niryuu/sni-each-converted huggingface dataset:
Emerging and re-emerging pathogens and bioterror threats require an organized and coherent response from the worldwide research community to maximize available resources and competencies with the primary goals to understand the pathogen and enable intervention. In 2001, the Structural Proteomics In Europe project prototyped the pan-viral structural genomic approach, and the SARS outbreak in 2003 accelerated the concept of structural characterization of all proteins from a viral proteome and the interaction with their host partners. Following that approach, in 2004 the center for Functional and Structural Proteomics for SARS-CoV related proteins was initiated as part of the US NIH NIAID proteomics resource centers. Across worldwide efforts in Asia, Europe and America, the international research teams working on SARS-CoV have now determined experimental structural information for 45% of the SARS-CoV proteins and 53% of all its soluble proteins. This data is fully available to the scientific community and is providing an unprecedented level of insight to this class of RNA viruses. The efforts and results by the international scientific community to the SARS outbreak are serving as an example and roadmap of a rapid response using modern research methods.
Output: International Research Networks in Viral Structural Proteomics: again, lessons from SARS
The aim of this study was to demonstrate how latent epidemics can potentially evolve into a pandemic instantaneously due to globally mobile human population in recent times, as can be seen in the ongoing Ebola epidemic in West Africa. Selected cases of current epidemics are used in this study to identify emergent patterns. These cases exemplify the need for a comprehensive analysis of infectious diseases and serve as an initial stage when developing appropriate strategies in improving epidemic management. This study can help better understand the complexities of infectious diseases and assist in developing a specific set of preventative processes from the individual to international levels when developing strategies to reducing the effects of an epidemic outbreak.
Output: The potential of recurrent epidemics and pandemics in a highly mobile global society
In felids, feline leukemia virus (FeLV) infection results in a variety of outcomes that range from abortive (virus readily eliminated and never detectable) to progressive infection (persistent viremia and viral shedding). Recently, a novel outcome was postulated for low FeLV infectious doses. Naïve cats exposed to faeces of persistently infected cats seroconverted, indicating infection, but remained negative for provirus and p27 antigen in blood. FeLV provirus was found in some tissues but not in the bone marrow, infection of which is usually considered a necessary stage for disease progression. To investigate the impact of low FeLV doses on young cats and to test the hypothesis that low dose exposure may lead to an unknown pathogenesis of infection without involvement of the bone marrow, 21 cats were infected oronasally with variable viral doses. Blood p27, proviral and viral loads were followed until week 20 post-infection. Tissue proviral loads were determined as well. The immune response was monitored by measuring FeLV whole virus and p45 antibodies; and feline oncornavirus-associated cell membrane antigen (FOCMA) assay. One cat showed regressive infection (transient antigenemia, persistent provirus-positivity, and seroconversion) with provirus only found in some organs at sacrifice. In 7 of the 20 remaining cats FOCMA assay positivity was the only sign of infection, while all other tests were negative. Overall, the results show that FeLV low dose exposure can result in seroconversion during a presumed abortive infection. Therefore, commonly used detection methods do not detect all FeLV-infected animals, possibly leading to an underestimation of the prevalence of infection. FeLV / pathogenesis / infection outcome / abortive infection / FOCMA assay
Output: Exposure of cats to low doses of FeLV: seroconversion as the sole parameter of infection
The overhunting of wildlife for food and commercial gain presents a major threat to biodiversity in tropical forests and poses health risks to humans from contact with wild animals. Using a recent survey of wildlife offered at wild meat markets in Malaysia as a basis, we review the literature to determine the potential zoonotic infection risks from hunting, butchering and consuming the species offered. We also determine which taxa potentially host the highest number of pathogens and discuss the significant disease risks from traded wildlife, considering how cultural practices influence zoonotic transmission. We identify 51 zoonotic pathogens (16 viruses, 19 bacteria and 16 parasites) potentially hosted by wildlife and describe the human health risks. The Suidae and the Cervidae families potentially host the highest number of pathogens. We conclude that there are substantial gaps in our knowledge of zoonotic pathogens and recommend performing microbial food safety risk assessments to assess the hazards of wild meat consumption. Overall, there may be considerable zoonotic risks to people involved in the hunting, butchering or consumption of wild meat in Southeast Asia, and these should be considered in public health strategies.
Output: A Review of Zoonotic Infection Risks Associated with the Wild Meat Trade in Malaysia
The baculovirus expression vector system (BEVS) is a versatile and powerful platform for protein expression in insect cells. With the ability to approach similar post-translational modifications as in mammalian cells, the BEVS offers a number of advantages including high levels of expression as well as an inherent safety during manufacture and of the final product. Many BEVS products include proteins and protein complexes that require expression from more than one gene. This review examines the expression strategies that have been used to this end and focuses on the distinguishing features between those that make use of single polycistronic baculovirus (co-expression) and those that use multiple monocistronic baculoviruses (co-infection). Three major areas in which researchers have been able to take advantage of co-expression/co-infection are addressed, including compound structure-function studies, insect cell functionality augmentation, and VLP production. The core of the review discusses the parameters of interest for co-infection and co-expression with time of infection (TOI) and multiplicity of infection (MOI) highlighted for the former and the choice of promoter for the latter. In addition, an overview of modeling approaches is presented, with a suggested trajectory for future exploration. The review concludes with an examination of the gaps that still remain in co-expression/co-infection knowledge and practice.
Output: Co-expression vs. co-infection using baculovirus expression vectors in insect cell culture: Benefits and drawbacks
Essential oils are complex mixtures isolated from aromatic plants which may possess antioxidant and anti-inflammatory activities of interest in thye food and cosmetic industries as well as in the human health field. In this work, a review was done on the most recent publications concerning their antioxidant and anti-inflammatory activities. At the same time a survey of the methods generally used for the evaluation of antioxidant activity and some of the mechanisms involved in the anti-inflammatory activities of essential oils are also reported.
Output: molecules Antioxidant and Anti-Inflammatory Activities of Essential Oils: A Short Review
Introduction. Posttraumatic stress disorder (PTSD) is accompanied by poor general psychological status (GPS). In the present study, we investigated the effects of a Chinese herbal formula on GPS in earthquake survivors with PTSD. Methods. A randomized, double-blind, placebo-controlled trial compared a Chinese herbal formula, Xiao-Tan-Jie-Yu-Fang (XTJYF), to placebo in 2008 Sichuan earthquake survivors with PTSD. Patients were randomized into XTJYF (n = 123) and placebo (n = 122) groups. Baselineto-end-point score changes in the three global indices of the Symptom Checklist-90-Revised (SCL-90-R) and rates of response in the SCL global severity index (GSI) were the primary endpoints. A subanalysis of the nine SCL factors and the sleep quality score were secondary endpoints. Results and Discussion. Compared to placebo, the XTJYF group was significantly improved in all three SCL global indices (P = 0.001∼0.028). More patients in the XTJYF group reported "much improved" than the placebo group (P = 0.001). The XTJYF group performed significantly better than control in five out of nine SCL factors (somatization, obsessivecompulsive behavior, depression, anxiety, and hostility (P = 0.001∼0.036)), and in sleep quality score (P < 0.001). XTJYF produced no serious adverse events. These findings suggest that XTJYF may be an effective and safe treatment option for improving GPS in patients with PTSD.
Output: A Chinese Herbal Formula to Improve General Psychological Status in Posttraumatic Stress Disorder: A Randomized Placebo-Controlled Trial on Sichuan Earthquake Survivors
An SEQIJR model of epidemic disease transmission which includes immunization and a varying population size is studied. The model includes immunization of susceptible people (S), quarantine (Q) of exposed people (E), isolation (J) of infectious people (I), a recovered population (R), and variation in population size due to natural births and deaths and deaths of infected people. It is shown analytically that the model has a disease-free equilibrium state which always exists and an endemic equilibrium state which exists if and only if the disease-free state is unstable. A simple formula is obtained for a generalized reproduction number R g where, for any given initial population, R g < 1 means that the initial population is locally asymptotically stable and R g > 1 means that the initial population is unstable. As special cases, simple formulas are given for the basic reproduction number R 0 , a disease-free reproduction number R d f , and an endemic reproduction number R en . Formulas are derived for the sensitivity indices for variations in model parameters of the disease-free reproduction number R d f and for the infected populations in the endemic equilibrium state. A simple formula in terms of the basic reproduction number R 0 is derived for the critical immunization level required to prevent the spread of disease in an initially disease-free population. Numerical simulations are carried out using the Matlab program for parameters corresponding to the outbreaks of severe acute respiratory syndrome (SARS) in Beijing, Hong Kong, Canada and Singapore in 2002 and 2003 . From the sensitivity analyses for these four regions, the parameters are identified that are the most important for preventing the spread of disease in a disease-free population or for reducing infection in an infected population. The results support the importance of isolating infectious individuals in an epidemic and in maintaining a critical level of immunity in a population to prevent a disease from occurring.
Output: Original Articles Generalized reproduction numbers, sensitivity analysis and critical immunity levels of an SEQIJR disease model with immunization and varying total population size-NC-ND license (http://creativecommons.org/licenses/by-nc- nd/4.0/)
within the receptor binding domain (RBD) of the MERS-CoV S protein. We used a complex consisting of the epitope peptide of the MERS-CoV S protein and CpG-DNA encapsulated in liposome complex to immunize mice, and produced the monoclonal antibodies 506-2G10G5 and 492-1G10E4E2. The western blotting data showed that both monoclonal antibodies detected the S protein and immunoprecipitated the native form of the S protein. Indirect immunofluorescence and confocal analysis suggested strong reactivity of the antibodies towards the S protein of MERS-CoV virus infected Vero cells. Furthermore, the 506-2G10G5 monoclonal antibody significantly reduced plaque formation in MERS-CoV infected Vero cells compared to normal mouse IgG and 492-1G10E4E2. Thus, we successfully produced a monoclonal antibody directed against the RBD domain of the S protein which could be used in the development of diagnostics and therapeutic applications in the future. [BMB Reports 2019; 52(6): 397-402] BMB Rep. 2019; 52(6): 397-402 www.bmbreports.org
Output: Generation and characterization of a monoclonal antibody against MERS-CoV targeting the spike protein using a synthetic peptide epitope-CpG-DNA-liposome complex
Bats are known to harbor multiple paramyxoviruses. Despite the creation of two new genera, Aquaparamyxovirus and Ferlavirus, to accommodate this increasing diversity, several recently isolated or characterized viruses remain unclassified beyond the subfamily level. In the present study, among 985 bats belonging to 6 species sampled in the Belinga caves of Gabon, RNA of an unclassified paramyxovirus (Belinga bat virus, BelPV) was discovered in 14 African sheathtailed bats (Coleura afra), one of which exhibited several hemorrhagic lesions at necropsy, and viral sequence was obtained in two animals. Phylogenetically, BelPV is related to J virus and Beilong virus (BeiPV), two other unclassified paramyxoviruses isolated from rodents. In the diseased BelPV-infected C. afra individual, high viral load was detected in the heart, and the lesions were consistent with those reported in wild rodents and mice experimentally infected by J virus. BelPV was not detected in other tested bat species sharing the same roosting sites and living in very close proximity with C. afra in the two caves sampled, suggesting that this virus may be host-specific for C. afra. The mode of transmission of this paramyxovirus in bat populations remains to be discovered.
Output: Identification of an Unclassified Paramyxovirus in Coleura afra: A Potential Case of Host Specificity
The Flavivirus genus comprises many viruses (including dengue, Zika, West Nile and yellow fever viruses) which constitute important public health concerns worldwide. For several of these pathogens, neither antivirals nor vaccines are currently available. In addition to this unmet medical need, flaviviruses are of particular interest since they constitute an excellent model for the study of spatiotemporal regulation of RNA metabolism. Indeed, with no DNA intermediate or nuclear step, the flaviviral life cycle entirely relies on the cytoplasmic fate of a single RNA species, namely the genomic viral RNA (vRNA) which contains all the genetic information necessary for optimal viral replication. From a single open reading frame, the vRNA encodes a polyprotein which is processed to generate the mature viral proteins. In addition to coding for the viral polyprotein, the vRNA serves as a template for RNA synthesis and is also selectively packaged into newly assembled viral particles. Notably, vRNA translation, replication and encapsidation must be tightly coordinated in time and space via a fine-tuned equilibrium as these processes cannot occur simultaneously and hence, are mutually exclusive. As such, these dynamic processes involve several vRNA secondary and tertiary structures as well as RNA modifications. Finally, the vRNA can be detected as a foreign molecule by cytosolic sensors which trigger upon activation antiviral signaling pathways and the production of antiviral factors such as interferons and interferonstimulated genes. However, to create an environment favorable to infection, flaviviruses have evolved mechanisms to dampen these antiviral processes, notably through the production of a specific vRNA degradation product termed subgenomic flavivirus RNA (sfRNA). In this review, we discuss the current understanding of the fates of flavivirus vRNA and how this is regulated at the molecular level to achieve an optimal replication within infected cells.
Output: The Multiples Fates of the Flavivirus RNA Genome During Pathogenesis
Coronavirus disease 2019 (COVID-2019) has been recognized as a global threat, and several studies are being conducted using various mathematical models to predict the probable evolution of this epidemic. These mathematical models based on various factors and analyses are subject to potential bias. Here, we propose a simple econometric model that could be useful to predict the spread of COVID-2019. We performed Auto Regressive Integrated Moving Average (ARIMA) model prediction on the Johns Hopkins epidemiological data to predict the epidemiological trend of the prevalence and incidence of COVID-2019. For further comparison or for future perspective, case definition and data collection have to be maintained in real time.
Output: Application of the ARIMA model on the COVID- 2019 epidemic dataset
An increasing body of evidence highlights the role of host genetic variation in driving susceptibility to severe disease following pathogen infection. In order to fully appreciate the importance of host genetics on infection susceptibility and resulting disease, genetically variable experimental model systems should be employed. These systems allow for the identification, characterization, and mechanistic dissection of genetic variants that cause differential disease responses. Herein we discuss application of the Collaborative Cross (CC) panel of recombinant inbred strains to study viral pathogenesis, focusing on practical considerations for experimental design, assessment and analysis of disease responses within the CC, as well as some of the resources developed for the CC. Although the focus of this chapter is on viral pathogenesis, many of the methods presented within are applicable to studies of other pathogens, as well as to case-control designs in genetically diverse populations.
Output: Chapter 28 The Collaborative Cross Resource for Systems Genetics Research of Infectious Diseases
We investigated the structure of the hydrophobic domain of the severe acute respiratory syndrome E protein in model lipid membranes by x-ray reflectivity and x-ray scattering. In particular, we used x-ray reflectivity to study the location of an iodine-labeled residue within the lipid bilayer. The label imposes spatial constraints on the protein topology. Experimental data taken as a function of protein/lipid ratio P/L and different swelling states support the hairpin conformation of severe acute respiratory syndrome E protein reported previously. Changes in the bilayer thickness and acyl-chain ordering are presented as a function of P/L, and discussed in view of different structural models.
Output: SARS Coronavirus E Protein in Phospholipid Bilayers: An X-Ray Study
Interferon-inducible transmembrane proteins 1, 2, and 3 (IFITM1, 2, and 3) are recently identified viral restriction factors that inhibit infection mediated by the influenza A virus (IAV) hemagglutinin (HA) protein. Here we show that IFITM proteins restricted infection mediated by the entry glycoproteins (GP 1,2 ) of Marburg and Ebola filoviruses (MARV, EBOV). Consistent with these observations, interferon-b specifically restricted filovirus and IAV entry processes. IFITM proteins also inhibited replication of infectious MARV and EBOV. We observed distinct patterns of IFITM-mediated restriction: compared with IAV, the entry processes of MARV and EBOV were less restricted by IFITM3, but more restricted by IFITM1. Moreover, murine Ifitm5 and 6 did not restrict IAV, but efficiently inhibited filovirus entry. We further demonstrate that replication of infectious SARS coronavirus (SARS-CoV) and entry mediated by the SARS-CoV spike (S) protein are restricted by IFITM proteins. The profile of IFITM-mediated restriction of SARS-CoV was more similar to that of filoviruses than to IAV. Trypsin treatment of receptor-associated SARS-CoV pseudovirions, which bypasses their dependence on lysosomal cathepsin L, also bypassed IFITM-mediated restriction. However, IFITM proteins did not reduce cellular cathepsin activity or limit access of virions to acidic intracellular compartments. Our data indicate that IFITM-mediated restriction is localized to a late stage in the endocytic pathway. They further show that IFITM proteins differentially restrict the entry of a broad range of enveloped viruses, and modulate cellular tropism independently of viral receptor expression. This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.
Output: Distinct Patterns of IFITM-Mediated Restriction of Filoviruses, SARS Coronavirus, and Influenza A Virus
There is currently a lack of pathologic data on the novel coronavirus (severe acute respiratory syndrome coronavirus 2) pneumonia, or coronavirus disease 2019 (COVID-19), from autopsy or biopsy. Two patients who recently underwent lung lobectomies for adenocarcinoma were retrospectively found to have had COVID-19 at the time of the operation. These two cases thus provide important first opportunities to study the pathology of COVID-19. Pathologic examinations revealed that apart from the tumors, the lungs of both patients exhibited edema, proteinaceous exudate, focal reactive hyperplasia of pneumocytes with patchy inflammatory cellular infiltration, and multinucleated giant cells. Hyaline membranes were not prominent. Because both patients did not exhibit symptoms of pneumonia at the time of operation, these changes likely represent an early phase of the lung pathology of COVID-19 pneumonia.
Output: Pulmonary Pathology of Early-Phase 2019 Novel Coronavirus (COVID-19) Pneumonia in Two Patients With Lung Cancer
Viruses have evolved elaborate means to regulate diverse cellular pathways in order to create a cellular environment that facilitates viral survival and reproduction. This includes enhancing viral macromolecular synthesis and assembly, as well as preventing antiviral responses, including intrinsic, innate, and adaptive immunity. There are numerous mechanisms by which viruses mediate their effects on the host cell, and this includes targeting various cellular post-translational modification systems, including sumoylation. The wide-ranging impact of sumoylation on cellular processes such as transcriptional regulation, apoptosis, stress response, and cell cycle control makes it an attractive target for viral dysregulation. To date, proteins from both RNA and DNA virus families have been shown to be modified by SUMO conjugation, and this modification appears critical for viral protein function. More interestingly, members of the several viral families have been shown to modulate sumoylation, including papillomaviruses, adenoviruses, herpesviruses, orthomyxoviruses, filoviruses, and picornaviruses. This chapter will focus on mechanisms by which sumoylation both impacts human viruses and is used by viruses to promote viral infection and disease. Keywords SUMO • Ubc9 • DNA viruses • RNA viruses Viral proteins were among the first defined substrates for sumoylation, beginning with the demonstration in 1999 that the human cytomegalovirus (HCMV) immediate-early 1 protein (IE1)) was SUMO modified (Muller and Dejean 1999).
Output: Viral Interplay with the Host Sumoylation System
Ubiquitin (Ub) and the ubiquitin-like modifier interferon stimulated gene 15 (ISG15) participate in the host defense of viral infections. Viruses, including the Severe Acute Respiratory Syndrome human coronavirus (SARS hCoV), have co-opted Ub/ISG15-conjugation pathways for their own advantage or have evolved effector proteins to counter pro-inflammatory properties of Ub/ISG15conjugated host proteins. Here, we compare substrate specificities of the papain-like protease (PLpro) from the recently emerged Middle Eastern Respiratory Syndrome (MERS) hCoV to the related protease from SARS, SARS PLpro. Through biochemical assays, we show that similar to SARS PLpro, MERS PLpro is both a deubiquitinating and a deISGylating enzyme. Further analysis of the intrinsic deubiquitinating enzyme (DUB) activity of these viral proteases revealed unique differences between the recognition and cleavage specificities of polyUb chains. First, MERS PLpro shows broad linkage specificity for the cleavage of polyUb chains, while SARS PLpro prefers to cleave Lys48-linked polyUb chains. Second, MERS PLpro cleaves polyUb chains in a "mono-distributive" manner (one Ub at a time), and SARS PLpro prefers to cleave K48-linked poly-Ub chains by sensing a di-Ub moiety as a minimal recognition element using a "di-distributive" cleavage mechanism. The di-distributive cleavage mechanism for SARS PLpro appears to be uncommon among USP-family DUBs, as related USP family members from humans do not display such a mechanism. We propose that these intrinsic enzymatic differences between SARS and MERS PLpro will help identify pro-inflammatory substrates of these viral DUBs and can guide in the design of therapeutics to combat infection by coronaviruses.
Output: SARS hCoV papain-like protease is a unique Lys48 linkage- specific di-distributive deubiquitinating enzyme HHS Public Access
Viral 2=,5=-phosphodiesterases (2=,5=-PDEs) help disparate RNA viruses evade the antiviral activity of interferon (IFN) by degrading 2=,5=-oligoadenylate (2-5A) activators of RNase L. A kinase anchoring proteins (AKAPs) bind the regulatory subunits of protein kinase A (PKA) to localize and organize cyclic AMP (cAMP) signaling during diverse physiological processes. Among more than 43 AKAP isoforms, AKAP7 appears to be unique in its homology to viral 2=,5=-PDEs. Here we show that mouse AKAP7 rapidly degrades 2-5A with kinetics similar to that of murine coronavirus (mouse hepatitis virus [MHV]) strain A59 ns2 and human rotavirus strain WA VP3 proteins. To determine whether AKAP7 could substitute for a viral 2=,5=-PDE, we inserted AKAP7 cDNA into an MHV genome with an inactivated ns2 gene. The AKAP7 PDE domain or N-terminally truncated AKAP7 (both lacking a nuclear localization motif), but not full-length AKAP7 or a mutant, AKAP7 H185R , PDE domain restored the infectivity of ns2 mutant MHV in bone marrow macrophages and in livers of infected mice. Interestingly, the AKAP7 PDE domain and N-terminally deleted AKAP7 were present in the cytoplasm (the site of MHV replication), whereas full-length AKAP7 was observed only in nuclei. We suggest the possibility that viral acquisition of the host AKAP7 PDE domain might have occurred during evolution, allowing diverse RNA viruses to antagonize the RNase L pathway. We also reported that the rotavirus VP3 C-terminal domain (VP3-CTD) cleaves 2-5A and that it may rescue ns2 mutant MHV. Here we report that a cellular protein, AKAP7, has an analogous 2=,5=-phosphodiesterase (2=,5=-PDE) domain that is able to restore the growth of chimeric MHV expressing inactive ns2. The proviral effect requires cytoplasmic localization of the AKAP7 PDE domain. We speculate that AKAP7 is the ancestral precursor of viral proteins, such as ns2 and VP3, that degrade 2-5A to evade the antiviral activity of RNase L. RH. 2014 . Murine AKAP7 has a 2=,5=-phosphodiesterase domain that can complement an inactive murine coronavirus ns2 gene. mBio 5(4):e01312-14.
Output: Murine AKAP7 Has a 2=,5=-Phosphodiesterase Domain That Can Complement an Inactive Murine Coronavirus ns2 Gene
In this article we review important established, newly emergent and potential viral diseases of cats, dogs and rabbits. Topics covered include virus epidemiology, disease pathogenesis, existing and prospective immunoprophylaxis against the viruses. For some feline viruses, notably the immunodeficiency virus, leukaemia virus and peritonitis virus, available vaccines are poorly efficacious but there are good prospects for this. A further challenge for the industry is likely to be due to viruses jumping species and the emergence of more virulent variants of established viruses resulting from mutations as has been the case for the canine parvovirus, coronaviruses and feline calicivirus.
Output: Review of companion animal viral diseases and immunoprophylaxis
Estimating key infectious disease parameters from the COVID-19 outbreak is quintessential for modelling studies and guiding intervention strategies. Whereas different estimates for the incubation period distribution and the serial interval distribution have been reported, estimates of the generation interval for COVID-19 have not been provided. Methods: We used outbreak data from clusters in Singapore and Tianjin, China to estimate the generation interval from symptom onset data while acknowledging uncertainty about the incubation period distribution and the underlying transmission network. From those estimates we obtained the proportions pre-symptomatic transmission and reproduction numbers. Results: The mean generation interval was 5.20 (95%CI 3.78-6.78) days for Singapore and 3.95 (95%CI 3.01-4.91) days for Tianjin, China when relying on a previously reported incubation period with mean 5.2 and SD 2.8 days. The proportion of pre-symptomatic transmission was 48% (95%CI 32-67%) for Singapore and 62% (95%CI 50-76%) for Tianjin, China. Estimates of the reproduction number based on the generation interval distribution were slightly higher than those based on the serial interval distribution. Conclusions: Estimating generation and serial interval distributions from outbreak 1 . CC-BY-NC-ND 4.0 International license It is made available under a author/funder, who has granted medRxiv a license to display the preprint in perpetuity. is the (which was not peer-reviewed) The copyright holder for this preprint .
Output: Estimating the generation interval for COVID-19 based on symptom onset data
h i g h l i g h t s • Symptoms, formulae, herbal drugs, and their relationships in the Treatise on Cold Damage Disorders are described and analyzed based on complex network. • Topological attributes analysis suggested some prescription laws that could be validated in clinical trials. • The transitions among diseases were explored by analyzing the strengths of the relationship between six channel subnets. Investigating the underlying principles of the Treatise on Cold Damage Disorder is meaningful and interesting. In this study, we investigated the symptoms, herbal formulae, herbal drugs, and their relationships in this treatise based on a multi-subnet composited complex network model (MCCN). Syndrome subnets were constructed for the symptoms and a formula subnet for herbal drugs. By subnet compounding using MCCN, a composited network was obtained that described the treatment relationships between syndromes and formulae. The results obtained by topological analysis suggested some prescription laws that could be validated in clinics. After subnet reduction using the MCCN, six channel (Tai-yang, Yang-ming, Shao-yang, Tai-yin, Shao-yin, and Jue-yin) subnets were obtained. By analyzing the strengths of the relationships among these six channel subnets, we found that the Tai-yang channel and Yang-ming channel were related most strongly with each other, and we found symptoms that implied pathogen movements and transformations among the six channels. This study could help therapists to obtain a deeper understanding of this ancient treatise.
Output: Physica A Complex network model of the Treatise on Cold Damage Disorders
Ebola virus outbreaks, such as the 2014 Makona epidemic in West Africa, are episodic and deadly. Filovirus antivirals are currently not clinically available. Our findings suggest interferon gamma, an FDA-approved drug, may serve as a novel and effective prophylactic or treatment option. Using mouse-adapted Ebola virus, we found that murine interferon gamma administered 24 hours before or after infection robustly protects lethally-challenged mice and reduces morbidity and serum viral titers. Furthermore, we demonstrated that interferon gamma profoundly inhibits Ebola virus infection of macrophages, an early cellular target of infection. As early as six hours following in vitro infection, Ebola virus RNA levels in interferon gamma-treated macrophages were lower than in infected, untreated cells. Addition of the protein synthesis inhibitor, cycloheximide, to interferon gamma-treated macrophages did not further reduce viral RNA levels, suggesting that interferon gamma blocks life cycle events that require protein synthesis such as virus replication. Microarray studies with interferon gamma-treated human macrophages identified more than 160 interferon-stimulated genes. Ectopic expression of a select group of these genes inhibited Ebola virus infection. These studies provide new potential avenues for antiviral targeting as these genes that have not previously appreciated to inhibit negative strand RNA viruses and specifically Ebola virus infection. As treatment of interferon gamma robustly protects mice from lethal Ebola virus infection, we propose that interferon gamma should be further evaluated for its efficacy as a prophylactic and/or therapeutic strategy against filoviruses. Use of this FDAapproved drug could rapidly be deployed during future outbreaks. Filovirus outbreaks occur sporadically, but with increasing frequency. With no current approved filovirus therapeutics, the 2014 Makona Ebola virus epidemic in Guinea, Sierra PLOS Pathogens |
Output: Interferon-γ Inhibits Ebola Virus Infection
Objective: To determine if immune phenotypes associated with immunosenescence predict risk of respiratory viral infection in elderly nursing home residents. Methods: Residents $65 years from 32 nursing homes in 4 Canadian cities were enrolled in Fall 2009, 2010 and 2011, and followed for one influenza season. Following influenza vaccination, peripheral blood mononuclear cells (PBMCs) were obtained and analysed by flow cytometry for T-regs, CD4+ and CD8+ T-cell subsets (CCR7+CD45RA+, CCR7-CD45RA+ and CD28-CD57+) and CMV-reactive CD4+ and CD8+ T-cells. Nasopharyngeal swabs were obtained and tested for viruses in symptomatic residents. A Cox proportional hazards model adjusted for age, sex and frailty, determined the relationship between immune phenotypes and time to viral infection. Results: 1072 residents were enrolled; median age 86 years and 72% female. 269 swabs were obtained, 87 were positive for virus: influenza (24%), RSV (14%), coronavirus (32%), rhinovirus (17%), human metapneumovirus (9%) and parainfluenza (5%). In multivariable analysis, high T-reg% (HR 0.41, 95% CI 0.20-0.81) and high CMV-reactive CD4+ T-cell% (HR 1.69, 95% CI 1.03-2.78) were predictive of respiratory viral infection. In elderly nursing home residents, high CMV-reactive CD4+ T-cells were associated with an increased risk and high T-regs were associated with a reduced risk of respiratory viral infection.
Output: Immune Biomarkers Predictive of Respiratory Viral Infection in Elderly Nursing Home Residents
The consumption of diet-based naturally bioactive metabolites is preferred to synthetic material in order to avert health-associated disorders. Among the plant-derived polyphenols, kaempferol (KMF) is considered as a valuable functional food ingredient with a broad range of therapeutic applications such as anti-cancer, antioxidant and anti-inflammatory uses. KMF acts on a range of intracellular as well as extracellular targets involved in the cell signaling pathways that in turn are known to regulate the hallmarks of cancer growth progressions like apoptosis, cell cycle, invasion or metastasis, angiogenesis and inflammation. Importantly, the understanding of mechanisms of action of KMF-mediated therapeutic effects may help the scientific community to design novel strategies for the treatment of dreadful diseases. The current review summarizes the various types of molecular targets of KMF in cancer cells as well as other health-associated disorders. In addition, this review also highlights the absorption, metabolism and epidemiological findings.
Output: Kaempferol -A dietary anticancer molecule with multiple mechanisms of action: Recent trends and advancements
Understanding the significance of human genetic diversity in modulating host susceptibility to opportunistic infections is an emerging challenge in the field of respiratory illnesses. While it is recognized that diverse bacterial strains account for differential disease manifestations, emerging data indicate that host genetic diversity is an important determinant factor that influences the severity of opportunistic infections. With particular regard to respiratory illnesses mediated by the gramnegative bacterium Pseudomonas aeruginosa, diverse genetic background is also emerging as a key contributor. Humangenome-wide association studies are a common approach for determining the inter-individual genetic variation associated with variability of the pulmonary infections. Historically, diverse murine inbred mouse strains and ex-vivo cellular models were considered complementary to human studies for establishing the contribution of genetic background to P. aeruginosa respiratory infections. More recently, the development of a new mouse model of infection, mirroring human airway diseases, combined with innovative murine resource populations, modelling human genetic variation, provides additional insights into the mechanisms of genetic susceptibility. In this review, we cover the recent state of the art of human and animal studies and we discuss future potential challenges in the field of P. aeruginosa respiratory infections. The Collaborative Cross, a community resource for the genetic analysis of complex traits.
Output: The impact of host genetic background in the Pseudomonas aeruginosa respiratory infections
House ßies, Musca domestica L. (Diptera: Muscidae), were examined for their ability to harbor and transmit Newcastle disease virus (family Paramyxoviridae, genus Avulavirus, NDV) by using a mesogenic NDV strain. Laboratory-reared ßies were experimentally exposed to NDV (Roakin strain) by allowing ßies to imbibe an inoculum consisting of chicken embryo-propagated virus. NDV was detected in dissected crops and intestinal tissues from exposed ßies for up to 96 and 24 h postexposure, respectively; no virus was detected in crops and intestines of sham-exposed ßies. The potential of the house ßy to directly transmit NDV to live chickens was examined by placing 14-d-old chickens in contact with NDV-exposed house ßies 2 h after ßies consumed NDV inoculum. NDVexposed house ßies contained Ϸ10 4 50% infectious doses (ID 50 ) per ßy, but no transmission of NDV was observed in chickens placed in contact with exposed ßies at densities as high as 25 ßies per bird. Subsequent doseÐresponse studies demonstrated that oral exposure, the most likely route for ßy-tochicken transmission, required an NDV (Roakin) dose Ն10 6 ID 50 . These results indicate that house ßies are capable of harboring NDV (Roakin) but that they are poor vectors of the virus because they carry an insufÞcient virus titer to cause infection.
Output: Experimental Evaluation of Musca domestica (Diptera: Muscidae) as a Vector of Newcastle Disease Virus
This investigation enrolled 570 healthy young males gathered from all over the country for military service at the Republic of Korea Air Force boot camp. It confirmed RSV IgG seroprevalence by utilizing the enzyme immunoassay method just prior to undergoing basic training. The mean age of this study was 20.25 ± 1.34 yr old. The results of their immunoassay seroprofiles showed that 561 men (98.4%) were positive, 2 (0.4%) were negative and 7 (1.2%) were equivocal belonging to the grey zone. It was confirmed that RSV is a common respiratory virus and RSV infection was encountered by almost all people before reaching adulthood in Korea. Nine basic trainees belonging to the RSV IgG negative and equivocal grey zone categories were prospectively observed for any particular vulnerability to respiratory infection during the training period of two months. However, these nine men completed their basic training without developing any specific respiratory illness.
Output: Seroprevalence of Respiratory Syncytial Virus IgG among Healthy Young Adults in Basic Training for the Republic of Korea Air Force
AlGaN/GaN high electron mobility transistors (HEMTs) were used to sense the binding between double stranded DNA (dsDNA) and the severe acute respiratory syndrome coronavirus (SARS-CoV) nucleocapsid protein (N protein). The sensing signals were the drain current change of the HEMTs induced by the protein-dsDNA binding. Binding-site models using surface coverage ratios were utilized to analyze the signals from the HEMT-based sensors to extract the dissociation constants and predict the number of binding sites. Two dissociation constants, K D1 = 0.0955 nM, K D2 = 51.23 nM, were obtained by fitting the experimental results into the two-binding-site model. The result shows that this technique is more competitive than isotope-labeling electrophoretic mobility shift assay (EMSA). We demonstrated that AlGaN/GaN HEMTs were highly potential in constructing a semiconductor-based-sensor binding assay to extract the dissociation constants of nucleotide-protein interaction.
Output: Investigation of C-terminal domain of SARS nucleocapsid protein-Duplex DNA interaction using transistors and binding-site models Biographies
Genetic and environmental factors will influence the growth of an RNA virus, but their relative contributions are challenging to resolve because standard culture methods mask how virus particles interact with individual host cells. Here, single particles of vesicular stomatitis virus, a prototype RNA virus, were used to infect individual BHK cells. Infected cells produced 50 to 8000 progeny virus particles, but these differences were lost upon subsequent culture, suggesting the diversity of yields reflected cell-to-cell differences rather than viral genetic variation. Cells infected at different phases of their cell cycle produced from 1400 (early S) to 8700 (G 2 M) infectious virus particles, coinciding with the middle-to-upper range of the observed distribution. Fluctuations in virus and cell compositions and noisy gene expression may also contribute to the broad distribution of virus yields. These findings take a step toward quantifying how environmental variation can impact the fitness distribution of an RNA virus.
Output: Growth of an RNA virus in single cells reveals a broad fitness distribution
One word can be used to best describe the theme of each day that has transpired since the onset of the COVID-19 pandemic: uncertainty. Urologic surgical residents around the nation are faced with the unknown when they walk through the doors of the hospital each day. While experience has taught us navigational strategies to handle these circumstances, the COVID-19 pandemic has undoubtedly brought new meaning to this concept. Priorities have quickly transitioned from closely following our previously developed academic curriculum and enhancing our surgical skills, to limiting physician-patient encounters and ensuring the safety and health of our team. Normalcy within our professional and personal lives is completely lost. Yet, as health care providers, we must and will forge on. We review the techniques and guidelines that our institution has implemented in order to allow us to do just that. We believe that our leadership, both at an enterprise and program level, has taken the necessary and early measures to prepare our residency cohort for the uncertain future and challenges posed by COVID-19. This plan emphasizes social and professional distancing, allows residents and faculty to stay current on academic topics, and provides reasonable opportunities for personal wellness, all while emphasizing safety and rationalization. Most importantly, however, we have continued to provide our patients with exceptional urologic care at 2 adult hospitals and 1 children's hospital in the Greater Akron, Ohio area. While we understand each residency program has a unique curriculum with a different number of residents that cover a range of different hospitals, we hope to provide insight into our personal experience. We believe that this method of organization allows a residency program to continue to grow professionally, socially, academically, and personally during the uncertainty that is COVID-19. This framework could serve as an immediate action plan for future pandemics and natural disasters, especially for residency programs that cover multiple hospitals and health care settings.
Output: Editorial Cleveland Clinic Akron General Urology Residency Program's COVID-19 Experience
In the present studies , we report the cloning and structural characterization of the HFGL2 gene and its functional role in human fulminant hepatitis. The HFGL2 gene is approximately 7 kb in length with 2 exons. The putative promoter contains cis element consensus sequences that strongly suggest the inducibility of its expression. From the nucleotide sequence of the human gene , a 439-amino acid long protein is predicted. The overall identity between the murine fgl2 and hfgl2 coded proteins is over 70%. About 225 amino acids at the carboxyl end of these molecules are almost 90% identical , and correspond to a well-conserved fibrinogen-related domain. Both HFGL2 and FGL2 encode a type II transmembrane protein with a predicted catalytic domain toward the amino terminus of the protein. Transient transfection of Chinese hamster ovary (CHO) cells with a fulllength cDNA of HFGL2 coding region resulted in high levels of prothrombinase activity. Livers from 8 patients transplanted for fulminant viral hepatitis were examined for extent of necrosis , inflammation, fibrin deposition , and HFGL2 induction. In situ hybridization showed positive staining of macrophages in areas of active hepatocellular necrosis. Fibrin stained positively in these areas and was confirmed by electron microscopy. These studies define a unique prothrombinase gene (HFGL2) and implicate its importance in the pathogenesis of fulminant viral hepatitis.
Output: Molecular and Functional Analysis of the Human Prothrombinase Gene (HFGL2) and Its Role in Viral Hepatitis
During the last decade, the application of both qualitative and quantitative nucleic acid detection techniques has had a major impact on diagnostics in clinical virology. Both signal and target amplification-based systems are currently used routinely in most if not all virology laboratories. However, commercial assays are only available for a very limited number of targets, and this has resulted in the development and introduction of assays developed in-house for most viral targets. With improved and automated nucleic acid sample isolation techniques, as well as real-time detection methods, a new generation of assays for most clinically important viruses is being developed. These technological improvements also make it possible to generate results with a very short turnaround time. As an example of a more individual-patient disease-management concept, we have introduced in our clinical setting the quantitative detection of Epstein-Barr virus (EBV) in T-cell-depleted allogeneic stem cell transplant patients. This has enabled us to develop models for pre-emptive anti-B-cell immunotherapy for EBV reactivation, and for reducing not only the incidence of EBV lymphoproliferative disease (EBV-LPD), but the virus-related mortality. It is now also feasible to introduce molecular testing for those viruses that can easily be detected using classical virological methods, such as culture techniques or antigen detection. Prospective studies are needed to evaluate the clinical importance of the additional positive samples detected. It should, however, be clear that a complete exchange of technology is unlikely to occur, and that complementary methods should stay operational, making possible the discovery of new viruses. Furthermore, the ability to characterise viruses more easily by sequencing opens new possibilities for epidemiological studies. There is also an urgent need, with regard to molecular diagnostic methods, for the introduction and use of standardised materials and participation in international quality control programmes. Finally, with the introduction of a universal internal control throughout the whole procedure, the accuracy of the results generated is warranted.
Output: REVIEW Molecular and diagnostic clinical virology in real time