niryuu/sni-each-converted huggingface dataset:
Influenza pandemics have occurred throughout history and were associated with substantial excess mortality and morbidity. Mathematical models of infectious diseases permit quantitative description of epidemic processes based on the underlying biological mechanisms. Mathematical models have been widely used in the past decade to aid pandemic planning by allowing detailed predictions of the speed of spread of an influenza pandemic and the likely effectiveness of alternative control strategies. During the initial waves of the 2009 influenza pandemic, mathematical models were used to track the spread of the virus, predict the time course of the pandemic and assess the likely impact of large-scale vaccination. While mathematical modeling has made substantial contributions to influenza pandemic preparedness, its use as a real-time tool for pandemic control is currently limited by the lack of essential surveillance information such as serologic data. Mathematical modeling provided a useful framework for analyzing and interpreting surveillance data during the 2009 influenza pandemic, for highlighting limitations in existing pandemic surveillance systems, and for guiding how these systems should be strengthened in order to cope with future epidemics of influenza or other emerging infectious diseases.
Output: The use of mathematical models to inform influenza pandemic preparedness and response
Background: The common cold questionnaire (CCQ) is used to discriminate those with and without a viral infection. Its usefulness in people with acute asthma is unknown. Our aim was to assess the ability of the CCQ to detect viral infection and to monitor recovery during a viral induced asthma exacerbation and confirmed by virological testing. Methodology/Principal Findings: We studied subjects ($7 yrs) admitted to hospital with acute asthma and diagnosed as positive (n = 63), or negative to viral infection (n = 27) according to molecular and virological testing from respiratory samples. CCQ, asthma history and asthma control questionnaires were completed and repeated 4-6 weeks later. Sensitivity, specificity, and response to change of the CCQ were assessed by receiver operator curve (ROC) analysis and effect size calculation respectively. The CCQ did not discriminate between viral and non-viral infection for subjects with asthma (sensitivity = 76.2%; specificity = 29.6%). ROC analysis could not differentiate between positive or negative virus in subjects with asthma. The CCQ had a large response to change following recovery (effect size = 1.01). 39% of subjects recovering from viral exacerbation remained positive to virological testing at follow-up despite improvement in clinical symptoms. The CCQ reflected clinical improvement in these subjects, thus providing additional information to complement virological testing. Conclusions/Significance: The CCQ is a useful instrument for monitoring response to viral infection in people with asthma. Reliable differentiation between viral and non-viral asthma exacerbations was not achieved with the CCQ and requires specific virological testing. When combined with virological testing, the CCQ should be a useful outcome measure for evaluating therapies in viral-induced asthma.
Output: Validity of the Common Cold Questionnaire (CCQ) in Asthma Exacerbations
Human viral pathogens are a major public health threat. Reliable information that accurately describes and characterizes the global occurrence and transmission of human viruses is essential to support national and global priority setting, public health actions, and treatment decisions. However, large areas of the globe are currently without surveillance due to limited health care infrastructure and lack of international cooperation. We propose a novel surveillance strategy, using metagenomic analysis of toilet material from international air flights as a method for worldwide viral disease surveillance. The aim of this study was to design, implement, and evaluate a method for viral analysis of airplane toilet waste enabling simultaneous detection and quantification of a wide range of human viral pathogens. Toilet waste from 19 international airplanes was analyzed for viral content, using viral capture probes followed by high-throughput sequencing. Numerous human pathogens were detected including enteric and respiratory viruses. Several geographic trends were observed with samples originating from South Asia having significantly higher viral species richness as well as higher abundances of salivirus A, aichivirus A and enterovirus B, compared to samples originating from North Asia and North America. In addition, certain city specific trends were observed, including high numbers of rotaviruses in airplanes departing from Islamabad. Based on this study we believe that central sampling and analysis at international airports could be a useful supplement for global viral surveillance, valuable for outbreak detection and for guiding public health resources.
Output: Metagenomic analysis of viruses in toilet waste from long distance flights-A new procedure for global infectious disease surveillance
Accumulating evidence indicates that MERS-CoV originated from bat coronaviruses (BatCoVs). Previously, we demonstrated that both MERS-CoV and BatCoV HKU4 use CD26 as a receptor, but how the BatCoVs evolved to bind CD26 is an intriguing question. Here, we solved the crystal structure of the S1 subunit C-terminal domain of HKU5 (HKU5-CTD), another BatCoV that is phylogenetically related to MERS-CoV but cannot bind to CD26. We observed that the conserved core subdomain and those of other betacoronaviruses (betaCoVs) have a similar topology of the external subdomain, indicating the same ancestor of lineage C betaCoVs. However, two deletions in two respective loops located in HKU5-CTD result in conformational variations in CD26-binding interface and are responsible for the non-binding of HKU5-CTD to CD26. Combined with sequence variation in the HKU5-CTD receptor binding interface, we propose the necessity for surveilling the mutation in BatCoV HKU5 spike protein in case of bat-to-human interspecies transmission.
Output: Structure of the S1 subunit C-terminal domain from bat-derived coronavirus HKU5 spike protein
publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active. Viral infections in solid transplant patients p M DHPG combinated with 5 U / d IFN (Y and 95 f 5% inhibition with 1 l . l p M DHPG in combination with 0.2 ng/d IFN y (n = 3). Conclusions: IFN (Y and IFN y decrease HCMV infection in monocytic-like cell line THP-1 and may lead to an improvement of the available chemotherapy against this important human pathogen. Combination of IFNs with DHPG after lnfection showed a synergistic effect. PCV has a well-documented inhibitory activity against herpes simplex virus and varicelia-zoster virus. By contrast, data on its activity against CMV are limited. We evaluated the in vim activity of PCV against 3 CMV WS (#1 and #2 from marmw transplant recipients, #3 from a neonate) and against CMV strain AD169, and compared the results with those obtained in parallel with acyclovir (ACV), ganciclovir (GCV), and foscarnet (FOS). A plaque reduction assay was used to determine the mhibitory drug concentration reducing plaque numbers by 50% (IC50). The drugs were tested in 6 human fibroblast cell lines. The results were as follows: Median ICsg of 13 p M (630) indxatmg a rerkunce to ganclclovlr.
Output: I P103q Activity of Penciclovir (PCV) in vitro against Cytomegalovirus (CMV) Wild Strains (WS) and against Strain AD169
Purpose: To explore the clinical, microbiological and immunological features of patients with fever and thrombocytopenia. Methods: Patients with unexplained fever and thrombocytopenia were enrolled. Viruses were detected using real-time PCR, and bacteria were measured by culturing methods. Serum cytokines, platelet antibody IgG (PA-IgG) and Helicobacter pylori (HP) were detected using ELISA. Results: Pathogens were detected in 74.68% of patients, which included single fungal/viral/bacterial infection and multiple infection. The pathogens could not be unidentified in 25.32% of cases. Cytokines including Interleukin (IL)-6, IL-10, interferon-γ(IFN-γ), platelet activating factor (PAF) and PA-IgG were significantly higher in patients as compared to healthy controls (P < .01 or P < .05). Principal component analyses extracted four groups of parameters that have a strong positive predicting value, revealing that disease status evaluation would be more accurate if we combined the platelet parameters and inflammatory biomarkers. While event-free survival (EFS) that indicates the time of platelet elevated after therapy was the highest in patients with single bacterial or fungal infection, EFS was affected by the levels of cytokines and PA-IgG. Conclusions: Differences in immune function may be the main factors affecting the prognosis of patients with fever and thrombocytopenia, while treatment based on precise etiological diagnosis is important for therapeutic efficacy.
Output: Serum cytokines and clinical features in patients with fever and thrombocytopenia syndrome
Although pneumococcal pneumonia is one of the most common causes of death due to infectious diseases, little is known about pneumococci-lung cell interaction. Herein we tested the hypothesis that pneumococci activated pulmonary epithelial cell cytokine release by c-Jun-NH 2 -terminal kinase (JNK) Methods: Human bronchial epithelial cells (BEAS-2B) or epithelial HEK293 cells were infected with S. pneumoniae R6x and cytokine induction was measured by RT-PCR, ELISA and Bioplex assay. JNKphosphorylation was detected by Western blot and nuclear signaling was assessed by electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP). JNK was modulated by the small molecule inhibitor SP600125 and AP1 by transfection of a dominant negative mutant. Results: S. pneumoniae induced the release of distinct CC and CXC, as well as Th1 and Th2 cytokines and growth factors by human lung epithelial cell line BEAS-2B. Furthermore, pneumococci infection resulted in JNK phosphorylation in BEAS-2B cells. Inhibition of JNK by small molecule inhibitor SP600125 reduced pneumococci-induced IL-8 mRNA expression and release of IL-8 and IL-6. One regulator of the il8 promoter is JNK-phosphorylated activator protein 1 (AP-1). We showed that S. pneumoniae timedependently induced DNA binding of AP-1 and its phosphorylated subunit c-Jun with a maximum at 3 to 5 h after infection. Recruitment of Ser 63/73 -phosphorylated c-Jun and RNA polymerase II to the endogenous il8 promoter was found 2 h after S. pneumoniae infection by chromatin immunoprecipitation. AP-1 repressor A-Fos reduced IL-8 release by TLR2-overexpressing HEK293 cells induced by pneumococci but not by TNFα. Antisense-constructs targeting the AP-1 subunits Fra1 and Fra2 had no inhibitory effect on pneumococci-induced IL-8 release. Conclusion: S. pneumoniae-induced IL-8 expression by human epithelial BEAS-2B cells depended on activation of JNK and recruitment of phosphorylated c-Jun to the il8 promoter.
Output: Respiratory Research Streptococcus pneumoniae induced c-Jun-N-terminal kinase-and AP-1 -dependent IL-8 release by lung epithelial BEAS-2B cells
Encephalitis literally means inflammation of the brain. In general, this inflammation can result from a viral or bacterial infection in the brain itself or alternatively from a secondary autoimmune reaction against an infection or a tumor in the rest of the body. Besides this, encephalitis is present in (believed autoimmune) diseases with unknown etiology, such as multiple sclerosis or Rasmussen encephalitis (RE). This article summarizes the existing data on the role of T-cells in the pathogenesis of three types of human encephalitis: RE, paraneoplastic encephalomyelitis, and virus encephalitis. In all of them, T-cells play a major role in disease pathogenesis, mainly mediated by major histocompatiblity complex class I-restricted CD8 + T-lymphocytes.
Output: T-Cells in Human Encephalitis
A number of features were included in the final models, including article counts, indicator counts and slopes. In Table 2 -1, the ten features with highest Gini importance are listed for Model 0 → 1 and Model 1 → 0, predicting Y 1 i jt and training on all available weeks. There is substantial overlap between the lists for the two models. For both models, the article count and the mortality, outbreak worsening and novelty indicators were among the most important features. The mortality indicator describes whether or not fatalities were reported during the week, the outbreak worsening indicator captures mentions of increasing cases or worsening conditions, and the novelty indicator measures whether the disease is described as new or unfamiliar. The finding that the novelty indicator was among the most important features is consistent with previous research that has shown that outbreaks of novel diseases are more likely to have associated social response (Fast et al, 2015; McGrath, 1991) . Table 2-1: The ten features with highest Gini importance for Model 0 → 1 and Model 1 → 0 Model 0 → 1 Model 1 → 0 Social Response Indicator EWMA as a Percentage of UCL In this section, we present results for the 30 countries used for model specification and tuning and compare with the overall results in order to access the extent to which tuning and model specification may have affected results for these countries. We experimented with different model specifications and combinations of features on a subset of data consisting of 30 countries, prior to applying our models to the entire collection of countries. Table 2 -2 presents the model performance metrics for both the entire collection of 72 countries and for the subset of 30 countries used for model specification and tuning. Model performance was slightly diminished on the entire collection of countries compared with the 30 countries used for model specification and tuning. In part, the poorer performance can be explained by the fact that the average number of articles per week in the entire collection of countries was lower than in the 30 countries used for model specification -0.14 articles per week versus 3.50 articles per week. We have shown that in general our models perform best on country-disease pairs that receive substantial news coverage.
Output: Predicting Social Response to Infectious Disease Outbreaks from Internet-based News Streams Online Resource 2: Supplemental Model Results Article Count without Duplicates 3 Week Slope of EWMA Article Count with Duplicates Disease Name Mortality Indicator Article Count without Duplicates 3 Week Slope of Mortality Indicator Article Count with Duplicates Outbreak Worsening Indicator Mortality Indicator 3 Week Slope of Outbreak Worsening Indicator Outbreak Worsening Indicator Population Fear Indicator Novelty Indicator Novelty Indicator Officials Fear Indicator 2 Results for the 30 Countries Used for Model Specification and Tuning
The High-speed Railway (HSR) network in China is the largest in the world, competing intensively with airlines for inter-city travel. Panel data from 2007 to 2013 for 138 routes with HSR-air competition were used to identify the ex-post impacts of the entry of HSR services, the duration of operating HSR services since entry, and the specific impacts of HSR transportation variables such as travel time, frequency, and ticket fares on air passenger flows in China. The findings show that the entry of new HSR services in general leads to a 27% reduction in air travel demand. After two years of operating HSR services, however, the negative impact of HSR services on air passenger flows tends to further increase. The variations of the frequency in the temporal dimension and the travel time in the spatial dimension significantly affect air passenger flows. Neither in the temporal nor spatial dimensions are HSR fares strongly related to air passenger flows in China, due to the government regulation of HSR ticket prices during the period of analysis. The impacts of different transportation variables found in this paper are valuable to consider by operational HSR companies in terms of scheduling and planning of new routes to increase their competitiveness relative to airlines.
Output: The implications of high-speed railways on air passenger flows in China
To examine data in support of the viral hypothesis of atopic disease. Data Sources: We retrieved review articles and original research from MEDLINE, OVID, and PubMed (1950-June 2009) that addressed our topic of interest, using the terms respiratory virus, asthma, IgE, atopy, and viral-induced wheeze. Study Selection: Articles were selected for their relevance to viruses and their role in asthma. Much of the data in support of the viral role in asthma focuses on rhinovirus and respiratory syncytial virus. Epidemiologic studies have used factors such as day-care and family size as surrogates for infection in studies that support and negate the role of viruses in the development of asthma. A large volume of literature supports the theory that virus exacerbates preexisting asthma by setting off the inflammatory cascade. No mechanistic studies fully explain how viral infections can translate or exacerbate atopic disease. We provide information from our mouse model that suggests that dendritic cells, IgE, and FcRI are critical to the induction of atopy. Studies of patients taking antiviral agents (eg, ribavirin or palvizumab) support the notion that interfering with respiratory viral infections may decrease the development of atopy. Conclusions: Many studies suggest strongly that viral infections may predispose patients to the development of asthma and other atopic diseases. Further, mechanistic studies are necessary to allow for the development of targeted therapeutics to prevent the translation of viral into atopic disease.
Output: The role of viruses in the development and exacerbation of atopic disease
Introduction: The research of auxiliary diagnosis has always been one of the hotspots in the world. The implementation of auxiliary diagnosis support algorithm for medical text data faces challenges with interpretability and creditability. The improvement of clinical diagnostic techniques means not only the improvement of diagnostic accuracy but also the further study of diagnostic basis. Traditional research methods for diagnostic markers often require a large amount of time and economic costs. Research objects are often dozens of samples, and it is, therefore, difficult to synthesize large amounts of data. Therefore, the comprehensiveness and reliability of traditional methods have yet to be improved. Therefore, the establishment of a model that can automatically diagnose diseases and automatically provide a diagnostic basis at the same time has a positive effect on the improvement of medical diagnostic techniques. Methods: Here, we established an auxiliary diagnostic tool based on attention deep learning algorithm to diagnostic hyperlipemia and automatically predict the corresponding diagnostic markers using hematological parameters. In this paper, we not only demonstrated the ability of the proposed model to automatically diagnose diseases using text-based medical data, such as physiological parameters, but also demonstrated its ability to forecast disease diagnostic markers. Human physiological parameters are used as input to the model, and the doctor's diagnosis results as an output. Through the attention layer, the degree of attention of the model to different physiological parameters can be obtained, that is, the model provides a diagnostic basis. Results: It achieved 94% ACC, 97.48% AUC, 96% sensitivity and 92% specificity with the test dataset. All the above samples are drawn from clinical practice. Moreover, the model predicted the diagnostic markers of hyperlipidemia by the attention mechanism, and the results were fully agreeable to the golden criteria. Discussion: The auxiliary diagnosis system proposed in this paper not only achieves the accurate and robust performance, and can be used for the preliminary diagnosis of patients, but also showing its great potential to discover new diagnostic markers. Therefore, it not only can improve the efficiency of clinical diagnosis but also shorten the research period of researching a diagnosis basis to an extent. It has a positive significance to the development of the medical diagnosis level.
Output: Deep Learning-Based Method of Diagnosing Hyperlipidemia and Providing Diagnostic Markers Automatically
Cardioviruses are members of the Picornaviridae family and infect a variety of mammals, from mice to humans. Replication of cardioviruses produces double stranded RNA that is detected by helicases in the RIG-I-like receptor family and leads to a signaling cascade to produce type I interferon. Like other viruses within Picornaviridae, however, cardioviruses have evolved several mechanisms to inhibit interferon production. In this review, we summarize recent findings that have uncovered several proteins enabling efficient detection of cardiovirus dsRNA and discuss which cell types may be most important for interferon production in vivo. Additionally, we describe how cardiovirus proteins L, 3C and L * disrupt interferon production and antagonize the antiviral activity of interferon effector molecules.
Output: Innate Immune Detection of Cardioviruses and Viral Disruption of Interferon Signaling
Rapid detection of infectious disease outbreaks is often crucial for their effective control. One example is highly pathogenic avian influenza (HPAI ) such as H5N1 in commercial poultry flocks. There are no quantitative data, however, on how quickly the effects of HPAI infection in poultry flocks can be detected. Here, we study, using an individual-based mathematical model, time to detection in chicken flocks. Detection is triggered when mortality, food or water intake or egg production in layers pass recommended thresholds suggested from the experience of past HPAI outbreaks. We suggest a new threshold for caged flocks-the cage mortality detection threshold-as a more sensitive threshold than current ones. Time to detection is shown to depend nonlinearly on R 0 and is particularly sensitive for R 0 !10. It also depends logarithmically on flock size and number of birds per cage. We also examine how many false alarms occur in uninfected flocks when we vary detection thresholds owing to background mortality. The false alarm rate is shown to be sensitive to detection thresholds, dependent on flock size and background mortality and independent of the length of the production cycle. We suggest that current detection thresholds appear sufficient to rapidly detect the effects of a high R 0 HPAI strain such as H7N7 over a wide range of flock sizes. Time to detection of the effects of a low R 0 HPAI strain such as H5N1 can be significantly improved, particularly for large flocks, by lowering detection thresholds, and this can be accomplished without causing excessive false alarms in uninfected flocks. The results are discussed in terms of optimizing the design of disease surveillance programmes in general.
Output: Detection of mortality clusters associated with highly pathogenic avian influenza in poultry: a theoretical analysis
Global warming is believed to induce a gradual climate change. Hence, it was predicted that tropical insects might expand their habitats thereby transmitting pathogens to humans. Although this concept is a conclusive presumption, clear evidence is still lacking-at least for viral diseases. Epidemiological data indicate that seasonality of many diseases is further influenced by strong single weather events, interannual climate phenomena, and anthropogenic factors. So far, emergence of new diseases was unlinked to global warming. Re-emergence and dispersion of diseases was correlated with translocation of pathogen-infected vectors or hosts. Coupled ocean/ atmosphere circulations and 'global change' that also includes shifting of demographic, social, and economical conditions are important drivers of viral disease variability whereas global warming at best contributes.
Output: Impact of global warming on viral diseases: what is the evidence? This review comes from a themed issue on Pharmaceutical biotechnology Edited
The management of comprehensive and extensive, multi-lateral and multi-national programmes and projects in the field of coastal and ocean management poses numerous organisational problems encompassing co-ordination between: the actions of individual participating countries at the regional level; the national level actions of institutions from different sectors; and actions that are designed to address issues as diverse as: biological diversity conservation and sustainable use; fisheries management; maritime transport; and the control of land based pollution. Most large multi-lateral projects focus on sound scientific knowledge and information, and pay less attention to the design of a management structure that will ensure coherence and co-ordination of the interventions once the programme or project is under implementation. The project entitled "Reversing Environmental Degradation Trends in the South China Sea and Gulf of Thailand" was complex since it addressed three priority areas of concern namely the loss and degradation of coastal habitats, over-exploitation of fisheries in the Gulf of Thailand, and land-based pollution. It is suggested that the success of the management framework reflects the following key design elements: The framework permitted and encouraged both "horizontal" (inter-country) and "vertical" (intra-country) interactions and networking between individuals at all levels of project implementation and execution; Inclusion of a body (the Regional Scientific and Technical Committee) that served as a forum for reconciling both sectorial and national interests and priorities; The clear separation between discussions of scientific and technical matters from discussions dealing with policy and principles at both the national and regional levels; The framework facilitated the incorporation of sound scientific and technical advice and information into politically based decision-making; The use of regional experts and consultants from the participating countries fostered "ownership" of the activities and outputs; Restriction of the membership of the Project Steering Committee to government representatives only, and exclusion of observers from regional and international agencies and institutions other than UNEP; and, The framework allowed for adaptive management and was not a rigid unchanging structure.
Output: Managing multi-lateral, intergovernmental projects and programmes: the case of the UNEP/GEF South China Sea project
While the 2002-2003 outbreak of severe acute respiratory syndrome (SARS) resulted in 774 deaths, patients who were affected with mild pulmonary symptoms successfully recovered. The objective of the present work was to identify, using SARS coronavirus (SARS-CoV) mouse infection models, immune factors responsible for clearing of the virus. The elimination of pulmonary SARS-CoV infection required the activation of B cells by CD4 þ T cells. Furthermore, passive immunization (post-infection) with homologous (murine) anti-SARS-CoV antiserum showed greater elimination efficacy against SARS-CoV than that with heterologous (rabbit) antiserum, despite the use of equivalent titers of neutralizing antibodies. This distinction was mediated by mouse phagocytic cells (monocyte-derived infiltrating macrophages and partially alveolar macrophages, but not neutrophils), as demonstrated both by adoptive transfer from donors and by immunological depletion of selected cell types. These results indicate that the cooperation of anti-SARS-CoV antibodies and phagocytic cells plays an important role in the elimination of SARS-CoV.
Output: Phagocytic cells contribute to the antibody-mediated elimination of pulmonary-infected SARS coronavirus
Background: Lower respiratory tract infections (LRTI) are responsible for a considerable number of deaths among children, particularly in developing countries. In Egypt and the Middle East region, there is a lack of data regarding the viral causes of LRTI. In this study, we aimed to identify the relative prevalence of various respiratory viruses that contribute to LRTIs in young children. Although, nucleic acid-based methods have gained importance as a sensitive tool to determine the viral infections, their use is limited because of their prohibitive cost in low-income countries. Therefore, we applied three different laboratory methods, and presented the different virus prevalence patterns detected by each method. Methods: We collected nasopharyngeal aspirate samples, demographic data and, clinical data from 450 children under five years of age who presented with LRTI at Abou El Reesh hospital in Cairo during a one-year period. To identify the viral causes of the LRTI we used direct fluorescence assay, real-time reverse-transcriptase polymerase chain reaction (rt-RT-PCR), and shell vial culture. We tested for eight major respiratory viruses. Results: Two hundred sixty-nine patients (59.9%) had a viral infection, among which 10.8% had a co-infection with two or more viruses. By all three methods, respiratory syncytial virus (RSV) was the most predominant, and parainfluenza virus type 2 (HPIV-2), influenza B virus (FLUBV) were the least predominant. Other viral prevalence patterns differed according to the detection method used. The distribution of various viruses among different age groups and seasonal distribution of the viruses were also determined. Conclusions: RSV and human adenovirus were the most common respiratory viruses detected by rt-RT-PCR. Co-infections were found to be frequent among children and the vast majority of co-infections were detected by nucleic acid-based detection assays.
Output: Viral etiologies of lower respiratory tract infections among Egyptian children under five years of age
Containment of the SARS coronavirus (SCV) outbreak was accompanied by the rapid characterization of this new pathogen's genome sequence in 2003, encouraging the development of anti-SCV therapeutics using short interfering RNA (siRNA) inhibitors. A pair of siRNA duplexes identified as potent SCV inhibitors in vitro was evaluated for in vivo efficacy and safety in a rhesus macaque SARS model using intranasal administration with clinical viable delivery carrier in three dosing regimens. Observations of SCV-induced SARS-like symptoms, measurements of SCV RNA presence in the respiratory tract, microscopic inspections of lung histopathology, and immunohistochemistry sections from 21 tested macaques consistently demonstrated siRNA-mediated anti-SCV activity. The prophylactic and therapeutic efficacies resulted in relief of animals from SCV infectioninduced fever, diminished SCV in upper airway and lung alveoli, and milder acute diffuse alveoli damage (DAD). The dosages of siRNA used, 10 to 40 mg/kg, did not show any sign of siRNA-induced toxicity. These results support that a clinical investigation of this anti-SARS siRNA therapeutic agent is warranted. The study also illustrates the capability of siRNA to enable a massive reduction in development time for novel targeted therapeutic agents. We detail a representative example of large-mammal siRNA use.
Output: Application of siRNA Against SARS in the Rhesus Macaque Model
Newton's Principia introduces four rules of reasoning for natural philosophy. Although useful, there is a concern about whether Newton's rules guarantee truth. After redirecting the discussion from truth to validity, I show that these rules are valid insofar as they fulfill Goodman's criteria for inductive rules and Newton's own methodological program of experimental philosophy; provided that cross-checks are used prior to applications of rule 4 and immediately after applications of rule 2 the following activities are pursued: (1) research addressing observations that systematically deviate from theoretical idealizations and (2) applications of theory that safeguard ongoing research from proceeding down a garden path. #
Output: Do Newton's rules of reasoning guarantee truth . . . must they?
Although the structural diversity of sialic acid (Sia) is rapidly expanding, understanding of its biological significance has lagged behind. Advanced technologies to detect and probe diverse structures of Sia are absolutely necessary not only to understand further biological significance but also to pursue medicinal and industrial applications. Here we describe analytical methods for detection of Sia that have recently been developed or improved, with a special focus on 9-O-acetylated N-acetylneuraminic acid (Neu5,9Ac), N-glycolylneuraminic acid (Neu5Gc), deaminoneuraminic acid (Kdn), O-sulfated Sia (SiaS), and di-, oligo-, and polysialic acid (diSia/oligoSia/polySia) in glycoproteins and glycolipids. Much more attention has been paid to these Sia and sialoglycoconjugates during the last decade, in terms of regulation of the immune system, neural development and function, tumorigenesis, and aging.
Output: Advanced Technologies in Sialic Acid and Sialoglycoconjugate Analysis
Equine rotaviruses were first detected in foals over 30 years ago and remain a major cause of infectious diarrhoea in foals. During this time, there has been substantial progress in the development of sensitive methods to detect rotaviruses in foals, enabling surveillance of the genotypes present in various horse populations. However, there has been limited epidemiological investigation into the significance of these circulating genotypes, their correlation with disease and the use of vaccination in these animal populations. Our knowledge of the pathogenesis of rotavirus infection in foals is based on a limited number of studies on a small number of foals and, therefore, most of our understanding in this area has been extrapolated from studies in other species. Questions such as the concentrations of rotavirus particles shed in the faeces of infected foals, both with and without diarrhoea, and factors determining the presence or absence of clinical disease remain to be investigated, as does the relative and absolute efficacy of currently available vaccines. The answer to these questions may help direct research into the development of more effective control measures. ß
Output: Equine rotaviruses-Current understanding and continuing challenges
Purpose of Review-Interferon-induced transmembrane protein 3 (IFITM3) is a cellular restriction factor that blocks fusion between virus and host membranes. Here, we provide an introduction to IFITM3 and the biochemical regulation underlying its antiviral activity. Further, we analyze and summarize the published literature examining phenotypes of IFITM3 knockout mice upon infections with viral pathogens and discuss the controversial association between single nucleotide polymorphisms (SNPs) in the human IFITM3 gene and severe virus infections. Recent Findings-Recent publications show that IFITM3 knockout mice experience more severe pathologies than wild-type mice in diverse virus infections, including infections with influenza A virus, West Nile virus, Chikungunya virus, Venezuelan equine encephalitis virus, respiratory syncytial virus, and cytomegalovirus. Likewise, numerous studies of humans of Chinese ancestry have associated the IFITM3 SNP rs12252-C with severe influenza virus infections, though examinations of other populations, such as Europeans, in which this SNP is rare, have largely failed to identify an association with severe infections. A second SNP, rs34481144-A, found in the human IFITM3 promoter has also recently been reported to be a risk allele for severe influenza virus infections. Summary-There is significant evidence for a protective role of IFITM3 against virus infections in both mice and humans, though additional work is required to identify the range of pathogens restricted by IFITM3 and the mechanisms by which human SNPs affect IFITM3 levels or functionality. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http:// creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
Output: Antiviral Protection by IFITM3 In Vivo HHS Public Access
The masked palm civet (Paguma larvata) has been suspected to be the host of a SARS-like CoV virus that causes severe acute respiratory syndrome in humans. In China, the palm civet lives wild and is farmed, but even though the species is a potential carrier of the virus, its geographic distribution and genetic diversity have never been studied. We report the isolation and characterization of six polymorphic microsatellite markers for P. larvata. To characterize each locus, two farmed masked palm civet populations from Shanxi and Guangxi provinces in China were genotyped. The number of alleles per locus ranged from 3 to 15, and the observed heterozygosity for these populations was 47.1 and 68.7%, respectively.
Output: Isolation and Characterization of Polymorphic Microsatellite Markers for the Masked Palm Civet (Paguma larvata)
Porcine epidemic diarrhea virus (PEDV) is a causative agent of porcine epidemic diarrhea (PED). PED, characterized by acute diarrhea, vomiting, dehydration, has caused serious economic losses in pig industry worldwide. Here, we demonstrate that activation of a disintergrin and metalloprotease 17 (ADAM17) induced the decrease of PEDV infection in HEK293 and IPEC-J2 cells and the downregulation of cell surface aminopeptidase N (APN) expression, an important entry factor for PEDV infection. Furthermore, overexpression of ADAM17 suppressed PEDV infection in HEK293 and IPEC-J2 cells, whereas ablation of ADAM17 expression using ADAM17 specific siRNA resulted in a corresponding increase of PEDV infection and an upregulation of cell surface APN expression. Taken together, these data demonstrate that modulation of APN expression by metalloprotease ADAM17 regulates PEDV infection. Hence, the reduction in APN expression represents another component of the anti-PEDV infection response initiated by ADAM17.
Output: Metalloprotease ADAM17 regulates porcine epidemic diarrhea virus infection by modifying aminopeptidase N
The Sec7 domain ADP-ribosylation factor (Arf) guanine nucleotide exchange factors (GEFs) are found in all eukaryotes, and are involved in membrane remodeling processes throughout the cell. This review is focused on members of the GBF/Gea and BIG/Sec7 subfamilies of Arf GEFs, all of which use the class I Arf proteins (Arf1-3) as substrates, and play a fundamental role in traYcking in the endoplasmic reticulum (ER)-Golgi and endosomal membrane systems. Members of the GBF/Gea and BIG/Sec7 subfamilies are large proteins on the order of 200 kDa, and they possess multiple homology domains. Phylogenetic analyses indicate that both of these subfamilies of Arf GEFs have members in at least Wve out of the six eukaryotic supergroups, and hence were likely present very early in eukaryotic evolution. The homology domains of the large Arf1 GEFs play important functional roles, and are involved in interactions with numerous protein partners. The large Arf1 GEFs have been implicated in several human diseases. They are crucial host factors for the replication of several viral pathogens, including poliovirus, coxsackievirus, mouse hepatitis coronavirus, and hepatitis C virus. Mutations in the BIG2 Arf1 GEF have been linked to autosomal recessive periventricular heterotopia, a disorder of neuronal migration that leads to severe malformation of the cerebral cortex. Understanding the roles of the Arf1 GEFs in membrane dynamics is crucial to a full understanding of traYcking in the secretory and endosomal pathways, which in turn will provide essential insights into human diseases that arise from misregulation of these pathways.
Output: Large Arf1 guanine nucleotide exchange factors: evolution, domain structure, and roles in membrane traYcking and human disease
After the outbreak of the severe acute respiratory syndrome (SARS) in the world in 2003, human coronaviruses (HCoVs) have been reported as pathogens that cause severe symptoms in respiratory tract infections. Recently, a new emerged HCoV isolated from the respiratory epithelium of unexplained pneumonia patients in the Wuhan seafood market caused a major disease outbreak and has been named the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This virus causes acute lung symptoms, leading to a condition that has been named as "coronavirus disease 2019" (COVID-19). The emergence of SARS-CoV-2 and of SARS-CoV caused widespread fear and concern and has threatened global health security. There are some similarities and differences in the epidemiology and clinical features between these two viruses and diseases that are caused by these viruses. The goal of this work is to systematically review and compare between SARS-CoV and SARS-CoV-2 in the context of their virus incubation, originations, diagnosis and treatment methods, genomic and proteomic sequences, and pathogenic mechanisms.
Output: Systematic Comparison of Two Animal-to-Human Transmitted Human Coronaviruses: SARS-CoV-2 and SARS-CoV
Sequence analysis revealed that rice dwarf phytoreovirus segment S12 is 1066 nucleotides long with a small out-ofphase, overlapping open reading frame (ORF) as well as a major ORF. The large ORF (positions 42 to 960) encodes 312 amino acids, while the small one (bases 313 to 591) encodes 92 amino acids with an additional in-frame AUG codon (positions 337-339) 24 nucleotides downstream from the first one. Transcripts from a full-length cDNA directed the in vitro synthesis of three polypeptides of 33 (considered to be translated from the long ORF), 8, and 7 kDa. Alteration of each of the two ATG codons on the small ORF demonstrated their involvement in the generation of the 8-and 7-kDa polypeptides. Although it is still unknown whether these proteins are expressed in t&o, the small ORF is shown to be conserved in S9s of two other members of the genus Phytoreovirus, rice gall dwarf virus and wound tumor virus, suggesting its common, important function.
Output: Rice Dwarf Phytoreovirus Segment S12 Transcript Is Tricistronic in Vim
We encapsulated tumor necrosis factor-(TNF-), a major proinflammatory cytokine, into cholesteryl pullulan (CHP) to prepare TNF/CHP nanoparticles. In this report, we describe the immune-enhancing capability of the nanoparticles to act as a vaccine adjuvant. TNF/CHP nanoparticles showed excellent storage stability and enhanced host immune responses to external immunogens. The nanoparticles were effective via the nasal route of administration for inducing systemic IgG 1 as well as mucosal IgA. We applied the nanoparticles in a model experimental influenza virus infection to investigate their adjuvant ability. TNF/CHP nanoparticles combined with a conventional split vaccine protected mice via nasal administration against a lethal challenge of A/PR/8/34 (H1N1) influenza virus. Mechanistic studies showed that the nanoparticles enhanced antigen uptake by dendritic cells (DCs) and moderately induced the expression of inflammation-related genes in nasopharynx lymphoid tissue (NALT), leading to the activation of both B and T cells. Preliminary safety study revealed no severe toxicity to TNF/CHP nanoparticles. Slight-tomoderate influences in nasal mucosa were observed only in the repeated administration and they seemed to be reversible. Our data show that TNF/CHP nanoparticles effectively enhance both humoral and cellular immunity and could be a potential adjuvant for vaccines against infectious diseases, especially in the mucosa.
Output: Cholesteryl Pullulan Encapsulated TNF-Nanoparticles Are an Effective Mucosal Vaccine Adjuvant against Influenza Virus
The nucleocapsid protein gene of transmissible gastroenteritis virus, 1 149 bp in length, was amplified by RT-PCR from isolated strain HB06 and cloned into pMD18-T. Sequence comparison with other transmissible gastroenteritis virus (TGEV) strains selected from the Gene Bank revealed that the homology of N gene complete sequence shares more than 97% in nucleotide. N gene was cloned into BamHI and EcoRI multiple cloning sites of the prokaryotic expression vector pET 20 b, and named pETN. After being induced by isopropyl-b-D-thiogalactopyranoside (IPTG), the recombinant nucleocapsid protein was expressed. The result of SDS-PAGE and Western-blot showed that the recombinant nucleocapsid protein was 47 kDa and had strong positive reactions with TGEV-specific antibody.
Output: Cloning and expression of nucleocapsid protein gene of TGEV HB06 strain
Since late 2013, after an absence of seven years, outbreaks of porcine epidemic diarrhea virus (PEDV) infection have reemerged and swept rapidly across Japan, resulting in significant economic losses. In this study, we report the emergence, mixed infection, and genetic characterization of 15 novel field PEDV variants with large genomic deletions. The sizes of deletion varied between 582 nt (194 aa) and 648 nt (216 aa) at positions 28-714 (10-238) on the S gene (protein). Among 17 PEDV samples isolated from individual pigs, all of them contained at least two distinct genotypes with large genomic deletions, and 94.1% of them were found to consist of strains with an intact S gene. These variants were found in eight primary and nine recurrent outbreaks, and they might be associated with persistent PEDV infection in the farms. Full-length S and ORF3 genes of eight variants derived from 2 samples were characterized. This is the first report of mixed infections caused by various genotypes of PEDV and would be important for the studies of viral isolation, pathogenesis, and molecular epidemiology of the disease.
Output: Novel Porcine Epidemic Diarrhea Virus (PEDV) Variants with Large Deletions in the Spike (S) Gene Coexist with PEDV Strains Possessing an Intact S Gene in Domestic Pigs in Japan: A New Disease Situation
Porcine epidemic diarrhea virus (PEDV), a member of the genus Alphacoronavirus , has resulted in signifi cant economic losses in the European, Asian, and North American swine industries in previous years. PEDV infection causes acute diarrhea/vomiting, dehydration, and high morbidity and mortality in seronegative neonatal piglets. In this chapter, materials and methods for performing immunohistochemistry (IHC) for the detection of PEDV antigens in frozen or formalin-fi xed, paraffi n-embedded (FFPE) tissues are provided. In IHC of frozen tissues where viral antigens are well preserved, the use of specifi c antibodies labeled with fl uorescence dyes provides excellent advantages and convenience, resulting in high sensitivity and specifi city of IHC and reduction of operation time. In IHC of FFPE tissues where tissue or cell morphology is well preserved, the use of specifi c antibodies labeled with enzymes, such as alkaline phosphatase, also gives rise to signifi cant advantages in defi ning the correlation of viral antigens with histopathologic lesions. PEDV antigens in frozen tissues are visualized as green staining in the cytoplasm of infected cells by fl uorescent dyes conjugated with antibodies when activated by exciting light of a specifi c wavelength under a fl uorescence microscope. In FFPE tissues, PEDV antigens are visualized as red staining in the cytoplasm of infected cells by the deposition of the substrate chromogen, Fast Red.
Output: Chapter 2 Immunohistochemical Staining for Detection of Porcine Epidemic Diarrhea Virus in Tissues