niryuu/sni-each-converted huggingface dataset:
One hundred avian Pasteurella multocida isolates recovered from cases of fowl cholera and related infections in England and Wales over a 13-year period were characterised by capsular PCR typing and analysis of outer membrane protein (OMP) profiles. Sixty-eight percent of the strains were of capsular type A, 14% were type F, 5% were type D, 4% were type B and 9% were untypable. Nineteen distinct OMP profiles (OMP-types) were identified based mainly on molecular mass heterogeneity of the heat-modifiable (OmpA) and porin (OmpH) proteins. Fifty-six percent of the isolates were represented by 15 OMP-types, whereas 44% of the isolates were associated with four OMP-types. The extensive molecular mass heterogeneity of the OmpA and OmpH proteins supports previous findings that avian P. multocida strains are very diverse. Furthermore, the isolates studied were associated with different clinical symptoms and were recovered from a wide range of lesions and tissues. The high degree of strain diversity together with the wide variety of clinical symptoms suggest that certain avian strains of P. multocida are opportunistic pathogens of relatively low virulence. Strains of capsular types B, D and F, as well as the untypable isolates, were associated exclusively with specific OMP-types and represent distinct and widely disseminated clonal groups. These observations support the view that avian strains of P. multocida have a clonal population structure. Based on previous studies, the molecular mass heterogeneity of the OmpA and OmpH proteins might provide a selective advantage to P. multocida by generating antigenic variation. #
Output: Diversity of avian Pasteurella multocida strains based on capsular PCR typing and variation of the OmpA and OmpH outer membrane proteins 5 ( 0 2 ) 0 0 3 0 0 -0
emetine, and homoharringtonine inhibit SARS-CoV-2 replication in vitro, Antiviral Research, https://doi. ABSTRACT An escalating pandemic by the novel SARS-CoV-2 virus is impacting global health and effective therapeutic options are urgently needed. We evaluated the in vitro antiviral effect of compounds that were previously reported to inhibit coronavirus replication and compounds that are currently under evaluation in clinical trials for SARS-CoV-2 patients. We report the antiviral effect of remdesivir, lopinavir, homorringtonine, and emetine against SARS-CoV-2 virus in Vero E6 cells with the estimated 50% effective concentration at 23.15 µM, 26.63 µM, 2.55 µM and 0.46 µM, respectively. Ribavirin or favipiravir that are currently evaluated under clinical trials showed no inhibition at 100 µM. Synergy between remdesivir and emetine was observed, and remdesivir at 6.25 µM in combination with emetine at 0.195 µM may achieve 64.9% inhibition in viral yield. Combinational therapy may help to reduce the effective concentration of compounds below the therapeutic plasma concentrations and provide better clinical benefits.
Output: Journal Pre-proof Remdesivir, lopinavir, emetine, and homoharringtonine inhibit SARS-CoV-2 replication in vitro SHORT COMMUNICATION Remdesivir, lopinavir, emetine, and homoharringtonine inhibit SARS-CoV-2 replication in vitro
In the last few decades the Chikungunya virus (CHIKV) has evolved from a geographically isolated pathogen to a virus that is widespread in many parts of Africa, Asia and recently also in Central-and South-America. Although CHIKV infections are rarely fatal, the disease can evolve into a chronic stage, which is characterized by persisting polyarthralgia and joint stiffness. This chronic CHIKV infection can severely incapacitate patients for weeks up to several years after the initial infection. Despite the burden of CHIKV infections, no vaccine or antivirals are available yet. The current therapy is therefore only symptomatic and consists of the administration of analgesics, antipyretics, and anti-infl ammatory agents. Recently several molecules with various viral or host targets have been identifi ed as CHIKV inhibitors. In this chapter, we summarize the current status of the development of antiviral strategies against CHIKV infections.
Output: Antiviral Strategies Against Chikungunya Virus
At the end of December 2019, a novel coronavirus, 2019-nCoV, caused an outbreak of pneumonia spreading from Wuhan, Hubei province, to the whole country of China, which has posed great threats to public health and attracted enormous attention around the world. To date, there are no clinically approved vaccines or antiviral drugs available for these human coronavirus infections. Intensive research on the novel emerging human infectious coronaviruses is urgently needed to elucidate their route of transmission and pathogenic mechanisms, and to identify potential drug targets, which would promote the development of effective preventive and therapeutic countermeasures. Herein, we describe the epidemic and etiological characteristics of 2019-nCoV, discuss its essential biological features, including tropism and receptor usage, summarize approaches for disease prevention and treatment, and speculate on the transmission route of 2019-nCoV.
Output: The epidemic of 2019-novel-coronavirus (2019-nCoV) pneumonia and insights for emerging infectious diseases in the future
OBJECTIVE: Recent experiences in the United States with unprecedented terrorist attacks (9/11) and a devastating natural disaster (Hurricane Katrina) have demonstrated that the medical care of mass casualties during such disasters poses ethical problems not normally experienced in civilian health care. It is important to 1) identify the unique ethical challenges facing physicians who feel an obligation to care for victims of such disasters and 2) develop a national consensus on ethical guidelines as a resource for ethical decision making in medical disaster relief. STUDY DESIGN: A survey of pertinent literature was performed to assess experience and opinions on the condition of medical care in terrorist attacks and natural disasters, the ethical challenges of disaster medical care, and the professional responsibilities and responsiveness in disasters. CONCLUSIONS: It is necessary to develop a national consensus on the ethical guidelines for physicians who care for patients, victims, and casualties of disasters, and to formulate a virtuebased, yet practical, ethical approach to medical care under such extreme conditions. An educational curriculum for medical students, residents, and practicing physicians is required to best prepare all physicians who might be called upon, in the future, to triage patients, allocate resources, and make difficult decisions about treatment priorities and comfort care. It is not appropriate to address these questions at the time of the disaster, but rather in advance, as part of the ethics education of the medical profession. Important issues for resolution include inpatient and casualty triage and prioritization, medical liability, altered standards of care, justice and equity, informed consent and patient autonomy, expanding scope of practice in disaster medicine, and the moral and ethical responsibilities of physicians to care for disaster victims.
Output: Making difficult ethical decisions in patient care during natural disasters and other mass casualty events
Viruses are replication competent genomes which are relatively gene-poor. Even the largest viruses (i.e. Herpesviruses) encode only slightly .200 open reading frames (ORFs). However, because viruses replicate obligatorily inside cells, and considering that evolution may be driven by a principle of economy of scale, it is reasonable to surmise that many viruses have evolved the ability to co-opt cell-encoded proteins to provide needed surrogate functions. An in silico survey of viral sequence databases reveals that most positive-strand and double-stranded RNA viruses have ORFs for RNA helicases. On the other hand, the genomes of retroviruses are devoid of virally-encoded helicase. Here, we review in brief the notion that the human immunodeficiency virus (HIV-1) has adopted the ability to use one or more cellular RNA helicases for its replicative life cycle.
Output: Role of RNA helicases in HIV-1 replication
Coronaviruses are of major importance for both animal and human health. With the emergence of novel coronaviruses such as SARS and MERS, the need for fast genome characterisation is ever so important. Further, in order to understand the influence of quasispecies of these viruses in relation to biology, techniques for deep-sequence and full-length viral genome analysis are needed. In the present study, we compared the efficiency of two sequence-independent approaches [sequence-independent single primer amplification (SISPA) and single primer isothermal amplification (SPIA, represented by the Ovation kit)] coupled with highthroughput sequencing to generate the full-length genome of bovine coronavirus (BCoV) from a nasal swab. Both methods achieved high genome coverage (100% for SPIA and 99% for SISPA), however, there was a clear difference in the percentage of reads that mapped to BCoV. While approximately 45% of the Ovation reads mapped to BCoV (sequence depth of 169-284 944), only 0.07% of the SISPA reads (sequence depth of 0-249) mapped to the reference genome. Although BCoV was the focus of the study we also identified a bovine rhinitis B virus (BRBV) in the data sets. The trend for this virus was similar to that observed for BCoV regarding Ovation vs. SISPA, but with fewer sequences mapping to BRBV due to a lower amount of this virus. In summary, the SPIA approach used in this study produced coverage of the entire BCoV (high copy number) and BRBV (low copy number) and a high sequence/ genome depth compared to SISPA. Although this is a limited study, the results indicate that the Ovation method could be a preferred approach for full genome sequencing if a low copy number of viral RNA is expected and if high sequence depth is desired.
Output: Single primer isothermal amplification (SPIA) combined with next generation sequencing provides complete bovine coronavirus genome coverage and higher sequence depth compared to sequence-independent single primer amplification (SISPA)
Under acute perturbations from the outside, cells can trigger self-defensive mechanisms to fight against genome stress. To investigate the cellular response to continuous ion radiation (IR), a dynamic model for p53 stress response networks at the cellular level is proposed. The model can successfully be used to simulate the dynamic processes of double-strand breaks (DSBs) generation and their repair, switch-like ataxia telangiectasia mutated (ATM) activation, oscillations occurring in the p53-MDM2 feedback loop, as well as toxins elimination triggered by p53 stress response networks. Especially, the model can predict the plausible outcomes of cellular response under different IR dose regimes.
Output: Dynamic modeling of cellular response to DNA damage based on p53 stress response networks
ThermoBioStar's and Biota's £u optical immunoassay (FLU OIA) is a rapid test designed to diagnose in£uenza A and B infection using a variety of specimen types. The assay uses highly sensitive thin-¢lm detection methods, coupled with speci¢c monoclonal antibodies to the nucleoprotein. The test is simple to perform, requires no instrumentation and is intended to provide a result within 15 min of test initiation in the`point-of-care' environment. In initial clinical studies, the assay was demonstrated to be equivalent to culture in identifying infected individuals. Subsequent independent studies using a variety of sample types have demonstrated sensitivity ranging from 48 to 100% and speci¢cities ranging from 93 to 97%. In addition to detecting human strains, this assay has been demonstrated to be capable of detecting a variety of avian and non-human mammalian in£uenza viruses. The FLU OIA test has been used in large-scale surveillance schemes intended to provide rapid epidemiological data during normal in£uenza seasons and has demonstrated the potential for ful¢lling a similar role for multispecies surveillance in, for example, conditions that o¡er challenges for conventional virus isolation methods. Conceivably, such use should facilitate the timely recognition of in£uenza outbreaks and prioritization of positive specimens for more conventional, laboratory characterization, leading to improved interpandemic surveillance and rapid reaction in the face of the next pandemic.
Output: A¯u optical immunoassay (ThermoBioStar's FLU OIA): a diagnostic tool for improved in¯uenza management
Viruses are dependent on the cellular translation machinery for protein synthesis. Part of the innate immune response to infection is activation of the stress kinase PKR which phosphorylates the alpha subunit of the initiation factor eIF2. This results in inhibition of translation and is intended to block virus replication. A downstream effect of translational shutoff involves the formation of cytoplasmic granules, termed stress granules (SGs), that contain mRNAs, initiation factors, ribosomal subunits, and other mRNA regulatory proteins. SGs hold mRNAs in a translationally inactive state until cells recover from stress. Recent studies have begun to elucidate the impact of SGs on virus replication. Not surprisingly, viruses from diverse families have been found to modulate SG formation in infected cells by associating with important SG effecter proteins. This review describes the current knowledge on SGs and their interaction with and impact on virus replication. The most highly regulated stage of protein synthesis occurs at the initiation step. The translation initation factor eIF2 plays a crucial role in this process. In non-stressed cells, eIF2 complexed with GDP associates with eIF2B, a nucleotide exchange factor, which exchanges GDP for GTP. This exchange allows the eIF2:GTP complex to associate with initiator methionine tRNA to form ternary complex (eIF2:GTP:tRNA Met ). Ternary complex brings the initiating methionine to the 43S ribosome pre-initiation complex. The 43S complex contains the 40S ribosome and a variety of additional initiation factors that play important roles in translation. The 43S complex then forms the 48S ribosomal complex by binding mRNA, which has itself been activated for translation via association with additional initiation factors. The 60S ribosomal subunit is then recruited, at which point GTP is hydrolyzed to GDP and eIF2:GDP is released from the ribosomal complex to again associate with eIF2B and be recharged with GTP to start the process anew [reviewed in [1, 2] ]. Following cellular stress, the alpha subunit of eIF2 is phosphorylated by one of four stress activated kinases; GCN, which is activated during nutrient starvation, PERK, which is activated following ER stress, HRI, which is activated following oxidative stress and heme deficiency, and PKR, which is activated following virus infection [reviewed in [3] ].
Output: Stress Granules and Virus Replication HHS Public Access
Highly pathogenic avian H5N1 influenza viruses that are currently circulating in southeast Asia may acquire the potential to cause the next influenza pandemic. A number of alternate approaches are being pursued to generate cross-protective, dose-sparing, safe, and effective vaccines, as traditional vaccine approaches, i.e., embryonated egg-grown, are not immunogenic. We developed a replicationincompetent adenoviral vector-based, adjuvant-and egg-independent pandemic influenza vaccine strategy as a potential alternative to conventional egg-derived vaccines.
Output: New Pre-pandemic Influenza Vaccines: An Egg-and Adjuvant- independent Human Adenoviral Vector Strategy Induces Long- lasting Protective Immune Responses in Mice
Background: In Sweden, knowledge about the role of enteropathogenic Escherichia coli in neonatal calf diarrhea and the occurrence of antimicrobial resistance in E. coli from young calves is largely unknown. This has therapeutic concern and such knowledge is also required for prudent use of antimicrobials. Methods: In a case control study Esherichia coli isolated from faecal samples from dairy calves were phenotyped by biochemical fingerprinting and analyzed for virulence genes by PCR. Antimicrobial susceptibility was tested by determination of minimum inhibitory concentration (MIC). Farm management data were collected and Fisher's exact test and univariable and multivariable logistic regression analysis were performed. Of 95 E. coli tested for antimicrobial susceptibility 61% were resistant to one or more substances and 28% were multi-resistant. The virulence gene F5 (K99) was not found in any isolate. In total, 21 out of 40 of the investigated virulence genes were not detected or rarely detected. The virulence genes espP, irp, and fyuA were more common in resistant E. coli than in fully susceptible isolates (P < 0.05). The virulence gene terZ was associated with calf diarrhea (P ≤ 0.01). The participating 85 herds had a median herd size of 80 lactating cows. Herds with calf diarrhea problems were larger (> 55 cows; P < 0.001), had higher calf mortality (P ≤ 0.01) and calf group feeders were more in use (P > 0.05), compared to herds without calf diarrhea problems. There was no association between calf diarrhea and diversity of enteric E. coli. Conclusions: Antimicrobial resistance was common in E. coli from pre-weaned dairy calves, occurring particularly in calves from herds experiencing calf diarrhea problems. The results indicate that more factors than use of antimicrobials influence the epidemiology of resistant E. coli. Enteropathogenic E. coli seems to be an uncommon cause of neonatal calf diarrhea in Swedish dairy herds. In practice, calf diarrhea should be regarded holistically in a context of infectious agents, calf immunity, management practices etc. We therefore advice against routine antimicrobial treatment and recommend that bacteriological cultures, followed by testing for antimicrobial susceptibility and for virulence factors, are used to guide decisions on such treatment.
Output: Antimicrobial resistance and virulence factors in Escherichia coli from Swedish dairy calves
Currently, a number of structurally and functionally different temperature sensitive elements such as RNA thermometers which control a variety of biological processes in bacteria, including virulence, are known. Based on computer and thermodynamic analysis of completely sequenced genomes of 25 Salmonella enterica isolates, the algorithm and criteria for the search of potential RNA thermometers were developed. It will make it possible to carry out the search for potential riboswitches in the genome of other socially impor tant pathogens. For S. enterica, apart from the known 4U RNA thermometer, four hairpin loop structures were identified which may probably act as additional RNA thermometers. They satisfy the necessary and suf ficient conditions for formation of RNA thermometers and are highly conservative uncanonical structures, since these highly conservative structures were found in the genome of all 25 isolates of S. enterica. The hair pins forming a cruciform structure in the supercoiled pUC8 DNA were visualized by atomic force micros copy.
Output: Search for the New Potential RNA Thermometers in the Genome of Salmonella enterica EXPERIMENTAL ARTICLES
study, we present the results of comprehensive bioinformatics analyses of the abundance and roles of intrinsic disorder in 3,411 ribosomal proteins from 32 species. We show that many ribosomal proteins are intrinsically disordered or hybrid proteins that contain ordered and disordered domains. Predicted globular domains of many ribosomal proteins contain noticeable regions of intrinsic disorder. We also show that disorder in ribosomal proteins has different characteristics compared to other proteins that interact with RNa and DNa including overall abundance, evolutionary conservation, and involvement in protein-protein interactions. Furthermore, intrinsic disorder is not only abundant in the ribosomal proteins, but we demonstrate that it is absolutely necessary for their various functions. Abstract Intrinsic disorder (i.e., lack of a unique 3-D structure) is a common phenomenon, and many biologically active proteins are disordered as a whole, or contain long disordered regions. these intrinsically disordered proteins/regions constitute a significant part of all proteomes, and their functional repertoire is complementary to functions of ordered proteins. In fact, intrinsic disorder represents an important driving force for many specific functions. an illustrative example of such disordercentric functional class is RNa-binding proteins. In this Z. Peng and C. J. Oldfield contributed equally to this study. Electronic supplementary material the online version of this article (
Output: A creature with a hundred waggly tails: intrinsically disordered proteins in the ribosome
Polyomaviruses are naked viruses with an icosahedral capsid that surrounds a circular double-stranded DNA molecule of about 5000 base-pairs. Their genome encodes at least five proteins: large and small tumor antigens and the capsid proteins VP1, VP2 and VP3. The tumor antigens are expressed during early stages of the viral life cycle and are implicated in the regulation of viral transcription and DNA replication, while the capsid proteins are produced later during infection. Members of the Polyomaviridae family have been isolated in birds (Avipolyomavirus) and mammals (Orthopolyomavirus and Wukipolyomavirus). Some mammalian polyomaviruses encode an additional protein, referred to as agnoprotein, which is a relatively small polypeptide that exerts multiple functions. This review discusses the structure, post-translational modifications, and functions of agnoprotein, and speculates why not all polyomaviruses express this protein.
Output: Agnoprotein of mammalian polyomaviruses
Lymphadenopathy refers to any disease process involving lymph nodes that are abnormal in size and consistency. Lymphadenitis specifically refers to lymphadenopathies that are caused by inflammatory processes. Cervical lymphadenopathy is a common problem in the pediatric age group and is largely inflammatory and infectious in etiology. Although most patients are treated successfully by their primary care physician, surgical consultation is frequently required for patients who fail to respond to initial therapy or for those in whom there is an index of suspicion for a neoplastic process. This article addresses current approaches to the diagnosis and management of cervical lymphadenitis in children.
Output: Acute, subacute, and chronic cervical lymphadenitis in children
Coronaviruses have a wide host range and can cause a variety of diseases with varying severity in different animals. Several enteric coronaviruses have been identified that are associated with diarrhea in swine and that have caused substantial economic losses. In this study, a newly emerged porcine enteric alphacoronavirus (PEAV), PEAV-GD-CH/2017, was identified from suckling piglets with diarrhea in southern China, and a fulllength genome sequence of PEAV was obtained for systematic analysis. The novel PEAV sequence was most identical to that of bat-HKU2, and the differences between them were comprehensively compared, especially the uniform features of the S protein, which was shown to have a close relationship with betacoronaviruses and to perhaps represent unrecognized betacoronaviruses. In addition, Bayesian analysis was conducted to address the origin of PEAV, and the divergence time between PEAV and bat-HKU2 was estimated at 1926, which indicates that PEAV is not newly emerged and may have circulated in swine herds for several decades since the interspecies transmission of this coronavirus from bat to swine. The evolutionary rate of coronaviruses was estimated to be 1.93 × 10 −4 substitutions per site per year for the RdRp gene in our analysis. For the origin of PEAV, we suspect that it is the result of the interspecies transmission of bat-HKU2 from bat to swine. Our results provide valuable information about the uniform features, origin and evolution of the novel PEAV, which will facilitate further investigations of this newly emerged pathogen.
Output: Newly emerged porcine enteric alphacoronavirus in southern China: Identification, origin and evolutionary history analysis
Mouse models are important tools both for studying the pathogenesis of infectious diseases and for the preclinical evaluation of vaccines and therapies against a wide variety of human pathogens. The use of genetically defined inbred mouse strains, humanized mice, and gene knockout mice has allowed the research community to explore how pathogens cause disease, define the role of specific host genes in either controlling or promoting disease, and identify potential targets for the prevention or treatment of a wide range of infectious agents. This review discusses several of the most commonly used mouse model systems, as well as new resources such as the Collaborative Cross as models for studying infectious diseases. (Clin Ther. 2019;41:1912e1922) 
Output: Mouse Models as Resources for Studying Infectious Diseases
The predisposition of cancer patients to infectious diseases which contribute to the gravity of their prognosis is well documented. The current success in therapy of both malignancies and infections is unprecedented. However, the overall co-morbidity of these conditions is still a major problem in management of these patients. Paradoxically, to some degree the problem of containing infectious complications is directly associated with the vigor of the anti-cancer therapeutic regimens. The objective of this chapter is to provide an up to date overview of our understanding of the infectious complications in cancer patients based on the type of infection and immune responses.
Output: Infectious Diseases in Cancer Patients: An Overview
Bamboo mosaic virus (BaMV) has a positive-sense single-stranded RNA genome with a 5′ cap and a 3′ poly (A) tail. To characterize polyadenylation activity in the BaMV replicase complex, we performed the in vitro polyadenylation with various BaMV templates. We conducted a polyadenylation activity assay for BaMV RNA by using a partially purified BaMV replicase complex. The results showed that approximately 200 adenylates at the 3′ end of the RNA were generated on the endogenous RNA templates. Specific fractions derived from uninfected Nicotiana benthamiana plants enhanced the polyadenylation activity, implying that host factors are involved in polyadenylation. Furthermore, polyadenylation can be detected in newly synthesized plus-strand RNA in vitro when using the exogenous BaMV minus-strand minigenome. For polyadenylation on the exogenous plus-strand minigenome, the 3′ end requires at least 4A to reach 22% polyadenylation activity. The results indicate that the BaMV replicase complex recognizes the 3′ end of BaMV for polyadenylation.
Output: Characterization of the polyadenylation activity in a replicase complex from Bamboo mosaic virus-infected Nicotiana benthamiana plants
Background-While screening programs have reduced the risk of infectious disease transmission by donors in human and veterinary blood banking, bacterial contamination of blood products has emerged as a major complication in human medicine. Objectives-To describe a Pseudomonas fluorescens (Pf)-contaminated feline packed RBC (pRBC) unit and experimentally investigate Pf-contaminated canine pRBCs. Methods-Canine pRBCs were inoculated with Pf-rich pRBCs from the sentinel feline unit and stored at 4°C or 20°C for 72 hours. Aliquots from the pRBCs were serially evaluated by microscopy, culture, and a eubacterial 16S rRNA real-time PCR assay. Pf-contaminated feline unit turned black after 22 days of storage and was removed from the blood bank; a source was not found, and no other contaminated units were identified. Canine pRBCs spiked with 5 or 25 μL of the sentinel unit became culture-and/or 16S PCRpositive at ≥8 hours at 20°C and 48 hours at 4°C and developed a color change at ≥24 hours. Sensitivity studies indicated that without incubation, inoculation of ≥100 μL Pf-rich pRBCs was necessary for a positive 16S PCR test result. Conclusions-P. fluorescens grows in stored pRBCs slowly at 4°C and rapidly at 20°C. Screening of blood products for color change, estimating bacterial concentration with microscopy, and 16S PCR testing are simple and fast ways to detect bacteria in stored blood. Aseptic collection, temperature-controlled storage, and regular visual monitoring of stored units is recommended. Discolored units should not be transfused, but examined for bacterial contamination or other blood product quality problems.
Output: Pseudomonas fluorescens contamination of a feline packed red blood cell unit and studies of canine units
We utilized one-step multiplex reverse transcription-PCR (RT-PCR) and Luminex xMAP technology to develop a respiratory multiplex liquid-chip assay (rMLA) for China, Middle East Respiratory Syndrome coronavirus (MERS-CoV). Performance of rMLA was evaluated by comparing with real-time RT-PCR. Detection data from clinical specimens showed that the rMLA had diagnostic sensitivities of 97.10% for FluA, 94.59% for FluB, 98.68% for PIV-3, 94.87% for RSV and 95.92% for MPV (No Data for MERS-CoV due to the lack of positive specimens). Data of analytical sensitivities showed that the detection limits of the rMLA assay were 5-25 viral RNA copies per μl for FluA, FluB, PIV-3 and MERS-CoV, approximate to the real-time RT-PCR assay; while the values were 8 and 22copies/μl for MPV and RSV, lower than the real-time RT-PCR(78 and 114 copies/μl respectively). The results indicated that the rMLA is a sensitive, specific detection tool and comparable to real-time RT-PCR, especially suitable for high-throughput detection of respiratory specimens.
Output: A multiplex liquid-chip assay based on Luminex xMAP technology for simultaneous detection of six common respiratory viruses
Griffithsin (GRFT) is a broad-spectrum antiviral protein against several glycosylated viruses. In our previous publication, we have shown that GRFT exerted antiviral activity against Japanese encephalitis virus (JEV) infection. Herein, we further elucidated the mechanism by which GRFT inhibits JEV infection in BHK-21 cells. In vitro experiments using Pull-down assay and Co-immunoprecipitation (CO-IP) assay showed that GRFT binds to the JEV glycosylated viral proteins, specifically the enveloped (E) and premature (prM) glycoproteins. The binding of GRFT to the JEV was competitively inhibited by increasing concentrations of mannose; in turns abolished anti-JEV activity of GRFT. We suggested that, the binding of GRFT to the glycosylated viral proteins may contribute to its anti-JEV activity. Collectively, our data indicated a possible mechanism by which GRFT exerted its anti-JEV activity. This observation suggests GRFT's potentials in the development of therapeutics against JEV or other flavivirus infection.
Output: Griffithsin binds to the glycosylated proteins (E and prM) of Japanese encephalitis virus and inhibit its infection
Influenza viruses with multiple subtypes have highly virulent in humans, of which influenza hemagglutinin (HA) is the major viral surface antigen. Simultaneous and automated detection of multiple influenza HA are of great importance for early-stage diagnosis and operator protection. Herein, a magnetism and size mediated microfluidic platform was developed for point-of-care detection of multiple influenza HA. With multiplex microvalves and computer program control, the detection process showed high automation which had a great potential for avoiding the high-risk virus exposure to the operator. Taking advantage of magnetism and size mediated multiple physical fields, multiple influenza HA could be simultaneous separation and detection depended on different-size magnetic beads. Using high-luminance quantum dots as reporter, this assay achieved high sensitivity with a detection limit of 3.4 ng/mL for H7N9 HA and 4.5 ng/mL for H9N2 HA, and showed excellent specificity, anti-interference ability and good reproducibility. These results indicate that this method may propose new avenues for early detection of multiple influenza subtypes.
Output: Simultaneous and automated detection of influenza A virus hemagglutinin H7 and H9 based on magnetism and size mediated microfluidic chip
Dysregulation of the ubiquitin-proteasome system (UPS) has been implicated in a wide range of pathologies including cancer, neurodegeneration, and viral infection. Inhibiting the proteasome has been shown to be an effective therapeutic strategy in humans; yet toxicity with this target remains high. Deubiquitinating enzymes (DUBs) represent an alternative target in the UPS with low predicted toxicity. Currently, there are no DUB inhibitors that have entered the clinic. To address this situation, Progenra has developed a novel assay to measure the proteolytic cleavage of ubiquitin or UBL (ubiquitin like protein) conjugates such as SUMO, NEDD8 or ISG15 by isopeptidases. Here we will discuss current platforms for detecting DUB inhibitors and underline the advantages and disadvantages of the approaches.
Output: Strategies for the Identification of novel inhibitors of deubiquitinating enzymes
Fecal virus shedding, seroconversion and histopathology were evaluated in 3-7-year-old gnotobiotic calves orally inoculated with porcine deltacoronavirus (PDCoV) (9.0-9.6 log 10 genomic equivalents [GE] of OH-FD22-P5; n=4) or porcine epidemic diarrhea virus (PEDV) (10.2-12.5 log 10 GE of PC21A; n=3). In PDCoV-inoculated calves, an acute but persisting fecal viral RNA shedding and PDCoV-specific serum IgG antibody responses were observed, but without lesions or clinical disease. However, no fecal shedding, seroconversion, histological lesions, and clinical disease were detected in PEDV-inoculated calves. Our data indicate that calves are susceptible to infection by the newly emerged PDCoV, but not by the swine coronavirus, PEDV.
Output: Calves are susceptible to infection with the newly emerged porcine deltacoronavirus, but not with the swine enteric alphacoronavirus, porcine epidemic diarrhea virus
Biomedical research in human beings is largely restricted to in vitro studies that lack complexity of a living organism. To overcome this limitation, humanized mouse models are developed based on immunodeficient characteristics of severe combined immunodeficiency (SCID) or recombination activating gene (Rag) null mice, which can accept xenografts. Peripheral constitution of human immunity in SCID or Rag null mice has been achieved by transplantation of mature human immune cells, foetal human thymus, bone marrow, liver tissues, lymph nodes or a combination of these, although efficiency needs to be improved. These mouse models with constituted human immunity (defined as humanized mice in the present text) have been widely used to investigate the basic principles of human immunobiology as well as complex pathomechanisms and potential therapies of human diseases. Here, elements of an ideal humanized mouse model are highlighted including genetic and non-genetic modification of recipient mice, transplantation strategies and proposals to improve engraftments. The applications of the humanized mice to study the development and response of human immune cells, human autoimmune diseases, virus infections, transplantation biology and tumour biology are reviewed as well.
Output: Mouse models with human immunity and their application in biomedical research Molecular Cell Biology • Introduction • Recipient mouse selection for engrafting xenogeneic human haematopoietic and immune cells • Pre-conditioning regimens for establishing humanized mice -Depletion of innate immune cells in recipient mice -Implication of human growth factors -Making 'space' for donor cells by irradiation or chemical agents • Transplantation strategies to establish humanized mice -Humanized mice achieved by directly implanting mature human immune cells -Humanized mice established by engrafting human HSCs -Humanized mice achieved by engrafting human thymus and HSCs • A proposed ideal humanized mouse model • Applications of humanized mouse models in biomedical research -Ontogeny of human HSCs and immunocell lineages -Autoimmune diseases -Virus infections -Immune response or tolerance to allografts or xenografts -Anti-tumour immune response • Conclusions and perspectives
In China, national regulations and standards for health care waste management were implemented in 2003. To investigate the current status of health care waste management at different levels of health care facilities (HCF) after the implementation of these regulations, one tertiary hospital, one secondary hospital, and four primary health care centers from Binzhou District were visited and 145 medical staff members and 24 cleaning personnel were interviewed. Generated medical waste totaled 1.22, 0.77, and 1.17 kg/bed/day in tertiary, secondary, and primary HCF, respectively. The amount of medical waste generated in primary health care centers was much higher than that in secondary hospitals, which may be attributed to general waste being mixed with medical waste. This study found that the level of the HCF, responsibility for medical waste management in departments and wards, educational background and training experience can be factors that determine medical staff members' knowledge of health care waste management policy. Regular training programs and sufficient provision of protective measures are urgently needed to improve occupational safety for cleaning personnel. Financing and administrative monitoring by local authorities is needed to improve handling practices and the implementation of off-site centralized disposal in primary health care centers.
Output: Investigation of health care waste management in Binzhou District, China
Foot-and-mouth disease virus (FMDV) can infect domestic and wild cloven-hoofed animals. The non-structural protein 3D plays an important role in FMDV replication and pathogenesis. However, the interaction partners of 3D, and the effects of those interactions on FMDV replication, remain incompletely elucidated. In the present study, using the yeast two-hybrid system, we identified a porcine cell protein, DEAD-box RNA helicase 1 (DDX1), which interacted with FMDV 3D. The DDX1-3D interaction was further confirmed by co-immunoprecipitation experiments and an indirect immunofluorescence assay (IFA) in porcine kidney 15 (PK-15) cells. DDX1 was reported to either inhibit or facilitate viral replication and regulate host innate immune responses. However, the roles of DDX1 during FMDV infection remain unclear. Our results revealed that DDX1 inhibited FMDV replication in an ATPase/helicase activity-dependent manner. In addition, DDX1 stimulated IFN-b activation in FMDV-infected cells. Together, our results expand the body of knowledge regarding the role of DDX1 in FMDV infection. Keywords Foot-and-mouth disease virus (FMDV) Á Interaction Á DEAD-box RNA helicase 1 (DDX1) Á Antiviral function Á Interferon Electronic supplementary material The online version of this article (https://doi.
Output: The DEAD-Box RNA Helicase DDX1 Interacts with the Viral Protein 3D and Inhibits Foot-and-Mouth Disease Virus Replication
The etiology of most neurodegenerative diseases of the central nervous system remains unknown and likely involves a combination of genetic susceptibility and environmental triggering factors. Given that exposure to numerous infectious pathogens occurs during childhood, and that some viral infections can lead to neurodegeneration and demyelination, it is conceivable that some viruses may act as triggering factors in neuropathogenesis. We have previously shown that the prototype OC43 strain of the common cold-associated human respiratory coronavirus has the capacity to infect human neuronal and glial cells and does persist in human brains. Moreover, it has neuroinvasive properties in susceptible BALB/c mice, where it leads to a chronic encephalitis with accompanying disabilities. Here, we show that mutations in the viral spike glycoprotein, reproducibly acquired during viral persistence in human neural cell cultures, led to a drastically modified virus-induced neuropathology in BALB/c mice, characterized by flaccid paralysis and demyelination. Even though infection by both mutated and wild-type viruses led to neuroinflammation, the modified neuropathogenesis induced by the mutated virus was associated with increased viral spread and significantly more CD4+ and CD8+ T-lymphocyte infiltration into the central nervous system, as well as significantly increased levels of the proinflammatory cytokine interleukin (IL)-6 and the chemokine CCL2 (monocyte chemoattractant protein [MCP]-1). Moreover, recombinant virus harboring the S glycoprotein mutations retained its neurotropism, productively infecting neurons. Therefore, interaction of a human respiratory coronavirus with the central nervous system may modulate virus and host factors resulting in a modified neuropathogenesis in genetically susceptible individuals. Journal of NeuroVirology (2010) 16, 279-293.
Output: Mutations in the spike glycoprotein of human coronavirus OC43 modulate disease in BALB/c mice from encephalitis to flaccid paralysis and demyelination
In a feeding trial, sows and piglets were fed with the probiotic bacterium Bacillus cereus var. toyoi as a feed additive, and the effects on immune cell populations were examined. The development of the gut immune system was determined for piglets at the ages of 14, 28, 35 and 56 days post partum. Tissue samples of the Jejunum and the continuous Peyer's patch were used for enumeration of intraepithelial lymphocyte populations by fluorescence activated flow cytometry and fluorescence microscopy. Both independent methods of investigation led to similar results: the population of intraepithelial CD8+ T cells was significantly enhanced in the probiotic group piglets ( p 0.05), and the numbers of gd T cells tended to be higher in the intestinal epithelium ( p < 0.1) at the time of weaning (day 28). Lamina propria lymphocytes were also influenced by the treatment. Application of B. cereus var. toyoi resulted in significantly more CD25+ lymphocytes and gd T cells in the probiotic group post-weaning. The occurrence of pathogenic Escherichia coli serogroups was also less frequent in the feces of piglets from the probiotic group. The finding that the CD8+ T cell population in the intestinal mucosa showed changes on day 28 indicated that the influence of B. cereus var. toyoi supplementation on the intestinal immune system started before weaning, an observation supported by changes in the intestinal microflora observed during the suckling-period. The results suggest that feeding of B. cereus var. toyoi to sows may result in beneficial effects on piglet health status independent of their feed supplementation. #
Output: Influence of the probiotic Bacillus cereus var. toyoi on the intestinal immunity of piglets
Background: Non-pharmaceutical strategies are vital in curtailing impacts of influenza and have been intensively studied in public health. However, few strategies have explicitly utilized the weekend effect, which has been widely reported to be capable of reducing influenza infections. This study aims to explore six weekend-extension strategies against seasonal and pandemic flu outbreaks. Methods: The weekend-extension strategies were designed to extend regular two-day weekend by one, two and three days, respectively, and in combination with either a continuous or discontinuous pattern. Their effectiveness was evaluated using an established agent-based spatially explicit simulation model in the urbanized area of Buffalo, NY, US. Results: If the extensions last more than two days, the weekend-extension strategies can remarkably reduce the overall disease attack rate of seasonal flu. Particularly, a three-day continuous extension is sufficient to suppress the epidemic and confine the spread of disease. For the pandemic flu, the weekend-extension strategies only produce a few mitigation effects until the extensions exceed three days. Sensitivity analysis indicated that a compliance level above 75% is necessary for the weekend-extension strategies to take effects. Conclusion: This research is the first attempt to incorporate the weekend effect into influenza mitigation strategies. The results suggest that appropriate extensions of the regular two-day weekend can be a potential measure to fight against influenza outbreaks, while minimizing interruptions on normal rhythms of socio-economy. The concept of weekend extension would be particularly useful if there were a lack of vaccine stockpiles, e.g., in countries with limited health resources, or in the case of unknown emerging infectious diseases.
Output: Agent-based simulation for weekend-extension strategies to mitigate influenza outbreaks
Background: Nurses leaving their jobs and the profession are an issue of international concern, with supplydemand gaps for nurses reported to be widening. There is a large body of existing literature, much of which is already in review form. In order to advance the usefulness of the literature for nurse and human resource managers, we undertook an overview (review of systematic reviews). The aim of the overview was to identify high quality evidence of the determinants and consequences of turnover in adult nursing. Methods: Reviews were identified which were published between 1990 and January 2015 in English using electronic databases (the Cochrane Database of Systematic Reviews, MEDLINE, EMBASE, Applied Social Sciences Index and Abstracts, CINAHL plus and SCOPUS) and forward searching. All stages of the review were conducted in parallel by two reviewers. Reviews were quality appraised using the Assessment of Multiple Systematic Reviews and their findings narratively synthesised. Results: Nine reviews were included. We found that the current evidence is incomplete and has a number of important limitations. However, a body of moderate quality review evidence does exist giving a picture of multiple determinants of turnover in adult nursing, with -at the individual level -nurse stress and dissatisfaction being important factors and -at the organisational level -managerial style and supervisory support factors holding most weight. The consequences of turnover are only described in economic terms, but are considered significant. In making a quality assessment of the review as well as considering the quality of the included primary studies and specificity in the outcomes they measure, the overview found that the evidence is not as definitive as previously presented from individual reviews. Further research is required, of rigorous research design, whether quantitative or qualitative, particularly against the outcome of actual turnover as opposed to intention to leave.
Output: The determinants and consequences of adult nursing staff turnover: a systematic review of systematic reviews
Hepatitis C virus (HCV) is a major cause of liver disease. However, the detailed mechanism underlying hepatocyte infection with HCV is not yet completely understood. We previously identified a novel C-type lectin-LSECtin predominantly expressed on liver sinusoidal endothelial cells. Here we demonstrate that LSECtin can interact with two HCV receptors, DC-SIGNR and CD81, through its central ectodomain. Furthermore, cells expressing LSECtin specifically can be attached by the naturally occurring HCV in the sera of infected individuals. This binding was found to be mediated by the HCV E2 glycoprotein and could be efficiently inhibited by EGTA but not by mannan treatment. The present study suggests that LSECtin interaction with DC-SIGNR might contribute to HCV binding to liver sinusoidal endothelial cells.
Output: C-type lectin LSECtin interacts with DC-SIGNR and is involved in hepatitis C virus binding