niryuu/sni-each-converted huggingface dataset:
Background: Better understanding the etiology-specific incidence of severe acute respiratory infections (SARIs) in resourcepoor, rural settings will help further develop and prioritize prevention strategies. To address this gap in knowledge, we conducted a longitudinal study to estimate the incidence of SARIs among children in rural Bangladesh. Methods: During June through October 2010, we followed children aged ,5 years in 67 villages to identify those with cough, difficulty breathing, age-specific tachypnea and/or danger signs in the community or admitted to the local hospital. A study physician collected clinical information and obtained nasopharyngeal swabs from all SARI cases and blood for bacterial culture from those hospitalized. We tested swabs for respiratory syncytial virus (RSV), influenza viruses, human metapneumoviruses, adenoviruses and human parainfluenza viruses 1-3 (HPIV) by real-time reverse transcription polymerase chain reaction. We calculated virus-specific SARI incidence by dividing the number of new illnesses by the person-time each child contributed to the study.
Output: Population-Based Incidence of Severe Acute Respiratory Virus Infections among Children Aged ,5 Years in Rural
The ability to subvert intracellular antiviral defenses is necessary for virus to survive as its replication occurs only in the host cells. Viruses have to modulate cellular processes and antiviral mechanisms to their own advantage during the entire virus life cycle. Autophagy plays important roles in cell regulation. Its function is not only to catabolize aggregate proteins and damaged organelles for recycling but also to serve as innate immunity to remove intracellular pathogenic elements such as viruses. Nevertheless, some viruses have evolved to negatively regulate autophagy by inhibiting its formation. Even more, some viruses have employed autophagy to benefit their replication. To date, there are more and more growing evidences uncovering the functions of many viral proteins to regulate autophagy through different cellular pathways. In this review, we will discuss the relationship between viruses and autophagy and summarize the current knowledge on the functions of viral proteins contributing to affect autophagy process.
Output: Commentary on the Regulation of Viral Proteins in Autophagy Process
Respiratory viral diseases can be spread when a virus-containing particle (droplet) from one individual is aerosolized and subsequently comes into either direct or indirect contact with another individual. Increasing numbers of studies are examining the occupational risk to healthcare workers due to proximity to patients. Selecting the appropriate air sampling method is a critical factor in assuring the analytical performance characteristics of a clinical study. The objective of this study was to compare the physical collection efficiency and virus collection efficiency of a 5 mL compact SKC BioSampler ® , a gelatin filter, and a glass fiber filter, in a laboratory setting. The gelatin filter and the glass fiber filter were housed in a home-made filter holder. Submersion (with vortexing and subsequent centrifugation) was used for the gelatin and glass fiber filters. Swabbing method was also tested to retrieve the viruses from the glass fiber filter. Experiments were conducted using the H1N1 influenza A virus A/Puerto Rico/8/1934 (IAV-PR8), and viral recovery was determined using culture and commercial real-time-PCR (BioFire and Xpert). An atomizer was used to aerosolize a solution of influenza virus in PBS for measurement, and two Scanning Mobility Particle Sizers were used to determine particle size distributions. The SKC BioSampler demonstrated a U-shaped physical collection efficiency, lowest for particles around 30-50 nm, and highest at 10 nm and 300-350 nm within the size range examined. The physical collection efficiency of the gelatin filter was strongly influenced by air flow and time: a stable collection across all particle sizes was only observed at 2 L/min for the 9 min sampling time, otherwise, degradation of the filter was observed. The glass fiber filter demonstrated the highest physical collection efficiency (100% for all sizes) of all tested samplers, however, its overall virus recovery efficiency fared the worst (too low to quantify). The highest viral collection efficiencies for the SKC BioSampler and gelatin filter were 5% and 1.5%, respectively. Overall, the SKC BioSampler outperformed the filters. It is important to consider the total concentration of viruses entering the sampler when interpreting the results.
Output: Comparing the performance of 3 bioaerosol samplers for influenza virus
Significant concerns have been raised owing to the rapid global spread of infection and disease caused by the mosquito-borne Zika virus (ZIKV). Recent studies suggest that ZIKV can also be transmitted sexually, further increasing the exposure risk for this virus. Associated with this spread is a dramatic increase in cases of microcephaly and additional congenital abnormalities in infants of ZIKV-infected mothers, as well as a rise in the occurrence of Guillain Barre' syndrome in infected adults. Importantly, there are no licensed therapies or vaccines against ZIKV infection. In this study, we generate and evaluate the in vivo efficacy of a novel, synthetic, DNA vaccine targeting the pre-membrane+envelope proteins (prME) of ZIKV. Following initial in vitro development and evaluation studies of the plasmid construct, mice and non-human primates were immunised with this prME DNA-based immunogen through electroporation-mediated enhanced DNA delivery. Vaccinated animals were found to generate antigen-specific cellular and humoral immunity and neutralisation activity. In mice lacking receptors for interferon (IFN)-α/β (designated IFNAR − / − ) immunisation with this DNA vaccine induced, following in vivo viral challenge, 100% protection against infection-associated weight loss or death in addition to preventing viral pathology in brain tissue. In addition, passive transfer of non-human primate anti-ZIKV immune serum protected IFNAR − / − mice against subsequent viral challenge. This study in NHP and in a pathogenic mouse model supports the importance of immune responses targeting prME in ZIKV infection and suggests that additional research on this vaccine approach may have relevance for ZIKV control and disease prevention in humans.
Output: ARTICLE In vivo protection against ZIKV infection and pathogenesis through passive antibody transfer and active immunisation with a prMEnv DNA vaccine
Temperature-sensitive mutants of the munne coronavirus JHM induced a sub~ acute demyelinatin 8 encephalomyelitis (SD~E) in youn~ rats. Neurological symptol~,; were associated with marked lesion3 of primary d~my¢;lination ".m the white matter of the central nervous system (CNS), and developing after an incubation time of several weeks to months. Many rats survived this infection and rco3vered completely from this CNS disease. Amon 8 43 survivors of SDE, 9 ra'~s developed a ~'elapse 27-153 days after onset of the first attack. Neuropathologica.l ex~n~ation ol~ these animals revealed areas of fresh| ¢~emyelination together with old remyelinated lesions. V'md antisens were detectable in the neighbourhood of fresh les:ions and in some ca~ infectious virus was re-i~lated from rats revealing low antibl~y titers to JHM virus. These results demonstrate that mutants of JHM virus can induca~ a relapsing demyelinating disease process, associated with a persistent in fection, which some similarities to chronic experimental allergic enceph~dor~ayel/tis.
Output: Relapsing Subacute Demyelina~:ing Encephalomyelitis in Rats during the Course of Coronavirus JHM Infection
A multiplex reverse transcription-nested polymerase chain reaction (RT-nPCR) method was developed for the detection and differentiation of wild-type and vaccine strains of canine distemper virus (CDV). A pair of primers (P1 and P4) specific for CDV corresponding to the highly conserved region of the CDV genome were used as a common primer pair in the first-round PCR of the nested PCR. Primers P2 specific for CDV wild-type strains, were used as the forward primer together with the common reverse primer P4 in the second round of nested PCR. Primers P3, P5 specific for CDV wild-type strain or vaccine strain, were used as the forward primer together with the common reverse primer P4+P6 in the second round of nested PCR. A fragment of 177 bp was amplified from vaccine strain genomic RNA, and a fragment of 247 bp from wild-type strain genomic RNA in the RT-nPCR, and two fragments of 247 bp and 177 bp were amplified from the mixed samples of vaccine and wild-type strains. No amplification was achieved for uninfected cells, or cells infected with Newcastle disease virus (NDV), canine parvovirus (CPV), canine coronavirus (CCV), rabies virus (RV), or canine adenovirus (CAV). The RT-nPCR method was used to detect 30 field samples suspected of canine distemper from Heilongjiang and Jilin Provinces, and 51 samples in Shandong province. As a result of 30 samples, were found to be wild-type-like, and 5 to be vaccine-strain-like. The RT-nPCR method can be used to effectively detect and differentiate wild-type CDV-infected dogs from dogs vaccinated with CDV vaccine, and thus can be used in clinical detection and epidemiological surveillance.
Output: Open Access SHORT REPORT A multiplex reverse transcription-nested polymerase chain reaction for detection and differentiation of wild-type and vaccine strains of canine distemper virus
Wistar rats were inoculated subcutaneously with either type 1 (HSV,) or type 2 (HSVJ Herpes simplex virus at 5 days of age. Animals were killed in extremis or at the end of the 14-day observation period postinoculation. Acute destructive meningoencephalitis with hemorrhage and leukocytic infiltration was observed in both groups. Polycaryocytes comprised of cells of the internal granular layer of the cerebellum were observed in some animals inoculated with HSV,. These multinucleated cells appeared to be formed by fusion of virusinfected cells, and intranuclear inclusion bodies were observed. Lesions in the leptomeninges were particularly striking in animals inoculated with HSV,. Viral replication in resident cells of the leptomeninges was demonstrated by electron microscopy.
Output: Leptomeningitis and Poiycaryocyte Formation in the CNS of Rats Inoculated Subcutaneously with Herpes Simplex Virus
The yeast two-hybrid system (Y2H) is a powerful method to identify binary protein-protein interactions in vivo. Here we describe Y2H screening strategies that use defined libraries of open reading frames (ORFs) and cDNA libraries. The array-based Y2H system is well suited for interactome studies of small genomes with an existing ORFeome clones preferentially in a recombination based cloning system. For large genomes, pooled library screening followed by Y2H pairwise retests may be more efficient in terms of time and resources, but multiple sampling is necessary to ensure comprehensive screening. While the Y2H false positives can be efficiently reduced by using built-in controls, retesting, and evaluation of background activation; implementing the multiple variants of the Y2H vector systems is essential to reduce the false negatives and ensure comprehensive coverage of an interactome.
Output: Mapping the Protein-Protein Interactome Networks Using Yeast Two-Hybrid Screens
Background: Sporozoite immunization of animals and humans under a chemo-prophylactic cover of chloroquine (CPS-CQ) efficiently induces sterile protection against malaria. In humans, CPS-CQ is strikingly more efficient than immunization with radiation attenuated sporozoites (RAS), raising the hypothesis that this might be partially due to CQ. Chloroquine, an established anti-malarial drug, is also well known for its immune modulating properties including improvement of cross-presentation. The aim of this study was to investigate whether co-administration of CQ during sporozoite immunization improves cellular responses and protective efficacy in Plasmodium berghei models. Methods: A number of experiments in selected complimentary P. berghei murine models in Balb/cByJ and C57BL/6j mice was performed. First, the effect of CQ administration on the induction of protection and immune responses by RAS immunization was studied. Next, the effect of CQ on the induction of circumsporozoite (CS) protein-specific CD8 + T cells by immunization with P. berghei parasites expressing a mutant CS protein was investigated. Finally, a direct comparison of CPS-CQ to CPS with mefloquine (MQ), an anti-malarial with little known immune modulating effects, was performed. Results: When CQ was co-administered during immunization with graded numbers of RAS, this did not lead to an increase in frequencies of total memory CD8 + T cells or CS protein-specific CD8 + T cells. Also parasite-specific cytokine production and protection remained unaltered. Replacement of CQ by MQ for CPS immunization resulted in significantly reduced percentages of IFNγ producing memory T cells in the liver (p = 0.01), but similar protection. Conclusions: This study does not provide evidence for a direct beneficial effect of CQ on the induction of sporozoite-induced immune responses and protection in P. berghei malaria models. Alternatively, the higher efficiency of CPS compared to RAS might be explained by an indirect effect of CQ through limiting blood-stage exposure after immunization or to increased antigen exposure and, therefore, improved breadth of the immune response.
Output: Studying the effect of chloroquine on sporozoite-induced protection and immune responses in Plasmodium berghei malaria
Experimental studies were conducted to evaluate two species of cotton rats, Sigmodon hispidus and Sigmodon fulviventer, as a model for severe acute respiratory syndrome (SARS). Blood and turbinate wash samples, and lung tissue were collected from each animal at different time points after SARS coronavirus (CoV) infection for determining the growth curve of virus, if any, by the standard infectivity assay in Vero E6 cells. In addition, sections of the lung, liver, spleen, and kidney were taken and used for histology analysis. All animals were observed daily for signs of illness, and in some experiments, animals were weighed on the day when they were sacrificed. The results indicated that the cotton rat species, S. hispidus and S. fulviventer, were not a useful model for either SARS-CoV infection or disease. This observation was supported by the absence of any signs of illness, the failure to consistently demonstrate virus in the blood and tissues, and the absent of any notable histopathology. However, infected animals were capable of producing neuralizing antibodies against SARS-CoV, suggesting the seroconversion did occur. Further studies are warranted to consider other animal species in efforts to find better animal models for the evaluation of SARS-CoV vaccines and antiviral drugs. Key Words: Cotton rats-SARS-Model animal.
Output: Evaluation of Cotton Rats as a Model for Severe Acute Respiratory Syndrome
Previous studies have shown that mice can be protected from a lethal infection with the neurotropic JHM strain of mouse hepatitis virus (JHMV) by the adoptive transfer of delayed-type hypersensitivity (DTH)-inducer T cell clones specific for the virus. Protection does not involve the suppression of virus replication in the central nervous system (CNS) or via augmentation of the antiviral antibody response. In the present report we have compared the CNS lesions induced by JHMV in lethally infected and T cell clone protected mice. The presence of virus-specific T cell clones induced a transient increase in mononuclear cell infiltration into the parenchyma of the brains of protected mice, consistent with previous data suggesting that a DTH response was responsible for protection. Immunohistochemical studies suggested further that virus was not replicating in the ependyma or cellular infiltrate, but that the presence of the T cell clone prevented neuronal infection. While the mechanism of effectively altering the in vivo cellular tropism is unknown, survival is accompanied by increased specific destruction of target tissues with fulminant CNS demyelination and an increased incidence of persistent infection.
Output: Studies on the mechanism of protection from acute viral encephalomyelitis by delayed-type hypersensitivity inducer T cell clones
Angiotensin-converting enzyme, a member of the M2 metalloprotease family, and endothelin-converting enzyme, a member of the M13 family, are key components in the regulation of blood pressure and electrolyte balance in mammals. From this point of view, they serve as important drug targets. Recently, the involvement of these enzymes in the development of Alzheimer's disease was discovered. The existence of homologs of these enzymes in invertebrates indicates that these enzyme systems are highly conserved during evolution. Most invertebrates lack a closed circulatory system, which excludes the need for blood pressure regulators. Therefore, these organisms represent excellent targets for gaining new insights and revealing additional physiological roles of these important enzymes. This chapter reviews the structural and functional aspects of ACE and ECE and will particularly focus on these enzyme homologues in invertebrates.
Output: Structure, Evolutionary Conservation, and Functions of Angiotensin-and Endothelin-Converting Enzymes
Background: Embryonated chicken eggs have been used since the mid-20th century to grow a wide range of animal viruses to high titers. However, eggs have found so far only limited use in the production of recombinant proteins. We now describe a system, based on a Sendai virus minigenome, to produce large amounts of heterologous viral glycoproteins in the allantoic cavity of embryonated eggs. Results: Soluble forms of human respiratory syncytial virus (HRSV) and human metapneumovirus (HMPV) fusion (F) proteins, devoid of their transmembrane and cytoplasmic domains, were produced in allantoic fluids using the Sendai minigenome system. The first step was rescuing in cell cultures Sendai virus minigenomes encoding the proteins of interest, with the help of wild type Sendai virus. The second step was propagating such recombinant defective viruses, together with the helper virus, in the allantoic cavity of chicken embryonated eggs, and passage to optimize protein production. When compared with the production of the same proteins in the culture supernatant of cells infected with vaccinia recombinants, the yield in the allantoic fluid was 5-10 fold higher. Mutant forms of these soluble proteins were easily constructed by site-directed mutagenesis and expressed in eggs using the same approach. The simplicity and economy of the Sendai minigenome system, together with the high yield achieved in the allantoic fluid of eggs, makes it an attractive method to express soluble glycoproteins aimed for structural studies.
Output: High level expression of soluble glycoproteins in the allantoic fluid of embryonated chicken eggs using a Sendai virus minigenome system
medRxiv preprint [Abstract]Objective Coronavirus disease 2019 (COVID-19) has become pandemic in the world. The need for IgG-IgM combined antibody test is booming, but data on diagnostic indexes evaluation was inadequate. The aim of this study was to evaluate diagnostic indexes of a rapid IgG-IgM combined antibody test for SARS-CoV-2. Methods A total of 179 patients were enrolled. Serum were collected for IgG-IgM combined antibody test and corresponding nasal and pharyngeal swab specimens were collected for SARS-CoV-2 RT-PCR. According to SARS-CoV-2 RT-PCR results, patients under study were categorized as PCR positive group in 90 patients and PCR negative group in 89 patients. Results 1. Of the 90 PCR positive samples, 77 were tested positive by SARS-CoV-2 IgG-IgM test kit, yielding a sensitivity of 85.6%. Meanwhile, of the 89 PCR negative sample, 8 samples were detected positive, resulting in a specificity of 91%. Positive predictive value, negative predictive value and accuracy of this test kit was 95.1%, 82.7%, and 88.3%, respectively. Kappa efficiency between IgG/IgM test kit and RT-PCR were 0.75. 2. Accuracy in mild/common and severe/critical subgroup were 73.9% and 97.7%, respectively. Accuracy in clinical confirmed, suspected cases and other disease subgroups were 70%, 60%, and 100%, respectively. 3. Patients were further divided into '0 -7', '8 -15' and '>= 16' groups according to the time from illness onset to sample collection. Sensitivity, specificity and accuracy in these three groups were 18.8%, 77.8% and 40%; 100%, 50% and 87.5%; 100%, 64.3%, and 93.9, respectively. Conclusion The sensitivity and specificity of this ease-of-use IgG/IgM combined test kit were adequate, plus short turnaround time, no specific requirements for additional equipment or skilled technicians, all of these collectively contributed to its competence for mass testing. At the current stage, it cannot take the place of SARA-CoV-2 nucleic acid RT-PCR, but can be served as a complementary option for RT-PCR. The combination of RT-PCR and IgG-IgM combined test kit could provide further insight into SARS-CoV-2 infection diagnosis.
Output: Diagnostic Indexes of a Rapid IgG/IgM Combined Antibody Test for SARS-CoV-2
Viruses cause a large number of diseases in humans, some of which are fatal, while others are highly debilitating. A majority of viral diseases attack infants and young children, while others strike people in their prime. Development of preventive measures against viral diseases is, therefore, of paramount importance. Vaccination is the most cost-effective medical intervention for preventing mortality and morbidity against infectious diseases. A number of effective and safe vaccines are currently available against several viral diseases of significant medical importance. Many of these manufactured in India, are at par with international standards and are affordable. For many other viral diseases, for which vaccines are currently not available, research is underway at various national laboratories, as well as in the private sector companies in India. The present overview highlights the various vaccine preventable viral diseases that are of special importance to India and aims to provide a glimpse of the various vaccines that are currently available, or are under development in India. India has a strong presence in the global vaccine scenario. Currently there are at least 13 major vaccine manufacturers in the country, with the number steadily increasing. India is a major importer as well as exporter of vaccines [1], with the Indian market for vaccines being valued at over USD
Output: Viral Vaccines in India: An Overview
Background: Personal protective equipment (PPE) is known to be a crucial means of preventing influenza pandemics; however, the amount of PPE that should be stored in hospital settings has been unclear. Objectives: The purpose of this paper is to propose a PPE calculation system to help hospitals to decide their PPE stockpile. Methods: We searched influenza guidelines from a number of countries and research papers on protective devices and infectious diseases. The PPE calculation system included factors such as the influenza pandemic period, risk classification by health care workers (HCW) type, and the type and number of PPE for a HCW per day. Results: We concluded that 4 sets of PPE (N95 respirators, double gloves, gowns, and goggles) per day should be prepared for HCWs in a high-risk group. Similarly, 2 sets of appropriate PPE, depending on the risk level, are required for medium-and low-risk groups. In addition, 2 surgical masks are required for every worker and inpatient and 1 for each outpatient. The PPE stockpile should be prepared to cover at least an 8-week pandemic. Conclusion: Purchasing a PPE stockpile requires a sizable budget. The PPE calculation system in this paper will hopefully support hospitals in deciding their PPE stockpile.
Output: Stockpile of personal protective equipment in hospital settings: Preparedness for influenza pandemics
Ecological perturbations caused by biotic invasion have been identified as a growing threat to global sustainability. Invasive alien plants species (IAPS) are considered to be one of the major drivers of biodiversity loss and thereby altering the ecosystem services and socio-economic conditions through different mechanisms. Although the ecological impacts of IAPS are well documented, there is a dearth of studies regarding their economic quantification, livelihood considerations, biotechnological prospects (phytoremediation, bioenergy, phytosynthesis of nanoparticles, biomedical, industrial applications etc.) and human health risk assessments of IAPS. In this context, the current panoramic review aimed to investigate the environmental, socio-ecological and health risks posed by IAPS as well as the compounded impact of IAPS with habitat fragmentation, climate and land use changes. To this end, the need of an integrated trans-disciplinary research is emphasized for the sustainable management of IAPS. The management prospects can be further strengthened through their linkage with geo-spatial technologies (remote sensing and GIS) by mapping and monitoring the IAPS spread. Further, the horizon of IAPS management is expanded to ecological indicator perspectives of IAPS, biosecurity, and risk assessment protocols with critical discussion. Moreover, positive as well as negative implications of the IAPS on environment, health, ecosystem services and socio-economy (livelihood) are listed so that a judicious policy framework could be developed for the IAPS management in order to mitigate the human health implications.
Output: Invasive alien plant species: Their impact on environment, ecosystem services and human health
Acute disseminated encephalomyelitis is a rare disease of central nervous system, which can present with a variety of clinical manifestations. That is why first attack of ADEM, in particular remains a diagnostic puzzle. Early anticipation and diagnosis is important for better outcomes. We present a case of acute disseminated encephalomyelitis which initially had atypical clinical features with cough, expectoration, fever and later manifested strange neurological features, diagnosed to be a case of acute disseminated encephalomyelitis based on radio-imaging.
Output: Acute disseminated encephalomyelitis: a call to the clinicians for keeping this rare condition on clinical radar Case report Open Access
Purpose: The Coronavirus disease 2019 reminds us of the SARS outbreak in 2003, and up to date, corticosteroid is commonly administrated to severe patients with COVID-19. Osteonecrosis of the femoral head (ONFH) is a common disabling complication among convalescent SARS patients who received corticosteroid therapy. In China, a considerable number of convalescent SARS patients with steroid-associated ONFH had undergone conservative treatment by Traditional Chinese Medicine (TCM), and this study aims to evaluate the long-term results of a spleen-invigorating Huo-Gu Formula (HGF) therapy in these patients. with bilateral steroid-associated ONFH (66 hips) were enrolled in this study. All patients received oral HGF therapy for six months when they were confirmed the diagnosis of steroid-associated ONFH. They had been regularly followed up at an interval of one year. Harris hip score and medical imaging modalities, including plain radiography, computed tomography, and magnetic resonance imaging, were performed to evaluate the outcomes. Results: Based on average 14 years of follow-up of HGF therapy (ranging from six to 16 years), 38 hips (57%) among the 66 hips developed definite osteoarthritis, and 14 hips (26%) in 53 pre-collapse hips (ARCO stage I or II) progressed to femoral head collapse(ARCO stage III or IV). Only five patients (also five hips) underwent total hip arthroplasty, and the mean hip survival time was over 15 years by the Kaplan-Meier analysis. We observed a mean Harris hip score of 63 points, which represented the reserve of 55% in pain score and 70% in physical function score. The severity of groin pain was not correlated to the severity of osteoarthritis. Chinese herbal HGF therapy demonstrates beneficial effects on preventing femoral head collapse, delaying total hip arthroplasty (THA )surgery, and maintaining physical function in the treatment of steroid-associated ONFH. HGF therapy might be therefore a good alternative for the treatment of steroid-associated ONFH secondary to rheumatologic and infection diseases.
Output: Journal Pre-proof Chinese herbal Huo-Gu Formula for treatment of steroid-associated osteonecrosis of femoral head: a 14-years follow-up of convalescent SARS patients Chinese herbal Huo-Gu Formula for treatment of steroid-associated osteonecrosis of femoral head: a 14-years follow-up of convalescent SARS patients
doi: bioRxiv preprint 65 required for the antiviral activity of both IFITM3 and IFITM1 [9]. The subcellular localization of 66 IFITMs is a key determinant of their antiviral profile. When expressed singly, IFITM3 and IFITM2 67 preferentially localize to early and late endosomes and lysosomes, and restrict viruses that enter via 68 these endo-lysosomal compartments. In contrast, IFITM1 primarily localizes at the cell surface and 69 can restrict viruses that enter through the plasma membrane [11-14]. Indeed, mutants of IFITM3 70 that lack an N-terminal endocytic sorting motif 20 YEML 23 localize to the plasma membrane and lose 71 their ability to inhibit influenza A virus (IAV), alphavirus and coronavirus infection by endosomal 72 routes [14-18]. 73 74 Studies focusing on IFITM3 restriction of IAV and Semliki Forest Virus (SFV) indicate that virus 75 internalization is unaffected by IFITM3 expression and, for SFV at least, the viral envelope 76 . CC-BY-NC-ND 4.0 International license author/funder. It is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/737841 doi: bioRxiv preprint 109 knockout mice show enhanced morbidity after infection with IAV, alphaviruses and flaviviruses [33-110 .
Output: Comparative analysis reveals adaptive evolution of bat IFITMs and a novel 1 antiviral determinant
Background: Immunosuppressive therapy for renal allograft recipients has changed substantially since the introduction of the anti-CD25 monoclonal antibody, basiliximab. We hypothesized that recent improvements in immunosuppressive treatment may reduce the incidence of osteonecrosis of the femoral head (ONFH). This study aimed to investigate transitional changes in the incidence of OFNH among renal transplant recipients by MRI. Methods: Participants comprised 110 patients who had undergone renal transplantation from 2003 to 2012, during which time basiliximab was in regular use at our institute (Recent group), and 232 patients who had undergone RT between 1986 and 2003 (Past group). We compared ONFH incidence between the two groups and evaluated risk factors for ONFH, including immunosuppressants (calcineurin inhibitors, basiliximab, and/or steroids) and postoperative renal function. Results: Incidence of ONFH was lower in the Recent group (0%) than in the Past group (3.4%; p ¼ 0.043). In the Recent group, age was greater, ABO/human leukocyte antigen incompatibility was worse, while steroid dose was decreased and post-transplant renal function was improved. Cumulative methylprednisolone dose at postoperative week 2 and delayed graft function were identified as risk factors for ONFH. Conclusion: Risk of ONFH after renal transplantation has fallen with the advent of regular use of basiliximab, although this agent does not appear to be a factor directly associated with the incidence of ONFH. Study design: Clinical prognostic study (Level III case control study).
Output: Original Article
Background: Micro-organisms transmitted from vertebrate animalsincluding livestockto humans account for an estimated 60% of human pathogens. Micro-organisms can be transmitted through inhalation, ingestion, via conjunctiva or physical contact. Close contact with animals is crucial for transmission. The role of intensity and type of contact patterns between livestock and humans for disease transmission is poorly understood. In this systematic review we aimed to summarise current knowledge regarding patterns of human-livestock contacts and their role in micro-organism transmission. Methods: We included peer-reviewed publications published between 1996 and 2014 in our systematic review if they reported on human-livestock contacts, human cases of livestock-related zoonotic diseases or serological epidemiology of zoonotic diseases in human samples. We extracted any information pertaining the type and intensity of human-livestock contacts and associated zoonoses. Results: 1522 papers were identified, 75 were included: 7 reported on incidental zoonoses after brief animalhuman contacts (e.g. farm visits), 10 on environmental exposures and 15 on zoonoses in developing countries where backyard livestock keeping is still customary. 43 studies reported zoonotic risks in different occupations. Occupations at risk included veterinarians, culling personnel, slaughterhouse workers and farmers. For culling personnel, more hours exposed to livestock resulted in more frequent occurrence of transmission. Slaughterhouse workers in contact with live animals were more often positive for zoonotic micro-organisms compared to co-workers only exposed to carcasses. Overall, little information was available about the actual mode of micro-organism transmission. Conclusions: Little is known about the intensity and type of contact patterns between livestock and humans that result in micro-organism transmission. Studies performed in occupational settings provide some, but limited evidence of exposure response-like relationships for livestock-human contact and micro-organism transmission. Better understanding of contact patterns driving micro-organism transmission from animals to humans is needed to provide options for prevention and thus deserves more attention.
Output: Human-livestock contacts and their relationship to transmission of zoonotic pathogens, a systematic review of literature-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
Porphyromonas gulae is a major periodontal pathogen in dogs, which can be transmitted to their owners. A major virulence factor of P. gulae consists of a 41-kDa filamentous appendage (FimA) on the cell surface, which is classified into three genotypes: A, B, and C. Thus far, inhibition of periodontal disease in dogs remains difficult. The present study assessed the inhibitory effects of a combination of clindamycin and interferon alpha (IFN-α) formulation against P. gulae and periodontal disease. Growth of P. gulae was significantly inhibited by clindamycin; this inhibition had a greater effect on type C P. gulae than on type A and B isolates. In contrast, the IFN-α formulation inhibited the expression of IL-1β and COX-2 elicited by type A and B isolates, but not that elicited by type C isolates. Furthermore, periodontal recovery was promoted by the administration of both clindamycin and ifn-α formulation to dogs undergoing periodontal treatment; moreover, this combined treatment reduced the number of fimA genotypes in oral specimens from treated dogs. these results suggest that a combination of clindamycin and ifn-α formulation inhibit P. gulae virulence and thus may be effective for the prevention of periodontal disease induced by P. gulae.
Output: inhibition of Porphyromonas gulae and periodontal disease in dogs by a combination of clindamycin and interferon alpha
An 11-year-old female American shorthair cat was presented with a 3-month history of hindlimb ataxia and knuckling of the left forelimb. Clinical abnormalities included weight loss, hyperaesthesia of the neck and back, cardiac murmur and systemic muscle atrophy. The cat died 10 days after the initial presentation and a necropsy examination was performed. Grossly, extensive pale lesions were seen in the wall of the left ventricle and the septum of the heart. There were no detectable masses in the heart, skeletal muscles or peripheral nerves. Histopathological examination revealed diffuse, extensive infiltration of atypical lymphoid cells in the heart; the cardiac muscles were markedly degenerate and atrophic and were replaced by the neoplastic cells. Neoplastic cells with similar morphology were seen in all specimens of the skeletal muscles and peripheral nerves. Clonality analysis of the paraffin wax-embedded heart tissue revealed a monoclonal rearrangement of the gene encoding the T-cell receptor g chain. Based on these findings, the case was diagnosed as T-cell lymphoma with tropism for striated muscle and peripheral nerve.
Output: A Case of Feline T-cell Lymphoma with Tropism for Striated Muscle and Peripheral Nerve ScienceDirect
Bioaerosols (particles of biological origin) can be produced from living or dead plants and animals. They can potentially serve as the cloud condensation and ice nuclei (CCN and IN). Their role in global carbon cycle further highlights importance of studying their variability to link up with climate relevance parameters. Focusing on tropical region reveals that it holds wealthy number of human population and has massive vegetation cover-area. From Indian region, production estimates of bioaerosols from human population (current: *1.25 billion; of which over 45% resides in Indo-Gangetic Plain: IGP) and Wildlife Sanctuaries and National Parks (100 in numbers, situated from north to south and east to west) is not known. Most of the forest fires in India occur during March-June (hot and drier season). The detailed information on chemical composition, fingerprinting and radiative forcing from regional forest fires is also lacking. Unlike natural sources (forest cover and fires), the seasonal variability of pollutants emission characteristic and chemical, optical and radiative forcing are relatively well studied from anthropogenic biomass (post-harvest paddy-and wheat-residue and biofuels) burning emission in India. However, the abundance of bioaerosols and their variability over a large stretch of IGP (north-west to north-east) was not well documented. Towards this, we have undertaken a year-long campaign to study and document (first-attempt) bioaerosols variability over a complete annual cycle from central IGP. We observed a parallel enhancement in concentrations of fine-particulate matter (PM 2.5 in October-November: 158 ± 89 µg m −3 as compared to June-September months: 40 ± 18 µg m −3 ; two-tailed t = 8.2, p < 0.05) and bioaerosols (particularly Gram-negative bacteria: GNB, a source of endotoxin in ambient air; 186 ± 87 CFU/m 3 during October-November as compared to 114 ± 58 CFU/m 3 ; t = 4.0, p < 0.05) with the biomass burning emissions intensification period. The abundance of bioaerosols exhibits influence of ambient meteorology, for example GNB exhibited negative correlations with T, wind speed 93 and heavy (>4 mm daily) precipitation, whereas it showed positive correlations with RH and low precipitation amount (<4 mm). Studying bioaerosols and establishing its linkage to health and climate appear to be of utmost importance. CFU Colony forming units EU Endotoxin units GNB Gram-negative bacteria GPB Gram-positive bacteria IGP Indo-Gangetic Plain K þ BB Biomass burning derived K + LPS Lipopolysaccharides OC Organic carbon in particulate phase RH Relative humidity (in %) T Ambient temperature (in°C)
Output: Bioaerosols Over the Indo-Gangetic Plain: Influence of Biomass Burning Emission and Ambient Meteorology
Background: current tools to predict the severity of respiratory syncytial virus (RsV) infection might be improved by including immunological parameters. We hypothesized that a combination of inflammatory markers would differentiate between severe and mild disease in RsV-infected children. Methods: Blood and nasopharyngeal samples from 52 RsVinfected children were collected during acute infection and after recovery. Retrospectively, patients were categorized into three groups based on disease severity: mild (no supportive treatment), moderate (supplemental oxygen and/or nasogastric feeding), and severe (mechanical ventilation). clinical data, number of flow-defined leukocyte subsets, and cytokine concentrations were compared. results: children with severe RsV infection were characterized by young age; lymphocytopenia; increased interleukin (IL)-8, granulocyte colony-stimulating factor (G-csF), and IL-6 concentrations; and decreased chemokine (c-c motif ) ligand (ccL-5) concentrations in plasma. The combination of plasma levels of IL-8 and ccL-5, and cD4 + T-cell counts, with cutoff values of 67 pg/ml, 13 ng/ml, and 2.3 × 10 6 /ml, respectively, discriminated severe from mild RsV infection with 82% sensitivity and 96% specificity. conclusion: This study demonstrates that the combination of cD4 + T-cell counts and IL-8 and ccL-5 plasma concentrations correlates with disease severity in RsV-infected children. In addition to clinical features, these immunological markers may be used to assess severity of RsV infection and guide clinical management.
Output: cd4 + t-cell counts and interleukin-8 and ccl-5 plasma concentrations discriminate disease severity in children with rsV infection RSV Monoinfection Is Associated With Disease Severity, Irrespective of Viral Load
The rat (Rattus norvegicus) is used in a broad field of biomedical research, and numerous animal models for human diseases have been developed. The rat genetic map, however, remains poorly documented. Hedrich (1990) described a rat linkage map consisting of 13 groups, of which only 6 were assigned to chromosomes. Levan and coworkers (1991, 1992) collected mapping information from the literature, including their own works. Their tables and figures contain gene chromosomal assignments, cytogenetical localizations, and comparisons of the rat G-banding pattern with those of mice and humans, but do not include any information about gene orders or distances. Recently, an informative rat genetic linkage map has been reported by Serikawa and colleagues (1992b). It is based on the segregation of 125 polymorphic markers in seven rat backcrosses and two F 2 crosses, and all of the linkage groups are assigned to particular chromosomes. The linkage map and the information on microsatellite markers became a great help for genetic studies with rat models for human diseases. Since then, a considerable amount of new data for the rat linkage map has appeared in several publications. We, therefore, have collected mapping data published up to the middle of 1993, including our recent reports, and have summarized it here in a list of mapped loci. This genetic map, constructed by combining several linkage data, and two comparative maps for mouse or human homologous rat genes should be very informative to many researchers working on genetic studies in rats, mice, or humans. Rat genetic linkage map
Output: Special Report A rat genetic linkage map and comparative maps for mouse or human homologous rat genes
Coronaviruses (CoVs) are positive-sense single-stranded RNA viruses and contain the largest known RNA genomes, ranging from 27 to 32 kilobases in length. CoVs are capable of transspecies movement as evidenced by the Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) epidemic in 2002-2003 [1,2]. Additionally, the emergence of Middle East Respiratory Syndrome coronavirus (MERS-CoV) in 2012 demonstrates that CoVs continue to cause severe and lethal human disease [3] . Exactly how CoVs maintain the integrity of their large genomes while generating the population diversity required for emergence and adaptation has been a major question in RNA virology. The discovery of 39-to-59 exoribonuclease (ExoN) activity within CoV nonstructural protein 14 (nsp14-ExoN), which is critical for CoV high-fidelity replication, has challenged the long-held paradigm that RNA viruses cannot proofread and raises the possibility of an entirely new model for how RNA viruses regulate replication fidelity. We will summarize: 1) the data supporting proofreading during CoV replication; 2) the possibility of a multi-protein fidelity complex, using E. coli DNA polymerase III as a conceptual framework; and 3) the promise of genetic and therapeutic interference with fidelity regulation as an approach for attenuation and treatment of CoVs.
Output: Coronaviruses as DNA Wannabes: A New Model for the Regulation of RNA Virus Replication Fidelity
The renin-angiotensin system (RAS) is a critical regulator of hypertension, primarily through the actions of the vasoactive peptide Ang II, which is generated by the action of angiotensin-converting enzyme (ACE) mediating an increase in blood pressure. The discovery of ACE2, which primarily metabolises Ang II into the vasodilatory Ang-(1-7), has added a new dimension to the traditional RAS. As a result there has been huge interest in ACE2 over the past decade as a potential therapeutic for lowering blood pressure, especially elevation resulting from excess Ang II. Studies focusing on ACE2 have helped to reveal other actions of Ang-(1-7), outside vasodilation, such as antifibrotic and antiproliferative effects. Moreover, investigations focusing on ACE2 have revealed a variety of roles not just catalytic but also as a viral receptor and amino acid transporter. This paper focuses on what is known about ACE2 and its biological roles, paying particular attention to the regulation of ACE2 expression. In light of the entrance of human recombinant ACE2 into clinical trials, we discuss the potential use of ACE2 as a therapeutic and highlight some pertinent questions that still remain unanswered about ACE2.
Output: Angiotensin-Converting Enzyme 2: The First Decade
Rubella virus is a small enveloped virus that assembles in association with Golgi membranes. Freeze-substitution electron microscopy of rubella virus-infected cells revealed a previously unrecognized virion polymorphism inside the Golgi stacks: homogeneously dense particles without a defined core coexisting with less dense, mature virions that contained assembled cores. The homogeneous particles appear to be a precursor form during the virion morphogenesis process as the forms with mature morphology were the only ones detected inside secretory vesicles and on the exterior of cells. In mature virions potential remnants of C protein membrane insertion were visualized as dense strips connecting the envelope with the internal core. In infected cells Golgi stacks were frequently seen close to cytopathic vacuoles, structures identified as the sites for viral RNA replication, along with the rough endoplasmic reticulum and mitochondria. These associations could facilitate the transfer of viral genomes from the cytopathic vacuoles to the areas of rubella assembly in Golgi membranes.
Output: Structural maturation of rubella virus in the Golgi complex