niryuu/sni-each-converted huggingface dataset:
The severe acute respiratory syndrome (SARS) caused tremendous damage to many Asia countries, especially China. The transmission process and outbreak pattern of SARS is still not well understood. This study aims to find a simple model to describe the outbreak pattern of SARS cases by using SARS case data commonly released by governments. The outbreak pattern of cumulative SARS cases is expected to be a logistic type because the infection will be slowed down due to the increasing control effort by people and/or due to depletion of susceptible individuals. The increase rate of SARS cases is expected to decrease with the cumulative SARS cases, as described by the traditional logistical model, which is widely used in population dynamic studies. The instantaneous rate of increases were significantly and negatively correlated with the cumulative SARS cases in mainland of China (including Beijing, Hebei, Tianjin, Shanxi, the Autonomous Region of Inner Mongolia) and Singapore. The basic reproduction number R o in Asia ranged from 2.0 to 5.6 (except for Taiwan, China). The R o of Hebei and Tianjin were much higher than that of Singapore, Hongkong, Beijing, Shanxi, Inner Mongolia, indicating SARS virus might have originated differently or new mutations occurred during transmission. We demonstrated that the outbreaks of SARS in many regions of Asia were well described by the logistic model, and the control measures implemented by governments are effective. The maximum instantaneous rate of increase, basic reproductive number, and maximum cumulative SARS cases were also calculated by using the logistic model.
Output: The outbreak pattern of the SARS cases in Asia
Bacterial infections of the respiratory tract constitute a major cause of death worldwide. Given the constant rise in bacterial resistance to antibiotics, treatment failure is increasingly frequent. In this context, innovative therapeutic strategies are urgently needed. Stimulation of innate immune cells in the respiratory tract [via activation of Toll-like receptors (TLRs)] is an attractive approach for rapidly activating the body's immune defenses against a broad spectrum of microorganisms. Previous studies of the TLR5 agonist flagellin in animal models showed that standalone TLR stimulation does not result in the effective treatment of pneumococcal respiratory infection but does significantly improve the therapeutic outcome of concomitant antibiotic treatment. Here, we investigated the antibacterial interaction between antibiotic and intranasal flagellin in a mouse model of pneumococcal respiratory infection. Using various doses of orally administered amoxicillin or systemically administered cotrimoxazole, we found that the intranasal instillation of flagellin (a dose that promotes maximal lung pro-inflammatory responses) induces synergistic rather than additive antibacterial effects against antibiotic-susceptible pneumococcus. We next set up a model of infection with pneumococcus that is resistant to multiple antibiotics in the context of influenza superinfection. Remarkably, the combination of amoxicillin and flagellin effectively treated superinfection with the amoxicillin-resistant pneumococcus since the bacterial clearance was increased by more than 100-fold compared to standalone treatments. Our results also showed that, in response to flagellin, the lung tissue generated an innate immune response even though it had been damaged by the influenza virus and pneumococcal infections. In conclusion, we demonstrated that the selective boosting of lung innate immunity is a conceptually advantageous approach for improving the effectiveness of antibiotic treatment and fighting antibiotic-resistant bacteria.
Output: Therapeutic Synergy Between Antibiotics and Pulmonary Toll-Like Receptor 5 Stimulation in Antibiotic-Sensitive or -Resistant Pneumonia
Surprisingly little is known regarding the human mixing patterns relevant to the spread of closecontact infections, such as measles, influenza and meningococcal disease. This study aims to estimate the number of partnerships that individuals make, their stability and the degree to which mixing is assortative with respect to age. We defined four levels of putative at-risk events from casual (physical contact without conversation) to intimate (contact of a sexual nature), and asked university student volunteers to record details on those they contacted at these levels on three separate days. We found that intimate contacts are stable over short time periods whereas there was no evidence of repeat casual contacts with the same individuals. The contacts were increasingly assortative as intimacy increased. Such information will aid the development and parameterisation of models of close contact diseases, and may have direct use in outbreak investigations.
Output: Emerging Themes in Epidemiology Mixing patterns and the spread of close-contact infectious diseases
The objective of this paper is to evaluate a panel of statistical algorithms for temporal outbreak detection. Based on a large dataset of simulated weekly surveillance time series, we performed a systematic assessment of 21 statistical algorithms, 19 implemented in the R package surveillance and two other methods. We estimated false positive rate (FPR), probability of detection (POD), probability of detection during the first week, sensitivity, specificity, negative and positive predictive values and F 1 -measure for each detection method. Then, to identify the factors associated with these performance measures, we ran multivariate Poisson regression models adjusted for the characteristics of the simulated time series (trend, seasonality, dispersion, outbreak sizes, etc.). The FPR ranged from 0.7% to 59.9% and the POD from 43.3% to 88.7%. Some methods had a very high specificity, up to 99.4%, but a low sensitivity. Methods with a high sensitivity (up to 79.5%) had a low specificity. All methods had a high negative predictive value, over 94%, while positive predictive values ranged from 6.5% to 68.4%. Multivariate Poisson regression models showed that performance measures were strongly influenced by the characteristics of time series. Past or current outbreak size and duration strongly influenced detection performances. Citation: Bédubourg G, Le Strat Y (2017) Evaluation and comparison of statistical methods for early temporal detection of outbreaks: A simulation-based study. PLoS ONE 12(7): e0181227. https://doi.org/10.
Output: Evaluation and comparison of statistical methods for early temporal detection of outbreaks: A simulation-based study
Plasmid DNA (pDNA) gene delivery is a highly versatile technology that has the potential to address a multitude of unmet medical needs. Advances in pDNA delivery to host tissue with the employment of in vivo electroporation (EP) have led to significantly enhanced gene expression and the recent demonstration of clinical efficacy with the platform. Building upon this platform, this study reports that enzymemediated modification of the muscle tissue extracellular matrix structure at the site of pDNA delivery operates in a synergistic manner with EP to enhance both local and systemic gene expression further. Specifically, administration of chondroitinase ABC (Cho ABC) to the site of intramuscular delivery of pDNA led to transient disruption of chondroitin sulfate scaffolding barrier, permitting enhanced gene distribution and expression across the tissue. The employment of Cho ABC in combination with CEL-LECTRA Ò intramuscular EP resulted in increased gene expression by 5.5-fold in mice and 17.98-fold in rabbits. The study demonstrates how this protocol can be universally applied to an active prophylaxis platform to increase the in vivo production of functional immunoglobulin G, and to DNA vaccine protocols to permit drug dose sparing. The data indicate the Cho ABC formulation to be of significant value upon combination with EP to drive enhanced gene expression levels in pDNA delivery protocols.
Output: Active Immunoprophylaxis and Vaccine Augmentations Mediated by a Novel Plasmid DNA Formulation
Microbes and microbial components potentially impact the performance of pigs through immune stimulation and altered metabolism. These immune modulating factors can include endotoxin from gram negative bacterial outer membrane component, commonly referred to as lipopolysaccharide (LPS). In this study, our objective was to examine the relationship between intestinal barrier integrity, endotoxin and infl ammation with feed effi ciency (FE), using pig lines divergently selected for residual feed intake (RFI) as a model. Twelve gilts (62 ± 3 kg BW) from the low RFI (LRFI, more effi cient) and 12 from the high RFI (HRFI, less effi cient) were used. Individual performance data was recorded for 5 wk. At the end of the experimental period, ADFI of LRFI pigs was less (P < 0.001), ADG not different between the 2 lines (P = 0.72) but the G:F of LRFI pigs was greater than for HRFI pigs (P = 0.019). Serum endotoxin concentration (P < 0.01) and the acute phase protein haptoglobin (P < 0.05) were greater in HRFI pigs. Transepithelial resistance of the ileum, transport of fl uorescein isothiocyanate labeled-Dextran and-LPS in ileum and colon, as well as tight junction protein mRNA expression in ileum, did not differ between the lines, indicating the 2 lines did not differ in transport characteristics at the intestinal level. Ileum infl ammatory markers, myeloperoxidase (P < 0.05) and IL-8 (P < 0.10), were found to be greater in HRFI pigs. Alkaline phosphatase (ALP) activity was signifi cantly increased in the LRFI pigs in ileum and liver tissues and negatively correlated with blood endotoxin (P < 0.05). Lysozyme activity in the liver was not different between the lines; however, the LRFI pigs had a twofold greater lysozyme activity in ileum (P < 0.05). Despite the difference in their activity, ALP or lysozyme mRNA expression was not different between the lines in either tissue. Decreased endotoxin and infl ammatory markers and the enhanced activities of antimicrobial enzymes in the LRFI line may not fully explain the difference in the FE between the lines, but they have the potential to prevent the growth potential in HRFI pigs. Further studies are needed to identify the other mechanisms that may contribute to the greater endotoxin and acute phase proteins in the HRFI pigs and the greater FE in the LRFI pigs.
Output: Intestinal integrity, endotoxin transport and detoxifi cation in pigs divergently selected for residual feed intake 1
Background: Prevention of infection with airborne pathogens and exposure to airborne particulates and aerosols (environmental pollutants and allergens) can be facilitated through use of disposable face masks. The effectiveness of such masks for excluding pathogens and pollutants is dependent on the intrinsic ability of the masks to resist penetration by airborne contaminants. This study evaluated the relative contributions of a mask, valve, and Micro Ventilator on aerosol filtration efficiency of a new N95 respiratory face mask. Methods: The test mask was challenged, using standardized methods, with influenza A and rhinovirus type 14, bacteriophage ΦΧ174, Staphylococcus aureus (S. aureus), and model pollutants. The statistical significance of results obtained for different challenge microbial agents and for different mask configurations (masks with operational or nonoperational ventilation fans and masks with sealed Smart Valves) was assessed. Results: The results demonstrate >99.7% efficiency of each test mask configuration for exclusion of influenza A virus, rhinovirus 14, and S. aureus and >99.3% efficiency for paraffin oil and sodium chloride (surrogates for PM 2.5 ). Statistically significant differences in effectiveness of the different mask configurations were not identified. The efficiencies of the masks for excluding smaller-size (i.e., rhinovirus and bacteriophage ΦΧ174) vs. larger-size microbial agents (influenza virus, S. aureus) were not significantly different. Conclusions: The masks, with or without features intended for enhancing comfort, provide protection against both small-and large-size pathogens. Importantly, the mask appears to be highly efficient for filtration of pathogens, including influenza and rhinoviruses, as well as the fine particulates (PM 2.5 ) present in aerosols that represent a greater challenge for many types of dental and surgical masks. This renders this individual-use N95 respiratory mask an improvement over the former types of masks for protection against a variety of environmental contaminants including PM 2.5 and pathogens such as influenza and rhinoviruses.
Output: Assessment of a respiratory face mask for capturing air pollutants and pathogens including human influenza and rhinoviruses
Recent molecular diagnostic methods have significantly improved the diagnosis of viral pneumonia in intensive care units (ICUs). It has been observed that 222G/N changes in the HA gene of H1N1pdm09 are associated with increased lower respiratory tract (LRT) replication and worse clinical outcome. In the present study, the frequency of respiratory viruses was assessed in respiratory samples from 88 patients admitted to 16 ICUs during the 2014-2015 winter-spring season in Lombardy. Sixty-nine out of 88 (78.4%) patients were positive for a respiratory viral infection at admission. Of these, 57/69 (82.6%) were positive for influenza A (41 A/H1N1pdm09 and 15 A/H3N2), 8/69 (11.6%) for HRV, 2/69 (2.9%) for RSV and 2/69 (2.9%) for influenza B. Phylogenetic analysis of influenza A/H1N1pdm09 strains from 28/41 ICU-patients and 21 patients with mild respiratory syndrome not requiring hospitalization, showed the clear predominance of subgroup 6B strains. The median influenza A load in LRT samples of ICU patients was higher than that observed in the upper respiratory tract (URT) (p<0.05). Overall, a greater number of H1N1pdm09 virus variants were observed using next generation sequencing on partial HA sequences (codons 180-286) in clinical samples from the LRT as compared to URT. In addition, 222G/N/A mutations were observed in 30% of LRT samples from ICU patients. Finally, intra-host evolution analysis showed the presence of different dynamics of viral population in LRT of patients hospitalized in ICU with a severe influenza infection.
Output: Frequency of respiratory virus infections and next-generation analysis of influenza A/ H1N1pdm09 dynamics in the lower respiratory tract of patients admitted to the ICU
The ability to rescue an infectious, recombinant, negative-stranded, RNA virus from a cDNA clone, has led to new opportunities for measuring viral replication from a viral expressed reporter gene. In this study, the enhanced green fluorescent protein (EGFP) gene was inserted into the human parainfluenza virus type 3 (HPIV-3) antigenome and a recombinant, infectious virus was rescued. Maximum EGFP expression levels, measured by fluorescence, were seen at day 3. Comparison of a three-day, viral expressed EGFP fluorescence assay to a seven-day, neutral red assay, based on complete cell destruction in virus infected MA-104 cells, yielded Z′-factor values of 0.83 and 0.70, respectively. A three-day, endpoint EGFP-based antiviral assay and a seven-day, endpoint neutral red based antiviral assay were run in parallel to establish antiviral sensitivity profiles of 23 compounds based on selective index (SI) values. Using an SI threshold of 10, the EGFP-based antiviral assay had a sensitivity of 100% and a specificity of 54%. Thus, the use of an EGFP-based antiviral assay for testing potential antiviral compounds against HPIV-3 in a high-throughput format may be justified.
Output: A recombinant, infectious human parainfluenza virus type 3 expressing the enhanced green fluorescent protein for use in high-throughput antiviral assays
The outbreak of coronavirus disease 2019 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in China has been declared a public health emergency of international concern. The cardiac injury was dominate in the process. However, whether N terminal pro B type natriuretic peptide (NT-proBNP) predicted outcome of COVID-19 patients was unknown. The study initially enrolled 102 patients with severe COVID-19 pneumonia from a continuous sample. After screening out the ineligible cases, 54 patients were analyzed in this study. Results found that patients with higher NT-proBNP (above 88.64 pg/mL) level had more risks of inhospital death. After adjusting for potential cofounders in separate modes, NT-proBNP presented as an independent risk factor of in-hospital death in patients with severe COVID-19. : medRxiv preprint Figure 1. The NT-proBNP for in-hospital death of coronavirus disease 2019 (COVID-19) by receiver operating characteristic (ROC) curves. The area under the curve (AUC) of NT-proBNP was 0.909. The best cutoff of NT-proBNP for prediction in-hospital death was 88.64 pg/mL with the sensitivity of 100% and the specificity of 66.67%. 95%CI, 95% confidence interval. All rights reserved. No reuse allowed without permission. the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint (which was not peer-reviewed) is . https://doi.org/10. 1101 Figure 2. Kaplan-Meier plots showing the cumulative survival rate of COVID-19 patients who were stratified into two groups according to plasma NT-proBNP cutoff point at baseline (Dotted line, NT-proBNP ≤88.64 pg/ml, n=24; Solid line, NT-proBNP >88.64 pg/ml, n=30; log-rank test for trend, P<0.001). All rights reserved. No reuse allowed without permission. the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
Output: Prognostic value of NT-proBNP in patients with severe COVID-19
Viral gain-of-function mutations are commonly observed in the laboratory; however, it is unknown whether those mutations also evolve in nature. We identify two key residues in the host recognition protein of bacteriophage l that are necessary to exploit a new receptor; both residues repeatedly evolved among homologs from environmental samples. Our results provide evidence for widespread host-shift evolution in nature and a proof of concept for integrating experiments with genomic epidemiology. Many viruses can expand their host range with a few mutations 1-3 that enable the exploitation of new cellular receptors 2,3 . Such mutations may be the first steps toward an epidemic outbreak; this observation has driven an expansion of theoretical 4 , experimental and surveillance studies of host-range shifts in emergent pathogens, including avian influenza 5-8 , coronaviruses 9,10 , HIV 11 and ebolavirus 12 . Ideally, laboratory evolution experiments could be used to accelerate our understanding of how viruses expand their host range. However, it is not clear whether viral evolution observed under the chemical and physical environments of a laboratory can faithfully inform us about viral evolution in nature, for at least two reasons. First, evolutionary trajectories might be sensitive to differences in environmental conditions between the laboratory and nature. Second, the number of evolutionary paths sampled in laboratory experiments is very small compared to natural virus diversity due to the enormous size of viral All rights reserved. No reuse allowed without permission.
Output: Viral gain-of-function experiments uncover residues under diversifying selection in nature
The successful use of any adenoviral vectors is predicated upon the use of a serotype that is not neutralized by circulating antibodies. However, efforts to develop a diverse repertoire of serologically distinct adenovirus vectors may be hindered by the necessity to generate cell lines to allow for the successful propagation of vectors deleted of essential genes. A strategy to construct chimeric adenoviruses whereby the rescue and propagation of an E1 deleted HAdV-B -derived adenoviral vector can be achieved using existing cell lines such as HEK 293 is reported. It is further shown that this strategy may be more widely applicable.
Output: Rescue of chimeric adenoviral vectors to expand the serotype repertoire
Background: Theaflavins are major polyphenols in black tea which is the most widely consumed tea in the world. They possess a broad spectrum of biological activities, such as antioxidant, anti-tumor, anti-inflammatory, and cardio-protective effects. The present study was aimed to evaluate the protective effect of theaflavin on glycoprotein content and tricorboxylic acid cycle enzymes in high-fat diet and streptozotocin-induced diabetic rats as there was no study on this aspect. Diabetes was induced in male albino Wistar rats by feeding them with high-fat diet and injecting them intraperitoneally with streptozotocin (40 mg/kg b.wt). Results: Different doses of theaflavin (25, 50, and 100 mg/kg b.wt /day) were administered orally to high-fat diet and streptozotocin-induced diabetic rats for 30 days for fixing the glucose lowering dose. However, the dose at 100 mg/kg b.wt showed a significant reduction in the levels of plasma glucose and Homeostatic Model Assessment of Insulin Resistance with concomitant elevation of insulin when compared to the other two doses (25 and 50 mg/kg b.wt). Hence, 100 mg/kg b.wt was fixed as an effective dose and used for further analysis. Theaflavin administration restored the altered glycosylated hemoglobin, hemoglobin and glycoproteins (Hexose, hexosamine, fucose, and sialic acid) and TCA cycle enzymes (isocitrate dehydrogenase, α-ketoglutarate dehydrogenase, succinate dehydrogenase, and malate dehydrogenase) near the normal levels by correcting hyperglycemia. Improved histological changes were observed in the pancreas of diabetic rats upon treatment with theaflavin which supported the biochemicals investigated. Conclusion: The effect produced by the theaflavin on various parameters was comparable to that of metformin-a reference antidiabetic drug. These findings suggest that theaflavin can replace the commercial drugs which could lead to reduction in toxicity and side effect caused by the later as well as reduce the secondary completions.
Output: Protective effect of theaflavin on glycoprotein components and TCA cycle enzymes in high-fat diet and streptozotocin-induced diabetic rats
Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most economically devastating and pandemic diseases of swine, which is poorly controlled by current methods. The inhibition of specific genes by small interfering RNA (siRNA) has been proven to be a potential therapeutic strategy against viral infection. Previous studies have indicated that the nonstructural protein 1α (nsp1α) of PRRSV may take an important role in virulence of PRRSV. The present work was involved to explore the effect of siRNA targeting nsp1α on the replication of PRRSV in MARC-145 cells, and the results showed that over-expression of nsp1α enhanced the replication of PRRSV and that siRNAs specifically targeting nsp1α significantly inhibited the replication of PRRSV in MARC-145 cells. In conclusion, this work indicated that nsp1α may be a viral pathogenicity factor of PRRSV and that siRNAs specifically targeting nsp1α may be a new strategy to control PRRSV in the future.
Output: Small interfering RNA targeting nonstructural protein1 α (nsp1α) of porcine reproductive and respiratory syndrome virus (PRRSV) can reduce the replication of PRRSV in MARC-145 cells
14 Zika virus is a single-stranded, positive-sense RNA virus of the family Flaviviridae, which has 15 recently undergone a rapid expansion among humans in the Western Hemisphere. Here, we report 16 a high-resolution map of ribosomal occupancy of the Zika virus genome during infection of 17 mammalian and insect cells, obtained by ribosome profiling. In contrast to some other flaviviruses 18 such as West Nile, we find no evidence for substantial frameshift-induced ribosomal drop-off 19 during translation of the viral polyprotein, indicating that Zika virus must use alternative 20 mechanisms to downregulate levels of catalytically active viral polymerase. We also show that 21 high levels of ribosome-protected fragments map in-frame to two previously overlooked upstream 22 open reading frames (uORFs) initiating at CUG and UUG codons, with likely consequences for 23 the efficiency of polyprotein expression. Curiously, in African isolates of Zika virus, the two 24 uORFs are fused in-frame into a single uORF. A parallel RNA-Seq analysis reveals the 5' end 25 . CC-BY 4.0 International license is made available under a
Output: The translational landscape of Zika virus during infection of mammalian and 1 insect cells 2 3
Children in pediatric long-term care facilities (pLTCFs) have complex medical conditions and increased risk for health careeassociated infections (HAIs). We performed a retrospective study from January 2010-December 2013 at 3 pLTCFs to describe HAI outbreaks and associated infection control interventions. There were 62 outbreaks involving 700 cases in residents and 250 cases in staff. The most common interventions were isolation precautions and education and in-services. Further research should examine interventions to limit transmission of infections in pLTCFs.
Output: Health careeassociated infection outbreaks in pediatric long-term care facilities
Background: Amino acids are well known to be key effectors of gut protein turnover. We recently reported that enteral delivery of proteins markedly stimulated global duodenal protein synthesis in carbohydrate-fed healthy humans, but specifically affected proteins remain unknown. Objective: We aimed to assess the influence of an enteral protein supply on the duodenal mucosal proteome in carbohydrate-fed humans. Design: Six healthy volunteers received for 5 h, on 2 occasions and in random order, either an enteral infusion of maltodextrins alone (0.25 g $ kg 21 $ h 21 ) mimicking the fed state or maltodextrins with a protein powder (0.14 g proteins $ kg 21 $ h 21 ). Endoscopic duodenal biopsy specimens were then collected and frozen until analysis. A 2-dimensional polyacrylamide gel electrophoresis-based comparative proteomics analysis was then performed, and differentially expressed proteins (at least 61.5-fold change; Student's t test, P , 0.05) were identified by mass spectrometry. Protein expression changes were confirmed by Western blot analysis. Results: Thirty-two protein spots were differentially expressed after protein delivery compared with maltodextrins alone: 28 and 4 spots were up-or downregulated, respectively. Among the 22 identified proteins, 11 upregulated proteins were involved either in the cytoskeleton (ezrin, moesin, plastin 1, lamin B1, vimentin, and b-actin) or in protein biosynthesis (glutamyl-prolyl-transfer RNA synthetase, glutaminyl-transfer RNA synthetase, elongation factor 2, elongation factor 1d, and eukaryotic translation and initiation factor 3 subunit f). Conclusions: Enteral delivery of proteins altered the duodenal mucosal proteome and mainly stimulated the expression of proteins involved in cytoskeleton and protein biosynthesis. These results suggest that protein supply may affect intestinal morphology by stimulating actin cytoskeleton remodeling. This trial was registered at clinicaltrials.gov as NCT01254110. Am J Clin Nutr 2015;102:359-67.
Output: Enteral delivery of proteins enhances the expression of proteins involved in the cytoskeleton and protein biosynthesis in human duodenal mucosa 1,2
Background. The Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe respiratory infection with a high (~35%) mortality rate. Neutralizing antibodies targeting the spike of MERS-CoV have been shown to be a therapeutic option for treatment of lethal disease. Methods. We describe the germline diversity and neutralizing activity of 13 potent human monoclonal antibodies (mAbs) that target the MERS-CoV spike (S) protein. Biological functions were assessed by live MERS-CoV, pseudotype particle and its variants, and structural basis was also determined by crystallographic analysis. Results. Of the 13 mAbs displaying strong neutralizing activity against MERS-CoV, two with the immunoglobulin heavy-chain variable region (IGHV)1-69-derived heavy chain (named MERS-GD27 and MERS-GD33) showed the most potent neutralizing activity against pseudotyped and live MERS-CoV in vitro. Mutagenesis analysis suggested that MERS-GD27 and MERS-GD33 recognized distinct regions in S glycoproteins, and the combination of 2 mAbs demonstrated a synergistic effect in neutralization against pseudotyped MERS-CoV. The structural basis of MERS-GD27 neutralization and recognition revealed that its epitope almost completely overlapped with the receptor-binding site. Conclusions. Our data provide new insights into the specific antibody repertoires and the molecular determinants of neutralization during natural MERS-CoV infection in humans. This finding supports additional efforts to design and develop novel therapies to combat MERS-CoV infections in humans.
Output: Ultrapotent Human Neutralizing Antibody Repertoires Against Middle East Respiratory Syndrome Coronavirus From a Recovered Patient
Early innate and cell-intrinsic responses are essential to protect host cells against pathogens. In turn, viruses have developed sophisticated mechanisms to establish productive infections, counteracting the host innate immune responses. Increasing evidence indicates that these antiviral factors may have a dual role by directly inhibiting viral replication, as well as by sensing and transmitting signals to induce antiviral cytokines. Recent studies have pointed at new, unappreciated mechanisms of viral evasion of host innate protective responses including manipulating the host ubiquitin system. Viral inhibition of antiviral factors by ubiquitin-dependent degradation is emerging as critical evasion mechanism of the antiviral response. In addition, recent studies have uncovered new mechanisms by which viral encoded proteins inhibit ubiquitin and ubiquitin-like modification of host proteins involved innate immune signaling pathways. Here we discuss recent findings and novel strategies that viruses have developed to counteract these early innate antiviral defenses. Early events in viral infection include attachment to the host cell membrane and entry, release of the viral RNA, DNA, and protein complexes into the cytoplasm of the cell and early recognition by the host innate immune system. At each of these steps, host cells have developed mechanisms to limit virus infection. In turn, viruses have rapidly evolved to counteract host defenses by different mechanisms. Many recent studies have pointed at the importance of cell type and host specific expression of antiviral factors as critical for
Output: Viral evasion mechanisms of early antiviral responses involving regulation of ubiquitin pathways NIH Public Access
S-palmitoylation is a reversible, enzymatic posttranslational modification of proteins in which palmitoyl chain is attached to a cysteine residue via a thioester linkage. S-palmitoylation determines the functioning of proteins by affecting their association with membranes, compartmentalization in membrane domains, trafficking, and stability. In this review, we focus on S-palmitoylation of proteins, which are crucial for the interactions of pathogenic bacteria and viruses with the host. We discuss the role of palmitoylated proteins in the invasion of host cells by bacteria and viruses, and those involved in the host responses to the infection. We highlight recent data on protein S-palmitoylation in pathogens and their hosts obtained owing to the development of methods based on click chemistry and acyl-biotin exchange allowing proteomic analysis of protein lipidation. The role of the palmitoyl moiety present in bacterial lipopolysaccharide and lipoproteins, contributing to infectivity and affecting recognition of bacteria by innate immune receptors, is also discussed.
Output: Protein Palmitoylation and its Role in Bacterial and viral infections
Pneumococcal/lobar pneumonia and empyema have an important impact on the health of children worldwide. There has been no epidemiological study of pneumococcal/lobar pneumonia and empyema in Taiwan, a middle-income Asian population. Using Taiwan's National Health Insurance database, we collected and analyzed data obtain from medical care claims related to pneumococcal/ lobar pneumonia and empyema for children below the 18 years old from 1997 to 2004. We found the annual population-based incidence to have significant year to year increases and the average annual incidences of pneumococcal/ lobar pneumonia and empyema in children under five to be 44.9 and 10.5 episodes per 100,000 children-year, respectively. About 64% of children with pneumococcal/ lobar pneumonia and empyema were under 5 years old. Children 4 to 5 years old had the highest incidences of both pneumococcal/lobar pneumonia and empyema. Incidence was the highest each spring. The odds ratio of the case fatality among pneumococcal/lobar pneumonia patients complicated with empyema to those without was 118 (95% confidence interval 28-492). In conclusion, the populationbased incidences of pneumococcal/lobar pneumonia and empyema among children under five in Taiwan were 44.9 and 10.5 episodes per 100,000 children-year, respectively, and 4-to 5-year-old children had the highest incidences of both pneumococcal/lobar pneumonia and empyema. This population might benefit from a universal pneumococcal vaccination program which might cover about 70% of invasive pneumococcal diseases in Taiwanese children under 5 years old.
Output: The epidemiology of hospitalized children with pneumococcal/ lobar pneumonia and empyema from 1997 to 2004 in Taiwan
The B lymphocytes of the common marmoset Callithrix jacchus can be immortalised by infection with Epstein-Barr virus (EBV) in vitro (Desgranges et al., 1976) . C. jacchus is susceptible to infection with the blood stages of several species of malaria parasite including the line designated MVF1 (Mitchell et al., 1988) from which it recovers and shows immunity to reinfection. By exploiting these two phenomena, EBV-transformed, marmoset lymphoblastoid cell lines secreting antibodies to malaria parasite antigens have been generated and cloned. We believe this to be the first time that monoclonal antibodies (MAbs) have been raised from common marmosets. Since numerous and diverse human pathogens can infect this small primate in the laboratory, these methods may prove generally applicable for the generation of MAbs whose specificities derive from immune responses to infection.
Output: Monoclonal antibodies from Epstein-Barr virus-transformed lymphocytes of common marmosets (Callithrixjacchus) immune to malaria
Among 489 bats of 11 species in China, three novel paramyxoviruses [Tuhokovirus 1, 2 and 3 (ThkPV-1, ThkPV-2 and ThkPV-3)] were discovered in 15 Leschenault's rousettes. Phylogenetically, the three viruses are most closely related to Menangle and Tioman virus. Genome analysis showed that their 3'-leader sequences are unique by possessing GA instead of AG at the 5th and 6th positions. Unlike Menangle and Tioman virus, key amino acids for neuraminidase activity characteristic of rubulavirus attachment proteins are present. The genome of ThkPV-1 represents the largest rubulavirus genome. Unique features between the three viruses include perfect complementary 5'-trailer and 3'-leader sequence and a unique cysteine pair in attachment protein of ThkPV-1, G at +1 position in all predicted mRNA sequences of ThkPV-2, and amino acid substitutions in the conserved Nterminal motif of nucleocapsid of ThkPV-3. Analysis of phosphoprotein gene mRNA products confirmed mRNA editing. Antibodies to the viruses were detected in 48-60% of Leschenault's rousettes.
Output: Identification and complete genome analysis of three novel paramyxoviruses, Tuhoko virus 1, 2 and 3, in fruit bats from China
To satisfy a user's need to find and understand the whole picture of an event effectively and efficiently, in this paper we formalize the problem of temporal event searches and propose a framework of event relationship analysis for search events based on user queries. We define three kinds of event relationships: temporal, content dependence, and event reference, that can be used to identify to what extent a component event is dependent on another in the evolution of a target event (i.e., the query event). The search results are organized as a temporal event map (TEM) that serves as the whole picture about an event's evolution or development by showing the dependence relationships among events. Based on the event relationships in the TEM, we further propose a method to measure the degrees of importance of events, so as to discover the important component events for a query, as well as the several algebraic operators involved in the TEM, that allow users to view the target event. Experiments conducted on a real data set show that our method outperforms the baseline method Event Evolution Graph (EEG), and it can help discover certain new relationships missed by previous methods and even by human annotators. ✩ This article is an extension version of a conference proceeding published in Cai et al. (2013) [1], and some notations, definitions, formulations, descriptions, figures, tables and so on are reused to make new contributions smoothly in this article. The new contributions of this article are (1) new methods of event ranking and temporal event map construction; (2) algebraic operations of the event map; (3) more examples, case studies, and metrics in experiments; and (4) more comprehensive literature review and descriptions.
Output: Temporal event searches based on event maps and relationships ✩
20 This work aimed to evaluate the cytotoxic potential against cancer cells of Passiflora genus 21 plant species cultivated in Brazil and identify the mechanism of cytotoxicity induced by the 22 most promising extract. Leaf extracts from 14 Passiflora (P.) species were obtained ASE and 23 in vitro cytotoxicity evaluated against cancer cell lines using MTT assay at a single . CC-BY 4.0 International license author/funder. It is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/337253 doi: bioRxiv preprint 2 24 concentration of 50 μg/mL. Additionally, the IC 50 of the P. alata (ELPA) leaf extracts was 25 determined against both tumor (HCT-116, SF-295, OVACAR-8, and HL-60), and non-tumor 26 cells (PBMC). The ELPA flavonoids were identified by HPLC-DAD and UHPLC-MS/MS. 27 The morphological analyses used light and fluorescence microscopy, and cell cycle and DNA 28 fragmentation analyses used flow cytometry to determine the mechanism of cell death induced 29 by ELPA in HL-60. Among the Passiflora leaf extracts evaluated; ELPA stood out with high 30 cytotoxic activity, followed by P. capsularis and P. quadrangulares with varying high and low 31 cytotoxic activity. ELPA presented high cytotoxic potency in HL-60 (IC 50 19.37 μg/mL), yet 32 without cytotoxic activity against PBMC, suggesting selectivity for tumor cells. The cytotoxic 33 activity of ELPA may well be linked to the presence of ten identified flavonoids. Cells treated 34 with ELPA presented the hallmarks typical of apoptosis and necrosis, with cell cycle arrest in 35 the G2/M phase. Conclusion: From among the studied species, ELPA presented greater 36 cytotoxic activity, possibly a consequence of synergistic flavonoid action which induces cell 37 death by apoptosis and necrosis.
Output: Evaluation of the cytotoxic potential of extracts from the genus Passiflora 2 cultived in Brazil against cancer cells
Oncolytic virotherapy is a promising form of gene therapy for cancer, employing nature's own agents to find and destroy malignant cells. The purpose of this review is to provide an introduction to this very topical field of research and to point out some of the current observations, insights and ideas circulating in the literature. We have strived to acknowledge as many different oncolytic viruses as possible to give a broader picture of targeting cancer using viruses. Some of the newest additions to the panel of oncolytic viruses include the avian adenovirus, foamy virus, myxoma virus, yaba-like disease virus, echovirus type 1, bovine herpesvirus 4, Saimiri virus, feline panleukopenia virus, Sendai virus and the non-human coronaviruses. Although promising, virotherapy still faces many obstacles that need to be addressed, including the emergence of virus-resistant tumor cells.
Output: Mini-review Oncolytic viruses in cancer therapy
The available databases that catalogue information on traditional Chinese medicines are reviewed in terms of their content and utility for in-silico research on Chinese herbal medicines, as too are the various protein database resources, and the software available for use in such studies. The software available for bioinformatics and 'omics studies of Chinese herbal medicines are summarised, and a critical evaluation given of the various in-silico methods applied in screening Chinese herbal medicines, including classification trees, neural networks, support vector machines, docking and inverse docking algorithms. Recommendations are made regarding any future in-silico studies of Chinese herbal medicines. (D.J. Barlow). It is vitally important to any in-silico studies of CHM that the associated phytochemical data are available in a format suitable for virtual screening (VS) or other informatics applications. Over recent years the information available for Chinese herbs has increased 0378-8741
Output: In-silico studies in Chinese herbal medicines' research: Evaluation of in-silico methodologies and phytochemical data sources, and a review of research to date
The goal of this project was to better define the relationship between the endoribonuclease activity of murine hepatitis virus (MHV) Nsp15 (mNsp15) and its role in virus infection. Molecular modeling demonstrated that the catalytic residues of mNsp15 are superimposable with its severe acute respiratory syndrome coronavirus ortholog. Alanine substitutions at three key residues in the mNsp15 catalytic pocket (H262, H277, and G275) and a double-mutant version (H262P and H277A) generated proteins with greatly reduced but detectable endoribonuclease activities. Furthermore, these mutant proteins demonstrated lower cleavage specificities for uridylate than wild-type (WT) mNsp15. These mutations were successfully incorporated into viruses named vH262A, vH277A, vG275A, and vH262P؉H277A. All four mutant viruses formed plaques with diameters similar to that of MHV-A59 1000 (WT virus) on several different cell lines. Interestingly, viruses with a mutation at a noncatalytic residue, D324A, could not be recovered despite repeated attempts, and expression of mNsp15 containing the D324A mutation in Escherichia coli resulted in an insoluble protein. Plaques derived from vH262A produced approximately 6-to 13-fold fewer PFU than those from WT virus. Cells infected with mNsp15 mutant viruses accumulated lesser amounts of plus-and minus-sense subgenomic RNAs and spike protein than WT virus. The expression of mNsp15 in trans by transient transfection partially restored RNA synthesis by vH262A. These results demonstrate that mNsp15 is required for optimal infection by MHV.
Output: Biochemical and Genetic Analyses of Murine Hepatitis Virus Nsp15 Endoribonuclease ᰔ Downloaded from
Knowledge of implicated food vehicles and contributing factors derived from foodborne disease outbreak (FBDO) investigations allows consumers to be educated on decreasing high-risk behavior to reduce the risk of being affected by foodborne diseases. Food safety regulatory authorities also need summary of outbreak data, as these data indicate where the existing food supply system should be improved. To obtain information on epidemiology of FBDOs in China, FBDOs reported to the China National Foodborne Diseases Surveillance Network by 12 surveillance provinces that include 43% of the Chinese population was summarized. Between 2003 and 2008, 2795 FBDOs were reported, resulting in 62559 illnesses, 31261 hospitalizations, and 330 deaths. Outbreak size ranged from 2 to 464 cases, with a median of 14 cases. The outbreak rate had decreased from 1.37 per 1 million population in 2003 to 0.46 per 1 million population in 2008. Of the 2176 outbreaks with a single known etiology, bacteria (1051 outbreaks, 48%), man-made chemical hazards (550 outbreaks, 25%), and animal and plant toxins (536 outbreaks, 25%) were the main courses. Only one outbreak was caused by virus. Of the 1930 outbreaks with a single commodity, plant-based foods were the most common reported (930 outbreaks, 48%), followed by animal-based foods (590 outbreaks, 31%). Outbreaks most frequently occurred in private residences (32%), workplace cafeterias (21%), and restaurants (17%). The most common factor reported in the 2190 outbreaks with known contributing factors were improper cooking (510 outbreaks, 23%), contaminated ingredient (503 outbreaks, 23%), cross contamination (475 outbreaks, 22%) and improper storage (295 outbreaks, 13%). It is considered that FBDOs continue to be an important public health problem in China.
Output: Surveillance for foodborne disease outbreaks in China, 2003 to 2008
Porcine Epidemic Diarrhea Virus (PEDV), Porcine Delta Corona Virus (PDCoV), and Transmissible Gastroenteritis Virus (TGEV) are major threats to swine health and contaminated feed plays a role in virus transmission. The objective of our study was to characterize inactivation of PEDV, PDCoV, and TGEV in various feed ingredient matrices. Samples of complete feed, spray dried porcine plasma, meat meal, meat and bone meal, blood meal, corn, soybean meal, and corn dried distillers grains with solubles were weighed (5 g/sample) into scintillation vials and inoculated with 1 mL of PEDV, PDCoV, or TGEV. Samples were incubated at room temperature for up to 56 days. Aliquots were removed at various time points followed by preparing serial 10-fold dilutions and inoculating in cell cultures to determine the amount of surviving virus. Inactivation kinetics were determined using the Weibull model, which estimates a delta value indicating the time necessary to reduce virus concentration by 1 log. Delta values of various ingredients were compared and analyzed as to their nutrient composition. Soybean meal had the greatest delta value (7.50 days) for PEDV (P < 0.06) as compared with all other ingredients. High delta values (P < 0.001) were observed in soybean meal for PDCoV (42.04 days) and TGEV (42.00 days). There was a moderate correlation between moisture content and the delta value for PDCoV (r = 0.49, P = 0.01) and TGEV (r = 0.41, P = 0.02). There was also a moderate negative correlation between TGEV survival and ether extract content (r = -0.51, P = 0.01). In conclusion, these results indicate that the first log reduction of PDCoV and TGEV takes the greatest amount of time in soybean meal. In addition to this, moisture and ether content appear to be an important determinant of virus survival in feed ingredients.
Output: Environmental persistence of porcine coronaviruses in feed and feed ingredients