niryuu/sni-each-converted huggingface dataset:
The CVTree web server (http://tlife.fudan.edu.cn/ cvtree) presented here is a new implementation of the whole genome-based, alignment-free composition vector (CV) method for phylogenetic analysis. It is more efficient and user-friendly than the previously published version in the 2004 web server issue of Nucleic Acids Research. The development of whole genome-based alignment-free CV method has provided an independent verification to the traditional phylogenetic analysis based on a single gene or a few genes. This new implementation attempts to meet the challenge of ever increasing amount of genome data and includes in its database more than 850 prokaryotic genomes which will be updated monthly from NCBI, and more than 80 fungal genomes collected manually from several sequencing centers. This new CVTree web server provides a faster and stable research platform. Users can upload their own sequences to find their phylogenetic position among genomes selected from the server's inbuilt database. All sequence data used in a session may be downloaded as a compressed file. In addition to standard phylogenetic trees, users can also choose to output trees whose monophyletic branches are collapsed to various taxonomic levels. This feature is particularly useful for comparing phylogeny with taxonomy when dealing with thousands of genomes.
Output: CVTree update: a newly designed phylogenetic study platform using composition vectors and whole genomes
Societies in the 21st century require more proactive management of risks in many areas owing to the complexities people have built into socioeconomic systems, ranging from science and technology, economics, and finance to education, entertainment, and tourism infrastructure. All these systems thrive on stability, which can easily be challenged by unexpected risks. This study compares zooanthroponosis and climate change-induced sea level rise through a cost-benefit analysis in Korea. Borrowing from other methodological approaches, this study shows that the cost-benefit estimation is consistent with the existing macroeconomic speculations, which assume potential loss of GDP due to the two risks. This paper also presents a policy alternative of creating research institutions specializing in the two risks from a cost-benefit perspective as a prerequisite for the "Creative Economy".
Output: Comparing the economic effects of climate change and zooanthroponosis in Korea: Prerequisites for the creative economy? ☆
Objectives: The aims of this article were: to summarize the pharmacology, pharmacokinetics, and efficacy of daptomycin; to explore its safety profile', and to discuss its current and potential roles as an antimicrobial therapy Results: Phase III study results suggest no difference in efficacy or tolerability between daptomycin 4 mg/kg IV QD and vancomycin or semisynthetic penicillins for complicated skin and skin-structure infections. Animal studies suggest daptomycin may be useful for the treatment of endocarditis. Daptomycin is not indicated for pneunionia, with poorer outcomes than conventional treatnient. It is available as an IV niedication and exhibits 92% plasnia protein binding in vitro. In healthy adult humans, daptoniycin has a volume of distribution of 0.1 Ukg and a plasma elimination half-life of -9 hours, and is eliminated primarily by renal excretion (-54%). In patients with reduced renal function, including those receiving hemodialysis and peritoneal dialysis, the dose interval should be 48 hours. No dosage adjustnient appears to be necessary for mild to nioderate hepatic impairnient. The use of daptomycin in patients with severe hepatic irnpairnient has not been assessed. The niost comnionly reported adverse events include constipation, nausea, injection-site reactions, headache, and diarrhea. Patients should also be nionitored regularly for skeletal niuscle toxicity. Conclusions: Daptoniycin may be useful for complicated skin and skin-structure infections and gram-positive pathogens resistant to conventional antimicrobials. However, limited data are currently available for duration of treatment beyond 14 days and at doses >4 mg/kg QD. (Clin Ther.
Output: New Drug Daptomycin: A Cyclic Lipopeptide Antimicrobial Agent
Macroscopic descriptions of populations commonly assume that encounters between individuals are well mixed; i.e. each individual has an equal chance of coming into contact with any other individual. Relaxing this assumption can be challenging though, due to the difficulty of acquiring detailed knowledge about the non-random nature of encounters. Here, we fitted a mathematical model of dengue virus transmission to spatial time-series data from Pakistan and compared maximum-likelihood estimates of 'mixing parameters' when disaggregating data across an urban-rural gradient. We show that dynamics across this gradient are subject not only to differing transmission intensities but also to differing strengths of nonlinearity due to differences in mixing. Accounting for differences in mobility by incorporating two fine-scale, density-dependent covariate layers eliminates differences in mixing but results in a doubling of the estimated transmission potential of the large urban district of Lahore. We furthermore show that neglecting spatial variation in mixing can lead to substantial underestimates of the level of effort needed to control a pathogen with vaccines or other interventions. We complement this analysis with estimates of the relationships between dengue transmission intensity and other putative environmental drivers thereof. License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited.
Output: Big city, small world: density, contact rates, and transmission of dengue across Pakistan
Ten strains of avian infectious bronchitis virus (IBV) were titrated as plaqueforming units in primary chick embryo fibroblast cells. In the absence of trypsin, plaques were only formed by Beaudette-42 and Iowa-609 strains. When trypsin was incorporated in the overlay medium of cell monolayers, all the IBV strains tested produced plaques within 4days after inoculation. Incorporation of 20--40 ~xg of trypsin per ml of the overlay medium seemed to be suitable for plaque formation of IBV. A preliminary investigation was made of the mode of action of trypsin.
Output: Archives of Virology Plaque Formation by Avian Infectious Bronehitis Virus in Primary Chick Embryo Fibroblast Cells in the Presence of Trypsin
Coronavirus disease 2019 (COVID-19) is a newly emerged infection of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and has been pandemic all over the world. This study described acute kidney injury (AKI) at early stage of COVID-19 and its clinical significance. Three-hundred and fifty-five COVID-19 patients with were recruited and clinical data were collected from electronic medical records. Patient's prognosis was tracked and risk factors of AKI was analyzed. Of 355 COVID-19 patients, common, severe and critical ill cases accounted for 63.1%, 16.9% and 20.0%, respectively. On admission, 56 (15.8%) patients were with AKI. Although AKI was more common in critical ill patients with COVID-19, there was no significant association between oxygenation index and renal functional indices among COVID-19 patients with AKI. By multivariate logistic regression, male, older age and comorbidity with diabetes were three important independent risk factors predicting AKI among COVID-19 patients. Among 56 COVID-19 patients with AKI, 33.9% were died on mean 10.9 day after hospitalization. Fatality rate was obviously higher among COVID-+19 patients with AKI than those without AKI (RR=7.08, P<0.001). In conclusion, male elderly COVID-19 patients with diabetes are more susceptible to AKI. AKI at early stage may be a negative prognostic indicator for COVID-19.
Output: Acute kidney injury at early stage as a negative prognostic indicator of patients with COVID-19: a hospital-based retrospective analysis
Porcine epidemic diarrhea virus (PEDV) has caused extensive economic losses to pig producers in many countries. It was recently introduced, for the first time, into North America and outbreaks have occurred again in multiple countries within Europe as well. To assess the properties of various diagnostic assays for the detection of PEDV infection, multiple panels of porcine sera have been shared and tested for the presence of antibodies against PEDV in an inter-laboratory ring trial. Different laboratories have used a variety of "in house" ELISAs and also one commercial assay. The sensitivity and specificity of each assay has been estimated using a Bayesian analysis applied to the ring trial results obtained with the different assays in the absence of a gold standard. Although different characteristics were found, it can be concluded that each of the assays used can detect infection of pigs at a herd level by either the early European strains of PEDV or the recently circulating strains (INDEL and non-INDEL). However, not all the assays seem suitable for demonstrating freedom from disease in a country. The results from individual animals, especially when the infection has occurred within an experimental situation, show more variation.
Output: Inter-laboratory study to characterize the detection of serum antibodies against porcine epidemic diarrhoea virus
For many enveloped viruses, binding to a receptor(s) on a host cell acts as a first step in a series of events culminating in fusion with the host cell membrane and transfer of genetic material for replication [for review see 1,2 ]. The envelope glycoprotein (Env) trimer on the surface of HIV is responsible for receptor binding and fusion. While Env can tolerate a high degree of mutation in five variable regions (V1-V5), and also at N-linked glycosylation sites that contribute roughly half the mass of Env, the functional sites for recognition of receptor CD4 and co-receptor CXCR4/ CCR5 are conserved and essential for viral fitness. Soluble SOSIP Env trimers are structural and Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.
Output: Open and Closed Structures Reveal Allostery and Pliability in the HIV-1 Envelope Spike
Conventional monoclonal antibodies (mAbs) have been widely used in research and diagnostic applications due to their high affinity and specificity. However, multiple limitations, such as large size, complex structure and sensitivity to extreme ambient temperature potentially weaken the performance of mAbs in certain applications. To address this problem, the exploration of new antigen binders is extensively required in relation to improve the quality of current diagnostic platforms. In recent years, a new immunoglobulin-based protein, namely variable domain of new antigen receptor (VNAR) was discovered in sharks. Unlike conventional mAbs, several advantages of VNARs, include small size, better thermostability and peculiar paratope structure have attracted interest of researchers to further explore on it. This article aims to first present an overview of the shark VNARs and outline the characteristics as an outstanding new reagent for diagnostic and therapeutic applications.
Output: Diagnostic and therapeutic potential of shark variable new antigen receptor (VNAR) single domain antibody
Porcine hemagglutinating encephalomyelitis virus (PHEV) is a typical neurotropic coronavirus that mainly invades the central nervous system (CNS) in piglets and causes vomiting and wasting disease. Emerging evidence suggests that PHEV alters microRNA (miRNA) expression profiles, and miRNA has also been postulated to be involved in its pathogenesis, but the mechanisms underlying this process have not been fully explored. In this study, we found that PHEV infection upregulates miR-142a-3p RNA expression in N2a cells and in the CNS of mice. Downregulation of miR-142a-3p by an miRNA inhibitor led to a significant repression of viral proliferation, implying that it acts as a positive regulator of PHEV proliferation. Using a dual-luciferase reporter assay, miR-142a-3p was found to bind directly bound to the 3' untranslated region (3'UTR) of Rab3a mRNA and downregulate its expression. Knockdown of Rab3a expression by transfection with an miR-142a-3p mimic or Rab3a siRNA significantly increased PHEV replication in N2a cells. Conversely, the use of an miR-142a-3p inhibitor or overexpression of Rab3a resulted in a marked restriction of viral production at both the mRNA and protein level. Our data demonstrate that miR-142a-3p promotes PHEV proliferation by directly targeting Rab3a mRNA, and this provides new insights into the mechanisms of PHEV-related pathogenesis and virus-host interactions. Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Output: miR-142a-3p promotes the proliferation of porcine hemagglutinating encephalomyelitis virus by targeting Rab3a
Many examples of the emergence or re-emergence of infectious diseases involve the adaptation of zoonotic viruses to new amplification hosts or to humans themselves. These include several instances of simple mutational adaptations, often to hosts closely related to the natural reservoirs. However, based on theoretical grounds, arthropod-borne viruses, or arboviruses, may face several challenges for adaptation to new hosts. Here, we review recent findings regarding adaptive evolution of arboviruses and its impact on disease emergence. We focus on the zoonotic alphaviruses Venezuelan equine encephalitis and chikungunya viruses, which have undergone adaptive evolution that mediated recent outbreaks of disease, as well as the flaviviruses dengue and West Nile viruses, which have emerged via less dramatic adaptive mechanisms.
Output: Factors shaping the adaptive landscape for arboviruses: implications for the emergence of disease
Background: Human immunodeficiency virus type 1 (HIV-1) has infected more than 40 million people worldwide, mainly in sub-Saharan Africa. The high prevalence of HIV-1 subtype C in southern Africa necessitates the development of cheap, effective vaccines. One means of production is the use of plants, for which a number of different techniques have been successfully developed. HIV-1 Pr55Gag is a promising HIV-1 vaccine candidate: we compared the expression of this and a truncated Gag (p17/p24) and the p24 capsid subunit in Nicotiana spp. using transgenic plants and transient expression via Agrobacterium tumefaciens and recombinant tobamovirus vectors. We also investigated the influence of subcellular localisation of recombinant protein to the chloroplast and the endoplasmic reticulum (ER) on protein yield. We partially purified a selected vaccine candidate and tested its stimulation of a humoral and cellular immune response in mice. Both transient and transgenic expression of the HIV antigens were successful, although expression of Pr55Gag was low in all systems; however, the Agrobacterium-mediated transient expression of p24 and p17/p24 yielded best, to more than 1 mg p24/kg fresh weight. Chloroplast targeted protein levels were highest in transient and transgenic expression of p24 and p17/p24. The transiently-expressed p17/p24 was not immunogenic in mice as a homologous vaccine, but it significantly boosted a humoral and T cell immune response primed by a gag DNA vaccine, pTHGagC. Conclusion: Transient agroinfiltration was best for expression of all of the recombinant proteins tested, and p24 and p17/p24 were expressed at much higher levels than Pr55Gag. Our results highlight the usefulness of plastid signal peptides in enhancing the production of recombinant proteins meant for use as vaccines. The p17/p24 protein effectively boosted T cell and humoral responses in mice primed by the DNA vaccine pTHGagC, showing that this plant-produced protein has potential for use as a vaccine.
Output: Expression of HIV-1 antigens in plants as potential subunit vaccines
Alere i RSV is a novel rapid test which applies a nicking enzyme amplification reaction to detect respiratory syncytial virus in point-of-care settings. In this study, we evaluated the Alere i RSV assay by using frozen nasopharyngeal swab samples that were collected in viral transport medium from children hospitalized with acute respiratory tract infection during the 2015-2016 winter season. Alere i RSV assay results were compared to those for Altona RealStar RSV real-time reverse transcription-PCR (RT-PCR). We found that the overall sensitivity and specificity of the Alere i RSV test was 100% (95% confidence intervals [CI], 93% to 100%) and 97% (95% CI, 89% to 100%), respectively. Positive samples were identified within 5 to 7 min from sample collection. Overall, the Alere i RSV test performed well compared to the RT-PCR assay and has the potential to facilitate the detection of RSV in pointof-care settings. Citation Peters RM, Schnee SV, Tabatabai J, Schnitzler P, Pfeil J. 2017. Evaluation of Alere i RSV for rapid detection of respiratory syncytial virus in children hospitalized with acute respiratory tract infection. J Clin
Output: Evaluation of Alere i RSV for Rapid Detection of Respiratory Syncytial Virus in Children Hospitalized with Acute Respiratory Tract Infection
We present a stochastic model for the spread of smallpox after a small number of index cases are introduced into a susceptible population. The model describes a branching process for the spread of the infection and the effects of intervention measures. We discuss scenarios in which ring vaccination of direct contacts of infected persons is sufficient to contain an epidemic. Ring vaccination can be successful if infectious cases are rapidly diagnosed. However, because of the inherent stochastic nature of epidemic outbreaks, both the size and duration of contained outbreaks are highly variable. Intervention requirements depend on the basic reproduction number (R 0 ), for which different estimates exist. When faced with the decision of whether to rely on ring vaccination, the public health community should be aware that an epidemic might take time to subside even for an eventually successful intervention strategy.
Output: Ring Vaccination and Smallpox Control
Colloidal gold lateral flow immunoassay strips (AuNPs-LFIS) have been widely applied as qualitative diagnostic tools for point-of-care tests (POCT). If strip readers were incorporated, their use could be extended to quantitative analysis. However, their cost and non-portability render commercial strip readers unavailable for use in either home testing, community or rural hospital diagnosis. This is particularly true for on-site testing. Here, a smartphone-based reader was designed and 3D-printed for quantitatively assess AuNPs-LFIS. The basic principle of the devise was relying on a smartphone's ambient light sensor (SPALS). This sensor was harnessed to measure the transmitted light intensities originating from the T-lines on the strips, the transmitted light intensities vary with concentration of AuNP on the T-lines. To validate this approach, our newly developed smartphone's ambient light sensor-based reader (SPALS-reader) was used to readout AuNPs-LFIS of three analytical targets: cadmium ion (Cd 2+ ; limit of detection (LOD) was 0.16 ng/mL), clenbuterol (CL; LOD was 0.046 ng/mL), and porcine epidemic diarrhea virus (PEDV; LOD was 0.055 g/mL). The result showed good consistency with the results of conventional image analysis approaches, indicating that the smartphone-based device is appropriate for use in AuNPs-LFIS readouts. Compared with the traditional analysis method, the developed AuNPs-LFIS reader is easier operated, lower cost and more portable, which provided an on-site quantitative analysis tool for AuNPs-LFIS and enhances the applied range of AuNPs-LFIS.
Output: A simple and compact smartphone-based device for the quantitative readout of colloidal gold lateral flow immunoassay strips
The laboratory diagnosis of dengue has largely relied on serological assays, although many different RT-PCR protocols have been reported. Owing to its limited use, the value of RT-PCR in the clinical laboratory has not been fully evaluated. During the outbreak of severe acute respiratory syndrome (SARS) in Singapore in 2003, RT-PCR to detect dengue viral RNA was used as a rapid diagnostic tool to differentiate dengue from SARS among patients who presented to a hospital designated to manage and quarantine SARS cases. A total of 343 results for RT-PCR and 439 results for serology were analysed and compared with the final discharge diagnosis. Our experience indicates that RT-PCR for dengue can be set up rapidly in a clinical laboratory, with very sensitive and specific results for the diagnosis of dengue, particularly in the first 5 days from onset of symptoms.
Output: The performance of RT-PCR compared with a rapid serological assay for acute dengue fever in a diagnostic laboratory
Suckling C57BU6 mice infected with mouse hepatitis virus strain JHM (MHV-JHM) develop either a fatal acute encephalomyelitis or a late onset demyelinating disease, depending on whether they are nursed by unimmunized or immunized dams. To determine the localization of virus-specific RNA, serial sections of brains from infected and uninfected mice were annealed with a %-labeled antisense RNA probe and analyzed by film autoradiography. In the mice with acute encephalomyelitis, viral RNA was present in the mesencephalon, hypothalamus, hippocampus, basal ganglia, subcortical white matter, and thalamus. Viral RNA was detected in the spinal cords of all mice with the late onset, demyelinating encephalomyelitis, but was distributed into three different patterns in the brains of these mice, even though all had the same clinical disease. In the first group, viral RNA was detected only in the brainstem. In the second group, viral RNA was detected in the brainstem, thalamus, and cerebral grey matter. This distribution was consistent with viral spread along well-defined tracts connecting these parts of the brain. In the third group, viral RNA could be detected both in the brainstem and in several white matter tracts within close physical proximity to the optic chiasm. This distribution was consistent with viral spread by an extracellular route from one white matter tract to other tracts which were physically close, but which were not part of the same pathways. These results suggest that MHV-JHM spreads through the central nervous system both along well-defined neuronal pathways and by spread from contiguous structures, but also suggest that viral replicates preferentially in a limited number of areas of the brain. The technique of in situ hybridization with film autoradiography should be generally useful for analyzing macroscopic movements of virus within infected organs. Q 1998 Academic press. hc.
Output: Regional Localization of Virus in the Central Nervous System of Mice Persistently Infected with Murine Coronavirus JHM
Tissues from nine ferrets with granulomatous lesions similar to those seen in feline infectious peritonitis were examined histopathologically and immunohistochemically. Four main types of lesions were observed: di¡use granulomatous in£ammation on serosal surfaces; granulomas with areas of necrosis; granulomas without necrosis; and granulomas with neutrophils. Other less commonly seen lesions were granulomatous necrotizing vasculitis and endogenous lipid pneumonia. FCV3-70 monoclonal antibody produced immunolabelling of group 1 coronavirus antigen in tissue samples from eight animals, the antigen being present in the cytoplasm of macrophages in the di¡erent types of granulomatous lesions. r
Output: Identification of Group 1 Coronavirus Antigen in Multisystemic Granulomatous Lesions in Ferrets (Mustela putorius furo)
The vascular endothelium can be considered as an organ/tissue which comprises a monolayer of endothelial cells which serve as a semipermeable cellular barrier separating the inner space of blood vessels from its surrounding tissue and to control the exchange of fluids and cells between the two compartments. Since the pulmonary circulation receives the entire cardiac output, the large surface area of the lung microvasculature is well suited for sensing mechanical, chemical, and cellular injury by inhaled or circulating substances. This endothelial barrier is dynamically regulated through exposure to these various stimuli of physiological and pathological origin and serves to regulate multiple key biological processes (including lung fluid balance and solute transport between vascular compartments). For example, an increase in vascular permeability is a necessary feature of the body's defense mechanism to provide injured tissues with access to leucocytes, resulting in tissue edema due to fluid extravasation. However, during conditions of intense lung inflammation such as observed in acute lung injury or its severer form of acute respiratory distress syndrome, the large surface area becomes a liability and provides the opportunity for profound vascular permeability resulting in massive fluid accumulation in the alveolar space and progressively leading to pulmonary failure. Alterations in vascular permeability occur not only in acute inflammatory lung disorders primarily caused by sepsis, pneumonia, and trauma which result in high rates of patient morbidity and mortality, but are an attractive target for therapeutic intervention in subacute lung inflammatory disorders such as ischemia-reperfusion injury, radiation lung injury, and asthma. Thus, understanding the mechanisms of endothelial barrier dysfunction is vital for the management and treatment of key and enigmatic pulmonary disorders.
Output: Acute Lung Injury: The Injured Lung Endothelium, Therapeutic Strategies for Barrier Protection, and Vascular Biomarkers
The potential of DNA microarrays for detection of plant viruses is hampered by underutilization of sequence-independent amplification methods for target nucleic acid enrichment. A microarray system is described for an unbiased detection of plant viruses using both short (30 nt) and long (50 and 70 nt) oligonucleotide probes. The assay involves amplification of target nucleic acid using random primers followed by in vitro transcription whose cRNA product is labeled chemically, fragmented and used as target for hybridization. Initial optimization tests with Turnip vein clearing virus and Cauliflower mosaic virus showed increased hybridization efficiency with shorter cDNA targets (100 bp) and longer probes (50 and 70 nt). The system was validated in pure and mixed samples by detection of three Tymovirus species: Asclepias asymptomatic virus, Kennedya yellow mosaic virus and Turnip yellow mosaic virus. The method could detect sequence variants with 70-75% or higher sequence identity, indicating the possible utility of the approach for virus discovery. Array performance comparison of long probes demonstrated the competence of 50-mers to provide a satisfactory balance between detection sensitivity and specificity. The work described is a significant step towards a method to assess, in one assay, the presence of a large diversity of relatives of known viruses of plants.
Output: Oligonucleotide-based microarray for detection of plant viruses employing sequence-independent amplification of targets
Four out of five people in the world with diabetes now live in low-and middle-income countries (LMIC), and the incidence of diabetes is accelerating in poorer communities. Diabetes increases susceptibility to infection and worsens outcomes for some of the world's major infectious diseases such as tuberculosis, melioidosis and dengue, but the relationship between diabetes and many neglected tropical diseases is yet to be accurately characterised. There is some evidence that chronic viral infections such as hepatitis B and HIV may predispose to the development of type 2 diabetes by chronic inflammatory and immunometabolic mechanisms. Helminth infections such as schistosomiasis may be protective against the development of diabetes, and this finding opens up new territory for discovery of novel therapeutics for the prevention and treatment of diabetes. A greater understanding of the impact of diabetes on risks and outcomes for infections causing significant diseases in LMIC is essential in order to develop vaccines and therapies for the growing number of people with diabetes at risk of infection, and to prioritise research agendas, public health interventions and policy. This review seeks to give an overview of the current international diabetes burden, the evidence for interactions between diabetes and infection, immune mechanisms for the interaction, and potential interventions to tackle the dual burden of diabetes and infection.
Output: The double burden of diabetes and global infection in low and middle- income countries
The healthcare industry is experiencing a major transformation towards e-healthcare, which delivers and enhances related information through the Internet among healthcare stakeholders and makes the electronic signature (e-signature) more and more important. This paper uses a mature framework, Technology-Organization-Environment (TEO), in information system discipline to identify factors that affect hospitals in adopting e-signature. A survey was conducted on regional hospitals and medical centers in Taiwan to verify the validity of the research framework. The results show that TEO framework is useful in distinguishing hospitals as adopters and non-adopters of e-signature. Based on the research findings, implications and limitations are discussed.
Output: Factors affecting the adoption of electronic signature: Executives' perspective of hospital information department
Bacterial and viral co-infections of the respiratory tract are life-threatening and present a global burden to the global community. Staphylococcus aureus, Streptococcus pneumoniae, and Streptococcus pyogenes are frequent colonizers of the upper respiratory tract. Imbalances through acquisition of seasonal viruses, e.g., Influenza A virus, can lead to bacterial dissemination to the lower respiratory tract, which in turn can result in severe pneumonia. In this review, we summarize the current knowledge about bacterial and viral co-infections of the respiratory tract and focus on potential experimental models suitable for mimicking this disease. Transmission of IAV and pneumonia is mainly modeled by mouse infection. Few studies utilizing ferrets, rats, guinea pigs, rabbits, and non-human primates are also available. The knowledge gained from these studies led to important discoveries and advances in understanding these infectious diseases. Nevertheless, mouse and other infection models have limitations, especially in translation of the discoveries to humans. Here, we suggest the use of human engineered lung tissue, human ex vivo lung tissue, and porcine models to study respiratory co-infections, which might contribute to a greater translation of the results to humans and improve both, animal and human health.
Output: Port d'Entrée for Respiratory Infections -Does the Influenza A Virus Pave the Way for Bacteria?
Although mosquitoes serve as vectors of many pathogens of public health importance, their response to viral infection is poorly understood. It also remains to be investigated whether viruses deploy some mechanism to be able to overcome this immune response. Here, we have used an RNA-Seq approach to identify differentially regulated genes in Culex quinquefasciatus cells following West Nile virus (WNV) infection, identifying 265 transcripts from various cellular pathways that were either upregulated or downregulated. Ubiquitin-proteasomal pathway genes, comprising 12% of total differentially regulated genes, were selected for further validation by real time RT-qPCR and functional analysis. It was found that treatment of infected cells with proteasomal inhibitor, MG-132, decreased WNV titers, indicating importance of this pathway during infection process. In infection models, the Culex ortholog of mammalian Cul4A/B (cullin RING ubiquitin ligase) was found to be upregulated in vitro as well as in vivo, especially in midguts of mosquitoes. Gene knockdown using dsRNA and overexpression studies indicated that Culex Cul4 acts as a pro-viral protein by degradation of CxSTAT via ubiquitin-proteasomal pathway. We also show that gene knockdown of Culex Cul4 leads to activation of the Jak-STAT pathway in mosquitoes leading to decrease viral replication in the body as well as saliva. Our results suggest a novel mechanism adopted by WNV to overcome mosquito immune response and increase viral replication. PLOS Pathogens |
Output: Cullin4 Is Pro-Viral during West Nile Virus Infection of Culex Mosquitoes
This paper describes a public health alerting approach that has the potential to improve patient care during a public health outbreak and reduce healthcare costs, streamline the process of public health alert management and dissemination, and heighten the crucial feedback loop between public health officials and clinicians. The approach ties public health alerts into the diagnostic process and allows clinicians to more easily determine when an observed medical condition may be related to a more widespread disease outbreak. A prototype Alert Knowledge Repository (AKR) service using this approach was demonstrated within the Health Information and Management Systems Society (HIMSS) and the Public Health Information Network (PHIN) interoperability showcases in April and September 2009, respectively.
Output: An Informatics Solution for Informing Care Delivery of Immediate Public Health Risks to Their Patients An Informatics Solution for Informing Care Delivery of Immediate Public Health Risks to Their Patients
The essentiality of zinc in humans was established in 1963. During the past 50 y, tremendous advances in both clinical and basic sciences of zinc metabolism in humans have been observed. The major factor contributing to zinc deficiency is high phytate-containing cereal protein intake in the developing world, and nearly 2 billion subjects may be zinc deficient. Conditioned deficiency of zinc has been observed in patients with malabsorption syndrome, liver disease, chronic renal disease, sickle cell disease, and other chronic illnesses. Major clinical problems resulting from zinc deficiency in humans include growth retardation; cell-mediated immune dysfunction, and cognitive impairment. In the Middle East, zincdeficient dwarfs did not live beyond the age of 25 y, and they died because of intercurrent infections. In 1963, we knew of only 3 enzymes that required zinc for their activities, but now we know of >300 enzymes and >1000 transcription factors that are known to require zinc for their activities. Zinc is a second messenger of immune cells, and intracellular free zinc in these cells participate in signaling events. Zinc has been very successfully used as a therapeutic modality for the management of acute diarrhea in children, Wilson's disease, the common cold and for the prevention of blindness in patients with age-related dry type of macular degeneration and is very effective in decreasing the incidence of infection in the elderly. Zinc not only modulates cell-mediated immunity but is also an antioxidant and anti-inflammatory agent.
Output: REVIEWS FROM ASN EB 2012 SYMPOSIA Discovery of Human Zinc Deficiency: Its Impact on Human Health and Disease 1-3
The West African Ebola virus outbreak underlined the importance of delivering mass diagnostic capability outside the clinical or primary care setting in effectively containing public health emergencies caused by infectious disease. Yet, to date, there is no solution for reliably deploying at the point of need the gold standard diagnostic method, real time quantitative reverse transcription polymerase chain reaction (RT-qPCR), in a laboratory infrastructure-free manner. In this proof of principle work, we demonstrate direct performance of RT-qPCR on fresh blood using far-red fluorophores to resolve fluorogenic signal inhibition and controlled, rapid freeze/thawing to achieve viral genome extraction in a single reaction chamber assay. The resulting process is entirely free of manual or automated sample pre-processing, requires no microfluidics or magnetic/mechanical sample handling and thus utilizes low cost consumables. This enables a fast, laboratory infrastructure-free, minimal risk and simple standard operating procedure suited to frontline, field use. Developing this novel approach on recombinant bacteriophage and recombinant human immunodeficiency virus (HIV; Lentivirus), we demonstrate clinical utility in symptomatic EBOV patient screening using live, infectious Filoviruses and surrogate patient samples. Moreover, we evidence assay co-linearity independent of viral particle structure that may enable viral load quantification through pre-calibration, with no loss of specificity across an 8 loglinear maximum dynamic range. The resulting quantitative rapid identification (QuRapID) molecular diagnostic platform, openly accessible for assay development, meets the requirements of resourcelimited countries and provides a fast response solution for mass public health screening against emerging biosecurity threats. ; Tel: +44(0) 191 215 6623 † Electronic supplementary information (ESI) available. See
Output: Field-deployable, quantitative, rapid identification of active Ebola virus infection in unprocessed blood †
Since the discovery of the RNA interference (RNAi) phenomenon, RNAi-based therapies now present a huge potential for the treatment of many diseases, including inflammatory and infectious diseases and cancers. While numerous reports have described the development of small interfering RNA (siRNA) delivery systems for in-vivo applications, only a small number of siRNA-based therapies are currently under clinical development. This is essentially due to the lack of efficient and safe siRNA delivery systems for intravenous administration. However, the delivery of siRNA after local injection could represent an attractive route of administration to limit the issues of toxicity associated with systemic injection. We will describe here the different synthetic vectors which have been developed for the local delivery of siRNA in various organs.
Output: Local siRNA delivery by non-viral vectors
Background: Gastrointestinal (GI) symptoms, such as diarrhea, vomiting, abdominal pain and nausea are not an uncommon manifestation of an acute respiratory infection (ARI). We therefore evaluated clinical and microbiological factors associated with the presence of GI symptoms in patients consulting a general practitioner (GP) for ARI. Methods: Nasopharyngeal swabs, stool specimens and clinical data from patients presenting to GPs with an ARI were prospectively collected during two winter seasons (2014)(2015)(2016). Samples were tested by quantitative real-time PCR for 12 respiratory pathogen groups and for 12 enteric pathogens. Results: Two hundred and four of 331 included patients (61.6%) were positive for at least one respiratory pathogen. Sixty-nine stools (20.8%) were positive for at least one pathogen (respiratory and/or enteric). GI symptoms were more likely declared in case of laboratory confirmed-enteric infection (adjusted odds ratio (aOR) = 3.2; 95% confidence interval [CI] [1.2-9.9]; p = 0.02) or human coronavirus (HCoV) infection (aOR = 2.7; [1.2-6.8]; p = 0.02). Consumption of antipyretic medication before the consultation seemed to reduce the risk of developing GI symptoms for patients with laboratoryconfirmed influenza (aOR = 0.3; [0.1-0.6]; p = 0.002). Conclusions: The presence of GI symptoms in ARI patients could not be explained by the detection of respiratory pathogens in stools. However, the detection of enteric pathogens in stool samples could explained by the presence of GI symptoms in some of ARI cases. The biological mechanisms explaining the association between the presence of HCoVs in nasopharynx and GI symptoms need to be explored.
Output: Clinical and virological factors associated with gastrointestinal symptoms in patients with acute respiratory infection: a two-year prospective study in general practice medicine
The genus Torovirus (order Nidovirales) includes a number of species that infect livestock. These viruses have a linear positive-sense ssRNA genome of ~25-30 kb, encoding a large polyprotein that is expressed from the genomic RNA, and several additional proteins expressed from a nested set of 3'-coterminal subgenomic RNAs. In this brief report, we describe the bioinformatic discovery of a new, apparently coding, ORF that overlaps the 5' end of the polyprotein coding sequence, ORF1a, in the +2 reading frame. The new ORF has a strong coding signature and, in fact, is more conserved at the amino acid level than the overlapping region of ORF1a. We propose that the new ORF utilizes a non-AUG initiation codon -namely a conserved CUG codon in a strong Kozak context -upstream of the ORF1a AUG initiation codon, resulting in a novel 258 amino acid protein, dubbed '30K'.
Output: Virology Journal A case for a CUG-initiated coding sequence overlapping torovirus ORF1a and encoding a novel 30 kDa product
Magnetic resonance imaging (MRI) can detect atherosclerotic lesions containing accumulations of ultrasmall superparamagnetic iron oxides (USPIO). Positing that improved USPIO with a higher affinity for atherosclerotic plaques would yield better plaque images, we performed MRI and histologic studies to compare the uptake of dextran-and mannan-dextrancoated USPIO (D-USPIO and DM-USPIO, respectively) by the atherosclerotic walls of rabbits. We intravenously injected atherosclerotic rabbits with DM-USPIO (n = 5) or D-USPIO (n = 5). Two rabbits were the controls. The doses delivered were 0.08 (dose 1) (n = 1), 0.4 (dose 2) (n = 1), or 0.8 (dose 3) (n = 3) mmol iron/Kg. The dose 3 rabbits underwent in vivo contrastenhanced magnetic resonance angiography (MRA) before and 5 days after USPIO administration. Afterwards, all animals were euthanized, the aortae were removed and subjected to in vitro MRI study. The signal-to-noise ratio (SNR) of the aortic wall in the same region of interest (ROI) was calculated in both in vivo and in vitro studies. Histological assessment through measurement of iron-positive regions in Prussian blue-stained specimens showed that iron-positive regions were significantly larger in rabbits injected with DM-rather than D-USPIO (P , 0.05) for all doses. In vivo MRA showed that the SNR-reducing effect of DM-was greater than that of D-USPIO (P , 0.05). With in vitro MRI scans, SNR was significantly lower in rabbits treated with dose 2 of DM-USPIO compared with D-USPIO treatment (P , 0.05), and it tended to be lower at dose 3 (P , 0.1). In conclusion, we suggest that DM-USPIO is superior to D-USPIO for the study of atherosclerotic lesions in rabbits.
Output: Evaluation of atherosclerotic lesions using dextran-and mannan-dextran-coated USPIO: MRI analysis and pathological findings
Nielsen, K.H., Wright, P.F., Kelly, W.A. and Cherwonogrodzky, J.H., 1988. A review of enzyme immunoassay for detection of antibody to BruceUa abortus in cattle. Vet. Immunol. Immunopathol., Enzyme immunoassay has gained wide acceptance for serological diagnosis of bovine brucellosis because of its ability to detect antibody of all isotypes unlike the conventional tests. The indirect enzyme immunoassay, however, presents several parameters that require careful analysis. These parameters include the choice of antigen and antiglobulin-enzyme conjugate reagents for use in the assay, dealing with the large amount of data the semi-automatic or automatic assay can generate and the inter-and intralaboratory standardization and quality control. This review considers the various methods described in the literature and, briefly, how some of the problems have been overcome or how they might be dealt with.
Output: A Review of Enzyme Immunoassay for Detection of Antibody to BruceUa abortus in Cattle
Identification of epitopes which invokes strong humoral responses is an essential issue in the field of immunology. Various computational methods that have been developed based on the antigen structures and the mimotopes these years narrow the search for experimental validation. These methods can be divided into two categories: antigen structure-based methods and mimotopebased methods. Though new methods of the two kinds have been proposed in these years, they cannot maintain a high degree of satisfaction in various circumstances. In this paper, we proposed a new conformational B-cell epitope prediction method based on antigen preprocessing and mimotopes analysis. The method classifies the antigen surface residues into "epitopes" and "nonepitopes" by six epitope propensity scales, removing the "nonepitopes" and using the preprocessed antigen for epitope prediction based on mimotope sequences. The proposed method gives out the mean F score of 0.42 on the testing dataset. When compared with other publicly available servers by using the testing dataset, the new method yields better performance. The results demonstrate the proposed method is competent for the conformational B-cell epitope prediction.
Output: Conformational B-Cell Epitope Prediction Method Based on Antigen Preprocessing and Mimotopes Analysis
High consequence human pathogenic viruses must be handled at biosafety level 2, 3 or 4 and must be rendered non-infectious before they can be utilized for molecular or immunological applications at lower biosafety levels. Here we evaluate psoralen-inactivated Arena-, Bunya-, Corona-, Filo-, Flavi-and Orthomyxoviruses for their suitability as antigen in immunological processes and as template for reverse transcription PCR and sequencing. The method of virus inactivation using a psoralen molecule appears to have broad applicability to RNA viruses and to leave both the particle and RNA of the treated virus intact, while rendering the virus non-infectious.
Output: Psoralen Inactivation of Viruses: A Process for the Safe Manipulation of Viral Antigen and Nucleic Acid
Arthritogenic alphaviruses comprise a group of enveloped RNA viruses that are transmitted to humans by mosquitoes and cause debilitating acute and chronic musculoskeletal disease 1 . The host factors required for alphavirus entry remain poorly characterized 2 . Using a genome-wide CRISPR/Cas9-based screen, we identified the cell adhesion molecule Mxra8 as an entry mediator for multiple emerging arthritogenic alphaviruses including chikungunya (CHIKV), Ross River, Mayaro, and O'nyong nyong (ONNV) viruses. Gene editing of mouse Mxra8 or human MXRA8 resulted in reduced viral infection of cells, and reciprocally, ectopic expression resulted in increased infection. Mxra8 bound directly to CHIKV particles and enhanced virus attachment and Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.
Output: Mxra8 is a receptor for multiple arthritogenic alphaviruses
siVirus (http://siVirus.RNAi.jp/) is a web-based online software system that provides efficient short interfering RNA (siRNA) design for antiviral RNA interference (RNAi). siVirus searches for functional, off-target minimized siRNAs targeting highly conserved regions of divergent viral sequences. These siRNAs are expected to resist viral mutational escape, since their highly conserved targets likely contain structurally/functionally constrained elements. siVirus will be a useful tool for designing optimal siRNAs targeting highly divergent pathogens, including human immunodeficiency virus (HIV), hepatitis C virus (HCV), influenza virus and SARS coronavirus, all of which pose enormous threats to global human health.
Output: siVirus: web-based antiviral siRNA design software for highly divergent viral sequences