niryuu/sni-each-converted huggingface dataset:
Infectious bronchitis virus (IBV) is responsible for significant economic losses to the poultry industry across the world. The enormous genetic diversity of IBV poses difficulty in diagnosing and controlling the virus. To understand the nature of IBV prevalent in the Kashmir Himalayas, we characterized two field strains, isolated from non-immunized broiler chickens, by sequence and phylogenetic analysis of S1 subunit of the spike glycoprotein. The analysis revealed both the isolates are identical to each other, with nucleotide and amino acid sequence identities of 99.4% and 98.4%, respectively. They exhibit variable sequence divergence in the S1 gene to that of the reference serotypes. Both are of ''Massachusetts type'' belonging to GI-1 lineage of the IBV génotype. The phylogenetic analysis revealed both of the isolates clustered into the same branch as that of many IBV strains recently reported from China and Iran. Likely, these regionally-related isolates represent revertant vaccine strains which may have been disseminated across the region by wild migratory birds. This study provides the first report of molecular evidence and phylogenetic characterization of the IBV from the Kashmir Himalayas and implicate the possible role of wild migratory birds in the spread of IBV in the region.
Output: Genotyping and phylogenetic analysis of infectious bronchitis virus isolated from broiler chickens in Kashmir
To identify management practices associated with an increased within-herd prevalence of Cryptosporidium parvum shedding on dairy farms in southern Ontario, fecal samples were taken from 1089 calves aged 7-28 days, from 119 herds. Information on management practices was obtained by administering a questionnaire compiled using a modified Delphi technique. Data were analyzed using univariable and multivariable negative binomial regression. Overall, 30% of the calves in the study were shedding C. parvum oocysts, with at least one positive calf detected in 77% of herds. Within-herd prevalence ranged from 0 to 80%. Predictors significantly associated with an increased prevalence of shedding in multivariable modelling were the use of calf scour prophylaxis in cows (risk ratio [RR] 1.70, P < 0.01) and calves (RR 1.38, P = 0.02) and the feeding of milk replacer in the first week of life (RR 1.40, P = 0.02). In contrast, the presence of concrete flooring in calf www.elsevier.com/locate/prevetmed Preventive Veterinary Medicine 83 (2008) 11-23 * Corresponding author. housing areas (RR 0.59, P < 0.01) and the use of soap or detergent when washing calf feeding utensils (RR 0.61, P < 0.01) appeared to be protective. #
Output: Association between management practices and within-herd prevalence of Cryptosporidium parvum shedding on dairy farms in southern Ontario
Current influenza vaccines provide hemagglutinin strain-specific protection, but rarely provide cross-protection against divergent strains. It is, therefore, particularly important to develop a universal vaccine against conserved proteins or conserved regions of the virus. In this study, we used N-terminal extracellular region of the influenza virus M2 protein (M2e) as the target antigen and constructed two optimized M2e DNA vaccines (p-tPA-p3M2e and p-p3M2e) with increased antigenic epitope density and enhanced antigen secretion. Both vaccines induced high M2e-specific humoral and cellular immune responses in the vaccinated mice. These two vaccines also conferred protection against a lethal infection of homo-subtypic H1N1 virus, with p-tPA-p3M2e being the most effective. In addition, p-tPA-p3M2e also showed cross-protection against different subtypes of the influenza virus (H9N2, H6N6, and H10N8) at varying rates (80%, 40%, and 20%, respectively). After passive immunization, M2e DNA vaccine-induced antibodies in the sera provided complete protection against homologous virus challenge. An analysis of the mechanism underlying this immunization-mediated protection indicates that M2e-specific IgG and T-cell immune responses may play critical roles in the prevention of infection and viral clearance. Taken together, our results indicate that this optimized M2e DNA vaccine is a promising candidate for the development of a universal, broad-spectrum influenza virus vaccine.
Output: Protection against homo and hetero-subtypic influenza A virus by optimized M2e DNA vaccine
This overview describes the main categories of specific occupational disorders and it covers also how work exposures are potential determinants of common respiratory conditions. Acute inhalation injuries may present as inhalation fever or as acute tracheobronchitis and pneumonitis. Occupational asthma is the most frequent work-related respiratory disease. It may be caused by allergic sensitization to macromolecules of biologic origin or to chemicals of low molecular weight, as well as by (heavy) exposure to workplace irritants. The pneumoconioses are caused by the accumulation of dust particles or fibres in the lungs. They include silicosis, coal workers' pneumoconioses, asbestosis and other less common pneumoconioses. Chronic beryllium disease is caused by a cell-mediated sensitization to beryllium and resembles sarcoidosis. Hard-metal lung disease is caused by sensitivity to cobalt and resembles hypersensitivity pneumonitis. Extrinsic allergic alveolitis or hypersensitivity pneumonitis is generally caused by sensitization to aerosolized biological antigens. Several types of infections may be related more or less specifically to work. Chronic obstructive lung disease is mainly caused by cigarette smoking, but exposure to dusts and gases contribute to its incidence. Similarly, bronchopulmonary cancer is not only caused by smoking, but also by occupational agents, most notably asbestos. Asbestos is also a cause of nonmalignant and malignant pleural disease.
Output: OCCUPATIONAL DISEASES
a b s t r a c t Feasibility of degradation of Triton X-100 as a widely used and resistive surfactant in aqueous media was studied via some homogeneous and heterogeneous AOPs of UV/TiO 2 , UV/H 2 O 2 and UV/S 2 O 8 2− . For treatment of solutions containing 20 mg/L of Triton, the optimum obtained conditions are: 5.0 mg/L of nano TiO 2 , 270.3 mg/L of KPS, and 34.0 mg/L of H 2 O 2 (1 mM of the oxidants), initial natural pH of 5.4 and temperature of 45 • C. Under these conditions, the degradation efficiency for the UV/TiO 2 , UV/H 2 O 2 and UV/S 2 O 8 2− processes exceeds 71.9% (in 60 min), 80.9% (in 60 min) and 98.5% (in only 30 min) respectively. It was found that simultaneous application of these heterogeneous and homogeneous AOPs (UV/TiO 2 /H 2 O 2 or S 2 O 8 2− ) is not desirable due to some physico-chemical retarding effects. The influence of temperature on the reactions was examined in the range of 15-45 • C and a kinetic power law model jointed with the Arrhenius equation was introduced. A pseudo first order reaction rate is appropriate for UV/S 2 O 8 2− and UV/TiO 2 processes under optimum conditions, while this order for UV/H 2 O 2 process is 2.27. Meanwhile, the initial rates of degradation in UV/TiO 2 process can be described well by the Langmuir-Hinshelwood kinetic model. Analysis of energy consumptions (thermal and electrical) revealed that increasing in temperature is an effective factor for lowering the energy cost of the preferred process of UV/S 2 O 8 2− .
Output: Homogeneous and heterogeneous AOPs for rapid degradation of Triton X-100 in aqueous media via UV light, nano titania hydrogen peroxide and potassium persulfate
In a patient with acute respiratory illness (cough, sputum production, chest pain, and/or dyspnea), the need for chest imaging depends on the severity of illness, age of the patient, clinical history, physical and laboratory findings, and other risk factors. Chest radiographs seem warranted when one or more of the following are present: age Ն 40; dementia; a positive physical examination; hemoptysis; associated abnormalities (leukocytosis, hypoxemia); or other risk factors, including coronary artery disease, congestive heart failure, or druginduced acute respiratory failure. Chest CT may be warranted in complicated cases of severe pneumonia and in febrile neutropenic patients with normal or nonspecific chest radiographic findings. Literature on the indications and usefulness of radiologic studies for acute respiratory illness in different clinical settings is reviewed. Acute respiratory illness (ARI) is defined as Ն1 of the following: cough, sputum production, chest pain, or dyspnea (with or without fever). The workup of a patient with ARI, including the need for chest radiography and
Output: ACR Appropriateness Criteria ® on Acute Respiratory Illness
Background: The homogeneous mixing assumption is widely adopted in epidemic modelling for its parsimony and represents the building block of more complex approaches, including very detailed agent-based models. The latter assume homogeneous mixing within schools, workplaces and households, mostly for the lack of detailed information on human contact behaviour within these settings. The recent data availability on high-resolution face-to-face interactions makes it now possible to assess the goodness of this simplified scheme in reproducing relevant aspects of the infection dynamics. Methods: We consider empirical contact networks gathered in different contexts, as well as synthetic data obtained through realistic models of contacts in structured populations. We perform stochastic spreading simulations on these contact networks and in populations of the same size under a homogeneous mixing hypothesis. We adjust the epidemiological parameters of the latter in order to fit the prevalence curve of the contact epidemic model. We quantify the agreement by comparing epidemic peak times, peak values, and epidemic sizes. Results: Good approximations of the peak times and peak values are obtained with the homogeneous mixing approach, with a median relative difference smaller than 20 % in all cases investigated. Accuracy in reproducing the peak time depends on the setting under study, while for the peak value it is independent of the setting. Recalibration is found to be linear in the epidemic parameters used in the contact data simulations, showing changes across empirical settings but robustness across groups and population sizes. Conclusions: An adequate rescaling of the epidemiological parameters can yield a good agreement between the epidemic curves obtained with a real contact network and a homogeneous mixing approach in a population of the same size. The use of such recalibrated homogeneous mixing approximations would enhance the accuracy and realism of agent-based simulations and limit the intrinsic biases of the homogeneous mixing. Mathematical models provide a theoretical framework that can be applied to improve our understanding of the spread of infectious diseases in a host population [1] [2] [3] [4] . A vast range of approaches has recently been developed for the analysis and interpretation of epidemic data,
Output: Recalibrating disease parameters for increasing realism in modeling epidemics in closed settings
Porcine deltacoronavirus (PDCoV) is a newly discovered coronavirus, which belongs to the family Coronaviridae. It causes watery diarrhea, vomiting, and dehydration in newborn piglets. A sensitive RT-PCR method is urgently required to detect PDCoV infection. In this study, we developed and evaluated a conventional RT-PCR assay and a SYBR green-based real-time RT-PCR assay that targeted the PDCoV gene. Both assays are specific and have the same limit of detection at 2 × 10 1 copies of RNA molecules per reaction. Eighty-four clinical samples were subjected to both conventional RT-PCR and real-time RT-PCR, and the same positive rate (41.7%) was achieved, which was much higher than the positive rate (26.2%) using a previously described onestep RT-PCR technique. In summary, a conventional RT-PCR technique was successfully established for the detection of PDCoV with the same detection limit as a SYBR green-based real-time RT-PCR assay.
Output: Research Article
Dickeya species are high consequence plant pathogenic bacteria listed among the quarantine pathogens of the European Union; associated with potato disease outbreaks and subsequent economic losses worldwide. Early, accurate, and reliable detection of Dickeya spp. is needed to prevent establishment and further dissemination of this pathogen. Therefore, a multiplex TaqMan qPCR was developed for sensitive detection of Dickeya spp. and specifically, D. dianthicola. A signature genomic region for the genus Dickeya (mglA/mglC) and unique genomic region for D. dianthicola (alcohol dehydrogenase) were identified using a whole genome based comparative genomics approach. The developed multiplex TaqMan qPCR was validated using extensive inclusivity and exclusivity panels, and naturally/artificially infected samples to confirm broad range detection capability and specificity. Both sensitivity and spiked assays showed detection limit of 10 fg DNA. The developed multiplex assay is sensitive and reliable to detect Dickeya spp. and D. dianthicola with no false positives or false negatives. It was able to detect mixed infection from naturally and artificially infected plant materials. The developed assay will serve as a practical tool for screening of propagative material, monitoring the presence and distribution, and quantification of target pathogens in a breeding program. The assay also has applications in routine diagnostics, biosecurity and microbial forensics.
Output: Comparative genomics reveals signature regions used to develop a robust and sensitive multiplex TaqMan real-time qPCR assay to detect the genus Dickeya and Dickeya dianthicola
Background. The negative binomial distribution is used commonly throughout biology as a model for overdispersed count data, with attention focused on the negative binomial dispersion parameter, k. A substantial literature exists on the estimation of k, but most attention has focused on datasets that are not highly overdispersed (i.e., those with k$1), and the accuracy of confidence intervals estimated for k is typically not explored. Methodology. This article presents a simulation study exploring the bias, precision, and confidence interval coverage of maximum-likelihood estimates of k from highly overdispersed distributions. In addition to exploring small-sample bias on negative binomial estimates, the study addresses estimation from datasets influenced by two types of event under-counting, and from disease transmission data subject to selection bias for successful outbreaks. Conclusions. Results show that maximum likelihood estimates of k can be biased upward by small sample size or under-reporting of zero-class events, but are not biased downward by any of the factors considered. Confidence intervals estimated from the asymptotic sampling variance tend to exhibit coverage below the nominal level, with overestimates of k comprising the great majority of coverage errors. Estimation from outbreak datasets does not increase the bias of k estimates, but can add significant upward bias to estimates of the mean. Because k varies inversely with the degree of overdispersion, these findings show that overestimation of the degree of overdispersion is very rare for these datasets.
Output: Maximum Likelihood Estimation of the Negative Binomial Dispersion Parameter for Highly Overdispersed Data, with Applications to Infectious Diseases
Renal ischemia-reperfusion injury (IRI) is a major cause of acute kidney injury (AKI), which could induce the poor prognosis. The purpose of this study was to characterize the molecular mechanism of the functional changes of CD11b + /Ly6C intermediate macrophages after renal IRI. The gene expression profiles of CD11b + /Ly6C intermediate macrophages of the sham surgery mice, and the mice 4 h, 24 h and 9 days after renal IRI were downloaded from the Gene Expression Omnibus database. Analysis of mRNA expression profiles was conducted to identify differentially expressed genes (DEGs), biological processes and pathways by the series test of cluster. Protein-protein interaction network was constructed and analysed to discover the key genes. A total of 6738 DEGs were identified and assigned to 20 model profiles. DEGs in profile 13 were one of the predominant expression profiles, which are involved in immune cell chemotaxis and proliferation. Signet analysis showed that Atp5a1, Atp5o, Cox4i, Cdc42, Rac2 and Nhp2 were the key genes involved in oxidation-reduction, apoptosis, migration, M1-M2 differentiation, and proliferation of macrophages. RPS18 may be an appreciate reference gene as it was stable in macrophages. The identified DEGs and their enriched pathways investigate factors that may participate in the functional changes of CD11b + /Ly6C intermediate macrophages after renal IRI. Moreover, the vital gene Nhp2 may involve the polarization of macrophages, which may be a new target to affect the process of AKI.
Output: Bioinformatics Analysis of Genes and Pathways of CD11b + /Ly6C intermediate Macrophages after Renal Ischemia-Reperfusion Injury *
Coronaviruses devote more than three quarters of their coding capacity to encode two large polyproteins (1a and 1ab polyproteins), which are proteolytically processed into 15-16 mature, nonstructural replicase proteins (nsp1 to 16). These cleavage products are believed to play essential roles in replication of the giant RNA genome of ∼ 30 kb and transcription of a nested set of 5 to 9 subgenomic RNA species by a unique discontinuous transcription mechanism. In this report, one of these replicase proteins, nsp9 of the coronavirus infectious bronchitis virus (IBV) is systematically studied using both biochemical and reverse genetic approaches. The results showed that substitution mutation of a conserved Gly (G98) residue in the C-terminal α-helix domain with an Asp greatly destabilized the IBV nsp9 homodimer and abolished its RNA-binding activity. Introduction of the same mutation into an infectious IBV clone system showed that the mutation totally abolishes the transcription of subgenomic RNA and no infectious virus could be recovered. Mutation of a semi-conserved Ile (I95) residue in the same region showed moderately destabilizing effect on the IBV nsp9 homodimer but minimal effect on its RNA-binding activity. Introduction of the mutation into the IBV infectious clone system showed recovery of a mutant virus with severe growth defects, supporting that dimerization is critical for the function of this replicase protein. Meanwhile, mutations of some positively charged residues in the β-barrel regions of the IBV nsp9 protein significantly reduced its RNA-binding activity, but with no obvious effect on dimerization of the protein. Introduction of these mutations into the viral genome showed only mild to moderate effects on the growth and infectivity of the rescued mutant viruses.
Output: Formation of stable homodimer via the C-terminal α-helical domain of coronavirus nonstructural protein 9 is critical for its function in viral replication
Biochar, that is, carbonized biomass similar to charcoal, has been used in acute medical treatment of animals for many centuries. Since 2010, livestock farmers increasingly use biochar as a regular feed supplement to improve animal health, increase nutrient intake efficiency and thus productivity. As biochar gets enriched with nitrogen-rich organic compounds during the digestion process, the excreted biochar-manure becomes a more valuable organic fertilizer causing lower nutrient losses and greenhouse gas emissions during storage and soil application. Scientists only recently started to investigate the mechanisms of biochar in the different stages of animal digestion and thus most published results on biochar feeding are based so far on empirical studies. This review summarizes the state of knowledge up to the year 2019 by evaluating 112 relevant scientific publications on the topic to derive initial insights, discuss potential mechanisms behind observations and identify important knowledge gaps and future research needs. The literature analysis shows that in most studies and for all investigated farm animal species, positive effects on different parameters such as toxin adsorption, digestion, blood values, feed efficiency, meat quality and/or greenhouse gas emissions could be found when biochar was added to feed. A considerable number of studies provided statistically non-significant results, though tendencies were mostly positive. Rare negative effects were identified in regard to the immobilization of liposoluble feed ingredients (e.g., vitamin E or Carotenoids) which may limit long-term biochar feeding. We found that most of the studies did not systematically investigate biochar properties (which may vastly differ) and dosage, which is a major drawback for generalizing results. Our review demonstrates that the use of biochar as a feed additive has the potential to improve animal health, feed efficiency and livestock housing climate, to reduce nutrient losses and greenhouse gas emissions, and to increase the soil organic matter content and thus soil fertility when eventually applied to soil. In combination with other good practices, co-feeding of biochar may thus have the potential to improve the sustainability of animal husbandry. However, more systematic multi-disciplinary research is definitely needed to arrive at generalizable recommendations.
Output: The use of biochar in animal feeding Distributed under Creative Commons CC-BY 4.0
Objective: Coronavirus disease 2019 (COVID-19) is an escalating global epidemic caused by SARS-CoV-2, with a high mortality in critical patients. Effective indicators for predicting disease severity in SARS-CoV-2 infected patients are urgently needed. Methods: In this study, 43 COVID-19 patients admitted in Chongqing Public Health Medical Center were involved. Demographic data, clinical features, and laboratory examinations were obtained through electronic medical records. Peripheral blood specimens were collected from COVID-19 patients and examined for lymphocyte subsets and cytokine profiles by flow cytometry. Potential contributing factors for prediction of disease severity were further analyzed. Results: A total of 43 COVID-19 patients were included in this study, including 29 mild patients and 14 sever patients. Severe patients were significantly older (61.9±9.4 vs 44.4±15.9) and had higher incidence in co-infection with bacteria compared to mild group (85.7%vs27.6%). Significantly more severe patients had the clinical symptoms of anhelation (78.6%) and asthma (71.4%). For laboratory examination, 57.1% severe cases showed significant reduction in lymphocyte count. The levels of Interluekin-6 (IL6), IL10, erythrocyte sedimentation rate (ESR) and D-Dimer (D-D) were significantly higher in severe patients than mild patients, while the level of albumin (ALB) was remarkably All rights reserved. No reuse allowed without permission. the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. : medRxiv preprint lower in severe patients. Further analysis demonstrated that ESR, D-D, age, ALB and IL6 were the major contributing factors for distinguishing severe patients from mild patients. Moreover, ESR was identified as the most powerful factor to predict disease progression of COVID-19 patients. : Age and the levels of ESR, D-D, ALB and IL6 are closely related to the disease severity of COVID-19 patients. ESR can be used as a valuable indicator for distinguishing severe COVID-19 patients in early stage, so as to increase the survival of severe patients.
Output: Potential Factors for Prediction of Disease Severity of COVID-19 Patients
Previous studies have demonstrated that BR-931, a hepatic peroxisome proliferator, can induce liver tumours in mice and rats. Since alterations in gene expression may play a critical role in multistage hepatocarcinogenesis, the present studies examined the expression of the c-myc, c-H-ras, epidermal growth factor (EGF) receptor and ODC (ornithine decarboxylase) genes, as well as endogenous retrovirus-like sequences, in F344 rat liver during the first 8 weeks of feeding a 0.16% Br931 diet and in liver tumours induced by chronic feeding of this diet. Northern blot analysis of poly A+ liver RNA samples showed an increase in the level of RNAs homologous to rat leukaemia virus (RaLV) but no significant change in the level of 30S-retrovirus related RNAs in the liver RNA samples obtained from rats during the first 8 weeks of feeding the diet containing BR931. An increase in the levels of c-myc, c-H-ras and ODC transcripts was also seen in the liver RNA samples from the treated rats. Of particular interest was a decrease in the abundance of EGF receptor transcripts in the liver RNA samples from rats fed the BR931 diet. Increased levels of RaLV, c-myc, and ODC RNAs were also seen in the tumours induced by BR931, but this was not the case for 30S and c-H-ras. The liver tumour samples also showed a decrease in EGF receptor RNA. These changes in cellular levels of specific RNAs resemble, in several respect, those we previously described in rodent liver during regeneration and tumour promotion, and also those seen in rodent hepatomas induced by other agents. Therefore, they may reflect a common profile of gene expression relevant to liver proliferation and carcinogenesis.
Output: Changes in expression of cellular oncogenes and endogenous retrovirus- like sequences during hepatocarcinogenesis induced by a peroxisome proliferator
Viral diseases remain serious threats to public health because of the shortage of effective means of control. To combat the surge of viral diseases, new treatments are urgently needed. Here we show that small-molecules, which inhibit cellular anti-apoptotic Bcl-2 proteins (Bcl-2i), induced the premature death of cells infected with different RNA or DNA viruses, whereas, at the same concentrations, no toxicity was observed in mock-infected cells. Moreover, these compounds limited viral replication and spread. Surprisingly, Bcl-2i also induced the premature apoptosis of cells transfected with viral RNA or plasmid DNA but not of mock-transfected cells. These results suggest that Bcl-2i sensitizes cells containing foreign RNA or DNA to apoptosis. A comparison of the toxicity, antiviral activity, and side effects of six Bcl-2i allowed us to select A-1155463 as an antiviral lead candidate. Thus, our results pave the way for the further development of Bcl-2i for the prevention and treatment of viral diseases.
Output: Antiviral Properties of Chemical Inhibitors of Cellular Anti-Apoptotic Bcl-2 Proteins
Background-The genome annotations of rhesus (Macaca mulatta) and cynomolgus (Macaca fascicularis) macaques, two of the most common nonhuman primate animal models, are limited. Methods-We analyzed large-scale macaque RNA-based next-generation sequencing (RNAseq) data to identify un-annotated macaque transcripts. Results-For both macaque species, we uncovered thousands of novel isoforms for annotated genes and thousands of un-annotated intergenic transcripts enriched with non-coding RNAs. We also identified thousands of transcript sequences which are partially or completely 'missing' from current macaque genome assemblies. We showed that many newly identified transcripts were differentially expressed during SIV infection of rhesus macaques or during Ebola virus infection of cynomolgus macaques. Conclusions-For two important macaque species, we uncovered thousands of novel isoforms and un-annotated intergenic transcripts including coding and non-coding RNAs, polyadenylated and non-polyadenylated transcripts. This resource will greatly improve future macaque studies, as demonstrated by their applications in infectious disease studies.
Output: Assessment and improvement of Indian-origin rhesus macaque and Mauritian-origin cynomolgus macaque genome annotations using deep transcriptome sequencing data
O. is a 37-year-old male with no significant past medical history who presented to the Emergency Department with a one week history of worsening dysphagia and odynophagia. He reported he was usually in good health until the current symptoms began. Scott said that he had been unable to swallow solid foods over the past week, largely due to increasing pain on swallowing, and was now unable to swallow liquids as well. Although he stated that his appetite was unchanged, he estimated a fivepound weight loss over the last week due to poor oral intake. He otherwise denied fever, respiratory or gastrointestinal symptoms, or any other complaints. He takes no medications at home except for rare acetaminophen. He is married, has a twoyear-old son, and works as an attorney. He denied use of tobacco, alcohol, or illicit drugs. Family history was noncontributory. On physical exam, he was afebrile and his vital signs were within normal limits. Cardiovascular, respiratory, abdominal, extremity, and neurologic exam were unremarkable. There was some mild oropharyngeal thrush, palpable bilateral inguinal lymphadenopathy, and a 1 cm painless ulceration on the penile shaft. Laboratory evaluation was unremarkable.
Output: When a Diagnosis Is Reportable The Patient
Coronaviridae and causes highly contagious respiratory disease in chickens. Innate immunity plays significant roles in host defense against IBV. Here, we explored the interaction between IBV and the host innate immune system. Severe histopathological lesions were observed in the tracheal mucosa at 3-5 days post inoculation (dpi) and in the kidney at 8 dpi, with heavy viral loads at 1-11 and 1-28 dpi, respectively. The expression of mRNAs encoding Toll-like receptor (TLR) 3 and TLR7 were upregulated at 3-8 dpi, and that of TIR-domain-containing adapter-inducing interferon (IFN) β (TRIF) was upregulated at 21 dpi in the trachea and kidney. Myeloid differentiation primary response protein 88 (MyD88) was upregulated in the trachea during early infection. Tumor necrosis factor receptor-associated factor (TRAF) 3 and TRAF6 were upregulated expression in both tissues. Moreover, melanoma differentiation-associated protein 5 (MDA5), laboratory of genetics and physiology 2 (LGP2), stimulator of IFN genes (STING), and mitochondrial antiviral signaling protein (MAVS), as well as TANK binding kinase 1 (TBK1), inhibitor of kappaB kinase (IKK) ԑ, IKKα, IKKβ, IFN regulatory factor (IRF) 7, nuclear factor of kappaB (NF-κB), IFN-α, IFN-β, various interleukins(ILs), and macrophage inflammatory protein-1β (MIP-1β) were significantly upregulated in the trachea and downregulated in the kidney. These results suggested that the TLR and MDA5 signaling pathways and innate immune cytokine were induced after IBV infection. Additionally, consistent responses to IBV infection were observed during early infection, with differential and complicated responses in the kidney.
Output: Responses of the Toll-like receptor and melanoma differentiation- associated protein 5 signaling pathways to avian infectious bronchitis virus infection in chicks
We compare established docking programs, AutoDock Vina and Schrodinger's Glide, to the recently published NNScore scoring functions. As expected, the best protocol to use in a virtual-screening project is highly dependent on the target receptor being studied. However, the mean screening performance obtained when candidate ligands are docked with Vina and rescored with NNScore 1.0 is not statistically different than the mean performance obtained when docking and scoring with Glide. We further demonstrate that the Vina and NNScore docking scores both correlate with chemical properties like small-molecule size and polarizability. Compensating for these potential biases leads to improvements in virtual screen performance. Composite NNScore-based scoring functions suited to a specific receptor further improve performance. We are hopeful that the current study will prove useful for those interested in computer-aided drug design.
Output: Comparing Neural-Network Scoring Functions and the State of the Art: Applications to Common Library Screening
Important advances have been made in the immunodiagnosis of tuberculosis (TB) based on the detection of Mycobacterium tuberculosis (MTB)-specific T cells. However, the sensitivity and specificity of the immunological approach are relatively low because there are no specific markers for antigen-specific Th cells, and some of the Th cells that do not produce cytokines can be overlooked using this approach. In this study, we found that MTB-specific peptides of ESAT-6/CFP-10 can stimulate the expression of CD40L specifically in CD4 + T cells but not other cells from pleural fluid cells (PFCs) in patients with tuberculous pleurisy (TBP). CD4 + CD40L + but not CD4 + CD40L 2 T cells express IFN-c, IL-2, TNF-a, IL-17 or IL-22 after stimulation with MTBspecific peptides. In addition, CD4 + CD40L + T cells were found to be mostly polyfunctional T cells that simultaneously produce IFN-c, IL-2 and TNF-a and display an effector or effector memory phenotype (CD45RA 2 CD45RO + CCR7 2 CD62L 2 ICOS 2 ). To determine the specificity of CD4 + CD40L + T cells, we incubated PFCs with ESTA-6/CFP-10 peptides and sorted live CD4 + CD40L + and CD4 + CD40L 2 T cells by flow cytometry. We further demonstrated that sorted CD4 + CD40L + , but not CD4 + CD40L 2 fractions, principally produced IFN-c, IL-2, TNF-a, IL-17 and IL-22 following restimulation with ESTA-6/CFP-10 peptides. Taken together, our data indicate that the expression of CD40L on MTB-specific CD4 + T cells could be a good marker for the evaluation and isolation of MTB-specific Th cells and might also be useful in the diagnosis of TB.
Output: ): e20165. 2008ZX10003011), the National Nature Science Foundation of China (no. 30872300), university basic scientific research expense, the Youth Development Project (no. 09YKPY76), the China Postdoctoral Science Foundation (no. 20090460804) and the National Key Basic
For the purpose of this article, Asia refers to WHO's combined South-East Asia and Western Pacifi c regions and thus includes Australia and New Zealand. Asia has the highest number of tobacco users and is the prime target of transnational tobacco companies. The future of global tobacco control rests in this region and the challenges are clear. China, India, and Indonesia are key markets and Asia is a frontrunner in tobacco control measures, such as plain packaging of cigarettes. Some countries in Asia have a long history of tobacco control activities beginning in the 1970s, and WHO's Western Pacifi c Region is still the only region where all countries have ratifi ed WHO's Framework Convention on Tobacco Control. We reviewed the history, research, epidemiology, tobacco control action, obstacles, and potential responses and solutions to the tobacco epidemic in this region. Levels of development, systems of government, and population size are very diff erent between countries, with population size ranging from 1500 to 1·3 billion, but similarities exist in aspects of the tobacco epidemic, harms caused, obstacles faced, and tobacco control actions needed.
Output: Tobacco Control 2 Tobacco control in Asia
We collected information on demographic characteristics, exposure history, and illness timelines of laboratory-confirmed cases of NCIP that had been reported by January 22, 2020. We described characteristics of the cases and estimated the key epidemiologic time-delay distributions. In the early period of exponential growth, we estimated the epidemic doubling time and the basic reproductive number. Among the first 425 patients with confirmed NCIP, the median age was 59 years and 56% were male. The majority of cases (55%) with onset before January 1, 2020, were linked to the Huanan Seafood Wholesale Market, as compared with 8.6% of the subsequent cases. The mean incubation period was 5.2 days (95% confidence interval [CI], 4.1 to 7.0), with the 95th percentile of the distribution at 12.5 days. In its early stages, the epidemic doubled in size every 7.4 days. With a mean serial interval of 7.5 days (95% CI, 5.3 to 19), the basic reproductive number was estimated to be 2.2 (95% CI, 1.4 to 3.9). On the basis of this information, there is evidence that human-to-human transmission has occurred among close contacts since the middle of December 2019. Considerable efforts to reduce transmission will be required to control outbreaks if similar dynamics apply elsewhere. Measures to prevent or reduce transmission should be implemented in populations at risk. (Funded by the Ministry of Science and Technology of China and others.) a bs tr ac t Early Transmission Dynamics
Output: of Novel Coronavirus-Infected Pneumonia
CEACAM1 (carcinoembryonic antigen-related cell adhesion molecule 1), a type I transmembrane glycoprotein involved in cell-cell adhesion has been shown to act as an angiogenic factor for mouse and human endothelial cells. Based on the ability of CEACAM1 to initiate lumen formation in human mammary epithelial cells grown in 3D culture (Matrigel), we hypothesized that murine CEACAM1 may play a similar role in vasculogenesis. In order to test this hypothesis, murine embryonic stem (ES) cells stimulated with VEGF were differentiated into embryoid bodies (EB) for 8 days (−8-0 d) and transferred to Matrigel in the presence or absence of anti-CEACAM1 antibody for an additional 12 days (0-12 d). In the absence of anti-CEACAM1 antibody or in the presence of an isotype control antibody, the EB in Matrigel underwent extensive sprouting, generating lengthy vascular structures with well-defined lumina as demonstrated by confocal microscopy, electron microscopy, and immunohistochemical analysis. Both the length and architecture of the vascular tubes were inhibited by anti-CEACAM1 mAb CC1, a mAb that blocks the cell-cell adhesion functions of CEACAM1, thus demonstrating a critical role for this cell-cell adhesion molecule in generating and maintaining vasculogenesis. QRT-PCR analysis of the VEGF treated ES cells grown under conditions that convert them to EB revealed expression of Ceacam1 as early as −5 to −3 d reaching a maximum at day 0 at which time EBs were transferred to Matrigel, thereafter levels at first declined and then increased over time. Other markers of vasculogenesis including Pecam1, VE-Cad, and Tie-1 were not detected until day 0 when EBs were transferred to Matrigel followed by a steady increase in levels, indicating later roles in vasculogenesis. In contrast, Tie-2 and Flk-1 (VEGFR2) were detected on day five of EB formation reaching a maximum at day 0 on transfer to Matrigel, similar to Ceacam1, but after which Tie-2 declined over time, while Flk-1 increased over time. QRT-PCR analysis of the anti-CEACAM1 treated ES cells revealed a significant decrease in the expression of Ceacam1, Pecam1, Tie-1, and Flk-1, while VE-Cad and Tie-2 expression were unaffected. These results suggest that the expression and signaling of CEACAM1 may affect the expression of other factors known to play critical roles in vasculogenesis. Furthermore this 3D model of vasculogenesis in an environment of extracellular matrix may be a useful model for comparison to existing models of angiogenesis.
Output: Role of Ceacam1 in VEGF induced vasculogenesis of murine embryonic stem cell-derived embryoid bodies in 3D culture NIH Public Access
Phylogenetic estimation from aligned DNA, RNA or amino acid sequences has attracted more and more attention in recent years due to its importance in analysis of many fine-scale genetic data. Nowadays, its application fields range from medical research to drug discovery, to epidemiology, to systematics and population dynamics. Estimating phylogenies involves solving an optimization problem, called the phylogenetic estimation problem (PEP), whose versions depend on the criterion used to select a phylogeny among plausible alternatives. This chapter offers an overview of PEP and discuss the most important versions that occur in the literature. R. Bruni (ed.), Mathematical Approaches to Polymer Sequence Analysis and Related Problems,
Output: Estimating Phylogenies from Molecular Data
This study was carried out to further the available information on adult cases of human metapneumovirus (hMPV), a recently described cause of respiratory infection. Among a cohort of 741 symptomatic patients tested since 2003, the virus was diagnosed in six adults using reverse transcriptase polymerase chain reaction. Of the six, two were from the community, two were hospital inpatients with chronic obstructive pulmonary disease and two were immunocompromised patients, both of whom required ventilation and later died. This report discusses the clinical features, epidemiology and diagnosis of hMPV, highlighting that this infection may be associated with death in high-risk adults. For adults presenting with respiratory symptoms and a background of pre-existing respiratory disease or who are immunocompromised, nucleic acid-based techniques are a cost-effective means of making the viral diagnosis in a clinically relevant time frame.
Output: Human metapneumovirus in adults: a short case series
An important effort has been performed after the emergence of severe acute respiratory syndrome (SARS) epidemic in 2003 to diagnose and prevent virus spreading. Several types of vaccines have been developed including inactivated viruses, subunit vaccines, virus-like particles (VLPs), DNA vaccines, heterologous expression systems, and vaccines derived from SARS-CoV genome by reverse genetics. This review describes several aspects essential to develop SARS-CoV vaccines, such as the correlates of protection, virus serotypes, vaccination side effects, and bio-safeguards that can be engineered into recombinant vaccine approaches based on the SARS-CoV genome. The production of effective and safe vaccines to prevent SARS has led to the development of promising vaccine candidates, in contrast to the design of vaccines for other coronaviruses, that in general has been less successful. After preclinical trials in animal models, efficacy and safety evaluation of the most promising vaccine candidates described has to be performed in humans.
Output: Vaccines to prevent severe acute respiratory syndrome coronavirus-induced disease
H9N2 Avian influenza virus has repeatedly infected humans and other mammals, which highlights the need to determine the pathogenicity and the corresponding mechanism of this virus for mammals. In this study, we found two H9N2 viruses with similar genetic background but with different pathogenicity in mice. The A/duck/Nanjing/06/2003 (NJ06) virus was highly pathogenic for mice, with a 50% mouse lethal dose (MLD 50 ) of 10 2.83 50% egg infectious dose (EID 50 ), whereas the A/duck/Nanjing/01/1999 (NJ01) virus was low pathogenic for mice, with a MLD 6.81 50 of >10 EID 50 . Further studies showed that the NJ06 virus grew faster and reached significantly higher titers than NJ01 in vivo and in vitro. Moreover, the NJ06 virus induced more severe lung lesions, and higher levels of inflammatory cellular infiltration and cytokine response in lungs than NJ01 did. However, only 12 different amino acid residues (HA-K157E, NA-A9T, NA-R435K, PB2-T149P, PB2-K627E, PB1-R187K, PA-L548M, PA-M550L, NP-G127E, NP-P277H, NP-D340N, NS1-D171N) were found between the two viruses, and all these residues except for NA-R435K were located in the known functional regions involved in interaction of viral proteins or between the virus and host factors. Summary, our results suggest that multiple amino acid differences may be responsible for the higher pathogenicity of the NJ06 virus for mice, resulting in lethal infection, enhanced viral replication, severe lung lesions, and excessive inflammatory cellular infiltration and cytokine response in lungs. These observations will be helpful for better understanding the pathogenic potential and the corresponding molecular basis of H9N2 viruses that might pose threats to human health in the future.
Output: Two Genetically Similar H9N2 Influenza A Viruses Show Different Pathogenicity in Mice
ISG15 is a ubiquitin-like modifi er that is expressed in response to type 1 interferon signaling (IFN-α / β ) and plays a role in antiviral responses. The core E1, E2, and E3 enzymes for ISG15 are Ube1L, UbcH8, and Herc5, respectively, and these are all also induced at the transcriptional level by IFN-α / β . We recently showed that Herc5 associates with polysomes and modifi es target proteins in a cotranslational manner. Here, we describe the expression of the core conjugating enzymes in human cells, the detection of ISG15 conjugates, and the methods for fractionation of Herc5 with polysomes.
Output: The ISG15 Conjugation System
The Saudi Arabian Ministry of Health implemented a pro-active surveillance programme for Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV). We report MERS-CoV data from 5065 Kingdom of Saudi Arabia individuals who were screened for MERS-CoV over a 12-month period. From 1 October 2012 to 30 September 2013, demographic and clinical data were prospectively collected from all laboratory forms received at the Saudi Arabian Virology reference laboratory. Data were analysed by referral type, age, gender, and MERS-CoV real-time PCR test results. Five thousand and 65 individuals were screened for MER-CoV: hospitalized patients with suspected MERS-CoV infection (n = 2908, 57.4%), healthcare worker (HCW) contacts (n = 1695; 33.5%), and family contacts of laboratory-confirmed MERS cases (n = 462; 9.1%). Eleven per cent of persons tested were children (<17 years of age). There were 108 cases (99 adults and nine children) of MERS-CoV infection detected during the 12-month period (108/5065, 2% case detection rate). Of 108 cases, 45 were females (six children and 39 adults) and 63 were males (three children and 60 adults). Of the 99 adults with MERS-CoV infection, 70 were hospitalized patients, 19 were HCW contacts, and ten were family contacts. There were no significant increases in MERS-CoV detection rates over the 12-month period: 2.patients had a significantly higher MERS-CoV infection rate (63/2318, 2.7%) than females (45/2747, 1.6%) (p 0.013). MERS-CoV rates remain at low levels, with no significant increase over time. Pro-active surveillance for MERS-CoV in newly diagnosed patients and their contacts will continue.
Output: Screening for Middle East respiratory syndrome coronavirus infection in hospital patients and their healthcare worker and family contacts: a prospective descriptive study
Severe acute respiratory syndrome-associated coronavirus (SARS-CoV) Annexin A2 Autoantigen Anti-spike domain 2 (S2) Interleukin-6 (IL-6) Interferon-␥ (IFN-␥) a b s t r a c t Severe acute respiratory syndrome-associated coronavirus (SARS-CoV) infection causes lung failure characterized by atypical pneumonia. We previously showed that antibodies against SARS-CoV spike domain 2 (S2) in the patient sera can cross-react with human lung epithelial cells; however, the autoantigen is not yet identified. In this study, we performed proteomic studies and identified several candidate autoantigens recognized by SARS patient sera in human lung type II epithelial cell A549. Among the candidate proteins, annexin A2, which was identified by mass spectrometry analysis and had the highest score by Mascot data search, was further characterized and investigated for its role as an autoantigen. By confocal microscopic observation, SARS patient sera and anti-S2 antibodies were co-localized on A549 cells and both of them were co-localized with anti-annexin A2 antibodies. Anti-annexin A2 antibodies bound to purified S2 proteins, and anti-S2 bound to immunoprecipitated annexin A2 from A549 cell lysate in a dose-dependent manner. Furthermore, an increased surface expression and raft-structure distribution of annexin A2 was present in A549 cells after stimulation with SARS-induced cytokines interleukin-6 and interferon-␥. Cytokine stimulation increased the binding capability of anti-S2 antibodies to human lung epithelial cells. Together, the upregulated expression of annexin A2 by SARS-associated cytokines and the cross-reactivity of anti-SARS-CoV S2 antibodies to annexin A2 may have implications in SARS disease pathogenesis.
Output: Annexin A2 on lung epithelial cell surface is recognized by severe acute respiratory syndrome-associated coronavirus spike domain 2 antibodies