niryuu/sni-each-converted huggingface dataset:
Coccidiosis and necrotic enteritis (NE) are among the most significant diseases affecting the poultry industry. These diseases have become more prominent in the wake of policies to reduce the use of antibiotics in animal production. This has led to more research focused on better understanding the immune system and its responses to pathogen challenge, and thus developing informed strategies to exploit immune responses that can support enhanced disease resistance and growth performance. Some chicken breeds and lines show greater resistance or susceptibility to various diseases, and thus these birds maybe able to shed light on immune processes or pathways that contribute to the more resistant/susceptible state. This review attempts to identify potentially important genes that show some consistency in (relative) up or downregulation in key tissues between the resistant and susceptible chickens. For coccidiosis and NE, relative downregulation of IL-10 and (slightly less consistently) upregulation of IFNγ appear to be features of more resistant birds. Data for IFN-α, IL-12, and IL-17D are currently less consistent. Gene expression data from NE studies have identified some potentially interesting, perhaps less well understood, immune-related genes (e.g., TCF12, BCL2, IRF2, TRAF3, TAB3, etc.,) that maybe associated with the resistant and/or susceptible phenotype. Salmonella and Campylobacter are important foodborne pathogens harbored by the chicken intestinal tract, while infectious bursal disease and infectious bronchitis are also important viral diseases of poultry. We, therefore, consider whether there are consistent features from resistant/susceptible disease models with these pathogens that relate to findings from the coccidiosis and NE studies. It is not anticipated that ideal immune responses to these pathogens will be identical but rather that consistent elements maybe identified that could help inform breeding or alternative strategies to support general disease resistance and enhanced (and efficient) flock productivity.
Output: Deciphering desirable immune responses from disease models with resistant and susceptible chickens
A novel SYBR Green based real-time RT-PCR assay for detection of genogroup III bovine noroviruses (BoNoV) was developed and the assay applied to 419 faecal samples from calves with and without diarrhoea. The samples were obtained from 190 Norwegian dairy and beef herds. BoNoV was detected in 49.6% of the samples from 61.1% of the herds indicating that BoNoV is ubiquitous in Norway. The overall prevalence was not significantly different in diarrhoea and non-diarrhoea samples. Analyses of polymerase gene sequences revealed both genotype III/1 and III/2 with genotype III/2 (Newbury2-like) being the most prevalent. Detected capsid sequences were restricted to Newbury2-like and the chimeric Bo/Thirsk10/00/UK strain. The RNA polymerase genotypes of the circulating BoNoVs in Norway were predicted by melting temperature analysis. Additional data from a challenge experiment suggest that a high proportion of young calves are shedding low levels of BoNoV for a prolonged time after recovering from the associated diarrhoea. The findings may explain some of the discrepancies in detection rates from previous studies and explain why some studies have failed to detect significant prevalence differences between calves with and without diarrhoea. It may also shed new light on some epidemiological aspects of norovirus infections.
Output: SYBR Green based real-time RT-PCR assay for detection and genotype prediction of bovine noroviruses and assessment of clinical significance in Norway
Severe acute respiratory syndrome-coronavirus (SARS-CoV) causes an infectious disease through respiratory route. Diagnosing the disease effectively and accurately at early stage is essential for preventing the disease transmission and performing antiviral treatment. In this study, we raised monoclonal antibodies (mAbs) against the nucleocapsid (N) protein of SARS-CoV and mapped epitopes by using different truncated N protein fragments. The mapping of those epitopes was valuable for constructing pair-Abs used in serological diagnosis. The results showed that all of the six raised mAbs were divided into two groups recognizing the region of amino acids 249-317 (A group) or 317-395 (B group). This region spanning amino acids 249-395 contains predominant B cell epitopes located at the C-terminus of N protein. One pair-Abs, consisting of N protein-specific rabbit polyclonal antibody and SARS-CoV N protein-specific mAb, was selected to construct a sandwich ELISA-kit. The kit was able to specifically detect SARS-CoV N proteins in serum samples.
Output: Characterization and application of monoclonal antibodies against N protein of SARS-coronavirus
Proteolytic processing of the mouse hepatitis virus strain A59 (MHV-A59) replicase gene product, pp1a, results in polypeptides p28, p65, p50, and p240 in infected cells. Based on previously identi ed p28 and p65 cleavage sites, a p50 cleavage site was proposed to occur between Ala-1262 and Ala-1263. Results of mutagenesis and in vitro cleavage assays show that PLP-1 was able to cleave in trans when the proposed p50 cleavage sequence replaced the p28 cleavage sequence. Mutagenesis was also used to investigate cleavage between Gly-904 and Val-905, a cleavage site predicted to produce a precursor of p65, p72, that was detected in cells infected with MHV strain JHM, but not with MHV-A59. No cleavage could be detected using substrate that carried both the p65 site and the predicted p72 cleavage sequence. Thus, it appeared that PLP-1 could recognize the proposed p50 sequence but not the predicted p72 site under the in vitro conditions used.
Output: Further in vitro characterization of mouse hepatitis virus papain-like proteinase 1: Cleavage sequence requirements within PP1a
Disease spreads as a result of people moving and coming in contact with each other. Thus the mobility patterns of individuals are crucial in understanding disease dynamics. Here we study the impact of human mobility on HIV transmission in different parts of Kenya. We build an SIR metapopulation model that incorporates the different regions within the country. We parameterise the model using census data, HIV data and mobile phone data adopted to track human mobility. We found that movement between different regions appears to have a relatively small overall effect on the total increase in HIV cases in Kenya. However, the most important consequence of movement patterns was transmission of the disease from high infection to low prevalence areas. Mobility slightly increases HIV incidence rates in regions with initially low HIV prevalences and slightly decreases incidences in regions with initially high HIV prevalence. We discuss how regional HIV models could be used in public-health planning. This paper is a first attempt to model spread of HIV using mobile phone data, and we also discuss limitations to the approach.
Output: The Impact of Human Mobility on HIV Transmission in Kenya
The bone marrow contains heterogeneous population of cells that are involved in the regeneration and repair of diseased organs, including the lungs. In this study, we isolated and characterized progenitor epithelial cells from the bone marrow of 4-to 5-week old germ-free pigs. Microscopically, the cultured cells showed epithelial-like morphology. Phenotypically, these cells expressed the stem cell markers octamer-binding transcription factor (Oct4) and stage-specific embryonic antigen-1 (SSEA-1), the alveolar stem cell marker Clara cell secretory protein (Ccsp), and the epithelial cell markers pan-cytokeratin (Pan-K), cytokeratin-18 (K-18), and occludin. When cultured in epithelial cell growth medium, the progenitor epithelial cells expressed type I and type II pneumocyte markers. Next, we examined the susceptibility of these cells to influenza virus. Progenitor epithelial cells expressed sialic acid receptors utilized by avian and mammalian influenza viruses and were targets for influenza virus replication. Additionally, differentiated type II but not type I pneumocytes supported the replication of influenza virus. Our data indicate that we have identified a unique population of progenitor epithelial cells in the bone marrow that might have airway reconstitution potential and may be a useful model for cell-based therapies for infectious and non-infectious lung diseases.
Output: Epithelial Cells Derived from Swine Bone Marrow Express Stem Cell Markers and Support Influenza Virus Replication In Vitro
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. between virus names and species names would be to change the current names of virus species into nonlatinized binomial names. Such a system, which has been advocated by plant virologists for many years, consists in replacing the word 'virus' appearing at the end of the existing species name by the genus name which also ends in '-virus'. Measles virus then becomes Measles morbillivirus, Hepatitis A virus becomes Hepatitis A hepatovirus, and Tobacco mosaic virus becomes Tobacco mosaic tobamovirus. The advantage of such a system, which could be implemented without problems for about 98% of all virus species names, is that inclusion of the genus name in the species name provides additional information about the properties of the virus. A changeover to binomial species names would not affect the common names of viruses in English or other languages since names such as measles virus or 'virus de la rougeole' would remain the same. The ICTV is currently debating the possibility of introducing binomial species names and some decision is likely to be made in the near future. Given that the common names of viruses are used repeatedly in scientific texts there is a need for abbreviating them and the ICTV has published several lists of recommended acronyms for virus names. Since the names of virus species are used only very seldom in publications, there is no need to abbreviate them. If binomial names of virus species were introduced in the future, the abbreviations of common names of viruses will of course not be affected.
Output: Viruses and Bioterrorism
GHS; USAID; CDC; WHO Background: In 2016, as a component of the Global Health Security Agenda, the Vietnam Ministry of Health expanded its existing influenza sentinel surveillance for severe acute respiratory infections (SARI) to include testing for 7 additional viral respiratory pathogens. This article describes the steps taken to implement expanded SARI surveillance in Vietnam and reports data from 1 year of expanded surveillance. The process of expanding the suite of pathogens for routine testing by real-time reverse transcriptase-polymerase chain reaction (rRT-PCR) included laboratory trainings, procurement/distribution of reagents, and strengthening and aligning SARI surveillance epidemiology practices at sentinel sites and regional institutes (RI). : Surveillance data showed that of 4003 specimens tested by the RI laboratories, 20.2% (n = 810) were positive for influenza virus. Of the 3193 influenza-negative specimens, 41.8% (n = 1337) were positive for at least 1 non-influenza respiratory virus, of which 16.2% (n = 518), 13.4% (n = 428), and 9.6% (n = 308) tested positive for respiratory syncytial virus, rhinovirus, and adenovirus, respectively. The Government of Vietnam has demonstrated that expanding respiratory viral surveillance by strengthening and building upon an influenza platform is feasible, efficient, and practical. adenovirus, global health security, influenza virus, respiratory syncytial virus, rhinovirus, severe acute respiratory infection, Vietnam | 633 ALROY et AL.
Output: Expanding severe acute respiratory infection (SARI) surveillance beyond influenza: The process and data from 1 year of implementation in Vietnam
This is a preprint version, not peer-reviewed yet, and readers should treat it accordingly. 2 Summary Background: The COVID-19 disease has turned into a global pandemic with unprecedented challenges for the global community. Understanding the state of the disease and planning for future trajectories relies heavily on data on the spread and mortality. Yet official data coming from various countries are highly unreliable: symptoms similar to common cold in majority of cases and limited screening resources and delayed testing procedures may contribute to underestimation of the burden of disease. Anecdotal and more limited data are available, but few have systematically combined those with official statistics into a coherent view of the epidemic. This study is a modeling-in-real-time of the emerging outbreak for understanding the state of the disease. Our focus is on the case of the spread of disease in Iran, as one of the epicenters of the disease in the first months of 2020. We develop a simple dynamic model of the epidemic to provide a more reliable picture of the state of the disease based on existing data. Building on the generic SEIR (Susceptible, Exposed, Infected, and Recovered) framework we incorporate two behavioral and logistical considerations. First we capture the endogenous changes in contact rate (average contact per person) as more death are reported. As a result the reproduction number changes endogenously in the model. Second we differentiate reported and true cases by including simple formulations for how only a fraction of cases might be diagnosed, and how that fraction changes in response to epidemic's progression. In estimating the model we use both the official data as well as the discovered infected travelers and unofficial medical community estimates and triangulate these sources to build a more complete picture. Calibration is completed by forming a likelihood function for observing the actual time series data conditional on model parameters, and conducting a Markov Chain Monte Carlo simulations. The model is used to estimate current "true" cases of infection and death. We analyze the future trajectory of the disease under six conditions related to the seasonal effects and policy measures targeting social distancing. The model closely replicates the past data but also shows the true number of cases is likely far larger. We estimate about 493,000 current infected cases (90% CI: 271K-810K) as 1 A Persian summary of the article is provided as an appendix. ‫است‬ ‫موجود‬ ‫انتها‬ ‫ضمیمه‬ ‫در‬ ‫فارسی‬ ‫به‬ ‫مقاله‬ ‫خالصه‬
Output: Simulation-based Estimation of the Spread of COVID-19 in Iran
Background Characterisation of the severity profi le of human infections with infl uenza viruses of animal origin is a part of pandemic risk assessment, and an important part of the assessment of disease epidemiology. Our objective was to assess the clinical severity of human infections with avian infl uenza A H7N9 virus, which emerged in China in early 2013. Prevention. We estimated the risk of fatality, mechanical ventilation, and admission to the intensive care unit for patients who required hospital admission for medical reasons. We also used information about laboratory-confi rmed cases detected through sentinel infl uenza-like illness surveillance to estimate the symptomatic case fatality risk. 17 patients who were still in hospital, we estimated the fatality risk for all ages to be 36% (95% CI 26-45) on admission to hospital. Risks of mechanical ventilation or fatality (69%, 95% CI 60-77) and of admission to an intensive care unit, mechanical ventilation, or fatality (83%, 76-90) were high. With assumptions about coverage of the sentinel surveillance network and health-care-seeking behaviour for patients with infl uenza-like illness associated with infl uenza A H7N9 virus infection, and pro-rata extrapolation, we estimated that the symptomatic case fatality risk could be between 160 (63-460) and 2800 (1000-9400) per 100 000 symptomatic cases. Interpretation Human infections with avian infl uenza A H7N9 virus seem to be less serious than has been previously reported. Many mild cases might already have occurred. Continued vigilance and sustained intensive control eff orts are needed to minimise the risk of human infection. Funding
Output: Human infection with avian infl uenza A H7N9 virus: an assessment of clinical severity
Porcine aminopeptidase N (pAPN) is a cellular membrane protein and a functional receptor for porcine coronaviruses. Here, we describe the heterologous expression of pAPN without signal peptide in BL21(DE3)pLysS host cells. The Escherichia coli (E. coli) harboring the recombinant construct was efficiently induced to express the pAPN protein at a high level. The most optimal expression profile for pAPN expression was investigated. By inoculating a rabbit with the purified pAPN, a high tittered specific antibody was achieved. Biologically, the antibody reacted with either pAPN-expressing E. coli or native pAPN on the surface of swine testis cells. The pAPN and its specific antibody blocked transmissible gastroenteritis coronavirus infection in vitro. Furthermore, the localization of pAPN on the small intestine of swine was analyzed by immunohistochemistry.
Output: Expression and functional analysis of porcine aminopeptidase N produced in prokaryotic expression system
Accumulating evidence suggests that human γδ T cells act as non-classical T cells and contribute to both innate and adaptive immune responses in infections. Vγ2 Vδ2 T (also termed Vγ9 Vδ2 T) cells exist only in primates, and in humans represent a dominant circulating γδ T-cell subset. Primate Vγ2 Vδ2 T cells are the only γδ T cell subset capable of recognizing microbial phosphoantigen. Since nonhuman primate Vγ2 Vδ2 T cells resemble their human counterparts, indepth studies have been undertaken in macaques to understand the biology and function of human Vγ2 Vδ2 T cells. This article reviews the recent progress for immune biology of Vγ2 Vδ2 T cells in infections.
Output: Immune biology of Ag-specific γδ T cells in infections
Background: We describe human rhinovirus (HRV) detections in SaKaeo province, Thailand. Methods: From September 1, 2003-August 31, 2005, we tested hospitalized patients with acute lower respiratory illness and outpatient controls without fever or respiratory symptoms for HRVs with polymerase chain reaction and molecularlytyped select HRVs. We compared HRV detection among hospitalized patients and controls and estimated enrollment adjusted incidence. Results: HRVs were detected in 315 (16%) of 1919 hospitalized patients and 27 (9.6%) of 280 controls. Children had the highest frequency of HRV detections (hospitalized: ,1 year: 29%, 1-4 year: 29%, $65 years: 9%; controls: ,1 year: 24%, 1-4 year: 14%, $65 years: 2.8%). Enrollment adjusted hospitalized HRV detection rates were highest among persons aged ,1 year (1038/100,000 persons/year), 1-4 years (457), and $65 years (71). All three HRV species were identified, HRV-A was the most common species in most age groups including children aged ,1 year (61%) and all adult age groups. HRV-C was the most common species in the 1-4 year (51%) and 5-19 year age groups (54%). Compared to controls, hospitalized adults ($19 years) and children were more likely to have HRV detections (odds ratio [OR]: 4.8, 95% confidence interval [CI]: 1.5, 15.8; OR: 2.0, CI: 1.2, 3.3, respectively) and hospitalized children were more likely to have HRV-A (OR 1.7, CI: 0.8, 3.5) or HVR-C (OR 2.7, CI: 1.2, 5.9) detection. Conclusions: HRV rates were high among hospitalized children and the elderly but asymptomatic children also had substantial HRV detection. HRV (all species), and HRV-A and HRV-C detections were epidemiologically-associated with hospitalized illness. Treatment or prevention modalities effective against HRV could reduce hospitalizations due to HRV in Thailand.
Output: Human Rhinovirus Infections in Rural Thailand: Epidemiological Evidence for Rhinovirus as Both Pathogen and Bystander
Background: Protein ubiquitination and/or degradation by the ubiquitin/proteasome system (UPS) have been recognized as critical mechanisms in the regulation of numerous essential cellular functions. The importance of the UPS in viral pathogenesis has become increasingly apparent. Using murine cardiomyocytes, we have previously demonstrated that the UPS plays a key role in the replication of coxsackievirus B3 (CVB3), an important human pathogen associated with various diseases. To further elucidate the underlying mechanisms, we examined the interplay between the UPS and CVB3, focusing on the role of ubiquitination in viral lifecycle. Methodology/Principal Findings: As assessed by in situ hybridization, Western blot, and plaque assay, we showed that proteasome inhibition decreased CVB3 RNA replication, protein synthesis, and viral titers in HeLa cells. There were no apparent changes in 20S proteasome activities following CVB3 infection. However, we found viral infection led to an accumulation of protein-ubiquitin conjugates, accompanied by a decreased protein expression of free ubiquitin, implicating an important role of ubiquitination in the UPS-mediated viral replication. Using small-interfering RNA, we demonstrated that gene-silencing of ubiquitin significantly reduced viral titers, possibly through downregulation of protein ubiquitination and subsequent alteration of protein function and/or degradation. Inhibition of deubiquitinating enzymes apparently enhances the inhibitory effects of proteasome inhibitors on CVB3 replication. Finally, by immunoprecipitation, we showed that coxsackieviral polymerase 3D was post-translationally modified by ubiquitination and such modification might be a prerequisite for its function in transcriptional regulation of viral genome. Conclusion: Coxsackievirus infection promotes protein ubiquitination, contributing to effective viral replication, probably through ubiquitin modification of viral polymerase.
Output: Ubiquitination Is Required for Effective Replication of Coxsackievirus B3
In cats, primary or secondary immune-mediated thrombocytopenia have rarely been described or characterised. The objective of this study was to determine platelet-bound antibodies (PBA) by a flow cytometric assay in both healthy and thrombocytopenic cats. Direct PBA testing was performed in 42 thrombocytopenic cats (platelet counts 6e179 Â 10 9 /l, median 56 Â 10 9 /l). Of these 42 cats, 19 had positive PBA test results, 17 of which were considered to have secondary immune-mediated thrombocytopenia (sITP). Underlying diseases included fat necroses (four cases), feline infectious peritonitis (three), feline leukaemia virus (two) or feline immunodeficiency virus (two) infections, lymphoma (two), leukaemia (one), hepatitis (one), pyelonephritis (one), or hyperthyroidism (one). In two cats, no underlying disease was found suggesting a primary immune-mediated thrombocytopenia (pITP). The PBA test was negative in 23 cats diagnosed with varying underlying diseases and in 47 healthy control cats with platelet values within the reference range. Only seven of the 42 cats with thrombocytopenia (platelet count 10e57 Â 10 9 /l, median 34 Â 10 9 /l) had spontaneous bleeding. This study suggests that immune-mediated destruction of platelets might be an important pathological mechanism for feline thrombocytopenia caused by various underlying diseases. In cats, pITP appears to be rarely diagnosed.
Output: Platelet-bound antibodies detected by a flow cytometric assay in cats with thrombocytopenia
The highly infectious porcine transmissible gastroenteritis virus (TGEV), which belongs to the coronaviruses (CoVs), causes diarrhea and high mortality rates in piglets, resulting in severe economic losses in the pork industry worldwide. In this study, we used Lactobacillus plantarum (L. plantarum) to anchor the expression of TGEV antigen (S) to dendritic cells (DCs) via dendritic cell-targeting peptides (DCpep). The results show that S antigen could be detected on the surface of L. plantarum by different detection methods. Furthermore, flow cytometry and ELISA techniques were used to measure the cellular, mucosal, and humoral immune responses of the different orally gavaged mouse groups. The obtained results demonstrated the significant effect of the constructed L. plantarum expressing S-DCpep fusion proteins in inducing high expression levels of B7 molecules on DCs, as well as high levels of IgG, secretory IgA, and IFN-γ and IL-4 cytokines compared with the other groups. Accordingly, surface expression of DC-targeted antigens successfully induced cellular, mucosal, and humoral immunity in mice and could be used as a vaccine.
Output: Immune response characterization of mice immunized with Lactobacillus plantarum expressing spike antigen of transmissible gastroenteritis virus
Cardiotoxicity is a well-known side effect of doxorubicin (DOX), but the mechanisms leading to this phenomenon are still not completely clear. Prediction of drug-induced dysfunction onset is difficult and is still largely based on detection of cardiac troponin (cTn), a circulating marker of heart damage. In the last years, several investigations focused on the possible involvement of microRNAs (miRNAs) in DOX-induced toxicity in vitro, with contrasting results. Recently, several groups employed animal models to mimic patient's condition, investigate the biological pathways perturbed by DOX, and identify diagnostic markers of cardiotoxicity. We reviewed the results from several studies investigating cardiac miRNAs expression in rodent models of DOX-treatment. We also discussed the data from two publications indicating the possible use of circulating miRNA as biomarkers of DOX-induced cardiotoxicity. Unfortunately, limited information was derived from these studies, as selection methods of candidate-miRNAs and heterogeneity in cardiotoxicity assessment greatly hampered the novelty and robustness of the findings. Nevertheless, at least one circulating miRNA, miR-1, showed a good potential as early biomarker of drug-mediated cardiac dysfunction onset. The use of animal models to investigate DOX-induced cardiotoxicity surely helps narrowing the gap between basic research and clinical practice. Despite this, several issues, including selection of relevant miRNAs and less-than-optimal assessment of cardiotoxicity, greatly limited the results obtained so far. Nonetheless, the association of patients-based studies with the use of preclinical models may be the key to address the many unanswered questions regarding the pathophysiology and early detection of cardiotoxicity.
Output: Role of microRNAs in doxorubicin-induced cardiotoxicity: an overview of preclinical models and cancer patients
h i g h l i g h t s • A modified community network model with heterogeneity among communities is proposed. • A mathematical epidemic model for each community is presented based on this network. • Study the effect of the location of initial infection node on epidemic spreading. • Study the impact of the heterogeneity among communities on epidemic spreading. a b s t r a c t A large number of real world networks exhibit community structure, and different communities may often possess heterogeneity. In this paper, considering the heterogeneity among communities, we construct a new community network model in which the communities show significant differences in average degree. Based on this heterogeneous community network, we propose a novel mathematical epidemic model for each community and study the epidemic dynamics in this network model. We find that the location of the initial infection node only affects the spreading velocity and barely influences the epidemic prevalence. And the epidemic threshold of entire network decreases with the increase of heterogeneity among communities. Moreover, the epidemic prevalence increases with the increase of heterogeneity around the epidemic threshold, while the converse situation holds when the infection rate is much greater than the epidemic threshold. (B. Song). example, the severe acute respiratory syndrome (SARS) in 2003, the H1N1 influenza A virus in 2009, the H7N9 avian influenza virus in 2013, the Ebola virus in 2014 and the Middle East respiratory syndrome coronavirus (MERS-CoV) in 2015. The problem of epidemic spreading has gained great attention over the years and people want to predict the epidemic spread trend and take effective public health measures with limited vaccine supply. As the topology properties of networks have a profound impact on the dynamics of epidemic spreading, it is necessary to consider the effect of community structure on epidemic spreading. So far, a lot of results on epidemic dynamics in community networks have been obtained [12, 14, 16, 29, 30] . To simulate the real network, many different kinds of community network models were constructed based on classical networks, and some individual behavior characteristics in real networks (such as random walk, long-range jump and awareness) were also taken into account. Liu and Hu studied the SIS (susceptible-infected-susceptible) dynamics on a random community network model with probability p (q) of intra-(inter-)
Output: Modeling and analysis of epidemic spreading on community networks with heterogeneity
Biomolecular NMR now contributes routinely to every step in the development of new chemical entities ahead of clinical trials. The versatility of NMR -from detection of ligand binding over a wide range of affinities and a wide range of drug targets with its wealth of molecular information, to metabolomic profiling, both ex vivo and in vivo -has paved the way for broadly distributed applications in academia and the pharmaceutical industry. Proteomics and initial target selection both benefit from NMR: screenings by NMR identify lead compounds capable of inhibiting protein-protein interactions, still one of the most difficult development tasks in drug discovery. NMR hardware improvements have given access to the microgram domain of phytochemistry, which should lead to the discovery of novel bioactive natural compounds. Steering medicinal chemists through the lead optimisation process by providing detailed information about protein-ligand interactions has led to impressive success in the development of novel drugs. The study of biofluid compositionmetabonomics -provides information about pharmacokinetics and helps toxicological safety assessment in animal model systems. In vivo, magnetic resonance spectroscopy interrogates metabolite distributions in living cells and tissues with increasing precision, which significantly impacts the development of anticancer or neurological disorder therapeutics. An overview of different steps in recent drug discovery is presented to illuminate the links with the most recent advances in NMR methodology.
Output: Biomolecular NMR: a chaperone to drug discovery This review comes from a themed issue on Combinatorial chemistry and molecular diversity Edited
Middle east respiratory syndrome coronavirus International travel Pilgrims a b s t r a c t Objective: We aimed to evaluate the level of knowledge of Middle East respiratory syndrome coronavirus (MERS-CoV) among Hajj pilgrims before and after an education health programme during international vaccine consultations in France. Methods: Consecutive adults (>18 years old) who attended for pre-Hajj meningococcal vaccination were eligible to complete an anonymous questionnaire with closed answers to evaluate their level of knowledge about MERS-CoV. To evaluate the effectiveness of the information given during the consultation, the same questionnaire was completed by the Hajj pilgrim before and after the consultation, where the information about MERS-CoV was provided. Results: Among 82 Hajj pilgrim adults enrolled in the study, less than 25% were aware of the routes of transmission, symptoms and preventive behaviours to adopt abroad or in case of fever. Pilgrims had a higher rate of correct responses on each question at the time they completed the second questionnaire, as compared with the first, with 11 of 13 questions answered significantly better after delivery of educational information about MERS-CoV. However, although the rate of correct answers to the questions about routes of transmission, symptoms, preventive behaviours to adopt in case of fever and time delay between return and potential MERS-CoV occurrence increased significantly after receiving the information, the rates remained below 50%. Conclusion: Information given during travel consultations significantly increases the general level of knowledge, but not enough to achieve epidemic control.
Output: Effectiveness of an education health programme about Middle East respiratory syndrome coronavirus tested during travel consultations Public Health
The ribosome is a molecular machine that converts genetic information in the form of RNA, into protein. Recent structural studies reveal a complex set of interactions between the ribosome and its ligands, mRNA and tRNA, that indicate ways in which the ribosome could avoid costly translational errors. Ribosomes must decode each successive codon accurately, and structural data provide a clear indication of how ribosomes limit recruitment of the wrong tRNA (sense errors). In a triplet-based genetic code there are three potential forward reading frames, only one of which encodes the correct protein. Errors in which the ribosome reads a codon out of the normal reading frame (frameshift errors) occur less frequently than sense errors, although it is not clear from structural data how these errors are avoided. Some mRNA sequences, termed programmed-frameshift sites, cause the ribosome to change reading frame. Based on recent work on these sites, this article proposes that the ribosome uses the structure of the codon-anticodon complex formed by the peptidyl-tRNA, especially its wobble interaction, to constrain the incoming aminoacyl-tRNA to the correct reading frame.
Output: Ribosome structure: revisiting the connection between translational accuracy and unconventional decoding
Before the SARS outbreak only two human coronaviruses (HCoV) were known: HCoV-OC43 and HCoV-229E. With the discovery of SARS-CoV in 2003, a third family member was identified. Soon thereafter, we described the fourth human coronavirus (HCoV-NL63), a virus that has spread worldwide and is associated with croup in children. We report here the complete genome sequence of two HCoV-NL63 clinical isolates, designated Amsterdam 57 and Amsterdam 496. The genomes are 27,538 and 27,550 nucleotides long, respectively, and share the same genome organization. We identified two variable regions, one within the 1a and one within the S gene, whereas the 1b and N genes were most conserved. Phylogenetic analysis revealed that HCoV-NL63 genomes have a mosaic structure with multiple recombination sites. Additionally, employing three different algorithms, we assessed the evolutionary rate for the S gene of group Ib coronaviruses to be ∼ 3 × 10 − 4 substitutions per site per year. Using this evolutionary rate we determined that HCoV-NL63 diverged in the 11th century from its closest relative HCoV-229E.
Output: Mosaic Structure of Human Coronavirus NL63, One Thousand Years of Evolution
The central importance of cell polarity control is emphasized by the frequency with which it is targeted by many diverse viruses. It is clear that in targeting key polarity control proteins, viruses affect not only host cell polarity, but also influence many cellular processes, including transcription, replication, and innate and acquired immunity. Examination of the interactions of different virus proteins with the cell and its polarity controls during the virus life cycles, and in virally-induced cell transformation shows ever more clearly how intimately all cellular processes are linked to the control of cell polarity.
Output: Upsetting the Balance: When Viruses Manipulate Cell Polarity Control
The fusion proteins of enveloped viruses mediating the fusion between the viral and cellular membranes comprise two discontinuous heptad repeat (HR) domains located at the ectodomain of the enveloped glycoproteins. The crystal structure of the fusion protein core of Mumps virus (MuV) was determined at 2.2 Å resolution. The complex is a six-helix bundle in which three HR1 peptides form a central highly hydrophobic coiled-coil and three HR2 peptides pack against the hydrophobic grooves on the surface of central coiled-coil in an oblique antiparallel manner. Fusion core of MuV, like those of simian virus 5 and human respiratory syncytium virus, forms typical 3-4-4-4-3 spacing. The similar charecterization in HR1 regions, as well as the existence of O-X-O motif in extended regions of HR2 helix, suggests a basic rule for the formation of the fusion core of viral fusion proteins.
Output: Structural characterization of Mumps virus fusion protein core
Background: To control the spread of Corona Virus Disease , 30 screening large numbers of suspected cases for appropriate quarantine and 31 treatment is a priority. Pathogenic laboratory testing is the diagnostic gold standard 32 but it is time consuming with significant false negative results. Fast and accurate 33 diagnostic methods are urgently needed to combat the disease. Based on 34 COVID-19 radiographical changes in CT images, we aimed to develop a deep 35 learning method that could extract COVID-19's graphical features in order to provide 36 a clinical diagnosis ahead of the pathogenic test, thus saving critical time for 37 disease control. 38 Methods and Findings: We collected 1,065CT images of pathogen-confirmed 39 COVID-19 cases (325 images) along with those previously diagnosed with typical 40 viral pneumonia (740 images). We modified the Inception transfer-learning model 41 to establish the algorithm, followed by internal and external validation. The internal 42 validation achieved a total accuracy of 89.5% with specificity of 0.88 and sensitivity 43 of 0.87. The external testing dataset showed a total accuracy of 79.3% with 44 specificity of 0.83 and sensitivity of 0.67. In addition, in 54 COVID-19 images that 45 first two nucleic acid test results were negative, 46 were predicted as COVID-19 46 positive by the algorithm, with the accuracy of 85.2%. 47 Conclusion: These results demonstrate the proof-of-principle for using 48 artificial intelligence to extract radiological features for timely and accurate 49 COVID-19 diagnosis. 50
Output: Breast Cancer Prevention and Therapy, Ministry of Education
Porcine epidemic diarrhea virus (PEDV) is a porcine enteropathogenic coronavirus that has received increasing attention since the emergence of a PEDV variant worldwide. Previous studies have shown that PEDV ORF3 encodes an ion channel protein. However, its influence on cell cycle and subcellular structure still require more research. In this study, we developed a Vero cell line that stably expresses PEDV ORF3 gene. Subcellular localization and influences of PEDV ORF3 on host cells were investigated. We further verified whether or not this gene enhances virus production. The results showed that PEDV ORF3 protein localizes in the cytoplasm and affects cell cycle progression by prolonging the S phase. In addition, the ORF3-expressing Vero cells had more vesicles than the host Vero cells. Furthermore, the attenuated PEDV rather than virulent PEDV could grow better in ORF3-expressing Vero cells. The expression level of the PEDV nucleocapsid protein also increased. These results provided information on the function of PEDV ORF3 and were helpful in understanding the mechanisms of PEDV replication.
Output: Porcine epidemic diarrhea virus ORF3 gene prolongs S-phase, facilitates formation of vesicles and promotes the proliferation of attenuated PEDV
Respiratory viral infections cause mild to severe diseases, such as common cold, bronchiolitis and pneumonia and are associated with substantial burden for society. To test new molecules for shortening, alleviating the diseases or to develop new therapies, relevant human in vitro models are mandatory. MucilAir™, a human standardized air-liquid interface 3D airway epithelial culture holds in vitro specific mechanisms to counter invaders comparable to the in vivo situation, such as mucus production, mucociliary clearance, and secretion of defensive molecules. The objective of this study was to test the relevance of such a model for the discovery and validation of antiviral drugs. Fully differentiated 3D nasal epithelium cultures were inoculated with picornaviruses, a coronavirus and influenza A viruses in the absence or in the presence of reference antiviral drugs. Results showed that, rupintrivir efficiently inhibits the replication of respiratory picornaviruses in a dose dependent manner and prevents the impairment of the mucociliary clearance. Similarly, oseltamivir reduced the replication of influenza A viruses in a dose dependent manner and prevented the impairment of the epithelial barrier function and cytotoxicity until 4 days of infection. In addition we found that Rhinovirus B14, C15 and influenza A(H1N1) induce significant increase of β Defensins 2 and Cathelicidin release with different time course. These results reveal that a large panel of epithelial functions is modified upon viral infection and validate MucilAir™ as a pertinent tool for pre-clinical antiviral drug testing.
Output: Antiviral drug screening by assessing epithelial functions and innate immune responses in human 3D airway epithelium model
Canine parvovirus (CPV-2) remains an important cause of devastating enteritis in young dogs. It can be successfully prevented with live attenuated CPV-2 vaccines when given at the appropriate age and in the absence of maternal antibody interference. Rapid diagnosis of parvoviral enteritis in young dogs is essential to ensuring suitable barrier nursing protocols within veterinary hospitals. The current diagnostic trend is to use multiplexed PCR panels to detect an array of pathogens commonly responsible for diarrhea in dogs. The multiplexed PCR assays do not distinguish wild from vaccine CPV-2. They are highly sensitive and detect even a low level of virus shedding, such as those caused by the CPV-2 vaccine. The aim of this study was to identify the CPV-2 subtypes detected in diagnostic specimens and rule out occult shedding of CPV-2 vaccine strains. For a total of 21 samples that tested positive for CPV-2 in a small animal fecal pathogens diagnostic multiplexed tandem PCR (MT-PCR) panel during 2014e2016 we partially characterized the VP2 gene of CPV-2. Vaccine CPV-2 strain, wild type CPV-2a subtypes and vaccine-like CPV-2b subtypes were detected. High copy number was indicative of wild-type CPV-2a presence, but presence of vaccine-like CPV-2b had a variable copy number in fecal samples. A yardstick approach to a copy number or C t -value to discriminate vaccine strain from a wild type virus of CPV-2 can be, in some cases, potentially misleading. Therefore, discriminating vaccine strain from a wild type subtype of CPV-2 remains ambitious.
Output: MT-PCR panel detection of canine parvovirus (CPV-2): Vaccine and wild-type CPV-2 can be difficult to differentiate in canine diagnostic fecal samples
Polysaccharide Production Extraction Structural elucidation Bioactivity A B S T R A C T Cordyceps (Ophiocordyceps sinensis) sinensis, the Chinese caterpillar fungus, is a unique and precious medicinal fungus in traditional Chinese medicine which has been used as a prestigious tonic and therapeutic herb in China for centuries. Polysaccharides are bioactive constituents of C. sinensis, exhibiting several activities such as immunomodulation, antitumour, antioxidant and hypoglycaemic. As natural C. sinensis fruiting body-caterpillar complexes are very rare and expensive, the polysaccharides documented over the last 15-20 years from this fungal species were mostly extracted from cultivated fungal mycelia (intracellular polysaccharides) or from mycelial fermentation broth (exopolysaccharides). Extraction and purification of the polysaccharides is a tedious process involving numerous steps of liquid and solid phase separations. Nevertheless, a large number of polysaccharide structures have been purified and elucidated. However, relationships between the structures and activities of these polysaccharides are not well established. This review provides a comprehensive summary of the most recent developments in various aspects (i.e., production, extraction, structure, and bioactivity) of the intracellular and exopolysaccharides from mycelial fermentation of C. sinensis fungi. The contents and data will serve as useful references for further investigation, production and application of these polysaccharides in functional foods and therapeutic agents.
Output: Recent advances in Cordyceps sinensis polysaccharides: Mycelial fermentation, isolation, structure, and bioactivities: A review
A Resequencing Pathogen Microarray (RPM) is a single, highly multiplexed assay for detecting and differentiating similarly related pathogens by using closely overlapping probe sets to determine a target organism's nucleotide sequence. In this study, a new RPM (RPM-IVDC1) that consisted of 224-bp detector tiles corresponding to 9 influenza A subtypes, 11 rhinoviruses, 28 enteroviruses and 38 other respiratory viruses was developed and optimized to provide individual and simultaneous detection sensitivities ranging from 15 to 750 genomic copies for 16 common respiratory pathogens. A total of 110 consecutive patients with community-acquired pneumonia (CAP) admitted to 5 district general hospitals in Beijing during a 1-year period were assessed using the new assay. Among the children (under age 5) and adult patients (above age 18), respiratory syncytial virus (RSV) and rhinovirus (RV) were the most common etiological agents, respectively, which is consistent with reference assays. Atypical pathogens that may cause CAP-like illness, including rubella virus, measles virus, influenza type C virus, human herpesvirus (HHV) were also detected. The results show the capability of RPM-IVDC1 for the accurate detection and identification of multiple virus types, which may be of significant use in epidemic surveillance and outbreak investigations of atypical pathogens. Citation:
Output: Acquired Pneumonia
Infectious bronchitis virus (IBV) infection has been a major threat to the poultry industry worldwide. Current commercially available ELISA kits detect group-specific antibodies; however, to understand the status of field infection, a monoclonal antibody (mAb) blocking ELISA (b-ELISA) against local IBVs was developed. The selected mAb showed specificity to Taiwan IBV strains but had no cross-reactivity with the vaccine strain H120. Using the hemagglutination inhibition (HI) test as a standard, the cut-off value, sensitivity, and specificity of a b-ELISA using this mAb were evaluated in 390 field samples. The typespecificity of detection was validated using a panel of chicken hyperimmune sera. The results showed that the b-ELISA demonstrated high sensitivity (98.0%) and specificity (97.2%) of detection. The agreement between the results of the b-ELISA and the HI test was statistically significant (Kappa = 0.95), and there was no significant difference between these two methods (McNemar p = 0.72). The b-ELISA specifically detected Taiwan IBV serotypes but not three non-Taiwan IBV serotypes nor sera against other avian pathogens. This b-ELISA provides type-specific antibody detection of local IBV strains. It has the potential to serve as a rapid and reliable diagnostic method for IBV clinical infections in the field in Taiwan.
Output: A type-specific blocking ELISA for the detection of infectious bronchitis virus antibody