK1/2
+TE self-regulatory mechanisms
+1926
+detectable levels of viral RNA
+GBP5
+centrifugation
+travel restrictions
+flow cytometry
+macrolides or flouroquinolones
+92.8%
+Targeting host cell factors
+Dominant negative
+18 years or greater
+humans
+LpKS9 and LpAM9
+Cysteine residues within the peptide
+Sixty-one
+89%
+Data
+trivalent inactivated vaccine
+Genomic DNA
+ε m
+pleiotropic
+minor nucleotide substitutions
+eight
+acute respiratory distress syndrome
+paramyxoviruses
+relapses in MS patients
+I-TASSER server predicted 5 models
+influenza vaccination status
+individual student health data
+cellular prohibitin-1 and -2
+hydrolytic enzymes
+1999
+36 hpi
+GC content
+Respiratory diseases
+5.6 to 8.1 Å
+CTLA4
+HLA-A*02
+Detailed clinical information
+HA 1 and HA 2
+AM
+Mafb
+a-proteobacteria
+pathophysiological
+282
+0 to 20%
+first-pass uptake
+Purified M145K sample
+Child-Pugh score
+Comparative genomics
+troubleshooting and refinement of specific procedures
+Contracting an infectious disease
+polyhedrin
+bioinformatics tools
+Patients, parents, and/or their legal guardians
+Nanoparticle size, shape, and capacity for surface modifications
+the reporter protein
+predictive or explanatory
+induced sputum samples
+virus
+CEACAM1
+pneumonia
+every 10 minutes
+Beyotime Biological Technology Co., Ltd
+allele designations
+two
+55-64
+viral replication
+VP4/VP2 sequencing
+Innate responses
+most stakeholders
+CD8 T cells
+viscosity
+branching
+770
+one RFID tag
+31.0%
+Bonferroni tests
+temporal changes in lipids prior to disease onset
+favipiravir
+5%
+viral RNA abundance
+The pathogenesis of hantavirus infections
+the number of genes per spot
+discovery
+Mutagenesis of cj0669
+genetic evolution and dN/dS selection pressure
+60 days
+last distribution
+different levels of contact
+a doctor's certificate
+thiol reagent 2-Mercaptoethanol
+30%
+FOXP3 -Tr1 cells
+Peritoneal lavage fluids and serum samples
+all disasters are "local"
+15%
+TLR4
+GIV NS4
+their host's genome
+a docking software
+Archosauria
+12
+5%
+Four
+highthroughput sequencing technologies
+Membranes
+facultative
+infectious virus
+Disease modeling
+exposure to the virus
+Five
+pulmonary hyperinflammatory response
+200.6%
+reporting disincentives
+an algorithmic guide to action
+Five
+Anopheles stephensi and An. gambia
+r
+PS matching and multivariable adjustments
+FACScan flow cytometer
+A DNase treatment
+ubiquitin and Nedd8
+EBOV infected mice
+Equations 7 and 10
+Microaary analysis
+aqueous KCl
+IAV-responsive kinases
+4%
+anti-CTA1
+polymer-based
+late 2003
+EEG reactivity
+Unpaired t-test
+Synthetic constructs, incomplete and wrong sequences
+16S rRNA
+social and physiological
+fibroblasts and lymphocytes
+Bid
+bloodstream infection and the infection pathogen of New Bunya virus
+FIV
+exogenous siderophores or host proteins
+PepsNMR and speaq
+Ferritin
+Softmax pro 4.8
+312 K
+missense or nonsense mutations
+IFNλ4
+CYR61
+7.2 ± 2.1 pups
+approved and proven therapeutics or vaccines
+FHV-1
+plasmacytoid DCs
+r-gene products
+ssDNA
+melanoma differentiation-associated gene 5
+OH of Thr2
+argB-37
+viral antigen detection
+flow
+Evolutionary models that incorporate protein structural domains
+ABCB1-mediated
+Local sensitivity analysis
+CrebA
+FluA and FluB DNA-encoded monoclonal antibodies
+infectious diseases
+p1 or p5
+Bidimensional ultrasonography
+GLM models
+90 μL supernatant
+1,200
+Dehydroepiandrosterone
+LuxScan TM 3.0 software
+Disease similarity tools
+soluble viral receptors
+suboptimal base stacking energies
+H7N9 influenza susceptibility
+master equations
+ex-over str
+restrictions on publicly-available transcriptome assemblies
+1.2, 0.1 and 0%
+changes in oral health
+G1 and S-G2-M phases
+18 h
+60 %
+0.3-8.4%
+a helix
+Contact tracing
+1,675,933
+sequencing
+Table 1
+3 or 4
+Factors that change the translation fidelity and kinetics
+more resources for infection control
+Zika virus
+Additional file 1
+chloroform
+2 weeks
+23.1 g
+50 ng/l Proteinase K and 0.15% SDS
+structural SP-D polymorphisms
+Mean-field models
+cells without PA83 adding
+HindIII site
+Pre-stained Protein Ladder
+83.7%
+Erythrocyte sedimentation rate
+community gatekeepers
+LoxP sites
+444,751
+>7.5%
+ingestion of contaminated fecal pellets shed by infected mice
+absence and symptom reports
+subgenomic flavivirus RNA
+two
+NHE1
+five
+autophagy-associated proteins
+10
+Emerging infectious diseases
+galactosidase
+IL-17A
+compound 3a
+SVM algorithms
+AE
+medical journals
+single-species studies
+81%
+diabetics
+Post-death transmission
+Ekachai Jenwitheesuk
+Apdm09
+sialic acid receptors
+linear regression
+10 mg/ml
+three
+weak
+domesticated ungulates
+Average raw luminescence units
+plasmacytoid dendritic cells
+Ae {Bn
+374
+25%
+LightCycler 480
+1571
+Supplementary Text 10, Supplementary Table 8 and Supplementary Figure 20
+growth inhibition
+NSs-mediated PKR downregulation
+HE glycoprotein
+pcDNA3.1-SynORF5 plasmid
+BiP
+10 %
+three
+pregnancyassociated malaria
+3.74±0.18 μM
+CD8+ T cell infiltration into the CNS
+cystathionine γ-lyase
+crested ibis
+Uganda
+TRI Reagent
+transcription of both DRD2 and NCAM1
+Coutinho
+restriction digestion
+high-dose steroids
+no association of BK virus with nephritis
+further studies
+Allelic variation at Lsh and H2 loci
+a functional PPXY late domain
+R-Mix culture system
+2 days
+size exclusion chromatography
+an arginine
+PGs
+hygiene measures
+gravity model and the two-step floating catchment area method
+98%
+MTT-assay
+loss of fitness in mutants
+they only contain trace amounts of glycolipids
+27%
+12
+20,000
+MultiGauge software
+1000
+maternal antibodies
+differentiation of Tfh producing IL-21
+Aminoacylation
+binds and inactivates
+Ten
+Five
+methylene-THF
+QIAamp DNA Mini Kit
+qPCR analysis
+absorbances
+genotype 3
+the very ends of the segments
+acute inflammatory
+antimicrobial resistance
+hRID-fusion
+solvent
+260 million
+Species-specific miRNA-targeting of influenza A virus
+8
+30 minutes
+two
+*6,996 nt
+ERMS
+disease-related information
+Wilcoxon signed rank test
+NE-PER Nuclear and Cytoplasmic Extraction Reagents
+the D pocket
+PN, DN, NN, MC and Time
+Vimentin
+erasure of imprinting
+eggs from each hen
+D85
+high nucleotide sequence conservation
+>0.99
+0.22 mg/ml
+2-4 log
+Autophagy
+Glu
+proinflammatory mediator production
+4% PFA
+400
+24 to 32 hours
+a highly bioavailable supplement of organic Se
+2011
+reverse genetics
+14
+epidemiological change
+apoptosis
+jain
+18
+0.005 to 0.014 μg/mL
+28,616
+adaptive immune response
+IL-15
+three
+more than 200 mg/L
+March 11, 2020
+CD8+ T cells
+chaffinches
+Rickettsiae
+Nasal wash, serum and spleen samples
+Caraparu orthobunyavirus
+non-tumoral cells
+cholesterol-depleting agent
+alveolar macrophages
+2 to 9%
+one of the best performances of the challenge
+One-color Spike-in Kit
+three
+decreased ACE2 and increased ACE concentration
+transmission rate
+constant comparison method
+35%
+500
+mock-infected
+pyroptosis
+14 days
+Magnetic targeting
+probe-based real time amplification techniques
+Cytoplasmic tail of the A/M2
+PAK1, MINK and MAP4K2
+inhibitor quality
+FCV
+V5
+two
+interfere with cell cycle regulation
+38
+36-39
+multilevel
+charantia
+164
+Astrocytes
+redox imbalance
+Korean bat paramyxoviruses
+blue
+use the nuclear transport machinery and access the MW
+antiviral selectivity
+age and URI
+SDS loading buffer
+Two adjacent prM C-terminal transmembrane domains
+those at risk of disease progression
+170
+73.84%
+Anti-CD4 mAb
+mutation 6K1 T1210M
+Galactokinase recombineering
+≈100%
+a Kunitz-type serine protease inhibitor
+higher thermodynamic stability and RNA-like structural properties
+November 2004 to November 2014
+similar ones
+Semliki Forest virus
+18.8 kg/m 2
+ISG15
+DNA molecules in higher eukaryotes
+p j
+50%
+Immunoprecipitation
+aspartic acid/proline linker
+a non-TIB region
+TNF receptor type 1-associated DEATH domain protein
+Twenty-five
+2610 9
+TDMD of miR-27
+one day
+transient worsening of colonic disease
+A. albopictus
+increased
+10% water or 100 mM DTT
+burial rites
+cytopathic protection assays and multistep growth assays
+Photocatalysts
+six
+Santa Cruz Biotechnology
+flow trigger
+10
+6
+Hillary Clinton
+347 nt
+2=-O-methylation
+rib_host
+immobilized
+PRRSV glycoprotein 5
+13
+Displacement of the tRNAs
+obvious phenotypes
+13 C NMR
+T12 FEI electron microscope
+Sina Weibo
+25.0%-20.8%
+non-tuberculous
+0.15
+79
+Trans-Proteomic Pipeline
+their property in tertiary structure
+Dengue haemorrhagic shock
+42
+three
+siM2
+epitope mutations
+879
+nutrition
+severe acute respiratory syndrome and Middle East respiratory syndrome
+Tails
+κ = 1
+lack of national coordination
+CPB-caused oxidative stress
+Caco2 cells
+one
+an extended MDT
+The ER
+Behavior changes
+peripatetic workers
+Antibody scFvG36
+FeLV antigenemia
+neutrophil chemotaxis
+risk of exposure versus risk of serious illness and death
+early childhood
+Four hundred and thirty six
+10.1371/journal.pone.0006681
+GeoChip 2.0
+a physician
+two waves
+isolation and contact tracing
+HLA
+improved health
+Over 6%
+all possible sequence changes
+75%
+N-terminal caspase activation and recruitment domains
+codon optimization
+proline-rich peptides
+a private network of hospitals
+brain CT scan
+monoclonal
+Inherited and acquired variability in host immune responses
+assays
+commercial enzyme-linked immunoassay kits
+Viperin
+viral strain names
+pVSV-XN2
+MnmC
+United States and Australia
+two
+antibiotics usage and resistance
+β-casein
+sensitivity
+N63Y
+inter-patient variability
+ascovirus genes
+two
+the attending or on-call physician
+Relatively little
+intercellular adhesion molecule 1
+Biomarkers
+to avoid hydrolysis
+SuperScript III
+pharmacological agents
+the degree to which data correctly reflect the real world event being described
+under specific pathogen-free conditions
+May 22-June 10, 2015
+a node that exerts control over at least five other nodes
+Polymyxin B
+LA/DG
+Total RNA
+100 nM primers
+strong or good
+Influenza A pdm09
+cloning all predicted ORFs into flexible recombinational vectors
+a random distribution
+A fraction
+strategic alignment and alignment with regional/national priorities, policies and objectives
+experimental validation
+western medicine
+Unsupervised
+Th9 cells
+a dose of ten 50% lethal dose of VV-WR
+2.21 fold
+a, α 1 and α 2
+three
+98.1%
+E of M4 and M5/6
+similar to that observed the previous year
+antibodies
+Flavonoids
+North America, Asia and South America
+SMZ-CO and echinocandin
+in tubes with EDTA
+webchem
+aspects of resilience
+65.0 probable and confirmed cases
+EpiQuick Tissue Chromatin Immunoprecipitation Kit
+microbes and infection pathways
+five
+scattered light
+311
+rabbit anti-lprG antiserum
+flow cytometric
+powerful adjuvants
+CTSL
+anti-infective antibodies
+Birds and primates
+three
+uracil
+wprctile
+CCR8
+2.99
+Japan and South Korea
+serum-free growth medium
+the purity of the circular TFO RNAs
+Ribosome bound eEF2
+study methods
+Gene expression
+Animal Care and Use Committee
+3 million
+detergent-free PBS
+Pygmies and chimpanzees
+Viral load
+IV cidofovir
+18 days
+20
+ϳ1%
+injection site pain
+Hybridization
+DNA ligase
+Vero cells
+HCV diagnosis
+two or three
+efficient NSs accumulation
+Prospective cohort
+2
+20%
+after every few years of human circulation
+how people travelled here
+no impairment of chemotaxis
+Chromosomal
+NF-kB
+Seven
+Outbreaks
+Known copies of plasmid carrying the CCR5 gene
+404
+98%
+both the upstream SD sequence and the downstream hairpin
+RDP v4.0
+Antibody-directed modulation of immune cell checkpoint receptors
+small grey circles
+OvAstV-1
+rhizosphere
+pcUL132sigHA
+99.9%
+live-attenuated and inactivated/killed pathogens
+Communication systems
+inflammatory cells derived from the periphery
+the sum of the highest score obtained for each of 13 symptoms
+TCID 50
+2.5 hours
+Eight
+virus isolation
+spore levels
+119,334-bp
+surveillance cultures
+inflammatory mediators
+partial HIV-1 pol sequences
+RNA interference
+six
+it will fund the whole genome sequencing of Raja erinacea
+DENV2 infection
+sites for virus assembly
+BMDMs
+keep the ORFs after endogenization
+eight
+isolation or the molecular detection of MP
+protein kinases and epigenetic enzymes
+provisions to avoid renal failure
+how to prevent EVD
+10%
+outbreaks
+Class cancelation
+by using numbers
+surfactant proteins
+ULTRASCAN
+RPI1807
+respiratory diseases
+in vitro and in vivo experiments
+Six
+31
+LDH cytotoxicity assay kit
+42
+no significant differences in weight loss or survival were detected
+exosomes
+PCR-based methods
+improved durability of antibody
+Arvind Patel
+1.7 to 3.7
+Arginine deaminase
+55.5%
+mononeddylated
+rpoS
+S598 determinant
+IgG2 deficiency
+62
+LB, iron-depleted M9 and iron-rich M9 media
+Foxp3 − IL-10 high Tr1 cells
+protein aggregation
+Changes in cell permeability
+did not exacerbate EAE
+One millimole of R 1 OH and 1-ethyl-
+provincial laboratory system
+0.1%
+Vi-CELL cell viability analyzer
+IFN-γ
+F-measure
+10
+2,237
+molecular
+60%
+conflicting data
+targeting expression
+23%
+homogenous spot morphology as well as low background
+IBM SPSS Statistics 20
+106
+293T cells
+Alteration of SSTR2 expression in the MGT
+IRF1
+Atypical pneumonia and hepatitis
+50, 10, and 2 µM
+Residual impedence
+quantitative real time polymerase chain reaction
+cascaded hybridization events
+the transcriptome
+plasmapheresis
+Siddhartha Mukherjee
+human IgG Fc
+eighteen
+24
+log-normally distributed
+Fc Receptor γii Surfactant protein D
+Cirrhotic
+irrigation canals
+WS hMSCs
+paucity of data
+Internal forward and reverse primers
+GTPase RAB5
+120% of the relaxed length
+E. coli b-galactosidase
+mAb CR9114
+19
+1%
+two washes with cold D/B
+Src
+10
+interest
+multiple cell systems
+Flavivirus
+24.4%
+5-10%
+transportation of newly synthesized NPs to the nucleus
+P2Y12 −/− microglia
+Dendritic cells
+P1
+27
+Phi29 polymerase
+host-parasite
+sepsis
+public health
+20 hours
+PVR body mass
+Atg9
+66.4%
+polyethylene glycol 6000 and sodium dextran sulfate
+Vaccines
+50% and 100%
+relative light units
+$17%
+c-src kinase activity
+NCBI Basic Local Alignment Search Tool
+acute respiratory distress syndrome
+methanol
+individual sequence variants
+oxidative burst
+large variability in droplet size
+6 items relating to norms about male-female relationships and interactions
+Samples
+~10 kDa
+changes in the stop codon position
+TissueLyser
+3 min
+West Nile virus
+1 to 3 weeks
+100%
+LPS-induced lung injury and inflammation
+parasite persistence
+k − 1 quartet
+Disease transmission
+selective suppression of virus reproduction without adverse effect on the viability of host cells
+Stabilization by fusion to Nuc
+F. tularensis
+Attachment of polyethylene glycol polymer
+kakkonto
+WHO
+fresh medium
+RSV
+nine
+antibody fragments
+an S.pombe homolog of antizyme
+Cost-effective interventions
+2007
+less than one year
+multi-tasking
+95% and 70%
+green color
+Over 95%
+.
+straightforward estimation of the age-specific cumulative incidence of infection
+Unpaired t-test or Mann-Whitney U-test
+overloading
+lower
+binding and infection of PSV
+higher vector particles-to-cell ratio
+no differential effect of TAAR1 on cancer survival
+stress
+tetraspanin proteins
+LMP1 activation of NF-NB signaling
+Univariate
+HBoV
+Neurocognitive sequelae
+four
+genebased vaccines
+Epidemic intelligence
+circulating erythrocytes
+changes in bacterial numbers
+HTNV-triggered NEAT1 elevation
+b-Actin
+Cryo-EM data
+Sn 1
+Figure 3A
+CC mice
+antibody dependent intracellular neutralization
+cysteinyl-tRNA synthetase
+67.5%
+tRNA exon halves
+44
+Drug users, prostitutes and itinerant workers
+Respiratory health and function in adulthood
+B-WICH, NoRC and SWI/SNF
+standard deviation divided by mean
+V
+K efflux and mitochondrial reactive oxygen species
+sensitivity analyses
+Gingivitis
+proteasomal degradation of cyclin D1
+17%
+6A 2 to 1A 0
+hemorrhagic shock
+Greater than 95%
+ABCB1
+Monte Carlo simulation
+claudin 2
+Bacterial MOIs of 0.1 and 0.01
+environmental factors, school opening, and climate
+interstitial
+scale-free networks
+mouse anti-human antibody response
+calpastatin
+defensive
+potential key mechanisms for the host defense against NDV
+69/1113
+16 mg/dL
+14
+Escherichia
+More than 17,300
+recognize the ␣Gal epitope
+all year round
+colonic mucosal tissues
+Mathematical modeling
+serum β-D-gulcan and chest CT findings
+10 mg/mL low SPP dose
+mobile phones
+virus-infected cells
+phosphorylation of mammalian target of rapamycin
+83
+27.3%
+DB32-6
+104
+4
+rabbit reticulocyte lysate
+advance knowledge of major weather events
+lymphocyte-epithelial cell adhesion
+HIV-1, hCMV, HSV and KSHV
+Patients with destroyed lung secondary to other causes
+Rhabditia
+12 h
+ovarian
+automated term selection by double penalty smoothing 53
+LightCycler Nano
+an evolutionarily highly conserved superfamily of proteins
+lectin-glycoprotein interactions
+three out of seven
+sera of experimentally T. gondii immunized mice
+Saccharomyces cerevisiae
+chromatin immunoprecipitation assay
+ARIMA model
+CD4bs
+traditional plaque assays
+interfering with Vps3/Vps8dependent integrin recycling
+twice
+80%
+cytoplasmic
+1500
+The titer of the progeny virus
+cessation of granulocyte recruitment
+Three
+Med8
+Significant binding
+January 13
+light and dark gray
+138
+respiratory tract infections
+Rift Valley fever virus
+anti-CD70 therapy
+H9N2-subtype influenza
+three
+structure of database
+chaperone function
+CDOCKER
+90 min
+a bus station, a bus compartment, and a hospital
+Mouse monoclonal antibodies
+Pillar cells
+complementrelated
+The Journal of Infectious Diseases
+CD8 ϩ IFN-␥ ϩ T cells
+0.12
+MCPyV
+twice daily
+Cell one in the sensor chip without antigen
+ϳ20%
+laboratory fish
+by quantitative RT-PCR
+three
+future studies
+Smad1
+5 years
+1-43%
+March 2005
+viral
+FLAG-PCP
+Syk activity
+all the features derived from global alignment
+innate immune response
+sensitive
+high interindividual differences
+mRNA coding sequences
+mutations within SSP
+59
+mortality
+inflammatory
+natural selection
+peroxidase-labeled anti-mouse IgG
+Four
+ELISA kits
+370-Gln→Arg
+2-CTC resin and standard Fmoc chemistry
+CD11b + Ly-6C lo monocytes
+the system
+TSG-6 production
+any qualified researcher
+GM-CSF expression and immune tolerance
+a century
+Paris dicistrovirus
+bactericidal activity of GRA and GR-SU
+primers
+130
+acetic acid
+antiviral drugs
+63.96%
+mycological, histological, and genetic tests
+disease
+realistic parameter values and model based formulae and simulations
+12.6%
+93,390
+small and quiescent
+Polaxamer 188
+À1 RF induced NMD
+major immune mechanisms
+fusiogenic Env species
+14%
+CD4 + IL-17A + cells
+asthma
+ESCRT proteins
+elevated amounts of PB1
+seven
+Figure 1
+An ESE in exon 2 of CD200
+two models
+low temperature treatment of soybean seedlings
+5 to 100 nm
+type assignments
+TBP and YWHAZ
+relative gene expression
+delaying proper ventilatory support
+6 hours
+Oran Young
+contagious intranasal tumors of sheep
+methicillin-resistant S. aureus
+nanopure or Milli-Q quality water
+Phylogenetic
+twice
+type 1
+significantly reduced
+LRTIs
+Eight
+global changes in the chromatin structure and interactions of chromatin-binding proteins
+Phylogenetic clade
+Flowminder 13
+5 ml of 4x SDS PAGE sample buffer
+three
+1-phenyl-2-thiourea
+an OTU-like motif
+centrifugation
+TNF-α
+PBS
+ribosomal reinitiation after sORF2
+35
+phylogenetic
+severe pneumonia
+mathematical model
+two
+VP1 specific primers and DNA sequencing of the PCR products
+Teachers and other staff
+Virus inoculum
+30
+Longitudinal data
+B. subtilis
+lentiviral
+Heterorhabditis indica transcriptome dataset
+30-45 minutes
+chemokine
+30 minutes
+periderm
+it does not allow naked-eye visualization of G4s in solution
+2%
+45.4 ± 20.8 years
+symptomatic infection
+five
+pathogenesis
+10%
+4029
+a random association of mononucleotides
+20
+24 h
+macrophages and dendritic cells
+zero
+inflammatory
+74
+heterogeneous
+setting-appropriate
+nonspecific binding
+virulence
+2009
+TNFR
+humans
+Macrophages
+0.0387
+6 months
+VRC01
+41.4% increase in sensitivity
+Tedros Adhanom Ghebreyesus
+substrate accumulation
+rDNA copy number
+iron acquisition from hemoglobin or heme
+directed physical connections
+Lipofectamine 2000
+KAPA HiFi polymerase
+EIT parameter
+55.98%
+LH-H
+133
+Efficacy, noninferiority, and superiority
+PS1
+2-hour
+releases the complex of T0 and H0 into next circulation
+stable basetriplet interactions
+JEE
+n*m
+identifying the highly similar/dissimilar block in the unknown sequences
+Ordered and continuous data
+regions with sequences similar to transcripts of proteins from human, mouse and rat
+Metagenomics
+tracking and connecting all of the components of a model
+Parkinson's disease
+siRNAs
+subtractive
+genes expressed at or near the background level
+every 3 months
+100%
+greater differences
+10-days
+LDH release assay
+epidemics in various regions and subsequent acquisition of herd immunity
+negative selection
+IL-2
+a characteristic of the specific cell type
+adaptive online estimation
+type I IFN induction
+infiltration of macrophages
+veterinarians
+GraphPad Prism
+Indirect-ELISA
+30
+comparison between severe and non-severe cases
+clustering of genes
+Temperature and specific humidity
+Perturbation of mitochondrial membrane potential
+436
+overexpression of tRNA Lys mcm 5 s 2 UUU
+C7 and C8B
+aberrant methylation
+viral RNA quantities
+four
+Western blot analysis
+The University of Melbourne Animal Ethics Committee
+soft convergent overlap
+72 hours
+conductance
+Heuristic algorithms
+A twotailed Student's t test
+R VH 0
+27
+sera
+Viral phylogenetic analysis
+1, 3 and 24 h
+600 seconds or 900 seconds
+θ
+14th, 21st and 28th
+APOPercentage Apoptosis Assay
+percentages of neutrophils
+antiviral responses to IAV infection
+Immunosuppression
+Brassicaceae
+rOpenSci
+N
+to enable the calculation of subgroup averages
+Littermate controls
+higher response efficacy
+no significant similarity with human pathogens and other closely related pathogens
+airway epithelium
+viral
+39 days
+long-lived plasma cells
+Acyclovir
+49
+50
+15
+GLT-1
+Glutathione, SOD2, and ATP
+8
+5,000
+intubation
+Roughly 17, 000
+infiltration of CD8 + T cells into MM tissues
+local disease spread
+13%
+ERK pathway
+40-fold
+1:200
+MusD
+R6
+Autophagy
+65%
+75 years
+satellite data
+RSV
+multi-agent geosimulation
+TERA
+Nrf2 and HO-1
+C, NS3 and NS5
+Extensive PMN influx into the lungs
+early childhood
+trifluoromethanesulfonic acid /water
+ethidium bromide staining in 1× TAE buffer
+3,169
+a larger supply of beneficial, compensatory mutations
+2.53 μM
+non-parametric tests
+it did not internalize cells in such an efficient manner
+53
+social and ecological
+caveolae
+mutant PfCRT
+rMVA-GFP infected cells
+Firmicutes and Bacteriotedes
+Transfer of exosomes to B-CLL cells
+orchestrating immune responses
+Ebola GP
+ethical reasons
+standard deviation
+LOX and RUNX2
+dual color ELISPOT
+GFs like AREG or HB-EGF
+prevention measures of VAP
+FAST proteins
+new computational methods had to be developed
+ribosomal frame-shift sites
+Argonaute
+Similarity among county groups of the included environmental factors
+influenza virus A/WSN/33
+NALP4
+NGS assays
+a TMB kit
+10.20±1.23 μM
+Liu, Yong; Li, Jinxiu; Feng, Yongwen
+epitopes showing weak interactions with HLA alleles
+putamen and the primary motor cortex were activated
+IL12p70
+Passaging, immortalization and cloning
+management, the reconfiguration of our radiology department, and the workflow
+decreased
+HA-mediated binding to the receptor
+between 0.2 and 0.75 × 10 6 cells/mL
+Sufficient ART
+control IgG
+22
+CCK-8
+glutathione Sepharose beads
+Astroviridae
+Extracellular vesicles
+1,439
+95%
+ACE2
+prokaryotic
+immunoglobulins
+alveolar structure disorder-associated ILD
+Charadriiformes
+endocytic pathways
+pharmacological
+Table 4
+4% formaldehyde
+77.9 kDa and 64.7 kDa
+36 h
+45
+33.1 kDa
+immunocompetent hosts
+pediatric septic shock
+C. noxius and C. suffusus
+4%
+relatively mild
+RG-RV-A16
+Total RNA from infiltrated leaves
+resistance
+4%
+67%
+archival collections of Select Agents
+modulates FACT binding
+gaps
+YX, LT, YL, and SM
+IMB-1406
+enhanced proliferation
+11
+information about the study setting, time, vaccination
+Infection with both "classical" and highly pathogenic strains
+Over 80%
+memory CD8 T cells
+heteroclitic
+physical units of surface radiance
+ΔNLS-hTDP-43
+192
+blood glucose level
+recycling of β1 integrins
+ImageQuant
+Protemist XE robotic protein synthesizer
+inter-rater reliability
+HIV neurovirulence
+dimers
+bat flies
+488 nm
+I t
+when apoptosis is suppressed
+discontinuation of treatment exposes patients to immunization against the transgene product
+10
+cc-by
+paediatrics
+Nursing Care Plan
+Bacteria
+xenobiotic induction
+amantadine
+Phe 339
+definite
+Gift of Life
+nausea, vomiting, or diarrhea
+pentamidine
+gene flow between Eurasia and the Western Indian Ocean can occur
+rhesus macaques
+adult asthma exacerbation
+90%
+airway resistance
+linear regression analysis
+fever, cough, sore throat, body aches, nausea and vomiting
+revertant
+10
+the content, and all legal
+conserved antigenic epitopes
+proprietary dye
+high viral concentration
+mass spectrometry
+CD8+ T cells
+hypercoagulable
+Open Biosystems
+Variations
+research coordinators
+high titer serum IgG
+treatment with drugs
+36 and 48 h
+credit card
+Neutrophil enrichment
+682
+85
+systemic and local sources
+Unconditional logistic regressions
+1 year
+dynamin 2
+influenza Apdm09
+a focus on those at society's margins
+FAK P875A/P881A SCC cells
+affinity toward human serum albumin
+maximin
+half maximal inhibitory concentration
+0.5%
+Coxsackievirus B3
+30 min
+calf intestine alkaline phosphatase
+Unique pathways
+random-effects meta-analysis
+RSV viral genomes
+40-50 per minute
+the key factors shaping the interests of individuals and public health officers
+survival
+retaining virulent parasites in the population
+healthy diet, regular exercise, limiting cigarettes and alcohol, and mental harmony
+151
+18%
+ZIKV production
+risk assessment
+cortisol hormone
+live cell imaging microscopy
+ASLV-K
+the intercodon
+statistically significant
+green
+brain resident cells
+activation of JAK kinases and activation of ras-mediated signaling
+24 to 48 hours
+metabolic
+lactate dehydrogenase LDH 11
+19
+Three
+six
+microbiota
+Warning fatigue
+freeze-dried samples
+Excretory and Secretory Products
+moderately attenuated inflammation
+The bone marrow
+249
+RNeasy Mini Kit
+Reaction dynamics
+silicone injection compound
+28.4%
+1713
+significant role of these proteins in influenza infection
+WT bacteria
+Sven Ove Hansson
+gp120 and gp41
+Travel patterns
+100%
+commensal bacteria that are resident in the nasopharynx
+OmpA
+Subclade 2
+a dimer
+VLPs
+nonreceptor tyrosine kinase
+chicken plasma
+children under the age of 5
+air sampling
+Sandwich ELISA
+INSERM Jean Mérieux BSL-4 laboratory
+CD8
+northern blot analysis
+IFITM3 7
+increased breath sounds with no crackles
+STORM super-resolution
+Sixty-one percent
+12.8%
+community-acquired pneumonia
+protease
+17 years
+heterogeneous cell types
+the treatment level
+unreliability of their clamps
+141
+MHC class I
+800 sec
+GEE models
+exacerbation of liver damage
+microbial GO annotations
+Horizon Discovery
+One to three
+3
+study replication
+worse outcomes
+preclinical
+A/WSN/1933
+soft agar colony formation assay
+Viremia
+data journals
+internal consistency
+co-infection rate
+Thirty-nine
+2
+RNA3
+toll-like receptors
+lung macrophages and dendritic cells
+anti biotic
+a high value
+HTSeq-count
+100% and 80%
+simulated data
+one
+101
+lipid
+elevated capsid expression
+adverse effects of ART or symptoms of opportunistic infections
+LMP1
+q
+miRNAs
+hemagglutinin and neuraminidase
+Immunofluorescence
+reverse remodeling
+2012
+Epidemic potential zone
+5 min
+antiviral
+K d
+a table with a list of potential binding sites
+cycloheximide
+six
+IgG isotype
+virus
+chikungunya virus
+vaccine antigen selection
+health professionals' recommendations
+35 d
+seroconversion
+$200
+fungi
+430
+an extended PK
+IIF with anti-F and anti-N antibodies
+50%
+infection-protection
+Metasim
+the structure of the model 14
+24 hr
+700,000
+15 days
+HA and NA
+ACE2
+Panel analysis with two biomarkers
+foreign peptide insertions
+f 12 and f 13
+expression of the viral structural protein prM
+Anti-HBs mAb
+Forty six
+very light
+cleared tissue culture supernatant containing virus
+malaria, tsutsugamushi, and shigellosis
+chromatin condensation and apoptotic bodies
+408 to 419
+TCR-pMHC structures
+234
+nuclear-encoded transcripts
+precipitation titration of LAMP products
+Gabinete de Prensa
+TLRs
+multiple organs
+Myricetin
+molecular signatures
+2017-2018
+5 days
+daily or more frequently
+8 weeks
+local mucosal and systematic immune responses against PEDV infection
+9 dpi
+3
+controllable
+chemically conserved regions
+epidemios
+preferential mixing
+Platinum ® SYBR ® Green qPCR SuperMix-UDG
+nuclear factor erythroid 2-related factor 2
+Environmental factors
+serine
+500
+five
+τ 0
+94%
+>500
+αor β-integrin homologues
+ICIs
+fluorescence recovery t 1/2
+analogous conditions
+dramatically reduced sensing capabilities
+12,500 tons
+more difficult cases
+Fn-bound exosomes
+2009
+CIA
+to the amount of total proteins in the cell lysates
+Vegetative spread and growth structure
+760
+560
+Chongqing City
+static control measures based on reasonable but imperfect parameter estimates
+mass drug administration of praziquantel
+1310-1653 amino acid residues
+listening to their peer farmers and observing what they do
+Aedes aegypti mosquitoes
+4.5578 and 5.8000 keV
+autophagy
+information on common causes and associations of febrile illness
+ACE2
+dilemmas of connectedness
+regulations
+specific cell-mediated and humoral protection
+Motifs F1 and F2
+chloroquine, ribavirin, and arbidol
+oligomerization of unconjugated NP
+rhinovirus infection
+Binding of the cell receptor CD4
+encephalopathy
+photosensitizers
+99.98% and 100% identical
+China
+30 mL agar
+PB2
+internalization
+TNF-α, IL-1β, and IL-6
+CD63
+Biotinylated target sequences
+Human adenoviruses
+Cellular translation
+Statistical estimation of 0
+two-to sixfold
+one third
+Up to eight
+language
+kernel methods and support vector machines
+positive predicted value and negative predicted value
+neutralizing antibody titer
+high levels of full-length antibodies
+1µg/ml doxycycline
+sterile equipment
+0.8 ± 0.2 Å
+Biotin signal intensity
+Supplementary file 3
+sneezing and coughing
+191871919
+5 9 10 9 transducing units/mL
+condoms
+clade 1 bat CVs
+Sex-and age-matched controls
+Yangtze River Delta
+serine or phenylalanine
+sterile saline
+anti-Ago2 antibody
+Dr David Tyrell
+leader
+42%
+64.61 kDa
+24 hour
+posttranslational
+12
+anaphylatoxin C5a
+-yNpl4 113-580
+18,823
+France
+Reverse Transcription System of Promega
+sensitivity
+Index
+The combined keyword index
+±0.3 nm
+Mouse GE 4x44K v2 Microarray Kit
+refractometer
+harboring a pathogen
+Nurses who work in the community
+Viridans streptococcal bacteremia
+5,568
+West Nile virus
+multiple linear regression analysis
+pseudoacinar
+251
+Rate4site algorithm
+UK EMRSA-15 transmission parameters
+P21
+Virus species specific extraction efficiency biases
+thirty
+caring
+SL-5S
+MAPK
+CFA
+psychological distress
+EEG and GSR
+Types I, II, and III
+Epidermal growth factor receptor tyrosine kinase inhibitors
+adenovirus
+SIRP
+2013-08-07
+VCP
+Exploring how data can be shared more openly and quickly
+Tissue specimens
+oxidation of DNA, protein, and lipid peroxidation
+infection with emerging influenza viruses
+Cell proliferation
+70%
+collate microbiology data of isolates from hospital patients
+Fisher's exact test
+The asterisk
+IL2
+3
+size-separation
+3.5%
+less inflammatory mediators
+proliferation in the blood
+infected horses
+viral supernatants
+ROK 84/105
+881
+Aliberti and colleagues
+current trends continue
+to control the docking run
+type I
+250, 000-500, 000
+Dual Use Research of Concern
+10 mL equilibration buffer
+R 0
+Ovation RNA-Seq
+1575
+differential
+Orphan Drug
+Three
+IFNγ
+Flight data
+Acute variceal bleeding
+14 days
+separate populations
+local characteristics, patient composition, and the demands of hospital professionals
+RT-LAMP assay
+four
+IFN-ß and IL-6 production
+φ t
+2-4 µg/ml
+real time monitoring
+0.62
+CHIKV
+Poland
+2-D Quant kit
+the links
+FastPCR and GeneUp
+1.0
+Stronger neominophagen C
+bovine serum albumin
+outbreak and emergence events
+virus titer and D-antigen concentration
+ELISA
+the internal market for biomedical journals
+innate immune recognition of herpesviruses
+mild
+broad-spectrum
+EGFR
+Luciferase specific activity
+SARS PLpro catalytic mutant
+103
+Cyclic nucleotides and ions
+GTW04 and GTW05
+feasibility and bioactivity testing
+AMPK
+5 µl of the resultant cDNA
+enrichments for these functional categories of genes
+FUS
+neutralizing
+antigen detection immunofluorescence assay
+Gap and ambiguous positions
+MRSA and VRE
+University of Toronto Health Research Ethics Board
+3 h
+LMP2
+156
+stronger correlations
+tryptic soy broth
+oxidative stress
+5 nmol/L
+M- Gleason 3 and M-Gleason 5
+5%
+45%
+26
+refractory
+early viral gene expression
+The Netherlands
+Iterative HFold
+all four amino acid substitutions
+innate immune response
+6.83×10 12 M -1 s -1
+luciferase reporter expression
+climate variability
+22.8%
+slightly higher estimates
+viral segments
+E13.5
+between 7 and 42 pfu
+significantly decreased
+C of JEV
+logistic regression modeling
+ability to easily map functional roles into subsystems
+specimens sent to participating laboratories
+cleave a DR6 ligand peptide from APP
+site I
+1 hr
+Group 1 and 2 viruses
+A524V and S528N or S528T
+recombination
+proinflammatory
+359.4
+0.5
+conventional
+Nosema apis
+odds ratios and 95% confidence intervals
+polyubiquitination of the target protein
+5.76 log 10
+pathway enrichment
+RVFV
+p.Lys329Glu
+throat swabs
+P. alecto or P. conspicillatus
+low response rate
+autophagy machinery
+A simple PSEP
+blockade
+antigen-specific functional antibody titers and T-cell frequencies
+2002
+sequence homogeneity
+Disease relapse
+two division cycles
+epitope records
+humoral
+they might have different functions and be regulated by different biological processes
+Ultracentrifugation
+mice
+between 18 and 44%
+collagens, albumin, and fibrins
+Predicted regions encompassing recombination break-points
+Dysregulated
+HIV-1 CM22-261
+to determine a future foundation for common language and understanding
+acute respiratory distress syndrome
+Glutamate
+24 hrs
+flowCore R package
+3 days
+Demographic characteristics
+2.7 × 10 4 cells/0.1 mL
+further examination
+n*m
+Parkinsonian features
+bone crystals, collagen molecules, and non-collagenous organic proteins
+treatment procedures
+3.2%
+lymphocyte
+functional antibody titers
+EPs 7630
+5
+autoimmune
+Bronchitis or bronchiolitis
+3
+V2C cells
+One microliter from each dilution
+mixed LBMs
+80%
+Protective behavior associated with influenza outbreaks
+GenBank
+11 days
+APP processing
+Six
+DCs and macrophages
+0.5 %
+Branch #2
+pGEM-T-Easy vector
+caveolae-mediated
+monolayers of HEp-2 cells
+Mycobacterium tuberculosis
+less efficient envelopment of mature virions
+0.1 mg/ mL
+signs of active gastrointestinal bleeding
+P<0.05
+Thirty
+the sites interacting with ALP
+opsonic
+differential usage of three low frequent codons
+Acinetobacter baumannii
+asymmetric viral RNA replication
+reinforcing local suicide prevention activities
+10
+proinflammatory
+six
+Vpg
+how we would respond to that
+A list of all the dental faculties
+cellular locus of NKG2D ligand expression
+the opposing line
+Mineral oil
+A chance to become resistant to PRRS
+may act in the same manner and bind similar factors in human cells
+infectious virus production
+Dendritic cells
+ACL300
+CD1D-restricted NKT cells
+Sixty-one
+fiber-optic probe
+yellow
+siRNAs
+four
+difficulty with aerosol delivery, cost and potential harm to healthcare workers
+Phylogenetic
+identified roles
+q m Þ
+stochastic gradient boosting
+dose selection for phase 2b
+viral, parasitic and bacterial infections
+α4GnT
+two
+DUBs that formed covalent adducts with the indicated probes
+15
+quantitative PCR
+SupTOC-LPS-24h
+1996
+MDCK
+longer
+nucleolin, B23 and fibrillarin
+10D3 and Mab51
+May 2017
+zip code regions
+BHK-21 cells
+1 × 10 6 /µl
+Bacillus anthracis
+P
+22.8 ± 6.8
+N V and N H
+codon usage and dinucleotide composition
+Vasopressor therapy
+Eleven
+PNA coupled to Alexa Fluor 488
+Amyloid plaque burden
+ALI
+poly-L-lysine coated glass coverslips
+2 min
+prolonging the effectiveness of antiviral drugs
+preferential
+IL-1α
+compactness factor
+indirect ELISA
+6% to 16%
+commercial trypsin inhibitors
+Faecal
+clustering of receptors within the same cell surface
+DCs
+western blot analysis
+template-strand T30
+1%
+R software
+IFN-ω
+three
+10 days
+6.8%
+137,000
+children and young adults
+outcomes of collaborative efforts
+IDP profile analysis of hypothetical proteins
+October 20, 2014
+citrate buffer
+Disaster food
+10 kb
+monoclonal antibodies
+H. pylori WT or Δggt
+protective
+advance our understanding of post-EVD immunology
+Protein sequence alignments
+351
+phage libraries
+95%
+Means restriction
+public ground transport
+Leeds Clinical Trials Research Unit
+the maximum likelihood
+6 hours
+25%
+four
+volatile metabolic signatures
+Streptococcus pneumoniae
+critical
+frameshift
+high ventilation rate
+twice
+D 2 DR
+PD-L1
+fine scale discrimination
+Seizure-like
+5
+2 days
+dispanin family
+Adult stem cells or progenitor cells
+specific
+conjugation of SUMO molecules on multiple lysine residues
+paramyxoviruses
+flattened pellets at the bottom of tubes
+MRPL19
+higher titers of HA-specific antibodies and stronger T cell responses
+enolase
+University of Utrecht
+every 2 weeks
+10 min
+541
+50 µL min −1
+7%
+250-370 g
+an institutional review board -approved research protocol
+P1F12
+the cap of the viral mRNA
+8
+Ang II
+lymphocytopenia and hypoxemia
+one
+the development of robust vaccines
+57%
+significant difference in expression of total bactin
+0.3360.09
+HIV replication in cell cultures
+C3a and C5a
+ESTScan
+specimens
+PTGS2
+additional ORFs encoding putative proteins
+free movement of people
+six hours
+765
+gel electrophoresis
+translation of HIV-1 structural proteins
+6 mm
+amino acid sequences
+AIC and an F-test
+Four
+MxA
+620 000
+variability
+seven
+Circular dichroism
+45
+1 mo
+water-soaked diet
+informative transmission events
+The above sRNA dataset
+50%
+cisatracurium
+Viral RNA
+five
+human rhinovirus
+black and white
+strong support
+Eight week old female BALB/c and C3H mice
+200 million
+Separate Neighbor-Joining trees
+poor
+canonical
+ANOVA
+Purine or pyrimidine biosynthesis inhibitors
+twisting of 15
+95%
+thousands
+71%
+FRNT
+316
+sensitivity
+C and K
+glycoprotein processing
+computer-aided approach
+$1750 per day
+Body mass index and plasma albumin concentrations
+TcdC
+low viral copy number
+Five
+Escherichia Coli
+Plugins
+binding to a partner
+When fatal outcome was analyzed
+Wza
+export factors and adaptor proteins
+chemical, structural and biological
+2 CFU
+high-quality reads
+translation
+recombination estimates
+55
+Viral burden
+interleukin-2dependent T-lymphocyte proliferation
+10 h
+Free energy dG values of folding
+11.5 ± 2.5 μM
+5000
+overlap PCR
+vaccine properties that promote efficacy
+12 h
+sodium pentobarbital
+logarithmic scale
+Laboulbeniales
+diarrhoea
+Cotton
+pET32a
+the infection has the potential for sustained transmission
+within-household transmission
+Antibody titers
+SeqMan
+KX756441
+Collection of real-time translation traces
+high number of included studies and patients
+postentry stages
+intermediate monocytes
+kidney protective effects
+250
+20%
+1:40
+negative
+wildtype CCHFV
+A trafficking checkpoint
+half
+PKV
+28,392
+cysteine proteases
+Titres of IgM and IgG anti-HEV antibodies
+privacy and ethics
+Adrenal suppression
+ASFV
+piecewise constant function
+More than 2000
+four
+Renilla Luciferase Assay System
+50x MOI
+I C
+Fourteen
+V2-apex bnAb epitope
+14 to 120 days
+7 days
+oxidation
+levels of +1 frameshifting
+200,000 days
+iterative
+27
+SDS-PAGE
+collagen deposits
+Hit drugs
+S2 Protocol
+Corticosteroids
+three
+low molecular weight protein
+three proteins
+higher
+15.9%
+filovirus entry into host cells
+postnatal respiratory morbidity
+55 ± 4%
+4%
+payments to NIH and some NIH scientists
+cytokines and chemokines
+.
+equation
+2166
+95%
+Creative Commons Attribution Noncommercial License
+cytotoxicity
+sporulating EV
+Ca 2ϩ
+cognitive impairment, depression, and autonomic disturbances
+Trp371 at the coil and Ile375 at the short helix
+PhyML 3.0
+regions of predicted disorder
+enhanced local dynamics
+anti-atherosclerotic
+Constitutive expression of antiviral ISGs
+efficient clearance of HCV and prevention of posttreatment relapse
+method 3
+untreated cells
+5 μl of RNA template
+four
+gene set enrichment results
+155
+expectations with antiviral Abs
+Promega
+climatic variables
+Farm-1
+node to node connectivity
+Three
+1.0
+separate computer runs
+monitoring of a fluorescence amplification curve
+airborne transmission
+ketamine
+Physical HRQOL
+an epidemiologic risk factor
+eight
+pACYCT2
+severe hypoxemia and uncompensated hypercapnia
+who infected whom
+a 3'CITE
+access to leave
+virusadsorption-elution
+Belgian Science Policy Office
+Peroxidase-linked assay
+Photoshop CC
+3 h
+48-72 hours
+altered islet blood flow
+Mut-2 infection
+PX-UV
+Protein concentration
+~2%
+Trypsin
+1AE4-1AE5
+ISGs
+97 to 100%
+Pseudorabiesvirus
+virus allantoic fluid
+raw milk
+90-95%
+10 million
+intraoperative transfusion
+infants
+positive
+leukosis
+IgA
+Integrated optical density to area ratio
+Monocyte-derived
+subcutaneous, intradermal, and intramuscular
+injection of tunicamycin can induce acute liver and kidney damage
+58
+4G2
+move towards the front
+Recombination event 3
+mobile communities
+positive predictive value
+Madin-Darby Canine Kidney
+IFN1 phylogeny
+quantitative RT-PCR
+V79A
+WS
+maternal Abs
+ACE2
+NoV
+E 0
+300 to 450 nm
+glorious progress
+the copyright holder
+Parameters
+C++
+15 × 15 minutes of arc
+Fmoc-Lys-Wang resin
+Targeted sequence amplification strategies
+ruminant
+marginal
+CCID50
+68
+21% higher accuracy
+intracellular
+network structure
+1 h
+β-Propiolactone -inactivated virus
+register an account associated with a user-provided email address and password
+1 minute
+FAK-expressing cells
+sensitivity analysis
+$60%
+higher level of cytokine secretion
+5%
+antiviral
+8, 350 Da
+~10%
+ATII cells
+Transthyretin
+intermediate
+Mammalian cell culture
+soluble guanylate cyclase
+ten
+refuse to be seen by a health care provider
+Four
+boredom
+nsp11
+NF-κB
+picorna-like viruses
+Trizol
+Age-related increases in leakiness
+Brain samples
+2%
+12
+animal bleeding
+NMD-resistant
+swine flu
+PPI
+anti-Fas
+self-reported information
+100%
+oocyte maturation
+helix
+virus replication
+23°C/50% RH
+Parameter distributions for N and p
+critical illness polyneuropathy and myopathy
+lower
+Glyceraldehyde 3-phosphate dehydrogenase
+neutralization titers
+Probit analysis
+Phenix refine
+antimicrobial treatment
+phase analysis
+Node color gradient
+intensive turbulences
+DNA
+rheumatoid arthritis
+miR-HA-3p antagonist or control antagomir
+IF staining
+saline group
+pfcrt cDNA
+17,993,689 to 27,248,309
+Three
+dangerous clones that react with self antigens
+IL-8
+NEAT1
+novel functions of noncoding genome
+JEOL JEM-2100F
+MAPK signaling
+Quercetin
+the treating physician
+RPB2
+p2luc reporter vector
+92
+Various models
+pathogenic
+health workers
+tunable roadblocks
+3%
+natural selection
+high levels of PV proteins
+75%
+6247
+BALs and lung homogenates
+lower uncertainty of root state reconstructions
+Six hr
+IBOPE International net-AGB Nielsen Media Research
+Ubiquitination
+possible
+Wheezing
+high-throughput
+Slope FE
+pigs
+Geographic information systems
+receptor interference pattern
+o-phenylenediamine and H 2 O 2
+Evolution
+2 days
+0.916
+viruses
+Ammonia stripping
+a hallmark of SFTS
+four
+twice a week
+cancer pathogenesis
+Paired T-tests
+licensed
+T cells with the γδ receptor chains
+day 4 kallistatin
+inversion sites
+Clinical trial design
+cellular membrane
+real time PCR
+time-ofaddition and dose response experiments
+p ij
+diverse inorganic nanoparticles
+csn8
+vaccinia
+Student's t-test
+incidence rate ratio
+24
+chronic heart disease and bronchial asthma
+puncta positive
+13.5
+mouse M13 mAb
+ETEC infections
+intestine, lung, and liver tissue
+Fisher's Exact Test
+SAMD9L haploinsufficiency
+four
+when using the anti-bird IgY secondary antibody
+Gq
+Seven
+BCA Protein Assay Kit
+ferritin
+Improvements in surveillance and diagnostics
+Descriptive
+p65/RelA
+Genomic DNA
+cleavage of eIF4G
+Box and whisker plots
+WGD-derived
+7 days
+CART
+Estimated prevalence
+preexisting immunity and cold chain requirements, and lingering safety concerns
+rabbit hemorrhagic disease virus
+Crustin
+carboxyfluorescein-tagged PMOs
+Cell lysates
+fluorescence intensity
+Sepsis
+cholinergic hypofunction
+yeast-optimized
+tryptophan and cysteine
+95%
+PENK
+targeted biosensor
+survival rates of 90%-100%
+1,997
+digestive enzyme secretion and gastric motility
+mean fold changes ± standard errors
+monoclonal antibodies
+FeLV envelope protein gene
+allows the insertion of any sequence to generate the fusion protein
+The proper representation of both the sequence and structure of the interacting partners
+vesicular stomatitis virus pseudotypes
+neurons expressing high levels of viral proteins
+Four
+High-Capacity cDNA Reverse Transcription Kit
+5a,b
+52 ms long
+drops glanapon
+5 µl of lyzed solution
+Hantaviruses
+coinfecting variants
+A 5 diag
+569
+a natural leaky stop codon
+agarose gel electrophoresis
+three
+ceiling effects
+11
+pdpC
+Decoy receptor 3
+J. communis and J. oxycedrus
+inversely regulated
+difference in race
+27
+chi-squared tests
+0.26 mmHg
+hypoxic
+allograft fibrosis
+faster diluted
+60
+NHC-5=-triphosphate
+dry and dusty
+Dengue virus infection
+electric field force
+Isopropyl thiogalactoside
+a Control Area
+T cells
+perceived authority, trust, and situational control
+macrophages
+virus-specific antibody and T cell responses
+DUB specificity
+TransIT-LT1
+Driving pressure
+six
+including livestock
+low intensity noise
+blood and lung tissue samples
+to remove SDS and renature the proteins
+CRISPR/Cas9 system
+biological duplicates
+>10 kb
+1 week
+Site-specific binding of several inhibitors
+global defects in induction of IFN
+Thirty-three
+empty arrowheads
+deciduous
+expression by >5 fold
+hundreds
+GPC
+PR2
+phage display based epitope mapping
+> 50 %
+Excellent comprehensive reviews
+dual-host affiliated ISFs
+mass spectrometry
+compound partitioning and energy estimation of appropriate fragments
+lack of similarity
+diversify
+wound agents
+the stability of the pMHC-I complex
+γ = 1
+hMPV infection
+Rule induction
+mRNA decay assays
+HMPV A2
+RNApure Virus Kit
+January 2007 to December 2013
+anchorage-independent growth
+skunks and the foxes
+systemic inflammation
+0.1% sterile buffered peptone water
+AmelSCRB8
+Peak number and peak height
+recent data
+25.38%
+Ten
+distinct activation profiles
+Δ F max
+85%
+Endoplasmic reticulum
+350 -1800 Da
+quantitative information of θ
+an ICOA
+tattooing and scarification
+84%
+peripheral inflammatory stimuli
+In-hospital mortality and length of stay in the hospital
+significant reduction in both intracellular and extracellular virions
+Western blot and RT-qPCR analyses
+liver and the lung
+the distance between atom 2 and atom 1
+1
+proinflammatory chemokine profiles
+Media samples
+4,322
+microcephaly
+formation of atrial septal defects
+terminal
+IRES-dependent
+100
+postoperative morbidity and length of hospital stay
+training
+immunofluorescence
+N
+five
+11
+Proteomic data analysis
+Ulcer
+50 mg
+seniors
+breakdowns in IC measures
+peptides N10 and C12
+epidemic potential
+in vitro model of the lung
+60
+50-100 million
+temperature
+membrane-associated capsid
+10-20 mg/ml
+infections of RV1B
+Microarray
+100 GPID 50 of homotypic virus
+Sampling volume
+gp350
+radiation attenuated sporozoites
+dsRNA
+An increase in volume and acuity
+KGH
+45 years
+ASFV NP868R
+5950
+Catalan Influenza Reference Laboratory
+statistically significant differences between treatment groups
+Argentina
+PET
+original articles published in Chinese
+LC3 conjugation system
+Íris Eva Hauksd��ttir
+estimation
+The number of macrophages containing engulfed cells
+3 h
+Video S2 NA-deficient influenza virus
+mRNA poly tail shortening
+data on the degree distribution of contact networks
+strong IFNβ promoter activation
+efficacy data
+enhanced viral replication
+different phenotypes
+previous TB infection and diabetes mellitus
+N-acetylmannosamine and pyruvate
+nurses and paramedics
+surface residues
+32
+Syndromic surveillance of influenza-like-illness
+70%
+future transcriptomic analysis
+Parvoviridae and Coronaviridae
+conclusions over all possible parameter values
+community data
+virus-induced apoptosis
+20 to 61
+the most dispersal-limited
+8 years
+human defensins
+10,000
+Th1 and Th17
+vascular endothelial walls
+p53
+81%
+Metropolis-Monte Carlo
+54
+11.3
+less than 5%
+15%
+230
+oxidative stress
+IFN2
+viral replication
+0.0195 and 0.0053
+ZINC36728034
+interpretation
+SLAM
+suspension multiplex
+GC-rich
+livestock industry
+Monoclonal antibodies coupled with the blockade assay
+positron emission tomography
+GENSCAN
+Cervix cancer
+RIPK1
+midnight
+Active Motif
+seroconversion
+immunoglobulin
+confocal
+loxP-STOP cassette
+60 min
+monoclonal antibody 17b
+VRC01 CDRL1 and CDRL3 loops
+mesenchymal stroma cells
+ISRE
+400
+biosecurity
+EF, -TUB, CypA, and RPL12
+15,054 nt
+hierarchical logistic regression model
+each set of partial haplotypes
+IFN-α/β
+reduce quantity and quality
+automated
+Milk sample
+MicroRNAs
+697
+passive
+B. bronchiseptica
+C 16 -palmitic acid
+qRT-PCR
+Enteroviruses
+12,285
+helical stent retraction
+p=4.86E-03
+papilloma virus, scaly leg mites and mycotoxins
+near-native molten globule-like folding intermediates and orphan subunits
+alert and response mechanisms
+helper phage VCSM13
+immunoconfocal
+Médecins Sans Frontières
+isotopic
+30 min
+SV-A
+high titer
+Three
+Aspergillus foetidus slow virus 2
+risk stratification
+myosin heavy chain expression
+pre-and post-peak milk production status
+extremely low
+pneumococcal outbreaks
+Pearson's analysis
+Student's t-test
+Hypoxia inducible factor-1α
+SEV-induced activation of the IFN-β promoter
+increasing time of divergence between types
+trachea and lungs of infected chickens
+64%-82%
+biopsy specimens
+Th1and Th2-type helper cells
+2007 Uganda outbreak
+interaction terms
+acute phase reactant response
+in vitro cell line assays
+12 hpi
+The control of antibiotic resistance
+The sequences surrounding AUG1
+Feces
+Invitek MSB Spin PCRapace Kit
+immunoglobulin replacement
+Three
+lysate from cells infected with UL21a deletion virus
+KYN
+-29.9704 kJ/mol
+87
+decapitation
+Myeloid differentiation factor 88
+10%
+55
+Seven
+onset of transmission
+aberrant recombenases transcription
+nonspecific psychological distress
+increased virus sensitivity to antibody neutralization
+copy choice recombination
+ICTV 8th edition
+ILI
+various cells
+Screening of libraries and studies on derivatives of small molecules
+Cell networks
+Linear regression analysis
+incurable cancer
+TLR3, TLR7/8, and TLR9
+CD4 + CD25 + T cells
+IFNG
+candidate constructs
+BVDV-1c strain AO554
+when the genome sequence has been fully resolved
+VB
+Ischemia-associated retinal degeneration
+understanding the implications of changing exposures on public health
+three
+hypertension, diabetes mellitus, coronary artery disease, and chronic kidney disease
+potential risks of zoonotic disease exposure
+4 to 15%
+PADRE
+colistin
+two
+tumor weight and volume
+the greatest dilution with OD ≥0.1 after background subtraction
+domestic or international pandemic outbreaks
+7 days
+one
+three
+the manufacturer
+ethanol
+via the exo-probe
+Mas receptor
+A system
+High Yield Capped T7 RNA Transcription Kit
+T oxoplasma gondii
+novel methods for the prevention and treatment of schizophrenia
+4
+PNG
+CUCUCU
+30 min
+otherwise
+induction of a robust antibody response
+fever, anorexia, and marked hematologic changes
+probiotic
+one
+IPO8
+Viral
+OCT4B mRNAs
+knee movement
+DNA repair, chromatin organization and DNA binding
+Bill & Melinda Gates Foundation
+three
+21 mmHg
+source control
+Institutional Biosafety Committee
+twice or once daily
+six
+early and sustained replication
+culling
+Ebola
+western blot analysis
+90%
+increased
+peripheral blood and lung samples
+over 30%
+higher than estimated
+vectors
+Active serological surveillance for viral antibodies
+PiCCO and Swan-Ganz
+increased exponentially
+Enterovirus A
+molecular beacons
+Euclidean distance
+fragment I, fragment II and fragment III
+by obtaining the vaccine on time
+complete lethality
+.100 cells/mouse
+nylon wool column passage
+DNASE I hypersensitivity studies and gel shifts
+Relative dinucleotide bias
+to correct hypovolemia
+unpaired t test
+hemodynamic parameters
+Short-chain fatty acids
+Cell culture medium
+3.8
+1999
+PCR-based techniques
+10 μ g/ml
+Six-eight week
+interest
+how the predicted TS probability distribution differs from the predicted neutral probability distribution
+nursing documentation of hypoxemia
+pinyin
+0.5 µmol/L
+100%
+Open Bable
+emerging infectious diseases
+fewer HFMD cases and a lower search volume
+lower protection
+viral genotype
+disruption of the leader± body TRS duplex
+Neural precursor cells
+30 h
+ClustalW version 2.1
+fluc genes
+Phylogenetic
+a minimum number of parameters
+30%
+DBS samples
+Obesity
+feedlot transport
+AT-II cells
+30 days
+CaMV is able to recombine
+two samples
+monitor the child and ensure proper hygiene
+ViaFect
+pseudotyped-virus
+NS1
+22%
+TRM is reduced
+TMP-SMX and fluoroquinolones
+two
+Induction of miR-21 expression
+glucose
+intervention focused on children
+60%
+Recombinant 4EBP1
+mechanical
+71
+FEI Tecnai Spirit transmission electron microscope
+sepsis
+the experimental condition
+the scattering curve
+sequential evolution information
+11
+a national response
+more than 3-fold EC50
+Biolayer interferometry
+500 million
+shRNAmediated silencing and nanobodies
+78%
+rats and mice
+Image J Software
+the number with symptom onset on day s
+59
+50 µM
+Plasmid DNA
+The first imported patient
+three
+viruses
+Rituximab
+38%
+miRanda and TargetSpy
+Nutrient Mixture F-12 Ham
+G ¼ À t 0
+increasing nasal residence time of antigen
+piezoelectric dispensers
+37.3 ± 3%
+1 mM PDS
+dengue infection
+virions
+broad functions that relate to the growth and development of a cell
+St. Boniface Hospital
+different factors
+binding with various compounds
+328
+to conserve the protein sequence
+T-cell factor /lymphoid enhancer factor transcription factors
+Type I IFNs
+k b
+a family of small non-enveloped viruses
+oncolytic and tumor vaccination
+Institutional Animal Care and Use Committee
+over a thousand
+6.34
+Tris-glycine gel
+Serum from healthy flounder
+Spray factor
+Mtb
+PMA
+malaria infection
+Smart Minimizer
+22, 23, 25 GeoSentinel and EuroTravNet
+Dimethyloxalylglycine
+Kaplan-Meier survival plots
+robust levels of PSMA-specific human IgG
+ACE2, Ang- and Mas
+Na + and Clions
+the diagnosis of ONFH
+assessable walking passes
+ISPPD-12
+Autophagy
+full-length RIG-I or melanoma differentiation-associated protein 5
+Facts and figures
+three
+anti-polyHis monoclonal antibody
+crescent-shaped forms
+mean values ± SEM
+Thirteen
+IPA core analysis
+lytic replicative cycle
+CCL21
+18 kDa
+Tail vein blood
+Package DESeq2 version 1.14.0
+Effective surveillance
+phagocytic cells
+triclabendazole
+10%
+Drugs that target host proteins
+Multiplex detection
+TUNEL-positive cells
+Pseudonyms
+10.3389/fcell.2020.00099
+GraphPad Prism 5
+1′-OH-MDZ
+adverse fitness effects
+wild type mice
+epigenetically controlled genes in the SP cultures relative to ST
+exon 51 in the DMD gene
+LWL1
+ECoV
+silica gel column chromatography
+core oligosaccharide
+cells acquiring exogenous mitochondria
+different markers and traits
+ABTS peroxide substrate solution
+eight
+three
+expert
+CPIs
+1.5
+control resources
+Pneumocystis jirovecii
+cell lysates
+I expression and bound peptides
+four
+Twelve months
+41
+B cells
+Picornaviridae
+Carbohydrates
+PFC's
+Aedes aegypti
+Data on statin dose or frequency of administration
+wrist watch and jewellery
+influenza vaccinations
+10 fg of genomic DNA
+Sixty
+delaydifferential equations with constant delays
+a regression curve
+inhibitory cellular responses
+Primates
+SEM
+Fifty-five
+knockdown of human SAMD9
+demographic
+137
+80-90%
+Pyroptosis
+50
+acquired immunity to the transgene product
+Artiifact
+metagenomics/transcriptomics
+the pylorus
+24 h
+Acute respiratory distress syndrome
+16
+Gram-stain
+Mexico and Victoria
+Protein Data Bank
+complementary
+stem 1
+bi-phasic
+intermediate or negative
+20%
+Image Lab
+data
+Biodegradable
+88
+Quantitative real-time reverse-transcriptase PCR
+bovine PDC-E2
+lymphnode, bone marrow, liver biopsy as well as autopsy material
+½A{B/C
+5 min
+instructive roles
+20
+IMG/VR v.2.0
+two
+1 h
+Rice cropping intensity
+1 month
+CT imaging, FDG, and NaF PET
+reduced
+flesh eating disease
+2 months to 10 years
+molecularly targeted therapies
+type I
+short half-life of immunoglobulin
+clinical
+Maxadilan
+an alternative inoculation route
+likely matches
+100 kV
+11
+vancomycin MIC
+the dose-response relation
+3 weeks
+temperature and the relative humidity
+The efficiency of deletion
+IBVs
+Karin Boucke
+Santa Cruz Biotechnology
+Four
+Infection with RSV
+five
+compensatory base pair substitutions
+Protein Data Bank
+New Zealand
+putative false positives
+both live and permeabilized cells
+asymptomatic infections
+viral replication
+FP7
+Purified gp90 protein
+microenvironmental
+HRV natural evolution
+Household-based studies
+satisfaction or knowledge acquisition
+sepsis
+good precision and repeatability
+16
+protein composition
+Anopheles stephensi
+91%
+The accuracy of expected value calculation
+Haemodialysis
+tse TSE
+western blotting
+Information Technology
+210/µL
+no additional steps for vector preparation were needed
+60-70%
+16%
+LPS and bacterial DNA
+139
+CXCL10
+Informed consent
+1 ml of faecal preparation
+cleavage site prediction
+light chain attachment
+cellulitis
+biomarker pattern recognition software
+Endotoxin-induced ARDS
+MatInspector
+representation of heterogeneity across different wards
+survival of virus in high titres for prolonged periods
+CCL20, CD36 and IL18RAP
+standard deviation
+China
+assessing the strength of various muscles groups in the upper and lower extremities
+active T cell response
+hepatitis C virus
+2009
+PCD
+oligonucleotides SF226 and SF227
+2000
+compensatory changes in the pathogen genome
+increasing the concentration of scrambled siRNA control
+total protein
+Santa Cruz Biotechnology
+comparably
+eEBLL-1
+global climate change
+Chun-Huei Project
+VEGFA
+Nelfinavir
+99%
+noroviruses
+Supplementary Information
+87
+newly identified alleles
+chronic complications or sequelaes
+Blood samples
+10000
+50%
+cross-protective immunity
+Non-ionic detergents
+36%
+a central part of an antibody
+Lagos State
+A/Vic/75
+Blood
+50
+restriction endonucleases
+RV
+seasonal
+macrophage protein expression levels
+greatest
+coffee ringspot virus and orchid fleck virus
+forward stepwise approach
+murine rotavirus
+four
+autoregressive model
+15 minutes
+Two
+over 10 000
+rapid localized amplification
+HCV epistasis
+secondary bacterial or viral infections
+Hand-washing
+C-2 0
+polymorphic rash, conjuctival changes and lymphadenopathy
+a professional textbook
+Four
+vaccination
+48 h
+full human adaptation
+KLH carrier proteins
+mouse hepatitis virus and equine arteritis virus
+control staining of cell nuclei
+eluate
+Shimadzu 2550 spectrometer
+interfering HMGB1-heparan sulphate interactions
+Saudi Arabia
+Ang II
+2019-nCoV
+15 µM
+Immunoglobulins
+outbreak data
+ILD
+all index case-patients
+38
+BTV induced cytopathic effect
+Eleven
+interview methods
+our ability to predict and control the expression of randomly inserted transgenes
+Human-to-human transmissions
+4-20%
+32
+regulation of protein sorting
+synthetic peptide conjugate
+surface Abs and LIVE/ DEAD Fixable Blue
+stable mesothelin overexpressing Panc02 tumors
+AIV
+traditional medicine
+very limited
+allergens and anti-metabolite proteins
+40%
+three
+enveloped
+dS values
+three
+70%
+less than 10%
+A negative HIV certificate
+127
+iatrogenic immune suppression
+FITC
+H7N9
+43-64%
+XBP-1
+time-since-infection model
+Table 2
+cell shrinkage, membrane blebbing and karyorrhexis
+published data
+Mean Absolute Percentage Error
+national health security
+rVSV
+PKR
+antioxidants
+HPRT1 and GAPDH
+low pathogenic
+one day
+antimicrobial resistance
+aas 149-157
+Two
+Heterogeneity
+ADAMTS13
+young adults
+Much further work
+relative risk reduction
+cleaved receptors
+AIV
+four
+influenza
+preventative counseling and condoms
+High-altitude pulmonary edema
+human-tohuman chains
+when γ is varied
+the derivative of the numbers in compartments with respect to the time
+cell death
+results
+ABCPred
+extracellular or secreted proteins
+Sin3-associated protein 30
+Two
+Infectious diseases
+D. discoideum
+γ
+cj0623, cj1575 and cj0669
+33.1 million
+lineage 9
+lymphopenia
+infectious virus persistence
+Addgene
+expression of early viral genes
+locally determined empirical measures
+immune
+ρ
+DNase I
+material resources or emotional support
+Creative Commons Attribution 4.0 International License
+130 μl of supernatant
+16
+the presence of isothermally generated amplicons
+6 months
+IBV
+nine
+conditioned medium from PPRV infected cells
+AP peptide conformation
+according to their average binding energy
+tumor cell killing by parvoviruses
+Neisseria gonorrhoeae
+Commensal
+exfoliation of superficial urothelial cells
+90 min
+gallotannins
+18.77, 15.48, and 12.82
+Hepatic inflammation
+MG132
+CMFDA
+liver, spleen, heart, salivary gland, and brain
+Four
+variation in the minimum budget
+VEGF signaling
+primary infection
+deep sequencing
+Twenty four
+near the octameric interface
+complementary
+48h
+desialylation endpoint titre
+Twelve
+intervening AO within the fragmented DNA
+Further investigation
+school-going
+soluble factors and metabolites
+38
+536.4 mg/ml
+an extract of Chinese star anise
+LPS and supernatants
+each city's error level reaches nearly 35.68 cases per week
+Targeting via extracellular activation of the nanocarrier
+validation
+endothelial cells
+Duration of exposure and ambient concentration of the substance
+10
+Markov chain Monte Carlo
+2Á5 9 10 4
+Macrophage plasticity
+influenza protein type a
+Trizol
+hepatic and renal
+8.7%
+maintenance of viral persistence
+age older than 65 years and hypoalbuminemia
+Fifth Center Hospital of Tianjin
+Bhattacharyya distance
+conformation and function
+P I
+E protein
+a passage of greater than 5
+13%
+the nucleus
+sudden temperature changes
+treated cells
+influenza A and measles
+Pseudomonas syringe
+ATP-fuelled molecular motors
+immune cells
+AS1411
+Hot and humid
+improved
+uptake of beads
+1942
+influenza
+Pa2 and Pb1
+temperature
+a commercial license
+Th2 differentiation rate
+27
+Nucleotide BLAST analysis
+À1 RF motifs
+Nineteen
+3
+Ae. albopictus
+G+C% atypicality
+obtaining a meaningful quanta generation rate
+5 th June 1963
+distrust of authorities
+89 to 100%
+Skin abrasion using an abrasive paper
+immunological recovery
+molecular replacement method
+mecA gene
+absorption
+ADAR-deficient MEFs or HeLa cells
+human pathogens
+production levels of more than 1 g IgG
+5%
+70
+infected
+attachment to the diaphragm
+BTV-1
+text mining
+0% to 40%
+three
+PiCV infectious status
+Dhx58
+648
+Data about transmission to healthcare workers
+HRCT of the chest
+base pairs
+Illness onset
+ZNHIT3
+recombinant virus
+their specificity
+p65
+heavy metals
+γ i
+quantitative
+multiple de novo assembly tools
+Excessive ROS production
+topologically complex and dense parts of the human PPI network
+another house was randomly chosen for inclusion
+ISG ORFs
+enveloped
+Nonlabeled oligonucleotide
+80 μL
+Protein Data Bank 49 entry 3ZZA
+the most conserved genome areas
+Samples
+40%
+7,000
+influenza
+Nucleic Acid/Protein Analyzer DU 1 800
+Temperature dependence of the inhibition constants
+δ-Crystallin
+commuting across provinces
+Previous reports
+7
+30 min
+ADRP/perilipin 2 protein expression
+Que-treated WS hMSCs
+non-retroviral integrated RNA virus sequences
+transplant vasculopathy
+strain-dependent transmissibility
+293T cells
+German psychologist Schwarzer
+Zymo DNA clean column
+absence of active
+interplay
+Outer primers
+3 of 11
+rabies epidemiology
+coevolve
+PER1, PER2, CLOCK, and BMAL1
+intestinal lamina propria DCs
+day 2-3
+NCBI Insights
+5,000
+VP2 and VP3
+intestinal focal adhesion kinase
+FFA
+genetic drift
+pneumococcal
+BAL
+symptom severity
+cardiac failure
+The preservation of A 4 under increased GC pressure
+1 h
+12
+laminin 332
+PQC factors
+prostate-specific membrane antigen
+JEE scores
+CD45-positive
+Acute respiratory distress syndrome
+similar to Survey 1 and 2
+new probes
+19
+0.81 ± 0.04
+FlowJo
+pre-existing immunity
+An interaction term between study year and intervention receipt
+GO assignments
+Leishmaniases
+Atg8 lipidation and elongation of the autophagosome
+ventricular fibrillation
+H5N1
+0.78 to 1.56 µg/mL
+H1N1-specific antibody responses
+One hundred and four
+More evidence on the underlying biological mechanism of HFMD transmission
+ten
+Carl Zeiss LSM 710 confocal laser scanning microscope
+liver-specific
+further annotation
+15%
+Physiological changes associated with pregnancy
+GCSF
+total number of carbons and double bonds
+expression of IFITM3 isoforms
+seven
+liposomes
+7 d
+8mM
+mineral nucleation
+reversible Markov chains
+rgPB2-K627E
+IAPV
+circular dichroism
+environmental trends
+increase the death rate
+Labeled RNA
+enhanced Gag cleavage
+diabetic
+TSB
+three point bending assay
+decreased SP-D serum levels
+severe disease outcome
+an MG
+19-22%
+enhancing epitopes
+Changes in TFH transcription factors
+Antigen-specific human memory B cells
+5%
+within first day of the fever
+arthropod borne
+15%
+168
+4%
+mathematical
+one
+Table 1
+gp41 and gp120
+raccoon and Canis lupus familiaris
+Peculiar
+2 g/ml human fibrinogen
+gene order
+species evenness in clusters
+personal hygiene, water treatment and food production
+human corneal and conjunctival tissue
+Trx1 and CD30
+adenosine-stimulated
+Juliana Idoyaga
+China's 2010 population census
+five days
+strengthen their capacities
+Log viral titer reduction
+two
+nine
+organizational culture
+87%
+All data supporting the findings of this work
+Information on healthcare use
+Profiler
+lack of strong inflammatory immune response
+The supernatant
+pragmatic decisions
+pairwise Significance Analysis of Microarrays
+Ponceau S
+A max
+hydrogen peroxide
+1.9
+UV absorption method
+ISG54
+regulation of the invasive and non-invasive tumors
+disclosure of HIV status to neighbors and low quality of HIV services
+Public health actions
+PRR ligands
+CGR-16
+EBV-mediated B-cell transformation
+macrophages
+the most promising
+its biological presence
+Cryptosporidium
+ADAR1
+Inhibition of NHE by EIPA
+Haploview 4.2
+PK domain
+PD98059
+0.25 mL
+40%
+stroke and heart attack
+HPV-16
+A549 lung cancer cells
+acute respiratory failure
+Figure 3A and Table 1
+R 0
+100%
+Davinch-K
+10-40 years
+Shortest path length
+Motion properties
+Pools containing varying numbers of heads of bodies
+IFNc
+ΔGDD
+28
+a temporally differential expression of transcript isoforms
+7%
+obesity and diabetes
+SHESIS
+high-energy projectiles being released from the explosive
+a structure for avoiding duplication of resources
+age, school class size data, and proximity between schools and households
+BCA Protein Assay Kit
+Twitching
+Platinum SYBR Green qPCR SuperMix-UDG with ROX
+a comprehensive list of kinases
+AT 1
+unstable inflation
+more than 400
+its role of regulator of the secretory pathway
+ELISA
+positive end-expiratory pressure
+IFNLR1
+Sixteen-week
+Time until recovery
+multifactorial
+Piggery workers
+movement through habitats unsuitable for infections
+CYP3A4
+4JK4
+350,000
+13
+S10
+16,529
+A properly calibrated model to data
+Rotavirus
+free fluorophore excess
+23,000
+host macromolecules
+2009
+LDH
+E1 and E2 sumoylation enzymes and SUMO-1
+A Hopf bifurcation
+Cufflinks
+Propionibacterium acnes
+RNA polymerase III
+AFR
+0.12-0.3%
+59 triphosphate RNA
+UCSC-GWAS Genome Browser
+weak buffer capacity
+isoflavonoids, saponins and polysaccharides
+10%
+Day 90
+important aspects of its biology
+1.8 Å resolution
+autophagosome
+post hoc Bonferroni tests
+human rhodopsin C9 tag
+antigenic recycling
+Virus-mediated T cell cross-reactivity
+The cell cytoplasm
+Aerial bronchograms
+tendencies of physical
+Further studies
+two fragments
+kinases
+54
+biogenic atmospheric O 2
+unchanged
+pFLAG-CMV-2
+5 days
+severe acute respiratory syndrome
+seasonal
+0.7%
+complete prevention or eradication of the disease
+six
+three
+3
+K m and V max
+P max
+UL44
+three weeks
+Fig. 3
+RvE1 analogue
+1-10 SFV DNA copies per 500 ng cellular DNA
+Escherichia coli
+four hour
+The PI
+lithium chloride and diammonium glycyrrhizinate
+6 months
+respiratory and influenza-like diseases
+Patient brains
+AMPKα1/SIRT1 signaling pathway
+INH prophylaxis
+MAMPs
+intoxicate the inoculated cell culture
+essential features to consider in relation with corresponding European or French standards
+5% glycerol
+Non-tuberculous mycobacteria
+means ± standard deviation
+The same forward primer and a different reverse primer
+Bacillus anthracis
+multiple lineages
+mMessage mMachine T7 Kit
+2 weeks
+ImageJ
+Mayotte
+Cap-selection
+Increasing ventilation rates in all locations
+16 hours
+the reason for the differences
+serum amyloid A
+cc-by
+IFNL4-TT
+PUFAs
+non-specific
+849
+intermediate snail host control, water, sanitation and hygiene programs
+biological
+spontaneous variations in length
+human diseases
+Indonesia
+Capture ELISA test
+An HAI titer of ≥1:40
+Inflammatory bowel disease
+Faster convergence and tighter bounds on R
+Sepsis
+IL29
+r
+spring 2009
+non-invasive tests
+C-type
+hospital-acquired pneumonia
+Follistatin
+spike-mediated axonal transport
+S1
++ cells
+Institute of Allergy and Infectious Diseases
+street onlookers and relatives
+partial information known about the structures of gp6 and gp3
+COPII turnover
+ShedP
+systemic hypotension
+Five
+1005.83 mU/mL
+EADock or MolDock
+18%
+NS5
+30 min
+vaccination programs
+aortic cross clamp time
+Travel restrictions
+lesser noddies
+nine
+IPI
+18
+T and B cells
+17%
+Genes with a correlation coefficient of -0.5 or less
+twice daily
+international diversity
+A/WSN/33/H1N1
+Stigmatising myths
+ES/MCDB201 medium
+MyoD family-a domain-containing protein
+38,775
+8.9 Â 10 4 /mol
+20 years
+14
+9%
+polar residues
+gallic acid
+increased severity of disease symptoms
+five
+khp γ /hki
+17
+woodchucks
+high-performance
+Byrnes et al
+four
+ran at their expected positions in the gel
+6 hpi
+GENIE3
+ERa
+Group 1 and 2 viruses
+mortality at the longest follow-up available
+198
+inhibited
+pathways related to cancer
+wild-type RSV or other RSV vaccine controls
+deep convolutional neural networks
+GADD34
+polyadenylation
+six
+critical
+p ij
+World Health Organisation
+Metabolism of vitamin D
+vesicular stomatitis virus
+GAPDH
+factor analytic findings
+luciferase
+elevated cardiac ACE
+systemic and LRT disease
+Maricopa county
+Hematoxylin -Eosin
+1{ Ð T 0 ldt
+WHO guidelines and methodology
+30-day mortality
+0 to 12
+Gel Doc EZ Imager
+68uC
+Twenty µl
+6 months
+60 μL
+NaAc
+diminishes phosphorylation of MTOR
+zeros
+6.5 min
+Image Lab Software
+an effective, robust and safe form of vaccination
+nuclease activity
+P78
+NF-kB, NFAT and survival genes
+Slide-A-Lyzer dialysis membrane
+recombinant OppA protein
+10
+extracellular matrix formation
+thermal cycler
+Clara cell 10 kDa protein
+Breakthrough Therapy
+$1525
+57%
+amyloid
+PPG co-treatment
+airway crosssectional area
+Surface water resources
+mortality
+Kazakhstan
+guided groups
+10
+237
+RSM
+marine invertebrates
+respiratory epithelial cells
+traditional Watson-Crick base pairing geometry
+straw-coloured fruit bat
+inhibition of cell proliferation
+spleen and liver
+African bats
+Dots and dashes
+Ebina et al.
+Dependence
+Pooled organ tissue
+IC II
+LIPS fluidphase
+diabetes, heart disease and kidney disease
+Type I and type III IFN signaling
+440 days
+DNA-coated gold particles
+A. nodosum
+data visualization
+153,880
+Bronchoalveolar lavage
+William MacEwen
+the pulse width
+improve
+20 percent
+multifaceted surveillance measures
+discrimination matrix
+Stephane Daffis
+Eleven
+Increasing the affinity for heparan sulfates
+13
+200
+a sequence profile
+susceptibles
+elderly
+normal rabbit IgG
+Poly A RNA cDNA
+clinician-scientist
+16 nt in the unstructured loop portion following the PBS
+elevated transcript and protein levels of B cell trafficking and organizing chemokines
+efficient binding
+HCVpp
+Apoptosis
+101,179
+eight
+having omitted this relevant information
+67%
+total NICD1 level
+broad-spectrum neutralizing antibodies
+Renal histological
+REMD-averaged
+hepatitis, hemorrhage, and abortion
+twice
+four
+The IFN signaling pathway
+herpesviridae
+V IDP
+TARG1-G123E
+four
+Superscript III RT
+AVE 0991
+774
+host cell death
+epithelial-mesenchymal transition and metastasis in malignancies
+PDI
+6 of 506
+a lack of oxygen in the blood
+age, sex, hospital and APACHE III
+to maintain the production of progeny virions
+UBF and B23
+579
+printing buffer
+school-wide transmission
+2-3 times per week
+an extended pathogen panel
+water
+proteomics and next-generation sequencing
+cc-by
+mainland China
+lectin
+24.9%
+summary statistics
+pleiotropic
+crossreactivity
+Selected reaction monitoring
+Taxol and doxorubicin
+24 hr
+H2
+hPOP1 and Nopp140
+IFN-λ4
+Avastrovirus 4
+segregation of p10 into speciesspecific microdomains
+NA R103K
+1.2 days
+closely connected with MNs
+one
+FccRIIB genetic polymorphism
+38%
+viral
+Complicated course
+shigellosis
+HIV-1 gp120
+regulatory/modulatory
+A549 cells constitutively expressing influenza A virus NS1 protein
+Palivizumab
+Lys170-Met179
+25 ml of methanesulfonic acid
+Samples without reverse transcription
+extrinsic
+one out of seven
+redundant
+Phenuiviridae
+population mobility
+viral pathogenesis and induction of immune response
+260-fold
+Th17
+retinoic acid signaling dysregulation
+lymphocyte proliferation
+24
+intracellular signalling pathways
+fold enrichment within astrocyte upregulated transcripts
+fitted hurdle regression models
+Supplementary Figure S1A
+nuclear localization of hLysRS
+Angiotensin-I antagonists
+Epigastric pain radiating to the back, nausea, and vomiting
+gaps introduced during alignment of additional sequences
+non-significant
+young adults
+Microbiological diagnosis
+7 days
+radioimmunoprecipitation assay buffer
+Proline
+lower titre ratios
+careful bioinformatics analyses
+10 times higher
+1000 times
+the connectivity map
+30-100 nm
+Gaussian
+HIV-1
+EFIRM
+tombusvirus VRCs
+3 hr
+13
+Environmental stressors such as chemical contaminants
+Immune-gene candidates from other insects
+males
+measles and flu
+119
+domestic and peridomestic mammals
+the SEM for duplicate PCRs
+medium-term mortality
+late 1980s
+antigenic variation-independent, universally active defensins
+280uC
+proportionality and reciprocity
+autoimmune diseases
+the original cut edges are restored
+mRNA levels and DNA alterations
+PRRSV
+Cytotoxic T lymphocyte activity
+24 h
+SGTs and SGAs
+scintillation counting
+Mayotte
+4
+investigators
+VRC-FLUDNA057-00-VP
+Monitors
+Genome-wide
+once per month
+54
+120
+11
+81%
+34
+454
+Phylogenetic
+atrophy and oncogenesis
+protection
+c-di-GMP
+TGUide Virus DNA/RNA Kit and T-Guide instrument
+Cystatin E
+Age
+flavivirus endemic regions
+weak anion exchange magnetic beads
+a tentative function
+ELISA kit
+DO mice
+Restrictive transfusion practice
+Seasonality
+exponential and the Cauchy model
+future studies
+individual inventory tables
+index patients
+AUG4
+each phase
+526
+Unpaired student's t-test
+increased to more than 1.0 × 10 9 /L
+epidemiological categories
+hydrogen bond surrogates
+454
+Primary porcine PTEC or PBEC
+wood wool
+CME
+baculovirus-expressed VLP vaccines
+drug-metabolizing enzymes and efflux transporters
+susceptible cells from infection
+miRNAs
+transendothelial
+activated CD8
+GenBank
+1,318/4,552
+Dmus51::su8-1 marker
+Peyer's patches
+human immunodeficiency virus
+transcription of host mRNAs
+higher 90-day mortality
+44
+10 min
+2% Alizarin Red S solution
+12
+inhibited
+ethical reasons
+location data
+random seroprevalence datasets
+13%
+eIF2a and PKR
+GenBank
+58
+New Zealand
+confocal microscopy
+1.1 × 10 −2 μ m 2 /s
+PBS
+Six
+RNase-free ddH 2 O
+trans-membrane domain
+17 nt
+Four
+lung injury
+66 %
+Late Presenters and AIDS presenters
+CV diseases
+no increased risk of intensive care admission or death
+accumulation of mistranslated proteins
+4.6
+Geelong, Victoria
+pre-diluted 1:100
+10 h
+constant region of mAb KZ52
+32
+2001
+Hantaan virus
+Orthomyxoviridae
+V1
+59%
+Bayesian Network Analysis
+broader social issues
+95
+25μl of Nano-Glo luciferase assay reagent
+.
+AT-II cell growth defect
+neuropathy
+piglets
+Destabilization of these short-lived host proteins
+SVR rate
+Gapdh mRNA
+1.1, 1.9, and 1.8-fold
+virucidal assay
+H9N2 viruses
+26%
+fat and connective tissue
+overlapping mutagenic PCR
+viruses
+parvoviruses
+on the surface of hepatocytes
+DEGs
+4
+important identified risks, important potential risks and missing information
+Feline pancreatic lipase immunoreactivity
+multiple TLR-ligand interactions
+90%
+Bed capacity and diagnostic capabilities
+individual risk of bias assessment
+bacterial substrates
+cDNA
+arthritogenic anti-CII specific Abs
+anti-DNA antibodies or autoimmunity
+Bibliometric
+293T cells
+cellular apoptosis
+Whole genome sequencing
+six
+two
+γ-glutamyl-ρ-nitroanilide
+the antiviral state
+delay
+insufficient levels of secreted IFN-β
+sufficient social investment
+block internalization and infection
+Jackson Laboratory
+physiological stress
+6.32
+Residues
+20%
+102
+0.4 to 0.8 μM
+phase contrast microscopy
+relatively short
+Sir Christopher Wren
+SRIPs
+30-to-140%
+5,000
+more than 1000
+hybridoma cells
+positive thinking
+coverage
+Caution
+MR volume and feeding frequency
+FDP-lysines
+40%
+laboratory analysis and patient interview
+Mann-Whitney test
+8AE3%
+Cooperation between the humoral and cellular arms of adaptive immunity
+55,000
+lipopolysaccharide -stimulated microglia
+100%
+nano-LC-ESI-Orbitrap MS
+Development of lung injury
+PKR degradation
+Seven
+70 %
+Carcinoembryonic antigen
+Nine
+SSSV
+Codon adaptation
+identical 59 and 39UTRs
+distant organ injury
+DC-SIGN
+two
+low absolute TEM frequencies in blood
+cc-by
+therapeutic
+36
+shorter CldU tracts
+D. Natarajan
+Illumina
+13 million
+noroviral CNS disease
+30%purified WT and ompB STOP ::tn bacteria
+2.4 and 0.46 µg/mL
+SO animals
+cause low pH-dependent hemolysis and fusion
+rapid advances and need for a new vaccine platform
+Phospholipase activity
+amino acid 560
+Digitonin
+resilience theory
+Soluble
+public health agencies
+2.5%
+Brazil
+lateral flow and microfluidic devices
+densely connected clusters
+10%
+39
+10 mM staurosporin
+Manders Overlap Coefficients
+2%
+VirD4-89K
+Oseltamivir
+three
+60%
+Conditioned media
+objective measures
+SYBR Green qPCR
+13%
+duck Tembusu virus
+contact tracing data
+TCID 50 values
+GBV-C glycoprotein E2
+bronchoalveolar lavage 20 fluid
+Adobe Photoshop
+TLR8 or TLR9
+in vitro transcription
+metastatic
+50% dystrophin expression
+lower expression of IL-10
+myofibroblasts
+antigen-specific CTLs
+growth arrest
+Sigma H
+CDK9-dependent phosphorylation of the Pol II CTD
+distinct HSV genotypes
+self-protection and personal health
+strong data
+68.1%
+when the same publication has multiple records in the literature resources
+46%
+discordant samples
+Labeled fragmented single-stranded cDNAs
+Self-limiting dyspnoea
+435,000
+LASV
+their attending physicians
+microscopic lesions
+C-C motif chemokine receptor 5
+pathway and network analyses
+15%
+necrotic cells
+incidence of wound
+decentralization
+proinflammatory
+de novo reconstructed gene models
+4 weeks
+ac30
+oxygen
+physiological
+92
+10.1007/s00247-017-3827-8
+xenophagy
+Sir William Leishman
+80/50 mmHg
+insulin clearance
+74
+400
+seven out of eight
+perfect matches to the genome
+Three
+proenkephalin
+Pearson's productmoment correlations
+genotypes PC48 and PC55
+12.5%
+measures to prevent renal impairment
+Peripheral venous blood samples
+two co-ordinating reviewers
+baseline cholesterol level and diabetes
+biomarkers
+more than doubled
+Viral screening of the NS
+inflammatory responses
+blood pressure and cardiovascular disease risk
+Middle East respiratory syndrome coronavirus
+diabetes mellitus, cirrhosis and various lung, renal and cardiac conditions
+10% SDS-polyacrylamide gel electrophoresis
+2004
+3-8 days
+two
+Analyst v. 1.4.2
+1:1
+crosstalks between MAPKs
+Spatial reasons
+sheep
+CXCR3
+half
+P5-LX-P1
+Shanghai Fifth People's Hospital Research Ethics Committee
+one value of d N /d S
+Cytoscape
+704
+rendered ineffective
+the kernel
+exponentially distributed
+Cold 10% TCA
+MicroRNAs
+speciestypical
+moved free
+slowing
+10%
+neuraminidase
+GP
+eIF4F complex formation
+influenza-like illness
+113
+protective
+Molrep 31
+MPXVs can be used as potential bioterrorism agents
+33.6 kb
+replicating isolates
+647
+semisolid medium
+decision support
+lignocellulosic and algal
+Influenza
+tRNA binding to the ribosomal A-and P-sites
+Biological Industries
+iNKT cells
+altered bases
+four
+iHsp70 upregulation
+increased ecto-ATPase levels
+killing all hosts in a local spatial cluster
+Accessing diversified antibody sources
+sex, gender and pregnancy
+IFI6 and IFIT1
+Nuclei
+21.7%
+Specific values for intercept and slope
+something that we did not already know
+25
+Viral infection
+3.73-fold
+Atomlab 500 Dose Calibrator
+73%
+World Health Organization
+pathogens and their toxins
+rates-of-influenza-related illness
+Bradford method
+Expanded molecular assays, full-length genomes or virus isolates
+GTP hydrolysis
+Early prevention
+global elimination of canine rabies
+prophylactic and therapeutic
+larger pitches would result in too much airway collapse
+convalescence sample
+Fig. 3
+Western blot analysis
+mobile phones
+V5 or V3V5
+atypical trajectories
+Supernatants
+confirmed their antigenic activities
+fever, rash, and conjunctivitis
+nucleotide constraint under mutation pressure
+adenovirus
+temperature
+CK-C
+aerobic
+Mycobacterium tuberculosis
+respiratory syncytial virus and influenza viruses
+Bed Rest
+Armed Forces Institute of Pathology
+ANNIE
+p38 MAPK pathway
+short tandem repeat iterations
+5.6 kg
+past events encountered by the immune system
+Horseradish peroxidase
+14
+sampling coincidence
+LCMV GP-α-dystroglycan interaction
+all forms of aspergillosis
+viral entry into target cells
+viral genome
+rectal swabs
+screening and ranking vaccine candidates
+30.1%
+Senegal and Israel
+DVG junction reads
+50%
+relational database management technology
+6269
+5%
+antibiotic
+steps 1 to 4
+fluorescent
+sensitivity, specificity and accuracy
+systematic blood culture and intravascular extremity cannula culture
+Specific synonymous changes
+p � 0.05
+in vitro assays
+proline
+8 and 24 hrs
+insulin-like growth factor binding protein 7
+different time points
+Yuma
+total or phosphorylated Iκ Bα levels
+twice a day
+reporter eGFP expression
+averages of the duplicates
+IFNc
+Specifi c
+BioEdit software v7.2.0
+fluorescence
+myeloperoxidase
+luciferase
+Chief Medical Officer
+USP-46
+Acute respiratory tract infection
+gastrointestinal
+3D7-KAHRP-KO
+National Cancer Institute
+household contacts
+conference proceedings and dissertation abstracts
+obtaining nutrients from the host
+a proper evaluation of several candidate genes
+partial frameshift
+HCV JFH1 virus
+PCR
+late spring and fall
+activates the PERK signal pathway
+ARHGAP15 and ZEB2
+2013
+>60% amino acid identity
+CedPV L protein
+Animal Welfare Act
+UV measurement
+2 times per week
+enzymatic
+Biosen C-Line
+three IAV strains
+6 weeks
+UL29, UL30, and UL39
+3' poly-A
+43
+poor
+infectious
+the median of the pairwise dissimilarities per cluster
+Cellular uptake of CPPÀPMO conjugates
+3.8% to 24.4%
+17 weeks
+MDSCs
+LPS induced production of proinflammatory cytokines
+matrix effects and the different extraction procedure
+intracellular Foxp3
+the size of a pixel
+National Control Institute of Veterinary Bioproducts and Pharmaceuticals
+1 nM and 7 nM
+mediating LMP1-induced oncogenic signaling
+DENV-2
+infection
+up to five
+paired Student's t test
+World Health Organization
+Supernatants
+90%
+both the sequence data and the antigen structure
+nosocomial
+bone-and tendon transplant material of deceased donor patients is stored
+Thr297
+June 11
+51
+down-regulated genes
+translational mechanism
+Pathogen recognition
+most domestic and wild animals
+stepped up HIV/AIDS control efforts
+IFITM3
+ELISA plates
+1.7
+Griess reagent
+virus invasion
+siRNAs
+DCs
+cinanserin
+mRNA secondary structure
+NiV M, F and G-protein-containing VLPs
+NLRs
+factors associated with increased risk perception of pandemic influenza in Australia
+RT-PCRs
+6-fold
+144 kDa
+15
+future reduced cat handling in their shelters
+antiviral
+two or more
+26%
+a fomite
+liver and lung cells
+1100
+Twenty two
+cholesterol
+IL-12+ IL-18
+S1-S2 sites
+Phylodynamics
+the reference genome
+FlowJo 7.6.2
+type I and III IFN-activated JAK/STAT signaling
+C-fms
+2005
+supportive
+three
+NK cells
+early, late and ori-Lyt
+increased knowledge of each other's roles, responsibilities, and expertise
+Stratagene
+gene expression with greater than two-fold up-regulation
+Dot1L
+eight
+to prevent VSV-G cleavage
+0.25 mg/ml
+5
+Ching-Chuan Liu's repository
+EXO84
+molecular biology, immunology, and medicine
+HAdV-5
+3
+ventilator time and survival
+A BAR
+Contact
+core protein expression and genome replication
+multidrug resistance
+information
+RA, SS, and SLE patients
+24
+enhances lymphocyte infiltration and causes lung tissue inflammation
+public debates
+99
+nucleus and cytoplasm
+respiratory syncytial virus
+Animals that serve as the natural host reservoirs
+TBFVs
+dasatinib
+rising
+24h
+Thermo Scientific Pierce Protein Research Products
+animal model results
+dystrophin exon 6 recognition and processing
+viral
+affects the immune response
+class III PtdIns3K activation and BECN1
+RNeasy Plant Mini Kit
+U3 snoRNA
+tumor suppressor
+HTNV infection
+Dr. Z. Matyáš
+imposed restrictions on their collection
+binding to cell membranes
+6 to 31 months
+greater
+The extent of aquaculture
+Motif 4
+gp41 transmembrane protein
+Incorporation of rhA3G Y
+500
+macaques
+SyBr Gold staining
+slow reaction, drowsiness, restlessness or convulsions
+A protein interaction network
+boceprevir and telaprevir
+avian influenza
+Safety
+DNA double-strand breaks
+METH and cocaine
+partially vaccinated
+Intramuscular fat
+two
+virus dependence on some host functions
+interesting characteristics at microscopic level
+A and g r
+23
+investing in preventing NiV
+59
+The estimated number of ventilators that can be used
+46
+0.05
+increasing interferon gamma release
+Monte Carlo simulation
+50%
+81%
+MP-12 and TSI-GSD-200
+PVDF-nitrocellulose membrane
+⌬%S
+peptidyltransfer
+Z jh
+clinical judgment and the patient's renal function
+PCV7
+formulations for routing mRNA to other tissues
+acute ischemic stroke
+85%
+responding to hurricanes
+PMN immigration
+a brief overview of anxiety and mood disorders
+vaccines, medications, and health advice
+GalNAc/GalN utilization pathway
+RPMI
+1 IFN receptor-deficient
+viruses that infect eukaryotic and prokaryotic cells
+molecular features of the entry process
+luciferase activity
+betagalactosidase reporter gene expression
+Improving the proliferation and migration of MSCs to a target tissue
+cdN
+positive
+four
+microglial development
+MAGEA3 and MART1
+10-1074
+more than 100h
+7111 nt
+1.1:1
+T cell activation
+IFNAR
+one week
+greater generic conspiracist ideation
+angiogenic
+the strain and its adaptation to the host
+2.4 ± 0.7x10 6 IU/mL
+Direct-zol RNA miniprep kit
+32
+HIV infection
+wells
+inflammatory
+0.45 mm-pore-size filters
+HCO 3 and CaCl 2
+TatB and TatC
+AP2-G
+8
+those in mock-infected cells
+labINR
+three
+Europe and the Middle East
+TP53 and STAT3
+novel therapeutic strategies
+immune response against viruses
+passive
+viral contamination of animal cells
+tens
+Functional group
+100 μ g mL
+production of VLPs
+control over their workload
+GGT activity
+226
+high sensitivity in detecting functional antibody responses against influenza HA antigens
+252
+100 µM L-cisdiltiazem
+cell differentiation
+GPS-data-loggers
+WeChat
+time of sample retrieval
+50%
+Table 4
+virus
+l C
+50
+RESCUE-ESE and ESEfinder
+MEDI-565
+ef®cient IMV assembly
+LP and MT
+ribozymes/viroids
+Chest
+70/100 000
+mouse cytokine antibody arrays
+CD8+ T cell response
+1.1
+tracing data
+six months
+Table S2
+maximum surface tension
+P12
+2-pentylfuran
+nine
+Less than 3 %
+tissue displacement
+H3.3
+acute respiratory distress syndrome
+household structure
+intravenous rocuronium
+6-fold
+pro-inflammatory
+increased β-galactosidase activity
+mega cities
+mortality rate
+50%
+Betulinic acid
+Five
+Large-scale experiments
+piglets
+Brefeldin A
+uneven allocation of resources
+multiple transfers of nucleic acids between different tubes
+Cryptosporidium
+Overlapping genes
+Dr. Adadevoh
+Sixteen
+anti-H5N1 effects
+u
+the staff asks the patient about
+online
+an OTU knock-out virus
+Qiaquick PCR purification kit
+DC activation markers
+basic cellular functions
+Two
+ArcGIS
+binding to the chromatography column
+cDNA
+centromeres
+19,238
+preschool attendance
+random-effects model
+PMN accumulation
+pull down the other
+SP-D
+vertebrate
+CD4-dependent
+rodents in Japan
+91Á4%
+medical-grade silicone and Platinum-Iridium poles
+sample size
+quantitatively calibrate the model for the processed municipalities
+monthly income and residence area
+0.48000
+Rapid tests
+optogenetics and infection biology
+ACE-1
+AEC Substrate Set
+ALG1 and ALG2
+200,000
+four
+GraphPad Prism 5.0
+80%
+genetic modifications
+phylogeny
+cloverleaf
+100%
+DBI and SMI
+Black African
+polar amino acids
+information sharing protocols
+n, n and n
+MDCK
+Acute respiratory distress syndrome
+transmit cytotoxicity inducing signals
+50, 100, 200, and 500 nM
+Library generation primers
+47.4%
+GAPDH
+HAV
+IL-18 secretion
+a factor six
+age
+PEEP = 6_noRM
+Fitting models with explicit individual factors
+age group and sex
+The incidence of the infection
+ribavirin
+individual patient emergency and nonemergency access to investigational drugs
+90%
+144
+-IIA
+α = 0.05
+12
+388
+nitroso or nitro adducts
+one hour
+Waist-to-hip ratio
+8.42%
+3,083
+statistical model
+Eleven
+16.3%
+metagenomic surveys of environmental samples
+more transcytosis
+Circoviruses
+5 minutes
+Ran Binding Protein
+detailed requirements for planning an MG
+6%
+viral load
+muSOX
+72 h
+Four
+1 day before illness onset
+>84%
+myricitrin
+12
+activated microglia
+9-40%
+Bim and PUMA
+genic lncRNAs
+caveolae-mediated endocytosis
+nucleotidylation of the NS5 Y26 residue
+Detection of the HA protein
+Animals Act 1986
+three
+polymerase activity
+dysfunctions in cerebro-cerebellar pathway
+Lung section slides
+CVP
+SLC14A2
+8.5 hours
+by considering different positions of one ion relative to the second ion
+1,4-dioxane
+5%
+Curcumin wt%
+viral M1 protein
+36 days
+common method bias
+Formalin
+IL-6, TNFα, and CXCL10
+23,221
+solubility or membrane location
+Phosphorylation of JNK or p38
+TLR7
+plaque assays in Madin-Darby canine kidney cells
+10 μg of fragmented aRNA and hybridization controls
+massive remodelling
+personnel changed each
+participate in the intracellular maturation of HNP1
+Variola
+Cell viability
+3 times daily
+VOCs profile
+critical
+Atlas.ti
+A human pegivirus
+anthropogenic
+water molecules
+FKBP11
+suicide
+The possibility of intentional contamination
+anti-phagocytic
+induce the genetic alteration at the chromosome level
+CpG10103
+Ying Wei Yau
+transplacental and transmammary transmission to puppies and kittens
+Sigmagenosys
+conformational change at a Leu residue
+AAY spacers between two adjacent epitope fragments
+RT-qPCR
+100 %
+PF-C cells
+CD4 + Foxp3 + Treg pool
+DDP
+Processive nucleic acid polymerases
+DUBs
+taxonomic
+Levels of PERC
+furin expression
+malignant
+November 17
+HeLa cells
+two
+antigen-production, delivery and adjuvanticity
+Vector-borne flaviviruses
+five
+the expected value of the relevant quantity
+Insight into the ecology of bird populations
+Epitope length
+GraphPad Prism Software
+firefighters and police
+2 μM monensin
+high virulence
+Meningococcal
+low
+predictive performance
+induced Gag retention
+different dietary practices and methods of food preparation
+7.5 Pa
+Acute phase proteins
+regulating immune system activity
+R V
+7%
+palatal fusion
+once
+UTY
+lift these macroscopic quantities to consistent microscopic realizations
+Placing the threshold at a minimum point in the distribution
+The efficiency of À1 PRF
+five days
+MP-12-NSs-Flag or its mutant viruses
+bioinformatics
+to speed up computing time
+linoleic acid
+hemodynamic instability
+important
+phosphate buffered saline
+our study results
+two-way analysis of variance
+160-320 and 320-640
+one
+2.1 km
+feedlot calves
+STS risk grade
+haemolymphatic
+membrane ruffling
+FEI Tecnai Spirit G2 transmission electron microscope
+PCR amplification product
+fold change from pre-vaccination
+4 h
+Graphs
+π i and π j
+10%
+dynamic age-specific fertility rates and death rates
+ERp57
+250 mg
+inflammation
+both cleaved fragments of caspase 9
+viral RNA and bacterial DNA extraction
+agarose gel electrophoresis
+93%
+Southeast Asia
+more than 20,000
+Escherichia coli BL21pLysS competent cells
+June 2017
+protease activity
+HLA-A * 01:01
+The ability to respond to a public health emergency
+metabolic activity
+murine latency model
+Radioactivity
+combat antimicrobial resistance
+Prevalence
+mitogenic
+The transition durations
+Valap
+P
+datasets
+An adoptive filter
+authentic culture models
+increased
+a very complex metabolic network
+four
+0.16 and 0.61
+ROS
+Θ
+The virus-containing AC flowthrough
+surveillance systems
+hypoxemic cerebral perfusion
+1000
+surface expression of CD4 and CD8
+20 μL/h
+poly
+Single round selection
+seventeen
+seven
+zero
+Breeding section 2
+microvascular endothelial cells
+reach receptors on the cell surface
+1′-OH-MDZ
+Tr1 induction
+Seven
+New England Biolabs, Ltd
+to facilitate binding to cell-surface CLR
+a common litter environmental effect and direct genetic effects
+avian-adapted strain
+one
+nucleoprotein antigen test kit
+Total RNA
+cc-by
+Vascular endothelial growth factor
+HFold-PKonly
+non-absorbent polyester
+TTF-1
+0.5 mM IPTG
+PERV restriction
+decreased bacterial uptake over time
+EGCG
+linear combinations of the original variables
+HBP1 and fgl2
+rotarod assay
+differences between the two groups were significant
+The position of a non-specific band
+surgical resection, radiotherapy, and chemotherapy
+MA
+The PI
+eight
+mean human case forecast error
+expression of RORγ t
+two-to threefold
+comparative methods
+VLPs
+80 million
+D. Gerlier
+a third fellow
+T-helper cells
+6-fold
+Africa
+15%
+Phytohemagglutinin
+the local background
+γδ T cells
+Cam R /Tet R
+Genomic DNA
+IL-6
+Q
+3.3
+Primer Premier and Primer-blast software
+Wildlife
+hemorrhage, thrombosis and infection
+assay buffer and 2 mM ethanol
+viral replication
+TLR2 with the ENV TMD
+low-and middle-income countries
+Preclearing beads
+mardi viruses
+antigen persistence and defects in viral clearance mechanisms
+5
+S. pneumoniae
+TT
+Primary LNEP-enriched cells
+MEGA4
+50000
+IRAV
+respiratory failure
+16%
+MxA GTPase
+cleavage
+Grubbs' test of outliers
+four
+Non-specific binding
+probe-target combinations containing many mismatches and dInosines
+IL-12p70, IL-6 and IL-15
+questions on suicidal behaviour
+Coinfections
+alpha-COPI functions
+10 mg/mL
+Vaccination
+challenge infection
+68 ± 7
+quantitative analytical approaches
+CD4 + LTi-like cells
+The infection
+VAP
+34.3%
+30-day mortality
+antigen-specific immune responses
+59 phosphate group
+Pseudotype HA
+magnetic wells
+Vaccines
+lipid composition and lipid type
+Multiple logistic regression
+Mina
+25%
+vesicular membranes
+ecological factors
+antiviral factors
+1957 and 1968
+TFH and GC B cells
+45%
+Sixty-nine
+previous work
+6-diamidino-2-phenylindole
+AMR reference laboratory
+f C and f RS
+insulin resistance
+20 mM
+unknown
+HAV1Cb probe set
+UFS duplex
+Crimean-Congo hemorrhagic fever virus
+a hospital admission for an elective procedure
+relationships either between or within the major clades
+lower motor neurons
+protein-protein interactions
+CARD9
+leucopenia and multiple patchy shadows
+macro-steatosis
+E.coli TG1 cells
+Beijing
+C-terminal
+Cell lysates
+226
+fish
+group IIA phospholipase A2 and complement factor H
+Right censoring
+total phenolics
+Organoid
+17.38
+reverse transcriptase
+cardiovascular diseases
+specificity and sensitivity
+10 µM E64
+24th November
+209 million Euros
+tissue homeostasis and repair
+negligible to low
+genotype Ia consensus sequences
+SIINFEKL peptide
+humanwildlife contact
+key items
+2009
+phagocytic function
+make their influenza sequences publicly available for analysis
+The LXXC lipoprotein motif
+comparison of genetic similarity and differences between African and global strains
+80-90%
+Poly-A pull-down
+Protein abundance
+Reducing air travel
+improvements in public health infrastructure
+western Panama
+Donor organizations
+2014
+soluble factors
+by overlying individual grids
+palmitoylated and myristoylated proteins
+lower percentile rank
+infectious RG3 patho gens
+mediates virion attachment and fusion to susceptible cells
+ligand-defined cavities
+186
+clear quarantine and isolation rules
+Mmp9
+skeletal development and maturation
+0.87
+3 weeks
+anti-inflammatory
+deprotonated
+hyperactive acute response
+Cerebrovascular diseases
+VSV-EBOV
+K562 and U937
+543 nm
+qRT-PCR
+information on the available overexpression plasmids and strains
+T-cell exhaustion
+FARV vOTU
+DENV-2
+oily, clear to yellow-brown liquid alkylating agents
+Japan
+PA, PB1 and PB2 subunits
+six
+respected
+excess base
+IFN signalling pathway
+estrogen receptor/progesterone receptor positive breast cancer
+bronchial smooth muscle cells
+0.1-0.6%
+a new family of demographic variables
+two-thirds
+18, 500
+24 hours
+A reduction in length of viral proteins
+GSH-ethyl ester
+villagers from Dielmo and Ndiop
+cleavage sites in candidate substrates
+lock onto a part of the foreign body
+Eighteen
+basic amino acids
+The FPKM
+Pan American Health Organization
+Tannins
+Cy3-labeled WGA
+msconvert
+metal binding
+VP1, VP2, VP3, and VP4
+7
+short and long-distance movement of the virus
+ligands
+private homes
+Y527 and W529
+iDVG-derived RNAs
+preservation of potentially-antigenic epitopes on the surface of target cells
+RCSB Protein Data Bank
+Bone marrow -MSCs
+four
+ra TiO 2 20
+hepatic and/or extrahepatic
+250 million years
+the ratio of the standard deviation divided by the mean
+prevalence data
+1.0 kcal/mol
+Sixty-four
+cellular mRNAs
+Proteomic
+regions of internal and terminal repeats
+AUG and UGG
+0.7 ± 0.5 μm
+liquid scintillation counting
+wild-caught snakes
+7-10 days
+TGFB1 and VEGFA
+Each image taken from different color channels
+antibody-secreting plasma cells
+30
+NLRP3 and caspase-1
+Caspase-8
+2013-2016
+CW WC DD YH
+1-605 and 1-619
+1/N
+12
+pulmonary edema and long-term fibrotic evolution and pulmonary function
+1 × 10 10 CFU/ml
+bioinformatics
+2.45 and 5.8 GHz
+18
+seven
+Eight days
+Hepatocellular carcinoma
+more than half
+adenovirus and M pneumoniae
+the national schedule
+novel overlapping genes
+March
+ancestral branches
+autocorrelation
+key contacts
+regulates host immune responses
+Amira
+12 days
+entropy
+passive immunization with an equine antitoxin
+30 000
+The chi-square test
+ClustPW
+limited clinical material and high CT value
+low fog machine
+NF-κB
+significant reduction in both intracellular and extracellular virions
+diversifying selection and correlated evolution
+fifth fraction
+TMHMM server v2.0 41
+23 November 2016
+samples
+10 − 4
+21 days
+10
+versatility
+Relative Luminescence Units
+prM protein
+spatial clustering of spill-over events
+H5Nx viruses
+rapid local depletion of susceptible individuals
+Interdigitated electrode
+unknown
+spacing
+$42 BILLION
+underestimating the extent of noise in the data
+their own helicases
+Marine Clade 1
+DNA High Sensitivity Chips
+LMP1 and LMP2
+down-regulation of inflammatory cytokines
+three
+30 min
+twice a week
+shrimp alkaline phosphatase
+0.009
+rbcL and atpA
+Nontuberculous mycobacteria
+Standard curve
+the Americas
+15 min
+flaviviral
+ROC analysis
+future productivity losses due to death
+symptoms
+cytokines and leukocyte markers
+host proteases
+Flaviviral NS1 protein
+lineagespecific
+10%
+COPI-coated vesicles
+at the host cell surface
+RB =ED 50 / ED 50
+codons within predicted epitopes
+actin-driven
+QIAamp MinElute Virus Spin Kit
+protective
+conflicts of interest
+mononuclear phagocytes
+Max
+electronic medical records
+gravity-diffusion models
+Transdisciplinary collaboration
+RBC, HGB, and PCV values
+infecteds
+B2M and PPIA
+densitometric
+Antigen preparation
+Loci with poor amplification
+10
+Basic information on market type and location
+antigens
+2.5
+5%
+Mann-Whitney test
+breathing room air
+Margarita RNA
+Westerners
+Parameters for modeling of disease outbreaks
+ABI3130XL Sequencer
+19
+PEI
+heterosexuals
+variable processing
+2
+σ
+HIV-1 neutralizing antibody 2G12
+lysosomal degradation
+IFITMs
+preclinical and clinical research
+an obvious À1 or +1 frameshift site
+functional shifting
+infectious mucus
+10
+Class-switch recombination
+therapies that prevent pneumonia and intractable lung injury from IAV infection
+10
+pJFH1-AM120-LacZ
+PROCHECK
+red spheres
+fetal microcephaly
+42%
+fluorophore conversion
+a tissue
+Simulated contact tracing data
+Ethical Committee of College of Medicine
+VSIG4 + RAW264.7 cells
+day 4 post infection
+uncoupling oxidative phosphorylation
+subunit associated protein 1-like 1
+manufacturing and distribution of vaccines
+Neal and Roberts
+neutralization antibody evasion
+TH1, TH2, and TH17
+broadens the total transmission-peak profile
+real-time RT-PCR
+1 mM
+CD8 T cell dysfunction
+anti-CMV treatment
+944
+hyperplasia of neuroendocrine cells within bronchioles
+39 years
+NetMHC 3.2 server
+optimal used codons with corresponding amino acid
+Acetylation
+IL-10
+Forty-one
+5
+EBV
+Licensed inactivated monovalent H1N1 influenza vaccine
+76
+interesting
+p53 activation
+H&E staining
+concepts
+0.3%
+every 2-3 days
+iterative
+Tracer
+Interferon
+halocins
+previous ZIKV exposure
+Monitoring of key physiological parameters
+SCSDVs
+p65-Tag2B
+1.6 million
+low amount of informative data
+intensely stained
+CFSE lo T cells
+2 hours
+African green monkey kidney cells
+chlorinated pyrrolnitrin
+IFN-b production
+epoprostinolium 11
+rituximab
+air passenger flows
+20%
+41
+1.6 million
+7 days to 13 years
+lower breadth and depth of sequencing coverage
+neutrophil infiltration
+mature seed sequences
+112
+4 days
+India
+a dimer
+ethanol
+clinical symptoms
+lessons
+ATA
+transforms the raw image file to a simplified file format
+antibody
+2D plot
+KCl
+TBEV from successful replication
+The basic reproductive number
+Publishers
+hospital-acquired anemia, iron deficiency anemia or chronic disease
+a region of the gene upstream of the ClosTron insertion site
+serological data
+consensus statement
+cataphoresis
+generalised linear models
+dextran sulfate
+87%
+six
+Circular dichroism
+woody
+similar clinical and functional results
+bacteriophage electron microscopy
+World Health Organization
+Rab5 GTP
+severe post-traumatic distress
+T cells-independent
+ν
+hits
+one
+rhesus macaques
+lymphocytes
+two-factor model
+intraperitoneal injection of LPS
+involved in the establishment or maintenance of a certain location at the membrane level
+similar to mammalian cell-derived counterpart antigen specificity
+UniProt database
+two-component compartmentalization assay
+Malaria
+Retroviruses
+cellular receptor SCARB2
+all but one
+GEO NCBI database
+intramuscularly
+two
+Influenza viruses
+five
+ferrets
+ZIKV
+at least two major open reading frames
+the unpaired apical loop of SL6
+20 mM HEPES, 150 mM NaCl, pH 7.5
+general population and health workers
+AllerHunter
+PKA
+0.5
+bivariate and multivariate logistic regression models
+AECs
+16%
+MW ligand
+33
+Aplysia california
+L11 and L1
+12%
+the anomalies
+p.Lys329Glu
+CMTR1
+Noroviruses
+HIV
+PRV
+10
+1%
+efficiency of the Bst DNA polymerase
+SC75741
+The right-hand side of the state system
+studies investigating zinc's potential effectiveness
+GDP at PPP
+CD11b hi CD103 -cDCs
+ICUs
+dual ethidium bromide /acridine orange staining
+100,000
+Streptomyces
+5-10%
+David L. Swerdlow
+asymptomatic
+PCR approach based on SYBR Green chemistry
+ICU mortality
+83
+whether improvements were due to the natural course of emotional crisis resolution
+32
+The mass ratio maintained between the two phases
+IFN-l3
+349
+sialometabolism
+F ear
+AIDA software and 2D densitometry
+enhancing
+24%
+Gas chromatography with mass spectrometry
+3.5%
+logistic regression
+ampicillin/sulbactam
+an effective measurement for assessing the quality of screening assays
+Nuclear DNA
+infectious diseases
+130 077
+1 to3.8%
+a binary coding of psychological distress
+32-33kDa
+occupational risk pyramid
+Digital Micrograph
+6
+halophilic
+Five
+miR-15a-3p
+EIT
+matrix protein
+Superdex 200 10/300 GL gel-filtration column
+decreased IFN-l3 plasma levels
+tissue samples
+90-day mortality
+blood meal
+zero coverage
+SIK1
+discriminate the SNPs
+RC i
+25%
+NPV
+CP6
+Table S1
+flying-foxes
+better health
+laser-scanning confocal microscope
+more than 375
+Lung tissue homogenates
+the level of gene expression
+Wolfgang Wende
+intramolecular hydrogen bond energy
+5 min
+pyramidal neurons
+CVTree
+82
+100%
+either with or without the polymerase expression plasmids
+temozolomide
+sheath and core
+inducible
+human genome annotation
+hSAMD9
+B cell translocation gene 2
+virion DNA produced by BC-1
+APC inducible vaccine universality
+molecular function, biological process, and cellular component
+repopulation of corpus callosum lesions
+71%
+generation of NO
+mass flowmeter
+Ketamin/Xylazin
+desiccation stress
+enhanced
+Type III IFNs
+brain tissue
+34
+mice
+universal coverage
+multi-ion permeation
+1 to 2 months
+Transverse mutations
+Investigational New Drug
+egg-based or cell-based
+MimoPro
+Data recorders
+Mass vaccination
+4,291
+virus replication
+bats
+ISGylate
+genetic
+lower
+Gotzsche
+PSI-BLAST
+σ i > 0
+8200
+steroids, retinoids, and thyroid hormones
+the stem region of HA
+3%
+what should be governed and how?
+99%
+immune evasion mechanisms
+FMV09-1180503
+Astrocytes
+host shutoff
+VHDL
+supernatant
+Covaris E210
+Chinese
+Groups of cells
+10%
+viral envelope glycoproteins
+high scores for PTSD in children and parents
+5-7 days
+HIV Tat-ADEVs
+lung hemorrhage and lung injury
+H7
+influenza and RSV
+macrolide and a 3rd generation cephalosporin
+534
+Richards model
+50%
+OCT
+combinatorial queries
+young pigeon disease syndrome
+Rab5b up-regulation
+Simian Immunodeficiency Virus
+neoplastic
+March 2014
+10-12 weeks
+10 min
+twice
+pMHC
+HCV796
+levels
+344
+from the patient's mother
+Cesarean section, and colostrum derivation
+owning a car in households with children
+IHC
+drug withdrawal group
+variables
+Theorem 1
+5 days
+Common risk factors
+CD40 ligation
+Thirty-six
+530-550 nm
+All authors
+IκBα expression
+incidence and severity
+Seventeen
+Guangdong
+28
+Drosophila
+leukocyte-driven
+250,000-500,000
+Viremia
+recent travel history from China
+Lactimidomycin
+Image-Pro ® Plus 4.5
+radixin and moesin
+wt-AMP structure
+different patterns are observed in nuclear eukaryotic genes
+additional studies
+AAAAAA
+English
+F1, F2 and F3
+neutral substitution rate
+~100-fold
+cell-surface HSPGs
+results consistent with those obtained from the ECGs
+apoplast and symplast
+exposure science
+Ebola
+HSV-1 UL11 and UL16
+HSP90
+HCV core
+ecotropic
+cough, difficulty breathing, and cough with vomit
+p.Lys329Glu
+Cristal Global
+nuclear accumulation of NFAT
+rapid VSIG4 downregulation
+immunomagnetic separation
+David Resnik
+to avoid clonal deviation
+North Asia
+mechanical
+306
+sequencing
+IFN-γ secreting cells
+Three
+protection
+0.45%
+AdHu5-OVA and MVA-OVA
+12
+40%
+inflammatory
+attendance records
+74
+26%
+N
+Weak X-Gal staining
+Single and double stranded RNA
+immunosuppressive
+2.8%
+Over 90%
+96
+1
+autophagy induction
+what is the subject of such regulations
+1.4%
+neither univer-sally good nor bad, but rather context specific
+devastating
+contact ferrets
+early diagnosis, treatment and isolation of patients
+81
+1.77-fold
+the usage of probes with a degeneracy greater than 10
+cases passage times
+money, time, staffing and parents
+worse outcomes
+MRC-5 and WI-38
+a viral ailment of poultry
+another cluster of viruses
+80
+four
+2.5 nm and 5 nm
+thrice
+microtubules and/or the actin cytoskeleton
+Zika virus infection
+Protein lysates
+Panel A
+Tables A1-A3
+membrane fluidity
+50 million
+pH1N1
+5 ml dispase I
+Links between nodes
+Carbamidomethylation of cysteines
+TSD
+methanol
+two influenza seasons
+0 to 1
+early syndromal information about disease
+Infection of oligodendrocyte cell bodies
+Pseudotyped particles
+WT
+PDZ domains
+Kilifi County in Kenya
+elemental
+shRNA-mediated silencing of the Tsg101 gene
+The PERK pathway
+NF-kB
+intraosseous
+BRD and the birth of persistently infected calves following transplacental infection
+χ2 test
+Old World and New World complexes
+Results for inhaled dose
+Immunoglobulin G
+back-translocation
+modest levels of human IgG
+326 nm and 20 μ L
+DPIs
+pathogen-associated molecules pattern
+CAR + /mPSCs Oct-4_hi clones
+Acute Respiratory Infections and lower respiratory tract infections
+Three
+dog TfR1
+virus absorption
+EBOV
+Guidelines for Blood Sampling in Nonhuman Primates
+complete genome sequences of bacteria
+CD4+ T cells
+viral uptake
+20 months
+APCs
+Certolizumab pegol
+PSI-BLAST
+years of obsessive uncertainty
+Luminex assay LiquidChip system
+weeks of local circulation
+two
+pericytes
+VEGF
+papain
+80S initiation complex
+cell surface glycosaminoglycan
+HRV-B104
+>26%
+CXCR2
+Bluetongue virus
+~25 Å
+coexistence and deep phylogenies
+folinic acid
+Aerosols
+7.0%
+30 nm
+Fibroscan
+Inflammation and photoreceptors degeneration
+mirVana miRNA Isolation Kit
+50 µl/min
+American Journal of Respiratory and Critical Care Medicine
+both frameworks
+73%
+SINAN
+95%
+post-translational modifications
+tetramethylbenzidine
+rs12252-CC
+high-throughput
+their genotype
+2%
+1 nm
+macrophages and MSCs
+6-carboxyfluorescein -NGR
+hand hygiene
+increase reliability of the diagnosis
+3,000
+HH
+20.7 days
+mice
+more than 50 ng/mL
+developing a general tool for de novo pMHC geometry prediction
+5
+CW3 persistence
+host, microbial and environmental factors
+mechanical signals
+39
+North America
+immunomodulatory
+Influenza NS1
+viral loads, viral clearance, and resolution of clinical symptoms
+proportional to its daily volume of passenger traffic
+enhanced neutrophil accumulation and tissue injury
+Globin cDNA
+reduced-intensity conditioning
+five
+age-dependent mortalities
+20
+Airway inflammation
+v hr
+clear signs of sickness
+3,600,000
+better
+early endosomes
+% of the travel costs
+concurrency
+LC-MS
+Thailand, Brazil, and the United Kingdom
+17%
+CRTCs
+antibiotics
+Primer Explorer
+standardization of sample procurement, testing and reporting procedures
+NDP52 and TAX1BP1
+different orientations
+miRNA screening
+SOCS-3 and IFNb mRNA induction
+PB1-F2
+C3′-endo
+targeting DI particle formation
+Partek Genomic Suite and the RefSeq data base
+AG129 mice
+illegal or unreported animal trades
+failure for recovery
+those in the natural precursor
+an alternative conformation
+social contacts
+2.5 billion
+lack of glycoprotein-specific antibodies for NSDV
+24 hours
+Leftover plasma
+cE80
+social vulnerability and disaster effects
+Ribosomal proteins
+Viral RNA/DNA
+migratory granulocyte dysfunction
+IRES-mediated expression systems
+Bead-bound antibodies specific for either HA or V5
+acute lung injury in vivo damage environment
+1980s
+cerebral tissues
+1 : 28 to 1 > 2560
+EK-X2
+patients' experiences
+5.4
+six
+10 min
+A third fluorochrome
+co-transfection with activated H-ras
+C-WS
+40%
+200,000
+differences in viral biology
+100
+deeper
+amplifiers of transmission
+1-5%
+10 gene copies/reaction
+practical
+China's Ministry of Health
+vital registration data
+65.90%
+Cycloheximide and staurosporine
+1820 cpm/well
+broader categories and themes
+Luminex 200
+Tanzania, Malawi, Zambia, Mozambique, and South Africa
+other causative agents of febrile illness
+to allow severe pathology to develop in susceptible lines
+0.1%
+TMEV
+within 7 days of the report of symptom onset
+severe pneumonia
+increased
+RML
+B cells
+650
+Quantitative reverse transcriptase polymerase chain reaction
+type 1
+70%
+1 mM IPTG
+5%
+␣ 3
+flow cytometric
+74.2%
+reassortment
+PFT-mediated
+red blood cells count
+SeqTrack
+immortalized cells
+Human population density
+Ifnar1 SA
+Streptococcus pneumoniae
+CD39 + CD4 + T cells
+USP46 activity
+disease management
+fluorescence
+Viral IDPs NS3 serine protease activity
+Biovermiculations
+phylogenetic incongruence
+DNA
+statistical and mathematical
+R v,obs
+lipid rafts
+57
+CNS production of transforming growth factor -β
+MT
+sublibrary
+Five
+Triglycerides
+collagen type II loss, and network integrity
+5 þ 4 ¼ 9 days
+DMTI Spatial
+52.6%
+Streamline-Heparin SN
+25%
+vimentin, Met, and FAK
+Itraconazole
+lymphopenia and anemia
+relaxed molecular clocks
+biosafety level 2 containment facilities
+101
+pcDNA3.1-HA-ULK1
+Chase-ABC
+membrane reservoir templates
+10
+7.3%
+TIA-1 and G3BP1
+phylogenetic incongruence
+avian pathology laboratory
+14B
+Mann-Whitney U test
+nicked dsDNA molecules
+Kidney Injury
+irrelevant variables
+miR-451, AMPK complex, and mTOR
+Th1, Th2, Th17, and Treg cells
+MERS prevention
+all-atom molecular dynamic simulations
+10%
+converted to uridylates
+bioavailability
+Heatmap
+Jotun Hein method
+the release of HMGB1 from apoptotic chromatin
+GraphPad Prism 6.0
+Early administration of antimicrobial therapy
+eight
+the edges
+Unambiguously aligned positions
+22%
+standard deviations of three repetitive measurements
+10
+Immunocompetent and neutropenic
+ClustalW
+Human enterovirus 71
+Results
+RSCU values
+Penh
+Ellman method
+Pneumonia
+2005
+transcripts and proteins
+augmented
+105
+optimism is significantly correlated with the internal locus of control
+Differential frequency of zoonotic and vector-borne transmission
+putative complete genomes
+disbelief in the effectiveness of measures
+Supplementary Table 3 Reagents
+bone formation
+0.05 Å /ps
+Benyviridae
+ten
+cell-free virions
+E271, R563, and R565
+RV, RSV, and IFV
+27:1%
+Candid#1
+laboratory
+important immune-activating effects
+Immune suppression
+one
+QuickCal software
+a sample of newspaper articles
+replication
+90
+severe joint and muscle pain, rashes, and fever
+<5 gene copies/reaction
+30
+an enhanced anti-tumor response
+nan
+7-16%
+muscle damage
+embryonic stage
+diminishing returns
+low-income countries
+PHASE statistical software
+neurobiology and immunology
+pro-surfactant protein C
+linear regression analysis
+a molecular chaperone
+cancer as a chromosomal disease
+63
+cells infected with influenza viruses
+Five
+TMB
+o1%
+additional datasets of AM images
+2,581
+methanol
+average number of SFU
+96.3%
+Western blot analysis
+hemiparesis to the locked-in syndrome
+Tissue DNA Kit
+52 ± 6%
+seven
+Intensive insulin therapy
+nectar
+every two weeks
+electrical impedance tomography
+plasma lipids
+IRAK1
+to prevent rejection of the fetus and placenta
+390-420 bp
+Muellerius capillaris
+TBEV
+crucial
+Dengue epidemics
+cross-linking reaction
+Treatment of rapamycin
+A longer residential stay or quarantine
+preventing HAIs
+Autoimmune hepatitis
+up to 8 weeks
+100%
+TRIM5α
+3569
+VLP-based
+interleukin-10
+Asp 20
+rabies, canine distemper and parvovirosis
+Method 2
+using both the numbers and the durations of contacts between individuals
+BBMap
+GraphPad Prism 7
+16
+translational efforts
+standard flask productivity assays
+drug treatments
+IFN1s
+Asians and Caucasians
+unity for two identical peptides
+Microcon Ultracel YM-10 filter devices
+BHK-21
+80
+pharmacological
+autophagy-regulating
+results
+Autophagy
+Redox stress
+25
+when all patients were considered
+MS
+adenovirus pneumonia
+homologous modules
+24 h
+The participant pathway
+Entropy
+blactamases
+ACTB
+HCV genotype
+Independent nuclear data
+chemotherapeutic agent
+eight
+399
+LC-MS/MS
+None
+Defensin
+Spumaretrovirinae
+complementarity determining region
+-80 o C
+Primer extension reactions
+fluorescence brightness values
+whether delayed chain termination is a unifying mechanism of inhibition
+CT
+1.35 billion and 573 million
+HPBV
+35
+suppression of humoral immunity
+three
+many pieces of the puzzle
+co-morbidity
+Stacking interactions and solvent displacement
+peptide-MHC-I tetramers
+one-third
+0.05%
+technical errors or PCR amplification inhibitors
+23.3-42.1%
+RSV
+Microsoft Excel
+size-exclusion chromatography
+2002-2003
+Chinese biomedical journals
+0.03%
+less than 10%
+hightemperature field sites
+24 hours
+dropping sutures
+linear regression analysis
+Meta-genomics
+CZ
+qPCR
+human IFN-l4
+H244A mutation
+four
+syncytia
+Forty-eight hours
+Children
+flexibility of our admission policy
+protective antibody response
+Petechiae
+at desk
+7.8 mg
+serum of patients with atypical pneumonia
+the need for informed consent
+Global gene expression profiles
+IFN-γ, TNFα, and gzmB
+off-target Env-specific responses
+ZIKV blood and tissue viral loads
+8096
+λ
+translation of the viral genome
+Plans
+research conducted in high-income countries
+alternate approaches are validated
+Esophageal candidiasis
+P Ͻ 0.05
+Gown and gloves
+Amplification of specific transcripts
+400 million
+Vero cells
+2014-08-12
+viral persistence
+CD4 + CD8 − T lymphocytes
+a trimeric core
+helix-lipid
+browse the questionnaire
+Soluble forms of TLRs
+Eight
+standard deviation of the observed C q values
+12 May 2017
+28.6%
+sotrastaurin
+chest
+deliberately selecting children's samples
+Deoxyribonucleic acid
+Presence of airflow obstruction
+solubilizing tag
+Fluosol DA 20%
+10 contiguous bps
+SIV infected macaques
+HeLa
+-6.96 mv
+95%
+Nine
+Free State Province
+influenza, dengue, or OFI
+plaques
+50%
+longer survival time
+Takashi Fujita
+different underlying biological mechanisms
+live attenuated tachyzoites
+grey scale
+IFN-c producing capacity
+protein-arginine deiminase 4
+transmission
+Four
+50µL
+30%
+C6
+apoptotic
+three
+a-cyano-4-hydroxycynnamic acid
+twenty
+Bavarian Data Protection Office
+5.8 mm
+cross-protection
+future crises in the HR sector
+one fourth
+P-I-type protease
+25%
+2-40 µM
+recurrence-free survival
+circRNAs
+internalizing EVs into recipient cells
+Lipid peroxidation
+Proteomic technologies
+EL4 lysates
+increases paracellular permeability
+16
+2-fold
+RNA ligase activity in HeLa cell extracts
+HBVspecific T cell response
+transcriptional activity of CRTC1 and CREB
+vaccination levels also increase
+2018-02-20
+32
+nitrocellulose filter binding assay
+15,589
+conversion from vendor formats into open data formats
+Coronaviridae
+shock-multiple organ failure
+inactivate the virus
+K 93 FITSRCRL and F 57 GYMTFVHF
+4500
+90%
+blockage of hippocampal LTP
+ATC code level 2
+high
+broad-spectrum diaminopyrimidine
+increased efficiencies in À1 frameshifting
+biosafety level 3
+two
+gene III fragment
+Complete medium
+3k sequences in D
+a segmented dsRNA virus
+waning vaccine efficacy, the influx of susceptible displaced people
+C3P3-G1 enzymes
+42%
+clustered regularly interspaced palindromic repeats /associated system
+3 × 10 4 lux
+Swiss albino mice
+most cases of early-stage ONFH were painless
+protein homeostasis, protein trafficking, and translation
+invading the surrounding brain tissue
+40
+Island of Yap
+human or animal
+seven
+sustaining public awareness and alertness
+2.67 μM
+Flavivirus genome replication
+enveloped virus
+n
+Ad5HVR7epB
+Aleatory
+delayed onset of disease signs
+mutations in ENaC
+29
+five
+53BP1, MDC1, and Claspin
+Cross-protection
+a regulatory link between oxidative stress and lymphocyte function
+130 µL
+1.4 million
+oxidative stress and lipid peroxidation
+traumatic
+PML NBs
+Ile-91
+product contamination, genetic instability, and residual virulence
+Haplotype D
+individual outcomes and better infectious disease control
+liver and vascular damage
+genetically stable
+six
+Cary Eclipse fluorescence spectrophotometer
+99%
+above 90%
+Gatekeeper training
+infection
+Nine
+a search probe
+polypeptide size
+positive
+sense chemical gradients in the environment and move toward favorable conditions
+pathogenic retroviruses
+transfusing to a level equal to or greater than 100 g/l
+10%
+the best parameter configurations
+helper virus
+mice that were heterozygous for the targeted mutation
+hyper-vigilant
+Macrolide efflux pump
+strong activities against parasites and pathogens residing in animal digestive tract
+cap-dependent
+R 0
+caseating lung lesions
+VAR2CSA-reactive monoclonal antibodies
+Q s
+viral pathogenesis and viremia
+15.8 µM
+psychometric evaluation
+1000-fold
+proof of identity
+DAVID
+HPLC fingerprinting coupled with chemometrics
+fractionated OrCRTs and MrCRT-60 kDa
+bi-functional
+influenza virus NS1
+C. albicans
+MDCK cells or HAE cells
+Pogostemon cablin Benth
+along the airway epithelium
+pandemic planning
+decreased cytokine production after infection
+ConA and recombinant mBAP31
+VE estimates specific to the elderly
+Rabbit anti-human polyclonal-HRP conjugate
+Box 2 in Section 3.1.6
+Full influenza vaccination
+ligand concentration dependent
+an exact match of the first target value
+Cytokines
+small sample size
+20 ng/ml
+a PL-CP knockout recombinant virus
+meningitis, otitis media, diarrhea and upper respiratory tract infections
+14
+Flag-tagged hnRNP A1
+a translational enhancer
+4.7%
+proteasomal degradation
+89
+de novo assembly
+unified
+mRNA with poly primers and AMV reverse transcriptase
+Shigella spp.
+>98%
+929
+20.4 ± 3.2 nm
+mice and primates
+viral RNA molecules
+real-time surveillance
+LR Clonase II reaction
+interferon system
+25 days
+Viral infections
+4 days
+Scientific Report
+CD11b + Ly-6C hi monocytes
+BSI and WPI
+three
+fluorescence microscope
+Psychological stress
+EBV integration sequences
+22
+hantavirus antibodies
+interfere with some of the important physiological functions carried out by NTCP
+Tubulin mRNA control
+respiratory syncytial
+20 seconds
+insertion of electrode needles into the skin
+from the position in the mapping
+The domains and items
+95%
+two
+systemic amyloidosis
+HRP-Streptavidin
+prism statistical package
+ZIKV
+Single-use nasal cannulas
+FSCN1 and VIME
+HI and MN
+ATG5
+nine
+Retroviral and lentiviral vectors
+Identifying new disease-associated variants
+Viral competence
+46/167
+eight
+an alternative information storage molecule
+93,744,624
+endosomal escape
+when disease expansion will either be most likely or least likely
+CARD9 deficiency
+widens the loop region
+H1N1
+50 μL of 0.16 M sulfuric acid solution
+viral genomic RNA
+reactogenicity
+oligos #3629 and #3716
+1 h
+26
+2006
+rotavirus
+5%
+ten
+AP-1 and Sp1
+A linear model
+Single base-pairs
+the epidemic dynamics
+dysfunction of TRP channel in mitochondria or lysosome
+lack of a statistical association
+Chi-square test
+laminar flow hood
+360
+Dengue fever
+80%
+antibodies
+37
+stochastic
+107
+other facilities
+Network centrality
+molecular methods
+their animal is usually pretty sick
+microglial receptors
+IL-10
+clinical risk factors
+Google Scholar
+psychotropic
+Uncertainty analysis
+Ten
+15 minutes
+intermembrane domain 1 and the intracellular loop
+time from symptom onset and time before the development of lower respiratory tract complications
+Relatively little
+1,440
+1
+1918–1920
+Stevioside
+Seventeen
+cross-linking between the viral RNA genome and the protein coat
+a key gene in the G1 to S phase transition
+Xrn1
+four
+S. exigua
+Acox1 and Cyp4a10
+ECMO
+vector-induced insertional mutagenesis
+Peptides
+Anti-rabbit HRP
+PCR and RPA amplicons
+ribozyme sequences
+bicarbonate
+The prior density p
+50 l of Bright-Glo substrate
+diminished cell growth
+RNA-dependent RNA polymerase
+glm
+spatial heterogeneity
+Single cell
+48%
+General linear models
+mice
+NK cells
+Psychotherapists
+65 years
+366
+beneficial and adverse community compositions
+RoundUp Ready™
+325 nm
+deoxyadenosine
+orange and numbered
+potential infectious confounders
+canonical correspondence analysis
+10 mM
+African green monkey cells
+Peptides containing polyarginine analogues
+TLR4
+Pulse oximeters
+GAPDH
+relapses and infections of systemic candidiasis
+VHFs
+G. dewevrei
+79.7%
+39 701
+group 1
+Hoogsteen interaction
+aerobiological
+Ongoing studies and increasing amounts of experimentally-verified PHI data
+innate immune cells
+glutamine
+insulin receptor and membrane metalloendopeptidase
+Regulated on Activation Normal T-cell Expressed and Secreted
+BCG
+A contrast
+Fisher's exact test or the Mann-Whitney test
+conserved
+addition of GalNAc in vitro
+93.0%
+1,075
+1 h
+18.5%
+SMARTselection algorithm
+pancreatic cancer
+to retain the integrity of the host sequence
+ÁÁC T method
+two
+Behavioral changes
+between 15 and 20 minutes
+look down upon us
+several pathways
+Information on health behaviours
+geographic level estimates of wealth
+cardiac or chest
+Publication order
+retention of particles expelled inside the masks
+UU
+89K-borne integrase
+plasma cytokine contents
+2%
+random numbers
+dromedary udder morphology
+six
+scale, resolution and pixel
+Royal Melbourne, St Vincent's, Austin, and Alfred Hospitals
+HCV particle formation
+means and standard deviation or median and interquartile range
+Respiratory syncytial virus
+tissue from four mule deer
+two
+apolipoprotein B100
+whether and how compassion is enacted
+The pharmacist and the statistician
+the vaccination itself
+PD-1/PD-L1 and CTLA-4
+Osteonecrosis of the femoral head
+surveillance
+cancer and autoimmune diseases
+their families
+nestin expression
+Lentivirus stock
+liposomes
+Nasopharyngeal aspirates
+medical provider costs or patient and carer costs
+increased expression of cell adhesion molecules
+100 μL of 0.25 M H 2 SO 4
+t+1 to t+D
+the α-chain of the IFN-I receptor
+Mice
+rapid test and western blot
+Eight
+CD14 + expression
+tracheal phantom
+recoding through -1 ribosomal frameshifting
+EV71
+bacterial pneumonia
+60 nm to 140 nm
+NW, CW, and RS samples
+2005
+oseltamivir
+very few
+pulmonary surfactant proteins
+modified IL-6 dynamics
+translation efficiency
+0%
+exhaustive
+1A and 1A 5
+S. maltophilia
+nil
+ten
+cellular endocytic machinery
+Creb3L1
+inflammatory
+α-secretase ADAM10
+227
+2%
+FITC-conjugated BSI-B4 isolectin
+AGR2
+79,656
+antagonistic proteins
+17
+IFNstimulated gene factor 3
+broncho-alveolar lavage
+breed- and/or subline-dependent
+identification of the optimal primer set/sets
+Product fluorescence
+over 25 thousand
+2-fold serial dilutions
+56
+bound to the active site
+6
+CXC
+44h post-infection
+homologous controlled human malaria infection
+age-associated deficits in Tcell signalling
+respiratory syncytial virus
+economic
+negative
+Total nuclear count
+BCA protein assay kit
+MERS-CoV
+24 h
+Thirty-nine
+€25
+34 years
+HRV-A 2A
+many variables
+Eighteen
+a reaction of foreign body granulomas
+clearance of microorganisms from the blood stream
+Non-informative priors
+AdC7-GRN
+Caspase-mediated processing of VP90
+Alphaviruses
+191871919
+14.333, 17.640 and 25.716
+20 hrs
+environmental health and food safety and inspection
+insect and plant viruses
+survivability of AIVs
+greater DNA-loading capacity
+childcare
+five week
+692
+Serum from mice immunized with OVA protein
+Interpretative Phenomenological Analysis
+CRT
+PCR
+p-TSC2
+two
+LIVE/ DEAD1 fixable dead cell stain kit
+four
+risk-benefit, risk mitigation and risk management
+3.448
+ten
+30-fold
+interevent contact time details
+three
+6 months
+Filter aerosol penetration
+endocytic vesicles
+human sepsis
+amiRNAs
+rodents
+25
+transcript-binding capacity
+Smad adaptor protein β2SP
+β-lactam antibiotics
+Transdisciplinary collaboration
+Post-fixed brains
+SNV prevalence
+CCHF viral and antibody kinetics
+the drug has no effect
+20 min
+inocula
+during lymphocyte maturation
+Mock-infected
+the need to exact expectations
+binds both Zn 2+ and Mn 2+ with high affinity
+Perl
+activation of an antiviral response
+80%
+Ethical approval
+1 mM CaCl 2
+Cote d'Ivoire
+glucuronyl transferase UGT1A1
+dual defect in secretion and potency
+botulinum neurotoxicity, inflammasomes and other immune system pathways
+Twelve
+Marmoset
+immunocompetent
+gap-repair procedure
+mineral oil
+p c *
+0.5
+CD11c Microbeads
+450
+PolyPhen
+DHE dye
+mucin glycosylation
+restrictive
+100 mm 3
+unusual mechanisms
+More intervention research
+28
+Building design and operation
+increased demand for psychological support services
+two
+500ng of RNA
+17
+all four parameters of disease and inflammation
+to obtain the highest surfactant effects
+minimal
+ethical responsibilities for individuals, collectives, governments, and donor agencies
+cystic fibrosis and hemophilia
+Correction for sliding base pairing
+protective
+Orbitrap Lumos
+NMR chemical shifts
+capsid C protein
+26
+Eight weeks
+visualization of contaminated air flow
+pairwise homoplasy index
+Maraviroc
+Renal cell apoptosis
+U01 AI-068636
+merozoites invasion and replication within red blood cells
+8,16
+MMTV entry
+Trypsin buffer
+simplifying
+a receptor for S. pneumoniae and H. influenzae
+decreased
+viral pathogenicity
+antibiotic exposure
+11
+three
+20 µl
+household size factor Household
+6 and 25
+viral DNA evolution
+the level of sg RNA7 synthesis
+optical density value
+10 min
+mutations affecting host receptor binding as well as pH dependency
+ionotropic as well as metabotropic receptors
+Super RX film
+Sera Laboratories International Ltd
+high fish densities and fast maturation
+antigen dose
+9
+naïve T cells
+48
+480 million
+cc-by
+secondary structural element
+primers for viral transcription
+collection volumes
+the sensitivity declared by the manufacturer
+meta-regression models
+Noninfected macaque serum
+lncRNA-protein interactions
+Genome size
+total disagreement between prediction and observation
+parasitism by schistosomes
+15.01
+Viral protein 2
+mRNA levels of target genes
+260/280 nm
+232,051
+IFNs
+NoV genogroup I
+bi-cistronic vector system
+secondary envelopment
+hairpin secondary structures
+1-3 kcal mol -1
+positive personal hygiene practices, health behaviors and perceptions of disease prevention
+indicator bacteria
+NEDSS architectural, software, messaging, and data specifications
+repeated acts of non-compliance
+difficult
+Germany
+F protein
+10 8 per hour
+viral growth
+similarity in various physical and chemical parameters
+life-lasting cognitive and psychosocial deficits
+disease transmission
+Increasing levels of tobacco smoking
+Bim
+myeloid cells
+40 AID 50
+deca-aspartate
+>97% of target regions
+The global community
+0.35 µM
+The requirement to maintain subject confidentiality
+23%
+Gluc1 and Gluc2
+Endothelial cells
+classical t-test
+poor cross-protection between different types of IBV
+well-studied human responses and pathways
+1/ 0
+events occurring in the endosome
+Pathological changes
+transient state of data collection
+23 months
+experimental wildtype DENV data
+Production of kits for the major farm animals
+synthesis of ISG56 mRNA
+high
+citizens
+lymphocytopenia and neutropenia
+Chronic pain
+absorption, distribution, metabolism, and excretion
+myeloid-derived suppressor cells
+TRAF1 −/− T cells
+500 million US$
+2862
+3 h post-treatment
+RVA
+Serum TG immunodetection measurements
+Blood and respiratory samples
+DMXAA
+4-hour
+369
+3.2%
+four
+Apolipoprotein E
+µM
+The date and time of AF
+Kaplan-Meier curve
+culture
+herd immunity to wane more quickly
+2B
+associated uncertainty in mapping
+Cellular ERK signaling pathway
+Δ t,i → g
+six
+stress and anxiety
+1 month
+viral gene products
+a humanized version of the murine antibody A5B7
+20 min
+HDL-bound esterase
+Unpaired Student t test
+yeast
+Western Pacific Region
+Figures 1
+POWV IgG
+NCBI Entrez Protein Database
+SAMtools
+Freeman-Tukey double arcsine transformation
+IL-21 and IFN-γ
+12
+cutaneous lesions, gastroenteritis, and/or progressive respiratory paralysis
+46
+How to properly examine the prediction quality
+912
+85.96 nM
+ex-vivo
+SGC7901 cells
+20 min
+Vacuolar ATP synthase
+Tsg101
+10
+Medical and public health needs
+H1 and H3
+oseltamivir
+M-NAPPA
+illegal feeding of swill to pigs
+13
+Volz model
+RTA
+modify the susceptibility to infection of specific tissues
+at doses of 5 and 10 lg
+53
+supernatants
+HAstV
+to urgently assess the needs of HIV patients
+structure or function
+24
+lipid mixing
+Non-significant
+homologous
+Translating the qualitative notion of fitness into quantitative terms
+5
+Student's unpaired t test
+No overlap in the location of significance
+Ceftriaxone and clotrimazole
+Marek disease
+phosphate-buffered saline
+Initiation factors
+Peak areas
+six
+political or socio-cultural
+increasing signs
+98.2%
+non-redundant
+MIF receptors
+proteomic studies
+adenovirus
+China
+Blood samples
+Ribozymes
+Animal Welfare Act
+the uncertainty during the model calibration period
+Orbitrap Fusion Lumos Tribrid
+herbal medicine 42, 43 and homeopathy
+216 bp
+the transit peptide and the protein product sequence
+increased immune activation and the inhibition of viral replication
+Further work
+maternally derived
+glycophorin B and complement receptor 1
+K
+Day 14 post-infection
+2500
+4°C
+error bars
+Elution buffer
+The influence of macrolevel events and conditions on psychological variables
+enhanced the notchedwing phenotype
+RSV
+below the detection limit
+TAT-Casp3
+aerogenous viral infections
+antifungal
+Hawaii and New Zealand
+real-time reverse transcription-polymerase chain reaction analysis
+blue
+5-10 min
+lysine 406
+Iba1 immunofluorescence
+antibiotic treatment
+Research Gaps
+2 to 3 weeks
+Alveolar
+ECL immunoblotting detection reagents
+cancer reductive
+Influenza A virus
+to avoid the facilitating effect of HDL on HCV entry
+T RACHEOBRONCHOMALACIA
+evaluating an H7N9 influenza vaccine
+enhanced the cytokine induction
+71
+Etf-1-GFP
+Illumina MiSeq paired-end reads
+cyclin D1 levels
+a nine-step protocol
+kB
+inhibited asthmatic responses
+the Sponsor
+catalytic activity
+reduced endothelial activation and protection of lung epithelial cells
+diarrhea, prevention of allergies, and treatment of a wide range of bowel diseases
+antigenically
+48%
+as soon as travel is booked
+AlkB homologues
+72
+oncolytic MV
+The University of Minnesota and the USDA
+43
+66%
+a simple adjunct next to the bedside
+CD15
+more vulnerable
+UV lamp
+33%
+an antigen
+the smoothing spline
+Peptide mass tolerance
+the unknown fraction
+American Type Culture Collection
+12
+Hazard ratio and 95% confidence intervals
+lowest
+metal binding sites
+AO
+CV titer
+UBF 1 and B23.1
+opportunistic
+55%
+trapped
+a predicted total mass of 60 kD
+homology
+Rb
+30 min
+C5aR
+Two
+functional trafficking network
+marked follicular and paracortical hypertrophy
+2 hrs
+pH 5.5 or 6
+24 hr post-inoculation
+KYL and GWYN
+five
+viral genome
+H1N1
+100:1
+34
+SOFA renal subscores
+uncertainties linked to population movement and records of infected individuals
+ϳ10%
+Reduction of the disulfide bond within the host cell
+cholangiocytes
+FKBP11
+three
+Hippocrates
+10.1186/1471-2334-14-21
+14th, 21st and 28th
+Ramachandran plot
+amino acids, small molecular peptides, and nucleotides
+formation of DNA:RNA hybrids
+age distribution and activity type data
+polarised transport from REs to the apical plasma membrane
+100 and 500 ng/ml
+one-third
+160
+latency I, II and III
+2014
+73
+bisphosphonates
+Dissociation curves
+suboptimal fertility
+host cellular RNA control pathways
+mutational
+two
+ACE2 receptor
+SPMs and lipid mediator class-switching
+Broad-reactive anti-M2 protein antibodies
+50%
+20%
+42%
+−80 °C
+1.42 million
+Shapiro-Wilk normality tests
+Thrombin
+LIVE/DEAD fixable near-IR cell stain
+five
+electron coupling reagent
+hybridizing complementary natural nucleic acids
+Quantity One
+SINV-G
+viral suppressors of RNA silencing
+Luminex R Bead-based Multiplex Assay
+cases in other dogs
+RNA
+six
+test set and Fischer randomization methods
+AA
+UV
+methanol-d4 and DMSO-d6
+serious injuries
+VP24 and VP35
+Microglia
+SsTroA
+endotoxins
+Cerebral toxoplasmosis
+DMF devices
+Four
+Bacillus thuringiensis operon
+ArcGIS version 10
+very tight binding
+196
+Formulation
+every 2 days
+high-intensity laser diode
+buffer A
+timeof-addition assay
+Jetprime
+spatial
+V FS
+respirable aerosol particles
+porous surfaces, non-porous surfaces, skin and mucous membranes
+glu-to-ala
+Regulation of the microbiota
+polymicrobial insult
+10%
+full-length SMN2
+homoscedastic
+activation of the innate immune system
+proximity between home locations addresses
+synplot2
+less than one hour
+VacA-mediated
+immune
+491
+F17
+Syk del/del and Syk inhibitor-treated
+real-time PCR
+Fisher and Paykel Health Care
+TRAF3 ubiquitination
+GBS
+low immunogenicity
+two plastic caps
+viral genomes
+OVA-specific IgE responses
+pneumonia
+manually
+SF162 and VI 1888
+UV light
+crucial
+Ginsenoside Rb1
+edema, neovascularisation and scarring
+Imperial College of London
+early, late and recycling endosomes
+Influenza A H1N1pdm
+PF-03084014
+full maturation of macropinosomes
+specific substitutions
+Vacuolation
+Interleukin 1 and 6
+191871919
+G proteincoupled receptors
+4 hpi
+attenuates both early and late inflammatory responses after reperfusion in MI
+50
+Statistical Analysis
+Campylobacter species
+The tomogram of a linear region of the Ebola virus
+nearly every month
+splicing and downstream transcriptional induction
+The phylogenetic tree
+78°
+written weekly reports
+N i
+interferon-alpha
+Glucose regulated protein 78
+electrophoresis
+good clinical conditions
+Efficacy
+nearby uninfected cells to produce interferon
+recent infection
+smaller
+Representative simian and avian sapelovirus reference strains
+randomized controlled trial
+violet-coloured
+four
+TAIL proteins
+PathoChip v3
+compound 9a
+eosinophilia
+8 hours
+bnAbs
+33
+4% PEG-8000 and 3% NaCl
+HPRT1 and HMBS
+Seroconversion
+inflammatory reactions
+a reassortant strain
+143
+fatal
+paired t-test
+18C/cycle
+containment becomes possible
+low-density
+panic, anxiety, and insecurity
+24%
+Brad Lowell
+phosphorescence oxygen analyzer
+267
+Acetylated targets
+miR-124
+Student's t-test
+emotional
+peptide-binding repertoire size
+IncuCyte ZOOM live cell microscope
+401
+Differentially expressed genes
+controlled, clinical studies
+additional neurological deficit
+Cytofix/Cytoperm
+Packaging in plant viruses
+Interferon-stimulated genes
+45%
+Total RNA Extraction kit
+different matrices will function best
+GBV-B
+leukocyte lineages or subsets
+MBP
+model
+17 months
+GBV-B
+antiviral defense
+IPTG
+increase frameshifting
+fresh Opti-MEM
+DNA templates
+Protein assay
+10.1%
+Drug target identification
+17.3 kDa
+cc-by
+immunologically privileged site
+25 h
+d
+ECL Plus Western blotting detection kit
+group 1
+SAB-155
+2 mM
+Single cell suspensions of splenocytes
+300Mb
+amine
+11
+Hepatitis B type e antigen
+Twenty
+Haploview 4.2
+191
+~20 nt
+adenovirus real-time PCR
+2012
+copper ion
+34%
+six
+model B
+79
+Maternal immunization
+Early and accurate diagnosis of PPRV infection
+WT and IFIT2 KO mice
+0.668
+two
+mean number of nucleotide substitutions per site
+moderately impaired LV
+14
+greater
+One third
+virophages and single-stranded DNA viruses
+11
+body temperature, and SOFA score
+mt cox1
+marginal likelihood estimation
+HY
+negative
+August 2010
+suffering
+D. virilis
+selenoprotein transcripts
+suboptimal
+7-10 d
+degradation
+nausea, nervousness and dizziness
+45
+Taiwan
+greater probability to elicit an immune response
+two-tailed Student's t-tests
+James Allison and Tasuku Honjo
+virus infectivity, fitness and pathogenesis
+1 day
+155
+physically more realistic
+Zeiss LSM 710 confocal microscope
+Western blot analysis
+twice
+25,421
+Data
+immunocompromised
+Mutational changes in the LTR regions
+onset of symptoms
+42%
+stronger immune responses against the delivered antigen
+four
+a likely realization of all possible connections that can occur between them
+bacterial culture
+glycoproteins
+new starting parameters are chosen at random and estimates are re-evaluated
+versatile natural products
+bacteriophages
+Human memory NK cells
+likelihood based method
+consultant and speaker fees and grant/research
+thymus
+Objective risk assessment
+loxP sites
+independence
+SA11 rotavirus
+cross protective antigens
+big data
+confocal microscopy and flow cytometry analyses
+1.4
+cell-surface receptors
+Yokoyama laboratory
+to restrict the spectrum of host usage
+DIs
+altered intranuclear distribution of UL44
+Antibiotic exposure
+data that has been extensively collated and analysed
+evolutionary tree alignment
+Table 1
+Isg15-deficient
+preventing moral complacency
+displaying a particular epitope
+Purified, quantitated vaccinia Lister strain DNA
+late March to July 2009
+Fit factor
+UV spectra of 9 and enzymatic product 9a
+ongoing transcription
+E5 protein
+two
+absolute quantification
+OPCML
+the society that is being modeled
+mucosal-protective
+Total VP5-positive/pfu particle numbers
+anatomically accessible self-constituents
+regulatory approaches to preventing prion-disease transmission
+A 1
+A pseudonymised extract
+24
+plaster of Paris
+online tutorials
+pneumococcal population structure
+GpSGHV and W. glossinidia
+the surface
+by translating different proteins from a common mRNA
+VFF testing
+whether the nuclear pore complex is involved or not
+p k
+IFNAR
+γ
+A compilation of our own sequence analysis
+circulating IL-6 and IL-10
+0.108-0.207
+different wells
+clinical
+recombinant VSV/LASV and reassortant ML29
+a specific biomarker
+1.4.1
+240
+38
+45 minutes
+decreases
+Born solvation
+stable 6-HB
+Dr. Yount and co-workers
+Eritoran from Eisai
+multiplication of viral hemorrhagic fever-causing LASV
+clinically comparable
+Monocyte Chemotactic Protein 1
+2009
+liver and bone regeneration
+High rates of CRAB and MRSA detection
+guanidine
+three cysteine residues
+8
+24%
+vimentin and Pol b
+DUF4280
+Soluble N-ethylmaleimide sensitive factor Attachment Protein
+information about less ill or asymptomatic pandemic patients
+de novo integration or recombination
+respiratory
+1:25-50,000
+RNA helicases
+82.4%
+15 nm gold layer
+218 or 219
+manidipine
+Comparative molecular field analysis and comparative molecular similarities indices analysis models
+Annotated ELM instances
+IRR
+sequence analysis of 24 randomly selected PCR
+25
+renal ADAM17 protein expression
+aerodynamic particle diameter, mass, and density profiles
+15 min
+Lorne Tyrrell and Norman Kneteman
+five
+Animal Welfare Act and the Guide for the Care and Use of Laboratory
+B cell-mediated humoral responses
+Seasonal influenza
+apoptotic morphological changes
+Cayman Chemicals 61
+42
+Real time PCR
+Platelet response
+Inactivation of the b-casein gene
+Cellfection ® II Reagent
+high morbidity
+lower reactivity
+crosstalk
+sub-Saharan Africa
+ionized air
+Medium 199
+132,048,347
+Understanding the mechanisms by which populations adapt to distinct environments
+crowdsourced
+knowledge-based
+a library of antibodies
+38
+E-protein
+2 days
+0.2 to 0.3
+higher compliance of the respiratory system
+zinc-finger
+5-h
+real time PCR test
+HTN
+participate in a research study
+IL-2, IFN-γ and TNF-α
+Table S9
+AMSTAR
+sequencing
+26
+recruitment of Egr-1 to ORF50P
+when the microbiota is reconstituted
+three
+Two
+1 h
+AP peptide conformation
+PHHs with IFNL4 TT/TT genotype
+GI disorders
+D'Alessio and De Lorenzo
+innate responses
+Astrocytes
+GII.11
+Sanger sequencing
+The availability of these libraries
+SUMOeome
+inflammation, opsonization, and membrane perturbation
+activation of the TLR/NF-κB and MAPK pathways
+600657
+Pulmonary hemorrhage
+DEPC-treated water
+3 weeks
+0.76
+Csl4-NT
+GSE76220
+polyI:C
+circular
+R A and R P
+Surveillance methods that can detect disease at an earlier stage
+maintaining normal intestinal function
+T4 Pnkp
+I=log
+a certain transition at a defined temperature
+oral cyclosporine
+diagnostic testing
+Seventy-six
+Zixing Huang and Shuang Zhao
+The environment
+meningitis
+1922
+three
+bronchiectasis and chronic sinusitis
+3, 7 and 8
+95% confidence interval and 80% power
+high glucose and Ang II
+cervical dislocation
+56.21
+their transmission
+cell type
+82 nucleotides
+6%
+naive CD4 + T cells
+TNF-␣ levels
+non-specific antibody binding
+Respondent-driven sampling
+99.96%
+physical units of surface radiance
+zero
+adjusted regression models
+in-gel trypsin digestion
+alkalie
+P. knowlesi
+M protein release
+Peptide or antibody libraries
+Six
+detailed comparison of each theme across the studies
+isothermal
+motor neuron perikaryon
+>40-fold
+perceived fear
+Regulatory T cells
+splenocytes
+strong oxidants
+high throughput methods
+RRIL
+adaptive immunity
+socialize action 1
+a motif directing mRNA to the perinuclear space
+10,000
+number of cases that occur before detection and initiation of an effective response
+CD8 T cells
+cellular responses to viral infection
+MagNa Pure LC Total Nucleid Acid Isolation Kit
+heat-unfolded nuclear reporter proteins or cytosolic proteins
+type I IFN
+Biomarker
+Sigma-Aldrich
+EBNA1 amino acid position 640 *
+>1000-fold
+better reactivity of the immune system
+functional protein
+PESTLE
+six
+MagNA Pure Compact RNA isolation kit
+3
+XML
+blast cells
+98%
+significant responses
+376
+Histidine
+three days
+70%
+sentinel surveillance system
+they do not have any contact with terrestrial vertebrate species
+5
+C. hominis DNA
+Eight
+842,000
+stimulates RIDD signalling to decrease ER protein folding load
+EZR
+46
+circular dichroism analysis
+37°C
+P 2
+floral
+bacteria
+system-level
+somitic
+Forty-two
+The existence of strains
+dynamic change
+21
+transcription factor binding differences
+linear regression analysis
+decreased virulence of the host
+macrophages and fibroblasts
+29%
+V E
+Midtemp t and Hightemp t
+US census data
+One Health approaches
+deregulation of viral protein accumulation
+R0
+Total cell DNA
+wild-type cells
+recycling endosomes
+Total RNA concentration
+projecting a health care systems' surge capacity for large-scale PHEs
+B. subtilis
+PDI
+PPRV Nig75/1
+two a-helices
+Z v,w
+Poor nutritional state and hypoalbuminemia
+51%-68%
+nonionic
+Tunneling nanotubes
+15.6 days
+Benjamini-Hochberg method
+EMSA
+LC3 puncta
+Zeiss Axioskop microscope
+1:10,000
+high-income countries
+Antiviral treatment
+specificity
+Antiuricosuric drugs
+mouse
+An investment case
+inter-clade cross-protection
+Germline alignment
+pooled serum samples of each flock
+selection for bronchoscopy
+Five hundred
+16 h
+one hydrogen bond
+traits known to affect mate choice
+sensitivity to γ-sec inhibition
+RIDD
+Eastern and Southern Africa
+TwitterScrapper
+macrophages and DCs
+nontrivial transitivity
+5 µL of EDAC or NHS
+10 2 copies of synthetic RNA
+diminished morbidity
+µ t and s t
+65
+cell-free virions
+RNA-binding proteins
+ORF54
+membrane fission
+adverse
+1997
+ATG7 and Beclin-1
+PCR products
+High viremia associated with hepatic necrosis and increase of liver enzymes
+system integrity and maintenance
+four
+DNase activity of IgGs
+Human embryonic stem cell-derived progenitor cells
+Poisson regression model analysis
+cyanurate degradation
+23
+ligand competition studies with other ligands
+our sample size
+viral loads
+outbreak 1
+a prototype downstream effector
+septic shock
+an intracellular viral restriction factor
+biogenesis of ribosomes
+70 kDa
+NS4B and NS5A
+infectious diseases
+50%
+simulation and analysis of complex network models
+108
+autophagy flux
+assumptions of independence
+Csl4 exosome
+ecological network theory
+33
+using standard techniques
+diminazene
+functional
+binding and entry assays
+lead responses
+increased copying fidelity of shorter segments
+hepatocellular carcinoma
+intrahost selective pressures
+low levels of immunoglobulins
+ER morphology
+plasmid DNA
+BCA protein assay reagent kit
+s n
+0.6 g CaCl
+Mfold
+statistical significance
+Mitochondrial function
+60 min
+1 s days
+113
+5,000
+relevant information
+methanol
+viral proteins
+P. Fortes
+unprecedented
+over 31 000
+alternative macrophage polarization
+twice
+Total RNA
+network degree distribution
+brain cells
+more rapid diagnosis
+92 %
+Hepatocellular carcinoma
+5%
+Staurosporine
+large-scale genes
+300
+cathepsin cleavage
+0-5 months
+mouse-adapted ZEBOV
+TGF-β
+repressed
+Co-morbidities
+ReverTraAceqPCR RT Kit
+viral
+identical
+inhibition of cytopathic effects
+Packaging signals
+PVDF
+Furin-mediated prM cleavage
+heterogeneous
+5.8%
+ATF4
+detection of serum HBsAg, HBeAg and viral DNA copies
+1,889
+different virulence factor genes
+Over 100 000
+SMIA
+a needle
+pPICZαA-NS2B-NS3 pro
+232
+Building unit
+three
+another dose of MTSSL
+40
+eRF1 concentrations
+mild hyperthermia
+3-fold
+Human DC-SIGN
+Ebola GP
+means ± the standard errors of the mean
+Inflammatory responses and intestinal microflora composition
+cellular invasion
+symptomatic and positively screened
+0.90
+2.6 cm
+36 hours
+Adjuvants
+poor
+ABCB1
+Danshen
+Rev-responsive element
+amyloid fibrils
+target cells expressing SCT-Y84A
+SSRs
+Purified PCV3 VLPs
+Free radical induced oxidative stress
+covalent attachment to other proteins
+Immobilon Western Chemiluminescent HRP Substrate
+endoplasmic reticulum
+human CMV
+PCR product of the TEF4 gene
+Meta-analysis
+medical record review
+Importance of community partnerships in disasters
+Unfamiliarity with the signs and symptoms
+Label-retaining cells
+molecular testing
+CentOS 5.4
+neurological
+air change rate
+enteritis
+peptide
+to give fold differences and standard deviations
+SHAKE
+serum-free medium
+single and double mutated variants of PeB-Lys
+MSM
+24-h
+Tanzania
+HRV and HEV
+Extensive poultry farm surveillance
+IL-10
+volunteers and participants' willingness to have more than one child
+Sec16A
+mediates fusion of viral and cellular endosomal membranes
+40%
+the Ho score
+vaccination
+peak airway pressure
+network structure of the form of communities
+day 8 p.i.
+differently
+the secondary structure
+pathogens
+anthorse
+GEO2R
+94
+9
+Acinetobacter spp
+Médecins Sans Frontières
+3057
+45.8%
+SPSS statistical package
+MSF and MSFsc
+bacterial
+Nationally aggregated data
+prevention of further disease spread
+TIRF
+ameliorated
+Coilin
+over a third
+viral pseudotypes
+5-fold
+0.2794
+49
+30 min
+The sequences of putative germline counterpart
+proteomic
+Hardy-Weinberg disequilibrium
+Sichuan province
+APOM coding exons
+seventy-five
+a certain time period post infection
+macrophages
+prevents AhR translocation
+ethical
+magnetic field distortions
+Sepharose
+PrimeScript™ 1st Strand cDNA Synthesis Kit
+m 6 A
+Animal models
+Institute for Health Care Improvement
+95%
+2 r IDP
+vaccine
+0.9
+65%
+APC-CD45
+Two
+Victor 3 V 1420 multi-label counter
+Asthma and obesity
+Ribozymes
+a system capable of meeting these benchmarks
+T 0
+cox proportional hazard model
+2004
+loss of the nuclear localization signal
+lipids, proteins, nucleic acids
+fragments of the abovementioned hypothesis
+antiviral response
+À1 FS
+lipid metabolism
+20,000
+the overall circumstances of infectious intestinal diseases
+Ag-specific baiting
+Space-time scan analysis
+0.99
+rotary
+High level of knowledge
+120
+read depths
+virologic surveillance
+nanodrop spectrometer
+prophylactic
+non-specific adsorption onto hydrophobic surfaces
+b-Actin
+biomarker levels
+ProSeq grouping Task results
+disease severity
+TLR9
+HRCT
+Durect Corporation
+Octet 7.1
+2014 to 2015
+SOCS3-siRNA therapy
+GraphPad Prism v6.0
+long-term maintenance of therapeutic levels of vector-delivered transgenes
+equation 1
+Ap4A
+anti-viral therapies
+79%
+One-way ANOVA, Tukey post hoc test
+bronchopulmonary
+accelerates
+five
+36.6%
+spring and fall
+haemocytometer
+HAART
+cytokines
+p56
+antimicrobial drug prescribing
+MyrB
+whether time taken off work influenced compliance or whether taking leave had a financial impact
+anti-interferon -c mAb AN18
+ulinastatin
+blood samples
+knowledge that may help people in the future
+G3
+Rabies
+878 m
+phalloidin-FITC
+mortality
+physical and biological laws
+one of those possibilities is chosen at random and recorded in the consensus sequence
+gene expression
+stem-loop A
+ON and 300
+Lamin B1
+lipid peroxidation products
+VP1 protein
+Contact tracing
+Climate Change Adaptation Roadmap
+population coverage tool from IEDB
+MX1 expression
+GNAS
+parameters usually associated with poor prognosis
+Vimentin
+Reverse-Phase Chromatography
+three
+0.9 to 4.6
+serve as the assembly platform for downstream signaling intermediates
+.85%
+higher lifetime expected risk
+cross-linking assays
+ClustalW
+IPO
+Mating with empty pGBKT7
+2.04 Å
+The initiation of CEACAM1-S-mediated IL-2 production
+excellent sensitivity
+knowledge about the host biology as well as societal and environmental factors
+19
+103
+one
+Urine
+The ratio between the motif and no-motif frameshifting frequency values
+Positional clustering
+Eight
+n A m
+4 mg/ml
+rgH7N9
+significant
+IFIT5-oligo-C complex
+P3N-PIPO
+4
+Gαi3-mediated
+oligomerization
+reverse transcriptases
+2008
+messenger RNA-based vaccines
+80 years
+Aspergillus species
+higher risk of pancreatic cancer
+Isoform 2
+QIAEX II Agarose Gel Extraction Kit
+COVID-19 disease
+Trauma, bleeding, cell injury, and irritant particles
+when inter-degree is big
+the specific swine flu symptoms
+communication and outbreak response activities
+215
+accuracy, relevancy, value-added data and interpretability
+respiratory disease
+pro-inflammatory
+52 kDa
+SILVA_123 database
+Ninety-nine
+PrCR
+98Á33%
+16:8 h
+Treatment with antiviral agents
+compression and contusion models
+Thirteen
+215
+generalists
+27
+4 h or 24 h
+1915-16
+neurological symptoms
+Aortic cross-clamp time greater than 85 min
+6
+IFIT1
+HCl or NaOH
+NPC1
+spacers
+10
+L2
+health informatics and practical concerns
+three
+25
+6
+90%
+decrease the overall compensatory potential of ACE2
+7.162.03 days
+Public health messages of emergency
+virgin coconut oil
+3c, 3d, and 3e
+SDS-PAGE
+temporary
+One single part to one figure and one experiment
+UG4
+size-biased household distribution
+Natural RNA extracted from virally infected cells
+70%
+a template
+PCR, Southern blot, northern blot and western blot
+demonstrating the possibility of using PI as an efficient tool to tackle novel tasks
+mRNA related to inflammation
+aequorin
+48 h
+cancer progression
+EBV-associated
+traditional methods
+affinityeluted fractions
+half
+Japan
+Early recognition
+human AEII cells
+0.2g, 0.6g and 1.0g
+single amino acid codon mutations
+40
+NGS
+190
+pathogen virulence
+MO2
+polydnavirus particles
+31
+27
+two-step qPCR
+species diversity
+Bonferroni elements
+BAG6 and AIF1
+different growth factors
+the pathophysiological context
+cell lines are well characterized and comply with regulatory guidelines
+significant compound crystallization
+respiratory dysfunction
+inappropriate use of antibiotics
+9
+Psoriasis
+10 8
+guinea pigs
+5
+0.5%
+Imported dengue
+CD8 + T-cell responses against Ad5 delivered vaccine antigens
+PB2 E627K, HA E190D and G225D
+IgG Fc
+45%
+the variable is not useful for prediction
+Viral RNA
+tryptophan-rich
+12
+cell survival
+Cytotoxic-T-lymphocytes
+clinical suspicion
+four
+proinflammatory cytokines
+hyperfilamentation
+LaSota and R2B
+2%
+cell cytotoxicity
+A threshold of 13% divergence on VP1 nucleotide sequences
+16 years and older
+desirable gene variants
+Levene's test for equality of variances
+its potential therapeutic use
+RPL19
+Fold change
+less than twenty
+2 0 -AMP
+humoral immunity
+1951
+Culture
+12,000
+six
+diethylstilbestrol ingestion
+0.5%
+10.360.6 Å
+50% inhibitory doses
+Na +
+MHCI
+315
+to ensure stable and consistent conditions
+1.92 Å
+therapy of genetic diseases
+Compound 61
+phylogenetic trees
+four
+20
+Immunosuppression
+vaccination and antivirals
+PARG
+identifying APC's involved in generating T RM within the nasopharynx
+Macrophages
+Sangeh
+22
+ten
+contamination with the wild type virus
+lipidation
+cytopathic
+The precise mechanism
+Ross River, Sindbis, and chikungunya viruses
+defining specific clinical target applications
+39%
+Dr. Hermann Katinger
+issues of reflexivity
+mallard duck
+1978
+all other linkages
+induce broadly reactive antibodies
+linearity
+human participants or animals
+abiotic stresses
+alanine
+1.7 million
+peak inspiratory airway pressure
+1 h
+liver accumulation
+common shrews
+significant
+twice a week
+F4-specific binding antibody responses
+Rotavirus-like Particles
+§2
+gD2-specific IgG and HSV-2 neutralizing antibodies
+the common structure
+Gag
+Unstimulated PBMC
+Ty1 retrotransposon
+younger age groups
+92
+homologous
+nurturance
+alkaline phosphatase-conjugated secondary antibodies
+Culture supernatant
+mid-September 2014
+airway hyperreactivity
+1:3.5
+shedding of cell surface proteins
+GEO
+The investigator and staff
+induced conformational changes
+four
+Persian
+Acute liver failure
+forward variable, reverse variable, and variable
+RNAdjuvant ®
+50 ms
+Demand-Control Model
+±12%
+White Leghorn
+Figure 4A
+MSC-mediated wound healing and revascularization
+7a
+1%
+7.9%
+radiation
+Presence of extracorporeal circuits
+S. cerevisiae
+Serum antibody titers
+neoliberalism
+Nucleic Acid Database
+0.15 M
+8-30%
+single nucleotide polymorphism in the amplicon sequence
+Pulmonary
+RIG-I
+functional HA
+UnaG green fluorescence reporter
+Direct and indirect ancestries
+human
+PONDR VLXT
+mild clinical signs
+policy guidance documents
+609.59 million
+Nephropathogenic infectious bronchitis virus
+177.8
+SGIV assembly in VAS
+lncRNAs
+University of Wisconsin-Madison
+cells or parasites
+The mucosal immune system
+GAPDH
+CD55
+fitness
+mammalian
+nonsmokers
+A 10% normal hamster brain homogenate
+Early identification of the disease
+hematophagous
+9.5%
+Seventeen point eight percent
+WM-115
+translational
+mononuclear
+LAIVs
+experimentally determined parameters
+technology to support rapid, high-volume, accurate annotation of genomes
+Pattern Recognition Receptors
+homeostatic genes
+come to work
+antibodies specific for cell surface antigens
+Predicting RNA secondary structures with pseudoknots
+Amersham ECL Prime Reagent
+1,294
+p40
+primer S 2865
+HSV-2 12
+clinical results generated by dPCR
+extensive purifying selection
+8 days
+HLA-B types
+comparison across HCW types
+temperature
+five
+Steric-blocking antisense oligonucleotides
+function on a per-cell basis decreases
+fluorescence-based thermal shift assay
+reduced accumulation of NP
+16.2%
+laboratory diagnostic tests
+Eight weeks
+mass spectrometry
+48 hr
+3%
+homology of viral and host genes
+RNA interference
+evidence of positive selection
+many weeks
+superoxide dismutase activity
+vital
+synergistic
+sialytransferases
+pulmonary surfactant
+rapidly succumb to sepsis or spontaneously recover
+a 5 sequence tract
+total population size
+Potential classes that were identified but not selected for detailed examination
+C-rich RNA motif
+internally developed clinical assays
+HBV sequences
+30-60 min
+17-26 %
+DTT
+a larger number of degenerated probes
+Thomas using lucinactant
+Coptis sp. and Berberis sp.
+SensiMix SYBR No-ROX One-Step Kit
+18-70
+virus-associated Gag
+100 nM
+enhance influenza A virus replication
+IL-10 and IL-15
+Contextualised detail about health-sector responses
+EXT
+potent
+performance of ecological niche models
+Nasal washes
+T cells
+any industry group or government organization
+GP 1,2
+acidosis
+≈5%
+Reed and Muench
+mimicry of short motifs
+Taiwan-CDC
+TEM
+BD Biosciences
+three
+Texcell
+amantadine
+Infected cells
+HiPerFect Transfection Reagent
+Appendix 1
+>90%
+hepatocytes
+to accommodate weak or strong inconsistencies
+23
+Immunity against EBOV GP
+DAPI
+immune stimulation and inflammation
+Professor Jiahuai Han and Dr. Jianfeng Wu
+InstantBlue
+attenuate the vascular permeability caused by viral infection
+apoptosis
+13
+20,000
+Protease activity
+Frameshifting
+A distribution with a larger variance
+six hours
+RAS1s
+viral miRNAs
+250:1
+weak
+men's susceptibility to disease
+Luciferase activities
+liver tumors
+hemagglutinin-neuraminidase gene
+Vaccination
+Carcinoembryonic antigen-related
+Pale-yellow
+2ʹ-OMe and PMO based ASOs
+three in vitro-transcribed full-length H9 HA gene RNA
+to determine the number of viable cells in cultures
+2009
+2.05
+Sequence complementary
+1 week
+The regulation of CSC self-renewal
+Founding Research Center for Emerging and Reemerging Infectious Diseases
+1%
+fluorescence
+E. coli ATCC 25922
+the longest estimated incubation time
+to minimize space
+The weighted distance matrix
+Fluvastatin
+allergenicity
+90%
+innate immunity
+resemblance
+Creb3L2/BBF2H7
+IL-10 and IL-28R
+1995
+phase-contrast
+FPS expression
+forcing the system out of the disease-free state
+Bid
+100 mm and 50 mm
+Far-UV
+Ticks
+AMPure XP system
+Organized lymphocytic foci
+48
+10 min
+1 hour
+Group IV
+SeV positive
+Propargylglycine co-treatment
+swine tracheal EVOC system
+,2-fold
+Ribavirin and 6-azauridine
+pentacyclic
+goblet cells
+1.15 hours
+Shewhart chart, CUSUM chart and EWMA chart
+Acute respiratory distress syndrome
+information about the peptides and the epitopes reactivity
+released into the blood stream
+Lanes 1 and 2
+Fisher's exact test
+nonredundant
+IFN signal transduction
+three
+D NA methylation
+1,234
+public health systems
+387
+27
+human immunodeficiency virus
+31.8%
+HBoVs
+neoplasms of lymphocytes and endothelial cells
+M pneumoniae reference strain FH
+to engineer mesenchymal stem cells
+clade 7
+Easy access
+mTreg lymphocytes
+conjugated them
+Q75FL0 and Q72PD2
+clinical scoring, temperature, and weight change
+frequency of EGFP + cells
+Se treatment
+junctional space
+17 AE 6 months after the estimated time of infection
+6 days
+Zoonoses
+Amino acid substitution of Tyr324Ile
+Intracellular
+three
+Crude correlations
+SGs
+The formation of the CypA:Cs complex
+5-fold
+Epidemic keratoconjunctivitis
+lower
+74.6%
+the corresponding standard derivation
+Chromatin
+LPM closure
+37.0%
+nucleocytoplasmic transport system
+immunoparalysis
+Bayesian
+poor pre-quake mental and physical health status and lower monthly wage
+The diameter of exposed bone
+Iowa
+Genetic selection
+The transmission of influenza infection
+the expression of DR5
+distinct patterns of dose dependence
+vaccine failure
+non-amplified whole genome extracted DNA
+infection outcomes
+ferret transmission model
+alphacoronavirus
+Influenza A virus H9N2
+Balb/c mice
+Cobalt protoporphyrin
+three
+no significant change
+posit ive
+LC3positive
+IFN-a species
+PSG1-FLAG
+antigenic variationevents
+GMCSF
+DNAeasy Tissue Kit
+30 nm
+20
+transcranial brain stimulation
+opportunities across sectors
+Porcine CCL25 high-expressed clone
+TPCK-treated trypsin
+Epithelial Adherens Junction Signaling
+seropositivity
+four
+antibiotic activity
+24
+Accu-Chek Performa System
+high-arousal positive affective states
+Two
+Nuclease-free water
+IFITM3 rs12252-C
+MAS
+E protein ectodomain
+large plaques
+side chain length and negative charge
+Intracellular trafficking
+Shared competencies
+42
+15
+one week
+~25 mg/kg
+potential therapeutic applications
+50 min
+Olympus FV10000 laser-scanning confocal microscope
+anti-inflammatory and associated complications
+naked HEV
+Additional file 4
+reports of retrospective diagnosis
+with LPS and/or IFNγ
+Greece and Turkey
+standard cultivation techniques
+The display mode
+Consistent predictions of CTL epitopes
+80%
+intact IFITM3
+25
+GenBank
+seven
+two
+Ceacam1-knockout
+less than one third
+phylogenetic implications and interpretations
+RUO
+72
+employee SWB and health
+endoplasmic reticulum
+codon:anticodon pairing
+Salmonella
+Identification and functional characterization of serine hydrolases
+AMV reverse transcriptase and random hexamers
+enhancing virus translation, RNA replication or playing a role in regulation between these processes
+Genome-wide purifying selection
+kinetic modelling
+ubiquitination and deubiquitination
+futile translocation
+TNF-α release
+4
+Enrichment analyses
+immunotherapeutic
+24 to 48 h postinfection
+10.1155/2018/2514901
+10%
+Quantity-One
+knock down rather than remove all DNA
+4-fold
+a relationship between two proteins
+glycosylated spike protein
+gluteal region
+Gram-positive
+RSV
+Sonidegib
+The whole signaling network
+Recovered viruses
+CD8 + T cells
+PO1
+possible risks/ harms as well as benefits
+low detectable viral load
+end-loop
+depletion of the BAC plasmid backbone containing the GFP expression cassette
+680 mm
+Atg5
+health gaps
+hydrophobic immune complexes
+stem cell-like characteristics
+proportional
+CXCL10
+any gaps in sphingolipid packing
+469
+a higher number of differentially expressed genes
+activation of Ire1's nuclease
+plateau pressure
+an intermediate and realistic level of sequence divergence
+more than a year
+means ± SEM
+300 dpi
+17,000
+HCV-specific T-cell immunity
+a new era
+general practice resilience
+substrate specificity
+2004
+IFNs
+IL-6
+greater than 2610 10 gc
+The estimator
+antigen-positive tumor cells
+NGI-1
+Communication with the pregnant women
+traumatic damage
+14.2%
+KP276585 to KP276611
+80%
+Toni Hoffmann
+cytoplasmic
+TNF␣-converting enzyme
+1,204
+taxane-induced cell death
+terminal branches
+synthesis and antiviral testing
+RPMI complete medium
+gp41 fusion intermediates
+52
+Membrane lipid oxidation
+p53 expression
+more than half
+Salmonella enterica and Helicobacter pylori
+patients presenting with severe fever and headache
+adapt to Vero cells
+wild-type homozygotes
+Stanford Shared FACS Facility
+quantitative real-time PCR analysis
+24%
+protein synthesis
+pneumococcal polysaccharide vaccination
+19
+Appendices B and C
+DNeasy Blood and Tissue kit
+Antibody fragments
+15
+wTNFα
+RVA
+direct antiviral activity
+CRISPR/Cas9
+2
+cell death
+presence of EBOV GP and VP40
+Innate antiviral immune defenses
+.95.9%
+complement binding
+20
+87%
+exposure to precipitation, soil moisture, and humidity
+>10
+to share new 'facts' and communicate advised control measures
+interstitial fibrosis
+EIA
+global translation attenuation and cellular stress conditions
+delirium
+Retail LBMs
+HRV infected primary human tracheobronchial epithelial cells
+3
+Individual study subjects
+antioxidant
+Gram-positive
+peptidoglycan recognition domains
+1.2 mL SPT TruTips
+economic, regulatory and practical
+SEN4030
+individuals who can infect a disproportionately large pool of susceptibles
+cross-presentation from these sites to APCs
+67%
+TBE
+the Cox regression model
+diterpenoid
+serological assays
+21
+overlapping ORFs
+10% fetal bovine serum
+4,710
+1.4
+25.49%
+stimulation of the interferon response to-and control of-RNA viruses
+DnaG
+Type I
+43 breaths per minute
+MS scans
+11,000, 12,110 and 16,940 cm −1
+women suffering from polycystic ovarian syndrome
+a vicious cycle
+Figure 3
+DI formation during passage in BHK cells
+Blood culture
+stimulation index
+diarrhea, abdominal pain, nausea, abnormal liver enzymes and decreased lymphocyte counts
+pathogen monitoring
+Ciliated cells
+RNA interference
+cure S. cerevisiae of the L-A virus
+misincorporation of A nucleotides
+quantitative temporal viromics
+Genes unchanged between test and control
+3500 Da to 2,000,000 Da
+assay
+TBK1
+distort its conformation or substantially rearrange the active site
+Ye Tian Shi
+reduced
+baseline
+Proteins
+3-4 months
+Minimal histological changes and inflammatory infiltrates
+dynamic problems
+nine
+RON tyrosine kinase
+two ER chaperones
+translational efficiency
+consensus sequence
+Mitochondria
+Austin Pets Alive!
+bank voles
+aberrantly used sites
+raw Ct values
+13 C NMR
+Sigma Genosys
+vascular remodeling, PAH, and atherosclerosis
+UDP-glc
+strong immunostimulatory activity
+stability of DNA
+clathrin and caveolae
+0.06% APS and 0.43% TEMED
+Synergy HT plate reader
+Multi-exon frame-shifting deletions
+viral replication
+thymic dysfunction
+monodispersed
+collecting blood for bacterial culture and sensitivity test
+62
+23
+viral
+increased fungal burden and pathogenesis
+Densitometry data
+EHPV1
+Milk
+CSC specificity
+impaired
+mice
+modulation of their physico-chemical properties
+At least three
+an acceptable representative
+50%
+treatments and cultures
+free amino groups
+76%, 71%, 75% and 37%
+ERAD tuning
+Influenza
+Protein concentration of cell extracts
+five
+a geographic link
+host transcripts
+Peak area of the SRM peaks
+93 million
+RTS,S
+lengthening the baseline period
+DNA from pathogens associated with respiratory syndromes
+cure or obviously remission of symptoms and signs of VKC
+20
+Plantago and Streptocarpus
+at the time of patient enrollment
+differential interference contrast
+AccSig results
+accuracy, precision, selectivity, sensitivity, and reproducibility
+10.3389/fmicb.2019.00050
+Fifteen
+companion animal owners
+Kruskal-Wallis test
+gene functional studies
+Real-time reverse transcriptional polymerase chain reaction reagent
+low MBL producers
+very active promotors of the field
+hepatitis E virus
+360 o every 10 bps
+Micro-computed tomography imaging
+80%
+SK2 mRNA or activity or S1P levels
+40-97%
+6.32
+samples sizes and prevision
+ferret
+Gag retention
+68-96%
+Short generation times and low reproduction number
+illumination time, illumination source and energy dose
+manual standard microbiological methods
+DCt method
+free-form text
+secretory IgA
+affinity enhancing effect
+11,308
+filamentous
+poor PM probe quality
+cancers and AIDS
+Thrombosis
+Coupling between translation and transcription
+protoberberines
+application of recombinant adeno-associated viruses
+1918 pandemic virus and recent H5N1 isolates
+October 2014
+mechanical unfolding experiments
+anti-ZIKV IgM
+PBS
+TCID 50
+Creative Comm ons Attribution 4.0 International License
+Stanford Large Network Dataset Collection
+massive accumulation of triglycerides and cholesterol
+67 nm
+autonomic nervous system
+60 minutes
+resting splenic NK cells
+Ceramonematina
+haemorrhagic disease
+Fiji software
+Plasmin and FXa
+CD4M9, G1 and 12p1
+100
+35.9%
+training and knowledge of psycho-traumatology
+88%
+PMN migration
+coinfecting variants
+10000
+three
+airborne infection
+E. coli strain Rosetta
+contact reduction and selective mixing
+necrosis
+The scale effect
+two silver NP populations appeared during the synthesis
+passive movement
+quantitative real-time PCR analysis
+social, political and ecological
+cerebral malaria
+global gene expression patterns
+PMA/ionomycin treatment
+eEF1A inhibitors
+37,400
+Rostock H7N1
+20%
+1426
+hepatitis C
+extra-pulmonary infectious diseases
+abrogate
+Rab GTPases
+Phylogenetics
+late 2002
+834
+Circular
+severe aggregation
+transmission among domestic poultry
+genomic
+SOF
+13.4 × 10 9 /L
+weeks
+Bootstrap methods
+safe technologies
+Rdisop, GenFormR and enviPat
+columnar rosette structures
+Natural HNP1
+if targets were up-or downregulated
+viruses with specific mutations on NP
+EPX-mAb
+increased surveillance
+progression of E. multilocularis infection
+aligned and conserved nucleotides
+most recent common ancestor
+retrograde transport
+no neutrophil infiltration
+Cytoplasmic Arg I and mitochondrial Arg II
+64%
+HMG CoA reductase
+developed countries
+Viral load
+linear, polynomial, and radial basis function
+Consistent differences due to probiotic feeding
+99.1%
+inflammatory cytokines, proteases and free radicals
+how things work at a systems level
+1 mm
+evaluation of the distribution of staining
+Standard curves
+Sepsis
+3 days
+an ancient bornavirus
+enhanced the antibody response in mice
+more than ten
+90.5% to 98.5%.
+mechanistic links between each scale and the next scale of organizational complexity
+mix of clinical services and patient case mix
+70%
+4
+Ang/Tie signalling
+the same school
+gel bottles
+to have the right
+MolProbity server
+0.63
+4
+undetectable
+cc-by
+nine
+1993
+recognition of the substrate-attached Ub chain
+accepting new packages
+Granulocytes
+Bayesian Skygrid coalescent model
+14%
+spectroscopic
+WHO
+receptor-destroying enzyme
+25%
+ImageXpress Micro XLS and MetaXpress PowerCore software
+77
+25 μM
+medicinal
+EDV
+ACE2
+Porosity
+SIB
+50 mins
+egfp-pbrB amplification
+bacteria to eukaryotic organelles
+5%
+H7 DNA and H7N9 MIV
+A short stimulation time
+generalized linear mixed models
+Cu 2
+CEACAM1
+Air sampling
+7
+HCC
+according to randomly assigned numbers
+55%
+protein regulation and abundance in the cell
+MaR1
+IE2
+RANBP2
+most of the affected Asian countries
+CHO-Neo
+2.54
+gastric
+to detect novel strains of influenza
+Mouse Diversity test A-array
+m 1 and m 2
+R 0
+eight
+T4 polynucleotide kinase
+Pneumovirinae
+96
+toxicity
+means ± standard deviation
+caspase-dependent pathway
+all putative mutation calls
+0.45
+1:2
+a non-fermenting Gram-negative bacillus
+meta-transcriptomic
+Peptides A and B
+one fifth
+capside protein encoding gene
+Celiac disease
+k-means clustering
+which duration, if applied to every edge, would produce the correct average probability
+RNAgraphdist
+months to years
+Graphpad Prism 5.03
+ensuring their own maintenance in nature
+LAMP test
+Ti
+Non-resolving ER stress-induced apoptosis
+hepatitis B virus
+One percent
+three
+Sequence data for P. cristatus
+slide labelling
+CEACAM1+
+simulated breathing frequency
+experimental data
+Protocols
+poor mucosal IgA antibody and T cell responses
+ethical
+1.6 M nBuLi in hexanes
+pathogenicity
+pathway analysis
+Sunnie Thompson
+using different cutoffs
+Tehran virus
+CRLs
+8-126
+synonymous codon usage bias
+TSP 1
+Eleven
+insufficient sample volume
+productively infected
+24,658,823
+transcriptional activity of BMP target genes
+T lymphocytes
+Complete inactivation of B. thuringiensis Al Hakam spores
+diisopropylfluorophosphate
+three
+10 to 50%
+SAMtools
+culture-specific supernatural thinking
+ventilation-free days
+interest and skill
+polio
+different cellular compartments
+host-mediated inactivation of viral RNAs
+IURs
+nutrient acquisition
+60 ∘ C extension step
+Candida albicans
+BTV-8 or Great Island virus
+GAPDH
+three weeks
+Combination therapies coupling with antiviral and immunomodulatory drugs
+hydrophobic stretch
+enteral nutrition
+hNPCs support H5N1 influenza virus replication
+five
+50%
+Carbamidomethyl cysteine
+11 months
+protein translation time lag
+Supernates
+dengue, hanta-virus and acute hepatitis
+20%
+five
+bleomycin-induced mortality
+5 days
+at the level of transcription
+temperatures
+options
+inter-individual variations
+Biomarker discovery
+broad-spectrum property
+1 h, 1 frame/min
+hairpin derivative
+shorter
+NCBI Reference Sequences database
+three
+Total effect rate
+Molbio
+better control and elimination of HBV infection
+cpe and PCR
+experimental
+ultracentrifugation
+winter resource shortage
+variation in C t values
+Primary antibody omission
+Disease occurrence data
+assessment and management of mental disorders
+CpG
+inhibits ubiquitination
+technical
+A manometer
+serum
+CD11b + myeloid cells
+allergic
+nonsurgical dental procedures
+ER-to-Golgi transport
+β
+phosphorodiamidate morpholino oligonucleotide
+direction
+amino acid sequence variations
+four
+genes involved in development
+natural caves
+IL-10 knock-out mice
+conventional monoclonal antibodies
+flow cytometry
+supplementary material
+PTB risk
+Queensland Institute of Medical Research Human Research Ethics Committee
+5 × 10 9 CFU/ml
+twice per day
+Sigma-Aldrich
+Horizontal transmission
+metabarcoding
+ten
+fever, lymphadenopathy and worsening respiratory symptoms
+Benjamini-Hochberg false discovery rate
+a series of infected events
+RNA and DNA
+SigmaPlot
+34%
+42%
+both local and global features
+blood
+puzzling
+treatment, severity and relapse
+Images
+Four
+fully stained cells from mice vaccinated with AdHu5-empty
+two primer pairs
+North America, France and Japan
+Macrocyclic peptides
+large droplets
+ZR Viral RNA ™ Kit
+21
+A variable
+isothermal amplification of targeted DNA
+180
+3918.34
+wt equilibrium
+PV-as well as HRV-infected cells
+Saksena et al.
+NAP-5
+inability to identify the cell type responsible for the change in gene expression
+TMS
+20%-30%
+placental
+procoagulant environment
+neutrophils
+hepatitis B or C
+epithelial cells
+early diagnosis and proper management
+siNC
+unactivated
+mean air pressure and mean vapor pressure
+Mascot Generic files
+specific B cell inhibition or a generalized state of immunosuppression
+HSPG
+Everybody
+a sample-based accumulation curve
+Sabin poliovirus type 1
+TYMP
+every 3 days
+100%
+2006
+averages of real data over 2003-2006
+ACE-1
+cleavage site sequence
+Easily cleanable receptacles
+20%
+Ca 2+ -mediated CaMKKβ and cellular energy
+hemacytometer
+health workers
+TIBV
+artifacts
+drug users and sex workers
+Additional studies
+high sensitivity
+98.1% to 99.6%
+nonadjuvanted or traditionally adjuvanted antigen
+inherent simplicity
+construction of an indoor contact network
+stabilizing
+blocked autophagy
+standard system development
+Semi-quantitative
+11
+hTERT
+N-terminus
+regulations/legislations
+Shaanvirus
+insufficient data
+8 hours
+data previously reported by several studies
+non-specifically recognizes DNA in the cytosol
+cathespin G
+eleven
+Wilcoxon rank sum test
+endocytosis
+Clade c
+neither control PP nor Idea-PP were toxic to host cells
+higenamine
+SJL mice
+Two
+attitudes
+decreasing kernel function of the distance
+Astrovirus-like contigs
+physical forms or non-physical forms
+0.017
+complete coding sequences
+two
+Google Flu Trends
+post-attachment neutralization assay
+synthetic hydrocarbons or higher-chain alcohols with high energy content
+Highly sensitive
+20
+P n
+confounding factors
+Enteric HAdV-F40 and F41
+Ten
+The catalytic cysteine
+Bacterial systems
+B cell clone
+ACE2
+two
+Alexander Fleming
+DVGs
+PF-S stem cells
+H3-WT TM-dependent
+4-fold
+756
+patients' arrival/discharge and outbreak detection and declaration
+4 hours
+R 0
+long-term control issues
+runny nose, sore throat and cough
+geographic, demographic, and psychological
+larger
+qPCR
+country of origin
+protein engineering and directed protein evolution
+26%
+an introduction and background to the classification project
+16942
+ECGs
+Europe, Africa, and the Americas
+observed
+1:40,960
+goat anti-pig IgA
+host-synthesized nutrients
+Branches
+Clustal alignments
+the MoA of compounds
+The basic reproduction ratio
+chimpanzees
+nasopharyngeal swabs
+Pressure ulcers
+high-dose corticosteroids
+Highresolution
+three
+Na + /K + ATPase
+patients that had more potent responses
+biotic
+Mann-Whitney U-test
+Cell viability
+Virulence
+1967
+1U6R
+Graph Pad Prism 5
+acidosis
+poor tumour differentiation and tumour embolus of portal vein
+flexible
+CD8 + T cells
+unstable
+Gasteiger-Marsili charges
+ERK5
+mice
+30 days of age
+Long-lasting, age-specific antigenic imprinting
+Nonspecific human IgG1 R347
+71
+hematoxylin and eosin
+Real-time quantitative PCR
+modern electronic devices
+fine-tuned
+post-operative hospital stay
+dysregulation
+2.0 ns
+Entomological
+total disagreement between prediction and observation
+Serum IL-10
+Peptide stocks
+20%
+producing DHF
+propargylamine
+IFN-γ
+ion mobility spectrometry
+10 min
+eIF2 GTP
+age and immune
+Urumqi City and in Yining City of Xinjiang Province
+hyperglycaemic hormone
+biological
+IL-8
+fold change from pre-vaccination
+neurodegenerative
+AdV DNA
+host-pathogen interactions
+B cells
+Fifteen
+Holm-Sidak procedure
+1.6 to 1
+IFNb-YFP reporter mice
+The number of contacts
+55%
+multidisciplinary
+Infectious diseases
+B cells
+preventing or delaying the development of diabetic renal disease
+100%
+95%
+brightfield
+The load generated when the wearer moves
+immunoglobulin genes
+ammonium buffer
+C:U mis
+Uninfected Mus dunni cells
+post exposure prophylaxis
+lung host defense
+2,000
+severe malaria
+Image-Pro ® Plus
+viral entry or replication steps
+7905
+X4%
+complete protection against HK68 heterosubtypic virus
+four
+cytokine dysregulation
+Fructus mume extract
+Erp72, ERGIC-53 and Golgin-97
+viral pneumonia
+10,000
+diffuse bilateral peri-hilar infiltrates
+1:1
+LBM environments
+inflammatory cell trafficking
+Th1-or Th17-type
+lfadherence
+mutations
+H5N1
+Total RNA
+4
+95%
+Five-hundred sixtyseven
+BD Biosciences
+8,870 to 18,300
+26 Å
+numerical titers
+head-tail junctions
+an incorrect strain
+more aggressive recurrence of PBC
+less than ½ inch across
+Disease dynamics
+axonal regeneration
+scanning electron microscopy
+,60-90%
+HBoV1-4
+24 µm
+immune response tests
+KLY-B
+increases the pH
+symptoms and signs linked to immunosuppression
+SSP myristoylation
+mouse and human full-length ORFs
+40
+ClusterPicker software
+native gel mobility shift assays
+5-10%
+proliferation, differentiation and survival of monocyte lineage cells
+fall of 2009
+medicine
+18,449
+essential travel
+good
+every 0.010 ps
+>75%
+rRNA
+trial case record forms
+one hour
+physiological processes
+AO length and target sequence
+fourth-order clades
+Gblocks 0.91b
+envelope glycoproteins
+viral antigens
+viral antigen and antibody levels
+inflammation, excessive secretion of respiratory mucus and pulmonary fibrosis
+21
+Two-tailed t test and ANOVA
+regulatory T cells
+human or animal derived substances
+One hundred and twenty-eight
+dynamic exclusion setting duration of 30 s
+GV
+molecular docking methodology using GOLD 5.0.1 program
+The Bonferroni method
+DCs
+225 ng
+black lines
+prematurity, low birth weight, birth trauma and asphyxia
+trimers, dodecamers and higher-order multimers
+EDTA-coated tubes
+250 μL of each solution
+Alissa Weaver
+Viability
+data-adaptive
+porcine aminopeptidase N
+Tf localisation
+p53 mRNA levels
+anti-adhesion
+13%
+lipid rafts of the plasma membrane
+0.49 μm
+an estimate of the severity of seasonal influenza epidemics
+HRP-conjugated secondary antibody
+FHV-1 nucleic acid
+allocating the existing resources and identifying new sources of investment
+Simulation study 2
+chronic obstructive pulmonary disease
+Information on delay of presentation and reason of travel
+65.6 ± 12.08
+five 85
+AEII cells
+heart rate variability
+pulmonary
+pET GST-Rluc-1
+Inhibition of Hsp90 activity
+>25%
+4.661 nM
+Valovirus
+Levi-Montalcini
+BALB/c and C57BL/6
+24
+bla NDM
+neurological toxicity
+The DermaVir Patch
+2.7-3.9
+5 0 -3 0 RNA ligase mechanisms
+Harbin
+Cy3-conjugated donkey anti-goat secondary antibody
+Nelson and Worobey
+viral life cycle
+senescence
+focus formation assay
+blood flow redistribution and an increased oxygen extraction ratio
+aquaporin 5 protein
+insect cells
+foodborne viruses
+reducing the incidence of disease by preventing its occurrence
+aerosol
+Chebolu and Daniell
+Mammalian IFITMs
+Mandarin
+Thirty-nine
+interferon-α
+eukaryotic pathogens
+protein
+mean ± s.e.m. P value
+A protein thus formulated can contain its most complete information
+duck RIG-I
+densitometry
+UCSC genome browser
+50 to 100 million
+NDV and AIV
+RT-PCR
+more uniform crops
+126 μm/s 2
+HBZ mRNA
+Student's t test
+specific causes of deaths
+frameshifting
+ZC3H4
+a more moderate initial culling intervention
+3AE0 days
+higher reliability of the luciferase signal
+extreme low coverage variants
+further study
+mitigation of epidemics
+increased tissue permeation and accessibility to the myocytes
+each candidate protein target
+Time of addition experiments
+NOESY
+the square brackets
+TEV protease
+propidium iodide
+GraphPad Prism 5.0
+12%
+four
+alveolar macrophages
+severe pathological injury or even death
+doctors
+TER levels
+icosaedral symmetry
+three
+micro-RNA Enrichment Analysis and Annotation with Over Representation Analysis
+Yca1 and Aif1
+inflammatory
+5 out of 10
+0.4 mL/min
+4-HNE
+RIG-I and melanoma differentiationassociated gene 5 product
+36.4%
+House Brackmann grade
+Bonferroni correction
+1 mg of HEK293 cell lysate
+five
+Adenovirus vectors
+cementation and even recrystallization
+cytoplasmic acetylated-lysine
+NL4-3
+45 min
+recombinant NP protein
+10%
+Viral quasispecies
+Prosearch
+mobilization of hematopoietic stem cells
+administration
+88%
+SV40, the growth hormone gene, and the b -globin gene
+HER2/ neu
+severe hepatocellular necrosis
+Twenty
+Complementary
+professional self-control
+100% of the signal
+a plasmid encoding the T7 RNA polymerase
+North-south
+2 h
+smaller
+384-well white plates
+Dulbecco's Modified Eagle's Medium
+Viral RNA
+4.948 Â10 À 3 sub/site/year
+2000
+5%
+institutional review board
+1 h
+two days
+94%
+unmanned aerial vehicles
+CD133 expression, ALDH activity, and chemoresistance assays
+Average Number of Students per Teacher
+SPOT CHEM SP-4420
+TranslatorX
+Primary
+Every effort
+obligate
+IFNγ
+20 min
+#VitalSigns
+mortality
+1.62 × 10 −6
+5%
+novel virus host factors
+adenoviral vectors
+4668
+two
+64-85 mmHg
+directly restoring the CFTR function
+Eight
+BMV RNA replication
+2015 and early 2016
+E1E2
+Positive end-expiratory pressure
+UV irradiation
+Zhejiang University Experimental Animal Ethics Committee
+866
+Probes targeting DUBs based on monoubiquitin
+consensus score accuracy
+Enzyme-linked immunosorbent assay
+10 mM of dithiothreitol
+GASBOR
+pressures
+73,33 %
+5%
+36%
+novel
+novel
+16%
+screen each specimen for a suite of microbial agents
+738
+65
+ILCs
+90%
+level of conservation
+five
+daily ring vaccination/case tracking capacity
+Auto Dock Tools soft
+Haloperidol and quetiapine
+WNV titers
+IgG
+immunological
+100 µL of the anti his-tag monoclonal antibody
+encapsulation and surface location of the Ag
+33.4 ± 16.6
+translation
+10
+Filter-binding experiments
+stimulation
+thymic stromal lymphopoietin
+τ
+fitness
+nine
+H3N8 subtype viruses
+WT, PC55, and PC48
+MAIT cells
+Cell free culture supernatant
+mixed response
+maximax
+schools
+496
+ColorPhylo
+Dera Ghazi Khan and Qalyub orthonairovirus
+long-term complications and subsequent disabilities
+rAd5 boost regimen
+heparin
+2001
+VAChT
+AKT activation after insulin treatment
+Microscopic
+18 years old or younger
+male
+6
+1.5 times higher
+61
+annexin A2
+1,447
+IAR
+19
+retention time, m/z, and intensity
+net positive charge
+RNA Integrity Number
+Primary HHV-6 infection
+NF-kB-dependent production of inflammatory cytokines
+PA T97I
+natural selection
+to be realistic regarding what a particular model is measuring
+every 5-7 days
+5xSDS-loading buffer
+RT-qPCR
+Variant or drifted viral strains
+Student's t-test
+2.13 log
+ROS-related DNA oxidation
+high-temperature, short-time method
+dendritic cell migration
+Twenty
+higher expression of p-c-Met
+interactions between natural selection and mutation pressure
+DAMMIN 54
+maximal signal
+30%
+antibiotics
+Diletta Valentini
+eIF2 and eIF4E
+specific activity
+their assembly
+six
+repetitive DNA and extensive non-coding regions
+Blood samples
+A/H7N9
+NF-kB
+suck hard candy, chew gum, or use repeat mouthwashes
+Spatial maps
+Qiagen One Step RT-PCR Kit
+Demographic and clinical data
+NNM or MNN
+PBL
+Primers
+hexadecyl
+arrhythmia
+Organisational
+relative fluorescent units
+13.8 and 1,042
+Day 0
+1016
+stable
+Cholera
+less than 12 hours
+WHO
+SeV LD RNA
+anti-HCV replicon activity
+American Type and Culture Collection
+75%
+8 hours
+pharmacologic agonism
+55-70%
+crystals from both the surface and deeper within the polymer phase
+Pfs48/45 protein
+NP
+SPSS 11.5
+NPC1 binding
+11.0%
+the average over all households sizes
+length
+Bone morphogenetic protein
+less risk of potential off-target side effects
+mice
+Semiquantitative scoring
+4
+totarol
+Translation blocking
+ITGB1
+Influenza B virus
+minimal variation between runs and far less variation
+RVFV Gn and Gc coding sequence
+MassARRAY MALDI-TOF System
+kaempferol
+origin-destination matrices
+15
+two key assumptions
+1 μg/ml doxycycline
+Sangon
+neutralization titer
+Two
+95%
+Clodronate -loaded liposomes
+Two
+42%
+published gene datasets containing corresponding patient survival data
+US$87.0 per patient
+immunomodulatory therapies
+69%
+Study weights
+Calcium ions
+NS1
+adaptive immunity to the vaccine antigen
+K11-and K33-linked polyUb preferentially
+phenylpropanoids and diterpenes
+49
+gB, gD or gH
+instruments
+hantavirus replication
+Rluc expression
+Genes inducing either a significant decrease or increase in RSPs production
+Fifteen percent
+HIV Pr/RT and Influenza H/N
+17.65%
+host-virus interaction and response to wounding
+detailed
+gating control
+Almost 25 %
+thrombo-inflammatory
+temporal or spatial
+1.0 mM
+CCR5
+90-95%
+DB s D
+expression of β2 integrins
+DAB-positive
+EPIFIL
+10 weeks
+West Nile virus
+Common contaminants
+7 -194-fold
+variability in species composition
+heavy metal ion tags
+15 min
+Th17 cell differentiation
+TMHMM version 2.0 server
+LC3-II
+inhibited TNF secretion
+RNAlater
+N7
+30 minutes
+TNF-α
+precast linear IPG strips
+secondary and exploratory
+Guidelines
+raw counts across samples
+10% to 15%
+3 μg total RNA per sample
+ImageJ/FIJI
+microcomputer-imaging
+Serum
+acidified, NPC1-positive
+1%
+Q s,t
+An audit
+Those entrusted with governance roles
+Protease B
+> 95%
+Sivelestat sodium
+those that are being treated
+IMOD
+ALS
+HEV infections
+qPCR data
+at the cytoplasm
+patients with very high MELD scores
+A galactose and GlcNAc residue
+siPTB-treatment for 72 h
+supernatants
+Commensal microbiota and myelin autoantigen
+IFAT
+five
+Two
+cancelling public gatherings
+a suitable cysteine in close membrane proximity
+once daily
+Chimeric antigen receptor
+servo-controlled centrifugal pump
+functional and non-functional
+self-splicing
+viral pathogenesis
+two groups
+antiviral
+PV-T362I
+Illumina HiSeq2500
+A549 and Calu-3
+peripheral T cells
+pmacs
+standard infectious particles
+ELISPOT assay
+127
+vehicle group
+Autophagy
+aa position 14
+1990s
+Genetic drift
+reductions in splenic or bone marrow macrophages
+4 mg/ml
+three
+growth phase
+deficiencies in desmosome processes
+14
+Control and STNx rats
+70%
+A response with such a large jump
+provides up-to-date information about viral biology
+incomplete sequencing
+11 cm
+SDS polyacrylamide gels
+hexon and penton base proteins
+HCV-infected
+Table 2
+Antibiotic therapy
+acute damage
+chemical and bioactive
+red
+10-15%
+The activity of known ISGs
+whooping cough
+winter
+detection of antibodies against different viruses
+100%
+0.8%
+77
+83.9%
+62.0%
+mol2db2
+farm-level sheep population numbers
+17.5824
+yellow
+likelihood ratio test
+window-type
+CD4+ T cells and monocytes
+Sepsis and multiple organ dysfunction
+311
+clinical guidelines
+Total RNA
+Intron-retaining transcripts
+fewer than half
+viral load
+Mann-Whitney U-test
+pgsA-expressing vector
+Plaque morphology
+JH6 gene family
+protein disulfide isomerase
+Hantaan virus infections
+mutation bias
+Many elements of uncertainty
+180 days
+TempEst
+density gradient centrifugation
+396
+1x MEM non-essential amino acids
+flat pre-GCs
+E-test and in-house PCR
+LA County Jail
+efficient
+inflammatory responses
+planning and evaluation
+3-fold
+48 h
+electrophoretic mobility
+Hurricane Ike
+every 2-3 days
+Termination-reinitiation
+assumptions
+systematic
+increased AMPK activity
+IFN-γ
+erythromycin
+25
+directs the fusion protein to the inner membrane of the mitochondria
+five
+H1N1 Viruses
+MFS-type transporter
+dust
+spread
+Fresh frozen and formalin-fixed tissues
+The contribution of randomness
+CD8+ T cells
+over-expression of the bak gene
+mutation site features
+performing such analysis with the best available evidence
+2014-2015
+A/H1N1
+The level of significance for asymmetry
+10%
+H1N1, H3N2, and H7N8
+receptor functions
+Glutamic acid
+immune model
+30 minutes
+32
+lyse
+Bayesian MCMC
+concrete suggestions for the national level
+B. burgdorferi
+malaria and tuberculosis
+the probability of observing the same or higher enrichment purely by chance
+cis-cleavage activity
+Ontology development software
+7a
+two linked Ub modules
+Enhanced BMV RNA replication
+Q7R and NAC
+max pooling
+cells treated with vehicle control
+individual-based models
+precursor cells in fetal liver
+polymerase chain reaction
+significantly decreased injury scores
+pattern recognition receptors
+red
+Hospital de Clínicas, Montevideo, Uruguay
+several hours
+Eleven
+ten
+16 h post-treatment
+a value v
+5 days
+Pfu polymerase
+USD 250.00
+lack of practical and affordable animal models
+G-C
+amines and amides
+more than a third
+macrophages
+GitHub
+Agilent Feature Extractor software
+0.2264, 22.022 and 0.4647
+PCR
+30 min
+signal transduction mediated by AFPR
+TLR4 signaling
+crystals of polyhedra
+MI
+standby
+50 million
+Western blot and immunofluorescence assays
+ImageJ
+5 to 3
+ACK lysis buffer
+All masked bases
+a progress note
+19
+twice
+twelve years
+diagnosing and monitoring of pulmonary diseases
+epidemiological data
+Bacteroidetes
+substantial
+immunodepression
+cc-by
+43
+A stock solution
+western blot
+logistic and Cox proportional hazards models
+The secondary entry receptor complex
+host immunogenetic variation
+12 kDa
+sixteen
+once every 3 d
+identification of possible pathway imbalances and eventually new therapeutic targets
+OCT
+inadequate
+MSA
+nuclear, granule and cytosolic proteins
+MHC-II peptides
+stent length, diameter and position with respect to the vertebrae
+Random jitter
+ViDiT-CACTUS virus discovery method
+50 g/ml BNeV VLPs
+Borrelia burgdorferi
+congestive heart failure
+nocturnal habits
+30% to 56%
+resistance to HIV progression
+serine monophosphorylated STAT1
+Language preference
+cave roofs and walls
+22%
+15 %
+five-year
+binding medium
+15%
+nine volumes of cold dilution buffer
+calibrators
+B
+immunocompetent
+India
+Biological Pathway Exchange
+> 70%
+1 hour
+14
+60-75%
+Mallard ducks
+rejection from PVAN
+105
+RIG-I/MDA5-dependent type I IFN signaling
+cytotoxic
+genetic and environmental
+K44 and K48
+tRNA-like
+75%
+drug sales data analysis
+sub-exponential growth models
+Total PEEP
+250 nm -650 nm
+did not change the levels of phosphorylated ERK1,2
+length K of the oligopeptides or oligonucleotides
+differential growth kinetics of wt versus HA mutant viruses
+63.40±3. 36
+Trinity assemble program
+Ebola
+16
+existing
+pragmatic selection of truly problematic assay plates
+severe disruption of the normal morphology of the microtubule cytoskeleton
+4,370,000 copies/ml
+caseinolytic protease
+CI
+>97%
+The required duration of a recurrence prophylaxis
+serine/threonine kinase p90Rsk
+gp41
+Cytological and biochemical
+12
+Ebolaviruses
+57
+statistical
+P63 and KRT5
+a hairpin structure and an aromatic T-stacking
+23%
+627 and 701
+polymorphisms
+Idea-PPs
+FIgM proteins
+the remaining genotypes
+statistical methods
+Myeloperoxidase
+more education
+6 ml of culture medium
+over one million
+bacteria from the nasopharynx samples
+0 to 36%
+high incidence of infection
+N protein
+variations in trapping catch rate
+1983
+RNase independent
+original research articles and case reports/case series
+L protein
+1.5 hour
+Formation of large syncytia
+2-3 days
+DNA templates
+metagenome scaffolds
+IL-1β production
+late endosomes and lysosomes
+37.5%
+Sigma-Aldrich
+mucosal effector cells
+27 February 2020
+26
+chemotherapy
+expansion segment 31
+decades of war, extreme violence, and deep oppression
+unambiguous
+cells
+lactose
+Biacore T200 Evaluation Software
+Breast cancer
+66
+dengue fever
+56 days
+traditional serological assays
+very fast or very slow
+The ISM
+containment strategies are not always accommodated within a single model
+pregnancyspecific antigens
+Responses
+mechanical ventilationassociated detrimental effects
+GP5 protein
+daily weather conditions
+88%
+38%
+eight
+Vector-specific antibodies
+Romosozumab
+Complementarity between numbered OSD domains
+Gram-negative bacterium
+neovessels
+human bronchial epithelial cell line
+2013-08-05
+1%
+five
+immune activation
+3 days
+real-time PCR
+curated
+cytoskeletal architecture
+more than five thousand
+Data derived from unfolding curves
+Influenza and respiratory syncytial virus
+DDX19
+HEK-293T cells
+RNeasy Plus Kit
+2 3 ¼ 8
+49
+4 h
+RT-PCR
+fairly good efficacy and acceptable tolerability
+$20 mM
+2015
+29
+G6PD deficiency
+an RNAdependent RNA polymerase
+58 kd
+negative correlation
+biological toolbox
+H-7650 transmission electron microscope
+1 mg/kg BW/ day
+antidopaminergic antipsychotic
+the Abstract
+Synonymous codons composition of a coding sequence
+absolute data counts
+H5 ectodomain-coding sequence
+EP-assisted intramuscular pDNA delivery protocols
+processes
+49% to 66%
+maturation signals
+Sigma Aldrich
+82%
+48-60%
+5.04%
+H1N1-infected MDCK cells
+patients who died within 21 days
+genetic regulation of embryonic myogenesis
+mortality
+e-week 31
+RT-qPCR
+350
+lineage-specific expansion
+59
+FLEXMAP3D
+various virus strains
+preserving its conserved epitope
+to identify potential protective antibodies induced with BCG
+coercive public health measures
+Kruskal-Wallis test
+jainScore
+GII.4 NoVs
+ARI
+a micro-stirrer
+non-matching residues
+Spearman correlation-of-rank coefficient
+T cell responses and virus control
+shuttling this complex to the HIV promoter and guide HIV transcription
+Nikon eclipse T300
+3
+345bp
+fusion protein expression
+hepatic lipid accumulation
+Oct-4 hyperexpression
+18
+immuno-compromised patients from the industrialized nations
+IL-6-induced CRP production
+80%
+indirect immunofluorescence
+Lima, Peru
+Golgi retention factor
+cc-by
+primer/adaptor
+influenza infection
+HCMV
+T s
++1 and −1 PRFs
+30 min
+electronic triggers
+85%
+viral replication
+specificity
+mathematical models
+Serum-free MEM-α medium
+seasonal festivals
+p33, p13, and p18
+digital high-speed videomicroscopy
+2,084 to 2,645
+AP and TM
+Re-5, Re-6, and Re-9
+below detection
+21
+2 to 79 days
+Confocal
+38%
+39%
+Vasoconstriction
+inflammatory
+reliable alignments
+necrosis of hepatocytes
+symmetrical
+influenza virus glycoproteins
+$15,516
+Guillain-Barré syndrome
+sequence data
+ICU mortality
+increasing amounts of pathogen metadata with higher resolution
+information about the underlying physical mechanisms that connect the signaling proteins to transcription factors
+Chen, Pei-Jer; Wu, T-C
+3 days longer
+internal consistency, split-half reliability, and test-retest reliability
+56 • C
+foamy
+24
+HMPV genome sequence data from Africa
+publication bias
+16
+infectious supernatant medium
+to avoid any induction of IFN-ab by the plasmid itself
+airway obstructive disease
+canarypox vector
+Background Medulloblastoma
+induced cell death
+imperfect sample purification
+MPO
+nucleotide composition analysis
+viral infection
+pseudo-mass
+ACBD3
+5 min
+Italy
+3 hour
+similar
+100
+2007
+positive natural selection
+386
+Big Sioux River Virus
+the possible mechanism of the improved anticancer effect
+when new infections are generated at the same rate at which infections are lost
+four
+fibrinolysis
+rhesus monkeys
+product quality, reduced antibiotic treatment, improved consumer protection and increased animal welfare
+airway epithelial cell
+monitoring the host's immune-response to infection
+Forward selection
+severely impaired F-actin polymerization
+ASGPR
+À1:5 kcal/mol
+mobile
+8%
+two
+IFN-γ
+nasal washes
+damage upon muscle contraction
+Virus
+disease severity
+cathepsin double knock-out cells
+four
+viral replication
+major histocompatibility complex encoded genes
+areas where Neu5Ac was added
+repeated chemoreflex stimulation of the sympathetic nervous system
+Forty one
+Non-receptive cells
+cytosolic oligomeric protein complexes
+natural regeneration and reforestation efforts
+three
+T cell treatment with SOCS3-siRNA
+direct
+x-ray
+347
+A3021-01
+long double-stranded precursor molecules
+120
+Eighteen
+Diagnosis and Treatment Program
+APMV-1
+Endogenous peroxidase
+human serum albumin
+Blood samples
+miR-30
+local convex hulls
+respiratory conditions
+curcumin
+clinical obesity
+FluoroTag TM FITC Conjugation Kit
+39.68 weeks
+Reed and Meunch method
+specific cell-mediated immune responses
+tuberculosis and Herpes B virus
+human
+the product of frequency and efficacy of the cleaning event
+Total RNA
+induction of increased TLR2 surface expression in lung endothelial cells
+nutrient starvation or pathogen invasions
+activation of SOCS3
+Reverse phase liquid chromatography
+species borders
+stimulation of the assembly of the viral replicase complex
+16.7 %
+Ad-induced IFN-ab
+85%
+92%
+color" or dual-reporter viruses
+1 hr
+sepsis
+cytotoxic T-lymphocyte antigen 4 inhibitors
+viGEN
+population size
+further details on passengers, frequency or duration of car use
+2010
+2-3 weeks
+discrete convolution function
+14%
+10 kilobases
+uridines
+Electrospray ionisation
+Thirteen
+metabolome
+zDOCK
+FlowJo
+preferences, tastes, obligations, information, habits and financial circumstances
+strand transfer
+increased pathogen prevalence and virulence
+69% lower
+murine antibodies
+HA and NA pairs that had not co-evolved
+Advancement in development and standardization of various kinds of PCR techniques
+increased rates of hospitalization or fatality
+turboRFP and Gaussia luciferase
+43%
+1 day
+age, sex, BMI and disease duration
+N160 glycan
+twothirds
+treatment with high-dose ribavirin
+glutathione and iron chelators
+Ethyl -epoxy-4-oxo-butanoate
+viral adaptation
+11
+UVA
+fulllength native protein
+three
+Picobirnavirus and HAdV-C
+how the virus moves
+Tight junctions
+epidemic
+UMR-CNRS 5558
+Relative gene expression
+80.8%
+22Á6%
+14
+n=3
+Asia
+N63Y mutant CVB3
+an infectious period
+deceased
+Oxidative stress
+45 min
+Cross-cultural data
+Ubiquitination
+GraphPad Prism 6
+indirect interactions
+rabiesspecific
+26G needles
+acute infection
+four
+its structure and its sequence
+Mast cells
+anywhere in the 5'-UTR through the start of the coding region
+technical and organizational
+45 min
+10%
+8%
+10 lg/ml
+SCV
+second
+similar growth kinetics
+T m À1
+cellular PAR levels
+predictive modelling
+77.5%
+higher
+triplicate
+anti-CD4 and antimyeloperoxidase antibodies
+no conflicts of interest
+UV-cross-linking
+2610 6
+biological tools
+6.8%
+macrophage SFM medium
+12-18 months
+12%
+no one evaluation was significantly different from that of the others
+plasmon-enhanced fluorescence
+illness
+65
+Lymphocytes in peripheral blood, spleen, and head kidney
+complex
+national or international performance standards and manu facturer's instructions
+master switch
+KSOS and HYA
+391
+Synthetic lethality
+0.044%
+40 and 60%
+enhanced Pr55 gag cleavage efficiency
+The expression of unigenes
+PPARα, PPARγ, and PPARδ
+Anthony Sadler, Hudson Institute of Medical Research
+deleted residues
+secondary Ab Alexa Fluor 594 goat anti-rat IgG
+Sequential Organ Failure Assessment score 19
+A single Zn 2+
+0.1%
+35980 out of 43010 RPIs
+data about zoonotic and emerging pathogens
+one
+thousands of years
+59-UTR
+endocytosis
+4/10
+discontinuous
+Data mining
+C
+the value of λ
+1573
+Molecular recognition features
+T cells
+5-95%
+Digital array
+SP cells
+uninfected
+High Pure Viral RNA Kit
+IL-2
+74.4%
+three
+Alveolar
+20 ppm precursor ion tolerance
+viral persistence
+HAE and in vivo
+MicroPoly Purist Kit
+54%
+the NTD's origins
+Herpesviridae
+chemical properties of individual amino acid
+Alveolar macrophages
+968
+Digital PCR
+Asterisks
+monoclonal
+B6 mice
+17
+basal constitutive activity
+cheetahs
+conserved regions of important antigens
+the diagnostic odds ratio
+Advance catheter
+17
+control or I.M. immunized mice
+vehicle treatment
+Cigarette smoking
+1/ times units
+Children less than 5 years of age
+MD90 and MD91
+expectations of recovery from influenza
+respiratory syncytial virus
+$3.5%
+5
+one-way
+T cells
+tight
+International reference standards and proficiency panels
+LoxP-fl anked stuffer DNA sequences
+oxidative and inflammatory damages
+pathogen
+6
+activated protein C
+CP ST11
+the HP
+Astacin
+immune evasion
+ADAM 10
+mass spectrometry instrumentation
+amino acid residue position
+drug addiction
+job demands
+three
+Lymphadenopathy
+Temporal
+Other types
+IAPV
+at the significant internal nodes
+Inflammatory responses
+L, M and S
+tRNA maturation
+less than 10 days
+0.99 Å
+human cells
+fine-scale pathogen identification and near-neighbor discrimination
+3.6
+gamma, Weibull and log-normal distributions
+inhibits the expression of Blimp-1
+the intensity of a negative control protein
+Conserved cysteines and aromatic residues
+four
+ELISA
+CIH
+Real-time US
+10
+A
+presenting epitopes to be recognized by the host immune system
+The column #
+C ik
+Ghana
+two
+mAb
+proinflammatory
+Tenericutes and Bacteroidetes
+24 hr
+E. siliculosus
+four
+zebrafish
+human ISG15-AMC activity
+suitability of homology modeling and docking studies
+PCR/ESI-MS
+zoster vaccine
+two-sample t test
+helical
+1.3 million
+regulators of adaptive immune cells
+six
+Cabb-S and Mark-S
+Six
+Public health
+Goat anti-rabbit 488
+15 kb
+acetylated testosterone glucoside
+blood flow
+postgraduate training for physicians from Lao PDR and China
+strain 17+
+Transfer of genetic information from mRNA into proteins
+increased influenza vaccine coverage
+eight
+Diprotodontia and Primates
+support those who are burdened by complying with restrictive measures
+tissue factor -TF pathway inhibitor imbalance
+IFN-a/b signaling pathway
+March 2012 and April 2014
+forecasts that can be hedged upon
+HF power
+recovery rate is the same for all compartment
+the number of correctly predicted positive and negative pairs
+17
+12%
+p38 MAPK signalling
+Restriction factors
+DMF
+Aurum Total RNA mini kit
+mildly neurovirulent
+an MOI of 1
+240 million
+index #
+9.4
+184
+heterogeneity
+public opinion
+RR2Y primers and probe
+Cathepsin inhibitor E64
+infectious virus
+UGTs and SULTs
+2
+a veterinarian
+13 years
+capture antibody against mouse IFNγ
+abruptly
+the ligand
+two
+cardiac fibrosis
+150 nt
+adequate immunity
+five
+wellbeing-reads
+Nairoviruses
+PTB
+purified lipopolysaccharide
+their correlation to the related Rfam structure annotation
+SQLite
+Fugu and Yijun
+Non-influenza respiratory virus infection
+memory B cells
+means ± the standard errors
+decreased CD81 binding
+Influenza
+NiV
+Aggregation of data
+18
+PB method
+ethical
+pathogen metadata
+environmental data from satellite imagery
+Treg cells
+hematological
+24th of November
+a TI cell marker
+infiltrating macrophages
+Pandemic H5N1 Influenza virus and SARS virus
+AME
+sialic acid
+circulating dendritic cells
+seventeen
+four
+qPCR
+adherence of P. vivax-infected red blood cells
+DC maturation
+95%
+5 days
+Decreased bacterial clearance and deteriorated lung injury
+DNAzol TM
+SL5 and the PPT region
+Ca 2+permeable ion channels
+densitometry analyses of DR6 protein expression
+to investigate the clinical characteristics and etiology of Bell's palsy
+thrombosis of the arteriovenous fistula
+human resources and laboratory
+HCoV
+supportive
+120 alleles
+SVG
+mean ± SEM
+active trading places
+UL39
+by plating serial dilutions
+DENV replication process
+qRT-PCR
+almost perfect
+Pooled samples
+FIV epidemiology and distribution
+chronic inflammation
+orientation of the pattern of interest
+IL-23
+respiratory syncytial virus
+7 min, 72 C
+DNA damage repair systems
+craniofacial abnormalities and growth retardation
+0.916
+infectious dust
+Cxcl5/6
+91
+co-infection
+VACV
+1,038
+cleavage probes
+microtubule cytoskeleton
+70 %
+Thirty
+VRC 500
+medium containing virus
+prevention of influenza-attributable pneumococcal disease
+gene gun and electroporation
+susceptible-only equilibrium
+unstable
+honeybees and wild bees
+Further information on research design
+seven
+Bta-miR-205
+43.5%
+A i and B i
+Design cues
+C. difficile toxin A and B
+WT
+2 mL of the culture
+45%
+patient trials
+MG756 and MG770
+transcription factor analysis
+− 10.0 ± 1.2 s −1
+monoclonal high affinity memory B cells
+samples that were compared to one another
+Table 2
+5.1 µM
+Six
+163 ng/ml
+activation relation
+RESP score
+SWISS-MODEL 43
+fluorescence recovery
+PN-SIA49
+Higher risk
+The Wilcoxon test
+low sensitivity
+8
+WNV and Japanese encephalitis virus
+LoFreq and VPhaser2
+Anti-apoptotic
+different subsets of ISGs
+Thirty minutes
+192 nm
+acetylcholine
+three
+ONT
+Matrigel
+Shading
+gRNA nuclear export
+angiopoietin-like protein 3
+storage vesicles
+an HIV test
+switch from the innate to adaptive immunity
+more detailed guidance
+to recruit cytosolic SNXs and retromer
+competing ASL conformers
+benefits outweigh risks
+the effect of very recent interventions manifest weakly in current
+achieving infection
+hybridization equilibrium
+58
+SR group
+86% identical
+phylogeographic
+36
+titer
+antibacterial
+DNA Ladder Extraction Kit
+a short sequence of k nucleotides
+cytochrome P450
+obese and morbidly obese
+Behavioral Leading
+differentiation, proliferation and survival of monocyte progenitor cells
+assessment of minimal residual disease
+0.99 mg/ml
+salivary lysozyme
+PCV
+HBZ-specific antibody production
+#0.2%
+antibody against a malaria antigen other than AMA1
+CCR4+ Mac1 tumor cells
+hypodermic
+HEV71 P1 and 3CD proteins
+eEF1Bc
+70 kVp
+Seven
+higher
+5 mins
+deciding which processes should be included
+Folding RNA secondary structures
+discrimination between the expression levels of four candidate target genes upon different treatments
+safe
+high levels of immunity
+whether gastroenteritis had developed within a week after departure
+higher copy number of r-genes
+enhanced PNA·RNA-RNA triplex formation
+13%
+Nitrite oxide
+15 min
+Ae. albopictus
+RNA viruses
+b 1 -AR
+optical tweezers
+HN mutants
+there is no identification
+multi-analyte
+quercetin
+Oct4 + swine stem/progenitor lung epithelial cells
+Colubraria attack
+pig farms
+Cyclophosphamide/total-body irradiation
+ferrets
+linear polyethylenimine
+Prism 5
+CD13
+phospholipase-and ROS-mediated glycocalyx damage
+11
+13
+48
+antivirals and vaccines
+HIV-1 Integrase
+2013
+Cowling, Benjamin J; Leung, Gabriel M
+nine
+NPT2
+gatherings of more than
+900
+mBed cluster size
+30 ∘ C
+110
+cap-dependent and IRES-dependent translation
+pET SUMO vector
+WT estimator
+DNA vaccines
+permeabilization
+the specificity of these kits
+10%
+T G 1 ¼0.28 s
+cytosolic compartment
+two studies
+bioinformatics analysis
+TDC
+IFNL4
+UV-fluorescent
+four
+specific pathogens
+1
+0.5 µg of total RNA
+viral replication
+Egress of enveloped viruses
+darker grey
+330-350 μm
+Escherichia coli
+red dot box area
+National institutes of Health and Suburban Hospital
+incidence and severity of symptoms
+IFN-γ
+Standard vaccination coverage, nutrition and mortality survey instruments
+−9.9 KJ/mol
+PD-L1
+infectivity estimates from studies of seasonal strains of influenza
+up to three days
+confocal microscopy
+IFNγ or IL-4
+calibration peaks
+sustained transcription of the transgene in muscle
+50%
+glycyrrhizin
+an outer housing and an inner cable
+5563
+LUS
+18
+10:1 to 15:1
+keratanase II
+The cleavage rate
+FTY720
+PCR product
+mTOR-inhibition
+Three
+COX-2
+the influence of genetic background and the choice of the correct tissues
+60 min
+HepG2
+R 0
+A glossary
+herring sperm DNA
+Fig. 2
+VZV infection
+two
+attenuate the loss of muscle mass
+fusion peptide
+Matrigel Matrix GFR
+A rise in sea level
+four
+457
+Figshare
+Adobe Photoshop
+hypothermia
+disease mechanisms and drug discovery
+Three
+NASH
+Chest
+Formalin-fixed, paraffin-embedded lung tissue
+4%
+ASP
+15, 60, and 80
+Type I IFN secretion by PDCs
+ER-Golgi trafficking
+20%
+high improvement on the efficacy of the treatment
+the unwinding resistance of stem S1
+blood
+1918
+CRISPR
+comparison groups
+40-60 nm
+p85α
+Maternal Oct4 expression
+primer walking method
+significant bias
+Integrin binding to the ECM
+detection time
+Africa
+immunomic regulatory networks
+up to 10 days
+WT mouse bone marrow-derived macrophages
+CD47/SIRPA ligation
+one
+Thirty-five
+Page Blue or Periodic Acid Schiff
+Immunofluorescence
+DNA replication and repair
+anonymous
+6 hrs
+12 weeks
+mimivirus-associated CAP
+world air traffic network
+infectious disease events
+astrocytes, endothelial cells and inflammatory cells
+glutamic acid
+100% protection
+to be doing that in the context of the health of the population
+corals
+170,000
+43
+N-terminal tagging
+Live bird markets
+102
+Multi-task Group LASSO
+L10H
+four
+Three
+antibiotic resistance
+d
+HB-EGF
+anti-inflammatory and anti-angiogenic
+Insertion of tail-anchored proteins into the ER membrane
+aliphatic side chain of leucine
+12
+glutathione affinity chromatography
+what we think is possible to observe in the new influenza season
+ABACBC PKs
+Antagonism of JAK/STAT signaling by both DNA and RNA viruses
+nephrotoxicity and myelosuppression
+VSV-ΔP technology
+30,600 Da
+spike recovery
+Increased worldwide mortality
+24
+an intracellular iron-storage
+inhibit the activation as WT lead to viable virus
+inspiration synchronized aerosol
+9.5 %
+one G residue
+R240A and R247A
+37
+filovirus entry
+non-specific
+Kenya
+TLR4
+hospitalisation
+ferrochelatase
+low and significant
+70 to 90%
+immunocompromised
+NK cells
+Trust
+0.05 mg/ml
+the stem cell
+eight
+similar
+AtRH2 and AtRH5
+Plasmid DNAs
+15 years 23
+5741
+TRIzol
+Complex CIII
+1 to 618
+Zanamivir and carrageenan
+transcriptional effects
+α and λ
+herpes viruses
+100 nm/s
+diffusion and sedimentation
+Zanamivir
+a molecular scaffold
+K562 leukemic cells
+attenuated
+Increased horizontal transmission and within-host parasite competition
+autophagy-dependent
+mannose trimming or ERManI
+16,977
+480±53 nm
+15%
+infectious disease risk and impact
+33%
+Quantifying transmission-relevant contacts among children at schools
+Pathway
+200
+Cathepsin E
+1302
+Histologic
+neoplastic
+López-García, King, and Noakes
+Alveolar
+17
+1.8 per million
+ΔΔCt
+3109
+phylogenetic signal
+30 min
+replication data and analysis scripts
+None
+antiviral gene upregulation
+CodonCode Aligner
+Duchenne muscular dystrophy
+four
+Singapore
+prevalence
+miR-30b
+RM cells
+71.4 ± 14.7 years
+Cronbach's alpha
+macrophages
+intra-regional trade bloc and extra-bloc imports of live poultry
+2014
+platelets
+enhanced tumor growth
+LC3-GFP
+Table 7
+Granger causality Wald testing
+FMP-specific CTLs
+1,942
+parasite
+5%
+Uranyl salts
+smear and culture tests of sputum, blood and urine
+pathway and network centric
+type I interferon production
+RIVM
+extracellular and intracellular viral particles counts
+temporal class
+amoebae
+adipocyte dysfunction, dyslipidemia, insulin resistance and mitochondrial dysfunction
+ten
+physical methods and chemical methods
+loss of cilia
+CD8+ T cells
+plastid transformation
+chromosomal DNA from C. difficile 630Derm
+at least 10 passages
+the i th age group
+antiviral cytokines
+Zhang Zhongjing
+PDB structure of 2BPV_A
+132
+Trials
+R 0
+cellular kinases
+Episode questionnaires
+perianal area
+Ten wt %
+conserved CTL epitopes
+Br-PepC7
+H7N9
+Dr. Shin Yonehara
+Electrostatic force
+3.5
+frequency of positive cells
+stochastic gradient boosting
+2000
+food intake data
+Human rhinoviruses
+population genetics
+T cell
+3, 7, 11, and 35
+Two days
+three
+the allele found on the most common haplotype
+written informed consent
+H7-specific antibody responses
+Lymphocyte count in BAL fluid
+one QTLR
+detergent-resistant membrane fractions
+≥57%
+Fida M. Khan
+,1/40
+over 80%
+mouse monoclonal 11G5a
+observations at focal points that are at wild/ domestic bird interfaces
+hypergeometric P-value calculation
+Transformants
+the government
+TNF, IFN-β, and IL-1β
+intracellular
+x 2 2
+CSF
+liver inflammation
+2BP
+US$15 billion
+CBPV
+immunomodulators
+CD8 + Vb8 + T cells
+IAV-infected human epithelial cells
+Cisatracurium
+renal replacement therapy
+Cell-and tissue-specific delivery of cmRNA
+STORK data manager
+Bid
+calnexin
+PPV and CMV
+15 min
+880
+8 µl
+de novo synthesis of nucleotide precursors
+4,045
+essential viral function
+0.84
+redox-regulated
+10 µg/mL of blasticidin
+European bank voles and South African four-striped mice
+binds DNA and regulates transcription
+education
+90%
+30.0%
+PRRSV
+three
+population level mixing and transmission
+,20
+Xing Tan and Miao-Ling Li
+T ventilation without RM
+ProteinPilot software
+2009
+Education
+Intensive Care Syndrome: Promoting Independence and Return to Employment
+Influenza research
+Molecular
+99.5%
+ρ H M Z Y H M
+three
+neomycin resistance
+larger study populations
+bleeding, infection and care
+Differentially expressed genes
+Y2HGold
+Cathepsin D
+1AE18
+The investigator of each participating center
+Costimulatory molecules
+Multiple comparisons
+reverse genetics platforms
+lesions
+aae-miR-263a-3p
+48 hours
+accurate representation of actual contact patterns
+First Strand cDNA Synthesis Kit
+insoluble aggregates
+2-21 and 28-39
+removed from display
+CPV 2a and 2b
+cathepsins B and L
+protecting mice against H1N1 IAV infection
+cross-contamination
+The first Nash equilibrium
+P-glycoprotein
+recombination
+Hypertension
+7.5% DMSO
+The Hoechst channel
+Five
+QIAamp DNA Mini Kit
+90%
+cholesterol
+100
+175
+expression of surface ESA
+1.75%
+1 mg/mL
+cleavability of the 3 0 -terminal phosphodiester bond
+adenocarcinoma
+400
+24 hours
+10 min
+routine
+prokaryotic IF2
+80%
+an ER stress inducer
+transient non-viral gene therapy
+Eleven
+ST cells
+CCR5 + CD4 + T cells
+10 to 44
+straight and confined migration
+PmaSLRNAs
+convergent coevolutionary patterns
+4 µM
+geometric centers
+biased
+NPPTL
+R
+43.75 ± 16.46 years
+v
+hyperglycemia, infection, disturbed wound healing, or gastrointestinal bleeding
+34
+3.75 × 10 7 PFU/mL
+inefficient metabolism of microbial products in the liver
+8% polyacrylamide gels
+Western blotting band
+Phylogenetic
+1/16 394
+antigenic
+20%
+significantly different
+calcium-dependent enzymes
+microbiome
+HLAassociated selection
+∆Br T
+disparate levels of FPS and SQS transgene products
+five
+STT3A
+act as an oncogene
+assessing the potential of metabolomics to establish vaccination status in infected animals
+insomnia, depression, and anxiety
+Silent codon modification
+11Thr/Thr
+pneumonia
+lung cancer
+The use of biomarkers
+acute myeloid leukemia and breast cancer cell lines
+2F5, 4E10 and 2G12
+eukaryotes
+predisposed
+Transcriptional slippage
+38%
+receptors
+probes for norovirus and rotavirus sequences
+adequate selection of parameters
+purified DNA
+Indonesia
+lighting on roads
+DSPA1 and DSPA3
+laboratory confirmed or suspected influenza Apdm09 infection
+PFU/mL
+fluorescent dye
+Chinese Han
+Fluorescently labeled target-specific probes
+cell rounding and syncytia
+IFNT
+autophagy
+Exosomes
+annexin A6
+oropharyngeal bacterial translocation
+IPP
+higher
+high MOI
+2-5 days
+Understanding the genetic basis of adaptive phenotypic change
+50%
+structural conformation
+oncogenesis and IFN-activated responses
+booster immunization with Tdap
+cIAP1/2 and NIK
+stay focused on the health of populations
+40%
+Kurtzke's Expanded Disability Status Scale
+higher
+Established sepsis/MODS
+cathepsin D and trypsin
+36
+63%
+process measures
+Specific revalidation
+by passing the extract through the column
+θ
+assay
+humans and chimpanzees
+2
+Three
+Gharwar
+22
+mitosis phase
+genetic diversity
+Glycyrrhiza glabra
+NK cells
+1980
+E/E1
+Inhaled corticosteroids
+genome sequencing method
+202
+455 and 360/HLA-A*0201
+poor outcome after HCT
+pCA-Dest14xx
+IFN-c
+QIAamp DNA Blood Mini Kit
+existing diary-based studies
+high fat diet
+SAP130
+Five
+H5N1
+energy
+Vero E6 cells
+5 min
+COA
+changes in the affinity/disaffinity between groups
+8 days
+epitopes having significant median similarity score lower than the non-epitopes
+Normal
+4%
+Sixty-nine
+alternative tests
+136
+Population health
+sale
+three
+live attenuated vaccines
+Akt-mTOR pathway
+HIV protective behaviours
+Traumatic spinal cord injury
+PCV2
+logistic regression models
+Exosomes
+heterologous infection systems
+Uncertainty
+self-tumor ags
+Alcaligenes faecalis
+HIV-related stigma
+avian to humans
+povidone-iodine
+statistical significance over control
+95%
+15
+Microglia
+ubiquinone biosynthesis
+Fn
+conventional antibiotic therapy
+IL-10
+heterogeneous
+around three weeks post-infection
+hepadnavirus
+8 weeks
+potential multicollinearity
+the timeline of a higher level process
+disease is eradicated
+Lipoid CO., Ltd
+urine and faeces
+structural cohesion
+500,000
+quantitative real-time reverse transcription PCR
+pyrimidine-rich
+low pH in the endosome
+acute cuprizone demyelination
+H3N8
+nearly 60 years
+five
+Core A, Core B, and Core C
+virus
+Four hundred
+De novo reconstructed gene models
+411
+2 weeks
+considerably off trend
+San Jose
+supertree
+poor self-rated health
+covering cough
+darker color
+15
+The cytoskeleton
+ISRE, IFN, and NF-κB promoter activities
+similar effects have been found for different epitopes derived from unrelated viruses
+methanol
+N i
+Gyrodactylus
+Availability of resources
+OriL-RNA1
+defense against C. albicans
+chimpanzee
+to bypass the HG barrier
+24 h
+one day
+Bm-P12A3C
+Integrated DNA Technologies
+80 mmHg
+H
+proteasomal degradation
+15.3%
+Corosolic acid
+33.3%
+heart rate and heart rate variability
+plaque assay
+viral genes or sometimes complete genomes inserted into host genomes
+NetMHCIIpan
+TLRs
+signal peptidase
+human epidermal growth factor
+infected cells
+dengue antibody
+Laboratory surveillance
+Intestinal tissue
+0.7%
+RBPs
+the mammary gland
+population structure
+AGR2-GST fused protein
+Status as a developed or resource-limited region
+independent monitoring
+LbrPGF2S and AKR1C3
+identified challenges
+Cotton effect
+fluorescent anisotropy-based binding analysis
+6 h
+Wnt/b-catenin signaling
+3 -disulfide functionalized PMO
+31%
+79.6%
+B3LYP
+SignalP and PrediSi
+the construction of synthetic cells
+plant cancer
+constant
+Microbiome profiles from 16S sequencing
+50%
+8.1
+80%
+Gaussian distributions
+eukaryotic expression plasmid
+a duplex semi-nested-RT-PCR
+acute respiratory distress syndrome
+biosignatures
+CMV pneumonia
+Eighteen of 21
+90%
+0.45
+schizophrenia, bipolar disorder and major depressive disorder
+463
+24 h
+57%
+antigen-encoding vaccines
+TRAF6 and UbcH7
+Three
+MS n
+detrimental
+remyelination
+30 mM-1 M NaCl concentration
+lower values
+human polyclonal antibodies
+Mann-Whitney test
+sIgA
+40 days
+ring vaccination
+SPSS statistical software version 12.0
+carbon fixation during photosynthesis
+C-6 of glucose core
+immunofluorescence
+essential
+sequentially and spatially conserved
+one
+3
+CMV-TRAF6 cells
+immune components in host cells
+flow cytometric
+detection reagent
+endosomal/lysosomal cholesterol accumulation
+25
+RStudio
+40
+P27 or replicase expression
+Protocol adherence
+twenty-four
+PrP Sc
+human spread
+seven days
+local political constraints
+one-third
+1964
+Major histocompatibility complex haplotype
+mean AAR
+exons 45-51 and exons 53-55
+Perkinsozoa
+90%
+scanning
+consistency in describing public health
+Five
+Five
+5 min
+data are available
+cleavage of VP4 by trypsin
+increased expression
+one single residue at position 134
+ovalbumin
+PMOs
+H. pylori
+potential epidemiological links between cases for a given data source
+Emerging and re-emerging infectious diseases
+551
+864
+More than 600
+low inter-and intra-group variation
+Interactions between time and treatment
+28.4 µg l -1
+Stepwise forward logistic regression
+open-source
+a number of subgroups
+PCNA
+TLR3 signaling
+cc-by
+complex life histories
+cc-by
+Translation of the no-stop mRNA
+plasmacytoid DCs
+In Vivo Imaging System kinetics system
+bone marrow progenitor cells
+allergens
+disaccharide repeats
+pancreatic islet hyperplasia
+surveillance systems
+40-min
+IL5 activates eosinophils and cause airway inflammation
+Estimating the growth rate of the outbreak
+luminescence expression
+respiratory intensive care unit
+3 to 12 weeks
+four
+35-40%
+Over-stabilized UFS
+Chart review
+Three
+affinity chromatography
+51%
+efficient
+cheetahs
+1:1
+ML inference
+infants and adolescents
+non-bound virions
+Retroviruses
+Yosef et al.
+Nineteen
+I. scapularis
+recombinant receptors
+8 negative single-strand RNA segments
+novel mutations
+Atg32
+Atom numbers
+X-31ca
+morphine addiction
+ataxia-telangiectasia
+the public health classification
+dropout rates were lower
+Tautomerism
+colonic ulceration
+10%
+One week
+SERCA2a
+cervical ectopy
+autophagy
+parasite biology
+153
+maximum likelihood estimation
+50%
+maximum temperature, specific humidity and latitude
+Rab5a
+epigenetic silencing of tumor suppressor genes
+Recombination Detection Program version 2
+potent
+3:10:22
+peripheral arterial
+lysosomes
+Specific
+31
+Brazil
+4 months
+binary logistic regression
+raw images
+non recurrent
+pediatric
+2012-2013
+80
+viral clearance
+new method of epidemic evaluation
+HCI
+asymmetric
+TGF-β activity
+Alphaviruses
+The NIH Institutional Biosafety Committee
+age, gender, and specific pathogen
+FccR polymorphisms
+written information
+5
+how the probability of contact between farms scaled with distance
+Induction of cell vacuolation
+pneumococcal HIS
+pressure and natural selection
+p.Lys329Glu
+disease duration, functional derange ment, age, gender, or smoking
+Plasmid pCDNA3.1-UL44-FLAG
+ILC2 cells
+state-run/funded public health care systems
+China, Japan and Korea
+lack of 'clean' seed yams
+24 h
+materials-based
+Maximum likelihood phylogenetic trees
+longer latent infection period
+morbidity and mortality from disease
+SFV
+RT-qPCR
+33 months
+pneumonia and sepsis
+Aligned nucleotide sequences
+the scale's factor structure
+increased ACE2 shedding from tissue
+Five
+inflammatory
+their etiology
+Antibiotic exposure
+higher
+H3K4 monomethylation
+toeprinting
+colorectal
+280uC
+190 kb
+trVLP
+asthma and COPD
+Juliana Idoyaga
+four
+Bronchoscopy
+three
+a single transcript
+Breast cancer
+3.9%
+alpaca
+STATA
+virulence factors of different pathogens
+scFvG36
+TC sensitivity to PI3K isoform protein inhibition or PKC inhibition
+microarray
+ORFs
+socioeconomic conditions
+unusual characteristics or high morbidity or mortality
+15
+quantitative
+three
+Cochran's nonparametric statistical test
+30 min
+85%
+hundreds and thousands
+Uncertainty
+mice
+MMPs
+TLR15
+R P isomer
+no band of NS5A-LacZ
+CD150/SLAM
+all sites have the same ω ratio
+mosquito dynamics
+multiple linear regression analysis
+Echography
+Rendered Z-stacks
+15 mM reduced glutathione
+The integrity of the innate/adaptive immune interface
+Pip6a
+RT-qPCR-based relative expression data
+culture, antigen detection, and PCR
+HER2-positive breast cancer
+Substitution S101N
+any risks
+100%
+canine sapovirus and canine kobuvirus
+silicone
+infectious contact
+local scale
+pivotal/registrational Phase 2 studies
+primary progressing remitting course and secondary progressing course
+1:1
+infection control systems
+Proteolytic digestion
+meat and egg production
+HEK293
+complement-mediated and/or antibody-dependent cytotoxicity
+Ϫ1.6
+HT
+Bars sharing the same letter
+Hela-S3 cells
+45%
+39
+Pass-through events
+tapeworms
+CD4+
+receptors predominantly expressed on neuronal cells
+Yap1 and Skn7
+between pH 6 and pH 7
+72 h
+the highest value obtained within 3 days of acute visit sputum collection
+adaptor ligation amplification
+EEA1
+fluorescence
+Quantitative phosphoproteomic
+Fragments per kilobase of transcript per million fragments mapped
+high and low priority diseases or pathogens
+tetraethylammonium and acetylcholine
+between 2 and 6 h post-infection
+endosomal release
+p
+1 week
+C6/36 cells
+T-bet
+500 µl of culture medium with 10% FBS
+VE decreasing
+the frame with the greatest mean brightness
+perinuclear area
+catalytic activity and transporter activity
+20
+its own translation
+1975
+Avian influenza
+Bacteriophages
+PtDds
+Nonspecific interstitial pneumonia
+cyclophilin A
+hours to days
+clumping and precipitation of the antigen out of solution
+Cell viability
+histological
+Binding site similarity
+keyhole limpet hemocyanin
+HSP90β
+IL-5, GM-CSF and IL-3
+management
+wt RNA
+LRTI
+a critical element of protection against pathogens
+1.67%
+Physicians
+a human telomerase-immortalized retinal pigment epithelial line
+deoxypodophyllotoxin
+CSFV-infected swine serum
+Fawa-l-luc-based
+fullerene
+IRAK4
+100 μL methanol
+70%
+induced folding to take place
+moral decisions
+three
+diffusion Eq
+an Figure 2 is not to scale
+SAND and eEF-1a
+Supplementary Information S3
+poor
+Halophilic
+TBC2target
+R 0 j
+NUPACK
+four
+Actin
+7
+mutations
+dehydration of lipid head groups
+pandemic
+random between-patient variation
+55
+HIV-1 nucleic acid amplification testing
+Public awareness of risk factors in relation to cancer prevention
+8-weeks
+regression models
+Japanese encephalitis
+Influenza pseudotypes
+Respiratory failure
+-TUB, EF, and CypA
+cc-by
+Evolutionary model
+50-100
+1976
+40% or less
+up or down regulation of other specific pathways
+five
+Statistical Complexity measures
+CD44, Sox2 and ALDH1
+methicillin-resistant Staphylococcus aureus
+statistically significant
+55
+Plates
+bio-security
+biological
+N-Terminal 6xHIS tag
+p38 MAPK pathway
+sCT targeting and localization to osteoclast
+gene expression data
+Glycosylphosphatidylinositol anchors
+increased mortality, duration of MV and paediatric intensive care unit stay
+Expression data
+tumor incidence and size
+2.05
+IGF-1R
+Glycoprotein D
+cluster members
+APOC1
+more Internet users
+R-squared, AIC and significance of the coefficients
+2 h
+enhances the NF-kappaB-dependent inflammatory cytokine production
+systematic bias in observed outcomes
+α
+CD8+ T cell and NK cell
+interleukin-7
+2.22 ng
+epithelial and endothelial cells surface
+7
+destabilization of USP18
+700 000
+IMGT-Ontology and Gene Ontology
+15-20 mg/L
+RNA
+immunosuppression
+Leukocytes and plasmacytoid dendritic cells
+four
+agr quorum sensing system
+106,682,518
+RF antitumor model
+residues Cys391 to Gln419 of BLV Env
+antigen dose-rather than magnitude-dependent
+Cambodia
+L-O2-X cells
+59
+Enhanced cmRNA Stability and ACE2 Protein Translation
+10 µL 1 m ethanolamine
+terms of hospital operation volumes
+induction of T-cell immune responses
+overall LOT-R scores
+Zymo Research viral RNA kit
+further analysis
+saline
+500 and 1000 meters
+a questionnaire
+chloroplast NADH dehydrogenase complex
+two
+CsrA activity
+creating custom interfaces
+MPRC, Pocheon
+2256
+the height of the entire stack of residues
+innate response
+neuraminidase
+coexpression of at least two nonstructural proteins
+30 min
+Bat capture and sampling
+Chihuahuas
+55 mmHg
+clinical course of HE
+comparative genomics tools
+350 copies per mL
+four
+stability
+strong anti-viral systemic responses
+Extracellular matrix deposition
+higher
+326,552
+30
+temporal autocorrelation
+Prior knowledge about sensitivities
+two
+robust multifunctional T-helper and cytotoxic T cell responses
+days to minutes
+viral progeny
+In vivo expression of vector-delivered firefly luciferase
+eHEV particles
+Cyclophosphamide
+Supernatants
+Th17
+splenic lymphocytes
+substrate
+Manila
+20
+Optimal codon
+TGFBR2
+UK Department of Health Critical Care Contingency Planning Working Group
+ID
+evidence
+The nucleus
+inflammatory
+N l
+piwi genes
+50%
+MeV inhibitory
+Cochrane collaboration's tool
+highly curved fission products
+Graphs
+Tukey's multiple mean comparison test
+total JNK or β-actin
+EGR1 mRNA levels
+Losartan
+bioinformatics
+ecological and epidemiologic
+Important biomarker patterns
+Phage rescue
+stable ensembles
+Hemagglutination inhibition
+analytical protocols
+tolerance exercise in ARDS survivors
+28 and 90 days after admission
+2 weeks
+Six
+completely degraded
+H9 HA protein
+Type I IFNs
+Younger age
+pigeon cells
+Adjusted values
+phagocytic ability
+patient safety
+5%
+9.9 million
+PsVs
+Twenty-one
+asymptomatic
+automorphism orbits
+Richard Hatchett
+IgH D-J rearrangement
+10%
+regulating secretory capacity
+RNA isolation or ACE2 protein assays
+Proxy measures
+immunogenic
+IL-10 receptor alpha-chain
+23%
+University of Pennsylvania Institutional Review Board
+dolichol-linked oligosaccharides
+6 hours
+Delphi 14 method
+eight
+disease transmission
+smallmolecule chemotherapeutic agents
+bisbenzimide
+apoptotic markers
+NaCl
+ventilation
+NCBI
+PROCR
+17-mer GCrich and AT-rich ssDNA oligomers
+media practices
+NS5A movement properties
+refractory fluid overload
+1988-1989
+dynamic phosphorylation pattern
+to revert the non-germline framework amino acid changes
+up-regulated discriminatory peaks
+shape features
+potential adverse effects
+β-lactam antibiotics
+Rice
+0.107
+Management guidance
+rabbit anti-GII norovirus polyclonal sera
+trypsin
+b and c
+Pomc expression to drop and NPY to increase
+canonical activators of SG formation
+AIDS patients
+a strong type I interferon response
+one hour
+ECDC
+climatologic data
+Voxels
+FACS Diva
+Polyomaviruses
+1 : 30; 1 : 90; and 1 : 180
+Oligonucleotide probes
+7.0
+two
+cysts
+9.9
+miRNAs
+Subviral particles and infectious virions
+19 days
+Between weeks 5 and 6
+Sleeve anastomosis
+its folding route would be riddled with kinetic traps and dead ends
+Each spectrum
+H3K4 trimethylation
+the primary recipient
+AMPKα1
+lymphoid
+pDUAL-HIV
+IRES-mediated initiation
+IL-23
+Methionine
+physiological relevance and greater clinical significance
+Little
+WBCs
+16
+Minkowski distance
+doctors and nurses
+inside the lesion
+one
+fancy hardware
+shRNA1110 and shRNA1755
+clearance of viral infection
+GraphPad Prism 6
+ρ
+ILT7
+diffuse pancreatic infiltration
+Bright-Glo Assay System and POWER SCAN HT
+T362I RdRp
+BALF
+splicing variants and the shed variants of RAGE
+huORFZ embryos
+chronic CD
+diphtheria toxin-like ADP-ribosyl transferases
+to ensure the precision of the exponents
+asf
+5 months
+single-molecule fluorescence
+American Type Culture Collection
+36.1%
+H1N1 and H5N1
+moderate malnutrition and clinically severe pallor
+One hour
+red spheres
+bactofection
+VLP for CHIKV
+definitions and management
+infection of the same host cell
+4,500
+XMRV
+thromboembolic
+Logistic regression analysis
+TNFR1deficient
+endoplasmic reticulum
+0.017% and 0.019%
+Dr. Klaus Strebel
+reduce the intact cat populations
+1,000
+binding to the N-RNA
+generalized linear models
+Orphan Drug
+histological analysis
+Kenya
+Five
+37
+enthalpy-entropy-compensation
+a one-way switch
+366
+a higher secretion
+transient adoption of social distancing measures
+mutual trust
+60-70%
+PE-conjugated streptavidin
+37%
+IFNγ and IL-10
+early critical factors
+1970s
+Collibacillosis
+200/μl
+ImageJ
+Xi'an
+6
+children with a limitation of intensive care treatment
+ACBD3
+GST-UL44
+Fwt
+LI-COR Odyssey or HRP substrate
+humoral immunity
+Healthmap or Medisys
+nucleic acids and peptides yearly trends
+500
+an MOI of 0.1 TCID 50 /cell
+BioTek plate reader
+two
+fifth
+inflammatory
+Flow Jo
+gold particles as fiducials
+angiotensin II-induced cardiac hypertrophy
+NF-κB
+RNeasy kit
+50%
+negative
+2,000 fold
+no cobblestone-like colonies
+SOF
+distributions and ratios
+bind to the MHC molecules
+Twenty seven
+multiple protective effects
+Bayesian
+meningoencephalitis
+TYMV PRO
+1 min
+eighteen
+Airway epithelial lining
+Alveolar
+Data
+24 hour
+nontarget tRNAs
+International Classification of Diseases
+tissue-resident macrophages
+Hecke and the Maitlands
+positive end-expiratory pressure
+number of sensitivity, specificity, and precision tests
+protection
+chromatin remodeling and/or transcription modification functions
+GLMNET
+melanoma
+decreased or unchanged reactivity
+IAV-infected
+60 min
+PA
+IFN-a
+Human TNF-a
+Inosine
+four
+the interaction of PTX3 with C1q
+Three
+PAMs and MARC-145 cells
+the number of living cultured cells
+F4/AS01
+A human norovirus
+Goggles
+monitor the spread and severity of the pandemic in real-time
+Non-stimulated PBLs
+Twenty-three
+S *
+face masks
+3
+agent based models
+tRNA modification
+C CUCCAGCGCGC
+24 hours
+3, 7 and 28
+the average number of secondary infections
+endemic
+mul-tinucleated giant cells
+eight
+susceptibility and infectivity
+the average from 10 animals per experimental group
+difference between survivors and non-survivors
+The envelope gene
+specific overlap of EGFR and CD151
+fear of side effects and doubts about the efficacy of the vaccines
+GenBank
+National Hospital for Tropical Diseases
+24
+CEACAM1
+Virus titration
+The inset
+firefly luciferase
+heparin-Sepharose beads
+IL-23
+Myf5
+Supplementary Table S1
+simple modifi cations of the widely used C2 algorithm
+type 1 regulatory T cells
+Ketamine and Xylazine
+Figure 18A
+IgM
+5 to 89 days
+cryo-electron tomography and microscopy
+macaque PBV
+once daily
+proliferation and migration region
+Serum NGAL levels
+hemagglutination tests
+myeloid
+four
+Influenza A
+7H10
+ApoE4
+more severe systemic inflammation
+DNA inversion
+5729
+11
+group 1
+acrylic board processing equipment kit
+hematoxylin and eosin
+augments
+1,6-hexanediol
+Fifteen
+limited
+Node color gradient
+influenza transmission
+0.22-µm-pore-size filter
+0.990 and 0.899
+Metadata on whether specific sequences originated from clinical sample or culture material
+2.5% goat serum
+extracellular
+after the project gets running
+27
+properties of both the basic reproductive number and the ultimate proliferation rate
+30 min
+~4 × MCD
+antiviral
+reducing cellular cAMP levels
+knowledge gaps
+hypertension
+162
+~10%
+endosomes or basolateral membrane
+Genome sequences of H5N1 influenza A viruses
+up-regulated
+Legislation and ministerial directives
+1104
+Cladograms
+N proteins
+marginal likelihood estimation via path sampling
+598,473
+faster Tl2
+banning large gatherings
+8
+general health, rectal temperature and signs of abortion
+critical
+100%
+distribution of each genetic group
+TLR target genes
+peptide-MHC microarrays
+Cell-surface-linked
+HRV-C
+ZsGreen-positive cell ratio
+0.024
+3
+IL-10 secretion
+Low heterozygosity
+26
+PCR reactions A and B
+asynchronous entry into the lytic cycle
+O/KEN/10/95
+22.3%
+ðDSÞ j i ¼ @S i @q j
+GRA24/p38
+Youden's Index
+2012
+acridine-based
+October 2010
+77%
+pulmonary metastases
+standardised physical assessments
+Laboratory data
+partial L-gene
+0.59%
+H3N2 and H1N1 influenza viruses
+cytochrome c
+Equatorial African
+flow cytometry
+Chlamydophila pneumoniae and Mycoplasma pneumoniae
+cattle, sheep, pigs and humans
+no genomic deletions
+Pediatric and pregnant/postpartum mother mortalities
+50-250 ppb
+more complex non-linear models
+IBV reassortants
+24 h
+actual travel patterns in South Africa
+fetal lung epithelial cells
+severe sepsis
+increased replication and pathogenicity in chickens
+previous or recent presence of infectious agents in a given population
+cross-presentation pathways
+ATG8-specific
+NF-B and mitogen-activated protein kinases
+49
+PfEMP-1 and EBA
+Docking sites for inhibitors of HIV-1 binding
+Remaining material
+peripheral blood
+autoantibody production
+NS gene reassortant
+anonymized
+QGIS
+linear regression models
+Beta-2 microglobulin expression
+viruses
+RefFinder
+lipids, proteins and nucleic acids
+C rs
+ELISA and IFA
+High hydrolytic capacity of cells
+Western blotting
+viral nucleic acid
+36,000
+endocytosis
+USA, Spain, and UK
+Lipofectamine™ 2000
+Pseudomonas spp., grampositive cocci and fungi
+Viral serology
+within the nucleoprotein gene
+Fisher's exact test
+three
+ciliated and non-ciliated airway cells
+Ratios for the protein of interest
+NSP2
+RNA interference
+128,119
+Odyssey Imaging Station and Image Studio software
+one third
+hepatitis G
+Newcastle Ottawa scale
+10%
+the edge of the insert
+maintainance of heterochromatin, DNA damage response and aging
+ΔMx
+neuronal cells
+generalized machine learning
+hypercaloric feeding
+T4 RNA ligase and -pCp
+34
+changing mortality and morbidity patterns in time and place
+48 h
+Administration of fluids
+influenza A
+the validation strategy
+.1%
+lamivudine
+systemic dysregulation of the inflammatory response
+Cytokines
+complete tumor rejection
+P. vivax
+FcγR-mediated binding and internalization of ADCs
+peak timing
+0.5 ml FBS
+Ͼ32
+~55%
+non-monocyte derived cell lines
+arbitrarily primed 454 sequencing
+CC IFN-l3
+mechanistic model
+logistic regression
+3
+Granzyme A
+host factor
+BSL-4
+150
+q B and q A
+EVD survivors
+four
+injured TI cells
+comparisons with certain types
+control of inflammation, metabolism and tissue repair
+sensitivity estimates
+w6/32 monoclonal antibody
+core self-evaluation
+500 million
+principal component analysis
+polydimethylsiloxane
+12%
+PureLink PCR Purification Kit
+198.8 ± 82.6 × 10 9 /L
+Confusion, Urea nitrogen, Respiratory rate, Blood pressure index
+R t
+molecular
+addition of the LIPS
+Taxonomically related host species
+0.3 mL/min
+2009
+Ebola parameters
+at least twice daily
+2009 and 2018
+3900
+32
+less than 10 days
+limitation of the availability of antibodies to Neovison vison proteins
+easier detection of the -1PRF product
+C200
+Fourteen
+nitrocellulose membranes
+RNeasy Plant Mini Kit
+85%
+Burkholderia cenocepacia
+many DNA and RNA-containing viruses
+electrophoretically homogeneous
+5 days
+80%
+65.0%
+naïve CD8 + T cells
+One-way repeated measures analysis of variance
+sek-1 MAPKK
+protein secondary structures
+HTLV-I viral proteins
+6
+two globular protein domains
+Extracorporeal membrane oxygenation
+70
+2.4 Å
+immunocompetent
+HBV-transgenic
+concomitant, and alternating glucose and drug infusions
+ketamine
+structural data retrieved from the PDB and comparative modeling studies
+Neutrophils
+PB1-F2
+U2AF 65
+Parreira and colleagues
+ε i
+88,000
+PI4P
+Cell-free
+risk score
+Lysozyme
+international political issues
+Tamiflu
+Plasmids containing each event
+BGI-Shenzhen
+73%
+14,381
+It starts to recombine
+five or six
+receptor-binding and neuraminidase activity
+IL-10
+A2
+introducing auto-correlation
+many infecteds will be detected before becoming infectious
+ICP4
+a computational approach for RBP -mRNA interaction prediction
+ProteinLynx Global Server 2.2.5
+1800 V
+17.7%
+Bangladesh
+9 years ago
+rapidly stimulated
+risk-factor associations
+Myeloid DC
+the same specific mutation
+5
+miRNA expression
+Pricing
+chloroquine and desethylchloroquine
+Global protein synthesis
+surgical procedures
+Meta-analysis
+a set of true transmission chains
+septic shock
+271
+Spectramax M3 Multimode Spectrophotometer
+relative light unit
+emergency preparedness
+GTP hydrolysis
+Tunicamycin
+inhibits virus adsorption and penetration in the early steps of virus replication
+v obs
+compound 6 and compound 66
+34.2 days
+50%
+AID iSpot EliSpot Reader
+positional overlap
+bronchioalveolar lavage fluid
+lymphocyte receptor complex
+Infectious disease
+24 h
+cells sensitivity to chemotherapy and androgen
+pheochromocytoma
+Nasal and pharyngeal swabs
+IL6
+ssc-miR-30d_R-1 levels
+E5564 and TAK-242
+GOLD fitness score
+an immune response to HA proteins
+programmed ribosomal frameshifting
+A3114-01
+unidentified host factors
+luciferase
+estrogen receptor alpha
+CD69
+proinflammatory
+TRIzol
+to ensure stable and consistent conditions
+HBV covalently closed circular DNA
+three
+One hundred fifty-three
+rs1042031
+size
+IFIT3
+dropwise 2 × 10 -6 M FB solution
+Geneious
+XRN1
+DNA or protein sequence
+IFAT
+SBE2/3 motif
+48 h
+vesicular
+44,4%
+100 μl of the neutralization mixture
+exon junctions
+consumers are left to interpret this uncertain data
+Chemometric
+96-well
+T, AT, and TT
+no evidence of infective endocarditis
+trimester of vaccination
+companion diagnostic test
+VALI
+MDT clinic
+no or very limited reactivity
+within the first 12 months
+EBOV VP40-associated EVs
+100 nm
+seasonal modification
+exogenous pr peptide
+CUG2-expressing cells
+Arenaviridae
+immortalized
+NSP4 + IFNa + pDCs
+microtiter
+aquatic birds
+Thirteen
+adult-onset hearing loss and refractive errors
+Genetic information
+RFID-based
+205
+weaning difficulties
+biosafety level 3
+Results
+77%
+1990s
+the substrate and concomitant generation of oxygen radicals
+decrease of replicative intermediates of WHV DNA in the liver
+6
+FF farms
+K189
+signaling receptors to transport machines
+a pathogen's
+Ribosome profiling
+mucus viscosity and respiratory exacerbations
+antigen processing and presentation
+immuno¯uorescent staining
+control variables
+Ribosomes
+sharing data and materials
+Nucleospin RNA Plus Kit
+20 min
+at least once daily
+IAVs
+Toll-like receptors
+universal SHI coverage
+Method 1
+138
+TAN buffer
+Transformants
+c
+low-density lipoprotein particle levels
+Hand hygiene
+unstimulated cells
+MLST website
+diagnostic tests with procalcitonine, urine antigen and blood cultures
+A/H5N1
+one-third
+486
+10 % nonfat milk TBST
+Prediction accuracy
+distinct genotypes
+impurities
+617
+HIV-1 gp120
+15
+NKG2D + CD8 + CD45 hi CTLs
+by detecting the virus titres
+a ranking of potential peptides
+IgG1
+non-ribosomal random hexamers
+eIF6
+kx v
+syntenic mapping
+HLA supertypes
+Myocardial ischemia/reperfusion injury
+inflammatory
+long-term infected cultures
+x azm
+L1 and IAP retrotransposition
+aerosol and droplet inoculation and infectivity
+K63-linked polyubiquitination of TRAF6
+RNA enriched for non-polyadenylated bacterial mRNA
+V2-apex bnAbs
+biological layers in the link
+three
+2 μM siRNA
+anti-ZIKV envelope protein mAb clone 0302156
+Adenoviral vectors
+many factors
+Bim
+Black blocks
+72%
+67.6 ± 1.2 kDa
+Caspase-1 activation and IL-1β maturation
+Omega RH32 meter
+clinicians for clinicians
+50%
+2 ± 0.2%
+MicroSpin Sephacryl S-400 HR columns
+medicinal
+recycling of selected cargo proteins
+three weeks
+2019-03-15
+Twelve
+3A
+natural history
+health
+eosinophilic and neutrophilic alveolitis
+culture supernatants of infected MDCK cells
+sandwich ELISA kits
+suspected pneumonia
+efficient rMP12-rLuc replication
+varied its breathing
+seizure or coma following fever
+both viral and bacterial replications
+morbillivirus antigen
+this was not a phenotype the model was trying to identify
+nine
+south East Asia
+equal probability
+30%
+influenza 127 and pneumococcal vaccinations 128, 129
+two-tailed
+ruminant
+chronic portal inflammation and granulomas
+pivotal
+PowerSoil Kit
+PGE2 and adenosine
+production of the Gag-Pol polyprotein
+immunized animals
+a combination of traits
+inadequate thoroughness
+4.8%
+cholesterol
+Brazil
+continued provision of better risk information
+secretory pathway
+3
+1,001/1,449
+malaria
+UPP1
+detection based on data collected routinely for other purposes
+The log copy number of the NDV genome
+RNA secondary structure analysis
+1980s
+Baculovirus vectors
+comparative Ct method
+T4
+MH976520
+hand-washing
+>500 nucleotides
+1
+high intracellular levels of tTA
+Maximum clade credibility trees
+brain tissue
+interstitial lung disease and lung involvement due to connective tissue disease
+200
+12 million
+human pathogens
+Phage display
+9A11
+a viral entry step
+82%
+small sample size
+febrile
+2.4-fold
+whether lamin A is a specific substrate for caspase-6
+giant component
+nonparametric
+54%
+expression
+one ELM instance
+2/16
+Competition experiment
+condom use
+poor phylogenetic resolution
+Orbitrap Lumos
+pathogenic
+cotranscriptionally
+36 days
+their expression at the surface of NIPARAB-infected producer cells
+local formation of thrombin
+amidine groups
+17
+infection free
+edematous
+IPTG
+NCBI's BLAST
+skin, footpad and eye
+Plasmacytoid dendritic cells
+KSHV-infected endothelial cells
+Infection transmission
+where pairwise differences between extraction protocols were significant
+DharmaFECT 1 transfection reagent
+Chlamydiaceae
+100 µl/well of anti-mouse IFN-γ
+flavivirus
+pessimism
+Nanodrop measurements
+Five
+insertions
+3
+6 years of age and older
+multiple potentially infective natural misfolded protein fibrils
+mast cell degranulation-related
+maintenance of cell polarity, tight junctions, and regulation of apoptosis
+Insects
+84.5%
+di and triubiquitin probes
+visual cues
+Ministries of Health and of Agriculture
+D°G 1 8
+Cyclin D3
+glycan interference
+microbicidal
+influenza viruses
+Child-Pugh class C
+Xiao, Yun; Zhang, Jingpu; Deng, Lei
+1.28263 KDa
+LLC-MK2 cells
+how recently the relevant literature had been published
+more people being correctly diagnosed and administered with antiviral drugs
+hindered the free movement of prostitutes and beggars
+27
+ARC -Onderstepoort Veterinary Institute
+B 0 AT1
+ECMO
+activation of the IFN-beta promoter
+CVs and dissimilarity between CV pairs
+activation of immunoproteasomes
+liquid handling
+Nonspecific-priming
+herpes virus-like particles
+general supportive care with management of symptoms
+viral antigens
+World Health Organization
+Three
+status
+oxygen demand
+c13C6
+Full distance matrices
+essential
+10
+72.7%
+a tendency for improvement
+Millipore
+100 mM to 1 pM
+hexon
+Richards model
+Hepatitis B immune globulin
+Synergy HT plate reader
+65 °C
+substantial improvements in forecasts of the trajectory and size of the epidemic
+methodological limitations
+IFN-γ
+528
+good efficacy
+capillary density
+Antifungal
+a similar phenotype
+TLS Pol kappa
+The basic reproduction number
+2.32
+mouse
+using patient identifiers
+levofloxacin
+IFN-I signaling
+how likely an individual changes its states at a step
+Reed-Muench method
+Thymic depletion and body weight loss
+mean + SEM
+DNA polymerase and RNase H
+data quality control and manual curation
+less than 10%
+GC13
+Vaccination against streptococcus pneumonia
+ICTV Committee
+Leon Cantas
+HP-PRRSV
+ALP, ANGL-NUB, and SAAN
+distinct gene signatures
+B. floridae Bfl-AGO2
+differential lectin-binding analysis
+12
+18
+system problems
+five months
+9.64 contacts per hour
+prognosis and survival
+CD3ζ-chain expression
+sorting occurs only when cargo molecules reach the TGN
+thirteen
+non-infectious causes
+9
+7
+E. coli BL21
+reagent and instrument specifications
+ActD
+growth
+1,081
+1%
+82
+VEEV
+inactive
+codon usage variation and nucleotide composition
+Middle East respiratory syndrome
+Network spreading processes
+ramified or activated states
+AMPK
+80:20
+rapid loss of cell function
+5 days
+Intrinsic host features
+renal tissue
+55%
+glucagon signaling
+59
+75%
+cartilage development and endochondral ossification
+3%
+whether it benefits a population
+alveolar macrophages
+2-4 days
+extracellular degradation
+spatial
+lower body and visceral adipose tissue weight
+mildly virulent selflimiting viral infections
+Italy
+lack of more detailed historical data
+8-12%
+reduction
+American
+Pulmonary surfactant
+Lipofectamine
+Viruses
+DNAMAN and DNASTAR
+0 to 71
+67
+30 and 22%
+internal loops
+Gene markers
+new growth
+spin filtration
+Germany
+Cu/Zn superoxide dismutase 1
+PromoCell
+endosomal acidification
+typhoid fever and Streptococcus pneumoniae
+rapidly changing guidance
+Carver College of Medicine Biosafety Level 3 Core Facility
+antiviral wastage
+Fever
+24 weeks
+differences in solvent accessibility
+Mantel-Cox log-rank test
+ecosystems
+strand synthesis
+ADAM17
+rhabdomyolysis
+Toll-or NOD-like receptors
+pre-existing immunity against adenovirus
+58
+three
+genus, species, and subspecies of priority zoonoses
+The epitopes
+HERV-K
+newly synthesized lipids and virus proteins
+DNA
+Cxcl1 and Ccl2
+Pichia pastoris
+0.63
+7.5, 8.2 and 8.0
+PCR target products
+hydrocortisone
+consistency in attribute measurement
+Mekelle
+16S rRNA gene
+variable subjective norm
+The chest radiograph
+four
+cytokine bead array
+Sequence alignment
+natural processes
+1/350
+the minimal distance found
+96% of the vesicle population
+clustering
+Tripartite motif family
+Soluble Barium salts poisoning
+Oleic and palmitic acids
+Five
+40%-90%
+four
+zero
+gaps
+G attachment protein and F fusion protein
+Liquid-liquid phase separation
+ATMPs
+simpler patient administration
+Cy5-dCTP
+World Reference Center for Emerging Viruses and Arboviruses
+GraphPad 5
+delivery
+through skin and respiratory mucosa
+verbal autopsy study
+Parasitology
+low and short-lived
+Aphid transmission
+Eastern cluster
+PTX3
+Cat L, Cat B, and Cat S
+type III L-lactic dehydrogenase
+pDCs
+NSDV/GV
+Rare copy number changes
+molecular assays
+activation of cell mobility and activation of actin cytoskeleton contraction
+health security
+Infection by the Sendai virus Cantell strain
+rop18
+LE/L membrane properties
+regenerative medicine
+to examine the activities of cell grown in tissue culture
+Global Outlier and Batch Effect Detection TMM-normalized LCPM
+spindle shaped
+Immunopurified Flag-RPB1 or GST-CTD
+An Assessment of Understanding
+cdh15
+hamsters
+expected
+pandemic
+100 μL pure DMSO
+equal to the product
+ion mapping
+red
+repeated structures of N-acetyllactosamine
+inflammasomes
+5-fluorouridylate
+good
+enzymatic and cytotoxic
+light microscope
+qualitative
+1.0 × 10 6 copies/mL
+size exclusion chromatography
+concomitant treatment
+host machinery
+identical extinction coefficients
+Cell death
+PI3K and PKC
+mass-spectrometry
+seaports
+CRP
+β-Actin
+malT
+standardized, molecular biology-based monitoring of large sample cohorts
+three
+1 mg ml -1 brefeldin A or 2 mM monensin
+>25%
+local transmission
+the termini of the MNV-1 genome
+between 414 nm and 496 nm
+supernatants
+DLS
+Gillespie-type
+plasma levels of 7.8-31.9 ng/ mL
+E2 glycoprotein and Capsid protein
+biological
+Dodie Bryce
+highly efficient cleavage
+norepinephrine
+An. gambiae mosquitoes
+Enzyme recognition
+Francisella tularensis
+inflammation
+3
+CTP synthase and ATP synthase beta subunit
+osteopenia
+1948
+37 • C
+87%
+phosphorylation of p-38MAPK
+injection of tunicamycin
+Standard enoxaparin dosing
+Empirical antimicrobial therapy
+91%
+LDPs
+62%
+purified or cell-free
+20
+Primer concentration and annealing temperatures
+clinical data
+intra-hepatic
+mock-infected
+97.6%
+recombinant adenovirus
+to maintain homoeostasis
+protein conformation
+daily
+IL-4 and IL-10
+apolar residue side-chains
+UBF
+more than 25
+arginase levels
+loss of infectivity
+a protein which has repeated ankyrin motifs
+culture
+12.8 AE 1.0 pN
+Luciferase kit
+Thirty-seven
+Water buffalo
+induction therapy
+vesicular stomatitis
+The apposition of the two membranes
+plasma
+Dujiangyan
+antiviral activity against HSV-1
+Access to food resources in clan territories
+shortages of ventilators
+45
+EBOV and VSV
+s 2 q
+micromolar
+diagnosis
+Additional file 1
+Detection of CHIKV antigen and viral RNA load
+12
+61 years
+inhibits
+An alternative structure
+a greedy algorithm
+toxic
+mutation rate and mutational tolerance
+cell-type specific antibodies
+the presence of neighbourhood hubs
+80-US210 nm
+a lookup table of exit tags
+serum cytokine concentrations
+Fluorescence imaging
+W2 algorithm
+immunofluorescence
+Asp151 and Glu228
+BD Biosciences
+evidence for divergence
+100
+58 ± 16 pN
+habitat heterogeneity
+HIV-1 gp120
+the PI
+quiescent
+N61A
+5%
+seven
+RNA viruses
+Table 2
+infection risk
+Atlas of Coiled Coils
+Cpb1 KO cells
+6 days
+72 h
+act at multiple points in the virus lifecycle
+acute hypoxemic respiratory failure
+Quantitative real-time PCR
+inhibited cell proliferation
+random hexamer oligonucleotides
+sequence redundancy
+genes that shape antibody diversity between species
+one-third
+160,742
+dengue viruses
+viruses with co-evolved glycoprotein pairs
+Root posterior probabilities
+glutamate toxicity
+preterm, severe postnatal respiratory infection, and maternal smoking
+Inhibition of IL-1b
+697
+genomic RNA
+64
+AMR
+conditional regulation of gene expression
+catalytically-dead versions of Xrn1p
+developing world communities with different population or healthcare characteristics
+isoliquiritigenin dimethylallyltransferase
+k
+HPeV
+fluorescence
+ISG induction
+p-JNK and p-p38
+bacteria, toxins and other macromolecules
+CV replication
+More than 100
+create a barrier to resistance
+Rcpp and RcppArmadillo
+according to different genetic models
+n
+mean and standard deviation
+1:160 and 1:640
+cough or fever
+genedeleted
+covariate
+plasma input functions
+rehydration therapy
+VAE, and VA-LRTI
+1:20
+13-18%
+attention-deficit-hyperactivity disorder
+General data
+The Health Belief Model
+E. Tabarés
+Virus titer
+48 hpi
+modifications in the E2 protein coding sequence were stably maintained
+less than 5 %
+0.39 g/d
+Four PERKspecific siRNAs
+group I
+arginine
+DogPicker
+.98%
+severe acute large bowel inflammatory disease
+3%
+luciferase activity
+titers calculated from our assay
+autocrine and paracrine
+3
+dysplastic lesions
+Plasmacytoid Dendritic Cell isolation kit II
+PPs
+P<0.05
+calculation of V −1
+Parity Rule 2
+ICAM1 high / CXCR1 low
+10 sec
+to Bax
+Ad proteins
+significant differences compared to control
+Influenza A/H7N9
+24 h
+1.6%
+inhibitory activity
+1918
+covalent intermediate
+KEM1 and SPA2
+Keratin
+opsonophagocytic
+28
+lectins-like receptors
+cholesterol
+SeV copy-back
+10 5.44 TCID 50 /mL
+dramatically reduced
+Actin polymerization
+Respiratory failure
+dopamine and norepinephrine
+IL-17 and IL-22
+F. tularensis LVS
+25%
+early surveillance and early diagnosis
+viral
+E. coli
+.10%
+innate immune pathways
+Diagnostic and typing
+133
+4-μm-thick sections of tissues
+Bradford assay
+Dr. Paul Rothman
+conspiracy theories
+expected log likelihood
+immunoprophylaxis
+138
+by ultrafiltration
+severe type 1 respiratory failure
+MNGC formation of macrophages
+Stain-Free
+Cry5B versus tunicamycin
+Col. Soltau
+815
+87
+C-reactive protein and procalcitonin
+SU-modified HSA
+adenoviruses or retroviruses 46
+DHE dye
+RNASET2
+35%
+a2,6-linked sialic acids
+165
+14/45
+Invasive Hia disease
+Immunofluorescence
+NCBI Gene Expression Omnibus
+-1.6 to +2.6 L/min
+unsufficient quantity and quality of the sample
+fluorescence polarization assay
+twelve weeks
+epistasis
+Kaposi's sarcoma associated herpesvirus
+Accreditation
+Intracellular trafficking of macropinosomes
+0.26
+Final individual per ferret values
+14
+validation criteria
+60
+viral load
+26
+becomes a constant scalar
+vDNA
+species-specific miRNAs
+Pneumonia and sepsis
+Aromatase
+Venn diagrams
+intracellular Ca 2+
+Denaturing PAGE assay
+Astroviruses
+5%
+therapeutic
+p38 MAPK and ERK1/2
+two
+Culture medium
+did not reverse this suppression trend
+9
+relative gene expression of the targeted genes
+Human case contact
+Expression of the target virus
+cc-by
+microscopic
+land-cover variables
+5%
+SLA-1*0401
+eight
+BD FCAP Array Software
+demographic and environmental covariates
+One hour
+NKV
+resistance to two antibiotics
+self-resolving acute UPEC infection
+Human IFNa
+five to six days
+MS² spectra
+sequential point predictions
+data from studies involving non-pregnant women
+50%
+regulates the expression of Fgl2
+99.96%
+cluster analysis
+PF-429242
+Anti-Ebola NAB
+p75NTR
+EPX-mAb based
+CD14, CD1D, and CD163
+Seventeen
+five groups
+Micrococcus Luteus
+14 amino acids
+intervention levels
+essentially the same risk estimates
+PBS
+high-avidity
+probabilities
+pUC57-p72 plasmid
+job conditions
+mean ± SD
+Revised taxonomy box
+subjects
+223.6 mg/dL
+field level diagnosis
+Membrane fusion
+CD55, CAR, and CD81
+2016-09-21
+changes
+Flanking sequences
+Inhaled administration of the peptide
+five
+EAV sg RNA synthesis
+ATCC
+Bisphosphonate-related ONJ
+glutinoic acid dilactone
+maleoyl-diamide 15
+mice
+167
+ERGIC-53
+rhabdomyolysis and acute kidney injury
+sitting-drop vapor diffusion method
+type 2 AEC
+macroecological host traits
+monkey kidney
+correlation coefficients and linear regression
+at least three
+effective management
+chisquare test
+SPSS 15.0
+18
+39
+99
+mechanical
+intraoral ulcerations with or without labial involvement
+11
+23%
+Se and selenoprotein function
+UV-visible
+the sponsor
+hypertension
+ten
+SMO and Gli1
+any amino acid
+a rapid increase
+antigen specific
+the DBD and IAD
+Statistical Package for Social Science version 20
+dysregulate host cell proteins
+AF2-helix
+A/ California/7/2009
+Project MTM2014-58091-P
+4a-j, 4l-n and 7a-e
+S pneumonia and Haemophilus influenza
+the balance of de-and remyelination
+deviations
+free days
+14 days
+Independent sample t test or one-way analysis of variance
+GenBank
+unchanged
+spatial heterogeneity
+how pedestrians are defined
+rhesus macaque genome scaffold Mmul_051212
+mean percentage of four independent experiments
+eight influenza transmission parameters
+RNA
+aging-related decline in cognition and neurodegeneration
+monoclonal
+Tumor necrosis factor alpha converting enzyme
+NPL-PEDV/2013
+Impaired p38 MAPK/AP-1 signaling
+72 h
+InfinityTM Cholesterol Liquid Stable Reagent
+activation of host DNA synthesis
+IRE1
+4-20%
+90%
+living cells
+288
+two-thirds
+minor discrepancies
+IntraHealth International
+virulent NDV
+IAV, RSV and HRV
+infectious disease
+strict ethical approval and monitoring
+DMSO
+CARNAC, Tfold and hxmatch
+adenovirus
+serum inflammatory
+95%
+polyadenylation
+socio-cultural
+1 h
+33
+anti-vector immune responses
+27%
+insect cells
+94:30%
+LNPs
+Five
+seven
+Jingxin Cao
+between the 32 nd and 20 th epidemiological weeks
+non-targeted lipidomics
+Serion ELISA classic M. pneumoniae kits
+15.0
+clinicians and record-keepers
+mPK-SL
+t-test
+HRP Color Development Reagent
+increased adiposity
+phylogenetic node
+context-dependent
+the predominant circulating strain
+activation of the IFNb promoter
+177
+the recommendations of the 1975 Declaration of Helsinki
+spinal cord parenchyma
+EndoFree Plasmid Mega Kit
+retention within cytoplasmic vesicles
+publics from danger
+reservoir of influenza virus
+cellular quality control function
+Vaccination
+10 1.5 -10 6.0 TCID 50 /mL
+physiological
+Peduncular
+18 weeks
+3
+dramatically reduces the levels of PA excreted into the environment
+0.67
+Laboratory biosafety
+Pierce Chromatin Prep Module
+five
+Viral RNA
+N-protein
+deep sequencing
+James Hilton
+bacterial expression system
+CON-PEDV
+fragmentary
+reporting bias
+VSV
+indepth
+cell debris
+3
+the highest number of people showing symptoms due to the pandemic virus infection
+cross-linked recombinant gp120
+benefit
+517
+threefold
+most of the respondents were prepared for the Zika outbreak
+Sweden
+Invitrogen
+25μg/well
+Cluster Resource's MOAB
+one
+Source data
+the corresponding standard derivation
+more hospitalizations and greater use of antibiotics
+30 days
+The number of participants experiencing DLTs
+10 and 15 days
+post-translational modification
+antiviral Group A
+Plots of the estimated means for trajectory solutions
+metatranscriptomic analyses of secondary lymphoid organs
+Two weeks
+poor
+66
+ten
+3 h
+explicit criteria
+12
+codon level information
+we were unable to extract all subgroup data from these trials
+TiO 2
+two years or more
+1%
+Felsenstein's peeling algorithm
+Influenza A nucleoprotein
+Unigene 32070 with 2182 bp in length
+HADDOCK v2.1
+seven
+at least twice
+over the course of a year
+Recombination
+Hwacheon
+Concentrations
+92%
+Untreated cells
+Angiogenesis
+antiretroviral activity
+30%-65%
+DuPV-2
+suppressed
+volume state therapy
+higher compliance to preventive practices
+genomic information
+whole-genome-based
+fold change from pre-vaccination
+aggressive and violent
+two
+bta-miR-455-3p
+G3BP1
+deep sequencing of RNA
+Ten
+Alpine goats
+TLS55
+fragilis
+Log drop 1
+nuclear pSmad1/5/8
+49
+an animal model
+losartan and pirfenidone
+PiCV
+Cryptococcal antigen
+DPGs
+23
+SYBR Premix Ex Taq TM Kit
+spo0F allele
+structural vaccinology
+pharmaceutical profiles
+2008
+cc-by
+logarithmically
+binding site comparison
+9
+losing their hydrogen bonds
+twice a day
+emotional exhaustion and burnout
+300
+TMB Substrate Set
+Adaption mutations in viral proteins
+elastic
+3
+a triage protocol for critical care
+Clarified supernatant
+salt bridges
+broad-spectrum
+between 2014 and 2015
+KPN_00 363
+the difference between the bottleneck inference of the optimal model and the baseline expectation
+cell surface expression of two adhesion molecules
+recruitment maneuvers and inhaled nitric oxide
+102
+HIV Tat protein
+119
+10%
+80
+Four
+Estimates of years lost due to disability
+RANTES and TRAIL
+40
+more than 1 peak in a year
+IsoMIF
+seven
+vertebrates and plants
+RIG-1
+alcohols, aldehydes, iodine, phenols, and chlorine
+intravenous insulin therapy
+IFIT1
+prophylactic
+conditioned media from cultured cells
+12, 33, 90 and 91
+16,000
+microtubules
+16
+purity and selectivity
+68%
+L. interrogans Copenhageni
+myelomonocytic cells
+USA Centers for Disease Control and Prevention
+performed the statistical analyses
+identification of target genes linked to a given locus
+EV71, influenza A virus and HSV-1
+TreeAnnotator
+archival samples were used
+independent
+metaanalysis
+91.5%
+35%
+23
+10.1042/bsr20182028
+StemFect RNA transfection kit
+Three
+Viral vectors
+Empirical evidence for unifying principles in biology
+root mean square error
+quantitative labelfree
+63%
+cytotoxicity
+Combination therapy
+surface-based molecular similarity method
+Macrolide resistance genes
+keeping cats in groups of ≥5 cats/group
+30%
+simplified techniques
+Eight
+formic anion
+cc-by
+BPD
+epochal evolution
+dental caries
+HTS
+American Association for Accreditation of Laboratory Animal Care
+nonantibiotic drugs
+four
+knock-out
+OVA/OVA/BAIC mice
+immunosuppressive
+patients with probable CIPNM
+WT gB
+wildtype mice
+GitHub
+ORF1 and ORF2
+gene sequence truncation
+Three
+The collection of data on perceptions associated with precautionary behaviors
+full tryptic specificity
+Susan Sontag
+M1 polarized microglia
+OD percentage of maximal binding
+CD41 and CD81 T cells
+RNA granule
+reduced
+demyelinization nodi
+whether viruses in general
+Epigentek protocol
+320
+Snail
+nine
+absolute vaccine efficacy
+one out of 1,790
+32
+A plasmid for DI-244 rescue
+viral replication
+more severe
+Diabetes mellitus
+multiple replicates and/or site-directed mutagenesis
+ZyMax TM streptavidin alkaline phosphatase conjugate
+70%
+ribonuclease inhibitor
+Microscopic
+antibodies against the virus
+mitogenic stimulation and cellular proliferation
+tailor-made model
+Quantitative
+logistic equation
+glycoprotein lactoferrin
+Five
+E i
+replacement therapy
+m E k
+phosphorylation, dimerization, and translocation into the nucleus
+infections, AGN, obstetric causes and nephrotoxins
+Data from 3 biological replicate experiments
+TBFVs
+SIRS
+regulator of pulmonary surfactant lipid levels
+urbanicity
+EBV integration positions
+whole antigen prepared from infected cell lysate
+University Hospital Medical Information Network Clinical Trial Registry
+Glutathione
+87%
+Exophiala
+more participants, particularly young adults, and newly diagnosed persons
+cardiac involvement
+rotary evaporator
+Hanyin
+2
+EGF
+Six
+Articles
+lack of cell specificity
+Identification of and targeting viral important components
+The funders
+neighborhood properties
+human rotavirus proliferation
+increased neutralization to infectious H5N1
+Pse-in-One
+1000 fg L. monocytogenes DNA template
+cc-by
+T low
+h ε
+The need to identify and address corruption and weak governance
+environmental and/or socio-economic variables
+Ethical review and approval
+ELISA
+recent advances in public health data collection
+assembling the cough measurement system and conducting the experiments
+five
+MAS3.0
+population social structure
+Total nucleic acid
+RNA-seq
+4
+protease inhibitor
+Cryptococcus yeast cells
+60 ms
+cell fusing agent virus
+males
+three
+eIF4E
+passive transfer of IgG
+QTL
+Kaplan-Meier method
+SAON-CD
+Sensitivity
+Cleared lysates with adjusted protein concentration
+nisin
+rate preferential mixing
+Mexican mestizos
+328
+YIP3
+1-adamantanamine hydrochloride
+Montreal Children Hospital Foundation
+UKR ECMO database
+under 500
+cytometric bead array technique
+NKp46, DX5 and CD43
+alphabetic
+HA alanine mutants
+Six-week
+withaferin
+by annotating the protein domain interacting with the respective motif
+TRAPPC6A
+clinical sample
+long repeat domain
+properties of individual amino acid residues and pairs of residues
+RNeasy Lipid Tissue Mini Kit
+100 μL 0.2 mol · L −1 H 2 SO 4
+library preparation
+Two weeks
+strain or subtype identification
+increased contact between people and distribution of pathogens in floodwater
+S11 and S6
+immunofluorescence
+Accurate assignment of primary infections
+reductions in ECMO flow
+95%
+nonspecific
+Four
+Genie III Instrument
+z-value calculations
+2% isofluorane
+acute fever stage
+Figure S1
+14
+2017
+severe acute respiratory syndrome
+five
+insights into the impact and efficacy of the DREAMS suite of prevention interventions
+once a week
+Bliss independence drug interaction model
+clinical signs
+56
+recurrent hepatitis
+SGs
+Rabensburg virus and Krasnodar virus
+6
+The bands containing the human 60S and 40S ribosomal subunits
+interfacial free energies
+2.38
+m
+reference sequence
+DRC, Malawi, and Uganda
+identified similarities
+eight
+pifithrin-a
+ICU admission criteria
+4%
+T helper cells
+Mwaiwathu
+NMR
+Blood
+human immunodeficiency virus-1
+Anti-angiogenesis therapy
+Sar1, Sec23, Sec24, Sec13 and Sec31
+Evolutionary ranking of genomic positions
+B2M and CA2
+bead beater
+to promote efficient internalization
+MirTarget2
+immobilized pH gradient strips
+20.9%
+Metadata management
+plasmatic protease factor D
+Fig. S1
+CEACAM1
+GAPDH, -TUB, and CypA
+the transition of the system from endemic to a disease-free state
+Frequent meetings between different service sites
+DENV-1
+TSEN54 variants
+SAMD9
+a convolutional layer
+Hamster tetherin
+marginal zone B cells
+Risk assessment
+nutrient-rich
+Non-acute events
+Viral richness heatmap
+volunteers
+50%
+subgraph centrality
+H2
+PseAAC
+Two
+Mathematical modeling techniques
+two
+Two weeks
+CD30
+MnmEG
+HCV 1b
+20
+11,323
+0.12-10 mM
+K
+VRC-FLUDNA057-00-VP
+Firmicutes and Bacteriodetes
+PHAX
+DCs
+1×10 −2
+putting the entire record together in chronological order would have been hopelessly confusing
+Four
+state sovereignty
+Pulmonary alveolar proteinosis
+Felis catus
+48 h
+VCR with higher antitumor effects
+nasal virus shedding
+borate buffer
+to check their stabilities under physiological stressful conditions
+Sequential testing
+1
+Africa
+N
+inflamed tissues
+L
+Actin
+Monthly mean near-surface air temperatures
+syndromic surveillance
+total RNA
+22%
+flow cytometry
+24 hrs postinfection
+Densoviruses
+Société de Réanimation de Langue Française
+informative priors
+supernatant
+protective
+RNA genomes
+BA and ER networks
+working and/or studying
+Neutralization
+pleiotropic
+sequence of the tails and the inter-domain linkers
+NaOH-NALC processing
+endocytic vacuoles
+stable STAT5bER pos memory B cell clones
+similar
+when more detailed data is available
+pathogenic infections to allergies and cancer
+P-site
+Short Tandem Repeat analysis
+reduced sensitivity
+a discrete region of the viral genome
+High levels of ZIKV RNA
+TRIzol reagent
+social distancing
+CAV1
+PaO 2 /FiO 2
+cELISA
+vector copies/spleen
+contact between two nodes
+25.55
+mfold
+six
+104
+penetratin
+84%
+accurate propagation of parameter uncertainty
+Factors predicting in-ICU mortality
+five
+AgPath-ID™ one-step RT-PCR reagents
+universal vaccination acted as a protection by creating an immune barrier
+PRISM software
+evaluation
+1 million
+Source data
+Degree
+a nuclear targeted LacZ reporter
+Metabolism
+BMI ≥ 30
+ROR1 and/or LMO3
+one
+overall reduction of B cells
+pyrimidine-rich
+N-linked deglycosylation
+Ubc
+the ventilator
+Bottleneck inference
+Frozen stocks
+MSC target homing to injured lung tissue
+AMCase2/2 mice
+Yields of the symptom consultation and CXRAY
+antibiotic regimens
+dendritic cell populations
+burden
+ubiquitination and degradation and dephosphorylation
+Mycobacterium tuberculosis
+mannosebinding lectin
+35
+2005
+each original variable's contribution
+Bérbérati
+Free ISG15
+mechanistically address this issue
+enhanced scientific understanding
+KCl or LiCl
+apoptosis pathways
+VH polymorphism
+strand displacement amplification
+rabies
+12 h
+humoral
+efflux activity of ABC transporters
+five
+hippocampus
+54
+late liver stage development
+10
+Imperial College
+RABV phosphoprotein P
+pericardial effusion or myocarditis
+DMSO
+Omniscript Reverse Transcription kit
+intradermal
+pcDNA3.1 and pEGFP-C3
+ZIKV
+Poly I:C
+δ ns
+1.3%
+antibody activity against human rotavirus
+English
+NO
+cell monolayers
+apicomplexans and ciliates
+an ancestral sequence
+560 IU/ml
+TranAlign
+western blot analysis
+48 h
+CrebA
+Demographic characteristics and pre-operation test data
+misfolding, unfolding, and functional inactivation
+low-molecularweight PEI
+FSC-H
+high seroprevalence places with larger sample sizes
+random contacts
+Hypogammaglobulinemia
+how to overcome infectious diseases caused by viruses
+4 weeks
+spoVG
+adverse outcomes such as ARDS and death
+Between 10 and 80 percent
+species jumps
+a more naïve population
+1 to m
+UCH L1 and UCH L3 inhibitors
+Redundant items
+The Battle Against
+Forsythia seeds
+1997
+infected
+western blot and again on the protein microarray
+5,852
+48 h
+supplemental oxygen-free days
+polynucleic acids
+Violence
+test set
+60 to 80 kDa
+50-fold
+western blot analysis
+IPTG
+increase the Cmax as well as the Cp in the first hour
+p B m
+most of the Gag-Pol
+PAMPs
+DDI-CPI
+7 days and for 14 days
+RNA viruses
+myocarditis and acute respiratory distress syndrome
+Apoptotic cell and erythrocyte contamination
+p53, p63, and p73
+Numerous organisms consistent with Leishmania species amastigotes
+Small interfering RNA
+1918
+LASV and ML29
+2004
+public health systems or specific legislative frameworks
+five
+9 days
+PCV3
+transgene expression
+experimentation
+keratinocytes
+a face shield
+nine months
+dashed light green line
+5 µg
+13 days
+19
+Adding new birds to cages already holding birds
+demographic and poultry exposure data
+skin samples
+epithelial barrier
+Stata/IC 10.0
+P i1t
+20
+essential
+proteolytic activity
+miRNAs
+20
+oligonucleotide primers
+T cellmediated cytotoxicity and death receptor signaling
+Biosafety laboratory 3
+RNA sequencing and ribosome profiling
+tRNA
+week 8
+flexibility
+Acquisition of HS binding
+Immunization with DNA
+AD
+Quik-Change mutagenesis
+Eighteen hr
+16
+specificity and sensitivity
+an active Ire1 nuclease domain
+De novo lipogenesis
+economic level and classification of the hospital
+blood-pressureregulating system
+7 days
+881.83 seconds
+H3N8
+a list of taxa with at least one Unclassified rank would be shown
+PRRSV
+Overzealous or non-resolving inflammatory responses
+individuals entering the infectious environment
+ER membranes
+twelve hours
+5 min
+1993
+Clonal malignant T cells
+trauma
+antiviral
+microarray and sequencing approaches
+VP5
+different mechanisms
+around half
+MRI
+χ 2 test
+almost 3 weeks
+Clostridioides difficile
+PPMOs
+Duck papillomavirus-3
+exchange flexibility
+DNA hybridization arrays
+Ginseng
+Longitudinal research
+four
+increased TNF-␣ and CCL5/RANTES
+microbially generated magnetite
+rifampicin and teicoplanin
+five
+1,560
+40
+lack of O-antigen
+mice
+Six weeks
+mice and cynomolgus macaques
+Hazard ratios
+definition, reported incidence rates and management recommendations
+SPDEF
+WT RdRp
+cleavage activation
+60 min
+a well-seasoned field scientist
+CGU
+Motif 2
+FBXO3
+sphingosine accumulation
+a control group
+The Na/K-ATPase signaling cascade
+1:1
+three
+CV-B5
+broad amplification of the host innate immune response
+microtubules
+command
+66.6%
+20
+higher total outbreak sizes
+transcription factors and signaling pathways
+assay
+typical dengue fever symptoms
+1980
+cage-like DNA structures
+CFH
+Section 3
+reversed associated pulmonary oxidative stress and lung inflammation
+62%
+autofluorescence is much lower than in Vero cells
+Italy
+probe-based real-time PCR and SYBR Greenbased PCR
+physiological function
+Alnylam
+0
+viral titer
+inside the 59 UTR
+EBVpositive
+data from randomized controlled trials
+3-4 days
+three
+41/137
+threequarters
+RNA-RNA recombination
+Blood samples
+COOT
+6
+the need for a separate elution step
+post-transcriptional gene regulation
+rDolphin
+Accurate identification of new antifreeze proteins
+5.3%
+50 min
+À1 RF
+hematomas
+Figure S8
+Total serum protein concentration
+DOX/GL-ALG NGPs
+villitis
+whom they shared a meal with
+nuclear export of all cellular mRNAs
+4
+Sterile phosphate-buffered saline
+heat-related illness
+self-sustained outbreaks in other countries
+Student's t-test
+orange and green
+GM-CSF overexpression
+pack years
+VSIV G
+cysteine proteases
+Statistical
+microscopy
+SPSS
+enhanced virulence
+better prognosis and chemosensitivity to sorafenib
+no conflicts of interest
+98%
+circulating granulocytes
+Syncytium formation
+381
+Natural Science Foundation of Jiangxi Province of China
+1918
+GraphPad Prism 5.0d
+Sephacryl S-200 resin
+six times per week
+phosphorylation
+sneezing, nasal discharge, and ruffled feathers
+inertial microfluidic system
+LT
+hydroperoxide
+infect cells
+cough, tachypnea and exercise intolerance
+HI metrics
+differences in time zones
+experimental
+Wnt signalling
+public health work
+4 °C
+200
+Shape and Spicoli
+0.01
+at the cell surface
+Studies reporting distribution of data only as ranges
+18 h
+low tidal volume therapy
+UAC
+5%
+capillary flow or filtration
+216
+enhancers
+93
+general composition
+wildlife
+5 days
+48
+R *
+vector control
+20
+higher number of B cells
+2494
+The error of each parameter
+Pathogenicity
+KT247592-KT247609
+20
+lymph tissue
+specific
+Bayesian Tip-association Significance
+two
+scl
+Forecasts
+Viable influenza A
+25
+0.45 μm
+viruses grown in H5 HA-transduced producer cells
+every 20 ps
+520
+Arrow
+challenge infection with a closely-related A virus
+Institutional Animal Care and Use Committee of the Centers for Disease Control and Prevention
+SuperSignal West Pico Chemiluminescent Substrate
+oxidative stress
+Partnering
+adaptive accessibility
+μ cell
+2.76
+−80 C
+PR8
+interactive
+CEACAM1
+endogenous
+RA-induced neuronal differentiation of P19 cells
+additional relevant articles
+significantly suppressed
+22.6%
+ELISA, virus microneutralization and ELISpot
+100
+a human viral diagnostic tool
+IFN-c expression
+4E11 anti-E monoclonal antibody
+Equation
+vegetative tissues in mature plants lost their ability to form callus
+384
+Unblinding a patient's treatment allocation
+apoptosis
+71
+a signaling cascade producing multiple biological active intermediates
+Bone marrow transplant
+VSVDG/LASVGP
+Mechanical ventilation
+Total nucleic acid
+virus-induced cell killing
+stochastic extinction
+19
+Behavioural
+tropical
+10 min
+antiviral
+Antibiotic susceptibilities
+up to eight
+Institutional Animal Care and Use Committee
+self-reported complications during the gestation period
+HIV, RSV, and autoimmune diseases
+a single 2A autocleavage site
+confocal
+ESCRT scission machinery
+binds
+to find nodes that connect to multiple communities
+kinetic tests on reporter cleavage
+52 kDa
+6 hr
+the patient's legal guardian
+6 × His-tag
+HRV-C
+mTOR
+propidium iodide
+24 h post-transfection lysates
+respiratory protection
+sampling recruitment will be ceased
+ifnlr1 cDNA
+leaf disks
+our alignment model
+immune signalling pathways
+Tulathromycin
+Fig
+0.5%
+RNA interference
+serine threonine
+Student's t test
+1 hr
+2
+ADV replication
+EBOV and VSV
+ZBP1
+Chronic kidney disease
+twelve
+medical-legal
+B-cell expansion
+141
+IFN antagonists
+cell type
+16 days
+Classical ecology
+the role of human mobility
+31
+low
+MATLAB
+SLAC
+2006
+Ensembl Biomart tool
+cysteine-glutathione disulfide
+worse
+24
+BALF cellularity
+PCR products
+43:1
+monomers
+non-labile
+type and polarity of the genomic nucleic acid
+two metagenomics tools
+97.83%
+Underground spaces
+partially RNase and protease insensitive
+cachexia
+Palmitic acid
+USP11
+binding to CAP256 UCA Ab
+IL-6
+EBV
+different effectiveness, associated costs, payoff structures and time scales
+Thirteen
+Sixteen
+obesity
+Programmed ribosomal frameshifting
+mutation
+influenza-specific CD8 + T-cells
+Thermo Scientific HyClone
+muscle protein metabolism
+H4N6 and H6N2
+nine
+Bangladesh
+Electrical impedance tomography
+potential natural or plant products
+Usp44 null mice
+VACV and HCMV
+negativity
+Quick-ligation kit
+41
+sensory nerve dysfunction, Friedreich's ataxia and Alzheimer's disease
+aphid species
+Chest
+type III IFNs
+T cell polarization
+data on ILI
+family and friends
+acute CHIKV infection
+Computational methods
+exposes its membrane lytic protein
+intraepithelial DCs
+two
+Africa
+internal ribosomal entry sites
+a perfect correlation
+232
+REMD simulations
+Frozen hydrated virus
+Four
+spleen and liver
+ubiquitination of proteins
+millimetres
+Coronary artery lesions
+DM
+bacteria
+a clinical algorithm
+productive infection
+75%
+Ingenuity IPA
+inducing Th1biased cellular responses
+C, C++, Java, and Matlab
+cytosolic components
+three
+47
+2009-12-17
+drug discovery
+unsaturated fatty acids
+gyrase
+2%
+intrinsic connectedness
+Enteric and respiratory diseases
+First strand cDNA
+aberrant
+segmented individuals
+3 days
+mitochondrial dysfunctions
+macaques
+coupled models
+1 week
+Linearized DNA
+the script used to calculate weighted averages of multiple effect sizes
+microRNAs
+ceftobiprole
+NaCl and 6% polyethylene glycol
+chemical synthesis
+alpha-omega complementation
+level of infection and wing hyphae score
+H1N1
+22.75%
+Gag-Pol polyprotein
+F10-like IgG titers
+19
+11
+163
+GPS Explorer 3.5
+Southbound voyages
+English and Chinese
+biacore data
+Sufficient information
+Nishiura, Hiroshi
+liver
+bicinchoninic acid -based protein assay
+restriction of virion release
+Galectin-3
+450 mT/m
+Jamaican fruit bats
+housekeeping genes
+Predictive
+regulating this synergistic induction
+viral loads
+hamsters
+slightly skewed
+White arrows
+7% to 30%
+10
+541
+1.15 days
+more than half
+fever, myalgia and headache
+G120A substitution
+39
+1881
+mutation of three codons under purifying selection
+RIG-I signaling
+High replication efficiency, broad tissue tropism and systemic replication
+Human mobility
+lactate dehydrogenase
+hemagglutinin and neuraminidase
+planning mitigation strategies for future pandemics
+472 nucleotides
+to provide comparable datasets and access rules to share data
+483
+autophagy and apoptosis
+500
+they will rush them to the hospital
+increased surveillance
+Eastern Cape
+A RNA structure
+Method 2
+PRINCE
+CM doctors
+viruses circulating in the Yangtze River Delta region
+GAPDH mRNA
+more complex conditions existed
+the number of sequences that contained a given predicted TM segment
+variably
+a functional inhibition of IFN-induced STAT activation and gene expression
+polyclonal goat antibody
+240.4 pg/mL
+normal
+R61A
+increased levels of collagen
+>90%
+rVV-N25 immunization
+specific culture inserts
+NOF Co.
+other relevant specimen types
+Porcine epidemic diarrhea virus
+30: 1
+13%
+twice a week
+Mon, Di, Ba and Fun clades
+human phenotypes
+Amentoflavone
+proteasome inhibition
+two
+to report the amount of RCA product fluorescently
+10%
+zero
+lack of awareness
+V x : V y
+2 weeks
+decrease antimicrobial prescribing and improve patient and pet owner satisfaction
+pBB-LEH
+chemokine and migration receptors
+replication
+Six
+correlation analysis
+12-month
+60 minutes
+Respiratory Syncytial Virus
+reduce levels of LDL-cholesterol and improve the inflammatory changes
+SAA and haptoglobin
+differential transition state energy barriers
+Pneumonia
+60 kDa
+antigen-specific T cell, B cell, and antibody responses
+DFMO
+40 min
+epidemiological
+Theoretical and experimental techniques
+β-actin
+loss of a repeat
+loops
+Clinical research associates
+numbers and percentages
+multiple
+NO synthase 54
+virus replication
+twice
+moderate
+IFIT-1 mRNA expression
+High minute ventilation
+immunogen-specific IgG
+to minimize de novo lipogenesis
+HPV, HSV and HIV
+Gene Set Enrichment Analysis
+14 dpi
+Erythrocyte invasion
+300 mL
+Student's t test
+natural reassortment
+Organ transplantation
+Begomovirus mutant spectra heterogeneity
+Human rhinoviruses
+leukocytes and edema-related protein
+Two 20 ml aliquots of PBS
+lipid-lowering statins, antibiotics, and anti-cancer drugs
+proinflammatory
+Spain
+Q
+nuclear localization
+<2 W
+nuclear matrix proteins
+Five
+good performances
+clathrin-dynamin endocytosis
+fever, diarrhea, and flu-like disease
+All the data obtained
+atomic bomb
+reducing gene flow at the level of the compatibility filter
+whole bacteria
+95%
+network visualisation of gene-metabolites relationships
+52
+genes up-regulated in infected larvae
+to maintain lymphoid homeostasis
+CaCl 2
+NOS-1
+their assembly
+barrier function
+orthologous
+Orthomyxoviridae
+SVQYH-PLA
+mathematical modeling
+transparent melting glue
+heterologous viral vectors and/or unrealistic dosing regimes
+simple models
+443
+53%
+bivalent vaccine antigen
+MHV-68
+influences HN's dimerization and its activation of F
+7.0 per 100 PY
+6h post-infection
+hippocampal abnormalities
+clusters of individuals with extreme TNF-a protein expression
+Penicillium purpurogenum Li-3
+no or weak external selection pressure
+10%
+age
+discrete syncytia
+randomly partitioning the alignment into equal sized subsamples
+T-001 and T-016
+accuracy of physicians' decisions
+long-lived antibody and memory T cell responses
+pSmad3
+large-scale protein production and antibody screening
+venovenous and venoarterial
+e ijk
+Select patient and standard DBS-RNA
+Renin-angiotensin
+5 min
+G
+IRs to drugs
+the positivity
+cell-selective pathogenesis
+mitigating the influence of the influenza virus
+long incubation period
+A/H1N1pdm09
+Age
+12
+72°C
+human factors
+Traumatic SCI
+clinical disease and macrophage infiltration
+T3SA+
+107
+Hospitalization
+PB1 and PB2
+entry border points
+PaBV-4
+a list of the most similar sequences stored in the DB
+clinical treatment
+5-10 min
+HMGB1-induced TLR4 signaling
+controls
+The stent wire
+intestinal mucosa
+infecting plants
+five
+15.8%
+external validity of previous findings
+type I IFN signaling
+inflammatory
+directly inactivate HSV-1 particles
+diagnosed patients with infectious diseases
+Health Commission of the People’s Republic of China
+Ventilator-associated pneumonia
+intact
+nonimmunocompromised
+676 amino acids long
+DisCVR
+high numbers of vaccines
+contact tracing
+ROS and iNOS
+The elderly, young children, pregnant women, and those with underlying medical conditions
+activity change comparison plots
+inhibition of viral RNA-dependent RNA
+non-enveloped, positive and single-stranded RNA viruses
+cyclin A protein expression
+increasing land-use, urbanization and climate change
+reverse genetics method
+JAK-STAT
+NMDA receptors
+The effect of a delay in each tracing step
+dependencies between opposite loops and stems
+Aldosterone
+healthy donors do not produce spontaneous sputum
+two
+Georeferenced environmental data
+Sixty six
+CC genomes
+Ad-infected mice
+390,650
+serious ARI
+infectious cDNA clones
+Borna disease virus
+13,321
+cell proliferation
+nine
+contact network models
+a node pair
+nanS
+Logistic regression modeling
+organic molecules
+ECO
+Ded1p
+one third
+anchoring the progeny virions to the cell
+Fourier decomposition theorem
+Lightning-Link HRP Conjugation Kit
+tobacco smoking
+7 cases per 100,000 individuals
+transcriptional
+eight
+99%
+illness
+differences in fluorescent intensity
+vectors containing His-tag or GST-tag
+30
+rheumatoid arthritis, amyloid dementia and cancer
+Clostridium botulinum
+platelet-derived growth factor α
+cAR1
+FACS
+inflammatory cells
+Eurosurveillance
+460 nm
+Canine parvovirus enteritis
+nonparametric
+destruction of ecological integrity
+Eighteen
+antirenalase monoclonal antibodies
+IMT
+oral
+intronless
+a bacteriophage
+Gentra Puregene Kit
+Huangshan
+5 weeks
+Virus infection
+wells of a chamber slide
+antibiotic therapy
+insect and bat behavioural ecology
+skin lesions
+enteric
+new therapeutic targets for neurodegenerative diseases
+immunofluorescence staining
+Several pathogens
+Guanidine
+every second day
+Clone Manager Professional v 9.3
+bleach
+endogenous naïve and activated CD8 + T cells
+coloric method of Kean
+RepeatMasker
+three
+HeLa
+10%
+translocates to the plasma membrane
+prevention of HIV infection
+Apaf1 IRES
+Tlr22
+several outbreaks
+destroy
+MELD-Na
+293T cells
+twice
+CHOP-induced apoptosis
+Thirty-five
+MEK1 and MEK2
+54.5-83.3%
+6770
+Vamp2
+three
+natural vertical transmission
+30
+two
+inflammatory cellular responses
+pollution
+Gut
+information on bacterial species/ strains, antibiotic resistance, or nonbacterial pathogens
+5%
+PfEBA-140
+NTMIs
+Henrietta Isabella Thurburn
+levels of inflammatory cytokines
+violence
+their behaviour
+IFN stimulation
+analytical
+two
+a regulator of complement cascade
+tuberculosis and meningococcal disease
+sodium ingestion
+increased expression of Hsp70
+phylogenetic
+213
+health concerns
+Bacteriocins
+rhinovirus
+HLA-A*02:01
+electric field gradient
+Induces focal adhesion
+respiratory illness surveillance
+amino acid differences at the receptor binding site
+1-34 g/mL
+huge amounts of enzyme secreted
+The proper selection of important interacting residues
+Potyviridae
+Illegal gutter oils
+Prof Deborah J. Lenschow
+proteasome α-4
+pneumonia
+1,677
+lack of dystrophin protein
+87.41-94.50%
+10 min at 72 C
+neutrophils
+reduced response to drug and motor complications
+14.4 days
+less than 10%
+malachite green aptamer
+worm counts
+aerosols
+TPM
+Tick-borne encephalitis virus
+X-bridge Amide column
+baroreceptors
+48h
+higher antibody levels
+20%
+dendritic cells
+truncated power law
+four
+seasonality
+CellC software
+Norway
+nsP2 and nsP4
+identification of new therapeutic targets
+Inflammasome activation
+broad-spectrum antibiotics plus voriconazole
+8
+linearity and sensitivity
+1
+decrease
+resilience training, contemplative practices, and peer support
+4
+eIF4E
+Figure 9
+Over 2,500
+structural
+advanced cirrhosis
+Nine
+Pam 2 Cys
+83%
+50 mm
+T7-DVG 546
+necrotic-ulcerative
+pulmonary exudation and consolidation regions
+2010
+elimination, equilibrium, and escape
+Empty vector transfection samples
+large-scale sequence analysis
+ACE2
+phosphonoacetic acid
+CXCL6
+day 8 post-infection
+dose response kinetics
+real-life epidemic investigations
+it can search for terms
+geometric mean antibody titers
+Specimens for histopathologic examination
+at or near the start of the repeats
+DQ485230
+BD FACS Aria III
+Tulathromycin
+5%
+1.5 g every 8 hours
+caspase-8 cleavage site prediction
+3 days
+after adjustment on the type of positive antibody
+52
+potential toxicities
+ImageJ 1.41
+older individuals and sometimes the very young
+F1-V protein
+2-year
+Short interfering dsRNAs
+foreign glycoproteins
+88.9%
+average and standard deviations
+Grafit 3.0-Grafit 5.0
+March 20, 2020
+36 weeks gestation
+RNaseL
+Malachite green-based assay
+endothelial cell tube formation
+Solid black line
+proteasome activity
+bacterial and viral infections
+the start of the 59 arm of stem 29
+Physiological scores
+overexpression of human PKR
+n i
+commonly observed traits in cardiac and renal pathologies
+host cell amino acids
+Imbalance
+53%
+one-way analysis of variance
+fission yeast
+Akira Ishihama
+5.65%
+the existence or absence of a social dilemma
+1 mM azide
+Sarcoplasmic reticulum
+active endosomal acidification
+Dual-Luciferase Reporter Assay System
+coronary artery lesions formation
+fold-C ave
+structured
+Lyon, France
+12-24 hr
+viral RNA synthesis
+White-tailed deer
+deterministic center manifold theory
+Xpert assay
+4 hours
+1%
+statistical method
+Ceftriaxone and clotrimazole
+supplemented brain heart infusion broth
+C-strain Riems
+Seven
+AorTech International
+Parsonnet Lab
+following inhibition of complex III
+Caspase
+observed data and R 0 inference
+basic processes essential to the virus life cycle
+87
+34
+NADPH oxidases and mitochondria
+myocarditis
+5000
+D-Se
+APCs
+deISGylase activity
+a claims data source
+Pneumococcal
+individual rights
+65°C
+387
+8200
+Beta-hydroxy-beta-methylbutyrate
+31st
+mutations in the E2 protein gene of enzootic
+two
+2
+ABI7500
+Acute Respiratory Distress Syndrome
+GeneAmp RNA PCR kit
+Tyr254
+0.35 s
+2.2%
+two
+few
+different targeting mechanisms are in operation
+Colistin
+Microscopy
+its prospective design
+innate lymphoid cells and lymphocytes
+Group A rotavirus
+Dysesthesias and peripheral paresthesias
+France
+Donor chimerism
+1959
+antibody production and purification
+NS1
+30%
+functional antibodies
+gene overlaps and protein multi-functionality
+HPRT
+the product of the separate dimension dissimilarities
+Delaunay tessellation
+confocal
+location allocation model
+water permeability
+non-immunized cows
+1% to 30%
+macaques
+VacA mediated-apoptosis
+56
+Three
+more than a decade
+mice
+statistical basis
+65 to 86%
+ic Virus
+animals will then either be passively immune or susceptible
+PI3K
+normal
+CHBAH
+f
+health care associated pneumonia
+Contact between humans and animals
+Five
+More than 11,000
+K125
+Ebola
+12 hours
+Programmed death -1
+Prism 5
+PEDV infection
+lung, liver, and spleen tissues
+9.8 K/mL
+hyperplasia
+89,856
+40%
+temperature ≥100.4°F
+TCs sensitivity to treatment with multifunctional cytokines or signal pathway inhibitors
+higher-order epistasis
+12 hours
+pathogen-associated molecular patterns
+CXCL2
+reversed the protection against H/R injury
+IL-4
+insufficient information about its construction and original item pool
+more protein abundance in T0 or 8 h versus baseline
+good
+159
+multi-looked image
+long lasting
+0.107-0.124
+Opa proteins
+DockTope 17
+at least yearly
+serious AEs and new-onset chronic medical conditions
+a coarse level view of unfolding events
+trans infection of HIV-1 in vitro
+Hepatitis C virus infection
+plasminogen
+minimize animal suffering
+anti-factor IX monoclonal antibody
+a heritable antiviral defence mechanism
+cell monolayer permeability
+one nurse to 1251 population
+prior knowledge of the genes
+2014
+natural SHFV reservoirs
+cap-dependent
+transmission dynamics
+infectious diseases
+10 μL of 10% CHAPSO
+five
+H7N9 infection
+Dkk3a
+NEBNext rRNA Depletion Kit
+4.58 days
+Node color gradient
+30 min
+Silent infection
+H4 and H6
+high titre stocks
+protein-sufficient
+730,000-1,151,000 N/m
+cytokine polarization and the expansion of Th17 cells
+two
+Thirty
+RIG-I RD
+the microtubule-organizing centre
+microvascular
+reduced expression of the total glycoprotein complex
+NS1, NS2 and NS3/NS3a
+Mary O'Riordan
+high inflammatory responses
+myelinated fibre diameter in cortical WM increased with age
+Differentiation between severe pulmonary oedema and ARDS
+May 17, 2009
+regulates the secretion of IL-1b
+fostering global health
+herpesvirus consensus PCR
+polyubiquitylation
+Burst size of infected cells
+urbanization
+six
+1-100 nm
+The alignment shown in Supplementary Table 1
+Deviance Information Criterion 36
+Clinical history and hospital admission dates
+Repetitive sequences
+one
+vaccination alone
+SINV genomes
+First-strand cDNA
+six
+less than 0.07 EU/mL
+.50%
+131
+four
+neutrophil and eosinophil binding to epithelial cells
+the observed frequency of the dinucleotide XY
+-80°C
+GraphPad Prism 5
+IFN-I signaling
+NDM-1
+20% to 30%
+RCSB Protein Data bank
+30-64 years
+twelve
+haplo-insufficiency
+histone H2B
+Ub1
+π and e
+one-step multigene metabolic engineering
+syndromic surveillance
+migratory birds
+disease severity
+t1
+superspreades
+redundant recognition of a single SG
+risky
+Phylogenetic analysis
+95%
+Up to 10
+sex, age, current marital status, highest educational qualifications, and ethnicity
+85-89 years
+I. Mechnikov
+PPXY
+Fibrillarin
+obvious motor deficits were present
+non-Dutch airlines
+Public health surveillance data
+2 µg/ml of puromycin
+ISG49, ISG54, and ISG56
+ribavirin and 5-fluorouracil
+preliminary
+antidiabetic
+an IFN-stimulated response element
+Adenovirus
+New technologies
+Amoeba
+differences in population-level attack rates decrease
+Iba1 and GFP
+viral transmissibility and replication in different host species
+serum-derived bovine immunoglobulin/protein isolate
+Trojan horses
+Expression and purification
+1147
+the x and y axes
+1 week
+magnetic streptavidin beads
+an efficient inflammatory response
+headache, fever, myalgia and fatigue
+MouseOx™ Pulse-oximeter infrared sensor collar clip
+thrombomodulin
+highly correlated sensor responses
+stabilizes heterologous protein production
+3
+performing statistics
+the functionality of these cells
+Homoplasy
+His-129, His-144, and Lys-173
+tamoxifen/clomiphene/ U18666a
+56
+3.2 µM
+Vimentin cDNA
+dihydroberberine and sunitinib
+68%
+CTNNB1 and CD44
+three
+C5AR1
+LASV GP
+cellular RNA degradation
+endogenous levels in plasma
+80
+Nucleotide second messengers
+PI4KB
+Y517
+neuroectodermal matrix cells
+mature and star miRNAs
+prepared protein structure
+Tymoviridae
+YFP-ZUFSP recruitment to DNA lesions
+Deoxyribonuclease
+delayed growth
+Analgesics
+Non-parametric
+2.5%
+1,250,000
+hepatocyte apoptosis
+Twenty-one
+amino acid
+Respiratory distress
+14
+titer
+three
+2 C-methylated compounds
+The demographic history of PPRV
+suboptimal host response
+Freeze-fracture
+oil extraction and chromatography
+faster
+oriRNA
+DC-SIGNR
+progress
+500,000
+Nanoluciferase signal
+pre-exposure prophylaxis
+Solieria filiformis and Ecklonia arborea
+639
+35%
+38
+Further information on research design
+Dengue virus
+there will be too few synonymous positions for synplot2 to assess
+Trial site coordinators
+Neuroinflammation
+H. influenzae
+prevention and control
+2009
+200 bp
+60 days
+calves are very sensitive to LPS
+Six
+A, C, and D
+DNA polymerase III alpha
+The media
+Co-infected
+limited
+tubescanner
+activation of GRK2
+PCV2 Rep and Cap proteins
+5 days
+B 1 and B 2
+parameters for selection of vaccine strains
+autophagy
+controls
+impaired fibrinolytic activity
+Cells
+SnapGene
+diminished IFN-λ, α, γ and β responses
+6 h
+55
+significant differences in infectious virus
+C5a
+IAI
+CRL-2455
+nine
+cytolysis
+25°C
+76
+24%
+JEM-2200FS transmission electron microscope
+RNA
+abundance
+7-Amino-Actinomycin
+NM_021822 and NM_001097446
+30
+multilocus sequence typing
+the point where the linkage stem forms
+cross-border infections
+proprietary SMART technology
+54
+124
+U6
+treatment of CCHF
+reactivation of human herpesvirus-6
+Ags associated with micro-/nanoparticles
+H5N1 and H7N7
+k
+1,000-10,000
+rhMPV
+Recombinant HA vaccines
+100uC
+the value of a year of life
+Over one fifth
+Reverse transcriptase-polymerase chain reaction
+Neuroblastoma
+MSMS protein sequence identification and future quantitative prospective MRM or antibodybased validation
+bloodstream and pneumonia
+X i
+nosocomial transmission
+maturing vesicles transitioning from early to late endosomes
+a dimer
+protocol
+HeSCs
+viruses with the avian-like residue
+health-evidence.ca registry
+S/B >3
+XPG and ERCC4
+117
+major histocompatibility complex
+Ifitm2
+phytochemical
+red
+ILI consultation rates
+STAT1 protein
+two complementary approaches
+quinine
+79,656
+ten times
+age
+LTβR −/− cells
+EM
+optimal collection and laboratory conditions
+Detectable antibody responses
+TLR signaling
+July
+immunological activities
+HFNC gas flow and patient inspiratory flow
+diagnosis and hospitalization
+ovarian cancer
+mass vaccination
+terrestrial
+presence/absence of indicated treatment
+3 of 506
+90%
+MEME
+participants' influenza infections
+Breseq and SNVer
+primary
+enhancer RNA
+ZLL
+d36-42
+1,170,000
+cysteine peptidases
+admissions data
+Pneumocystis jirovecii pneumonia
+two
+A40 and A41
+the starting location of a simulated epidemic
+IGF-1R
+in vitro, in vivo and clinical trials
+D b NP 366
+sputum-smear negativity
+whether docking is sampling sufficiently
+an influx of neutrophils
+23
+NK cells
+M180 and K243
+ppGalNAc-T2
+Deprotonation of the His37 tetrad
+potential connections
+157
+pharmacovigilance activities and aRMMs
+Luciferase expression
+packing in coiled-coil structures
+permission directly from the copyright holder
+24 hours
+alternative antiviral strategies
+Ten mL
+controlling infection after lethal challenge
+spectrophotometrically
+20%
+89
+1 h
+80 cfu/m 3
+reduce risk
+14Á8%
+mature NK cells
+Logistic regression
+two
+exacerbations
+A pool from all fractions of the gel filtration step in buffer C
+α5-integrin maturation
+20
+systematic, quantitative
+RPS25 and RPS5
+1
+move out of nucleus
+berberine and emodin
+whether T cell cross-reactivity is mostly a stochastic phenomenon
+ammonia
+four
+100%
+Bovine respiratory disease
+100% lethal infection
+by adjusting its pathways of escape
+Minkowski distance
+Kimura model
+12.0 days
+incident-light fluorescence and confocal microscopy
+between 16 and 38%
+SDDV
+Nuclear-targeted eGFP
+tri-antennary structures
+their enrolment status
+CcAstV
+Twenty-two
+false alarms
+Temporal data
+clotting factors
+polyphosphate kinase
+Shanghai Synchrotron Radiation Facility beamline BL18U1
+nonsense-mediated
+1200 bpm
+296
+Ecological and evolutionary theories
+aa-tRNA slippage
+Ext-KpnI et Ext-BamHI
+suicide prevention activities
+molecular
+106
+OmpB
+DENV infection
+chromosomal epigenetic modi fi cations
+MR766 and PR209
+Spn4A.RRLL and PF-429242
+10%
+18
+10,080
+non-coding regions
+ROS
+viral infection
+viremia
+GT-1a
+to monitor the variation in the process
+15 min
+52,293
+experimental data
+NeuN
+25.8%
+cancer growth
+10 copies/µl
+influenza virus infection
+45
+lack of awareness or recall bias
+molecular mimicry
+VSV-EBOV
+June 2012
+97.5%
+Relative mRNA accumulations in cells harvested at 24 h
+DNA microarrays
+24 h
+Screening
+distributed memory implementation
+Sixty-four
+Dr. Kevan Hartshorn
+HGF
+pre-processed ligand binding sites
+global climate change
+younger individuals
+172
+Dex
+5.74610 -6 M
+PVR body mass
+flow cytometry
+3% BSA
+23
+63%
+Zauberkugel
+NF-κB siRNA
+viral loads
+RNA Mfold
+12 hours
+137
+three
+hematoxylin-eosin
+rational and peaceful
+Electron
+catalytic cycle
+4%
+host genotype-specific responses
+FastTree v2.1.7
+Ultraviolet germicidal
+15 days
+Cis-splicing
+anachronistic diagnosis
+high-throughput sequencing approaches
+new tools
+cap-dependent mechanism
+Small non-coding RNAs
+pEF-GFP vector group and untransfection groups
+H5N1 neuraminidase activity
+24 h
+True Blue chromogenic substrate
+Cell proliferation
+PCNA or the viral DNA polymerase accessory factor UL44
+128 ng/ml
+t-test
+η
+TRAF6
+infiltrated inflammatory cells
+FastDNA spin kit
+Eclampsia
+ISG15
+Aspiration of the pathogenic gram-positive and gram-negative bacteria
+additional lateral forces or additional stiffness
+meta-CATS
+issuing a new plan
+239
+Genotypes and Phenotypes repository
+cc-by
+Reassortment
+Geneious assembler
+887
+genome copy titers
+PvuII site
+kusagin or verbascoside
+transient
+interpretation of the results
+Leishmania infantum
+serogroup A meningococcal disease
+real-time PCR
+BALB/c mice
+peptide dens25
+Astellas Pharma Inc.
+anti-trypanosomal
+Habitat
+previously described procedures
+Images from each hybridization
+biotinylated goat anti-mouse IgG
+lytic genes
+sodium
+Weibull distribution model
+cytoplasm
+bone length between the tibia plane and ankle part
+2
+H5-immobilized magnetic beads
+RNA1, RNA2 and RNA3
+Havcr1
+NH 2
+SPSS
+polyvinylidene fluoride filters
+Sveriges Radio
+more complete phylogenies
+25%
+large volumes of crystalloids
+enthalpy-entropy
+glutaraldehyde
+mapping the rural-urban transition
+milk yield, milk gross composition and udder morphology
+2%
+protoplast transformation of H. jecorina QM9414
+analysis of available data and literature
+severe clinical signs
+high quality
+HCV pseudoparticles
+stable
+WT mice
+Twenty
+1M Tris HCl pH 9.2
+EndNote
+1.3 to 13%
+100% susceptible
+Quantification of MOG immunoreactivity
+ImageStream system
+Slow waves
+781,000
+when the virus infects closely related hosts
+proinflammatory
+guinea pigs
+injection of type I IFN
+Written informed consents
+outcome
+proteomic heterogeneity
+three
+A drug module
+OR
+2 M HCl
+adenovirusmediated gene transfer
+Genome sequence data
+11
+36
+increases
+prevalence of high psychological distress
+Mannose-binding lectin
+sum of the elements m j=1 h j = 1
+purity
+355 kb
+AMBER score 11
+stem formation
+sap
+initiate age-dependent cell apoptotic processes
+chikungunyaassociated arthritis
+31,442 bp
+recognition of the stop-start motif
+3
+residue
+vertebrates
+2016-07-01
+machine learning
+case reports or retrospective studies
+Lack of quality dose/concentration response data
+Trypanosoma brucei rhodesiense
+fever, headache, visual and motor skill dysfunction
+early onset of respiratory insufficiency in adulthood
+innate effector cells
+kindergartens
+seven
+mild to severe
+dysbiosis
+positive, increasing, and concave
+six
+non-invasive mechanical ventilation
+CEO birds
+C ¼ 6:1
+tentative consensus
+PERK
+11
+RIG-I
+a disease or a disease concept
+remarkably
+Human BALF
+Management of patients on mechanical ventilators
+UPR or apoptosis
+Eighty-six
+glycolipid-associated a2,3-terminal SA
+peramivir
+Annual cycles
+Ly294002
+Blood
+Data
+eight
+once every hour
+rabbit reticulocyte lysates
+RNA
+8 h
+GENIE3
+Angiotensin-converting enzyme 2
+components of the nuclear transport machinery
+Lung capillary filtration coefficient
+Benjamini-Hochberg
+Acetylation
+phosphorylated
+RTIs
+acute respiratory illness
+IFN-γ production by T cells
+prevention and control of disease
+vagal reflex
+TW MRSA
+26%
+reac- tive oxygen species
+Crisis-affected community engagement
+0.3%
+the product will be replaced
+Translation
+GloGerm
+Registering both infarcts and interventions
+eIF2α
+2
+90 mM, 15 mM, 3 mM
+SOX2 expression in BCC tissues and cell lines
+Leica DMi8
+four
+FDA-Approved Drugs Bactericidal
+its reliability
+72
+HIV-1 sequence evolution
+7,070
+Australia
+real-time computation
+lung and blood DEG
+Enfuvirtide
+resazurin metabolism assay
+Mx activity
+PPE
+Extracted DNA from the buccal swabs
+persistent inflammation-immunosuppression and catabolism syndrome
+Confusion
+Electrophoresis on a 1% agarose gel
+multibasic cleavage sequence
+on request
+90 minutes
+direct evidence of HEV zoonotic infection
+GraphPad Prism 7
+Argentina
+1.4%
+an NdeI and an XhoI cleavage site
+negligible
+severe disease pathologies
+intact
+vacuolization of individual or groups of cells
+lysosomal proteases
+4
+non-pathogenic bacteria and attenuated pathogen bacteria
+Figure 1B
+data availability
+anti-toxin
+hyperimmune sera
+airborne and droplet transmission could occur between animals
+3% PEG-6000
+10
+early, guideline-informed DOF administration in shock
+reversion occurs
+freezethaw
+RSV and Rhinovirus
+literature
+disease incidence data
+underdetermined
+exosomes
+90%
+Cleaned data from each site
+eqolisins
+Written informed consent
+EMAN2 software package 61
+peptidase activity
+87.8%
+480
+SAa2-3Gal
+Harvard Gene Therapy Initiative
+any bias toward ssDNA sequences
+12% SDS-PAGE
+total duration of infectiousness
+263
+NF-kB
+three
+Frozen LV sections
+human population, agricultural, climatological, and ecological measures
+Microsoft Excel
+parasite glycoproteins
+Thrombocytopenia
+Asia, Africa, and North America
+smaller lungs
+tracheal epithelial cells
+Primer Express
+HapMap
+Merck
+reasonable
+2-3%
+10 11
+conflicts of interest
+flavin cofactors
+6-12 month
+1.1%
+ZODCK Server
+37 • C
+w i
+4-7 log 10 FFU/g
+N-terminus of prM protein
+SupTOC-LPS-24h
+Peak heights for extracted ions
+8 dpi
+orally
+1 week
+activated macrophages and dendritic cells
+fitness of individuals
+a standard curve
+10 copies/reaction
+one-sixth
+EXOC4
+900-fold
+Hydrogen bond and salt-bridge interactions
+mouse models
+188
+dynamic light scattering particle size analyzer
+influenza virus infections in males and females
+reduce the final epidemic size
+TNF-a expression
+hematologic malignancies and in rheumatoid arthritis
+SheddomeDB
+agarose gel electrophoresis
+6A n
+6 g/day
+probability mass functions
+CD4+
+jump
+NAFLD and NASH
+strong inhibition of b-gal expression and less color formation
+Pathguide.org
+partial sequencing
+70%
+interact with RelAp43
+calculations need some manual oversight
+BCMA-specific CAR-T cells
+Background gene lists
+Adult flies and cells
+off-target effects
+separate samples
+54-164%
+eosin
+IL-1β and IL-8 release
+TNF and IL-10
+2% agarose gels
+June 23 2007
+Student's t-test
+CD151 nucleation at viral particle binding sites
+ten
+advanced mapping strategies
+15 min
+terms of higher orders
+80%
+human HP strains
+public health
+SPSS 17.0
+gold standard reference set
+those for which a single edge connects them
+cardiomyocytes
+23.000
+ELISA
+five
+The curves
+equation
+FIV
+field-based studies
+Public health
+cell apoptosis
+EDTA, sodium citrate or lithium heparin
+neuroprotective
+20 minutes
+1a and 1b
+Purified HRV-B14 and -A16 virus stocks
+overlapping genes
+VP4
+Vacuolating cytotoxin A
+internalisation of S. epidermidis
+unclear
+one
+IRAV
+a wide range of actors in a participa-tory process
+virus:cell binding
+clear alveoli without inflammatory cell infiltration
+induce IL-10 secretion
+568RU
+87
+lower
+ACK lysis buffer
+cells
+pathways involved in acute inflammation and innate immune response
+mild type II
+electron microscopy
+surrogate neutralization assay
+Those under 18 years
+similarity between evolutionary profiles
+recruitment of HDACs
+RSV or VSV
+2 days
+891
+PTBP1 binding
+The evolutionary rate of each gene and concatenated genome
+translesion DNA synthesis
+drug resistance
+15
+lethality
+Quantitative
+influenza C virus
+knock-out models
+course of infection
+infectivity would decrease
+IFN type I suppression
+>25%
+12 h
+Asp18Ala and Ile70Ala
+30 min
+infected cells
+Ebola Virus Disease
+CellQuest Pro
+CD4 and CD8 T cells
+stop codons
+Neutralizing activity
+intestinal barrier-related genes
+CAG
+seven
+H3N2 and seasonal H1N1
+it does not require thermal cyclers
+FLUAV
+Influenza-Induced Inflammation
+3 days
+serum
+endocytic
+pandemic influenza
+Secreted proteins
+5,013
+alveolar macrophages
+enhanced understanding of the burden of disease
+VeroE6 or LLC-MK cells
+an increase in both phenotypes
+ConSortß
+asthma and COPD exacerbations and the common cold
+Supportive
+CNS dysfunction
+most closely related
+X
+eight
+incubation period
+trained-group
+20,698
+Most enolases
+Alouatta pigra
+Colchicine
+NO production
+identification and management of risk
+reticuloendothelial system
+lungs
+large protein complexes
+Four
+electron
+μCT x-ray imaging
+CD9-targeting siRNAs
+313
+F-scores
+South Africa
+assign unique patient identity numbers automatically
+cellular pathways
+vaccination behavior of adults
+M. musculus and T. gondii
+female
+20 h
+6-year
+selective
+wind-speed, rain and temperature
+curcumin
+79%
+overall performances of a classifier
+HuNoV-specific IgY
+cc-by
+SeV iDVGs
+fecal-oral route
+phosphoserine-dependent
+53 %
+Hypoxia
+bind to DNA directly
+5 minutes
+14 or 29 days
+direct binding of this transcription factor to DNA upstream of several putative target genes
+enhanced
+75
+BAL fluid
+CRTCs
+28
+more than half
+one or two variables
+100
+antiviral agents
+223
+PA E377K M1
+case-record forms
+801 × 106/L
+collagen
+l 63
+daily
+implementing temporary quarantine measures
+March
+CNPase
+haematoxylin and eosin
+cellular glutamine and glutamate
+mental health literacy
+daily
+337
+4 mm biopsy punches
+DH5α
+1952
+33
+influenza A viruses
+the third premise of the presumed consent argument
+over ten thousand
+12
+PLA2G16
+reduce or eliminate the incidence of specific diseases
+increasing disease emergence
+887
+18 years of age
+Human enterovirus 71
+untreated hBEC
+Further research
+The Consistency between Intersection and Union
+differ
+1.20 to 1.77 µm
+97%
+theoretical and experimental
+15
+flow cytometry
+cell supernatants
+Sigma
+Commercial kits
+bloodstream infection and pneumonia
+FRT-rpsL-neo
+>50%
+RNA structure
+E protein
+R i
+ID consults
+RT-qPCR
+it is most efficient to target the S patches only
+a family of controller proteins
+more rigorous inclusion and exclusion criteria
+degraded RNA molecules
+Epithelial cells
+Levy behavior
+intracellular virus particle yields
+probabilistic forecasts
+novel compounds
+ClustalW
+Sonication
+Anaemia
+p53 proteolysis
+March 11, 2020
+GlaxoSmithKline Biologicals S.A.
+default
+Linear epitope mapping
+decreased appetite
+TRIzol Reagent
+Platelet recovery time
+PEDV
+Sendai virus
+logistic regression
+a two-tailed Student's t-test
+20 ml
+over 60 years
+convection enhanced delivery
+IEDB population coverage prediction tool
+QuickGO user
+TiO 2 photocatalyst
+Mapping
+75%
+signal peptide
+Thirty-two
+cytoplasmic extracts following removal of replication complex membranes and nuclei
+patients who quickly improved upon antiviral treatment
+143
+108
+proinflammatory
+how uncomfortable
+SNARE complex assembly
+Hot spot analysis
+having data that point to where the needs for improvement exist
+7589
+10%
+Incomplete KD
+relative infection rates
+no cytopathic effect
+mean square
+LTA4 binding K565
+9 days
+LGAC
+increased cardiovascular expression of ACE2 and plasma Ang levels
+sequences of bona fide viruses
+wells coated with anti-human IgG or Gn
+uncontrolled hyperglycemia
+Pfold model
+56.6 kDa
+the ratio of the amount of Ub plus Ub2 over total Ub
+Incorporated EU
+20
+nucleotides +1 and +2
+Monte Carlo sampling of pose conformation
+progression of autoimmune disease
+2.06 Å
+vimentin solubility
+The observed distances
+1% deoxycholate
+infectious diseases
+TSEN54:p.Tyr119Glu
+western blot
+CO 2 gas
+1 and 2 days
+Health equity
+moral inspiration
+QseC
+lipoproteins
+usual principles of clinical ethics
+males and females
+Functional
+S. eriocheiris
+sinus mucosal organ cultures
+Est2p
+rRNA processing
+225 nM
+An immune cascade
+95%
+primary cultures derived from healthy cells
+avianlike
+21/100,000 persons
+phylogenetic
+27
+roach-allergic asthma
+50-90%
+100%
+Sepsis
+Innate immunity
+Percentages and 95% confidence intervals
+to provide the maximum concentration of chloroquine free base in the organic phase
+3 days after infection
+toxicity
+NTM, ARHGAP15 and ZEB2
+overt or subclinical disease
+Saudi Arabia
+stability of codon-anticodon interaction
+neuropsychiatric conditions
+indexed
+Genetic variation
+the time for the next alternating infusion
+standard gloves and 3 mask designs
+white
+Rab8
+three
+10%
+oligonucleotide adaptors
+neuronal activity
+Viral proteins
+CMC
+PRRSV replication
+five
+Adh1p
+Bio Med Central
+40%
+Lipofectamine TM 2000
+refractory persistent hypoxemia
+1 h
+mice
+fever, thrombocytopenia and leukopenia syndrome
+rapid degradation of the unstable PGH2
+baseline and emergent resistance variants
+Precision Antibody
+the N-terminal portion of the internal fusion loop
+the days by which all the animals died
+end-stage renal disease
+VEEV-induced apoptosis
+their own local-QTL
+50%
+conformational changes
+Biodistribution and persistence of DNA vaccines
+50%
+rhinitis
+increased SNA
+autophagy
+aMU
+8
+genes required for growth and differentiation
+Changbai Mountain
+3 weeks
+nonsynonymous substitution and synonymous substitution distances
+N-terminal 13aa region
+Binding of sH5 3
+2-3%
+nomenclature of FcR
+16 days
+phenotypic variance
+non-responders
+À12.5 to À10.6 kcal/mol
+33
+PXD008881
+discordant results
+Guillain-Barré syndrome and congenital microcephaly
+>80%
+Trim21 and Trim30
+transformation of the nuclear genome
+probability density function
+pgRNA encapsidation
+cardiovascular events
+every 4
+neurocognitive disorders and neurobehavioral deficits
+Lipinski rule-of-five
+Bliss independence model
+1.5 hours
+Kar2/Bip
+Ma5TE
+CLIR
+UCSF Interstitial Lung Disease Blood and Tissue Repository
+ssDNA PI
+phase-contrast
+45
+Hantavirus
+homologies to the putative epitope
+protein folding and secretion
+parameter inference and forecast of infectious diseases
+a technique aiming at detecting species-specific differences in a short region of DNA
+100% lethality
+Open surgical repair
+unclear
+a cold spot
+DMPG
+mediates nucleotide-binding and oligomerization
+Total cell lysate
+intrinsic stochastic fluctuations
+retroviral Env
+DMV formation
+the operators of the SSA is used
+a team approach
+Lamivudine
+nine
+sequencing error or intrahost diversification
+antigens
+MutS selectivity factor
+Implementation of diagnostics
+50%
+Transmissibility
+TBSV genomic RNA accumulation
+ribavirin, arbidol hydrochloride, and T-705
+arthropod-borne viruses
+nine
+taxa with morphologically indistinguishable eggs or oocysts
+A, B, D and E
+cross-correlation
+35,273.37 nM
+29
+LASV and ML29
+IAV NP
+2010 revisions to McDonald diagnostic criteria
+it requires interactions with the other species
+LPS
+11
+A 2 5 statistical design of experiment
+IL-1β
+Two hundred
+diarrhoea and faecal shedding
+country
+passage 4
+Lactate or sodium hydrate
+Mortality at 28 days and at 6 months
+cigarette smoking
+4%
+stability
+several fold
+EVPI
+people with direct or indirect exposure to swine
+> 10 5 nm 2
+Poor knowledge and skill
+Mobile phone call detail records
+negative colony effects
+Previous work
+Mycoplasma OTUs
+vimentin mRNA
+18 bp
+5%
+GAPDH
+0.1%
+their function
+cows and pigs
+Imatinib
+1949
+Immunohistochemical
+light microscopy
+IL-4
+Duct cells
+A fixed effects meta-analysis
+KAT2
+meticulous volume optimization
+larger antibody formats
+cell cycle arrest
+Scienti fi c Advisory Board
+Activation of caspase-9
+2009
+contact tracing information
+10% human serum
+Antibody-mediated enhancement
+labile intermediates
+Article 8
+TNF-α, IL-1β, and IL-6
+PAMs
+weighted networks
+limit of detection
+haplotype A
+47
+the area of MT in the jth sample
+estimates of individual connectivity and transmission of a directly transmitted pathogen
+MLV-infected B1 cells
+inside the nucleus
+40 min
+equilibrium in cytokine production
+t-test or Wilcoxon test
+60
+misclassification
+final candidate sequence
+between their residential patches and a common destination patch
+four
+emergence or destruction of the bistability
+cysts
+10 days
+isoflurane
+Fatty acid uptake
+9 days
+mineral-oil-spread
+PGE2
+potential differences in the degree to which specific viruses may influence these pathways
+MK-801
+The interactions predicted by cross-species conservation
+paclitaxel
+0.053
+subverts
+six months
+300 ns
+smaller LRT P-values
+Germany
+genomic DNA
+20
+10
+Intuition
+FiO 2
+Eco-social tipping points
+Immune/inflammation responses
+1
+Middle East respiratory syndrome
+sepsis and septic shock
+hepatocyte growth factor
+UVGI
+phloroglucinol units
+Appropriate anesthesia
+household intervention group assignment
+RVFV
+CD3-induced
+unsupervised hierarchical clustering
+hypothesis generating
+log-rank test
+Influenza
+Almeida-Filho
+by coach
+the choice of a drug target
+HA gene sequences
+Ni-NTA resin
+Neutralizing antibody response
+sugar residues
+Viral diarrhoea
+viral replication
+lysozymesensitive
+Excessive systemic TNF
+Genome cyclization
+ONO-6818
+Ten
+HPeV
+hypertension and atherogenesis
+infectious
+bicinchoninic acid protein assay
+text based examples
+Eurasian avian-like
+pYD-C235
+dynasore
+laboratory mouse
+Viral load
+pathogenicity of IBDV
+sub-population for whom risk beliefs are particularly low
+Anionic liposomes
+93.5-95.5%
+dsRNA regions and single-stranded RNA regions
+Random mutagenesis
+fungal aerosol sampling
+anti-plasmodial
+6
+146 selected variables
+AMR
+3-7 days
+substantial increases in plasma Ang- levels
+PLEX-ID
+nucleotide 2060
+a pool of all samples in the analysis
+viral clearance
+Autoregressive models
+NS1
+nine
+no difference in morphology between the right and left hemispheres
+exposure to LPS and hypoxia
+Intracellular
+dendrites and post-synaptic densities
+crucial physical terms
+diverse computational approaches
+three broadly neutralizing anti-HIV-1 antibodies
+outside lipid rafts
+to function adequately
+OAS1
+13,046
+Cell Profiler
+virus-contaminated objects
+1-3 million
+vibratome
+Gene Expression Omnibus
+linear regression
+DC-SIGNR VNTR
+cytopathic effect
+explicit household and school-based transmission
+western
+viral entry assay
+good
+953
+autopsic
+Three
+marrow aplasia
+12/61
+developing acute kidney injury
+future studies on the origin and function of enterovirus ROs
+ibalizumab
+40,430
+Accurate metrics for national epidemic and pandemic preparedness
+Detailed analyses of the locations of confirmed cases and their demographic and economic characteristics
+lack of precaution
+insects
+20% or more
+influenza or SARS
+TBP and YWHAZ
+oral swabs, anal swabs and blood
+viral protein 35
+bovine serum albumin
+Th e vector
+3 and 36 hpi
+EpiFlex
+2%
+3
+Ten
+accessing health care
+further work
+φ
+1,000
+DNAzyme
+calculate costs of a future intervention to prevent NiV
+cell proliferation and cellular redifferentiation
+The Database for Annotation, Visualization and Integrated Discovery version 6.8
+Department of Chest Diseases of Ege University Medical Faculty
+over half
+The amount of time elapsed since disease onset
+28 kDa
+dependent
+eRF1
+Margetuximab
+generation time
+IBM SPSS Statistics version 20
+inflammatory cell infiltrates
+4:1
+antigenic profile and reported in vivo efficacy as an animal vaccine
+Diagnostic test development
+52.2%
+western blot analysis
+overlay of c-di-GMP
+imaging probes of NSCLC
+DAD
+the corresponding author
+recombinant rVSV-VP1
+S. suis 2
+PB1 function
+systemic delivery to the central nervous system
+HRP-conjugated anti-human IgG antibody
+National plans
+invasion
+safety
+ISfinder
+5.0.1
+21 days
+Blood and serum samples
+Private disease-risk mitigation
+mild upper-airway diseases
+50-60%
+14 days
+natural
+less than 0.01
+DCs
+six
+growth promoting functions
+Quantitative
+77%
+increasing number of viral species they contain
+rapid and minimally invasive biomarkers of disease
+Temperature dependence of the inhibition constants
+antibodies from psittaciformes
+Rabbit anti-MBP antibodies and mouse anti-NF-H antibodies
+withdrawal of ongoing intensive care support
+p.Tyr67His
+FACS Diva Software
+12.3%
+165
+eosinophils
+between 20 and 30 years
+staphylocidal activity
+Group 1
+three
+inhibits the degradation of autophagosome
+syndromic
+ethics
+Model bias
+Four
+stem cells
+atypical antipsychotics
+Young adult and adult individuals
+its probability of replicating and producing progeny
+Bio Tool Kit
+five
+vector-insertion genotoxicity
+electrostatic interactions
+22 kDa-31 kDa
+Six weeks
+repetitive
+closed all live poultry trade markets
+Brazil
+18
+abbreviation
+Binding of the top three de novo derivatives to H1 site
+Bayes factor = 50
+no differences in the regulation
+by eye
+poor results
+uniform suppression of several innate immune parameters
+CD8 + T cells
+95%
+Three
+H1N1 strain
+4.13
+0.2
+δ 18 O
+2005
+Dorylaimia
+HA-8
+more rapid amplification
+unlinked
+Chinese herbal medicines
+Ecology
+Hexon positive cells
+24
+strong immunostimulatory activity
+8
+eight
+24 hpi
+90%
+propidium iodide
+JEOL JEM-1011 transmission electron microscope
+empirical measurements of distance and travel time
+threedimensional
+chromatin immunoprecipitation assay
+Signal transduction
+therapeutic failure and increased microbial resistance
+discirminaiton based on racial or ethnic origin
+bacterial pellet
+three
+HNF4a and HNF1
+Nuclear magnetic resonance spectroscopic
+Continuous bile flow
+Mutants of proISG15 and nairovirus OTUs
+Vb5.1/5.2
+BioLegend
+Fluorescence
+Maximum likelihood estimation procedures
+Cough
+Experiments that manipulate habitat
+very low
+270%
+primary injury
+in-depth proteomics studies
+creating a Master Cell Bank
+indirect immunofluorescence assay
+a clonal control
+infl uenza virus vaccine
+Bohle Iridovirus
+elevated
+France
+AutoDock parameter set-and distance-dependent dielectric functions
+28.8 h
+3
+CEP
+interventions
+1-day-old
+SuperScript IV reverse transcriptase with Oligo20 Primer
+peripheral residues
+none of the databases reviewed here requires strong passwords
+agent-based model
+825 children
+non-specific cross-reaction toward the other viruses
+Recombination between wild type virus and vaccine strains
+Twenty-four plaques
+PER1, PER2, CLOCK, and BMAL1
+counter-acting regulatory T cell activity
+65%
+Phylogenetic
+host anti-virus defense systems
+two
+differential immune responses
+PTN
+Eight
+Agilent human miRNA microarrays
+real-time surveillance of bacterial pathogens and foodborne disease
+release of intracellular IFNλ4
+owl monkeys
+P < 0.000001
+AmBisome and Abelcet
+outlying groups
+consultative
+The 4-nt bulge
+16
+NP and L CDS
+dissemination of the bacteria
+Arginine
+six
+pseudoknot
+host-microbe interactions
+more robust and reliable
+viral
+metagenomic
+2000
+Micro BCA protein assay kit
+24
+Twenty three
+The time evolution of the epidemic
+placental trophoblasts
+Deng Yiqun
+Fifty-two
+hepatic stellate cells or vascular endothelial cells
+148
+bone turnover markers
+55
+Bill and Melinda Gates Foundation
+Infectious disease outbreaks
+Apilimod
+Streptococcus pneumoniae
+viral strain
+IFN-c
+10
+CD4 or CD4bs-specific mAbs
+75%
+tris-phosphonium hexafluorophosphate
+marginal significance
+statistical algorithms
+Plasmodium knowlesi
+nucleotide changes
+a management perspec tive
+around 1000
+practical clinical use
+high degree of heterogeneity
+third microdomain
+its capacity to examine the effects of inhibitors on IAV entry
+macrophages and DCs
+daily
+2,700
+MGI
+Adequate preparation
+3DEM Loupe
+genotypes IV and II/III
+combination therapies
+27%
+Samples
+strains of JEV
+ten
+neutralization
+TLRs
+proteolytic cleavage of the ACE2 ectodomain
+The dimension of the polytope
+10
+5 mins
+the window of time for effectively applying control measures
+TLR, inflammasome and dectin signaling
+IBB-1
+allantoic fluid from mock-infected eggs
+every two days
+Spleen
+E Gn 3, AP-8 and AP-9
+nonconserved nucleotides
+11.7 T
+sialylated KS proteoglycan
+178
+antigens
+0.5 mg/mL
+substrate targets of viral proteinases
+site D1
+10%
+3.12 years
+2011-05-16
+12.7%
+SWI/SNF complex
+19
+an incumbent strain
+multifunctional
+prime T cells for the production of IFN-gamma
+mild to moderate
+BSSVS or a distanceinformed prior
+to guide further developments
+10%
+inflammatory cells
+Hospitalization history, previous antibacterial therapy, physical decline, and mechanical ventilation
+Palivizumab
+Inflammatory
+cathepsin C and Z
+LPS 10 ug/ml
+NADTs
+ImageJ
+HAstV
+Virus in imaging buffer
+double-precision arithmetics
+Purity and integrity of RNA
+immunomodulatory and proinflammatory responses
+dense smoke visualization
+13%
+enteric
+Biosafety concerns
+genotypes of mutant and wild-types
+778
+BCA kit
+sequencing quality
+immunocomplexes
+409
+2
+quantitative structure-activity relationships
+AI viruses
+cytoplasmic distribution
+its likelihood of being a genuine miRNA
+1-h
+IRF-3
+Four hundred nanograms of RNA template
+seed servers
+BiostaTGV 1
+4 hours
+three
+September 2012
+lack of full scientific certainty
+oxygen and steroids
+dsRNA
+poorly understood
+enterovirus RNA
+Cavernous
+Cross-reactive immune responses
+immune cells
+54%
+Homing endonucleases
+Total RNA
+good
+Influenza
+861
+intracellular cytokine staining
+NMR chemical shifts
+forward stepwise elimination
+50 nM pooled primer mixture and TaqMan PreAmp Master Mix
+0.1%
+Tat, Rev, and Nef
+intrinsic and innate pathways activated by foreign DNA
+Nakagawa Shinichi
+1
+internal distances
+inequality
+81
+196
+national security and national interests
+4%
+Ecological niche
+37°C
+National Institutes of Health
+aggressive tumor phenotypes
+Seal/H10N7
+alcoholbased
+hepatitis B surface antigen
+210 nm
+TMP/SMX
+Bafilomycin
+as 1 mm-thick layers
+NucZip
+Cell supernatants
+relatively modest
+systemic replication and neurotropism
+Proteases
+5
+subunit interactions
+functional mobility and partial dystrophin restoration in skeletal muscle
+necroptosis
+American Type Culture Collection
+below and above the diagonal
+48 hpi
+100%
+Functional avidity
+a functional PPXY domain
+134
+treatment facility
+GenBank
+intrahost CHIKV evolution
+10-20 ng/mL
+Oligonucleotides
+Internal mismatches
+10
+40 minutes
+Junwei Sun
+12%
+Beclin-1
+500 pg to 100 ng
+TCID 50 assay
+DNA library
+rapid induction of SOCS-3 expression
+high reliability of the assay
+CD4+ T cells
+Bond rotations or flexions
+acacetin
+dsRNA
+6
+200 µl diluted samples
+250 million
+technological, environmental, nutritional and internal
+ILI data
+immunity boosting
+a rapid investigation
+NIV-specific antibodies
+antibody fragments
+position 32
+Full length protein
+repopulation of the mouse liver with human hepatocytes
+phase separation
+uridylate
+Sigma-Aldrich
+Nuclei
+Understanding transcription factor mediated control of gene expression
+three
+ethanol
+>10%
+15 min
+Deletion of pbrB
+IL-12
+SBV infection
+24 h
+Nine
+acyclovir treatment
+new strategies for combating diabetes and other metabolic diseases
+IFN-β
+damaged cells and myelin debris
+effector T cells
+Samples
+89 Zr
+95.2%
+five
+January 2014 until June 2015
+Protein aggregates
+mitotically active basal keratinocytes
+vectorial
+Figure 3b
+NF-κB
+final concentration of 1 mM and 5 mM
+TCR/CD28
+10,000
+BTV-1
+vaccine perception
+ClustalW 24
+16 nm
+early pro-inflammatory responses
+three
+a random sample of residents in the village with the largest number of reported cases
+Formalin-inactivated JEV vaccine
+plasmid-driven
+early 2009
+three
+calciumdependent RNase activity
+BLASTN
+126/174
+Significance
+evidence of Ang/Tie involvement
+Patient 3
+NMIgG and NHIgG
+0.9
+country-specific time-Varying
+genome-wide
+proinflammatory
+IRF1-dependent
+intraspecific competition
+50-200 nm in diameter
+JEV
+2009
+CD73, CD90, CD105
+blood donors
+innate immune response and apoptosis
+a ratio of the estimates of animal to phenotypic variance
+oocyst excretion
+query structures
+more than 6000
+14 to 16 months
+binders
+28
+Network-based models
+AKT
+single-cell analyses
+undeniable
+fly cleaning
+the gel filter
+patients undergoing deep plexus or deep peripheral block
+South China Agriculture University Institutional Animal Care and Use Committee
+2009
+phenylalanine
+90%
+trend surface analysis
+insufficient inflammatory response
+autophagy
+Distinct Hsp70 isoforms
+financial
+28
+ammonium and glycine
+expert readers
+qPCR
+GM
+immunological response and wound healing activities
+434
+a platform for associating clustered gene expression data with specific cell types
+similar
+A minus RT control
+magnetic bead separation
+97.3%
+CD39, NPP and CD73
+excessive farm capacity
+a multifunctional protein
+automated Oases and PRICE assemblies
+twenty-five
+more than 50%
+C5aR
+InfluSim
+more potent proinflammatory
+many of the functions that have been demonstrated on other cells
+Eighteen-day-old
+trace homologues, and analyse evolutionary relationships
+All authors
+viral pellets
+antibiotics
+protein misfolding diseases
+5 min
+Viruses
+Stanford University IRB and the SCVMC IRB
+inflammatory
+ECP and EDN
+60%-90%
+cautious selection of appropriate patients
+ZS
+80%
+Socioeconomic factors
+8 August 2014
+nine
+driving pressure
+ϳ2 ml
+miRNAs
+E. coli LacZ gene
+Protein engineering
+cholestatic injury
+100%
+seven
+59.59%
+3 kcal/mol
+cryopreserved
+buffers under acidic conditions
+5.3%
+isopropanol
+increased mortality
+Impeding or evading the antiviral response
+Tarone-Ware test
+carbonated
+Antizyme
+Physicians
+endogenous kinases
+IFN-l3
+Eight
+1:1
+1977–1978
+D 2 DR/β-arrestin-2 interaction
+MALS
+parasite-released
+cell lysates and supernatants
+S 0
+s i
+post-transcriptional regulatory
+upon longer image exposure
+advanced warning of respiratory depression with fewer false alarms
+Normalized Shannon Entropy
+comparative threshold method
+a system to transport seriously ill or injured South Korean patients back to Korea
+decreased significantly and continuously
+Molecular characterization of measles virus
+reverse-transcriptase polymerase chain reaction
+airborne droplets
+287
+pigs
+quantitative real time polymerase chain reaction
+five
+diverse investigation processes
+Corsica
+expansion
+more-severe disease
+dementia and diabetes
+worse
+three
+1 hour
+one
+higher-level classification and standards activities
+microtitration infectivity assay
+low influenza vaccination rates
+72
+24
+180
+ds-RNA adducts
+PKR-dependent translation arrest
+Febrile status epilepticus
+6
+TS mutants
+revolt
+2 weeks
+50 to 60%
+80%
+HCV
+elastase-1
+CHMP6 and HDAC1
+acute respiratory distress syndrome
+Total RNA
+51
+longitudinal timing
+ParmEd
+recombinant human IL-13, -31 and -27
+active site titration assay, assembly assay and the dissociation assay
+mortality
+prophylaxis
+Supplementary Table S1
+cellular distress induced by viral infection
+A ratio of 1 : 9
+scanning and recognition of the AUG codon
+cell proliferation, migration, and morphogenesis
+NSP1
+monoclonal antibody clone 48
+P. alecto
+IL-18R
+anti-chicken IgY
+endothelial cells
+Illustra GFX PCR DNA and Gel Band Purification Kit
+BIPAP SB group
+IRF7
+Bayesian hierarchical logistic regression models
+PostgreSQL
+AT-9010
+Module Q
+36
+endosomal acidification
+non-TNBC breast cancer cells
+infections
+Image Studio software
+Vaccination
+gradually contaminated
+CO
+19
+seven
+27.34 μ M
+24 h
+laser scanning microscopy
+approximately
+a new collection of possible hosts
+differential degradation
+VSV-EBOV
+CDKN2C/p18
+0.01
+1,000
+solutions for population health
+serum-free medium
+domestic animals
+175
+extent
+1 mass
+Recombinant Inbred Strains
+Five
+258
+p.Tyr158His
+other individuals' choices
+100
+Climate change
+RNA structures that individually produce only small biological effects on virus replication
+down-regulation
+RMA+DABG algorithm
+an increasing trend
+direct binding of CBF1 to promoter sites
+628.286187.88 copies/ng DNA
+they suspected few people noticed it
+sepsis
+epithelium, vascular or interstitial components
+f 7 and f 8
+Eubank model
+Group 2d-1
+Newcastle disease virus
+17 days
+stainless steel
+relevance, significance, and utility
+Standprecision scoring function
+50
+systemic
+STATA statistical software
+it might reflect differences between categories in the alignment depth per gene
+single particle optical sensing
+w pq~c czb pq À Á
+two
+Bacterial clearance mechanisms
+late endosomes and lysosomes
+3= on the last ribose
+Institutional Animal Care and Use Committee
+cellular response to the infection
+Twelve
+adaptive immunity
+PFTs
+ancestral
+Associations with diseases caused by intracellular pathogens
+bacteriophage
+condom use or HIV prevalence
+extracellular ATP
+1.9 %
+Dexamethasone
+twice daily
+uPAR, gC1qR and cytokeratin-1
+stimulate myelin uptake
+early August 2014
+48%
+284
+astrocyte and microglia cells
+local compliance variation
+Saliva
+its ER-specific distribution
+alveolar
+interferon-γ and interleukin-12
+radio, bicycle, mobile phone, light source, television, and refrigerator
+55
+fluorescence
+80
+demographic, clinical, and outcome data
+overestimates
+6
+ribavirin
+protective
+Denmark
+heterologous
+a plasmid encoding the T7 RNA polymerase
+Biotinylated anti-Rabbit IgG
+4
+serial lumbar punctures
+ECG-grade emery paper
+epidemiological
+5= phosphorylated RNAs
+29
+more accelerated liver fibrosis progression
+Patients from rural areas
+cellular uptake
+asymmetrical
+mild EV cases
+end-matured
+multi-well spectrophotometer
+Lipoid
+120,000
+Student's t test
+lysis of cells
+Dual-Luciferase Reporter Assay System kit
+629
+IFIT1
+a role in maintaining the basement membrane
+millions
+UDP glycosyltransferase
+age or number of years
+10 days
+24,000
+the underlying process of disease transmission
+MyD88 and IRAK1 expression
+100
+ϳ11%
+cell growth
+19-year-old
+RNeasy Mini kit
+Many stakeholders
+∆E3 structure
+dasatinib
+clear viral particles
+CMV viral loads
+the Regulator
+n
+Albany and Madang
+consistent with the observation of clinical signs
+H1N1 infection
+p6 gag
+mediation
+acquaintance immunization
+SB, RK, ES and WH
+immune response
+five
+heterogeneity
+iVAX platform
+eight
+CRF01_AE subtype
+absorbance
+pro-inflammatory
+per minute of each type of breathing cycle
+endocytosis
+five-day
+Expelled secretions
+Free radical damage
+1.5 to 2.8 mM
+Pico Input Mammalian
+polypeptides of the expected molecular weight
+4%
+>30 days and ≤12 months
+Sera from pcDNA3.1 injected fish
+IRB ethical
+a signal peptide
+CCR2 molecule
+Hopf bifurcation
+Seven
+90.8-94.6%
+Antigenic shift
+14 dpi
+chemiluminescent substrate reagent
+persistently infected tick cells
+potential important functions that miRNAs have in host and pathogen interactions
+nsP2 and nsP3
+meta position for the addition reaction
+hybrid capture assays
+\0.05
+mucosal and keratinized epithelia
+four hours
+cc-by
+subcritical
+SI
+26.5 mm rainfall
+externalities
+10.1155/2014/540463
+statistical testing
+active replication of the virus
+incomplete protection
+2%
+7 days
+angiotensin type 1 and AT2 receptors
+A 3D structural model of the DENV-MINI RNA
+TPN-independency
+biomarkers
+sepsis
+mapping ADP-ribosylated targets during DNA damage
+Ni-affinity
+Supplementary Data 3
+ARDS
+Anderson and May
+CPV infection
+attributable fraction of cases exposed
+disease cases
+IL-10
+extensive
+57.71 ± 2.93%
+Zanamivir
+47%
+breakthrough infection during quarantine
+MDCK cells
+confocal
+Genbank
+0.16 mg/ml
+Human Respiratory Syncytial Virus
+Integration of syndromic and virologic surveillance
+10.6 mg/L
+24%
+neurological deficits
+risk factors that contributed to the spread of HPAI H5N1
+4
+SCARB-2
+public health authorities
+human CD200
+1 A
+health systems
+ongoing diversifying selection
+42
+raw Ct values
+light-activated
+Mass spectrometry
+>440,000
+6
+polymerase-dependent
+5099
+exercise and essential tasks
+0.4 mm
+NP surface charge
+pocket-binding domain
+onefold
+48 hours
+human telomerase RNA
+perceived or actual economic impact
+1
+viral gene expression
+EBM
+106
+≥2
+conservation awareness
+up to seven days
+a cascade of events initiated by the activation of insulin receptor substrates
+hydrolysable
+gammaherpesviruses
+cell-based
+A/H3N2
+Harbone
+IFN-γ and lytic molecules
+Mapping
+10.3%
+23 amino acid from the human tyrosinase signal peptide
+IFN-γ and tumor necrosis factor alpha
+The level of correspondence with the information environment
+steatosis score
+Berlin
+9.4
+type 1 pili
+canine transferrin receptor binding
+50 µl of the homogenate
+36 hours
+2 mM of ATP
+Four
+chemically deplete IgM Abs
+visualization of enterovirus ROs
+40
+macropinocytosis
+age-related mixing
+1 day
+two times the SD at each antibody concentration
+whiskers
+novel avian influenza viruses
+β-actin
+virus-infected, non-APC cells
+four
+30 min
+counter select any new mutant clones
+less suitable RGs
+the mechanisms that sustain hypertension during normoxia
+NS1
+November
+six
+risk-adjusted hospital mortality
+every week
+four
+cholestasis syndrome
+systems-level
+Collagen Type 1
+Hepatitis B virus
+8
+five
+Digidata 1322A
+Ficoll gradient
+4%
+desorption/ionisation time-of-flight
+P3 and P9
+minimal gene expression
+room temperature
+HEV71
+repeated introduction
+Antibody dependent enhancement
+α-helices
+RNA lacking 2'-O-methylation
+Gompertz model
+to avoid the extrapolation of divergence times too far into the past
+COX-2
+40 and 60%
+Aspergillus
+negative binomial autoregressive model
+inversion status
+5%
+5-10%
+the use of ECMO in patients with H1N1 influenza
+signs of disease
+AS-136A
+Rheumatoid factors
+China
+Begomovirus
+Eurogentec
+accommodation of the first codon
+Glycoproteins gB and gH
+Arg 705
+Review Manager
+particle size intervals
+exosomes
+Qiagen Viral
+CalcuSyn
+between 40,000 and 220,000
+epoxy resins
+Chikui behavior
+Celigo cytometer
+January
+141
+delayed fusion kinetics
+tumor progression
+to avoid direct contact transmission
+CPE and syncytia
+up-regulating transforming growth factor-β
+Cell membrane C1qR
+collaboration
+minks, pigs or cattle
+The safe and effective transportation of samples
+the structure that is predicted
+China
+Fuyang, China
+K1L and C7L
+developing a shared understanding between patients and providers
+Aptamers
+Dr. Dietrich Keppler
+pneumonia, acute respiratory distress syndrome, and death
+fusion partner
+DNA microarrays
+1030
+two
+Specific cDNA
+308
+crude mortality rates
+27
+Rockville
+dendritic cell maturation
+NK cells
+Sequence and structure
+antigen-specific B cell
+3 cm
+viral RNA synthesis
+six
+capillary electrophoresis
+Radio Immunoprecipitation Assay buffer
+mitochondria and the endoplasmic reticulum
+5-AZC
+least-squares fitting
+BDNF
+Flow cytometry
+overexpression or knock-out of the CHOP gene
+evolutionary pressure
+RanBP2
+VSV-G-pseudotyped lentivirus particles
+À70 C
+immunoblotting
+culture flasks
+feasibility reasons
+3.6%
+0.05
+ECL Plus Immunoblotting Detection Reagents
+any nonviral sequence
+generalized physiological state of an individual
+non-cardiac comorbidities
+0.11
+a system of coupled S-I-R equations
+positive detection of Mean 6 standard deviation
+Antigen I/II family proteins
+Bayesian network models
+MFE
+Time from symptom onset
+the known characteristics of the disease
+four
+the treatment of many infectious diseases
+isolates from Cameroon and Ethiopia
+Kenya
+one probe of the array
+IRF3 and IRF7
+c j
+calf diarrhea
+4
+release of LCMV DI particles
+Antiviral state
+ALV-J infected cells
+FOXO1, activator protein-1, and NF-κ B
+Biolayer interferometry
+IL-2 and CD25
+27-month
+no tissue fi xation and disruption are required
+survival
+H1N1 and H3N2
+serine monophosphorylation of STAT3 at S727
+E
+all four viruses
+OTPs
+Glutaraldehyde cross-linking
+1,998
+0.5 g RNA
+Viral genomic RNA
+one-seventh
+anti-inflammatory
+SSX2 and GAGE1
+Weight loss and temperature changes
+gradient SDS-PAGE and MALDI-TOF-MS
+HepG2 cells
+parasite switches
+22
+Pietrain pigs
+current standard opinions
+immune-fluorescence
+400
+LC16m8-derived recombinant vaccinia viruses
+T25
+FACSAria
+Phylogenetic
+spurious
+molecules of 4 Vpu
+MAVS
+amantadine
+virus replication
+Written informed consents
+Stockley, Twarock and Dykeman
+166
+each epidemic
+golden hamster, rat, and mouse
+14.9
+glyceraldehyde 3-phosphate dehydrogenase
+January 1, 1976
+double-layered microfluidics
+Antibody engineering
+78.8%
+recognition of sequence similarities following non-specific nucleic acid amplification
+5.86 nM
+Radiologic progression
+100,000
+PNA
+his writing desk
+log-rank test
+1 h
+CD4 + Foxp3 + regulatory T cells
+mosquito saliva
+Nikon X71
+positive signs
+CAIX expression
+APMV-4 and -5
+90%
+275
+over 8000
+HLA-DR
+HAV
+rRNA maturation defects
+LC3-II
+the uncertainty during the model calibration period
+61%
+progeny virions were produced
+20 min
+173
+chloroplast
+EasyChrom
+5%
+IFNγ
+58
+ubiquitin-proteasome and 20S proteasome
+Evidential Gene 62
+chemokine
+phenolic
+Professor Juraj Ivanyi
+0 and 302
+12,240
+bacterial pneumoniainduced AKI
+GII
+non-crossing
+dec-RVKR-CMK
+annual variations in the intensity of contact between children
+2fold
+BCA Assay Kit
+whether the codon biases of genes are influenced by mutation
+Tumour necrosis factor alpha
+2.4 Â 10 4 /mol
+myofiber necrosis
+macropinocytosis
+Direct correlation
+72°C
+ACTB and ALB
+Ag-specific Tfh cells
+87.41%
+one third
+The complete list of genes
+10%
+44-80%
+phase II clinical trials
+Thirteen
+ESI-05
+significant changes
+20 and 10 mM
+CATS
+vaccination failure
+0.011 ± 0.008 mg m −3
+DHF
+organs
+RR 0.66
+vasoconstrictors
+400 nM
+342
+TOCs
+Length of stay
+conversion of GL
+IFN-ab
+pathogenicity and immunogenicity
+E. coli dsb or B. subtilis bdb
+RIPA buffer
+quarantine
+viral genomic double-stranded RNA
+Alum
+the DO process
+poxvirus
+ED overcrowding
+bidirectional manual respiration valve
+250-fold
+identification time
+Dimension 1
+PCV3
+747
+45.9%
+Sepsis
+PCA1 combined with PCA2
+angiotensin type 1 and AT2 receptors
+Genetic studies
+16
+PCNA, BMP2 and IL-6
+anti-NP antibody
+feeding costs
+2 μg hepatoma mRNA
+Calf temperature
+MeN_TMF
+Dr E.Karsenti
+a snapshot from seven diagnostic laboratories
+secondary necrosis
+ZIKV
+grifonin-1
+another way of targeting a drug delivery system
+Pig density
+MOE
+15.5Å
+q
+disappear from the circulations in a few seconds
+Forty-four
+Spline smoothing
+amifostine
+antioxidant, anti-platelet aggregation, and anti-inflammatory
+venous thrombus formation
+immunosupression
+Forensic epidemiology and law enforcement/security
+MDM2
+M MRW
+March 10, 2004
+Viela Bio
+gel filtration chromatography
+measure of exposure to the virus
+1 per 2,000-10,000 nucleotides
+oseltamivir and zanamir
+current clinical practice
+polypeptide size
+αA-crystallin
+Five
+Real-time RT-PCR 29
+10 fg of L. monocytogenes DNA
+an anti-PD-1 antibody
+retrovirus
+high-fibre prescription veterinary diet
+zinc-dependent endoproteinases
+1%
+Amantadine
+Broken capsids and capsid swelling
+Flowjo version Legacy
+Orthologous relationships between IFITM family members
+triage
+25 th of June
+N-terminal signal peptide
+Dysregulation of the local RAS
+neuronal signaling-mediated regulation
+chain recognition and cleavage specificity
+IDO-KD MSC
+Carbo-free TM
+30%
+Plumbago indica
+10-76%
+verbal padding and hesitations
+KPNA2
+culture supernatant
+the science is unclear
+P50
+Few
+R Q 0
+data gathering, collaboration, needs assessment, and expert advice
+NE, and metalloproteases
+GEO database
+Diagnostic algorithms
+61
+whole-genome sequencing
+Spearman's correlation coefficient
+special
+HR-based DNA repair
+Lung lobes
+IFN-γ
+≥4
+October 2015
+340
+vital
+alum
+Supportive data Table S1
+immunological novelty
+2-3 weeks
+15N and 46R
+RHDV evolution
+two
+AMAs
+75%
+high-sensitivity C-reactive protein
+Canberra
+histopathologic evaluation
+the average of two biological replicates for each strain
+Antioxidant capacity
+antigen-specific tumor lysis
+higher η
+6.7610 23 nucleotide substitutions
+IFNAR1
+deep CNN models of high capacity
+immunity levels of individuals
+45%
+mixed lymphocyte reaction experiments
+identify
+3%
+56
+the effect of the threshold
+4% paraformaldehyde
+bacterial and viral infection
+Chinese natural language processing
+Median Tissue Culture Infective Dose
+cell division
+23.6%
+>90%
+several residues in GP2
+peptide A and peptide B
+endocytosis, actin dynamics and cell polarity
+ellipse
+exonic, intronic, or intergenic features
+sCJD and PD
+feline URI disease
+Resistance Monitoring System and AgConnect
+epoch change point
+Amiloride and the more potent derivative EIPA
+the invasive phenotype of infected cells
+stereomicroscope and digital camera
+16 hpi
+7.2 ± 0.6%
+conformationbased design
+less than 1
+30 min
+CEACAM1-4S
+Mini-Mental State Examination for Dementia Screening 35
+transitivity
+an open source data mining package
+inflammatory gene expression
+The dynamics of the system
+HI titers
+Reaper-15-065
+viremia control and spontaneous resolution of HCV infection
+macromolecules
+1{ P
+negative results
+MAP kinase
+global genomic cytogenetic arrays
+21,618
+inflammatory
+oseltamivir
+12
+stage IV
+73%
+H1N1 and H3N2 Influenza viruses
+further efforts may be necessary to foster enrolments
+20%
+random effect
+vaccination effectiveness, treatment efficiency and their associated costs
+z j
+5 days
+RANTES and CXCL10
+citation counts from different databases
+plaque assay techniques and immunofluorescence techniques
+2
+infection with velogenic NDV
+eight
+Western blotting
+malaria rapid diagnostic test
+recovered efficiently
+August 1999
+71%
+194
+19 days
+envelope interactions with viral entry receptors
+pMSCV-FLAG-HA-IRES-Puro
+1 U shrimp alkaline phosphatase
+bacterial infections
+29 days
+DNA and RNA
+promotion of structural interactions among viral proteins
+recombinant plasmids
+β-casein protein
+high affinity, class-switched antibodies
+Upcoming approaches based on systems and synthetic biology
+fatality, hospitalization and ICU usage data
+10-fold
+5%
+integrated surveillance
+tunicamycin
+early translation termination of the open reading frame
+inflammation, starvation, mechanical stress during development, and ER stress
+tRNA Lys mcm 5 s 2 UUU
+cytopathic effect reduction method
+primer-extended product
+Bio Med Central
+coercion of individuals
+b-actin immunoblot
+Peripheral blood samples
+refraining from GOFR
+Precise characterization of population structure
+suppressive T cells
+international collaborative investigation
+T cell activity
+occupational health departments
+CARD effector domains
+Bax
+EVD
+elevated expression of ISGs
+An assay for cell protection
+2015
+enzymes
+translation and protein expression
+phylogenetic
+Acute respiratory distress syndrome
+real-time PCR assay
+5-15%
+immune protection and bacterial copathogenesis
+the effective reproductive rate
+PETfold
+an observed variable
+5 bases
+GTG
+921
+flatworms, annelids, and mollusks
+MS/ MS spectra
+DiscoTope
+99.2%
+recombinant
+17%
+center manifold theory
+Losartan and Candesartan
+frequency of infections
+fusion pore formation and expansion
+ribavirin and oseltamivir
+DNASTAR 7.1
+λ i
+Superscript III and random hexamers
+Csk activity
+Sustained expression of pro-inflammatory cytokines
+conformation of the ring finger
+M2b or M2c polarization
+375
+T2 and V1 treatments
+strong translational selection
+lysines
+37 days
+3 coils
+anti-GP IgG titres
+four
+RNA library
+12%
+limited the initial infection
+passenger data
+DENV NS4B
+25-46
+within the firewall of a health system
+Seven
+two
+2011
+influenza
+interventions focused on domestic travel, population density, and climatic factors
+three
+7 days
+1998
+BAL fluids and lung samples
+LI-COR Odyssey CLx imaging system
+55
+phosphorylation of the regulatory light chain of myosin II
+summer of 2009
+probability density
+TRIM56
+hot springs
+targeted, site-specific imaging
+national governments
+25,000
+troponin I
+characterization and better knowledge of virus-induced inflammatory responses
+.RPX
+once every 4 weeks
+Physiological
+Monocytederived DC
+10218
+intestinal tract
+Pre-eclampsia toxemia
+on the indicated days of infection
+late-exponential phase
+12,543
+N protein
+MNV49.7
+1 week
+CFX96 Touch Real-Time PCR Detection System
+transcription artifacts or splicing noise
+H1N1 infection
+any other form of alternative aggregation
+interacting with the substrate
+Riksmusei Vänner
+FRET-based titration assays
+Alignment of the sigma class GSTs of trematodes
+alanine 149
+Infectious cDNA clones
+mixed bone marrow chimeras
+eIF4E
+Vago
+visual detection of nucleic acid on the dipstick
+autophagosome maturation
+Quercetin
+Ha Noi wholesale markets
+55%
+1 and 20
+p63
+chemical modification and denaturation-renaturation
+5 min
+Materials and Methods
+part_of relationships between classes
+180
+reverse genetics techniques
+day 49
+C/EBPβ
+14,037
+hnRNP A1
+bony ankylosis
+Lec2 sialylationdeficient cells
+2002
+21.0 mg/dL
+49 ± 17 and 19 ± 9 points
+41.5%
+20 nm
+Tumor dormancy
+27
+tumor metastasis
+when clinicians received laboratory results confirming influenza in their hospitalized patients
+IFN-γ and lytic molecules
+the microbiome
+Climate change and/or habitat loss
+Tumour mutational burden
+a formal comparison group
+Jamu
+by overlying individual grids
+gag and pol
+less than a million
+six
+45 min
+Human adenoviruses
+phosphorylation of its substrates Tks4 and Tks5
+63uC
+cells
+N1 eigengene
+30 min
+The coding sequence of GFP
+Suicide registration
+armored RNA
+Kullback-Leibler divergence
+determinants of antibiotic resistance
+the network's mean residual degree
+Odyssey CLx Imaging System
+HMS
+refractory
+overlap
+1 week and 4 weeks
+Suicide prevention
+513
+Rhizoctonia solani mycovirus 2
+42
+one putative parent lineage of AB476401/011C
+recovered
+FL3 channel with FSC
+Response costs
+quantitative rapid real-time PCR assays
+one mouse
+Exercises
+by injecting 5 milliliters of cell culture media through the trachea
+7.1.2
+M, V, T, and S
+RABV, VSV and NDV
+corneocytes
+Two
+Cell membranes
+430
+4%
+CD80
+88%-93%
+cardiac arrhythmia, pneumothorax or hemoptysis
+72 hours
+nine
+10%
+dynasore
+significant differences
+three times weekly
+H5N1
+microsatellites
+lack of the Cterminus
+endogenous progenitors
+p53
+reovirus type 3
+HCPs
+1.12
+intubation or mortality
+92%
+1918
+mobile coils
+Three
+the attending physician
+cyanobacterial genera
+every 3 days
+predictions that use only CDC ILI in all seasons
+CD204
+insufficient RNA for library preparation
+six
+KSFLVHREW
+Polio
+maturation of microglia within the CNS
+cc-by
+Mass spectra
+Primary microcephaly
+main blood cell populations
+aminopeptidase N
+mutation pressure and natural selection
+regulating cell growth and proliferation, inflammation, and cytokine production
+additional genes
+Reduced glomerular filtration rate and increased albuminuria
+adolescence
+HCV-infected
+ghrelin
+OriGene
+Daejeon St Mary's Hospital
+Self-efficacy
+Sequencing protocols
+one
+KT777545-KT777564
+pDCs
+1973
+Tyrosine kinase
+radiation protection
+> 95%
+deviation from optimal internal and external conditions leads to stress
+Endosomal escape
+60%
+Pneumonia
+Various interventions
+wildlife
+pBeloR26_E2rpsLneo
+high mortality rate
+factors required selectively for replication of influenza virus or propagation of dengue virus
+2019
+cc-by
+integrins
+CD21
+Saltless buffer
+ZetaView
+transparency of the selection process
+the given genome
+JNK and p38 MAPK signalling pathways
+80%
+twenty-six
+a pattern of highly correlated microbial and transcriptional abundances
+1389
+differences
+renal or circulatory dysfunction
+Myeloma culture supernatant or rabbit negative serum
+80%
+0.65 mV
+Reverse vaccinology
+Ethical frameworks
+An extended binding surface for RNA substrates
+NS2A V117
+Transcript subsets
+immune gene stimulation
+Bruker Avance III 600 MHz
+geocoding
+70%
+13
+0.065%
+mutations in the receptor-binding domain of HA
+1.0
+Adeno-associated viruses
+1,594
+dryness of the skin's surface
+169
+viruses actively infecting hosts and transient viruses acquired from diet or the environment
+cleave the MLV Env protein
+English
+their foreign policy
+IL-6 and IP-10
+biotin-conjugated rat anti-mouse IgE
+Alphapartitivirus
+R 0,V
+Bovine respiratory syncytial virus
+VP1
+NaOH-NALC processing
+Aldo1 and Eno3
+protective
+D222G
+All authors
+VAR2CSA
+two
+114
+Phenotypic and genotypic heterogeneity of PIDs
+STAT1
+Virulence genes
+∼50,000
+20
+intraosseus cannulation
+RT-qPCR
+more than four thousand
+24-48 hours
+a dengue diagnostic algorithm
+Electron Microscopy Data Bank and the Protein Data Bank
+hydrophobic domains
+BNP
+1292
+high fat diet
+TLR2 activation
+Curcumin treatment
+Photinus pyralis firefly luciferase
+86.5%
+Saturated fatty acids and cholesterol
+Vaccination against any of the Influenzas
+10 μg of each sample
+1.3%
+Heart transplantation
+hepatic γδT cells
+a measure of diversity
+Results-correlation
+nearby communities
+14,000
+endocrine emergencies
+6 months
+failure of the algorithm to establish good decision rules
+NPV and IRR
+increased virus titers
+the hybridization signal from a perfectly matching probetarget duplex
+mucosal cells
+M 1
+understanding of structure and function of WNV proteins
+African tropical rain forests
+varied arrangements of functional domains among paralogs
+pBeloR26_E2gif
+UK
+8,912
+it enables an analytically obtainable Bayesian score of model fitness
+Non-significant results
+Parasitaemia
+Computer-aided drug design
+level of proficiency
+signal peptidase
+RNA structure
+proper innate immune responses
+11
+p67 phox
+6750
+hospitals or travel clinics
+multiple RNA-binding domains as well as large intrinsically disordered regions
+258
+TRIM56
+mAb targeting PD-L1
+3% FBS
+isolation
+sterile
+on the side of the first exhaust filter
+The genomic region amplified by PCR
+culturing the live viruses
+12 h
+fusion lag time
+monopoly
+increases in ROS
+Prophylaxis
+1038
+human diseases
+Blue areas
+Respiratory syncytial virus infection
+sensitivity and precision
+2015
+the liver
+The Chinese Medical Journal
+AZIZ
+The ideals of the Open Data movement
+G36-CD28z CART cells
+LPS in sterile phosphate-buffered saline
+serine
+microglial cells
+less than 32610 23 ng of DNA
+total mRNA extraction kit
+0.00001
+an informative prior
+selected virus subtypes
+562
+specific
+more efficient implementation
+B and T cells
+Virus neutralisation assays
+0.04 to 0.06
+once every four months
+serum or serum albumin
+GAPDH primers
+lipids
+the minimum virus titres for positive reactions
+skeletal frameworks
+fluorescence-based
+Thirty-three
+621
+low
+3200
+disruption of the BBB
+Limited gene expression changes
+PND4
+two-period
+six
+three-month mortality
+GenBank
+small maximum population-level attack rates
+Healthcare workers
+PTX
+6 days
+G25 columns
+MAGT1 and TUSC3
+BF2
+Helicases
+Soluble histidine-tagged GP 1,2 and sGP
+1%
+parentheses
+Phylogenetic transmission networks
+Chile
+British Heart Foundation
+linear regression models
+pathogenspecific antibodies in host serum or plasma samples
+38.3 kDa
+log-phase cells and attractene reagent
+His287/ Gln288 and Arg294/Asp343
+APCs
+intracellular marker expression
+travel rates
+75%-80%
+four
+CC
+fibrogenesis
+MetShot
+production of fully infectious, filamentous virus
+C57BL/6 MEF lysates
+Reporting delays and underreporting
+The number of cells for each cell line
+prone positioning
+three
+highly specific to each species
+twice
+human movement
+10%
+an alternative structure may be formed
+knowledge of proteins
+Trizol-LS
+Gel 3100 Chemiluminescent and Fluorescent Imaging System
+LCMV RNA synthesis and budding
+assist Englishspeaking clinicians
+0.09
+33.4 million
+100% oxygen
+patients with expected outcomes
+viral fitness
+54
+the DDR
+50%
+pR16.939
+S/SE Asia
+RT-PCR
+Cell culture supernatant fluids
+25
+gradually
+uptake of BTV-1
+cleave cellular protease substrates
+1.8 ϫ 10 5 infectious particles
+training and testing our method
+antibody-mediated neutralization
+CCDC 996592
+Noroviruses
+Najmi et al.
+FastPrep-24instrument
+Q j
+brain tissue
+6 cm H 2 O
+after the peak of the hospital admissions in the series
+mature
+P max
+mosquito simulation model and a dengue simulation model
+50.91, 48.99 and 44.45
+6
+AD-like
+IFN-α levels
+EM Data Bank
+1 week
+modification of PRR pathways
+Sendai virus and human parainfluenza virus 1
+TLR2
+12
+events that threaten public health
+Earl Brown
+IFN-γ
+EMT
+Nikon Eclipse Ti
+4 days
+hurricanes or earthquakes
+functional validation
+gastrointestinal pathogens
+twice
+The blood fraction
+three
+small multi-look size
+145
+F10 and CR8020
+MED50%
+subtype identification
+anti-viral
+mortality
+Figure 1
+via the respiratory secretions
+expression of IL-18
+partial responses
+cholesterol
+bivariate X 2 tests
+collecting information on various forms and in personal journals
+30
+53
+Statistical
+cyclic nature
+9
+grp94 and PDIA6
+AgaR2
+BALB/c mice
+STRUCTURE_DIST
+46.1 %
+50%
+deconvolution assay
+Lymph vessels
+Shengmaiyin
+significantly better
+HCV p7
+a list of 1000 new peptide sequences
+The amount of scFv
+UV at A 280
+the varying dominance between HRV species
+neutralizing antibodies
+four
+1
+15%
+physiological health
+type 1 diabetes, rheumatoid arthritis, and multiple sclerosis
+malaria, tuberculosis and HIV
+CMs
+if they alone comprised the reservoir
+a substantially larger stockpile
+48
+fungal
+rab1b
+K6 score
+missing studies
+SDS-PAGE, western blot analysis and indirect ELISA
+RT-PCR
+clockwise
+Friction compensation
+tubular-shaped vacuoles
+A recent origin of plant viruses
+intrinsically disordered
+a role in mRNA destabilization
+MAFFT 41
+six
+E protein
+evolutionary model-based techniques
+clear cloacal shedding
+DAD
+pseudotyping lentiviruses with RABV-G
+luciferase
+Marburg virus GP immunogens
+35
+the intact wild type Sp1 site
+type 1
+ELISA titres
+time-dependent competing risks of treatment failure
+ribavirin
+10
+SRST2 and the S. aureus MLST profiles
+68
+impaired glucose utilization
+2
+cdN
+44
+leave-one-out cross validation
+the resulting annotations
+234
+55.1 ± 10.2 years
+continuous variables
+The level of SF2/ASF
+miR-1
+Laparoscopic surgery
+thermal control
+20 min
+dynamics
+19,537
+50 nm
+Lack of recovery of platelet count and persistence of leukocytosis
+Sanger sequencing
+individual variability of transmission rates
+Expert opinion
+degradation behaviour and tissue in-growth
+social distancing, use of antivirals and immunization
+Creative Commons Attribution License
+influenza
+~20%
+TCS
+ulcers in the oral cavity, tongue, or gingival regions
+host cell signaling pathways
+exhausted HBV-specific T cells
+twice a week
+efficacy
+optical
+flow cytometry
+short-range and longrange transportation data
+AQ treatment
+Grubbs' test
+>1,000 miles
+low frequency of GFP + events
+Pimobendan
+influenza
+Real-time PCR
+47%
+a population of intact cells
+nucleic acids
+a garden workplace
+enhance their entry or egress processes
+Graph visualization
+the tempo of replication
+up to 30 mins
+mobile phones and web based portals
+16 to 45
+puff
+6-8 h in permissive cells
+Mineral oil
+a local file
+Oxytetracycline
+pQuattro-tTA
+colleagues
+Coxsackievirus B3
+motifs for RNA binding proteins that bind to introns
+tidal volume measurement
+None
+ODYSSEY
+100%
+the type of information that underlies the ABC summaries
+chaperone cyclophilin A
+569
+ACE2 protein expression
+1557
+plaque assay
+antiviral prophylactic control
+The query that contributes to non-poliovirus matches
+23
+eight
+Fig. 7 D
+weighting
+40%
+Fever
+7.2
+cancer progression
+virologist
+LANA2
+124 406
+0.01%
+excessive activation of NETs
+83% recall on 3FP per patient
+neuroaminidases
+biotechnology and vaccine
+schematic
+Rab5
+80%
+LTβR signaling
+anti-parasitic
+CS, JN, and MM
+10 days
+15 min
+multifunctional regulators
+further analysis
+One-way or two-way
+pseudotyped
+GSE5418
+SBVp32
+53
+all forms of movement and contact between farms
+mouse and piglets
+aggression and impulsivity
+up to 3 months
+Information about social networks
+clinical drug development
+Basic Local Alignment Search Tool
+deep intronic mutations
+80%
+A single O. volvulus L3
+four
+NDPITools custom extract to TIFF/mosaic plugin
+leukocyterich buffy coats
+490
+Decision space
+Real-time PCR
+L-DNA
+the pandemic
+social distancing interventions
+x g sires
+4
+>18 years of age
+26%
+Japan
+cry wolf dilemma
+marine and freshwater
+by limiting dilution
+50%
+11
+Micro BCA TM Protein assay
+higher binding activity
+Gamma-camera imaging of infection
+human enterovirus C species
+172,833
+abrogation of particular DDR processes
+age and health status
+optimized techniques
+GAmediated neuroprotection
+lncRNAs
+12.45 Pa
+8
+93%
+30 000
+biosafety level-3
+Qiagen OneStep RT-PCR Kit
+EB4
+fuzzy connectedness image segmentation algorithm
+four
+posterior
+high false positive rate
+rapamycin has a dose-dependent effect on viral replication
+Plastid engineering
+behaviourally induced increases in colony temperature to combat parasites
+heterotrimeric
+contaminated hospital water supplies
+Behaviour change
+5 µM PERK inhibitor
+monocytes
+Polyphenols
+abundant surface proteins
+Genetic factors
+Microglia
+161
+IRES-dependent translation
+PCR techniques
+50.5%
+4
+1 hr
+serotype 1 carriage reservoir
+plant tannins
+mixing-vessel model
+PS liposome and apoptotic cells
+Hypoglycemia
+Uganda
+intensive acre unit rooms
+a stop codon or a nucleotide deletion
+Emil von Behring
+severe sepsis
+8 weeks
+146
+1.3%
+1111/100 000
+CC 50 /IC 50
+Student's t-test
+to draw and understand the real interactome
+3 to 14
+densitometry
+pathways enriched among proteins downregulated >2-fold
+standardized protocols
+DMSO
+three
+frequency
+nuclease-free water
+pooled WMDs
+1652 cost units
+a unidirectional air flow and a dry salt aerosol
+experimental testing
+fresh medium
+S epsis
+ECL Western Blot Detection Kit
+HRV-C
+allergic inflammation
+Responses
+World Association for the Advancement of Veterinary Parasitology
+12000-18000 Da
+elevated levels of exhaled ethane
+hospitalisation dates
+The Jackson Laboratory
+no significant changes in lymphocyte count dynamics
+OD 600 0.45
+ciliated cells and goblet cells
+many confounders
+self-interested use of domestic monies
+The United Nations' Human Development Index
+single nucleotide polymorphisms
+1.36-time higher
+2 Well ProPlate module
+uni-and multiparameter models
+maternal immunity and active immunity
+OHL
+cytoplasmic nucleocapsids
+significance at p < 0.05
+6-8 weeks
+the first author
+subways, offices, and schools/daycares
+MySQL
+intention-to-treat
+preliminary
+CellTiter Glo luminescent cell viability assay kit
+Saudi Arabia
+187,426
+smokers
+exudates containing 100% of free-ranging tachyzoites
+red blood cell
+limited exercise tolerance or the need for long-term oxygen therapy
+50 mL cultures
+strong reactivity
+peripherals
+VEGF receptors 1 and−2
+EEA1 + endosomes
+1%
+assays
+RNeasy mini kit
+muscle damage
+10 4.5 TCID 50 /mL
+Activation of PERK
+TLM B
+to decide the target condition
+95%
+200 lg of total protein
+LepA gene
+CM-leucine
+11
+Gene ontology
+very specific
+100-mm petri dish
+Heat
+LK and OAG
+to provide temporary support to the circulatory system
+betweenness centrality measure
+ELISA
+Memory T cells
+conservation consciousness
+proprotein convertase furin
+20 min
+Stimulatory elements
+18
+viral pathogenesis
+SOFA scores
+proinflammatory
+Thermotolerance
+no significant change in susceptibility to NFV
+did not changed
+rapid
+95%
+Unlabelled shRNA
+24 hrs
+two
+the virus-amplifying hosts
+LCMV PPXY late domain
+south-eastern China
+molecular
+biased hypermutation
+z j
+its solubility
+anti-PECAM antibody
+acute respiratory distress syndrome
+30
+interferon-stimulated genes
+1 and 2
+agonist-mediated
+in triplicate
+special
+geNorm
+apoptosis resistance and collagen synthesis
+Odyssey infrared imaging system
+Poly-induced severe liver injury
+Articles
+50%
+Guatemalan
+20 to 100 nm
+replication and spread
+Loss of myocyte contractile function
+μ
+viral loads
+infection
+m and n
+HCV persistence
+behavioral
+IL8
+6
+12-fold
+À7.1 AE 3.4 mV
+apelin-13
+metalloproteinase production
+Maximal CRP sensitivity of 92%
+mixed lymphocyte reaction
+α-helical
+agents' roosts
+coping appraisal
+Virus-derived sequences
+environmental
+an important step in the maturation of progeny virions
+0.391
+protein-and ligand-surface construction
+Group M
+0.9 days
+ADORA3
+less than 60 mmHg
+15.6 weeks
+RT-qPCR and western blot assays
+P c
+higher
+10
+inflammatory
+cGAS
+MN titer
+IFNAR1
+pleiotropic
+P2X 7 receptor and src tyrosine kinase activity
+three
+Dataset S1 KML
+Understanding the potential of a strain to produce pandemic-capable progeny
+four
+to prevent photocatalysis
+reaching the TGN
+speed, ease of purification and low cost of production
+MycoCosm
+its native promoter
+15
+anti-viral therapies
+CHP
+Forty-eight hours
+carbon chain linker
+shortening of the leg and gait abnormalities
+Kilpatrick, Chmura
+139
+Immunofluorescent
+circumstances
+Three
+seven
+mRNAtransfected CAR T cells
+Type 1 PRRSV strains
+inhibitory
+rodents
+America
+Victor 3 plate reader
+baloxavir marboxil
+α/β
+60-65 • C
+oil-covered pixel
+TIBV
+bleeding
+5.2%
+16%
+250 and 64
+both slaughter and sale stalls
+15
+germacrone
+Psychological and humanistic care
+2-35%
+Weibull
+Cardiovascular disease
+80%
+values from father's cells
+to allow us to be as comprehensive as possible in viral detection
+isoflurane
+female social status
+70-80%
+over 10 million
+cutoff used at the pruning step and assumed reporting rate
+paraffin-embedded sections of lung
+The 160 kDa band
+every 3 hours
+aging
+2
+Deletion
+seven
+Medical treatment
+anti-viral
+Acute pneumonitis
+Ensuring that the community receives appropriate health care
+85 %
+16%
+nucleotides 10 and 11
+steroids
+p53
+2.5 days
+natural killer cells
+0.08 kcal/ mol
+7
+12
+neutrophils
+1230
+Escherichia coli TE1
+hundreds of thousands of bits
+part of ORF1629
+33
+HTx
+LDH, CKMB and infarct size
+different viruses
+71%
+Ligand clouds
+cytochalasin B
+kanamycin
+69%
+CRP-XL-induced Ca 2+
+174
+Figure 4
+four
+unreliable
+25
+scabs
+3 weeks
+48 hpi
+5%
+restrains the differentiation of esophageal SCC stem cells
+indirect immunofluorescence
+COA
+R267 and F338
+StackReg plugin
+Forty-eight
+rearranged intracellular membranes
+CD8 + T-cell poly-functionality
+PEG 4000
+Secretion of GM-CSF
+76
+Catchment areas
+125 nM
+peptide
+vendor software
+Virus-like particles
+West Nile virus and Rift Valley Fever virus
+K63-linked Ub chains
+expression of the HPV oncoprotein E7
+hair-like pili
+6 h
+10.3390/v4102097
+chi-square or Fisher exact test
+cleanup columns
+Any technological progress
+Civets
+427
+1400
+13 th May 2014
+ruin, destruction, deterioration, damage, unhappiness, and loss
+ADV and coronaviruses
+NetMHCpan
+public health
+Acute respiratory distress syndrome
+40%
+FLUOstar Omega microplate reader
+prior information about the disease decayed slowly
+adeno-associated virus and rabies virus
+COX-2
+10 min
+PS-minus and non-cognate RNAs
+significantly inhibited mitogen-induced and virusspecific lymphocyte proliferation
+83%
+medium
+Neoproterozoic Era
+Logistic regressions
+yeast OTU DUB
+p53 levels
+a blue box
+focusing and astigmatism correction
+Old World and New World ancestral states
+Node color gradient
+multidetector CT scan results
+68 weeks
+β -actin
+39-KEALSDGI-46
+5%
+further calculations
+15 min
+health needs and benefits
+suicide prevention
+enhanced green fluorescence protein
+clinical judgement
+6.16
+Bcl11a
+Zika
+Mantel-Haenszel method
+11
+Clinical characteristics
+15.6%
+5%
+False-colors
+two
+horizontal and vertical velocity components
+RTE cycling rate
+four
+neurocysticercosis, tuberculoma, or brain tumor
+Elisa Plate Reader
+twice
+maintenance hosts
+starting material
+discrete large-effect substitutions in hemoglobin
+quantitative reverse transcription polymerase chain reaction
+Sigma-Aldrich
+one
+more than 3-fold
+thirty-one
+activates the PERK signal pathway
+GPM6B
+antigen stimulation
+legumain DNA vaccine
+acute gastroenteritis
+mitigation/containment policies
+R 11 R 22
+10
+12 factors that supported successful health event response
+daily
+Kozak
+Figure 18
+sterically crowded conformations, homogeneous controlled sizes, and structural stability
+Bayesian inference
+key
+Moloney murine leukemia virus reverse transcriptase and random primer
+20%
+PreScission Protease
+Motif 1
+20-37 residues
+skewed towards intermediate density
+desmin
+platinum-based
+Antithymocyte
+pMUM4/RhaGT/UgpA
+hexameric
+23.3%
+MassLynx 4 SP4
+E1
+mice
+lactalbumin alpha
+30 min
+RPMI 1640
+Pyruvate dehydrogenase E1 and E2
+magnetics, optics, and electronics
+HIV-1 vaccine design
+Serum samples
+140
+the native determinant
+M1 macrophages
+membrane tears and stretch-activated channels
+How to discriminate AFPs from other proteins
+bays 1 and 3
+neutralizing antibodies to CedPV
+no evidence for a discrete organization of T and B cell regions
+Western medicine
+lives may be lost and money wasted unnecessarily
+eIF4E-dependent survival signaling
+DAA sofosbuvir plus ribavirin
+zero-mode
+MouseOx™ Pulse-oximeter infrared sensor collar clip
+Immune and wounding-related genes
+a kind of nonlinear and dynamic model formulated by a differential equation
+2 statistic
+S
+host cell compartmentalization and the built-in molecular recognition features of networks
+30 min
+New Zealand
+95.2%
+academia
+measurement and process error
+75%
+a process that leads to the production of virus progeny
+Eight
+53/169
+TLR9 and/or TLR7
+binding site flexibility, bound ligands, and the binding site definition
+Paris, France
+K356R and S409N 21
+four
+ACA, cAR1 and PdsA
+influenza virus infections
+28S rRNA levels
+10.1186/1743-422x-8-494
+Protocol violations
+Ten
+NK cells
+surgery
+106
+research performed in developed societies
+hydroxylysine
+feces
+6,298
+TNF-α and IL-1β
+spore-forming
+daily
+public, commercial, or not-for-profit
+predominantly specific IgG1 serum antibodies
+three
+HCMV AD169
+17 days
+extraordinarily complex
+Primer pairs
+7
+June 2015
+more specific alleles and genes
+T RM cell markers
+polyepitopes
+EnVision detection system
+E45R, E121R and A142R
+humoral
+biophysical applications
+CFTR
+to review the current status of appropriate European monitoring systems
+GC B cells
+sub-Saharan Africa
+immune reconstitution
+expensive
+red triangles
+multi-dimensional
+Kaplan-Meier method
+twice daily
+422
+acute diarrhea
+DNA
+one
+exciting new therapeutic opportunities
+Contagious viral diseases
+electron transport chain and oxidative phosphorylation
+Virus isolation
+food
+textual sources
+H5 A/Vietnam/1194/2004
+limited number of sequences
+sugar and amino acid requirements
+biochemical approaches
+responsive hits on natural protein arrays
+recombinant genotype L22
+OD values
+2 −ΔΔCT threshold cycle method
+all available health data sources
+Figure 7
+ISG15 knock-out mice
+Exon 45 and 46 exclusion
+other vascular pathologies
+RiboMinus Eukaryote kit v2
+Amersham ECL western blotting detection reagent
+CD4 + T cells
+to better understand the acquisition and development of cryptococcosis
+BCL11A
+differences between the expressed and viral materials
+existing professional and scientific ethical principles
+Health
+Asialo-FET
+60%
+Cryptosporidium
+convulsions
+influenza virus infection/pathogenesis
+early termination of the NS1 and NP1 ORFs
+the main features of the life course
+thrice
+Figure 2
+TGF-β3
+I. ricinus
+western blot analysis
+2%
+N protein
+facilitative downhill diffusion at a rather low turnover
+10
+poor candidates for ICU admission
+Virus titers
+Measured activity
+Equivalent volumes of solubilization buffer versus supernatants
+ΔE vdW and ΔE elec
+None
+Pearson's correlation coefficient
+narrow-ranging species
+alphaherpesvirinae
+exercise
+an accelerated decline
+pol r,p,j
+5 days
+25
+ten
+24%
+GC content
+Aedes albopictus
+T3SS
+retroorbital bleeding
+n 1
+SCXK 2011-002
+21 days
+coagulation-related genes
+one third
+surfactant-producing human AEII cells
+B cell cytolysis
+The contribution of each gene to the variance of normalization factor ratio
+endoribonuclease-prepared siRNAs
+MicrobanH
+events
+the ER membrane
+21
+Ym-1
+Toxoplasma gondii and Neospora caninum
+Linda Aiken
+Proteins
+50%
+500
+severe hypoxaemia
+fibrosis
+1.4%
+The AQT
+general health preparedness measures
+MVA vaccines
+in vitro disassembly experiments
+NS1
+differences in experimental conditions
+LL-HA1/L/AcmA
+host specific
+underestimate GV
+AURKA
+unchanged
+Bowtie-0.12.8
+information
+50%
+to allow the formation of single-cell clones
+13 ± 2%
+viral components
+residence within intracellular or immune-privileged positions to hide
+14 days
+multiple linear regression analysis
+methods
+CH01 UCA Abs
+five
+SUMO-mediated post-translational modifications
+Receiver operating characteristic
+PyMOL molecular graphics program
+insertional mutagenesis
+by adding the corresponding empty vector
+26.5 μmol/L
+GTP
+18,342
+virus
+Bayesian
+V18, V120, A129, and I131
+zebrafish
+six
+62%
+an initial case date of April 13
+degenerate neurons
+P1-Thr
+easier access to specialized cells
+membrane disruption and cell death
+serious adverse events
+short-duration contacts
+Siglec-8binding ligands
+protein-free liposomes
+apoptosis
+Trizol reagent
+10À15 min
+Lanes 1 and 2
+2006
+increased
+improved collection and identification with parent collection
+Tat and TAR
+IC1
+Palivizumab
+age
+hepatomegaly
+phosphorylate cGKII
+via the respiratory tract
+functional MT, HEL and RdRp domains
+36
+PB2
+IFN-a/ b-induced ISGylation
+Addgene
+430
+30591
+entry of HSV-1 into receptor-negative CHO cells
+increased levels of the chemokine
+Particles
+Aal DNV
+lactobacilli
+diphtheria toxin receptor
+liver toxicity
+17
+80%
+naïve lymphocytes
+The Linear Constraint Solver algorithm
+2006 to 2007
+sodium sulfite
+3-5 days
+HAF-induced γδ T cell activation
+Gabon
+Histological confirmation or typical imaging presentation of HCC
+increases
+The ability to protect key assets and personnel
+t′
+Six
+1000 Å 2
+5%
+travel plans
+only the class or immediate teaching group was closed
+CD3, CD4, and CD8
+two-tailed Student's t test
+2.9 million
+plant immunity and responses of bacteria and archaea to threats to their genomes
+Th1 and Th2 cells
+the hospital's ethics committee
+5 μL aliquots
+F-7-G
+Gene sets
+The existence of an optimal control
+Microsoft Excel
+3-5 days
+HEK293T cell pools with stable knockdown RNF166
+a piece of the time series after the transients have decayed
+RNase L
+Overprinting
+pre-standing genetic variation
+nsP2 and nsP3 bound to dsRNA
+cannula colonisation
+receptor recognition
+guinea pig
+6 years
+when the knee angle is changed by the motion of wearer
+Venovenous ECMO
+Uninfected cells
+NLRP3 inflammasome/IL-1β secretion axis
+Nascent
+Western blotting, immuno-electron microscopy or functional screens
+structural alteration
+0.6 and 0.4
+R 0
+article search, identification, selection, data extraction, and coding process
+É 3
+little
+covalent complexes with ubiquitin
+aae-miR-286a-3p
+SINTBAD, TANK, and AZI2
+A quarter
+FXIIa
+A3079-01
+article 3
+three
+to eliminate frameshifting events occurring before the assay site
+PBS
+clathrin-mediated phagocytosis
+M
+twice
+3-amino ethylamine
+2500 cells/mm3
+actively use these tools
+Thirtythree
+two hours
+larger vesicles
+6%
+10-15 days
+allergen sensitization
+20 and 40 mM
+functional
+83
+why its expression was not enhanced by H5N1 infection
+limited signal dispersion
+infectious and inflammatory
+Drak2 -/-T cells
+Structural lung disease
+Serum lactate level
+three
+HIV replication
+50 min
+VUS
+22.2%
+CD14
+a two-arm fulllength IgG molecule
+viral protein synthesis
+565
+viral infections
+10%
+Serum HI-antibody positivity
+an AT
+data limitations
+N d i
+isolates
+4-9
+Gen Bank
+neutrophils
+member M2
+humoral
+modulating immune responses
+GeneXplain
+endothelial cell proliferation
+Streptococcus pneumoniae
+LASV NP
+60.4%
+PTMs of this protein
+four
+14 days
+10-15 min
+Epidemiologic
+50,000
+PathData
+years of post-MDA mf prevalence data
+GO
+32
+viral titer changes
+simulations of SEIR epidemics
+expression of the VP2/fluc product
+DNA vaccines
+influenza A
+PAF53
+PMA
+cardiovascular disorders
+60 hours
+10
+E. coli Origami strain
+reasonably small
+Logistic regression
+lower numbers of hospital admissions and reduced resource use
+CRISPR-Cas9
+1 week
+Asymptomatic Ebola virus infection
+IFNλ4 treatment does not cause cell death
+exercise
+pathogenic avian influenza H5N1 viruses
+IgK-VP2
+the frequency of mononucleotides x and y in a given sequence
+the author
+local Moran's I
+IFN-a/ß
+RNeasy
+HATU and DIPEA in NMP
+TNF-α
+decreased in number and faded
+data
+strand exchange computation modules
+medical therapies
+AMCase activity
+husbandry and environmental factors
+PA T97I
+four
+lack of PBD
+platelet aggregation
+14
+GFP u
+transcription factor binding activity of E1A proteins
+p.Ala52Val of aD N
+α-interferon atomization
+40-60%
+what should or should
+2
+IL-10
+SOAPsnp
+influenza and other viral infection
+a Q-Q plot
+RPMI 1640 GlutaMAX
+37
+1 × 10 1 copies/μL per reaction
+inorganic G4 probes
+1 μL USER enzyme
+38%
+65%
+Illumina sequencing
+disseminated injury
+3.3 days
+PCR inhibitor residues in nucleic acids
+Thermo Fisher Scientific shRNA library
+the probability of randomly picking a healthy individual
+handwashing with soap
+USP15 wild-type and catalytic mutants proteins
+apoptosis
+arrays
+44
+unidirectional
+ancient vaccinology
+Criminality
+PSV
+innate
+any advantage offered by the water
+glycan cap
+a diverse array of lymphoid tissue-like organization
+glycosylphosphatidylinositol
+333
+the upper dot
+centrifugation
+RSA59 and RSMHV2
+nuclearlocalization
+backward bifurcations in compartmental models
+114
+lick
+1 µg/mL of LPS
+357
+WGASA
+two-month olds
+numerical sequences
+very mild and focal inflammatory infiltrations
+Intensive network models
+host cell autophagy
+1 hour
+Equation
+colonic
+12
+increased apoptosis
+CiRNAs
+cardiovascular remodeling
+stimulates macrophages to release TNF-α and IL-6
+99.5%
+tissue kallikrein
+An adverse event
+multimeric SP-D protein
+Sialic acid
+dynamic light scattering and transmission electron microscopy
+translated ORF
+Sweetwater Branch virus and Beatrice Hill virus
+Cx. taeniopus
+M. pneumoniae
+Neue Hygiene- und Verhaltensregeln
+ImageJ
+the genome
+twice daily
+Nasopharyngeal swabs
+interferon and pneumonitis
+3 dpi
+improvement in left ventricular function
+severity, relationship to treatment, onset, duration and outcome
+Bernoulli random variables
+E6 or E7
+using a standardized questionnaire
+vaccinia-specific CTL responses
+54%
+four
+mammalian
+common allele matrix analysis
+anticancer drug, a liposome carrier, and targeting peptide
+cellsurface receptors
+complementary DNA oligos
+antibody-based immunoaffinity purification
+contact tracing
+Berthold luminometer
+the linker loop
+positively charged peptide
+15
+74%
+bioterrorism
+ischaemic heart disease and cerebrovascular disease
+one at a time
+enhanced neuronal survival
+G93 and D95
+2019
+236
+Expression
+virulent
+immune-induced demyelination
+>5%
+Node robustness
+phylogenetic oligonucleotide arrays
+reducing waste and promoting efficiency
+Gibbon
+The Frameshift Correction Model
+Nine
+The time varying diagnosis interval
+Maxquant MS Analysis Software
+H4b/H5
+Thirty to 35%
+PureGene DNA Isolation kit
+134
+inhibit the acidification of endosomes
+expression of Fgl2
+5-30%
+CREB-binding protein
+Ile
+neutrophils
+unpaired nucleotides in loops or bulges
+The ability to detect and respond to known and emerging pathogens
+ferret model
+cell-mediated
+poultry health problems
+StepOne TM System
+Positive predictive value
+knowledge about the frequency of diseases
+67%,
+no reactivity change
+normal
+201
+34 years
+neutralize much fewer viruses
+canonical LPS inducible cytokines
+Blood samples
+intra-sample cv
+discomfort and safety
+their effects on vertebrate ribosomes
+CRABP1
+Alexa Fluor-conjugated antibodies
+Phosphoinositide actuators
+epidemic cycles
+two
+1 × 10 4 CFU
+pathogenic microorganisms
+mobility capillary electrophoresis
+improves binding and neutralization activity to the H5 HA subtype
+siderophores
+interact with DNA
+predicted mortality
+1:10
+mammary gland alveolus
+global translation
+constant-1 Ig superfamily domain
+1:2
+T CM cells
+proteomic
+NMR spectroscopy
+Galloyl-HHDP-glucose
+Aglaia foveolata
+14 days after the first dose
+socio-economic
+Ten
+genes that vary across all conditions
+viral spreading
+Failure of RHA to properly restructure viral RNP
+the number and size of the pixels making up the representation of the region
+every 48 h
+cGAS
+Chi test
+PDK2
+melt-curve dissociation analysis
+Aggregation
+four
+epile psy
+Neutrophil extracellular traps
+underlying mechanisms of cell-to-cell heterogeneity of infection
+more than 0.4 ms
+late 1990s
+4%
+standard deviations of the mean
+indicative of myocarditis
+Mean number for RPA
+0.7 µg/ mL
+GTs and glycosidases
+Pomc
+four
+endstages
+passenger locator cards
+infected
+blue
+a whole year
+frozen 8 µM-thick OCT-embedded mouse lung tissue sections
+MS 1 data
+upon fusion of the MVB with the plasma membrane
+weight loss
+Alzheimer's disease
+15-30 min
+F cleavage site sequence
+influenza pandemics
+EF
+94.9%
+f L
+strict liver tropism
+the network of contacts
+k-means clustering algorithm
+stability of EHV-1
+an exact overview of the extent of infection and the affected fascial spaces
+100 and BLOSUM 62
+diffusion rate
+antivirus treatment
+Room air
+TEM
+pupal lethality
+Radiographic
+Input DNA
+age and urban/rural
+51
+rBN-N15D/R46K-R
+hate speech laws
+disease and injury causes
+normal human airway epithelial cells
+30-day
+a more controlled, time-matched study
+CHCA
+4 weeks
+one
+32-33kDa
+similar AUCs with multivariable models
+Sodium bicarbonate
+Hannover, Germany
+haemaglutination test
+Seven
+ligandconjugated liposomal anticancer drugs
+EPIFIL
+gray matter
+7.4-fold increased
+synergistic
+INSOC index
+weak
+CPE typical of PRRSV in MARC-145
+High-dose exposure
+extraintestinal diseases
+ionic
+6.8 billion
+damage to the developing airways and altered immune responses
+interaction with cell factors
+Microscopic
+160 million
+5 days
+reactogenicity
+EC and IEC
+32-bit
+Gene Ontology
+SRP033717
+viral subtype
+IL-25, IL-33 and TSLP
+50-95%
+IRF9
+Sequence composition and coaxial stacking
+ribosomal frameshifting
+asymptomatic
+90.2%
+colorimetric assay
+37 C
+recombination
+Temporal or spatial invasion of non-native pathogens
+drug screening studies
+its function as a p-eIF4E inhibitor
+The intramembrane helices of the first hydrophobic domain
+China1
+R software version 3.3.12016
+selected constituent genes of the N1 module
+Human genetic variation
+a linear regression model
+immunodiagnosis of S. japonicum infection
+quantitative structure-activity relationship study
+990 000
+EBV-related tumor progression
+sequencing errors
+Conformational maturation
+preventing diabetes
+leukocytes count
+RT-PCR
+allergic reactions
+Seasonal variations in the contact rate
+key actions
+decontamination protocols
+14 mM Magnesium acetate
+CC
+Intense patient pressure
+One-way hierarchical
+transmembrane
+dynasore-treated cells
+digital
+IFN-β1
+ori-Lyt
+Data/ analytical capacity and infrastructure
+Written informed consent or parental consent
+CO 2
+Detailed inspection
+the cytoplasm
+host susceptibility to HIV-1 infection
+CaCl 2
+30 min
+virus particles
+control subjects
+the sum of utilities of the individuals
+Hospital A
+Methionine and tryptophan
+nanoprecipitation
+Viral titers of ZIKV-Paraiba
+four
+maternal vaccination
+Deoxyhypusine synthase
+Marc Lipsitch
+ABCB1
+SD/09
+2D3 binding
+antioxidation capabilities
+genes reported to have pro-inflammatory activity
+ACTB
+mRNA silencing foci
+Newcastle disease virus
+293T cells
+4 weeks
+three
+Deep sequencing
+1918-1919 and 1919-1920
+HDI and health workforce
+lung T RM
+ZT33 and ZT39
+19.4%
+English, French, and German
+Alternative outbreak detection and declaration hypotheses
+Proteomic analysis
+Nm and Hi as well as M. catarrhalis
+126/96 mmHg
+notified a research assistant
+15
+pRNA3-DXhoR
+concomitant infection
+inference model
+numerous experimental constraints
+oseltamivir
+DENv1-4
+In-depth formative research
+PARP-1 auto-modification
+extraintestinal
+epithelial cell responses
+Materials and Methods
+further studies
+provide education in residential settings to indigenous people who live in remote areas
+nine
+cost per person in the modelled community
+PRNT
+upon request
+optimize therapeutic decision making
+a functional loss of protein
+universal vaccination in humans
+complex
+differential gene expression associated with the innate and the adaptive immune response
+flaviviruses
+6
+ciliated airway epithelial cells
+2
+Two
+Mcl-1-targeted
+respiratory disease
+CC 50 values >100 µM
+Synechococcus and Flavobacterium
+1.15
+aberrant polyadenylation
+87.5%
+rational shaping of immune responses
+mice to nonhuman primates
+the TSS
+Absorbance at 590 nm
+a model
+endosomal entrapment of Pip6a-PMO
+80%
+glycolipid-type
+inactivating a wide range of microorganisms
+chemokines, cytokines, and growth factors
+memory B cells
+Airborne transmission
+Hypothetical structures
+autocorrelation
+24
+1%
+Conditioning
+2
+Sequest data analysis software
+252
+PS-KH RdRp
+N.A.R.
+Streptococcus suis
+inter-specific virus recombination
+pulmonary capillary permeability
+anti-gB antibody titer
+shorter skeletons and some bent bones
+ф04ф44EE4
+copy numbers/mL
+genome-wide mutational pressure
+0 -self-isolate-to 1 -resuming normal activity
+9
+a panel of variants
+over 40
+Early radiation
+3 ′ poly tail
+CORINA
+Many years of research
+the academic community
+AcpS
+n
+CNP
+changes in diet, microbial intake and antibiotic exposure
+CD4 + T cells
+one fifth
+regulate excessive complement activation
+ATF4-CHOP
+H i
+Twenty-eight
+5 m
+2 log PFU/g liver
+NIV
+molecular
+0, 40, or 120 mM
+~40%
+class II aPMV-1
+molecular dynamics
+12
+Umbilical cords
+2007
+Picornaviridae
+291
+208
+conformational changes in substrate proteins
+18
+stimulation of IFN-target genes
+Picard
+K63 linkage
+Syp1
+9-14 days
+28
+PBS-only samples and S. aureus ΔisdB::erm
+RNA-sequencing
+long planning horizons
+6K and TransFrame
+8%
+1Á5 ml of serial dilutions prepared
+1%
+polybasic amino acids
+inappropriate sequestration of critical cellular signaling proteins
+mucus obtained from children
+rapid diagnostic tests
+6.73E-4 s/s/y
+>25% difference in complete VP1 nt sequences between isolates
+less than 50 kDa
+52
+Ingenuity Pathway Analysis
+six
+leukodystrophy
+Ebola Hemorrhagic Fever
+repRNA accumulation
+fifty-six
+0.5%
+SSP
+201
+cross-breeding
+Pre-stained markers
+how the emission probabilities are modeled
+anti-CYDV-RPV
+adverse events
+cough and wheeze
+NP-40
+day 10
+28 weeks
+phenolics
+unwell
+attitudes towards pH1N1 vaccination
+pulmonary disease
+hydro dynamics
+subsyndromes
+49
+nested RT-PCR
+Sar1, Sec23, Sec24, Sec13 and Sec31
+hundreds to few thousands
+through communities of potential vector organisms
+Mass data stored in the medical system
+biochemical and computational "selection" of particles
+cross-species transmission
+Understanding emergent disease theats
+on-going
+Natural herbs
+138 × 10 3 /μL
+spo0A and sigH
+reproduction number
+live virus
+restricted peptides from CSP
+Non-recognized peptides
+SDS
+Cox proportional hazard modelling
+Perturbation of the rafts
+A broad distribution of sites under positive selection
+asialoglycoproteins
+4 days
+susceptibility
+Agilent Feature extraction software
+Lachrymal fluid
+TransIT-mRNA Transfection Kit
+Co-infected
+977
+air travel patterns
+Step 2-4
+Nucleoprotein
+Data-driven individual-based simulation models
+three
+glass coverslips
+the folding of hLysRS and assembly of MSCs
+through control lines
+hijacking the replication apparatus of the host
+apoptotic bodies
+congenital tremors, reproductive failure, and multi-systemic inflammation
+13
+country-specific
+IgM
+Toll-like receptors
+Poisson
+higher amounts
+ECG leads
+Ad-SCT-HHD
+RSV
+X-ray scattering
+branching theory
+sedimentation in a sucrose gradient
+40
+6
+90-day
+19
+Interstitial pneumonia with secondary PH
+PCC
+A hot water bag
+20
+Reconstruction algorithms
+Situationist moral psychology
+mutational silencing of CBPs
+150 million
+Unsupervised PCA models
+higher processing capabilities
+time
+dipeptidyl
+correlation coefficient
+physical-dynamic properties of PcG
+mutation of the C:R interaction sites
+downstream
+v 0 and v s
+maritime quarantine
+IL-7 plasma levels
+physical barricades
+261
+3BEV
+RNA-seq
+10 min
+epidemic threshold theorem
+Central and South America
+collagen deposition and pulmonary fibrosis
+constant number, constant volume, and constant
+DENV infection
+Gleason 3 pattern
+smoking status
+P
+MDA5
+Treatment
+Six
+SLO and SpeB
+rnTrpL
+15
+4uC
+2-5A
+three
+increases
+PRISMA
+SPR analyses
+important
+the two terminal residues of the peptide
+Medical imaging
+18.0
+CP-binding conformation
+two
+force clamping
+Poly I:C
+10 angstrom
+nonspecific multiple displacement amplification
+surveillance
+3.7%
+dates of report of the infected animals
+acclimation ability
+N-linked glycosylation
+weather extremes
+humans
+four
+VECTASHIELD mounting media
+5 minutes
+they are far more abundant than the viral RNA
+stimulate chemotaxis and decrease viral infectivity
+B-CLL
+knowledge about the antigenicity and immunodominant region
+97%
+type I IFNs
+Preventive Medicine Association series
+tight junction formation
+suicide risk
+angiogenic
+anti-inflammatory
+""
+PML mobility or normal assembly into NBs
+More specific reagents
+Peptide arrays
+lower immunogenicity and increased stability
+NGR-modified nanocarrier
+Fisher exact test
+A, A, and A
+War and violence
+C-terminal tetraspanin
+P3 and P9
+ACE2 −/y mice
+in-silico
+modest increases
+2
+structural analysis
+Rituximab
+mice
+intraperitoneal ketamine/xylazine injection
+FreeBayes 78
+3 h
+30,000 MDCK II cells
+early 1919
+lifestyle factors and co-morbidities
+elevated levels of IRF4
+System dynamic models
+100 ng of the DT neutralizing antibody
+95%
+convenience methods
+Cloning and sequencing
+N63Y
+envelope-mediated
+43 g/l
+proteolytic
+options for selecting the SVM kernel type to be used
+Ubiquitin-specific proteases
+maternal and infant clinical characteristics
+cc-by
+seven
+pharmaceutical
+SUMOconjugated proteins
+electrochemical
+CQ
+ACC1
+1998
+residues Glu164, Glu205 and Lys344
+TMEV-specific IHC
+IFN-γ
+10%
+SLO-like ELFs
+61.9%
+different modeling steps and all available surveillance, genetic and experimental data
+≥50%
+HO-1
+Saccharomyces cerevisiae RTase
+defining genetic influences on the host response and outcomes in patients with sepsis
+Student's T-test
+transition rates between life and infection stages
+bacteria from the nasopharynx samples
+affinity purification
+pyrophosphatase
+Acidic fibroblast growth factor
+survival
+1248
+25
+EV71
+strains
+cross-neutralization studies and phylogenetic relationships
+10 min
+SA11 rotavirus
+the fraction of all trimmed segments which match their counterpart
+Indel mismatches
+Parameter values
+Medium
+NA
+34%
+MYC activity
+Immunostaining
+means ± SEM
+2 weeks PV
+cytotoxic T cells
+EDTA-free protease inhibitor
+endangered wildlife
+RV16
+1 mM Mn 2+
+zinc, potassium, and calcium
+binding of C. difficile Spo0A
+ACU
+schwannomin
+N-X-T/S
+96%
+binding of sera
+school closure
+inhibit HMGB1 release
+Guangxi and Hunan
+vasoconstrictor effect
+virus isolation and antibody detection in serum and milk
+Postoperative pulmonary complications
+the OST complex
+ACE2
+QDE-2
+NK cells
+tissue culture
+CLEC4C DTR mice
+ACE2
+GlcCER
+real-time RT-PCR
+a large number of new programs
+expression levels of all downstream genes
+canonical and noncanonical
+padlock probe
+GAPDH
+the normal barrier
+selected cellular gene transcripts
+the PI
+CEACAM1 BAC2 DNA
+the level of aggregation
+SKM-1 cells
+MDCK cells
+SD rats
+decreases
+malls, hospitals and public transport
+December
+10-fold
+infectious entry
+Dg and Dwt
+regulating the mechanical stability of red blood cells
+4 days
+RMSD calculations
+VSN model
+HCV
+tumor micro-environment
+Kindling
+43.59 %
+25%
+cc-by
+Arterial blood gas saturation
+how many people each case actually infects
+SGG-A, MJ-C and MXJ
+V but not F antigen
+The level of significance for terms and groups
+encodes 3A
+0 copies/ml
+Probiotic agents
+environmental surveillance data
+95.2%
+MERS
+AMR
+GRP170
+RC
+D502F
+Simply having those HLA types
+endosomal exit
+an irreversible T3SS inhibitor
+QIAamp Viral RNA Mini Kit
+altered expression of hepatic microRNA
+110
+Visitor data
+Singleplex PCR
+the trees
+other receptors play a role in viral entry
+Module N0
+polar and hydrophilic
+the antigen used for immunization
+pleiotropic
+Inhibition of hemolysis
+Two
+Interferon-induced transmembrane proteins
+Twentyfour
+30-min
+in triplicate
+Oneway ANOVA
+airborne transmission
+security and dissemination of sensitive human data
+F5L
+senior intensivists in charge of the respective ICUs
+losing bistability
+viral capsid
+6 months
+>0.6
+SJPL cells
+Thailand, Japan and China
+administrative positions held by senior workers
+WHO's regional and country offices
+RV-C and RV-A
+Hemolysins produced by GAS
+95%
+observations
+founder-specific modifiers
+rs2233860CC
+seven days
+repeated dosing of nanoparticles
+Pulmonary alveolar proteinosis
+iron-depleted
+Substitution rates and dates of ancient divergence
+6
+214 million
+increased faster
+BglII and subcloned into pQCXIB
+relative humidity
+deleterious
+Black pepper powder
+DAPI staining
+translocate to the action point
+hours
+Dengue virus
+30 sec
+protective antibodies
+VA supplementation
+10.3389/fimmu.2016.00535
+1.2-1.5 ×10 6 cells/mL
+premature aging and/or death of pathogenic immune cells
+obesity
+pulmonary hemorrhage
+8,825
+percentages
+quantitative meaning
+72 h
+Control group and LPS group
+PaO 2
+17.8%
+eliminate the collection of the top 25 most abundant ions
+Prohibitin
+diagnostic codes
+third pandemic waves
+protein factors
+correlation
+delphinidin 3-sambubioside
+Fifty-five
+formation of atelectasis
+DEFA1
+Core FertiQoL
+VSV-I and V920
+SCARB2
+albumin and transferrin
+reduce the inflammatory response
+12 months
+14,772
+leaky ribosomal scanning
+challenge
+rs12252-C
+35-40
+2
+C2a/Bb
+membrane anchor protein
+increase the ability to suppress bacterial replication
+Hitachi 7100 transmission electron microscope
+second half of the twentieth century
+449
+CD spectra
+cc-by
+extremely inconclusive
+TaqMan Array Cards
+integrative therapy
+arabinose
+thirteen
+HPV infection rates
+Newcastle disease
+24 hour
+114
+Transfection and expression protocol
+1 hour
+Protscale
+high background signal
+Whole blood
+13 weeks
+Adherence to simultaneous HIV and Mycobacterium TB treatment
+paired sera
+peacock
+CalcuSyn
+IFNAR1
+13
+Asian American
+corticosteroids
+Binomial response rates
+intrastrain variability
+62%
+Ratio A-Ratio Ao
+IL-4/ IL-13
+methylcellulose medium
+median confidence intervals
+Supernatants
+Three
+Proteolytic cleavage
+0.2 mg/mL
+eIF2α phosphorylation and ATF4
+the slopes of these lines
+25
+inflammatory
+67:11
+Protein-based lateral-flow devices
+nitric oxide
+splice correction assay
+Box1, Box2, and Box3
+Delaney et al.
+Phage therapy
+Three
+inflammatory cytokines
+mean m ¼ 9 days
+our prediction
+diastolic dysfunction or symptoms
+PV replication
+signaling transduction pathways
+at Ն20,000 ϫ g
+50 pmol of Pd 6 random hexamer primer
+EplBA holotoxin
+diversity in modeling approaches, and differences in measures of accuracy
+ten
+Romania
+poor diseasefree survival
+1,094,505
+5
+Table 4
+severe lung injury and catastrophic respiratory failure
+intron 16
+infection hazard function and survival function
+The link between our epidemiological model and the data
+virulence
+Sham-inoculated control animals
+non-uniform circular travelling-wave electroosmosis
+frustration, anger and anxiety
+preliminary
+February 2019
+narrow population bottlenecks
+2.2 ± 0.8 g/dL
+Fugong virus
+Kolmogorov-Smirnov and Shapiro-Wilk tests
+3.7%
+528
+RefSeq
+50%
+234
+truncated proteins
+ciliary beat pattern
+endpoints
+1
+PCR
+environmental and genetic
+5
+Circular dichroism spectra of peptides
+Zika Conformations and inhibition of Zika NS2B-NS3pro
+emergence or extinction
+chitin-binding
+chloramphenicol
+five
+Molecular evolutionary analysis
+PN-SIA28
+diffraction-limited dots
+11
+nonlinear
+3
+MAPE
+relative search volume
+Fibrotic diseases
+2004
+50 µM
+41%
+hemagglutinin
+probabilities
+naked virions
+extracorporeal blood purification modality
+46.89 KDa
+SE Asia
+urea
+Concanavalin A
+all viruses manipulate cellular processes to proliferate within the host
+double-stranded RNA-induced RNA silencing
+Sixteen
+RT-PCR
+16
+acidified LAMP1-positive
+five imputations
+37%
+close to the detection limit
+5 to 8 nt downstream of the slippery sequence
+10 ml
+0.25
+Three
+an epidemic stain
+4-6 h
+6.50 days
+Trizol LS
+luciferase reporter gene activity
+species-specific differences in miRNA expression
+averted productivity losses among caregivers
+21 days
+V iral respiratory tract infections
+21 292 and 31 083 TTF-1-binding peaks
+appropriate methods or models
+one week
+I49
+performance in multiple environments 1,2 and evolvability
+rapid neutralization tests
+wobble decoding efficiency
+airway smooth muscle cells
+p i
+lower risk
+324
+manufacturer-specific methods and algorithms
+a quencher dye
+satisfaction with money
+SEC61G, IL17RA, and HDAC11
+deadenylation
+error
+Coagulation disorders
+U46619-mediated
+Sinusal
+34-month
+Contaminants or pathogens
+Multiple measures
+10%
+1,737
+two hours
+Supplementary Table 2d
+Basigin/CD147 and CD36
+carryover
+À8.3 kcal/mol
+multiple sclerosis, inflammatory intestinal diseases and autoimmune diseases
+Sunshinevirus genus
+Twenty
+excellent internal consistency reliability
+gray-colored items
+standardize differences test
+thermal, mechanical and chemical
+10
+GII.4-2004
+vector survivorship
+when an intervention is introduced
+17,931 person-years
+an incorrect shape
+targeting of the ROCK pathway
+12% SDS-PAGE
+2′-Deoxyzebularine Incorporated into ssDNA
+uninjured TI cells
+Titanium dioxide or titania substrates
+18 days
+real time 3D simulation
+43710
+modernisation
+S-OIV
+hepatocellular carcinoma
+Table 2
+restrictions of informed consent
+as the sum of the scores for each parameter
+MPP software
+re-infection
+demyelinating
+delayed, transient or narrowly focused T cell responses
+3 days
+6
+JEV infection
+Activation of NF-B early following infection
+Participants with ARDS
+293T cells
+JSKM virus
+real-time polymerase chain reaction -based confirmation of Apdm09 infection
+1984
+CesT/CsrA polymerization
+10-fold cross-validation
+CRAB
+complete regeneration of the skin and the absence of scar formation
+15 minutes
+j f
+ice-cold buffer
+translational
+insufficient interaction with the epitope structures
+KD
+time series analysis
+Enhanced expression of Rab5 and dysfunction of the endothelial barrier
+m 1 G at position 37 of yeast tRNA Asp
+three
+nosocomial influenza infection
+0.5%
+15 June 2007
+the serial interval distribution
+six
+The GFP coding region
+nine
+N0
+Full sequence length recombinant F. hepatica Sigma Class GST
+migrant workers and their families
+half
+isobutyraldehyde or butanol derivatives
+0.02%
+Forty-four
+physiological and pathological
+MimoPro
+Taiwan National Health Research Institute
+Cys178 and His607
+N160 substitutions
+long-term
+18-24 hours post-infection
+100 μl of DMSO
+USP15 C250
+better survival with a higher BMI
+7 days post-infection
+close monitoring
+G protein-mediated
+multifunctional
+ten
+E804
+protects bacteria against alcoholic disinfectants
+high fever
+134,986
+schizophrenia
+AML cells
+my depression
+myelin basic protein
+1252 m
+27
+personal protective equipment and infection control measures
+60 L/min
+five
+A careful and targeted study design process
+surface capsid proteins
+neovascularization zones
+11%
+Two weeks
+28
+optimized binding to the pre-fusion E structure
+1.0
+Nanocarriers
+4 to 8 weeks
+sick animals and corpses
+six
+10
+cytokine signaling-6
+cancer and AIDS
+necrotic populations
+phylogeographic
+serum procalcitonin
+SIR epidemics
+RNeasy Mini kit
+14
+$285.70
+NHBE cells
+Cross-species transmission
+1,000
+respiratory epithelial cells
+two RNA species from rhMPV-infected cells
+CompaRNA
+p27 and p21 activation
+0.04%
+E T
+Twelve
+rhinovirus
+phosphorylated JUN
+Aspartic acid and asparagine residues
+Dynamic driving pressure during first 3 days of ECMO support
+Short interfering RNA
+transmission dynamics model
+Noroviruses
+dsRNA-binding
+Phylogenetic trees
+verbal consent
+reduced viral loads in the lungs
+Reduced gross and histopathological lesions
+glass extracellular
+572 years ago
+epidemiological
+every three days
+74% ± 2%
+mean generation time
+mass spectrometry and 1 H-NMR
+antiviral treatment
+10
+high phylogenetic resolution
+five
+growth, elevation, and midline fusion of the palatal shelves
+complex patterns of individuals arriving at and leaving a location
+1 week
+86%
+aerobactin
+78%
+PDGF-BB
+standard deviations
+AA 97 to 195
+containment strategy
+Filoviruses
+temperature and relative humidity
+ligation between fragments C and D
+dose
+Santa Rosa surveillance
+a macrophage
+2 minutes
+manage symptom and personal health data and organise diagnostic testing
+28%
+CPE
+An MS friendly solvent
+TssC
+1 hour
+225
+MZP inhibition
+The funders
+opportunistic screening
+Treatment of a variety of human ailments using mAbs
+32 million
+underdosing
+penicillin
+1 µl
+Alzheimer's disease
+four
+S k
+SNP plus VC
+CTLs
+Culture supernatants
+sIgA
+Cross-reactivity
+three
+1989
+cc-by
+Transferrin receptor
+immunosuppressive
+increased circularity and reduced area of microglia
+emergency services
+Downregulation of rDNA transcription
+urban slums
+Bio-Safe™ Coomassie G-250 stain
+CapoNPV
+44.55%
+unmethylated CpG recognition in DNA molecules
+high efficiency
+Short-term intubation ventilator
+viral infections
+normal coronary arteries
+IL-1β and IL-18
+Percoll gradients
+Growth medium
+pigs
+IAV replication
+26
+660
+Red
+> 95%
+kaempferol, ellagic acid derivative, and other bioactive molecules
+24 hours
+Incidence
+noroviruses
+selected SNPs and IA infection
+nursing
+non-treated
+psychological care and chronic illness management
+sweat chloride
+bind NE more rapidly
+105
+Correlation analysis
+Directional transsynaptic specificity
+Baseline data
+glutamine
+allosteric modulators
+10.4%
+global contribution to vaccine strain selection
+399
+73.2%
+Nearly two million
+240
+cc-by
+zebrafish and pufferfish
+Type 1 IFN responsiveness
+Q k
+proteins, lipids and carbohydrates
+6 months
+$33%
+cldn5
+8 pg/ml
+cytokine-induced lung injury
+GenScript USA Inc
+6
+vaccine supply
+Liver transplantation
+Mermithida
+to assemble all reads into a single genome sequence
+chronic neuroinflammation
+statistical significance
+twice the radius of gyration of the IDP domains
+oncogenic, immune evasion and EBV pathogenesis properties
+Mitochondria
+high viral titers in the lungs
+PtO 2
+12
+eight
+NF-κB
+16,529
+verapamil
+improving population mental health
+overlapping or obscured keypoints
+12,000 x g
+10 min
+0.898
+6 months
+nucleolar cavities or interstices
+the need for study participant consent
+27
+124
+outcomes of only patients undergoing non-ablative allogeneic transplants
+Perceiving risk
+we know exactly how many individuals they subsequently infected
+regulate key factors in the immune system
+PureLink ® RNA purification kit
+severe injuries
+logistic regression
+EPF
+caregivers
+Prp19 and Syf1
+cryo-electron microscopy of vitreous sections
+532
+phenol/chloroform extraction and isopropanol precipitation
+Sixteen
+Ty5
+fusion tags
+MHCI system
+bare polystyrene
+nuclear factor-B
+acetylation, phosphorylation and oxidation
+p 0.05
+Recombination
+~ 0,17 PFU/cell
+DAPI
+15%
+does not change
+usability, comfort, dexterity and impact on communication with patients
+7.26
+three
+limitations on cost, delivery and sustainability
+penicillin, cephalosporins and azithromycin
+linear epitopes or conformational epitopes
+CC
+NF-κB
+13%
+coping appraisal
+Adaptive Focused Acoustics™
+DAPI
+APOC1, SERPINA3, and CFLAR
+microscopic
+upstream intergenic promoters
+personalized
+40%
+coil-like
+4 days
+risk communication regarding protective behaviours
+PCR inhibition
+culture medium
+ALK testing
+Jackson Laboratory
+the membrane
+July 2008
+38.6 %
+storage temperature
+P. falciparum
+55.9%
+All data
+fresh medium
+awareness
+cyclophilin B
+two
+CAP patients at high risk of cardiac complications
+protein expression 161
+60 to 80%
+MMs
+AdV
+six
+hepatic infection
+E. Coli BL21
+each infected individual is removed with probability c
+29
+64.5%
+a5, b1 and b3 integrins
+9
+The emergency department
+highly specific
+prevention of human deaths
+total RNA
+Reed-Muench method
+Sierra Leone
+5
+IFITM3
+1.2 nM
+GraphPad Prism
+castration or death
+Sodium cations
+type 1
+Four
+a negatively-charged residue at position 250
+over 40
+untimely reporting, aggregation, and publication of data
+percentage analyses
+July 2014
+Hand washing
+interventions
+MgCl 2
+susceptibility, infectiousness, and mortality
+side-chains
+closed-format 3point scales
+selection for vector pesticide and antimicrobial resistance
+515F primer and 806R primer
+cell specificity
+patient-centred
+NO production
+adjuvant
+near completion
+neurological
+http://datasus.saude.gov.br
+RABV, VSV and NDV
+household-specific genomic variation
+similar results
+intracellular protein trafficking
+key elements of the successful real-time research response
+signaling pathways or proapoptotic Bcl-2 family members
+it undergoes rapid antigenic variation
+β SD t
+50%
+ICU
+histological
+15,000
+Western blot analysis
+2,000
+improve their service quality
+glycoprotein
+lavage fluids and cells
+upstream of the NS4 ORF
+natural selection
+immunosuppression
+YL, YZ, WZ
+NanoDrop 2000 UV-Vis spectrophotometer
+twenty-five
+CD29, CD44, and CD73
+β-galactose or N-acetylgalactosamine
+genome sequence data
+CD4 and CD8
+macrophages and dendritic cells
+pro-apoptotic signaling pathways
+urban
+approximately three dozen
+FKBP11
+National security
+11,325
+the combination of two distinct underlying mechanisms
+CpG TLR9
+quarantine
+AIV
+30 min
+GGO and consolidation
+S.D.
+genistein
+197
+45 min
+serial interval and human movement parameters
+hypoxemia
+increased risk of mortality
+statistical significance
+decreased virus production
+Integrase-mediated precise excision of mobile elements from the chromosome
+White spot syndrome virus
+P-gp
+the sample
+clearance/SVR
+public
+interfering with effective treatment
+silico
+spectral matching or clustering
+Eighteen
+E2-derived peptides
+green
+431
+∼5%
+After 2 d
+bacterial infection
+endoplasmic reticulum lumen
+seven
+10.53%
+less than 5%
+additional, useful information
+tRNA Gly CCC
+a transmembrane protein activated by protein misfolding
+Illustrated
+R2R correspondence
+HCV infection
+10 nM
+FLDS
+dynasore and chloroquine
+BF:BW ratios
+Schistosome genome-wide microarrays
+exon 3 skipping
+2019-nCoV
+almost no residual immunity
+Phosphorylated tau load
+lethal
+no relevant pathologies
+efferents
+both policies
+50%
+glutathione resin
+E5, E6 and E7
+large transmission clusters
+Mitochondrial
+immuno-active metabolites
+TLR4 antagonists
+up to 8 d
+the APC
+low-affinity p10 multimer interactions
+Bridge hosts
+two
+cellular biomarkers of illness
+reproduction number R and the reporting rate π
+day 3 post-infection
+11%
+STRING database
+1.37
+WST-1 cell proliferation assay
+vector-borne
+sanitation
+neoplastic tissue
+LN-resident DCs
+nine
+floating brain sections
+microbial
+nearly a hundred
+1,411,420 to 41,066,808
+cc-by
+Nsp2
+1 h
+10.1186/1471-2164-14-819
+low bacteria concentration in the sample
+3 years
+mammalian and mosquito cells
+host resistance
+binding buffer and column filter
+constitutively and continuously
+enzyme-linked immunosorbent assay
+Juan Carlos de la Torre
+host tropism
+The activity of b-glucuronidase
+3
+HRV-A25 and -A62
+21
+template size of amino acid sequences
+single chain Fragment variable
+innate effector cells
+pc4-LAIV
+BSEP, FXR1, and FXR2
+residues Thr77-Met84
+leukocytes
+2
+confirmation of the genuineness of the slow wave activity
+42%
+1.0
+leukocyte parameters
+health care providers
+nucleic acid
+fluorescence intensity
+more than 25%
+adenosine
+Sweden
+conserved coding sequences
+hippoboscid louse flies
+Seventy percent
+active
+automated image-based tracking methods
+212 m 3 /h
+snRNA U6
+400
+astrocytes
+18.3%
+prostaglandin E 2
+14 days
+collecting all relevant publication
+5%
+confidence interval
+temporal-window techniques for the change of parameter estimates with time
+protein signature candidates
+ACMSD
+Gene products
+78.8-78.9%
+Quantity One
+two protein products of env
+group 1 heterosubtypic protection from H5N1
+Bonferroni post-tests
+99%
+aneuploidy or gene fusions
+their workload
+Rt = 0 and there is no more
+delayed viral clearance
+The diffusive Network 1
+GraphPad PRISM7
+whole-blood cells
+Sputum
+G36-CD28z CART cells
+Quantitative real-time PCR RNA
+76-100%
+higher PTX3 release by human or murine DC
+a unique cohort of IQ memory-discrepant older adults
+Transplantation
+the start codon
+269,389
+controls were put in place
+Five
+dextran sulfate
+S6K
+3.87 ± 0.11
+caveolae-mediated endocytosis
+twice a day
+IL-6
+one year
+recruitment of processing proteins
+endogenous Hsc70
+Protein Sciences Corporation
+hypothyroidism and thyroid autoimmunity
+plasma COL1A1 content
+cc-by
+implement more informed actions
+Influenza A, B and C
+reconstituting different types of transporters
+effects on nutrient metabolism
+NANOG and L1TD1
+Bombyx mori nucleopolyhedrovirus
+scientific principles, available scientific evidence or WHO advice
+25
+ERK1/2, JNK, and p38
+homopolymers, isolated errors and hybridization artifacts
+CD8 + and CD4 + T cell epitopes
+HIV-1 Gag
+mutational pressure and natural selection
+ZIKV and USUV
+12 h
+PRRSV infectious clones
+A549 cells
+stochastic process of neutral drift
+6-week
+winter
+Dr. Mikhail Balayan
+H7N9
+allosteric
+JEV infection
+50-80%
+robust estimates of lung mechanics
+nucleotide regions that corresponded to each mature DENV protein
+301,651
+2.9
+John Sheehan
+Two microlitre of the FPM
+16.0.1
+rNMR
+the derivative or time rate of change
+vivax malaria
+Titrations of fluorochrome-conjugated anti-human secondary antibodies
+Flow cytometry
+Cuffmerge
+Turkey2004
+a very well-preserved mechanism for nucleolar retention
+exploration of a variety of approaches to cohort retention strategies
+Reduced gestational age
+interstitial pneumonitis and acute respiratory distress syndrome
+Pyruvate
+glyceraldehyde 3-phosphate dehydrogenase
+a 15-nucleotide thrombin-binding DNA aptamer
+Paladur mixed Cyanoacrylate
+2
+10
+70
+Polymorphisms
+higher splenic viral load
+U0126 or NH4Cl
+X-31
+catastrophic health expenditure
+three
+whether these microorganisms were causative pathogens
+hexagonal cells with 50 m radius
+higher cellular proliferation rates
+that for WT
+The slides
+to identify clinical and inflammatory features of airway inflammation
+Tri Reagent LS
+two-tailed Student t-test
+host movement
+defining a prior distribution for the parameterization and initialization of the underlying model
+contacts with a finite number of other individuals
+past outbreaks of Ebola virus disease
+one
+cell growth and apoptosis
+Three
+Bacillus Calmette-Guérin
+higher fluorescence-intensity populations
+blood-stage merozoites
+user-friendly
+heritable variation
+SEI300
+epitope spreading
+10%
+constrained disorder
+Olle Engkvist Foundation
+2.041
+protects colon epithelial cells from TNF-induced apoptosis
+PML NBs
+cytopenias, infections and infusion reactions
+situation report
+168h
+lack of fit
+A general and effective defense
+lung cancer cell growth
+MHV-68
+13
+M. gatae
+12 h
+1952
+by refolding the holo and apo quintuple mutant together in vitro
+chemical modification
+disordered domains
+immature type-II pneumocytes
+respiration
+ACE2 enzymatic activity
+Five
+computational evidence
+Matlab 6.1
+97%
+University of Rochester Committee of Animal Resources
+replicate
+MS2
+scoring systems
+Data parameters
+unclear
+More than 90%
+Area under the curve analysis
+antimouse IFN-c and IL-4 antibodies
+influenza transmission factors
+early growth response factor-1
+porcine MoDCs
+asthmatic wheeze and severe lower respiratory infections
+Bioinformatics approaches
+hospital crisis prevention plans
+clinical practice
+chemokine and cytokine profiles
+HGF
+Mitomycin C
+sleep disturbances
+selection
+Ontario
+new genes regulators of SG formation
+sodium vanadate
+age-dependent death rates
+A and B
+Glycogen amount
+lncRNA NRIR
+50%
+29 years
+collaborative cross
+a large study
+1 3 10 6 cells/well
+biospecimen
+Andrea Leibfried
+rifampicin
+antimicrobial management
+1
+greater antiviral potential
+Jonathan Yewdell
+aggregated NP
+APMV-1
+Huh7 and Hep3B cells
+five
+25%
+1%
+which patients were assumed to be susceptible
+surface exposed clusters of amino acids
+forty four
+transmission via food to humans
+New Zealand White rabbits
+AMPK and mTOR
+seasonal
+the original cDNA preparation
+BedTools
+time
+respiratory syncytial virus
+15
+CD8 + CD28 -T cells
+fluorescence polarization and isothermal titration calorimetry
+SES
+2.5% glutaraldahyde solution
+signs of disease
+AutoDock
+lack of data of bone marrow aspiration
+Neuroinflammation
+anthraquinones
+Espirito Santo
+RIPA lysis bufferextracted protein lysates
+0.99253 to 0.99980
+structure-function
+once or several times
+sex and age
+1992
+PCV3 cap gene
+JMP 7 or SAS 9.1
+a mixing matrix
+IFN-α-mediated cell apoptosis
+May 2009
+Hyperthermia
+no mutations in CORO1A and CD3D
+30 min
+antigenicity
+Sixty
+Prokaryotes
+FoxP3
+Influenza NA glycoprotein
+pulmonary alveolar hemorrhage and larvae
+Eighty-three
+Equine
+mice
+50,000×
+adaptation through mutation and selective pressure
+3.9
+suicide
+NPC-TW01
+negative pressure
+Thirteen
+Eighteen
+Calcein-AM
+7 months
+identical 5′ and 3′ crossover boundaries
+2%
+host cell machinery
+supplementary eIF3
+Supernatants
+ImageJ and Aperio Imagescope
+various autoimmune disorders
+Masopust
+3.5
+16
+sPLA2
+20 minutes
+SASP mediators
+2005
+BSL-4
+Increasing the time
+REPLACE
+Angiotensin-converting enzyme 2
+ABL90 Flex Blood Gas Analyzer
+fever, nausea and myalgia
+Oxidative stress
+graphdistance measure
+A plaque assay
+Autophagy
+helium analyzer
+cells isolated from these animals
+Publications that undoubtedly failed to meet all of the inclusion criteria
+Half
+trapping microorganisms
+mRNAs Dissimilarities
+Renilla luciferase 33
+13
+MitoSOX
+Consensus sequence coding target antigens
+subgenomic RNAs
+3,168
+streptococcal studies
+Animal research
+increases
+host genetic variations and sex differences
+MSFsc
+cytopathic
+Maternally expressed gene 3
+stepwise logistic regression with binomial errors
+bound to TAMRA-labeled mUb-PA
+the animal losses some of the characteristics valued by buyers
+five
+Nepal
+specific ladder bands
+Vero and BHK cells
+TRIzol
+growth-inhibited hybridoma cells
+The particle size of AnExILs
+Direct delivery of ODNs or nucleases into skeletal muscles
+agents
+compartmentalization of the viruses
+an edge
+endemic equilibrium
+70% to 80%
+eight
+15 min
+Caco-2 cells
+Gene ontology
+the probe
+Complement activation and consumption
+54
+STL
+20 mM ascorbic acid solution
+Mat0-RNA3 vector
+3-MA treatment
+higher mRNA stability and higher translation potential
+anti-viral therapies
+total effect rate
+peripheral lymphocytosis
+orange
+Dysregulation of the mucosal immune system
+six
+EAPC1
+totarane
+cathepsin G-like
+SL and PWH
+Recovery events
+two
+the mean of the serial interval
+independence between latent period 0 and the infectious period
+endomysium
+TNF-a and IFN-g
+RAN translation and frameshifting
+Structural details
+stigmatization and discrimination
+the next-generation matrix
+a species ability to respond to disturbance
+GADD34
+iatrogenic anaemia
+the correlations between the variables and component
+Continuous surveillance and genome sequence analysis
+Household epidemics
+Houghton and colleagues
+Exhaustive investigation
+overly disruptive
+36 weeks
+30 bp to 107 bp DNA fragments
+Bligh & Dyer lipid extraction technique
+C069
+Sequencing from LoFi-infected muscle
+90%
+influenza A
+Indonesia, Malaysia, Singapore and Thailand
+18
+Over-reliance on genomic studies
+relatively high
+total bilirubin levels
+Log-rank test
+Pulmonary TCs
+Culture aliquots
+4,096
+mousepox
+Scenario b
+30%
+1,000
+Twelve days
+important
+glycine
+RSV
+Arms races
+Kaplan-Meier product-limit method
+reduced RTA transcripts
+three
+does not significantly decrease viral replication
+0 to 2.7
+88541
+RelA
+oxidative
+HmE
+dusky
+Benjamini and Hochberg method
+short-term economic returns
+Intrinsically disordered proteins
+implemented interventions earlier
+The concentration of extracted RNA
+MAb 6D6
+resistance to common pathogens
+PCA
+hormones
+swine
+reduced viral protein
+10 mM phosphate
+Group C
+leucine
+primary C-OH
+p53 and the Bcl-2 family of proteins
+FlowJo
+0.1%
+slow
+NS3 protein of flaviviruses
+proteins
+6 months
+between 4-12 hrs
+HCV protease
+iSOCKET
+TMP/SMX
+90%
+Target gene expression
+Nucleic acid based testing
+the ability of the neural networks in dealing with alignment problems
+novel strategies
+restrictive strategy
+20
+99%
+milk production
+pro-inflammatory
+understanding this complex system
+temperature and rainfall
+Pneumocystis carinii and P. jiroveci
+5-fluorouracil
+candida's ability to evolve and ultimately escape the host immune surveillance
+Flower Pollination Algorithm
+Bradford method
+Humira
+cell type-specific ITAFs
+alter tumor cell morphology and status
+sourcing clinical specimens
+protein-protein interactions
+simulations
+ALI
+real-time PCR
+acceptable internal consistency and good patterns of construct and convergent validity
+activate the expression
+use of mobile devices
+1 minute
+bystander tissues
+agent-based models
+physiological
+complement activity blocker 2
+liquid impinger
+close to 100%
+Hepatoma stem cells
+GI dysfunction and nutritional feeding intolerance
+inhibits the replication of different families of DNA viruses
+53%
+CD4 − 8 − αβ T cells
+delta and sigma oxygen
+necessary basic precautions
+pinpoint novel targets to address DENV infection
+In vivo studies
+12
+MCF7
+The need for a common behavior
+1:40
+ScFv
+MRSA 63718
+12
+an aggregation of MDR-Ab cases
+3D finite element method
+HILIC-HPLC
+T~RzV
+Google Scholar and ISI Web of Science
+diagnostics
+coverage
+359
+EMCV ; IAV ; ZIKV ; HCVcc
+mAbs
+21
+laboratory information system datasets
+supply and demand for oxygen
+Naegleria
+SelP
+difficult decisions
+positive responses
+260
+H5
+off-diagonal cell
+pyrethroids
+the infection
+integration into host genomic DNA
+357
+Institutional Standards for Use of Animal Laboratory Animals
+SimPlot
+EBOV infection of murine peritoneal macrophages
+COVID-19
+Three
+serial interval
+GraphPad Prism 6.04
+lethality for chicken
+Five
+Physician factors, insurance status, hospital policies, and maternal preferences
+contribute data and implement metadata standards
+pleiotropic
+NIAID Influenza Research Database
+Based Oxygen Carriers
+ROC analysis tool
+influenza A
+4%
+K25
+anti-HCV activity
+14, 5, and 35
+how similar to their own circumstances were those who had died
+A263E
+14 %
+RNA
+more than 8 hours
+the above procedure
+spleen and lymph nodes
+wPipI
+the long-term outcome of the patient's neurodevelopment
+tenderness and pain
+quercetin
+concatemers
+innate immune responses
+DNase stop solution
+respiratory viruses
+390 million
+preS1 peptide
+A branching according to the feeding group
+97%
+Fc-dependent
+Codon optimization
+very low numbers of or no new infections per time period
+brain function and brain repair
+perceptions of swine flu
+viral shedding profiles or HI antibody titres
+76% and 96%
+multi-dimensional
+The corresponding authors
+50%
+108
+The cleavage site sequence
+ABCB1-mediated efflux
+junctional proteins
+Parr and Yang
+Sierra Leone
+decreased
+improved cross-reactivity
+tissue-resident immune cells
+sooty mangabey
+a graphical risk 10 assessment tool
+life-threatening blood-borne infections
+delays in seeking assessment and treatment, diarrhea, and poor nutritional status
+bats
+Genetic variations
+Circle size
+Anhydrous potassium carbonate
+3417
+horizontally transferred genetic elements
+no change in this gene expression
+7.6 ± 0.2 min
+reverse vaccinology
+VOSviewer v.1.6.5
+one fifth
+5 0 -OH groups
+DNase I treatment
+Qubit Fluorometer
+102
+tidal volume and resistance of the respiratory system
+distribution inequality
+particle-antigen linkages
+KAT2 enzyme activities
+Activated CD4 T cells
+Females
+Reducing land travel
+compartmental model
+Severe PAP
+residue 77
+targeted quarantine/vaccination
+stable RNA G4s in the 5 0 -UTRs
+One-way ANOVA
+HY
+chromogenic and fluorogenic
+inhibits Plasmodium invasion
+6%
+U3 and RNP
+12
+Nanozoomer C9600 Whole Slide Scanner
+19-fold
+36%
+C→T
+35 d
+more aggressive therapy
+VPg
+43
+Fish host NNV resistance
+adverse events and worsening of symptoms
+lower levels of disability
+a patient sample
+160
+four
+Rainbow trout sequences
+purifying selection
+hens eggs
+reverse transcription-polymerase chain reaction
+capped RNA
+murine ELISA development kits
+serum M2e-specific IgG response to the vaccine
+Listeria monocytogenes
+twice
+Acinetobacter baumannii
+study methodology
+clinical
+> 0
+divergent influenza subtypes
+0.3
+delivery of splice-switching oligonucleotides
+a prior suicide attempt
+18S rRNA
+individual differences
+regression of KS lesions
+cc-by
+28 days
+hV D i
+hematoxylin and eosin
+768
+30
+OPLS-DA
+the patients' medical records
+six
+clinical staff competency testing
+28
+52.7 ± 11.6 years
+Anopheles albimanus
+systemic corticosteroids
+12-15 hours
+The amounts of nitrites
+infections or non-survival
+domestic dogs and wild carnivores
+cloud-based
+pathogen associated molecular patterns
+IL-4 rs2227283 and IL-10 rs1800871
+NanC
+36
+ORFs
+hybridization with a perfectly matching target
+Univariate analysis
+electromagnetic, piezoelectric, electrostatic, and electrothermal
+inflammatory arthritis and autoimmune encephalomyelitis
+One hundred and ninety three
+gentamicin administration and oligomer-induced exon skipping
+hydrogen bonds of 5.0
+two
+differences in genetic background and environmental context
+SHC1, PI3K, and PLC-γ-1
+oxidized low-density lipoprotein
+I-TASSER online service tool
+adipocyte differentiation
+5
+meningitis
+AAT
+insane
+The dashed reference line
+EcSGA1
+Rabbit IgG
+high and stable expression levels
+Blood samples
+three
+A
+methanol-d 4 and DMSO-d 6
+Predicting the course of AMR
+Figure 4b
+two
+Sepsis
+Fifty-three
+Heparin
+mast cells
+2 hemagglutination units containing 2Á10 7 virus particles
+50%
+Gene ontology annotation
+72% identical
+Zn 2+ binding motif
+BLAST
+paracrine
+Sigma
+lower
+Respondent-driven detection
+nonlinear
+metabolic stress
+longer
+γ
+3
+mutation scanning throughput
+induction of IFN-c expression by Tregs
+duplicate ports
+NoLS candidate segment region
+Identification of specific pathways
+Two
+2%
+a i = 1
+12 IU/L
+four
+Exhausted CD4+ T cells
+1 h
+understanding how and where they put their resources
+risk assessments from authorities
+viral metagenomic
+nucleoside transporters
+Role-playing
+DNA, RNA, proteins, and other biomolecules
+35,394 nt
+clinical interventions
+availability
+papain
+a wash in
+1:1,000
+functionally consistent
+six
+Partek Genomics Suite
+3
+UCSF CHIMERA and MOE
+Bacillus anthracis
+Sabin oral poliovaccine
+mice
+bidirectional Sanger sequencing
+two-thirds
+Inhibitors against C3 and C5
+six
+alveolar neutrophil emigration
+communicational activities
+DAPI
+inner-body viruses
+10%
+Co-infection
+5-nt helical region
+p
+community doctors
+Icosahedral virions of 18 nm
+p38
+clustered transmission
+896
+Microarray data
+metabolic
+haplotypes E and E1
+University of Chicago
+chemical kindling
+prion-like fibrillary aggregates
+severe bottlenecking
+Univariate analysis
+Group 1 species
+3,080
+Z-FA-FMK
+P.F.S.
+Monoclonal
+anemia and the need to restore adequate oxygen delivery
+A/Victoria/361/ 2011-like virus
+VIGOR
+protein kinase A
+randomly
+more optimistic
+B cell survival
+serial passage of the wt RVFV ZH548 strain
+595
+1 hr
+RC i
+IL-8 and CXCL-1
+18 bp sequences
+polyclonal serum
+impediments to granularity and generalisability
+31%
+Affinity grid maps
+protective immune responses to T. gondii
+Nucleospin Plasmid QuickPure kit
+cholesterol mislocalization
+in-patients
+Five
+variation in the strength of directional selection against mutation pressure
+1:4 and 1:40
+80 to 100%
+ensuring patient safety
+dried bitter leaves
+kidneys and myocardium
+PI uptake
+343
+SEOV
+1.3 × 10 5 per well
+minimal
+in vitro
+eRF1
+1989 nucleotides in length
+Milstein Award
+stable
+10 μL
+R=2
+high cautious infection control measures
+One hundred
+vesicular stomatitis virus
+forty six
+4 hr
+vimentin intermediate filaments
+G1/S transition
+two
+1 min
+miR122
+New predictive biosurveillance supply/ demand architectures
+fecal-oral routes
+Physicians and health care providers
+two
+GNMT
+BCC cell migration and invasion
+health information technology services
+FlowJo software
+equine-derived products
+the lung
+cancer cell proliferation and metastasis
+preexisting immunity and immunological potency
+hepatic GFPdgn protein levels
+5.3%
+neuraminidase inhibitor resistance
+2 h
+total B cells
+shellfish
+Astrocytes
+experimental animal systems
+nm 5 U
+bDNA
+17
+Johns Hopkins Medicine Institutional Review Board
+Cell lysates and culture supernatants
+symptom score
+influenza A subtype H1N1
+regulating EV71 viral protein synthesis
+differences
+14 days
+four
+Colless Index
+Toll-like receptors
+$2300
+mut pcDNA3.1-NS1
+considerably high or completely abolished gliding activity
+low
+the nucleoprotein complex
+hemangiomas
+demographic change and sparsely populated areas
+reverse transcriptase negative control
+my thesis
+47%
+10218
+Six-week-old
+formation of pseudo-particles
+binding consequences
+The rank column
+Sewage metagenomics
+surface expression of WT or Δ F508 CFTRs
+Barach
+influenza periods
+1:3 forty eight hours
+>75%
+Transition probabilities
+k max
+trichloroethylene
+.90%
+respiratory infections
+increased host specificity and an innate immunity defect
+epigenetic regulation
+IgA and IgG
+Peste des petits ruminants
+using PicoGreen and a plate reader
+0.09
+Bat Circovirus Porto Alegre
+MSC-CM
+13,206
+CMV promoter
+naïve mice
+2020
+abrogates the radiationinduced increase in BRCA1 level
+2009
+anti-cancer, anti-inflammatory and anti-microbial effects
+few
+Tky/05
+a promising future for cancer therapy
+7
+increased expression levels of LC3-II and LC3 puncta
+ellipsometry
+alternative control measures
+cell membrane-derived vesicles
+gel electrophoresis
+half
+female
+apoptotic death of infected cells
+summer and Christmas holidays
+Figures 2C-E
+mass action mobility
+more than 3000 l
+liver cirrhosis
+33%
+Ն20 SFCs/10 6 PBMCs
+reasonable
+inhibits IRF7 translation
+2.8 days
+NeuroHIV
+to inform or change behavior
+electrophilicity index
+45%
+polyclonal anti-RSV antibodies
+known case counts
+serious consequences
+99 per cent
+Pneumonia
+a self-administered survey
+network sizes
+T7 RNA polymerase
+MarvinSketch
+Q5 site directed mutagenesis kit
+ORFeomes
+20%
+specific factors relating to disease severity
+Band intensity
+Scrub and murine typhus
+environmental context
+four
+90% in trans and 10% in cis
+astrocytes
+poorer prognosis
+insufficient data in Level I
+their roles in regulating host mRNAs
+Table 4a
+45
+414
+software name
+Foxp3 Transcription Factor Staining Buffer Set
+574
+nuclear localization of NP
+inhibits the human IFN-b gene
+multidrug-resistant
+AMA positive PBC sera and control negative sera
+832/13 cell line
+Abiotic reactions
+Real-time RT-PCR
+75%-80%
+three
+daily
+Creative Commons Attribution License
+Ser92, Glu72, Pro143, and Arg227
+14%
+Section 4.2.2
+2
+Guinea pigs
+ICU
+368
+13
+randomized controlled studies
+Risk as hazard
+10.6%
+20 L/min
+µ t and s t
+Six
+5 days
+37.5 ml min −1
+EGFR
+sources of contamination
+Differential cell counts
+S-foci
+Virus titration
+120 minutes
+licorice root
+1.6
+assay sensitivity
+N34, N44, and N51
+Qiagen-RNeasy Mini Kit
+fluorescent antibodies
+Vimentin
+outbreak dates
+seven
+lysosomes
+1%
+13
+Corticosteriods
+hepcidin
+Safety Review Committee
+quenched
+>70 mmHg
+Alternative reading frames
+3.6 kDa
+Centrifuge
+Functional residual capacity
+action potential duration shortening
+piperacillin/ tazobactam susceptibility
+pB ijk
+Guillain-Barré Syndrome
+more complex
+two
+reduces the growth
+r 2
+0.08-0.12mm
+ggplot2
+HCV reference sequence AF00906.01
+Antagonistic
+age, exposure history, medical-seeking behavior and underlying diseases
+influenza-associated encephalopathy
+iCyt Reflection or SY3200 Cell Sorters
+to reverse the cycle of neglect
+diVerent strategies
+non-radiative energy transfer
+cold
+quantitative pharmacological
+Robustness
+compromised cell fitness
+state-space model
+Magnetic Fluid Hyperthermia
+probability of cell activation
+low expression levels
+Oral and respiratory mucosa
+unchanged
+2.79610 -8 M
+Seventeen
+nucleic acids of pathogens
+Ribosome biogenesis
+low relative deviations
+ZIKV E protein
+2.5
+GRA and GR-SU
+ISG15 species-species differences
+lysosomal acid lipase
+P. amnii
+0.5%
+human NTCP
+Fold difference
+human TfR1
+Mean field theory
+Emerging diseases
+they will be followed until they achieve one of the aforementioned outcomes
+0 -negative
+Mann Witney Utest
+disulfide exchange in domain 2 of CD4
+Interest in research on IL-35
+inactivated monovalent
+39
+human embryonic kidney epithelial 293T cells
+Neutrophilic pulmonary infiltration
+PPE and procedures
+pulmonary inflammation during viral infection
+cryptococcal meningitis
+efficient direct N 1functionalization
+comparative genomic
+3%
+PEG-precipitated RSV
+2%
+multivariate
+by decreasing magnitude of difference between non-carriers and carriers
+25%
+Annotations
+1 mg/ml fetuin per well
+AAV-Ova
+air filtration
+weekly
+high-speed counter-current chromatography
+Drosha
+1000
+breast cancer survival
+immunized mice
+Ten
+4 days
+environmental aspects
+five
+aldehyde dehydrogenase
+solid Karmali media
+infect a wider host range
+lacZ
+Feedback regarding the mobile app and its content
+10
+phosphorylation of tyrosine resides in STATs
+phenolic
+Lemma 2
+antisense oligonucleotides
+RTA transport to the cytosol
+easy synthesis, relatively low cytotoxicity, and good degradability
+27 neuraminidase inhibitors
+2
+CT-scan
+HA
+resistant microorganisms
+pronounced genetic variation
+1 week
+headache, fever, nausea, or vomiting
+recombinant RNA 3s
+TREEVIEW
+exogenous IFN-g
+Maintaining animal health
+regression analysis and analysis of variance
+Sequence alignments
+oral fluid
+IFITM3
+November 1918
+the condition of the samples
+21 days
+8 weeks
+death
+lowest
+Quant-iT™ PicoGreen® dsDNA Assay Kit
+A statistically significant drop in nAb levels
+tissue damage and inflammation
+haplotypes shared by groups of strains of various sizes
+hypertension
+urine metabolites, blood glucose, pH value, liver function, and infectious agents
+6
+October to January
+Macrophage-tropic HIV-1 Env
+public health classification
+FP7
+GenScript USA Inc
+mutational pressure
+82 C
+Selecting culturally tailored messages and frequently used local communication networks
+stochastic branching process model
+mutations in one specific gene -GATA2
+DX600
+29
+Magmax Total RNA Isolation kit
+Keywords
+pro-apoptotic
+H 2 O 2 to oxygen and water
+four
+DC protein assay
+four
+Road traffic accident
+January 1, 2003 and December 31, 2008
+non-randomness index
+Xiuchen Guo
+the relevant university ethics committee
+− G non polar
+85% or 55%
+three
+increase
+Construction of porcine CCL25
+arthralgia
+spectrophotometry
+two stable DNA hairpins
+stx-positive
+oncolytic
+Statistical
+non-permeabilized condition
+working with highly pathogenic avian influenza viruses
+50 mg/mL
+B and C
+19
+3 years
+Humanistic care
+completion of the form
+IL-10
+46,864
+oxygen solubility
+Class cancelation
+MS data
+negative extraction control
+GraphPad Prism
+viral
+less than 12 weeks
+Dr. Stephen Dewhurst
+Pre-disaster preparedness, response planning, and policy initiatives
+cDNA template
+30-50%
+Serum
+interstitial fibrosis
+16 h
+University of Alberta Health Sciences Laboratory Animals Services facility
+X protein
+200,000
+Cryptococcal meningitis
+depressive-like behaviors
+VP4/VP2 coding region
+the number of mammalian species that overlap with the target species' geographic range
+52%
+Over two dozen
+12 h
+45 minutes
+Granzyme A
+enhanced the proliferation
+four
+63%
+Bradford reagent
+personal protective equipment
+heteroxenous
+improved
+Levey-Jennings plots
+γ-irradiation
+electrophysiology and immunohistochemistry
+experimental design of nucleolar targeting
+anti-ADAMTS13 antibodies
+poor clinical prognosis
+Pairs of sera
+bacterioruberin
+IP-10 and I-TAC
+herpesvirus
+10
+Physical interactions between human proteins
+northern, central and southern areas
+H9N2
+a stool sample and a nasopharyngeal swab
+5
+trade, demography, transportation and economics
+cathepsin B
+highly standardized
+poor cross-cultural communication
+Autophagy
+Tolllike receptor 3
+endogenous lamin is cleaved
+total cell or pre-IP extracts
+The construct bearing the double mutation
+24,604
+host sumoylation
+Cervical cancer
+comparative
+rLuc activities
+62%
+Amino acids
+VEEV, WEEV and EEEV
+statistical
+expression of genes involved in cell cycle progression
+J5E1 and J2G7
+77-01
+46
+CTP
+Chytra and colleagues
+60-day mortality
+Apoptosis
+Logistic Organ Dysfunction System score
+caveolae
+errors produced by the Taq polymerase
+Docking results
+Bound antibodies
+~30-32
+mild multifocal heterophilic infiltrates
+alignment of peaks across spectra and samples
+Data on clinical signs and symptoms
+cycle transit
+p
+Introgression of domestic Bactrian camel genes into wild camels
+two
+seven months
+220 per 100 000
+81 amino acids
+horses
+20-49
+maintenance of animal health, fertility and growth
+β-Actin
+membrane proteins
+decision-making
+KY and YXH
+10%
+five
+HLA-DR trafficking
+inclement
+Table 1
+N-linked glycosylation
+0.238 mg/ml
+MimicDB mimicDB
+SL6
+24 hours
+local ethics committee
+University of Pittsburgh Regional Biocontainment Center
+CPV-2c
+confocal microscopy
+P aramyxoviruses
+endpoint fluorescence reading
+Neutralization titers
+retained their unusually high connectivity
+a neutral alanine
+Beijing Municipal Center for Disease Control and Prevention
+improved clinical response outcomes
+set up a new control structure for infectious diseases
+glycosyltransfer
+48 h
+a
+country × attitudes and country × subjective norms
+Twenty-four
+the value R 0,9
+Definition-driven methods
+personal resources
+virus interaction with liposomes
+global species biodiversity
+11
+biologically active transcriptional changes
+A weight
+Number of amino acids from the target included in the alignment
+2341
+52 ms long
+α-cells
+m = N M /N H
+Surfactant
+Emiliania huxleyi
+Proteinase K
+KPN_03668
+cleavage of MLV Env by furin
+FACS LSR II
+cytopathogenic and noncytopatogenic
+50%
+Acute respiratory failure
+randomized placebo-controlled trials
+immune surveillance, metabolic activity, and detoxification of blood
+jackknife test
+a patient presenting with a symptom complex
+x
+IL-XPCI technique
+degeneration and necrosis
+50%
+moral technologies
+24%
+template
+ACE2
+Geoinformatics
+faecal diversion
+class-switched memory B cells
+bafilomycin and concanamycin
+Angiotensin
+phylodynamics
+13
+Bacterial infection
+δ-Secretase
+chronic hypernatremia
+206.1
+Apoptotic cells
+All-Stars Negative Control siRNA
+An abscess
+differences in immune-mediated pathology
+growth
+efficiently detect SNP
+IFN-γ
+frameshifted proteins
+ERAD regulation
+changes in systemic functions
+11
+54
+less than 1%
+MiR-210
+A, B and C
+110
+via a network of hydrogen bonds
+cell debris
+Scopus
+TonB
+eotaxin
+up to ten passages
+Spatial methodology 20
+F and HN
+54 probable and confirmed cases
+unfolded proteins or misfolded proteins can accumulate
+sex
+Determination of dominant covariates of polio incidence
+Jerusalem
+NF-kB and mitogen activated protein kinases
+an undirected weighted network
+cephalosporin
+three
+depletes M proteins
+alkaline proteases
+Bio Med Central
+147
+Switzerland
+PRP infectivity
+Cell fusing agent virus
+PE
+2-3 animals per cage
+arresting the cell cycle
+branch elongation induced by the within-host evolution model
+CMV promoter
+ROC analysis
+a gastrointestinal virus
+impulsivity
+David Relman
+partial protection at higher doses and evidence of increased acquisition at the low dose
+HopPER
+5 min
+The PERCH integrated analysis
+BAC DNA
+hCT oligomers and fibrils
+pulmonary edema
+25,421
+over 80%
+seven
+>0.338
+peptides with sequence length equal to 15
+tumor necrosis factor receptor-associated factor 6
+suicide monitoring effort
+.faa
+who has most contacts
+URTI
+author keywords and the title of articles
+overall pairwise comparison among the reference genes
+Reducing meetings and interpersonal communication
+bovine potency test protocol
+published reports
+25%
+Tables 7 and 8
+AutoFluo Quencher
+pdb1ji0A
+E. coli b-galactosidase
+RCA-based assay
+Fifteen
+Humanized mouse models
+cellular antiviral factors
+miniaturized and integrated
+analyze the validity of interventions
+Pseudomonas aeruginosa
+thromboelastogram, D-dimer, or other tests
+37.98%
+logistic regression
+Cell lysates
+lipid raft mediated, caveolin-1 associated endocytosis
+high power field
+Probiotics
+one
+taxonomic diversity
+12
+70%
+keyword searching
+any cleaved GP2 subunit
+Three to four
+pulmonary function problems or neurological function problems
+significant increase
+Luciferase activity
+150 cm 2 flask
+HA-signal
+epithelial progenitor cells
+13
+cytoskeletal structure maintenance, RNA processing and mitochondrial biogenesis
+2002-2003
+Sensitivity
+βselective
+chronic meningococcemia
+75%
+no major impact of missing data on GA
+Intranasal delivery
+two
+credibility tree
+reduced IFN responses
+mucosal airway edema
+elements of the host response may be maladaptive
+three
+the Study Coordinator
+viral immunity
+steric hindrance
+PyMOL
+1,785
+CT, LT-I and LT-II
+Richards growth model
+Jackson Immunoresearch
+Telomerase
+GLuc activity in cell lysates
+loses charge and detaches
+OVAspecific GC B cell response
+8 min
+logistic regression model
+between 28,715 to 29,102
+Trojan horse
+The Codon Adaptation Index
+80%
+geNorm
+sophisticated statistical procedures
+93
+Thirty-seven
+lipid accumulation
+respiratory failure, and poor outcomes
+Establishing the time of infection
+Two
+one
+significant viral replication
+FACSAria
+Student's t-test
+PaO 2
+Interspecific pathogen transmission
+90 days per year
+nutrients
+cell lysates
+k
+antibiotics
+pLHgb-PVX-m vector
+AA
+generated a PCR product of 302 bp
+regional climate models
+NPE
+morphological characteristics
+TI cells
+DVG-324NC ⌬70-114
+compensatory redundancy
+34
+ten
+reduces
+N/5/03
+fall-winter seasons
+Cation 105C
+Twelve
+human primary bronchial epithelial cells and smooth muscle cells
+every two days
+Mann-Whitney U test
+Confocal
+over 100
+Smad3
+L2
+adipocytes dysfunction
+RSV viral load from nasal swab and nasal wash
+7.5 mL/bag
+ligation
+pH sensitive
+IL-10-capturing T cells
+A sample of 100 pairs
+upregulation of ISG expression
+8000
+low concentration of TGF-b 1
+medical records
+lower
+HepG2.2.15
+High Capacity cDNA reverse transcription kit
+fourfold
+3-4 d
+IF
+continuous trait phylogeographic modeling
+Beijing
+TNF-α
+false
+predicted 7-O-GT activity
+T-cell epitopes
+NdeI
+65
+Marseille
+14
+IgG
+meta-analytical
+tension
+RGD-independent integrin
+COVID-19
+those at highest risk of complications
+syndromic surveillance
+anti-apoptotic
+viral RNA templates
+8.1%
+data expression
+Student's t-test
+c and w
+iScript™ cDNA Synthesis Kit
+31%
+time point of challenge and quantity of the pathogen
+Multivariate logistic regression analysis
+Alternative estimation methods
+Expression of siRNA-targeted proteins and actin
+three
+PCR and serological tests
+MBL-AB
+Whole inactivated virus influenza vaccines
+exhaustion
+Clinical specimens naturally exposed to disease
+nucleophilic water
+spore-forming bacterium
+poorer outcomes
+Migration positions of HiMark-prestained standards
+DNA vaccines
+Semi-quantitative RT-PCR
+N-terminal conjugation
+ZNF4
+0.05%
+limit of detection
+MA, MH, MMH and MAH
+dimethyl sulfoxide
+rhesus macaques
+Baseline data
+relative abundance of a bacterial genus
+QM5 fibroblasts and Vero epithelial cells
+peptide
+Vaccination
+Desktops
+Non-parametric Wilcoxon signed-rank test
+limited
+caspase-1
+18
+univariate regression
+three weeks
+CX3CR1 protein
+four
+RNA viruses
+NetCTL v1.2 server
+HSP90
+water
+exaggerated or dysregulated immune cell responses
+Point-of-care ultrasound
+antiviral ISG mediators
+overlapping PCR
+100 μM
+dox-repressible library
+Kolmogorov complexity
+Univariable meta-regression
+hepatitis B morbidity
+4.8 days
+optimal recruitment of YFP-ZUFSP to DNA lesions
+amino-terminal
+3-to 4-fold
+80%
+Equation
+enhanced virulence
+pH
+CUG
+eight
+Asn 26 and Ser 27
+disease
+2010
+two cesium chloride gradient centrifugations
+evidence of natural infection and spillover
+three
+diffusivity
+angiotensin
+septic shock-related deaths
+eleven
+Source Data
+specific treatments
+1100
+sequences similar to the query sequence
+21,223
+Central and South America
+more than 3 days
+week 5
+to understand the correlation between preparedness capacity and demographic information
+7 d
+10%
+membrane integrity
+5
+biological element cycling with isotopic fractionation
+three ω ratios
+tympanocentesis samples
+Protein kinase A
+Ultraviolet light
+60°C
+astrocyte function
+1:20
+the probability of each state
+a major shift
+wild-type rRNA base modification profile
+Concurrency
+not yet well established
+Mae Sot, Thailand
+The arrangement of the boxes
+sufficient data
+zoonotic disease management
+two-way repeated measures
+Immunosuppressive
+HT-29 cells
+demyelination syndromes
+counterfactual conditions
+overlapping substrates
+Ten
+RT-PCR with oligo dT primer
+primary cerebral lymphomas
+detailed
+Met and Thr
+NMDA receptors
+each group
+Cohen's effect sizes
+the normalized frequency of each triad in P
+C-SVM-classification
+5 days
+plasma samples
+taxonomically described viruses
+Twentyseven
+PathoChip assay sen-sitivity
+six
+40
+150,000
+SAS version 9.4
+urinary vanin-1 and NGAL
+glucocorticoid cortisol
+Antimicrobial resistance
+through its CTD1
+helix stability
+residue 17
+coagulation test
+Lab-on-a-Chip
+Seed characteristics
+hierarchical relationships
+patients
+FK506-binding protein family
+physiological
+PyMol
+recipient cells
+Methicillin-resistant Staphylococcus aureus
+CBP/p300
+Statin treatment
+asked questions
+Polymerase speed
+reagents
+CCK-8
+three
+T-cell activation
+106
+22
+17-DMAG, BGB324, and NCK-8
+persistent HRQoL decrements
+FASTA
+wooden
+3417F and 3417R
+English
+AEC I death
+polyethylene glycol 6000
+Gram-positive
+Fourier transform infrared spectroscopy
+5
+Mexico and the United States
+NKp46
+surveillance system or prospective study
+Insectivorous passerines
+kanamycin resistance protein
+1.90
+unclear
+H. Ghiasi
+a 1 mm, 34 gauge needle
+20%
+10%
+18
+school officials
+cc-by
+Validation of Instruments, Supplies, and Reagents and Personnel Qualification
+respiratory drive
+q x,i
+equally dire
+key cell types involved in innate immune defence
+inhaled air pollutants and cold
+shared protocols
+statistical significance
+19
+steroid metabolic process
+enveloped, positive-sense, single-stranded RNA viruses
+maps
+20 μM
+dose-response curves
+twice a day
+Flys-GCN
+Opti-MEM
+porcine cells
+x kj
+transmissibility
+T cells and macrophages
+funding for the prevention and control of NCDs
+2004
+RNeasy Mini kit
+MAVS
+MasterPure Gram-Positive DNA Purification Kit
+four
+ML-HSA
+attractive
+spatial distance between affected farms
+venoms
+quantitative polymerase chain reaction
+147
+pediatric
+striped field mouse population cycle dynamics and seasonal climate change
+20%
+R-con
+Bioanalyser
+lung diseases and obesity
+Thibaut Dort
+Inactivated HRV
+2A
+Quiescent endothelial cells
+hydrogen bonding
+applied pressure p, position, and dent depth h
+submicromolar concentration
+two
+ovocalyxyn 32
+Excessive ROS production
+IL-6
+HCMV infection
+administrative/organizational, environmental, and personal protective measures
+Egr-1 depletion
+an initial RNA3 transcript
+61%
+B cell malignancies
+epithelial proliferation
+encoded the M and H genes downstream from the p10 and P H promoters
+purified protein
+species susceptibility to infection and disease
+co-immunoprecipitation
+>90%
+Influenza
+protonation of histidines
+alcoholic
+Twenty two
+223
+nematode
+mast cells
+Cardiac remodeling
+The cloned fragments of all constructs
+serotype-specific
+Fourteen
+P. alecto and P. conspicillatus
+P. falciparum malaria
+RT-PCR
+mouse
+CD8+ and CD4+ T cells
+viral receptor binding, fusion, transmission, virulence and pathology
+logs
+influenza and vesicular stomatitis virus
+mitophagy
+Four days
+60%
+Singleheaded black arrows
+swine influenza virus
+N f and N i
+proper overexpression of scFv
+ancestral strains
+CD4 T cells
+stressinduced mutagenesis
+34
+12 weeks
+best practice approaches to aid effectiveness
+nine
+Escherichia coli and Enterococcus faecium
+gingivitis and peridontal disease
+54
+PI3 kinase
+reduced compliance
+chi-square test
+fails to inhibit necroptosis
+the nucleus
+Brogan et al.
+Almost three billion
+viral replication
+24
+184
+DISC1
+24 h
+a check list
+R
+7-15
+mouse synaptic-defective 1A
+angiogenic
+PRE9
+human serum albumin
+three
+Gene Ontology databases
+TIA-1, HuR, PABP, and TTP
+442
+Tan Tock Seng Hospital
+loopamp DNA amplification kit
+1/3
+SIRIC BRIO
+hepatopancreas
+5-20%
+Optical interferometry
+ACE2/Ang- axis
+R227
+2.13 to 5.57 L
+host shutoff defective
+Transient recombinant protein production
+higher
+linear regression
+Haploreg v4.1
+10 min
+hypoxic
+76
+treatment of the disease
+Paracrine
+GCK
+CD68
+the arithmetic mean
+antiviral treatment
+respiratory or unknown primary site of infection
+2-3 million
+50%
+Miamiensis avidus
+10
+a cluster of IFN-stimulated and immune mediating genes
+GSE79766
+UV
+Beclin1 and UVRAG
+walker motif B
+Vimentin
+permissive
+0.25%
+protein degradation
+amino acid sequences
+GraphPad Prism
+05SSU0968
+twice
+Folin-Ciocalteu method
+MLKL phosphorylation
+conflicting
+moral technologies
+5%
+107
+successive and mixed outbreaks of respiratory viral infections
+30%
+1.46
+43
+Oseltamivir
+severe iron uptake defects
+I VV and I VH
+Amidoblack staining
+Student's t test
+RIGID mode
+nine
+immunogenicity with a single dose
+the 3D structure of a protein-bound peptide
+gp18 LP
+Eleven
+object system
+Chi-square test
+None
+36
+α5β1 integrin
+Bariatric surgery
+autophagy
+Heat stress
+loxP sites
+Gene ID
+millions
+RSS
+randomized controlled trials
+Streptococcus pyogenes
+diuretic initiation
+CD 4+ CD 25+ T cells
+6 min
+b-TrCP
+c-fos
+evolutionary innovations related to the biochemistry of feeding
+3/24/2020
+Gene-targeting methods
+electron density difference curve
+Low tidal volume protective MV
+PTMs
+Katnal1
+issues of notification, response to minimal risk, responsibility and legal requirement
+wildlife
+HAART therapy
+7
+Creation and destruction of links
+discrepancies in specific areas
+Cas9 expression
+northern Arizona counties
+Menzies School of Health Research
+less good
+Human RNaseP gene
+80%
+50 µl PCR reaction system
+cachexia and weight loss
+to avoid false result
+62
+Respiratory protection
+CQ
+163
+EF, RPL12, and -TUB
+6 hours
+Eight
+Vaccination
+interspecies transmission of primate immunodeficiency viruses
+Pathogens
+an early type I interferon response
+CRISPR/Cas9
+Passive immunity
+TERA
+GAMs
+knowledge-driven matrix factorization
+Programmed ribosomal frameshifting
+decomposition method
+Osteocalcin
+28%
+20-fold
+highest load
+RNA Fragmentation Module Protocol
+5596
+GraphPad Prism 7.0
+TM967
+WNV
+11
+antioxidant defence
+seroconversion
+one-tRNA slippage mechanism
+6 months
+Investigator Statement
+secreted proteins
+38%
+cytomix
+The use of networks
+incorrect nucleotide incorporation
+one third
+120,940
+Stata
+307
+45 of 715
+four
+gene-specific
+lymphoma development
+at least three stages
+genome replication
+226
+X-ray-based
+intravenous corticosteroid treatment
+hapten-sensitized liver NK cells
+methylcellulose
+KSHV lytic
+DNA vaccination
+two PTB signals
+3,168
+monocytes or macrophages
+T-bet and IRF4
+a methodology
+four
+14
+Necrotic
+11
+Olig2 nuclear/EGFP cytoplasmic staining
+65
+influenza viruses
+binding of these proposed inhibitors with papain like cysteine proteases
+UniProt and GO
+the asthmatic phenotype
+long terminal repeat
+Hasegawa-Kishino-Yano model
+test paper
+institutional and social environments, partnerships, and locations
+chemokines
+Twitter messages and Facebook posts
+Human blood samples
+HIV-1
+5
+promiscuous epitope binding of HLA-DRB1 alleles
+0.4488
+Restriction
+four
+RSV vaccines
+3,5 days
+that of definite CAP patients
+mechanistic
+those of controls
+100%
+11.4 per 100 000 population
+12 cm H 2 O
+body mass
+flow cytometric
+HPAI H5N1
+IL-8
+immunohistochemistry
+18
+Five
+over two years
+RNAi
+categorical
+residual bilateral basal consolidations
+Codoncode
+mucosal protective barrier
+MAP into feces
+30
+CAIX + tumor cells
+A. fumigatus and lipopolysaccharides
+Cerebral vasculitis
+Rhat
+proteases, peptidases, and glycohydrolases
+0.54
+bacterial and protozoan pathogens
+means and SEMs
+Waterfowls
+specific cleavage of the isopeptide bond
+cellular metabolism and ECM-receptor interaction
+0.908
+HIV-1 Clade C
+arthropods
+attributable fraction and latent class analysis approaches
+Tetraspanins
+HCVpp bearing concurrent and later glycoproteins
+early-or recycling-endosomes
+60 minutes
+90-day
+LPSinduced activation of p-65-NF-κB
+Cefepime associated neurotoxicity
+minimal
+Australia or Europe
+232
+Fortyfour
+eukaryotic elongation factor 2 kinase
+1 year
+Shc
+viral RNA
+45 min
+PA63
+Group I
+glutamate cysteine ligase
+proteins
+ΔP
+lead-like molecules
+heterologous VLPs of the other three HBoVs
+inactivated vaccines
+contacts of much larger duration than the average
+intraoperative transfusion of packed RBCs
+ZMapp
+u X and u Y
+procoagulant activity
+left ventricular dysfunction
+Total RNA
+early ICU admission
+absolute humidity
+P/L-Selectin-mediated leukocyte migration
+2.5 Pa
+30 hr
+6%
+Chemical prophylaxis
+Exploratory
+600
+DegFact values and 95% confidence intervals
+serine-arginine protein kinase 2
+their function
+900 thousand
+biology
+USPs
+two
+Plasmid pTP-GP
+over 4 years
+3.77
+to replenish and maintain the airway T RM cell pool
+490 nm
+7−10-fold
+Shielding of viral RNA from interacting with OAS
+The R t of each of the nine jurisdictions
+Image J and SPSS
+16 hrs
+C-type
+an ensemble of connecting subnetworks
+taxa
+biotic or abiotic
+neuraminidase inhibitors and adamantanes
+To and colleagues
+QuantityOne
+5.8 cases per 100,000 people
+PolyJet In Vitro Transfection Reagent
+the subject's legally acceptable representative
+chromatography
+seven
+intestinal lesions
+MEGAclear
+enveloping vesicle
+CHO cells
+Escherichia coli and Klebsiella pneumoniae
+12
+Dr. Wakita
+urine output
+TAT peptide
+immunosuppressive
+34 kDa
+IBL Adenovirus IgG ELISA Kit
+text-mining
+real-time RT-PCR
+DN57opt
+p xy
+visual plausibility
+IBB-1
+fresh media
+groups differences in terms of the mean
+ModFit LT software
+MHV-A59
+Emergency medical service
+43.5 days
+to identify fungi
+antibiotic susceptibility testing
+pDCs
+SG dynamics
+sociodemographic
+1 hour
+Meteorological data
+when high amounts of PV 2A pro are synthesized
+posttranslational modifications
+single stranded viruses
+A more comprehensive measurement study
+AC4
+Programmed ribosome frameshifting
+accidents or specific cancer sub-types
+21
+down-regulated proteins
+ambient particulate matter pollution
+167
+residues 100-137
+manual checking of representative reads
+HSP70 and 90
+liberal oxygenation
+MSBH Spin PCRapace kit
+16.5%
+breast carcinoma
+MVA replication
+2 dpi
+pleiotropic
+Fig. 2a
+LDV
+10.1371/journal.pone.0147041
+Pseudoknot detection
+Aedes albopictus
+PB1-S704T
+three
+15 min
+NA-dependent hemagglutination
+Epidemiological and clinical
+observations
+various kinds of porters
+stage II and III melanoma
+long tubules
+antibody affinities
+Mechanical ventilation
+16 hours
+adaptors molecules
+B and influenza Th epitopes
+mutations in the dystrophin gene
+mitochondria-mediated pathway
+the nature of the host
+ACE2
+rAd/NP
+the reader
+A, B, and H7N-subtypes
+Nineteen
+B2M and CA2
+the average of the 32 model variants
+The probability of type 1 error α = 0.05
+less than 3%
+spo0A and sigH
+10
+2.1%
+rs368234815-DG
+26.7
+À31.2 kcal/mol
+HRA-III
+syndromic
+a further antigenic site for Asia-1 strains
+TPK1 and TPK2
+lytic reactivation is needed
+Parasite schizont samples
+50%
+glycosylation and disulfide-bond formation
+one
+polio persistence and population size
+post-infection lungs
+protein or some of its homologues
+United States Armed Forces Research Institute for Infectious Diseases
+IL-1b maturation
+cortical and thalamic
+11
+Coincidence filtering
+supernatant
+binding
+titer and productivity
+low binding rates
+Lungs
+Pili
+activation of proteolytic enzymes and auto-digestion
+U266-NC
+toxin levels
+60%
+two
+epicatechins
+8 mM MgSO 4
+eight
+clinically insignificant safety laboratory abnormalities
+658
+Prostaglandins
+PepMapper
+sensitise tumours cells depleted or over-expressing DUBs
+32% ± 5%
+j f
+no significant difference
+Martin-Loeches
+translocates to the nucleus
+MP-12 vaccine strain
+suppressive
+cough, purulent sputum, dyspnea or pleurisy
+The sizes of the family-level primer sets
+2 mL of cDNA
+South America
+pro-inflammatory
+endogenous and exogenous
+10 min
+4,300
+M. glareolus hepacivirus clade 2
+16
+Expression of Ciita mRNA transcripts
+disease severity
+Cellular restriction factors
+to prevent the possible reassortment of the hemagglutinin segment
+tube formation in vitro
+transmission distance
+treatment with AppDapxIDapxIIC culture supernatant
+PSV infection
+wireless proximity sensors
+MVA
+Ranunculaceae
+a triangle
+natriuretic
+HIV-1 entry
+autophagosome
+antibody titer
+fluorescence
+breath by breath impedance of the whole lung
+airway epithelium
+Phagebased
+hairpin-like
+a low number of printed pages
+the second 163-nt repeat
+G-quadruplex formation
+Data on examination findings, diagnoses, and antibiotic prescription
+5
+genotoxic
+QIAamp DNA 144 Blood Mini Kit W
+99%
+Peptide dens25
+G affinity columns and concentration of the mAbs
+80-90%
+Duplicate titles
+adenovirus
+genotypic diversity
+S. hadar
+three
+physician criteria
+increased ADG
+TLR3
+tolerogenic
+Latin America
+A stainless steel tray
+Hepatocellular carcinoma
+fluorescence
+SGH
+frequent colonizers
+Live viral load
+Hong Kong
+Genes
+WebLogo
+ten
+inflammatory
+the presence of neighbourhood hubs
+NKp30, NKp44, and NKp46
+IRF8
+>90%
+poikiloderma with neutropenia
+CD8 + T cells
+CELLO and SOSUI
+Cp values
+Vanin-1
+porcine pancreas lipase mix
+Fourteen
+8 hours
+RSV
+LC-MS
+High Capacity cDNA Reverse Transcription Kit
+15
+24
+beads proteome
+Dark grey shadows
+cDNA
+hundred twenty-eight
+60%
+64
+7-fold
+0
+140, 180, 70, and 40 μM
+viral protease
+epidemic curves
+prevention of serious illness
+ADM Protexin Ltd
+Tip dating
+chromosome 10q22.2-q23.1
+Seven
+B cells
+Further full genome sequencing and analysis
+6 h
+quaternary structure
+91.1%
+strict restriction on the interaction between HBV virions and the cell membrane
+feasible and safe
+5000
+lime
+Modification patterns
+by budding
+cases of influenza
+virus titers
+oligomerisation and autophosphorylation
+DENV growth
+SPSS
+Viral persistence
+200
+histopathological lesions and PCV antigens
+codon-anticodon
+1,988
+SEM
+extensive genetic mapping
+Fecal samples
+Europe
+four
+Novel cell culture models
+5%
+1.5.2.8
+flee
+valoneoyl
+Knowledge and beliefs
+2
+Vector Laboratories
+APCDD1
+donor 11 and donor 42
+reduced HRQoL
+all-atom root-mean-squared fluctuations
+HBSS
+10%
+RT-PCR from bronchoalveolar lavage
+the system's implementation and the general features of the collected data
+FEI Tecnai T12
+Reduced protection against heterologous influenza strains
+Tukey's honestly significant difference test and Bonferroni
+primary virus
+augmented
+viral core proteins
+daily
+Binding of the Large T antigen to the viral origin of replication
+purifying selection
+Six
+purpura and arthralgia
+linear fit model
+4%
+methylglyoxal
+2005
+cardiologists blinded to biomarker analyses
+The antigenome
+71
+small prospective uncontrolled trials
+B1 and B2
+lymphocytic
+CRT recombinant proteins
+secreted inflammatory mediators
+linkage stems and the root domain
+Jingshi Shen
+guinea pigs
+ISG expression and viral load
+À1 PRF efficiencies
+four
+application of RM in patients with healthy lungs
+A549 and Calu-3
+Àlog 10
+virus-specific and cell-specific
+Sackin's Index
+the globular fold of the CTD
+solid line and bigger
+β-glucuronidase
+Twelve
+genotype
+PBs
+Hypoxic preconditioning
+eight
+Core Hopping
+Western blot analysis
+Eight
+mRNA:rRNA interaction
+BaTS
+Three
+neutrophil elastase
+GRA24
+773.4 mg/L and 848.2 mg/ L
+Guillain-Barré syndrome
+2
+ISG
+antibody-dependent enhancement
+by email
+483
+normality
+40
+Immunohistochemistry
+serum medium
+antibody half-life extension technologies
+Commission of the European Communities
+Ubiquitin E3 ligases
+Corticosteroids
+hospital entry
+21.07 fold
+fusion of the viral and the host endosomal membranes
+Twenty-one
+Weather conditions and seasons
+full-length human IgG1
+47%
+Amnibacterium
+rs12979860 T/C and rs8099917 T/G
+107
+Heart failure
+the germline V, D and J gene matches to the query sequence
+13 days
+Nine
+70
+2,229
+Roche
+respond to it in some way
+positive and negative
+Xbal I and Xhol I
+treatment with MSCs
+intracellular cytokine staining and flow cytometry
+10 mg/mL
+S-phase cells
+RNAs
+purifying selection
+isoflurane
+Serine hyperphosphorylation of IRS-1
+907
+Presence of the intrinsically unfolded VPg domain
+lack of exposure to mosquito bites
+protein NS5B
+between 200 and 500 nm
+healthcare workers
+Herpes simplex virus
+target cells
+inhibits the formation of ion channels
+8
+Homologous structural analysis
+optical density
+2 x
+F up gi
+community cats
+11
+improvements in delivery strategies and the safety and stability of siRNA
+pigs
+~100 nm
+positivity
+multiple different polypeptide species
+analysis of the deep sequencing data
+bleomycin-induced the Ly6C hi monocyte pool expansion
+the corresponding author
+PI4P
+further validation
+H9N2 or H7N9
+allowed for an order of magnitude decrease in pulling speed
+upper respiratory and gastrointestinal tract
+less
+0.5 ml Stop-solution
+compositional constraints
+85%
+10%
+transduction frequency
+65.9%
+Hippocrates
+167 hours
+Nineteen
+African domestic carnivores
+Fourteen
+Vibrio anguillarum
+AP-9
+6
+60 min
+Peripheral blood samples
+NCBI
+additional eligible studies
+24 h
+efficient use of scarce health care providers and resources
+phylogenetic
+Leica DMi8
+11
+Principal Component Analysis
+more than one pathogen cultured from the same specimen
+SIM-SUMO dependent recruitment
+Cas9 mRNA and sgRNA
+virus-cell binding
+inflammasomes
+PCR based method
+proinflammatory mediators
+sumoylation
+reading and brisk walking on treadmill
+The phylogeny
+cytolysis
+dramatically increased
+7.12% ± 1.51%
+1536
+50 nM
+costly and detrimental
+100
+Table 5
+Clinical Pulmonary Infection Score
+HBoV
+neocortical regions
+sampling of young animals
+storage and binding conditions
+HCV core protein
+Toll-like
+allograft
+type I interferon response
+emergency
+using the integrated fraction collector
+samples
+Cholera
+Excess power
+3, 5, and 7 days
+Asthma Index
+36 years
+NK cells
+continuous chemical exposures, recurrent acute inflammation, or specific pathogens
+cell-based
+The hypothesis of human playing a role in ebolavirus maintenance
+pseudoknots
+Repeated follow-ups
+2165
+general practice and the broader primary care sector
+flow-cytometry
+Cleavage of the 5 0 transfer RNA leader by RNase P
+fluorescent dye of resazurin
+NIH ImageJ
+phosphoinositide 3-kinase /protein kinase B signaling
+patients and prescribers
+LPS-induced ALI
+detection sensitivity
+100%
+hubs
+by-stander DCs or unchallenged DCs
+virus replication
+High-throughput
+24 h
+Chemokines
+Contact surveillance
+Capsid protein modification
+a coronavirus
+viral-induced acute exacerbation of chronic airway inflammatory disease
+Yamagata and Victoria
+66
+45
+4%
+pulmonary thromboembolism
+microinjection of semisynthetic N-Ras
+H5 HPAI pseudotyped viruses
+QiagenOneStep RT-PCR Kit
+11
+40%
+all junctions of the canonical structural protein genes
+Human RNAse P
+Activity-based protein profiling
+genetic typing module
+two
+Rabbit hemorrhagic disease
+IR
+postoperative maintenance doses of corticosteroids
+Proteobacteria
+NF-κB activation
+conserved epitopes
+dityrosine C-terminus
+cytokine storms
+intermittent repeats of fast/directional and slow/confined migration
+20
+N-myristoylation or prenylation
+peptidyl Transition State inhibitors, latent TS inhibitors and TS mimics
+ventilator-associated pneumonia
+health individualism and gender
+proliferation, IFN-g production and memory phenotype
+iNR-Drug predictor
+Endosomal acidification
+Direct logistic regression
+GeneJET Gel Extraction kit
+one third
+52
+anti-inflammatory
+YWHAZ
+Parasitaemia
+consistent
+adhesion of those leukocytes to endothelial cells
+the distance to the next stop codon
+phylogenetic trees
+Hockey
+Camera trap protocols
+Harmony Analysis Software
+large-scale vaccine production
+immunofluorescence
+receptor-ligand pharmacophores
+Western blotting
+20 to 30 minutes
+proviral and viral loads
+ablate
+Signal Transduction PathwayFinder cDNA array
+Compound 18
+ROS scavengers
+13
+17
+IFN-g inducible protein 10
+CMV, EBV and HHV-8 DNA
+5138
+severe plasma leakage, severe bleeding, and severe organ impairment
+Gene Ontology
+antigenic recycling hypothesis
+0.81
+30.7%
+household systems
+stress granules
+adenovirus-infected cells
+long-term outcomes
+Systematic and ongoing training of staff in disaster skills and equipment usage
+T-helper cells
+correct identification and access privileges
+Zebrafish
+48 h
+San Francisco
+means ± SEM
+social, cultural and environmental
+homologs to the proteobacterial cmo 5 U genes
+risk/benefit
+hydrophobic residues
+PD-1 signaling
+Points shown as diamonds
+6
+a compound GA tablet
+ROS generation
+Ha3 as well as Eagan
+pseudotyped HIV-1/EBOV-GP
+rabbit anti-capsid antibody
+the immediate need
+macrophage activation
+vacuolar-type H + -ATPase
+late January to early February 2015
+2, 304, 700 km
+Supernatants
+cytosolic
+MessageAmp TM II-Bacteria RNA Amplification Kit
+mechanistic verification of the selected biomarkers
+T-box transcription factor T-bet and Eomesodermin
+2.95
+30 min
+a balance between pro-and anti-inflammatory cytokines
+95%
+trauma
+0.612
+The protein universe
+Hits with an e-value greater than 1610 23
+Arg
+immune responses from Th1 to Th2
+infection of genetically diverse WNV lineage I strains
+new or worsening impairments in physical, mental and cognitive functioning
+mice
+One SMRT cell
+the lung
+BEVS expression fields
+30 min
+86%
+0.5
+JMP 9.0
+particle production
+44
+MeanDecreaseAccuracy measure
+Ire1 R cells
+64%
+3 months
+1%
+probe-to-gene mapping
+a set of sequences representing a specific locus from a group of organisms
+Gene Aminopeptidase N
+African swine fever
+aberrant ER morphology
+differential consequence
+endogenous miRNAs
+adult stem cells
+alpha diversity measures
+ethanol/sodium acetate
+Carbosynth
+public attitudes and behaviour
+0.05 mg/mL
+TLR2
+τ
+colorimetrically
+primary prophylaxis
+BnAbs
+Surveillance with metal ions
+structural data
+T FH cells
+content validity of the overall scale
+30-day
+genetic differentiation
+dorsal and lumbar pain
+The accumulation of recombinant proteins
+watery diarrhea, nausea, and abdominal cramps
+the ATCC
+impaired neurogenesis
+6-month
+day-light
+residues with >25% reduction or enhancement in levels of cleavage
+DMD
+acrolein
+immune status
+alpha, beta and theta
+150-170
+other factors
+diapause incidence
+PE-Alexa Fluor 610 conjugated antimouse IFNc
+lack of control of virus replication in myeloid cells
+HIV Gag
+Vaccination with commercially available HBV vaccines
+TLR4-MyD88-NF-κ B signaling
+alternative pathways of dsRNA on primary hPAECs
+Acclimation ability and thermal tolerance
+chemokine-dependent PMN migration and inflammatory cytokine secretion
+CHIKV infection
+DNA damage
+ventilator-associated events
+by flow cytometry
+12-hour
+Ssd
+stabilizing leucine residue
+q of the bilayers
+80,000 Da
+niche-specific
+Figure 1
+vaccination intention
+memory B cells
+DeconSeq
+World Health Organization eHealth Technical Advisory Group
+the community
+3 billion
+HRP conjugated goat anti-chicken IgA
+a transmission pair
+Our method
+increases in morbidity and mortality
+PocketMatch and RAP-MAD
+40 years
+53
+110
+1.51, 2.53, and 1.59
+10-15%
+antibody secreting plasma cells
+number of reported contacts
+a standard PCR tube
+cytokine expression
+Sequences of the ITS region
+thermodynamic cycle
+statements made without citation to a verifiable source
+6
+cellular apoptosis
+STEM tomography
+ICU
+developing a safe and effective means of directing the fate of iPSCs
+entry mediated by a Marburg virus GP
+equinotoxin II and sticholysin II
+TRPT1 plasmid
+significant protection against MNV challenge
+interferon
+PI3K/AKT
+Gene Ontology
+AS
+FD Rapid GolgiStain Kit
+enhances cathepsin expression
+effector T cells
+.50%
+5 days
+Paraffin tissue sections
+cell regulatory mechanisms
+Íris Eva Hauksdóttir
+downregulating HLA antigens
+mRNA levels
+two
+infectious disease
+2009
+PEGA
+Peroxisome proliferatoractivated receptors
+Bonferroni correction
+quasispecies
+Yeast total protein samples
+Repeat virologic testing in lower respiratory tract specimens
+luciferase
+1,421
+spinoculation
+spo0A
+PRRSV NC
+RanBP2 depletion
+SHRiMP2
+degradation of the endothelial glycocalyx
+HIV-1 Gag-specific cells
+KP EMRs
+VE
+-1, -5 and -11
+the average expected surprisal of the transcriptome
+Single sequence prediction methods
+Four
+GCS above 8
+assuming one homogeneous human host population of infinite size
+viral RNA or protein synthesis
+3.6
+620
+mock-infected animals
+optimal control theory
+neutralization of EV71
+mr7000 microplate reader
+self-isolation
+2
+functional recovery
+viral particle release
+Santa Cruz
+55
+Drug resistance
+Environmental health/sanitation and food safety specialists
+Cytoplasmic protein
+cellular compartmentalization
+REBs
+type III
+16%
+Traditional Chinese Medicine
+membrane protein structure
+mouse
+over three quarters
+16 weeks
+bends down fastest
+SJS and TEN
+IPTG
+host ribosomal RNA
+1000
+size
+mammalian adaptation
+USDA, ARS DOE, or ORAU/ORISE
+a trimer of kinase dimers
+major variants
+3
+Viruses
+United Kingdom, Italy and France
+model B
+pFPAV227-HA
+Wsv477
+Turkey
+initiation efficiency
+Puromycin
+congeners
+59
+Samples for histological examination
+17
+nuclear egress
+IFN-c production
+15%
+LPA
+Source Data
+therapeutic
+Five
+C6/36
+taxonomical
+41,651
+RIPA lysis buffer
+FGFR1
+50 μl of RVFV-4seGFP
+948
+TNFα
+human rhinovirus
+22
+C57BL/6J mice
+to inform the prospective planning and continual evaluation and adjustment of health service provision
+S. pneumoniae and H. influenzae
+CD4bs bnAbs
+P ≤ 0.05
+85%
+a separate regression model
+protein/alum
+SuperSignal West Pico Kit
+UVinactivated
+mathematical models
+Paired ttests
+high-computational cost
+phosphorylation of ERK
+whether it could be involved in substrate interaction
+shorter
+16.3%
+cutaneous; gastrointestinal; and inhalational
+N p
+CASP9
+Cady and coworkers
+tethered proteins
+KT726940-KT726955
+15 min
+Batch processing
+West Nile virus, Hepatitis C virus and Japanese encephalitis virus
+3
+threshold
+8-fold
+enterotoxigenic Escherichia coli O86
+RLU
+induce pH-independent syncytium formation
+Gln 41
+taxonomically close species
+all the positions across each variant's genome
+The association between gender and the addressed behavior
+haemorrhagic nairoviruses
+viral metagenomics
+NCBI Gene Expression Omnibus
+drama, art, youth dialogues, music, and comic books
+NS4B 34
+murine herpesvirus-68
+SP-D
+BMV ER-derived invaginations
+t
+5 days pi
+E90R and T88G
+19
+features
+Deficiencies of the classical pathway
+Nanoparticles
+GATA2
+l E −1
+>100,000 RNA copies/ mL
+phylogenetic signal in a given trait
+total costs
+weekly data on the percentage of visits due to ILI
+MKK3/6 phosphorylation
+SignalP
+7
+Cellomics nucleus factor-B activation kit
+high rates of morbidity and mortality
+mediate RNAi
+Twenty-two
+1.5
+filovirus infection
+365
+AMC peptide substrates
+ten
+Epitope topology and membrane proximity
+Serum samples
+Anti-sense oligonucleotides
+extend their analysis and add additional experiments
+Beckman XL-A analytical ultracentrifuge
+hemophagocytic phenomenon
+cessation of proliferation and inhibited mitochondrial respiration
+peptide-based compound libraries
+0.958
+immunogenicity and protective efficacy
+CED -3
+special sequences of the antigens
+1-2 µmol/L
+352
+DIII
+nine
+Multiple Sclerosis Therapy Consensus Group
+structure-based hLTA4H inhibitor design
+a minigenome
+dialysis membrane
+2 hr
+enrichment of ligands over physically-matched decoys
+Gn and Gc
+deep sequencing, ever-more advanced imaging, and microscopic methods
+chronic remission
+Pseudotyped viruses expressing VN HA antigen
+385
+surface expression of CD86 and HLA-DR
+5 mg/ml actinomycin D
+Nf
+fitness reversion
+80
+15 μL of Ni-NTA agarose beads
+Pfu polymerase
+a specific gene
+1918
+International Health Regulation 2005
+JEOL JEM-1011 transmission electron microscope
+1 day and 4 days
+Failure to consider evolutionary trade-offs
+RSV
+high replication rates
+autophagy and apoptosis
+Candida albicans
+adenovirus and mutated coronavirus
+Donald Trump
+3700
+BioTek EL406 washer
+255,683
+40
+15%
+translation of T cell stimulation
+converge
+viscosity
+BMDCs
+less
+37.6%
+Infections
+92°
+information
+peptides
+balanced and unbalanced
+inflammatory myopathy
+Henipavirus and the unclassified proposed genera Shaanvirus
+understanding the specific role of each of these receptors in RSV infection
+61%
+Infl uenza
+Smoking status
+adverse
+ICAM-1 and P-selectin
+RBC-ghosts
+42
+194
+post-stroke BBB disruption
+T cells
+more potent Bi compounds
+Student's t test and Mann-Whitney U tests
+EBNA
+300 mM
+synchrony
+11
+disease prediction
+0.01%
+θ
+E. coli DH5α
+514
+Mas receptor
+Drosophila Schneider 2 cell expression system
+Z-scores
+CMV-ALI
+low-speed centrifugation
+Foxp3 RFP IL-10 GFP dual reporter mice
+CRY-DASH
+PSI scoring system
+Th1/Th2
+three
+0 to 5%
+7 weeks
+132
+internal human migration flows
+IL-8
+155
+phenotypic features
+5.7 days
+Genetic engineering
+three
+Neutrophils
+Bradford assay
+summer
+IFIT1
+0.1
+CDC
+13
+The conditions for the detection from the public health community of the intentional release
+1/ω H
+diagnosis of asthma
+bipartition
+conformational
+FTO gene
+Six
+CD62L and CCR7
+32
+Disabilities
+28.6%
+C839T
+253 years
+Intraregulatory links
+basic research on HPV
+18
+receptor-mediated
+exponential growth
+intensity of the signal generated by the probe
+10.34%
+Decreased survival of these cells
+Time points with significant correlations
+March 19, 2013 to October 31, 2016
+N145K
+Nine
+all the successive four bases in a given RNA sequence
+0.8%
+Lysate containing EHEC
+comparable to the divergence seen between the rat and mouse
+I 408 and N 410
+NS5
+10 6
+1 week
+3
+distant tumor nests
+MCS Wong, N Lee, TF Leung, TH Rainer
+SNAP
+paths
+loxP sites
+pGAD-BT2-N-His33
+organ edema and dysfunction
+1 out of 100
+1 h
+10
+inhibitory
+oral infection
+1, 3, and 5 quanta/hour
+SARS 209-221
+antibody level and symptom severity
+36.5 million
+10%
+Predicting the origin and emergence
+no effect on stress and coping
+PowerLyser ® Powersoil Isolation DNA kit
+45
+ClustalX 2.1
+calf intestine alkaline phosphatase
+innate immunity
+a list of contents
+25%
+CD200/CD200R
+7 or 9
+twice daily
+DisCVR
+amino acids
+March 11, 2020
+Optimism
+C T values
+clinical specimens from patients with sexually transmitted infections
+Asn77 and Glu114
+exogenous sterols
+heterodimeric gp130/LIFRβ receptor complex
+2016
+ChHV
+important
+DNA fragmentation
+morbidity and mortality
+Streptavidin-alkaline phosphatase
+LNPEP
+sales of over-the-counter remedies
+leishmaniases
+University of Alabama at Birmingham
+0.33% to 0.69%
+MyD88-dependent signaling
+Single splenocyte suspension
+Toxoplasma gondii
+hundreds
+heterogeneous
+The concentrations of circulating cytokines
+characteristics of the virus
+the blood circulation
+9-12 h
+α-catenin
+anti-HIV p24 capsid antibody
+Reactome Functional Interactome plugin
+platelet aggregation -Intensity of contact coagulation
+diminished
+protective
+1.5 and 2.0 mg/ml
+RNAi
+RSV and HRV
+every 10 minutes
+high mutation rates of RNA virus genomes
+1 h
+excess mortality
+ACE2
+0.01%
+C. albicans sc5314 17
+Cancer
+three
+relevance, publicity, appeals and revision and enforcement
+disorder prediction
+Akaike's information criterion
+Bst 2.0 WarmStart DNA Polymerase
+failure to feed via the enteral route
+Cell-permeant Halo-tag ligands
+Pain interference
+TvT c
+103
+n N
+post-HS nuclear translocation
+actual gaps
+DpAV4
+45%
+anti-inflammatory
+viral biofilm
+disruption of UFS base pairing
+111
+age-related decline in the immune function
+luminescence
+95%
+MicroRNA
+Samples of lung, intestine or bone marrow
+genomic and sgRNAs
+Pilot trial data
+nuclear import of parental vRNPs
+g ij
+10-months
+RNAi
+spermatogenesis
+decreases
+sneezing
+ligands enriched in flamed milieu
+0.818
+compromised HCV entry
+immune individuals living in endemic areas
+100 fold
+37
+alternative points of intervention
+CRP, LDH, leukopenia, and hypoxemia
+1 20 years
+Cell lysis
+limulus amoebocyte lysate test
+zero
+Epitope repeat protein gene
+PCR
+employers
+one
+20 % to 40 %
+Table 1
+P
+P,0.05
+acute, acute plus persistent, and persistent infections
+Frameshifting
+PhenDC3
+RdRp ORF
+lung
+supernatants
+Statistical analysis
+20 μM Ubc13/ MMS2
+1% aerosolized OVA or PBS
+drug resistance mutations
+decriminalized suicide
+allogeneic stem cell transplant
+Del155-160
+the virus lacks the necessary mammalspecific mutations
+results of strong clinical relevance
+nascent transcripts
+629
+high-fidelity immune phenotyping studies
+tension in the membrane-attached VP1 N terminus
+mangostin and y-mangostin
+chemotherapeutic
+mice and chicken
+The following criteria
+near the ATP binding region
+50%
+CV values of 1.740 and 0.824%
+58-59 of VP3 and 286-290 of VP1
+zoonotic cycles
+human proximal airways
+Taoyuan, Taiwan
+NOD-like
+10
+simplified versions optimised for speed
+Amoebozoa
+Asterisk
+HA/NA ratio
+IFN1
+Table 24
+model-specific weighting schemes
+Vero cells
+rRNA processing
+Faecal samples
+JEV and WNV
+Glycocalyx
+△G binding
+cheetahs
+maintaining homeostasis
+venovenous-extracorporeal membrane oxygenation
+Tabular and graphical summaries
+.3,000
+AAV mediated gene expression
+IAPV IGR IRES
+Acts of discrimination
+unusual light pigmentation, slow growth on PDA and hypovirulence
+1 %
+contact structure between individuals
+40-60%
+a wide dynamic range
+immunoglobulin receptor
+human PBMC cells
+Ten thousand
+AngII
+IFITM3 inhibits viral entry
+Identification of a putative ESE
+Isoflavones
+21
+a framework
+three
+Autophagy
+error-prone TLS
+HHV-6
+Cuautla
+1989
+N
+filovirus infection
+312-328
+a conventional feed-forward neural network
+Finding Longest Common Subsequence
+aliquots of the supernatants
+37,000
+889
+A and B
+receptors for growth factors and hormones
+good cell uptake
+role of tRNA binding on structure-functional relationships
+liver and lung cells
+IEDB population coverage tool
+diseases
+5% vaccination
+intramuscular
+treatment and/or prevention of a disease
+Toll
+Vaccination
+Stratification before surgery
+EV71 infection
+intestinal barrier-related genes
+Isolation of infected hosts
+Two
+0.25 % glutaraldehyde
+two groups or lineages and four sublineages
+LightCycler 96
+flow cytometric
+India
+70%
+a smaller reproduction number estimate
+12%
+Indonesia
+Sub-cellular fractions
+increased 25%
+The translocon
+IL-4
+additional resolution of non-vaccine serotype carriage
+one
+cancer therapeutics and treatments
+four
+The Sabin live, attenuated vaccine
+g ij
+43
+0.16 mg/ml
+compositional constraint
+10.1371/journal.pone.0222321
+15921
+results
+when readily available
+cell viability
+phone numbers, email, texting, social media and internet searches
+Nature Research Reporting Summary
+Two
+GdmCl
+perinucleolar heterochromatic masses
+25%
+pyrrolidinone
+Digoxigenin RNA Labeling Mix
+six
+stimulation with A. fumigatus
+inhibits
+red alga Eucheuma denticulatum
+flavivirus-derived NIRVS
+15 min
+65
+January 2, 2017
+cellular transcription
+viral
+DNA binding proteins
+toxicity
+miR-127-5p
+270 to 293 codons
+activate NF-kB pathway
+six
+CCHF
+mean ± SD
+sulfo-NHS-LC-biotin
+15 minutes
+OD280 nm
+Cu 2
+Physicians
+Tp2-class C9 protein
+Colony collapse disorder
+ALT levels
+neutrophil numbers
+4.7-6.4 Å
+Cell-penetrating-homing peptides
+HCV NS3 PRF
+Effective prevention and control
+The impact of PI on time to infection
+fluid overload, congestive heart failure and pulmonary embolus
+ANF and β-MHC
+five
+PDI and ERp57
+monolayers
+Infected cell images
+2,400
+additional filtering
+Rolling-circle amplification
+K127 and K164
+4
+ligand-inducible transcription factors
+Paraspeckles
+genome reduction
+cattle and buffalo
+Frequent displacement and limited contact information
+DNA fragmentation
+Rhabditida
+12
+all entries of vector n are equal
+nail biting
+caused a reduction in CatB release in rat pancreases
+Hand, foot, and mouth disease
+EBV
+biological mutations and crossovers
+Proteinase 3
+10.3390/molecules16086489
+57
+Specificity of the antibody
+pseudorabies virus
+QExactive mass spectrometer
+20
+16
+1:8, 1:4, and 1:2
+SRPK1
+48. 5 years
+14
+5
+138
+1968
+Serology testing
+14
+the aid community
+Very little
+viral replication
+Increased laboratory capacity
+Recombination frequency
+ubiquitin-dependent signaling
+Nonspecific antinuclear antibodies and/or smooth muscle antibodies
+conventional piglets
+Purified Drop-seq cDNA libraries
+bortezomib
+HIV-1 infection
+TSB
+4 DU/10 7 CCID50
+fluorescence microscopy
+tympanocentesis
+lytic
+42.5%
+72 h
+28
+Ubiquitin
+overall predictive power
+IFN-γ
+rational drug design
+suicidal behavior
+IgG, IgM, and complement component 3 and C4
+three
+mean 6 SEM
+salivary PoCT diagnostics
+9.5 hour
+HPVinduced caspase activity
+10%
+strategies
+A3B C-terminal domain
+helminth T. vulpis
+Kazan Federal University
+BCL2L11
+HMGB1
+replicase proteins
+Arizona
+BCA Protein Assay kit
+respiratory alkalosis
+RIP1 kinase
+SP-D
+the more extreme aspects of climate
+MHV-induced demyelination
+Cavalli-Sforza chord distance
+50%
+host resources
+Normalized cross correlation
+CD4 + CD25 + Forkhead box p3 + T lymphocytes
+no policy is implemented
+a defect in one of the final stages of glycoprotein complex assembly
+signal transduction pathways
+Lipofectamine 2000
+2012
+arterial
+IRF7
+Electrophoresis with 1.5% agarose gel
+Spo0A binding
+Multi-person pose estimation
+pGEM-2KS and pET21
+Fmoc-lysine-OH
+CRF07_BC
+reactions that occur in the absence of oxygen
+those with the highest IgG titers
+A waiver of consent
+Minor ion suppression/enhancement
+Neutralize the receptor binding sites
+invade to deeper areas of the cell layer
+7
+dengue hemorrhagic fever
+lower oxygen transfer rate
+accumulation of type I interferon
+meaningful phenotypes
+two-photon
+LexA system
+Ethiopia
+1 h
+complexity to ethical analysis
+a zoonotic disease
+sites evolving in a correlated manner
+NP and VP35
+patients with septic shock
+33%
+mammalian
+phlorotannins
+Dunn's test with correction for multiple comparisons or Bonferroni correction
+EVD diagnosis and isolation is immediately performed
+drive the maturation
+day 0 and at the time of euthanasia
+AP30451
+probabilistic evolutionary model
+Leica TCS-SP confocal microscope
+Internet search query data
+An HIV-1 DNA linearity panel
+by neutral proteases
+H. longicornis
+Kupffer cells
+mothers
+£30 000 per QUALY
+oseltamivir
+50%
+enhance the survival
+Seven
+sialic acid
+inflammation, excessive secretion of respiratory mucus and pulmonary fibrosis
+flow cytometry
+sGP
+Platelet recovery time
+Seeplex Meningitis ACE Detection kit
+total RNA extraction method
+SkT~38:98
+linear regression model
+entropy-based formalism
+cell migration
+6.0 per 100 PY
+Src
+2F5, 2G12 and b12
+hospital
+Baidu
+1957
+serpins
+amino-terminal sequencing
+influenza, nidoviruses, and rotaviruses
+VLP infected cells
+inflammasome-associated caspase-1
+safety issues surrounding environmental contamination or secondary immunization of non-target species
+20.7 months
+1 to 8 B to T cells
+C f
+immunohistochemical
+Wheat Germ Agglutinin
+genotype specific and host restriction
+APOBEC3G
+2 × 2 factorial trials
+30
+Complementary DNA
+docking and MD simulation
+negative controls
+the remainder of the collagen sequence
+50 μM of SB203580
+32
+CD8 + T cells
+EDS1 and PAD4
+RNA editing
+Persistent GC responses
+Computational docking
+cough
+EIA
+LacZ
+molecular ion mass fragmentation
+PGF2S
+palpation
+gentler epidemics
+40
+DISC1
+36
+21
+to safeguard successful resolution of inflammation
+labINR
+mitochondrial extracorporeal
+nine
+Range
+HSF1
+28 nt in length
+nucleotide composition and gene expression level
+Fligner-Killeen test
+vaccination
+pMAL-RH20
+Ago2 protein
+greater incidences of underlying diseases and poultry exposure history
+490
+b^2:3
+separate regulators
+18,156
+2/18
+1919
+CVID
+~3,000
+4:1
+clinical data
+relative humidity and cell growth conditions
+post-translationally
+computer vision
+Cisatracurium
+49
+de novo initiated RNA synthesis and the affinity of RNA binding
+C-statistic
+gp350
+7SK-associated
+cytopathic
+Nine
+Student's t test
+neutrophils
+The ER
+Caspase activity
+1 Â 10 7
+BD Biosciences
+Cellular lysates
+0.30 mg/kg
+reductions in pneumonia-attributable mortality
+Derepression of the nmt1 promoter
+over 50%
+65
+GRAVY and aromaticity
+Pneumonia
+14
+DENV-infected cells
+50 mM etoposide
+the relationship between CpG and RSCU
+image-based high-content assay
+High-quality genomic DNA
+salivary glands
+1.083 ± 0.083
+pseudovirus in vivo assay
+ROS
+Four
+30
+supernatants
+the flu
+hanging drop vapor diffusion
+Invitrogen and Jackson ImmunoResearch
+Didemnin B and Gamendazole
+eliciting
+interleukin-6 levels
+ESCs
+influenza A virus
+CISDCP
+RdRp
+high concentration of cytokines
+camels
+a trick of escapologism
+2,159
+Bio-Rad ChemiDoc system
+equal medians
+too much information too soon
+HEK 293 or VR1BL E1 cells
+GFP-positive
+SpO2 data
+IL-2, IL-6 and IL-10
+an existing PPE training program
+species diversity and SNV prevalence
+a productive infection
+APP/PS1
+ribonuclease
+TNF-a production
+TLR
+porcine alveolar macrophages
+EM-map normal mode analysis with elastic network model
+western blot analyses
+.50%
+swine and bovine
+870/14
+28%
+L-arabinose
+E3 Network
+eIF2α
+33 months
+33.3%
+individual selection coefficients
+Patients with malignancies
+coagulation
+15%
+Mushroom bacilliform virus
+susceptibility to several diseases
+secretions
+43%
+Nitric oxide
+at the top of the β-prism structure
+factual disease-related information
+recurrence rate
+P100-I
+140
+the standard deviation of duplicate data
+October
+TNF-α
+Ch25h
+extended regions of structural conservation
+acute deep vein thrombosis
+configuring each breath guided by the previous one
+Natural Killer cells
+CellQuest
+24 h
+postictal
+Bangui, Central African Republic
+cotranslational translocation, vesicle formation and trafficking
+high-resolution electron micrograph
+x i
+Epitope mapping by phage display 64-66
+systemic inflammation
+1a and 1b
+all genomic loci
+increased extracellular matrix proteins deposition in the heart
+40 mM citric acid wash
+The result below
+44%
+NK1 and NK2
+translation initiation factors
+microbial contamination level
+Macrophage activation syndrome
+tropical
+3.3% to 38.5%
+GPC 1, 3, and 4
+Our experimental system
+immunoblot
+lowers the pH
+how positively-charged amino acids or polyamines contribute to protease activity
+kappaB
+2012
+theoretical models
+overweight
+rcdk
+pro-inflammatory
+mutation of the catalytic residues
+35.5%
+sophisticated phylogenetic inference
+genetic instability
+NK cells
+Mueller Hinton
+Four
+454
+plating on laminin-coated plates
+A drain valve
+68.8-79.0%
+-COOH of alginic acid
+~80 bp
+RRVcholangiocyte binding and viral replication
+unclear
+culture-based assays and the Endospore Germinability Assay
+Corriere della Sera
+rolipram
+19
+to study a limited number of genetically similar target pathogens
+ticks
+NADC30-like PRRSV and HP-PRRSV
+biochemical
+ECG and GSR
+Spatial analyses
+four
+FMNH Pritzker Laboratory
+24
+apoptosis
+VP1, VP2, and VP3
+chains
+2U DNAse Turbo
+139
+granzyme A
+ribbons
+Generation time
+the averaged output of nine neural networks
+1997
+altered CQ binding
+6 days
+Arctic Environment, People and Health
+10 days
+the correct transgene DNA length
+HRP conjugated anti-goat IgG
+culture supernatants
+Grey
+Binding of IFNa/b to its receptor
+direct ribosomes to slip by one nucleotide in the 5 0 direction
+IFNc-induced gene expression
+patients with more severe illness
+standardised laboratory tests
+superior
+RSV G protein
+pigs have a full set of innate and adaptive
+viral
+ribavirin, lopinavir and ritonavir
+25
+Dr Mathias Faure
+Nonspecific amplification
+degrade only denatured proteins
+RT-qPCR
+The balance between revealing extant diversity and the continual evolution of new species
+80% to 90%
+cell lysates
+particle bounce on the agar surface
+FGFR1-4
+ImageJ software
+cellular trafficking
+Laser-capture microdissection of lumbar spinal cord sections
+15%
+membrane-spanning domain
+less abundant
+EMT
+1.2 days
+Ni 2+ -NTA agarose resin
+the number of people who consulted
+α-defensins
+1 pfu
+1.5-2 times higher
+markedly enhances
+The correct length of the peptides
+diminished virus neutralization activity
+sequence composition
+6 hours
+NCDs
+IL-2 and GM-CSF
+the final neck repeat of DC-SIGNR
+key factor
+Red Blood Cell Lysis Buffer
+GFP-LC3 vesicles
+3-7
+too few hits
+ATP
+endogenous gene regulation
+gp91phox and p22phox
+GoScript Reverse Transcription System
+human host defence
+it is also elevated in patients with decreased renal function
+Feature Extraction Software version 7
+Three
+an immunoreactive band
+2
+Maximum Likelihood Estimation
+VEGF and COX-2
+L10L and L10H
+non-enzymatic
+LTβR
+better correlation for the method
+one-third
+Variants with count input <10
+recent advances in the field of protein-protein interaction prediction
+quantitative RT PCR assay
+using the inertial microfluidics system
+the corresponding CV file will be kept
+increased affinity for human receptors
+defective viral particles
+RsYN1
+four
+gradient centrifugation
+CVTree3
+>0. 5 Secquence
+redirect elongating ribosomes to premature termination codons
+Reassortment
+a group of individuals with both clinical expertise and methodological expertise
+programmed cell removal
+MNP-mAb conjugates
+Riyadh and Al-Qassim
+compositional constraint
+Intratracheal delivery via microsprayer aerosolizer
+the time when the patient was at the ward for unrelated illness
+Sawyer et al.
+educated decisions
+virus-induced membrane structures
+22%
+wt HsIFNλ4
+Influenza virus and sindbis virus particles
+30%
+smaller volumes of hIgG products
+murine
+10 minutes
+Student's t test
+PPIA and HSP90
+REG3γ
+protection
+RSV G protein
+56.43%
+drug-induced cytotoxicity
+meningococcal, influenza and pneumococcal
+relatively stable
+HaeIII digestion of the COI PCR products
+pilot programs
+flow chart
+48 hours
+Six
+radioimmunoassays
+genetically engineered
+cell culture methods
+4 and 7
+<.05
+pivotal
+RNA structure opposing repression
+gene microarray
+Hipposideros pomona
+gene-level synonymous probesets
+1 hr
+g i
+Sweden
+SEOV and DOBV
+three
+endosome alkalinization
+GFP neg bystander cells
+15
+greater alignment with DGA recommendation and better diet quality
+41
+CD8 + T cell deficiency
+complete resolution of partial respiratory insufficiency
+Molecular surfaces of pMHC complexes
+through contact
+risk analysis, surveillance and response
+50-100%
+2,000-3,000 ps
+epitope tags
+low quality
+asymptomatic
+Old World fruit bats
+mid-summer to early fall
+proteins with specific biological activities
+type I interferons and TNFα
+9.2
+Epstein-Barr Virus
+MODELLER 9.11
+Public opinion
+The estimated copy number per PCR reaction
+actual risk
+suilysin
+Z-FA-FMK
+Four
+1.0
+hepacivirus RNA
+115
+The load generated when the wearer moves
+Plasmacytoid dendritic cells
+liver and renal functions
+the environment
+misdiagnosis and delayed treatment
+369
+112
+558
+differential conservation spanning protein length
+12.5% acrylamide gels in duplicate
+charge-charge interaction and hydrophobic forces
+repressive histone marks and a lack of gene expression
+Helicobacter pylori
+SBV
+when mismatches are centered
+VCR-OA
+CD59
+binds to IFNλR1
+ribosome profiling data
+calcium
+133
+Ningnanmycin
+three
+YM KI EK
+human administration and elicit an antibody response
+inflammatory control, autophagy and apoptosis
+1001
+white light
+on the ward
+cristae
+50%
+weight-loss
+public health
+the difference value of potential latency
+>70%
+EVD mathematical model
+3 h
+robust protection
+Wzi allelic typing
+haemagglutination inhibition assays
+HIV and tuberculosis infection
+Src kinase
+1975
+α i
+SREBP-1
+translation of mutant RNA
+not skewed
+cell-permeable protease inhibitors
+due to many internal and external factors
+leukocytes and physiological regulators
+clinical pulmonary infection score
+The location of capture
+Nuclear receptors
+deoxyribonucleotides
+near the diagonal line
+Collected serum
+nitrocellulose membranes
+ER-stress
+Toronto, Canada
+pulmonary injury
+Peptidases
+lysates
+very low
+neutralizing antibodies
+long term carriers
+all cause lethality rates
+2007
+21-28 days
+1956
+different dynamics
+PD-98059
+ECP and EPX/EDN
+r COM
+Early growth response 1
+Focus Group Discussions and individual interviews
+base composition
+8 d
+The firefly and Gaussia luciferase genes
+collect any available data
+codes of ethics
+Fibronectin CH50
+short incubation, high mortality, and fluid shift
+Macaca sylvanus
+hamilton depression scale
+leads to infection
+PCV-2
+conformational changes
+microtubule inhibitor drugs
+75,000
+spatial access to medical resources
+trans-epoxide 4
+higher IgG titers and DENV-2 specific neutralizing antibodies
+Fit Score value determination
+ACE2
+remodeling or bronchiectasis with segmental fibrosis
+5%-10%
+gp41
+three sequentially acting kinases
+19
+to assess national-level preparedness
+three
+ACE2
+26.7%
+qRT-PCR
+Long distance horse transportation
+PRRSV infected cells
+400
+January and February 2011
+Ribosomal RNA
+Provider orientation materials
+sELR1
+more than 15 000
+Real-Time RT-PCR
+Drug likeness
+liver samples
+peak shedding
+March 23 2014
+One-hundred and fifteen
+2.5%
+Table S2
+Network and pathway analysis
+5% skim milk
+10
+develop pandemic preparedness plans
+getting patients to practice better health habits
+Nine
+Storm phosphor-imager
+increasing age, extent of burn and presence or absence of inhalational injury
+110
+10 days
+Use of the Internet and social media
+immunity/antigenic
+Expression of glyceraldehyde 3-phosphate dehydrogenase
+intensive research
+S. Enteritidis strain 125109
+Vaccination
+one-way ANOVA
+the minimum number required for accurate monitoring
+Sweden
+ViDiT-CACTUS
+elevate the pH of acidic intracellular organelles
+stimulate the synthesis and accumulation of interleukin 12
+ALG1 and RDE1
+3.4 ± 0.1 kJ/mol
+Glycera
+300 mM imidazole
+excitatory and inhibitory
+cysteine residues
+high dose intermittently or low dose continuously ribavirin
+their role of signaling infectious patients
+mean alveolar pressure
+99%-100%
+cc-by
+tracks the input conformations
+PKE
+lignocellulose
+early detection of H. contortus
+goodness of fit tests
+Clinical, laboratory, and imaging data
+80%
+L. Glimcher
+effectiveness of PRRSV infection and lesions
+ARB algorithms
+two weeks
+winter
+1976
+therapeutic strategies
+Sardinia
+Obesity
+milder inflammation
+TGFBR1
+θ-defensin
+0.8 mg/ml
+LPS from Escherichia coli
+infections by a variety of pathogens
+phenol/chloroform/isoamyl alcohol
+Genome transport and entry to the nucleus
+Western Lightning Plus-ECL reagent
+68
+Affinity Purification-Mass Spectrometry
+cytochalasin D
+Pip6a
+molecular epidemiological methods
+S evere Fever with Thrombocytopenia Syndrome
+3.0 × 10 6
+cytokeratin 18
+EcoRI and XhoI
+12
+Sentinel 2
+SDS-PAGE
+Enrichment ratios
+≤ 2 days
+3 nt
+an overlapping 9-mer peptide pool
+different pathways that promote PB assembly
+nutritional
+RABV glycoprotein
+48
+Protecting immunosuppressed providers
+disease enhancement
+107
+to ensure their own survival and transmission
+colors and shapes
+U modification at position 3
+TSP
+different trends for sepsis risk
+30 min
+treatment with anti-HER2 therapies
+pH 7.0
+ELISA
+95%
+10.1155/2013/194976
+Peroneal motor and sural sensory single NCS
+TNF
+low yields
+Hematoxylin and eosin
+chronic stress
+Finland
+nosocomial transmission
+males
+lethal infection
+HA-driven
+MHC/peptide tetramer
+cases in which infection existed prior to hospitalization
+H9N2
+end-expiratory lung volume
+antiviral therapy
+PAMP dsRNAs
+Antigen detection tests
+cynomolgus macaques
+COPD
+an ''arm-like'' projection
+5%
+alveolarization
+better pandemic planning
+Chonbuk National University
+424
+four
+residue substitutions and receptor density
+KoRV
+16 days
+2 ACH
+IMOD
+1/20
+CS
+Uncertainty in the estimation of model parameters
+activating
+5/3/2020
+genomes with size more than 100 kb
+small receptive fields
+interdisciplinary
+the path cannot be divided into two equallength paths
+IL-4
+influenza A
+cooperative effects
+ubiquitinylation
+quantitative PCR
+A and B
+0.05%
+translational
+40%
+Rotavirus
+Thirteen
+stem cell differentiation
+NK cells
+pSTMV and pRP
+excitation light
+13
+B cells
+three
+lymph node
+gastrointestinal stromal tumor
+11
+high levels of specific IgG
+pulmonary infection and by hyperoxia
+IRE1a and PERK genes
+MobA89K
+840
+2017-12-07
+microscope
+Interactions between the epitopes in the context of the superstructure
+rHc-CS antigen based indirect-ELISA
+different functional variants
+DIG High Prime DNA Labeling and Detection Kit
+7,184,391
+N-acetylcysteine
+Phe, Met, and Ile
+pregnancyspecific P. falciparum antigens
+Nineteen
+transmissibility of virions
+rabbit anti-CD31 antibody
+a HIS4A::lacZ reporter cassette
+Diarrhoea cases
+Paleartic region
+74%
+Catabolism of the nucleotide sugars
+decreased the proportion of the lethally wounded AT I cells
+2009
+Tecan Infinite 200 PRO
+gene loss or gene reduction events
+deletion of genomic elements
+Kern's model
+47
+unmanned aerial vehicles
+3
+103 N
+Richness
+1,194 Å 2
+ea-utils
+NF-κB or AP-1
+firefly derived luciferase
+leukocytes
+IgV and IgC
+three
+Control animals
+48
+FRET-by-FLIM
+restrictive lung disease and pulmonary dysfunction
+1308
+endogenous ISG15
+U1
+2,352
+niche similarity in environmental dimensions
+act as DN inhibitors of CME and block uptake of transferrin
+angiogenesis
+Chi-square test
+the core, the matrix protein and the viral envelope
+an accessible sample matrix
+569/58.7 pg/ml
+explicit deterministic susceptible-infectious-recovered models
+hemoadsorption
+improved statistical methods
+Surfactant protein D
+Wnt signaling pathway
+CMV
+383
+fair sharing of research benefits and burdens
+RV
+FLDS
+cytotoxicity
+General practice response
+modified techniques
+policy-makers and public health experts
+anaerobic Gram positive bacteria
+pvmdr1 levels
+reduced ER chaperone production
+0.5 µM
+copies
+2005 ATS criteria
+ansamycin antibiotic GA
+HIS mice
+epidemiologic studies of sepsis
+1:1
+RNA extraction efficiency
+FAK-deficient
+16%
+Th2-type
+UFSP2
+95
+124.5
+Y
+Pattern recognition receptors
+• O 2 production
+T = 41 days of observations
+687
+antitumor efficacy
+20μl
+safe local practices of child care
+monocytes
+Immunohistochemistry
+pentamidine
+inadequate application of PEEP
+distant sites
+Viral infections
+15%
+Seventy-two hours
+nucleolar compartments or additional nucleolar bodies or aggregates
+electron
+IFITM1, 2 and 3
+Nitric oxide
+inhibition of HIV-1 reverse transcriptase
+12-day
+25%
+London, UK
+anti-inflammatory activities
+clinical and animal research
+representative photomicrographs of ACE2 immunohistochemical labelling
+Partial effect plots
+control procedures
+extracellular matrix
+mitigate motor deficits
+neutrophilic inflammation
+TS
+Theory of Heat
+the operational process
+rats
+Staffing pressures
+R igraph
+Mutations Y271A and I274A
+anti-apoptotic ability
+100-fold
+Diabetic nephropathy
+fresh medium
+10% of their preimmunization body weight
+how it was implemented
+yeast surface display
+national laws and regulations
+Written informed consent
+RT-PCR
+NdeI and NotI
+reduction of Entropy
+specificity
+infection of dengue viruses
+ROC curves
+an organ from one mouse
+33.3%
+tertiary transmission
+25% to 30%
+4 days
+70%
+H7N9
+antiproliferative and antigrowth effects
+C-Myc
+trypan blue exclusion method
+triggers the activation of specific repair mechanisms
+BioCaster
+RTIs
+28
+May 12, 2015
+missing information
+blood urea nitrogen
+good reliability for internal consistency
+25 µL reaction system
+acute respiratory distress syndrome
+capturing images at different places for one lesion
+cells
+isothermal amplification techniques
+Two mL of diluted tail DNA
+Whole-genome approaches
+Autophagy
+54%
+Nineteen
+circulating lymphocytes
+Graphpad Prism software
+CD226 and CD40 genes
+2.5 mg/ml
+severity of DSS-induced colitis
+embryonic
+Studying the sign of the eigenvalues of the Jacobian matrix
+Hantavirus
+intraluminal
+DNASTAR Lasergene
+median
+methodological
+containment
+baseline mortality
+early IFN expression
+discriminate different oligosaccharide structures
+359
+ImageJ
+immune response
+noncanonical functional residues
+reproductive number
+MARV GP 1 RBS
+GO annotation
+written informed consent
+29
+173
+The effects of scan rate
+TL2 of the 3 0 DB
+visual analysis of CT images
+6
+cellular therapy strategies for epithelial diseases
+Stealth™ RNAi Negative Control Duplex
+≈50%
+descriptive analyses
+478
+The structure of the full-length N protein
+Immunization with large number of plasmids
+CCR5
+Tukey-Kramer test
+3 fluorescent substrates
+Six
+flow cytometric
+Angiopoietin-like 4
+down-regulated
+two
+cDNAs
+endothelium
+Titer
+a subset of ALI patients who survived hospitalization
+Modifications
+a K consecutive base pairs set of TMEV molecules
+IFIT2 KO survival and lower kidney fungal titer
+Master PureTM Genomic DNA-Purification Kit
+Multiple plasmodial genomes
+Epithelial injury
+interstitial inflammation
+reduce mite numbers in a colony
+CaCl 2
+S 1 and S 2
+RV-A16 RNA
+intermolecular structure
+reaching 30 minutes per session
+Th1 and Th2 cells
+990
+when p,0.05
+QCapture 2AE70AE0
+cytoplasmic
+BJ, SD, and HN
+FDCs
+Two
+asymptomatic
+GFP fluorescence
+lipid matrix of H. volcanii
+free amines
+1984
+λ and α
+64
+Identity and purity of all compounds
+1 h
+procollagen II
+apicomplexans
+distribution pattern of comorbidities
+Our results
+innate immune responses
+ticks
+886
+1:2
+>70
+protects and soothes inflamed peri-wound skin
+18.449
+15-40%
+Two
+84
+Gram negative bacteria
+27
+pericellular fibrinolysis
+morphological
+DNA quantification in BAL
+HSP70
+MicroRNAs
+MyD88
+18
+two concepts c1 and c2
+host's transcriptional machinery
+2.7
+distance/ time/economic metrics
+MHCI and MHCII
+18
+TLC
+viral fitness
+numerous putative overlapping genes
+Beijing
+Passive
+QW101
+GHQ-12
+infection
+Leptospira
+α2,6-linked
+ferrets
+influenza
+translation of replication-associated protein
+30 min
+Heart failure
+defective immunoregulation of the middle ear inflammation
+when this IRES is activated and utilized during the virus replication cycle
+Multipotent hematopoietic stem cells
+increased expression of Bax protein
+v-ATPase inhibition
+8.4%
+three
+dermatitis, skin irritation, and DNA damage
+North America
+8
+Microscopy
+Ethics approval
+Japanese encephalitis virus
+0.1e5 mm
+simulation results
+responsive cytokines/chemokines
+full-length clones for each identified gene
+32
+a potent oxidant
+exponential fluorescence accumulation
+high level of homology
+82%
+Throat and nose swabs
+36.3%
+slight differences in the viral genomes
+Two
+1, 2 and 3
+24h
+Ψ and T.
+muscle and unmodified Morpholinos
+0.45 μm
+Cell culture supernatants
+155
+4
+Env protein
+Polymerase activity
+A slippery sequence
+Reed-Frosttype epidemics
+15
+4 weeks
+1/100 000
+24 days
+Glutamine
+enhances antiviral CD8 + T cell responses
+Details of the jurisdictions and/or portfolios that have endorsed the plan
+BCL2 family
+SWISS-MODEL
+the additional Exposed compartment
+p10 MPER
+The Freedom House
+EndNote X7
+systemic RAS independent mechanisms
+condom use
+tens of thousands
+crystal violet
+11
+strong cell-mediated immunity
+99.99%
+ρ
+two
+programmed À1 frameshifting
+depleted
+Netica software
+IBM SPSS statistics software
+packaging or labels
+MCP-1 and other cytokines levels
+chimpanzee
+Annotation counts
+M2
+Metastases
+AC cows
+Golgi-derived membranes
+Women
+phospho-PKR band
+DCt method
+pyruvate and Man-NGc
+10%
+atipamezole
+ammonium sulfate
+Phage Qb
+Bacterial vaginosis
+targeting of essential viral function
+text-based documents
+19%
+data from the recent 2009 H1N1
+magnetic bead method
+airway epithelial cells
+2016
+mouse
+2
+HPRS-103
+50 mg/mL high SPP dose
+2,712,033
+59.2%
+ligation mixture
+Michaelis-Menten dynamics
+240 million
+SDS 1.4
+lowering the temperature
+À26.9 kcal/mol
+Endogenization of retroviruses
+high-fidelity mutations
+participate in this research
+12 th day post infection
+MVASAG1
+Four
+314
+Twenty-four
+GEO
+Mumps
+flavivirus persistence
+The Immune Epitope Database
+1014
+class II transactivator
+hyperhomocysteinemia induced cardiovascular disease
+fluorescent tags
+conservation of the broad antiviral spectrum
+avian influenza A virus H5N1
+Blood glucose
+current observations with PBMCs
+PCT
+essential regulators of the immune response
+2.18.0
+bovine serum administration
+self-renewal and maintenance of glioblastoma stem cells
+HIV associated neurocognitive impairment
+Ad5
+L-arginine metabolism
+Africa and Asia
+pro-inflammatory cytokines
+astrocytic reactivity
+mucosal dysfunction, microbial translocation, and persistent immune activation and inflammation
+asexual
+14 day
+over 1,000 hours
+porcine enteric calicivirus Cowden strain
+fast linking dynamics
+EGFP
+stem S1 of the pseudoknot
+uranyl acetate
+single-cycle viral yield experiment
+large-scale manufacturing of cell-free products
+VP2
+immunosuppressive
+yeast HR
+5 days
+cc-by
+higher fluorescence readout
+2-4 h
+viral particles
+free energy minimization
+experimental details
+LMP7 was specifically lost by 50% and 80%
+plasma
+general practitioner
+monocytes, macrophages and dendritic cells
+fewer lung inflammatory cells and decreased acute lung injury
+bisdesethylchloroquine
+Type 1
+16
+Figure 11
+important
+18S ribosomal RNAs
+the weight of the two distributions
+More than 100
+One month
+300 K and 312 K
+four
+3
+the spleen
+histidine
+ligands that modulate autophagy
+cynomolgus macaques
+FACS
+COVID-19
+black
+antibiotics
+80%
+anomalous phasing
+V27A mutation
+bacterial etiology
+take part in the ETT
+3.2 mg/mL
+Hsp27
+several events
+Vaccination and challenge experiments
+PI
+antibody titer
+1
+12
+100% prevalence rate of infection with one or more viruses
+Examining the ethical perspectives motivating foreign policy for health
+The significance of the computed r value
+difficult
+France
+98%
+Gilbertiodendron dewevrei J. Leonard
+CO
+reversible
+seven
+60
+problems
+36
+75%
+2005
+2-fold
+10-day
+RIG-I and IPS-1-dependent signaling
+Untransformed M13 phage binding titers
+sM2 fused with or without CTA1
+CFSE and CMTPX
+side chain of mcm 5 s 2 U34
+35%
+RT 2 First Strand Kit
+importation
+17.2
+5 hours
+macrophages
+step up and administer the most immediate and effective punishment
+PBoV1
+extreme viral pathogenicity
+HBV DNA
+preferences for optimal AT-rich codons
+three
+susceptible depletion
+Holme and Kim
+T cells
+Cattle
+TANGO1
+Suddenonset severe chest or back pain
+97, 14, 6 and 0
+24 hours
+CD4+ or CD8+ T cells
+severe acute respiratory syndrome
+50−65 nm
+four
+sumoylated proteins
+relatively normal
+glycine decarboxylase
+haemolymph
+Baboons, macaques, and chimpanzees
+Cigarette smoking
+Hitachi 3300H spectrophotometer
+protein produced in the liver
+Britelite and XTT
+three
+increased transcript abundance and protein secretion
+increased viremia and decreased clearance from serum
+PhenDC3
+Rhipicephalus appendiculatus
+doxorubicin or camptothecin
+CellTiter-Glo ® Luminescent Cell Viability Assay
+Eight
+Phosphodiesterase
+HUVEC and THP-1 cells
+β i
+17
+neurodegenerative
+Small molecular inhibitors
+MyD88
+rosette structure
+Enrichment
+1-2 hours
+influenza A virus replication
+Media reports
+IL-10
+one of the two origins of viral lytic replication
+chloride currents
+oral inactivated PEDV
+ARDS
+cervical and iliac
+WT system
+viral load
+Little
+Two
+Superinfection exclusion
+NFkB activation
+apoptosis or autophagy
+herpes simplex virus type 1
+15 ml/kg
+2.5 mL of coupling buffer with 10% KLH or BSA
+a change in the nuclease resistant HCV replication complexes
+nurturance
+IFNGR1-IFNGR2
+An infectious biological agent
+BamHI/HindIII site of pET32a plasmid
+4.2%
+444
+nine
+ClustalW2
+Mov-Avg Cusum
+mCherry
+a large reduction in Ub-AMC cleavage
+weakened purifying selection
+Host immune mechanisms
+on the cellular membrane
+marsupials
+AffinityScript QPCR cDNA Synthesis Kit
+mortality
+Histofine Simple Stain MAX-PO kit
+Infiltrated spots
+E1 region 265-296
+data from three different representative mice
+four
+Daily ultrasound scans
+dietary sodium content
+Medical judgement
+hemolytic anemia
+5.5 days
+Professor Changjiang Weng
+85.7%
+seven different algorithms
+receptor-mediated endocytosis
+0.15 μM
+meeting abstracts
+6 months
+159
+six
+ELISA
+83
+linear regression
+312
+2001
+four
+host caspase-3 activity
+late July
+10
+phosphorylation dependent dimerization
+70%
+Detection microarrays
+normalized spectral abundance factor
+flow cytometry
+patient safety
+HCRC or MHCRC
+co-infections of virus and bacteria
+six-weeks
+pSUMO/Scorpine
+communication
+errors
+virions without virus diffusion
+97.4%
+10
+irRECIST and imRECIST
+siRNA library screening, western blot analysis, and northern blot analysis
+231
+a six-helix bundle
+drop-in surveillance
+MEGA6
+Niclosamide
+DTMUV
+programmatic access to the SEED data and methods
+ICOS
+seven
+oral and maxillofacial
+370
+two
+ten-fold
+Four
+Mayo Clinic Arizona Pathology Database
+PALS1 levels
+SDS-PAGE
+126
+phenol red-free complete RPMI
+the aortic volume
+Fecal transplantation
+Vaccines
+Selection bias
+grey arcs
+cloning into a T-vector
+doxycycline
+N-linked glycosylation
+three
+Diacylglycerols
+52
+viral attachment and membrane fusion
+position 461
+Anticonvulsants
+Xenograft rejection
+plus-strand G-to-A hypermutation
+SHAPE-predicted single-stranded regions
+virulent IBV challenge
+weight loss
+Systematic screens
+human or animal
+Vehicle or LPS
+1968
+systematic
+GTV strain DXM
+termination-reinitiation
+acetone/olive oil
+any assumption about the future benefits and risks
+20 mg/kg
+categorical
+-β
+leak contents
+Double-stranded RNA
+protein evolution
+Xofluxa
+HA stem-based
+decrease
+quasispecies
+a model analogous to that for minute virus of canines
+sex, age category, or the interaction between sex and age category
+biological
+Roche Fast Start Essential DNA Green Master Mix
+antigenic alteration to the viral particles
+Xin-Yi-Qing-Fei-Tang
+twice
+ARDS
+PNG
+100%
+6%
+down-regulated transcription of these genes
+Venn diagram analysis
+more stable
+a value of.9.5
+deteriorates
+CC 50
+pH
+4-6%
+dimethylaluminum chloride
+transmembrane anchor
+SCAU#0014
+climatic conditions
+E. ovinoidalis
+GIB
+DSPA/IFITM
+T705-RTP
+FAK-Ambra1 complex
+transmembrane domain
+7
+specialized centers
+Crohn's disease and ulcerative colitis
+high homology
+vaccinations
+Freshly trypsinized TZM-bl cells
+viral loads
+nine
+30% to 50%
+dissociation of RAGE homodimer
+respiratory etiquette and hand hygiene
+30%
+Age and gender
+Acinetobacter baumannii
+Hepatitis C virus
+viral glycoprotein-expressing cells
+8-9 and 37-40
+high E-CO
+ILP-based method
+kupffer cell
+39,305
+60
+decades
+T cells 1
+EFIRM
+ketamine or Telazol
+88%
+elevated mortality
+Patient recruitment
+MTT method
+signalto-noise cutoff
+from sick or dead poultry to humans
+how to respond to environmental and self-antigens
+10%
+viral protein synthesis
+6-12 weeks
+9
+Huh7
+Exploiting the underlying mechanism
+functional equivalence
+statistically significant
+PA replication
+OPLS-DA
+AUCs
+500:15,000
+13,672
+binding of a secondary receptor
+stem cells
+515.2 mM
+Dnmt3a activity
+every 3-4 days
+kernel parameter estimates
+serum
+LPA-induced DR6 expression
+mucosa
+17.3%
+intestinal amebiasis
+Int1
+presence-only maximum entropy
+gaps in current laboratory leadership learning programs
+an adaptive mechanism to refold unfolded and misfolded proteins in the ER
+LaSota
+every step in the viral life cycle
+passive lateral transfers
+early detection of a GI disease outbreak
+Asian countries
+4
+HCWs
+21
+02:55 pm
+transferred to seawater
+Other TPR-Containing Proteins
+one
+transmembrane densities
+ubiquitin
+ducks
+302
+the gene proportion associated with the respective term
+VEGF
+19%
+Ligands that bind G4 RNA
+disparate cultures and ethnicities
+chimpanzees
+ARRDC1
+inflammatory
+1/10th of the cell culture volume
+cerebral endothelial cells
+twenty-two
+96
+feces
+kip1
+unique substitution analysis
+b-actin
+Attributes key informants and health officials
+anti-Ly6g antibody
+trypan blue dye exclusion
+appropriate
+antisense-interfered SHAPE strategy
+R 0
+latently infected neurons
+caution
+multi-step
+1000
+24-hour
+Keimig
+fugitive
+one day
+cycle threshold values of the diluted M-vRNA standard with known copy numbers
+Two hundred
+Homocysteine
+18S
+38
+bioluminescent signals
+drug stockpile
+neutral proteases
+HepaRG
+deletion of codons +28 to +61
+levels of U6 snRNA
+PMO chemistry
+Arenaviral proteins
+type 1 interferon system
+100%
+21%
+544
+EL and the sensitivity of the test
+geocoding
+1 or 10 μg/ml
+Deafness
+RS
+41%
+B lymphocyte
+handheld devices
+five
+more than 50
+48 hpi
+moderate agreement
+$10-to 14-fold
+seed dispersal
+chloroplasts
+79%
+65%
+four
+poly particles
+Renal failure
+effective tetherin antagonist
+RIG-I
+Versions of the prototype for several isothermal techniques
+77.5 years
+RT-qPCR
+T-cell activation
+TGF-b 1
+macrophage infiltration
+Kupffer cells
+by using the telescopic locking nut and rotating locking nut
+29%
+37˚C
+less than 50%
+40 million
+Inspect3D
+translation, rotation, and differences in internal geometry relative to the initial predicted pose
+H9 infection
+RTA promoter activity
+À70 C
+dimeric
+Arterial blood gas
+F81 cells
+clinical and epidemiological
+AutoDimer
+small molecules
+poorer
+nine
+80uC
+different types of data
+5
+tribromoethanol
+cerebral blood flow
+some bias
+pro-inflammatory
+cardiomyocyte phenotype and morphology
+Supplementary
+Univariate
+20
+phase-contrast light microscopy
+binding to 2H5
+25-30%
+4
+mild to moderate gingivitis
+growth form
+ICU attending physicians
+host phylogeny
+Identifying important nodes to affect diffusion on networks
+273
+log ACE2 and age
+nsp2
+Respiratory failure
+increased transmission
+QY
+pattern recognition receptor
+immune cells
+poliovirus
+two
+NDP52 and TAX1BP1
+Twenty-five
+bacteria
+State R5
+A module-based regression
+Six
+ts and cold-adapted phenotype
+22.1
+blood stasis, hypercoagulability and vessel damage
+5%
+by dividing the wet weight by the dry weight
+33.5%
+contaim
+Sixty-eight weeks
+telomeric multimeric G4 structures
+5 nm for excitation and 10 nm for emission
+Chemoprevention
+nonmultiplicative effects of double genomic manipulations on growth
+relativestaff
+the deletion
+1930s
+less than 30 min
+496
+age-or location-specific subsets
+Type II pneumocytes
+increased capacity
+Upon target binding through the scFv domain
+L
+NGS technologies
+rs12252
+Western blotting
+CReP
+random effects model
+Fisher Scientific
+SCR-modules
+individual-based and other stochastic models
+culture media solution
+epithelial
+101
+three
+homotrimeric glycoprotein complexes
+herpes
+f i
+Blood samples from mice, ferrets and non-human primates
+AMR K. pneumoniae
+cluster-specific PTSD and depressive symptoms
+relative fluorescence intensity
+The link between infection rates and obesity
+Defensins
+G1 to G5
+Actin
+7 days to 6 months
+30 min
+virus biology
+extensive RNA structure
+selenomethionine
+Gaussia luciferase
+woodchuck model
+ratios
+10-fold
+Student's t test
+Over 168 million
+Phylogenetic
+three
+1 h
+invest more in global disaster surveillance
+5%
+14 November 2007
+Actin and actin-related proteins
+34%
+RGs
+0.25
+p value cutoff level
+disease management and control, and biosecurity measures
+protein unfolding
+NCL1-HT2A-Lin41
+destabilize
+EGR-1
+Central Africa
+midiprep kit
+108
+ischemic
+published conventional PCR assays
+cross-reactive
+The effect of drugs on mitochondrial DNA quantity per cell
+immune-checkpoint inhibitors
+10
+RPS15, ACTB and B2M
+MALDI-TOF-MS
+10%
+Activation of the TLR5-NF-κB signaling pathway
+three
+metal chelating motifs
+temperatures
+Four
+50 min
+inhibits the activity of intermediate molecules of the TLR-pathway
+PRWz and PRWWz
+ELISA reader
+closer collaboration and long-term commitments
+controversial
+intense work
+Spontaneously hypertensive rats
+4 h
+a population bottleneck
+interacting RNA molecules
+NSF-IOS-1831988
+good absorption, distribution, and oral bioavailability
+six
+ENC plot
+pr-E binding
+Victoria-and Yamagata-like lineages
+Zanamivir
+15
+organismal death
+surfactant proteins
+four
+chromatin
+Spectral analysis
+17
+Bronchial epithelial cells
+agar disc diffusion test
+independently
+Seven
+micrograms/kilogram body weight/minute
+58.46% and 53.84%
+vaccines and antivirals
+mucosal cellular responses
+To describe the strategy and the emergency management and infection control
+viral replication
+adjuvant function
+latency
+increase
+SPSS 18
+34%
+an adjuvant
+43
+11
+degradation
+zinc-finger
+human immunodeficiency virus
+new human pathogens
+Recombinant LCMV expressing LASV and MACV GPs
+daily
+lesion diameter
+>7 days
+patients who did not receive a prescription for malaria chemoprophylaxis
+Female A129 and 129Sv/Ev mice
+Critical care triage
+TIPs
+MAFFT 7.3
+epidemics
+National Hospital for Tropical Diseases
+exogenous as well as endogenous virus
+Three
+hydrophobic
+32
+baseline, or post CIH sympathetic activity
+Avastrovirus 4
+Microscopic Agglutination Titre
+IASOS
+7876
+Cas9 expression
+mTOR
+1918
+therapeutic
+diffusion-limited
+Four
+translational studies
+wild type mice
+an immunocompetent mouse model
+transcriptional silencing of the telomerase promoter
+OCT4
+Lung sections
+Inferred clusters
+intracellular
+rdrr.io
+The establishment of bat primary cell cultures
+distilled water
+future clinical treatment
+H9 rRT-PCR assay
+Log-rank test
+Programmed cell removal
+5%
+Bangui
+202,602
+Listeria monocytogenes strain EGD
+urbanicity
+water-saturated ethyl acetate
+trifluoromethanesulfonic acid /water
+63 years
+empty control vector DNA
+Grey
+cloning and expression
+Protein-bound 3-nitrotyrosine
+Gene duplication
+cytoplasmic fractions
+PIV
+PepTag ® Non-Radioactive Protein Kinase Assay kits
+apoptosis
+27 months
+Developing diagnostic tools and strategies
+112 bpm
+those obtained during the development steps
+inflammation
+Necrotic and apoptotic cells
+GC3S
+85.4%
+RNA
+abated the progression of renal disease
+SP-D, and KL-6
+Cy3labeled
+memory/plasma cells
+51%
+Oral ribavirin
+Intracellular proteases
+to constitutively activate NF-kB
+Th cells
+77.4%
+SSj14
+quadratic
+interference with a protein F-mediated membrane merger
+Sub-group analyses
+devastating pandemic
+via i.n. route
+Surgical-grade
+DENV NS2B3-dependent inhibition
+IFI6
+TGF-b/Smad3-dependent
+noise
+selective pressure for amino acid change coming from host immunity
+one
+chimeric
+digital
+various fatty acids
+additional allele values
+to reach public health decision makers
+elaD
+output structure of HFold-PKonly
+infl uenza viruses and other respiratory pathogens
+RPKM values
+blood samples
+2003
+interval
+co-expression of the C protein
+that observed in the crystal
+49
+between 5 and 10 M
+cytoplasmic counterpart
+All herd owners
+oxidative stress
+reproduction number
+NCBI Short Read Archive
+Further information on research design
+Anti-β-actin mAb
+Cushing's
+Bax
+Four
+5.7%
+215
+Anti-S1PR1 and anti-CD31
+normal
+different distance value cutoffs
+pro-inflammatory
+myofilament changes
+PRoVENT Writing Committee
+friends and relatives
+user-friendly
+50
+in vitro and in vivo
+NHI
+RhoA-binding kinase α
+extract B
+confer protection from viral pathogens to wild feline species
+90%
+Gene editing
+hepatoma cell growth
+suppressing the yield of virus particles
+MEDLINE
+treatment of various diseases
+influenza
+an in-frame control reporter
+low codon usage bias
+A fragment of BLV env encoding amino acid residues 326 to 418
+VIP information
+Effective vaccine and therapies
+fairness and legitimacy
+VERO cells
+21
+Ni 2 +/IDA metal chelating affinity column chromatography
+paediatrics
+ITGA3-mediated
+13
+uncertainty in clusters sizes
+new functions of ubiquitin
+Ecological and environmental factors
+country level intercepts β 0j and slopes β 1j
+a 0 = 0
+immunostaining cells
+animal medicine
+ZL, DW, and DL
+1-3%
+DAPI staining
+volunteers
+high dosages of cisatracurium
+gross domestic product per person
+reduced exacerbation/infection rates
+four
+ameliorated oxygenation
+1
+DAPI
+influenza
+serine protease 23
+a surplus
+1 mM
+age and BMI
+BCA protein assay kit
+Serum
+two
+The transcriptional profile of PBs
+ER stress-mediated
+Zheng Banqiao
+specificity and sensitivity
+does not cleave mRNAs encoding essential ER proteins
+up to 11 dpi or dpc
+participatory modelling
+six
+multifunctional biophotonic
+survival of lung tissue-resident memory CD8 + T cells
+regression from antiviral to susceptible status
+disseminated intravascular coagulation
+Nasal, buccal and fecal swabs
+39.1%
+20 and 10 hours
+mice
+HRV variability
+promoter activity
+10%
+genomic regulatory blocks
+Spunlace masks treated by ethanol
+primary infection
+The bound eEF1A
+HIV database
+a paracrine effect
+48%
+1930
+target-specific extension
+plasma HK
+homing efficiency
+ΔP
+15%
+five
+Reversible phosphorylation
+protection
+12-18%
+β Qkj
+inhibition of innate immune gene expression and impaired host defense
+prospective targets for modulation of host innate immune responses
+A21U, C24U, A26G and A28G
+law enforcement and EMS personnel
+suspicious
+vaccinia virus and hepatitis B virus
+size and surface charge
+the requirements specified by the reagents' manufacturers
+0.1 and 0.7
+second hairpin sample including compound 5
+p19
+TLR4, 5 and 6
+Student's t-tests
+interaction with other drugs
+MTT
+10
+Gene ontology and pathway enrichment analyses of pathogen-targeted host proteins
+Bid
+À1 RF signals
+least-squares
+evidence quality
+genetic association studies
+0.87
+Diffuse alveolar damage
+Arginine
+68%
+promiscuity
+ARDS
+α and λ
+cell culture medium
+48 h
+by supplying essential genes and mechanisms
+Whole cell yeast extract
+CSF and urine
+improved, stable or worsening
+polymorphisms
+Dr. Salvato
+to obtain valid sequences
+Virus isolation
+HuNoV
+RNasefree DNase
+EP
+human leukocyte antigen system
+GLmnet
+PAM8.1
+regulation of constitutive early expression of antiviral genes
+Twelve
+20
+minimum path length algorithm
+proteoliposome
+136
+Influenza
+chronic obstructive pulmonary disease
+peripheral blood
+Virus neutralisation
+improving the major theoretical and technical issues
+power analysis
+2006
+substantial differences from the WT results
+0.8 mg/dl
+licorice root
+64
+>99%
+nPCR
+Luminex multiplex technology
+Proteomic
+IL4, IL5, and IL13
+Berlin definition criteria
+Splenic macrophages
+ProteinChip PBS II reader
+1960s
+transient
+1 year
+total RNA
+Melanization
+M2 gene-end sequences
+antigen titer level
+molecular microbiological techniques
+amino acid position
+Total Internal Reflection Fluorescence
+noninfected cells
+rCD4 binding
+H2A.X
+strong proliferative and invasive capabilities
+4-8 kinase-dead mutants
+121 base pairs
+Oxidation of methionine residues
+260 nm absorbent
+April 18 to 20
+the value of normalized intensity texture map
+0.25% Trypsin-EDTA
+90.2%
+30 min
+data acquired from a sufficient number of participants
+19 and 20 July
+HCV persistence
+means ± SD
+PI3K/Akt/mTOR signaling
+shrunken class means of biomarker protein abundance
+added during the virus inoculation
+bleach
+Plos One
+ribosomal protein L22
+delayed dissemination from the lung
+Ifi27l2a
+RT-qPCR
+nine
+AQ 11
+indirect negative signals
+lack of power
+530
+110
+72%
+covalent binding to the electrophile
+mouse antibody test
+CV5
+size permutation test
+all Indigenous Australians
+Memorial University Institutional Animal Care Committee
+Age groups and admission diagnoses
+uncoupling protein 2
+PGD 2
+monkeys
+c-Jun and c-Fos
+VP2 and VP5
+Thirty-three
+the importance of maintaining access to a diverse group of funding institutions
+The funders
+nose washes
+needless aggression and violence
+5-NitroIndole
+CAMAG Automatic TLC Sampler-4
+WW1 isolate
+255
+PEDV RNA
+autoimmune encephalomyelitis
+decreased proliferation and migration
+pol trc-leave
+11
+parrot bornavirus 4
+37.1%
+Quil-A 25
+in vivo electroporation and gene gun delivery
+croup
+by changing the length of the outer housing
+ZIFIT Targeter
+blood, liver, heart, lymph nodes, spleen and other organs
+half
+causal
+fibrotic
+SP-D concentration
+Source control measures
+Mouse cytokine bead array kits
+151
+Ingestion of food or water contaminated with V. cholerae
+5 to 71%
+Diaminobenzidine
+bind to NPC1
+51%
+CSF
+novel non-coding elements
+useful tools to design stem-based immunogens
+HSAJB
+how infected cells and T cells may contribute to disease severity
+16s339F and 16s926R
+Superscript VILO cDNA synthesis kit
+prenatal GC exposure related hypertension
+prodromal
+absence of positional bias
+PRRSV-infected isolator piglets
+blood samples
+Ribavirin
+LASV infection
+capillary-like
+63
+interest
+TiO 2 NPs
+740
+Immunohistochemical
+pneumonia and exacerbations of chronic pulmonary disease
+tetraspanin CD151
+recall bias
+IRF-1
+2006
+the same transformation event
+behavioral traits
+which macrophage activation markers are relevant to the IRs
+molecular modeling
+excluded from further antiviral analysis
+Solanaceae and Cucurbitaceae
+an organizing element
+GRAS status
+Pulmonary aberrant immune response
+DOX-mediated cardiac dysfunction
+training data
+to categorise web-based information resources
+Detrimental signaling pathways in astrocytes
+Evolutionary entropy
+35% to 47%
+adrenaline and noradrenaline
+nuclear delivery
+viral load
+Population genetics
+sGP epitopes
+AP2
+15
+it is a major circulating subtype over long periods of time
+filamentous
+important and complex
+antiserum to U2AF65
+Axygen PCR cleanup kit
+Mann-Whitney U test
+Sigma-Aldrich
+Phylogenetic
+Placenta-derived stem/progenitor cells
+synthetic substrates
+molecular dynamics
+to penetrate through the openings of sewn seams
+1000
+pigs and cows
+A strong maternal immunization platform
+~7 s
+negative virus dissociation values
+infected individuals from either its own group or other groups
+an after-season assessment of severity and burden
+∼2%
+acetylation
+inhibition of IAP transposition by RNase L
+waterfowls
+9
+Fifty
+PGD2
+33,000 Da
+inhibition of cap-dependent translation initiation
+CD107a antibody
+Latency II
+efficacy and side effects
+19.3
+virus replication or transcription
+BD birthdeath model
+Recombinant plasmid pAHV-1 concentration
+400
+to ensure the isolation chamber internal pressure is both stable and secure
+14%
+oral triple therapy
+CSFV
+avian origin
+virologic suppression
+every 30 min
+C, D and E
+inhibits Ebola virus multiplication
+viral counter measures
+regulating mitophagy
+XRN1 and the exosome subunit gene RRP40
+more than double
+all splice sites
+key informants, TAP members and senior HERO staff
+factors for ribosome assembly
+GAPDH
+20%
+299
+13
+homodimeric
+nervous tissue
+TLR7, TLR8, and TLR9
+Morphometric
+3%
+7 × 10 11 pfu
+the corresponding author
+to avoid reinfection from littermates
+self-efficacy
+restricted feline immunodeficiency virus
+microbial virulence factors
+higher computational performance and better operability
+64%
+52.7%
+error filtering
+AEP
+ARDS severity
+1973
+Madang
+differences in infection at early time points
+a smear
+Ubiquitin
+gastric acid and pepsin
+septic shock
+five times
+Student's t-test
+Vaccination
+SF12 mental component score
+Mov-Avg Cusum method
+early-endosomes
+WT sequence
+30 minutes
+replication
+Inversion of the status quo
+30%
+90-95%
+100-500 times
+Diagnosis, Epidemiology, Therapy and Microbiology
+33
+500 meters
+biocatalyst
+Bliss independence model
+quantitative real-time PCR
+stimulated systemic immunity and mucosal immunity
+60
+Initial recruitment after the applied breath
+4 more days
+a swab of fecal or gut contents
+postpartum
+uninfected
+Principal components analysis
+selection markers
+the ultimate causes for colonial aggregation
+Lasergene
+1 h
+selected bacterial pathogens
+Midwives and nurses
+enlarging L2
+large
+oxytocin
+manage colonies
+cellular
+resourcetrade.earth
+upregulated mRNAs
+weak-to-no MPO inhibitory activity
+online learning
+understanding the more complex population biology of multi-host pathogens
+absence of AQP4
+pandemic influenza
+IE1 transcript
+western blot analyses
+nine
+immune responses
+10-fold
+Hepatocellular carcinoma
+live attenuated vaccines
+30 min
+Filgrastim
+in steps following the formation of immature virus
+packaging the WSSV 300 kb genome into the nucleocapsid
+continued surveillance of contacts
+28
+compounds that are enriched in the protein incubation with natural product extracts
+synthesis and secretion of AeET
+PKR dimerization
+Blood samples
+disordered carbon surface
+Mutual relationship analysis
+Pralidoxime
+Irf7
+C-terminal helix
+influenza virus infections
+33%
+via the aerosol route
+by a specific cytokine milieu
+Lys278 and Lys361
+12 km
+S k
+BSA
+Lcd/1
+BCL6
+an ensamble X
+our preclinical model
+abolished
+8
+anti-V mAbs
+80%
+tissue-print hybridization
+20-50%
+fit to theoretical underpinnings
+M protein
+878-Gly s -Ser s -879
+Mouse Anti-Nuclear Antibody IgG ELISA Kit
+LPBE-antibody titer
+60
+PDB files with the highest resolution
+specialized methods
+DNA sequencing
+Oncology and autoimmune diseases
+0.817 to 1.225
+viral loads in amniotic membranes
+fragments
+70% to 90%
+interactions
+A buffer injection
+A follow-up study with this regimen
+cytoplasmic loop
+bands or dots
+NPInter
+3 days
+37
+BTV1-induced autophagy initiation
+.80%
+HCMV UL40 peptide-induced conventional memory NK cells
+the cell nucleus
+nuclear SREBP-1
+2 hours
+therapeutic agents to targeted organs
+edges
+320
+The role of infectious agents
+18-26 nm
+single-stranded 59-ends
+RV-A and RV-C
+81%
+R30K
+livestock tracing schemes
+mild
+IFN-c
+recombination
+SPSS
+WT mice
+t-butanol
+IFN-c
+Six months
+weekly refresher training
+sepsis and septic shock
+80,000
+Neighborhood
+helix 26 of 18S rRNA
+single station WBGT observing platforms
+PPIA, B2M, and RPL4
+mutant viruses
+AQ 11
+protein-protein interactions
+less robust depletion of the targeted mRNA
+full-length precursor of membrane plus Env
+Basal Medium Eagle
+90% trans and 10% cis
+antigen presentation
+100%
+cc-by
+studies that model the human condition
+RNAi
+London
+170 μl
+100
+G1, S, G2, and mitosis
+rural areas
+a series of protein bands
+DNA fragmentation
+Glucose-6-phosphate dehydrogenase
+1457delA and A1475G
+proteins in the airways
+spatial correlation analysis
+Vaccine-specific residue changes
+2H5-A14 binding
+risk appetite and triggers
+the same direction of response
+close linkage
+Sociodemographic
+up to 42 days
+High Capacity cDNA Reverse Transcription Kit
+4%
+two weeks
+13,728.54 Da
+filamentous growth in haploid cells
+122
+polyethyleneimine I
+H5N1
+WT
+pre-MG surveillance
+region, sex, age and method
+Niclosamide, 600655, 600653, and 500199
+exon skipping
+Table 1
+Intensity functions
+CSE
+thermoregulation
+8.3
+four
+Oligomerization
+disease outbreaks
+Singapore
+The present study
+Refractory CMV disease
+CD4 + T cell-dominant response
+3
+making edge threshold less stringent
+The dose-response curve
+OriS
+relatively modest
+the type of cell and its state of activation
+number of patients
+cell culture media
+IFITM5 mutants
+cutoff values
+0.5
+15
+every 10 ps
+most infectious diseases
+The Jackson Laboratory
+2
+Center 9
+One microgram of the total RNA from each sample
+amino acid positions
+17
+PRINT technology
+DNA hypermethylation
+mental health issues
+twice
+491
+praziquantel
+Ag-specific effector and central memory T cells
+introduce disease into host populations
+18
+truncated forms of viral genomes
+90%
+the parameters of the network structure average degree n and clustering coefficient Φ
+necroptosis
+effective prevention and control measures
+3 mg/L
+SR proteins
+allergic asthma
+Copy number
+Oude Munnink, Bas B.; van der Hoek, Lia
+Pride
+SYNERGY
+Acute respiratory distress syndrome in adults
+17
+tTA gene
+CCHFv
+Tyr202
+viral sequence data
+bracoviruses
+Collinearity
+tomato Ty-1 resistance allele
+Coated microneedles
+200 μL
+VirB6-89K
+MG-132 and Bortezomib
+associated unique enzymes
+full-length or unskipped transcript
+59 end labeled using ATP and T4 polynucleotide kinase
+Major airway and bone landmarks
+scFv 10FG2
+10%
+0.5-4 kb
+a regulator of the homeostatic function of these cells
+1,300
+potato dextrose agar
+lysosomal proteins
+Severity of illness score
+99%
+The posterior distribution of indicator values
+plastic
+emancipatory theory
+Richards model
+seasonality problem
+Quantitative
+52%
+post-defervescent decline of IFN
+Four
+B regulatory cells
+the class level
+Analysis of the targeted mutant
+two
+1Á6 log 10 TCID 50 per 100 mg or gram
+individual-level variables
+SPSS version 12.0
+IfitmDel
+feature
+no-stop mRNA
+E. coli Rosetta cells
+agriculture personnel
+aortic glutathione peroxidase
+acute and self-limited
+presentation of a difficult diagnosis case in a young lady
+licensure
+mass-corrected residual trait values
+Sepsis and use of mechanical ventilation
+5 mg/mL of the respective polypeptides
+PPE
+false
+duplicate ports
+6%
+Thirty-one
+eliminated
+influenza RNA
+4
+cell tropism
+new antibiotic treatment or hospital admission
+d = 2
+80%
+enlarged end-systolic and enddiastolic diameters
+oxygenation index
+non-allergic rhinitis and influenza like-illness
+Affymetrix
+closure of triangles
+JEV progeny yields
+supplementary material
+Viral load detection
+human bocavirus and rhinovirus
+maintaining the ECMO run carefully and avoiding ECMO-related severe complications
+student t-test
+ADE-mediated severe dengue disease
+guanidine-cytosine
+Creative Commons Attribution 4.0 International License
+Arf1
+GraphPad Prism
+Neurophysiological
+adaptive
+hypertension
+intermediate
+1000 kDa
+regeneration of living tissues
+reduced phosphorylation of Csk
+better influenza vaccines
+1.5 million
+1189
+diaminopimelic acid-containing peptidoglycan
+8
+normality
+bovine tuberculosis, bubonic plague, and glanders
+Doxorubicin
+binding of Ang II to PT AT 1 receptors
+1.2%
+213
+tissue controls
+levers
+statistical power would be generally increased
+methylcellulose
+50%
+Detergent
+disease severity
+5552
+blocked infection at a step after viral attachment
+30%
+Oxygen affinity
+16
+high
+GTG-to-ATG
+269
+HEV permissive and nonpermissive
+Health individualism
+Innate immune response
+breeding catteries
+most efficient siRNA
+decline
+conceptualized and designed experiments
+CC10/FOXJ1 double Cre mice
+by introducing MyD88 or TRIF inhibitory peptides
+Humanized mouse models
+536
+CD4 + T-cell help
+ART
+nasal tissue
+Ghana
+conventional kinesin
+Respiratory virus infection
+40
+5%
+Oseltamivir
+300
+70%
+The PI
+microscope
+PPE use
+every 3-4 days
+three
+an extra 54 nucleotides
+1.5 h
+330
+125
+Sex and age
+Parenchymal pacifications
+accurate and early diagnosis
+low enzyme productivity, low catalytic efficiency, and pathogenicity
+macrophages
+polarized cells
+Lymphocytes
+Two
+conjugation
+both intravascular and topical administration of target agents
+linear dose
+weak cytosolic signals
+dihydrotestoesterone and testosterone
+~0.01
+Mechanisms
+an individual test using a serum sample
+dehydrogenase
+TRAIL-dependent
+viral plaque assays
+Dengvaxia
+ARDS
+four
+HBV
+TPIC without DOX
+1
+USP14
+reduction in nuclear factor-κB activity
+suppressive
+Jamieson
+ProMED-mail
+Nuclear factor kappa B
+dry
+healthy
+Molecular Imager5 Gel Doc6 XR
+use
+isoflurane
+filamentous growth
+DC-SIGN and L-SIGN
+targeted SpO2 range
+VP88GFP
+BAC2-12 transgenic mouse liver, kidney and small intestine
+50 µL
+8
+myeloperoxidase and elastase
+the interaction between evolutionary processes and spatial-temporal domains
+fetal hydrocephalus
+88 000
+morphological
+editing for clarity, grammar, and syntax
+international health risks
+viral dissemination and neurotropism
+11
+132
+multivariable logistic and proportional hazards regression models
+77%
+real-time
+over-the-counter medicines
+102-198%
+improving vaccination efficiency
+Enzymatic reactions
+serologic
+Vaccines
+continuous antigenic drift of seasonal influenza viruses
+high levels of MR
+TAAR1 RNA
+20 to 25 kGy
+further studies
+networks of higher quality
+GISs
+E2F8
+angiogenic blood vessels
+2009
+screening for bornavirus-related sequences
+wet-to-dry weight ratio of the lungs
+fewer and longer contigs
+Sip protein
+implementation
+interview studies
+gravity models
+healthy
+0.599x
+BCA Protein Assay Kit
+expression and secretion of functional antibodies
+reduced release of RSPs in the cell supernatant
+self-complementarity
+two weeks
+H5N1 pseudotype
+24
+6 months
+Immunoglobulin G
+microenvironment
+extracellular domain
+beneficially and detrimentally
+5.6%
+teleost
+h-index
+x k
+two
+Univariate and multivariate Cox proportional hazard regression models
+unfolding of H4b and H5
+bovine serum albumin
+similarities between proteins that share no obvious global similarity
+viral replication
+Tuberculosis
+important
+Rates of molecular evolution
+293T-Gluc
+EBOV
+epitope mapping
+substrate targets of viral proteinases
+attenuated and recombinant vectored
+every six months
+Gene expression
+inflammation, oxidative stress and fibrosis
+fecal material
+SP-D-deficient
+interventions
+two color western blotting
+Nestin-, GFAP-, and β-III tubulin-positive cells
+underlying chronic respiratory insufficiency and bacteremia
+interchangeable
+important
+PyMOL
+DMF technology
+3.2.4
+144
+300
+seryl-tRNA Ser CAG
+12 days
+46
+NPC1
+Table S4
+Fc epsilon receptor 1A surface receptor
+reovirus uncoating
+S510
+More than 500
+accumulation of a small degradation product
+new CPV-2a
+Survival time
+rat clathrin heavy chain
+TRAF6
+3
+2009
+GraphPad 6.0
+adoptively transferred T cells
+three
+ribosome production
+Aedes aegypti mosquitoes
+VSV
+neutralizing serum antibodies
+minority
+structural
+the nucleus
+GCs
+SDS-PAGE
+virus replication in the eye
+mutant viruses
+30
+1 : 30
+Duck embryo fibroblast monolayer
+Four
+four
+CD11b high Gr1 intermediate cells
+the specificity of SIBA
+chest CT
+metabolism cages
+pentraxins CRP and SAP
+Stochastic fluctuations on signaling networks of miRNAs
+Three
+spontaneous behavioral changes
+high rate
+log 10 2 −∆∆Ct value
+type II alveolar epithelial cells
+Ongoing inflammation
+15
+endoplasmic reticulum
+17-30 %
+high levels of cytolysis
+eukaryotic sequences
+98.2%
+UNAIDS and WHO
+four
+Knowledge of the likelihood of a large number of health professionals attending
+gel shift assays
+sources and model
+capsid stability, endosome penetration and endosomal escape
+Ratio scaling
+less than 7
+Genome signature
+reporting gaps or biases
+Imiquimod and CL264
+EGR1
+a group of genes participating in cellular homeostasis preservation under stress conditions
+Bhidden
+1.5x10 5 A549 cells
+CFRs
+CDCMN
+base composition
+autophagy
+low-to-intermediate weight loss
+definitive radiographic evidence of vascular ischemic pathology
+15
+16 and 24 h p.i.
+at least a 2 fold greater cytokine response
+novel exposure metrics
+humoral
+48 and 9
+bind to either or both EF and LF
+new sequences are easily detected
+to ensure complete literature retrieval
+very low
+Monomers
+angiogenesis
+% GFP reversion
+HPVE7, Survivin and WT1
+11.8%
+54%
+high affinity neutralizing IgG response
+Ikbke
+icteric syndrome
+EJC-independent NMD
+3
+18
+CYP450
+cDNA
+IRES
+Diseases that once killed millions of people
+Tumor volumes
+85%
+individuals who may be negatively affected by such communicative undertakings
+Mother-to-child transmission
+structural features of the network
+three
+Determinants of health
+Exergen
+Lyophilized
+efficient translation initiation
+PPE and hand hygiene
+peer-recruitment
+84%
+autoclave
+Hydrogen bonds with polarizability activity
+recombinant Scorpine
+1,000
+29%
+A glove port bung
+a component of the cytoplasmic exosome
+SD of the mean for each group of mice
+AT 1 -receptor blockade
+Southeast Asia
+eukaryotic and prokaryotic
+4 weeks
+G-quadruplex formation
+10%
+glycoconjugates
+spontaneous preterm birth
+The display mode
+␤-Globin divergence
+eIF2α
+polyproline-II helix
+Beijing Ditan Hospital Ethics Committees
+k-fold cross-validation
+500
+capillary electrophoresis
+MEGA4
+the base of the cell culture insert
+80%
+500
+binds
+TRAF6
+Optimization
+cattle herds
+27%
+Reassortment events
+1.5Å
+AST, ALT, and serum albumin
+GH signaling
+over-expression of the four genes of interest
+development of viral resistance or AIDS progression
+PRNT
+96
+IC interference
+Poor HRQoL
+Cell lysates
+tertiary care
+increases tumor cell adhesion
+NCBI GEO 165
+hematologic malignancies
+milder disease severity
+The Virus Variation Resource
+65%
+six
+IRF pathways
+insertional mutagenesis
+RNA structures formed by the repeats
+a protein cavity
+olefinic bond
+Transcription of negative RNA into positive sense mRNA
+Time-calibration of the evolutionary history
+nonlinear regression of concentration-response curves
+women
+antiviral strategies
+rib i
+total RNA
+HCV clearance
+61.6 kDa-long
+Escherichia coli lipopolysaccharide and Poly I/C
+Specific nucleic acids
+precipitating
+Sequence conservation
+renal XOD
+debris
+reduction of REE
+5%
+three
+Yang, Jing-tian; Ma, Bing-cun
+370 and 2736 copies/mL
+one week
+lactate, urea and pH
+Offset correction
+universal standards for data sharing
+n
+48 hours
+development and maturation of the ovary
+1.1 mg
+65.5 years
+5 ml of standard plasmid or cDNA sample
+3.23-fold
+higher airborne spread risks
+18
+Three
+lysis buffer
+No association
+14.5 μL
+S 0
+antimicrobial function of macrophages and Th1 adaptive immune responses
+Vitamin E radical
+mock inoculated with cell culture media
+10%
+Peak timing and intensity
+Electronic
+Sec16A
+BLAST
+TRIzol Ò reagent
+232
+IL-1β
+Sensitivity and specificity of the single peptide candidates
+ImageJ
+linear regression
+15 min
+1mm
+2.00 and 3.187
+immunosenescence
+disease distribution
+urbanicity
+21%
+pig
+close
+normal levels
+1 µg RNA
+polymeric
+GAPDH
+IFNb-YFP
+allergic airway resistance
+fluorescein
+% suppression = 100 × ]
+Edward Jenner
+Spleen weights
+none
+10%
+dramatic inhibition of HIV-1 replication
+19%
+hypoglycemia
+accelerates the epithelial repair
+1%
+viral lytic replication
+pathological consequences
+7,553
+risky
+Calculation of X
+reduce the death rate from CM
+Random forest probability estimation
+infection clusters
+force probes
+Qiagen QIAamp MinElute virus spin kit
+Dose-response curves and cytotoxicity
+avian
+age, sex, and prognosis
+CIb
+Forty
+appropriate messages
+bovine serum albumin
+MERS-CoV RNA
+U test
+Clinical CBC parameters
+83%
+South Africa
+Intravenous contrast-enhanced CT
+2339
+detectable viral sequences
+cc-by
+SLC35B2
+antigens
+2.78 days
+A1PiZ
+PSMA-DMAb
+Electricity
+astrovirus
+chemiluminescent
+XLPF
+Rituximab
+Specificity
+12month
+orders of magnitude less efficient
+JdP-C
+lipid peroxidation
+based on the probability distribution function of the training data along each feature
+a separate translation
+familyspecific genome size effects
+1:1.1
+pattern-recognition receptors
+immunohistochemistry
+TopoPSA-topological polar surface area-descriptor
+SARS-CoV-2
+880
+residue 701 of PB2
+communication and coordinated outbreak response
+CpG-methylated silent rDNA
+man-specific
+Sigma Chemical Co., St. Louis, MO, USA
+loading buffer
+polarized distributions of HA and NA
+2 hours
+poly I:C
+regions of statistically significantly reduced variabil- Transcription-regulatory sequences
+anti-oxidative
+Mixed messages from official sources
+10.1155/2017/7535320
+15
+18S rRNA
+moderate health consequences and a minor lifestyle impact
+three weeks
+BALF and lungs
+class A scavenger receptors
+in or near the apheresis donor area
+280°C
+important regulators of host response
+apoptosis
+galactosylation and rhamnosylation
+six
+four weeks
+Tapestation 4200
+Helicobacter pylori and Hantavirus
+inducible cells
+six
+Escherichia coli pHrodo bioparticles
+Viral evolution
+Integrin av
+genotype specific and host restriction
+T7 RiboMAX Express RNAi System kit
+annotated models
+2-3 hr
+74
+venoarterial
+FGF10 mRNA synthesis
+rZIKV
+SCSDVs
+vascular integrity
+airway epithelium
+syncytia
+bronchial lymph nodes
+nine
+NS
+PtdIns3P
+VQ29 and ADK2
+crystallization
+non-redundant functions
+twice daily
+pandemic influenza
+Korea
+100-fold more sensitive
+percentage of cells infected with NiV
+poly-L-lysine solution
+60
+Prompt management of the disease
+2AE7 or 3AE2 days
+inhibition of hsp90
+Ang 1-7
+making sense of such large-scale biologic sequence data
+vaccine candidates
+DAVID pathway analysis
+infection by the wild-type virus
+oseltamivir and ventilators
+hematoxylin and eosin
+mRNA regulation
+Fisher's exact test
+10
+Maxent model
+adhesion medium
+poor nutritional status
+200 nM
+eight
+polyclonal antibodies or anti-sera
+decreased
+ICPI and MDT assays
+membrane
+resource reallocation and immune evasion
+Pub1
+Odyssey 1 IR scanner
+NE-induced increases in lung compliance and mean linear intercept
+an epidemic
+116
+two
+Informed consent
+LAMC2-silenced Penl1 and Penl2 cells
+model-based methods
+winter and spring
+cryo-EM
+quit their job
+exhaled VOCs patterns
+Bid
+yolks
+PRRSV 1-4-4
+anti-WHs antibodies
+Gastroenteritis induced by RV
+6.96 nm
+90% to 95%
+hypertension
+continuous-time differential equation model
+inactivate a variety of pro-inflammatory and coagulation mediators
+Transform-derived baseline and noise values
+Regulatory T cells
+β-actin
+the number of host range expanding mutations and their frequency of appearance
+six
+Sepsis
+1 out of 66
+H275Y
+longer overall survival
+160.25 ± 9.47 mg/dL
+Lactobacillus brevis SP
+the fraction of pairs of links that overlap in time
+with Exportin
+44.9%
+China, India and countries of the former Soviet Union
+0.3 and 0.05 mm alumina powders
+specific input data
+viral exposure
+experimental validation
+skewed variables
+WT protein
+inadequate staffing
+oseltamivir carboxylate
+RBM4 and eIF6
+Twenty-eight days
+media
+reduces
+phagemia
+25
+social distancing
+2.7 Â 10 6 /mol
+running water
+HHV-8-infected plasmablasts
+Eight
+Targeted delivery of therapeutic payload
+GraphPad prism software
+when therapeutic intervention could be effective
+25 to 30%
+85
+four
+Bartha-DupGreen
+4
+E5, E6 and E7
+59ppp moiety
+Dispositional optimism
+24 hr
+after all individual infections have been accounted for
+immobilized ricin toxin
+38 kilodalton protein
+pseudo-distance
+outcome prediction and guidance to human and financial resources use
+a unique index primer
+monolayer cells
+virtual screening
+Interferon c
+fall-winter seasons
+DENV3
+Flv r
+−7.7 kcal/mol
+diabetic animals
+YPD-broth
+dynamic transmission models and economic analyses
+dcl-1
+slug tip
+447-687
+Th1
+7 days
+930
+1610
+36 hrs
+the state
+Sigma-Aldrich
+VersaMax ELISA microplate reader
+Dysregulation of the antibody response
+2 µg/mL
+graph based
+biosafe antigens
+50
+domain antibodies and single chain antibodies
+TLR4
+LC3
+Humoral immunity
+50 nm/min
+95%
+amino acid phenylalanine
+horses
+Ifit2
+structural remodeling
+0 0 4 4 0
+Whole-genome sequencing
+synergism
+6.0%
+intron retentions
+SDS-PAGE
+poxvirus
+niclosamide
+four
+212
+Pasteur pipette
+ZXH
+parsimony
+analytical traction
+ventilatory
+53.5%
+An unpaired t-test
+anticancer mechanism
+The binding of a peptide to MHC-I molecule
+Shanghai
+Suicide
+linearized plasmid DNA
+Vector biodistribution
+5-20%
+isothermal nucleic acid amplification techniques
+2 months
+a viral fusion protein
+sera
+1 h
+Metrics
+MEGAscript T7 Transcription Kit
+22
+more efficacious
+weekly rates
+three
+Formaldehyde or 5 to 10% chlorine bleach
+variola
+30 %
+Microarray data
+37uC
+many forms of acute critical illness
+IFN
+evidence of local reaction
+T pure
+1.10
+negative depletion of magnetically labeled cells
+humans, simians, and bats
+50%
+compares the sensitivity and specificity for different k-mer thresholds
+CLOCK and BMAL1
+6-8 weeks
+FlowJo.10
+HSV entry
+LM mice
+cell proliferation and apoptosis
+increases
+radiolabeled
+Scoring systems
+Western blotting
+4 weeks
+Early administration of antiviral treatment
+seven
+617
+advanced therapy medicinal products
+PrP Sc formation
+enhanced oxidative stress
+DDIT-3/CHOP
+group means
+current US CDC guidelines
+QAAFI/399/13/MLA
+kidney and spleen
+pre-emptive vaccination
+Malignant melanoma
+their own lytic-development independent promoters
+Water temperature
+primates and humans
+farnesyltransferase
+30 nm
+Carollia perspicillata
+red
+R 0
+treatment services
+med ik
+Extracted RNA
+Pan T Cell Isolation Kit
+14
+1 OD 600 of cells
+bacteriostatic
+phase separation
+the absolute count of white blood cells
+60 min
+2001
+Norwegian Veterinary Institute in Oslo
+wholesale markets
+pro-inflammatory
+probability
+Mechanisms, efficacy, and safety of rhAPC
+DLS
+substitution T70S
+USP48
+Richards model
+HuRef.chrY
+long-distance PCR
+the level of a threat
+three
+Cse
+public health emergency
+2%
+60 minutes
+AP2 and SP1
+33
+every 12-18 months
+Sister Vivian Bullwinkel
+95%
+AhR
+phenotypic DC maturation
+HIV-1-specific T-cell responses
+cell lysates
+anti-inflammatory, anticancer, and antiviral
+55c per dose
+9,700
+cartilage, bone, mammary glands or pancreas
+twice every day
+55.8%
+E1E2 global folding
+ten
+the corresponding author
+wheat germ agglutinin
+Chronic wasting disease
+four
+row-wise independent algorithm
+NBD and rhodamine
+bats
+situations
+SiO 2 /Au nanoshells
+CIH
+degradation of ER domains that contain misfolded and aggregated proteins
+0.5 mL of nutrient media
+mice
+immune response
+1 week
+transcript abundance
+hyaluronidases
+one
+barrier function
+Continuous sampling desiccation
+samples with small number of cells
+large dynamin-like GTPases
+Water, food, and fomites
+their communities
+two
+antiviral agents
+21-22%
+Viral
+IFN and NFκB signaling
+IFITM3
+CD4+ T cells
+George Anderson
+decontaminate the water
+decrease in the viral titer
+autophagy
+antibiotics
+1976
+time-consuming
+four
+the hospital always has its own supply of donor bone material
+thirteen
+Lineweaver-Burk and Dixon
+four
+40%
+decreased levels of SMN proteins
+The plaque assay
+Mechanical ventilation with heliox
+11
+28
+Logistic regression analysis
+severe unexplained diseases or syndromes
+Substances present in the sample matrix
+higher cost of electronic equipment and operating software
+CDV-H
+rapidly internalized
+fibers
+dermatitis
+MERS-CoV
+vinblastine, VCR, and vinorelbine
+recent advances in the management of septic shock
+Messenger RNA
+data that sometimes be there and sometimes not
+Extracorporal membrane oxygenation devices and ICU ventilators
+C. pipiens
+Packard Flow scintillation analyzer
+2-11
+8 and 15 dpi
+interact
+HRVs
+LightCycler 480 SYBR Green I Master
+by interacting with host erythrocyte cytoskeletal components
+4 out of 6
+Sixteen
+Figure 4C
+0.14 and 0.16
+1100 elements
+CD8 + Vb8 + T cells
+UV Stratalinker 1800
+φ −1
+feces
+Over 90%
+Antiviral responses
+32uC or 37uC
+100%
+septicaemia and pneumonia
+mRNA expressions of BSEP and FXR
+29
+16 dpi
+Five
+1.7 days ± 1.5 days
+120
+World Health Organization
+reduced the unwinding force of the rod
+proportionate mixing
+lentiviral vector
+conventional PCR and real-time PCR
+10 minutes
+five
+-382 cal K -1 mol -1
+PR PLTs
+moderate to perfect
+four
+pBBSmal vector
+polymerase chain reaction
+sertraline and bepridil
+one hour
+12
+three
+six
+Dual-luciferase reporter assay system
+2003
+ABMs
+33 months
+Acridine orange/ethidium bromide
+3
+Pennsylvania
+bias
+cardiologist-supported
+topological
+promoter-bound STAT1
+12
+829
+10%
+MMP-9
+Fig 9
+apoptosis
+pulmonary sepsis
+higher
+3 working days
+ELISA
+k i
+recombinase
+44
+Targeted cancer, hyperthermia, photodynamic and gene therapies
+SBC
+326
+epidemiology and molecular biology
+Oseltamivir
+Boran and Holstein-Friesian
+pH-indicator
+X-tile software
+cap-dependent
+both innate and adaptive characteristics
+25%
+standard error of the mean
+Standard anti-viral nucleoside analogs
+RV infection
+Hypercapnic respiratory failure
+65
+P C L j F 1
+1.0 nM
+vaccination coverage surveys, nutritional surveys and retrospective mortality surveys
+the brain was sliced into 1-mm thick coronal sections
+for some time
+autophagic vacuole formation and maturation
+b
+dengue virus replication
+16
+Enterobacteriaceae
+MCDA
+CedPV genome
+0.03%
+multiplicity
+four
+Influenza A viruses
+changing population health status
+dynamics of the host
+gated cells
+the 3 genomic regions
+12.5%
+immunocompromised patients suffering from toxoplasmosis
+penicillin, vancomycin, and linezolid
+21.6%
+After 2002
+TestXpertⅡsoftware
+Th17 cytokines
+ATG13 and FIP200
+non-influenza-related care
+video
+59-deoxyribonucleotidase activity
+three
+Dr. Robert B. Tesh
+93.79%
+perlecan protein
+positive selection pressure
+three
+desaturation of palmitic and stearic acid
+qualitative disagreements of system behavior with a priori expectations
+few
+viral titers and viral DNA copies
+liver-resident cells
+every US practitioner
+2019
+mechanistic background
+50%
+qRT-PCR
+Machine learning
+28
+silent codon change
+asialoglycans
+unfolded proteins 4E-BP1
+serial-ET
+A gonorrhoea-like infection
+cross-reacting memory B cells
+host responses to a pathogen
+Retro-orbital bleeding
+stress granules and processing bodies
+older age of patients and pre existing rheumatic problems
+three
+pressurized vascular delivery, laser, magnetic fi elds and gene gun delivery
+100%
+Temperature
+sheep and cattle
+degradation does not preclude microarray analysis
+serum amyloid A protein and alpha-1-acid glycoprotein
+TrxR
+Chemically modified ssDNAs
+chronic underlying diseases
+those from physical analysis of adenovirus genome entry
+age misreporting
+19 months
+Figure 3
+autophagy
+six
+virus yield assays
+bovine parvovirus and minute virus of canines
+Sixty
+Hsp90
+bats
+a cascade of signaling responses to upstream signals
+Complementation
+28
+12.4%
+biodiversity or water/food security
+Ϫ2/Ϫ1 PRF
+PhH
+MOLCAD
+orange and numbered
+mecA
+nucleotide substitutions per site reactions
+apoptosis and necroptosis
+lung endothelial apoptosis
+Phycodnaviridae and Poxviridae
+Skin biopsies
+Octadecylamine and mannose
+The study of immunology
+oligodendrocyte precursor cells
+High abundance
+f dec
+cc-by
+38
+rhesus IgG-specific antibody
+13
+reverse transcription quantitative PCR
+KP120516
+36-fold
+2,559 ± 2,860 ml
+tic Protein rin
+aerodynamic particle size, dose exposed to, and respiratory rate and volume
+15 days
+OD 450
+low protein expression or activity
+Hardy-Weinberg equilibrium
+Cell-and tissue-specific delivery of cmRNA
+μl
+30
+Mutations found in replicate samples
+acidic
+33%
+IL-6
+zebrafish
+Warthin-Starry silver impregnation
+IFN-I resistance
+a tablet-based, easily transportable, touch pad body resource
+Six
+Tryptophan
+limp and arthrocele
+beagles
+300 mg/day
+red
+up to 25% of diaphragmatic
+The theoretical foundations of the cross linking entropy model for secondary structure
+virus-induced cytokine storms and inflammation-related immune pathogenesis
+FMD
+Selected contig sequences or sequenced PCR products
+cytokine
+Uniformed Services University of the Health Sciences animal housing facility
+a reduced range of neutralization
+several hosts are needed to maintain ebolaviruses
+the ratio between hMPV genomic RNA and mRNA
+ADAM17-depleted cells
+Th1 and Th2 cells
+$441 to $8550 per person
+immune suppressive drugs
+DAMPs
+B-SHADE
+pMLKL
+common febrile convulsions
+Whittaker
+IFN-β
+patterns
+Newbler software v3.0
+a proxy value
+synthetic genomics techniques
+whole genome array-CGH
+0.3
+propidium iodide
+norovirus replication
+mortality
+10 minutes
+seh
+mAb reactivity
+Vero, MRC-5 and LLC-MK2
+4 day
+inefficient antioxidation and scavenging of ROS
+7
+areas affected by violent conflict
+Golden Gate cloning
+uteroglobin
+Minimally invasive, reliable, and specific tests
+heparan sulfates
+Qiagen RNeasy Mini Kit
+virus replication
+to maintain the plasmid-based expression of O-antigen
+pfcrt
+Biomolecules
+diGTP-biotin
+voluntary organisations
+GAPDH and PP2A
+eight
+secretion
+Heteranthery
+significant activity of the compound against the virus
+social support
+Lymphangiomas
+six
+Additional surveillance
+N-terminal 6
+biological
+$0.5
+Skaar and Barber
+six
+MD refinement of the TLR4 structure
+7.007
+proinflammatory
+increasing competency
+WF10
+a single cause for the differences observed may not exist
+A and B
+risk factors for severe influenza disease
+Ficoll-Hypaque density gradient centrifugation
+chronic infectious diseases and malignancies
+an asparagine in the HUS domain
+Large carefully conducted clinical studies
+450 and 690 nm
+low ionic strength environment
+a day-by-day tick box framework
+consequent organ dysfunction
+hierarchical folding hypothesis
+200 ml
+chronic immunodeficiency
+young ages
+two
+Fluorescence activated cell sorting
+India
+MutPred
+Mycobacterium tuberculosis
+cholesterol metabolism and MP infection status
+Frameshifting for expression of C.elegans antizyme
+reverse migration
+S. aureus
+90%
+Six to twelve-week-old female animals
+articles published in English and Chinese
+0.34
+tryptophane auxotrophy
+1 h
+a baseline state
+Eqs 3-7
+immunodeficiency in athymic patients
+enveloped, ambisense single-stranded RNA viruses
+95% confidence intervals
+massive apoptosis
+Projections of age-specific probabilities of death
+Tunel
+containment and eventual termination of inflammation
+Twenty-seven
+HCV replication
+relevance to infectious disease research
+0.7536
+methanol extract
+tubules
+E. coli S17-1
+alphavirus replicon RNA
+nonlinear regression of the concentration-response curves
+three to five per cent
+226Q and 228G
+StemProH AccutaseH cell disassociation solution
+DEP force
+22
+Ang II-converting activities
+~30 atm
+mRNA encoding irrelevant antibodies
+diagnostic services
+C-C
+feline herpesvirus and feline calicivirus
+two
+Blastomyces dermatitidis
+>50%
+Knockout of STT3A
+80%
+Influenza A viruses
+polyethyleneimine
+a delay in intubation by use of NIV
+interferon-α response-associated genes
+recombinant canine distemper virus expressing dTomato
+median
+NS residues 1 to 230
+1-6
+age, sex, and military status
+viral infections
+CD-HIT v4.5.4
+Over 40
+R2 = 0.52
+Amino acid frequencies
+mice
+US Department of Health and Human Services
+0.3 mmol/L
+sentinel monkeys and sentinel mice
+Onchocerciasis
+TRIM56
+35
+blood culture and Widal's agglutination test
+repeated structures of N-acetyllactosamine
+Six
+induction of other immune-related genes
+damage
+immunoresolvents
+90%
+CypA-mediated
+45%
+N80%
+mannosylated proteins
+IFN-γ
+time, regions, and individual ICUs
+hematoxylin and eosin
+TP/
+20 μg
+sucrose gradient fractionation
+mouse data
+Hepatitis G virus
+85
+brick-shaped
+Notch1 signals
+Soluble factors present in conditioned media
+11
+ABM
+conserved regions of TGEV strain H165
+no significant differences
+20
+reactive oxygen species and restored pH
+Medrio
+chemoprotective
+150-200 nM
+Thermo Scientific Pierce
+mechanistic
+peacock evolution
+Severe respiratory failure
+phylogenetic
+improve H7-specific HAI titers and neutralizing antibody responses
+lack of specificity
+access to treatment
+misrecognition of the RNAs
+>86%
+its antigenic properties
+ethical standards
+Five
+Immunisation against influenza
+influenza antiviral agents
+Available data
+genome-wide association study
+a-helical coiled coil fragments
+older
+risk-wise
+by reading the T m values from the melting curve
+A control scheme
+winter
+oscillations
+EB spheroids
+24 hours
+tautomerase
+Vaccination
+genotypes 1-3
+movement protein
+post-TGN
+AF-594 succinimidyl ester
+8 months to 6 years
+Transmission dynamics model
+eIF2α
+cigarette smoking
+10%
+unravel basic concepts in cell biology
+up-regulated mRNA levels
+61.29%
+cellular sphingosine
+0.62
+220uC
+reverse transfection protocol
+influenza
+differences in intracellular stability
+PD-1
+viridans streptococci
+5%
+monomeric
+Perceived information reliability or trustworthiness
+20 to 61
+selected for different recombinants
+polyclonal
+80%-100%
+murine trachea and bronchi
+four
+winter
+Biotinylated goat anti-NP antibody
+CFA
+the cumulative exponential growth rate
+preparedness and response behaviours
+reduced antimicrobial responses
+IL-22
+1 mM
+chikungunya and dengue viral infections
+The reported clinical attack rate
+wild boar
+Thirteen
+pH-dependent
+71%
+delayed timelines
+isoform 2
+10ug/mL AMQMLKETI peptide
+changes in exposures to pesticides and other contaminants in water
+alanine substitution
+various infections
+mitochondrial apoptotic pathway
+look up their own resources
+buffalo
+QIAamp DNA Blood mini kit
+Sequence based predictions of disorder
+30 November 2009 to 27 December 2009
+RNA level
+NanoDrop 2000 spectrophotometer
+28.4%
+1,000
+plasma kallistatin
+308,498
+sequence change saturation and purifying selection
+inappropriate patient management and antibiotic misuse
+philosophical
+EVD
+6C
+epidemics
+forced-choice
+SCARB2 mRNA and EV71 RNA
+overnight resting
+good discrimination
+one-way ANOVA
+Jensen-Shannon Divergence
+multivariate Cox regression analysis
+growth of C4 melanoma and CT26 colon carcinoma
+Löwenstein-Jensen
+30 min
+Limulus amebocyte lysate test
+SPSS
+seven
+80-100%
+by dividing the fatty acid specific radioactivity by the plasma water specific activity
+adenine
+>10-fold
+Interdom
+74
+Figure S2
+liquid-liquid phase transition
+25%
+isolation of the agent or pathognomonic histopathological criteria
+cisatracurium besylate
+FB concentration
+Andonegui and colleagues
+subjects sitting
+clinical signs
+r
+proliferation
+300
+older than 15 years
+The ID number
+flow cytometry
+virological surveillance
+refined analysis
+proprietary adjuvants
+immune infiltrates and lung consolidation
+lower N e comparator
+1010
+up to 2h
+October 2016
+macrophages
+DNeasy Blood & Tissue Kit
+CD4 + T cells
+Hippoboscid flies
+>95%
+sex-specific education programs
+bronchiolar epithelium
+camptothecin
+adverse health outcomes
+inhibits ERAD
+E.coli Top10
+KZ52
+oxygen
+integration of information from different sources of public genomic data
+de novo cap-dependent translation initiation
+The cooperation of several of these extended TM oligomers
+Human respiratory syncytial virus infection
+Combination of the immunopotentiators with polyvalent vaccine
+transitions
+paired endoplasmic reticulum membranes
+increase cooperation
+6-7%
+72 hours
+10 μ l of Laemmli's SDS reducing buffer
+when they are applied rapidly and early in an epidemic before many cases arise
+American Type Culture Collection
+cough
+rabbit-anti-goat bridging antibody
+lower
+a control
+ribosomal RNA cleavage
+Ten CpGs
+genetic drift
+241
+Empirical antibiotics and antifungal agents
+12%
+The investigator and staff
+HPRT1
+porcine gene annotation
+80 nM
+humidity
+integral
+endogenous lamin A protein
+evolutionary rates
+inhibited synaptic accumulation
+7
+molecular
+PTBP2
+68 days
+non-smoking uncomplicated asthmatics
+does not enter cells through the endosomal pathway
+covalent binding
+One hundred years
+sixteen
+baseline oxygen saturation
+activated macrophages
+Two
+petechial
+communicable disease issues and their implications
+182
+HLA-A*0201 molecules
+following infection or exposure to other stimuli
+IRF3 and NF-κB
+viral RNA or the viral replication proteins
+eight
+Mesenchymal stem cell therapy
+sequence features
+Swine influenza virus
+total RNA
+challenging
+mortality related to ventilation
+study group B
+no difference in HRV
+Mac-3 ϩ resident microglial cells
+BAL T-lymphocytes
+non-viral mRNAs
+computational analyses
+GGI pairs
+Foot-andmouth disease virus
+100
+FIGURE 6
+antiviral eye drops
+58.5%
+distance of 2.5 Å between the donor and acceptor atoms
+The effusion in the middle ear
+the data observed
+non-antitumor compounds
+Viral RNA in plasma
+RAGE
+S57 in AP1/AP2/AP3
+Leica DM5500B
+17 days
+significant alterations
+ACTB, TUBB, and GAPDH
+7 366
+r age
+Cleavage of the NDV F protein
+turkey red blood cells
+9.2 million
+15%
+large volume of daily incidences
+translational recoding
+The size of the contig
+two
+GCL and GS
+Gabriel M. Leung
+the proportion of persons without information about their date of illness onset
+high population turnover
+tumor cell apoptosis and tumor growth inhibition
+essential
+Mitochondria
+moving bees and brood between colonies
+More than half
+15
+One hundred and sixty-seven
+binding to TG was substantially reduced after sialidase treatment
+3-day old
+Sorting Nexins 13
+2%
+10 cm
+aids in the homing of leukocytes
+Influenza
+VP1 and VP2 proteins
+Long-range interactions
+47
+sodium pentobarbital
+logistic regression analysis and t-tests
+Platelets
+innate immune stimulation
+undetectable
+Forsythin
+MRW
+k
+antiviral
+18 hours
+90%
+F-S MLV
+DC-ablated mice
+site and edge description files
+Retroviruses
+indirect immunofluorescence
+non-significant
+1988
+CVP
+adaptive immune transcripts
+dimeric
+they do not form plaques
+Western blot assay
+Mimotopes
+8054
+Descriptive data analysis
+to provide sequential updates on forecasts
+measures of convergent validity
+6 to 11 months
+A taxonomy
+Aligning Sigma class GSTs of trematodes
+Streptomyces
+public/community engagement, vigilance and resilience
+Rhabdoviruses and retroviruses
+seven
+synthesis of infectious virions
+27 • C
+37
+170
+apoptosis
+1-100
+Marburg virus
+ACE2
+Kaplan-Meier survival curves
+P-M region
+NdeI and BamHI
+MDCK cells
+PCR amplification efficiencies and correlation coefficients
+TLRs
+water
+60%-80%
+EBV-latent
+reduced CSNK1E levels
+VWF-R1597W multimers
+52
+A dose-response curve
+Mycoplasma pneumoniae
+viral infection
+Vitality
+by titration with buffer alone
+virus-host coevolution and intra-host duplication
+their enrichment with various sources of gene sets and pathways
+methicillin resistant
+1,387,377
+Coliform mastitis
+7.5.6
+NEP
+between the nineteenth and twentieth centuries
+2 /FiO 2 ≤ 200 and higher BMI on admission
+genetic increase and growth of the genome
+10 2 -10 6 bacterial cells/mL
+A reduction to a cubic algorithm
+AM
+18 Å
+residual solvent peaks
+nine-amino acid cyclic
+SI = 7 + /2+56/2 = 39-56 days
+6 h
+enhanced phosphorylation of Egr-1
+5%
+Ma-Xing-Gan-Shi-Tang
+Eukaryotic elongation factor 1A
+wt-phase
+death
+machine-learning approaches
+life history, physiological, and ecological trait data
+IL1
+glucocorticoid therapy
+137
+18
+an association
+juveniles
+viral sequencing
+Blood withdrawn from healthy volunteers
+At least 80%
+pro-inflammatory
+10
+Hotspot
+E. coli-induced and CLP-induced septic mice
+3.4.1
+In the nucleus
+nine
+pesticide self-poisoning
+sucrose
+good sanitation and hygiene
+baseline severity of illness and comorbidities
+5 µM
+catalytic and transport activities
+Cryptosporidiosis
+the overall size of the RNA
+trypan blue exclusion
+seizure
+8,236
+Damage to the lung epithelium by respiratory pathogens
+Salmonella Enteritidis S1400 colonization
+confidence region
+non-availability of vaccine and lack of time
+M. E. J. Woolhouse
+Chi square test and Mann-Whitney U test
+33
+four
+differences in VLPs, cell types, or the readout assay
+0.1 mL Triton X-100
+lectins or adhesins
+seven
+quantitative RT-PCR
+Maprik district of the East Sepik Province
+17.4 months
+HEK293 and Vero cells
+Group H M
+Contact reduction measures
+Buddha
+Stc1
+Proper implementation of previous exposure profiles
+51
+cc-by
+WHO
+causal
+RNA fragmentation
+DNA/RNA Shield solution
+Rluc activities
+day 63
+87
+to model a response variable in terms of one or more independent predictor variables
+April 30, 2020
+50%
+cave roofs and walls
+5-HT 1A receptor
+R
+the RGD-containing GH loop
+Neutrophil gelatinase-associated lipocalin
+a fomite or individuals' hands
+GraphPad Prism ® software
+50%
+hydrolysable
+Gtx mRNA
+protein activity
+Sigma-Aldrich
+4′-halogenated
+40 min
+2,665 epitopes
+Contrast dye
+cell lysates
+Two
+Operon Biotechnologies
+CI and CII
+11 days
+they did not use antihistamines
+broad-spectrum
+nine
+ALV-J
+Phyllostomidae and Pteropodidae
+75-120 μM
+virus binding to the cell surface
+one
+five
+2012
+Two
+M-T hook structure
+shutting down
+ACBD3
+35%
+C2, and CD1
+ACADM
+nucleic acid purification and non-specific readout
+reporting precision
+cigarette smoking
+no differences in activated WT donor CD4 T cell survival
+Staff
+25
+SPSS 19.0
+translational fidelity
+international travellers and international conveyances
+cap-independent translation
+high levels of IRF9, STAT1, and STAT2
+174
+chloroplast genome sequences
+Epidemic
+protein polyubiquitination
+199
+paediatric nurses
+south China
+a gradient
+12
+interactions
+R 0
+TPCK-trypsin
+rational antibiotic therapy
+EBLN and EBLG
+Mean C values, standard deviation and coefficient of variation
+75%
+enzyme-LTA4 complex
+five
+8%
+what is known from the USA
+1 Â E À11
+tires, buckets, and discarded vehicles
+Attachment to and entry into a host cell
+five
+viral lower respiratory tract infections
+limited virus progeny
+Japan
+Ribavirin
+upregulation of Cdx2
+0.206
+utrophin
+100 million
+amyloidosis
+k
+Homology modeling
+fasting or inactivity
+children
+Chroparaviruses
+TBC2target
+High Resolution Computed Tomography
+visualization and monitoring of G4s structures
+noninferiority
+human noroviruses
+pDC Isolation Kit
+Promega
+Thirteen
+it has explored an area where not much research has been done
+AcHERV-VLP
+Modification of ISG15
+five
+phylogenetic clade
+Transform-derived baseline and noise values
+48 and 72 h
+69%
+enhancing antitumor immunity
+barium removal and the correction of hypokalemia
+three
+Data
+raising alertness for possible exposure to uncommon infectious diseases
+a double-sector epon charcoal-filled centerpiece
+schizophrenia
+the damaged blood gas barrier
+day 0, 3 and 7
+stimulate the release of renin
+DHHC2
+seven
+Distinguishing DENV1-4 at the point-of-care
+The question of whether such harms may be justified or not
+15 min
+characteristic or unusual migration patterns
+0.611 and 0.396
+statistical significance
+limitations in the database
+high genomic A + T content
+FPs
+data
+ISG15 and MX1
+host and/or vector associations
+amino acids
+NASH
+Angiotensin 1-7
+Carbohydrates
+2 to 7 days
+11.3 months
+eight
+recombinant proteases
+90%
+its HA partner
+three
+268
+cryo-conserved bacterial stocks
+ϵ-edges
+virus replication
+gastrointestinal diseases
+indirect ELISA
+Bafilomycin A1
+d s
+stochastic metapopulation epidemic model
+160 kilodaltons
+HTNV-specific CTLs
+gray
+5-33%
+supernatants
+blood pressure and end-organ damage
+16,663
+dramatic changes in health and functioning
+cyclic threshold values
+the thymus
+cellular lysates
+relevant studies
+delphi method
+L and A
+covalent homodimers
+>97%
+alternative
+Wide-bore pipette tips
+37
+converts a mild illness into a life-threatening infection
+selfassessment
+County of Santa Clara
+4 days
+H7N9
+80%
+ImageJ
+g-tubulin
+Communicable disease prevention and control
+12
+RNA-Seq
+MALDI-TOF
+The TNA
+major histocompatibility complex class II
+Escherichia coli and Bacteroides
+deer tick I. scapularis
+RNA concentration
+NF-kB luciferase reporter plasmid
+Tumor Necrosis Factor
+13,183
+novel coronavirus
+viral RNA genome copy numbers
+K63 polyubiquitination
+anisomycin
+rotavirus strain-specific
+five
+semi-structured
+mutations
+ccl2
+a phylogenetic network
+1:40,960
+14.5%
+the mean time between illness onset of two successive cases in the chain of transmission
+transitions between confinement and straight relocation
+T7 RNA polymerase
+72°C/5 min
+IRT
+98-10
+Sydney
+1 h
+H162A and K224A
+all pairs of origins and destinations
+AECs
+entry receptor complexes
+exudative and atrophic
+Barbari and Tellicherry
+17.4%
+GO and COG
+Influenza A H3N2
+51
+Cryptococcus
+14 days
+100
+http://elm.eu.org
+2 ferrets
+Blockade of these inhibitory receptors
+TLRs
+intracellular antibody fragments
+serine
+uman immunodeficiency virus infection
+IgG antibody to human herpes viruses
+uridine phosphorylase
+6.60%
+Host genetic variation
+Zaire Ebola glycoprotein
+Lys48-linked polyubiquitylation
+a novel approach to target new organs
+differentiated tissues
+cyclic epidemic pattern
+Rhinoviruses
+fluorescent antibodies
+BNSP333-coNiV-G
+Digital PCR Analysis software
+compound failures in man
+short-term and in-hospital risk for death
+inhibited
+24 h
+permeability
+Three
+WW Group IV
+T cell monitoring
+30 minutes
+125
+fibronectin
+33
+100 μg/ml or 10 mg/kg
+seven
+translocates from the intestine to the systemic circulation
+600 s
+inflammation
+15
+dynamic compliance
+AUC
+Recombinase-mediated DNA excision
+scr/Egr-1/CBP siRNA
+two
+foci of Fluoro-Jade C positive neurons
+United Nations General Assembly
+Baroreflex sensitivity and autonomic function
+0.1, 1, 10 and 100 mg ml À1
+substantial expression of GCSF and neutrophil β2 integrin
+renal replacement therapy
+three
+Prevalence
+24
+high rates of morbidity and mortality
+TM-align and 3DCOMB
+Four
+an exposure of the wild-type IRES to oxidative stress
+L = −1
+Targeted lncRNA
+Oropharyngeal and cloacal swab samples
+dualuse
+Venny
+Statistics calculated at intermediate times
+Pneumonitis
+molecular specificity
+histologic response to a GFD
+cell senescence
+Global fitting of the time courses
+Ethical approval
+nine
+hand-reared Mallards
+LCMV strain Armstrong 53b
+250
+purified human apoD standards
+terminal chitobiose
+gRNA synthesis
+ICAM-1
+key
+Packard Cobra gamma counter
+Historical experimental data
+13
+Differences in health seeking behaviour or healthcare access
+interruption of blood supply to the bone
+unexpected and unwanted side effects
+Health people
+GBS stimulation of host immune pathways
+2020
+CD4+
+Kaplan-Meier analysis
+PDTC
+correlation analysis and signal detection comparison
+RIG-I and MDA5
+microliter of unpurified product
+Charcoal yeast extract agar and Lowenstein Jensen media
+cellular stress conditions
+dasatinib
+congenital Zika syndrome
+clinical condition
+US Department of Veterans Affairs
+AAA+ ATPase p97
+sequence-specific
+integrates information from multiple alleles to assess risk against a similarly matched data cohort
+security reasons
+IL-35
+all STATs
+25 to 0.006 µg/mL
+Kunitz-like protease inhibitors
+the APC binding domain
+30 minutes
+host
+interesting
+thermodynamic
+chemotaxis
+Lys at position 627
+lipid scavenger ATG9
+gene-based
+CMV reactivation status
+weight loss and 10-20% mortality
+Guangzhou Center for Disease Control and Prevention, China
+5.5-6.5
+~8,000
+internal class definitions and structure of components
+increased pTDP-43 accumulation
+homology modeling
+focal adhesion
+seven
+the globular head of MA
+PaKiT01 cells
+CD4 T cells
+Movement
+QIAamp Viral RNA mini kit
+read the card themselves
+daily
+total viral nucleic acid
+viral shedding
+ubiquitination and degradation of PDCD4
+general response efficacy, self-efficacy, and response costs
+naïve cells
+cellular resources
+180 389
+Resistance to immunotherapy
+VaxiJen
+equal pairwise transmission probabilities
+cutaneous manifestations
+4%
+epithelial cells
+two
+Zeiss LSM 510 laser scanning confocal microscope
+fell apart
+unlimited flight capacity
+calcineurin
+step 3
+unfavorable side effects
+HPV capsid-reactive
+SDS/PAGE
+Angiotensin II
+non-infection-based disease
+real-time quantitative reverse transcription-PCR
+Quick isolation of cases
+symptom scoring system
+pairwise nucleotide p-distances
+1979
+trypan blue dye exclusion method
+antimalarial
+there are currently very few accepted gold standards
+any effect of the downstream oligo
+coverage cut-off of 300
+study sponsors
+septic and nonseptic patients
+single-cause proportional model
+canonical splicing
+cholera prevention and control
+lectin receptor
+RNA-RNA recombination
+in vivo CTL assays
+Retroviruses
+multiple cardiovascular diseases
+Ang II signaling
+Hepatitis G
+100%
+vaccination
+Inducing apoptosis
+major bleeding and infection
+Five
+0.756 0.673-0.839
+fire treatment
+48 h
+highresource settings
+5%
+Sanger method
+plasmonic dimer probes
+sevoflurane
+income data
+instructions from rescue command centers
+NPs
+C and V
+drastically increases
+244 ± 91%
+induced changes in farmers' behavior
+day 11
+PTSD patients
+fold difference relative to control
+Specific primers
+Evolution of the OAS family
+Two amino acid substitutions in the 130-loop of the receptor binding domain
+an important causal link between inflammation and the host hepatic innate immune response
+capsid physical interaction with chitin
+very steep
+semi-empirically determined parameters
+nCAA
+components of the inflammasome
+infection
+JYW and LLL
+Animal Experimentation Guidelines
+20
+N214A
+Salvadorian Ministry of Health
+lowest dose
+2005
+seven
+observation errors
+grp78/BiP, grp94 and PDIA6
+chemical modifications
+factors associated with death
+HBS-EP buffer
+multilocus sequence typing
+insectivorous bats
+DNA repair processes
+five
+TERA
+greater disease severity
+confidence interval
+10.1186/s13054-020-2786-x
+1.5%
+sepsis, head injury, acute lung injury and HIV/AIDS
+2500
+Infection
+10%
+932
+HRP-conjugated streptavidin
+tissue samples
+FGFR dimerization
+Moral struggle
+»40 amino acids
+suitable health facilities and good links
+a discrete binding profile
+chemical modifications of the surface chemistry
+Mokola virus
+Antigenicity
+FlowJo
+March 11, 2020
+an increase in the secretory IgA titer
+NEBNext Ultra DNA library prep kit
+squalene synthase and b-amyrin synthase
+CandidaOrfDB
+tionary
+MEME analysis
+harringtonine
+RNA affinity
+activated macrophages
+3 min
+Seroprevalence surveys
+A random-effect
+human polymorphisms
+Activation and polymerization of Bax and/or Bad
+Xbp1 regulated genes
+Optical restriction mapping
+Population sample sizes
+number of AKI patients
+hvKp
+national/international consensus treatment guidelines
+a linear epitope on VP1
+Modification indices
+79
+metabolic regulation of DCs by TLR4
+Receptors for CSFV recognition
+virion secretion
+R 0
+The SH3 domain and its PRM ligand
+seed sequence presence in 39 UTRs
+inhibitors A2, A3 and B3
+Burkitt's lymphoma
+Shanghai Oebiotech Corporation
+mucoadhesive ability of delivery system
+Fc-dependent viral clearance
+biochemical
+wide sensitivity priors
+54%
+protein domains
+investigation of the HA/NA balance
+F. hepatica
+OptiPrep gradient centrifugation
+antigen
+100
+Mimiviridae
+identifying disease features directly in human tissue
+overdose death
+40%
+Abcam
+autophagic
+CXCL10
+pulmonary parenchyma, bronchial wall, and muscle
+neutrophils, monocytes, and T cells
+Euclidean distances between AMR features
+Yersinia pestis
+JFH-AM120-LacZ
+Sites
+polyproteins 1a and 1ab
+better delineate its effects and putative indications
+seven
+79
+angiotensin-converting enzyme 2
+Granzyme A
+last year
+autoimmunity
+4-12% BT running gels
+viral RNA extracts from various control viruses
+11,700
+phylogenetic tree
+ebolavirus-like filovirus
+Extensive AAI editing
+two
+the next generation of vaccines
+extracellular signal regulated kinase pathway
+glyceraldehyde-3-phosphate dehydrogenase
+NE
+health risks to themselves and their families
+human or animal
+Shannon entropy
+5142
+antiviral
+H9 HA gene RNA
+DNase
+28,338
+National Health and Family Planning Commission of P. R. China
+Visual OMP TM 7.0
+no enhancement
+permanent ischemia
+two
+on linear and log scales
+lipid, polymer, peptide, and even inorganic nanomaterials
+glucocorticoid betamethasone
+54/58kDa
+Linear regression analysis
+passage number and immortalization processes
+conformational
+Toll-like receptors
+ARDS
+LC3-II coated autophagosomes
+monocytopenia
+school closure
+potent gene-specific siRNA molecules
+density
+degree, betweenness centrality, and random-walk centrality
+rDNA technology
+functional differences between the different length variants
+restrict
+regional
+investigational
+Qiaquick gel extraction kit
+Mallard plasma
+literacy status and pregnancy history
+Three
+absorbent materials
+Primers for each target segment
+Respiratory tract washes and cerebrospinal fluid
+εHOMO
+L100F, M104V and Q108F
+35-38%
+decreased
+social conformity
+Western blotting
+K11 Linkages
+16-24 hrs
+excellent outcomes
+80%
+HBV
+at the ends of the genome segments
+HRQoL
+1 hour
+24 h
+Denmark
+inhibit the cytokine-stimulated production of MDC
+Breakthrough infections
+gross contamination
+further examinations
+Illustra MicroSpin S200 HR columns
+30
+via isofluorane inhalation
+closely related
+antigen-presenting cells
+viral replication
+201
+ZIKV E protein
+ANOVA
+supplementary information
+Specificity
+eIF5B
+Global climate change
+Radiological
+Live bird markets
+bottleneck sizes and selection
+significance of individual rates
+size
+meta-analysis
+0.38 M NaCl buffer
+0.5%
+hypothesis-based research projects
+cross-species transmission and emergence of viral pathogens
+HeLa-R19 cells
+95%
+features whose presence was contingent on a particular choice of training or test set
+75 percent
+local background measured next to the membrane sheets
+lysine
+vaccines
+group III
+contact between the vectors and farmers
+Normalized Difference Vegetation Index
+Neural progenitor/stem cells
+days of mechanical ventilation
+to gauge prevalence rates of hospital-acquired multidrug resistant organisms
+four
+GRP78
+Vero E6 cells
+parasite restriction
+24
+RSV
+RV envelope proteins
+2-7 fold
+systemic CMV reactivation
+intracellular anti-mitochondrial autoAbs
+influenza
+13
+Phage display
+15 million
+American Type Culture Collection
+epidemiological observables
+more than 100 %
+45 days
+immunohistochemical
+preferential mixing
+109
+Life Technologies
+Student's t-test
+Policy-oriented operational research
+30 days
+Twenty-five
+18
+Mesogenic and lentogenic
+10%
+Homologous recombination
+retain infectivity
+chimpanzee
+Nosocomial influenza
+indwelling tubes
+1998
+quantitative
+protein and whole cell vaccines
+moderate-severe CAP
+VP1
+forming an interagency group, and joint capacity training
+BCL2 homology domains
+improved
+ERK1/2 and p38 MAPK
+target detection
+translation factors, ribosomal proteins and RNAmodifying enzymes
+while there was low rainfall
+PRRSV infection
+neutrophil numbers
+Creative Commons Attribution License
+baseline patient characteristics and study outcomes
+systematic
+Leishmania donovani
+enhanced chemiluminescence
+central-point parenteral vaccination
+Angiotensin converting enzyme 2
+the ability of 89K to excise from the host chromosome
+local geography and traffic
+RSV
+Targeted exon skipping
+data from three different representative mice
+29
+T
+consistent data collection methods
+doxorubicin
+hospital and calendar day of ICU admission
+BioMax Scientific Imaging Film
+two
+cc-by
+Tpt1
+significant difference in expression level
+4 hours
+60 %
+acceptable internal consistency
+ion trap mass analyzer
+rectal temperature
+20 min
+MARC-145 and CL-2621
+backward elimination
+RSV
+Equal amounts
+RIG-I/MDA5
+Computer-Processed Personal Data Protection Law
+NRT
+15 kg
+thinking
+5 minutes
+conserved regions that do not represent overlapping functional elements
+whether infection turns to acute or persistent progression
+neutrophil infiltration
+cell cycle progression
+differentially expressed
+PIKfyve and PIP 2
+Exonucleolysis
+peptide tryptophan
+changing their behavior
+NO
+increased expression of neutrophil related genes
+pertussis toxin
+flow cytometry
+less than 6 months
+cohabitation
+pH 5.5
+Retro-Q
+Natural products
+lowest
+Four
+Mesothelioma
+10 μmol/liter
+within 24 h of respiratory symptom onset
+93%
+Gln438 and Lys439
+myc-His tag
+DENV-faR
+quality-adjusted life-years
+carrier animals
+immunoblotting
+assumes that the construct can be reduced to a single dimension
+low
+pEYFP-N2
+fucose
+disseminated zoster or varicella
+complementarity bias
+RT-PCR
+reverse fluorescent strategy
+muscle hypoplasia and demyelination
+nephrotixic
+HCV-infected patients with low antibody titers
+decreased
+the total number of occurrences of the superior codon in the gene
+ferrets
+Enterococcoceae and Streptococcaceae
+PDT
+Stress ulcer prophylaxis
+2 weeks
+I7 protease
+Prolonged colonization with P. aeruginosa
+34
+GB14925-2001
+Ifnar1 SA mice
+the viral genome
+The pulmonary endothelium
+H1N1pdm09
+1%
+penton base loops bearing RGD motifs
+media release by health authorities
+insects
+lithotrophic
+His p 862 and Thr p 824
+NOD-like receptors
+0.1N HCl
+sequence-specific, spatial self-complementarity
+Almost half
+Cronbach's a of 0.7
+Guadalajara
+ribosome profiling
+75%
+nasal washes
+microRNA 122
+90%
+trend, seasonal, and remainder or residual
+global environmental change
+reducd hepatic and/or pheripheral clearance of circulating cholesterol
+binding the PjCaspase promoter
+an unzipped hairpin region
+transcriptional repression of collagen expression
+larvicide application
+epitopes having significant median similarity score lower than the non-epitopes
+APCs
+complementary sequences
+E. coli
+6.9kbp
+10 µL of FAs
+10%
+Per a 2 protein
+60 s or more
+The upsurge in interest in AMR
+The peptide's binding mode
+ZIKV-infected cells
+IFN-λ
+NanoDrop 2000 spectrophotometer and SDS/PAGE
+minus-strand synthesis
+hepatic
+CDC
+QIAquick PCR Purification Kit
+A deep nasopharyngeal swab
+VITEK R 2 -Compact automatic bacteria identification device
+all 4 serotypes of DENV
+1%
+QIAquick PCR purification kit
+Uganda
+Rayleigh distribution
+annexin V
+7 y and older
+amplification curves with relatively lower Ct values and obviously stronger fluorescent signals
+partial immunity
+stimulates TLR3 signaling and induces immune activation
+non-glycosylated proteins
+50%
+13.6% and 8.2%
+zinc finger nucleases
+heparin
+15
+less severe symptoms
+3 days
+conflict management skills
+reverse substitution R227S
+last-observation-carried-forward method
+Host genetic polymorphisms
+mock infected samples
+red spheres
+temporal lobe epilepsy and absence epilepsy
+rotavirus
+1977
+pH-independent syncytium formation
+transmission
+alveolar macrophages
+ZIKV infectivity
+19.8 ± 7.1
+oligonucleotide
+no infectious units
+Ganciclovir and cidofovir
+human behavior toward vaccination
+49
+GenBank
+6-days
+29
+A shielding ring with four plastic restraints
+polymicrobial aetiology
+viral tropism
+β-1,4-linked galactose residues
+red
+24
+Six
+Cdh1 phosphorylation-mediated
+Four
+19
+S
+51
+>1 class of drugs may be associated with IMHA in small animals
+770
+reference standards, calibration and more time
+enhanced
+MEGA 4.0
+Modulation of IFN signaling
+HLA-A*0201 molecules
+less than a week
+2,4-dinitrophenol
+potency of CEA-directed lysis
+E3 and 6K
+BLAST
+Phage supernatant
+xcms and CAMERA functions
+an assignment of probability to possible values of multiple quantities
+74
+erythrocyte binding properties
+growth-inhibitory activity
+amphotericin B
+D. melanogaster
+Bentiu PoC Camp
+GBF1
+monocytes and Kupffer cells
+two weeks
+JC Renauld
+90%
+Accidental Status Reports
+macrophage
+extracorporeal membrane oxygenation
+The epidemic curve
+host tropism
+rational prediction systems
+severity of illness
+pathogens
+Orbi-trap™HF-X 27
+a retrovirus
+73.7%
+two
+molecular
+loading control, β-actin
+BCC tissue samples and BCC cell lines
+100 %
+penetratin or Tat 48-60
+Percutaneous
+Comparison of the proportion of patients with any grade 3 or 4 adverse event
+DI water
+252
+liquid N 2
+Lipid accumulation
+castrated male
+ion precursors
+TAMs
+2 g
+one week
+splice variants of CEA
+Network leadership and management processes
+586
+57%
+Ub-7-amido-4-methylcoumarin
+5 to 17 month-old
+1400
+10.1186/s12934-015-0326-1
+TLR2 and TLR4
+correlated mutations
+the binding constant
+20%
+CBS
+TransDetect ® Cell Counting Kit
+Western blot analysis
+RV-C
+Single substitutions
+Niemann-Pick C1 disease
+understanding of complement inhibition and blockade of cellular immunity
+Six
+Using stakeholders to identify and help to prioritize future research directions
+LC3-positive organelles or LC3 puncta
+detection by host pathogen recognition receptors
+nucleozin
+membrane anchor protein
+RNA binding curves
+nonspecific inflammation
+airborne infectious particles
+1,200
+several times
+enteric fever
+Zoonoses
+Michaelis-Menten model
+ethanol
+iron depositions
+different mechanisms of action
+engagement of FcR in the presence of HA
+single gene polymorphism
+Sample collection date and location
+27
+Sequencing noise
+a cell-surface receptor and co-receptors
+type I interferons
+gender, age, mechanical ventilation, PICC insertion, application of hormones
+use of guideline
+mRNA expression
+cc-by
+baseline characteristics
+1997
+interrupting the subunits interactions
+1 hr
+46,427
+Chemi-Capt
+the union
+The manuscript
+30
+735
+5% 2-mercaptoethanol
+Three
+accurate
+response to stimuli
+Electronic proximity devices
+sequence identity
+Mycophenolic acid
+total differentially expressed genes
+MTCP1
+VR-2332 and CH-la
+61%
+mouse models of viral encephalitis
+Error bars
+three
+TCID 50 assay
+TLR9
+33-48%
+Berenil
+parasites
+emphysema
+anti-acetyllysine
+IP culling
+other members
+The need for informed consent
+two
+serial dilutions of the samples
+538-nm
+buffer A195
+Brazil
+halo-gravity
+cancers
+Active site
+10%
+lower ACE-2 activity
+Bacterial coinfection
+52%
+Tomas Kay and Eric Tremblay
+Public Health Emergency of International Concern
+Statistical
+12.5 mg/kg
+HI titers of NDV
+Monoclonal antibody
+15 µg/ ml
+increased
+proteins
+L. interrogans
+bioinformatic
+rWR-PRRSV-M
+2-16 h
+Tyr111 and Arg114
+20%
+kappa
+11/36
+on the surface membranes of erythrocytes red cells
+C 0
+transplacental transmission of virus from mother to fetus or adult transmission
+6%
+timeliness and completeness
+workplace/social contacts
+XLStat
+mRNeasy
+multipotent inflammatory
+very specific changes to nutritional quality
+insulin resistance, dyslipidemia, and hyperglycemia
+8
+LC-3 -related peptides
+monocytes, macrophages and dendritic cells
+respiratory infection
+Dr Agis Tsouros
+membrane transport, carbohydrate metabolism, and amino acid metabolism
+CA-STAT5bER
+caffeine
+endosomal acidification
+sensitivity
+FACS lysing solution
+Viral antigenic drift
+increase in intracellular cAMP
+6%
+a critical binding element
+cysteinyl
+SFVs
+10.1371/journal.pone.0014163
+Ambient temperature
+285
+antiretroviral, immunomodulatory, and antioxidant approaches
+21 days
+3-7 days
+β 1 + β 2 + β 3 + β 4 + β 5
+SNARE-Munc18-1-mediated liposome fusion
+266
+theme, and refinements
+eIF2B
+80640640
+carbohydrate-active enzymes
+branch length
+trpDC mRNA
+heterotrimeric
+antimicrobials-related problems
+Stress granules
+finite system sizes
+Kalman filter
+Plots of several alpha globin genes
+1987
+Sputum cultures
+different responses for different pandemic severities
+.50 mM, 3.88 mM and 6.63 mM
+50
+WBC and erythrocyte sedimentation rate
+Three
+bound DNA
+1986
+OD450
+S. Herzog
+pigs
+chronic hepatitis B infections
+450 nm
+IL-10 high T cells
+Epithelial cells
+microbial taxonomic profiles and host transcriptomic profiles
+tunicamycin
+Modified Eagle Medium
+six
+5-10%
+by exsanguination via the carotid artery
+Streptococcus pneumoniae
+biotinylation and western blot analyses
+increased lipid ROS levels
+the physician is not present in the ICU
+twice daily
+0.22 mm Sterivex
+DB
+fluorescence
+lipoprotein
+Dr. Li Tang
+MBL
+plateau pressure
+16S rRNA gene sequence analysis
+follow-up vaccinations
+Lausanne DNA Array Facility
+arginine
+318 days
+acetylated
+the protection elicited by vaccination
+scalefree
+28
+NCBI gene identifier number AY847351
+Class A virions
+patients with low PCT values did benefit from antibiotics
+an independent investigator
+Techniques to fully recover human antibodies
+HSPG
+inhibits H5N1 viral replication
+insert-free
+Phalloidin-iFluor 555
+8.2 ± 0.6 days
+Controlling the disease within the poultry population
+increased SIV-specific antibody responses
+66%
+all benchmark methods
+capacity
+efficient cell-based screening models
+SEM
+mRNA
+the complex calibrations of acceptable risk compound exponentially
+three
+SH3 and PDZ
+thermodynamic model
+Two weeks
+3
+hightemperature field sites
+1797
+80%
+NS2A protein
+increasing membrane fluidity
+IU/mg
+inflammation, angiogenesis, immunity, and insulin resistance
+2%
+NP and M1
+Enhancing the immune responses to pathogens
+Boreholes
+E. coli and BP
+Human movement
+clinical
+Miro1 expression
+2
+1 µg/ml Actinomycin D
+building a global consensus on laboratory leadership competencies
+exacerbates the effect of allergens
+cytotoxic effects
+informationdriven research
+PCR
+EMBOSS CHIPS
+First-strand cDNA
+Discovery curves
+A rank-based method
+bovine surfactant
+direct quantitation of multiple marker compounds
+mutation of this residue
+Pseudoknots
+rotaviruses
+0.62 to 0.83
+4 Pst I restriction sites
+MTT assay
+Adenovirus 5
+binding and degrading
+half
+type I and II IFN induced transcription of genes
+9.65%
+Corticosteroid administration
+biomaterials
+10%
+centrosome microtubule nucleation ef®ciency
+100%
+manual selection of representative genes
+three
+there are many infection-related sub-classifications
+oligosaccharides
+Nearly three quarters
+Trees
+Fractions containing long Ub chains
+42
+HIV-1 5 0 UTR IRES
+ROC AUC $ 0.920
+host infectivity
+longer sidechain
+non-steroidal anti-inflammatory drugs
+cytokine storm
+TEs or REs
+Phang Nga Province
+390,000
+MFold 3.2 and DINAMELT
+the coming rise in case counts
+biological
+a significant hit
+18
+serial dilutions of MHV68 BAC DNA
+Detailed sample information
+2-Ethyl benzoquinoline carboxylic acid
+FRC
+3
+Red Cell-Tracker
+10-day
+inefficiencies
+2513^21
+semi-quantification analysis
+Mouse Phenome Database
+Ottawa
+trypsin
+photons
+Monk and Buysse
+immunogenic
+shell-less
+mean ± standard error of mean
+aldehyde dehydrogenase
+PMNs and macrophages
+Three
+C-terminal amino acid mutation
+Human respiratory syncytial virus
+An extended GO annotation system
+28
+a high or a low indication of whether or not to start contact tracing
+Ultrafree-MC centrifugal filter units
+flowers
+GTR+G
+ischaemic heart disease and cerebrovascular conditions
+immunomodulatory
+stable Env glycoprotein-dependent virological or infectious synapses
+CRX-526, E5531 and E5564
+self-limiting
+phage display
+1.28+/-0.91
+p67 phox
+SSC versus FL1 dot plot
+prevaccination GMTs
+anhydrous Na 2 SO 4
+western Kazakhstan
+Sterile immunity
+Novel A/H1N1
+bovine RSV-specific antibodies
+infections with A/H3N2 virus alone
+four
+JC-1
+time-dependent reproduction number R
+immunogenicity of oligosaccharides
+3
+isolation rooms and operation rooms
+pneumovirus disease
+10
+Ion displacement
+risk factors
+8
+stoichiometry
+1986
+virus replication
+much closer to the parental strain
+DTX 880 multimode detector
+Trained staff from local CDCs
+antimicrobial resistance
+More than 99%
+serological evidence
+previously published methods
+20
+100%
+b-tubulin
+2.361.4%
+quercetin
+spleen
+dextran sulfate
+human
+four
+Tel Aviv Sourasky Medical Center
+loss of infectivity
+ERK activation
+48 hours
+RNeasy 96 well kit
+the infectivity
+between the pairs of NT 50 and % IgG bound
+Duration and frequency of contacts
+7
+HA1
+59.7%
+modification, palatability, and storage life of all available sources of proteins
+Tracheal supernatants
+10-2 to 10-4 substitutions/ site/year
+plasma
+reporter RNAs containing the mutant DPKI IRES
+higher incidences of underlying diseases and impaired immune functions
+Immunoreactivity
+West Nile virus and Japanese encephalitis virus
+NDM-HK PCV
+CPCV
+HDAC5 exon 3 and exon 4
+two
+molecular mechanisms of TCs
+Neutralizing antibodies
+Hazard identification
+foveal granularity
+10
+other arteriviruses
+HWE
+Hypercytokinemia
+102
+Coomassie brilliant blue R-250
+five
+area under concentration-time curve
+improve the biochemical behaviors of proteins it is fused to
+FPV and dermatophytosis
+six
+Each value
+Reads that mapped to the Bacteria database
+an infeasibly tight level of quarantine
+HCV NS5B
+soluble oligomers that form micelle-like structures
+23.05%
+PCR
+antibody recognition of the protein surface
+15%
+June 11, 2009
+German influenza sentinel surveillance system
+5′-AT 3 CAT 3
+646
+four
+Xenopus
+the activity of Th1/Th17 responses
+simple personal protective measures
+amyloid phagocytes
+IL11R
+10-min
+12%
+the kosher phenotype
+15 min
+both infected others and been infected themselves
+Murdoch University Human Research Ethics Committee
+Detected clusters
+inhibition of toxin expression
+17
+Amber10 Generalized Amber Force Field library
+TLR2, TLR4 and MyD88
+accurate and timely diagnosis of ASF infections
+B and D
+I 2 test
+Three months
+affected side
+cAMP/PKA signaling
+sepsis
+Atmospheric PM 10 and PM 2.5
+productive, lytic replication and non-productive, latent infection
+19 KDa lipoprotein and lipoarabinomannan
+618
+MAPK signaling
+Gaussian
+intracellular
+0
+participate in the uptake for degradation
+Chemical or Molecular descriptors
+inhalation anaesthetic
+between 21 and 25 million
+IMG/VR
+30 mins
+infection of HEp2 cells
+scenario C
+acute myocardial infarction
+to promote virus egress
+αβ T cells
+Wulf Droge
+280uC
+Aligning all the remaining sequences at once using MUSCLE
+RAFT
+Exponential phase bacteria
+70%
+aveloz
+10 of 1000
+33.1%
+20%
+avian influenza-related keywords
+Melioidosis
+Complement component 1q
+Fisher & Paykel Healthcare
+ire-1-xbp-1
+causes the accumulation of unfolded proteins in the ER
+HBV and/or HDV infection
+strain virulence
+genetic diversity
+to account for possible tagged primer biases and cross-contamination
+indoleamine 2,3-dioxygenase 1
+colorectal cancer
+fomite transmission
+Tidal recruitment
+Klebsiella oxytoca 1
+two structured round table consultations
+fucosylation
+MitoCapture Mitochondrial Apoptosis Detection Fluorometric kit
+host plants
+Three hundred and eighty-four
+0.1 M NaOH
+genome position
+40%
+malaria diagnosis
+ML
+stability
+δ
+Acanthamoeba
+overexpression
+50 μ L elution buffer
+β-actin
+existing or previous education and training
+intensity of infection
+Fatigue and faintness
+TNF-a
+susceptibility to infectious diseases
+low efficiency
+March 17, 2020
+Diagnostics
+seven
+special or expensive instruments
+less viral shedding
+29%
+enzymatic activity resembling tRNA ligases
+Thirty
+contextual information coupled with sequence similarity searches
+mtLSUrRNA
+CAST and PWK
+bone
+appropriate weights
+our two-dimensional cell culture monolayer
+prophylactic or therapeutic agents
+SAA1A −97delG allele
+11%
+MPO
+Chronic HBV infection
+The European Region
+Thirty-eight
+transiently transfected Hek293 cells
+purinergic
+twelve
+cytopathic effect
+481
+4 days
+Nine
+IL-4
+cell growth, proliferation, differentiation, and apoptosis
+plasma cells
+persistence
+decreased species diversity
+1%
+SkV-L-A1
+no biases
+Coefficients
+suboptimal
+13
+three
+25
+65.55 % of the total variation
+precision
+rural areas
+Caliper LifeSciences
+dox-treated / untreated ratios
+deionized water
+reduced antibiotic susceptibility
+lung and spleen
+faster degradation of the 5S rRNA transcript by the exosome
+Recoding
+6A 2 -1A 0
+Nanobodies
+gradient
+homogeneous mixing
+allows the user direct access to the KIH interactions
+matrix protein
+the names of the three nearest neighbours
+Metabolism of IFITM3 isoforms
+HeLa cells
+Virus diversity
+10
+FLuc ORF
+synthetic attenuated virus engineering
+SG and PB dynamics
+60%
+five
+phospholipase A2 motifs
+HEK-293T cells
+Fold change in expression
+S eq
+limited access to healthcare
+Cronbach's alpha coefficients
+Propofol
+preparation studies
+cytopathic
+rapid virus clearance from the respiratory tract
+Cyclovirus
+three independent experiments
+Section B5
+nuclear proteins
+M2e-specific serum IgG response
+oral fluid
+similar
+calcium-dependent
+circular plasmid DNA molecules that encode the vaccinating antigens
+lesions
+toxicity
+MHV-3 infection
+different residue positions
+Zinc supplementation
+IgA Á/ICs
+the size of the library was very small
+foreign proteins
+Urethane
+three
+algorithms
+Proline
+Prodromal, asymptomatic and afebrile infections
+Dengue
+33 years
+SSMD
+ventilatory
+68
+20%
+resolvins, protectins and maresins
+inhibitory
+Zoetis
+close to 20
+30,000
+one part in 10 5
+GAPDH and PP2A
+inter-sectoral networks
+influenza infection history
+α S,i and α V,i
+prevention of RSV infections in neonates and children
+Purified ATII cells
+Macrophages and neutrophils
+several hundred
+HSV-1
+PS 3 and 4
+cohort differences
+four
+regulates the sensitivity of the small intestine to radiation injury
+intermediate quality simulated draft
+HT29 cells
+clinical and technical development
+serum protein, albumin, and glucose levels
+template-based designing
+Three
+dominant and over-dominant model
+27%
+307
+robust exon 45 skipping
+Human cytomegalovirus
+Abcam
+Hematological, liver and renal function
+22-45%
+1997
+antiviral state
+virus receptor types
+Vimentin
+Four
+Agroinfiltration
+March 15, 2020
+1986
+norepinephrine
+URI
+1,485
+the percentage of inhibition
+70%
+19
+host cell helicases
+six
+suppressed
+coagulation tests
+cc-by
+400 μL
+a chart
+Yellow, Orange or Red
+ten
+intracellular tau aggregation
+12
+GGC
+automated quantification of immunofluorescence images
+5.5%
+Simplified Acute Physiologic Score II
+ΔG 1
+5 -CUGCAG-3
+48 hpi
+FXYD proteins
+oral and nasal mucosa
+36%
+Five
+CHIKV
+Ferroptotic
+95%
+8-weeks
+PfRh5
+DNA vaccine delivery method
+Macrophages and dendritic cells
+Sequences of E and E1 types
+Polyethylenimine
+PCR and sequencing analysis
+36
+NiV F or G
+1
+same ligand
+Modeling and simulation
+Giemsa
+SFCs
+50ng of RNA
+reliable proteome analyses for other cellular systems
+local network information
+Johns Hopkins institutional review board
+myelin sheath thickness
+Ralf Bartenschlager
+15.7%
+Vector Laboratories
+myricetin and rutin
+Image J
+15 per cent
+replication
+Liver
+suicide
+three
+clinicians
+peripheral blood mononuclear cells
+natural killer cells
+RT-qPCR analysis
+Albumin
+2,673,768 kb
+over $100,000
+Mersana
+strong assumptions of conditional independence between variables and the need of choosing prior distributions
+one
+2-5 days
+GTPase Atlastin
+HGF
+a group of molecules that recognize the molecular patterns of DAMPs
+Absence of microglia
+Resilience
+gender equality issues
+programmed À1 frameshifting
+intoxicate the host cell
+70%
+diluted cDNA
+Unconjugated Stat3 siRNA
+APOA2
+an appropriate animal model
+liver biopsy
+Glc 3 Man 9 GlcNac 2
+t-distributed stochastic neighbour embedding
+1:1000
+alcoholic liver disease, hepatitis B-induced fibrosis or HCC
+planar
+roughly the same
+Sanger sequencing of both 5 and 3 ends
+Storage samples of peripheral blood mononuclear cells and serum
+six
+Creative Commons Attribution License
+immunofluorescent
+1.35%
+25%
+residues 517-525
+an alternative approach that exclusively involved local personnel
+67%
+Withdrawal of care
+threshold
+early assessment of the relative contributions of local transmission versus case importation
+target-decoy strategy
+Heparanase
+co-morbidity
+Protonation state of H59
+indoors
+colistin ARB
+polymyxin B
+August
+sepsis
+Dr. Deckmyn
+Within-sample diversity
+488
+mycoplasmas and infectious bronchitis virus
+S ijk
+focus
+slightly reduced performance
+TRIzol1 Reagent
+2 mg of RNA
+YALL GPC
+icosahedral
+72 hours
+contusion and compression simultaneously both dorsally and ventrally
+70 %
+244
+supernatants
+Attenuation mechanism
+multinational corporation
+Hoppenheim Fund
+56.4 %
+complex
+5
+Sputum neutrophils
+single-specialty
+Tetherin
+protected mice against lethal influenza virus challenges
+urine, pleural and lumbar cultures
+p53
+the spring wave
+␣2,3-linked terminal SA
+electronic screening
+plasmid copy number
+MAVS
+influenza infection
+t½S/I
+viral titers
+800 seconds
+Amino Allyl MessageAmp II aRNA Amplification Kit
+proinflammatory
+disease spread
+estimation accuracy
+a vision, a plan and a set of strategies
+Town Cats and Palo Alto Humane Society
+simultaneous nearest neighbors
+cytosolic viral RNA sensors
+2-8 mg per mL
+occupational health physician
+Ebola survivors and EVD family members
+CD8 T cells
+Three weeks
+i21
+0.66
+seven
+to prevent cellular Trp production
+18
+35
+A single non-targeting siRNA
+Generalized Born/Surface Area implicit solvent model
+higher dynamic driving pressure
+simulations of the current outbreak
+nineteen
+214
+454
+tomato plant
+99 %
+152 mg testosterone
+leaving the cohort aspect ongoing
+High copy number amplifications in bacterial hosts
+Cri du Chat syndrome
+a reservoir of microorganisms
+spontaneous preterm delivery and early cesarean sections for deteriorating medical condition
+Boix
+assay
+Written informed consent
+acute and chronic GVHD
+2009
+Schematic
+mild, moderate or severe
+9.1%
+the size of each module
+further GBM tumor characterization
+12 hours
+Alveolar epithelial cells
+real time epidemic control
+Bland-Altman plot
+CD8 ϩ T cells
+55
+ZIKV-infected lumbosacral spinal motor neurons
+2fold
+K. pneumoniae isolates
+CCR5
+800
+BALF from ARDS patients
+À7.0 kcal/mol
+Merck Millipore
+P2
+100 million
+age group and HIV status
+the interplay between virus and host
+α
+v
+75
+Renal replacement therapy
+six
+biphasic
+nitrite levels in blood
+RNA replication
+twice per day
+insufficient DLCO
+21
+transmission divergence
+gut associated lymphatic tissue
+r A m
+four
+570,563
+2.0 kb
+four
+Over 70%
+interstitial motility
+goblet cells
+GST-NS1
+Three
+American robins
+97%
+Comparison of the protection patterns between wild-type and mutant ribosomes
+to report the amount of RCA product fluorescently
+ONX-0914
+modifications at the YxxxK motif
+2%
+413 flocks
+RNAHybrid
+alternative approaches
+a general set of mechanisms by which acetylation can regulate protein activity
+MIP-1β
+Vaccination
+proper Gag maturation
+pathological changes observed in liver
+10.3390/v10040211
+eight
+Subcellular Protein Fractionation Kit for Cultured Cells
+Aciclovir
+t R
+five
+80-90%
+PIWIL1, Ascorbic Acid and MTOR
+host mRNA synthesis machinery
+less than 50%
+specific investigations
+door-to-door notifications, text messages, and telephone notifications
+49%
+phosphorylation of this domain at Y88
+Behavioural changes
+5700 to 13000
+GAPDH mRNA
+heme-oxygenases
+B. mayotimonensis
+MS, MC, and AG
+EBOV GP
+Bio-Plex Pro™ Mouse Cytokine 23-plex Assay
+2.1 and 5.1 mg Kg −1
+throughput
+2.35-fold-higher
+Motif C
+energy expenditure
+coaxial stacking and parallel stem interactions
+crisis clients' permission
+biospecimens
+glucose substitution
+315 nm
+10 dpi
+binary images
+GLA-SE
+parental consent
+General Purification Procedure
+T min
+BioProjects
+the degree of a node
+40 min
+data submitted directly to GenBank
+outbreak development in West Africa
+NF-kB-dependent
+IgG PN-SIA49
+luminescent
+Serum immunoglobulins G fraction
+T cells
+clathrin-dependent endocytosis
+genotoxic
+internationally recognized human rights
+deep brown
+blood agar plates
+pH
+the region from −230 nt to 699 nt
+EU-RMP
+120 mcg
+grid
+41.1 new cases/100,000 inhabitants/year
+Twenty-seven
+172
+chromatin looping
+Ms Martin-Granel
+A3082-01
+lower levels of clustering
+Extravascular lung water content
+30%
+immune system disorders
+mannose binding lectin
+tBLASTx algorithm
+deadenylation
+6.6 ± 0.6 dpi
+Virus stocks
+different subtypes profile
+Escherichia vulneris
+Illumina short reads
+Apical ENaC
+25-30%
+1.0 × 10 1 copies/reaction
+θ H and θ F
+hypertension, asthma, or chronic obstructive pulmonary disease
+H1 and H3 subtypes
+the knob residue
+the algorithm
+The spatial correlogram
+WSN WT
+to avoid negative hemodynamic effects
+Immunoperoxidase staining
+SIINFEKL Ova-peptide
+FFA
+3%
+9,400
+eCLIP
+reference protein-protein interaction network
+HBsAg VLPs
+severe septic shock
+10 mL
+neuroinflammation
+Royal Society
+68 weeks
+single immunization
+alanine transaminase
+490
+individual clones
+Qiagen RNeasy Mini Kit
+genome wide mapping association studies
+two
+clustering and scatter/group plot analyses
+colony forming units
+being moral and behaving morally
+biological sequences
+age, sex and species
+chemical antibodies
+zoonotic
+6.1%
+biological olfactory system
+3,3-diaminobenzidine
+enzyme immunoassay
+2005
+7
+compartmental models
+Sera
+Three
+Quantity One
+ubiquitinated
+ten
+59%
+CXCL12
+90 to 120 min
+SWOT
+48.7%
+propagation patterns
+membrane tropism and solubility
+positive end expiratory pressure
+positive
+obsolete
+60%
+M. tuberculosis
+SPSS version 23
+R&D systems
+optimizing the MCC
+up to three
+Signal transduction
+Local and global outbreak dynamics models
+RNase A
+macrophage TNF production
+cell-mediated immune responses
+RT-PCR
+SD
+RT-PCR
+10
+cytosolic receptor PGRP-LE
+significant decrease of anti-HIV-1 activity
+viral
+asthma, pulmonary fibrosis, and chronic bronchitis
+seven
+D
+influenza vaccines
+> 60 ml/min
+TLR4
+Exposure to index case-patients
+PRISM 5.0
+multiorgan and multisystem
+60% to 70%
+a meaningful reduction in global mortality
+The percentage of cells infected with Dengue
+2014
+NF-κB
+more references
+disease severity
+208
+multiple mechanisms
+virus replication
+Hsp70
+microglial responses to local signals
+2014-08-07
+hypochlorous acid
+Endoglycosidases F1, F2, and F3
+Quercetin and kaempherol
+microbiological and epidemiological data
+GeneSpring software and GeneSpring default normalization
+1 day
+gain-in-function
+no cytotoxicity
+Pearson's χ test
+Interpretive memoranda
+three
+12-18%
+New Cooperative Medical Scheme
+10
+MS-based proteomics
+Cys783-His869
+aggregation of the F protein-bound BLPs
+cholesterol and sphingolipids
+plasma concentrations
+durable DENV2 neutralizing antibodies
+plasma glucagon levels
+various genes
+a natural barrier for metal ions
+nucleocapsid protein
+Four
+3.3160.33 cm
+10%
+R A 0 and R B 0
+HBV Pol
+-1 PRF
+KEM1 deletion
+malaria
+surface plasmon resonance experiment
+D AS and R SA
+Plasmodium falciparum
+Poly I : C
+environmental
+13
+alterations
+IC2
+outcome evaluation
+12S particles
+The monitors
+CD4 + or CD8 + T cells
+48 hours
+specific gene signatures
+60 to 400
+facilitates Dicer degradation
+local information about accessibility to health care
+intermediates
+Osterhaus
+HTS settings
+dissociation temperature
+a presumed infectious source
+World Health Organization
+60-69 g/l
+10
+Gal4-based Y2H
+reemerge from viral obscurity to spread pandemically
+changes in viral gene expression
+CD3+ and CD20+
+30-day spaceflight
+health and disease
+small mammals, marsupials, and birds
+flow head
+Size exclusion chromatography
+influenza replication
+exon 7 of the STAMBP gene
+Unaided cellular uptake of PMO
+ARDS
+recombinant RNAs
+PBC
+DCs
+neurological outcomes
+the neck region
+56%
+16s and COI
+Person-to-person
+spectrophotometrically
+CSFV
+collagen and elastin fibers
+multi-organism membrane fusion
+five
+over 10,000
+endosomal compartments
+human diseases and plant pathology
+visual inspection
+3.3 ± 1.3 months
+Forty-nine
+shortcomings of the methods or technology involved with screening
+E1
+anti-cancer effect
+ABC
+80%
+35 mL
+Time series comparison
+live poultry
+novel gene targets
+Pro-Ser-Pro
+Wild-type and Bcl-2 transgenic FVB mice
+MMDS
+genomic tiling array and exon-exon junction array
+caspase-11-dependent
+Infectious virus
+10 min
+q k i k
+Confocal
+Bar graph
+low infectivity
+cDNAs from healthy NPR and PR controls
+BVDV infection
+over-dispersion
+syn
+log-rank test
+<0.1%
+36
+stronger inflammatory responses
+65
+SM934
+genome-integrated sequences of viral origin
+systemic administration of 3-PPMO
+238
+herpes simplex
+restoration of effective immune status
+death
+15
+MAP p = 0.034
+events that are highly localized in time and space
+2 6
+live model viruses
+1 hour
+Monika Slominska-Wojewodzka
+5'
+50%
+advantageous and potentially detrimental
+2 µg/mL
+genomes
+Vietnam
+antigenomes
+Cellular mitogen Phytohaemagglutinin stimulation
+Antibacterial activity
+R 0
+type 2a
+innate and adaptive immunity
+WDR5
+unclear
+filamentous
+25
+seasonal phylogenetic clusters
+low methodological quality and selective publication of positive results
+Lower respiratory tract infections
+cytopathic effect
+Psychological support
+LAL evaluation
+Data
+7
+98%
+detergent separation
+databases of small molecules
+P,0.03
+liver biopsies
+trypsin treatment
+RGNNV
+25.0 mL
+changes in M
+a wide variety of matrices
+acts in repression at the rDNA promoter level
+0.26
+immune responses
+logistic model
+crypts
+joint pain
+10 or 100 IU/ml IFN-α
+15 min
+acute lung edema
+72 h
+one year
+major and minor
+OptiMEM
+SLU
+24
+immune cells
+3.7-to 5.2-fold
+Livestock production
+EBC
+symmetric cell division
+P3
+L. iners
+GraphPad Prism v. 6.04 graphing software
+5.5%
+VRE contamination
+Bats
+contigs
+a definitive pathogen
+cc-by
+purification of nucleic acid analytes from clinical specimens
+MA Ab test
+control measures
+Apoptosis
+SHH
+10 to 20%
+increases morbidity and mortality
+Interrater agreement
+priming of viral mRNA synthesis
+evolutionarily diverse organisms
+influenza virus activation
+limited safety information
+1 h
+C. albicans CFU
+elderly and immunocompromised patients
+sepherdin
+33
+199
+98%
+400-to 520-nm
+Sf9 cells
+urbanisation and largescale crowding
+Malaria, Typhoid, Traveler's diarrhea, Yellow fever
+eIF4G-PABP interaction
+Splenocytes
+EAE
+three
+1918
+1%
+poly polymerase 1
+black
+Bioinformatic tools
+mice
+GPs
+chicken anemia virus
+hydrophobic
+indigenous or imported
+adulthood
+Chest radiography
+seven
+results
+The PI or delegated local investigator
+Göttingen, Germany
+lower reporting rates and higher quantiles
+18
+robust memory CD4 T cell responses
+vital for their survival
+SPDEF
+phosphor-Cdc2
+abnormal increase of white blood cells
+viral nucleic acid
+Restricted maximum likelihood estimation
+Apoptosis
+two hours
+good leadership involves attention to the ethical aspects of priority setting
+controlling this variability
+r q,i
+37uC
+chronic rheumatism
+8 days
+four
+Kenya
+0.02 M EDTA
+CLS scores
+80 ± 9%
+poor factorial validity
+stochastic
+The controls
+increased reactivity in multiple proteins
+10~12 weeks
+Institutional Animal Care and Use Committee
+Olympus BX-51
+testkits
+inspiratory
+inhibits the replication of different families of DNA viruses
+mouse monoclonal antibody isotyping kit
+Waldeyer's tonsillar ring
+1 mM
+dashes
+VP1
+woodchuck model
+1.73
+exostosins
+mouse lung macrophages and dendritic cells
+Genes upregulated by EBV compared with resting B cells
+Ub-AMC
+Recombination
+conservation and information content
+glutinoic acid dilactone
+millions
+Total RNA
+TORC1
+2,500
+glycerol
+71,865
+Confocal
+4 mg/ ml OVA
+16
+csv
+hematoxylin and eosin
+RC i
+Mg 2+
+Cyclosporin A
+regions within countries
+The Ross-MacDonald model
+circRNAs with internal ribosome entry sites
+Normalizing by the mean of the row
+intradermal, subcutaneous, and intranasal injection
+Sugammadex
+50~100 mg ml −1
+STE12-bound promoters
+pIFN-γ cDNA
+Charcoal-burning poisoning
+three
+over $20 M
+non-regenerative anemia
+Panels A and B of figure 8
+Mouse Mesenchymal Stem Cell Functional Identification Kit
+contacts
+anti-mite and antimicrobial treatments
+RV
+a limiting amount of polymerase subunits
+trans-well assay
+embryonated chicken eggs
+subclinical persistent in utero infection
+ExiPrep Viral RNA Kit
+self-reported symptoms
+A 4ϫ objective
+to describe and calculate the cost of an already implemented behavior change communication intervention
+Mac2 positive cells
+cGAMP and IFI16
+9
+Lung sections
+12
+oligonucleotide names
+hyperoxia and endotoxemia
+120 h incubation
+volume constraints
+overexpression of EGR1
+systemic delivery to the central nervous system
+cytoplasmic RNA-and DNA-sensing receptors
+3.7%
+Cytolysis
+baicalin and wogonin
+nickel-chelated
+brucellosis
+H5N1 replication
+host cell biology
+two
+Blomberg's K-values
+four
+Eight
+zero
+nuclear localization sequences
+Laziosanità
+Gapminder
+cytopathic effects
+symptomatic cases suspected of having EV-A71 infection
+nuclei
+cell survival, death and metabolism
+ELISPOTassay
+further research
+greater endorsement of a range of real-world conspiracy theories
+Duke University Medical Center
+countries with low CL
+10-20%
+cysteine dyad residue
+plaque reduction inhibition assay
+lymphocytes and fibroblasts
+intuitiveness
+deep evolutionary history
+10 2 CFU/mL
+300 mm
+20 h
+Increasing the number of communities
+The AUC
+nucleophilic water
+the probability of each state
+single position mutations
+vRNA replication of DENV2
+MS/ MS fragmentation
+3 days
+transcription initiation complex
+decreased HIV-1 receptor expression and stabilization of the Th1 profile
+Nikon SMZ1500 microscope
+983 bp products
+master-slave regulatory units
+TranswellH chambers
+oxidative damage
+Influenza A
+training schools
+4 weeks
+identifi cation of the precipitating factor and their prompt treatment
+LQTS
+Secondary and tertiary base pairs
+2 hours
+an appropriate in-frame initiation codon
+2
+control group that was treated using only a roaster machine
+λ max
+Ae. albopitcus
+structure-based
+climate change-related impacts
+The Database for Annotation, Visualization and Integrated Discovery version 6.8
+Recursive PCR
+primer mismatches
+RNA silencing
+a day-by-day tick box framework
+~15%
+p-STAT5
+GL7
+Anti-b-actin
+4421
+residential buildings
+associate the resistance genes conclusively with their respective organism
+IL-12p40
+c-secretase
+Vpu initiation codon
+tryptophan
+the successful isolation of the desired antibodies
+an internal control
+promoter recognition and integrate responsiveness to the external stimulus tetracycline
+ALK
+GraphPad Prism
+Dysbiosis
+1 dpi and 6 dpi
+RNase T1 refolding
+conformational
+amplicons
+4 hours
+increased severity of colitis
+Antibody avidity
+building trust or developing transparent legal agreements
+5-ethynyl uridine
+Global health studies
+metabolic
+Six
+rationales
+3D
+Arenavirus GPs
+baseline and emergent resistance variants
+pulmonary pathology
+IL-1β and IL-6
+DURC
+DNeasy blood and tissue kit
+TNA
+Weybridge, UK
+Beclin-1
+The introduction
+nonsevere aplastic anemia
+discharge diagnostic codes
+26%
+describing and representing models common to a repository
+94%
+eight
+50 pfu/mL
+tumors
+CD4 + T cells
+Csf2
+average life span
+PRAMS
+Labrador Retriever
+Three
+induced antibody titer
+HIV-1 p24 CA Antigen Capture Assay Kit
+viral RNA
+prior genetic knowledge
+122.8%
+Healthcare workers
+higher
+unknowns
+oxygenation parameter
+MEK/Erk
+PEIs
+2-3 fold
+20%
+simulations with no demographic turnover and low migration rates
+Leveraging existing resources while reinforcing networks and maintaining relationships
+an up-to-date guideline
+contagious adults
+0.5%
+7.9%
+maintenance of function
+Mitochondrial morphology and virion
+pig density; climate; and land cover
+25%
+virulent
+characteristics of natural pathogens
+Signal amplification
+p65-EGFP fusion expression plasmid
+protein composition analysis
+mouse ISG15-PA
+disease surveillance reports
+11 months
+CC001
+organ-specific autoimmune disease
+structured crowding
+65 of 67
+two
+S306, K307, T330 or T332
+Illumina TruSeq
+Tissues
+cleaves
+High Pure PCR Purification Kit
+1.1 to 1.5 bits
+>3,000
+OP differentiation into mature oligodendrocytes
+Antigen-expression
+Advanced respiratory monitoring
+mild ulcer and minimum inflammation
+VQ29 would not remain significant
+potential risk
+DNA sequencing
+25 days
+Meier Kaplan
+~19%
+22
+Varian Cary Eclipse
+PCR inhibitors
+general linear models
+122.2
+bmercaptoethanol
+USP18-deficient mouse embryonic fibroblasts
+one
+Antigenic reactivity
+post-transcriptional
+EDTA
+global trade and travel
+estimated sample size requirements
+increased
+enemy release
+75 amino acids
+shielding of the free Cys163 in the N domain
+southeastern China
+RSV
+immunohistochemical
+U0126 or NH 4 Cl
+stringently controlled
+10 days
+B cell
+Extremes of age
+dramatically decreased
+to compare resource capacities across geographic areas and resource types
+The eel virus European X
+three
+10%
+ADAR
+151
+h, k and l
+1 January 1997 to 30 November, 2016
+2%
+bi-ventricular pacemaker
+1.5-2 h
+two
+90%
+sZ0.821
+handles
+homomeric channels
+data output
+The RdRp domain
+tDC accumulation
+biphasic
+28%
+neutralize vacuolation induction
+z
+detecting microorganisms in human clinical samples and infectious viruses in numerous animal species
+N-linked glycan sites
+Table 2
+by bearing either fruits or flowers
+intravenous administration of zanamivir
+sperm
+9,300 km
+oedema, tissue injury and inflammation
+2-to 7-fold
+42.5%
+physiological and pathological
+MiniBEST Universal RNA Extraction Kit
+confidentiality of the donor's identity
+attenuates LPS-induced endothelial barrier dysfunction in vivo
+combining molecular genetic and epidemiological data
+four
+Gaussian
+72 h
+deteriorated
+3-5 days
+Beijing, Tibet, Shanghai, Tianjin, and Hainan
+leukocytes and mast cells
+South Korea
+The first tier
+Different procedures
+reduced hyperoxiainduced DNA damage
+1:1,213
+Ubiquitination
+5%
+Disulfide bonds
+Forty
+community structures and host and vector movement
+the emergence of new epidemic strains
+high mannose N-glycans
+Thai Ministry of Public Health
+Group B
+Optimization
+sadness, fear, surprise and happiness
+those traveling for leisure or those visiting friends and relatives
+2M H 2 SO 4
+Total V T
+8 weeks
+absence of negatively charged E271
+40%
+resazurin
+hospitalacquired
+cells
+age
+1 mg/ml
+Ungulates, carnivores, and rodents
+isolation specificity filter
+Positron emission tomography
+20
+eighteen
+High-energy collision activated dissociation -MS/MS
+Clinical manifestations of hepatomegaly
+70%
+Polymorphisms with the lowest P values
+excess serotonergic agonism
+several functional regions
+RevertAid First Strand cDNA Synthesis Kit
+their role and relevant laws and regulations
+eIF5B
+human-wildlife contact
+Dualluciferase assay system
+DAMPs
+migration fractions
+14
+measures of hypothesised variables thought to influence behaviour
+geographic boundaries
+a spring
+Ang-II-converting activity
+GraphPad Prism
+experimentally determined
+F GEV
+Dr. Siba Samal
+ZBDM-1
+dyspnea
+cytosine arabinoside
+B16 melanoma
+RT and p24
+phylogenetically
+epithelial cells
+pEF-GFP vector group
+codon substitution
+rabbit anti-HBV core antigen polyclonal antibody
+Fluorescent
+Zymosan
+Ang formation from Ang II
+surveillance
+mild
+a population health approach
+activation and suppression of host immune response
+1:200
+confidentiality
+aggregation of the intrinsically disordered protein, tau
+phylogenetic
+viral transmission and replication
+fluorescent marker and the ATP assay
+MDCK cells
+fever
+Canine calicivirus
+colinearity
+co-pathogenesis hypothesis
+Precise comparison of viral population composition
+environmental microbes
+Average percent transmittance
+10 2 copies
+500 mmHg
+Ub recognition and catalysis
+miRNA profiling
+38 years
+TCID50 assay
+three
+vaccines and therapeutic agents
+mouse-models
+ninety-two
+Duplicate reports
+15.2 kb
+DCs
+independent
+5572
+no shedding
+2.1%
+Mild exposure
+6 months
+Heilongjiang-SYXK-2006-032
+Tat peptide
+necrotic cells
+450
+Three
+very limited change in speed
+HaCaT cells
+almost two decades
+Modification indices
+Evolutionary models that incorporate protein structural domains
+antiviral CD8 T cell responses
+data for a specific sister clade comparison
+The presence of a foreign material
+CD4, and class I and II MHC molecules
+extremely violent offenders
+1.51 minutes
+ricin intoxication
+491
+10
+the maximum case number over a single phase of outbreak
+1.6 cmH 2 O
+cleavage of their interchain disulfide bond
+IL-18 and IL-1β
+enhanced SG formation
+clinal and seasonal
+224
+Stockholm, Sweden
+Mutagenesis by overlap extension PCR
+Processing Bodies
+MP-12 and NSs
+histidine moieties
+Table S2
+over 300
+serum samples
+cc-by
+4.3 ± 0.2 m
+ACE2
+PACSCAN
+rs12979860 5
+Baltimore Group VI and VII
+limited availability of antiviral agents
+genus Nairovirus
+10
+differences in gene transcription, genome replication and/or viral protein synthesis
+infection with prokaryotic pathogens
+Geneart
+1984
+30-50%
+cytokine profiles
+Pithovirus sibericum
+Developers B and D
+Ammonium sulfate
+seven
+severe capillary leakage syndrome
+Supernatants
+controls
+reduced FRC
+conserved
+guinea pigs
+High-dose systemic corticosteroids
+iGPCR-Drug
+Four hundred
+PCR and Sanger sequencing
+target selection
+remain at risk
+Urine peptide diagnostic and prognostic biomarkers
+by allocation of an estimated % surface involved
+infection
+gentamicin
+clumps of cellular debris
+Endocytic uptake of CPPs and their cargo
+TSEN54
+Agencourt AMPure XP beads
+minigenome replication
+PCNA and pUL44
+jl S
+outside the room
+all over the tumor sections
+two
+117
+seven
+71%
+Mixed effect models
+The extent of RNA degradation
+95% confidence intervals for bias
+bedside examination
+variance of dinucleotide frequencies
+the SN
+male immunity
+tuberculosis and meningococcal disease
+IL10 2592
+selection bias
+March 11, 2020
+fusion-defective
+STAT3-mediated
+46
+brown
+MPP software
+meropenem
+serum allergenspecific IgE antibodies
+4 to 5
+tumorderived connective tissue growth factors and SDF-1
+rapid protection against HPAI virus infection
+experimental models
+hit-and-run therapeutic application
+infection of about half a log
+blood capillaries
+adenosine-uridine -rich element RNA binding factor 1
+CPS misprocessing
+Free State Province
+L3 Thr 94 germline residue
+1889
+cell death
+M2
+Axl and TIM-1
+E protein-membrane interaction
+0.40
+MR volume
+pandemic-H1N1-09 influenza infection
+acute respiratory distress syndrome
+pyridylimidazopyridine derivatives
+de novo short RNA primers
+60 L/min
+increased inflammation and mortality
+Cα-Cβ-side chain model
+antigen-specific
+GraphPad Prism
+four
+seventh inpatient building
+AdoHcy hydrolase
+the Berlin definition
+3,3-diaminobenzidine
+N-glycosylation
+Tucson and New York
+Every row value count from the matrix G
+circRNAs synthesis
+1.49 mg/dl
+mean ± standard deviation
+specificity of these pathways to nonviral exacerbations
+NP1
+Chi-square or Fisher's exact test
+Hsp72
+Glycyrrhizin
+Nineteen
+trans-Golgi
+factors
+five
+mice
+3.6 • C
+BASV
+Seven days
+non-parametric testing
+Variant frequencies
+sub-Saharan Africa
+10%
+T ype I and III
+inconsistent results
+Exacerbations
+Ac-DEVD-AMC
+Illumina
+IL-6
+a single chromosome
+direct DNA binding of LRF
+monkeys
+clinical
+ordinal scoring
+48h
+less than 10 %
+risk of infection
+disease signal overlap
+neglecting infections with mal-adapted strains
+Neural precursor cells
+OTR and TS
+5.64
+Nup98
+apoptosis
+812.25 mg/m 2
+PF573228
+SEOV
+type-I and II
+citation exporter
+safety and others equity
+Twenty-one
+cell type-dependent
+89.6 Env
+made a mistake
+99%
+PEG8000
+5% to 8%
+Desmosterol
+blood pressure, cortisol, cholesterol, and cytokines
+chest
+0 and 1
+excellent linear agreement
+extensive sequence diversity among viruses in the same family
+FIGURE 1
+splicing
+intraperitoneal inoculation
+None
+a
+isometric polyhedral
+separately
+type 1
+X-ray diffraction data
+Quantitative real-time PCR
+High throughput screening
+antiviral activity
+when treated with methotrexate
+poor immune responses
+ambisense
+CARD-9
+39,756
+tumor-confining
+Angiotensin II
+Local Ethical Committee
+MUSCLE
+mixing patterns
+a minority
+75%
+export blockage
+95%
+Expression of the human CEACAM1 transgene
+All authors
+DVGs
+shorter turnovers
+1000 bp
+Metal toxicity
+TGEV
+2 fold
+interact with FKBP11 in the osteoblast cells
+bacteremia and urinary tract infections
+50%
+University of Pennsylvania School of Veterinary Medicine
+polyclonal immune stimulation
+receptor binding site
+highly pathogenic
+informatics
+PCNA ubiquitination
+Release of AMPs
+standard deviation
+Gel electrophoresis
+surgical fixation of their femur fracture
+eHAV
+nucleocapsid
+influenza
+cattle and monkeys
+synthetic
+multiple realizations
+five fold
+porcine
+0.9%
+two
+30
+severe acute respiratory syndrome
+C-type
+Plasma cells
+optical particle counter
+The Global
+Bayesian statistical frameworks
+South Africa
+Nonalcoholic steatohepatitis
+patients admitted to the critical care unit
+Future studies
+computed tomography
+inhibition of cell proliferation and angiogenesis
+Proteolytic cleavage
+Activated CD4+ T cells
+microglial cells
+tissue sodium concentration MRI
+Arab countries
+10%
+EVD
+Dr. Susan Weiss
+time from infection to symptom onset
+Total RNA
+The inset
+Cost effectiveness
+RAB5-DN
+the disease
+group 1 viruses
+the number of those vaccinated
+avian strains
+500
+FACSCalibur
+WebLogo
+air-supply/air-exhaust systems
+DestiNA Genomica SL
+excellent communications and coordination mechanisms
+PFGE
+KEGG pathway identifiers
+Pediatric Logistic Organ Dysfunction 2
+0 to infinity
+103-3308 ng/mL
+counter-selection
+89%
+variola
+VWF antigen concentration
+the predicted epitope
+13
+0.2 %
+funerals and transmission to health workers
+deleterious
+Five-to two-hundred microliters of clinical sample
+miosis, dim vision, headache, and eye pain
+a major redistribution
+complement activation
+AKC lysis buffer
+Human rhinovirus
+endosomal TLRs and most NALPs
+RR
+NSs proteins
+5 minutes
+Coomassie blue dye
+Amph-FL
+Secretion of IFN-γ by spleen cells
+1 litre of ethanol
+economic development
+four
+talocrural joints
+IL-18
+À7.4 kcal/mol
+single-stranded RNA
+Annexin A3
+SP-A
+Papua New Guinea
+5166
+activate ERK signaling
+17.8%
+Sample size
+class I, II, and III
+PXD012785
+18 to 20 g
+Figure 1
+similar clinical disease outcomes
+PCV2
+describing the level of knowledge and practice of nurses in pain management
+informal behavioural changes
+Build37 coordinates
+stem-loops
+three
+1.8 million
+ensure there are high quality reviews in all public health topic areas
+RIG-I, MDA5 and LGP2
+autophagy-associated proteins
+lytic transcripts
+all mothers
+5%
+NF-κB and MAPKinase activation
+a-2,6-linked sialic acid receptor
+L. lactis
+substantially change the pandemic wave
+SHP-2
+10 h
+10 −100
+different tissues of healthy juvenile orange-spotted grouper
+WGASA
+12
+IL-17
+NSs
+topical corticosteroids
+Y549H
+autophagy inhibitors
+DNA microarray analysis
+1.5
+compound and unitary
+the completion of Stanford IRB Serious Adverse Event case report forms
+endoplasmic reticulum
+the ER
+Monitoring P L through esophageal pressure assessment
+bacterial artificial chromosome
+Adenoviruses
+serve as the receptor for virus attachment and infection of cells
+ACE gene polymorphism
+Cambodia and China
+influenza virus replication
+Ded1p preparation
+629
+300 × g
+Transcytosis
+mouse
+Steered Molecular Dynamics
+x
+pharmacological arrest of the osteoclast
+ORs
+IL-12p35
+emergency transportation
+energy level of myocardial cells
+Caregiving in the home
+Emergency Response Coalition
+protecting women of childbearing age against rubella
+by adding 500 µl of 80% cold ethanol
+pilin domain
+four
+48.3%
+Blood samples
+age, sex, and weight
+Susceptibility and Worry
+translation initiation
+6 months
+war and conflict
+superspreading
+viral loads
+infection with A virus
+their structure
+gel filtration
+posting to Ebola treatment centres
+amino acid sequences of the M2 and NA proteins
+Disease/Phenotype web-PAGE
+P58 IPK
+the nucleus
+polyfunctional
+1000
+CTI
+Quantified GlyGly sites and the results of the t tests
+April 18
+Highly sensitive
+3%
+HIV
+influenza A viruses
+His-RIG-I
+reference materials
+swine flu
+common haplotypes on IA risk
+sequence dependent
+E1
+Biomolecules
+NP-31 and NP-450
+Intensity
+Fixable Aqua Dead Cell Stain kit
+alginate nanocarriers
+EPF supplementation
+119 000 to 206, 000
+Hoechst 33342 nucleic acid stain
+PRC1 and PRC2
+Germany
+success
+Fifteen
+27
+intergenic
+EGFR tyrosine kinase activity
+Spectral data
+13
+Nosocomial and imported infections
+6
+six
+12.55 ng/mL
+1 μg/mL
+78.70%
+Lys57 and others not yet identified
+male
+RSPs
+long noncoding RNAs
+low redundancy of interactions found between these databases
+alpha1-antitrypsin
+Data
+A parallel treatment with L-fucose
+Changing G4-C16 into A-U
+six months
+gamma
+enhanced the stimulatory capacity
+a series of NSs mutants
+30 days to 3 months
+Z ika virus
+2004
+Morita−Baylis− Hillman reaction
+gene chip technique
+disaggregated viewership data
+IAVinduced IL-1β
+describing the magnitude and characteristics of vaccine-induced immunity
+CORDS
+R
+EA
+Fractions showing high absorption peaks at 280 nM
+NPD
+sECP level
+PB1-F2 and PA-X
+ROC curves
+Bio-Rad Trans-Blot Cell
+a strong shift
+to ensure the uniqueness of the sets
+key host-parasite roles
+deSolve
+Medical diagnosis of historical figures based on textual evidence and other artifacts
+neurons
+35
+22.2%
+Bioworks 3.3
+three
+Paracrine adhesion factors
+predict option
+Python
+apron and gloves
+400,000
+Up to 11
+InvivoGen
+Salmonella-associated gastroenteritis
+0.2 mM
+physicians, respiratory therapists, and critical care nurses
+Energy functions
+100%
+5 kHz
+FHV-1
+Ten
+Kaplan-Meier method
+Man9GlcNAc2 oligomannose-type glycans
+homotypic parallel 3-helix coiled-coil domains
+infection and incubation
+generalized additive models
+Depletion of intestinal commensals
+influenzarelated search queries
+declined dramatically
+50%
+sulphated L-iduronic acid
+lower respiratory tract infections
+measles
+CD8 + T cell-mediated selective pressure
+MinElute Gel Extraction Kit
+In-vitro RNA
+Six
+AIV exchange risks
+secretion of type I interferon proteins
+Bonferroni correction
+56%
+Higher absolute lymphocyte numbers
+elevated plasma ACE2 activity
+Fig 5E
+acetone extracts of two plants
+RSV
+DAVID 6.7 Functional Annotation Tool
+Cleavage
+commercial layer chickens
+five
+SOCS3, Irf1, and Interferon-gamma
+NCBI gene identifier number AY847351
+Endocrine glands
+Over 60 %
+4 to 80 • C
+lung neoplasia
+Gag-specific CD8 + cells
+mild perivascular mononuclear inflammatory infiltrate and moderate congestion
+shedding amounts
+growth factor receptor tyrosine kinases
+LASV/MOPV
+six
+photocatalytic TiO 2 NPs
+Modified live vaccines
+Recognition and Tolerance, Immune Response, and Killing and Memory
+96
+A human challenge model
+500 μL RIPA lysis buffer
+Basic chemical principles
+significant differences
+Shotgun approaches
+25
+Rab5a-Rac-VE-cadherin
+Recombinations and mutations
+Acute kidney injury
+1931
+hydrophobic
+DEC205, Cadm1, and surface Clec9A
+photoreceptor arrestin
+latent infections
+1000
+inhibition of amplification
+U
+new models
+innate immune response
+TLR4-MyD88-NF-κ B signaling
+Genetic analyses of variants found in clinical screenings
+94%
+Public trust and confidence
+selected tissues
+enabling DIVA approach for FMD
+Myxoviruses
+prophylaxis
+consistent information
+Five-micrometer
+ternary complex
+equation 12
+Membrane-bound PDI
+349
+Co-translational misfolding
+less than that added experimentally
+luciferase induction
+per capita income
+438
+2003
+none
+Russia
+multiples of the G1 mean length
+ZL and YJ
+ELISA-array assay
+R18 and DiOC
+A and U nucleotides
+four
+rapamycin
+94.2-94.8%
+4%
+GAE
+modulation of autophagy
+twenty-seven
+distantly related vertebrate hosts and invertebrate vectors
+human
+Twenty-four hours
+1990
+cancer vaccination
+mice
+pressure equalization tube
+Knockdown resistance
+E. coli
+JD and ES
+9.9E-05
+FRC INview TM
+natural habitats
+Lung cytokine
+100 μl of elution buffer
+reduced kinetic stability
+Focused-echocardiography
+reversion
+89
+Gr-1 + CD11 + b cells
+NeuNAc
+Tfh cells and Th17 cells
+Explicit solvent MD simulations of nucleic acids
+Tumor protein 53
+as the mean
+BSL-3 conditions
+Cyclins and cyclin-dependent kinases
+5.2 deaths/10 000 population
+SPSS 17.0
+study protocol
+stable temperatures
+SYBR
+one of the non-bridging oxygens
+Nuuk Declaration
+Hepatitis C
+TRIzol reagent
+bind Siglec-8-Fc
+gastrointestinal diseases
+9%
+LC3-II
+slightly reduced
+multiple biomarkers may be able to overcome the limitations of one or a few
+human naïve CD4 + T cells
+Axio Imager A2
+One hind leg
+Blood samples
+dysregulation of SPM pathways
+tandem MS
+More than 10%
+inflammatory networks
+Rabbit polyclonal antibody against E protein
+YN IBV
+therapeutic, diagnostic, or prophylactic
+bovine IgG
+GA
+The NIH Institutional Biosafety Committee
+clinical ILI consultation rates
+public health policy
+pg cortisol/mg hair
+1 month
+500 μL aliquot
+Thirty-four
+patient characteristics
+January 1997
+RSAD2
+a detection antibody
+60 minutes
+IgM serology
+6A n
+2 h
+co-purified NAs
+recombination events
+thermal
+256
+consideration of methods for rapidly recruiting and training "surge capacity" translators
+other flaviviruses
+NF-κB
+publicly available
+Access to health care
+Comparison of plasma cytokines and chemokines
+receptor-destroying enzyme
+transmission electron microscopy
+reproductive and somatic
+Endothelial progenitor cells
+Three
+cellular movement, developmental disorders, cell cycle, molecular transport, and cellular development
+EBOV
+8
+five
+matrix-assisted
+mediate some unknown functions
+influenza
+Transfection efficiency
+65 °C
+the slope of each growth curve
+adjuvants
+unpredictable
+increase the OCT4 mRNA levels
+Table 1
+transmembrane
+furin
+resistance to matrix inhibitory drugs
+30 min
+serotype replacement
+viral RNA
+Northern blot analysis
+7 days
+95%
+direct fusion and receptor-mediated endocytosis
+trkA and p75
+five
+base compositional constraints
+Influenza A virus and the bacterium Streptococcus pneumoniae
+fluorescent WGA-labelling
+Six
+50%
+genetic diversity
+IFNL4
+Site-heterogeneous
+Phi29
+5 mM DTT
+endogenous AKT1
+90d mortality
+to identify any sample differences
+One hundred and five
+ischemic
+Data-driven methods
+knowledge of population susceptibility
+polyclonal antibodies
+AgaR2-recognizable sites
+two
+protected mice from RSV infection
+the ER
+Generating and characterizing transgenic mice
+A/Shandong/01/2013
+mouse
+failure in the formation of functional tertiary structure of the triplex formation
+four
+experimental validation in biological system
+psychological predictors and outcomes of endorsing conspiracy theories
+TLR9
+genomes
+USUV
+genes
+type 1 and 2 interferons
+83%
+preference for one type of codon over another
+at least 12 weeks of treatment
+Successful experiences of preventive model
+Asia
+Peak demand for both outpatient and inpatient care
+two
+more infections in the acute phase
+high shear stress
+16
+N-terminal
+knowledge
+S598 or S598 Q600Y
+80%
+Numerous infectious pathogens
+The overall effect from meta-analysis
+z-scores
+one-dimensional SDS-PAGE
+fruit bats
+mitigation effectiveness
+severe PAP with continuous need of oxygen
+explicit consideration of multiple introductions
+adjuvant
+base triples
+Flow cytometric
+RMA standardized method
+Linear and K29-linked di-Ub
+metabolic pathways
+10
+once-weekly
+MICROBExpress TM Kit
+infectious agents
+nine
+The pharmacophore with van der Waals surface
+William Coley
+China
+unclear
+DNEV
+adjacency matrix output
+3 0 ends of at least some cleavage products
+4 weeks
+CX3CR1
+crowded tropical cities
+the standard viral genome
+65%
+glycans
+DMD patients
+The capsule
+biological
+difficult
+RdRps
+low basal levels of IFR
+cell death
+11
+1 week
+high levels of incorporation
+26%
+4%
+H7N9
+30 min
+NaCl reabsorption
+Autoclaved mycelia
+The CLDB
+subtle contacts
+an HIV test that was negative
+three
+1 to 37 cases per 1000 infantyears
+1
+comparative threshold cycle value method
+12% SDS-PAGE
+all three viruses
+generality
+BVDV-1c strains
+inflammatory
+765
+IL-6 and IL-8
+a lineage 5 isolate
+emerging infectious disease threats
+90%
+An edge
+Germany
+65%
+7%
+3 days
+PyVs
+Phenylalanine tRNA
+2 mL
+E39
+viral infection prevention strategies
+Lck
+66.1% and 75.0%
+47
+65-74
+tau pathology
+HBoV DNA load
+purified HA protein
+16.9%
+covalent binding at the surface of particles
+38
+Vital dyes
+the same set of K
+Bioanalyzer RNA 6000 nano reagent kit
+DNA vaccines expressing only HBsAg
+26.8 ± 8.8%
+Sheath tissue
+cytolytic activity
+agarose gel electrophoresis
+high viral titers
+MinStem and MinLoop
+antifungal
+normalised relative risk values R k at exact case locations
+alternative activation by MR antagonism
+6 weeks
+280uC
+physicians' oversights and absenteeism
+1 week of age
+CVTree3
+Plasma samples
+genome composition bias
+polymerization of tubulins to extraordinarily stable microtubules
+Plasmodiophora brassicae
+noninvasive and specific circulating markers of several cardiovascular diseases
+Clone 5
+low number of interactions or binding site residues involved
+18,139
+three
+blood flow
+DPC-333
+35
+absent ; mild ; moderate ; severe and very severe
+G 1
+accuracies
+0.56 and 0.57
+American Type Culture Collection
+Genomic DNA
+ferrets
+silencing of LC3
+T cell differentiation
+filamentous
+GSH
+Rt
+by plating and counting CFUs and fluorescent intensity
+Guinea, Liberia, and Sierra Leone
+10 mM BrdU
+IRT images of an animal's eye temperature
+endosomal acidification
+Vero
+biospecimen practices
+appropriate model viruses
+to identify pneumonia and influenza cases
+95%
+one week
+cc-by
+hyperpolarization
+hepatitis B
+extracellular matrix components
+10%
+monocytes or dendritic cells
+general effects of nutrition on infection outcomes
+nine
+23
+IL-17
+using 1 ll of neat extract and running 25 cycles
+over 40
+Interferon-inducible PKR
+phenotypic correlations between leukocyte subsets and acute phase proteins
+pre-existing impairments in lung function
+real-time PCR
+yield
+three
+guinea pigs
+demyelination
+solvent
+708
+120
+Illumina Hiseq 2000
+alcohols, aldehydes, iodine, phenols, and chlorine
+intratracheally delivered
+δ-Secretase
+pathological tests
+518-L-infected 293T cells
+the true value of the parameter
+cell-free supernatant
+ordinary differential equations
+cytosolic
+measurements made from different wells during an experiment on the same day
+NSP1 protein
+Non-parametric Mann-Whitney tests and one-way ANOVA
+statistical significance
+Outdoor climate
+blood-borne virus infections
+milder acute respiratory tract infections
+W371A mutation
+guaranteed health insurance, workers' compensation and disability insurance
+normalized 4-gram frequencies
+100%
+a mRNA that is directly transcribed from the genomic S segment
+psychological
+b
+BBB injury and leukocyte recruitment
+June 2023
+antiviral
+Plasmacytoid dendritic cells
+Four
+It would be too late
+6A 2 -1A 0
+Endoperitrophic face
+r I ~I=N
+dilution and connectivity
+HeLa cells
+2009
+eight weeks
+NSD6-30 and NSD56-80
+partial protection
+membrane sialic acid residues
+5-15%
+44
+winter
+The SRM atlas
+pCR8/Gateway workflow
+Eosinophils
+mental health intervention work
+autophagosome-like functions
+SNPs of IL-28B
+factor
+CaseViewer
+beneficial
+11.8 amino acids
+59
+detergent
+Acute respiratory distress syndrome
+BHK-21 cells
+infection by SAFV-3 isolates
+Student's ttest
+clinical and laboratory characteristics or prognosis
+human rhinovirus and Adbased vector systems
+Pure household models
+Element k i j of K
+honey bee
+UN heterodimer
+Ten
+1968
+eIF2α
+yUfd1 NBM
+15
+use of non-sterile gloves
+Mtb-susceptible
+Klenow DNA polymerase
+NdP, CG, OP, HM and GP
+RNA
+High quality filovirus recombinant protein antigens
+an exacerbation
+increase the efficiency of replication
+early protection against RSV infection
+once every 3-4 weeks
+µ
+anti-rabbit secondary antibody
+Health related quality of life
+MDRI
+kidney and liver
+different determinants and drivers
+dsRNA
+seven
+one quarter
+branches of their phylogeny
+two
+chromosome 14q13
+WARS
+severe lung injury and pulmonary edema
+PPRV nucleic acids
+high-performance liquid chromatography
+human disease impact
+630
+directly transmitted infections
+68
+HIV-1
+NeoMarkers
+Two paralogues of the class III HDAC Sir2
+pathogen emergence events
+achievements and trends on current nanobiotechnology systems integration
+enhancing ACE2 activity
+animal welfare purposes
+27
+A
+proteins
+HDV infection
+mfold predictions of the secondary structure of the ''stop-start'' region
+CvME
+Bovine serum albumin and PBS controls
+modification of Ubiquitin
+immunoglobulin type domains
+100.000
+3
+cleavage activation
+0.54%
+A pseudoknot
+Kaplan-Meier method
+COPD
+age-and disease-dependent disruption of lipid rafts
+interparatopic distance
+virulence
+VAP
+110 rpm
+3 h
+0.5 g/ml
+spring 2011
+ImageJ
+pseudoknot thermodynamic parameters
+CPP-steric block ON conjugates
+pGDENV1 3.3
+anxiety, depression, and diminished self-esteem
+porcine IFN-β
+ANOVA
+15 min
+1980s
+HDONAs
+adenoviral transport
+under-reporting
+90 copies of an ORF2 dimer
+non-monocyte derived cell lines
+20
+6.5 g/dL
+invalid
+TLR9-independent
+one minute
+a gate including Lin À /Sca-1 þ cells
+RAGE
+ALV-J
+sheddase ADAM17
+NK cells
+0.1 Mbp
+SaO2 and SpO2
+pathogen exposure
+Cs 2 CO 3 and hydroxybromides or iodides
+wet electrochemical reaction
+influenza
+UW 14-537
+every 4
+H5N1
+pessimism
+Seasonal influenza
+downregulation
+competency in medical knowledge
+Luciferase activity
+neutrophils
+30 min
+DENV titers to WT levels
+Northern blotting
+0.5 mM
+30 min
+non-redundant datasets
+349
+MILLIPLEX MAP
+Geneious 7.0
+Human immunodeficiency viruses type 1 and 2
+the model produced by the training set
+TMEV
+Parameters of oxygenation, hemodynamics and lung mechanics
+Poly I:C
+methylation
+rapamycin
+correlated
+test kits developed for seasonal influenza A and B viruses
+resilience to mutation
+VS
+winter
+different gene expression trends
+mortality-related DNAm
+H5N1 and H7N9
+Consensus shuffling
+four
+Fc receptors
+infecting capsids
+inhibiting the translation of the cap 0-modified mRNA
+More than 2,000,000
+Circadian disruptions
+desert woodrat
+bronchopneumonia
+Dr. S. Ludwig
+individual immunity
+nonhuman primate models
+2 h
+susceptible
+Antemortem testing for human rabies
+claudin 1 overexpressing cells
+increases the antiretroviral potential of IFNa
+EVD
+Normal rabbit or mouse IgG
+functional divergence in AP2 group genes
+Supplementary Table 1
+a fraction
+10 days
+5 days
+a severe malaria patient's isolate
+relatively discrete groupings of control, mild MPP and severe MPP groups
+ventilator-induced lung injury model
+NLR proteins
+20:1
+Categorical variables
+94
+28 days
+enhances transcription of many oncogenes
+once their mobilization occurs
+normal lung parenchyma
+Arterial blood gases
+16
+Siglec-8
+negative
+30 days
+35fold
+H3N2 and H1N1
+WHO Rapid Advice Guidelines
+A DSMB
+52
+different epitopes at GP
+60 hours
+mutation pressure and natural selection
+highly flexible
+polyclonal human serum
+Binding of these inhibitors
+non-pulmonary
+G ¥ ¥
+autophagy
+van den Driessche and Watmough
+Sonication
+DAVID
+KstR
+C3
+routine diagnostic testing
+lipid-rafts clustering
+non-pharmaceutical measures
+formation of membrane tubules
+41%
+The filled area
+four
+Nucleospin Tissue XS kit
+BAX-BAK-mediated mitochondrial outer membrane permeabilization
+egr-1 and KSHV ORF50 transcriptional activity
+Biguanide
+Human CD4-IgG2 immunoadhesin
+intestinal microvilli
+primary amine coupling
+Trizol Total RNA Extraction Kit
+45.2%
+they might complement one another
+IFN-α
+manidipine
+the death certificate and registration of causes of death
+mild lysis
+host species, cell type and virus type
+M1 and M2
+sequencing errors
+low
+higher background
+supportive information
+trophoectodermal cells
+DL algorithms
+infants
+transferrin receptor
+189
+Bivariate data
+receptor-mediated endocytosis
+R563A
+auxin and cytokinin
+3-5 days
+CD3d gene expression
+CD spectra
+alkaline phosphatase
+dengue disease severity
+CD40-CD40L
+XJ
+346
+six
+Neoangiogenesis
+Shigella
+encapsulation with inspissated pus
+PRR ligation
+193
+Antisense oligomer-mediated exon skipping
+a rapid, easy, mobile, NAT method of high sensitivity and specificity
+Rt
+inhibit the formation of syncytia
+negative effect exerted by PHBs against TMEV infection
+M2 macrophage activation
+early anamnestic Ab responses
+Our focus groups and pilot testing
+255
+73%
+current research
+viral pneumonia
+GADPH
+pre NDV challenge growth rate
+psychometrically driven, definition-driven and data-driven methods
+survive the EBOV challenge
+caveolin
+polyfunctional
+22%
+two
+high resistance levels
+influenza
+ImageJ
+laboratory techniques or comparative information
+TRPM2 channel
+M-CSF
+524 APTYSW 529
+10
+abrupt onset thoracic pain
+PBS-immunized mice
+suppresses
+X-ray film
+EBOV
+transmission electron microscope
+Serum AST
+strong backward scattering of light
+at least 14
+de novo protein synthesis kinetics
+Five
+analysis of local characteristics of the protein chain
+viral attenuation
+activated stellate cells
+viral genomic RNA
+Vincenzio Tiberio
+additional references
+Cys31-32 disulfides
+human PBMCs
+MAb
+Government-funded public health activity
+10 min
+bacteria and viruses
+self and non-self
+low
+Total viral richness
+antigenic interaction
+DEP technique
+cyclocephaloside II
+Immediate implementation of effective isolation and infection prevention measures
+T-cells
+23
+Error bars of dose-response curves
+revolutionize healthcare
+IL-1b and IL-18 cytokine concentrations
+serum levels of RBP
+skin inflammation
+pigs
+real-time RT-PCR
+FHCRC database
+deposited calcium
+X-ray scattering
+56
+X
+membrane pore formation
+Interaction
+health care workers
+IFN-γ gene expression
+age specific
+inflammatory cytokines
+HTV ventilation induced damages of lung structure
+eight
+Creative Commons Attribution License
+Drosha, Dicer1, and Ago1
+22
+stopping research, informing public authorities or not publishing results
+Pine oil
+defects in enforced virus replication and a reduction in the innate immune response
+26%
+seven
+shorter lipid chain distances
+donor sex and BMI
+PiCV rCP
+P = 0.05
+To avoid false positive results
+698
+36
+branching processes
+Titration of virus stocks or samples
+the hierarchy of responses to either HCV or HIV antigen stimulation
+obesity
+predicted rates based on these 3 parameters and actual cholera incidence
+initial rates
+ABC parameter inference
+maxillofacial
+age and sex
+mean temperature, humidity, longitude and latitude
+Positive and negative controls
+2 min
+control group that was treated using only a roaster machine
+limited data
+alpha and beta diversity indices
+600 km
+lung endothelial cells
+1.25 mm collimation
+real-time reverse-transcription PCR
+southern Poland
+Calvin Schwabe
+The Ebolavirus Virus Pathogen Resource
+difference image
+FXII
+Retention of study participants
+few people have access to media and vaccination
+pseudoknot
+extra-pulmonary manifestations
+translation, replication or RNA stability
+IL-1b and IL-12
+accelerates healing
+gene therapy
+Turkey
+5%
+prior contacts
+488
+Southern blotting
+The difference in the quantity of the chemical components
+the first identified homomorph
+Western blotting
+V5-tag expression
+reovirus
+TNFα
+approximate post mortem interval
+Monsalvo and colleagues
+Virus-containing cell culture supernatants
+infection
+P. tomentosa
+E. chaffeensis 16S rDNA and mouse Gapdh
+antibiotics
+GFP-positive
+univariate analysis
+Student's t-test or one-way ANOVA
+larvae
+Multi-Tissue Dissociation kit #1
+between 2 and 15 days
+23%
+Favipiravir
+55%
+apoptosis or oncosis
+Isothermal titration calorimetry
+nonsteroidal anti-inflammatory drugs and/or simple analgesics
+Filter paper
+13
+30 min
+public health incidents
+a wide number of pathogens
+USP5
+local disease surveillance and risk communications efforts
+the information that is determined by the extent of homology among the compared sequences
+increased by more than 4% each year
+Twitter or other Internet data
+HRV-A and -C
+anti-goat AF488 antibody
+12
+acute respiratory distress syndrome
+NPPB
+spatiotemporal
+12%
+−1 frame stop codon
+directing the anti-viral activity of PML NBs
+Viral RNA
+Clinical algorithms based on biomarkers
+Broadly reactive
+62.1
+IL-6
+death
+4 million
+Further studies
+EBOV-GP 1976
+fluorescence quantification
+12 h
+essential for HBV gene expression
+Hardy-Weinberg equilibrium
+real-time identification and characterization of epidemics
+population migration
+Treatment with adult haemoglobin
+67%
+4'/G
+Hydrogen peroxide
+three
+similar results
+≥1:40 hemagglutinin inhibition titer
+phylogeny
+mutarotase
+Tracer 1.5
+6 weeks
+six days
+suppress Yop translocation 20 and protect macrophages from apoptosis
+Patient clinical data and serum samples
+41
+weak emphasis on duty to care
+Porod-Debye
+SBE2/3 motif
+immunomodulatory
+influenza B seropositivity
+Negative staining of viruses
+Fourier
+Figure 6
+Apoptosis
+293 FT cells
+a BF test
+rate of separation
+exacerbation
+viral respiratory infections and norovirus outbreaks
+integration time: 10 sec, sensitivity: 200 or 230 and Filter set 1
+DISMOD II
+SUMO modiWcation
+iNR-Drug predictor
+ribosomal mRNA entrance channel
+30 nM and 1 mg/mL
+STAT1 and GRB2
+intra-clade VP1 divergence
+Wild-type
+n
+14
+alerted the group members about the disease
+14.96 ±11.82
+SWBV and BAV
+Kolmogorov-Smirnov test
+SELDI-TOF technology
+HPAI H5N1
+ZIKV
+analyzed
+95%
+cellular lysates
+mixing within camps only and no mixing between camps
+HTNV infection
+three
+CCL-2 and MX-1
+HMGB1
+52
+3-Indolepropionic acid
+markers of HIV disease progression
+1 wk
+scatter plots
+parameters i and j
+12 min
+HCV and HIV
+HMPV A2
+Neutrophil longevity
+Pneumococci, S. aureus, and GAS
+RNase inhibitor
+viral DNA
+2× TBE urea sample buffer
+the loop of an extensive hairpin
+middle cerebral artery occlusion
+860
+Cerebral malaria and severe malarial anemia
+B-cell related trafficking and organization
+X-ray scattering
+A549 cell line
+CGI methylation
+RNA helicase DDX3
+two different random 6 nt sequences
+four
+99.99%
+10%
+a protein in the mitochondrial respiratory chain complex
+Genetyx 11.1
+volume of news coverage
+flow cytometry
+an association between susceptibility and levels of MatAb
+development of severe disease
+identification and analysis of bifurcations in the system dynamics
+Medical mask
+Autoubiquitinated TRAF3
+LFQP results
+replication and transcription of the viral genome
+highest
+Flow cytometry
+140
+camel agribusiness
+alternative splicing
+modernity
+More than half
+Spanish
+Zeiss Axiovert 200 M microscope
+complex
+Artifactual recombination
+Anomalies
+ReverTra Ace Kit
+Non-physiological artefacts caused by shRNA expression
+plasmacytoid dentritic cells
+Rapid and accurate identification of sexually transmitted infections
+100%
+EGFP reporter
+three
+murine leukemia virus
+more tests in different conditions
+Travel time
+548
+Turner et al.
+Fifty
+adherence to mucosal epithelial cells
+Annexins
+cycles
+CarboSil 20 80A
+anti-inflammatory
+reproductive number
+three separate PCA clusters
+28
+phosphorylate STAT1 and STAT2
+S, S1 and S2
+pGEM-2KS and pET21
+Twenty
+322
+to ensure that equal numbers of cells were infected
+PK15 porcine
+TRAF3 and TRAF6
+Female shrew #3
+mutations existent in templates
+King Abdulaziz University
+differentially expressed proteins
+TDP-43 depletion
+Retromer binding
+pre-processing of the binding sites
+BFRF1 and BFLF2
+preventive restrictions of freedom or exclusion from society
+23
+6 ± 0.7%
+Glutathione Sepharose 4B resin
+PRE ribosomal complexes
+an agreement to the reference
+31
+15
+implausible uninformative prior distributions
+Benchmarking experiments
+6.02e23
+InVS
+cleave
+7 of 13
+15%
+Alveolar macrophages
+The nucleus of a cell
+Supplementary Table S3
+information about the structural interactions between serum antibodies and their antigens
+unique lipid compositions
+BHK-21 cells
+polycyclic aromatic core
+biological
+more severe AOM
+homogeneous population mixing within a district
+VIDISCA-454
+31
+department within Peru
+100%
+cytoplasmic, perinuclear foci
+observable and unobservable modeling approaches
+kallistatin levels
+splenomegaly, rash and arthralgias
+1083099-2
+Standardising more microbiological diagnostics
+C γ
+complement fragments, ROS and pro-inflammatory cytokines
+CIb
+pDCs
+S0-F and F-S0
+5
+DNA damage and actinomycin D treatment
+A 260
+a drug that inhibits the helicase activity of eIF4A
+millisecond scale molecular dynamics
+Macrophages
+DQ red BSA
+D3
+ACLF
+Rao
+Olympus BX41
+hyperbolic
+mycobacteria, nocardia, herpes viruses, and fungi
+Day 2
+12
+rodent
+log-likelihood ratio-test
+2380
+560 000
+a measure of conspiracist beliefs
+polypeptide epitope
+Standardization of plate reading equipment
+A leader sequence from human tPA
+Measurement of visual-evoked cortical potentials
+the phagosome
+GA
+Piercy and colleagues
+H5-HA
+Daubenton's bats
+More than half
+PV EF3
+whether cancer is
+Simple Modular Architecture Research Tool
+Tables S1 and S2
+an opening through the membrane
+2
+56
+immunity, nutrients, energy, and bioactive factors
+1993-2004
+1:2 and 1:3 ratio
+SFTS
+Economic concern
+Nuclear factor kappa-B
+decreased virus shedding
+policy guidelines
+90 minutes
+Yoyogi Park
+protein mass spectrometry
+200.6%
+2003
+Melanoma
+delivery and stable expression of siRNA
+Solvent exclusion
+Four
+half
+potential contamination
+steady state
+phosphorylation
+carotids
+Influenza A
+Reassortant strains
+30 s
+chronic diseases, cancer, immunotherapy, and immunocontraception
+means ± SEM
+mycophenolate mofetil
+23
+225
+80%
+Precursor firefly and Gaussia luciferase reporter gene constructs
+Section 2
+Zika
+hundreds of millions
+increased surfactant degradation or lung tissue inflammation
+1.7 years
+whether the cellular immune response is protective or facilitates the onset of severe disease
+3 times a week
+correlated
+bornaviruses
+19,800
+fibroblast
+severe acute respiratory syndrome
+CD4 + T cells
+Heme oxygenase-1
+admission
+rapidity of manufacture
+coupon collector's model
+0.76
+the row and column labels
+Cases
+Dr. Y. Liang
+Abnormal protein expression
+Wizard SV 96 Genomic DNA Purification System
+TBE-C
+Mouse kidney cortex lysates
+Centers for Disease Control and Prevention
+MAGT1 and TUSC3
+covalent cross-links
+further investigations
+natural selection
+less than several hours
+ALV groupspecific antigen
+12
+prothrombin time-international normalized ratio
+Advantage 2 Polymerase Mix
+81.5%
+Reperfusion
+observable growth rate and duration of the infectious period
+Spain
+1789
+sepsis
+60 years of age
+external validity
+threshold dependent parameters and threshold independent parameters
+Cell Signaling Technology
+S1P
+SPSS version 13.0
+RiboPicker
+Influenza virus M2 protein
+analysis score of 4.0
+Ionotropic GABA A receptors
+57
+Excel
+IL-8 and MCP-1
+Latent tuberculosis
+different genetic backgrounds and environmental factors
+RESTV and LLOV
+Agencourt AMPure XP beads
+cytokine concentrations
+user-friendly and validated tools
+993
+wild-type or mutant peptide
+according to specific analytical approaches and the individual required steps
+Streptomycin
+tissue and aquaporin specific
+Letters
+Statistical
+29
+cells that do respond
+Site-directed mutagenesis method
+1%
+11 h
+oseltamivir
+Classically-activated
+flagellin
+18
+Two milliliters of the harvested virus-containing supernatants
+TNFα
+local membrane instability
+mechanical
+histologic evidence of cardiac damage
+growth medium
+Hippocrates
+SBML
+Beijing Children's Hospital
+The square root
+ZIKV-specific immunity
+suspended confessions and funeral ceremonies
+NF-jB
+Huntington disease
+mechanical ventilation
+PDCD4
+NH 4 Cl
+cell proliferation, cell differentiation, and apoptosis
+Close to one-third
+PCR
+September and October of 2014
+Molybdenum cofactor
+fibrinogen deposition
+interventional strategies
+Convincing people to adopt prudent health behaviors
+eEF1A
+Privacy issues
+1/10 th of the starting material for the IP
+Natural selection and mutation pressure
+mixed viral populations
+reverse transcriptase polymerase chain reaction method
+homeostasis or regenerative capacity
+> 100 days
+pluripotency
+40
+Sample size
+4809
+39.2%
+severe anemia
+testkits
+Bril regulatory sequences
+xcms
+56.7 months
+300 K
+non-linear
+DOR and codon usage bias
+emerging bat-borne viruses
+Type 2
+denaturation of template
+Low level expression of the replicative machinery
+replicative
+higher radiation energies and improved alignment
+21
+infection
+T cell immunity
+Lemma 1
+n overnight culture
+4, 842
+viral cultures, antigenemia, and PCR assays
+Object detection and tracking techniques
+viral yields
+V18A, R44K, and S195P
+vaccinated animals
+a new site
+6
+5
+Primers designed to mutate designated residues
+Nedd8
+11%
+contribute to the entry of Ebola viruses
+Incidence
+Aromatase
+MΦ polarization
+15
+Thirty minutes
+Different Lys and Arg isotope forms
+Systemic corticosteroids
+Metabolomics
+cofactor
+ELISA
+temperature effects
+residue 77
+8%
+recall of the poster's message
+virologic characteristics or molecular epidemiology
+Group 1
+Mann-Whitney U test
+39%
+Mesenchymal stem cells
+4,833
+nocodazole
+fully de-identified data
+Allocation concealment methods
+antibodies to currently circulating influenza viruses
+neuroprotective
+cTn
+37
+200 nm
+stochastic
+Six
+NG2, Nestin, Pax6 and Sox1
+computer-aided drug design
+Leica TCS SP5 Confocal Laser Scanning Microscope
+12
+7
+0.996
+mechanical stability
+mixed effects model
+75%
+DENV amplification
+the relative amounts of total sGP and GP 1,2 produced
+perilymphatic
+how many diagnostic samples they could process per week
+Surfactant administration
+CD163
+1:10000
+diagnostics, therapeutics and vaccines
+ileal tissue
+substitutions of G with inosine
+the ratio of the transfected reporter constructs
+ImageJ
+The endothelium
+neutrophils
+not robust
+91 days
+Co-immunoprecipitation assay
+Two-dimensional position information
+pro-inflammatory
+Hsp90 activity
+99%
+cancer antigen 125
+elevated induction of IFNb-stimulated genes
+57.0-66.3%
+mixing patterns
+significant differences
+inhaled diethyl ether
+WNV RNA replication process
+Pearson's chi-squared test
+low PaO 2 and low PaCO2
+West Nile virus
+14-21 days
+15
+conservative or moderately conservative rrs and groEL strategies
+Primary viral pneumonia
+the untranslated region of the PIV5 M mRNA
+MS2 and PhHV
+Nmd3 adaptor
+Traditional Chinese Emergency Medicine
+Flavones
+MDCK-SIAT1 cells
+aquaporin 4
+10%
+Spotfire
+Clonetech
+HBsAg
+70
+existing social ties
+CreERT2
+1 h
+targeting extracellular CIRP
+Six
+50%
+weak hypotheses on the dynamics of the time-varying parameters
+2 weeks
+25 July 2015
+72
+5%
+KX982264
+HeV or NiV
+One hundred
+a few hours
+Geneious
+fear
+-A2 or -A24 alleles
+Common cold
+SDHA/YWHAZ
+The unconstrained problem
+relative mrna expression levels
+viral plaque assay
+10%
+hospital
+gloves
+Percentage of number of ILI visits to number of total clinic attendances
+eighteen
+aromatase
+high cell-density fermentation
+IFNλ
+the specific RNA segment
+150 μL SDT buffer
+18.3 and 16.2
+descending paralysis, bulbar palsies and respiratory failure
+Acetylcholine
+Sexual transmission
+sepsis survival and/or organ dysfunction
+interfering with the formation of the apoptosome
+Over a quarter
+RIG-I RD
+priming of resident cells of the CNS
+abnormal nuclei
+Online Supporting Information S1, S2, S3, and S4
+MKP-1 expressions
+Forty-four
+Fifteen to 20
+University of Colorado Hospital
+Taiwan
+10
+an inhibitor of PAK1
+7
+Surveillance for hospitalized patients with severe acute respiratory infections
+two to three times
+spontaneous lymphoproliferation
+Neutralization
+proteins and RNAs
+co-infection
+Accession numbers, alignments, dates and locations of the isolates analyzed
+six
+AIV-specific CTL cytotoxicity
+IFITM variants 1-3
+cattle medicine
+severe RSV bronchiolitis
+16 layer variant
+DENV envelope protein
+the mutation
+Selection ''corrected'' recombination rate estimates
+lower respiratory tract
+t + 2 and t + 3
+Every 4 weeks
+the number of the initially responding B cells
+-Leu incorporation
+stability and cost
+levels of trust and transparency
+Aldevron
+a transition to a more malignant phenotype
+inflammation during HCV infection
+IRF7
+inhibited cell-binding
+58%
+neutralizing antibodies against target epitopes on the viral surface
+conservation patterns or co-evolution measures
+structure
+rifampicin
+4
+DMEM
+10%
+5 min
+four
+90 min
+homo-oligomers
+eleven
+experimentally obtained T cell tracks
+2 weeks
+2005-2006
+2
+on the periphery of the pocket
+weak
+SuperScript III First-Strand Synthesis System
+Four
+high body-wide skeletal muscle dystrophin production
+haematoxylin and eosin staining
+μs-ms conformational exchanges
+by sorting
+ADAM17
+less than 2 weeks
+help-seeking
+Bland-Altman plots
+sterile endotoxin free PBS
+TGF-β
+SARS coronavirus PLpro
+rural
+MHV-3
+mammalian cell lines
+Tetra-, penta-and hexanucleotide SSRs
+sorting of cell populations
+HPV01 and HPV08
+The County Education Officer
+Climate change
+RNAeval
+48 hours
+60 µL/min
+1957
+increased secondary bacterial infection
+WNV
+thin-layer chromatography
+a complete CDS
+iterative and reflexive
+weekly
+a signal to noise ratio of 5 and valley depth of 3
+Prism 6
+a putative trajectory of increasing viral fitness
+Hantaan virus
+four
+significant variance differences
+10.50 ± 0.48 μ g/mL
+R0
+OAS1
+Microscopic
+12h
+human influenza A virus replication
+1,000,000 JPY
+Clinicaltrials.gov
+microarray dot electrodes
+inducible expression of C6
+Cell culture supernatants
+increased expression of IL-1b
+RecoP51 ATPase
+vaccine efficacy
+prior infection
+sources of error
+gp41 binding
+proinflammatory cytokines
+no non-specific reactions
+antiviral medications
+144
+two-way approach
+efficient membrane vesiculation
+inhibitor experiments
+most of these postulated principles
+3
+Chronotype
+Cutaneous transmission of the hands, arms, and face
+Tautomerism
+relevant to influenza virus
+12.8 kDa
+397
+~300 hours
+P2 index
+Caspase-8
+IL-6, IP-10 and TNFα
+good
+ViennaNGS 38
+11,496
+Recombinant proteins
+mucosal homeostasis
+PE-conjugated mouse IgM
+X-31ca
+dead cells
+24h
+parasite growth, survival, and persistence
+0.01 M PBS
+MPER peptide
+14,000
+enhances surface expression of H5-HA
+TGF-β1 expression
+Backward stepwise logistic regression
+epitope characterization
+Seventy-five percent
+section 2
+65%
+key pathological features of encephalitis
+single nucleotide polymorphisms and short insertions/deletions
+One hundred
+inflammatory
+RNA
+bases that interact with specified L3 basic thumb amino acid side chains
+one
+undesirable side effects
+Aicardi-Goutières syndrome
+Nucleic acid hybridization
+0.7 second
+EDEM1
+EMR
+microtubules
+multi-looked image
+regulating cell growth and proliferation, inflammation, and cytokine production
+PMO, PNA, and 2¢-OMe/PS
+viral respiratory infection
+higher
+Megress C18 analytical column
+virus -infected cells
+Western-blot
+TRIZOl reagent
+at least three
+variability
+1% agarose gel electrophoresis
+a miniaturized automated fluorescence microscope
+three
+CDKN1A
+Variation of dinucleotide 1-2
+399
+More than 50%
+26.4 ± 8.1 mm
+Lassa Fever
+tools available from the EMBL
+Ghana
+surfactant proteins B and C
+70%
+prior or simultaneous evolution of new or modified transcriptional control sequences
+aggregation, adhesion and release response
+LD analysis
+bat
+virus-triggered apoptosis
+transcriptional activation of HDAC2
+Acute respiratory distress syndrome
+A proper patient selection, a cooperative patient, and clinician skills
+backward procedure
+six
+19.4%
+type-I pneumocytes
+vaccinia virus-infected HEp-2 cell lysate
+2DE
+vaccine growth and antigen production are not affected
+60-90%
+40%
+absolute humidity
+2 h
+IVIG therapy
+5
+Resveratrol and NS1619
+74.47
+illnesses
+MiPepBase
+cat odor
+Population-level selection
+oral mucositis and abdominal pain
+standard deviation from 3 independent experiments
+policy
+P < 0.05
+temporal immunofluorescence
+distribution
+clinical and education
+amphibole fibres
+adequate and neutral
+Sigma Stat 3.11
+polymorphism
+HSV-2 DNA
+Orf8 orf8
+Food and water quality
+surgical face masks
+acquaintance immunization
+Standard protocols
+Indicating medians as 12 well as minimum and maximum point estimates
+257
+24 h
+diarrhea
+compact interfaces
+published spore survival results
+one
+Chest tightness
+KE1 and KE3
+IFNλ1-4
+alamarBlue
+200 ml of pelleted yeast
+Two weeks
+applications and granted patents
+TB treatment using LOF
+Staphylococcus aureus
+encapsidation
+CTLA-4
+SOCS-3
+1.3 mg/mL
+nanorobots
+cc-by
+H1N1
+UNIFESP Research Ethics Committee
+I j and S i
+MicroRNAs
+Four
+nodes and links
+active lignin
+in vivo functional end points and histopathology and biochemical markers
+32 kilometers
+nuclear but not nucleolar staining of the Flag
+wild type but not Ifnar1 SA tissues
+SWISS-MODEL 32 and POLYVIEW-3D 33
+Nikon Eclipse Ti
+avidity
+PM0079652
+Cationic polymers
+Recombinant sequences
+thirteen
+integrating various inputs and responding appropriately
+Supernatants
+1000
+5.0
+PCR-based assays
+E 0
+highly specialized staff and equipment
+LAMP analysis
+spillover events and species jumps
+seven
+gender-and age-matched healthy adults
+variation in codon usage
+ribonucleoprotein granules
+antagomiRs
+PSII
+every 10 minutes
+538 nm
+0.5%
+E
+After 2 d
+three
+PIKfyve-dependent
+inactivating virulence associated proteins
+1%
+suicidal
+humans
+other active forms
+1,240
+100%
+V max
+diabetes
+DENV-2 E protein
+biological post-translational modifications
+high standards of infection prevention and control
+12
+mAb 4G2
+lower-level EAE and an earlier recovery from symptoms
+competing
+decreased the virus load
+111
+40
+Cytotox-One Homogeneous Membrane Integrity Assay
+Chromatographic separation before MS
+30 days
+the conditions within the GI tract
+cc-by
+ERdj4
+Sevag method
+3000-4000
+PfNHE1
+issues and questions
+D endritic cells
+histopathological changes
+Green bars
+0.5 %
+Specific PCR and RT-PCR
+Limiting the duration of prophylaxis
+CD11b + Ly-6C hi monocytes
+Chinese strains and foreign strains
+862.25
+STAR
+4 week incidence
+quantitative immunofluorescence
+cross-presentation of antigens and DC maturation
+genotype I and II
+12 h post-infection
+Biomphalaria
+Weekly R t
+the mutant background
+1,120
+high-speed straight migration of lung-infiltrating T cells
+rabbit anti-Influenza A Virus Nucleoprotein
+LPS and CTB
+residue 294G
+PCR primers
+Marburg virus
+Common sense
+WHO
+impaired
+enteric bacilli
+335
+parasites
+HRV infection
+disappeared from the genes they were switching off
+prostate biopsy samples
+Significant antigenic diversity
+sarcomatoid and biphasic
+hTDP-43
+70%
+detected in situ
+Pearson's correlation coefficients
+Grade 1 and 2
+TMPRSS2 expression
+AMR
+Gross pathologic
+the cognate receptor of brain-derived neurotrophic factor
+119
+enhance viral capsid expression and/or viral titers
+NGS
+evidence of T-cell exhaustion and/or senescence
+tubules
+350
+10 2 pfu
+2012-10-31
+six
+strong binding of 5S rRNA and rRNA-derived transcripts
+more than 3 weeks
+Bin Song
+cross-regional assistance
+chikungunya, dengue and West Nile
+Netherlands
+patient genetics
+salivary proteins
+chloride channel conductance
+À80 C
+10%
+another level of stringency
+membrane environments
+3D
+viral titration
+1.55
+R2, R6, and R7
+four
+enhancement of HAI surveillance activities and capacities
+Twenty
+inducible nitric oxide synthase
+twice
+discontinuous minus strand extension model
+Nikon Eclipse TE2000-U research microscope
+David H. Edgell
+AUP 1031
+Southern Africa, Eastern Africa, the Middle East and South Asia
+PAMPs
+ad hoc scripts in the R language
+DESeq2
+streptavidin-biotin-peroxidase complex method
+54
+Evaluation of an overall national response
+PRP-containing supernatants
+IFN-γ
+220
+Geographically weighted regression
+Lentiviral reporter viruses
+LysM-expressing
+48 hours
+Supernatants
+16 weeks
+carboxyfluorescein succinimidyl ester
+criminal law and public health
+100%
+pulmonary or other rare diseases
+APC activity
+elastase
+infection cases
+normal cell cycle
+Antibody of F4/80
+40 046 238
+1
+I622A
+direct contact
+Student's t test
+Incomputable clinical data
+PRJNA523863
+annual or seasonal reformulation of vaccines
+mouse cells
+Dulbecco modified Eagle medium
+Morphometric
+anti-sera to Olig2
+62.4%
+F
+4
+HIV genes
+more than 10-fold
+glycan array
+nine
+Southern blotting
+cardiomyocyte apoptosis
+MIP
+viral infections
+20%
+three
+inflammation and coagulation
+Bangladesh
+Antioxidant scavenging of free radicals
+synergistic and cross-talk effects
+15 Å
+MEDI4893*
+low-level lipid mixing
+Thimphu
+22 μg/ml
+the standard curve of the peak area and concentration
+37
+the process generating the data
+Libreville
+Ifnar -/mice
+impractical
+poultry trade
+Human cytomegalovirus
+38.3uC
+Autoimmune PAP
+protected cells P
+periods of extensive genotypic change
+K48
+intracellular compartments
+keywords
+E64d
+D'Agostino normality test
+The optimal amount of each studied tissue
+mortality
+1953
+type 1 interferon signaling pathway
+stroke, delirium and cognitive impairment
+Sialic-acid receptor expression
+occupancy density
+CSFV RNA
+alter
+three fundamental, yet simple observations
+Five of 10
+extrinsic
+Descriptive statistics and correlations
+particle deposition fraction
+4%
+1918
+Random Peptide Libraries
+hypertension and hyperglycaemia
+mice
+Decision trees
+plasmacytomas, hybridomas, CHO and BHK cells
+20.36 days
+reverse emergency call system
+Primer annealing
+10 mM NH 4 Cl
+necrosis and apoptosis
+Mann-Whitney U test
+NiV-specific total antibody levels
+Inhaled corticosteroids
+disulfide-stabilized
+10
+10-fold serial plasmid dilutions
+ERK, p38, and JNK
+Chi-square and two-tailed Fisher's exact tests
+4%
+influenza M2 protein
+53
+mild, moderate, severe, and critical
+active virus replication
+EMT
+mouse monoclonal vimentin or FLAG antibodies
+unknown mechanisms
+formal
+nationwide interventions
+a higher share of b-strands
+M2-2
+astrocytic or neuronal cell cultures
+VP1
+antiviral treatment and prophylaxis
+RV
+HPAIVs
+90 days
+pro-and antiinflammatory plasma cytokines levels
+6-8 weeks
+Genotype BA.2
+biologically active
+Paneth cells
+twice daily
+0.1 µg to 10 µg
+Tcf4, Pdca1, and Cx3cr1
+SNRca SNRt Post injection
+6
+The structure of the nesting
+GISs and visualized health data
+adolescence
+general limitations
+5.16%
+Recombinant
+Zenon Alexa Fluor
+Enzyme conjugate
+embryonic myogenesis
+IRES-dependent
+Molecular evolutionary rate and divergence times
+physical properties of mucus as a hydrogel
+epitopes on the lateral ridge and A strand of EDIII
+Glc 3 Man 9 GlcNac 2
+RNA complementary to the Leader gene
+19
+12/12
+MetaGenome Analyzer
+Braak staging
+PB1 D27N
+NanoDrop 1000
+vaccination
+48.4%
+NK cells
+R 0
+solute concentrations
+tracheal explants
+mouse anti-Flag and Cy3-labeled secondary antibodies
+Custom software
+C-reactive protein
+Group B streptococcus
+activated adhesion function of white blood cells
+binding to TLR9
+ozone
+Lesquerella fendleri
+0.7%
+Three
+Coalescent theory
+enrichment of virus particles
+low-temperature
+influenza
+5%
+genetic
+heterodimeric integrin Mac-1
+An analytical balance
+longer
+E. cava
+bats
+more reexperiencing, avoidance, and arousal symptoms
+Z-FA-FMK
+Vancomycin
+attenuated
+totivirus
+protease monitoring
+morphological changes
+high-density interval
+a trimeric molecule
+myocarditis
+to evade host immune response
+1%
+monoclonal antibody to a-tubulin
+CNGRC/PEG/PEI/DNA vector
+CXCL10
+one week
+underestimates the true value
+bone marrow suppression or teratogenicity
+Slime and capsular material
+14
+disease diagnosis
+boredom
+Vps4p
+cross-strand hydrogen bonding
+50 mL 1:10 diluted purified toxin
+NCBI Sequence Read Archive
+no swelling or other signs of inflammation
+lower risk of URI
+a web resource
+؊2/؊1 ribosomal frameshifting
+Cervia and Ravenna
+aZsKs
+nine
+persistent sub-lethal ER stress
+a network of interconnected hosts with different epidemiological roles
+1955
+dust, fumes, smoking
+cuboidal
+BC023105
+HVC studies and field studies
+lowered, but did not entirely prevent the IL-6 response
+cardiac malformation and death shortly after birth
+Humanistic care
+190
+106
+proinflammatory
+a serine protease inhibitor
+interferons, antiviral chemicals, and vaccines
+to maintain a roughly fixed rate of generation of filtered trajectories
+uncommon septal wall hyalinization
+three
+86%
+increased coal burning
+Alaska Native people and Asian/ Pacific Islanders
+90%
+10
+Isolates RV39 and RV610
+PCBP2
+amino acid sequences aligned using ClustalW2
+200-300 mg
+all investigators for the main trial
+1 day
+the effects of NS5 on the host cell cycle
+biliary glycoprotein-1
+Over 30
+Cohen's kappa coefficient
+Inactivated vaccines
+SGG-A, MJ-C, and MXJ
+viruses
+>30
+recovery
+decreased
+medians with interquartile ranges
+increased CPY secretion
+Custom scripts
+higher bocavirus prevalence
+two
+high quantum yields, and extinction coefficients
+controlling or preventing diseases
+19mer
+Manual counting with a hemocytometer
+HSV/CMV reactivation
+zones 1b and 2b
+viral replication
+β-glucuronidase
+Genome-Plex DNA and TransPlex RNA
+Category 1
+enveloped RNA viruses
+3.75 µg of HA per dose
+the numbers of the GBS isolates sequenced were small
+macaques
+increased duration of mechanical ventilation and length of hospital and ICU stay
+signaling properties and downstream cellular function
+lactobacilli
+600
+Restriction of the analysis to patients meeting the Berlin definition for ARDS
+a methyl donor
+seven
+Juniperus rigida
+4
+previous reported studies
+immunodiagnostic
+2007
+virus replication
+captured exosomes
+Asterisks or pound signs
+70
+1536
+using a response surface method
+vaccination campaigns and programmes
+6
+false positives
+type III
+45 %
+39
+2117
+MCF-7
+ATP
+high degree of risk aversion
+50%
+non-specific
+mortality, blood bacteria clearance, and cytokine response
+weighted histogram analysis method
+Orlando, Florida, Portland, Oregon and Honolulu, Hawaii
+July to November
+cleaves this polyprotein
+278
+RF model
+mucosal surfaces
+fibrinogen
+immunosuppressive drugs
+SRV-1 and baboon endogenous virus sequences
+½0,1
+19,218
+Closed-reference OTUs
+three to eight
+clinical, epidemiological and laboratorial
+30 min
+pskHBoV1 plasmid
+57.2%
+JHMV infection
+silkworm genomic locations
+increased resting energy expenditure and with reduced survival rate
+another species or genetic element
+28,000
+Band shifts
+parenteral vaccinations
+West Nile Virus transmission intensity
+complementary RNA
+GalK/kanamycin dual mutagenic cassette
+HMBS and HPRT1
+endogenous inflammatory cells
+6.7 g/kg/day
+nine days
+supernatants
+4
+on the cell surface
+over 4,000
+Four out of nine
+two
+new selectable markers
+active-site cysteine
+drop of DRM
+External stimuli
+protective against bovine as well as human RSV
+instant
+eight
+a trimeric core
+cellular replication and growth
+most of the globular N domain
+tremor, tachycardia, or arrhythmias
+KS or lymphoma
+day 10
+regulates the location of Src
+95 %
+Kernel-based metapopulation models
+below 1
+Pneumonia and other lower respiratory tract infections
+Z B,v i,j
+five
+89%
+eight
+40%
+CC10 protein
+cc-by
+Total RNA
+positive pressure mechanical ventilation
+Lipidation of Atg8 by PE
+CD4 and CD8 T cells
+1
+neuronal dysfunctioning
+bacterial
+to differentiate between type I and type III IFNs
+6 out of 11
+1.0 and 5.0 μg/ml
+Infections
+fold changes
+endosomal TLR signaling
+cell death
+Killer
+West Nile virus
+Mink enteritis virus
+RNA polymerase complex, viral RNA, nucleoprotein and nuclear export proteins
+Duchenne muscular dystrophy
+SSP C-terminal region
+susceptible-infected-recovered -like
+stress
+Five
+microglia
+improved therapies
+Two
+arrowheads
+179
+Tbf1p
+opportunistic infections
+oseltamivir
+measles
+the stem 1 hairpin
+ring vaccination together with contact tracing and isolation is likely to be successful
+40%
+one-third
+two
+220,305,266 filtered reads
+IL4 and IL4RA
+FlowJo
+99% on average
+80%
+the local Ethical Committee
+intragenic and intergenic
+LOF
+plaque reduction inhibition assay
+lentivirus-mediated siRNA
+age
+unclear
+antibody recognition of HA2
+low transplacental anti-pertussis immunoglobulin G levels
+High viral RNA levels
+Vic+Chick N1
+2.5 μl IAA
+ImageQuant
+STING
+social distancing
+Salmo trutta
+18 months
+point mutations
+Morbillivirus F GPs
+Imaris
+1 year
+ΔG RS 0
+17
+Half
+morphological and physicochemical
+bradykinin
+influenza viruses
+SinoGenoMax
+flow cytometry
+modern diagnostic and data management techniques
+a cell adhesion molecule
+5 days
+bacterial infections and accidental injuries
+FDG imaging FDG
+synaptotagmin IV
+Hepatitis B
+cc-by
+demyelination
+Epidemiological
+Spectra
+2
+formalin inactivation
+National governments
+Influenza vaccination status
+B2M and PPIA
+mutagenicity
+364
+NF-κB
+70.5%
+biased gene usage and decreased junctional diversity
+Normalized Difference Vegetation Index
+hepatitis C virus
+12% or 15%
+40 μg
+14-20%
+B. pseudomallei
+High flow oxygen therapy
+electronic medical records
+whispovirus
+5S rRNA, tRNA and miRNA
+37.9%
+six
+75%
+vesicular compartments
+cDCs displaying antigen uptake and processing capabilities
+48 h pi
+ARI rate
+lower transepithelial resistance
+µ i
+asterisks
+Acute diarrhoea
+70%
+influenza virus receptor α2,6-linked sialic acid
+50%
+Shannon entropy analysis
+reduced liver damage
+cardiomyocytes
+three
+Ru521
+Sendai virus
+recovered
+false discovery estimation
+Statistical
+charge density
+RlucCVB3
+WHO and CDC
+potential bio-markers of infectious disease
+cisplatin
+mildly hypertrophic
+novel host receptors
+30
+TNF-α
+1× non-essential amino acids solution
+5 0 -nucleotide-tagged primers
+immunization strategies employing E protein alone or subunits of E proteins
+ultra microspectrophotometer
+36
+4%
+bimodal
+8.15%
+the extent of disorder
+HySS
+infected erythrocytes
+reagent chemistry is delivered directly to the test well
+NaCl
+38
+95%
+40%
+cross-reactive
+membrane rafts
+molecular engineering
+40
+sumoylated products
+a set of nodes in which hosts reside
+Negative regulation of SFKs
+dsRNA
+immune
+non-hospitalized SARI
+pocket-binding domain
+chloral hydrate
+FNRG
+FC-ScSED1 cassette
+two-step models
+street location
+two major populations of peptides
+translation from input RNA
+normal distribution
+MegAlign
+neuroinflammation and proinflammatory cytokines
+macrophages
+equilibrium buffer
+Peroxidase-linked assay
+Ifnar1 SA animals
+335
+blood ion levels
+SB-265610
+pT7-SA-Rz plasmid
+diminishes
+diagnostic and therapeutic
+EV associated CD63
+BLAT
+Thirteen
+1807
+simplified
+a significant asymmetric trend
+VersaMax ELISA microplate reader
+Evoked
+Limiting antigen Avidity Enzyme Immuno-Assay
+38
+more than 100 times per year
+IBDV sequences
+independent dataset test, subsampling test, and jackknife test
+multiple steps of the viral life cycle
+GC7 incubation with the NP monomer
+HMGB1-A-BOX
+GeneJuice transfection reagent
+40-60%
+CD11b
+pigs
+amplification bias
+55
+sR R 0
+anaerobic respiration nitrate
+Targeting the reverse transcriptase
+Fever-CT
+Focal adhesion kinase
+RMSDs
+macropinosomes
+positive selection
+HIST1H1B
+promoting ongoing T cell activation and effector responses
+MMTV
+2763
+21 days
+3000 rpm
+increased perivascular recruitment of immune cells
+H7 cross-reactive cells
+dye absorbance
+Model 3
+increased binding avidity
+0.230 mg/ml
+350,000
+outer PCLSR primers
+MLV reverse transcriptase and random primers
+twice
+measured cell percentages with RNA-seq data
+heparinase I
+Scrambled siRNA
+sprawl
+chi-square or Fisher's exact test
+0.158 nm
+induction and in vivo cellular sources of IFN-I
+thymus-derived natural T reg cells
+Two microliters of the RT-PCR product
+JNK protein kinase
+7.8 pg/mL
+cardiorespiratory and laboratory parameters
+800
+Steroids
+tumor suppressor functions
+37
+continued risk assessment, surveillance, and vigilance
+60%
+the study of HIV release and spread
+12
+restoration of the absent dystrophin protein
+vacuolar alteration to subepidermal blisters
+electrostatic binding to nucleic acid
+Kaplan-Merier estimates
+host neutralizing antibodies
+acute and clinically signifi cant deteriorations of unidentifi able cause
+westeast
+Essential CL3 requirements and French/European standards
+224.2 kcal?mol 21
+for their newborn nutrition
+Protein ubiquitination
+ROS
+Herpesvirus saimiri
+10 thousands
+robotic manipulator
+40
+Yale University
+pairwise sequences as independent
+support vector machine and pair-wise sequence similarity
+three
+day 5
+resveratrol dry suspension
+CD4
+legal action
+EBV-mediated B-cell transformation
+overlap very closely
+50%
+1.4 years
+1.72
+tenth
+Mammal sympatry
+Bayesian relaxed clock
+10%
+Parkinson's disease
+167
+gPCs and cPCs
+all forms of life
+fixation monitoring
+Sec23a
+repressible
+weekly
+Gas trapping
+2 h
+microplate reader
+genome-wide evolution events
+archaeal genes
+flavonoids
+reduced symptoms and reduced virus shedding
+CD8+ T cells
+enrichment of eosinophils, basophils and mast cells
+all data from enrolled participants
+pertussis
+viral replication
+PCV evolution
+75%
+high in PRRSV-infected pig herds
+β-actin
+The experience of fear
+nuclear pore interacting protein family
+specific point mutations
+6-17%
+blue
+calculator
+ammonia
+eukaryotic translation elongation factor
+the general susceptible population
+no previous knowledge about distribution or models is needed
+powe rful
+five
+reversible myelosuppression, diarrhoea, nausea and vomiting
+140
+cellular and humoral
+three
+VLPs
+worse overall and recurrence-free survival
+template switching
+IFN-stimulated gene expression
+Twenty-four hours
+Truncated protease L
+HA glycosylation
+CpG and UpA dinucleotides
+a homolog of the pleiotropic regulator AbrB
+1 out of 2,430
+4
+Whenever a previous radiograph was available
+Transcriptome
+Lyme disease
+school-age children
+divided cells
+Combretastatin A4
+toltrazuril
+wire diameter of 0.51 mm
+five
+strong predictors of unfavorable outcome
+1984
+inhibiting tyrosine kinase or mitogen-activated protein kinase
+early warning systems
+amphotericin therapy
+D
+myocarditic
+6 to 8 weeks of age
+Bayesian phylogenetic
+Red deer
+interferon signaling
+time-consuming and costly purification steps
+decreasing clinical severity
+peak load reduction
+260aa
+0.43 months
+epithelial and endothelial cells
+Interaction with viral RNA
+Hsc70
+0.69
+Active and passive cigarette smoking
+PEG concentration
+forward and reverse primers
+the AME
+a midwestern child with fatal CA-MRSA sepsis
+potential scan rate and BS concentration
+knowledge acquisition bottleneck
+Y184F
+TNA
+chromatin binding of PcG proteins
+q
+absorbance at 280 nm in 6M guanidine hydrochloride
+SDS-PAGE
+close to 100%
+Exogenous cGAMP
+type II
+Compound 7e
+the second intron of AGAMOUS
+small molecules
+MQANFLW
+12
+community health workers
+B. tabaci
+omega peptides of ß-Gal
+RSV
+logarithmic width
+missense mutations
+AD
+JTT and variable rates
+S-TuD
+high ratio of seeing a doctor
+deliberate
+IL-1β
+7.59%
+three
+Linear Quantitative Profiling Method
+biomedical
+Positive or negative correlations
+40 minutes
+adverse effects on the gastrointestinal tract
+vegetables and bird eggs
+Ciprofloxacin
+experimental methods
+Zen
+amino acid composition, binary profile
+kissing dimers
+HBoV
+Animal Health Service, Deventer, The Netherlands
+176
+time lag in tracing for casual contacts
+66%
+Camel iPSCs
+quasispecies diversity
+higher total IgM and total IgG concentrations
+bornavirus infection
+Total RNA
+187,003
+stigmatisation and discrimination or material or economic harms
+Group 4 and 6
+hepatitis C
+The Web Interface
+ERK1/2 signaling
+5-10-fold
+23
+bicinchoninic acid
+PseAAC
+log
+GraphPad Prism 5
+pertussis toxin
+MDDCs
+15-30 min
+sick-days
+separately
+13%
+TNF-α
+SFTSV
+None
+positive
+multi-group SEM
+three
+rearrangement of the IgH locus
+Breast feeding
+proteins
+X-tremeGENE HP DNA transfection reagent
+56%
+Obtaining recombinant renalase protein and preparation of monoclonal antibodies
+centralized mitigation
+Q-TOF hybrid
+80%
+1960s
+safety
+to assess construct validity, reliability and acceptability
+r j
+IL-6
+late November, 2009
+gene expression changes
+HIF-1
+three
+plasma osmolality as well as blood volume and pressure
+kinetic data for GMP incorporation
+Glial fibrillary acidic protein
+biotinylated RT primers
+116
+10-45%
+GraphPad Prism
+LMP1 amino acid residues
+B cell
+Lorisidae
+Non-English articles
+GraphPad Prism
+per-protocol
+F. Fontana
+acute mesenteric ischemia
+alignments
+polymin P
+Firmicutes and Proteobacteria
+0.05
+> 80%
+Chemokines
+Protease inhibitor
+4
+Unit-length HBV linear DNA
+Lys48-linked polyubiquitylated GFP
+six
+CMV and EBV
+Algorithm 3
+5%-20%
+pi
+2000
+anterior mediastinal mass
+WNV
+chronic inflammation, respiratory infections, oxidative stress, and ART
+ANOVA
+Oxford Nanopore Technologies
+cytotolytic and/or noncytolytic mechanisms
+CARD9
+493
+Dr. Emanuel Goldman
+50%
+eight
+ACE2/ACE activity
+awk
+NADPH cytochrome P450 reductase
+VCSM13 interference-resistant helper phage
+no significant change in lung ANDV titers
+44 %
+conditions necessary for viral persistence
+splice correction-mediated up regulation of reporter gene activity
+negligent harm and non-negligent harm
+ESPLINE Influenza A&B-N and BD Directigen Flu A
+TSR models
+mir-21 and NLRP3 inflammasome
+fermentation of undigested carbohydrates by intestinal microflora
+Univariate
+localisation of active adhesion components
+PCV-2, PRRSV, PRV and SIV
+human or porcine donor trachea or bronchi
+acute respiratory distress syndrome
+1,394
+1968
+flow-limited uptake of donepezil
+50%
+Bergmann glia and Purkinje cells
+SPSS 17.0
+.4,000
+223,336
+5 EU/kg body weight/dose
+disease-free survival
+univariate analyses
+176
+21%
+Primers MA1197, MA1198, and MA1199
+IFN
+15
+six
+Facility for Biotechnology Resources of FDA/ CBER
+56
+11
+severely impaired cardiac function
+60%
+remote homology detection of proteins
+WNV replication, viremia, and peripheral spread
+public healthcare professionals
+650 nm
+70
+smaller
+genes from both North American and Eurasian swine lineages
+disease severity
+IRE1α depletion
+two
+by regulating components of their catalytic environment
+IRES activity
+sarcoendoplasmic reticulum Ca-ATPase
+not significant
+species-level identification
+efficient processing and secretion
+codons with the relative synonymous frequency <0.2
+reverse genetics
+timing and protein turnover
+Triathler TM multilabel tester
+R 0
+porcine
+CSF cell count and with CSF IgG index
+expression plasmids
+guinea pig sera against FMDV
+40-95%
+non-permissive or abortive infection
+defining the functional units of living organisms
+cc-by
+rVV-N25
+single-stranded RNA viruses
+interaction of cleaved L2 with an unknown intracellular receptor
+50%
+IgG Fc
+Ly6c and Ccr2
+SVM regression model
+two
+IL-10-expressing neutrophils
+host-receptor interactions
+mAb therapy
+one week
+pathological
+autophagy
+the sequence of native antigen
+Inclusiveness
+ρ *
+2014
+the distance of the corresponding data point from the restrain curve
+Three
+eight
+southern China
+3
+render patients asymptomatic
+1,793
+H 2 O
+methyltransferase, acetyltransferase and IL-10
+Acute kidney injury
+cells of the innate immune system
+OligoAnalyzer
+implemented the most aggressive and sustained community measures
+2020
+triangle on the 5 0 of the primer
+21 days
+m edges are formed
+Live-cell imaging
+Cochrane Risk of Bias tool
+lentogenic, mesogenic, and velogenic
+4 days
+second codon AT preference
+years old
+Kamlangdee et al
+green and orange
+Astra Zeneca Research Collection
+group 1B
+qRT-PCR
+a seasonal pattern
+stigmatisation
+prior definition of nonrecombining loci in the genome
+Allergenicity
+the sum of ordinal responses
+extraction from whole blood
+14.6 h
+the extent of an animal's range
+expansion of deleterious, nonsynonymous mutations
+France
+to maintain maximum efficiency in translation of viral gene products
+negative control
+Twentyfive
+genetic mutation
+cancer cell
+to increase section adherence to the slide
+mutation pressure
+multivalent
+280uC
+organisms
+transient CAL
+13.07 ± 2.95 days
+Supernatants
+R rs
+site-directed mutagenesis of our overexpression vectors
+making the HSES diagnosis
+a specificity index
+NTM diseases
+The respiratory database
+10 s
+vaccination history
+The chi square test
+placental Hofbauer cells
+influenza
+international recommendations on ventilation associated pneumonia prevention
+$252,851
+IFITM-mediated inhibition of IAV infection
+compound 14 to disrupt Hsp27/eIF4E interaction
+177
+pentamidine
+EBV
+patchouli alcohol
+both directly or indirectly
+1.06, 1.36 and 0.94 Å
+February 17, 2010
+CTMCs
+pancreatic
+normalizing circulating RAS activities
+NS1
+Comparison of means using student's t test
+vulnerable groups and hardto-reach populations
+paracrine factors
+DC-SIGN
+2 weeks
+Sixty-four
+18
+nsP3
+short peptides
+LOXL2
+nosocomial infection
+Macroglobulin complement related
+limitations in NGS technologies
+consensus
+IBV
+fluorescence
+standard operating procedures and guidance documents
+rat IgG
+a much larger pool of individuals
+HP and LP
+recombination-primed replication
+neutralizing antibodies
+24 hours
+15%
+ribavirin and Oseltamivir
+Figure 3A
+sCJD, ALS, and some sRPNDds
+mucosal immunity
+Cre and FLP
+Hydrophobic interactions
+chest
+Antigenic shift or mutation in the virus
+stable expression of mCLDN6 and hCD46
+biosignatures
+quantitative real-time polymerase chain reaction
+terminal gal-α-Neu5Gc
+14 days
+pET26b-CSFV-NS5B
+Salmonella Typhimurium
+Bonferroni
+Nrf2 activation
+cancer cells in the host
+ImageJ software
+Δt = 1 hour
+a meta-analysis
+Focal adhesions
+assembly sites
+a multimerization domain
+general hospital infection control policies
+searching strategies
+Twenty-two
+SREBP-1c and ACCα
+Nitric oxide
+fomites warmed to human body core temperature
+cross-reactive memory B cells
+nearly identical clustering
+Epithelial injury
+Peripheral blood
+Gaussian curvature
+gel-electrophoresis
+gp-340
+sizeable bias
+behavior concerns
+Experts' evidence
+14 days
+coefficient
+100 fg L. monocytogenes DNA template per reaction
+non-mammals
+Fomitopsis betulina
+13.4 ± 0.8 min
+a large population
+Relative adrenal insufficiency
+AP2Ls
+oranges
+EI
+M2, NP, NA, and conserved regions of HA
+π C
+Illumina sequencing adapters and barcodes
+CDRs
+AUG
+13
+promotes lipogenesis in the liver
+10%
+CuFi-8 air-liquid interphase cell cultures
+genes
+rabbit anti-PUMA antibodies
+Anemia
+population growth and movement
+MignovillardY02
+10 to 80 nm
+global OHQoL
+42
+hemorrhaging
+different concentrations /ml)
+50,000
+primer annealing mixture
+5.78-7.27 photons/s
+rebound phenomena at treatment discontinuation
+Ed395 and the deglycosylated form
+anhydrous Na 2 SO 4
+occurrence
+14 440
++886 4 22853487
+13
+combined mean/median lung inflammatory scores
+8-14
+22
+renoprotective effect nor cost-saving effect
+Oddysey Sa Infrared Imaging System
+endocrine
+321%
+27uC
+33
+the probability of drawing an edge between two arbitrary vertices
+IFN-λ
+day 7
+all of the added PEI interacts with oligo DNA probes
+Four to five
+compositional constraints under mutational pressure and natural selection
+complicated
+Streptavidin-coated magnetic beads
+proteomic
+Recombinant CypA
+RPMI-1640
+publication and dissemination of scripts, guidelines and scientific advice
+appropriately high levels of intracellular gene expression
+NA
+Env fusion activation
+ORF1p
+223
+19%
+14 continuous days
+TRAFs
+Chimera
+diagnostic sensitivity, specificity and efficiency
+Single-cycle kinetics
+audio recorders and field notes
+pathogenicity
+6.3 ± 3.7 days
+nine
+Site-directed mutagenesis and computational homology modeling
+enormous structural changes
+diabetic
+5 µg/mL
+E45 and E52
+murine macrophage cell line J774.1
+alpha-tocopherol
+inverted dT
+significant alterations in signalling pathways
+HDAC5
+23
+bl2seq program
+eleven
+bacteria, viruses, and protozoa
+animal brains
+positive for neutralizing antibody
+Respiratory epithelial
+moderated-t statistics
+integrin b3
+vesicular transfer between these compartments
+seven
+P and M2-1
+germ-line cells
+all species
+20%
+qualitative or at most semi-quantitative analysis
+Sabin I
+viruses, bacteria, fungi, and parasites
+Whether someone is choosing action for its own sake
+Annexin V-FITC and PI
+different amplification reactions
+convergent va-lidity
+mammalian myelin CNPase
+considerable differences in cellular adaptive immune parameters
+627,000
+conspiracist ideation
+protein clustering at postsynaptic sites
+Naso-pharyngeal swabs
+mAb murononab
+Seven
+Read length distributions
+Alternative forms of non-informative prior distribution
+43%
+Hsc70
+Negative-sense
+four
+Premix Ex Taq
+60 ml of 1:20 diluted sera
+human-mediated amplification of exotic milkweed
+LysoTracker Red DND-99
+panic attacks and delusions
+four
+12%
+suicide
+Mitochondrial ToxGlo Assay
+the TTX
+HDF5
+IFNλ4p179
+to accommodate the large rigid structure that is being forced on the space
+C. pipiens
+suppression
+influenza vaccines
+IL-10 and TGF-1
+NAs
+SAA
+Activation of the P2X7r
+rMVA-GFP + cells
+Peak 2
+self-efficacy and work related resilience
+two-step PCR
+Viral load
+herpes and dengue
+50%
+Information Theory
+arrows
+472 nucleotides
+ICD-9 577.0
+Luciferase expression
+limiting dilution assay
+receptivity, proximity, fragmentation, and lack of shared understanding
+8%
+GM3
+insertion and deletion probes
+NAC, trolox and PDTC
+non-specific changes
+FAPs
+a suitable correction procedure
+A neutrality plot
+nsP2 and nsP3
+substantial
+1918
+Bradford assay
+Akabane virus
+PRRSV
+the head kidney
+four
+orange, light blue, dark blue, and maroon
+neuroendocrine tumor
+Figure S11
+poly-ubiquitin chains
+immune responses
+cell shrinking, cell membrane blebbing and chromatin condensation
+MTT assay
+research, authorship, and/or publication
+planning, monitoring and evaluation tool
+cough
+mathematical models
+disease, chronic renal failure and any chronic inflammatory disease
+Purinosomes and glutamine synthetase foci
+severe infections
+pNL4-3.luc
+IAPV IGR IRES +1 frame translation
+Vanderbilt Children's Hospital
+macrophages, dendritic cells and microglia
+DMEM
+Prion diseases
+63%
+pHIV-1 NL4-3
+anti-inflammatory
+therapy with cidofovir
+increases neuronal excitability
+JF693612-23
+0.2
+Viral co-infections
+Purifying Selection
+Nidus
+mass spectrometry
+RV-induced acute diarrhea
+Michael Whitt
+fluorescence resonance energy transfer
+cytotoxic
+20.3%
+4.23 mM
+organotypic raft culture
+immunofluorescence
+National Guide for the Care and Use of Laboratory Animals
+engagement of the RNA sensor RIG-I
+Morpheus
+furamidine
+NCBI database
+Two tailed student t-test
+The procedure for the generation of these peptides
+small nucleolar RNAs and ribosomal RNAs
+Electricity
+Aβ
+alamarBlue viability assay
+cancer
+more protein abundance in T0 or 8 h versus baseline
+4.13%
+Gene therapy
+79
+pathway
+WH and AA
+RING domain
+multivariate linear regression analysis
+reducing viral load through anti-viral intervention
+Northern blot analysis
+HRV-16 nt 626-1045
+abundant numbers of antigen positive cells
+psychiatric taxonomy
+CD8 T cells
+N40
+SurveyTracker
+S1P-mediated cleavage of GP-C
+nsp1
+microglial
+digestive vacuole
+findings from the subjective perception of risk
+82
+extreme plasticity
+urban-based policies and programs
+greater protection of the target RNA against benzonase activity
+seasonal or pandemic outbreaks
+Saudi Arabia
+three
+CD 8+
+Vaccination
+NLM controlled vocabulary
+science communication
+Poland and Belgium
+eIF3f
+Mara Sullivan
+Neutrophils
+6.5 and 3
+The ability to use less pure CaO
+Mueller-Hinton broth
+antibody responses
+inflammatory
+Chikungunya
+rates of illness
+80%
+ZIKV infection
+quarantining interventions
+2010
+Innate immunity
+≈300 million doses
+0.685 to 0.909
+paths through a background physical interaction network
+targeted technical recommendations
+DNA titration curves
+U937 cells
+Stockpiling by the worried well
+one
+Cancer
+extracellular DAMPs
+four
+South Africa
+SPSS 16.0
+NETosis
+twice daily
+biomedicine
+FASTA
+v-crk sarcoma virus CT10
+preventing efficient binding to the protein complex
+specific regions of the brain
+64%
+DNA damage
+respiratory failure, sensorial disturbances, and petechiae
+rapid lateral flow test
+disulfide bonds
+differences in phagosome acidification
+>9000 J/L
+Exposure to successive drift mutants
+broadly overlapping
+warming-induced stress
+much higher
+Amino acid substitutions
+stable
+hubs
+Mint3 depletion
+Sepsis
+36-through 59-month
+interaction tests
+membrane-free
+fluorescence
+rectally
+a transient external force
+100%
+membrane-bound ribosomes
+100ng/well sRecE in TBS buffer
+taxonomy
+PTMs
+16
+10 years
+entrapped M2e-PP gradually
+Streptococcus pneumoniae
+1 × 10 −15 M
+Figure 4A
+two
+deterministic model
+co-localization with clathrin
+yellow
+20 μl
+programmed ribosomal frameshifting
+medical technical care
+WorldClim database
+superior microscopic imaging
+A nonessential viral gene
+valid values for parameters governing outbreak dynamics
+IL-10 and IL-15
+oxygen and energy
+7-9
+coverage of health topics
+Error bars of frameshifting efficiency
+Hemagglutination of erythrocytes
+cc-by
+liver-resident NK cells
+virus protection
+trophozoites
+DENV
+pro-inflammatory
+the value associated with the highest sum of sensitivity and specificity
+covalent
+3.55 years
+liver CD8+ T cells
+ISGylation
+NPs
+Twitter
+Titanium dioxide
+anti-HIV
+0Á25
+144
+two
+− 1
+5.6 per cent
+sequencing of the ITS region of rDNA
+Ribavirin
+ELISA
+neutralized SFTSV
+10-25%
+Coding sequences and the whole genome of bovine muscle proteins
+A thermal-cycler
+later peaks tend to be smaller and more variable than earlier ones
+Adhesion
+30%
+9 years
+2 d
+3-hydroxyphthalic
+DNase-like
+effective contact with the pathogen
+PEG linkers
+PMLI to PMLVIIb
+pyroptosis
+LLTTNKD to HIV gp120
+80-160 IU/mg
+concentration-dependent
+fusogenic
+TOR
+incorporated the genome
+454
+86.5%
+enhanced pathophysiology
+autoreactive B and T
+nongenomic
+host switching events
+outside the VAS
+Transmission hotspot, transmission foci
+Serum-free
+3
+longer
+Cuffquant
+neuronal cell death
+R. B. T.
+nurses and ambulance staff
+a split-plot design of independent experiments
+Th1 cells
+The radiographic score
+previously raised concerns
+3%
+three
+40%
+enteritis, pneumonia, polioencephalomyelitis and reproductive disorders
+156 CFU mL −1
+genotoxicity
+four
+high transmission in the acute stage of HIV infection
+Twenty-four hours
+Detection limit
+5 µL of eluate
+plant species, tissue types and culture conditions
+Fluorescence-activated droplet sorting
+indicators related to health, water, and sanitation
+myelitis and possibly encephalitis
+recombinant ZIKV-Env protein
+216
+2008
+10 4 RNA copies/ mL
+$15 million
+binding of AtRH5 to the RIII REN
+species are more likely to be polymorphic
+the binding of selectin P
+enriched
+vulnerable and destitute populations
+stem-loop tertiary interactions
+M9
+55% to 85%
+hydrogen
+2,000,000
+EBV
+classical SIR model
+Pneumonia and meningitis
+commensal
+T
+well-defined borderline
+Further research
+3
+4°C
+to ignore these issues
+Rotavirus vaccination
+2018
+pB12VG1 and pB3BG29
+blood supply
+B cells
+Severe cases of influenza in pregnant women
+ratios of oligo-dT:random hexamer-primed expression
+manufacturing of viral vaccines
+AhR
+Epitope mapping
+4 h
+AUF1
+high titers of virus
+Ion Ampliseq Designer
+female gender
+flow cytometric
+Department of Statistics
+Het.-heterogeneity
+0.05 mg/ml
+several nuclear receptor ligands
+3
+CTF RNA features
+bronchoalveolar lavage
+biological events follow each other sequentially
+2
+FADS
+Blood samples
+50-100 million
+15 years
+respiratory syncytial virus and parainfluenza virus
+two-thirds
+IFN
+January to September 2008
+PaDEL software
+80%
+48 hours
+Robert Tigerstedt
+the expression of a luciferase reporter gene
+through a graded series of ethanol and water
+PhosphorImager
+25%
+Transgenic mice
+10%
+Shannon entropy
+Endotoxemia
+$625
+49 h
+Mast cells
+RNA
+human immunodeficiency virus -1-associated morbidity and mortality
+Fisher method
+plasmids and bacterial arti fi cial chromosomes
+the profile of each protein sequence
+18
+0.2762 and 0.1939
+CD38
+Mitomycin C
+enveloped and nonenveloped
+PSG1 and FLAG-Fc
+three
+93-102%
+autoimmunopathies
+5%
+emergence of intronless IFNs
+neuropathy and nephropathy
+two
+higher
+hamster's sera diluted in 1% BSA
+virus neutralization
+Evaluation
+Immunological tolerance
+Mechanical ventilation
+RNA-binding proteins
+via a simple multinomial expression
+four
+initial signs and symptoms
+virus-satellite associations
+viral
+48%
+ICNARC database
+less
+Brosnihan
+as a fraction of the endpoint area occupied by cells over the baseline scratch area
+physiological temperatures
+by passing the information down the tree from the root
+Parasites
+ISGs
+24 of 28
+Paolo Freire
+5
+phenol/chloroform extraction and column filtration
+Tracing and quarantine
+lipid membrane fusion and infection with RNA viruses
+TLR
+all mediators
+CCR5D32
+4%
+bacterial-induced proteins
+weaning
+Venn diagramming functional annotation, hierarchical clustering, and pathway enrichment
+0.96
+10%
+contact diaries
+3 h
+tumor regression
+10
+tumor immunity
+negatively regulated
+13%
+greater than 4 hours
+pyridylimidazopyridine derivatives
+electric field and liquid flow rate
+Hepatitis B
+three
+swine flu
+proliferation and apoptosis
+total number of viral reads
+analyses
+lineages
+NG2 1 OP cells
+manidipine resistance
+functional gene diversity
+30 min
+the data from surveillance system j at time t
+periodic boundary conditions
+October 2009
+severe thrombocytopaenia
+detection
+formaldehyde
+67%
+Corporate managers
+respiratory tissue samples
+lymphocytes
+a single 33 mg/kg loading dose
+oneway
+DNA vaccination
+Computer software
+21
+Yersinia pestis
+0.8%
+Optimal case definitions
+Bacterial sepsis
+claudin 1 mRNA
+1 mM to 20 mM
+31
+The relationship between the biologic activity and molecular structure
+Gram-staining and observation of cell morphology
+Drug-resistant bacteria
+novel therapeutics
+alveolar
+HOCl
+A226V mutation
+IL21
+pathogen spread
+12
+a midiprep
+undetectable infection
+non-integrating, transiently expressing vectors
+SAa2-6Gal glycans
+Ang II
+between 1989 and 1993
+helical
+activating antigen-presenting cells of the innate immune system
+mutations at position taneously assigned to two distinct amino acids
+differential intracellular events
+a national GIS database
+polyvinylidene difluoride membrane
+X33 cells
+human IAV cases
+All the bases above the given threshold
+NF-kB
+RNeasy Mini Kit
+data
+Asthma or COPD
+HEV-specific PCR, sequencing and phylogenetic analysis
+meningeal
+One hundred nineteen
+PRNT
+EV71 and CV-A16
+replication of the influenza virus
+binding affinity, processivity and frameshift fidelity
+Osteonectin
+liposomes
+60%
+0.51
+95
+K562 human leukemia cells
+to assess their MLST types
+K TI :K TE ratio
+Public Health Emergency of International Concern
+The following equation
+autism, multiple sclerosis and various neurological syndromes
+Protein-templated reactions
+in biological triplicate
+Macrophages
+4--1--1-butanone
+two
+Flight traffic
+enhance the folding and assembly of down-stream target proteins
+Schlesinger group
+TPM2uf+I+G model
+logistic regression modeling
+Vietnam
+three
+MEDI8852
+1983
+a guide to 15
+14
+25%
+a consensus narrative
+limiting the extent of outbreaks and eliminating the infection
+PhysiScore
+inoculation
+transfer learning
+o5%
+renal tubular necrosis/apoptosis and inflammatory responses
+coat protein and three movement proteins
+27,534
+Rhodaminelabeled
+supernatant
+Streptococcus pneumoniae
+eleven
+changes in tropism or attenuation
+K119 ubiquitinated H2A
+very favorable
+intracranial
+CRISPs
+L-amino acid-oxidase1
+respiratory tract epithelium
+bias in capture techniques
+30min
+Magnisort human CD14 positive selection kit
+weak
+CBS
+mental reward
+accuracy
+Glucose-6-Phosphate Dehydrogenase deficiency
+27-nt Peptide-siRNA
+the best performing caller
+35,151
+Indirect ELISA assay
+PaO 2 /FIO 2
+FimA
+0.13-0.15 M
+RNA polymerase II-dependent promoters
+lnc-ISG15 and ISR2
+three
+28
+four
+86%
+Gaussian priors
+accuracy, precision, recall, G-means and Matthew's
+bicistronic mRNAs
+Mean ± SEM
+immune cells
+tobacco mosaic tobamovirus
+10-day
+Informed consents
+Timeliness and completeness
+TM-replacement
+41
+5
+limiting viral protease activity significantly hinders virus infection
+HPRT
+Clusters
+Enteric infections
+vaccines and antivirals
+mechanical pain hypersensitivity
+rotary evaporator
+mutation pressure
+2.8 million
+free hemoglobin
+3
+9102
+young people's wellbeing
+32
+TransIT-LT1
+immune response
+detailed data
+Hypersensitivity pneumonitis
+TGF-β and IL-10
+two novel nucleotides
+250,000
+variation
+27
+weeks or years
+3 out of 4
+pseudoknot
+cleavage
+early expansion of cd T cells
+Purified cDNA
+activate similar components of the JAK-STAT pathways
+heteromolecular
+nonparametric Friedman test
+linkage-specificity
+CSFV infection and proliferation
+serum samples
+yeast lifespan
+8, 121, and 392
+80%
+hemocytometer
+p38 MAPK
+#2089 and #3788
+Western blot
+ligands for multiple TLRs
+168 ± 56 and 215 ± 88
+two interrupted absorbable sutures
+Paraffin-embedded tissues
+weather changes
+1 January 2020
+1918
+IAV
+MDR-TB and low serum levels of antituberculosis drugs
+113
+24 hours
+DMSO
+a large repertoire of PRRs
+8
+DNA sequencing
+mass casualty incident
+septic shock and multiple organ failure
+an ion source, the mass analyzer, and an ion detection system
+Relative risks and weighted mean differences with 95% confidence intervals
+lymphoid and inflammatory tissue
+Sierra Leone
+18 candidate gene
+GO term
+234
+trauma, cancer, multiple comorbidities, and invasive device use
+January 21, 2020
+big data
+220
+Plasmid DNA
+5%
+Simplot
+host movement
+sequence-specific majorgroove triplex formation
+A second tRNA
+Descriptive statistics
+CapoNPV
+72 h
+qRT-PCR
+50ul packed volume of Protein G sepharose beads
+means ± SD of three independent experiments
+glycan cap and mucin-like domains
+in vitro transcription
+51.14557
+suicide prevention activities
+five
+80-83 nt
+respiratory compliance
+Thucydides
+presence of infectious virus
+IFN
+Public health surveillance and clinical surveillance
+kinetics
+environmental factors and inherited genetic predisposition
+Trigger factor chaperone tig
+TYLCMAV
+90%
+48 h
+three
+differences
+Text S1
+severe renal injury
+protein degradation
+6.3%
+drops rapidly
+39,000
+HCV modified membranes
+UUG and GUG
+The protocol
+Beyotime Institute of Biotechnology
+biological properties of cell populations
+BigDye Terminator Cycle Sequencing Kit
+they can be very efficiently transfected with plasmid DNA
+microwave selectivity heating
+loss or reduced expression of the transgenic insert
+host taxonomic classification and taxonomic rearrangements
+Raf, VEGFR, and PDGFR
+initiate innate or adaptive immunity
+intraplaque vascularization
+applications
+Chlorogenic acid
+wavelet analysis
+unmet medical needs
+73
+glycan identification or functional studies
+a lack of RNA editing activities
+10.1186/s40779-020-0233-6
+immunostaining for surface HA protein
+38-52%
+cc-by
+ribonuclease H
+Perforin
+acute myeloid leukemia
+L. monocytogenes
+death of the host
+Throat swabs
+30% to 40%
+the slippery site
+11
+367
+Total endospore concentrations
+PoS = PoA
+8
+postoperative length of stay
+de novo synthesized viral genomic DNA
+Partek analysis of variance tools
+PaLoc genes
+13
+identical viral sequences
+Five to 10 mL
+sCMV-fluc
+codon CUG
+hemodynamic changes
+networks
+hybrid-type N-glycans
+over 2000
+mAb targets
+12
+nasal epithelium
+gene silencing
+seed lysates
+mAbs 40G1 and 2D8
+three
+HK
+Four
+1462
+d
+Translational sciences
+inferior resolution
+NMA
+HA
+37
+30
+Idiopathic pulmonary fibrosis
+secretory membrane transport
+6%
+C to B
+MAPK
+0.9
+CXCL16
+12.5 µg/mL
+TMA
+A1
+C429
+10,000
+mDC cells
+Eight
+cellulose synthase
+airflow
+multiple existing gene and protein annotations
+Schistosomiasis
+elevated ground-state fluorescence
+developing, skilled and expert
+Pentobarbital-Natrium
+composition vector
+immunoreactive cells
+pneumonia
+78%
+sequence evolutionary patterns
+12,470
+9.4 days
+ACT and TUBB
+Supernatant
+putrescine and urea
+ssDNA
+tissue-drift
+virus titer
+non-evaporating collection media
+bronchiecstasis
+agents
+immunogenicity of NS1-truncated LAIV candidates
+β-actin gene
+2009-2010
+relative values
+450 mg
+tens of thousands
+to prevent bleeding after transplantation
+a dedicated group
+consensus shuffling and coincidence filtering protocols
+tRNA adaptation indexes
+Acetylation
+how much the terms of different genetic variants are overlapping
+5.42 ± 0.11 log CFU/g
+GPS
+PPMO
+antiviral
+ammonium sulfate precipitation and column chromatography
+World Health Organization
+HIV-1
+Sex
+Relatively little
+20 U/ml recombinant human IL-2
+intracardiac puncture
+autoimmunity
+significant sequence similarity
+AMD
+RDP4 Beta 4.97
+immunology and microbiology
+competing
+activating and maintaining TRegs
+H7 protein
+ER stress
+changes in 25S rRNA structure
+B and T cellular responses
+strand β4
+American Type Culture Collection
+changes in trading and commercial policies
+1.2 Â 10 6 /mol
+histological
+ERK activation
+multivariable models
+30 min
+pertussis and syphilis
+30%-purified or gradient-purified bacteria
+14%
+entry by filoviruses
+when they find a uni-
+DNA extraction kit
+SMS and FE
+sinus tachycardia with non-specific ST-T wave changes
+monocyte polarization
+distribution of these investigational products and education on their proper use
+Vitek2 compact
+lower viral loads
+translocates from the nucleus to the cytoplasm of the cell
+translation elongation factors
+M
+10%
+Motif E
+EMCV
+molecular mimicry
+α-2,6 linkage
+consumption coagulopathies
+H9N2-subtype
+fibronectin
+3.1 and 1.2 years
+to prevent or mimic phosphorylation
+L, C, and G
+Imaris
+TU212 and HEP-2
+α-PfSRA P3
+anti-inflammatory
+Runx2
+low-power micropumps
+XKB may be a promising agent for lowering of blood lipids
+Glycyrrhizin
+medium or water
+δ 13 C
+Hp
+lethal infection with influenza virus
+Phosphorylation of STAT1 and STAT2
+Analysis of HCV intrahost genetic variation
+14 to 17 kb
+innate immune defenses
+absolute quantification
+respiratory viruses and some bacteria
+estimation error
+the ts and ca phenotype
+25%
+DENV
+amphiregulin
+150 mM to 1M NaCl
+6 hours
+severe complications and even death
+I O based on justified initial infected population fraction
+19
+16
+SIVmac239
+OVA-HEL
+Tertiary interactions between underlined residues
+people are sufficiently aware of the infection to change their behaviour
+continuous medical education
+knockdown of IFITM3
+ISFVs
+PV-infected WT cells
+4.9%
+inhibits EV71 replication
+RPE-1 cells
+endoplasmic reticulum stress
+seven
+Student's
+DU156WT
+viral infection inhibition
+fixed length feature vectors
+Western blotting
+WGASA
+cytoplasmic
+30 sec
+Codon usage bias
+Twenty
+25%
+diseased lungs
+PF-C cells
+DIZE
+southwestern Minnesota and eastern South Dakota
+influenza nucleoprotein antigen positive cells
+immunohistochemical
+TBD
+Table 2
+COVID-19
+θ
+GAPDH
+Whole blood
+R55
+≥60 days
+ISGF3
+18
+proteasome
+nutrition
+Alcohol
+Isolated monocytes and macrophages
+WP disease signs
+a density of infected individuals
+89
+Sauls
+a remarkable overlap
+25 mM NaCl
+65uC
+random, thin collagen fibers with blood vessels
+viral replication
+WHO
+80S
+active during the period
+2004
+12
+fluorescent microscope or confocal microscope
+her parents
+week 3
+Takeda Science Foundation
+FASTA format sequences
+spinal muscular atrophy
+5
+47
+the large train
+breast cancer
+three
+6.1 AE 0.2%
+pyrimidopyridazine scaffold
+54.6%
+how the test statistic is considerably affected
+89 days
+Enrolment, follow-up and clinical event data
+herbicide tolerance
+seven
+0 to 1
+4-10%
+Tyr402
+Systemic immune system dysregulation
+11
+Functions of glycosylation
+BMCMC methods
+elemental
+Ligand binding
+statistical
+between 28 days to 12 years
+Hepatitis C virus infection
+Scavenging of oxidative stress
+43S PIC
+GBF1
+a meta-analysis
+light blue
+mineralocorticoid
+greater stability
+DP96R
+Dengue
+therapeutic
+several orders of magnitude
+privacy
+over 5000
+bronchoconstriction
+Helicobacter pylori
+ClustalX
+0.24 s −1
+DCs
+RNA transcripts
+lyses the infected tumor
+text mining
+gene transfer studies
+hybridization prediction algorithms
+30 of 47
+eosinophil cationic protein
+cascade invasive reaction and gold nanoparticle hybridization
+Statistical
+OsSGT1
+0.5%
+they are based on a relatively limited number of viruses
+35%
+cough and fever
+6.2%
+simplistic models
+Forty-nine
+One hundred and ninety-nine
+prospective controlled clinical trials
+viral fusion
+Collect and share experiences of Arctic stakeholders
+five
+11
+decreases
+30
+Limited T-dependent recognition
+completely degraded
+CDH UK
+Image J software version 1.48
+50%
+Alkhurma virus
+no cases will ever leave the source city
+prime-boost regimen
+random values
+hypoxia-regulated targets
+enrichment
+A supporting workflow
+12
+Two to four
+24
+gathering the data, designing the article, and discussing and editing the manuscript
+nonspecific
+Translation
+Model 6230B time-of-flight mass spectrometer
+RNA extraction
+All three segments encoding the different reporter genes
+infection models
+1943
+pluripotent
+40%
+Descriptive statistics
+SEC14L2
+development of left ventricular dysfunction
+outcomes
+ER proteins
+different stimulation of the immune system
+CD33
+1
+2H5 and m1Q
+28.39 μM
+2,321
+waning immunity
+eIF2 signaling
+GlcNAc
+correlation between some variables
+2 terabytes
+10% serum
+written protocols
+cell spreading
+Cytation 5 fluorescent
+leptospirosis
+MRSA 63718
+shape, size, number, composition, and disassembly process
+DNA
+antiviral Treatment T and Hospitalization H
+viperin
+C
+15 min
+24 h
+human VH domains
+multivariate
+absorbance
+928
+Blue
+nuclear factor of activated T cells
+9%
+Particle size and count data
+X_XXY_YYZ
+authorized users
+donor cells
+genetic relatedness
+nonstructural proteins 1 and 2 of human respiratory syncytial virus
+hidden Markov model
+ANOVA
+Angiogenesis
+31%
+Pregnant staff
+Triton X-100
+permutation tests and CV-ANOVA
+measureable loss of activated donor CD4 T cells
+65-69 years
+6
+Anionic lipids
+ADP-ribosylation
+20%
+43.6%
+repeating 7-day's CPI data
+cystine loop FP motif
+good disinfection of the floor
+45 min
+Pasteur Institute
+a significant decrease in binding activity
+Dectin-2 promotor
+RNA structure probing experiments
+no clinical signs or viraemia
+5
+a study that explored the attitudes and knowledge about NMC
+NSC-34 cells
+Decreases in B-ALP
+SUMO-1
+degree of an infected population
+2%
+geNorm
+Extrinsic
+power law dispersal model
+maximum-likelihood estimation
+Ginsenoside Rb1
+viral RNA
+sends electromagnetic backpropagated signals to the mobile phone carried with the person
+scanning electron
+40
+96-well plates
+HIV-1 Gag
+predictive modelling
+ability of influenza to spread by airborne transmission
+Cell Counting Kit-8
+ten
+invasion of vascular endothelial cells
+BS-RNase
+Alveolitis at BAL examination
+specificity and sensitivity levels around 70%
+innate
+~two-fold
+perfusion
+four
+higher RT efficiency and its greater stimulatory effect
+milrinone
+R 0
+40-50%
+DNA binding and transcriptional regulation
+Fasting times
+gene functional class
+expensive electrophoresis equipment and gel imaging systems
+kappa statistic
+9 August to 7 October 2014
+common ancestry
+The polymerase protein family
+Salicylaldehyde
+galT
+make metadata more easily findable
+blood
+Fcc receptors binding
+multimembrane spanning proteins
+80%
+World Health Organization
+6
+41
+RNA levels
+primary transmission vectors
+rats
+60%
+Relevance scores
+Development of an ethical and decision-making framework
+serum
+cAMP
+MoTra Prim and MoSp Prim cells
+normal distributions
+tick flaviviral infection
+equal to
+35%
+trait expression post cell entry
+alkylated hydrocarbons
+4.1
+48.26%
+92%
+proximity to
+classical expectations
+DENV-1
+MTT analysis
+27.3%
+fluorescence
+probable PTB
+5 min
+MAPKs activation
+two well-supported breakpoints
+RT-qPCR
+170
+The interaction of PrP C to PrP Sc
+twice as fast
+Georgia
+cytotoxicity
+256
+basic hygiene practices
+over 70
+A549 cells
+hemorrhagic stroke
+cell apoptosis
+OVA
+March 11, 2020
+serial 10-fold synthetic mimics dilutions
+MUSCLE
+Five
+reporting of patient data
+Negative and positive air pressure
+healthy
+IFN-γ
+Influenza Endpoint Case Report Form
+the ability for sorting target droplets simultaneous and continuously in real-time
+biofuels research and bioremediation
+buffer P0
+ROC curves
+survival and virulence genes
+22%
+Site-directed mutagenesis
+Antigen experienced
+absorbance
+10 min
+early intervention, education and rehabilitation
+1.1 weeks
+improvement of antibiotherapy delivery
+TQLV/TELV
+80.96%
+Sigma-Aldrich
+Monocytes
+four
+titer
+hemagglutinin and neuraminidase
+>25%
+2.5 μl of Mg acetate
+A portal-specific alteration
+prokaryotic
+100%
+low incidence in the other viruses
+RanBP5
+Beta-actin
+coinfection
+peptides of length L = motif length+2 * flank length
+phosphorylation and ubiquitination
+885
+1992
+secondary prevention
+RRAGD
+1.5%
+Mann Whitney test
+two
+improvement in sequencing technologies
+to minimize analytical differences
+~2-, 4-and 5-fold
+Random numbers
+44
+33
+R82
+loss of potency
+Alkyne functionalized acrylate and acrylamide
+CaMKKβ
+a member of the team
+selection
+TBSV RNA accumulation
+6-12 h
+Shikimic acid
+Myocardial hypertrophy
+removal increased the R-factor
+1900
+influenza
+Daniel Macharia
+loss of endothelial barrier integrity
+Clinical diagnostic assays targeted to nucleic acid markers
+an up-regulation of the target genes
+24 hours
+RTA secondary structure
+renal pathology
+48 h
+AAT proteolysis
+to evade the antiviral effects of the R99 peptide fusion inhibitor
+Flow cytometric analysis
+10 days
+Genome resequencing
+Total PEDV RNA
+ion conduction
+30 min
+endosomal membrane
+260
+High drug-toxicity and emergence of drug-resistant candida species
+apoptosis and autophagy
+one hour
+p53
+residual interaction with ACBD3
+an adjuvant
+4.32 ¥ 10 4 genome copies per microlitre
+GraphPad Prism software
+decreased
+Ceacam1
+COST Action on FAP
+Usurping ESCRT components
+fast-track management
+CFTR RT-PCR product
+Scorpions
+Primer3
+neutrophil
+causative pathogen
+Vps3/8 knockdown
+neural retina leucine zipper
+pandemic
+Ayurvedic and Unani
+dysfunctional
+mortality
+neutrophil dysfunction
+Tetherin
+white colonies
+combined intervention strategies controlling infection, inflammation, and necrosis
+Pleural effusion
+4%
+trafficking of the entire glycoprotein complex
+the tibia
+lung-resident NK and possibly NKT cells
+APMV-4 cDNA
+SP24
+serum IFN-α levels
+time-lag
+nearly similar intensity
+17
+N-terminal tag
+a major peak
+R
+E1, E2, and E3 enzymes
+20%
+airway epithelial injury
+measures of target protein expression
+equally strong T cell responses
+1 day
+White Leghorns
+upregulation of the UPR pathway within the ER
+conformational change
+febrile convulsion or seizure
+modified homozygosity values
+Tunicamycin
+Different proportions
+trachea, lungs, spleen, and brain
+Carbamidomethylation of cysteine
+myelin basic protein
+contact reduction measures and the isolation of cases
+TMEV-IDD and shamtreated mice
+modularity
+360.5
+Dr. Lonny Levin and Dr. Jochen Buck
+1,394
+artificial neural networks, and statistical models such as Hidden Markov
+11 days
+they possess strong homologies within a wide spectrum of organisms
+viral patterns
+7%
+2001
+four
+102
+abzymes
+120,000
+rank correlation coefficients
+10%
+synovial
+new accurate experimental approaches
+276
+Dr. Ralph Reisfeld
+technological limitations in molecular modeling and phenotypic assays
+infectious cell death
+functional and morphological
+China
+oxytocin
+woundhealing
+HAV
+generalized weakness so that the patient is unable walk or sit up without assistance
+exponentially distributed
+6 years 7 months
+cytoplasmic proteins
+species-specific miRNAs
+three
+CCL5 mRNA
+species analysis model
+tetraloop
+Increased IL-1β secretion
+rare
+0.25
+Transient airflow limitation
+counts
+41.6%
+Viable titers of H5N1 influenza virus
+immunohistochemistry
+cholinergic
+mRNAs
+R 0 estimates generated from initial growth rates
+strong
+1991
+95%
+CNS infiltration by peripheral innate immune cells
+CTA1
+protein stability
+Luminescence
+3
+how central a given node is in the network
+nine
+GP CL -NPC1 binding
+xanthine oxidase
+sLTF
+viral pseudotyping with a foreign glycoprotein
+physical trauma
+variability of three technical replicates within a single nAb experiment
+S1PR1 signaling
+thrombin and FXa
+pKa i A
+70%
+mannose binding receptors
+4 -PMO
+4%
+Cell surface levels of HG-CD147
+80 µl of the detection antibody cocktail
+22
+direct batto-human and human-to-human spread
+an organ donor
+The significance of differences among four groups
+10%
+250
+Rab5 positive macropinosomes
+hepatitis C
+8 to 10%
+cystatin F
+BHI broth
+cytochrome c
+RT-qPCR
+GP
+12 days
+Web Appendix 1
+the RNA template
+the AUC
+50%
+exogenous Tat injections
+DAPI
+target genes
+liquefaction and cavitation of the granuloma
+Id2
+Korea
+305
+DHHC protein
+other countries
+war-related displacements
+striatial functioning and the pathophysiology of Huntington's disease
+MicroBCA Protein Assay Kit
+single cell genomics
+Uganda
+Twenty-five
+three
+390 million
+genomes of LPAIV, EDSV, and NDV
+bone bank administrator and the responsible orthopaedic surgeon
+1.26
+75
+Google Maps
+lysis temperature
+G ik
+110
+CXCL9/10/16 ELISA Serum and BAL
+monodisperse lipoplexes
+10%
+XOD mRNA transcript
+mean C t values
+digital LAMP assays
+necropsy
+1 h
+cytoplasm
+Virus titers
+£2.6 billion
+strong in vitro expression of both antigens
+eleven
+Dulbecco's minimum essential medium
+70%
+scientific misinformation
+DCs
+16
+species-specific secondary antibody
+hypoglycosylation patterns
+ether
+14,786
+Results for the full study set
+annual mean temperature and annual precipitation
+30 minute
+ClustalW2
+MMTV
+Sigma-Aldrich
+Strong purifying selection
+WT1D
+local events
+a robust and distinctive immune response
+positive spatial autocorrelation
+P E
+74%
+phylogeny
+IP-10
+25%
+RLUC reporter vector pRL-TK
+HS-GC tandem MS
+Chi-squared test and Fisher's exact test
+a chemical that can be used to synthesize plastics, rubber or fuels
+prior MERS-CoV infection
+wild type genotypes
+mice, guinea pigs, hamsters, and non-human primates
+60 ng/μL
+30 min
+markedly enhanced PR-mediated Gag cleavage efficiency
+cytokine induction
+Forty-six
+5 min
+AML blasts
+niche similarity
+IL-6
+higher
+Nglycosylation of G N
+ecological niche theory
+one sample t tests
+human vaccine vectors for human pathogens
+natural
+The presence of any positive signal
+P2-Ser, P5-Asn and P9-Met
+HIV/AIDS
+Dithiothreitol
+1995
+RNA concentration and specific dye activity
+SAEs
+viral extinction
+thymidine kinase
+Individual gaps and lapses
+97%
+local
+APN
+assessing the importance of mask use in respiratory disease transmission
+attenuated replication and foot swelling
+post-translational protein modifications and interactions
+1% Triton X100
+Further efforts
+Mitochondrial DNA
+1.8-2.1
+80 PFU/brain
+quarantine-induced backward bifurcation
+protect against Ebola virus infection
+6.8
+Two
+Influenza associated accidental mortality risks
+conserved
+NF-κB
+formalin and UV
+mnm 5 U and Q modifications
+Yu and colleagues
+dsRNA thoracic inoculation
+three
+MHC class II-restricted
+Signals
+CD8 + memory cells
+Julian Gordon and Prasanthi Gandhi
+to describe in detail the contacts between individuals in a healthcare setting
+91
+bioactive agents
+The site of attachment of BAF to the ATPase
+pathological
+Six
+cardiovascular disease, carcinogenesis, and immune system diseases
+granulocytes
+HA
+visual cues
+40%
+HSGPs
+induced and constitutive immune assumptions
+3
+M1 macrophages
+one specific antibody per target protein/peptide
+monoacylates
+oval
+b P for Egger 9 s test
+novel
+-actin
+3.1 kcal/g
+both sensory and motor nerves were injured
+343
+Biodistribution of the vaccine
+S. aureus
+prolong transgene persistence and transcription
+21-nt Peptide-siRNA
+co-receptors
+measurement of kidney function, lipids, and troponin
+NN theory
+bullet-shaped
+Twostep qPCR
+PRJNA420089
+1 ml of media
+Peroxidase
+Two
+20%
+4 times biweekly
+CIp-P TET -GTW
+DCL-2 protein
+80
+RF prob
+2%
+IFN-γ, IL-4, and IL-10
+90 °C
+public clonotypes
+87
+none
+1000
+clinical signs consistent with FeLV or FIV
+AOX1
+male transmission model
+lipid
+RT-PCR
+1486
+100 ng
+survey
+Plasma
+optimal stability and activity
+a line for generating the profile map
+13-17h
+six
+426
+34
+IMPDH
+VSV*M q
+Completely overlapping sense and antisense DNA oligomers
+every other day
+Supernatants
+Chinese hamster ovary cells
+None
+glycoprotein cleavage
+endo H and PNGaseF
+16 classical HA and 9 classical NA subtypes
+AF induction
+Ago2 protein
+after birth
+0.05
+liposomal amphotericin B
+barotrauma or negative hemodynamic effects
+phosphorylation state
+TBSV repRNA replication
+p
+between nucleotide positions 140 and 434
+W86 and D89
+61
+JM
+the amount of amplified target DNA
+Five
+16S rRNA
+TANK-binding kinase 1
+induction in response to VacA
+cellular debris
+pHLsec vector
+resistant to virus infection
+NanoLuc-E6 fusion protein
+1%
+200-fold
+Kupffer cells
+White precipitate of magnesium pyrophosphate
+Minimum Essential Medium
+atypical
+advanced wavelet-based transforms
+AAP
+liver, thymus, spleen or lymph nodes
+M2e
+293T triple transfection of pCMV1MLVGP1
+morphine dependent rats
+>70 million
+proteins
+respiratory diseases
+108 months
+decreased antiviral activity
+Merck India Ltd
+glycerol
+bacterial
+immunogenic
+7.8-500 pg/mL
+distinct/genetic alterations in large regions of human genome
+simultaneous and successive mini-epidemics
+heritability
+miR-29b
+1.69 × 10 −3 substitutions/site/year
+headaches, vomitings, cerebellar signs, and seizures
+3,3′ -diaminobenzidine
+Eighteen
+Stigma against seeking help for suicide
+Twenty-eight
+Epitope A
+Macenta
+Wild-derived inbred strains
+synergy, no interaction and antagonism
+CedPV-specific sequences obtained from the high throughput sequencing
+sibling and UCB donor sources
+ISG-encoding lentiviral vectors
+by following normal national procedures
+homogeneous colors
+zero
+the impact of error
+Histamine
+PolyI:C
+CHIKV and H. sapiens
+Ͼ25%
+5 1
+phlebovirus entry
+homeostatic
+primate only, mammal only, and fish only
+28 April
+piglets
+extensive hemorrhage and nodule formation
+immunolabeling fixed cells
+SF370
+2 times
+post-second wave
+Formation of the first two canonical base pairs
+1 hour
+SARS-CoV
+SOD2
+17.2%
+microtubule-associated proteins
+A MOI of 0.4
+2020-02-05
+2 kb
+wortmannin and 3-methyladenine
+digitizable therapeutics and local synthesis
+six
+MEGA
+Bombali virus
+controlled in vivo human infections
+disappear
+HEV RNA
+hepatitis B
+case definitions, facility types, and eligibility determination
+Asymptotic decline
+antiviral
+viral titers
+chito-oligosaccharides
+treatment groups
+ANOVA
+Knowledge
+end-point titration in MDCK cells
+pFcRn mRNA
+China
+protection from heroin addiction
+10% FBS
+embryonated hens' eggs
+group 1
+Q B i,j
+cc-by
+Herpes simplex virus type 1
+Vital registration data
+by spinfection
+tissue protein analysis
+at acceptance events
+measurement refinement
+HCV-infection and Atg-proteins
+singletons
+Interstitial cystitis and irritable bowel syndrome
+VIDISCA-454
+VgrG
+EV exchanges in the 5 1 UTR
+intracranial
+ibuprofen
+confidence intervals
+diphtheria
+34
+RSA59 and RSMHV2
+rhIFITM3
+Over 60%
+Data in panels A, B, and G to J
+16 days
+74-100%
+strong antibody response
+transactivates the EGFR
+nano-size
+two
+10%
+838
+pandemic influenza planning decisions
+lymph nodes
+kidney injury molecule-1
+high α-helicity content
+Coreceptor usage
+2016
+HCMV
+viral propagation
+S. Typhimurium
+6-8 week old
+mCLDN6 or DisOva
+V HH s of cameloide heavy chain antibodies and single domain antibodies
+herbal group
+degradation properties
+react with bacterial surface antigens
+A genomic inversion
+heterozygosity
+20,000
+laboratory procedures employed in viral culture and RT-PCR testing
+6.4%
+LC-MS/MS
+KSHV
+Traditional Chinese Medicine
+C 16 -palmitic acid
+GA2
+September to November
+repetitive sequences
+DENV
+multiplex family level primers
+hydrogen bond
+β-actin
+odds ratios
+nine
+Pediatric Dengue Cohort Study
+home and work communities
+limit virus spread
+apoptosis
+Figure 8
+The total number of hospitalization days
+10.1186/1471-2334-11-128
+~40%
+11,399
+another direction
+adeno, squamous and small cell carcinomas
+Crude protein extracts
+Dr. Sulaiman Daud
+5
+MacroGenics and Zai Lab
+I=log
+the potential of the H5N1 virus to disseminate systemically
+Four
+Phylogenetic
+Viral Spectrum Assembler
+0.64
+antigenic drift
+autophagosome
+90-day all-cause mortality
+Hair
+fibrosis of the lung, allergic asthma, and COPD
+from days to several weeks
+Virus titration
+cell signalling
+cystic fibrosis
+apoptosis
+λ
+Length of hospital stay
+Subversion
+significant down-regulation
+13
+Pichia pastoris
+r~1:31
+Two sgRNA sequences
+50%
+1.1%
+92%
+Nineteen
+12
+100
+Significance Analysis of Microarrays
+Thirteen
+four
+disease prevention and control
+mortality
+RT of a UGA codon
+pyogenic bronchopneumonia
+Staff shortages and staff motivation
+C-terminal dependent cytoplasmic interactions
+Olympus CellR
+axonal transport
+0.41-0.60
+pathways associated with antigen processing and presentation
+30%
+S. aureus
+naked DNA
+uncontrolled cell death or abnormal gene expression
+Near infrared spectrometry
+health services
+MEME
+2 days
+antigenic drift
+10 times the mean standard deviation of the background fluorescence level
+12
+viral transmission
+134 and 135
+Expedited
+3 days
+viruses
+60 to 70%
+secures efficient viral translation
+Disaggregation of heat shock-induced SINT-speckles
+six
+NCBI Primer BLAST program
+the last figure
+BLASTN and BLASTP
+George Eliot
+NF-κB upregulation
+growth cues
+Figure S5A
+two
+circumsporozoite
+GFP-3035B
+WHO
+eEF1A
+Homotype-independent antibody
+inverted repeats
+acute and chronic
+10
+17
+30%
+5.12 and 4.39 log10 EID50
+fast clinical improvement and improvement of most laboratory abnormalities
+2009
+S2, S1, and S1 0 Ubbinding pockets
+Cellular pathogen recognition receptors
+vehicle or dexamethasone
+Nuc
+Montevideo, Uruguay
+two
+Gene-specific primers
+GM130 and Golgin 45
+nuclease activities
+ORF5
+IFN induction
+35,114
+Fifty-five
+5 µM
+−1 frameshift
+human antibody B cell repertoire
+sophisticated
+2008
+24 h
+k
+200μl
+334
+rs368234815
+578
+10 °C per min
+Bile acids and Farnesoid X Receptor agonists
+21RR22, 25RRK27, and 31RR32
+Creative Commons Attribution Noncommercial License
+The one spot that differed consistently between three independent experiments
+mMASS
+IFN-α
+eIF2B
+induce humoral responses
+MERS-CoV polymerase chain reaction test kits
+mice
+months
+DNA extraction
+491
+Protein folding
+mean ± SE
+competition between unwanted proteins for plastic binding spots
+sex and age
+15 min
+harm
+Peptide Ac2-26
+neighbourhood contact hubs
+being out of the ideal therapeutic window
+close interaction with computer sciences
+Predictive accuracy of MFE folding
+HLA-DQ/DR
+1393
+Stable expression of exogenous genes
+75%
+10.8 weeks
+polyubiquitination and subsequent proteasome-mediated degradation
+MEGA 7
+178
+173
+A/T bias
+2213 Dalton +
+62 years
+stockpiling of pharmaceutical agents
+Acute respiratory distress syndrome
+POCT-enabled spatial grids
+arthropod taxa
+FIV-infected
+PARG
+exogenous ALV infection
+P2 receptor antagonists
+IAP retrotransposition
+5%
+growth on selective medium
+Serological testing and removal of infected animals
+three
+Escherichia coli DH5α
+Chickens
+microglial
+Ventilator-associated pneumonia
+Pre-senescent astrocytes
+loss aversion
+75:25
+15
+25 copies/ g
+bootstrap value of 70%
+IFN-λ
+low GC%
+11
+MNV-1 replication
+Experiences of natural disaster, war and civil conflict
+2089
+1860s
+immune components in host cells
+α-defensin 5
+antiviral immunity
+movement networks and contact tracing networks
+>2-fold
+5 days
+cost effectiveness and safety issues
+Bleomycin
+Y34S
+frameshifting ef®ciency
+V2
+Influenza A virus WSN33
+N at 701
+Thirty-five
+any medically important laboratory abnormality
+PI cattle
+May 27, 2001
+morbid obesity
+titanium
+Macrogen Korea
+Finland
+11
+fluorescence
+100 ll of the culture medium
+relaxed sequence specificity
+CD38/CADPR/Ca 2+
+Seven
+PLEX-ID/Flu assay
+TDP-43 and FUS and SGs
+that of the WT virus
+wildtype
+Sanger sequencing protocol
+Luria Bertani
+VSV-G
+40 min
+p24
+S i
+rabbit polyclonal anti-NP antibody
+argon
+FMDV
+spontaneous DNA damage
+impairment of virus assembly and/or spread
+Integration and coordination of surveillance systems
+viral contamination
+mouse or human antisera
+physiology and metabolic rate
+90%
+Running water
+pairwise comparisons
+lipopolysaccharide
+14
+C-terminal
+bacterial proteins
+3 of 4
+MatrixMatchMaker v2
+vector-borne zoonotic diseases
+dye
+the impact
+Blood Service protocols
+cross-matching
+low levels of AR
+bats
+serum free DMEM media
+sepsis
+cold months
+PCT
+Detailed
+100 mm
+experimental error or interferences
+cross-species transmission
+the local/distal status of the QTL
+single nucleotide polymorphisms
+minimal
+host genetic factors
+930
+weakly acidic condition
+5%
+The diagnosis of influenza
+agarose gel
+53%
+its web link
+calculation of supplemental oxygen-free days per definition 2
+139
+PrimeScript RT reagent Kit
+by clicking at their names
+enormous variation among strains
+geminin
+Indonesia
+48 hours
+pH1N1
+a contact matrix
+type-II
+the average number of secondary cases infected by a single primary case
+less than 10 variant sites per kb
+chronic myelogenous leukemia
+greater transmission heterogeneity
+December 1, 2009
+Standard multiplex PCR
+influenza infection
+it is known to be one of the metabolites produced by the metabolism of oxygen
+medium
+the TSC
+Virus titer
+turnover rate
+blood gas changes
+mediates several-fold enhanced transfection
+Vaccines and antivirals
+1.5 million
+19
+mean with SEM
+2009
+60
+IFITM5
+Puromycin
+Transcriptomic
+challenge
+80%
+ferrets and non-human primates
+whether observed differences among results are compatible with chance alone
+decreased growth rates
+PyMol software
+Coulombic potential
+rank-sum tests and Fisher's Exact tests
+six1a
+10%
+toxicity
+62%
+DENV-faRexpressing cells
+formation of G-quadruplex
+XPR1
+two to three weeks
+24 hours
+South America
+Pichia pastoris
+1444
+Galangin
+ROS production
+pulmonary fibrosis
+electricity-free
+five
+I49, S29, S31, and S58
+Uganda and Nigeria
+different types and subtypes
+Equation
+T cells
+seven
+David Held
+low
+enhanced chemiluminescence ECL detection kit
+intervention at the root cause
+quenching procedures
+Staphylococcus aureus
+bnAbs
+fruit bats
+minimize side effects to normal cells
+Xbp1 regulated genes
+Human B cell hybridomas
+58
+reaction speed
+Bartels
+increased vaccinations
+short-tandem repeat analysis
+Rarefaction
+nsP3
+limited access to the materials
+The conformation of the ribosome
+infectious agents
+speciesspecific
+absolute humidity
+8-fold
+2009_4556
+clinical diagnostic uncertainty or error
+3/100py
+exposure or treatment with glucocorticoids
+PBS solution
+50-85% growth inhibition
+8
+neurons, immune memory populations, and long-lived plasma cells
+posttranslational processing
+increased transmission
+central nervous system
+A 5¢ common leader sequence of 65±221 nucleotides
+special considerations
+18000 to 19000
+90%
+geometric mean
+24 h
+ranks of data
+they all combine a diurnal with a nocturnal pollinator
+Population density
+Phosphorylation of STAT2
+previous relevant reports and experiences in day-to-day clinical practice
+less than 1
+frameshifting promoting signals
+The logarithm transformation
+normalized RNA samples
+an underestimation of the recombination rate
+cellular arm
+MPG
+R 0,N = √ 6
+Hayflick limit
+druginduced NP aggregation in cytosol
+pseudotyped viruses
+comorbid conditions
+Ethyl acetate fraction of the H. cordata extract
+20.9%
+HIV-1 gag-pol mRNA
+Pathogen spillover
+stratification
+functional
+confocal laser microscopy
+C 36 H 24
+lung morphology
+airway epithelium
+IL-21
+3 h
+proteasome-associated isopeptidase activity
+frog
+Area CA3
+jet injection or particle injection routes
+all of its neighbors becomes infected
+drugs
+BoHV-4
+extended backcalculation
+serum
+P. pastoris cell pellets
+confocal microscopy
+GIDEON
+CESAR
+Na +
+binding affinity to H1
+chelates potassium ions
+GPC shedding
+0.017
+pro-inflammatory and anti-inflammatory cytokines
+PROTEINTECH
+within the normal ranges
+Gene expression
+three
+2011
+vimentin
+liver stiffness level and extent of liver injury
+96.7%
+IgA responses
+d V
+ferret model
+a PL that is missing an acyl chain
+68%
+protection against EBOV
+nitric oxide
+complications and transmission of the disease
+surveillance of selected infectious disease agents
+KC411776-KC411814
+injury/ poisoning and diseases of the digestive system
+Supporting Notes
+low
+reporter activity
+homologous recombination repair
+A subset of Envs
+PICV
+all free strand regions
+128,119
+Diffraction data sets
+Construct T30/P2
+51
+a transcript that mimics the wild-type TCRV N mRNA
+four
+June 2009
+infectious viral progeny
+Broad-range PCR
+coping appraisal
+supplementary material
+influenza A positive or negative
+further infection
+54
+0.25 mL per dose
+biotin
+Stratagene GeneMorph II Random Mutagenesis Kit
+amantadine
+D 3 Ultra TM DFA Respiratory Virus Screening Kit
+Phage heads
+we further characterized selected genes identified at single-cell resolution
+CA9, coxsackievirus B2, and EC6
+pesticide restriction
+Mosaik alignment tool
+selective
+twelve
+influenza, hepatitis C, dengue and viral hemorrhagic fever viruses
+more than 1 hour
+Skyline
+major histocompatibility complex class I antigen
+Specific PCRs
+10.91, 38
+swine
+ADCC
+CCHFV vOTU DUB activity
+30,000
+ALI and ARDS
+antibody-mediated neutralization
+80%
+Phenylmethanesulfonyl fluoride
+PMTCT
+Amplify
+six
+10%
+22,000
+IMG/VR
+828
+i.n. and oral routes
+IBD rate
+45%
+Germination and culturing
+applications of CSF1-Fc in liver regeneration
+murine TOMM20 and duplicate FRB domains
+Xrn1p interacts with L-A Gag
+spatial segregation between populations
+ribonuclease activity
+essential information on the transmission and seasonality of influenza
+radiationattenuated
+antibody crosslinking the DEC-205
+rapid, label-free progenitor cell
+isotope labeled SILAC method
+influenza and henipaviruses
+poor
+relative gene expression of the targeted genes
+HS-Csn8KO livers
+block the activation of RIG-I CARD
+turripeptide
+decreased concentration of both KYNA and TSG-6
+GENIE3
+excessive levels of cytokines
+Manidipine-resistant virus
+288
+2 -phosphotransferase activity
+monocytes, tissue macrophages and dendritic cells
+stronger activation of pSTAT1
+NF-κB activation
+M4 and another replicate
+branch lengths
+comparison between survivors and non-survivors
+The temptation to become a standard
+pathological situations
+extraction kit, volume sample, and concentration procedure
+when influenza virus RNA is detected by host cell pattern recognition receptors
+luciferase activity
+FlowJo
+EPF
+6 weeks
+more than 100
+Heroin
+Microsoft Excel
+1918, 1968, and 2009
+antigen-antibody interaction
+RV-C9 and -C53
+Japan
+0% etiologic fraction
+access, egalitarianism, security and benefits
+HNSCC
+catalase
+267-Phe→Tyr
+rubber seal
+5.5
+polymorphonuclear cells from lymph nodes or myoblasts
+interstitial fluid concentration gradients
+Actin
+detected DNA from dead bacteria
+individual levels of each FFAs
+0-60%
+evolutionary hypothesis testing
+a region specific to the target gene and a high melting domain
+tandemly arrayed duplicated genes
+39
+5% non-fat dry milk
+9hpi
+preclinical and clinical drug/micro-organism exposure-response relationships
+Dr Margaret Chan
+parasite pressure
+degraded
+14 days
+hamster
+Homogenous mixing
+defense against a pathogen
+Serial dilutions of cDNA
+thermal stability
+degradation
+Lower variant frequencies thresholds
+expert opinion
+TBK1
+The venipuncture site
+regional or national intervention forecasts
+mAbs 447-52D and F425-B4E8
+Transcribing the glycoprotein gene
+fever, reduced consciousness, seizures, and focal neurological deficits
+Cytosolic NP
+cholesterol
+lung-derived virus-specific CD4 + effector T cells
+CD3 + T lymphocytes
+China
+1.02 per one frequency increment
+five
+10 6
+335
+epithelial or endothelial subsets
+blood transfusion
+the regression coefficient for human capital
+relatively modest
+75%
+pseudoknot
+NCBI GEO
+Storage samples
+Po 0.05
+75Á0%
+Mutagenic nucleosides
+reduced remyelination
+virus shedding and seroconversion
+45
+A list of known waterborne pathogens
+mouse studies
+Septic shock
+high abundance viral species
+efflux via the P2X7R
+UniProt Knowledgebase
+IL-12
+pregnancy
+Tumor necrosis factor alpha
+RVFV titer
+10,000
+1%
+Return array
+SigmaStat
+two
+Gln-89 and Ile-91
+anthropogenic
+to keep the reading frame intact
+reasonable
+natural polyphenols
+group masking
+CD4 + CD25 + Foxp3 + expression
+viral neutralization
+lung lesions
+the rate using the PEG as the crowding molecules
+2007-03-13
+70%
+0.2 volumes
+pre-pandemic vaccination
+ABC
+Quantity One
+spore dispersal
+RVF
+CifarNet
+Acoustic communication
+PepMapper
+51.3% to 7.0%
+XF culture supplements
+Antibody-mediated passive immunity
+April 17
+Five
+LTQ Velos Pro mass spectrometer
+MATLAB operations
+30
+vaxia trials
+-1 PRF
+4 days
+dendritic cells
+21%
+Student's t-test
+2 min
+80 GC/rxn
+one electrophysiology-trained physician
+Count data of the annotated transcripts from individual samples
+58
+cellular adhesion
+Hungary
+Pneumococcal surface protein A
+TMB and H 2 O 2
+macrophages
+day 18
+TG
+Thirteen
+human population density, land cover and land use
+Early identification of suspect cases
+a matrix protein and an RNA-dependent RNA polymerase
+time in minutes
+ABCG2 transporter
+multiorgan inflammatory disease
+10,000 Hz
+cdk2, -4, -6, and cyclin E
+1-mer features of sequence and structure
+FLOT2 and IZUMO
+dramatically diminishes the infection
+Ag85A
+memory inflation
+lower the titer of the virus
+RNA-Seq
+FerrD2
+age, sex and batch effects
+gshF
+IRE1 or ERN1, PKR-like
+let-7b and miR-26a
+Rab GTPases
+Erroneous matching read pairs in the plasmid control
+2,000
+negative
+high-ISG patients
+5 days
+implicit solvation models
+>70
+rational and user-friendly
+Tang Ben Cao
+blood samples
+good quality
+ensemble energies
+pathological IFN-α responses
+Forty-four
+cluster heart rate dynamics
+the census unit
+TCR
+pathogens
+Twenty-three
+sperm maturation process
+glucose
+highly attenuated mutants of Lm
+Patient-specific DNA vaccines
+Comparative genomic analysis
+Turning off all central air conditioners
+when Weekly CPS in a PHC jurisdiction exceeds 30.0
+multiple factors
+The reporting rate
+immunosenescence
+accuracy difference
+Group 3
+rimantadine
+Four
+physicochemical
+GP1 attachment glycoprotein
+unpaired
+methyl red indicator
+four
+probability ratio plots
+RIKEN BioResource Center
+Luciferase activity
+BRD4 and the transcription elongation factor P-TEFb
+host cell cholesterol homeostasis
+neuropathy
+hypoxia
+Subunits of the OST complex
+LIKHAAN
+Nikon TE300 inverted microscope
+XNT effects
+15
+gas exchange
+live bird retail stalls
+75%
+LIR-containing proteins
+space-time disease diffusion
+the degree of separation between positive and negative controls
+Y′
+Zn 2+
+antimicrobial
+less than 95%
+infection
+CpG island methylation
+outside of a patient's room
+19.6
+excitotoxicity & neuroinflammation
+February-March
+eight
+2009
+10 %
+Electrophysiologic abnormalities
+in vitro dissociation assay
+TNFa, MCP-1 and IL-6 secretion levels
+confocal
+to represent the range of log fold changes
+four
+Fibrogenic
+900 μL of recovery medium
+reverses IFITM3's inhibition of viral replication
+Fatty acids
+homotrimeric HA
+peptide H1-P25
+nucleic acid precipitant
+Clarifying the origin of DAECs
+four
+The ratio between Gag and Gag-Pol
+four
+pain and depression
+>0
+western blot
+VP1 capsid
+UTP
+Fifty-three
+induction of local immunity at the port of pathogen entry
+gross national product
+Type II cells
+significantly higher
+58.8 IU/mg 78
+Integrin 2 1
+Dbp3p
+The notion of proportionality
+Volatile
+5%
+change of tryptophan fluorescence
+47
+13%
+NMDA receptor
+hydrophobic part
+B
+583
+adaptive sequence divergence
+nephrology clinic
+PA-X degradation activity
+oligodendrocyte
+gestational stage
+24, 48, and 72 h
+21 days
+3
+academic credit and career advancement
+mechanical properties
+whether or not they had SP
+DEP
+hypoglycemic
+cleave
+active or inactive
+weighted least squares
+neuraminidase inhibitors
+PTX3 mRNA expression
+false discovery rate
+machine learning methods
+Down syndrome
+it is absent from known SBP homologues
+6 hours
+psychometrically driven and definition-driven methods
+Tukey's post hoc test
+1:20 dilutions
+female sex workers
+UV-irradiated samples
+specific viral proteins
+69.9%
+2
+30 ms
+s L i
+17
+× 10 6 colony forming units per milliliter
+Eleven
+14
+Cholera toxin B
+CD8 + T cells
+2009
+VSV infection
+waste of aerosol
+95%
+phylogenetic
+fungi and plants
+chronic renal disease and immunodeficiency
+Mutational bias
+42.6%
+35,151
+cis-acting mRNA destabilizing elements
+38.7%
+Lung injury
+11
+plasma levels of Ang-
+Multiple linear regression
+6
+vaccination uptake
+cynomolgus monkeys
+Ebola GP
+PmLac25-F and L25Re
+43
+32
+autumn and winter
+TNFα
+396
+DENV protein/lipid and protein/ protein interactions
+Coronavirinae
+variability
+VSIG4
+3.0%
+secondary
+odds ratios with associated 95% CI
+Equivalent volumes
+650
+Target DNA
+−80 • C
+fever-CT unit
+5.7 days
+CVTree3
+RT-qPCR
+1 to 3 cycles
+IFN-c
+Cytotox ® 96 assay kit
+Total RNA
+Natural Killer cell receptors
+high linkage disequilibrium
+45.028
+28-30 nm
+Mass gatherings
+weak CD4 binding
+RNAhybrid and RegRNA
+ImageJ
+its own promoter
+optimised
+worse
+Oil administration
+consistent
+Over a half
+5 μL
+improvement
+Markov chain Monte Carlo
+over 50%
+comparable
+Microglial cells
+acidic
+similar size
+58
+contact heterogeneities
+four
+29
+Sofosbuvir
+influenza tests
+microvesicles or secretory autophagosomes
+twelve
+TRAF6
+CMV viral load data
+LV ejection fraction nor plasma BNP levels
+NOD1 and NOD2
+Type 1 error adjustment
+receptors for host invasion
+ID
+Five
+rhino C
+DI particle release
+two
+positive
+four weeks
+transcytosed virus
+divergence and recombination
+twice daily
+357
+A nucleic acid test for HCV and HIV
+5.2 days
+microbes
+Viral entry glycoproteins
+An amiRNA targeting LacZ gene
+microvesicles
+developmental phase transition and flowering
+the generation of an accurate superposition
+hepatocellular injury and fibrogenesis
+various self-assembling viral proteins
+0.8 mg/kg
+Hepcidin
+Key Laboratory of Sericulture
+angiogenesis
+LigScore1 and PLP1
+five
+800 V/cm
+oxidative
+Nagelkerke R 2
+ELISA kits
+stop condition
+every month
+Centers for Disease Control and Prevention
+fluorescence spectrophotometer
+reduced
+5.5-6.8 minutes
+cc-by
+mediates growth, inflammation and apoptosis
+259, 694, 910, 1002 and 1023
+IFN-α
+Interleukin-18
+reverse transcriptase quantitative PCR
+Whole Blood Genomic DNA Isolation Kit
+Bright-Line Hemocytometer
+liberation of sugar chains from glycoproteins
+Acute lung injury and acute respiratory distress syndrome
+Self-administered feedback questionnaire
+Clinical evaluation, laboratory investigations, and electrocardiography
+Vaccinia virus
+Arieh Ben-Naim
+2,500 square meters
+viral and host factors and contact opportunities
+coagulation and fibrinolytic functions
+6%
+2
+FN1 and laminin
+16 h
+trained study personnel
+Over 100
+PPXY late domain
+the best ANFIS model
+0.1 %
+a careful assessment of their morphology
+Blood drawing
+IFNγ stimulation for mHLA-DR expression
+Community-acquired pneumonia
+Compound 14
+−20 ∘ C
+the earliest event associated with infection-viral entry into the host cell
+3,320
+one-way
+1918
+highly divergent sequences
+homeostasis
+a general set of mechanisms by which acetylation can regulate protein activity
+Clustal W 6.0 software
+A mutated site
+weekly
+size exclusion chromatography
+sunitinib and sorafenib
+information from the primary rescue response teams
+comparable to seasonal flu
+53 kDa
+non-neutralizing/interfering Abs
+Logistic regression analysis
+1998
+80%
+parenteral nutrition
+0.3%
+mathematical models
+elevated AST
+two
+two
+Interleukin 18
+An intervention targeting schools
+disintegrate
+implementation expenditures during the 2012-2014 interventions
+A sequence logo
+mitochondrial uncoupling and Ca 2+ sensitive potassium channel activation
+IFITM3
+15-fold
+striated muscle cells
+70%
+central nervous system pathology
+E protein's interaction with pr
+behavioral changes
+4.3 × 10 5 IFU/mL
+protein kinase B
+adapter ligation
+95%
+individuals
+THBD
+skeletal dystrophin
+3
+paracellular permeability of cell layers
+heteroskedacity
+consumption of the precursor proteins following KKS activation
+722 bp
+miniature computers
+Mutational pressure
+a future phenomenon risk
+PMAdifferentiated
+CD4 and Foxp3
+456
+IL-21
+HLH
+higher
+molar ratios of protein:HOCl of 1:1000
+C4 from Callitrichine herpesvirus 3
+within-host evolution
+social wellbeing and optimism for the future
+gluconeogenesis
+T. whipplei bacteremia
+two weeks
+1 hour
+monocytes
+The quantity β
+reverse genetic techniques
+Bonferroni correction
+monocytes and macrophages in mammals
+Ten
+WSN-PB2-GFP11
+earlier initiation of transmission-based precautions for symptomatic patients
+seven
+glycan sequences
+ROS
+development of ARDS
+CalcuSyn
+potential markers of bacterial infection
+GO and REACTOME
+3
+Corticosteroids
+structural proteins
+outliers
+Hashimoto thyroiditis
+209
+Ser78 and Ser81 of CHOP
+HIV Env
+MetaMorph
+cytokines
+Fifty
+efficient virus release
+the liver
+EGFP fluorescence
+Autophagy
+Ibrahim
+carnivores and ungulates
+culture dishes
+EV71 replication
+16.78%
+~60%
+lower
+emodin
+therapeutic
+7%
+dialysis modality, efficiency of dialysis, and nutritional status
+five
+2 ml of purified linear DNAs
+inflammatory
+Adenosine
+respiratory infection
+viral titer growth rate
+Tab. 1A and 1B
+c
+0.29
+four
+23
+High dietary fluorine
+up to two weeks
+Ub 75 -thioester
+supplemental near-patient air sampling
+epithelial damage
+dispersion models
+improvement in FVC after therapy
+senile
+averaged
+cycle threshold
+10
+iodine labels
+Single-nucleotide polymorphisms
+haematoxylin and eosin
+methanol/chloroform
+density gradient centrifugation
+95%
+to clarify the importance of the details of contact and propagation mechanism
+greater than 1
+lymphocyte penetration
+a series of orthogonal axes
+residue-and surface-based methods
+Asterisks
+nAbs
+4 days
+Alveolar TII cells
+projections at multiple time points
+SYTO9 and SYPROred
+electronic data collection methods and automated analysis
+80%
+0.5%
+six
+late-exponential phase
+30%
+Thirteen
+glucocorticoids
+Raul Andino
+effecting insulin clearance
+metapopulation model
+Survey datasets
+Recombination
+MDA5
+Polyethylenimine
+specific targets
+all nodes
+black horizontal dashed lines with arrows
+Trizol
+8,263
+CP-readthrough protein fusion
+4 days
+worsening disease outcome
+16
+image patches
+many tools for data analysis
+a drug or toxin triggering IMHA
+Nantou, Lianhua and Yuehai
+Viruses
+29 %
+living changes
+Genotyping of P. jirovecii
+R 0
+Effelterre et al
+6 to 7 days
+K153R and S223N/G
+Thermo Fisher
+Important Bird Areas and agricultural land
+IFN-α
+exothermic
+receptor binding
+high mortality in humans
+influenza
+all degrees of neuronal injury
+H. influenza, and pneumococcal isolates
+K1L and C7L
+four
+Negative binomial generalized linear models
+ruminant
+Mag and Hon
+higher
+N-terminus
+decrease in ACE2 is not a general response to kidney injury
+ACE2
+type 1
+Eid-Ul-Adha
+28
+1%
+infectiousness
+quantitative levels of antibodies
+2%
+normal kidney architecture
+hepatitis B
+EB-NPCs
+ISM
+goat-anti-mouse-Cy3
+none
+15-45%
+in duplicate
+both interventions were equally effective
+Statistical tests
+human health
+the band
+HIV-suppressive RNase 6
+Recombinant Cap protein
+tegument VP16
+angiopoietin-2 and markers of endothelial dysfunction
+1 H-NMR
+121
+cross-Validation
+reduces the viral titres of the four DENV serotypes
+65
+12
+5.51
+AS03 adjuvant
+VA IACUC committee
+Neurally adjusted
+direct inhibition of repair
+N 2
+twelve
+antiviral activity
+1 million
+29 days
+2-10%
+Mann-Whitney U-test
+B240818
+astrocytes and endothelial cells
+2012
+four
+NGS
+Host heterogeneity
+28
+stochastic Langevin equations
+SPSS 15.0
+codon115
+50%
+unrealistic and suboptimal
+Newcastle disease virus
+CV risk
+inhibit L. interrogans to mammalian cells
+visualizing certain texture patterns of lung diseases
+mild
+pDC and NK cells
+consideration of titer and thermal amplitude
+89
+180
+environmental viruses
+Metronidazole
+0.05
+55.5%
+5%
+Flow cytometry
+Ile45Arg/Thr49Arg
+John R. Mascola and Richard Wyatt
+interlaboratory data sharing and assessment
+Successive passaging of the viruses through the hosts
+3.6%
+Antibody production tests
+eleven
+protective
+50%
+38 %
+5%
+Anti-β-actin mAb
+patients with similar and suspected syndromes
+inhibits viral DNA synthesis
+chest radiograph
+more than one focus
+0.236
+ALI
+Statistical
+Table 1
+Smad2
+T-domain and receptor binding R-domain
+virion maturation
+Two
+Virus entry
+NucleoSpin Tissue kit
+low
+F O k,ν
+advances in basic understanding and vaccine development
+Partial F test
+Antimicrobial resistance
+Disability
+bacteria
+Treg deficiency
+ineffective repair mechanisms
+lipids
+NS5A
+anti-steatotic
+S M
+3 dpi
+estimate the posterior density
+IRV with fitness advantages
+public health messages
+the link between outer shell and capsid core of enveloped viruses
+improving the sensitivity, accuracy, speed and throughput of experiments
+Father
+origin and evolutionary patterns
+Hand hygiene compliance
+systemic actions
+Further studies
+62.2%
+life history traits obtained from the literature
+the treating physician
+pleiotropic
+carbohydrate-binding sites
+two
+trace amounts of DNA or RNA of a particular sequence
+GDZ and GDL
+Crossover regions
+Trypsin
+RIDD
+322.1 pg/mL
+APVs
+Strong 10 N95 masks
+disaster base hospital
+virtual screening
+N-acetyl group
+Cav-1
+ENaC phosphorylation
+small-molecule adjuvant
+amoxicillin
+2000
+A/California/04/2009
+adjuvants
+less than 1 %
+DNA glycosylases, nucleases and DNA polymerases
+Blood feeding
+ER stress
+influenza virus
+2 weeks
+Adaptation of pathogens
+alopecia
+Farm animal proteomics tandem MS analyses
+its own promoter
+Katja van Nieuland and Thales de Haulleville
+confirmed case data
+four
+84%
+SeV and MeV-Edm
+50%
+CRTC1
+viral
+Sleeve gastrectomy and Roux-en-Y gastric bypass
+62 420
+cell-intrinsic properties or other mechanisms involved in regulating viral replication
+biological denitrification
+CNS degeneration
+three
+CIITA
+bat specialized
+TFA salts
+2013
+femoral bone
+122
+various choices
+electrons
+flexibility
+weak-damping effect
+HA
+A summary of the secondary structure pointers
+IFNλ activity
+6-9 days
+vector age profile
+E-cadherin
+36,811
+KS and JD
+self-amplifying replicon systems
+Image J
+the protection index
+3 -adjacent to A 36 in phenylalanine tRNAs
+35
+toroidal-homotrimers
+host cellular processes
+Local prevalence
+Hsc70
+replication of the challenge virus
+innate and adaptive immune systems
+between three and four
+up to two weeks
+critical care
+EBOV GP
+provide important support to neurons and modulate synaptic activity
+17
+November 2012
+viral protease
+minipigs
+Idd9.2
+16S rRNA
+minimal
+ambiguous
+ARV drugs
+hormonal
+1990's
+Viral titer
+food and environmental virology
+viral docking proteins
+Pro-inflammatory
+four
+iBLOT transfer system
+privacy issues
+up-regulation of MHC class II molecules
+surgical treatment
+illness onset
+pulmonary manifestations
+62
+judgments about people
+Kruskal-Wallis test with Dunn's multiple comparison
+Glycosylphosphatidylinositol anchors
+diffuse occurrence of positive cells with high-intensity labeling
+15, 30, 60, 90 and 120 minutes
+infecting
+mechanically ventilated critically ill patients
+36 or 12 h
+quality of the modeled structure
+Cox2 transcriptional start site
+end-expiratory positive airway pressure and pressure support
+Identifying and Prioritizing New Preventive Vaccines for Development
+isothermal titration calorimetry
+1-2 nM heavy chain
+Genome-wide significance
+Age
+2A pro
+asymmetry
+more than a half million
+locally weighted scatterplot smoothing
+Demographic parameters
+four
+53
+IFNs
+27 to 49%
+cytokine production
+KE
+molecular simulations
+after composting
+Chris Weiss and Hongwei Liu
+phosphorylation of bcl-2 and apoptosis
+30 min
+avian influenza control
+Emphysema
+all probes derived from their respective sequence group
+CLONTECH vectors LNCX and pIRES2-EGFP
+Poly-L-lysine
+Paired Wilcoxon tests
+negative-sense RNA viruses
+IFNβ
+Three
+right lung tissue
+supplementation with omega-3 fatty acids
+Eleven
+person re-identification and distance estimation
+std
+fluorescence resonance energy transfer -based mixing assay
+5
+serum creatine kinase
+Demographic details
+Cancer
+occupation
+AGR2-GST-beads
+sitafloxacin
+5%
+MxA 60
+global body
+24 hr
+non-functional aggregates
+DeMAND and DE target predictions
+loose stool and fever
+Y148R
+when the diffusion constant decreases
+patterns of continual immune selection mechanistically
+Pediatric Cardiac Critical Care Consortium
+273
+KPN_00466
+plosntds.org
+individualized medicine and precision forensics
+chorioretinitis, abortions, mental defects, and death
+5%
+Phylogenetic
+1%
+controlled
+Hepatitis B virus
+CPP-ELD peptide administration
+Hunter strains
+personal, religious or ethical beliefs
+Altered CRP and ESR values
+high power field
+virus-infected sample labels
+Door to balloon time
+global health security needs to be a priority
+E protein
+geo-referenced data
+PD
+TAT peptide
+156
+nasal swab samples
+15 min
+three
+respiratory syndrome virus
+Hepatitis C virus VFs
+Identifying those LBMs that could act as viral reservoirs
+RORγ t and arylhydrocarbon receptor
+in advance
+the major domains that interact with the host receptor
+caution
+recombination
+feeding stages
+Semi-preparative or preparative column
+6-8 weeks
+7.1
+b' s,t
+50
+Beijing Children's Hospital
+sequence similarity
+Enterovirus
+naïve ferrets
+progress in our appreciation of the neutrophil biology
+the sill
+binding of these proposed inhibitors with papain like cysteine proteases
+the literature
+24
+T-helper type 2
+50% tissue culture infectious dose
+53.7%
+Bacterial culture
+Multitest Imk Lymphocyte kit and Trucount tubes
+Readthrough at the test stop signal
+more than 50 times
+300,000
+patients with high geographical mobility
+two more weeks
+Plates
+singletons
+twice
+vasoconstriction
+canonical AA metabolism
+impairs the virus cell-fusion step by inducing cellular membrane changes
+envelope-mediated membrane fusion
+150
+innate immunity
+their strategies for establishing and maintaining cooperative relationships with crisis clients
+canonical polyA
+Cancer
+SDIs
+14
+long-term improvements in cognitive function
+Argonaute-like
+27
+gp120
+Alveolar macrophages
+0.5 mg/mL
+2.6 million
+biosafety reasons
+N
+colorimetric MTT assay
+63
+8 seconds
+Base stacking energies
+molecular mimicry
+ANNOVAR
+5%
+heterosubtypic crossimmunity
+Cardosa and colleagues
+Multiplex PCR
+when the viral polymerase loses processivity during virus replication at high titers
+M and W
+60%
+ecosystem and land-use changes
+DMD
+1000
+RA
+our data suggesting that muscle and peripheral nerve functions are normal
+Threonine
+flow cytometry-based bead array systems
+SPSS
+neutrophils and macrophages
+quarantine
+the control coefficient
+7-day old
+10,000
+Thailand
+bias the polyclonal antibody response toward non-entry neutralizing epitopes
+1,440
+accuracy
+6
+rs12979860 polymorphism
+in vitro and in vivo models
+Matrix coding strategy
+Pathogenic
+The disease ratio
+IFIT3 and ICAM5
+Genetic engineering
+Anemia, advanced gestational age, and preeclampsia
+Blockade of AaHig
+one
+C
+1
+good
+Myr-47/WT b bait peptide
+activates apoptosis
+Env proteins
+de-identified data
+PLX5622
+attenuated or virulent ASFV strains
+cancer
+influenza A
+reducing permeability whilst preserving a pneumotropic effect
+mutational
+Specifi c primers
+turkey red blood cells
+ORF5
+M1
+Apoptosis
+citrate
+standardized test method and exclusive barcode tags
+Structural
+Netherlands Food and Consumer Product Safety Authority
+all mortality and reduced disease severity
+Crohn's disease and ulcerative colitis
+transparency data and measurements
+CD169 ϩ population
+homogenates
+firefly or Gaussia luciferase
+4,585 mg
+A batch of incomplete genomes
+detecting the binding of Egr-1 and CBP at RTA promoter
+anthelmintic treatment
+stem nucleation
+Myeloperoxidase
+chimpanzees
+Pneumonia
+Seattle, USA and Shanghai, China
+Ekman
+Cuffquant
+permeate a target via diffusion
+0.1 g/day
+coronary artery disease and type-2 diabetes
+steroids
+Creb3-Arf4 signaling
+actin
+Cathepsin S
+Paroxysmal hypertension
+10
+influenza A virus replication
+anisotropy
+639
+chronic disease prevention programs
+24
+type I
+Toll-like receptors
+increases the INR
+100 μL DPBS
+GU wobble pairing
+The 95% confidence interval of the effective reproduction number
+Influenza
+96 ng/µL
+195
+six
+preventing violent crime
+1 to 10 3 copies/ml
+cholesterol
+Dual-host flaviviruses
+congruent
+demographic characterisations
+remyelination
+four
+R247A
+implausible
+CC10 protein
+TT virus
+fast hopping between ssRNA and hairpin intermediate
+50%
+Muscle
+Estimates of the measles case reproduction number
+twice
+dynamic genetic interactions
+30 min
+tripeptide proteasome inhibitors
+PKV infection
+geometry
+potential infective contact
+Eluted RNA
+Xbp1 mRNA
+cardiovascular disease
+larger effective population size
+complementary scoring functions
+H5N1
+Population coverage analysis
+alveolar macrophages
+Residue 75
+Standard deviations
+60°C/h
+deleterious mutational fitness effects
+four
+72 hours
+national and international surveillance systems
+high variant allele rate
+antigen processing and presentation of exogenous antigen and regulation of T cell differentiation
+communicate and collaborate
+IFN-c-secreting
+Carbamidomethylation
+negatively
+Splenocytes
+1 hour
+Fourteen common peaks
+values over 600 V/cm 2
+higher rates of mislabeling
+autophagosomes
+3.5-fold
+9.7%
+Tracheas, lungs, mammary glands, and nipples
+1891
+the virus CSFV replication
+H7N9
+132
+short-and long-term projections
+adequate antibiotics
+regulated expression of the protein of interest
+Binding of epitopes to MHC-I molecules
+10 2 CFU/mL
+Mycobacterium tuberculosis
+IL-10 and TGF
+a coiled-coil domain
+two
+2015-06-08
+improving the stress management of employees
+hamsters
+CHIKV-caused disease
+erythrocyte membrane epitopes
+Coomassie dye R-250
+protein target identification
+crystallization solution
+repressors
+bicinchoninic acid assay kit
+the BMV genome
+111
+100%
+32
+geometric means
+A common language
+2415
+abzymes
+Dakar Bat and Bukulasa bat virus
+neural progenitor marker nestin
+Gray's test
+GC
+Studies describing barriers on clinical or research data
+Apps
+inhibition of cell proliferation
+semidark conditions
+curve of the Haitian hyperimmune sera
+surveillance
+Soybean oil
+sGP-reactive antibodies
+ELISA reader
+hot plate
+Expression levels
+1 hr
+H1N1
+virophages
+90-day mortality
+,1
+public, political and scientific credibility
+An amplicon from the V8 region of the 16 s gene
+the highest antibody titers
+it does not rely on the creation of any immunoaffinity reagent
+decreased the protein level HCVcc at 10 MOI
+algorithms
+Bats
+Bacteriophages
+filamentous
+University Research Company
+peakMonitor
+gold particles as fiducials
+vitro cell culture system
+BalTec HPM-010
+1:50
+viral mechanisms targeting type I IFNs
+FimA NMR model
+ImageQuant LAS 4000 system
+limitations
+dementia
+detection of toxoplasma
+PAMs
+P241L, R242K, and H552Q
+246
+overnight incubation of the transformed cells
+effects of additional counts on single days
+antiviral activity
+ICAM-1 overexpression
+mitochondrial disturbances
+High Capacity cDNA Reverse Transcription Kits
+The glycocode
+Ͼ5%
+Ancestral sequences
+further clinical validation
+MCAo
+Western blotting
+Qiagen Viral RNA Mini kit
+calcium phosphate precipitation and Fugene-6
+I. Indigotica
+50%
+kyphotic correction
+SPC-TNF tg mice
+24
+Sepsis
+Peptides
+Sex
+R&D system
+AS03 B -H5N1
+Animal survival
+YKR051W
+γ-CyDs
+8%
+a nasal spray
+proteins that promote DNA synthesis
+perivascular
+Jen Sheng
+how this matrix varies with hospital ward structure
+human infection
+case counts
+sRNA from virus-infected and virus-free plant samples
+516
+random-effects model
+understanding the pathophysiology of tonsillar disease
+escalation of the coverage and intensity of these interventions
+six
+structural matching
+linear regression analysis
+CCL2
+mediates viral entry
+histological confirmation
+M. pneumoniae
+Two hundred sixty-four
+60.6%
+Hymenopteran
+100 ms
+P2X7R
+salivary glands
+Adoptive transfer of BMDCs from SFB colonized mice
+analytical results on the interactions between mixing decisions and disease dynamics
+Therapy
+policy change
+Glu426
+Acinetobacter baumannii
+noricumazole A
+92.7%
+ouabain, digoxin and lanatoside C
+chloroplast transgene products
+traditional logistic regression models
+strong dilution in those patches, and weak connectivity
+low
+95%
+Lung toxicity
+The structure of a protein
+HCA and PCA
+weak affinity
+immunological
+B
+4
+Drug repurposing
+b-isomer
+MYC
+.90%
+one
+little or no effect on L-A copy number
+methylation
+genes
+Human anti-EBOV Zaire Glycoprotein IgG titers
+ABC transporters and metal ions
+A framework for MCDA model validity testing
+HFMD
+Three hundred ninety-one
+1, 2 and 5
+poxvirus-vectored
+baseline HVPG and mean pulmonary artery pressure
+Cell-cell fusion
+population aging
+27
+six times faster
+apoptotic
+Cirrhotic and non-cirrhotic
+fluorescence
+Optical density values at 450 nm
+stops
+4.5% to 12.7%
+Acetaminophen
+RSA59
+FACSDiva
+CD11c
+evolutionary
+2019-07-24
+M1 and NP
+RIG-I
+ocular conditions
+Treatment success
+Mutations affecting dystrophin exon 16
+39 and 59 MO treatments
+Onset of symptoms
+relatively better protection
+G1
+2 hour
+the Laplace transform
+1 µg of an unrelated antibody
+48 hpi
+cytomegalovirus
+two
+Jos Seegers
+using the free EGFP and free mCherry samples
+12-16 breaths per minute
+35.5% total calories supplied as fat and 14% as saturated fat
+21
+30 atm
+four
+four
+decreases
+60%
+30-45 kDa
+more than 50
+increased separation between the two distributions
+LAMP
+w i
+IFN-γ
+Pharmexa-Epimmune
+Hepadnaviridae
+3
+output consensus sequence
+rather short
+adjusted odds ratio
+lipid droplets
+novel treatments of prostate cancer
+collaboration across disciplines, sectors, organizations, and national borders
+December 2015
+Encephalomyocarditis virus
+HA
+household structure
+7.8-fold
+Thirty-six hours
+pathogenesis
+epithelial brushings
+Biased viral samples
+399
+56-100%
+resident memory T cells
+unresolved
+5 min
+transmission of HIV
+Parameter estimates
+Igf-1
+Anti-β-actin mAb
+pyrazole
+between QW170/218-like and Sw43-like strains
+Xbp1 signaling
+IL-1β and IL-18
+6ice
+augmented changes in histopathology
+PCR-based molecular diagnostic assays
+ROC curves and C-indexes
+Richard Smith and Jo Coast
+their protease activities
+Patient PBMCs or murine splenocytes
+β-casein
+phenol: chlororform extraction of the supernatants
+brain parenchyma
+a gift card
+0.16
+land-based surveillance
+higher titers of opsonic antibodies
+25%
+sequence-specific primers
+PUUV genetic differences
+Daimond-Blackfan anemia
+3 h
+5
+complications arising from selection of revertants of deleterious virus mutations
+21
+three
+1
+T
+renal tubule epithelial cells
+early and late viral groups
+UBP43
+immuno-stimulants
+selected for strong/weak folding
+lipid and fatty acid metabolism
+knowing when there may be an inaccurate report of a change
+PCR-based site-directed mutagenesis
+identifies the consensus or major viral genome present in a particular isolate
+D-dimer
+SNARE-Munc18-1-mediated liposome fusion
+AD-4 and AD-5
+21 dpi
+government authority and the rural raisers
+antigens
+viral dsRNAs
+Revolutionary Wealth
+pARDS
+sepsis-induced capillary leak and development of pulmonary edema
+Donor source
+TNF-α KO mice
+7
+RNA runoff transcripts
+ten
+VLPs
+bone repair and revascularization
+discovery SNP
+ten
+Macrocyclic
+mortality
+6 non-structural proteins
+570 nm
+Mg 2+
+An in-depth analysis
+7 days
+10:90
+Eqs 5, 6 and 7
+6-8 ft 2
+mast cells
+BHK-21 cells
+three
+151
+four
+E2 glycoprotein
+1343
+Dendrogram on Figure 1A
+group III
+Chinese herbal medicine
+The Effective Size
+EGR1
+loss of the FG-rich region
+high levels of CD11c and MHC Class II
+clinical outcomes
+local orientational disorders
+48
+the image
+6000
+it will be a transmission hotspot
+5-7
+less
+cumulative proportion of the population infected
+Simple sequence repeat
+ul3-ul4 and ul30-31
+PCR, real-time-PCR, and Multiplex PCR
+after resin cleavage and purification steps
+the highest value obtained within 3 days of acute visit sputum collection
+Serial 10-fold dilutions of the cloned plasmid
+1 mass
+112
+TNF-α
+TNF
+Proteins
+NCs
+CD4 T-cells
+0.011 ± 0.008 mg m −3
+Nonspecific sites in the membrane
+Influenza and Human Adenovirus
+homeostatic model assessment to quantitate insulin resistance
+Fc-dependent viral clearance
+Careful choice of efficient delivery
+Our next result
+volutrauma, atelectrauma and biotrauma
+centrifugal filter tubes
+5 min
+220
+20.78%
+the retroperitoneal region
+Establishing a healthy environment
+Ifnar1 SA mice
+low
+immune checkpoints
+292bp
+pessimism
+conventional nutritional supplementation or the infusion with an amino acid cocktail
+40
+chromosome 15
+HLA-typed normal tissue arrays
+porcine circovirus 3
+sexual promiscuity or moral degeneration
+7 days
+gene-expression profiling
+Met·tRNA MET
+structural determinants in the interstitium
+F4/AS01
+coinhibitory
+Transfection with high levels of gH/gL DNA
+peptide
+most cells examined by confocal microscopy
+hypertension
+3 h
+The sex of the individual flies
+all-regions conditions
+sumoylation
+liver diseases
+91%
+surveillance systems
+seven
+failure to accommodate the intention-behaviour gap
+chloramphenicol resistance
+cytoplasmic E7 production
+Calpain
+68%
+DC-SIGN
+Hsc70
+arrests the cell cycle
+seven
+disease outcome
+60
+5%
+luciferase activities
+single association signal
+break out
+19%
+encapsulation
+cholera and dysentery
+four
+Atg5
+acceptable
+0.45 mM PVDF membrane
+national epidemic curves
+focal adhesion
+Bayesian hierarchical model
+T526A, Y527A or W529A
+TGF-β signaling
+Sepsis
+artifacts of the particular partitioning of the data into training and test set
+TakaRa MiniBEST Universal Genomic DNA Extraction Kit
+undergo apoptosis
+NIH AIDS Reagent program
+control chart-based algorithms
+age 65 years
+mSTING R168A
+contingency planning
+50%
+belief state
+Antiretroviral therapy
+complementary RNA products
+lower
+3 days
+Hep-2 cell line
+phasic ASM contraction
+cerebral cortex
+increased viral replication
+using previously defined cutoffs
+NP 89-97 and NP 198-206
+99.6%
+harmful risk factors
+remifentanil and midazolam
+four
+β ρ
+independent dataset test, subsampling test, and jackknife test
+separate the different phases in the space of the parameters
+IMG/VR
+NF-κ B-dependent transcription
+X4%
+59 to 69.1 o C
+Pana et al
+3
+physiological and biochemical similarities
+IS/885/00 and IS/1494/06
+binding to GAGs
+An ongoing study
+biomolecule structure characterization
+ORF2
+London
+Affymetrix probe sets
+Lack of time
+partial correlation coefficients for mean daily prevalence and the value of a particular parameter
+Cell death
+Maximax
+Mutating the lower stem of IRENE
+p = 1
+long-term follow-up studies
+ZIKV
+>70fold
+disease severity, microbiological findings and anti-infective agents
+Cox Proportional Hazards regression analysis
+Fisher's exact tests
+Muc5AC
+C-terminal residues Arg73-Lys100
+CD36
+0, 15, 30, 45, and 60 min
+autocorrelation
+Iterative HFold
+Plasmodium, C t
+answer questions or follow instructions
+10 to 20
+Inhaled hyperosmolar agents
+every 3 months
+gut microbiota metabolism of dietary fiber
+systemic inflammatory response syndrome
+19 days
+19
+1.1
+Extended Data Table 2
+Forssman disaccharide
+65.8%
+T and B cells
+as findings are presented elsewhere
+WNVCp
+1:10
+TNF-α
+IL-17
+low
+Metabolic stability
+4 weeks
+Two-way
+Liberal oxygenation
+Four
+inflammatory
+internal controls
+cope, make decisions, and return their lives to normal
+87
+100 nM
+MBP columns
+pathogenicity
+GVHD
+GL-ALG NGPs
+6.3%
+higher order structures
+ATP and NO
+RT-qPCR protocol
+Genetic reassortment
+viral nuclear transport
+AIRS
+none
+index read
+PCR
+Water soluble dual function probe
+H1-influenza A-specific T cell responses
+Genome structural annotation
+EBOV
+25
+more reliable state
+115
+The plasmid linearized with the BamHI
+Roland W. Herzog
+0.05
+55
+hepatocytes
+Nine
+pBSTNAV
+2 months
+Pierce BCA protein assay kit
+phylogenetic error
+high resolution
+high
+practices and therapeutic schemes that are different from those of others
+1997-2004 and 2005-2010
+high seasonality
+a clinical isolate
+TNF-α-converting enzyme
+1996
+gel electrophoresis
+artificial detail
+bats
+pigs
+NNAlign
+DNase
+low-viral-load group
+Renilla luciferase assay
+six months
+distinct
+Chemokine
+Figure 7
+LGALS3BP and BST2
+No significant difference
+influenza pseudotypes
+significantly
+36
+20
+geographic distributions, growth conditions and harvesting seasons
+The motif length, encoding of flanks and peptide length
+vesicular trafficking
+ML-estimation and moment estimation
+pulmonary arterial hypertension and hereditary hemorrhagic telangiectasia
+Retroviral vectors
+nuclear transport
+no significant association
+The curves
+significant differences
+SUMO-HMGB1-A-BOX fusion protein
+1 h
+apocynin
+SA
+Seven
+FasL, LIGHT and TL1A
+100 μl GloLysis buffer
+Selected religious MG event of Tamil Nadu
+12%
+transit peptide cleavage sites
+myocardial dysfunction
+half an hour
+49
+The HI test
+Texas, U.S.A
+genital structure of males
+PPP-RNA binding
+1.8 mL of the supernatants
+15
+tandem arrays
+ribosomes
+the annotation with the highest Smith-Waterman score
+multiorgan
+kidneys
+sex and body weight
+over 100
+Lipofectamine LTX
+experimental evidence
+Search strategy and database name
+Three
+Portsmouth genome
+the same tree topology
+biochemical
+interventions to improve the health of the worst-off sub-populations
+trimerisation of the N-terminus of TM
+malaria, enteric fever and diarrhea
+fungal load
+conformation
+29
+54
+inefficiency means waste
+four
+Plum Island Animal Disease Center Institutional Animal Care and Use Committee
+limited availability of published results
+Direct exposure to body fluids or contaminated materials from infected patients
+five
+Tissue samples
+Having a household with children
+NDP52 and TAX1BP1
+1,282
+antigenically
+tripeptidyl peptidase II
+hydrophobic
+transgenic memory B cells
+162
+better thermal behavior, plasticity, toughness and biodegradability
+comparative parameters
+1892
+after the colonization of the New World
+VEP
+adenosine
+through ENTs or CNTs
+62%
+a relative ranking of country capacity
+Three hundred nineteen
+superinfection exclusion
+Apoptosis
+Flaviviridae
+secondary structures and RNA elements important for cyclization of the genome and virus viability
+infection
+miRNA-based antiviral therapeutic interventions
+aerobic processes
+Cox B5 and EV-D68
+antagomiRs and sponges
+Chase expression
+commitment, and vision
+bacterial, fungal, viral, and parasitic pathogens
+base compound
+ISGs
+a clear management plan
+chronic juvenile arthritisl CNS
+UNDP-PCR method
+large and aromatic side chains
+ELISA reader
+x i and x j
+LASV LCMV JUNV anti-LASV NP
+baseline drug resistance
+unnatural anthropogenic disturbances
+cerebral, circulatory and/or respiratory failures
+Correct integration of mCherry constructs
+71%
+Cellomics Multiparameter Cytotoxicity 3 Kit
+10.3390/v6125047
+MetaMorph microscopy analysis software
+20-24 hours
+50
+Figure S2
+inefficient
+over 885
+Sensitivity
+PG
+20%
+IL-1β
+control mAb reactivity by flow cytometry
+the same
+validation
+host cell proteins
+Early recognition and prompt treatment of severe pneumonia
+discontinuation of the causative agent
+proinflammatory
+Four
+BG-Sentinel traps
+94%
+SILAC Protein Quantitation Kit
+3%
+mucosal humoral and systemic
+novelty
+viral replication sites
+base excision repair
+transmembrane ER resident enzymes
+45
+non-linear increase in disease risk
+viral replication
+Site 1
+administration routes
+Liver diseases
+alveolar
+a selection marker
+the present study
+3
+60 min
+Anti-thyroid
+adhesion
+adefovir
+Japan
+3
+Heterophil/neutrophil recruitment to the infected site
+tracr-R, AF3 and AF2
+p47 phox
+immunochromatographic
+intracellular radioactivity
+Neutropenia
+TRAP
+erythrocyte receptors
+biological post-translational modifications
+a i = 0
+six
+cc-by
+ImageJ
+porcine trypsin and endoproteinase LysC
+982 nm
+codon usage
+32.9%
+IDEAL-Q
+q18S RNA gene
+inhibition of neutrophil elastase
+bioinformatic
+6
+hepatic venous
+Sidak
+PB2 627K
+12,630
+Benzonase and reducing agent
+VSV
+UV-visible
+small arteries, veins and arterio-venous anastomosis
+strong structuring of the FTLSV phylogeny by provinces or area
+antigenic site B
+adaptor ligation amplification
+200 mL
+eight
+Inhibition of the redistribution of ACE enzymes
+peri-urban
+30
+do not exchange genetic material frequently
+SM patients
+infant respiratory distress syndrome
+Nosocomial bacterial meningitis
+The BioProject database
+drug-resistant mutant
+mechanical damage to neural and vascular structures
+modifications
+natural disasters
+30.8%
+Salivary glucose oxidase
+distilled water
+three hours
+31
+influenza A
+January 1, 1995
+Twenty-six
+Fresnel diffraction theory
+wild-type mice
+muscle viability
+genotoxic
+unidentified importations, relapse cases or unreported locally acquired sources of infection
+12
+they use a little different set of tRNA molecules
+Peter Stä heli
+Blood spot-containing filter paper
+their ability to combat anoikis
+three
+Acquisition of data
+GAPDH
+Hsp42p
+serious suicide attempts
+weight gain
+IRF7
+Highfidelity
+Wilcoxon nonparametric test
+SYBR Premix Ex Taq
+selected results of clinical or animal-model research
+zoonotic infections
+transgene compartmentalization
+syncytium formation
+b-Catenin
+1975
+SpreaD3
+coincides with standard GA b-isomer crosspeak patterns
+synonymous codons
+Bourcier et al.
+mink
+codons
+1
+ISG15
+1/μ V
+Important information
+1/Z
+human, avian, and swine influenza viruses
+creating an effective regime of regulation
+Protein from the supernatant
+nine
+endocytosis
+Zika virus
+faecal bird-samples
+arterial or venous walls
+multifunctional
+alternative splicing
+pulmonary stem/progenitor epithelial cells
+RPMI-1640
+signaling pathway
+T cell-mediated immune response to various myelin antigens
+75.8%
+2,000
+ages that lie outwith the age range of humans
+average peptide spectral matches
+hundreds of nanomolar
+R IBM 0
+selectionist
+Phylogenetic trees with molecular clocks
+reduced F cleavage
+changes in virulence
+catalyzed thiol-disulfide exchange
+52%
+Escherichia coli strain DH5α
+Pneumonia etiology studies
+129
+community assembly data
+66, 89, 96, 99 and 100 per cent
+TRIzol Reagent
+65 ml/kg
+repair of the injured lens epithelium
+10
+A short region of the NS5 gene
+Biomed, China
+increased risk of heterologous A09 illness
+cytokine
+succinic semialdehyde dehydrogenase
+Pro76 and Gln73
+the infection in the lungs
+China
+Axioplan 2 Imaging
+Clontech's TALON Metal Affinity Resin
+Ther eaction
+Agilent Scanner G2505C
+CTL response
+Human tissue
+CC10-treated
+Apdm09
+machine learning
+ModFit LT curve fitting algorithm
+The ENC
+Myc-Sirt1
+The use of communications
+GP
+day 9
+increased survival
+twice
+1918
+Mutation sites targeted to influence overall activity
+Females
+FastDigest Restriction Endonucleases and Phusion polymerase
+216
+geNorm V
+lamin cleavage site
+10 min
+33uC
+pandemic
+CWP232228
+between 9 and 22 months
+circulatory shock
+4 h
+a trained study worker
+4,380
+31.1%
+acetylated histones and BRD4
+1.41 to 2.00
+composite primary key
+two-dimensional random diffusion model
+Peripheral
+Six
+39
+Qiagen RNAeasy columns
+4.3%
+differences in the ligands
+CD4 + CD25 + Foxp3 + Treg
+interferon-induced transmembrane proteins
+Termination-reinitiation frequency
+1975
+once a month
+Dry cough
+a signaling cascade
+did not exist
+TCR
+Subgroup FeLV-A
+20 µL
+Non-specific cross-reacting bands
+~30 nm
+an explanation
+20
+74
+face velocity, fiber diameter, packing density, filter thickness and charge density
+1968
+acute fibrinous or organizing pneumonia
+0.2
+public trust in government
+coinfecting agents
+three
+Mathematical models
+increased endothelial permeability
+NE
+6°C
+Strayer's group
+Hazard ratio with 95% confidence interval
+effector memory T cells
+industry guidance
+ZðtÞ
+extracorporeal membrane oxygenation
+29%
+molecular docking studies and thermodynamic analysis
+Elastase
+11
+Incident of renal replacement therapy
+functional NSs protein
+HEK293 cells
+anti-HIV drugs
+by adding up the number of daily cases every seven days
+viremia
+a gradient
+100%
+similarity to reference databases
+C5aR
+elongation mediated by viruses
+previous findings based on immunohistochemistry
+Ethics approval and consent to participate
+selenocysteine and pyrrolysine
+2 h
+clues for therapies
+inflammatory responses
+2,377
+À 1 frameshifting
+Oidium lycopersicon
+acoustic cavitation
+integrated relative error
+parts of the mature domain
+rotavirus infection
+non-sense mediated decay
+13 ± 5%
+The treatment showing greatest therapeutic efficacy
+novel vaccinal approaches
+diversified steroids
+myocardial infarction
+0.154 and 0.188
+Infection
+four days
+Herpesviruses
+Protein Data Bank
+strategies that optimally exploit the use of IL-17
+nongroup A streptococci
+30.6%
+endonucleolytic nicks
+research into human locomotion
+mRNA reduction
+critical
+five days
+African
+Uganda
+Vimentin and CD209
+Johnson & Johnson
+RPKMs
+poliovirus capsids
+particles
+1 µg 7SK-as RNA
+competitive exclusion, superinfection, recombination
+Public distrust in journalists
+Resource Description Framework
+ACE2
+1000
+red deer
+9
+four weeks
+Plasmodium knowlesi
+host RNA synthesis
+five
+one per 309,312 bp of sequence
+individual-cell components
+Negative template controls and positive controls
+viral antigens
+2019-nCoV
+1.02 nM
+78
+46 h
+close connectivity to China and south-east Asia
+logarithm-transformed antibody levels
+R. australis infection
+Serum-free DMEM
+oral health status
+RNase L antagonistic
+CP32M
+10
+necrotic
+effective therapeutic strategies
+IFNa production
+improvement of detection methods
+Chest-X rays
+stakeholder
+30 min
+large outbreaks occur with significant probability
+12 months
+poor/insufficient preventive practices
+54 days
+unknown
+vinyl chloride material
+1 × 10 1 copies
+local pharmacies
+chimpanzee studies
+GADD34
+integer number of segments
+CD8 + T cells
+more than 100 million
+Tissue
+membranous
+Intravenous or intrarterial injections
+RNA-seq
+Student's -test
+less
+cc0
+pattern recognition receptors
+viral structure and function
+hand washing and use of mask
+Toxocara infection
+progressive disease with high mortality
+bone marrow
+many studies used modified AKI criteria
+constant vs. age-dependent mortality rates
+21 days
+disintegrates
+cardiovascular disease
+microplate reader
+18
+3,000-fold
+MBP
+TP model
+Substrate binding
+six
+TLR7 and TLR9
+whether they are critical genes in the response to MDV infection
+men
+Thirteen
+diploid cells
+The nature of the release profile
+Lys291 and Lys292
+11,700
+Capillaria species
+Intracellular Zn 21
+Mca-APK-Dnp fluorogenic substrate
+Pregnancy
+23
+synthetic social contact networks
+to distance the fluorophore from the cleavage site
+non-toxic
+370
+people who are in
+Health
+vascular
+Dkk-3
+LAMP1
+Metropolis criterion
+Ca 2+
+LYC-OA
+acute respiratory distress syndrome
+141 mm
+2009
+18
+virus titration and pathology per day
+vivo
+Hasegawa-Kishino-Yano model
+Apoptosis
+45 days
+96
+2012
+140 μl of each sample
+353
+traditional lectures
+AMI
+16%
+NCBI's Gene Expression Omnibus
+25%
+22
+15
+50%
+responses to variation in sodium and potassium intake
+shRNA expression plasmids
+0.45%
+Cg1
+supernatants
+p38 MAPK
+L. braziliensis
+Weibo
+pulmonary pathophysiological
+intravenous
+Cell monolayers
+linkage-specific reactivity in EL4 lysates
+Three
+PD-1 and CTLA-4
+plasmon-enhanced fluorescence
+nine
+1-15%
+phosphorylation of eIF4E
+Immunity
+strict correlation
+proteasome activity
+12
+4G5
+mice and rhesus macaques
+300
+IRE1, PERK, and ATF6
+XML
+TII cells
+MMP7
+highly heterogeneous concepts
+28-day
+those reported in Hapmap
+sadness
+Independent Nearest-Neighbor Hydrogen Bonding model
+conserved regions of the genome
+30 min
+12°C
+Equine Arteritis Virus
+CD209
+host immunity and pathogen virulence
+500 μg/ml
+HHV-6 infection status
+reduced circulating lipid levels
+PRPF31
+Simplified Acute Physiology Score II
+Aqua
+antioxidants
+TRIM21
+NaCl
+Pearson χ 2 test
+ωP
+Image Pro Plus
+R2 = 0.78
+five
+controlling the population of active Kir2.1 at the plasma membrane
+64
+higher-transmissibility scenario
+A site
+January 20
+7000
+several questions
+Human memory B cells and plasma cells
+NZ European
+pneumonia-related ARDS
+bird counts with selected sampling and PCR testing
+Neutral red -containing viral stocks
+Sputum purulence
+S100
+genetic drift
+their genetic distance to their MRCA
+12.9%
+affinity on the edge of the OTU-ISG15 interface
+2012
+synergism
+in the following way
+135
+ts53 and wild-type viruses
+CFSE
+neutrophils
+guidelines
+the makeup of the matter between the respective electrodes
+the principle of close proximity interaction
+30
+excellent immunogenicity
+mice
+20
+knockout of expression of the corresponding viral protein
+data regarding vaccination status and oseltamivir prescriptions
+591
+LPSinduced NO and PGE2
+Cross entropy
+western blot analysis
+acute gastroenteritis and severe watery diarrhea
+2
+Cell Culture of Human Cell Lines A549 and HEK293 cells
+three
+0.69
+μ
+the peak and final size of the outbreak
+four
+CaCo-2 cells
+tumor size and location
+Herd immunity threshold
+Vaccination
+RNA integrity
+cm
+High force
+The density of the MAb 9.2 reactive bands
+protein-protein recognition
+influenza
+663
+protect commercial poultry operations and subsistence farmers
+Meleagris gallopavo β 1 -AR
+neutralizing monoclonal antibodies
+100
+white blood cells
+N6
+200
+Wet Bulb Globe Temperature
+immunofluorescence assay
+to develop effective preventive and control measures
+EMCV-infected wt mice
+30
+s
+an RNA virus mutagen
+rotary
+error rates
+Joint hypermobility
+higher mortality
+More detailed epidemiological studies
+high performance liquid chromatography
+F4/AS01 and AdC7-GRN
+preanalytical and the analytical procedures
+Four
+The amplification of GAPDH
+24 h
+direct contact
+Three
+ATP
+wavelet coherence
+>600,000
+McCloskey, Brian; Heymann, David L.
+heat shock
+Biochanin A
+macrophages or dendritic cells
+positive
+condition
+724
+host-derived lipid membranes
+prevalence
+1 min
+A threshold
+Five
+24 h
+6 months
+9 to 43 amino acid residues
+exceed the response
+10 mg/mL
+non-pharmaceutical intervention
+IL-8
+ventilator days
+canine airway tree
+PRV vaccine strain Barth K61
+90 days
+33 per cent
+critical
+chikungunya and Zika
+46.7%
+16
+additional factors were influencing drug delivery
+the background image
+mathematical models
+thirty
+animal lectins could be strong candidates of receptors for GPs
+Lentiviral particles
+infected or transfected cells
+Figure 6A
+CEACAM1
+cutoff choice
+inducible recombinase transgenic lines
+signaling cascades
+binding specificities for ClfA and alpha-toxin
+DS-Cav1-adjuvant mixtures
+twice
+predefined connectivity between locations
+thousands
+Influenza A virus
+feces of diarrheic pigs
+how the sequences can diverge
+entry and infection by members of other virus families
+over 100 million
+31%
+compound 3m
+rotavirus
+increased
+fourth site A
+HIV infection
+environmental factors
+The ACT
+gene expression-based molecular characterizations
+a functional emergency medical response system
+influenza H1N1 virus
+CFTR
+the corresponding author
+linear regression
+Acute lung injury
+18 h
+site 39
+Basic Local Alignment Search Tool
+Chinese CPV-2c strains
+pNP-saccharide
+87%
+PCR
+preoperative VA-ECMO
+controlling
+differential causes
+95,835
+ubiquitination
+disorders of the central nervous system, trauma and sepsis
+Related searches discovery tool
+six
+MapReduce
+491 and 581 bp
+16
+KSHV and EBV
+Immunofluorescence assay
+Investing on Aedes associated ZIKV advanced operational research
+C-type lectins
+0.35 to 10 µm
+yeast life span extension
+Imaris software
+GRK2 kinase activity
+oligomerization
+275
+11
+influenza A
+Cog4 and Cog7
+Two
+200
+bioinformatic
+between passages 3 and 10
+increased caspase 3/7 activity
+luciferase reporter constructs
+Transient association of functionally related components
+respiratory
+missing classifier
+myeloperoxidase and CD68
+signal transduction pathways
+initial similarity searches
+the wt
+36 weeks
+Colony forming units
+HFIP in DCM
+Ten
+1.3 years
+AIRS
+to ensure intracellular amastigote growth
+positive
+Mamu-A4*14:03
+three splice sites
+Additional file 1
+1 h
+health seeking behaviors of the population
+bacteriophages
+protection against weightloss
+three
+two
+Sangon
+coiled-coil
+29 pmol/ml/min
+Airway epithelial cells
+limited plasma volume available
+Western blot
+evolutionary adaptation of a species to novel environmental conditions
+almost five million
+PI3P production
+G_RUU_UUU
+C2
+postvention
+Microarray analyses
+intracellular membrane tubes
+slight differences among the different subtypes
+Multidrug-resistant
+Cuizhu, Huaqiang North and Huafu
+Accommodations and incentives
+counterintuitive results
+Membrane-destabilizing peptides
+NES3
+Camels
+3I14 in mediating ADCC
+daily data
+G. dewevrei
+1.72 nm
+immunological elucidation of other pig-pathogen interactions
+3 days
+hypotension, inflammation or prolonged survival
+0.5
+Adhesion
+model deviance
+more severe kidney injury
+32 weeks
+cc-by
+Neutrophils
+p68 Gag and p3 Gag
+platelet
+Transepithelial electrical resistance
+CRY2/CIBN fusion to inositol phosphatase
+1|5|5~25
+720
+The RNA extracted from FTA cards
+indirect selection of mutations
+apoptosis
+53
+E. coli O157:H7
+33
+antiviral
+96-well plates
+antiviral
+30.8 nM/min
+to assist clinicians in the diagnosis and treatment of viral diseases
+Blast2Go
+SDS-polyacrylamide gel zymography
+Progeny viruses
+Respiratory syncytial virus
+2 h
+clinical and radiological findings
+sSBV and SBVDNSs
+predominant
+68%
+phylogenetic
+attack rate
+47 and 62%
+age distributions in 5 year age bands by administrative area
+0.005 EU/mL
+Hereditary spectrin deficiency
+every 3 days
+sialic acid receptor binding
+antibody therapies using incomplete antibodies
+Bowman-Birk
+A broad set of haplotypes
+selfoligomerization
+Economic risks
+September
+identification mistakes
+cell viability of human osteosarcoma cells
+improved goodness-of-fit and somewhat improved discrimination
+16.28 units
+day −1
+~60-100 nm
+90.2%
+ITCH, WWP1 and Nedd4
+Cytokine-containing media
+family signature motifs
+Deborah Diamond
+protein
+human proximity
+cancer associated antigens
+reporter gene or modi fi ed gene expression
+to deliver Met-tRNA i Met to the ribosome
+ciliopathy
+bioactive
+Five
+expression patterns
+plasmodium infection
+TOTO-3 or Vectashield mounting medium with DAPI
+four
+the lung
+HRV 3C protease
+at the top of the circle
+Red Cross Children's Hospital
+100 KDa Millipore tubes
+16
+PRSS1 and PRSS3
+2-sided unpaired t-tests
+5%
+ISGs
+pharmaceutical immunomodulators
+TRIzol
+Age-and sex-associated differences in exposure and severity of infection
+2
+Travel as risk factor for an influenza infection
+G
+the sampling and the number of sessions
+broncho alveolar lavages
+150-300
+individuals
+MC filed
+93%
+texts
+70-80%
+glial cells
+negligible virucidal effect
+vaccination
+2010-04-27
+a vaccinia virus vector
+≥4
+Joshua Lederberg
+crucial
+2,851
+two identical inverted terminal repeats
+Spherical IAV particles
+250 × 10 3 /mL
+ACE2
+Nucleic acid diagnostics
+dystrophin restitution
+95%CIs
+their critical role in the initiation of Ag-specific response
+Educated and literate populations
+Korean bat Miniopterus schreibersii
+inflammatory
+a multigene family
+acute respiratory infections
+Paired-end sequencing 2 × 100 bp
+conspicuous
+15
+T cells
+5
+PS-dependent
+eight
+nuclear factor-κB
+disease severity
+lower
+150 µL of 1x dPBS
+hippuristanol
+2001
+membranes
+E. coli and S. cerevisiae
+murononab
+case reporting rate and specificity
+all protein import pathways
+co-morbid conditions
+30 min
+N-terminal half
+a volume of PBS equal to the volume of stimulation reagents
+zeroes
+nucleolar accumulation
+mechanical ventilation and oxygenation
+viral nucleoprotein
+L11 P-site loop
+two
+MRW
+TLR8
+random
+Nigeria
+Cytometric Bead Array Mouse Inflammation Kit
+human diseases
+latent class analysis
+the surface of the heart
+Autographa californica Nucleopolyhedrovirus
+2.5 3 10 5 to 2 3 10 7 events
+blockage
+three
+amino acid changes
+very similar results
+high-level expression and protein stability
+developmental time is a significant factor
+Aquavac IridoV
+graphic enhancement
+phosphorylation of Egr-1
+current technological advances
+under 40 years
+guinea pigs
+binding and catalytic activities
+larger
+ILI or other forms of surveillance data
+crawling and gliding
+two
+CX3CR1 and IRF4
+a devoted and reliable spouse
+interpretation of KIH interaction networks
+disease severity
+Logistic regression
+RANTES
+p50/p65 heterodimer
+62%
+~25 times
+intron
+83%
+EBV pathogenesis
+6
+θ
+100 µL of the mixture
+Pfam
+M
+2
+E154
+Parker Hydrophilicity
+continuous attempts in the rational design of melanocortin receptor molecules
+21 dpi
+2.8%
+21
+bioinformatics software tools
+70.3%
+6 and 12 ml/kg
+type II
+4 h
+HI metrics
+N protein expression
+Fc gamma receptors
+lower
+one hour
+indirect selection of polymerases with higher mutation rates
+U6 mRNA
+Hsp40 and P58 IPK
+reverse transcriptase-polymerase chain reaction
+public, commercial, or not-for-profit
+clonazepam
+5000-10,000
+One hundred twentyeight thousand four hundred twenty
+maximum likelihood estimation procedure
+inverted microscope
+The oil spill and oil-free surfaces
+combined intervention strategies controlling infection, inflammation, and necrosis
+1 h post-MRSA addition
+Influenza vaccination
+negative
+56 DCs
+Twelve
+spinal cord stimulation
+the standard deviation of the mean
+monocistronic
+0.2 µg/mL
+~20%
+eight
+E. coli
+Rio Declaration on Environment and Development
+fetal
+36%
+IgA
+the slope of the linear fit and its 95% confidence interval
+macropinocytic pathway
+haemolymphatic
+the prevalence of Borna disease
+65 years or over
+GAVVALSTTFA
+13.8%
+an uptake scan
+Sir Tim Berners-Lee
+surprise
+long TSS isoforms produced from the neighboring genes
+AUC
+Heat-killed SCHU P9 antigen
+myristylation
+passive
+33
+Colostrum and milk
+lipid metabolism and the interferon response
+2,992
+58
+three
+low frequency of GFP + events
+the geographic distance
+thaumatin-like protein 5 and 33-kD
+the virus circulating through the aphid
+essential
+GDS-15
+polyplex
+63.26%
+.50%
+IFN-λ 1, 2, 3 and 4
+Medium containing both chloramphenicol and spectinomycin
+haemangioma development
+surgical masks
+psycho-social
+6,500
+postcolumn infusion experiments
+means, standard deviations, medians, and percentages
+43
+RIG-I knockdown
+36
+TREM-1
+Forty-eight hours
+Oral rehydration solution
+Direct ascertainment of R a and R a,t
+cc-by
+pHylox2
+48 h
+filovirus infection
+total disagreement between prediction and observation
+four
+fragmentation of chromosomal DNA
+electronic
+unpaired t test
+229
+TG mRNA
+>40%
+2.9%
+natural killer cells and cytotoxic T lymphocytes
+serial interval events
+Western blots
+0.3%
+ketoconazole
+15
+holding places for suspected Ebola cases
+immunosenescence
+IL-4
+GO term enrichment analysis
+20%
+Molecular Medicine
+capped dicistronic
+endothelial cells
+chemoresistance
+alternative folds involving L2
+three
+high-quality
+Cholesterol, tocopherol, or bis-lipid moieties
+six-month
+poorly soluble in water
+repetitive sequences
+programed cell death
+immobilized metal ion affinity chromatography
+Oxidative stress
+MegaBLAST
+92%
+AIDS patients
+PfRH5 and PfRipr
+peptidoglycan spheres
+SMAD4 and TGFBR2
+Five
+mAb 8C6
+Ventricular hemorrhage
+4,168,266 bp
+73%
+stress-induced autophagy
+suppressive
+effect of soluble factors from PBECs on PDC functions
+strawberry preserves
+obesity
+A variety of methods
+mice
+6.7 Ϯ 0.5 hours
+Toehold switch RNA sensors
+temporal sequence of infections
+case report form
+pgsA/L. casei
+female
+extracellular matrix
+four
+National security
+a symmetric approximation of the empirical fluxes
+mutational bias
+limiting IFN-I's contribution to ongoing immune activation
+contagion
+Sera
+cells of the myeloid compartment
+Rep ctrl and rep exp
+lymphatic spread of liver tumours
+50
+clarithromycin
+Proteins
+inhibition of VEGF-mediated angiogenesis
+virus neutralization by VRC01
+gp120 disulfide bonds
+1.5-fold
+Severe fever with thrombocytopenia syndrome
+ferrets
+complex
+105,050
+ribosomes
+517
+50%
+Wild type VSR plasmids
+Eight
+lung
+100%
+9A8 mAb
+2017-05-11
+Knockdown of endogenous EK
+GSK-3β
+mediators
+regulatory
+a correlation with disease severity
+1,000
+Thirteen
+LacdiNAc
+10 µg/ml
+12
+four
+CodMod
+indirect information of the proteins role in disease
+apoptosis
+exhaustion
+c 0
+300 to 350 g
+if the solution used has a composition that is optimized for the LAMP reaction
+10%
+saturation
+MS/MS
+potential synergistic and antagonistic epistasis among variants
+10 cm
+downstream amplifier
+traditional ritualistic practices
+regression or time-series analysis of seasonal ILI data
+IECs
+CD11b + Ly-6C hi monocytes
+Atherosclerosis
+Caspase 10
+more efficient and effective use of these limited resources
+HIV-1 attachment and infection
+10%
+lung mechanics and oxygenation
+1.6
+USPs
+intracranial instillation of wtVSV
+mucosal immune barrier
+alveoli
+Open lung biopsy
+alveolar pressure
+52
+veno-venous extra-corporeal membrane oxygenation
+C3a, C4a and particularly C5a
+animal care
+18y
+copy number differences
+Area Under Receiver Operating Characteristic
+genogroup II
+four
+Media
+Multi-tasking
+physiological affinity range
+4,453
+100 FFUs
+Algorithm 1
+spleens
+Statistical analysis
+100% methanol
+selective autophagy adaptor proteins
+Phylogeographic inferences
+IFN-SNPs
+host species-specific difference in viral entry receptors
+those with neurological diseases
+498
+active bleeding or rebleeding
+NlaIII anchoring enzyme
+three-quarters
+German animal welfare act
+mRNA expression
+4 mg/mL
+3,064,887
+0.847
+limited number of sites and target pathogens
+indirect flight information
+Gram-negative bacteria
+NOX2
+SIGNR3
+Hematology and serum chemistry analyses
+super-resolution microscopy, nano-SIMS and EM
+59CCAGTCAGAACCGGAAAGCCA39
+modulates eIF4A activity
+1.56
+15 min
+F = 222.19
+HCMV replication
+between 1-5 days
+antigen-specific antibody secreting cells
+five
+Specific Abs
+SPIs
+serum PTX3 level
+Mann-Whitney U test
+Ribavirin
+TRIzol
+3 weeks
+IL-35
+Largest Population
+endothelial cell growth medium
+an OTU
+positively regulates
+isolation chambers
+100,000
+Serum samples
+34%
+USP18
+a path of length 1
+20 million generations
+Clonogenic assays
+>1000 revisions
+hydrophilic
+25%
+II
+simian adenovirus
+three
+Appion
+NO
+18
+porcine teschovirus
+more than double
+2,6-sialyllactose
+Trolox
+please fill all the GPS distance in the blank
+11ml
+IBM SPSS Statistics 20
+the infection with OPV
+linear and circular
+vision or intention
+1 h
+Poland, Italy, Spain, Denmark, Germany, and the United Kingdom
+Lipidomics
+Stable oligomerization of trimeric subunits
+a full consensus AU-rich element
+The trimerization of the CLZ domain
+cc-by
+The information sharing protocol
+Prolonged denudation of the basement membrane
+infected NHBE cells
+T cells
+an emerging epidemic
+6 months
+ACEI and ARB use
+81.5 years
+Relion3.0beta
+glass beads
+O:1a
+Clontech
+a mouse model of OIS
+accumulation
+$20 nt
+Matrix blank
+four
+20 μ m
+immunostaining in the HCs
+7-15 years
+unpredictably
+Oral and nasal/pulmonary
+viral
+Spermine
+substantial reductions
+100%
+related to this study
+pRb-binding domain
+identical
+Marburg virus
+1000-fold
+DHA
+antibody-dependent infection
+a contact matrix
+Western blot analysis
+fluorescent
+FeatureCountsv1.5.0-p3
+Eight
+Flexiviridae 1 and Closteroviridae
+health personnel, primary and critical healthcare facilities
+Rhipicephalus pulchellus Tetralaris
+endosomal release of vectors
+mosquitoes
+Growth medium
+pro-inflammatory
+~50%
+murine
+adaptations to the host
+TissueLyzer LT
+Group 3
+quantitative temporal viromics
+financial savings
+21,121
+infect
+jl S
+2ˆ10 5 cells/well
+100%
+4%
+Flow cytometric
+confocal microscopy
+highly significant
+influenza
+Zika modeling
+IL-2, IL-4, or IL-17A
+efficient function of the incoming viral genomic RNA
+DS and CP
+Overexpression screening
+2 × 10 3 TCID 50
+array
+telomerase
+binding immunoglobulin protein
+Pre-DCs
+water mean temperature
+human adenovirus
+Neutrophils
+Re-blot Plus Mild Solution
+cells
+12%
+women
+transmissibility
+Hyperactivation of some inflammatory cells
+3 days
+18
+pre-rRNA processing events
+encephalitis and pneumonitis
+drug administration error
+three
+PCR product
+four
+7 days
+Cox proportional hazards regression model
+to avoid immune surveillance
+antisense nucleotides nucleotide 2 or 2′
+Npl4 MPN groove
+cross-reactivity
+Leica confocal software
+hormonal
+Orthomyxoviridae
+672
+Foucauldian discourse analysis
+one
+12
+ALI in sterile systemic inflammation
+Six
+Isodielectric
+statistically significant
+51 to 80 per 100,000 under-five children
+twice
+inflexible
+global screening
+NSP2
+7 h
+macropinocytosis
+Three
+The Simulation Wizard
+blood monocytes and dendritic cells
+constant electron charge density
+Targeted temperature management
+35,854 mmHg/min
+QIAamp DNA Stool Mini Kit
+contaminated water or food supplies
+quantitative
+47.1 years
+The patient's consciousness and respiratory function
+tools from graph theory
+late stages
+immune-regulatory function
+sequence analysis
+38-41 kDa
+F incorporation into virions
+30 min
+cc-by
+ORF1
+The authors
+Spleen samples
+eighteen
+Taiwan
+influenza A
+barriers
+IRF1 occupancy
+RHuIFN-α
+evading mosquito immune response
+Thirteen
+100%
+A trimer of GP 1,2 molecules
+4
+American Type Culture Collection
+50%
+225
+YGS-DDI
+mouse
+Bell model
+Cow
+anti-Ub and anti-UFM1
+PVC
+HBoV1
+IFN-γ expression
+five months
+sterilizing microorganisms
+mutagenic
+iNOS
+10 µM
+rodent
+fair sharing of benefits and burdens
+middle to below-middle
+brain homogenate
+718
+2 h
+TRPML1/MCOLN
+Target-spike levels
+Mimivirus
+MPG
+FlowJo
+474
+40
+EST2 mRNA abundances
+Epistasis
+Prism 7
+eight
+C3a and C3b
+monocytes/macrophages and dendritic cells
+NAb titres to ChAdOx2
+Data of clinical characteristics obtained from our literature review
+neurotropic Pseudorabies virus and lymphotropic retroviruses
+log likelihood
+decreased
+The oral cavity
+Cultured Acanthamoeba trophozoites
+1 mg of total RNA
+90%
+Creative Commons Attribution 4.0 International License
+higher inflammatory state
+The overall effect from meta-analysis
+50%
+ectoparasites and a few nematodes
+two different combinations of 5 immunogens
+databases and Pubmed searches
+high-throughput sequencing technology
+Gene expression coefficient of variation between different groups of individuals
+ventilator dependence risk score
+9 lg of hemagglutinin
+MIR19A
+Fifty-one
+written informed consent
+protein processing and modification, proteasome synthesis, and galactose metabolism
+epidemics
+ΔG est,i
+TruSeq DNA Nano Kit
+ImageJ
+QIIME
+E62H
+Level of cognitive function and/or terminally ill status
+4,298
+blunting in vivo influenza A virus infections and preventing virus-induced disease
+100%
+leisure facilities
+its effect on the developing fetus
+restructuring one's perceptions to come to grips with situations
+4
+high specificity and PPV
+monobasic
+10 2 copies/ mL
+67.9%
+GeoChip 2.0
+50%
+evolutionary changes
+More than 50%
+30 µl
+Ribavirin
+at the early stage of PRV replication
+-strand synthesis
+1% mf
+the characteristics of the population studied
+qPCR
+48 h
+180
+cytotoxic
+β -galactosidase
+detection of cancer markers or interleukins
+PEG
+5.3 g/dL
+Fcgr2b signalling
+cultural differences
+all passengers will be quarantined
+90%
+apicolateral
+critical coverage
+Wuhan
+3.5 kDa
+IFIT1 or IFIT5
+Tlr4
+day 28
+22
+Filoviruses
+24.7 AE 3.8%
+Digoxigenin
+anti-NF-κB and anti-NLRP3
+metastatic mineralization
+LRTs
+not defined epitopes within gp120 or gp41
+HCV Amplicor Specimen Preparation kit
+PERCH
+Annexins
+HPV05
+Guangxi Zhuang Autonomous Region
+circular
+serotype replacement
+vectors
+Total nucleic acid
+Chi square or Fisher's exact tests
+Extracorporeal membrane oxygenation respiratory support
+Strep-tactin
+epithelial
+ARP1 and ARP3
+Reports of sample handling effects
+13
+effectors in saliva
+fluorescence
+Thirty-two
+cohorts with H1N1 patients
+A375 control cells
+threataffect
+acidic
+Amide hydrogen/deuterium exchange
+bucketed/integrated spectra
+target cell type
+Rhabdoviridae
+parrot bornavirus 1 to 8
+broad-spectrum
+American Type Culture Collection
+Tris-glycine gels
+33%
+3D-Gene FFPE Gene Expression Analysis Reagent kit
+use of mobile devices
+MN219409
+overexpression of Rev or hnRNP A1
+asthma
+cleavage of the probe
+airborne transmission
+Selleck Chemicals
+viral nucleoprotein expression
+USP18
+archive log
+Trajectories
+normal distributions and a Euclidean distance
+viroporin
+singletons
+conventional surgery
+39 and 59 end regions
+LDH
+four
+short time span estimates
+neutralization activity
+IFITM3
+Anti-ZIKV IgG antibodies
+77
+mitochondrial DNA-encoded protein expression
+1 week
+κ
+four-point scoring scale
+13
+potassium carbonate
+quality of notification data
+90%
+95% per year
+multipartitism
+statistically significant difference
+attachment to ERA was significantly lower than to PP
+several months
+RNA
+SpeI/SandI and SandI/EcoRI
+Interleukin 1a and IL-1b
+33 months
+C3a and C5a
+active viral replication
+T.K.
+93.2%
+reducing MT markers or improving metabolic health
+functions in the regulation of cardiovascular and renal functions
+highspeed spreading
+transgenic
+cytoplasm
+Five
+IgG
+chains of transmission across consecutive school days
+false
+R i
+5.0 µM
+37.84%
+CD Hybridoma
+One-dimensional
+TFR1
+metabarcoding
+Kaplan-Meier plots
+96
+human phospholipases
+two
+immunofocus forming assay
+Dilutions of PAA, GDA and the alcohols
+D 2 DR/βarrestin-2 interaction
+epidemiological
+an HA tag
+Between sub-populations
+water-insoluble toxic cell wall components of the bacterium
+Renilla luciferase gene expression modified
+apical side of palatal epithelium
+Malnutrition and diarrhea
+CN
+unmanned aerial systems
+stochastic simulations
+a measurement tool to assess systematic reviews
+Thermo Scientific Revert Aid First Strand cDNA Synthesis Kit
+English
+an immune response
+8
+DOCK 3.x programs
+reasonable speculations
+free radicals, fatty acids or inorganic phosphate
+mutation
+inflammatory cells and kidney cells
+7350
+490 nm
+T cell
+diminishes blood pressure and glomerular injury
+Viral RNA mini kit
+1%
+10
+AT-511
+stimulatory
+tracheal lavages
+glutathione
+b-glucuronidase
+HFNC < HFNC+PP ≤ NIV < NIV+PP
+enhances the type I interferon expression
+Pearson's, Spearman's or Kendall's
+Multi-run metadata
+54.8%
+HMPV positive clinical samples
+DnaSP
+March 2010
+buffy coats
+Tioman virus
+neurotropism
+clear cell tumorigenesis
+14 days
+GS-5734
+HCV and VSV replication
+158
+NK cells
+Molecular Medicine
+12
+Xs ik and Xa ik
+duck
+2 or 5 days
+>95%
+Hemagglutinin and neuraminidase
+>80%
+one-third
+HFMD
+opal stop codon
+endogenous opioid
+2026
+the precursor form GPC
+Twenty-four
+a ij
+Nigeria, Ivory Coast and Senegal
+Genome defence
+0.1 J cm −2
+one
+10.2/100,000
+17798
+mathematical models
+blastn
+protein quality
+genotype and allele frequency
+Array-Pro Analyzer
+The SPR phenomenon
+6.94
+overloading the cellular folding and post-translational processing apparatus
+silver
+gastroenteritis
+IGR IRES-mediated
+18
+QIAquick Gel Extraction Kit
+nine
+The parameters of the algorithms
+HIV-1 entry
+catalysis
+apoptotic DNA fragmentation
+epidemiology, clinical features, and treatment options
+excessive neutrophil activation
+ratio discrepancies in gene expression experiments
+low
+200 µL of dimethyl sulfoxide
+disease reproductive number
+virus-host interactions
+liquid nitrogen
+China and Uruguay
+Male Swiss-Cox mice
+70
+5-19 yr olds
+30 min
+RNA-Seq data
+102
+TNF-a
+∆F
+RQ1 RNase-free DNase
+Two
+neuroinflammatory
+Rhinoviruses
+anti-oxidative capacity
+elevated temperatures
+18 days
+SP6 transcription
+four
+hydrophobic
+112
+dissemination and neurovirulence
+different reports
+Evans blue dye
+standardized difference and p values
+Intuition
+R
+an aphid-specific watery saliva protein
+Kaohsiung Medical University
+Cell lysate
+Tf-EE
+Melting curve analysis
+SpectraMaxM5 plate reader
+significant
+kelch-like protein 9
+Health facility transmission
+worse
+palliation
+by promoting ERK pathway activation
+three
+Five hours
+10% to 50%
+its solubility
+Virus-derived epitopes
+ecological niche modeling applications
+Four
+Intractable
+Acute Respiratory Distress Syndrome
+less than 50%
+HLA-DQ/DR
+changing the social parameters
+KEX1
+500873
+N-Viral RNA complex
+GTR+G
+erastin's lethality
+UTRs
+bacterial alcohol dehydrogenase quinoproteins
+PCT
+cognate naïve T cells
+hippocampus
+4-fold
+Disposable protective gloves
+Correspondence analysis
+elimination of all P. falciparum
+30
+heavy metal ion tags
+200 pfu/gr
+Pathogens
+atrophy of immune system organs
+crystallographic
+four
+8 hours
+Macrophages and dendritic cells
+Titron X-100
+eleven
+STAT1
+IC-ELISA, LIPS and nucleic acid-based tests
+Bruker REFLEX MALDI
+group B
+NeST
+Sensitive reactions to recombinant antigen gD
+MeV-Alaska
+M1 and NS1B
+Modification indices
+respiratory
+Epigenetic changes
+Micro-Cal ITC200 isothermal titration calorimeter
+SIV plasma viremia
+46.8%
+30 minutes
+human RNAse P
+mutational spectrum of ASPM gene
+knee angle
+increased expression, distribution and re-organization of AQP9
+Dendritic cells
+colocalisation
+Edmonston
+dormant or quiescent cell nucleoli
+vascular development and trophoblast behavior
+5 ng/ml
+Fisher's exact test
+test method
+H2O
+AnchorDock
+276
+21,085
+complicated
+AUGUSTUS
+antibody-dependent
+7 months
+in-frame translation
+Comp#1
+cold CIT Wash Solution
+Genes
+Lipofectamine RNAiMax
+four
+B-1a cells
+15
+100 mg of LTA and 700 mg/kg Dgalactosamine
+Berberine
+release of transaminases and histology
+Bayesian prediction modeling
+WHO study coordinators
+a synthetic population
+aseptically
+bacterial pneumonia
+1 or 10 mM NaIO 4 pretreatment
+vertebrate prey
+cytoplasmic mCherry expression
+machine learning
+high serum levels of NSE
+M. glareolus hepacivirus RMU10-3382
+J399EM
+CaMKKβ -AMPK-mTOR
+reBmBac-silkworm expression system
+70-90%
+20 to 61
+those recently reviewed in the literature
+Linear multiple regression analysis
+significantly higher
+The arrangement of the genes
+87
+Stanford TNG Radiation Hybrid Panel
+feature extraction, amino acids classification, and residues deletion
+colonization in the gut and infection of the bladder
+Lipid vesicles
+25%
+data from individual mice
+apoptosis and inflammation
+22.8%
+10
+10 min
+publication of this article
+MEV NS1
+predicted mortality, sedation strategy and PEEP strategy
+non-random
+8
+reachability
+rRNA degradation
+social distancing
+human tetherin
+A detailed description of the different substrate trapping protocols
+ACE2-Ang -mas
+MCP-1
+Predicting the potential for vaccine reversion
+ART
+green fluorescence
+probabilistic models
+Pearson coefficients of determination
+E-toxate
+N-terminal sequencing of the products
+j
+β-glucuronidase
+1341
+SAS
+50 ng/ml
+epidemic
+4 weeks
+viperin
+pigs, bats, and cattle
+fibrosis
+threedimensional
+NHE-1
+HIV V2-apex bnAbs
+86%-100%
+direct inoculation of pathogen
+Proteins N, P, and L
+Cla and Clb
+intrinsic risks
+3I14 in mediating ADCC
+compartmental models
+protection experiments
+moderate to high
+H5N1 HPAI
+oneway ANOVA
+Structural studies
+social contact networks
+to assimilate the ILI/Wikipedia data into the transmission model
+bioluminescence
+Chemotherapy
+did not stabilise NSs
+post-exposure time-dependent and particle-specific differences
+proteinase K
+complex I deficiency
+fatigue, joint pain as well as loss of appetite and memory
+Tobacco mosaic virus
+Odyssey Imager
+were not significantly changed
+choose another hospital
+Western blot analysis
+TGF-β levels
+chronic inflammatory disorders
+evolutionary surveillance tool
+ability to act to reduce pathogen fitness
+6
+increased blood pressure
+enhanced
+NMM
+tumour progression, resistance to chemotherapy and poor prognosis
+21 days
+More than 3 billion
+compound 3a
+H74L
+The World Health Organization
+segments
+CSFV NS3
+The network of relationships between minerals and biology
+6.5 million
+open source databases
+how DIZE is mediating its effects
+subtype-specific primers
+anti-psychotic
+bound conformations
+20-30%
+Apical membrane antigen 1
+five
+2.54
+preparedness for infectious diseases
+fingerprint-based methods
+controlled infection of nasal cells from multiple individuals
+32
+easily identifiable brain lesions or birth defects
+kittiwake viruses
+t E nm
+180 days
+demographic
+three additional signs and symptoms
+tumors
+IPB-2011-6
+no incorporation
+Hemagglutination assay
+blunt-tipped microneedles
+ELISPOT reader
+human inflammatory bowel disease
+homologous
+QIAamp Viral Mini Kit
+TurboFect reagent
+196
+H1N1pdm09
+Pr160 gag-pol
+IFITM3
+cross-sectional
+septic rats
+transmission dynamics model
+95% quantiles
+cumulative cases of 280
+Structured crowding
+microbiology
+MSC homing to damaged lung tissue
+community-specific data
+Four
+Excess annealed probe
+transmission intensity
+four
+shrinkage
+IL-17
+4
+adenosine stretch
+mortality after lower respiratory tract infection
+26
+three
+mitochondrial DNA
+0.45 μm
+Weekly health status reports
+40
+T7 promoter upstream of the Rluc gene
+2.5 h
+electrophoresis
+RSCU
+VOSviewer
+logistic regression
+N-linked glycan sites
+125
+not efficient
+NA1/NA2
+T
+all full text articles
+PDF
+vaccination and treatment games
+anti-trypanosomal agents and DNA minor groove binders
+phosphoprotein P protein
+homologous proteins
+1,120
+R5
+0.1 mg/ml
+activate PKR autophosphorylation
+a week
+14
+10,669
+those for the positive control group
+public health decision makers
+surveillance period, name of medical facility, sex, and age 10
+969
+DNA-based
+NGAL mRNA expression in lung tissue was increased
+10%
+epithelial injury
+25
+HSBP1
+VCP status
+the amount of risk
+All authors
+neurons and glia cells
+30 min
+five-fold crossvalidation
+CD4 and CD8 T cells
+identical
+intubation and ventilatory support
+open work spaces
+the size of age groups
+reassortment of several relatively low pathogenic influenza strains
+optical tweezers
+Impairment of germinal centre reactions
+72
+BALB/c mice
+ABC target density
+flow cytometry and surface staining
+self-organizing maps analysis
+circulating RAS activity
+intussusception
+MOI of one
+Rapid diagnosis of involved pathogens
+cumulative result
+Swiss-PdbViewer software
+four
+up to two months
+High flow/AirVO
+2-CTC resin and standard Fmoc chemistry
+signal intensities
+Hepatocyte growth factor HGF HGF
+Prion diseases
+necrotic
+fitted well
+Sigma-Aldrich
+Relaxation of virus particle binding
+technical artifacts
+3
+anti-sense molecules
+673,624
+Diffusion-weighted
+10 copies/mL
+membranous
+2-tailed Student's t tests
+suffix-tree algorithms
+three
+safety and accessibility to the endothelium
+Species specificity index
+6408
+200 µL of bacterial overnight culture
+47.2618.1 years old
+influenza
+LAIV-LAIV
+late-endosomal/lysosomal compartments
+suboptimal dosing
+three continents along the equator
+1918
+Z -FA-FMK
+CF
+traffic congestion, e.g., rush hour, and severe winter weather conditions
+genetic and ecological
+UV-vis absorption spectroscopy
+Pneumonia
+Ca 2ϩ -dependent lectins
+Complex I
+eleven
+24 hpi
+155
+20 mL of RNase-free water
+strict insistence on certain criteria
+PXD009999
+fine-tuning regulations
+Wilson disease and autoimmune liver disease
+reactive gliosis
+ORF1a/1b
+10-fold
+seven
+5 years
+building local knowledge and capacity for action
+reduced infection of A549 cells
+estimates of dispersal scale and infection rates
+Eight
+dipeptidyl peptidase-1
+Six
+Drug screening
+four
+activation of signaling
+poor prognosis
+creatine phosphokinase activity
+iodixanol gradient centrifugation
+Vif plasticity
+four
+11%
+dual nuclear/cytoplasmic localisations of a given protein
+polyamidoamine
+Statistical analysis
+antibodies
+274
+Hepatic injury
+Cytoskeleton
+Mycetoma agents
+14
+maternal age, gestational age, and number of previous pregnancies
+1796
+8 out of 10
+improving the health of Taiwan's citizens
+Five
+Glaucoma
+a microtubule plus end-directed kinesin motor
+Zhi Ning
+Microbial biofilm
+more than a million
+Content analysis
+apoptotic and necrotic
+IgG
+SMN2-GFP
+2018-02-02
+innate immune impairment
+IFITM3
+above 0.90
+14
+China
+highly pleiotropic
+Cyclic dicarba analogues
+direct intraoperative analysis and histology
+17.7
+Receptor antagonists
+12%
+5 mM
+four
+wide-bore
+Actb
+11%
+February 11, 2020
+protection
+flight-based quarantining
+CCL5
+their reliability as reference genes
+7
+1 ~ 3 quanta/h
+T-cell costimulation
+distinctive
+necropsied
+effective
+visualization and monitoring of G4s structures
+Luciferase
+hepaciviruses
+details of how transmission may vary spatially
+measurable, low-level viremia and viral shedding
+severe viral hepatitis
+silent mutations
+6408
+data on contact networks
+Bright Model OTF Cryostat
+enlarged cistern magna and calcifications in brain parenchyma
+Tacit
+at least 10 years
+Timeliness
+2
+overfitting
+host response
+perforin-dependent
+g = 0
+the effective control of the disease
+Fecal samples
+support
+a bar
+return to oestrus rate
+the TGN and late endosomes
+six
+favorable for activity
+HP-PRRSV
+interactions of motif 1 with an unspecified molecule
+Amyloid-like
+callers' physical and linguistic capabilities
+the amount of, rather than resistance to, infection
+per min/per mole of enzyme
+pathogenspecific characteristics and venue-specific characteristics
+8
+BspE1 restriction sites
+lamina propria
+gene delivery by AAV
+ΔLAZ
+1,000 replicates
+2.0 to 2.5
+5.0
+Mycobacterium tuberculosis
+Sepsis
+The Schedule of Assessments
+Table 3
+IL-1b production
+protective
+Nineteen
+BSRI
+1, 2, 3 and 4
+suppression of tumor growth
+corruption and stealing of resources
+33
+low expression tumors
+trpD
+the discount rate
+1.38
+IFN-stimulated gene factor 3
+pGFP and pVSV-G
+p53, p27 and p21
+10%
+viruses, Nosema, bacteria, and Crithidia
+positive-feedback
+France and Switzerland
+Complementary DNA
+Ten
+negative results
+the active form of the kinase
+changes in the microbiology of the intestinal tract
+Xerostomia
+4,6-diamidino-2-phenylindole
+25 mL
+NP373 and NP458
+ARDS
+inflammatory cytokine and chemokine production
+10 days
+seryl-tRNA synthetase gene
+Egr-2
+habitat saturation processes
+criticism
+prolonged air leak
+gut microbiota
+Electrode gel
+10 min
+many Alphaproteobacteria
+18
+mild disease
+DNase I treatment
+growth disorder, glucose intolerance, and the suppression of the immune system
+Systematic synonymous-site mutational analyses
+Th2
+1072
+peroxisome proliferator activated receptor alpha
+influenza
+six
+bacterial superinfection
+aberrant regulation of viral transcription
+20 minutes
+viral attenuation
+50 mL
+HGT
+isoflurane
+Western blot analysis
+RNase A
+At least 20-50 clear ciliary cross-sections
+anaccumulation of multinucleated cells
+BD Biosciences
+12
+I and Q
+Institutional Animal Care and Use Committee
+binding
+enterovirus RNA
+53.9%
+EGFR
+bronchiolitis, pneumonia, croup or asthma
+high spatiotemporal contact network complexity
+threonine
+1:100
+HAP pocket
+ELISA kits
+adhesion
+QIAquick PCR Purification kit
+2002
+greater benefits
+position 465
+brefeldin A or monensin
+pneumotachograph system
+Recombinants
+1,486
+DNA microarray
+optimal immunogenic processing
+culture motion
+cryo-electron microscopy and X-ray crystallography
+3.4
+up to ten minutes
+twofold
+Nine
+Three
+Mechanical ventilation
+GDC and DS
+Dppa2, Dppa4 and Mvh
+42
+Bacillus anthracis
+Baird
+ALI
+∼78 MYA
+grey literature
+to suppress RSAD2 expression and apoptosis
+the cutoffs and the assumed reporting rate
+CAR + /mPSCs Oct-4_hi
+glyceraldehyde-3-phosphate dehydrogenase
+28
+7.1%
+Binding assays
+94%
+crawling and gliding motions
+cognitive behavioral therapy
+Autophagy
+vitamin C2
+1 μg/ml trypsin
+four
+NSs4KR
+Immunoblot images
+ORs with 95% CI
+Lumi-Light western blotting substrate
+45%
+viruses
+24 hpi
+RNaseL
+HD-Ad-lacZ
+Matrix gene
+418
+Procaspase 3
+Meta-analysis
+particle size
+potential EVD cases in their families
+37 years
+ovine developmental model
+Triglyceridemia and Hypofibrinogenemia
+15.4%
+10 mm
+YxY
+50%
+72 h
+Perceived susceptibility
+one pre-assigned day
+Maxent
+high relative expression
+a mobile virus source
+Three to four
+glucose levels
+4
+0.4 Å
+oxidized low-density lipoprotein
+coating and blocking
+March 2014
+propidium iodide staining assay
+high concentration of NAs
+ANOVA
+clinical prediction score
+HA
+Beclin 1
+two
+hyper-arousal
+36 and 48 h
+Acute organ dysfunction
+10.1371/journal.pone.0219321
+21
+spraying of all households
+human immunodeficiency virus-1 mRNA
+pDCs
+T-lymphocytes
+hepatitis B reactivation
+40 minutes
+Amplified PCR products of all actual cDNAs were sequenced
+7 days
+mMACS Streptavidin Kit
+antiviral
+Multi-walled carbon nanotubes and reduced graphene oxide
+global health and funding agencies
+0.05 Da
+Eighteen
+1979
+enzymes, ion channels, GPCRs, and nuclear receptors
+GAPDH
+GoogLeNet
+respiratory tract injury
+decreased viability
+3D structure
+EBV-specific
+four core experts
+plasma
+19%
+cytochrome c reduction
+regulatory and purchaser outlooks
+85%
+a single, relatively recent calibration
+clusters of significant marker -LogP values
+ACE2
+mosquito control and raising public awareness
+microbial cell membrane
+intermediate binding
+disease ecology
+E or Ed395
+patient age and sex
+its ability to promote autophagy evasion in immune cells
+Gene names and fold-changes
+98% room air
+24
+effective antiviral agents
+HPAIs
+infectious diseases
+2
+cc-by
+C S
+Not being vaccinated
+the corresponding author
+The mutation to the right of the amino acid position
+Binding site visualizations
+limited
+respirators
+SIRT7
+WHO
+Bayesian
+L-Arabinose
+significantly suppressed
+hypothalamus
+tenofovir disoproxil fumarate
+RODS
+430 BC
+redox
+1 and 2
+3.7%
+1 hour
+40 Kilodalton
+UV-C radiation
+Model 2a
+epidermal growth factor receptor
+S1 Text, section 2
+wound healing, cell therapy, and drug therapies
+13
+4.4%
+Nashville, TN
+A degree of control
+I-TASSER
+500 million
+Table 7
+Influenza-A
+β-defensins
+relapse
+COPI-coated vesicles
+50%
+subcellular localization of the viral protein
+two
+Atgus
+8
+Uric acid
+91% to 100%
+digital CCD
+not closing schools
+Shorter protein fragments
+Host factors co-opted for replication of plus-stranded RNA viruses
+health care codes of ethics
+bicinchoninic acid protein assay
+mismatch repair proteins
+Two
+1,280
+FLAG tag
+RNA7 synthesis
+cultural context
+CHK1 phosphorylation
+A tail of GGEKEKEK
+dsRNA
+0.1 M
+van Elden et al. 57
+ΔATG5 and ΔBECN1
+1/150
+63%
+Mowiol
+3.1-fold
+Public Health Physician
+Swabs from the choana or oral cavity
+Resveratrol
+Lelystad
+vaccine hesitancy
+45
+Polycomb-mediated epigenetic regulation
+robust primary assays
+1%
+repRNA
+high frequency of point mutations
+young adults
+overprinting
+cholesterol accumulation
+PHR2
+Hygienic
+RNA-Seq
+between 7 and 43 million
+40%
+monitoring and surveillance of diseases of economic importance to swine producers
+autophagic markers
+pH1N1
+high and low estimates of vaccination coverage
+three
+oxygenation improvement
+residues G502-A506
+À80 C
+4%
+12 to 29 weeks
+past influenza pandemics
+5%
+An increase in evaluations
+TDP-43 cytoplasmic inclusions
+males have a high mortality rate after infection with this MHV A59 strain
+human immunodeficiency virus and murine leukemia virus
+YFV-17D
+BFA-sensitive
+1000
+asthma control
+a standard tool to transfect cells in vitro
+SIB
+coiledcoil-barrel assemblies that have more than 6 helices
+hepatoprotective and antioxidant
+payment
+Alanyl aminopeptidase
+Carriage of pathogens
+Lipofectamine 2000
+anti-inflammatory
+one RFID tag
+35-40%
+Annexin V positive cells
+glass needles
+cytopathic
+5 minutes
+668.87
+50%
+dehydroabietic acid
+507 amino acids
+Infectious conditions
+cooperative contribution of minority variants
+70%
+8%
+two-way
+RNeasy Minikit
+five week
+exp
+nucleotides
+HIV/AIDS
+August
+Fresh guinea pig blood
+1.18
+alpha-satellites or Circoviruses
+ATHENA
+pGGVs
+neuroinflammation
+PrediSi
+excluded
+p65
+SHAPE
+51,265
+The NIH Database for Annotation, Visualization and Integrated Discovery
+17
+decreased bone mineral density and osteoporosis
+CCHFV
+estimation of key epidemiological parameters based on cumulative case counts
+GAPDH
+Monitoring the capping efficiency
+further sets of CBF1 dependent promoters
+2009
+efficacy
+IgM Heavy Chain µ
+5%
+Gwangju Center of Korea Basic Science Institute
+Herolab E.A.S.Y. Win32
+internal controls
+thermodynamic hypothesis
+U1 small nuclear ribonucleoproteins
+complement
+helix angles of 15
+a gradual decline in both innate and adaptive immune functions
+CO 2 gas
+virus-induced cytokine dysregulation
+H5N1 and pH1N1 strains
+xTAG RVP
+Limited availability of IFA
+non-specific amplification
+vivo-morpholinos
+seven-stranded beta sheet
+late 1990s
+public health experts
+Modified Vaccinia Ankara viral-vector
+E64d
+phenotypic
+epithelial cells
+MagNA Pure LC instrument
+polarised effector memory cells
+percentage of total working pressure of the respiratory system
+decreasing ILI
+80%
+50%
+30%
+Mayer's Hematoxylin
+CSIRO Black Mountain Laboratories
+30 min
+100 ng
+Histidine, tyrosine, and aspartic acid
+arterial hypotension
+cross-hybridization
+Google
+Perth, Western Australia
+201
+29 out of 30
+36
+MLB1
+they fail to induce an immune response in a short period
+November 9
+PKR
+depletion of immune cells
+Plasmodium
+IPV
+Viral titre
+485
+RFP-Flag-transfected PAMs
+nifedipine and ethosuximide
+Jennifer Pocock
+circulatory and respiratory
+Strategic risk assessment
+MD OCT-pool
+liver, spleen, and kidneys
+IL-17
+B j
+Restoration of circulating blood volume and perfusion to tissues
+HCV
+longevity of protection
+H60 and Mult1
+NIS-Elements BR 3
+co-infection
+practical considerations for clinicians and patients
+1.11
+South Africa
+3.8%
+38 weeks
+infection control personnel
+day 0
+Respiratory epithelial cell culture systems
+IL-1b
+19%
+100%
+60 min
+VFD
+calcium phosphate biomaterial particles
+nine
+The supernatant
+updated sensitivity estimates
+57%
+Wilcoxon tests
+male
+heparin
+CpG and UpA dinucleotide suppression
+tbage and tneub
+when there was a saturation of fluorescence intensity
+≥14 days
+0.22
+pro-inflammatory
+RNA sequencing
+Four weeks
+nucleomegaly
+HOMO and LUMO sites
+steric pressure from protein crowding
+19.4%
+BioRobot EZ1 Workstation
+LNPs
+The structure of LmPGF2S protein
+CHI 660C Electrochemical Analyzer/Workstation
+>80%
+suppressive
+JAK/STAT pathway antagonism
+molecular mass in daltons
+a switch in frequency
+Vpu
+Genomic DNAs
+137
+Ten
+4-14%
+RNA structural selection
+SAR114
+relative humidity variables
+98.9%
+pol t,i
+16
+Germany
+tumour necrosis factor-alpha and of interleukin -8
+six
+BSA, trypsin, thrombin, and IgG
+maximum likelihood methods
+ACE2
+FCGR3A 158V
+51.8%
+six
+biometric parameters
+NJtree.txt
+how results are to be interpreted
+toxin-containing supernatant
+Elovl7 and Rapgef5
+prepartum immunizations
+through TLRs
+NMA
+ACK lysing buffer
+40 to 80%
+Malawi
+The loop
+a constant risk of infection
+various portfolios of interventions
+age-dependent population size
+TGFBR2 3 -UTR
+K
+11,500
+antithrombotic activity
+RNA levels
+Comparable gene induction of 37 ISGs
+ν i
+a complete interacting profile
+137
+rapid rise in portal pressure
+Asian pacific region
+viral replication
+NP-specific CD4 + T EM cells
+generation 2
+consequences of in utero acquired silent pathology
+lung inflammation and injury
+eight
+A. terreus Li-20
+11,972 IEQ/kg
+4-6 h
+murine studies or in vitro human studies
+details of the spatial organisation of genomic signatures
+HIV Pr/RT and Influenza H/N
+Huh7.5-HCV cells
+complete workflow comparisons and comparisons of individual analysis steps
+reduced gradually
+they generally provide far more information than has been experimentally verified
+temperate regions
+COVID-19, and the
+IL-28 and IL-29
+10 am and 10 pm
+78%
+GenBank accession numbers
+The secondary structure of the selected aptamers
+72.3%
+phylogenetics
+reaction
+506
+Tef4p
+CaMV 35S promoter sequence
+plaque
+8
+nail polish
+increased length of stay
+ZIKV-infected
+Syndecan-1
+quick design and efficient production
+between 5.6 and 87.8%
+gC1qR/p32
+homologous recombination
+ϳ31 ng of antigen-specific IgG per l of serum
+Cell surface-specific labeling of proteins
+greater disease severity
+compliance factor
+flight records, Google Trends and the World Health Organization's FluNet data
+Twelve
+44.2%
+Immunomics
+web-based
+increased expression of CD27 on human memory B cell
+caution
+Hockey
+PolK
+ZBMD-1
+data points derived from the same intervention policies
+interferon-gamma
+increased promoter occupancy of C/EBPβ
+contact numbers and information
+HI assay
+The model
+cats
+lung epithelial
+cell culture, electron microscopy and serology
+eight
+coordinated coregulation
+Membrane fluidity of SLBs
+spring season
+A
+Figure 5
+proglumide
+temperate regions
+Purified heparan sulfate
+Error-bars
+fnbA and ica
+Food hygiene education of the consumers
+Translocation of mRNA and tRNAs
+prolonged viral and fungal prophylaxis therapy
+immunohistochemical
+process technology
+flaviviruses
+patients with AIDS who have survived and have received ART
+Coarse-grained models and allatom simulation
+Multivariate logistic regression
+15 min
+neutrophils or platelets
+mineral oil layer
+Protein disulfide isomerase
+a combination of different Ub-based probes
+seven
+ten
+blue
+age
+G6PD-deficient
+ELISA
+1 h
+an emerging new pathogen
+The orientation of the J-oligos
+Plasmodium detection
+three
+sensitivity
+unchanged
+ACE2
+Python
+50%
+ciliated cells and goblet cells
+2,318,115,958
+a waiver of parental consent and Institutional Review Board approval
+stepped-up pneumococcal vaccination
+K/R
+EBOV GPmediated infection
+Lipofectamine 2000
+humoral
+E MM
+Gott's rule
+Figure S2 TLR2
+Beclin-1 dependent
+plasma membrane and endosomes
+1.2 µg mL −1
+summer or autumn
+Multiple linear regression analysis
+replication and shedding of influenza virus
+27
+neuroinflammation
+β
+nanostructures
+mutation and recombination
+animal illness and old age
+Rhesus Macaques
+TBK1
+Tracey Baas
+The references of the eligible articles and relevant reviews
+RPL27A
+7.34 ± 0.22 days
+Predeveloped forms
+1-specificity
+vaccination
+amino acid tryptophan
+Bernoulli variable
+throughout the year
+glucocorticoids
+cDNA
+phophorylation of p50 and p65
+46%-75%
+between 17 and 26 minutes
+The CT of retrovirus Env
+111
+feed additives
+Praziquantel
+70
+8 to 3
+44
+GAPDH
+a relative risk of 1.0
+between one and seven months
+James Boyer
+stem/progenitor cells
+ACE2-Ang--Mas axis
+300,000
+Four
+difficulty of inducing incorporation of transplanted cells into the host cell structure
+Viral loads
+boceprevir and telaprevir
+nosocomial
+0.908
+orf8
+four
+stainless steel
+cholera
+Four
+Appendix B
+LXA 4
+Overall and substructure
+less inhaled and oral CS usage
+GFP
+mutational hotspots and cold-spots
+Travelling in public transport
+G∪G
+1 mg/ml
+rotavirus and hepatitis virus
+300 mM
+hierarchical folding hypothesis
+9,949
+Escerichia coli DH5a and E. coli BL21
+P low
+July 2014
+generating anti-tumor CD8 T cells
+42 years
+infection by inhalation
+SDS-PAGE
+elegant graphics for data analysis
+key
+drug discovery and biochemistry
+2013
+internal ribosome entry site
+GFP-NLS-tagged
+Five
+ϕ r
+it guaranteed that the smallest LTZ consisted of at least 100 individuals
+DAPI
+Primary Provider Medical Records
+other routes and gates
+Human tracheal and bronchial epithelium
+2009
+National Center for Biotechnology Information Sequence Read Archive
+picornavirus replication
+microscopic lesions
+20%
+IL-8 and CXCL-1
+Serum MDA levels
+viral excretion
+weak T-cell responses
+TUNEL-positive tumor cells
+Q-3.75 µgHA + AS03 A
+three
+7 months
+Increasing genotypic diversity
+Thirteen
+Excel
+Standardised
+the dysfunction of a7
+arrested internalization of Ankfy1 and EBOV
+Honeycomb lesions
+MAdV-1
+RT-PCR assays
+Additional descriptions and figures
+what constitutes a strain
+311
+high background in the negative control wells
+subtractive hybridization methods
+cell proliferation, migration, maturation, and apoptosis
+FMDV serotypes A, O, and C
+cc-by
+6
+phylogeographic parameters
+18
+29-37%
+mediates the binding of Fn to the exosomes
+directly carried out on the submitted tissues
+Brazil
+p38 MAPK pathway
+CXCL8
+23
+Microtubules
+Nineteen
+T cells
+cold-like symptom scores
+NRK-52E cells
+Pneumonia
+treatment to M1-like statuses
+sulfate
+23%
+HA and NA
+HEK293T cells
+shorter than 7
+preference for one type of codon over another
+Moelling, Karin; Broecker, Felix
+97.5%
+interactions
+MS2-mHCV
+3,066
+B3LYP/6-31G* level
+C. parvum
+inflammation
+enzyme-linked immunosorbent assay
+via peripheral venipuncture
+896/1433
+Anopheles darlingi
+NP-and M1-specific T-cell responses
+Thailand
+2 weeks
+innovative coping strategies
+human subjects
+two
+several positive regulatory domains
+virus replication
+projecting AMR
+extended key networks
+NTM-associated IRIS
+Vast chemical libraries
+stoichiometry
+Cryptosporidiosis
+HeteSim measure
+72 h
+MFold
+0.029
+25.1%
+nasopharyngeal aspirates
+innate immune responses
+increase bacterial pathogenicity
+277
+1142
+different time points
+Microparticles
+diet and exercise
+Figure 4I
+10
+RNeasy Mini kit
+MD simulation
+prevention and/or treatment of pulmonary fibrosis
+noise
+Three
+pTDP-43
+1,974
+labeling of proteins
+unpaired Student's t-test
+2010
+domestic chickens
+2008
+viral replication
+alveolar
+RNA-seq
+I C
+Metformin
+20 μM Z-FA-FMK or E64d
+worm-like chain model
+SBP, pneumonia, UTI, and bacteremia
+group II
+isolated pulmonary capillaritis
+increased ISG expression at baseline
+E2 peptide P9
+antibody detection systems
+96 %
+Infections
+previously conducted studies
+85%
+Centre for Disease Control Surveillance Weekly Reports
+Tumor-associated antigen-specific cellular immunity
+Corticosteroid
+specificity
+ovarian cancer
+synonymous site conservation
+fecal microbiome
+pro-resolving
+increases
+ORF1 and ORF2
+B.subtilis and E.coli
+Particulate antigens
+TAC1
+SH454
+technical challenges
+microplate spectrophotometer
+serum antibody-independent viral clearance
+BST2
+one in four
+clear ER and Golgi staining
+to identify dominant T-cell epitopes
+31
+biosafety level 3
+gp-340
+altered proton permeability and channel gating
+significant differences
+All the possible sequences
+Viral fusion proteins
+relative gene expression
+low molecular weight solutes
+DNA Lad-der™
+ImageJ
+IL-8
+ChIP-seq
+SARS to influenza to Middle East respiratory syndrome
+10.3390/jcm9020330
+340
+73%
+May to August 2010
+plaque assay
+92%
+the presence of neighbourhood hubs
+different arenavirus protein expression mechanisms
+Schistosoma mansoni glutathione S-transferase
+22
+Sequences of oligonucleotides and mutagenesis primers
+one hour
+inflammatory
+9.27 million
+TGFBR2
+6-10 mg/kg/day
+43
+2009
+T RM cells
+specific imminent threat
+3, 10, 12, and 6
+1958
+48 hours
+nuclear and cytoplasmic
+three
+BHQ
+52
+an amplicon
+activation kinetics and threshold induction temperature
+calculations may be made when only partial data for a given day are available
+Keratinocytes
+2 weeks
+lung tissue
+Twelve weeks
+urgent proposals for comprehensive suicide prevention
+asthma, allergic rhinitis, and atopic dermatitis
+Japan
+IP block
+ACE2 protein
+week 6
+improving the folding model behind the algorithmic framework
+HIV infection
+verification of predictions
+S-phase-dependent
+Cockroaches
+volatile organic compounds
+hematologic
+pUL21a
+TGFβ, IL-10, CSF, and EGF
+viremic
+caveolin-dependent
+basic virus research
+viral-vectored
+gene-level tests
+four-digit HLA typing
+79:18%
+Two
+Kinesin super family protein 2A
+exited the study
+0 % to 27 %
+HuH7 cells
+furin
+multimeric
+24 hours
+compensatory mutation
+93 patients
+12-14
+tumor
+fucose residues
+L pro
+poly-uracil stretch
+coagulation
+E. coli-induced decrement in arterial oxygenation
+defense against Gbps
+0.2%
+ITC analysis
+negative charge on the non-bridging oxygens
+extensive training
+airborne transmission of IAVs
+11 months
+Mag1-RNA3
+six
+NS1B protein
+stabilizes membrane tubules
+1918 pandemic
+CEACAM1
+improving function and compensating for deficits
+ImageJ
+bicistronic
+uridylates
+25
+six
+residue 60
+baseline data
+intracellular proteases
+nucleotide substitutions per site
+protozoan infection dynamics
+experimental groups and the pooled control
+MRSA
+HO-1
+control medium
+third
+pandemic influenza and West Nile Virus
+533
+N165S
+increases
+Unsupervised and supervised methods
+routinely collected information covering a whole country or a major part of a country
+168 hours
+31%
+pivotal
+MEK/ERK-dependent STAT1 activation
+increased numbers of CD163 ϩ macrophages
+10%
+homologous recombination via interspersed repeated sequence elements
+55%
+the condensed chromosomes
+strong
+1 hour
+Inhibition of the suppressor function of Tregs
+PE positive cells
+1 to 2 ACH
+Providing more knowledge about disease causes
+nine
+late 1990s
+public health
+degradation
+36
+35-40 %
+saxitoxin
+decreased
+CNKI
+Bio-Plex
+Chromas
+pleiotropic
+Benzoyl-L-arginine amide
+twice
+self-reporting
+5%
+125/134
+Naphthalene
+three
+high
+migration, waning efficacy, and demographic turnover through births and deaths
+working pressure of the respiratory system
+strong type I IFN production
+semiquantitative scoring system
+8,735
+television or newspaper
+steroidal glycosides
+HC and IDC
+UGT1A1
+9
+schools and workplaces
+a snapshot of the recombinant HBV strains
+Chloroquine
+OPHID
+7-week
+Amyloidogenic processing
+emergency/crisis response
+CD8 + T and B cells
+the unwinding force
+intestinal disorders
+impaired dimerization
+Biosecurity measures
+Empty backbone plasmids
+Virus dose and infection time
+Genetic information
+their respective HA subtype reference protein sequence
+artificial construct
+whether a hypothesised model has adequate fit
+Mosquitoes
+mammalian adaptation signatures
+42
+certain signaling pathways
+2 h
+hWJSCs
+FAK-expressing SCC cells
+the spread of infection between cities
+8
+models that allow for a behavioral shift
+Taiwan
+prevention
+Notch1
+1
+cycloheximide
+AP30451
+cc-by
+6.1
+plaque assay
+30
+0.025% Tween 80
+.4
+Melting point analysis
+ubiquitin C
+Wash buffer A
+54 h
+96 hr
+pSC11-M
+RO4929097
+arginine-proline-rich RNA binding domain
+anticodon binding and aminoacylation domains
+pairwise nearest-neighbor interactions
+P1F12 binding
+assembly platforms of processing complexes
+padlock probes and rolling circle amplification
+LNEs
+Table 1
+2.5 million
+Millipore Corporation
+pooled serum samples
+analogue
+Immunoprecipitated α5β1 integrin
+Subsurface environments
+The study
+90 minutes
+rVV-Empty
+17.9%
+nutrients
+standard error of the means
+50%
+Egr-1
+generation of a specific immune response
+by blating each gene in one cluster to NCBI and HMP database
+alignment analysis
+Purified goat-anti mouse antibody
+eukaryotic-1 frameshifting
+37.1%
+an increase in complex size
+log 2 9.560.6
+Y11
+2
+more references
+an intron
+information to local stakeholders and actors
+plasma viral load
+16
+Nc'
+genetic testing
+influenza virus nucleocapsid protein
+more rapid, sensitive, and specific detection of virus
+PPRV-F VLPs
+ganciclovir and cidofovir
+49
+RMS L
+Immunisation against IAV
+4%
+angioprotectin
+self-limiting mild illness
+adenosines and pyrimidines
+fibrinolysis
+Background scattering
+Anti-AFP antibody
+replication-associated proteins
+vesicles and tubules
+Lys-315
+binding virus genomic RNA
+tgfb
+The nucleolus
+intra-arterial RH
+glucuronide
+p24
+0.5 mL
+SENPs
+1296
+IL-18
+quasineutral mutation
+more severe hypoxemia and comorbidities
+IL-10
+64
+the potential interest of a lung biopsy
+Western blot analysis
+3%
+Differential equation-based models and cellular automata
+separation
+to identify the direct targets of each viral protein
+Ambion, Abcam, and LifeSpan BioSciences
+JEV and MVE
+ICU LOS
+vascular endothelial cells
+three
+25%
+underlying cardiovascular disease
+CH-E, KC, and GG
+Confidence intervals
+dsRNA
+clinical and climatic
+four
+cc-by
+phosphorylation of Bruton's tyrosine kinase
+1.5 million years
+COVID-19
+F a = 14%
+0.5 days
+further exploration of possible causes of heterogeneity
+Composite scores
+The expression of fgl2
+case definitions, facility types, and eligibility determination
+110 kDa and 75 kDa
+different cox-proportional hazards models
+fluorescence signals
+enhanced chemiluminescence reagents
+Clinician-Administered Posttraumatic Stress Disorder Scale
+standard deviation from the mean
+inclusion bodies
+54
+18 hours
+bias
+Disability
+VP40
+virus isolation using culture methods followed by complete genome sequencing
+positive
+PharmMapper
+Constructs lacking the uORFs
+their members
+60%
+scavenger receptor SR-A6
+spurious amplicons
+20.5%
+4 weeks
+PKC
+bacterial coinfections
+0.1%
+34
+enhances the maintenance of stem cells
+1.58
+novel technologies
+increased numbers of encephalitis cases
+Dulbecco's modified minimal essential medium
+intravenous pentamidine
+bronchopulmonary dysplasia
+autoregulator
+higher
+Acute Lung Injury
+123 mmHg
+chronic liver disease
+by treating purified virions with chymotrypsin
+improving access to vaccines in low-resource settings
+trypsin-like proteases
+infrared
+interaction tests
+280uC
+155
+F = −2
+30%
+Statistical modeling
+according to their individual schedules
+drought, aquifer depletion, and intractable local differences
+X, B and D-arginine
+support
+Randomization
+Nosocomial
+1297
+ATP
+high thermostability
+thousands
+rHPIV3 clinical isolate 1 -EGFP
+human cohorts
+synonymous codon positions
+higher parasite growth
+139
+values of viral RNA extracted from 19 viral respiratory pathogens
+R 0
+frontline HCWs with intensive patient contact and staff with no patient contact
+synovial tissues
+The Pneumonia Severity Index
+hf c i
+inducible expression of C6
+interpret the results of binding experiments
+Cargo receptors or transmembrane cargoes
+mortality of an aging population
+extensive blood vessel formation
+R 0
+whether the results of different herbal medicines were pooled
+RIG-I and MDA5
+compromised cell function and reduced contractile force generation
+mice
+Huh7.5.1
+A450
+impaired NOX/p38 MAPK/AP-1 signaling
+ATF4
+replication-dependent spread of virus to the lower respiratory tract
+sphingolipids
+proteolytic cleavage of GPC
+Ten-fold series dilutions of standard substance
+viral taxonomy and protein attributes
+57.7%
+mucins and gastrointestinal pathology
+strengthens the homology hypothesis
+OCT4 expression
+VEGF
+picornavirus RT-PCR hybridization assay
+six
+0.002, 0.025 and 0.153
+$80%
+children or elderly
+piglets
+females
+ENCODE webserver
+monensin
+Thirty-four
+Cell-free culture supernatant
+three
+NCBI PubMed
+bronchoalveolar lavage fluid cells
+DNA and RNA synthesis
+Akt-1
+129Sv and C57 SOD1 G93A mice
+light transmission
+43
+cytosolic factors
+surgical site infections
+situs inversus totalis and situs ambiguus
+written informed consent
+membrane fusion
+CD8 motility
+T1
+Metropolis Monte Carlo search algorithm
+antibiotic efflux
+differentially expressed genes
+dichotomous variables
+66
+changes to their addresses or phone numbers
+Antibiotics
+Basic epidemic models
+constraints on the protein structure
+free IgG molecules
+30
+Mass dog vaccination
+NF-κB activation
+diverse
+Amino acids
+a mutation on both alleles
+6 days
+Myd88
+duplicates
+Discovery studio
+PK
+Fifty ml of the dilutions
+Folliculitis
+irrefutable
+86%
+HIV-1 protease and HCV
+third
+zinc-dependent endopeptidases
+µW-level
+IZUMO and FLOT2
+nine
+IFNL4 expression
+negative and ambisense polarity
+dual antiplatelet therapy
+Nipah group
+a pair of primers and a probe
+IFNs
+73.4%
+293F cells
+1918
+twice
+Benjamini and Hochberg
+multiplex PCR subtyping assays
+life, dignity, and wishes
+40 million
+20 residues long
+purulent lung infection-induced ARDS
+miRNA expression
+proinflammatory
+repeat imaging
+false interpretations
+gp41 NHR
+br and k
+mock-infected controls
+Pearson correlation
+sulfated glycans
+mouse
+directional migration of leukocytes
+vague, ambiguous, or otherwise avoid explicit statements of position
+SERINCs
+IRF7
+10%
+full responsiveness to-and control of-RNA viruses
+13
+viral
+PubMed and Google Scholar
+MyD88-adaptor-like
+governmental initiatives and investments to improve infection control
+protein production
+Michael Weekes
+by thin-plate smoothing splines
+a very brief, non-articulate stereotyped voice
+Vesicular stomatitis Indiana virus
+θ ij
+virulence factors associated with viral pathogenesis
+inductively coupled plasma-atomic emission spectrometry
+increased immunogenicity
+PHP and PERL
+NaBH 3 CN
+0.35
+lower-respiratory-tract infections and bronchiectasis
+Old World
+adventitious viruses
+ANN-based algorithms
+duck-rice agro-ecosystem
+2008-11-02
+Fomites
+300
+Indirubin
+ILI
+10 μ M
+clear biological contexts
+radiographic features
+APMV DNA
+sialoglycoconjugate receptor
+specific molecular pathways
+h3H5
+highly pathogenic
+nosocomial
+a list of coordinates for each localization
+severe bronchiolitis
+deforestation of forest areas
+nasopharyngeal carcinoma
+> 86%
+low molecular-mass
+x β = 08β
+Host genotype
+myelin
+virus mammalian host adaptation
+21.1 million
+1960s
+infection after immunosuppressive therapy
+Monocytederived Macrophages
+11 568
+caveolin-1
+pH dependence
+wrong parameter settings
+type I interferon
+0.04 nM
+Mark Carney
+73%
+no significant difference
+Respiratory syncytial virus
+CW3 immunodominant
+ECL
+Arg-His-Arg-Arg
+serum viremia
+an insurance
+ability to induce dedifferentiation or reprogramming of RPE cells
+bacterial multidrug efflux pumps
+Non-invasive diagnostic tests
+TCID 50 titration
+communes and towns
+four
+contagion
+cyclase
+72%
+max
+renal Ang II content and intrarenal Ang II signaling
+International Institute of Tropical Agriculture
+biodiversity
+anti-Ki67
+116
+TMB
+Credentialing
+43.9 years
+VP30-RNA binding
+mesenchymal cell populations
+PageRuler TM Prestained Protein Ladder
+mouse macrophages
+multiple-organ failure
+spo0A and sigH
+11.7 %
+different patterns in vertebrate and invertebrate host organisms
+respiratory diseases
+two
+Ten
+pleopods
+Th1 and Th2 differentiation
+Presatovir
+50%
+Quarantine or isolation
+4-dimethylamiopryidine
+β -actin
+45 years
+all immunogenic nucleic acids
+the CHO genome
+Entrez search menus
+100%
+microbiological evidence of infection
+regulation of angiogenesis
+treatment of infected individuals
+mobile DR units
+bacterial entry
+ionic channels
+Juniperus
+10 3.6
+1 Â 10 7 VSV-specific B cells
+95
+March 2005
+pivotal
+trypsin
+The efficiency of fork restart events
+U-ISGF3
+capped, polyadenylated viral mRNAs
+~8900
+5% or less
+sentinel sites
+3.0, 2.3 and 2.9
+C-score value
+PROMALS
+clusters of significant marker -LogP values
+1991
+t 1
+Wuhan
+ST cells
+International Humanitarian Law and International Human Rights Law
+Nucline
+primary lung endothelial cells
+five
+70
+SC09
+South East Asia
+IFN-g
+proHNP1B
+female
+oxidative stress
+11
+causespecific hazards model
+1410
+70%
+Cord blood
+1 Airy unit pinhole diameter
+broth microdilution
+20 to 50%
+Dnmt3a
+a tracing probability p c *,121/R 0 pre
+TiO 2
+YFV-17D
+-2FS increases more than 2-fold
+0.22-μm
+immunity
+cancer, tuberculosis, and the self-monitoring of blood glucose
+127
+1,000,000
+51.7%
+Twenty
+pandemic
+pro-inflammatory
+clathrinmediated
+6
+DAPI
+supernatant containing viruses
+laboratory observations, mechanistic studies or pre-treatment assessment
+Intravenous drug abuse
+ran until no individuals remained infectious
+samples collected from the field
+solubilized sample
+aging
+37 • C
+1.32-to 2.26-fold
+shRNA
+Zeiss LSM 510 confocal microscope
+Lipofectamine 2000 transfection reagent
+Qualitative case study methodology
+TYLCSV
+REV specific diagnostic assays and epitope-based marker vaccines
+deaths that would not have occurred in the presence of sufficient resources
+5%
+induction of apoptosis and epithelial permeability
+anti-DBL3cVAR1 serum and IgG
+mild disease
+RV-C
+pPAM
+Fasciola hepatica and Moniezia expansa
+viruses
+antigen specific IFN-c producing CD8+T cells
+early 1990s
+25%
+poultry exposure and comorbidities
+mesenchymal stem cells
+GDC-central proteins and proteins in DSs of PPI networks
+8%
+Sample collection & handling
+phosphorylation of protein tyrosines
+CRP
+extreme mutation rates
+the family
+IFN-inducible transmembrane protein-1
+Lactobacillus species
+a much more stronger increase
+actin
+YYU Hospital
+Increased collagen deposition
+8
+three
+severely immunocompromised
+therapy failure
+total viral antigens
+ImageJ2x
+reconstructed epidemic trees
+hemagglutination
+18 h
+van der Waals interactions
+GFP
+Mouse-adapted EBOV
+aetiologies
+antiviral activity of TOCs treated with TLR ligands
+viral uptake
+The prevalence of specific serotypes
+SAP30, p62 and p44
+structural proteins
+mtDNA copy number in cells and lactate levels in cell culture media
+a TaqMan reaction
+IRB
+methods that lend themselves to predictability
+Eight
+TF TCF4
+5.6 9 10 6 /kg
+the acceleration of MW-RCA
+negative
+Cell-surface biotinylation
+severity of their hypoxaemia
+alveolar macrophages
+0.5 million
+natural intermediate hosts
+2-14 days
+remove another 5 μL from the tube
+in or beneath the epithelium
+nanolitre vapour diffusion
+Cells and supernatants
+Four
+fungal
+trial treatment, assessments, data collection and follow-up
+Turkey
+safety and efficacy
+Holistic Virgin Coconut Oil
+εHOMO
+full-length lamin C
+The molecular mechanism
+OP differentiation and oligodendrocyte regeneration
+Interferon peptides
+Five
+extracting NAs
+immunosuppressants
+When financial circumstances deteriorate
+RSVS Clinical Pathology Laboratory
+G1-PB2 627K
+1 year
+Oligonucleotides
+Live virus
+Protection after Lordsdale ORF2 VRP vaccination
+DVG 70-114
+Favipiravir
+meaningful
+Vaccinia Virus Infection
+PRJEB15275
+4513
+Coronavirus
+autophagic responses
+Increased morbidity and mortality
+Meropenem
+Hypoxaemia
+progenitor cells of lung
+mRNA
+nucleolar activity
+otolaryngologists
+Packaging with Hyperphage
+a single viral genealogy
+Feline immunodeficiency virus
+control at the airports where it is likely to have the largest relative marginal impact
+chronic obstructive pulmonary disease
+2.54
+>28,000
+PCR and double enzyme digestion
+NCPAP
+maintenance of good data quality
+22.77 and 20.1 kDa
+5 min
+100 ml/well of recombinant PyCSP protein
+Neutropenia
+50%
+two
+IgG 1 isotype control mAb
+Civil registration systems
+equal to 1
+Representative-hydrophobic-only
+viperin
+IgM levels
+95%
+Diffuse alveolar haemorrhage
+K77
+29%
+Vasculitis and subsequent multi-organ infection
+serological
+57.6%
+Node color gradient
+malaria, HIV, childhood vaccination, and maternity services
+mosquitoes
+six
+higher-order multimers
+GenePix 4000B
+three
+large structural deviations
+20%
+intervention arm
+measurements for which P 0 was between 0.7 and 0.9
+farmed fish
+Confocal immunofluorescence
+activin A
+access to STT3B
+fever, hemorrhage, hypotension, and renal injury
+biological
+morulae
+GBP5, RARRES3 and VAMP5
+host protein synthesis apparatus
+70%
+isolated protein
+24 hours
+MiRNAs with overlapping coordinates
+APPENDIX 2
+spatio-temporal mixed effects regression model
+cell growth
+4, 5, and 11
+failure
+The biological significance of HA stability
+neurons
+90%
+water temperatures
+Latent variable projection methods
+2008
+AVI-4658
+P56L, P58Q and P59N
+ethnic differences
+Spain
+PBS with calcium and magnesium
+once a week
+66
+backward' contact tracing
+fantasy
+metaphylaxis with anticoccidials
+2007
+poisson process
+five
+Sefton A
+challenge with divergent influenza subtypes
+Heart rate
+German animal care guidelines
+slow convergence rate
+21
+serum TG
+A P value of <0.05
+host protein translation
+expression of NP
+30 nm
+hyperglycemic
+1990s
+opportunistic and highly antimicrobial-resistant bacteria
+Spanish influenza
+attenuation
+26 SDS sample buffer
+a validated geriatric construct of increased vulnerability to physiologic stressors
+three
+weekly case counts
+100 nL of 3 × 10 10 ffu/mL rVSV
+UL122 and UL123
+Western-blot
+Group T
+cholera
+multiple edges
+ssRNA viruses
+24 hr
+megalocytiviruses
+BigDye terminator reagents
+Influenza in immunocompromised individuals
+the prediction of pseudoknots
+500 µl RIPA buffer
+All data
+Residues interacting with the second ATP
+recombinant viruses
+hemangioendothelioma endothelial cells
+Coupling between translation and transcription
+linear
+increases
+macrophages
+nucleolar dominance
+silver mirror reaction
+immunofluorescent
+regulates NOX -derived superoxide generation
+High
+landeri group
+liposomal delivery of the protein
+Vimentin
+every 4 to 8 hours
+12 heads per hectare of rice fields
+every 4 hours
+KPNA2
+149
+tentative
+Ingenuity Pathway Analysis tool
+VEGF and COX-2
+the Z-score of log2-transformed RPKM expression levels
+Dynactin 1
+microbial
+randomization and follow-up of some non-influenza cases
+University of Pittsburgh Institutional Animal Care and Use Committee
+13
+inflamed CNS and blood
+roe deer
+24 and 48 h
+inactivation of phospholipase A2
+baboon
+39.0%
+ORF1 and ORF2
+To confirm the presence of subgenomic RNA
+cathepsin B
+The accuracy of mass spectrum
+macrophages
+computational methods for genomic data analysis
+Alternative pathways
+differential subcellular trafficking and cytosolic partitioning
+a clickable map
+late-stage immune suppression
+the media
+Akt phosphorylation
+dampening the antiviral response
+pressure equilibration between the rooms
+according to the corresponding reported procedures
+17
+1920
+epidemics
+Dialysis incidence
+dInosines at these positions will restore hybridization
+memory B cells
+three generations
+biting insects and aerosols
+two
+Diagonal vector
+HYG
+SOD-1, HSP-70 and TRX
+All data points
+total loop length
+in-house real-time PCR
+PRRSV
+drought, varying external light conditions or in response to reactive oxygen species
+XD packed against the folded region of N TAIL
+HRV transmission, infection patterns and diversity
+20
+Conserved vRdRp domains
+our method
+fold change
+content validity ratio
+48 hours
+transmembrane pores
+viral lytic antigens
+0.80
+exert their inhibitory function by binding the target sequence
+the brain's ability to absorb new information
+invasive pneumococcal disease
+Network
+The Identical Protein Report
+Human papillomaviruses
+IL-17 may participate in suppressing local or systemic inflammations during viral infections
+Noninferiority
+Transmission prior to the rash
+cloacal shedding
+A history of recurrent wheezing or asthma
+Irf5 and Irf1
+102
+543
+restricted
+24 h
+≥65 years
+Conservation of the GA 6 sequence
+quantitative lethality assay
+Eye, conjunctival, and nasal turbinate tissues
+Social influence
+ρ
+spatial heterogeneities
+higher
+Spearman's correlation coefficient
+The front person
+eight
+Human Leukocyte Antigens 1
+signaling molecules
+specificity of the response
+mathematical modeling
+DNA metabarcoding approach
+interferon
+antisense oligonucleotides
+64%
+36
+2 days
+public health practice
+frequent mutations in the HIV-1 genome
+zinc ions
+sevoflurane inhalation
+The EMBO Practical Course on Computational RNA Biology
+15%
+TNT-PNA oligonucleotides
+1889
+seven
+between 70 and 96%
+MIP-2
+36 KDa
+1 to 30,000 nM
+562 nm
+Federal regulations and incentives
+38
+sequence analysis
+cellular viability
+IFITM3
+V-Quest
+OIE listed animal diseases
+Agencourt AMPure XP beads
+proteolytic enzymes and low pH environments
+lower infection rates
+Three days
+emerging zoonoses
+Cell count
+small particles
+Cytoskeleton-dependent intracellular transport
+>100
+.500 V.cm 2
+Zinc, potassium, iron, magnesium and calcium
+gene gain-loss events and mutation rates
+To evaluate the efficacy of adoption of mass vaccination programs
+89.5%
+41
+West Nile virus
+25
+immunocompromised
+RBC transfusion
+Stanford Shared FACS Facility
+Agrin signaling
+non-canonical
+endoprotease
+diarrhea
+Switzerland, France, and Belgium
+48 hr
+immunofluorescence
+to protect young infants from RSV infections
+Twelve
+personalized medicine, improved outcomes, and less dialysis
+Valine
+antidrug titers and affinities
+rhinovirus
+Chikungunya
+CAP
+Yonsei University Health System Institutional Review Board
+90 to 100% inhibition
+decreased antigen-induced spot counts
+continuous epidemiological surveillance
+2 months
+acute respiratory distress syndrome
+nanoscale movements of domains or loops
+VP4 and VP7
+thirteen
+subgroups
+Five
+15,495
+plasmid pTRC-fimA
+MEG3 and siRNA negative control
+24 h
+molecular components
+UV
+NA activity
+σA
+independently
+Bovine serum albumin
+The ABR
+The RNA genome
+12 h
+6.3 per 100,000 personyears
+histolopathologic
+M1 mRNA expression
+mortality
+TOPHAT2
+Eight
+statistically significant
+low social cohesion
+complexity
+1 to 2 h exposure
+Oct-4
+control virus infections
+significant
+8 weeks
+percent inhibition above or below expected
+unmodified uridine
+minimise the risks
+increased proteasome degradation
+Opensource Field Operation And Manipulation
+oral
+Solvent accessibility
+14%
+peripheral blood mononuclear cells
+10-fold
+ion migration
+active
+Peru
+the base of the cell culture insert
+54%
+Antiviral
+August 2016
+IMHA
+how we understand and talk about antibiotics
+Gastric mucosal biopsies
+FDR < 0.05
+three
+six
+cc-by
+murine
+Contig files
+conserved RGD and KGE integrin recognition
+40 min
+Nine per cent
+neurotropic viruses
+chimpanzee AdC7
+Unconditional logistic regression
+λ − µ
+the necessary convexity of the integrand in the objective functional holds
+Each term in the rate equation model
+Embryonic myogenesis
+Parasites
+USD 18,000
+62 %
+equal molarity
+keratinocyte monolayers
+mathematical modelling
+gallic acid
+ASD-like rather than schizophrenia-like behavioral impairments
+Cd 21 and Hg 21
+pneumonia
+p
+degradation
+36/45
+recalculation of BIC penalty functions
+frameshifting
+discriminate their variable contributions
+Sigma-Aldrich
+Recombination
+3 days
+a website registry
+bonetargeted
+82%
+RBC transfer to the target organ
+focus-forming units per milliliter of supernatant
+Serum samples
+substances, objects, and patterns
+Libraries of Ab V genes
+atg8
+tertiary and quaternary infections
+proteins of the retinoblastoma family
+mutational fitness effect
+inhibits viral replication
+downstream of the pseudoknot
+one
+Inflammation
+JNK
+Cross-protective antibodies
+retrospective frozen specimens
+Easterners
+86%
+328
+cholesteatoma
+The percentage of IFN-γ-positive cells
+Heparinized blood samples
+Uruguay
+low RH environments
+8
+CT imaging
+L1
+genes highly expressed in the brain
+atelectotrauma
+50-100 million
+CD200 tr
+VR2332 replication
+murine norovirus
+Zika
+mTOR
+WNV replicase
+Common motif/pattern with amino acid sequence and location
+1.4
+oral clobazam and levetiracetam
+16 hour
+Smad3 binding
+Comparable delays in onset of severe disease
+patient number of contacts, length of stay and contact tracing
+a protein of 161 amino acid residues
+Infection
+NCBI Basic Local Alignment Search Tool
+Three
+Seventeen
+3 to 10%
+lower or negative
+Blood-based testing
+Binding of both TRAP and regA
+enhances resistance to JE and reduces viral burden
+54,628,373
+GraphPad Prism 5.0
+shuts down host cell translation
+SLiMs
+TssL and TssM
+Gibbs sampling
+those vaccinated with intent
+volunteers
+19%
+one third
+50%
+90 to 95%
+EBNA2
+CD8α + LN-resident DCs
+Position 2 and 9
+six
+studies
+50 μg/mL
+disappear
+w = 1.00
+thin-layer chromatography
+QoC-scores
+coagulation factor XII
+Saudi Arabia
+at least 5 million
+G 1 phase arrest
+cellular uptake
+wollamide B
+proteomic analysis
+apilimod
+3.20 Å, 38, 39
+their scores are added
+Asn 578
+hepatocellular
+hybridization
+Binding of Fob1 at RFB
+no supporting evidence
+GCN4
+three
+CAIII
+24-well plates
+13
+passenger data
+Urine
+time and fast information
+7
+105
+IFN2
+SAPS II
+less than 5%
+sodium citrate buffer
+the injection loop
+transcriptional modules
+Acute lung injury and acute respiratory distress syndrome
+pulse rate
+cytomegalovirus promoter
+The inhibition of ICOS and ICOSL
+0.9166
+21
+oxygen
+13,701
+inferred GRN
+1-200 kDa
+dynamic
+cytoplasmic OCT-4B isoform
+compliance
+100%
+Dr. Defu Zheng
+50,000
+embedded depth
+gap columns
+an 8% acrylamide/8 M urea gel
+H
+lighter regions
+D51
+immunoregulatory cytokines or chemokines
+56,671
+tick cell receptors
+IL-1b
+Thr90, Pro88 and Glu190 of GRIK1
+CSFV 2.3
+Five ll of eluate
+20 ng/ml
+SJIA Urine Peptide Biomarkers
+Protein extraction and solubilization
+mRNA levels
+Qiagen PCR purification kit
+5 mm
+avian influenza H5N1
+Student's paired t-test
+Introduction of a watershed
+respiratory events
+patient safety
+p65
+protein kinase C activity
+The polyprotein
+Model-based evaluations
+T2 and T3
+DW, JT, EG, and BG-B
+spring
+one third
+Q fever
+activation of apoptosis and secretion of growth factors
+Cell-penetrating peptides
+1,645
+isolation
+HADs
+mitochondrial metabolism, glycolysis, and multiple cell signaling pathways
+RSV
+closed tube system
+UTP
+Horizontal transmission
+4% paraformaldehyde
+Seneca Valley virus
+quite different clinical pictures
+polyclonal anti-Cav-1 antibodies
+low-viral loads
+Capsular polysaccharides and anthrax toxin
+chemo-virus and chimeric systems
+1917
+Socio-economic status
+exosomal analysis
+extended toeprints
+CME
+Defining these factors
+Actin dynamics
+25
+dynamic range and sensitivity
+Lung protective ventilation
+vesicular trafficking
+The concept of robustness
+kinetic
+comparisons across viral families
+90%
+increase fastest
+a follow-up of the fixed population in the community
+reduced Ang II formation
+disorder in the C protein
+HIF-α
+nicarbazin treatments
+hyperresponsiveness to cholinergic stimuli
+48 h
+dual skipping of either exons 44 and 45 or 45 and 46
+IL-10 family cytokines
+plasmid
+gene transcriptional dysregulations
+12%
+H7N9
+Mimotopes
+Re-admission to hospital
+T20
+Biomedical Advanced Research and Development Authority
+Trp, Tyr, and Phe
+tuning the activities and relative abundances of the tRNA-modifying enzymes
+Histopathological
+Interleukin-1 receptor antagonist
+complexity
+Thr519
+unsold poultry
+CDR2 regions of heavy and light chains
+100 bp DNA Ladder Plus GeneRuler
+13
+600 ppm
+60 ms
+daily
+Cationinteractions between arginine and phenylalanine side chains
+150,000×
+17
+selective immunoadsorption
+four
+population-based
+suppress or facilitate viral replication
+pO 2
+M. hyopneumoniae
+means ± SEM of each group
+the value of k
+Ten µL
+8 : 1
+African DENV strain
+via needle puncture through the side of the tube
+viral replication
+RNeasy Mini Kit
+RNA sequencing
+Immunoblotting
+15.8%
+Vaccine use
+RAS
+F. tularensis
+TRAM
+Treatment planning software
+blood plasma IFN-α levels
+Ag85B
+tissue samples
+7G8 polymorphisms
+rs12252-CC
+chimpanzees, macaques, or marmosets
+Medical educators
+17
+497
+Ten microliters of CCK-8 reagents
+poly-lysine diluted 1:10 in milliQ H 2 O
+inflammatory responses
+Candida albicans
+peak VO 2
+0.0291
+4.8%
+site B
+2-3 weeks
+Airway T RM cells
+0.01
+pharmaceutical and pharmacokinetic challenges
+Doctors
+coffilin
+12
+3%
+Bayesian skyline plots
+30.5%
+His27
+NS4
+physicochemical
+Shallow insertion of the fusion loop
+recombinantly expressed ubiquitin, SUMO1 and ISG15
+Descriptive statistics
+Global fitting of experimental data to well-characterized binding reactions
+perfect sensitivity and specificity
+Dextra Laboratories
+FlowJo
+RAND Corporation
+duplicates/repetition
+Follistatin-Like 1
+30 μL of NT80/82 30% slurry
+Deployment of technical elimination teams
+uniform lethality
+DMSO
+slightly longer
+1918
+new cooperation among institutes in Kazakhstan
+0.2% saponin
+several dozen
+21 days
+Colorado
+Wildtype
+15 days
+more stable
+coat protein of CYDV-RPV
+51
+VHL
+IL-17
+diff erentiate patients with chronic carbon dioxide retention
+intrinsic connectedness
+ArcMap 10.2
+Protein Thermal Shift Dye Kit TM
+InfA-NP
+Peptides and proteins
+one week
+pierisins
+multistate
+NF-κB/p65 nuclear translocation
+lung pathogenesis
+Spearman correlation
+E2 and E1
+inflammatory conditions
+10-14.5 mg/mL
+1 × 10 −9 M
+zanamivir
+15.2 nm
+two
+Grenoble, France
+six hour timepoint
+binds immune complexes at acidic pH and releases them at neutral pH
+zero cases should be counted
+contrast
+greater
+Richards model
+dsRNA binding
+identical
+IFN-γ production
+frequent and direct response experience
+two ligand binding sites
+Geminiviridae
+codon choice
+IFN I, CCL2, and defensins
+154.7
+200
+2007
+effectiveness
+cytosolic proteins
+multidrug resistance protein 1
+polyubiquitin coat formation
+HEK transected cells
+PKR Ϫ/Ϫ cells in culture
+Yinpterochiroptera
+138
+more sophisticated methods
+H 2 -antagonists
+Avian infectious bronchitis
+310 363
+anti-H1N1 IgG
+23
+inactivated, live attenuated and DNA chimeric vaccines
+cardiotoxicity prevalence
+novel technological advances
+RanBP5
+compound 14
+nine
+viral supernatant
+complementation
+virus type
+4
+realists
+Enfuvirtide
+GraphPad Prism
+Q75FL0
+425
+proteolytic
+18β -glycyrrhetinic acid
+one potential N-glycosylation site
+intron 6
+10 min
+how far in advance travelers planned their itineraries
+mountains, lakes, and rivers
+new diagnoses
+pattern recognition receptors
+Renilla/Firefly luciferase bicistronic
+histidine label
+secondary structures of cmRNA
+inhibitory synapses
+Additional research
+15
+contacts within close proximity
+430
+control genome sequences from 8 wolves
+multiplex real-time PCR assays
+T
+eight
+clinicians
+acute trauma, extremely preterm birth, and late presentation to the emergency units
+lung mRNA silencing
+Desmognathus
+One Earth, One World, One Health
+interview and partner tracing
+2 h
+the toxicity of 4 ÀPMO
+17
+Increased media use
+relative ease of their implementation
+BIV
+p ≤ 0.05
+lack of data on clusters
+binding/entry of virions mediated by GP 1,2
+semilogarithmic
+1600
+increased
+leave-one-out cross validation
+IgYs
+ether
+BCL-6
+H5N1
+HIVrelated stigma
+bradykinin
+1184
+selepressin
+gradient
+influenza virus
+ω-O-acylceramide
+>90%
+honestly significant difference tests
+University of Zurich Centre for Travel' Health
+1892
+dopaminergic neuronal cells
+drug development; high throughput screening; reporter mice; age-related disorders
+The sequence conservation among orthologs
+0.7 Å
+the PI must inform the KCTF in writing
+viral titers
+sepsis
+persistent viral production up to 30 days post-infection
+FeLV viraemic
+40%
+mice
+African lion
+spo0A
+Mx1
+Phylogenetic
+Associations with proliferating T cells
+Syncytiogenic
+Blood samples
+hepatocytes
+3 days
+murine
+OA, soybean oil and soybean phospholipid
+physical knots
+sinusoidal and anteroinferior ST elevation
+GraphPad Prism4
+severe inflammatory diseases
+instability element 1
+10 min
+virusspecific
+Axio Imager Z2
+50%
+Complicated
+100%
+5
+lymphopenia
+two groups
+rice cultivation and flooding irrigation
+Constant returns to scale
+output feature maps
+real-time PCR assay
+Influenza A
+manipulating the genetically programmed basal or induced levels of defensin expression
+stochastic
+lovastatin
+HA imprinting
+contact rate between infectious and susceptible individuals
+tilmicosin and tylvalosin
+ZFNs
+resource-poor settings
+antiviral
+cosavirus A
+KOD-plus-Neo
+Stata software version 15
+5
+12
+Poly binding proteins
+CS
+The partition coefficient
+96
+IRF3
+GRADE
+KIH packing between the associated helices
+prior antibiotic treatment
+nuclear localization signals
+basal activity of AMPK
+Node ages and correspondent 95% highest posterior density intervals
+Angiotensin Converting Enzyme-2
+XLStat
+no seasonality
+two
+655
+H7N9 case reporting and identification
+2 to 180 kDa
+protective immunity
+Improved quality of care
+caution
+mechanical
+14 days
+inhibits acidification of the trans-Golgi compartment
+antigenomic
+increase BMV RNA levels per cell
+meta-analysis
+90
+reliable energy parameters
+PicoPure RNA Isolation Kit
+arginase
+middle of 1990s
+NCBI Influenza Virus Resource
+25 L of RNase A and 50 L of propidium iodide
+Mutation of His208
+preferred codons
+Frequency of transmission events
+misfolded proteins storage and proteostasis control
+PTIO
+11%
+immunocompetent
+five to nine
+200 µL of rVSV-VP1
+differences on ORF layout
+speeds up the identification of genes and proteins
+H5N6
+23%
+Four
+they offer no improvement over other established infection models
+tumor size
+IFN-β
+2 weeks
+Pollination syndrome theory
+G0-arrested cells
+Ni 2+ -NTA agarose resin
+Eight
+RPs
+300
+3500
+respiratory support
+Nasal cannulas
+wearing a nose clip
+Six hours
+2-CTC resin and standard Fmoc chemistry
+regulation of proliferation, differentiation, cell adhesion and apoptosis of cells
+The pathogenesis of rhinoviral infection
+GW motif
+NucliSens easyMAG
+Rev-responsive element
+20
+B cells, DCs, and NK cells
+Vero cell adapted PPRV Coimbatore field isolate
+putative regulatory mechanisms
+intent-to-treat principle
+asymptomatic controls
+Three
+low sensitivity
+HIV-2
+local translation of ACE2 in affected organs
+one per million
+DAPI-stained nuclei
+Developing and conducting trainings
+Agincourt AMPure XP beads
+host mimicry
+translocates to the nucleus to activate gene transcription
+eight
+V regions
+Bayesian
+Biological information stored in databases
+Complexity and dynamic range of protein concentrations
+a shift in the interference pattern
+Z-score
+biosynthesis and metabolism functions
+nuclear metabarcoding markers
+prediction algorithms
+exploration
+multiple strains
+higher MDA levels
+Ten
+fresh antibody
+check your spam filter
+3A
+cardiac
+Tannins
+99
+national security agencies
+fluorescent proteins
+1× PBS
+91
+those developed in clinical laboratories
+human kidney
+PKR, Hck, and p38
+TCM extract library
+CIRMF
+protective immunity against influenza virus infection
+Residue 294G
+ribosomes with ongoing translation
+One month
+three
+high-dose inotropes and vasopressors
+CD8 T cells
+27.3%
+30 mins
+interlaboratory strain variation
+E. coli or in P. pastoris
+non-blood fed, nulliparous and inseminated females
+a stricter, 1 m criterion for contact data retention
+recombinant technology
+P
+vitreous
+WBC
+Centre for Reviews and Dissemination guidelines
+changing viral receptors
+monoclonal
+10 cm and 50 cm
+Watson-Crick and wobble basepairs
+150-180 mg/DL
+polymorphic, conformationdependent epitopes
+Caspase-Glo 3/7 assay kit
+spleen and liver samples
+Department of Infectious Disease Epidemiology
+0.677 and 0.323
+types of land cover and agriculture
+Newcastle disease
+autoxidation and self-conjugation
+24
+Dr. Praveen K. Gupta
+16
+via the receptor CD155
+S6 Table
+reference category
+5 weeks
+SLLTEVETPTRSEWECRCSDSSD
+Parker et al
+Bob Darnell's lab
+CSPG GAG side chains
+Cathepsin S
+5%
+Blood-based testing
+fold change >1.50 and p-value < 0.05
+zero
+GUCCUUCCAA and UGUGU
+LBR and Rab5
+Supplemental oxygen use
+reduced proinflammatory cytokine secretion
+how it is perceived and dealt with by both the innate and adaptive immune response
+what percentage of the population is vaccinated
+Insulin-Transferrin-Selenium and 1 ng/ml EGF
+Ventilatory adequacy
+zoonosis
+ulcerative colitis and Crohn's disease
+MDA levels
+IMPUTE
+10 to 50 µm
+6 nM
+one bent or buckled end
+The schedule of enrolment, intervention and follow-up assessments
+Italy
+α5 integrin
+Rab GTPases 5 and 11
+congenic marker staining
+Sensing of HCV by RIG-I or MDA5
+proximal tubular cells
+70%
+LPS-primed BMMs and dendritic cells
+Participant samples with GST MFI levels above a threshold of 1,000
+15.2 ± 6.4 days
+SPSS 13.0
+Age-at-exposure related effect
+11
+DENV infection
+strikingly different
+30 minutes postinjection
+cellular machinery
+intestinal healing and anti-inflammatory function
+sporozoite proteoforms
+mouse tumor models
+Ravn GPcl
+Weibo
+viral infectivity
+particle detection and tracking, trajectory classification, and physical modeling
+15.4
+Metagenomics
+European Centre for Disease Prevention and Control
+π
+Vim À / À
+lytic agent
+chemical
+6000
+X-ray crystallography and NMR techniques
+Hardy-Weinberg equilibrium
+5%
+taphonomy
+notum
+21,000
+Ova-specific ELISA
+1 h
+Fieldworkers
+protecting a naïve population from pathogen invasion
+Dr. Ervin Fodor
+SCI
+rgPB2-K627E + Q591K
+Solvent
+luciferase assay
+Autophagy
+Model B
+Seryl-tRNA synthetase
+4E-BP1
+shorter QT and PR intervals
+thousands
+954
+monophyletic
+decreased
+temporal distance
+blood transfusion
+NH 4 Cl
+Sir Horace Smirk
+separate excel files
+vaccination planning
+lipid A
+interactions with Lsm11 NTD
+50%
+1.5%
+50 ng/ml
+interests
+Intranasal protein-based or attenuated vaccines
+inhibits Vsig4 gene transcription
+411 aa
+mucins
+US-guided punctures or injections
+9.1 ± 2.2 days
+illness
+μ
+50
+29
+F6
+neurotrophic factors
+TCS
+88
+binds to viral protein PB1-F2
+chemiluminescent
+serious consequences
+A probe and an enhancer
+Gly88
+HA and NA
+893.9 Å 2
+caplacizumab
+Cervix uteri cancer
+subendocardium
+overrepresentation of hospitalized patients
+non-segmented negative sense RNA virus replication
+throat and nose swabs
+univariate logistic regression
+cc-by
+50%-57%
+Olympus IX-70
+Error bars
+TLR-3
+Dr M. Harris
+Killer virus
+100%
+infectious matters
+A short fused-silica capillary with a tapered tip 37
+an item
+100
+inflammation
+Genetic algorithms
+CiteSpace V
+degraded
+100%
+3 to 6 days
+Quantitative real-time reverse transcription polymerase chain reaction
+a model using a simple regression
+Thyroid hormones
+serum nitric oxide levels
+APC8
+oropharyngeal cells
+Egr-1 mRNA upregulation
+16%-33%
+one
+Host shifts
+esophageal and intestinal smooth muscle
+sequence-specific geometry
+to determine viral propagation
+NIRVS
+six
+100%
+8 to 10 ml/kg
+prophylactic
+macrolide
+42-fold
+extinction risk
+SEED alignment
+progression of some CMV infection disease
+12%
+actinomycete
+high local concentrations of the toxin
+protective
+3 and 5
+Mock-infected mice
+Western Lightning Plus-ECL reagent
+a sample size of 158 patients
+past behaviour
+Outliers
+37 °C
+more than 10 million
+A concentration of 0.3 M and a high MOI
+2 hours
+six
+C-type
+inhibits viral attachment
+initial muscle strength
+Japan
+hospital ownership and geographic location
+more extensive molecular and genetic analysis
+deposition of collagen and fibronectin
+ivermectin and importazole
+a short temporary inability to perform liver transplantation
+Anti-HA antibody in peripheral blood sera
+five
+pPG-COE-DCpep/L393
+Lung tissue
+z-dock and Hex
+155 bp
+the end of the primers
+Pogge
+a standard Susceptible-Infected-Susceptible model
+Lipoteichoic acids
+Glasdegib
+28-day mortality
+PARRIS
+an N-terminal amphipathic helix
+throughput
+facilitating the release of LCMV virus particles
+dewaxing and hydrating
+predictive AUC
+sfRNA
+premature mortality
+specialized transcriptional coupled chromatin readers
+16
+5% Chelex 100
+Significance intervals
+protease sensitivity
+viral glycosphingolipids
+1
+4,735
+Multiple independent rescues
+TMB
+1.873 6 0.375
+human peripheral blood
+15
+activation of AhR signaling
+seven
+ESCRT pathway
+UN/N
+PDQuest
+basic reproduction number
+Chain B of PDB code 4WSB
+a terminal position
+Oseltamivir
+nucleotide 858
+disposable overalls and powered air-purifying respirators
+p A m
+10 min
+Monotonicity
+four
+metaarrestin
+10 ml of trypan blue solution
+LCMV production
+patients requiring mechanical ventilation
+ZIKV-prME pooled peptides
+TrxR
+IFNc
+high and similar
+monolayers
+Leiden, the Netherlands
+The sequence of scFv-A4
+Experimental variability
+Liquorice
+Approximate Bayesian computation
+Pseudomonas aeruginosa lectin LecB
+IL-10R blockade
+Lewis rats
+number of tips
+changes of nearest neighbors
+GL-treatment
+immunofluorescence
+volume capnography
+important mediators of apoptosis
+acetic
+medicinal materials
+to prevent harmful immune responses and inflammatory diseases
+Mutation of the catalytic residues
+37
+to identify and rank the most important factors driving the risks
+absorbance
+herpes simplex virus keratitis
+I/R injury, sepsis, and multiple organ failure
+H = 1
+UPR
+GADD34 expression
+0.003
+focus forming units /ml
+12 h
+Highly sensitive
+Protein Data Bank
+rank-based method
+30 to 50%
+28 weeks
+5-Fluorouracil
+Twenty-four hours
+SuperSignal West Dura chemiluminescent substrate
+PKR
+UV and heat-inactivated
+APC10
+Intrinsic
+Yang
+CD8+ T cell
+10 out of 10
+immunofluorescence microscopy
+EBV
+day 13
+GU325783
+Four
+natural reservoirs of HIV-1
+high costs associated with increasing inspection rates
+three
+data
+DENv2
+reaching sufficient vaccination coverage
+antidepressants to antiasthmatic and anti-inflammatory agents
+professional health care workers
+IgM
+matrix metalloproteinases
+SARS-CoV 7
+EGR1 upregulation
+graphlet degree centrality
+neutrophils, DCs and pDCs
+AD3BF2D
+viruses
+spatial dispersion parameters
+six
+planned road connections
+similar
+4,217 nucleotides in length
+the stem region of the hemagglutinin protein
+USP15
+Receiver operating characteristic curves
+Sekisui XenoTech
+signature performance
+␤-cell function
+epithelial cells
+transfected 293T cells
+HTSeq-count
+infection
+Identifying the binding motif and binding register
+Data on the in-hospital case fatality of different pesticides
+scores with biomarkers
+October 2003
+luciferase-tagged HCVpp
+Those studies targeting only the VLPs of the microbiota
+antibody recognition of the protein surface
+E. histolytica
+48 hour
+proinflammatory
+30 min
+Functional enrichment
+rare individual host susceptibilities
+GP 1,2
+antiviral tests
+to assist virus dissemination
+restricts influenza viruses
+Genomic DNAs isolated from r + or r 0 cells
+67
+r~0:2
+distributional
+a TLS
+Viral protein 3A
+1918
+Health education
+lamina of the cortex
+ImageJ
+126
+Logistic regression analysis
+cerebral palsy and epilepsy
+attenuated viral vectors
+Rhesus macaque and sooty mangabey RNA samples
+binding to its receptor CXCR2
+quality assurance procedures
+cases with onset
+mean ± SD
+an appropriate likelihood
+2 days
+Negative binomial regression models
+Central Nervous System Tumors
+a dose of 2.0 x 10 7 TCID 50 /fish
+42.51 months
+Equimolar amounts of Mag and Hon
+CmoA and CmoB
+high flow devices would not be withdrawn
+Jingmenviruses
+sterile cotton swabs dipped in normal saline
+forest rodents
+SMARCA2
+Ticks
+dengue virus
+anti-proteolytic potency
+Xpert induced sputum/gastric lavage results
+levels
+cyclin dependent kinases
+dendrimer
+intrinsic disorder
+40%
+site-specific
+Endosomal acidification
+national surveillance reporting and/or autopsy requirements
+2.5%
+inhibit viral infection
+200,000
+5099
+ENC values
+nucleoli
+attack rates and costs
+compartmental models
+an aliquot of the extract containing 700 mg of protein
+opposite and unintended consequences
+focus-forming units per ml
+Four
+very few mutations between ancestor and descendent
+1 week
+AT-II and bronchioalveolar stem cells
+anti-TIM-3 mAb
+94.2%
+46
+Y. pestis
+149-100 × 10 9 cells/L
+Particular attention
+21%
+CEM Liberty TM microwave peptide synthesizer
+cells clogging the NA binding membrane
+World Health Organization
+epsin N-terminal homology domain
+April of 2014
+Unconventional Protein Secretion
+one year
+amplified
+cellular
+outpatients
+pulmonary bacterial colonization
+36 h post Pm infection of mice
+attenuated bone erosion
+input data quality
+24 h after administration
+literature
+Defensins
+diverse abundance
+optimize parasite growth and development
+30 min
+Eq.
+impaired decision-making represents a potential endophenotype of suicide vulnerability
+candidates for development of novel cbDVG-based adjuvants
+1890
+C5
+linear
+neighbourhood contact hubs
+protein biosynthesis
+vesicles
+IRESes
+to ensure that the embryo will be supplied with sufficient nutrients and oxygen
+Regulation of protein translation
+Tetraspanins
+7 days
+significant change
+Lipid cores and fibrous caps
+Katnal1 1H/1H mouse brains
+pharyngeal
+71%
+Jackson Laboratory
+inflammatory
+Met residue
+20%
+Lys63-linked ubiquitination
+Klebsiella
+2003
+13
+Resveratrol
+Bl and Bt
+p
+Ͻ 300 g/mol
+mdx mice
+antiacetyl-lysine antibodies
+20,000
+further assay development
+2-month
+divergent fibrogenic diseases
+M V
+vibrating mesh nebuliser
+IRES elements
+their legal department
+PCR Kleen Spin Columns
+Malaria transmission
+catabolic
+seven
+Cd2? uptake into MDCK cells
+80%
+Gilead Sciences
+the effective irreversible uptake from the input
+μnx * 2 /α 2
+4
+Gram-positive
+phylogenetic
+Chemical siRNA Modification
+0.155
+Mitochondrial AntiViral Signaling
+more than 200 million
+Detailed studies
+Fluorescence intensity
+HCV RNA levels
+North Africa
+100 nM thapsigargin
+mamastrovirus
+more than 8 months
+lncRNA NKILA expression
+global health
+protein tyrosine phosphate
+parasite spread, disease severity and parasite evolution
+type I 0 and II 0
+antibodies to a variety of structural and nonstructural viral proteins
+externally regulated transcription
+B
+Arrangements
+pending
+Asian studies
+Super-Pose version 1.0
+CAV16
+PERK or IRE1a
+Fugene
+Research
+Computational methods
+55
+CSFV and PHA stimulation
+λ 1
+electronic, steric, geometrical, and quantum property profiles
+numerous dysregulated networks and cellular functions
+2 kbp
+DCs of four independent donors
+EcoRI and SalI
+divides the sequences of an RNA alignment into subgroups with different consensus structures
+dependent on contact with the host cell
+All military care providers
+5-7
+Dr Taubenberger
+1.84%
+29
+lack of sufficient host contact networks
+four
+public land
+Intelligence Program
+6.00 days
+Stockholm format
+prohibitive memory limitations
+flow cytometry
+IL-17A
+M1
+reminders
+3.4 to 7.2 mg/dL
+cell-cell adhesive junctions
+Short-Term Scientific Missions
+a series of weights
+adjustments using a constant correction factor
+7.4
+383
+1 d
+77.0%
+28%
+occupational status
+limits the interpretation of our results
+pBzMM150
+Transmission of GAS
+E1-A226V
+The virus organ system tropism
+HS
+LAG3
+120
+Consortium RNA spike-in control mix
+ORF29a and ORF65
+Cellular supernatant samples
+via the SecA secretory system
+2 h
+hemadsorption site
+five
+Andalusia
+dynamic global trends
+susceptibility and resistance after IV infection
+preventive
+equal to the following
+E1E2 global folding
+severe acute respiratory infection
+MRSA
+hemorrhage
+NLRP3
+8
+Strain 630Derm
+His60 Ni Superflow Resin
+APASL definition
+RT-PCR, IFA and TEM assays
+β-MAN, MAL and PLD
+1817
+endoplasmic reticulum
+intracellular
+G
+twice per day
+aged
+mechanistic
+physiological barriers
+decreases the chance of being infected
+accompanying adults
+University of Nebraska Medical Center and the National Institutes of Health
+24-h
+amplifying primers and additional internal sequence primers
+neuronal
+viral RNA
+10.1%
+other major gross or histological changes
+those of wild-type cells
+serology
+unclear
+116
+national suicide prevention strategies
+S. enteritidis or C. perfringens
+48 hours
+fetal intestinal cells
+hematoxylin and eosin
+C1-INH
+Pools 2 and 5
+0.4 to 0.6
+immunofluorescence
+statistically significant
+poorly vascularized
+30 and 40
+small number of patients
+gaps in oseltamivir
+RANTES
+H3N2 data
+HCV seropositivity
+20
+ambient temperature
+700,000
+output as raw data files
+hypothesis
+positively charged residues
+reference structures
+4 h
+58.3 per 10,000 persons
+genotyping in HRV
+Australia
+gametocyte formation
+13
+twice
+respiratory distress
+inconsistent adherence
+dementia and mental confusion
+history operation and current situation
+statistical significance analyses
+diabetes
+T-2
+RNeasy Mini kit
+upper and lower RTIs
+20-21 May
+Quantitation
+no viral replication is observed following challenge
+a near-absent upstream IFN induction
+L 2
+A-SAA
+levels of CTL activity
+Virus isolation
+The Adaptive Neuro-Fuzzy Inference System
+convincing effectiveness
+host cell entry of HIV and SIV
+300 µM E64
+28-day and 90-day mortality
+seven
+23
+lack of funding
+IL-8
+iodoacetamide
+National Institute of Standards and Technology
+warmer distal airways and lungs
+reducing biological threats
+tDCs
+MobA89K
+aliquots of GI digests
+Nine
+higher
+acute mountain sickness
+1957-1958
+ImageJ
+in vivo efficacy
+follicular B cells
+science
+53
+local information flow
+demonstration of absence of disease exacerbation
+gene genesis, lateral gene transfer, and gene loss
+greenblocks
+10
+24 hrs
+Five
+higher rates and levels of exposure
+RNA replicases
+30%
+C4 mediated neutralization of Ad5
+enhancing antioxidant enzymatic processes and free radical scavengers
+Occasional solitary fibers
+one typical infection person
+CD4 + T cells
+the location of distal-eQTL
+hydrochloric acid
+nuance and complexity
+several to hundreds
+15 days
+copyediting, typesetting and review
+Bypass surgery and angioplasty with stenting
+novel cellular proteins hijacked by KSHV
+54
+dichotomous variables
+robustness
+one day
+2 weeks
+Adobe Illustrator
+looking for adverse events
+preparedness and response to disease outbreaks
+oral fluid intake
+over a decade
+a black border
+Link density
+RNA viruses
+1 month
+MRSA
+eIF2a phosphorylation
+77%
+p62/SQSTM1
+23
+oxidative stress and chronic retinal inflammation
+its relatedness to the pathogens' original host
+30
+one gene
+a number of different cellular proteins
+cytoplasmic pathway
+WT mice
+33
+other, more important, activities
+10%
+lung edema
+12 or 13
+Unmanaged planning, limited public infrastructure and informal employment and economies
+-1
+PRDX1
+PEDV infection
+S. pneumoniae
+common vampire bat ecology
+actively transported to the cell periphery and released prior to cell lysis
+ACTB, TUBB and GAPDH
+peptide ligands
+SOFA
+immunohistochemistry and immuno flow cytometry
+1 : 9 or 1 : 12
+loss of the gene product or a substantial reduction in gene function
+Viral and bacterial infections
+EGFP and F4/80 cells
+opaque liquids
+89.1%
+clodronate-liposomes
+Sensitivity
+late June 2015
+28652
+susceptibility
+providing the information desired
+a family of IFN-and virus-induced proteins
+NF-κB
+competition between strains
+IFN-λ3 rs12979860
+nutrient availability
+controlling tumour growth
+protection against SIVs
+shedding of the L-selectin receptor from the cell surface
+I1R, I2R, and I3R
+standard formulas
+E53 IgG
+Anticoagulant
+20 minutes
+4 to 5 months
+80%
+Plasmid DNA cloned with HBV or HCV sequence
+passage bias mutations
+Isoflurane
+leukocytes
+IRF-7
+1%
+aberrant complement activation
+viable virus released during coughing
+higher than 80 %
+urinary ACE
+monkeys
+0.5 ml terminal transferase
+ANDV Gn-derived peptides
+158
+Eight
+GiRaF
+weakly
+cytolyctic
+allelic interactions
+treating other diseases
+490 nm
+thermodynamic
+penicillin
+species-dependent
+multicolor flow cytometry
+100 %
+Local room temperature and relative humidity
+constant factor β
+differentially
+Diagnosis and hospitalization
+0.3% H 2 O 2
+tertiary base pair interactions
+duplicate on cells
+93.4-98.9%
+non-pathogenetic control variants
+dengue haemorrhagic fever
+middle east respiratory virus
+Tekmira
+21,005 ± 870
+48%
+Membrane cholesterol
+macrophages
+5%
+induce inflammation and ALI
+100% sensitivity
+0.2%
+Abundance
+alcohol dehydrogenase
+V149A
+maternal physiology
+electrophoretic
+6
+HCWs
+ligand binding mode
+personal records
+neurological disease
+nine
+altered phagosomal compartmentalization of DENV
+adhesion of particles with Ag or Abs bound to their surfaces
+translation in cell-free translation systems
+Kanzlerin
+0.2 mg/ml
+gut recognition and binding
+ELISA assays
+caution
+crucial for reactivity
+glutamic acid
+HIV-1 entry inhibitors
+Integrated DNA Technologies
+Diagnostics
+Descriptive statistics
+upregulation of STAT1 and STAT6 expression levels
+to detect anti-PPRV antibodies
+isolates binding and fusion processes from endocytosis
+Humidity
+133
+epidemic network topology
+traditional phylogenetic methods
+antiviral drug
+ethical
+HHT
+MRSA
+PI
+2.7 million influenza-related deaths
+nucleoproteins or capsid proteins
+gloves, gowns, masks, respiratory protection, and positivepressure ventilation suits
+13.4%
+4
+size exclusion chromatography
+IFITM3
+viral secondary structure
+expression level of RTA
+overexpansion of hematopoietic precursors
+triangles
+2015100910396112v1
+24 h
+intermolecular interaction analysis
+A * 11
+E protein trimerization
+cell culture supernatant
+448
+infectivity factor
+antiviral
+statistically significant
+an attached lipid moiety
+mitochondrial ROS
+Symptomatic
+RT-PCR analysis
+exosome-less
+explicit within-host dynamics
+High-mobility-group-box chromosomal protein 1
+1/µ M
+10 days
+the number of steps required to find either a match
+1621
+AtRH2 and AtRH5 helicases
+two
+S. dysenteriae
+TTSuV1
+traffic crashes, residential fires and violence
+respiratory support including extracorporeal membrane oxygenation
+BRCA1
+human carcinogenesis
+IL-17A/F
+sterile solutions
+rMP12-SFSNSs
+AS03 A and AS03 B
+intimate
+4 weeks
+restoration of some negative charge at the N3 center
+weight gain and uncontrolled hyperglycemia
+ubiquitin-specific
+cap-dependent translation in HeLa extracts
+reinitiation efficiency
+Early detection
+4q27
+1333
+PCR product
+PI3K and Atg7
+four
+alters C-type lectin utilization
+2004
+hepatocytes
+potential therapeutic target
+amino acid metabolism
+three
+Compound Topographical Index
+i
+36 h post-infection
+ICU attending physicians
+146
+solvation environment
+developed countries
+Understanding the mechanics of a signaling pathway and its downstream targets
+little
+Dengue
+amodiaquine and chloroquine
+unit vectors
+tonometry
+reverse transcription
+Axl, Dtk, and Mer
+Enteral feeding
+6%
+milliseconds
+exponential
+human AFP may interact with these signalling molecules
+Glutamate
+bind pRB and displace E2F
+A to G
+Ubiquitination
+2000
+50 mL 1:10 diluted purified toxin
+4%
+filter paper
+exon-skipping efficiency
+epigenetic markers
+44
+Ultrasound
+NSs protein
+mRNA circularization
+sinI
+CFU and protein concentration
+an entire BAC clone
+rVV-Empty-inoculated macaques
+neutrophils
+WHO Programme for Prevention of Blindness and Visual Impairment
+Leishmania donovani
+rRNA
+CPT2
+Sterile 0.9% NaCl warmed to body temperature
+viral genetic complexity
+The dose of cuprizone
+Data
+improves
+Af1521
+w A ¼ P e2A wðeÞ
+changes in the periphery of the lung
+successful HPV16 infection
+no additional insight would have been gained
+18
+20%
+research groups
+MHV RNA synthesis
+95.8%-100%
+between 9 and 23 months
+0.26%
+HIV/AIDS
+3
+every 2 h
+cancer metabolism
+potential drug targets
+cysteine
+Becton Dickinson
+φ
+>97%
+PD-1△ex3
+1 day
+VRPs
+an episome
+overall AR
+Hundred percent
+pleiot ropic
+BBB permeability
+Rota A
+lipofectamine 2000
+reaching an effective intracellular concentration
+by flow
+Lamivudine
+Disheveled
+mitophagy
+7
+CD45RA isoform and chemokine receptor CCR7
+pre-existing conditions
+Bayesian hierarchical logistic regression models
+Three
+restricting vK1L -C7L
+zoonotic spillover
+5%
+60
+Card9 -/-cDCs or FLT3L-DCs
+Q
+-1 AUA
+423
+Receipt of pre-travel health advice
+school evaluation purposes
+25%
+2.7%
+plasmid
+Multiple Sequence Alignments
+pRen2 plasmid
+viremia
+mitogen-activated protein kinase ERK1/2 signaling pathway
+flexible models
+95%
+BiPAP-Vision™ ventilator
+hatcheries
+inositol
+2014 CDC guidelines
+WHO Class IV
+lack of standardization
+7%
+bariatric surgery
+ESKD
+TNF-α
+3526
+Ganciclovir
+clinical
+two
+enveloped
+three days
+PLOS Medicine Editors
+MAP3K7/mTOR
+cycloaddition reactions
+52,000
+CEACAM1
+68 nucleotides
+61
+Hc-CS
+ten
+thymic epithelial cells
+four
+highly efficient counterstrategies
+1 mg/mL
+VEGFR2 phosphorylation
+Ptrach
+intestinal immune system
+Furaciline and nistatine
+RABV and VSV
+antiretroviral therapy
+6 hour
+complete genomes of CRESS-DNA viruses
+Glyceraldehyde 3-phosphate dehydrogenase
+the binding of purified SP-D
+DMD mRNA knock up
+one hour
+100 μ l of Bright-Glo luciferase reagent
+5-8 million
+host ferritin
+50%
+wheeze, shortness of breath, chest tightness and cough
+400
+50 kDa Amicon filter
+active immunization
+28.2±25.2 months
+1918
+mobility model
+31 min
+CEACAM1
+1610 25 substitutions/site/year
+PubChem
+Restore PLUS stripping buffer
+HIV-1 capsid
+248,000/μl
+exhaled breath
+2.7
+least accumulation of inflammatory cells
+X and Y motifs
+SAPs
+Uruguayan
+DAVID
+immune suppression
+Cell Signaling Technology, Beverly, MA
+Conditioned medium
+3 min
+Cytoplasmic RNA
+n
+3-7 days
+TB-vaccine
+humoral immune responses
+a putative binding site for SF2/ASF
+macrophages or NK cells
+Nsp9
+Climate changes
+the number of closed walks that the node touches
+PBECs/growth factors
+ribosome binding and translational efficiency
+SLEV, YFV and DENV
+ModRefiner 33
+Figure 4A
+neuraminidase
+Ubc9
+fungi
+Controls
+humidity
+Safety issues
+GFP
+space group P4 1
+non-specific binding of the antibody
+straightforward diagnosis
+social distancing and isolation
+Fibrinolysis
+TCA
+clinical signs of infection
+Fluorescent Image Analyzer FLA3000 phosphorimager
+8-10-day
+robust NAb responses
+all the images collected in a single tomographic tilt
+656
+2009
+2.0 ps
+a health sector coordination body
+5%
+Carvalho and Lawrence
+pulmonary embolism, stroke, and deep vein thrombosis
+DNA
+m of K 2 hh
+integrin β1
+total protein concentrations
+trachea, bronchi and bronchioles
+20 min
+temperature, percent carbon dioxide, and humidity
+12.5%
+66 new-synthesized SAIs
+45.9 years
+bind to D 2 DR
+gradually
+six
+variability in infection age
+LoFreq
+sputum PCR
+Retinoic acid
+ICP4
+464
+six
+20 ng of human gDNA
+enzymes
+RR MScl and PP MScl
+18 h
+latent cysts
+Immunohistochemical
+Mr J.J. Gouws
+Azurin
+in vivo model
+Nikon Eclipse TE2000U photomicroscope
+R software
+293T
+EBOV entry
+Missing values
+enhance protein secretion
+Cell populations
+prevention of hematoma enlargement
+Apotosis
+Ducks
+population health benefit
+generalized additive models
+28-day survival rate
+JcDV capsids
+a new water
+CPB time
+based on staining intensity and fractional quantity of stained cells in a sample
+differences and similarities
+cGMP stimulation by natriuretic peptides
+time
+Multivariable Cox analyses
+0.5%
+differential cell counts
+Missing cytogenetic risk
+20.15% per household per year
+stochastic branching process model
+Non-replicating mRNA-based nanovaccines
+ER-associated degradation
+29
+antibody and cytotoxic T cell responses
+A-VPK
+goats and sheep
+calibration beads and a specifically formulated antibody-fluorochrome conjugate
+three
+proof of efficacy
+83,376
+more negatively charged
+infection
+pouchitis
+1000 mg/m 2 bd
+NP
+twice
+ALC on D7
+Hydras and planarians
+virus replication
+one
+different chemical groups of amino acids
+75 nm
+10 4
+Biotechnology Research in an Age of Terrorism
+7.23 × 10 8 cells/ml
+12.12 days
+viral infectious titers
+TDMD of miR-27
+10%
+60%
+innate immune response
+three
+Discrepancies
+Waterborne diseases
+preS1
+150-fold
+infectious bronchitis
+4 hours
+TGFB1, TNFA and IL10
+2 h
+Cytokine
+neurotropic viruses
+preferential mixing
+Anti-human IgG conjugated to HRP
+Oxidative stress
+five weeks
+The SAE reviewer
+PPI
+EPS 26a
+The ENC
+A/J mice
+CEA
+high affinity TCR specific for self-antigens
+2009
+temperature
+local STI clinics
+belief in a range of conspiracy theories are inter-correlated
+finding a novel and effective treatment
+immunofluorescence analysis
+by consensus
+lipoplexes
+Sindbis virus infection
+Respiratory infection
+1.54 to 2.21
+megalin
+inhibition of cGAS
+to demonstrate how community structure affects epidemic dynamics
+morphometric
+poor clinical outcomes
+recombination efficiency
+Bio-Rad
+Protein
+gels
+Veterinary Medicine
+depletion
+abundant glycogen granules and short microvilli
+capacity
+68%
+EV-A71 replication and dissemination
+Epistasis
+PEDV RNA
+alternative hypotheses
+frequency of journeys, infrequent but very long distance trips
+413
+hematopoietic and mesenchymal stem cells
+5 μL
+Ubiquitination
+mutants
+glutathione
+multivariate logistic regression model
+Relative rate parameters
+methionine
+5%
+higher
+Flow cytometry
+12
+desethylchloroquine
+Human noroviruses
+exponential distribution with the weakening parameter
+Confusing word choice
+mock-infected cells
+Cell surface asialoglycans
+glutamic acid
+less than 2%
+experienced surgeons
+JPRED algorithm
+model = 0
+the side chain and the main chain
+R. felis
+1.008
+inducible
+Tables A5 and A6
+B. subtilis
+K48 chains
+fivefold
+2005 International Health Regulations
+The Collaborative Cross
+18 months
+Plans
+pH 4.5
+oligopeptide
+13
+inflammation and necrosis
+Ub and/or ISG15
+transport and housing
+endocytic uptake of TPIC
+ambient aerosol concentrations
+HCV
+QY EON
+150
+short peptides binding specifically to the spike proteins
+Genomic Studies
+hatching rates
+Whole Rhesus Monkey Genome Microarray
+Human resource training
+437D PSK
+24 h
+Normalizer Signal and Batch Correction
+JTT matrix-based method
+Uganda
+Sanger sequencing
+endothelial activation may be an enhancing event
+0.5 mg/g of leaf mass
+Four
+S598 Q600Yspecific CTL
+western blotting
+15.49 ± 4.01%
+to provide a diverse set of epitopes for targeting
+cc-by
+good fortune
+antimalarial
+broader
+200,000
+matrigel
+necrosis
+Colume Viral DNAout Kit
+surveillance practices, population risk factors, transmission dynamics and pathogen evolution
+nanotechnological
+8.7 Â 10 5 /mol
+30 min
+eIF4E
+Hsc70
+143
+three
+ACE2 activity
+ε ij
+memory cells
+≥1.8
+WKY rats
+a-fibrinogen mRNA expression
+this effect
+a single peak
+60% and 50%
+Fob1
+No
+~10%
+Twenty-seven
+58 %
+17.0.0
+implementation of interventions
+clinical and epidemiological
+39.39%
+a stack of flat, closely arranged cisternae
+Phosphorylation of STAT1 at Tyr 701
+Further study
+GM-CSF
+snG:U mis assays
+Twenty-three
+insulin sensitivity
+One strain of HRV-C
+Salamanders
+1990
+more significant
+Cy3 fluorescence intensity
+the chorionic layer
+mouse
+samples
+CGMP
+CFTR expression
+glycoprotein
+selection bias
+hypertension
+ODE
+Renal replacement and mechanical ventilation
+910
+OsSGT1-catalyzed reaction
+RNase 2
+Successful introduction of PR PLTs into inventory
+Balb/c mice
+Prospective immunological studies
+one-third
+underreporting
+flow cytometry and immunoblotting
+Model 3
+13
+AAG
+veterinarians, farmers, ranchers, tanners and food processors
+expression of LPL and CD36
+glycyrrhizin
+LCMV-dependent B-cell activation
+maintain its specific functions
+50
+lower SP-D serum levels
+4 h
+Ψ
+New York City
+integrity of the GI tract
+antiviral costs
+BMG Clariostar
+Whole cell lysate
+prospective screening of fragment and lead-like subsets of ZINC
+100 million
+three
+1104
+CD56 dim NK cells
+DDBJ/EMBL/GenBank
+outbreaks
+Chemical protection experiments
+by way of a personal identification number
+maternal and foetal tissue
+Ag-specific tolerance mediated by Tregs
+chemical-space
+SIR models
+environmental contamination
+TCRγ/δ+ T Cell Isolation Kit
+ATP synthase
+three
+IL-12
+YFV-17D
+Odyssey imaging
+QIAmp ® DNA Blood Mini Kit
+Sf9-rHA
+a composition believed to impart conformational flexibility
+10
+25%
+Monocytes
+37%
+identification of the organ system targeted for diagnosis
+H274Y
+the main issues
+epidemic evidence synthesis
+every 30 min to 6 h
+twice daily
+CD141 + XCR1 + DCs
+11
+scatter plots and regression analysis
+the barrier of the nuclear membrane
+Ambient temperature
+a uniform and symmetric relevance measure
+impulsivity
+10.7 pg/ml
+13
+over two years
+712
+protein concentration
+diversion of resources to contacts of contacts is harmful
+two
+Twelve
+NFκβ, cFos, and AP-1
+3.1.1
+double-stranded RNA
+2008
+probability distribution models
+15 minutes
+50 ng of cDNA
+Epstein-Barr-virus
+Disrupting formation of the ectodomain cystine loop
+220
+Multiple logistic regression
+organ failure
+47.4%
+Proteomics
+35-100%
+a new protective antigen against TB
+nally
+EIA/RIA 1 × 8 Stripwell plates
+tools where the upper and lower quartile for the pairs do not overlap
+IFIT5-oligo-C complex
+N-glycosylation
+Dong Thap
+Bats
+N i
+20%
+499
+8h
+Q162 to S170
+Traditional Chinese medicine
+resequencing, microbial typing, and single nucleotide polymorphism discovery
+Alternative splicing
+unintegrated
+mean AE SEM
+Binding by DgB, DgD or DgH virions
+three to seven weeks
+EMT
+weak power caused by low levels of interspecies divergence
+The water molecule that coordinates with y39
+new members of the CE protease clan
+K E
+Enterococcus faecium NCIMB 10415
+High flow
+5,398
+gB
+non-neutralizing
+13
+CSU Institutional Biosafety Committee
+post-transcriptional gene regulation
+network building
+vascular remodeling and plaque instability
+insufficient geographical sampling
+STING signaling
+Written informed consent
+at delivery
+viral budding
+36
+CT values
+H1, H2, and H3 subtypes of influenza A viruses
+secretory components
+18 years
+IL-18
+Zero Heat Flux Cutaneous thermometers
+guinea pigs
+Kaplan-Meier curves
+high performance liquid chromatography
+five
+gut BT
+one week
+endocytic capacity of DC-SIGN and L-SIGN
+Infants who had unknown BPD status
+lagging research
+BAL
+30
+5
+50 per cent
+Linear mixed models
+novel approaches
+1, 459
+A terms
+31
+neuroinflammatory disorders
+Questionnaire
+20.6±0.1%
+Stakeholders
+DEC-205
+Further research
+the patient's primary care team
+production of infectious LCMV progeny
+hegemonic
+four
+inferring ribosome positions and reading frames
+Life Technologies
+intervention
+Bio-1D
+nuclear
+signs of diarrhoea and general well-being
+Total RNA
+VEGF
+rare
+robust PKR mRNA synthesis
+25
+slightly different
+ABI Prism Big Dye Terminator Cycle Sequencing Kit 3.1
+LOD 95
+viral groups
+aggregation according to logical rules
+three helix coiled-coil domains
+public confidence
+lactoferrin and vitamin D-binding proteins
+acute respiratory infection
+lung ANG2 expression as well as protein content
+QIIME
+48
+Tissues
+Antinociceptive data
+0.02%
+phosphorylation dependent dimerization
+SLE and RA
+chronological
+NLRs
+measurement of IgG antibody
+SP-A2 1A 1
+GenomePlex reactions
+TMV replication
+IFNλ4
+rodent
+HMGB1
+E. coli
+Early contact inhibition
+1/500
+Leviviridae and Cystoviridae
+5.0Å
+susceptibles
+15h
+three or four
+neuroprotective
+EFE promoter
+cytokines
+physician and laboratory reporting and manual analysis of surveillance data
+clotted plasma proteins
+PIAS
+774
+4
+One to two months
+48 hours
+population diversity
+CA clan
+Eight
+The prognostic value of NLR and of C-reactive protein
+STAT acetylation
+differential phosphorylation
+Berberine
+peripheral T-cell lymphomas non-otherwise specified
+LFA-1
+MATLAB
+Half credit
+HBc particles
+CSIRO Australian Animal Health Laboratory's Animal Ethics Committee
+30 min
+1 day
+neuronal NLGN2
+Mucin sulphation
+an overlapping epitope on ClfA001
+isotype PE control
+vivo-morpholinos
+pseudoatom representations of EM density maps
+Stability of chloroquine and desethylchloroquine
+supernatants
+higher DENV IgG titers and DENV2 specific neutralizing antibodies
+Adobe Photoshop
+Thorough cleaning
+tumor suppressor
+Ms. Inamine
+accumulation of Atg8
+Apoptosis assays
+12 h
+whether it could alleviate PEVD-infected diarrhea and intestinal injury
+statistician
+virus yield
+predictions
+two
+myelin base protein
+Poisson Regression
+phosphorimager analysis
+recombinant His-tagged PRRSV N protein
+Prioritization of predictions
+IVT RNA in solution
+Whole mouse lungs
+issued interim guidelines
+divergence and natural selection
+CXCL10 secretion
+phylogenetic incongruence
+components
+host range expansion
+ICAM-1
+one
+Global static compliance
+ten
+MS/MS fragments
+bacteria-infected and virus-bacteria coinfected patients
+C sto
+>2,000
+mice to nonhuman primates
+ISGs
+0.97
+if they had any sample positive for CRE
+4
+Multivariate statistical analysis
+strains that cause natural human diseases
+observe the lung from different angles
+transcription of a subset of genes transcribed by Pol II
+thirty-five
+30 min
+SIEMENS, Diff-Quik™ Stain Set
+2014/15
+17Á9%
+immunocompromised
+18
+decreased protein yield
+Over 90%
+Interferon drugs
+The investigator
+658
+1/τ o
+60%
+Small molecule inhibitors of protein translation
+diffuse occurrence of positive cells with high-intensity labeling
+Nearly half
+Any further responses from the reviewers
+Concurrent plasma
+polymorphisms in CLDN1 gene
+past 500 years
+84/50 mmHg
+GraphPad Prism 4.0
+four
+preprocessed data sets
+Fraction of inspired oxygen
+neurotransmitter abnormalities and occult diffuse brain injury
+biomolecules
+supportive care
+vaccination control
+Anakinra or Kineret
+12
+frequency counts, percentages, and exact 95% confidence intervals
+loss of bacterial infectivity
+20%
+adapting LABs
+120
+NMA
+Baidu
+time to exacerbation and each module's expression
+total growth inhibition
+Aministration of oxygen alone
+42
+four
+cells critical to regulating injury repair
+all the facets of infectious virion production
+James Cook University
+a dual reporter assay
+40%
+six
+BAY 11-7082
+serine residues
+IVIG refractory
+16S rRNA gene sequences
+54%
+35,424
+<100 per cell
+our choice of serial interval
+ANSM
+justified
+IL-12
+18 November 2016
+nasal cannula thermistor
+Bluetongue
+parametric
+s mzs
+LOcally WEighted Scatterplot Smoothing regression modelling method
+aggregation
+MEDI8852
+32
+hepatic neutrophil migration
+RFL11
+16S rRNA gene sequencing
+evaluation
+late July/ early August
+MnmC
+higher survival rates
+life chaos
+spleen and liver
+U 8 and A 8
+sequence no. 6-14
+porcine fetus samples
+Unpaired t-test
+2,773,479
+motor coordination
+20
+Latex
+16 h
+co-infections or multiple infections
+Opr-S3-ArgTAG 3
+anoikis
+De novo-synthesized sequence
+series preliminary experiment
+75 U/ml
+Infection events
+behaves so poorly
+6,000 L/cow
+more detailed genetic information
+chronic inflammatory myopathy
+0 to 60 μ g/ml
+213 SVQYHPL 219
+one-way
+PWK/PhJ
+macrophages
+ulcerative colitis
+RNA transcripts blocked with ribavirin
+31.4%
+patients who required liver support devices or liver transplantation
+30%
+geographic information systems and other geospatial tools
+rare earth ion-doped phosphors
+LOE
+lung/thorax index >0.24
+susceptibility, viral replication, or transmissibility
+twelve
+BM2fluc expression
+485 nm
+395 kDa
+alpha-macroglobulin
+VEGF
+Methods
+sequence X
+12
+glucose transport stimulatory
+seven
+Blood
+confidence intervals
+anti-ZIKV NS1
+Table S3 and Figure S4
+blood vessels
+angiogenesis
+fetal programing events and cardiovascular dysfunction
+epithelial cells of the respiratory tract
+10
+Erasmus MC
+serogroup classification
+the coefficients for the AR terms
+distributional assumptions
+Heparin
+inhibited the autophagosome accumulation
+The lungs
+molecular dynamics
+Leuprolide
+Student's Ttest
+mammals
+traditional media
+Extramedullary haematopoiesis
+G0/G1
+340
+30
+Shapiro-Wilk test
+8-isoprostane
+trend selection criteria
+Each protein ratio
+254
+bacteria, fungi and protozoa
+48.46%
+Nikon TS100 Eclipse inverted microscope
+vascular leak syndrome
+one-way
+high-dose
+24
+12
+2003
+monoclonal antibodies
+Wanfang and Chongqingvip
+isofluorane overdose
+200 µL of 0.2% crystal violet in 20% ethanol
+positive
+Sandwich ELISA
+Disruption of the mouse mdr1a P-glycoprotein gene
+mAb 4G2
+microplate reader
+Molecular dynamics
+3
+Arunachal Pradesh
+48 hours
+structural complexity and abundance variation of different constituents
+1,170
+dire consequences
+Radiation exposure
+site-directed mutagenesis
+plastic beakers
+Dengvaxia
+r0
+mild and severe
+posterior distributions that are maximally different from prior beliefs
+mouse
+antagonize influenza A virus replication
+VACV
+aerobic and anaerobic
+its own promoter
+Sequence based epitope prediction
+1 week
+CD4 + CD45Rb high T cells
+protection against enteric and other diseases in children
+gL
+Rabipur
+TBSV replication
+65uC
+antiviral immunity
+WH211 and WH303
+multi-omic
+2 weeks
+organelles
+P < 0.05
+oxygenation
+ligands
+the substrate
+Student's t-test
+102
+2175
+critical positions
+religiosity
+daily
+the average of Y
+adults
+cellular aggregation of hepatocytes
+PCR results
+ϕ P→Q
+China
+AmphoB
+50 μg
+Creative Commons Attribution Noncommercial License
+Nikon A1 MP multiphoton confocal microscope
+VP2 protein
+Seven
+95% of the variance in the transcriptomic and microbiomic data
+Chemically assembled electronic nanotechnology
+Efficient delivery of siRNA into cells or organs in vivo
+protective
+maintenance medium
+pleating
+antiviral
+recovered, infectious recombinant RABV
+elevated levels of STING dimers
+occupational stress traditions
+to illustrate that this method can apply to plant
+4 L
+exogenous adjuvants
+more than 3,400
+12Á7%
+FUS-like or hnRNPA2-like aromatic interactions
+High specificity, potency and safety
+24.7 ± 2.1 kg
+genes involved in oxygen transport, protection against reactive oxygen species, and host defense
+Z-scores for each individual nucleotide
+30 min
+animal models
+Dead cells
+Southeast Asia
+FoldX
+225
+Dinguiraye, Guinea
+population averages as box and whisker plots
+long non-coding RNA expression
+13%
+miRanda and TargetSpy
+the cell or host environment they infect
+zoonotic
+MAb8430
+93.5 days
+V9G and LS266
+WNV strain NY-99
+URA3 gene insertion
+Drew Weissman
+0.2% ethylenediaminetetraacetic acid
+empirical use of antimicrobial drugs
+ROs
+primary and immortalized cell types
+CPE, infectivity, cell susceptibility, and attachment activity
+type 1 regulatory T reg cells
+their respective double-stranded promoters
+zebra-conspecific and rhinos
+angiotensin-converting enzyme 2
+1 and 4 days
+lectin-carbohydrate interactions
+2-minute epochs
+DENV-2
+CVCVA5
+fragile
+goat anti-human IgG-HRP conjugate
+Death rates
+Three
+An internal membrane
+the fusion loop at the tip of flavivirus E DII
+IL-1β and IL-6
+18,000
+differences in the absorption route
+Wistar rats and C57Bl/6 mice
+ganglioside antigen GD3
+Oligonucleotides
+35
+Illustra GFX PCR DNA and Gel Band Purification Kit
+hematopoietic
+an adapter-linked random nonamer
+H1N1
+PPs
+Psychosocial
+E1
+MSC-secreted CXCL12
++5I
+H4a
+19
+antiviral
+periparasitic
+220
+NORs
+Replicate experiments
+PKR
+Numbers
+FgPV-1
+30
+75%
+Genomic DNA
+pairs detected by the PPI calculation
+Citrus tristeza virus
+Chondroitin sulfate proteoglycans
+4-6 week
+pVAK1
+herpesviruses
+small
+asthma and juvenile onset diabetes
+microarray
+488
+figure 2
+T. brucei infection
+terminal, poor body condition, further medical attention needed, and healthy
+ribonucleoprotein complex structure
+cytoprotective
+once per day
+a likely interaction
+weeks
+B21 haplotype
+their advice
+Two
+encouraging active discussion of pandemic issues
+Acute respiratory distress syndrome
+VACV and HCMV
+a relatively variable region flanked by conserved regions
+2 sub-sections
+hyaluronic acid
+three
+ICD codes
+Pseudomonas aeruginosa
+a k and b
+CD4 T cells
+Sigma-Aldrich
+UPF1
+A table of random numbers
+one third
+suppression of proliferation and elevation of apoptosis
+KRAS
+22%
+Validated constructs of interest
+southwestern
+subtype
+protein-folding machinery
+no preformed virus was present
+they allow insights into heterogeneities in the population
+Grape pomace
+1,562
+hepatomegaly and periportal edema
+2 ml of DpnI
+2013-11-22
+increased virus replication
+ADA
+anti-adhesion
+disease transmission
+the standard curve
+Epidemiological parameters
+outside of the lungs
+formation of the antiterminator SL2
+2
+Rho activation
+86.8%
+risk as hazard, risk as liability and risk and precaution
+transferring DNA plasmid to Caco-2 cells
+19%
+PubMed
+RNA structures that accelerate the replication of viruses
+lymphocyte count
+generate genetic diversity
+807
+Quercetin
+1.5 to 2 mM
+granulocyte macrophage
+Chi-square tests
+Unit-length HBV linear DNA
+American Type Culture Collection
+Single nucleotide polymorphisms
+three
+Four
+multiple sclerosis 29 and systemic lupus
+methyl cellulose overlay media
+33.8%
+once a month
+missing values in grey
+adjacent promoter activity
+direct-acting antiviral agents
+mild respiratory illness
+wortmannin
+1200
+Type II
+gene-dependent decrease or increase of mRNA copy numbers
+Cp > MIC
+DDCt method
+warming
+steroids and immunosuppressive drugs
+RNA viruses
+pre-formed immune complexes
+Supernatant
+8
+4
+NSP3
+spatial location, physiological traits and/or social behavior
+19
+developmental immaturity of innate and adaptive immune systems
+JACET
+four
+data dependent
+21
+79
+respiratory disease
+CVTree3
+changes
+340 bp and 320 bp
+societal interpretation
+T
+group 2
+128
+beta-adrenergic receptor and rhodopsin
+no conflicts of interest
+A H1N1
+pulmonary vascular leakage and the severity of acute lung injury
+B cell phenotypes accumulating in the CNS
+CNS infections
+the placenta in exosomes
+feedback and interventions
+Vasculotide
+malaria
+supplementary
+right-censored
+four
+101
+90
+>500 × 106/L
+19.4%
+CC 50
+animal disease detection
+14 days
+verbal consent
+all stakeholders
+five-fold higher
+6 grades
+200
+systemic inflammatory response syndrome
+17
+24
+Myeloperoxidase
+2.014 Da
+Animal Care Guidelines
+value of trust and the principle of transparency
+protective
+subgroup survival analysis
+therapeutic
+TNTs or endocytosis
+headache and confusion
+mammary gland
+6-month
+statistical
+rule changes
+120
+1483
+2243
+well adapted
+H1N1 virus
+579
+Accessory genes
+around the borders of Guatemala
+dengue
+Dr. Yount and co-workers
+decreased
+public health education
+antibody to F4/80
+humoral
+blocks Ebola infection
+␣
+alveolar
+protein A affinity chromatography
+control images
+disease
+EBOV
+60S
+viral
+lack of sustainable funding
+DB32-6
+Forty-eight hours
+PEDV and RVA
+over 10,000
+a sequence that was identified as an epitope
+a large portion of a network
+clathrin-independent uptake route that leads to acidic endosomes
+bovine blood
+suboptimal freezing, storage, or thawing of the cells
+higher
+12th-14th March
+perfectly matching stretches
+six
+TRIzol
+WT
+gag sequences
+pre-commit to vaccine purchases
+ρ I,R
+95%
+Phylip's SEQBOOT
+2,000 JPY
+increases in poultry stock and sales during Chinese New Year festivities
+pNGAL and UO
+PI
+severe
+95% confidence intervals of the median
+according to both their isoelectric points and their molecular weight
+filtered homogenate
+Acute Lung Injury
+hyperuricemia
+MEGAN
+binary and ternary
+PR-8
+haemagglutination test
+develop arthritis
+potential problems
+clinical FMD
+immunohistochemical analysis
+Servo-I ventilators and cuffed endotracheal tubes
+80%
+Argentina
+Hit drugs
+1
+SCII
+Rosiglitazone
+maintenance of R e below 1
+the amount of P*
+microbial clearance
+minimum selective concentration
+100%
+GPC 2
+10.3390/v11040379
+⎡
+2.4 ± 0.6 mm
+relationships
+3 and 5
+122
+37 1C
+a variety of functionalities
+allergic rhinitis
+VEGF
+compliance with targets
+Transfer RNAs
+the ratio of positive to negative absorbance value
+less than 3 fold
+degradation products of the RTP
+hemagglutinin
+GABA abnormalities
+surface plasmon resonance
+calnexin
+Proteases
+Four
+FAST CAT Assay kit
+more distant region of DFC
+phospholipid-transporting activity
+sizes and surface properties
+288 million
+Virus aliquots
+Microscopic
+CEACAM/PSG
+An array of optimal Minkowski coefficients
+inhibits hemagglutination
+the risk of a disease
+PCR
+macrophages
+means ± SD
+PKR
+fetal morbidity
+mass spectrometry
+T2D to stroke over time
+60
+0.05% saponin-TBS
+Noninvasive
+reduced short-term mortality and incidence of barotrauma
+children and psychopathy
+3AL4
+10.5694/mja2.50049
+urinary ACE2
+School of Informatics, Xiamen University
+high avidity antibodies and functional antibody responses
+100 µL of serum diluent
+transcription and translation of separate cotransfected genes
+JMN3-003
+overcoming IFITM3
+Effector cells
+Continued disease surveillance
+Pharmacology
+DNA sequences
+FluView
+qvalue � 0.01 and log 2 fold-change � 1
+the swine flu
+differences in mechanism in nuclear pore engagement and genome import
+136
+absolute data counts
+the small and large intestine
+Viroporins
+evolutionarily
+FCB2 strain gametocytes
+host response
+11,956
+p65
+more data
+South-East Asia
+Centers for Disease Control and Prevention
+trypsin
+uncertain
+attenuation
+signs of infection
+the extent of such a bias in the study is probably limited
+Nanodrop 2000c
+6 hrs
+highly pathogenic virus strains
+21
+PhusionH High-Fidelity DNA Polymerase
+4
+10%
+SET, a DNase inhibitor
+simulation models
+high-frequency oscillating needles
+Nasotracheal
+42.2%
+Accurate diagnosis of acute febrile illness
+Kraemer and colleagues
+mean signal intensities
+MIP algorithms
+a spectrum of phenotypically similar diseases
+above data
+genome assembly
+Lipofectamine 2000
+Influenza pseudotypes
+mechanisms of viral suppression
+public health monitoring
+PA-Cter
+Th17 cells
+siRNA
+three
+median and range or mean and standard deviation
+5 days
+MCD
+cleaved lamin C
+1/δ
+three
+Supplementary Data
+Voltage-gated
+High Pure Viral Nucleic Acid Kit
+Twenty four hours
+28%
+B2M
+CG processing of proHNP1
+hypervariable region
+RNeasy minikit
+77%
+intravital
+Caspase-3
+10 days
+Ebola
+Screening of immunogenic peptides
+Neutrophils
+1:1,600
+chromosomal position effects and epigenetic modi fi cations
+twice
+Consolidation
+four viral structural proteins
+stimulated systemic immunity and mucosal immunity
+the difference in fitness from WT
+by limiting dilution
+CD71 availability on reRBCs
+N MicrobeWiki
+upregulated
+Hedgehog signaling pathway
+Pentraxin 3
+prokaryotic adaptive immunity
+control of animal populations
+Jones-Taylor-Thornton substitution model
+antigen-specific B cell
+Frameshifting rates
+to inform further research on influenza forecasting
+if an equally satisfactory response follows the adjuvanted seasonal influenza vaccine
+Reassortment
+ESLD
+false positives
+peste des petits ruminants virus
+microscopically
+statistically significant differences between groups
+Rapamycin
+Polymerase chain reaction technology
+11
+predictive probabilities for exceedence of reporting thresholds
+IL-2 + CD40L + CD4 + T cells
+replicative senescence
+independent factors of MDRI
+disease risk
+fomite route
+RT-LAMP and rRT-PCR
+ferret
+300 km
+higher-order epistasis
+Influenza vaccination
+antibody repertoires from separate human tissues
+2009
+1%
+Seventeen
+pulmonary fibrosis
+enhancement of T cell responses against foreign or tumor antigens
+60%
+enteric fever
+solid tumors
+Temporal
+the structures of underlying diffusion networks
+four
+6C-Mut
+seasonal influenza infection cases
+three
+three
+Rhesus monkeys
+Serine/ Arginine-rich proteins
+operating characteristic curve analysis
+mitochondria
+Attribute weighting
+primed template
+immunosuppressive viruses
+Type and number of internal monosaccharides and their linkages
+serum SP-D
+Penicillium marneffei
+A manuscript with more than 2 authors
+10 days
+genome replication
+guinea pig Fcγ receptors
+compliance with PPE use and doffing protocols
+Control variables
+New Zealand White Rabbit
+10%
+3′-UTRs
+11
+tafenoquine
+viral clearance
+poor adaptive immune responses
+48 h
+aminoacyl-tRNA binding
+monoclonal
+large areas of necrosis and more mitosis
+dynamical models in the differential networks
+an extended shape
+CummeRBund
+serious risk of bias
+Po 0.05
+four
+China
+Anti-mouse F4/80 antibody
+secretory pathway protein-based inhibitors
+50%
+synonymous codon
+6
+30 minutes
+Interferon-induced transmembrane protein 3
+mRNAbased
+13
+Five
+any difference between the movement or cases on weekdays and on weekends
+hydrolysis of ubiquitin substrates
+Mock-inoculated tissues
+membrane
+Suppressor tRNAs
+VZV
+Red-billed teal
+4.4%
+60 mm petri plate
+0.611
+important
+Madang
+Inaccuracies in past predictions
+non-specific biding of the NDs
+N-terminal residues
+isotropic internal strain
+n
+2 weeks
+six
+Analysis of all three inflammatory parameters
+bronchitis
+Diarrhoea
+genes associated with complex disease susceptibility
+simplified acute physiology score
+exposure to pathogens
+manual analysis of the top 100 cited articles
+Bayesian
+29%
+thrombus formation
+resistance to pulling
+FCGR2B 232T/T
+Collection of exhaled breath condensates
+did not require oversight by an ethics committee
+SLE Responder Index of ≥4
+molecular pathways implicated in suicidal behavior
+nasal specimen swab
+237
+HIV-specific
+aggrecan
+Japanese university students aged 17-21 years with and without hypertensive parents
+30
+HPRT
+5.5
+R
+senescent neuronal cells
+on the Internet
+NAs
+72 hr
+PM 2.5
+Transient hypotension and transient hypoxia
+dsRNA RF
+systolic blood pressure
+1:100
+anti-FLAG mAb
+sequence mutation
+hTERT
+Five
+4 weeks
+Intralesional
+case incidence data and the distribution of the serial interval
+maximal interior thoracic breadth
+collection of exhaled breath
+0.02
+requirement for DDX19
+simulation
+HLA-B17, B18, B35 and DR-2
+CEACAM1
+physicians
+8
+physiology, gene expression, metabolism, and antiviral defenses
+volunteer
+IL8RNAi-HD-Ad
+10
+Public health and food control laboratories
+Molecular docking
+6.8%
+Anti-CD16/32 clone 2.4G2
+U-U and A-G
+543
+20
+equilibrium
+two
+72 hours
+Scars
+IFITM3 and SERINC5
+E2F-dependent apoptosis
+simple
+B. mori ribosomal protein s3 gene
+interactions between viruses and hosts
+patterns of episodic, divergent selection on surface exposed amino acids
+800 mg of respective PHAs
+Agent Based Models
+background noise
+wane
+transmission rates
+Glucagon
+Atg5conditional-knockout mice
+protein A-sepharose Fast Flow beads
+sepsis
+Tetrandrine
+16
+CTV
+A pdm09
+practical
+cellular architecture
+nosocomial
+deposition
+marked tumor
+IL6, TNF, TLR4 and ADIPOQ
+generate novel viral subtypes or strains
+hexokinase
+physician fatigue
+Camel
+vesicle fusion
+viruses
+host pattern recognition receptors
+neutralizing activity
+dengue virus
+antibody titers
+synergistic protective effect
+well founded
+hWJSCs
+15
+Metastatic disease
+eliciting elevated levels of serum neutralizing Abs and mucosal IgA
+CLIMEX, DYMEX, MIASMA models
+virulence
+constant factor β
+T cells
+Acute lung injury
+TRIzol LS reagent
+a plant factor
+acute myocardial infarction, stroke and inflammatory diseases
+linear mixed-effects model
+host factors
+TPIC
+Comparative molecular field analysis and comparative molecular similarity indices analysis
+binding positions
+20 g/m 2
+Statistically significant pairs
+C
+human polyclonal antibodies
+advances
+codon usage variation
+buffer or the indicated peptides
+Three main streams
+Department of Anaesthesiology and Critical Care Medicine
+mutate
+hydroxy fatty acids
+PPARγ transcriptional activity
+2D molecular fingerprints
+2011
+more than a decade
+rVSV/EBOV GP
+bias
+circular
+chicken beta actin promoter
+Rat primary hepatocytes
+Five
+continuous variables
+P owassan virus
+Glycopeptides
+Medicine and Public Health
+0.8 ml
+random phage libraries
+EV71
+5-day
+respiratory distress
+single doses
+lipid transporter activity
+1,932
+Leishmania elongation factor-2
+age and residential area code
+hematopoietic cells
+activating the IP
+water extraction and ethanol precipitation
+pValac
+Lenti-X concentrator
+dexmedetomidine
+17%
+Thef low-through
+DLD and ED
+Siglec1
+pseudotyping
+MV vectors
+Aneuploidy
+Meta-analysis and machine learning
+A 0
+viral host breadth
+contamination with infectious agents
+Tissue Plasminogen Activator signal sequence
+Bordeaux luteovirus
+written informed consent
+EdgeR algorithm
+US National Institute of Allergy
+GP targeted to the cell surface
+immunogenic antigens
+increases replication rates and infectivity of the virus
+subcutaneously
+63
+Optimism
+elevated production
+pDCs
+Chile
+8%
+Longdistance
+human monocyte-derived
+JavaScript
+induces vesicles that colocalize with ATG5 and LC3
+24
+0
+Cholinergic hypothesis
+Tunisia and Sudan
+12.8 ± 0.7
+Lysophosphatidic acid
+Two
+Dr. Robert Putnak
+HIV
+WP1130
+confocal staining
+two
+IAV
+High priority zoonotic pathogen subsets
+Eight
+mScarlet-i
+codon immediately 59 of the native reinitiation site
+Stem cells
+Microglia
+16S ribosomal RNA gene sequencing
+chimeric humanized mouse livers or primary human hepatocytes
+40%
+EBOV GP1
+50
+0.25%
+the 5 1 end of the genome
+MAbs
+26
+The knowledge of the role of a given biomolecule
+number of infected, recovered, deceased, and quarantined cases
+a simple 3-state HMM indel model
+rats, guinea pigs, and hamsters
+88.2%
+core epitope
+26%
+31 °C
+14%
+small libraries of viruses with single nucleotide substitutions
+Fluorescence in the FAM channel
+Evolution Surveillance and Tracking Algorithm for Resequencing arrays
+alveolar
+SDHA, GAPDH, and HRPT1
+Two-way ANOVA test
+RS and SCV
+Transwell membrane
+Unnecessary panic and disruption to society
+AND
+by passing the eluate pool over cation exchange resin
+non-homologous recombination events
+FACS caliber
+48-286 MB
+HKL-2000 38
+A site
+Virus titers
+TFRC and PGK1
+phosphorylation
+1976
+joint and/or comparative analyses with the DO and the founder strains
+Five
+Long-term use of corticosteroids and immunosuppressive agents
+114/60 mmHg
+A code number
+50%
+A. fumigatus
+Data processing pipelines
+slightly
+reciprocal
+Chronic inflammatory disease
+Analyses of different clones for each sample
+outside the STING dimerization surface
+EM ultrastructural
+XTT and CellTiter Glo staining
+MLV entry
+70%
+Fully quantifiable parasitaemias
+MetaDB
+sensitivity
+20 petabytes
+IRF8
+Autophagy
+C6/36 cells
+chemoenzymatic
+surgical site complications
+diminished pulse pressures, tachycardia, and hypotension
+Table 1
+100 nt
+significant
+Six
+eggs
+CPPs
+melting temperatures of approximately 60 • C
+FADS
+Attachment to sialic acid residues on target cell membranes
+34
+nucleoprotein
+decreases
+three
+HIV
+T88G
+enzymes as well as substrates availability
+StataMP 11.0
+Protein A Sepharose
+8,263
+three
+Th1/Th17-mediated autoimmune diseases
+Commercial aggrecan
+90%
+response costs
+amyloid-like
+Masquelet technique
+Transition and transversion
+tryptophan
+great modification and optimization
+445,000
+Variants that demonstrated enhanced stereoselective hydrolysis of compound 1
+Saudi Arabia
+58 years
+59-untranslated region
+release of all of these EV-associated proteins
+disease prioritisation
+Sec31 and Sar1 and Sec23
+Miro1 ablation
+7.4 hours
+DVGs
+lipidated
+pandemics and preparedness
+two
+Reverse transcriptase-PCR
+0.0330°/15.0479sec
+mouse IgG1 antibody and vehicle
+mammalian regulatory networks are incomplete for most biological processes
+1 hour
+Normalized Shannon Entropy
+murine
+AMCase
+West Nile virus
+Lung cancer
+2.31 IU
+mild HFMD activity
+disease severity
+1232
+polymerase slippage
+human myelin proteins
+Overflowed
+Eight
+QIAquick PCR purification kit
+titles
+they will be reported in the published results
+RACE-PCR method
+50-60% of VO2max
+localizing to either endosomal or lysosomal compartments
+fluorescence intensity
+Accumulation of ileal bile acids
+lymphoid follicles
+synergistic protective effect
+necropsy
+human dynamics
+Kir2.1 function
+Trial endpoints
+primers specific for the human beta-globin gene
+a frame shift within the first exon of IFNL4 gene
+2006
+48 hours
+increased adiposity, oxidative stress and dyslipidemia
+Western blotting
+three
+selection of pair-aware candidate paths
+confocal
+Twenty-four
+pair-housed
+CVA21
+E protein, premembrane protein and non-structural protein 1
+growth restriction
+excluding nonventilated patients
+Wambizzi
+phantom model
+42%
+2 h
+when antigens invade mucosa
+Hepcidin
+Langerhans cells and dermal dendritic cells
+15 kb
+crucial
+association and its N terminus
+hypersecretion of proinflammatory cytokines
+improve outbreak detection
+CAP-1
+four
+logistic regression
+Overall survival
+the level of gene expression
+rate of making and breaking links
+increase the frameshift efficiency
+congenital
+Hybridization
+masks
+transmission electron microscopy
+GFP- cells
+#359 and #1190
+underlying structures of networks
+PDBid = 2VIR
+HEK transected cells
+gastric and liver cancers
+RNA capping
+57 years
+SiglecH
+activities that are purely expressive in nature
+63%
+Kidney failure
+10-fold
+additional risk minimisation measures
+cell death
+Eighteen
+16,111
+clinical symptoms
+Bgp1
+inhibition of translation initiation, cell proliferation, and migration
+highly virulent
+HOX antisense intergenic RNA myeloid 1
+outcome and responses to mechanical ventilation
+an open conformation
+Elsevier B.V.
+intact ICOS
+BPV and CPV
+dyspnea
+cc-by
+heme binding, oxygen affinity, and protein stability
+Individuals with ARDS on presentation
+Mexico City and Washington, DC
+polyacrylamide gels
+72.2%
+lower
+BLAST
+respiratory inhalation
+Sharing of data
+non-infectious particles
+T j
+$1.4 billion
+KDEL
+correlation
+vaccine preparation
+k
+H5pp
+TAC1
+15-20%
+D_null
+Cox proportional hazards regression model
+Niclosamide
+Viral growth
+each location in each area
+Total RNA
+Golgi apparatus
+CREB
+peripheral blood
+phylogenetic
+nondiscrimination
+amino sugars
+viral mRNAs
+19.5%
+a puromycin resistance cassette
+less than $10
+protein aggregation
+autophagy activation
+trends observed in germinability
+12-30%
+T cells
+class probabilities
+SeqScape ® Software v2.5
+Nitric oxide
+all HA subtypes
+MAFFT v.7.221
+100%
+exogenous NK cells
+Fourier
+10 days
+75%
+RT-LAMP PCR
+LAMP reactions
+timelines needed to produce viral vaccines
+2 −△△Ct method
+influenza subunit vaccine
+Anti-S antibodies
+Tfh cells
+SL3-2-1m RNA
+criteria for institutional preparedness and contingency plans
+changed to alanines
+extent and location of the surgical incision
+98%
+public health units
+10
+four passages
+TLR9
+STAT2
+type I or I & II IFN
+10%
+>70%
+3406 grams
+well-informed
+TCID 50
+clinical disease
+renalase
+overt signs of distress
+MG132 and bortezomib
+the likelihood of malevolent use
+Small world networks
+ligand defined binding sites
+3034
+chemical exposures and environmental health
+p27
+enhanced CD8 T cell expansion
+fluorescent or luciferase
+10 minutes
+10-15 cm
+Foot-and-mouth disease virus
+two decades
+1.5 mTorr
+15
+Acute bronchiolitis
+plasma renin activity
+RESCUE-ESE and ESE finder
+ultracentrifugal
+C V and C H
+646 fitted sets of parameters
+54
+social distancing
+maximum likelihood methods
+40%
+Public playground
+Cas9 mRNA
+rules
+15 min
+15
+Log-rank test
+6
+The Coalescent Bayesian skyline plot
+trends in influenza
+11, 158
+27
+immunoblot
+false discovery rate
+DNA intercalating SYBR Green I dye
+freshly voided eggs
+VAP
+DEP
+15
+topical drops of atropine and tropicamide
+aminoglycosides
+rZHDNSs-GFP
+Kaplan-Meier log-rank test
+TLS Motion Determination server
+International Committee of Medical Journal Editors
+twice daily
+10 min
+better viral progeny production and release
+interfering with ribosome assembly
+protein expression
+original antigenic sin
+diverse cytokines and growth factors
+SpectraMax M2 plate reader
+age groups
+60
+97.55%
+Vaccination of household contacts
+21 days
+The total number of hospitalization days
+NF-κB
+HTx
+millimetres
+ligandreceptor binding
+the local state is specifically associated with the topologies of the phylogenies tested
+87%
+German-and English-speaking samples
+insect cells
+boxplots
+identifying new strategies that result in complete control of virus
+Axiovert 200M
+Grouping organisms by epidemiological functions
+circular TFO RNA
+Bangladesh
+.75%
+eight
+ancient retroviral germline infections
+Fig. 11b
+Estimation of model parameters
+five
+AC, LP and GR
+N-glycosylation motif NYS
+Ten percent
+sLAMC2 level
+public dialogue
+confirmatory diagnosis
+60uC
+40 μM importazole or 25 μM ivermectin
+NNAlign server
+HOXA10
+nonbinding species
+a serious illness
+pharyngeal viral RNA load
+bone development
+TLR-signaling
+14 days
+reduced viral control
+hipothesis
+protective
+novel genes
+overlapping functional elements
+Caribvet
+globalization and environment
+renalase monoclonal antibodies
+MAVS
+another viral resistant strain
+18
+antibody-dependent
+cytokine storms
+1.1%
+in vitro culture systems impose bottlenecks on RNA viruses
+deep changes in the patterns of host's gene expression
+ODEs
+none
+92%
+CNS-enriched
+48
+Global budgeting
+MEGA 7
+random regression weights
+Baidu maps
+PBL Interferon Source
+436
+NC mimics and inhibitors
+ribosomal frameshifting
+their genotype
+diarrhea index
+key internal structural proteins
+Standard admission criteria
+crystal violet
+small
+log 10 of the highest serum dilution
+chemiluminescence detection kit
+6-day
+significantly potentiated
+pRH3 0 /IRE and pYESTrp1/IRP
+intracisternal R-type particles
+IFN-γ
+provides the mechanism for recognition and response
+mean ± SD
+12.6%
+data set
+1.7-2.2
+cluster 4
+viral infection or malnutrition
+399
+Dengue disease
+inflammation
+16.5%
+mean excess degree
+viral attachment and endocytosis
+yeast alcohol dehydrogenase
+4 days
+pathogens
+C57BL/6 mice
+one hour
+2009
+gene duplication
+flaviviruses
+10 minutes
+grass silage
+dried blood spots
+5 to 32 years
+Silica gel
+4%
+78
+40 km/h
+early reverse transcription products
+M2-prone
+mass cytometry with dimensionality reduction algorithms
+markedly
+dengue virus nonstructural proteins
+twice daily
+more optimized HIV treatment protocols
+Long-range electrostatics
+7.7%
+CXCL4
+335.7±168.0 µm
+Pierce BCA Protein Assay Kit
+BCL11A transcription
+ZO-1
+CHIKV disease
+approximately linear
+IL-10
+25,963
+Rayleigh light scattering method
+stimulates the phosphorylation
+intensive care
+10
+DNA shuffling
+degradative removal of certain cytoplasmic components of the cell
+how dispersed the distribution of the alphabet elements is
+statistical testing
+Fugong virus
+Diphenhydramine and epinephrine
+African Green Monkeys
+colonization from infection
+medical treatment
+EGR1
+40-70%
+11-14 days
+100 µL per well of the TMB-Complete substrate
+Peptide affinity to HLA molecules
+RNA replication, RNA packaging, and intercellular spread
+protective level of the Group 1 stem-pocket directed BnAbs
+bodychecking
+Any variable found to violate the proportional hazards assumption
+25
+438
+clinical samples
+at an end of the peptide binding groove
+internalising the bacteria within epithelial cells and survival within macrophages
+according to the genus part of an organism's binomen
+CK/NJ/02 virus
+Restoration of functionally efficient adaptive responses
+degrades
+HIV/AIDS
+722
+endothelial cells were intact and proliferating
+a herbal medicine
+K
+radiotherapy
+65 to 75%
+4
+16, 884 antibody bound per cell
+2%
+a ligand-protein interaction analysis
+IRE/IRP interaction
+daily
+Gene expression profiling
+GAPDH and PP2A
+Molecular detection
+repeated antigenic boosts
+Lombardy, Italy
+231
+74
+ERK1/2
+TI cell cytokine production
+human respiratory syncytial virus and hepatitis C infection
+HHalign
+Xuorescence
+723
+gene-gene interactions
+high basal HSP expression
+mice
+pFLAG-CMV-2
+herpetic stromal keratitis
+275.7
+life-threatening
+dengue hemorrhagic fever
+A highly alkaline hand soap
+Reaction conditions
+920
+a preparedness kit
+FIV subtype B
+Rabbits, hares, and rodents
+classical and hybrid PRE states
+age
+staying at home
+noncanonical pathway
+New Zealand
+GP receptor binding sites
+population's aging
+day 38 and 56
+9.2 million
+interactions with negatively charged glycosaminoglycans
+Cefepime
+humidified
+Canis familiaris and Rhinolophus ferrumequinum
+IFAT
+N =10ϫ 10 6
+effective and safe
+5, 7, and 8
+copy-back DVGs
+external infections are relatively rare
+29
+1440 minutes
+previously published data
+Engstrom® and Hamilton G5 or Galileo®
+23 years
+IFITM
+selectivity determined by the tertiary structure of the substrate protein is lost
+oxidative stress induced senescence
+The strong recommendation
+transmission by the vector
+polymerase chain reaction
+Spatial isolation
+higher morbidity
+Reporter gene ZsGreen
+influenza
+acts as a marker for the pathway in porcine GCs
+9.1 ± 1.5 nm
+regression of the herpetic keratitis signs
+ELISA
+Table 14
+egr-1 expression
+twice
+m i I
+Oral hairy leucoplakia
+advice and entry screening
+336 nm
+TRP84
+temperature dependence
+Respiratory specimens
+predator blocking primers
+Caveolae-mediated endocytosis
+A standard curve
+respiratory samples
+ANOVA model
+One-way
+antigenic drift
+Table 3
+stromal tissue
+tolerance to low concentrations of virus
+four
+oxidative stress
+a set of rules
+promotes cell survival and cellular defenses
+February 2016
+27
+2 fold
+Visible light-responsive antibacterial photocatalysts
+5min
+fluorescent emission
+paired t-tests
+Extracted RNA
+8
+Reports about new mutations
+Flow cytometry
+iSOCKET
+Fisher exact test
+M
+the binding of a key silencer element
+hypotheses about the directions of associations
+vaccine strain
+taxa
+Prothrombin time testing
+15%
+Picornaviruses
+shelters with higher URI
+810
+trypsin
+delays
+Nanovaccinology
+colocalization with polyubiquitin
+comparable antiviral activity
+Glycomic
+78017
+multipotent stem cells
+Virus
+CSF B cells
+526
+monomeric and dimeric
+pathological inflammatory reactions
+Body mass index
+higher fraction
+5-10%
+unique estimates of variances and the influence of covariates
+Bart's Heart Centre
+200 nm
+random networks
+model-based detection algorithms
+ethidium bromide
+SAGV and GETV
+R2
+HIV-1
+John Sheehan
+ARDS patients
+microfluidic
+Contacts between infected people
+68
+1 day
+248
+cytokine storm
+Poisson correction method
+million
+transmission electron microscopy
+historical diseases
+global degradation of cellular RNA and inhibition of translation
+high viral load and severe disease
+sufficient microbiology laboratory testing
+PatchDock rigid-body server
+PCCs of both PPI pairs and GGI pairs
+double negative T-cells
+significantly increases EV release
+ethics committee of Affiliated Hospital of Guangdong Medical College
+ZFYVE9
+MrModeltest 2.2
+p38 and ERK MAPK pathways
+RNA easy kit
+>5 years of age
+liver disease
+mosquito surveillance programs
+NPC1
+1 ml of each reaction
+HA-8
+high
+down-regulation of Nup155 and IPO5
+1,482
+Table 2
+MAbs against definite epitopes
+every 2 d
+443 nM
+dogs
+Successful communication
+Three thousand and fifty-four
+False alarms
+association
+HA
+comp101225_c0_seq1
+630 nm
+three
+IRF7
+odds ratio
+59-deoxyribonucleotidase
+population average
+Nucleospin RNA XS
+1918
+worm egg production
+regulates cell morphology and motility
+apparent variability
+Semi-quantification
+The precise link between this PGF formulation and the pairwise approach
+sLAMC2
+inflammatory infiltrates
+cytokines
+SERINC3 and SERINC5
+autophagy and cathelicidin
+Chemokines
+NGR-TNF
+ORs for all AR clusters
+1525
+R package ape
+0.829
+43%
+mouse spleens
+Multiple sclerosis
+IL-1β
+destruction of vital cellular functions
+200
+influenza-related pneumonia
+70.8%
+δ-crystallin
+increased steric bulk
+30 min
+thousands
+galangin
+salty food preference
+microtubule dynamics
+Exposure to index case-patients for >12 hours
+xacerbations
+two
+binding of Coomassie blue
+more robust CD4 and CD8 responses
+297, 300, 305, 324, 375 and 426
+richness and diversity of structural and nucleotide variations
+cell context-dependent
+80-100%
+lower coverage
+Forty-four
+receptor
+salivary glands
+MHV-3 infection
+continuous ventilation
+similar to that in March
+MS2 phage
+γ1 Fc
+Median admission PCTs of 3.4 ng/ml
+The effects of these pathways on the regulation of other host defenses
+EV-G
+Multipartite viruses
+working with health workers to develop their own abilities to identify unhealthy working conditions
+Epstein-Barr virus
+3
+HRV and RSV
+SHCBP1
+3I14
+compartmental models
+FOS and KLK3/ PSA
+susceptible animals
+10 kDa dextran-AF488
+NDV
+mean + SD
+1-way
+glutathione
+interrelationships with genetic risk factors
+siRNA-mediated silencing efficacy
+IL-6 and CD40L
+acacetin is an inferior antioxidant to isoginkgetin
+3 w1
+NTAP-Tat
+generation of a recombinant strain
+50%
+an autophagy inhibitor
+dialectical and linear thinking
+100%
+gD
+PiCV
+Adenoviruses
+> 55,000
+asthma patients with naturally occurring viral infections
+low pH-dependent
+large surveillance populations
+venous blood
+significant effects
+neutrophil elastase
+Hepatic ischemia-reperfusion
+7
+Ubiquitination
+25%
+90 °C
+virus-induced cytopathicity
+Artificial gene sequences
+infections outside the intestinal tract
+temperate-zone
+Arms races
+DDX19
+forty-three
+alleviates proinflammatory cytokine production by LPS
+type I IFNs
+mixed method approaches
+acid fast bacilli
+differentiation of conventional CD4+ T cells
+2013
+dimethyl sulfoxide and glycerol
+the time for n to fill its demand
+Excel
+synergism
+Hofbauer cell hyperplasia
+SM934
+R 9
+systematic evolution of ligands by exponential enrichment
+Western blot
+KLK3/PSA
+EVs derived from L. rhamnosus GG
+75%
+NiV and HPiV3
+alkaline phosphatase-labeled mouse IgG
+antibody-based assays
+University of Manitoba
+monitoring the À1 PRF efficiency
+Alphaherpesviridae
+46 kDa
+TG levels
+PRNT 50
+early translation termination and ribosome dissociation
+Mycobacterium chelonae
+Hepatitis B
+H5N1 neuraminidase
+61
+gag, pol, and env genes
+metal shared
+three
+influenza-like illness
+whenever R 0 > 1
+PEDV
+CEACAM family genes
+on the outer edge of each monomer
+rearrangement of the IgH locus
+phylogenetic
+Flag-MAGE-G1
+Human mobility
+less than 1 month
+Seven
+peptide vaccines, recombinant protein vaccines, and virus-like particles
+hospital volume, surgeon volume, and the rate of laparoscopic surgery
+2 days
+A first tRNA
+63.3%
+less than 50 cells/mm 3
+nanotube number on macrophages increases after infection
+Mid-turbinate sampling
+antigenic distinct structures in brain tissue sections
+endodermal epithelium of the embryonic foregut
+Pooled cDNAs
+current functions
+53
+Hybridization
+protective
+34
+several
+three
+S1P recognition motifs
+16%
+development of regulatory T cells
+EDC/NHS chemistry
+cysteine protease
+epitopic amino acids
+Three microliters of template RNA or water
+Drs. Sun, Zhao, and Zhou
+56 o C to 70 o C
+escape mutants
+898
+immunosuppressive
+epitope sets
+infectious diseases
+VACV
+high confidence
+SGIV and RGNNV replication
+π j
+4061/6179
+three
+permutation test
+Drs. Linda Wyatt and Bernard Moss
+private disease-risk mitigation
+improve exogenous peptide presentation
+mucosal reaction
+Successive developmental stages
+1 million
+Pseudomonas aeruginosa
+RNA modification to m 5 C
+FlowJo
+Kolmogorov-Smirnoff test
+Protein arrays
+ECMO
+Tobacco mosaic virus replicase protein
+11
+negative controls
+Ventilator-associated pneumonia
+one of each viral segment
+genomics, proteomics and cellomics
+proteins
+7000
+cough
+Bayesian procedure
+rhesus monkeys
+45 hours
+South China Primate Research & Development Center
+it results in widespread infection
+viral RTI
+Burkina Faso
+eight
+IL-4 and IL-10
+CFSE
+BSA stock solution
+nearly certain premature death
+40%
+precedent vaccination or exposure
+precursor proteins
+meta-analysis
+CCL5 mRNA positive
+Respiratory syncytial virus
+induces apoptosis
+cross-reactive
+RNA Polymerase II
+QIAquick PCR Purification Kit
+social vulnerability
+carbohydrate-active enzymes
+Eight
+allergic sensitization
+any human proteins
+host demography
+26%
+2 years
+ducks
+Oligoribonucleotides P1 and P2
+Complete NA inhibition
+20
+within the paper
+minimal attention
+G6PD deficiency
+18
+219
+organ support, treatment of precipitating events and prevention of complications
+antifibrinolytic agents
+GTP hydrolysis
+Balapiravir
+SREBP-1
+6.34 PD 50 per dose
+siRNAs
+NS5B inhibitors RASs
+health needs overwhelm available human and material resources
+IL-17c
+alter interactions with HIV-1 capsid
+1.5 × 10
+external transmission rates
+DNA extracted from the corresponding specimens
+43 breaths per minute
+Pseudouridine
+56
+Noroviruses
+ROS
+health protection and health promotion
+novel and exploratory behavior
+AQP3
+Knowledge about complex structures
+1 h
+co-phylogenetic
+Statistical methods
+logistic regression
+the study of disease in humans
+Bonferroni correction
+viral load suppression
+phylogeny-instructed mutagenesis
+syndromic
+a small, N-terminal hydrophobic signal peptide
+35,955 Da
+Autoantibodies
+activity of conjugates
+early recognition and management of sepsis
+microbial biofilm formation
+DI-RNAs
+Rhipicephalus
+centrally operated
+1974
+V 388 G 389 P 390 E 392 and I 408 N 410
+Classical epidemic models
+Blood glucose concentration
+the number of class levels
+18 h
+free sulfhydryls
+Dame Sally Davies
+2900
+more compact
+HaMStR 13
+A rapid, specific and sensitive diagnostic test
+Baseline signal intensity values of 1
+2156
+20%
+10 min
+high
+subsequent bacterial infections
+25%
+10 million
+urban and rural
+54.6%
+hemagglutination
+E1 cleavage
+Herpesviruses
+cc-by
+basic life support courses
+vaccinia virus DNA
+cc-by
+complementary DNA encoding human RPE65
+pUC19-FR-HuFulHEV3f
+Oligonucleotide DNA sequences
+GATA3
+64 to 32
+ATPase subunit of terminase
+the input of the next hidden layer
+protection against higher APACHE II and SOFA scores
+NOS
+Cpb1
+detectable and high virus neutralization
+67
+sum of the cytokines secreted by all living cells in the culture
+Sequence complementary
+HCA, PCA and PCO
+12%
+Antibody repertoires
+tracheobronchial aspirates
+Caenorhabditis elegans
+four
+Ten
+Western blotting with an anti-Flag antibody
+Tubulin
+Bangladesh, Mexico, Oman and Algeria
+daidzein
+5 mL water
+2 h
+The true number of infected individuals
+virulence
+Hantaan virus
+stimulate TLR9
+frameshifting
+1
+betweenness centrality
+host cell-and pathogen-specific
+46
+1.9% ± 0.6%
+Succinate dehydrogenase subunit B
+subtle
+eleven
+113-580
+MegaBLAST
+likelihoods
+inflammatory monocytes
+P INF
+glucose, 10% FBS and 2 mM L-glutamine
+RNase T1
+Eighteen
+cardiovascular disease
+49%
+reverse transcription-PCR
+Chi-squared and I 2 tests
+overlapping read pairs
+binding of C. difficile Spo0A
+vaccine strain selection
+epithelial and sub-mucosal cells
+FFU per milligram of tissue
+cerebral
+DNA damage
+P60
+miR-21 inhibitor transfected cells
+a nuclear localization signal
+time after exposure when photographs were taken
+women
+three more days
+Cell Counting Kit-8 or CellTiter-Glo assay
+2-CTC
+H9
+one per cent
+limiting potential toxic side-effects
+2-chlorotrityl chloride resin
+9
+autoimmune
+any event supported by five or more methods with p-values #10 25
+25
+manual worker
+RV-C and RV-A
+France
+Almost two-third
+C160A
+influenza virus-inducible reporter genes
+detecting mixed infections of STIs
+their prevalence and distribution in the environment
+10%
+high levels of oxygen
+Inflammation
+100%
+infected mice
+segmented
+L
+psychological recovery
+Real time visualisation of chest expansion
+160 µM
+diffractometer setup
+arthralgias and myalgias
+13.9%
+3 weeks
+convergence
+coronary atheroma plaque vulnerability or acute coronary syndrome
+influenza
+SPSS 17.0
+monthly
+a complete diagnostic agreement
+Inebilizumab
+metabolite fingerprinting
+association
+Queensland Institute for Medical Research
+decitabine
+acetic acid
+75.7%
+staining intensity of foci
+Neuro2a cells
+poor homology between forward and reverse primer sequences
+lack of an adequate number of sufficiently homogenous studies
+China
+positive and negative selection
+environmental
+Lungs
+metatherian
+inability to identify the individual impact of each of the predictive factors
+CRC
+Ac-Phe-tRNA
+three weeks
+fourteen
+oxidative
+increased and prolonged expression of the viral interferon antagonist
+15 March 2020
+standard deviations tight and complex regulation of GalE expression in E. coli W
+CsrA
+oral acyclovir
+phagocytic activity
+anti-mouse IgA
+standard checkerboard titration procedures
+21% to 83%
+R-AFP fractions from gel filtration chromatography
+cell-secreted enzymes
+water, sanitation, and hygiene infrastructure
+Mobile phone-based surveillance systems
+Angiotensinconverting enzyme 2
+6
+mathematical model
+China
+Saudi Arabia
+Two
+9 days
+respiratory muscle failure or upper airway obstruction
+13%
+heterologous
+COX-2
+ward, MRSA type and study phase
+Julian Flowers
+UTRs
+Shelter staff
+34
+Branch-Site Random Effects Likelihood analysis
+NFκB
+four
+gastrointestinal symptoms
+spatial aggregation levels
+TA proteins
+the project's scope
+74%
+IFN-α
+six days
+phylogenetic
+JEV, WNV, or DENV-2 replicon
+genotype affiliations
+complex
+A discrete Gamma distribution
+45 min
+C-type lectin family
+The proportion of invariable sites and the number of bootstrap runs
+SPBN-Ig-Gag
+AP activity
+modulate the production of various cytokines and chemokines
+greater than 30
+30-50%
+deliberate strategies
+rs368234815
+pulse pressure
+axonal and synaptic defects
+Real-time cell growth curves
+pDCs
+hki
+replication of other APMVs
+CD8 + T cells
+RG-1 monoclonal antibody
+Unigene annotation
+Safety
+autonomy status
+another host population
+81%
+Schering-Plough
+Intermittent migration
+HA activity and plaque phenotype
+1 additional expected imported-and-reported case
+necrosis of hippocampal progenitor cells
+anti-arrhythmic
+Simulations
+59
+20 min
+trypsin
+Binding assays
+large-scale screens of common genetic variation and disease-causing mutations
+MHC-family
+primer redundancy
+3 x 10 5
+the corresponding author
+low concentrations
+J774A.1
+ImageJ 63
+the liver and other tissues
+food production, quality and food safety
+58
+tropical
+ISGs
+insects and arachnids
+IFN-λ
+methanolic RC stock
+R&D Systems
+trypsin
+virus infection
+79
+large-scale multiple simulations
+photomicrographs at higher magnification
+rugged and barren
+autonomy is classified into 6 Iso-Resource Groups
+Comparison of conserved DNA or protein sequences
+functional residues
+grouper and barramundi
+300 μ L
+macrophages
+Feed intake
+non-model-based algorithms
+naive
+sepsis
+dialectical
+axonal integrity
+A nasopharyngeal aspirate
+TADs
+cynomolgus macaques
+Y271A and I274A
+Loop Mediated Isothermal Amplification
+WS and HGPS
+rotavirus
+2009 H1N1 virus presence
+an IPTG inducible promoter
+reduction of surfactant production
+A proline in position +1
+Taoyuan, Taiwan
+three
+Naive T cells
+tumor suppressor
+Early mobilization
+1 H NMR
+HRV-A
+5 hours
+~90%
+Granzyme A
+1%
+pH 4.5
+IMHA
+neuroprotective properties
+Am ixture of H 2 and HD
+all-cause and cardiorespiratory mortality
+cytokines transcription
+Dromedary camels
+1AE49-2AE55
+Escherichia coli DH5a
+less than one
+three
+heterogeneity in study populations and study design
+$536,000
+1.49m
+3
+Vitribot Mark IV
+hemocytometer count
+TMA
+28
+96 mg/dl
+over 800
+ISDS Sustainable Surveillance Workgroup
+the adapter sequence to trim
+LBs
+genetically modified models and biological reagents
+Huh-7 hepatoma cells
+cecal ligation double puncture
+IL-6 signaling
+methanol
+frameshifting
+initiation or maintenance of the persistent infections
+viral gene expression
+microplate scintillation counter
+obesity
+polyhedrin
+CXC
+humoral immune response
+5-year
+6-8 weeks
+PPR infected hosts
+Limited datasets
+TAAR1 mRNA and functional protein expression
+identification and annotation of functional residues
+628 bp
+T cells
+B-cell and T-cell
+gas exchange
+increases in travel between the city and outside
+A single promoter
+decision making in health practices
+viral capsid protein
+subtropical area
+cell aspect ratio
+differentiation, proliferation, activation, and function of different effector cells
+K~12
+CPT-cGMP
+placement of Oscheius tipulae
+4
+0.0006 s
+DC-SIGN
+postoperative narcotic
+4,629
+Monte Carlo sampling
+15%
+19 kb
+survival
+The coiled coil
+2% BSA
+$1,525
+goat, pig, skunk, red fox, and gray fox
+observed values
+Phenol/chloroform extraction
+contact, mobility and transmission features
+17 hours
+10%
+virus induced inflammation
+Enterococcus hirae
+819
+Deficiency of NLRP3 or caspase-1
+two weeks
+total cholesterol
+controlling bath endemic and epidemic FMD
+ChemmineR
+Informed consent
+Droughts or extended dry periods
+structural
+NGS panels
+12 ± 1%
+37
+no reactivity
+ERM proteins
+incidences of ESKD, clinical remission, and death
+21 days
+cellular, biochemical, and molecular
+RID epidemic health protective behaviours
+pandemic response
+codon optimality and mRNA structure
+MIC and MBC values of the phenolic extracts
+79 years
+a protein of unknown function
+Small sensors
+classification purposes
+Linear regression
+Hosmer-Lemeshow statistics
+RAN
+those observed in other countries in the same year
+Pulmonary viral infection
+Strong assortative mixing patterns by age
+four
+1002
+The HA or Myc epitope tag
+293T cells
+OmniscriptH reverse transcription system
+Spleen, kidney, and liver of flounder fish
+B 2 -microglobulin
+complete hydrolysis of proteins
+higher risks and lower benefits
+drug development, disease diagnosis, and targeted therapy
+central nervous system
+SF206
+Twenty-five
+greater stability
+7
+Principal Component Analysis
+UV radiation
+Examination of patterns of host-pathogen adaptation across space
+endoplasmic reticulum
+16
+19
+cubic spline interpolation
+H7N9
+effective candidates
+AM
+K-Pax2
+VN3040
+IfitmDel
+Influenza
+parvovirus
+DSPB
+Newcastle disease virus
+Ubiquitination
+4 months
+Pulsoximetry
+Three
+849
+Mouse anti-human IgG1
+two hydrophobic pockets
+Tyramide signal amplification kit
+DMRIE-C reagent
+5.6 h
+finishing the analysis and writing of this article
+Rickettsia
+five
+IFNγ +
+DNA microarrays
+Fluorescence intensities
+68.6%
+the unfolded protein response
+42.30%
+Additional studies
+proviral DNA
+antimicrobial agents
+T3SS-secreted invasin IpaB
+Plasmodium falciparum
+viral mutation
+disease ecology
+mammalian expression cassette
+Cytokines and successive chemokines
+Codes of professional conduct
+MetaGenomic Species
+16
+viral homologues of human cytokines
+out-patient and in-patient settings
+Known or suspected adverse effects
+tracking HFMD trends
+Tissues
+NagA deacetylase
+Antimicrobial peptides
+252
+3,000
+reactivation of HIV-1
+functional macrophage polarization
+communication networks
+10% H 2 SO 4 solution
+hours
+synergistic
+chikungungya fever
+SDS-PAGE gels
+higher transmission rates
+administration of cAMP-elevating agents
+Caspase-11
+Forty-three
+17
+serological test of anti-BV antibodies
+GenomeScan and FGENESH
+60 min
+41.3%
+brivudine
+~5%
+Normal chicken Ig antibody
+both clinical and preclinical researchers
+8.3%
+Rab5a
+cytopathic effects
+autoimmune type and nonautoimmune type
+1:5
+HmC
+R *
+number of required clones
+rupintrivir
+reduced/oxidized glutathione
+All estimates of costs, outcomes, and cost-effectiveness
+phosphoprotein interaction networks
+standardization of modeling practice
+recombinant full-length IFNλ4p179 protein
+three
+chronic inflammation
+ratios
+dinucleotides
+normal
+0.05
+the distance from the tip to the bottom of the plate
+862
+midazolam
+eight
+Vaccine
+Vibrio cholerae
+high-flow nasal cannula
+Southern and Eastern Africa
+8
+a complete history recorded
+decrease to normal levels
+4070A
+missing amino acid
+1918 and 1919
+differential
+their most recent "ordinary" week
+Kernel densities
+seasonal changes
+innate immune activation
+30
+40
+random
+97
+colloidal blue staining
+EGFR tyrosine kinase activity
+research, authorship, and/or publication
+35.3%
+Significant sequence similarity
+cross-reactivity
+4°C
+GM-CSF
+mid-1980s
+Mean synplot2 p-value
+GNB4
+1%
+45
+Septic shock patients
+TRAF2 and TRAF6
+seven
+JY
+SY568
+disease
+language difficulties
+7 to 14 days
+Contact rates with contaminated environmental reservoirs and shedding rates
+Plasmid pHH-Gluc
+the patient's general condition
+wider spacing of ventilation supply/extract grilles
+Human norovirus infection
+bovine rotavirus
+viral load
+7
+13.6%
+experimental testing
+Pooled fractions from SGR cell lysate
+None
+ligated DNA
+endocytic pathway
+mild inflammation
+180 people/km 2
+6 ± 0.4%
+5 days
+96 h
+Percutaneous radiofrequency thermal ablation
+the system of equations
+Cs 2 CO 3 and 2-iodoethanol
+American Tissue Culture Collection
+liver injury
+S. lividans
+1952
+45 min
+50 μl of SLA-II marker
+875
+ethidium bromide stain
+16%
+fine filamentous skeleton
+S
+ARIMA model
+Over 25%
+119
+M2e
+Mouse IgG
+tested per cell culture flask
+664 million
+HCC cell proliferation
+The resource of ECMO
+computational methods
+20 µl RNA
+lung inflammation and collagen deposition
+5 to 30%
+Adherence
+residues 162-172
+P i
+52
+human respiratory viruses
+neutralize live virus
+the following points
+Saxifraga stolonifera
+IRF-3
+microglia and macrophages
+PowerPoint
+1953
+The ability to adapt to multiple species
+JTT+Ŵ
+travel insurance
+cell migration
+c continuous size distribution model
+Apoptosis
+80%
+infl uenza
+electrostatic interactions between the protein and the ligands
+level of variation in the average values of reference gene stability
+five
+agarosesupporting matrix
+0.44
+Negative or positive pressure state
+disease-modifying
+DNA replication
+3%
+positive correlation
+HSP90
+artificial RNA
+60-62%
+more of a role
+anti-inflammatory
+highly positively-charged
+co-immunoprecipitation method
+A more blood brain barrier permeable ARB
+mutation
+five
+every 10 minutes
+enzymatic
+six
+161
+IFN-α, TNF-α and IL-6
+tTNF-NGR
+five
+non-PAM-type
+CðtÞ
+QIAamp DNA kit
+Paramyxoviruses
+endosomal release
+enterobactin synthetase
+Scrambled shRNA
+four
+exon 2 exclusion
+wildlife host species richness
+Megrivirus
+0.15 casual infections per day
+isoflurane
+APC and GSK3β
+Over one hundred
+13
+deteriorating environmental foundations
+11.0 days
+Bradford's method
+VR1112
+51%
+diffusion
+20 pfu
+Tibet and Xinjiang
+1 week
+spoIIAA, spoIIE, and spoIIGA
+predictive performance
+Renilla luciferase activity
+Primer3
+anorexia
+complex relationships among variables involved in a disease process
+HFMD
+Junín virus
+10d treated cells
+61
+Rnf13
+10-30%
+heteromolecular system
+western blot analysis
+inflammatory mediators
+one
+areas which have been relatively neglected by local health information systems
+removal of the hydroxyl residue
+Three
+Airway T RM cells
+viroplasms
+Infusion hypersensitivity
+Ang II
+adamantanes and NA inhibitors
+Intra-host molecular evolution
+Abcam, Hongkong
+By choosing the taxonomy label and typing the appropriate keywords
+move away from the narrow biomedical model
+network analysis
+respiratory infections
+F = 1 − exp
+5′ UTR
+more than thousand
+PNPP substrate
+3 min
+table 1
+Accumulation of ATZ within the ER
+reduced NK cell number
+recombinant tissue factor pathway inhibitor
+host body temperature, immune pressure, codon and nucleotide usage patterns
+GC apoptosis
+infectious virus production
+consolidations
+293T cells
+International Prospective Register of Systematic Reviews
+good
+Geolocation approaches
+trypsin fragments
+RNeasy ® Mini Kit
+Plasmid pUC-Ad5-hex
+Brazil
+antigen binding
+Five
+Akonni
+equine antitoxin
+Atg6
+Renal cell carcinoma
+3.6
+August and September 2004
+accurate serological characterisation of CSFV isolates
+BZ-X710
+neuronal cells
+pulmonary cancer pathophysiology
+inflammatory
+positive
+virus collected from separate infected cell cultures
+rainfall
+neuraminidase inhibitors
+molecular pharming
+46%
+Early-life exposure to severe RSV infection
+low-cost system construction
+2017
+physiological functioning
+evolutionary information and structural features of the predicted proteins
+The -10bp mutation
+7000 pg/ml
+Lonza
+sialic acid receptors
+FACS analysis
+taxa
+constitutive ACE2 shedding
+Specific pathogen free
+Authors
+PBS
+SuperSignal West Pico Kit
+19
+6 months
+48 h
+mixed linear regression models
+VP4/VP2
+Beckman
+PTBP1
+Non-conservative substitutions
+C. albicans
+proteolytic cleavage of eIF4G
+25-60
+fetuin bt
+cough, respiratory distress, asthma-like symptoms, and chest tightness
+undiagnosed
+DI-244
+ROS
+$23.25
+Supportive care and antiviral agents
+influenza illness
+145
+60 million
+chlamydia
+cyanoacrylate adhesive
+10%
+JFH1
+one third
+Kaplan-Meier estimates
+SAS 9.3
+human infection
+flexibility
+13000×g
+55
+antigen-antigen comparisons
+MTB diagnostic NAATs
+veno-venous extracorporeal membrane oxygenation
+alveolar macrophages and dendritic cells
+Siberia
+a survival benefit
+chimeras
+CpG content
+β ≥ 0
+51
+Cohort studies
+protracted symptoms
+to ensure they elicit balanced immune responses
+A. aegypti actin
+Tetherin
+9.6%
+assembly of replication factories
+perfusion
+increased DC-targeting properties and subsequent activation of T cells
+bacterial presence and host responses
+pigs
+A standard ELISA
+41
+1%
+EcoRI and HindIII
+0.59%
+diseases and antimicrobial resistance genes
+serum
+laryngeal carcinoma
+NucleoSpin RNA kit
+PRRSV epitopes
+The quarantine of people suspected of being exposed to an infectious agent
+283
+cytokine secretion
+M.pneumoniae
+1 day
+formation of long tubules
+exposure to poultry and gender
+prognostic markers
+mathematical models and statistical methods
+DMSO solution
+how many recombinants of the same type were isolated
+1,049
+ARDS
+genetic distances
+9
+loose packing between proximal helices
+10000
+Ceacam1 2/2 T cells
+Sequence conservation
+avascular necrosis of the femoral head
+64
+Palmitoylation
+Dr Natalia Frias-Staheli
+viral transitions
+alveolar macrophage activity
+physical decontamination methods are better than chemical methods
+Source data
+decreased damage to the liver
+death certificates
+global governance
+West Africa
+enhances transcytosis
+45
+contaminating peptidases
+an order of magnitude faster
+enhanced virulence
+GIPSy
+immunoproteasome
+unusual stability
+BME-SIR
+12.6 Gr%
+viral non-structural proteins
+SV02
+spillover transmission
+AlkB-specific substrate binding
+Optimum-Gene ™ algorithm
+placebo control
+Respiratory Syncytial Virus
+single nucleotide polymorphism analysis
+HABP 36727
+13
+Inverse orientation
+TYLCMaV
+three
+bioactive messengers
+CD8 + T-cells
+Twenty-one
+economics and finance
+The human decision-making process
+Thorax
+continuous transmission of virus among animals
+Four
+1966
+NUP57, RNA15, SPC29 and YGR251w
+Thymidine kinase and gE
+CHBAH
+components of the type IVB secretion system
+41.6%
+nine-day window
+$37.0 billion
+B cell antibody production
+TRIzol Plus RNA Purification Kit
+ventilator setting
+dependent lung regions may be recruiting with adequate PEEP
+sections incubated without primary antibodies
+increasing membrane fluidity
+two hours
+142
+residue 134
+EH
+Total RNA
+Luciferase
+RACE analysis
+5 ng/mL
+system-wide unbiased molecular measurements
+15,000
+humoral
+flow cytometry
+1 day
+Ser222
+SZ and XW
+ImageJ
+N * V
+acute
+picornavirus
+Autoregressive integrated moving average modelling
+0.067
+inhaled material
+pAD-GFP
+intracellular Ca 2+ and ROS balance
+Ethanol
+cells viability
+IgG
+2%
+weekly
+2 Hz
+counselling
+30-day mortality
+edges
+IBa
+RNA recombination
+sub-epithelial SMCs
+age
+λ 1 = Λ1 µ1m * = 4.0
+44
+Metabolization of UDP-glc
+ADPribose
+sharing a health facility
+younger age
+polymerase chain reaction multiplex naso-pharyngeal swab
+Epstein-Barr virus
+TIP3P model
+Human RAB7
+control subjects without animal exposures
+winter
+Increased relative humidity
+Fifty to 100
+Trypanosoma brucei and Plasmodium
+Appendix A
+Mice and cottons rats
+five
+sacrificing predictive accuracy
+Catpac
+Senescence b-Galactosidase Staining kit
+NSIP
+three
+14
+SuperScript III
+RNAfold WebServer
+enhanced survival
+QAIzol reagent kit
+fieldbased tests
+UTIs, meningitis, and sepsis
+inflammatory cytokines
+decreased circulating lymphocytes
+elevated cell proliferation and reduced migration
+POLR1-mediated transcription of rRNA and rate of host translation
+five
+1 : 1600
+Tidwell RR et al
+genetic systems
+A solution
+bacteria, fungi and viruses
+hard upper bound
+RPA and PCR
+negative
+Variations in litter size
+azathioprine
+Actin or GAPDH
+CD8 T RM cells homing to the lungs and/or airways
+less than 70% amino acid identity
+at the surface
+PIAS1
+5000
+protecting cells from physical damage
+bioinformatics workflow
+16th of July
+epithelial
+late 19th century
+one hour
+118.1 Ϯ 3.4%
+Volumes of interest and corresponding maximum standardized uptake values
+LPS composition
+Post-transcriptional
+prompt treatment with medications
+science and security issues
+well-established viral features
+Chloroquine
+Telaprevir and Boceprevir
+the corresponding author
+site specific labeling
+DAPI
+recombinants
+48 hpi
+Thirty-two
+an extracellular matrix protein
+Numerous residues within the C:R interaction sites
+twice a week
+Gaelle Noel
+32,505
+GRP94, GRP78, ATF4, and CHOP
+county-level
+K391E and E51K
+prevent animals from weight loss
+LTA mediated cytokine secretion
+population growth and consumption habits
+rZIKV-RGN-mNS2A
+Nerve agents
+RT-PCR
+edge durations
+atomic layer deposition
+thin layer chromatography
+size
+25
+submicroscopic, membrane associated vesicles
+jasmonate
+f B
+LYPB
+Identification of drug-target interaction networks
+technical
+bronchitis
+six weeks
+Vector competence
+b R1
+Oseltamivir
+33%
+cc-by
+Memorial Sloan Kettering Cancer Center
+switches to primer-independent synthesis of full-length antigenomic RNA
+lipid peroxidation and cellular injury
+wild-type cells
+unpredictable clinical consequences
+eBioscience
+1002
+amino-terminal methionine
+prophylactic and therapeutic countermeasures
+Subtype B and C
+PAMs genomic DNA
+MTB infection
+viral RNA
+0.4%
+Plasma and PBMCs
+Quantitative PCR or Western blotting
+multi-step virus growth curves
+minuscule
+viral
+Maintaining a sufficient level of pressure in the tracheal tube cuff
+Caspases
+non-commercial
+water-exposed quenching profile
+21
+trypan blue exclusion test
+biological
+six
+GST pull-down experiments
+metabolic pathways
+nuclear accumulation of polyadenylated mRNA bulk
+classic sigmoidal curves
+neurological disorder
+FDA
+Hypsugopoxvirus
+five
+IgM and IgG2b isotypes
+affinity chromatography
+serine peptidase/prolyl oligopeptidase
+crucial
+at the entrance of the aerodigestive tract
+soluble scFv expression
+Mx1 mRNA
+L929-conditioned
+significantly different
+mice, rats and rabbits
+DC urine
+a multiplicity of 0.1 and 1
+sPLA2 activity
+pNL4-3-Luc.E-Rvariant
+seven
+postoperative outcomes
+Retinopathy of prematurity
+cell tropism, persistent infection, and vaccine candidates
+default values
+200 μl BlaM1 VLPs
+T7 polymerase
+982
+5 minutes
+The phylogram
+3
+pluripotency marker Oct4
+vaccine candidates for fasciolosis
+four criteria
+how uncomfortable
+T-cell
+ISG expression
+cAMP
+primeboost
+0.05
+international data
+E5
+Bioinformatics
+EBV infected cells
+international airplane flights
+phylogenetic networks
+IFITM3 trafficking
+10.1155/2020/9629747
+The corresponding author
+regional population clusters
+Spn4A
+24 weeks
+2-10 times greater than non-pregnant women
+10 centimeters
+30% to 45%
+hepatitis B virus and influenza A virus
+cell death
+SARS coronavirus PLpro
+antiarrhythmic
+36 h
+Binding of peptides to the HHD and H74L molecules
+Antiepileptic therapy
+2005
+41%
+rRNA synthesis and nucleolar size
+IU and IP HIV-1 infection
+the study
+severe respiratory acidosis
+increases
+recycling tubules and vesicles
+IDO1-induced nutrient depletion
+seven
+nanovaccine
+Prophylactic and the therapeutic formulation
+50 aa
+four
+adaptations to overcome genetic divergence between the reservoir and spillover hosts
+Phylogenetic trees
+the liver
+189
+airports for control
+reproduction number
+VRC01 CDRL1 and CDRL3 loops
+below and above its corresponding threshold values
+2149
+ELISA plates
+unique
+delayed response
+binds RNA
+40S
+S. aureus ATCC 25923
+the size of each module
+cell proliferation and oncogenic activity
+minor pathological changes
+transmission chain
+time windows one to three weeks shorter and longer than the proposed eight weeks
+0.2941
+USA, Australia, Hong Kong, and China
+over billions of years
+Latin America
+3,4-dihydroxyphenyllactic acid
+resources allocated to region l
+mounting a detectable antibody response
+mitochondria
+hydrogen peroxide
+IE adhesion to CSA
+Compound Topographical Index data
+carcinogenesis
+Sensitivity
+melanoma-reactive
+An alarm
+blood monocytes and dendritic cells and spleen macrophages
+29
+111
+serum
+Metamorph
+recombinant inovirus
+724
+pJD366-18
+degree of hypoxemia
+atopy and allergic sensitization
+research ethics
+novel
+infectious disease management
+20 µL
+the truncated N6 position of A37
+Scherle method of weight displacement
+loss of infectivity
+1 to 100 nm
+77.8%
+1.1-1.2
+RV-B
+active
+Anti-LTA mAb-binding kinetics to purified LTA
+71
+AIV H6N1
+hepatitis, liver fibrosis and cirrhosis
+EnzyChrom L-lactate assay kit
+12 days
+major T cell epitopes in VLP forming components
+establishes persistence
+Bio Med Central
+model
+Second Affiliated Hospital of Guizhou Medical University
+Figure 1A
+β-Actin
+Twenty-one
+offset correction strategy
+Ficoll-Paque gradient
+innate immune response
+Clathrin mediated endocytosis
+2004
+ADAM2
+Muguga Cocktail
+densitometry
+RR1 soybean DNA
+57.7%
+HuSiDa
+a potent immunosuppressive fusion protein
+Begg's test and Egger's test
+36
+critical information
+13
+Institutional Review Board 4
+centrifugation
+ER stress and UPR activation
+TNF-a
+immune reconstitution inflammatory syndrome
+iterative
+1,188
+washing with water
+subcompartments
+100 Species Vertebrate Multiz Alignment
+F and L
+gorillas and chimpanzees
+27
+outbreak duration
+T-cell immunity
+signal intensities
+Coronaviridae M protein
+critical knowledge gaps
+Pulmonary surfactant
+Noninfluenza viruses
+therapeutic
+Advanced Scholar Search
+Mann Whitney U-test and χ 2 test
+ΔcscAR + pBaSP
+Screening for CMV
+moment relations
+tryptophan
+severe preeclampsia
+100%
+Qiagen IPC
+IFN-α-induced apoptosis
+a medical doctor
+Two
+GraphPad Prism
+nisin controlled expression
+A soluble and flexible amino acid peptide linker
+women
+Pansinusitis
+multiple cellular factors
+CRISPR/cas9
+Formalin-inactivated influenza virus
+sites that are conserved between CypA and Ran-Cyp
+PCR and nested PCR
+Conflicting
+Angiogenesis
+initiate their escape from the endosomes
+Beilong virus and J virus
+ss469415590
+a segment of the M gene
+3,000
+endogenous antigen presentation
+11
+vRNA
+outlying cases of rapid movement or longer persistence of infection
+34 kb
+renal neutrophilic infiltrate
+3 days for reaction
+statistical significance
+5-to 25-fold
+64%
+HFD
+whole supernatants
+Picard
+Lamivudine
+Overall mortality
+vulnerable or underrepresented population groups
+two
+oseltamivir
+CD8 + T cells
+905 image slices from 120 patients
+12% intensity
+CBPV
+NK cells
+60 %
+KO mice
+fetal red blood cells
+attenuating viral protein synthesis
+inflammatory mediators
+stability during a drying process
+confounding
+10,000
+combinations of viruses that previously infected human, swine and avian hosts
+residue 77
+HDL
+Changes in the length and composition of this spacer
+rhinovirus or enterovirus
+21
+statistically significant
+b
+improvement of the underlying mood disorder
+lose focus
+GeneJET Gel Extraction Kit
+poor prognosis
+atipamezol
+reinnervates the paralyzed muscle fibers
+hemoglobin
+32
+Inaccessible trajectories
+Student's-t test and ANOVA
+Ebola Reston virus
+T and I
+hydrolase L1 protein
+1 mM DTT
+visualizing and analyzing trends and patterns in scientific papers
+Autoclaved nanopure water
+hypoxemia
+cell specific responses
+29%
+Plasmids for CRISPR-Cas9 genome editing
+misfolded, modified or unwanted proteins
+equal volume
+4
+480%
+selective packaging of BMV RNAs is not directly linked with membrane remodeling
+0.2
+colorimetric assay
+modulation of cell apoptosis
+200
+28
+isatin moiety
+mRMR with forward feature selection
+three
+mismatches
+Key human pathogenic arboviruses
+High consumption of dietary fructose
+to immobilize proteins
+30 days
+Traditional Chinese herbal medicine
+6.8 to 7.2
+10%
+guidance
+naïve T cells
+32
+α R
+Biomatters
+297.7 g
+Colon epithelial tissue
+LacZ staining of bladder wholemounts
+hemocytometer and Trypan Blue dye exclusion method
+Urea
+SPSS 12.0
+59 and 39 ends
+NSs-mediated transcriptional suppression
+discriminate viral targets at the level of both their genotype and subgenotype
+the functional IFN-λ4 protein
+mammalian-like
+proteins in the exocyst complex
+DAVID Bioinformatics Resource v6.7
+Interferons
+macrophage and T cell data
+Loop matching strategies
+managing and analyzing large amounts of gene expression and mass spectrometry data
+28 kDa
+IFN-γ signalling
+earlier
+MDCK cells
+full mediation
+g
+a library of HCV pseudoparticles
+55%
+83%
+39%
+Stress
+the intensity of the host inflammatory response
+the nature of arising hazards
+28 th April
+six
+≈0.4
+an influenza outbreak
+V1V2 domain
+radiological
+oxidative damage
+− 0.3 cut-off
+classical morphology
+924, 559 and 390 nt
+CellTiter-Glo kit
+saline and 2.5% ethanol
+QIAamp DNA Mini Kit
+to minimize the load
+Multiple organ dysfunction syndrome
+50%
+6 weeks
+lung TLR4 expression
+25%
+Markov chain Monte Carlo methods
+5 0 ends
+Recognition and Tolerance, Immune Response and Killing and Memory
+to semiquantitatively measure the fusion variants in a complex sample
+ECMO
+55%
+BSM of natural origin
+710
+1000 mU mL −1
+phase 4
+structured
+EJB
+thymic atrophy and polyclonal B cell activation
+Influenza NP
+more than half
+no relatedness at all
+microarray-based expression analyses
+23,801
+Nucleic Acid Amplification Tests
+IFITM3-positive
+pneumolysin
+α-SMA
+98
+An amplicon-based metagenomic library
+GO term and manual annotation
+patient #226
+10 Å
+Btk phosphorylation
+EF-P
+EIF2AK3
+8
+critical components of the innate defence system during pneumococcal infection
+three
+infection
+dysregulation of several key miRNAs
+L-CDR2
+0.74
+Science
+400 nM of each primer
+point of need testing
+RIII
+illumination-induced heat
+Four
+mosquito
+293T cells
+frameshifting
+47 to 81%
+HIV-1
+Mycobacterium abscessus
+airway infection
+Two week-old
+VA-MENGOC-BC
+10-23 days
+by checking the complete blood count
+self-reliance at individual nodes and clusters
+regenerative medicine
+Funding mechanisms
+3027
+M5
+Total RNA
+ACE2 marker
+SgrS
+mTOR, Raptor, Glb and DEPTOR
+two
+changes in behavior
+EBV
+University of Vermont
+120
+virulence plasmids
+150 kDa
+Rhythm control strategy
+16-34 min and 8-25 min
+GRM model
+surveys or cohorts geographically settled close to their residence
+Grubb's test
+1987
+1:1
+apoptosis
+1954
+glutamine
+fully validated
+3-AB
+Carbohydrates
+sensitivity
+ZIKV
+Living Image 3.2
+CS&T beads
+Titer reduction
+P. falciparum malaria
+STAT3 or STAT6 knockout cells
+to detect changes in threats
+bronchiolar obliteration and DAD
+7-day
+0.1%
+a set of detected pseudoknots
+0% survival
+denatured proteins
+PaLung cells
+vaccine development
+Werner syndrome and Hutchinson-Gilford progeria syndrome
+Mutations in the coding genes for HA and NA
+IFN-γ
+responses
+quantitative reverse transcription polymerase chain reaction assay
+statistically significant
+two
+27.3%
+four
+viral strategies
+PKR
+D23
+704
+cytotoxic
+Network models
+Fourteen days
+IFN-α
+IL-6, IL-8, and MCP-1
+Backbone flexibility
+The natural stop-start motif
+Ang II
+fluorescent
+biocompatibility
+a compendium of an approximately twice the size of full-text consultation work
+747
+stimulating the nitric oxide production
+cytoprotective
+Synthetic genomics and synthetic biology
+other miniaturized and large-size high-speed CE instruments
+the malfunction to control cell death
+60.1%
+T1-T17
+Highlighted sequences
+polysaccharide intercellular adhesin
+aminoacid substitutions
+caspase-3
+Image J version 1.48
+1
+Haploreg
+camels
+natriuretic peptides and their receptors
+Linear regression analysis
+50
+Complications of intensive care procedures
+China
+efficient replication of infected virus in respiratory epithelial
+Maxima with too close a spatial overlap or at an image edge
+six
+refseqgene
+a network of narrow pores
+higher
+DSBs
+heterologous prime-boost regimens
+tumor metastasis
+epithelial cells
+72 h posttransfection
+48 hr
+significant stalling
+two pairs of closely associated dimers
+limiting an ongoing outbreak
+QIAquick PCR Purification Kit
+stunted
+codon adaptability, mRNA structure, tRNA usage
+tumor-bearing mice
+negative-strand RNA viruses
+a third group of rhinoviruses
+Different groups DCs
+over 1200
+indirect
+24h
+4 weeks postvaccination
+parrot bornavirus 1 to 8
+elevated
+two
+PCR cross-contamination
+air travel
+115
+cysteine
+IFN-γ
+significant differences
+96 h
+19 kDa protein
+several
+Rhinovirus and Coronavirus
+HRP-conjugated
+Complex patterns of multiple crossovers
+less than 5%
+good ANFIS's parameter
+1,584
+pig
+HmA
+reverse vaccinology
+8.7 million
+a cellular protein continuously degraded by proteasome
+recombinant antigens
+exponential
+birth
+C = 10 6
+44%
+fear of illness, contagion and death
+NFKBIZ
+hostcell protein localization
+histopathological patterns
+synergistic
+Image J
+early risk factors for severe PJP and 90-day mortality
+information on HIS
+273
+quantitative and/or spatial transcript expression patterns
+Poisson
+ATPase activity
+bacterial composition
+addressing health issues in complex systems such as the Arctic
+type I IFN
+one
+30 minutes
+55-10%
+a suitable slippery sequence
+development of disease control strategies
+three
+miR-148a
+dynamical epidemic SIR model
+Annexin V
+true-nonmutation calls
+travel and tourism, vulnerable groups, social and demographic, and surveillance and reporting
+77-84
+Obstacles to the implementation of lung-protective ventilation
+adipocyte dysfunction
+ten
+Poly I:C and Sendai virus
+TGF-β 1
+Supernatants
+14 months
+265.4 weeks
+21
+NK cells
+an RSV outbreak
+zero
+the PLC
+hepatoprotective and antioxidant
+CPT1
+all regions we considered
+5
+BWA and Bowtie2
+The underlying network structure
+desmoglein-specific cytoplasmic region
+percent dimerization
+one or two
+Five-fluorouracil
+human AXL + DCs
+ZIKV Natal RGN SRIPs
+neurological disorders
+homology modeling
+278
+4
+16th
+The cell pellet
+denoising of lowerresolution density maps
+oncogenic
+by APCs
+Subcritical transmission
+6
+An entire living world
+conjugated antibodies
+H1N1 M1
+Six
+membrane fusion
+Elevated CK values
+1.75-and 2.40-fold
+989
+inflammatory
+nonspecific recruitment of cellular endonucleases
+real quotes
+93,326
+within tight junctions
+The Martini script
+2D electrophoresis
+CD8 + T cells
+a specific diagnostic test
+P-I
+billions
+scanning densitometry
+Blood samples
+HLA concentrations and bioactive lipids
+Sera
+antioxidant, antiviral, anticancer, antimicrobial and anti-inflammatory
+Standardised triaging and triage procedures
+Real-time PCR
+Sigma-Aldrich
+GSE129949
+Point-of-care ultrasound
+90 million
+methylene blue dye
+whether individuals perceive themselves to be at risk for type 2 diabetes
+histological
+3 h
+DNA nanoswitch
+PDI global knockout mice
+logrank test
+Deutero GmbH
+treatment
+60%
+axis 1
+convenience and short treatment times
+Acute chest syndrome
+apoptosis
+bacterial-specific
+infectious complications
+three months
+the migration graph
+cGAS K335 monoubiquitination
+Phe, Tyr, Trp, and Cys
+CCX754 or CCX771
+temporal class
+antigenicity/immunogenicity and accessibility
+induction of type I IFNs
+IL-17A
+Triton lysis buffer
+100:1 or less
+two
+Written informed consent
+Liver
+potential
+antiviral immunity
+18
+MDAs
+5-14 years
+serum levels of sCD86 were significantly elevated
+Endocytosis
+SDS-PAGE
+routine workflow processes
+F240 and T32
+hamster
+episodic diversifying selection
+~92%
+an investigational therapeutic
+Bound bacteria
+gp350-positive
+blood culture
+catalytic dyad
+LPS
+aerosol propagation
+Patient viral RNA copy numbers
+none
+2 -ΔC T
+two
+3 weeks
+ASOs
+Stromelysin-1
+poly-arthralgia
+two-tailed Student t-test
+mitochondrial kinase
+Rudolph Virchow
+Swiss-model server
+40-50%
+infection rate
+50-70%
+HSV-1-stimulated pDCs and CD4 T cells
+sentinel cells
+Th2
+containment failure
+sEV uptake and paracrine senescence activation
+704
+genomic signatures
+Immunofluorescence
+MutS homologue 5
+IC 50
+270uC
+2.1 days
+mean ± sem
+unacceptable
+S phase-specific DAC incorporation
+15 weeks
+18
+AIV
+docking scores
+initiation, propagation, and termination
+decolonized
+50%
+HEK293 Flp-In TREx cells
+60uC
+severe heart failure
+deliberative
+Overlap extension PCR
+Core Hopping
+norovirus assembly and release
+86%
+6
+Mmp9
+21
+BSL-2
+social processing and social cognition
+PCV13
+implementation of M&E activities
+an independent assessment of the national laboratory network
+15
+four
+pneumonia
+grifonin-1
+semantic-linguistic annotations
+HBoV-1
+Wuhan, China
+150 μL DMSO
+1000
+virus-like microorganisms
+Total Worker Health initiative
+a feature detected in four independent replicates
+RNA enzymes
+Defining the adequate cutoff
+type I interferon responses
+stability of helix H3
+Adherence to proper infection control measures
+uniform vectors of physicochemical properties of proteins
+mutagenic and tumorigenic properties
+in-season and off-season
+Mef2c
+The effect of MEDI8852 to prevent influenza transmission
+Fluconazole
+CAP
+48 h
+15%
+21.36 μg/ml
+superior safety
+Baseline characteristics, active problems and APACHE II
+excess B-1a cells
+Alveolar hemorrhage
+Eighteen
+recurrent infections and functional recovery
+add oligonucleotide tail to 3′OH ends
+neutralise the fusion protein
+The tet R gene
+␣2,3-linked SA
+three
+deamination
+ace2
+cell viability and tumor growth
+ECL detection
+Non-small cell lung carcinoma
+understanding how eHEV spreads
+mineral oil
+Disease severity
+mild and selflimited upper respiratory tract infections
+exogenous trypsin
+40-60 seconds
+The supernatant
+population homogeneity
+Control 11A minibody
+LC3B-positive structures
+interact with FKBP11 in the osteoblast cells
+different transmission clusters
+Car3, Fmo2, Hdc, and Ker13
+senescent
+normal pregnancy and immune responses
+human pathogens
+retroviruses
+different epitopes
+mice
+structures
+fasting glucose, insulin, triglycerides, and hepatic fat
+essential functional genomic elements
+Illumina Hiseq2000
+30 minutes
+Service provision to overseas workers
+MW2 and LAC
+IEDB
+78-88%
+mammals and marsupialia
+AQP3 water channels
+120
+five
+resistance can widely spread
+100% identity of their R. landeri with Bos taurus
+dependency insurance
+silence PDI expression
+MgNH 4 PO 4 •6H 2 O
+EGFR kinase activation
+viral load
+.50%
+moesin and radixin
+Non stem cells
+whether tDCs are also depleted
+the region's priority zoonoses
+Specificity, avidity and dynamics of influenza A virus -receptor interactions
+chicken
+heparinized microcapillary tubes
+Rs2563298
+the TM region
+211
+1
+seven
+chronic obstructive pulmonary disease
+oxidative stress
+90%
+NS1
+serodiagnosis
+confidence interval
+Gas6
+100 mL of C3 buffer
+transcriptome
+1%
+Branchiostoma floridae Bf--AGO2
+Four days
+analysis of multiple alignments for upstream regions of orthologous genes
+fusion inhibition or co-receptor modulation
+HRPs
+S. aureus
+genome sequencing
+immunosuppressive and immunomodulatory
+ACE2
+Mass spectrometry
+molecular mimicry
+pulse oximetry
+Malignancy
+sepsis-related organ failure assessment
+Plasma ACE2 activity
+Outer membrane vesicles
+five
+Supplementary Text S1
+An ECLS Service
+an artefact
+MBC assay
+Tumor Volume = /2
+Animalia
+519
+anesthesia
+Biojector 2000
+mycoplasma contamination
+Severe joint pain
+orders of magnitude worse
+11
+regional commanders
+Tri-pure reagent
+follow up with other small molecule analogs
+diarrhea
+PrimeScript RT-PCR Kit
+eIF3d
+electrical
+five
+antinuclear antibody and rheumatoid factor
+electrostatically charged polypropylene filters
+30 to 40
+cDNA
+25
+93
+flotation through a discontinuous iodixanol density gradient
+lower titer Nab specificities
+heat shock
+Addgene
+membrane fragments and viral particles
+ProteOn 3000 instrument
+B2M
+two-item measures
+The Red Queen hypothesis
+DC
+0.67 and 6.7 µg/g
+12.9%
+AUG and UGG
+antiinflammatory, antibacterial and antiviral
+Seventh Programme
+heart rate and cardiac output
+HI activity
+seven
+The scope and limits of self-control
+TGFE1
+Im-ageNet pre-trained
+Inappropriate initial antimicrobial treatment and transfusion of blood products
+AONs can only specifically target one exon at a time
+oncostatin M
+Apo E
+survival after liver transplantation
+nanoviruses or babuviruses
+twice
+Viral infectivity
+∼10%
+24 h
+Helium
+HIV, RSV, and DENV
+72
+taking antibiotic medicines
+the scenario in which the vaccine and vector share cross-immunity
+IL-15
+Titers
+Pulmonary/lung fibrosis
+centrosome function
+infectious bronchitis virus
+dsDNA
+Symmetry
+Health Research Innovation Centre 53, University of Calgary
+averages across the ensemble
+luciferase activity
+IDO-KD MSCs
+Glycan processing
+heterozygous-diploid
+T cells and B cells
+6 months
+tribromoethanol
+Spearman rank-order
+single-stranded RNA and reverse-transcribing viruses
+population density
+major
+Frameshift efficiency
+knowledge about Ebola virus transmission routes
+finer temporal resolution
+metabolic disease
+rapidly inserts in the target membrane
+antibody response
+inhibits Apdm09 replication
+key aspects of transmission dynamics
+immunotherapy of cancer
+higher order structure
+CDKN2C
+confined T cells
+Ω
+most probable links
+immunological pressure
+CTF + CGR and random forest
+Germany
+initial seeding events and small-scale outbreaks
+SITR trajectories
+ubiquitin binding
+MYC
+neurodegenerative
+infants
+.20%
+addressing the far q k space under attenuation of the specular axis
+traditional herbal medicines
+microvascular endothelial cells
+accumulate mutations
+Y. enterocolitica
+at the RPE and the photoreceptor level of the retina
+syndrome
+replication
+14%
+haplotype changes
+24 hours
+Diarrhea and rashes
+Hoechst dye
+ClustalW
+Twenty
+whole-genome sequencing
+a systematic and sensitive method
+Communication
+10 min
+glycyrrhetinic acid
+self-referral
+TREM2
+functional changes
+TIRAP and TRIF
+type II
+Matched fluorescein conjugated isotype control antibodies
+Adjusted P-value
+Ni2+ nitrilotriacetic acid column
+800 gene probes
+using separate sutures to the abdominal musculature and the skin
+second quarter of 2019
+biological
+De novo virus protein synthesis
+seven
+Substitution rates
+licorice root
+to facilitate pathogen survival and multiplication
+GOrilla
+peptide
+Murine BM-derived VSELs
+one bp
+A pause in unzipping
+3′SLe X
+8:40
+TfR1
+Natural reassortment
+supernatants of HUH-7 cells
+10
+Apoptosis and necrosis
+G, F and M
+intrinsic properties of the pathogen
+16.6 ml/cmH 2 O
+a level of an individual mouse
+Trained innate immunity
+cross-reactivity with HCV antigens
+DNA lesions
+assessing school performance
+Influenza Apdm09
+Tobler's First Law
+athymic
+whether NF-kB targeting would also alter cytokine production
+biochar yield
+individual siRNAs
+exogenous IL-1␤
+Belmont Report
+seven
+25 to 46 kcal/mol
+Stage II
+15
+1610 6
+initiation
+5.7 Å
+Enzyme reporters
+less than half
+50 %
+a group of proteins induced by heat shock, or hyperthermia
+97%
+Ebolavirus glycoproteins
+Changes in body weight
+eight
+Digital PCR Analysis Software
+52/250
+29
+60%
+10,000
+personalized
+Every question
+unglycosylated sites
+heroin−KLH
+TRIzol TM Reagent
+5 -UNN-3
+one fourth
+cardioprotection
+relapse
+4%
+viral RNA
+tuberculosis and meningococcal disease
+Imperiale and Casadevall
+professional groups
+1997
+negative peptides
+three
+arms race dynamics
+16-fold
+The T m at 295 nm
+P max
+cc-by
+100 μl
+TCS
+80%
+Nucleobond PC 2000 EF kit
+apolipoprotein D and RNase2
+isolation
+1990s
+the corresponding author
+7 days after each dose
+glycoprotein fusion activity
+highly focal movement of individuals
+to dryness under reduced pressure
+microtubule assembly in neurons
+a few hundred
+likelihood ratio test
+Y. pestis 91001
+HIV gp120
+The final refined structure without water molecules
+Gene content, number, and structure
+1.47-fold higher
+fluorescent-tagged
+MBC assay
+cryptdins
+mucous membranes
+I-TASSER
+Italy
+neuroticism and conscientiousness
+150
+oligo-A complex
+NS1 protein
+P. vivax malaria
+elevated plasma C-reactive protein and procalcitonin levels
+GFPpolyA
+morbidity
+Arbidol
+block the autophagic response
+33.4 years and 30.5 years
+to disinfect all hard surfaces
+16 000
+timeinvariant characteristics
+chloroquine treatment
+20 mg
+25%
+Upshaw-Shulman syndrome
+cell-or organ-specific delivery or the complexity of mRNA pharmacology
+IL-10
+28,648
+Text S1
+20-30%
+H5N1 infection
+The strategy producing the lowest mean cost
+Four
+ORRs of 50-60%
+50 μl
+174
+safety and tolerability
+13
+B-and T-lymphocytes
+influenza Apdm09
+EachÑ i
+therapeutic
+The text describing Fig. 5
+uncoupling
+multiple displacement amplification
+Wild birds
+3 hr
+ACE
+non-coding regions
+some of the segment termini lacked this consensus sequence
+tumorspecific antigens in the colon
+inhalation of excreta from infected rodent hosts
+a global order
+R. australis infection
+Kilifi Clinical Trial Facility
+vertebrate genomes
+653,519
+2-8
+b
+822
+Mann-Whitney and Chi-Square tests
+individuals across the lifespan
+quantitative analyses of host protein responses
+a short strand of RNA bound to a protein complex
+RTCD1
+sequence-based criteria
+Cellular infiltrate
+antigenic boosts
+Ang-
+Class II
+Viral
+inducing the cell-surface expression
+how it might exercise its relevant taxation or legislative powers
+γ carboxylate
+1.000
+detailed overviews of Rfam families
+High Pure RNA Tissue Kit
+all stakeholder groups
+fast breathing with confusion
+Applied Biosystems SDS2.2
+change in protein expression
+transcription of IFN-stimulated genes
+Ten
+TCI Chemicals
+distinct structures
+19
+SAMD9
+41.81 ± 10.29 × 10 9 /L
+three
+R0
+NsP1
+how to manage infected and affected persons
+CD206 + TAMs
+MEME and FEL analysis
+27
+by washing the filters in 1 ml of THY medium
+eight
+an active UPS
+Quorum Sensing
+their agreement
+CXCR3A receptor
+malignancy and infection
+CedPVinfected
+access to health care resources
+hundreds
+infectious progeny
+human albumin levels and alanine aminotransferase activities
+Timed phylogenies
+W ðjÞ k
+Ksv
+immunological memory cells
+Infectious diseases
+surface HLA-DR expression
+yeast genomic DNA
+The detailed mechanism
+virus entrance and amplification
+34%
+Disassembly of the viral capsid
+60 min
+specific memory mimicry
+>25%
+viruses and microorganisms
+pathogenic
+chemically modified antisense oligonucleotides
+environmental, medical and agricultural significance
+0.5%
+Serum samples
+sphingosine-1-phosphate
+ANGs
+Ficoll density-gradient centrifugation
+T cells
+evolutionary
+Mock-treated A9 cells
+GFP
+SARS-CoV 3a
+enhanced the transcription of the p35 subunit of IL-12p70
+PI-stained protoplasts
+chromatographic immunoassay
+>40-fold
+5 × 10 5 cells per well
+the HMM
+102
+two bacterial species
+respiratory pathogen transmission
+Triterpenoids
+AlphaView Software
+39%
+blockchain technology
+Transportan
+IL-12
+1 to 16 g/mL
+100 µM
+ACE2
+greater generic conspiracist ideation
+pyrimidine-based TSA nucleosides
+13 amino acids
+age-specific
+NL-means filter
+biotinylated
+real-time PCR
+55%
+mononuclear cells
+vitamin E
+IFN gamma
+Virus samples
+Ethical
+pcDNA3.1-LacZ
+tumors
+Nursing Care Plan
+essential
+Twenty
+inflammatory
+17 January 2020
+0.5 g of sequencing-grade modified trypsin
+0.057 to 0.437
+Balamuthia mandrillaris
+disease prediction
+identity
+student's t test
+sample size
+G23C
+12%
+below the value of 1
+excessive proliferation
+13 years
+N
+Creative Commons Attribution 4.0 International License
+layer chickens
+symptom onset times
+5 mM QX-314
+69%
+CHIKV nsP2 and nsP3
+63%
+Innate and adaptive
+overall separability of patient groups
+primitive streak stage
+Table 1 and Figs 1 and 2
+13%
+Four
+no disruption of nucleoli
+purveyors of risk communication
+many differentially expressed genes do not necessarily need to carry the responsible mutation
+illness
+epidemiological compartment models
+The length of these loops
+higher attack rates
+pAAV-MCS vector
+3 µg of immunogenic protein
+98.6%
+flow cytometric
+5 × 10 9 /L
+nine
+β-Actin
+low MHC class I and low TcR avidity
+2610 4 ffu/ml
+11,500
+2.66 weeks
+30 minutes
+water, sanitation and food habits
+89%
+electrocompetent E. coli cells
+M2 homotetramer
+in 100 μl water
+innate immune response
+mRNA encoding a reporter protein
+release of ACh
+VGSCs
+P½jT; M
+a large set of chest radiographs
+EH, SF, HH, and ME
+proximity to airports and the presence of national highways or freeways
+conservation consciousness
+RNAi
+R4
+SRA-toolkit
+NP868R capping enzyme
+261
+NGS
+Escherichia coli DH5a
+pediatric
+15
+3-7 days
+hyperoxic
+Response to antibiotic treatment
+single cell-encapsulation
+Public Health Service grants
+concentration-inhibition curves
+20 to 61
+Flaviviral NS5
+Panel a
+I mig
+2B and 3A
+translation of a second ORF
+sets of differential equations
+Characterizing unknowns
+GraphPad Prism 6
+503,124
+3,590
+STAT1 and JAK1
+F-test
+Nearly 50%
+Molecular detection
+HVR
+major obstacles
+0.5%
+SPSS version 17.0.1
+compartmentalization
+the localization of brainstem injury
+Toll-like receptors
+Triterpenic
+60%
+YFV
+tissues near the inoculation site
+Five-week
+five
+later in life
+71.4%
+f i
+12 hours
+compartment models
+STATA 12
+tumor antigens
+Delayed onset
+IL-6 and TNF-α
+16 hours
+pathogen growth
+Ϯ SE
+ARH3
+22%
+an elegant strategy for evading antibody-mediated immune responses
+2 min
+HCV subgenomic RNA replicon cells
+transcriptomic response
+17
+Leukocyte-associated immunoglobulin-like receptor 1
+Accurate interpretation of past and contemporary population demographic scenarios
+Antimicrobial stewardship
+features that did not appear in a majority of rules
+Madrid
+host RNA polymerase III
+nine
+IMX313
+Secondary bacterial infections
+270uC
+CX3CL1
+Commercially available PEI
+A pixel
+synplot2
+40
+other reports from previous studies performed in Mexico
+48 h
+tenfold
+laboratory capacity or expertise
+four
+straw-coloured fruit bats
+picornaviruses
+J-sL and X-wZ
+10 min
+two primary anchors
+the latent period
+discovering lead compounds with anti-trypanosomal activity
+5%
+72%
+77
+Src/ FAK-dependent
+recombinant baculovirus infection
+lower
+σ
+increased transmission
+BAG6 and AIF1
+TGF-b signalling
+carbon source, pH, temperature, and cofactors
+nine
+on the farm of origin
+doxorubicin
+k elec
+ROC curves
+Jensen-Shannon divergence
+Alternative splicing in RL2-SP1
+confounding
+Ang-2
+different levels of distinct proteins
+IL-10
+Brazilian state
+Surveyor TM Mutation Detection Kit Standard Gel Electrophoresis
+gold, carbon and silica
+the complexity of the health problem
+3 mins
+monophosphate
+development
+Induction of the gene of interest
+12% polyacrylamide gel
+XLSTAT
+GraphPad Prism software
+Bradford kit
+genetic complement abnormalities
+didactic teaching methods
+microplate reader
+added attention
+surveys or interviews
+research, education, clinical practice, product development and distribution, and health promotion
+Remodelling
+ERK, AKT, and STS3
+a p38MAP kinase inhibitor
+increased membrane-bound protein intensity
+997
+predicted
+almost total skipping of exon 23
+six hours
+Ag
+IL-17A
+Continued surveillance
+LPS
+L1 pixels
+adaptation to the host's immune response
+amplify conserved target nucleic acid sequences of the virus
+dissociates from the sensor molecules
+information on them is confined
+2016
+double-stranded RNA binding
+two forward primers, two reverse primers and one RPA probe
+inflated false-positive rates and/or reduced power
+4.4%
+6 bp index sequence
+stem dependent neutralization
+M-ABA
+proliferation and survival
+low
+univariate
+6%
+280,000-970,000 N/m
+epidemic preparedness
+HuR
+0.88 million metric tons
+molecules
+fib rinous
+neutralizes charge
+total inoculum size
+overuse of antiviral treatment and prescribing behaviour
+Dedicated Python scripts
+saponin, flavonoids, and plant oils
+E134N
+all of the n 0 old nodes
+vaccine for influenza
+she will be replaced
+ϳ3.5 h
+s + d
+1.0 ml/min
+450
+the most appropriate reference genes
+neurological abnormalities
+the set of selected primers to amplify all genomes in the target set
+RT-PCR
+higher replication
+Antibody-based passive immunity
+Spain
+Reductions in disease duration
+receptorbinding proteins
+R 0
+translation efficacy
+Spo0A
+1 day
+stable transformation and transient expression
+The number of M genome segments
+January 2012
+biologically active transcriptional changes
+field evaluation of ACE
+plastic
+efficient priming
+pericentriolar region
+4
+Benjamin Lemaire
+IPA
+unit mass resolution
+Red or purple boxes
+blood
+encephalomyocarditis virus
+insufficient oxygenation
+FastQC, version 0.11.2
+extraterrestrial coverup conspiracies
+DTMUV
+mouse
+DNA constructs encoding the GP protein and/or recombinant purified GP protein
+R 0
+5 min
+1946
+Resfinder
+nairovirus-infected cells
+IL-6
+decreased pH conditions
+ALB and ACTB
+PrimeScript5RT reagent Kit with gDNA Eraser
+Dr Margaret Chan
+2AE5%
+University Hospital Essen, Germany
+Spaniard
+MMR and MGL
+Sepsis-induced multi-organ dysfunction and injury
+CNS invasion by JEV
+temperatures
+NetMHCpan predictor
+DiGeorge syndrome
+Further studies
+immune
+The agreement with the Polymod data
+s
+Five
+30
+Effects either on binding avidity or on membrane structure and trafficking dynamics
+Nowotny
+0.8 to 3.8 mg per lane
+13%
+Robust Multichip Average -based
+cysteine residues
+a period of city economy development
+nonsynonymous amino acids
+CASP7
+27%
+new protein folds
+microorganisms
+69.7%
+probabilistic transmission dynamic model
+99%
+increases cell attachment and migration
+PI3K-Akt-mTOR
+endoscopic stapler-cutter
+replicative speed
+inspiratory limb
+selftransmissible
+4455
+Richards model
+Benzonase nuclease
+lactate clearance
+Kruskal-Wallis
+to be able to promptly test scientific hypothesis in proof-of-concept studies
+STAT1
+similarity
+competent vectors
+tyrosine-protein kinase Src
+Ly49C/I and CD62L
+six
+prophylactic treatment
+The amount of complications related to anti-malarial drug use
+79.8%
+CS Bio
+microarray
+pharmacophore potency
+Mechanical ventilation
+cell surface attachment factor and/or receptor
+improve growth performance
+ferroptosis of tubular kidney epithelium
+usual source of care, citizenship status, and ability to speak English
+lung perfusion
+false positive evidences
+over 65 year olds
+83.9% protein sequence identity
+early diagnostics of MS
+The innate immune system
+TRAIL-R
+16%
+seven
+500 kHz
+twice
+100 μL
+RV-A
+two orders of magnitude
+C-reactive protein
+RT-PCR
+human immunity and the dengue virus
+mRNA
+allosteric
+T2DM
+JASCO-815 CD spectropolarimeter
+astrocytes
+intracellular localization
+four
+siRNAs
+statistical significance between the groups
+Mean and standard deviation
+intercellular signaling systems
+mottle
+site-specific PEGylation and fusion to an Fc region
+experiment fold change datasets
+strengthened expression correlations
+Standard checkerboard microdilution method
+Total spleen MNCs and K562 tumor cells
+culturing techniques
+Feliformia and Caniformia
+disaggregate
+RPMI 1640
+SPSS version 16.0
+single cell suspensions of lung and spleen tissue
+Avian influenza
+Five
+SB diets
+4
+Endpoint OSD fluorescence
+three
+graph-theoretic
+96.4%
+the degree to which each emotion contains both negativity and positivity
+The Ethics Committee of the University of Yamanashi
+pathways enriched among proteins downregulated >2-fold
+H66
+72uC
+2 µl of cDNA
+Megachiroptera and Microchiroptera
+2/164
+using a hemocytometer
+splenocytes
+20
+transmission
+Institutional Animal and Ethics Committee of National Brain Research Centre
+ZipScore downstream+ZipScore upstream
+cell-free transmission
+sufficient similarity
+steroids
+birds
+personality psychology, experimental psychology, psychological risk factors, and developmental psychology
+proteins are digested into peptides
+Tumor size and lymph node status
+activates mitochondrial β-oxidation
+eight
+RNase A
+80%
+APC3, APC7, and APC8
+370 kDa
+GloMax luminometer
+98.4%-100%
+photoreceptors
+85%
+23
+more than two weeks
+prevention
+up-regulated
+MELD-Na
+Anything might go wrong
+in-hospital mortality
+protective
+the proportion of household contacts who exhibit symptoms
+NES domain of NP
+9 h
+influenza-derived dimeric peptide diINF-7
+separate reads
+32%
+the calculation is stable
+246
+September 2021
+plastid transformation
+cytokines
+direct
+haemolymph
+serum proteome profiles
+30 min
+three
+yellow fever virus and Japanese encephalitis virus
+300
+Pearson's Chi-Square test
+previously exposed mice
+relative expression levels
+coagulation, hemoglobin, and renal function
+mental health outcomes
+conceptual translations
+0.5 to 1.0
+ICD chapters or NCD categories
+L = 50
+pRSET-A expression vector
+synaptic structure, function, and remodeling in the central neurons
+paracrine senescence
+high resolution risk projections
+real-time PCR
+four
+29
+nerve conduction studies and needle electromyography
+9 months
+Movebank
+severe infection
+Lactic acid levels
+100%
+attenuated reporter activities
+25-50%
+Author names
+DP2-BSW
+cytochrome P450 enzymatic activity or cell viability
+a set of standards
+overemphasis on CD8 T cell stimulation
+LB medium
+Binding of DEHP and its metabolites to progesterone receptor
+luer catheter
+8-week-old
+V protein
+good reproduction of both the direction and magnitude of peptide expression measurements
+16 weeks
+E
+Copy number variation
+Adenovirus-derived Ad-5 vector
+hot wire anemometer
+GGU, GUU, GGA and GAA
+zfh2
+human prion protein
+49% to 66%
+16
+Droughts
+livestock bones
+random
+Toronto, Canada
+5 and 10 min
+7 days
+HISG
+24.96%
+98
+distance tolerance
+Saturated ammonium sulphate solution
+integrated
+buy bottled water
+50-100 million
+one year
+metastatic renal cell carcinoma
+miRNAs
+Understanding the structure
+Qiagen
+autophagy elongation complex
+1 year
+individual case data
+508 kDa
+Existing classification systems of relevance
+BRCC36
+107
+Data
+the virus needs to be present at a high concentration
+IELAGTLTL
+DNA fragmentation
+Melbourne, Australia
+four
+Supplementary Material Tables S2-S5
+poor
+each pig
+graphical
+ICP4 protein synthesis
+NoD web server
+several members of the mTBFV subgroup
+tissue damage of infected airways
+Foreign policy
+Influenza
+CA2 and ACTB
+twice
+Taxa
+structural and non-structural
+methacholine
+EOMA cells proliferation
+recombinant viral vectors
+Lnc-DC
+Cathepsin C
+AE PKR inhibition AE
+micromolar concentrations
+77
+94
+80,000
+High-resolution studies
+specific IgM level
+assays
+Fascaplysin
+51
+PpcD
+pathogenetic model
+male
+twice daily
+DOBV rN protein
+TC-containing wash products
+selection of resistant mutants
+fluorescent probe dihydroethidium
+Baroreflex sensitivity and autonomic function
+slightly more serum stability
+89
+Global Outbreak Alert and Response Network
+survival
+The level of significance for terms and groups
+mouse
+Saudi Arabia
+liquid nitrogen
+five
+nsP4
+Age-and sex-matched 8-to 10-weekold mice
+chimeric progeny
+veno-venous ECMO
+inertial impaction
+bacterial transmission
+recruitment of Egr-1 to ORF50P
+TMPRSS2 and HAT
+DotKnot-PW
+high titer of DENV antibody posi-tives
+log-normal
+IgG
+2004
+CAP
+TOPORS
+MaR1
+heparan sulfate proteoglycans
+arresting of mitochondrial motility
+most of the ORFs of a phylogenetically isolated virus
+optimized regression parameters
+9.6%
+ticks
+infectious laryngotracheitis virus
+combinatorially barcoded
+ISI Web of Knowledge
+smallpox
+colistin and temocillin
+T-cell reconstitution
+Recombinant EBOV glycoprotein antigen
+Base compositions
+0.1
+CRTC2
+by measurement of the eGFP expression level
+specificity of antibodies to the corresponding peptide
+their own context
+different mobility and travel capabilities
+uptake of SP and endosome acidification
+iteratively finer
+TDP-43
+Omadacycline
+polymeric immunoglobulin receptor
+Understanding the epitope-based antibody-mediated neutralization
+another individual is randomly chosen
+robust antibody responses
+highly trained personnel and undamaged mosquitoes
+MUpro and iStable
+69.7%
+62
+25%
+fire intensity and postfire climatic conditions
+compounds
+7
+manufacturer's directions
+10 ll
+mRNAs Dissimilarities
+Ct values from realtime RT-PCR
+clinical
+Ellis and Ramankutty
+binding of Spo0A-DBD
+twice
+Thyroid transcription factor-1
+Cx3cr1
+Venturi masks
+an elongation reaction of three steps of PCR
+larger animals
+colostral
+0.7%
+22
+thoracic
+QIAamp DNA Blood Mini Kit
+SFSV and PTV
+STAT6 activation
+20 µM
+providing
+D4, D5, and D6
+JEV infection
+DAPI
+Zeta potential
+surveillance of wild birds and LBMs
+Evaluation
+Brazil
+Computational docking operation
+DLMO
+LC3 conjugation system
+␥
+random hexamers
+organic fluorogenic ligands/probes
+100%
+state estimate
+Ubiquigent
+1969
+transfection with the kahrp knockout vector
+The algorithm
+Table 4A
+expression of surfactant-associated protein A and AQP5
+three
+B.Chiranjivee
+Viral persistence
+A site s *
+drug abuse and prostitution
+Viral RNA
+30 minutes
+miRDeep2
+contact timing details
+monocytes and macrophages
+serum markers of brain injury correlate well with the extent of CNS damage
+Bands corresponding to HeV G and NiV G
+70%
+over 50%
+complicated, severe, and fatal
+IPS-1-dependent RLR signaling
+1 ml of DMSO
+10-100 mM
+mutational pressure
+0.5-1 h
+situations in which a genotype becomes dominant in an evolving population
+easy preparation, biocompatibility, inertness, and intense light emissions
+Syrian hamster/Andes virus lethal disease model
+water
+does not change
+All risks included in the Summary of Safety Concerns regarding MEs
+higher human mobility
+differential activity in induction of ISGs
+Responses
+5 mL of the RT-PCR product
+hydrogen peroxide assay kit
+lentiviral titer
+bronze-standard data
+TatN12
+10 6
+bacterial non-coding RNAs
+asymptomatic
+drug-metabolizing enzymes
+site-directed mutagenesis
+MxA
+Kaposi sarcoma and non-Hodgkin lymphoma
+three
+cyclin A expression
+hearing loss involving mid-high frequency
+26%
+44.241 µM
+55
+informational privacy
+interaction model
+three highly ordered stem-loop elements
+Ebola, MERS-CoV, and now Zika
+Biological systems and processes
+hepatosplenic
+picoliter scale sample injection volumes
+highrisk agents/toxins
+infectious diseases
+31%
+inflammatory
+lipid
+the stalk domain
+non-linear
+one-way ANOVA or Student's t-test
+U2OS or HeLa cells
+68
+substantial heterogeneity in repeated vaccination effects
+Y148
+tyrosine phosphorylation site
+neurologic disease
+a tool to manipulate and analyze high-content screening data
+biofilm formation
+the gp1 alignment
+IFN-induction and RNAi by shRNAs
+4,158
+high neutralizing potency
+367
+candidate vaccines
+saturable quenching of benzoquinoline fluorescence
+56%
+125
+28.2 to 67.4%
+K0.2 to 0.2
+Five
+3
+48 h
+Supernatants
+linear curve
+nucleotide sequences
+scarcity of available data
+IFN-c
+8-pCPT-cGMP
+an alternative mechanism
+one million
+classical methods
+antitermination
+V920
+progeny accumulation
+common naive T cell precursors
+reverse transcription
+doctors
+PTGS
+poor satellite geometry or multipath signal errors
+Nine
+January 20, 2020
+Ref. 25
+Bayesian
+probes with reverse complementary orientation
+totipotent zygote
+via an amino C12 linker
+sodium cyanide
+fluorescence
+1/100000
+antibody phage display technology
+anion gap
+GraphPad Prism
+69
+Chongqing City
+12 weeks
+damaged tissues
+Biochemical
+250
+medical applications
+yearly
+GATHER
+High flow
+human papillomavirus
+low XC titers
+5 to 30 ml
+improved dystrophin diaphragmatic targeting
+the infection of Ebola
+the binding energy
+stable
+older
+the signal
+VLP
+pemphigoid and linear IgA
+virus replication
+transjugular
+GraphPad Prism 5.0
+24 hours
+Okadaic acid and GW5074
+1000
+596
+renal cell carcinoma and imatinib-resistant gastric cancers
+2016
+CD4 + T cells
+30 μg
+0.3 ng/mL
+efficient TRIM21 activity
+Boyden chamber migration protocol
+time to peak viraemia
+virus shedding
+Northern blot analysis
+HI metrics
+Projections of income per capita
+Defects in potassium channels
+immunofluorescence
+higher
+Type I
+0.97
+polymyxins
+labellings
+seven
+four
+excellent
+Horizontal dotted lines
+one professor
+high levels of QN resistance
+US-granted
+Environmental contamination
+40-50 times
+Sequence diversity
+MARC-145 cells
+7
+covalent
+extensive uptake of surfactant
+safety, efficacy, production and costs
+Body temperature
+4 days
+14 days
+number of contacts, length of stay and contact tracing
+salt-sensitive hypertension
+prostate
+disruption
+NanoDrop spectrophotometer
+receptor levels on the target cells
+EGR1
+Advance Purchase Commitments and other financial innovations
+SEC and glutaraldehyde cross-linking
+5 L/min
+African countries
+Empty EL4 targets
+22%
+EVD preparedness
+IFN-c
+tripeptide sequence RGD
+influenza A virus
+cell differentiation, phylogeny and RNA stability
+common parasites of camel and dhumba
+adipocytes
+4 hours
+combination therapies
+Anti-GALT serum
+21
+Herd size
+Protégé
+50%
+CD16 and CD66b
+Half
+respiratory mucosal cells
+CAST, PWK, and WSB haplotypes
+VER-155008
+shape parameter alpha
+DNA amount
+Seven-valent PCV vaccine-serotypes
+Data Snapshots
+poorly differentiated/stem cell phenotypes
+H antigen motifs
+lower macrophage protection
+uppercase
+25%
+Positive RT-PCR results
+L protein
+Ag concentration on target cells
+VP40 and GP
+Deionized water
+Outbreaks
+R t values
+cDNA
+4
+Antibody-mediated neutralization
+12/69
+a voucher for the local Farmer's Market
+IL-12p70
+immunoprecipitation with normal mouse IgG
+inhibition of RNA transcription
+via lentivirus transduction
+Foxp3 + CD4 + T cells
+by recording only patient date of birth and gender on the data collection form
+Tours, France
+ADAM17
+20%-40%
+miRbase and MetaMirClust
+comparative approaches and single sequence methods
+accountability, ownership, cultural engagement and diversity
+other criteria
+low-income countries
+organelle membranes
+antagonistic activity
+capability maturity model
+17,129-27,659
+two epidemic periods
+IFN-stimulated gene 20 kDa protein
+extracellular SOD
+Core body temperature
+Stress granules
+CypA
+classical methods of microbe discovery
+Bone marrow
+DNase/RNase free water
+plasmids encoding the HIV-1 Env
+Protein subunits in S-layers
+3308.5 g
+oxidizing conditions
+TD20/20 luminometer
+1 717
+aggregation of over 70% of total protein
+Specificity
+genome-wide
+p33
+translation elongation efficiency
+TRAF3 and TRAF6
+regulators of cell proliferation
+Stabilized Matrix Method
+population structure
+ducks
+enteropathogens, oncogenic viruses, and other respiratory pathogens
+C3aR
+14
+toilet facilities
+Loss of INPP5A
+discriminative metabolic features
+imperfect sample purification to eliminate eukaryotic nucleic acids
+WOR1F and WOR1R
+anti-gp120 Abs
+10%
+poor outcome
+type 1 and type 2
+PPARγ activation
+evolved dramatically
+toxin inactivation
+strategies for enhancing social distancing
+Eight
+PPV
+macrolide resistance
+LLPS
+CD4 ϩ T cells
+1/μ H,V
+from onset of pneumonia to onset of ALI
+S1P
+residues 1591-1605 of VWF polypeptide
+three
+WHO Global Health Estimates
+GLUT4
+RNA granules
+293T cells
+48 h
+Anti-β-actin
+affinity maturation
+US Environmental Protection Agency
+Raw animal blood
+realtime turbidimetry
+trends over time
+anticoccidial efficacy
+66.5 ± 5.4 kg
+dashed lines
+nucleotide position 2282
+4 days
+Normalized
+changes in S codons
+Between 500,000 and 700,000
+the cell cycle
+Expression Array Manager
+Five
+inhibit NK cell function
+address these issues
+Maurer's formula
+vaccination-induced effects on the immune system
+major histocompatibility complex, class II and IGJ
+Du et al.
+cyanobacteria
+APACHE III
+GenScript Inc
+cc-by
+dko mouse
+1988
+Serum samples
+Culture of nasopharyngeal secretions
+In vivo transduction of satellite cells
+PPRV H
+SEM
+a panel of time-ordered GII.4 VLPs
+active surveillance
+emulsion PCR
+sustained induction of NF-κ B
+GenBank
+hypodynamia, nausea and thrombocytopenia
+distance
+a week
+Determining the level of microalbuminuria
+generalized epilepsy and inherited epilepsy
+three
+seven
+pathogen
+Infant immune repertoires
+type I IFN
+66.67%-100%
+5,500,000 to 11,700,000
+DNA strands with different domains
+80%
+Lessons learned
+laboratory support
+residues K160 and R298
+a stable karyotype
+severity of disease
+Ethical Committee of Hospital Clinic
+confidence intervals
+87%
+prototrophy or nourseothricin resistance
+A1AT
+adenosine-dependent fibrosis
+10%
+SLY and RBMY
+866
+pIRES-Rgp
+70-80%
+rapid killing and a wide range of activity
+244
+Agarose gel electrophoresis
+The effect of reticulate evolutionary events
+recombinant viruses
+23.0 ± 13.3
+GeoChip 3.0
+cardiology
+9%
+URI
+it becomes inconvenient when organism number gets enormous
+665 μM
+phage-related
+four
+NPC1 ϩ /Rab7 ϩ vesicles
+Isoform 1
+RSV subtype
+they are not filtering layers
+bone erosion
+binding site comparison
+Correlation analysis
+O
+cathepsins
+Nairoviruses
+helical conformation
+H5N1 pathogenesis and therapeutic and prophylactic development
+30 ug
+Geometric means
+2014-2015
+Murine embryonic stem cells
+mathematical models of infectious disease epidemics
+Poisson
+high salt concentrations
+23
+Three
+an increase in the number of elderly people with tuberculosis
+progressive consolidation
+35
+to identify risk factors for the susceptibility to RTIs
+66%
+ImageJ or FIJI
+syndromic
+January and February
+Error bars
+20.5%
+2 weeks
+alternative health care providers
+sudden onset of fever, nausea, vomiting, weakness and jaundice
+Interstitial lung diseases
+lack of effective prevention or treatment
+recombination
+other proteins
+gram-negative pathogens
+Table A1
+E. coli BL21 cells
+inflammation
+seven
+microvascular endothelial cells
+Primary NHBE cells
+TLRs and NLRs
+differences in husbandry practices and herd structure
+initiation of ART
+selective proton line broadening
+microchip-based
+CPU-and memory-demanding
+four
+nucleotides +10, +11, and +12
+Over 800 000
+260±98 μmol/l
+ground-glass opacities
+structural integrity
+153
+eGFP pos -CC10 low cells
+acute respiratory distress syndrome
+pleural effusion
+A threshold of 13% divergence on VP1 nucleotide sequences
+P<0.05
+Elke Muhlberger
+Lab software
+10%
+N2
+predisposition biomarkers
+stable hydrogen bonds
+ScriptSeq v2 RNA-Seq Library Preparation kit
+g i~g
+TNF-α and IL-1β
+amino acids
+H120
+36%
+The PLPIHS framework
+Kit W-v -+/+
+a rigorous expert panel reference standard
+severe dehydration
+Forty-nine
+how to identify the selectivity ratio of the receptor subtype
+5-HT
+5.2%
+four
+does not result in consistently and significantly increased toxin levels
+Conserved regions of disorder
+Both data sets
+Macrophages
+14%
+workplace policies
+Identification of relevant interacting proteins
+2 μl
+antiviral use or the use of face masks
+gene expression
+Asia
+55%
+Drug likeness
+PubMed
+,45 amino acids in length
+C9 and E8
+33 days
+sister
+three
+the local environment
+89%
+NS1-27
+Budapest
+MGB modification
+unconjugated anti-RANK IgG
+neutral
+Molecular dynamics simulations
+numeric integral
+3
+organ lysates
+stomach probe
+yellow
+increase
+a predicted loop of 7 nt
+publishing this work
+29 years
+Complementary positive stranded RNA
+1980
+Pseudoknots
+60
+Predictive performance
+regulating the function of DCs
+9.3 days
+IL-10 and SOCS
+integrated framework
+5%
+667
+root, bulb, stem, leaves, flower, and anther
+IFN-α
+positive associations
+twice
+87%
+four to six
+29%
+binding to dsRNA
+~83 weeks
+inconsistent
+Tri-color flow cytometry
+Dr. Hong-Bing Shu
+R III 0
+exon skipping
+DNA
+physiological
+manufacturer
+1.7
+alters blood hemostasis and sustained leukocyte activation
+ELG1
+standard deviation
+S. Guerra
+infected neurons
+ISG15
+blue-white screening
+ferrets
+six
+most sequences had no hits
+70.6%
+the host
+HepG2
+biodegradable PLA nanoparticles
+Genome-wide
+predictions based on the Richards model
+nucleolin
+clonal loss or clonal dysfunction
+compressed file
+1 h
+safe communication
+ATP/P2 receptor/CaM
+molecular biology and biochemistry
+microtubules
+less than 5 M
+Western blot
+B. anthracis-derived peptidoglycan
+inside the nucleus
+kallikrein levels
+NFE2L2
+JAM3 and CLEC14A
+12
+2A and 3C
+pneumonitis
+relative concentration
+milk yield and ovarian function
+cystic fibrosis
+DENV3
+AS03 A and AS03 B
+Disease transmission models
+10-100 nm
+IL-15
+Farmers
+Adenoviruses
+within normal ranges
+a branching process
+linear regression
+transcriptome
+vertical diplopia
+yeast to mammals
+LASV and ML29
+Hospital de Clínicas, Montevideo, Uruguay
+AB462810/007Lm-1vp
+Dromen van vaccines
+0.5%
+Six
+macaques
+Seven
+1.6%
+the mean
+IV infections
+symptoms
+centrifugation
+Ecuadorian
+5
+atf-6, pek-1, and ire-1
+curcumin
+malaria
+pneumonia
+the ratio of the foreground to background median intensity
+4.91
+COLDAIR
+exceptionally severe
+adjacent cells
+text analysis
+stronger IgG titer and higher IgG/IgM ratio
+14 days
+2 %
+oxygen use
+Genomewide
+chimeric polyhedra
+CpAM-induced structural changes
+organisms
+disease in swine
+H5N1
+marmosets
+Smoking
+Human astroviruses
+the disassembly of HPV16 capsids
+Fatty acids
+aENaC
+trachea
+863
+513
+fourteen days
+three
+Thresholds for undertaking testing both in hospital and in the community
+toothpaste
+10%
+Serial dilutions of MAdV-1
+allantoic fluid
+3 × 10 5 cells per well
+two months
+NGO0326 and NGO1577
+viral-encoded antagonists of the immune response
+the best fit of the GGM to the data
+a capsid protein
+VP2
+rounded down to the nearest integer value
+three
+rotavirus infection
+Orthobunyavirus
+hostspecific adaptations
+proinflammatory
+neuroepithelial
+Near half
+TM fusion peptide binding
+cc-by
+mediates self-assembling of liposomes
+morphological and physiological
+viral RNA
+transdisciplinary
+five
+cc-by
+Disseminated intravascular coagulation and acute respiratory distress syndrome
+mean ± SEM
+3%
+heterogeneity
+26.4 nm
+Alpha diversity
+the following pattern
+15 min
+proinflammatory
+60%
+60%
+2019-03-05
+fluorescently conjugated monoclonal antibodies
+least-square fitting methods
+Colonic contents and feces
+inflation of test statistics and over-confidence in parameter estimates
+Transcriptome and proteome
+no cross immunity
+24 to 48 h
+5th century BC
+public health spending
+Root mean square error
+>1.00
+inhibited
+nine
+1.0 ng/mL
+Two
+IPM-infiltrating cells
+more than 100
+SIGLEC6
+The average value of the negative controls
+VIM
+Haploview
+Zero Truncated Poisson regression
+Serotype A
+Peptide surface accessibility
+Reagent compatibility
+disruption of the tetramerization motif
+corticosteroids
+insurgence of resistance
+G and SH
+a new infectious disease infrastructure
+comorbidities, different ages, and different life experiences
+wild type infected mice
+5 h
+miR-192
+Get4 and Get5
+HA and NA
+γ-catenin
+40.0%
+ILD
+days 11, 12, 22, and 23
+RBC lysis buffer
+H3 methylation
+stems
+sections
+outside the nervous system
+five
+55.1%
+sequence similarity
+Tetramerisation
+plasmid DNA or A20 cells
+weekdays
+d 0
+the variables suitable for Cox's multivariate proportional hazard regression model
+CHO cell system
+each GO category
+0.1%
+RAW cells
+less than 4 PFU per g of infectious PEDV
+B conjugated peptide
+1000 times smaller
+anti-DOCK2 and anti-GAPDH antibodies
+albumin
+Sox 2
+fluorescence uptake microscope
+purifying selection
+cc-by
+normal saline and human albumin
+Corticosteroid use
+high workload
+Y19/Y20
+LMW SP-D
+m 7 Gppp-cap
+Suitable concentration ratios
+PacBio contig 2 and Gallus gallus v4 and v5
+membrane fluidity
+HMG-CoA reductase inhibitors
+stem cell markers
+Descriptive statistics
+conformational changes
+21-64 years
+microscopy
+R 0
+invasion, adhesion, differentiation and development
+visit hospitals
+R t
+increased hydrophobicity and positive charge
+non-vaccine type replacement disease
+133 6 32 mM
+membranes
+cytokine response
+IMG/VR
+stress experience
+Images
+to prevent slippages
+Variations in host abundance
+seven
+pathophysiologically inducible factor
+RNA
+9 days
+standard deviation
+Existing and new methodology
+generation of soluble GST-fusion proteins
+reverse genetics system
+Ethiopia
+strong polyclonal CD4 and CD8 T cell responses
+93%
+Figure 2a
+APACHE-II
+20%
+Rio de Janeiro, Brazil
+social distancing
+CentroidFold v0.0.9
+communitybased scouts
+enhance the share of patient information among healthcare providers
+21 days
+human type II collagen
+antibodies against various complement factors
+irrelevant peptide
+5.65
+an expert pediatric cardiologist
+6
+high and low estimates of vaccination coverage
+RNeasy fibrous kit method
+optimism
+hPIV3-C
+developmental
+inhibition of histone deacetylation
+cell surface expression of ABCG2 protein
+Professor Steven Webb
+more relaxed constraints
+Nigeria
+six
+False mediation
+critical care
+connectivity of groups
+1 -4 year old
+acute meningoencephalitis
+PyMol v1.1rc2pre
+HCV infection
+peramivir
+1975
+Japan
+RNase 1 PEG-derivative
+100 ml of each infectious dilution
+Hyperpyrexia
+B-cell antibody responses and T-cell immunity
+Tryptophan fluorescence
+12
+1019
+34 000
+1%
+Leptospirosis
+100%
+8
+HBV/G core protein
+Co-infection
+Total RNAs
+A useful biomarker
+Maximum likelihood estimates of p, q, and s
+CF small airways
+a coincidence
+anorexia and nasal discharge
+mm9 mouse reference genome coordinates
+high glutathione-dependent lipid peroxidase activity
+Twenty four hours
+pASP
+28 days after the third dose
+prediction and circular dichroism
+unrelated antibodies
+three
+meta-transcriptomics
+hospital levels A, B, and C
+3900
+Bayesian model
+high titers
+the sequence of the analogue 2* 3* 4* 5*
+five
+An ACI sample
+bear bile
+early prophylaxis
+NS1
+SP-A
+EK Nordwest und Zentralschweiz
+proper functioning of the Golgi
+a calibration of anti-HA to HA binding
+the full structural cassette of SFV
+Filgrastimmobilized PBSCs
+12 h
+data
+A standard curve
+the sequence of applying tools
+antiviral factors
+robust surveillance and effective outbreak investigation capabilities
+Supernatants containing infectious virus particles
+central nervous system dysfunction and acute respiratory dysfunction syndrome
+ORF1a
+every 6 months
+implant-associated osteomyelitis
+low numbers
+Sixteen
+pan-cultural
+ePCR
+dynamic strain
+À1 PRF
+Compound 3b
+6
+one-third
+1-bromo-2-chloropropane
+120
+100%
+Ethyl isopropyl amiloride
+rats and dogs
+chemokines in the lung
+Climate Monitoring, Analysis, and Prediction
+Total RNA
+Natural selection and mutation pressure
+15 min
+29.2 years
+Eleven
+MHC haplotypes
+48 h
+predicted deaths
+to adopt the geometry of a Watson-Crick pair
+Applied Biosystems Perkin Elmer 7300 sequence detection system
+Mouse Inflammation Kit
+six
+Canine TfR
+JACR 5139
+fundamental
+extracellular and mitochondrial proteins
+eIF5 and ribosomal proteins S6 and L4
+7,200,092
+Ith
+mid-to-late nineteenth century
+top, middle and bottom panels
+gap of knowledge
+viral nucleic acids
+CRTC1 protein
+complementarity determining regions
+multi-dimensional, inclusive rather than exclusive, broad rather than narrow
+MAPKs
+parameterizing the heterogeneous transmission model of infectious diseases
+Enhancement of DENV2 infection
+human 293 T cell line
+Ga-citrate
+U18666A
+10 min
+compound 20
+Prism 6.0
+RT-PCR amplicons
+viral RNA translation/replication and virion maturation and secretion
+Six
+21/102
+T-cell-based
+2.5 hours
+117
+one week
+atf-6 mutant animals
+12
+2009
+mean ± SD
+RIG-I and PKR depletion
+dysfunctional mitochondrial systems
+10 %
+Amplicon sequencing
+ADAR
+MLN-4760
+1 × 10 3 p.f.u. ml −1
+infants with acute or chronic lung or brain injury often have abnormal HRC
+MDMs
+viral clearance
+March to August 2009
+planning process
+56,365 4 = 225,460
+R 0
+4%
+ALV-J gp85 protein
+X4
+7
+NanoDrop 2000 spectrophotometer
+16 ö¥M
+11,323
+allows the growth rate to change
+60 °C
+41
+17 years
+direct co-culture
+limited access
+HCV infection
+RIVM
+fresh DMEM medium containing 100 µg/ml ampicillin
+CEACAM1
+cytokeratin-positive epithelial cells
+Motif 19
+0.112 µM and 6.897 µM
+Variances in the expression levels
+12000
+Vaccination
+gallbladder
+cell cycle arrest
+body size and/or age
+Virological surveillance
+enhances sensitivity
+actions that qualify
+678
+Leukoreduction
+Wambizzi
+Larval Xenopus
+Seven
+Ras palmitoyl transferase
+5 μm sections
+5.7%
+4%
+NHS South West/Exeter research ethics committee
+influenza
+mutagen resistance
+caused by insulin resistance in the liver and muscle
+80%
+30 min
+immature myeloid cells
+5%
+PBS
+reach everyone in the population
+subtle shifts in cell populations
+Figure 4
+CD4 + CD25 + regulatory T cells
+virus isolation
+diarrhea
+antioxidant activity
+QXXS
+syncope, weight loss, rib fracture, and pneumonia
+innate immune regulators
+the EB4
+the liver
+7
+C-lectins
+10
+diagnosis and guided puncture of pleural effusion
+156
+limitations in available data
+50% GFP expression
+cartoon
+nomogram
+apoptosis and necroptosis
+data from the paper published first
+similar
+79
+low fidelity and processivity of their polymerase
+NMR and mass spectrometry analysis
+ISGylated proteins
+Bolt LDS Buffer and Bolt Reducing Agent
+PIV LRTD
+heterogeneous microenvironment
+100%
+μ i
+Genome sequence 3908
+5 days
+circadian variations
+increases HN oligomerization
+text messages
+p10 ectodomains
+Four
+3-to 4-fold
+normal neurodevelopment
+eight
+cross-species poxvirus infection
+Luciferase signal
+a transient reduction in
+HPAI viruses
+MODS and AKI
+improving
+specific examples and case studies
+Ubc9
+Viral vector expression of the sCHIKV proteins
+liver mass and perfusate volume
+positively regulate replication of HIV-1
+cellular debris
+homogeneity
+plaque assay
+NanoDrop
+pGEM-T Easy vector
+modified HE assessment scale
+febrile illness and a high rate of abortions
+Chitinase
+C-C motif chemokine receptor 5
+guavaSoft
+universal
+Luteovirids
+3.0%
+Sia
+ECs
+117
+starvation
+degradation
+12
+Total RNA from each sample
+Recovirus
+Fluidigm Real-Time PCR Analysis software
+post-traumatic osteoarthritis
+A semi structured questionnaire
+cell migration
+maintaining electrolyte balance and blood osmotic pressure
+HBeAg
+30 min
+mediates the structural integrity of axons
+DOWNLOAD
+general pathogenic mechanisms
+suboptimal responses
+80%
+daily
+refugees, internally displaced persons and the homeless
+capsid
+lethal
+2-12 day
+Transmission heterogeneity
+1 hour
+GenBank
+firefly luciferase
+quantitative real-time PCR
+An external data management agency
+The nucleoli
+Preparedness against pandemic influenza
+cellular transcription factors
+right ventricular dysfunction and valvular heart diseases
+microbial communities
+pre-cleared protein complexes
+2,128
+Pulmonary oxidative stress and lung inflammation
+well-characterized signal transduction cascades
+Fusion inhibitor aggregation propensity
+36%
+Japan
+inflammatory cells
+HD5
+EGFRvIII
+allocating existing resources and identifying new sources of investment
+DI-72 repRNA
+AS-IV
+A case definition
+a safe and reliable testing platform
+41
+hydrolysis of MBP
+human clinical trials
+vesicular
+asthma and COPD
+retrieving unigenes sharing the high sequence similarity with flavonoid GTs
+rhesus macaque
+eukaryotic elongation factor 1A
+contact tracing
+native antigens
+5 minutes
+Farnesylation
+SHG-44 and C6 glioma cells
+a software package for mining viral signals from microbial genomic data
+stay home
+virucidal
+removing all I and D placeholders
+a residue we have previously shown to be highly conserved in all clinical strains
+8,777
+nasal potential difference measurement and intestinal current measurement
+around the site of mutation
+bronchodilator responsiveness
+Virus growth
+Healthcare professionals
+36%
+SCARB2 3 0 UTR
+individual ZIKV or USUV cDNA clones
+NIH 3T3 and M. dunni cells
+severe impairment of gas exchange and respiratory failure
+partial subgraphs of a network
+a viral reference genome
+four
+two
+68.3 to 100%
+66 mM
+colorectal cancer
+PCR primers 515F and 806R
+Bias
+1918
+conserved quantities
+43%
+Csn8 deficiency in the liver
+Cellular reprogramming
+Antigenic epitopes of pathogens
+nc F1766L
+protein/peptide
+2001
+401
+nine
+6 days
+greatest
+P. falciparum
+suicide prevention interventions
+shear wave elastography
+further research
+Coupling between patches with non-identical parameters
+further studies to decipher the genotype-phenotype interactions for peacock
+phenylalanine assay
+AF
+positive strand-specific RT-PCR
+road segments
+the sample size in this present study is very limited
+to halt coronavirus spread
+virulence and host range
+1.4 Â 10 5 /mol
+eight
+reduced FRC
+Two weeks
+pH, temperature, antibody and antigen concentration, and incubation time
+BC
+77.3%
+standard SDS-PAGE and 2DE
+diagenesis
+Loop-mediated isothermal amplification
+IGF-1
+HCV replication
+EV-A71
+Proteomics
+10
+95.1%
+neuroinflammatorymediated
+IL-28B
+clinical trials
+treatment with valgancyclovir
+ablation and cervical conization
+Flavivirus NS2A protein
+bacillithiol
+euryale
+our medical center
+conduction of monovalent cations across the Vpu channel
+Fluorescent quantitative real-time PCR technique
+19,000
+Horizontal black lines
+Wnt3a
+repressed expression
+data variability
+2009
+global
+CEO groups
+stent outer diameter
+ERAD
+different steps of preparation and comparison
+6-12 weeks
+oral immunization
+A1pp
+353
+hilar height ratio
+Contemporary fragmentation of lion populations
+XhoI
+1 h 30 min
+RanBP2
+PON1
+fresh complete growth medium
+Pulmonary
+None
+all three ProSeqs
+standard deviations
+viral RdRPs
+4.82-fold
+sequential multi-drug chemotherapy
+strains that did not transform
+Population structure
+H5N1
+identify
+35823.62 ± 3598.81 renminbi
+non-linear least squares fitting
+43
+ampli®ed DNA
+50 %
+IL13
+tissue collapse
+Equal amounts
+biological, biochemical, and medical fields
+B n
+happy people
+5 h
+integrin expression and cell adherence
+LDHA
+rhesus and pigtail macaques
+mortality
+Splenic viral loads
+eight years
+zymosan
+second-trimester pertussis vaccination
+enteroendocrine and immune cells
+30 min
+p38 MAPK signaling
+functional and phylogenetic intraspecific and interspecific components
+Cryptococcus
+increased pathogen incidence
+k 3
+the way in which Emergency Committees develop their advice for the Director General
+viral loads
+Low ROS concentration
+2017-01-03
+clinical signs and symptoms
+host apparatuses and cellular processes
+increases PR8-specific mucosal IgA levels
+antibodies
+rabbits
+genetic diversity in the host population
+regularization
+blocks the antiviral effects of ISGylation
+five
+Appropriate ratios between staff and children
+100
+bacterial colonization epidemics in military
+A bistable area
+SLEV
+The selection of optimal immunogen
+apoptosis and necroptosis
+1.5%
+serum ferritin
+showed no improvement of disease outcome
+A g i
+all packaging elements
+acute respiratory distress syndrome
+smallpox transmission
+correct trafficking of peripheral proteins
+24 h
+validation of specific reference gene
+alternative immunization strategies
+Corticosteroids
+variable posttranslational modifications
+PEDV
+Re]
+promoting good community hygiene
+GFP-Trap agarose beads
+IL-12p70
+30 minutes
+C-reactive protein
+there were no significant differences between any of the time points
+rhinovirus
+0.26-0.88 pmole DNA/1
+Better lungs compliance and larger proportion of recovered functional lung size
+SPSS
+host erythrocyte
+90
+Filamentous phage particles
+viral dissemination medium
+the public
+Respiratory specimens
+30
+49
+3.5-fold
+Ifitm1, 2, and 3
+32
+National Center for Biotechnology Information GenBank database
+over 20
+six
+Acute renal failure
+bias
+DeBosT script
+directionality theory
+carbohydrate
+animal-vector-human interface
+13
+solid circles
+epithelial cells
+subtype B
+Retroviral vectors for expression of IFITM1, 2 and 3
+homology analyses
+Helper T-cell response
+the size of the bi-stability window
+anticipation
+effective responses
+greater depression, impulsivity, risky behavior, and aggression
+dynamic temporal
+heavy edges
+false positive rate
+Nine
+siNP
+Emulsion
+March
+low GC%
+paired sera
+9 days
+to prevent death of the host cell
+within or just outside of the D-loop
+6
+individual consent
+phylogenetic methods
+19
+four
+Docking experiments
+heart failure
+λ
+transient interactions
+480 × 10 6 / L
+Viruses with RNA genomes
+Production of type I IFN
+CAIX expression on bile duct epithelial cells
+Natural Killer cells
+30 min
+Spo0A
+10
+Protein expression
+Quantitative indicators
+6 months
+6146
+20%
+greatly reduced
+linear mixed-effect
+10 copies/reaction
+HFRS incidence in China
+1%
+56SDS sample loading buffer
+65% protection
+shifts into different families of dipteran vectors
+A, B and C
+pneumonia
+all the proteins included in at least one subject-specific signature
+USP18 C61A/C61A mice
+strong positive selection
+model projections
+replication
+0.1%
+Promoter context
+experimental strategy
+KLF4
+Staffed beds
+frameshifting
+altered appetite or vomiting
+Path model analysis with maximum likelihood
+0.738
+24 h
+Phosphorylation of eIF2
+548
+PBMC specimens
+Evos
+C and D
+764
+LPS
+MDCK cells
+The Institutional Ethics Committee of Tangdu Hospital
+Lentivirus
+2005
+equipment shipping and data management
+membrane fusion
+E488 and E491
+vaccinating whole households
+false-positive results
+more than four thousand
+cytosolic
+β-actin
+buffer substitute for NPs
+4 weeks postinfection
+238.439
+viral genotype status
+72 °C
+once
+NADPH oxidases and mitochondria
+seven
+large sampling intervals and high transmission rates
+leadership
+Accession signal
+bactericidal antimicrobial agents
+respiratory tract
+10%
+cough, sputum, and chest pain
+The structure of these networks
+precise HA0 cleavage
+Magnetic bead separation
+genetics
+1000
+transcriptional activation of a p53-responsive reporter construct
+penetratin
+45 min
+5 0 -ppp
+a single mouse
+17 hour
+8
+Egr-1
+compounds
+48
+favipiravir
+immune evasion and suppression
+Specific humidity
+cFLIP
+low
+SIgA
+polyvalent
+2003
+attitude questions
+China1
+1892
+Montreal Acute Hepatitis C Cohort study
+IFN-λs
+de novo
+All data pertinent to the cloning process
+three
+exo-hASCs
+fetal myoblasts
+Gateway™ destination vectors
+pcDNA3.1-HBc
+outer sequence space
+inherent complexities
+NetNGlyc 1.0
+measurement of immune mediators
+ARDS prognosis
+6 min
+giving more detailed information about the biological context of the respective motif
+Native VLPs
+polymerase chain reaction
+5%
+expression of genes involved in cell cycle progression
+arachidonic acid
+Ultrasound images and videos
+better PPV or NPV
+one
+SEQUEST software
+Finding a live virus in a healthy bat specimen
+Supervision and feedback
+Potentiometric
+3.4%
+Guidelines for use of personal protective equipment
+rotavirus infection
+T. cati
+Van and Dogubeyazit
+analytical sensitivity and specificity
+Flow cytometric
+systemic anti-IL-10R blockade
+dry-blotting system
+macrophages and lymphocytes
+250 ms
+Dura chemiluminescent substrates
+15 min to 18 hours
+28
+320
+reproducible quantities of vaccine antigen to the dermis
+Streptococcus pneumoniae and Haemophilus influenzae
+48 hours
+to improve cell attachment
+protein metabolism, cytoskeleton, and apoptosis
+environmental exposure to lithium
+Harbin04B
+MYY
+eight
+VILI and worse outcome
+Germany
+3 μg RNA per sample
+low cost of an ED visit
+Psoralen
+Sharan et al.
+Combination strategies
+SHIVIG
+The damage of TJ
+degree distributions
+39 kDa JV 2C protein
+96
+4 h
+a DxxxLV motif
+5 -3 direction
+1997
+CPPs
+516 bp
+flow cytometry
+8.3 %
+tissue culture isolation
+using the two expression systems
+SCD buffer
+NPC1 protein
+1000, 800, 600, 500, and 300 nts
+DAVID and UniProt
+Kpax2
+LC3B localization to autophagosomes
+Highthroughput shotgun mutagenesis
+trained interviewers
+The edges in the PGRN
+eIF4G and PABP
+The topology of the reconstructed tree
+knockdown of GADD34
+7
+twenty-four
+waterdamaged homes
+genotypic fingerprinting methods
+1.5 h
+hemagglutinin
+disturbed normal physiology
+three
+influenza
+membrane oxygenator infection
+teleconference and/or e-mail
+grown enormously
+May 8, 2015
+acute infections and chronic infections
+strong mucosal and systemic immune responses
+caricatures of actual social structures
+β -actin and GADPH
+Pulmonary microvascular endothelial cells
+χ = 1
+uncertainty of alignments
+Similar results
+Sec16A
+0.2
+1
+10.1155/2014/654712
+restriction enzymes
+Diagnostic equipment
+50 %
+102
+74 µg/g FW
+elderly persons
+streptavidin-biotin amplification step
+Chi-square or Fisher's exact test
+Hemera Biosciences
+species-specific hemoglobin capture
+Chonbuk National University
+MNV infectious culture system
+lipopolysaccharide
+tumour necrosis factor-α
+alanine aminotransferase
+BMI
+surprising results
+93
+two hours
+PIKfyve
+tissue damage
+273
+48.1%
+12/1,000
+5
+The image
+Kruskal-Wallis test
+over 300 y
+arenavirus
+G43, I44 and G123
+The corresponding authors
+14
+CD8+ lymphocytes and NK cells
+explosive injuries
+72%
+The last 28 kb of the prophage genome
+1.5 ± 0.1
+mRNA expression
+IFN-β
+dTDP-43 protein levels
+70%
+H60 and Mult1
+how viral infections influence the host response
+Müller glia
+Ͻ0.05
+logarithmic
+distinctive evolutionary and transmission dynamics
+pathogenesis
+phenylalanine
+our method
+CH25H
+nucleolar interior
+Dropout strategy
+a tool
+85%
+degraded
+viral sharing between humans and all mammals
+E. coli BL21
+168 h
+7% to 9%
+IL-21
+Dulbecco's minimal essential medium
+Clostridium difficile
+psoriasis, asthma and inflammatory bowel disease
+24 h
+red blood cells
+12
+33/170
+108
+occurrences of LD
+7
+flavivirus
+48 h
+Any matrix similar to a symmetric matrix
+four
+DNA samples
+5 min
+1918
+Viral RNA-specific probes
+children and educators
+Each random set of parameters
+molecular functions and regulatory pathways
+Nine
+American Type Culture Collection
+the chief thoracic radiologist
+H7N9 virus
+B lymphocyte and other inflammatory cells
+75
+Three or more calves
+septic shock
+public health managers
+comp107981_c1_ seq2
+in vitro transcription using templates
+chemotactic guidance
+analogue
+the GB
+ATG7
+X-ray computed tomography
+multiple periods
+H 2 O 2
+Secondary structure elements
+proteases that recognise motifs that are absent in wt NSs
+SF162, VI 1888 and 92RW009
+10.1017/s0950268820000254
+BCL11A
+120
+Thirty-one
+Fig 5D
+Further studies with larger sample sizes
+fungal fragments
+lower respiratory tract disease
+M. pneumoniae and IBV
+highfidelity
+Molecular docking
+Sequencing
+January 2008
+quantitative PCR
+Twenty
+release
+30,000
+increased
+1:20,000
+Inspection of the median and IQR of the y-inflection point
+Evolution
+Protein folding and response to stress
+fusogenic
+ciliary motions
+10
+NK cells
+Polly Roy
+18-20 hours
+70.4%
+Sequencher 5.0
+five
+vacuette tubes
+chest X-ray
+sophisticated
+relative node depth
+antileishmanial
+acetylation
+western blot
+no disruption to their shape
+four
+memory cells
+missense induced MCADD
+host proteins
+Type II
+The data
+Proteasome inhibition
+effective medium theory
+reactive oxygen species and ozone
+macrophage and neutrophil recruitment
+higher infection rates
+outcomes of infants in the NICU
+temporal trends and harmonic terms for seasonality
+a larger epidemic size
+aerosol transmission
+extracellular matrix protein production
+12 %
+Nine
+Ficoll density gradient centrifugation
+Four
+PBS
+14%
+tolerability
+100
+glycoproteins
+basic virus transmissibility
+protein a sepharose
+ρ
+more consistent
+93%
+targeting Bid
+acontextual, readily exchangeable 'units' of information
+splenic macrophages
+1-3%
+guanylate binding protein 5
+murine McCoy fibroblast cells
+5% hydrogen peroxide or 70% ethyl alcohol
+variations in sample size
+mosquitoes
+drowning effect
+= / ).
+1 µg total RNA
+an alternative frame
+14-days
+ER stress inducer
+the guanine in strand 2 is replaced by an adenine
+necessary for activity
+50%
+mutually consistent
+13
+LOF
+Colony collapse disorder KBV
+detrimental consequences
+KEGG
+four
+Cyclin-dependent kinase 2
+the type of agent and the method of its release
+UAP56/BAT1
+operator variability
+demographic characteristics and severity of lung injury and overall illness
+RNF125
+M <
+the area under the receiver operating curve
+lack of information
+2.39
+high sensitivity
+sphingolipids
+long-term effects on workers' health
+13
+1TAE-Mg buffer
+SR proteins
+0.64
+academic purposes
+rare human serotypes or non-human serotypes
+therapeutic
+acute respiratory distress syndrome
+Sanger sequencing
+the patient
+Arg-Ser
+age-, and in some strains also gender-dependent
+the hospital billing office
+Duck enteritis virus
+therapeutic studies
+regulation of RNA replication and virus assembly
+rabies outbreak samples
+synergistic
+HGF, FGF-basic and VEGF
+residue 4
+85
+6.4
+APACHE II, SOFA, and MOSAIC methods
+study personnel
+Gancyclovir
+Réunion Island
+Gene-start
+100 µL
+cell culture samples
+E. faecalis
+virus transmission strictly based on epithelial modes
+infectious pulmonary tuberculosis
+phase contrast microscopy
+5 μl
+TTF-1
+the transmembrane region of NPC1
+partially missing data
+assembly-defective Gag multimerization
+>60%
+Nano-immuno stimulators
+isoxazole
+35
+20 μ L Protein A/G Plus-agarose
+Three
+30
+15
+PrimeScript TM II 1st Strand cDNA Synthesis Kit
+Twenty-seven
+One unit
+50 beats per minute
+119
+85%
+cRNP formation
+IDO activity in astrocytes
+black grain
+pKa groups of the side chains
+GMTs
+evolution
+BigDye Terminator v.3.1 Cycle Sequencing kit
+homology-dependent methods
+2054
+Pairwise interactions
+IRF-1
+6-Azauridine
+housekeeping proteins
+Fuji LAS-4000
+30 minutes
+11
+cloacal swabs and blood samples
+a technique that allows a computer to recognize and analyze human language
+959
+individual records of all hospital stays
+50 pmol
+fecal samples
+24 hours
+primary targets of the underlying pathological processes
+centrifugation
+Antioxidant activities of the extracts
+Australian and New Zealand Intensive Care-Research Centre
+not being better informed about diseases
+endemic prevalences
+splenocytes
+external validation
+three
+Two microliters of sequencing reaction product
+BP-MS
+interaction with an ICAM-1-like molecule
+senescence
+acute kidney injury
+DAMPs
+apoptotic
+isolation and quarantine
+24 hrs
+the switchover position on the receptor RNA
+1,232
+effective long term inhibition against influenza A virus replication
+an HA tag
+force-field-based methods
+0.2 μm
+an extra translation product appeared
+two
+Leptopilina heterotoma
+graphdistance
+airways
+AgI/II proteins
+mitogen-activated
+muscular training
+SSM or LSQ
+level 2 biocontainment facility
+contact avoidance
+popular internet sites
+Treatment at 24 HPI
+phospho-Tyr
+The diagnosis of PRRSV infection
+weak signal intensity
+E. necator DNA
+two tetherin variants
+ORR
+Secreted LOX
+Aversive
+bicinchoninic acid assay
+Partial BglII digestion
+toxin domains
+astrocyte
+differences
+late endosomes and lysosomes
+Two
+four
+Global budgeting
+read-through of premature stop codons
+Hemolysis
+ENC
+diaminobenzidine dye-kit
+50 ml
+T cells
+Carrageenan containing nasal sprays
+computational subtraction
+dendritic cells
+high efficiency and stable knockout
+means ± SD of three independent determinations
+sensitivity analysis
+to induce a strong ER stress response in mosquito cells
+Global Virome Project
+Monitoring heparin regimen
+10.1371/journal.pone.0138138
+Edward Jenner
+10.1128/mra.01085-19
+multiple Br U residues
+viral evolution
+further analysis
+TBK1
+knowledge about glycan-binding properties
+two
+H2-Q10
+16 hours
+German hospitals
+Protein Sciences Corporation, Meriden, CT, USA
+2,253
+FIB-SEM
+Additional scenarios shaded grey
+in vitro assays
+the urgency needed for guidelines to be developed
+S n
+gene expression level and codon usage bias
+attenuates
+hexadecane
+several hundred
+E15
+53
+7 days
+EMCV and CV luciferase expression
+withdrawal of care
+90%
+20%
+over 4000
+71625 ng/ml
+35%
+an additional method to assess DNA repair capacity
+Positive reaction
+26,895
+DI/II H244A
+Applying machine learning techniques
+nine
+intracellular stores
+activation of the cascade systems
+new strategies for controlling FTLSV
+Candida and Aspergillus
+L.inn::vgc infected mice
+Large felid leukoencephalomyelopathy
+to formulate protein sequences
+Colour intensity
+fourfold
+0.5%
+more complex
+increased AR expression
+Protein-protein interaction patterns
+c n = C n /M n
+serum samples
+28%
+Nuclear Extract Kit
+kindergartens, primary and secondary schools
+hegemonic neoliberal socio-political pressures
+vasopressin and analogues
+Pathogenic
+LRF regulation of a truncated MBP promoter
+MD progression
+520
+Thermo Scientific
+puromycin
+Statistical
+p 1
+twice
+RHPA pseudovirus
+three
+95%
+11 respiratory RNA viruses
+reporter-expressing pseudoparticles
+Three
+29%
+TMPRSS4
+40-90%
+Lung and kidney
+XDS
+structural standards
+The height of the patients
+head-to-head
+CD4 T cells
+degree distributions p and p
+29
+S 0 and S ∞
+zymosan ALI
+15
+Pneumonia
+hospital acquired pneumonia
+16.9 o C
+Humira
+activating PKD2 and p38 kinases
+peptide sequences
+monitoring of those emergent strains with a shorter infectious duration
+The interactions of bacteria with the cell-expressed receptors
+tobacco control, sexually transmitted infections, Aboriginal health, and vaccination
+decreased viral load in hepatitis C virus infection
+Attribute weighting models, artificial neural network, deep learning, and decision trees
+16
+10 min
+Inactivated vaccines
+dalargin and PEGylated nanoparticles
+Drug-induced haemolysis
+Image J
+Reads with multiple reported alignments
+processing speed and sensitivity
+South-to-South migration
+relevant email contacts
+biological
+dry AMD-like pathology
+64.1%
+Reactive astrogliosis
+ΔG u 0
+how their driving, and thus their fuel consumption, impacts the environment
+simultaneously identify and subtype multiple respiratory viruses
+100%
+multidrug resistance
+20 days
+upregulation of Mcl-1
+4¢ 6-Diamidino-2-phenylindole
+adenovirus VA1 non-coding RNA
+Ahlquist
+FPASSA
+38
+inhibit
+flux balance and downstream routines
+Altered PR dimerization kinetics or activity
+skin and fur
+3 hours
+9
+27 June 2016
+RBC transfusion
+Microstrain
+Ca2 + -dependent
+summer and in the winter
+262
+viral
+monoclonal high affinity memory B cells
+0.05
+A421V
+Lysosomal dysfunction
+proteolytic
+preparing
+albumin levels
+MASCOT 1.9 search engine
+aged domestic and non-domestic cats
+Pneumonia
+350 ± 110 nM
+enzyme labelled immunocomplexes
+6 NU50CK000410
+zone of inhibition
+semi-quantitative
+Immunosuppressive therapy
+HIV
+docile behavior
+ISPM-36
+one year
+Cumulative NO release total
+6.6
+December 31, 2019
+8 four
+Prospective trials
+30%
+cardiac protection
+50%
+220-234 and 267-276
+consistent estimates
+Ranksum
+Chest/abdominal/pelvic
+sodium sulfite
+noteworthy
+Norovirus
+14
+Abundance
+aerosol or respiratory droplet transmission
+developing anti-cancer drugs
+DC
+Nineteen
+every two weeks
+200.6%
+nasal mucosa, lung, and brain
+20-30%
+0.787
+N-glycosylation pathway
+robust z scores
+198
+five
+cDNA derived from 20 ng total RNA
+complete knowledge of pathogenicity and deep research of efficacy
+white powder
+Statistica
+viral capsid proteins
+limited drug supplies
+population entities and mixing groups
+Correlation analysis
+to allow the calculation of topological properties of phylogenetic trees
+a cluster file generated using 270 samples from Hapmap2
+blockade of Ang II action or Ang- supplementation
+Significance
+shoot regeneration
+BioEdit software
+E-E dimer
+RBC transfusion
+75.25%
+all the class V, D and partial class R nodes
+different methods
+acts as an inhibitor of Nox assembly
+national and/or local organizations promoting animal welfare and responsible pet ownership
+late 1990s
+mucosal splashes with saliva from primates
+torsional restraint model
+Urine samples
+plaque assays and qPCR
+vaccination records of pilgrims
+76.8%
+10 to 70%
+facemasks
+a series of mass/charge ratio peak clusters
+AT-II cells and Club cells
+Nucleoli
+Monophosphoryl lipid A
+33
+Hemocytometer
+each modeler focuses on an individual area
+65%
+7-12 days
+Sir William Leishman
+within the epithelium
+more than one state variable
+acetylcholinesterase
+27.5%
+TLR9
+hemagglutination inhibition
+active infant immunization
+point-of-care lung ultrasound
+homophilic interactions between fulllength CEA proteins
+45
+hybrid -physical/digital -strategy
+Institutional Animal Care and Use Committee
+alleviating rheumatoid arthritis
+epoxygenases
+nontuberculous
+Fisher's exact test
+Normal distribution of data
+primary mammary epithelium
+HA16-5 and NZ-M16
+Aneurismal subarachnoid haemorrhage
+haptoglobin and apolipoprotein A-I
+When all inclusion and exclusion criteria are verified
+sample clustering
+Ads
+56 years
+Speed of deamination
+6 h and 18 h
+47
+ER stress pathways
+oil-degrading community members
+Antibody-mediated passive immunity
+viroplasms
+Twenty-eight
+vector-induced insertional mutagenesis
+5%
+Baptist Missionary Hospital
+98
+coelenterazine-h
+temperature, relative humidity and absolute humidity
+a week
+the discontinuation of drug therapy
+5 minutes
+HMBS
+GGA
+Human bronchial epithelial cells
+knowledge
+1,245
+urinary vanin-1 and NGAL
+Dendritic cells
+Table 1
+1 h
+which actions to take and when
+central China
+Mongolia, China, and Africa
+advanced PCs
+48
+an expanded tRNA pool
+27
+wild-type FUS
+20%
+10%
+endothelial function
+heparan sulphate and chondroitin sulphate
+ribosomal biogenesis pathway
+alveolar
+7.0
+Mutations within the WT GPC
+Biospecimen research programs
+Costar Highbinding 96 well plate
+Arg50
+the police
+limited receptor distribution
+SMP values and medical comments from doctors
+4
+passage through the late endosomal compartment
+RT-qPCR assay
+poorly understood
+Hawkes process and the Bellman-Harris process
+five
+active site water
+anti-and pro-phagocytic
+the foreign gene
+SDS 2.2 Software
+Sf9 cells infected with NPC1 domain A baculovirus
+17
+Discovery Studio 2016
+translational medicine
+added restriction enzyme sites
+RBC lysis buffer
+emergency medicine
+chronic inflammatory
+SARS and H5N1/97
+RNA
+CAPN1, CAPN7, CTSL
+transcriptional mechanisms
+LC3
+Levene's test
+Crucell
+8 days
+Bio Med Central
+Viral-induced cytotoxicity
+six
+345
+Cytoplasmic leakage of cathepsins
+effectiveness of the 2014/15 influenza vaccine against the A epidemic strain
+DNA/RNA shield
+transmission, establishment of sustained viremia and disease development
+specificity adaptors
+death
+CALCR and ADIPOQ
+Further information on research design
+increase control over the viral threats
+Rapid depalmitoylation
+bright field microscopy
+eleven
+by consensus and a third reviewer
+Five
+Renal involvement
+N = 6056
+long-term risk reduction
+17.0
+shorter
+Antigen/peptide specific immunotherapy
+3'-to 5'
+bacteria, fungi, protozoa, and viruses
+integrating these experimental resources
+40 out of 64
+false spike of reports
+malignancy
+two
+late stages of flux
+dilute suspensions of cylindrical rods
+downstream procedures
+waypoint stations
+Aspergillus fumigatus
+61
+Cross entropy
+within the structural coding region of the viral RNAs
+changes migration
+ISGs
+inflammatory
+amplify sequences spanning different exons
+respiratory failure and mechanical ventilation
+intravenous
+53.4% identical
+Radix Salviae Miltiorrhizae
+two
+Hemorrhagic fever with renal syndrome
+logarithmic values
+ZIKV
+Worksite immunization
+Deleting two different regions
+a toxin
+pCMV-Myc vector
+RNA tertiary interactions
+Eluted DNA
+overexpression analysis
+yellow
+Chicken Line 15I5
+fever-CT and fever-DR
+0.9%
+40
+within-host spatial structure
+type II
+17
+finding an appropriate immunogen
+12
+35 mm glass-bottom
+almost 60 years ago
+phycodnaviridae
+2% agarose gel
+SOFA scoring
+Bio-metric data systems chip
+Welldesigned
+excess monthly all-cause and respiratory-related deaths
+Nsp2
+hypoglycosylation of LASV GP
+low pH
+total RNA of synchronous parasite culture
+Laboratory tests
+PC5-2 bound to NSCLC cell surface
+one
+dendrograms
+N220HHDpBudCE4.1
+preventing contrast-induced nephropathy
+humans and swine
+HIV-1 protease
+Mesenchymal stem cells
+-3.34 Å to +3.68 Å
+Enrichr and STRING
+18
+2 months
+μ
+tubulin or actin-related components
+The spectrum of ThT alone
+N phi and N pho
+Gadolinium
+SAC j
+gentamicin
+Astrobiology
+ferrets
+PRBCs and WBCs
+full genome sequencing
+Respiratory syncytial virus infection
+85
+secure
+Serum samples from 77 healthy volunteers
+MS8MS8/RF3rf3
+BL21 Rosetta pLysS strain
+accuracy
+84
+219 to 221 amino acids
+USP18 C61A/C61A
+kinetic
+anti-inflammatory
+high control
+Jumia.com
+disease surveillance
+greater than 0.99
+12
+human FccRII
+overspecificity
+2MEM
+survey design and sampling weights
+67
+counts the occurrence frequencies of all 16 segments
+0.3%
+NanoTemper NHS NT-647 labeling kit
+10%
+Mycoplasma gallisepticum and M. synoviae
+generation of negative and positive ions
+12.5 mg
+Scores
+introduction of vasopressors
+antiinflammatory and immunomodulatory approaches
+decreased
+existing literatures
+systemic thrombosis, emboli, or circuit clotting
+bat SARS-related coronaviruses
+heart failure
+IgM natural antibodies
+10%
+Drug efficacy
+375
+five
+1,894
+Ginsenoside Rb1
+stakeholder vetting
+wheat, maize and chicken histone H4 genes
+F 2
+medium
+DIVA-GIS
+5%
+health-seeking behavior
+Sangon Biotech
+avian influenza A virus
+NNAlign
+preexisting disease
+chicken cells
+13.7 ± 5.7 weeks
+18%
+follow up and referral services
+15%
+notification database
+human reactions
+threading algorithms
+Normalized Shannon Entropy
+ApaI digestion
+135S-like particles
+HTLV-1 protein expression
+uniform cell population
+infectious diseases
+silkworm chrysalis ingestion
+graphically
+Immunoblot
+a pair of eigenvalues
+prematurely entering S phase
+X-ray diffraction data
+biochemical
+increased substantially
+four
+The site of onset and distribution of involvement between UMNs and LMNs
+Toll-like receptors
+Geminis 2-8
+Cuba
+patchouli alcohol
+8 min
+−80 • C
+χ 2 -or Fisher test
+actin-dependent
+1 h
+Red button formation
+rod-shaped
+until transmission drops to low levels
+RPA and PCR
+time
+3.7%
+Coxiella burnetii
+S100 series molecules
+TC-1 cells
+1.23-1.42
+P. falciparum strains
+stem-loop
+A protein
+Guidance
+standard deviations of the mean for each group of mice
+Kriging
+variability
+78.3% and 58.6%
+protocol adherence
+conformational states
+lungs
+45%
+tuberous sclerosis 1/2 complex
+alpha herpesvirinae
+World Association for Disaster and Emergency Medicine
+orthologous
+1 day
+3.7
+disease model
+epithelial cells
+conjugating enzymes
+Cultures supernatants
+heuristic
+10 pN
+67% c
+5% skimmed milk powder
+the protection of human subjects
+three
+unique exosomal profiles amongst cell types
+95% CI
+60-90%
+a facultative intracellular microorganism
+statistically significant interactions
+GeoChip 2.0
+fever, fatigue, and muscle ache
+Tumorigenesis
+AMPK
+Vaccination and intensive care with artificial ventilation
+18S rRNA
+tick-borne encephalitis
+6 months
+fifteen
+IFN-α signaling by specialized myeloid cells
+0.1 µl
+UTRs
+0.21 -1.50
+sea surface temperature
+Encapsidated pH1N1 RNA
+Thirty-three
+skin and eye tissues
+Hemagglutinin
+NAC-CESS
+flow cytometry
+high-density oligonuclotides microarrays
+Clusiaceae
+Infarct and border zone tissue
+glycoconjugate
+highest level
+vaccination
+enzymatic
+3a-d
+10 8 50% embryo infectious dose per ml
+7.4 and 7.1
+NAbs
+28 days
+culture supernatants
+2-3 s
+Sample volumes
+Acquiring detailed movement information
+edges
+outbreaks
+αA-crystallin
+Three
+Purified viral DNA
+HIV-1 nucleotide sequence data
+rpoB
+hind paws
+rhinovirus
+The optimal concentration of primer and probe concentration
+95
+Toremiphene and clomiphene
+summer of 2012
+446
+H1 NC 99 and H5 INDO 05
+K48-linked polyubiquitinated PCNA
+TRIzol
+E. ovinoidalis
+K114A, K115A, and K140A
+6 million
+L-arabinose
+His-tagged gHA1
+polymeric
+those mediating the protection
+2001
+boys
+4%
+small horizontal lines
+inflammatory cytokines
+AHR
+CFTR
+3
+PB2
+1.33 billion
+Polyadenylation
+26,747
+Fasta-Format
+SIS
+FUS has little charge
+Equal amounts
+HO-1 and β-actin
+dosage-dependence
+treatment for a secondary bacterial pneumonia
+significance
+12
+structural changes
+48 h
+scientifically
+3,000
+OATP1B1-mediated
+FRT, IEL, and LPL
+three
+investigational influenza vaccines
+50 μL of Ultra-Pure™ DEPC-Treated water
+A panel of short peptides derived from P5
+PR and ROC
+DTNF1 to DTNF7
+Mathematical models like InfluSim
+viruses and tumors
+Z-FA-FMK
+tiletamine and xylazine anesthesia
+112
+100%
+NLR family pyrin domain containing 3
+local translation of ACE2 in affected organs
+IFN1
+% GI covered
+Affymetrix GeneChip Porcine Gene 1.0 ST Array
+observed incidence
+chronic oto-sino-pulmonary
+virus
+Ad endosomal escape
+an experienced expert
+Amplification of the expected products
+Four
+nine
+ILI
+20 %
+Targets binding
+DNA-binding hairpin pyrrole-imidazole polyamide
+viroplasms
+10
+capturing all methods used by public health
+CypA
+ORF3
+rDNA promoter methylation
+caveolin-1
+Logistic regression
+H7N9
+SPSS 16.0
+The name and any other identifying detail
+VSEL images
+Hopelessness
+key temporal trends in polio incidence
+the Golgi
+walking and running abilities
+11,260
+Pten PCR products
+by adjusting ventilator settings
+2,200
+Companion animals
+gene expression
+host cell kinases
+higher opioid affinities and lower titers
+apoptosis
+fear of infection and illness
+MICRO-CHECKER 2.2.3
+Rv0341
+subtype C viruses
+bioterrorism
+0.2
+25 µL of the PCR master mix
+,1
+significant difference
+RNA replication
+lack of laboratory resource capacity and technology
+60 min
+Eq 1
+circular dichroism spectroscopy
+1225
+FIV Ple subtypes
+SDs
+unequal rates of evolution
+intraspecies
+immunogold labeling
+glutinoic acid dilactone
+all the eGFR equations
+IMOD
+chromogenic LAL endotoxin assay
+Clinicaltrials.gov
+92
+30 days
+GTP binds to the open form of the enzyme
+replication proteins
+Respiratory Unit
+castor
+37.88%
+attachment factors
+fast and opportunistic colonization of new niches
+disease
+Griffithsin
+eight
+PLP2 -strepII
+S. haematobium
+host response
+50 μl frozen stock
+RNase L ankyrin repeats 1 and 2
+efficiency of epitope processing
+The requirement for glutathione
+One day
+World Health Organization
+PrimeScript RT reagent kit
+labile colostral factors
+TNFα, IL-8, and MCP-1
+crosstalks between MAPKs
+IFN-γ
+C5L2
+adherent
+Tuning appropriate host response
+RNA binding proteins
+infectious pulmonary tuberculosis
+Drs. Kouacou Konan and Takaji Wakita
+many resources
+Efflux measures
+three months
+Sensitive survey research
+Receptor-ligand pharmacophores
+resistance-associated polymorphisms
+43
+5%
+cell-intrinsic control of intracellular infection
+4
+biotynylated anti-Ly-6 G antibody
+20%
+bibliometric analysis
+innate immunity
+monogenic
+Consecutive sites of inhibitor incorporation
+Folding of the peptides
+activated/transitional
+sheath and core
+increased mortality, weight loss, and pulmonary dysfunction
+21 days
+Linearity
+transcription factors, kinases, and ubiquitin E3 ligases
+Listeria species
+PAN
+57
+17
+unit cost data
+sequential
+2011
+idiotypic network regulation
+2 hours
+The study statistician
+substitution on cationic groups
+work will be stopped immediately
+5.8 days
+safety, specificity, and usability
+Anti-H9N2 mouse serum
+69Á5%
+final editorial amendments
+delivery of the polymerase genes by virus infection
+Th1
+García and colleagues
+Noteexpress
+2-3 million
+aptamers
+Epidemiological criteria
+1000-fold
+chickens
+when the estimator is not on the boundary
+travel time
+Microcirculatory dysfunction
+quarantine-free with mass action incidence
+Receptor-negative cells
+Identification of drug-target interactions
+risk
+MSCVH and MSCG primer mixes
+prognosis and diagnosis
+90%
+four conserved long imperfectly repeated sequences
+intramuscular
+70.7%
+79.7 kDa
+12
+bacterial coinfection
+20
+ferrets
+autophagy
+immune-surveillance escape
+Total RNA
+zoonotic viruses
+control reproduction number
+temperate staphylococcal phage 80α
+air-liquid
+a specific corneal layer
+viral shedding
+student's t-test
+T. gondii-challenge
+50
+Acute gastroenteritis
+20%-30%
+B. bronchiseptica
+MHV TRS
+20,000 per well
+30 min
+Two to three
+inflammation
+accessory functions
+Livedo reticularis
+JX978431 and U95501.1
+all proteins quantified
+virus-encoded
+competition assay
+everyone
+McCoy's 5a medium
+Clusters of dystrophin-positive fibers
+Albany model
+9-20 Å
+Tied values
+HCV RNA replication
+10000 FFU F-MuLV in RPMI
+phosphorylation dependent dimerization
+survival experiments
+nucleotide identities
+DICE
+1 minus the confidence limits of the relative risk
+30-40
+hands
+4% formaldehyde
+577
+control group that was treated using only a roaster machine
+cosmetics
+severe infectious diseases
+Fiji
+Proteomics
+dispersal
+Strain difference between field virus and vaccine candidate virus
+stochastic individual-based model
+21
+low HR variability punctuated by HR decelerations
+short circuit current
+six
+$85%
+experiments
+τ ij
+23.8%
+superoxide radical
+future external validation
+2007
+herpes genitalis
+full social networks at participating school and households
+colorimetric substrate
+ω-O-acylceramide
+GBD cause categories
+sizes
+18 hours
+CYBB
+dysfunction in epithelial tissues
+autocrine IFN action
+2,468
+dicotyledons
+53
+k
+10%
+I7 protease
+import their genetic material to the host cells' nuclei
+immune competence
+5% FBS
+hydrophobic pockets
+54 million
+Spo0A binding
+CD31
+28
+human interactome
+blood-feeding
+SGs
+ConSurf
+22.1%
+scavenging sites
+Protein concentrations
+eNOS
+at the slippery sequence
+Isotype-matched negative control antibodies
+post-processing
+Polyethyleneimine
+health care students and primary care providers
+15.2%
+fusion and cell-cell fusion
+PPRV
+encouraging results in the salvage treatment of mucormycosis
+34.6%
+Batypical
+basic hygiene measures
+highly consistency
+various Ca 2+mobilizing mechanisms
+heterogeneities in tree heights
+fibrinogen deposition
+To apply and assess the tools that we develop
+Copy numbers of LCMV S or L segment genomic RNAs
+barcoded primers 27F and 338R
+Pooled serum samples
+Three-day-old fungal cells
+methanol-d 4
+responses
+peptides
+choosing appropriate media channels and determining the best timing for release
+312
+Escherichia coli
+determination of predominantly autocrine IFN effects
+enter cells, migrate to nucleus, bind to nucleoli and induce cell death
+45
+microPET, microCT, and microSPECT modalities
+exponential growth model
+Six
+AGR2
+aspartic acid
+non-numeric data
+Nucleotides G 1 through C 5 and A 111 through A 118
+β-actin
+hemagglutinin
+neutralization or entry/infection studies
+nucleotide differences
+1 ml
+ST49
+80%
+Information gain
+trends
+Feed digestibility
+Cuprizone ingestion
+regression tree analysis
+statistically significant
+Humidity
+6 months
+Twenty μl CM-H2DCFDA
+tracheobronchial
+BepiPred
+antigenic and genetic analyses
+B25%
+Transmission electron microscopy
+20 minutes
+p38 MAPK activation
+three
+Decision tree
+0.2 ng
+GGT
+infect
+six
+the percentage of positive cells
+Cognitive dysfunction
+at least half a century
+mTOR
+Protease inhibitor 6
+0.5% crystal violet solution
+parents of children who were asked to go into quarantine
+Retro-2.1 and compound 25
+intestinal infection
+John Sheehan
+unknown clinical specimens with co-infection
+CAR
+16 hpi
+APCs
+crypt cells
+Infections
+contrast enhancement
+TGFβ
+East African clades
+0.92
+q~0:7
+LYS170-MET179 and LYS265-ASN274
+divergence parameter t
+peri-operative
+improving insulin tolerance
+bcyclocitral
+Univariate analysis
+phospholipids
+C and D
+to curb the excesses of government power
+blood
+HA-and FLAG-functionalized MPCs
+bicinchoninic acid method
+14 days
+daily cumulative doses of dexmedetomidine
+lung damage
+Disaster-resilient infrastructure
+102 cochleae
+parechovirus type 3
+N6-methyladenosine on mRNA
+NS1 protein function
+a linear salt gradient
+other polymorphisms in LD with the studied ones
+pro-apoptotic
+a spray of protonated ions
+Six hundred
+fear of being caught by police officers
+RAN
+flying-foxes
+non-pharmaceutical interventions
+lower values of the transmission rate t
+contact tracing
+ANN, SVM and MLR models
+hemagglutinin and neuraminidase
+1999
+78%
+atypical
+ELISA
+Homologous recombination
+99%
+WHO
+Olympus FluoView FV1200 laser scanning confocal microscope
+AMR
+activate NF-κ B
+48 h
+antiviral Th1 and CTL responses
+30% sucrose
+Grade 226
+tree age, cultivar, and horticultural care
+India
+increased
+luciferase activity
+antigenic mutation of the M2 protein
+Lyon, France
+to ensure the findings are based on a reliable statistics
+5%
+R. rosea
+ketamine and daptomycin
+pulmonary morphological changes
+Protein A chromatography
+multiple imputation
+rolling-circle amplification
+200-250 bp size selected cDNA fragments
+Individual liberty
+NM_013693
+688
+An effective disaster response
+recombinase polymerase amplification
+viremia, provirus load, and blood cytokine profile
+MNs and ZFNs
+Antigenic drift
+calpains and cathepsins
+infecting polarized HAE cultures
+several signalling pathways as deregulated
+LDH
+M1 with vRNA and NP
+catalytic function
+768,195
+Loss of air-blood barrier integrity
+Au-Ag nanorods and DNA cross-linked polymeric shell
+bacterial resistance
+Fever
+James Falvo
+0.1%
+ELISA Kits
+virulent strain
+Type A
+3.3%
+viral transmission to vertebrate hosts
+0.05%
+Peptide ligands
+expression of CD80, CD86 and MHC class II molecules
+Article 7
+20%
+18 million
+10 ml peripheral blood
+meta-analysis
+factorial
+by sequencing
+159
+enhanced
+Forty-five days
+palivizumab
+Mu Mup47
+UVC
+competitive antagonism for the TLR4-MD2 receptor complex
+2000
+4-5 weeks
+viral loads
+Vd and Cpeak
+IFIT proteins
+A & E wards
+lesions in both the spleen and liver
+medicinal
+social distancing
+interferogenic
+caspases 3, 7, and 9
+point mutation in NA
+b
+high SD value
+WR-LUC and VSV-FL
+protective immunity
+cell lysis of CHO-59C cells
+rapid fibrosis progression
+room temperature
+single agents
+PB1 T123A and PA T97I
+antibody testing
+upregulate
+DB32-6
+Sendai
+Meticulous
+visual based selection
+morbidity and mortality
+another cell
+Substrate rigidity
+an alpha helix
+recombinant Scorpine
+high-mannose-type
+Testing for EBV and KSHV
+immunological cross-reactivity
+Cardiac Resynchronization Therapy
+EI and EE aeration of the corresponding voxel
+Controlled studies
+I nfluenza A virus
+The conditions that must be met for such a gene to be discovered
+Adenoviral strains
+ILTV
+Rifampin
+any publication bias
+square root model
+1961
+RNase-free DNase I enzyme
+15-20 pN and > 20 pN
+full-length antihuman PCSK9
+RP-HPTLC
+ultraviolet radiations or redox inhibitors
+ProtTest
+system function
+Ca 2+ ATPase
+age, gender, and job
+molecular characteristics
+Avian influenza virus replication
+Nedd4 family ligases
+85
+unsecured decisions
+PLY and inflammasomes
+symbiotic
+Sample preparation
+1.5%
+EV-71 2A and 3C protease
+antigenicity
+communication and information gathering
+Tukey's honestly significant difference post-hoc test
+CAR + /mPSCs
+clathrin mediated endocytosis
+46
+morphological features of apoptosis
+Ni-NTA agarose columns
+immunohistochemistry and flow cytometry
+Multiple stepwise regression analysis
+South Africa
+Mixing
+VZV prophylaxis
+CPV-2
+BALF protein concentration
+mSAMD9L
+heuristic model
+pDNA-based gene delivery
+TissueScan TM Disease Tissue quantitative polymerase chain reaction arrays
+mature miRNA
+The need for reintubation after failed extubation
+air travel
+cytomegalovirus promoter
+adhere to the medication regimen
+GDP
+phospho-p38 MAPK level
+230 to 1011
+adding relevance to the discovery of novel viruses
+decreased mean arterial pressure and increased vasopressor support
+50 μL
+66
+parts of proteins sharing a common evolutionary history
+distance Gamma distribution
+phosphorylated and thus activated proteins
+organ failure
+qualitative assay
+peptides, supervised classification, bootstrapping, and ROC analysis
+GenePix 4000B Scanner
+15
+adults
+t
+DC maturation
+cc-by
+XIV century
+reactivation of only a subset of the cellular population
+four
+community structure
+562 nm
+epidemiological
+relatively small polymers of amino acids
+strong and engaged network leadership
+adhesins
+ovipository sites
+8
+CITE
+5.4 million
+ACE2
+all data
+36%
+α1AT
+dexamethasone and hydrocortisone
+two
+5′-RVIFLVI-3′
+PhenoSense HCV NS5B assay
+AMPure XP system
+expertise
+4:1
+SU6656-mediated reductions of viral replication
+42
+The Student's two-tailed t-test
+HPLC-qTOFMS analysis of the active fraction
+Transplantation
+0.1%
+luminescence
+Monte Carlo simulations
+interaction partners of MAGE-G1
+Grainyhead
+U937
+four
+optimization of the fermentation conditions
+68
+anti-BMP2, anti-VEGF and anti-tubulin
+FeLV viral RNA and provirus DNA
+GPSbased technology
+brain drain
+ST239
+two-way ANOVA or area under the curve analysis
+route of exposure
+Microsoft Excel
+pGBKT7-BM2C
+other infectious diseases
+ubiquitin-modification
+Qiagen RNeasy mini kit
+eight
+helicase activity
+neutralize or alter the activities of multiple host proteins
+epidemiology
+Non-adherence to anti-tuberculosis therapy
+Cells expressing NGFR
+637
+Vero cells
+lysosomal membranes
+lifespan
+Vector Laboratories
+63
+disease transmission dynamics
+Cytoscape5
+nylonspotted 60 mer oligonucleotides
+Quantitative PCR
+regulating its polymerase activity
+solutions
+stable or transient expression of CIITA
+reinitiation
+44,776
+fluorescence
+r j and r q
+non-parametric Spearman's rank correlation coefficient
+Pip6a-and Pip6b-PMO conjugates
+5.65
+heroin
+Hypervariable viruses
+conductivity
+point-by-point
+0.3%
+Recombinations and mutations
+ca. 15 kb
+Time
+Lack of selective cytotoxicity
+23.5 6 2 kDa
+Biacore T100 Evaluation Software
+Mesothelin
+at the apical pole of T84 cells
+Very few
+significant
+The readings
+DNA sequences encoding the matrix proteins of LASV or MOPV
+Prior engagement with communities
+Antibodies
+2 × 75 cycles
+divergent middle region
+Reproducibility
+velocity
+five
+log-rank test
+King Faisal University in Saudi Arabia
+any of the other two stop codons
+ECLIPSE and COPDGene
+p < 0.05
+Antimicrobials
+sex, prior receipt of seasonal vaccine, or VTEU site
+lost
+B3 days
+protease
+506
+pitavastatin
+MG132
+JEV
+inhibition of VF formation
+core protein
+Interested colleagues
+stable
+every 2 days
+Average Ratio
+Shapiro-Wilk test of normality
+a space
+trained and experienced farm personnel
+NMA
+95uC
+62%
+versatile
+FeLV-positive
+Veterinary thermometers
+DNA or RNA
+394delTT
+Written informed consent and verbal assent
+79%
+a small number of studies
+12 months
+7 days
+significantly elevated IL-13 levels
+single-membrane phagosomes
+32
+less than one-half
+enhancements in stability
+Human respiratory syncytial virus
+deficiency of complement inhibitors
+competition-ELISAs
+Randomised controlled trials
+The itinerary
+Increased severity of illness on presentation
+RNeasy Mini Kit
+FeLV
+Regression analysis
+MBX2254 and MBX2270
+CC-23
+recognition and tolerance
+0.87
+Recombination
+human surveillance systems
+Dilution
+75%
+Professor Rapp
+airway mucus and the epithelial lining fl uid
+Strongyloidiasis
+liver and kidney
+Serial dilution of virus stock
+0.3 mg/mL
+Infectious pestiviruses
+recorded symptoms
+lung and spleen
+lateral associations
+Eighty-nine
+ligand-inducible transcription factors
+death receptors
+Reagents and materials D 2 DR
+prolonged PP sessions
+integrated regulatory networks
+Virus-induced exacerbation
+toxin production
+multivariate analysis
+active heme metabolism
+serology tests
+42
+label
+molecular biology/microbiology subject area and presence of article keyword "hospital"
+Bio-Rad Gel Doc XR system
+tumor masses
+Clue gene ontology and CluePedia
+interdisciplinary and holistic
+SPSS 17.0
+5.7%
+expression of SeV NP protein
+Guatemala
+C3
+close association between HPVs and CD151-enriched domains
+Peptide-driven pharmacophoric hypothesis
+six
+APACHE II
+ZsGreen
+S-palmitoylated
+5
+Total RNA
+Sanger sequencing
+central nociceptive changes
+5%
+Dr. Hung-Jen Liu
+520
+All the dots
+ER membranes and ribosomes
+Three
+1918
+Fifty-seven
+RNA binding
+25
+dimer dissociation constant
+Kaplan-Meier Survival curve
+Alveoli
+Markov Chain Monte Carlo
+fluorescence
+3-dimensional
+protection against respiratory challenge
+tachyzoites and bradyzoites
+data entry and initial cleaning of the data
+brain monitoring of post-CA patients
+4 days
+a rooted, timed, bifurcating tree
+robust mucosal antibody responses
+Cytoskeletal
+Ceres
+reducing treatment costs and cytotoxicity
+99.7%
+clinical disease
+proteasome inhibition
+peripheral CD4+
+STAT1 levels
+Genomic coordinates and annotations
+6 days
+IRF1 genes
+livers, spleens, and head kidneys
+data from S = 100 epidemics
+secondary antibodies
+normalized gene expression level data
+MOIs above 100-200
+melanoma
+M8
+antiviral treatment
+CHIKV pseudovirus neutralization
+87.5%
+5 × 10 6 particles
+tiling arrays
+Descriptive
+viral replication
+28%
+constraints and capacities of locally operating public health systems
+5 days
+Transcription factors
+113
+ANOVA
+advanced quantitative spatially-resolved understanding of HCV replication dynamics
+lncRNA-mediated
+leishmaniasis
+NO
+density-dependent
+NTHi
+f T
+NF-κB p65 protein levels
+challenge experiments
+117
+Chi-square or Fisher exact tests
+seven
+morbidity and mortality
+cc-by
+different origins of lung pathologies
+Helium
+lower mortality
+TCID 50 values
+stronger adaptability to the host
+Thirty-four
+IFKKAG
+blood
+all the tweets in Cycle 42 containing a photo
+9600
+light and electron microscope
+2
+IFN-γ
+conformity without excessive loss of statistical significance
+48 hours
+eukaryotic
+log L*
+biennial
+LPS
+3630
+subtractive method
+Author names
+higher than controls
+Kruskal-Wallis test
+B cells
+60% to 70%
+ACE
+daily
+expression of SPI-1
+pandemic influenza
+every four months
+375
+economic
+a subset of primate CD4 receptors
+Vaccination
+phagocytic cells
+Two
+regulation of host immune responses
+complexity
+The sum of confidences
+157 and 53 ng/mg protein
+plates
+>90%
+A. caninum
+148
+plasmid with different dilutions
+enterolactone
+Molecular dynamics simulation
+diagnosis, procedures, drug administration, and facility descriptors
+pneumonitis
+map coordinates scaled to match the transcript map
+Peak R 0
+mean SI
+Elast-eon E2As
+chromosome 12p11
+To assess the association between growth and breadth of the developing immune system response
+YXXh
+blood, stool and bronchoalveolar lavage fluids
+SBP tag
+Viniferifuran
+failed
+social-contextual factors
+All authors
+construction and rescue
+2%
+pENTR-SH
+N-hydrogen
+bans on unsafe funeral practices and implementing local quarantines
+arenaviruses
+input data
+HRV-A
+tiger
+pre-oxidized, denatured proteins
+250 to 300kbp
+single stranded RNA
+MAb immunoglobulins
+real-time VOC sensors
+PAMGO Consortium
+ducks and geese
+IgM-positive
+1162
+hair follicle
+JTV1/AIMP2
+Bayes empirical Bayes approach
+friendship-formation dynamics models
+PLY
+syncytium formation
+22
+endosomal escape
+CLDNs
+1 in 4
+Sonali Kochhar
+5-10 days
+Propofol
+The Q matrix
+starlet
+ISGylation
+k B T
+10.7554/elife.48401
+HCs
+Expression of simian vacuolating virus 40 small T antigen
+metabarcoding diet studies
+histological
+statistical significance of differences
+no cytoplasmic release of cytochrome-C
+10 mM
+retrospective
+4-hydroxycoumarin
+Zeiss LSM 700 confocal microscope
+Shannon's diversity index
+Volume Control mode
+54%
+Shigella flexneri infection
+Linux
+blocks Golgi export
+COVID-19
+higher rates of hospitalization in males
+awareness
+urbanization
+2.4.0
+EST2
+endotoxins
+higher levels of viral mRNA transcripts in tissue culture
+700, 000
+oxygenation and compliance of the respiratory system
+ARDS
+yellow green
+they tend to be short, degenerate, and occur frequently throughout the genome
+real-time PCR
+translational selection
+Idelalisib
+biweekly
+6 months
+the averaged output of nine neural networks
+six hours
+grp94 and PDIA6
+low computational cost and independency from available crystallographic structures
+Sixty-six
+over 80,000
+molecular targets causal for human disease
+cough, dyspnea and eventually fever
+pathogens associated with STIs
+Two milliliter fractions
+PTX
+Department of Surgery
+5th and 95th
+polarized
+1 μg/ml of DAPI
+19.8%
+16%
+anti-CD4 antibody
+microplate reader
+detection policy
+reversed
+manidipine resistance
+HeLa and Huh7 cells
+twice per day
+SPSS 17.0
+The Bill and Melinda Gates Foundation
+motif-D active-site loop
+to health
+two different concentrations
+recombination between attL and attR sequences
+112
+Frameshift construct and oligonucleotides À1 FS
+impaired assembly and secretion of very low-density lipoproteins
+interpandemic years
+NCI-H460 cell viability
+Mouse models
+a set of genomes with the same nucleotide genome
+ultrafiltration
+Neuromuscular blocking agents
+symptom management
+immunofluorescence
+Table 3
+72 h
+135
+ROS
+Incorporation and the role of host proteins
+nearly as potent
+5,976
+photographs
+Changes in the natural environment
+80.8 mg/L
+Worry
+commercial laying flocks
+5.4 U/g Hb
+H5N1/H7N9 infection is independent of climate factors
+Angiotensin-Converting Enzyme 2
+A
+2 × 150
+influenza replication
+antiviral therapy
+myeloid cells
+85%
+Argentina
+C reactive protein
+public health insurance
+3.6 million flu-related tweets
+two
+modulating secretory capacity either during drug-induced or physiologic ER stress
+Creatine-kinase
+4.3 ± 2.64 years
+develop interventions tailored to specific cultural groups
+RNA extraction from lenses
+minors
+western blot analysis
+inflammatory
+restriction of virus replication
+HIV-1 entry inhibition
+5 days
+negatively affects STAT phosphorylation
+every three days
+75%
+Conservancy
+Lung consolidation
+neutral red staining
+5
+Ebola virus disease
+Airway epithelial cells
+M and NS
+50% of control levels
+destructive inflammation
+Laminins
+NAs
+ACLY
+HIV, and HSV-1 and -2
+Gene specific PCR primers
+35
+kobuvirus
+A/D
+9 days
+Bray-Curtis dissimilarity index
+25%
+Pediatric out-of-hospital cardiac arrest
+anti-PTX3 antibody-crosslinked magnetic beads
+anti-and pro-fibrotic
+the pathway of transitions to State C0
+24
+selective inhibitors
+overestimation of K
+medical emergency diseases
+FGL2-induction
+Mortality
+PTM score
+a comprehensive dataset of all the known MOKV isolates available
+RevertAid TM Premium First Strand cDNA Synthesis Kit
+16
+2-fold
+LD 100 baboons
+12.6%
+Sex and gender differences
+cytopathic effect
+delayed time-to-death
+GTPase Rac 1
+Commuting
+planned behaviour
+severe anaemia
+7.2K
+conoporin
+Stepwise binary logistic regression analysis
+ARVO X Multi Label Reader
+nucleotide constraint
+Efficient replication
+LCMV Z
+patients who received iNO and patients who were managed routinely
+Corticosteroids
+over two weeks
+Zika virus and Dengue virus
+4 and 7
+the sum of the scores divided by 20
+disease monitoring
+Gaithersburg, MD
+Web Appendix 1
+positive association
+LC-MS
+quick
+MKP-1
+62.4%
+37%
+mutated fragment
+LGALS3BP/90K
+Eight
+20%
+FACScan and CELLQuest
+inflammatory
+Tdh2p
+83%
+household size
+unfamiliar
+clinical
+NN-DNJ
+Environmental risk factors
+Verbal assent
+chronic social isolation
+sustained exposure to IFNs
+23
+cefepime or ceftazidime
+respiratory secretions
+Complementary DNA
+green, orange, and yellow
+RM cells
+Transcriptional activity
+SAC55
+plasmacytoid DCs
+important
+Further studies
+Benjamini-Hochberg procedure
+Pneumococcal vaccine
+Chi-square test
+the ER of host cells
+when we consider triples in addition to pairs
+JEVinfected BL/6 mice
+head and ovary
+5
+10 min
+237
+A single ontology
+resazurin
+N-terminal IL2 secretion leader peptide
+40-50%
+17
+1 nm
+canine norovirus RNA
+TUT1
+Phylogenetic and population genetic methods
+Large patient heterogeneity
+antigens
+doxorubicin
+CSFV infection and proliferation
+transcellular biosynth esis
+uncontrolled virus replication and spread
+.71
+oxcarbazepine
+Endometrium p-4E-BP1
+C H 2-C H 3 interface
+dsRNA
+2012
+12.05 per 100,000
+values for the parameters and states
+Akt and PI3K
+pairwise distances
+isopropanol wash
+ouabain
+students individually
+RAG1
+3.7 Å
+dissociation of the SecA dimer
+Bacillus and Lactobacillus
+The proportion of the ribosomal bands
+Nucleotide +1
+RIG-I and TLR7
+PDK4
+eHEV
+ATPase activity
+naïve B cells
+Metabolite-corrected donepezil
+critically ill
+the complement system
+ACE2
+phenol/chloroform
+soluble complex
+perturbation
+Enzo Life Sciences
+18 h
+Hitachi 7100 transmission electron microscope
+17 min
+APCs
+up-regulation
+virus mutants
+H275Y
+membrane permeability
+four
+RABV glycoprotein
+information about their structure, amino acid sequence and functional context
+bit-string representations of molecular structure and properties
+area, race, age and gender
+drug-drug interactions or toxicities
+Sinopharm Chemical Reagent Beijing Co., Ltd
+Social amoebas
+Igor Pro
+CEACAM1-Q89A-Fc
+Gendicine TM and Oncorine TM
+three
+SARS, hepatitis viruses, influenza viruses 16 or HIV
+Source-tracking techniques
+genomic GC skew
+Type III IFNs
+fever
+EM's mortality rate
+type II
+liquid cooling system
+119
+RIPA
+Guinea pigs
+Taqman Chromosome Conformation Kits
+10,639
+Eight
+CEACAM1
+19 years and 57 years
+clinical
+ISGylation
+62
+several
+20%
+116 billion pounds
+40%
+leukocytes
+Culture supernatants
+measurement issues
+epithelial dysplasia
+RPL27-GFP
+Forty negative sera
+twice
+86.5%
+10 trillion
+30 s
+100 per cent
+12-14 h
+DNA vaccines
+stress
+RNA viruses
+biological
+89%
+Influenza A virus
+virologic
+Amplicons
+Blood tubes
+leukocyte transendothelial migration signalling pathway
+TCID 50
+refolding of the pseudoknot after ribosome passage
+7 days
+bird cell proteins
+REML
+10 min
+Advanced Querying Tool
+5,142
+seven
+Community-acquired
+ESV, CYV and MXV
+hly and plcA
+caution
+RNA editing
+Dr. Oliver Schildgen
+20 mL fresh media
+42,918
+16 hours
+Gnotobiotic pig sera
+S. pneumoniae
+2442
+five
+ADAM9 and ADAM12
+normalized reporter value
+4.9 million
+database molecular alignment
+PCR products
+51
+8 weeks
+almost 5 times greater
+15%
+transporter and ion channels
+nanopore sequencing
+highly conserved viruses with two receptor-binding variants
+51.08 years
+residues within the transmembrane domain
+contact networks
+two
+cc-by
+MERS-CoV
+activation of the p53 tumour suppressor protein
+edema toxin and lethal toxins
+An ontology
+Solithromycin Solithromycin
+an entry gate for proteome wide analysis of the virus-host system
+AY628152-69 and AY633510-39
+oxycodone
+nonallergic individuals
+laboratory confirmation
+3:1
+T
+plain buffer
+Cox proportional hazards models
+nondominant
+Renal denervation
+t 1/2
+EP
+Seven days
+serious dangers will be possible outcomes of any course of action
+less favourable
+two
+3 days
+cross-reactivity
+relaxin
+CEL files
+agitation of the product during illumination
+a vector carrying components necessary for replication
+RSV
+day 25
+N, S-blocked glutathione diesters
+Gaussia luciferase
+three
+RFAMSEQ
+The resulting recovered protein
+Ten
+twice daily
+unbiased deep sequencing
+total protein content
+4-5%
+Ebola and Lassa fever viruses
+joint analysis of multiple alleles
+April 2009
+−26.5 ± 5.0 mV
+6-8 h
+1
+domain of M2
+relative input
+influenza vaccination for populations and antiviral treatment for individuals
+inactivation of the viral envelope protein
+eight
+remarkably similar
+IMEX
+discrete interaction sites on the viral genome
+6
+89-224 PFU
+Anti-CD8-APC-Cy7
+27
+Isotype antibody pull-down and uninfected cells
+unencapsulated phase variants
+develop and test the proposed predictive model
+7,200
+splenic CD8 + CD25 + Foxp3 + T cell populations
+Arabia
+810
+1 h
+16 h post-infection
+other factors
+14
+10%
+long distance dispersal
+Protein aggregates
+IFNAR-1 mRNA levels
+S1PR1 selective agonist CYM-5442
+less than 32 weeks
+phylogenies
+acute-on-chronic liver failure
+7-phloroeckol and dieckol
+80%
+R t
+localize to the outer membrane
+3 s
+Substrate concentrations
+metagenomics
+infectivity
+Supernatant
+temperature or vapor pressure
+IP-10, TGF-a, and PDGF-AA
+ECDC
+structural and functional
+0.2%
+identification of gene regulatory regions
+abundant experience
+ceftobiprole
+Stanford
+75%
+reference-free
+V2-apex bnAb epitope
+Supernatants
+overexpression of usp-46
+dengue-endemic areas
+slowly dissociate from the ribosome
+Beclin-1
+The set of results of ciliary ultrastructure and NO n measurement
+2018-07-16
+host DNA polymerase
+disease severity and mortality
+local activation of innate immunity
+γ irradition
+SP-D
+Streptococcus
+HI assays
+context specific
+immune electron microscopy
+398
+the patient's clinical information
+Identify-Isolate-Inform Tool
+Computing servers
+Weekly CPS based prediction
+26%
+Visualisation
+burn patients at risk for AKI
+six
+G, C
+sedation
+aggressive treatment
+demyelination
+novel preventative strategies or therapeutic modalities
+Liaoning Province
+LASV entry
+Nesteruk, Igor
+proton transport models
+matching of the circulating strains with vaccine strains each year
+sodium hydroxide standard solution
+inner capsid protein VP6
+50%
+European Virus Archive
+gender
+facilitate nuclear membrane transition
+20
+Dual-Luciferase Reporter Assay System
+28%
+goat anti-cat HRP or phosphate conjugated antibody
+6 hrs
+planning
+mathematical scenario models
+91%
+OCT compound
+pathogen
+7 days
+both M and C
+lymphopenia
+Short read data from the Western English Channel
+World War I
+hydrophilic
+4
+Mosquito-borne flaviviruses
+70%
+to better adapt to its primary host's environment
+damaged organelles, unnecessary proteins, and foreign substances
+pLD-FPS-SQS
+Proliferating T cells
+ethical reasons
+10.1186/1471-2334-7-17
+48-hours
+twelve
+Molecular docking technology
+K2CO3 and appropriate benzyl bromide
+twice every week
+SYBR green-based quantitative real time PCR
+oseltamivir
+14.71%
+Multiplex PCR analysis
+carbon and oxygen
+four
+histologic
+five
+nasopharyngeal carriage
+10
+outputs
+MLKL phosphorylation
+adhesion molecules and toxins
+3 weeks
+Twelve
+Ninety-four
+Ad5/HVR2-MPER-L15
+SAM software
+TAC
+20
+immunosuppresion
+Luciferase activity
+HBGAs
+data type
+0.136 and 0.167
+46-92%
+64
+6
+May, 2009
+real-time PCR
+function as tumor suppressors in lung cells
+TSC2 interference
+7.0 persons
+98%
+300m above mean sea level
+HMDP strains
+studies with larger sample sizes
+1.4%
+systemic or selective
+Hungary and Greece
+Iberian lynxes
+hs-CRP and PMN count
+Nose-Hoover temperature coupling and isotropic scaling
+ROS
+SW/WN03 genotype
+viral RNA of PUUV
+ignorance of the reporting rate
+oblique rotation
+16-20 h
+12 hours
+MEGAclear
+Analysis of pH-dependent protein stability
+ExomeDepth
+Ten
+significantly decreased anti-HTNV activity
+a screening protocol for healthy subjects who are interested in participating in vaccine clinical trials
+All systems with an H-index above the 75th percentile
+Birth weight
+Human bocavirus 1
+up to 3
+enhanced replication/transcription of the mutated segments
+possible response pathways
+15%
+increased relapse and a trend toward improved OS in the MA cohort
+amoeboid
+18
+cell viability
+2.3 ml
+5.5 to 6.0 ml
+isolation
+four
+6
+HFIP-mediated release from the solid support
+National Yang-Ming University
+reinitiation mechanism
+24
+33
+I
+non-viral macromolecular delivery
+the vertical average of the 500 ROC curves
+different types of constructs
+yawning or refractory
+texture information
+490 nm
+preparedness
+6 months to 14 years
+independent viral protein-interacting proteins
+89.8%
+two bilayers
+H1N1pdm
+survival
+modification CS with FITC or Cy5.5
+Proheads
+Lectin immobilization
+BAL fluid
+cc-by
+target-mediated clearance
+A H3N2 Switzerland
+GEDV
+XNT
+Limb muscle weakness
+catalytic subunits
+0.1% formic acid
+Biochemical
+Data
+Figures 2c and 2d
+apoptosis
+H1 and H3
+DNA sequencing and restriction endonuclease digestion
+urease
+2,145
+structural proteomics
+reaction mix in desalted and sterilized water
+six months
+39.6 weeks
+8 Open Reading Frames
+broad-spectrum inhibitors
+5%
+influenza infection and transmission mechanisms and absenteeism behaviour of symptomatic students
+local vampire bat-prey interactions
+a second TL2/PK1 pseudoknot
+ViSpA
+Dr. Zijian Xie
+secondary bacterial pneumonia
+increases the endosomal pH
+five
+Sections of paraffin-embedded organs
+levels of IgA
+ANDV and PUUV infection
+tRNA Arg mcm 5 UCU
+Bafilomycin A1
+constitutive
+mean ± SEM
+1997
+10%
+plasminogen
+Ad5.ZIKV-Efl
+single site antigen/epitope incorporation at fiber or protein IX
+flow cytometry
+Pregnancy
+29
+Belief in Conspiracy Theory Inventory
+0.813
+detection of anti-drug antibodies
+visa
+H-2D b
+Ub activity
+Th1-and Th17-type immune responses
+stringent selection criteria
+90 min
+S1 Database
+increase endosomal pH
+Sequential lobar collapse
+reducing or eliminating socioeconomic and racial/ethnic disparities in health and healthcare
+differences in the peptides sequences and their lengths
+JM109 competent cells
+100 μL 0.05 m iodoacetamide
+Human rhinovirus C
+Europe and the USA
+phagosomes
+Dendritic cell
+protocol deviations
+disrupted the integrity of polarized Caco-2 cells
+mammalian and human life
+1952.84 km 2
+T cells
+A lay summary of the results
+TIIA
+crowded living conditions and exposure to indoor air pollution
+70
+TLRs
+RNaseL
+reference lists of retrieved original articles
+10
+recovered
+in eye banks with specialised areas and trained staff
+338
+endothelial cell responses
+IL-17RA and IL-23
+Counter Selection BAC Modification Kit
+Moral distress
+reaction mixtures
+enhanced release of IL-10
+impacts on household well-being
+other enteroviruses
+differential transmissibility of segmented variants
+99%
+activation of STAT4
+basolateral or apical sides
+Congolese tropical rain forest
+test utilization
+T S
+10
+SUDV and BDBV
+surveillance
+CCL5, Mx1, and IL-8
+the variable
+9.4%
+September and October
+high IF medical journals
+only one neighbor can become infected
+quick clearance via digestive tract
+monensin
+irradiated BALB/c recipients
+2017
+local priorities
+air samples
+H7N9 positive
+modular
+information
+high-volume mechanical ventilation
+five
+M1
+ITCH, Nedd4, and WWP1
+pseudocenters
+2006
+anti-phosphotyrosine
+changes in actin morphology and polymerization
+NP adaptation to the importin-α isoforms of a particular species
+NEBNext Ultra RNA Library Prep Kit
+bidirectional influences
+146
+perl
+Purified PRRSV CH-1R antigen
+lipoproteins
+B&K Universal Group Limited
+AP180 CTD
+Betaine
+Spearman correlation coefficient
+synovial
+Activation of coagulation and alveolar epithelial injury
+Ifitm2
+Household observed serial intervals
+viroporin function
+capita birth rate and population size
+binders
+alternative
+62%
+SAL analogues
+edges
+19 days
+multiple stochastic runs
+cross-protective
+20%
+causal interactions between HDL proteins
+Dr. Bin Gotoh
+Parsonnet Lab
+a person
+spherical vesicular compartments
+95%
+IFN-a
+Rhinolophus ferrumequinum
+three
+TMP/SMX
+Chordopoxvirinae
+Darwinian evolution
+The large trophozoite
+zoonotic pathogens
+text mode
+Goat-anti-mouse IgG CyTM3
+to avoid cell debris
+30%
+Mucosal barriers
+2,928
+Syndecans
+serious pulmonary disease
+twice
+Cyst morphology
+Recombinant human apoM
+Anti-Nup62 siRNAs
+pEVL
+RTC13 and RTC14
+anti-FLAG, anti-HA, and anti-Ubc9
+its population size
+Serious Protocol Deviation
+Eight
+membrane protrusions
+plasmid DNA mutation
+low fidelity
+lycopene β-cyclase
+enhanced chemiluminescence
+TRIM56 E3
+595 Enoticumab
+deeper
+Free energy and network entropy
+1.28
+glycine GGC and alanine GCU codons
+117
+cell viability
+six
+2 h
+severe comorbidities or failure of ART
+IL-6
+Data acquisition
+The spectral range between 650-950 nm
+DEP
+CPV 2
+venules
+TIM3
+996
+nephrotoxicity
+necrotic
+RIG-I and MDA5
+information recorded in the hospitalisation data
+30 ng of RNA
+Degenerate primers targeting the glycoprotein gene
+5
+overarching ethical principles
+Statistica v10 software
+Transmembrane proteins with an N-terminal ectodomain
+6 hours
+transduce patient spheroids
+cell surface HS
+3-amino-9-ethylcarbazol
+cholesterol-enriched
+pDCs and NK cells
+computational efficiency
+consistent estimates of the peak attack rate
+4 hours
+33
+pcDNA 3.1 vector
+Sequence similarity
+twelve
+5-50 USD
+hantavirus amplification
+40 mothers
+Release of infectious VSV and DENV virus
+1.5 M NaCl
+NS3/4A
+half
+,3-fold
+Blast
+substrate-hydrolase screenings
+publications
+less weight loss
+120 h post-inoculation
+lack of available tap
+barcoded tetramers
+the exact paratope
+twice
+53
+10,000
+confidentiality agreements
+a three-domain polypeptide
+virus polymerase complex
+RNA polymerase II
+Vimentin
+Five
+tumor necrosis factor alpha and interleukin 1beta
+60 min
+an individual
+exonucleolytic
+a contact investigation
+Puumala virus
+sorafenib
+2013
+full growth medium with serum
+FlowJo
+human, avian, and swine influenza viruses
+55 kBq/kg
+FACSCalibur instrument
+Descriptive
+M-T hook structure
+Charlson-Deyo comorbidities
+30 m
+raw data from array scans
+ImageJ 1.47n
+Vaccinia virus infection
+a cut off at P,0.05
+autophagosomes
+eight
+0.2 v/v 300 mM HCl
+Vaginal discharge
+Continuous infusion of antibiotics
+SPSS version 13.0 and Amos version 7.0
+binding of HuNoV VLP to all three types of saliva
+normalized pseudoviruses
+Tick-borne relapsing fever
+read through the full text of each selected article and summarize key metadata
+GeneJet PCR purification kit
+three
+91%
+viral entry
+2500
+genetic variants conferring susceptibility or influencing progression and severity of disease
+31.4-39.7
+calcium
+peritoneal NK cells
+the specificity of the GFP reversion
+30 μL
+reovirus replication
+RT-PCR and/or virus isolation
+Ebola and Marburg viruses
+phosphorylation by various ligands
+PIRO score
+18
+nonspecific psychological distress
+an individual typically roams
+mcm 5 group of the near cognate Arg-tRNA
+Kampar, Malaysia
+H5N1 HA
+CleanCap
+Sample size
+Uganda
+endogenous peroxidase activity
+amino acid diversity
+2014
+PLY
+three
+S G
+one or two
+numerous mismatches
+400
+viral RNA
+cytoplasmic fractions
+10 2 -10 6 bacterial cells/mL
+purified mitochondria
+pressure ≤ 30 cm H 2 O
+39
+Drosophila melanogaster
+Substitution of Y = 0
+inflammation
+Local testing procedures
+insertion of miR-192 or scrambled targeting sequences
+Viral DNA and RNA
+Lipopolysaccharide
+100 nt
+basal autophagy
+Genetic resistance of more susceptible breeds
+frequency of non-synonymous mutations
+conventional molecular biological techniques
+HCPS
+DI particles
+Pleural effusion and diagnosis of adenoviral pneumonia
+Amyotrophic lateral sclerosis
+3.5 kDa
+7
+MVA
+BMP7
+engagement with Ub
+VCV
+myocardial ischemic and reperfusion injury
+Natural RNA G4s
+Human mAb reactivity
+Neostigmine and glycopyrrolate
+3 M TMAC and 45 C
+low transduction levels
+the attending physician
+three
+Systems Genetics Core Facility
+N
+remote enhancers
+Human respira t ory syncytial virus
+GraphPad Prism 5
+cellular antiviral restriction factors
+180
+forecasted strains
+clusters of isolates
+touching and removing tapes
+genomic changes
+complex pathways
+Universal primer-PCR
+RPMI 1640
+cervical, thoracic and lumbar
+CCL-141
+reductions in central subfield thickness
+raltitrexed
+oncolytic immunotherapy
+HA-specific antibody responses
+9
+8
+93%
+TLR7
+ChAT
+host attachment rate
+MicroRNA-133b
+H5N1 titres
+656
+Tuberculosis
+autumn
+haemagglutinin esterase gene
+fecal excretion of PA by bacteremic mice
+pancreatin
+the ratio of T helper cells to cytotoxic T cells
+3P54_A template
+Phylogenetic trees and matrices of phylogenetic distance from humans
+rice gall dwarf virus
+0% to 50%
+Alpl
+eleven
+acetyl coenzyme A carboxylase
+1 mL
+30 L
+negative control
+cytotoxic T lymphocyte antigen 4
+Influenza
+glycoproteins
+using 10 random sections of each brain, SC and ON of each animal
+cc-by
+a small gift
+Zn 21
+Signaling via TLR9
+potential O-glycosylation sites
+512 × 512 px
+24 hpi
+8.86
+broad-spectrum
+160 µg membrane protein extracts
+host cells and tumor cells
+written informed consent
+24 hr
+one extra strain of influenza B virus
+Identification of mimotopes
+2-3-4
+co-occurrence scores
+medical centers, regional hospitals, and local hospitals
+five
+a double-strand RNA
+fusion protein precursor/glycoprotein
+double-membrane vesicles and multilamellar structures
+mediated efficient primary infection
+ONOO
+sCR1/TP10
+AMREP
+Datasets
+VP088
+APACHE II
+major histocompatibility haplotype as well as DC subset frequency and function
+23,646
+Twenty-eight
+40%
+10 days
+an NS6 chimera
+virus-induced cell mortality
+Philips CM-10 electron microscope
+three
+CCP4
+PC3
+vector recognition and particle formation
+high neutralizing ability
+10 7Á7 50% egg infectious dose /ml
+immune reaction
+IGV and Artemis
+Java
+Venturi mask
+HA
+immunologic
+every week
+outpatients
+hydrophobic interactions
+Inflammation
+0.2
+consensus sequences
+cross-sectional study
+21.6%
+three
+TUL
+Flowcytometric
+Statistical models
+0%
+Viral DNA
+282
+succeeded beyond all predictions
+UV and visible light
+evasive strategies
+Hand washing, psychological stress, social support, and shift work
+cellular RBPs
+1.57
+2009
+Mann-Whitney U test
+DI water
+62
+cytokines
+NFkB-dependent
+34.4%
+better immune responses
+mouse serum
+5228
+The concentrations of fluoresceinated PPMO in liver and spleen
+388 × 850 cm 2 roller bottles
+cells
+sites or alternative slippages
+diminished disease activity index
+Node color gradient
+12
+acute replication of gammaherpesviruses in vivo
+213
+OneStep RT-PCR and TaKaRa Ex Taq kits
+Bottleneck
+Sphingosin kinases
+10 −3 -10 −5 s/s/y
+factors other than the effectiveness of interventions
+ST and FI
+Scaffold
+observations up to some fixed time
+forty
+Cell Counting Kit-8
+Thirty-one
+0.4%
+pneumonia
+Global Moran's I
+the average interval between infection of a primary and a secondary case
+β-herpesvirinae
+hospitalized noncritical patients
+Merkel cell
+P-LPE
+sex differences in the prevalence of HBV and development of liver cancer
+N2-N3
+biweekly SHIVIG administrations
+inhibits protein transport through the Golgi protein
+PCP
+370
+48 h
+admetox
+5765 mM
+adaptive networks
+parasites
+15
+structure
+44%
+6-8 week old
+standard deviation
+fever, rash, arthralgia, and conjunctivitis
+in-hospital survival
+electron microscopy, immunofluorescence, and ELISA
+RVs
+538
+disintegration of the rotor at speed
+"-"
+physiologic
+Loop-mediated isothermal amplification
+25 days
+Invitrogen Corporation
+Microarray data
+67%
+2 mM monensin
+additional modes of RNA synthesis
+ORFx
+5/9
+IL-10
+Cell apoptotic
+non-psychology journals
+23
+20-30%
+61.93%
+RNA
+modifications
+depressed
+virulence
+1,196
+2D molecular fingerprints
+flexible policies, frameworks and incentive structures
+association with the cell periphery
+COPD
+NF-κB
+telomerase activity
+simultaneous amplification and barcoding with a single oligo
+Ascosphaera apis
+neonatal ICU and a variety of health-care interventions
+six
+RPISeq models
+type I diabetes and Hashimoto's thyroiditis
+attacks
+1 week
+CBP
+two consecutive lysines
+reduced RSV-G protein synthesis
+33
+180 units of the capsid protein VP60
+non-ICH patients
+CCL4
+turkeys
+bushmeat
+protective equipment
+90%
+TNF-α, IL-1β, and IL-6
+526
+periphery
+HIV-1 specific primers
+unsaturated fatty acyl chains
+SPOT IMAGING Software
+viral RNA synthesis
+lags
+Double-stranded DNA
+influenza virus replication
+arginine-lysine
+HCV NS3 PRF
+densitometric quantification
+ACGIH's formula
+nuanced
+Haversian and trabecular
+absorbance at 450 nm
+Influenza Virus
+John Sheehan
+travel at all
+4.2%
+Over 60%
+RSPs of dengue 2, 3 and 4
+Outbreaks, emerging infections, and bioterrorism
+Middle East, Central Africa, and Egypt
+2138
+H7N9 and H5N1
+isobolograms
+mounting an inflammatory response
+causes other than the study agent
+a known association
+Kaplan-Meier method
+GraphPad Prism 6
+AlexNet
+HEK-293T cells
+seroconversion factor
+ER stress and DNA damage response
+Four
+7671-fold
+0.1% Triton X-100
+central tendency or other basic estimates AND variation or associated estimates of uncertainty
+confirmation of etiology by laboratory testing
+Ingenuity Pathway Analysis 5.5
+63 out of 68 associations
+1.38 out
+267
+Further information on research design
+dengue control
+frameshifting
+Receiver Operating Characteristic curve 27
+79%
+mobile
+apoptosis
+50-60%
+energy intake
+CMV
+1718
+2003
+two
+six
+PRRSV replication and proliferation
+10%
+84 hours
+monocyte-derived
+previous history of statin use
+the outbreak
+simplicity
+adverse events
+Further prospective validation
+high error rate of the polymerase
+CHOP and ATF4 cooperation
+human immunodeficiency virus rapid testing
+less than 5%
+PE_PGRS proteins
+SiglecH
+Ang II
+3219
+progressive disease
+PBMCs
+active migration of tumor cells
+IL-10
+Five
+Genomic coordinates
+medical applications
+1:229
+temperature, humidity, and illuminance
+Acute respiratory viral infections
+highly fluctuating
+IRAV
+The percentage of identity
+Optical density
+C 21 H 22 O 9
+AKT and PLK1
+6 mM
+extracorporeal
+hands-on practical training
+estimated transmission distance
+Acyclovir
+Asian populations
+a MM
+HRPs
+Soybean oil
+Three
+Datasets for TAAR1 expression
+transfer of contaminants by means of the door swing
+matrix protein M
+Fc-dependent viral clearance
+a regulatory network and a set of regulatory modules
+P bin
+pharynx epithelium
+IRF7
+14 days
+2014
+mouse lung
+precision criteria
+filamentous
+CPP mediated toxicity
+clinical and psychological
+viral plaque assay
+90 %
+their use in human therapy
+swine
+Immune complex and complement depositions
+immunogenicity
+co-infection by wt and variants
+1% Triton X100
+CPE
+Phosphate-buffered saline
+genetic drift
+H4a
+redundant mechanisms and incomplete C' depletion
+DNA sequencing
+24
+phosphorylation sites
+NOX-1
+b-G and b-GA
+current spillover surveillance efforts
+30,000
+phase C
+rRT-PCR
+substitution of T with X U
+statistically significant
+Inflammation
+IkB
+monosaccharides, amino acids, and fatty acids
+both strategies
+four
+absence of viremia and protection from swelling
+K359H
+human immunodeficiency virus
+men who have sex with men /bisexuals
+0.03
+Four
+cytoplasmic azurophil granules
+DSC
+tracing
+Wnt signaling pathway
+T-cell activation
+two sample Kolmogorov-Smirnov tests
+governs tissue-repairing environment
+12
+80%
+molecular dynamics
+labelretaining cells and BASCs
+PA induced IL-6 and IL-8 expression
+other studies made elsewhere
+three
+insoluble debris
+High-affinity CD8 + T cells
+Recombination
+4%
+one
+blood neutrophil count
+A combination of several features
+greater
+99%
+281
+IL-6 and IL-17A
+conserved primers
+molecular
+demographics
+nanomedicines
+one
+Algid malaria
+dramatically suppresses antiviral response gene activation
+epigean sites
+natural immuno-adjuvanticity
+85,652
+pathological changes in exosomal cargo and function
+pseudoknot conformational plasticity
+2,000 to 5,000 Chinese yuan
+ssRNA
+96.4% GFP-positive plaques
+identifying suspected cases that may have a higher chance of testing positive
+Golgi
+CO 2 inhalation
+alignment problems
+recombination in other RNA viruses
+35
+12
+a vasodilator peptide
+the standard deviation of the mean
+50, 60 or 100 mM
+molecular peaks with Na + adduction
+10,649
+environmental temperature and relative humidity
+paediatric intensive care unit
+NASFinder
+different recombinant lineages
+kDa
+corticosteroid
+MS analysis software
+individual vaccination status
+end-anchoring
+Module gene expression levels and cell differentials
+the need for Nef to antagonize SERINC5
+93.3%
+HSV-1 gB 3A or GS3217 virus
+Cre 2 control mice
+cellular protein translation
+sym-sub assays
+five
+Data
+Family members
+Pathogens and vectors
+Influenza
+3.96
+140