niryuu/sni-each-converted huggingface dataset:
Equine coronavirus (ECoV) is a known cause of fever, anorexia, and lethargy in adult horses. Although there are multiple reports of ECoV outbreaks, less is known about the clinical presentation of individual horses during a nonoutbreak situation. The purpose of this study was to describe the clinical presentation of horses diagnosed with ECoV infection that were not associated with an outbreak. Medical records of all horses admitted to Washington State University, Veterinary Teaching Hospital, during an 8year period were reviewed (2010e2018). The five horses included in this study were older than 1 year of age, were diagnosed with colitis, tested positive for ECoV using real-time polymerase chain reaction, and were negative to other enteric pathogens. Interestingly, 4 of 5 horses had moderate to severe diarrhea, 3 had abnormal large colon ultrasonography, 2 had transient ventricular tachycardia and 2 had clinicopathologic evidence of liver dysfunction. ECoV should be included as a differential diagnosis for individual horses presenting with anorexia, fever, lethargy, and colitis. Early identification of ECoV cases is key to implement appropriate biosecurity measures to prevent the potential spread of this disease.
Output: Equine Coronavirus-Associated Colitis in Horses: A Retrospective Study
Analysis of therapeutic targets for SARS-CoV-2 and discovery of potential drugs by computational methods, Acta Pharmaceutica Sinica B, https://doi. Twenty structures including 19 SARS-CoV-2 targets and 1 human target were built by homology modeling. Library of ZINC drug database, natural products, 78 anti-viral drugs were screened against these targets plus human ACE2. This study provides drug repositioning candidates and targets for further in vitro and in vivo studies of SARS-CoV-2. (Mengzhu Zheng), xingzhouli@aliyun.com (Xingzhou Li). † These authors made equal contributions to this work. Abstract SARS-CoV-2 has caused tens of thousands of infections and more than one thousand deaths. There are currently no registered therapies for treating coronavirus infections. Because of time consuming process of new drug development, drug repositioning may be the only solution to the epidemic of sudden infectious diseases. We systematically analyzed all the proteins encoded by SARS-CoV-2 genes, compared them with proteins from other coronaviruses, predicted their structures, and built 19 structures that could be done by homology modeling. By performing target-based virtual ligand screening, a total of 21 targets (including two human targets) were screened against compound libraries including ZINC drug database and our own database of natural products. Structure and screening results of important targets such as 3-chymotrypsin-like protease (3CLpro), Spike, RNA-dependent RNA polymerase (RdRp), and papain like protease (PLpro) were discussed in detail. In addition, a database of 78 commonly used anti-viral drugs including those currently on the market and undergoing clinical trials for SARS-CoV-2 was constructed. Possible targets of these compounds and potential drugs acting on a certain target were predicted. This study will provide new lead compounds and targets for further in vitro and in vivo studies of SARS-CoV-2, new insights for those drugs currently ongoing clinical studies, and also possible new strategies for drug repositioning to treat SARS-CoV-2 infections.
Output: Journal Pre-proof Analysis of therapeutic targets for SARS-CoV-2 and discovery of potential drugs by computational methods Analysis of therapeutic targets for SARS-CoV-2 and discovery of potential drugs by computational methods
Human monoclonal antibodies (HuMAbs) prepared from patients with viral infections could provide information on human epitopes important for the development of vaccines as well as potential therapeutic applications. Through the fusion of peripheral blood mononuclear cells from a total of five influenzavaccinated volunteers, with newly developed murine-human chimera fusion partner cells, named SPY-MEG, we obtained 10 hybridoma clones stably producing anti-influenza virus antibodies: one for influenza A H1N1, four for influenza A H3N2 and five for influenza B. Surprisingly, most of the HuMAbs showed broad reactivity within subtype and four (two for H3N2 and two for B) showed broad neutralizing ability. Importantly, epitope mapping revealed that the two broad neutralizing antibodies to H3N2 derived from different donors recognized the same epitope located underneath the receptor-binding site of the hemagglutinin globular region that is highly conserved among H3N2 strains.
Output: Broad neutralizing human monoclonal antibodies against influenza virus from vaccinated healthy donors
The study of human-specific infectious agents has been hindered by the lack of optimal small animal models. More recently development of novel strains of immunodeficient mice has begun to provide the opportunity to utilize small animal models for the study of many human-specific infectious agents. The introduction of a targeted mutation in the IL2 receptor common gamma chain gene (IL2rg null ) in mice already deficient in T and B cells led to a breakthrough in the ability to engraft hematopoietic stem cells, as well as functional human lymphoid cells and tissues, effectively creating human immune systems in immunodeficient mice. These humanized mice are becoming increasingly important as pre-clinical models for the study of human immunodeficiency virus-1 (HIV-1) and other human-specific infectious agents. However, there remain a number of opportunities to further improve humanized mouse models for the study of human-specific infectious agents. This is being done by the implementation of innovative technologies, which collectively will accelerate the development of new models of genetically modified mice, including; i) modifications of the host to reduce innate immunity, which impedes human cell engraftment; ii) genetic modification to provide human-specific growth factors and cytokines required for optimal human cell growth and function; iii) and new cell and tissue engraftment protocols. The development of "next generation" humanized mouse models continues to provide exciting opportunities for the establishment of robust small animal models to study the pathogenesis of human-specific infectious agents, as well as for testing the efficacy of therapeutic agents and experimental vaccines.
Output: Generation of improved humanized mouse models for human infectious diseases NIH Public Access
Responding to the worldwide outbreak of SARS in 2003, virus removal performance and mechanism of a SMBR were investigated by employing phage T4 as a model virus. Two membrane modules were compared in continuous operation for about 75 days. During stable operation, SMBR achieved almost complete phage removal for both membrane modules. For the 0.22 mm module, the cake layer, the gel layer and the membrane contributed 6.3 log, 3.1 log and 1.7 log, respectively to phage removal, confirming the importance of the cake/gel layer formed on the surface of membrane. The damage of the cake/gel layer resulted in the decrease of phage removal. As for the 0.1 mm one, the membrane alone played a major role in phage removal. Inactivation by activated sludge and adsorption by cake/gel layer contributed about 3.6 log to phage removal everyday so that there was no phage accumulation in bulk solution. The results demonstrated that SMBR was an efficient system and recommended for treatment of virus-bearing wastewater. #
Output: Virus removal performance and mechanism of a submerged membrane bioreactor
On average, more than two new species of human virus are reported every year. We constructed the cumulative species discovery curve for human viruses going back to 1901. We fitted a statistical model to these data; the shape of the curve strongly suggests that the process of virus discovery is far from complete. We generated a 95% credible interval for the pool of as yet undiscovered virus species of 38-562. We extrapolated the curve and generated an estimate of 10-40 new species to be discovered by 2020. Although we cannot predict the level of health threat that these new viruses will present, we conclude that novel virus species must be anticipated in public health planning. More systematic virus discovery programmes, covering both humans and potential animal reservoirs of human viruses, should be considered.
Output: Temporal trends in the discovery of human viruses
Interferon-stimulated gene 15 (ISG15) is a member of the ubiquitin-like modifiers (ULM) family, which adopts a βgrasp fold domain(s) similar to ubiquitin (Ub) with only minor sequence homology. ISG15 consists of two Ub-like domains and aids the immune system in neutralizing infections by numerous pathogens and plays an important role in defending cells against many viruses including influenza A. Recently, Ub was found to be a substrate for ISG15, which can be ISGylated on Lys29 and Lys48, while the former is more dominant. The discovery of such hybrid ISG15-Ub chains brought forward various fundamental questions regarding the nature and effect of this conjugation. To further investigate the role of hybrid ISG15-Ub chains, the pure homogeneous material of these chains is needed in workable quantities. By applying advanced chemical strategies for protein synthesis, we report the total chemical synthesis of a 231-residue ISG15-Lys29-Ub hybrid chain. During the synthesis we encountered insoluble peptide fragments, and therefore we developed a new reversible Acm based solubilizing tag to efficiently tackle this hurdle. This new Acm tag was compared with the known Arg based Acm solubilizing tag and was found to be more reliable in terms of incorporation and efficiency as demonstrated in the synthesis of the native ISG15-Ub hybrid chain.
Output: Total Chemical Synthesis of ISGylated-Ubiquitin Hybrid Chain Assisted by Acetamidomethyl Derivatives with Dual Functions
The expression of eukaryotic antizyme genes requires þ 1 translational frameshifting. The frameshift in decoding most vertebrate antizyme mRNAs is stimulated by an RNA pseudoknot 3 0 of the frameshift site. Although the frameshifting event itself is conserved in a wide variety of organisms from yeast to mammals, until recently no corresponding 3 0 RNA pseudoknot was known in invertebrate antizyme mRNAs. A pseudoknot, different in structure and origin from its vertebrate counterparts, is now shown to be encoded by the antizyme genes of distantly related invertebrates. Identification of the 3 0 frameshifting stimulator in intermediate species or other invertebrates remains unresolved.
Output: Identification of a New Antizyme mRNA 11 Frameshifting Stimulatory Pseudoknot in a Subset of Diverse Invertebrates and its Apparent Absence in Intermediate Species
Bovine respirovirus 3 also known as Bovine parainfluenza virus type 3 (BPIV3) is one of the most important viral respiratory agents of both young and adult cattle. Rapid diagnosis could contribute greatly in containing epidemics and thus avoid economic losses. However, the lack of robust isothermal visual method poses difficulty. In this study, a novel isothermal assay for detecting BPIV3 was established. The method includes a lateral flow dipstick (LFD) assay combined with reverse transcription recombinase polymerase amplification (RT-RPA). First, the analytical sensitivity and specificity of BPIV3 LFD RT-RPA were tested. The LFD RT-RPA assay has a detection limit of up to 100 copies per reaction in 30 min at 38°C. Then the performance of LFD RT-RPA was evaluated using 95 clinical samples. Compared to qPCR, the LFD RT-RPA assay showed a clinical sensitivity of 94.74%, a clinical specificity of 96.05% and 0.8734 kappa coefficient. These results have demonstrated the efficiency and effectiveness of the method to be developed into a point of care protocol for the diagnosis of BPIV3.
Output: A lateral flow dipstick combined with reverse transcription recombinase polymerase amplification for rapid and visual detection of the bovine respirovirus 3
Evidence has accumulated that adult hematopoietic tissues and other organs contain a population of dormant stem cells (SCs) that are more primitive than other, already restricted, monopotent tissue-committed stem cells (TCSCs). These observations raise several questions, such as the developmental origin of these cells, their true pluripotent or multipotent nature, which surface markers they express, how they can be efficiently isolated from adult tissues, and what role they play in the adult organism. The phenotype of these cells and expression of some genes characteristic of embryonic SCs (ESCs), epiblast SCs (EPiSCs), and primordial germ cells (PGCs) suggests their early-embryonic deposition in developing tissues as precursors of adult SCs. In this review we will critically discuss all these questions and the concept that small dormant stem cells related to migratory PGCs, described as very small embryonic-like stem cells (VSELs), are deposited during embryogenesis in bone marrow and other organs as a backup population for adult tissue committed stem cells (TCSCs) and are involved in several processes related to tissue or organ rejuvenation, aging, and cancerogenesis. The most recent results on successful ex vivo expansion of human VSELs in chemically defined media free from feeder-layer cells opens up new and exciting possibilities for their application in regenerative medicine. ELH SCs elutriation-derived stem cells EPiSCs epiblast stem cells ICM inner cell mass MAPCs multipotent adult progenitor cells Ratajczak et al.
Output: A novel view of the adult stem cell compartment from the perspective of a quiescent population of very small embryonic- like stem cells HHS Public Access
Background: The laboratory has always played a very critical role in diagnosis of the diseases. The success of any disease programme is based on a functional laboratory network. Health laboratory services are an integral component of the health system. Efficiency and effectiveness of both clinical and public health functions including surveillance, diagnosis, prevention, treatment, research and health promotion are influenced by reliable laboratory services. The establishment of the African Regional polio laboratory for the Polio Eradication Initiative (PEI) has contributed in supporting countries in their efforts to strengthen laboratory capacity. On the eve of the closing of the program, we have shown through this article, examples of this contribution in two countries of the African region: Côte d'Ivoire and the Democratic Republic of Congo. Methods: Descriptive studies were carried out in Côte d'Ivoire (RCI) and Democratic Republic of Congo (DRC) from October to December 2014. Questionnaires and self-administered and in-depth interviews and group discussions as well as records and observation were used to collect information during laboratory visits and assessments. Results: The PEI financial support allows to maintain the majority of the 14 (DRC) and 12 (RCI) staff involved in the polio laboratory as full or in part time members. Through laboratory technical staff training supported by the PEI, skills and knowledge were gained to reinforce laboratories capacity and performance in quality laboratory functioning, processes and techniques such as cell culture. In the same way, infrastructure was improved and equipment provided. General laboratory quality standards, including the entire laboratory key elements was improved through the PEI accreditation process. Conclusion: The Polio Eradication Initiative (PEI) is a good example of contribution in strengthening public health laboratories systems in the African region. It has established strong Polio Laboratory network that contributed to the strengthening of capacities and its expansion to surveillance of other viral priority diseases such as measles, yellow fever, Influenza, MERS-CoV and Ebola. This could serve as lesson and good example of laboratory based surveillance to improving diseases prevention, detection and control in our middle and low income countries as WHO and partners are heading to polio eradication in the world.
Output: c World Health Organization Intercountry Support Office, Ouagadougou, Burkina Faso d Expanded Program on Immunization, WHO Regional Office for Africa, Inter-Country Support Team
Chest X-ray is a "golden standard" for the diagnosis and severity assessment of community-acquired pneumonia (CAP). However, it cannot be used as routine examination of CAP in children. The present study aims to investigate the roles of prealbumin (PA) in CAP in children and further determine the usefulness of PA in diagnosis and severity assessment of CAP in children. This was a retrospective analysis of 174 cases of hospitalized children with CAP. The following indicators were recorded: vital sign, inflammatory indexes, PA, and respiratory pathogens immunoglobulin M antibody test results. A total of 33 healthy children were selected as the control group. The results of laboratory tests between CAP and control groups were compared. CAP group was further divided into mild CAP and severe CAP groups, and vital signs and laboratory examination results of 2 groups were compared. The total positive rate of Mycoplasma pneumoniae in this study was 27.4%, and there was no significant difference in different seasons (P = 0.356). Compared with controls, there was no significant difference between procalcitonin and C-reactive protein in CAP group (P = 0.355, 0.061). The white blood cell count, percentage of neutrophils, neutrophil count, and erythrocyte sedimentation rate in the CAP group were significantly higher than those in control group, and PA was significantly lower than that in the control group (all P < 0.05). In the traditional cutoff value (<170 mg/L), the sensitivity of PA for the diagnosis of CAP was 0.847, which was significant higher than traditional inflammatory indicators. Moreover, it was found that PA was an independent protective factor for CAP in children based on multivariate analysis (odds ratio: 0.974; 95% confidence interval: 0.956-0.993; P = 0.008). PA level in severe CAP group was significantly lower than in mild CAP group (P = 0.001). With a cutoff value of 125 mg/L, the sensitivity and specificity of PA for the severity assessment of CAP were 0.703 and 0.714, respectively. Combined with traditional inflammatory markers, PA may improve the diagnostic efficacy of CAP in children. PA can be used as a reference marker to complement the chest X-rays for severity assessment of children CAP. Abbreviations: CAP = community-acquired pneumonia, CRP = C-reactive protein, ESR = erythrocyte sedimentation rate, LRI = lower respiratory infections, MP = Mycoplasma pneumoniae, PA = prealbumin, PCT = procalcitonin, RR = respiratory rate, WBC = white blood cell count.
Output: Valuable hematological indicators for the diagnosis and severity assessment of Chinese children with community-acquired pneumonia
In mononegaviruses, cap-MTase activities have been involved in the 2'O methylation and N7 methylation of the RNA cap structure. These activities play a critical role in the viral life cycle as N7 methylation ensures efficient viral mRNA translation and 2'O methylation hampers the detection of viral RNA by the host innate immunity. The functional characterization of the MTase+CTD domain of Sudan ebolavirus (SUDV) revealed cap-independent methyltransferase activities targeting internal adenosine residues. Besides this, the MTase+CTD also methylates, the N7 position of the cap guanosine and the 2'O position of the n1 guanosine provided that the RNA is sufficiently long. Altogether, these results suggest that the filovirus MTases evolved towards a dual activity with distinct substrate specificities. Whereas it has been well established that cap-dependent methylations promote protein translation and help to mimic host RNA, the characterization of an original capindependent methylation opens new research opportunities to elucidate the role of RNA internal methylations in the viral replication.
Output: The methyltransferase domain of the Sudan ebolavirus L protein specifically targets internal adenosines of RNA substrates, in addition to the cap structure
Clinical metagenomics (CMg) is the discipline that refers to the sequencing of all nucleic acid material present within a clinical specimen with the intent to recover clinically relevant microbial information. From a diagnostic perspective, next-generation sequencing (NGS) offers the ability to rapidly identify putative pathogens and predict their antimicrobial resistance profiles to optimize targeted treatment regimens. Since the introduction of metagenomics nearly a decade ago, numerous reports have described successful applications in an increasing variety of biological specimens, such as respiratory secretions, cerebrospinal fluid, stool, blood and tissue. Considerable advancements in sequencing and computational technologies in recent years have made CMg a promising tool in clinical microbiology laboratories. Moreover, costs per sample and turnaround time from specimen receipt to clinical management continue to decrease, making the prospect of CMg more feasible. Many difficulties, however, are associated with CMg and warrant further improvements such as the informatics infrastructure and analytical pipelines. Thus, the current review focuses on comprehensively assessing applications of CMg for diagnostic and subtyping purposes. Crown
Output: Highlighting Clinical Metagenomics for Enhanced Diagnostic Decision-making: A Step Towards Wider Implementation
Essential oil extracted from Houttuynia cordata Thunb. (H. cordata) is widely used in traditional Chinese medicine due to its excellent biological activities. However, impurities and deficient preparations of the essential oil limit its safety and effectiveness. Herein, we proposed a strategy to prepare H. cordata essential oil (HEO) safely and effectively by combining the solvent extraction and the macroporous resin purification flexibly, and then encapsulating it using microemulsion. The extraction and purification process were optimized by orthogonal experimental design and adsorption-desorption tests, respectively. The average houttuynin content in pure HEO was then validated at 44.3% ± 2.01%, which presented a great potential for industrial application. Subsequently, pure HEO-loaded microemulsion was prepared by high-pressure homogenization and was then fully characterized. Results showed that the pure HEO-loaded microemulsion was successfully prepared with an average particle size of 179.1 nm and a high encapsulation rate of 94.7%. Furthermore, safety evaluation tests and in vitro antiviral testing indicated that the safety and activity of HEO were significantly improved after purification using D101 resin and were further improved by microemulsion encapsulation. These results demonstrated that the purification of HEO by macroporous resin followed by microemulsion encapsulation would be a promising approach for industrial application of HEO for the antiviral therapies.
Output: molecules Purification of Houttuynia cordata Thunb. Essential Oil Using Macroporous Resin Followed by Microemulsion Encapsulation to Improve Its Safety and Antiviral Activity
Quantitative analysis and chromatographic fingerprinting for the quality evaluation of a Chinese herb Scutellaria baicalensis Georgi using capillary electrophoresis (CE) technique was developed. The separation was performed with a 50.0 cm (42.0 cm to the detector window) × 75 m i.d. fused-silica capillary, and the CE fingerprint condition was optimized using the combination of central composite design and multivariate analysis. The optimized buffer system containing 15 mM borate, 40 mM phosphate, 15 mM SDS, 15% (v/v) acetonitrile and 7.5% (v/v) 2-propanol was employed for the method development, and the baseline separation was achieved within 15 min. The determination of the major active components (Baicalin, Baicalein and Wogonin) was carried out using the optimized CE condition. Good linear relationships were provided over the investigated concentration ranges (the values of R 2 : 0.9997 for Baicalin, 0.9992 for Baicalein, and 0.9983 for Wogonin, respectively). The average recoveries of these target components ranged between 96.1-105.6%, 98.6-105.2%, and 96.3-105.0%, respectively. CE fingerprints combined with the quantitative analysis can be used for the quality evaluation of S. baicalensis.
Output: Quantitative analysis and chromatographic fingerprinting for the quality evaluation of Scutellaria baicalensis Georgi using capillary electrophoresis
Somatostatin receptor 2 (SSTR2) is a negative regulator of cell proliferation in human breast cancer. Since there is little information about SSTR2 in canine mammary gland tumor (MGT), we clarified its distribution and expression level in normal mammary gland, benign MGT and malignant MGT. SSTR2 expression determined by immunohistochemical staining was observed in the cytoplasm of luminal epithelial cells. The intensity was negatively correlated with malignancy: normal tissues and some of the benign tumors had the highest levels, while the malignant tumors had little or no SSTR2 expression. As for the Western blotting, SSTR2 protein level in benign tumors was significantly lower than the normal mammary gland. On the other hand, SSTR2 protein levels in two of three malignant tumors were higher than the other groups. These results suggest that SSTR2 expression alters according to the malignancy of canine MGT.
Output: Alteration of somatostatin receptor 2 expression in canine mammary gland tumor
With the features of extremely high selectivity and efficiency in catalyzing almost all the chemical reactions in cells, enzymes play vitally important roles for the life of an organism and hence have become frequent targets for drug design. An essential step in developing drugs by targeting enzymes is to identify drug-enzyme interactions in cells. It is both time-consuming and costly to do this purely by means of experimental techniques alone. Although some computational methods were developed in this regard based on the knowledge of the three-dimensional structure of enzyme, unfortunately their usage is quite limited because threedimensional structures of many enzymes are still unknown. Here, we reported a sequence-based predictor, called "iEzy-Drug, " in which each drug compound was formulated by a molecular fingerprint with 258 feature components, each enzyme by the Chou's pseudo amino acid composition generated via incorporating sequential evolution information and physicochemical features derived from its sequence, and the prediction engine was operated by the fuzzy K-nearest neighbor algorithm. The overall success rate achieved by iEzy-Drug via rigorous cross-validations was about 91%. Moreover, to maximize the convenience for the majority of experimental scientists, a user-friendly web server was established, by which users can easily obtain their desired results.
Output: iEzy-Drug: A Web Server for Identifying the Interaction between Enzymes and Drugs in Cellular Networking
The breaking of tolerance or unresponsiveness to self-antigens, involving the activation of autoreactive lymphocytes, is a critical event leading to autoimmune diseases. The precise mechanisms by which this can occur are mostly unknown. Viruses have been implicated in this process, among other etiological factors, such as genetic predisposition and cytokine activity. Several ways have been proposed by which a viral infection might break tolerance to self and trigger an autoreactive cascade that ultimately leads to the destruction of a specific cell type or an entire organ. The process termed 'molecular mimicry' and the use of transgenic models in which viral and host genes can be manipulated to analyze their effects in causing autoimmunity have been particular focuses for research. For example, there is a transgenic murine model of virus-induced autoimmune disease, in which a known viral gene is selectively expressed as a self-antigen in 13 cells of the pancreas. In these mice, insulin-dependent diabetes develops after either a viral infection, the release of a cytokine such as IFN-y, or the expression of the costimulatory molecule BZ1 in the islets of Langerhans. Recent studies using this model have contributed to the understanding of the pathogenesis of virus-induced autoimmune disease and have furthered the design and testing of novel immunotherapeutic approaches. Abbreviations APC antigen-presenting cell CMV cytomegalovirus CTL cytotoxic T lymphocyte GP glycoprotein IDDM insulin-dependent diabetes type II IFN interferon IL interleukin LCMV lymphocytic choriomeningitis virus MBP myelin basic protein MS multiple sclerosis NP nucleoprotein RIP rat insulin promoter TCR T cell receptor
Output: Virus-induced autoimmune disease
Human metapneumovirus (hMPV), a newly discovered virus of the family Paramyxoviridae, has been associated with upper and lower respiratory tract infections in different age groups in many countries. The putative attachment (G) glycoprotein of this virus was previously reported to have shown more extensive nucleotide and deduced amino acid sequence polymorphism than any other genomic regions of this virus, leading to four sub-lineages. Using a maximum likelihood-based codon substitution model of sequence evolution, here we report that sequences of extracellular domain of 8 amino acid sites in lineage 1a, and 3 amino acid sites each in lineage 1b, 2a, and 2b have a higher rate of nonsynonymous substitutions (d N ) than the synonymous substitutions (d S ) with a posterior probability above 0.95, thus suggesting the evidence of adaptive evolution driven by Darwinian selection. Although it is unclear whether these amino acid adaptations are driven by differential immune pressure or some other factors, identification of these positively selected amino acid sites would help in better screening using epitope mapping technology to identify and localize the sites that can be recognized by the immune system. We also observed surprisingly higher nucleotide substitution rates per site, per year for each lineage of hMPV than the rates that were previously reported for the human respiratory syncytial virus, suggesting rapid evolutionary dynamics of hMPV.
Output: Positive natural selection in the evolution of human metapneumovirus attachment glycoprotein
Arabia and the Middle East in September, 2012, with 44 laboratory-confi rmed cases as of May 23, 2013. We report detailed clinical and virological data for two related cases of MERS-CoV disease, after nosocomial transmission of the virus from one patient to another in a French hospital. Methods Patient 1 visited Dubai in April, 2013; patient 2 lives in France and did not travel abroad. Both patients had underlying immunosuppressive disorders. We tested specimens from the upper (nasopharyngeal swabs) or the lower (bronchoalveolar lavage, sputum) respiratory tract and whole blood, plasma, and serum specimens for MERS-CoV by real-time RT-PCR targeting the upE and Orf1A genes of MERS-CoV. Findings Initial clinical presentation included fever, chills, and myalgia in both patients, and for patient 1, diarrhoea. for Orf1a for an induced sputum sample from patient 2), whereas nasopharyngeal specimens were weakly positive or inconclusive. The two patients shared the same room for 3 days. The incubation period was estimated at 9-12 days for the second case. No secondary transmission was documented in hospital staff despite the absence of specifi c protective measures before the diagnosis of MERS-CoV was suspected. Patient 1 died on May 28, due to refractory multiple organ failure. Interpretation Patients with respiratory symptoms returning from the Middle East or exposed to a confi rmed case should be isolated and investigated for MERS-CoV with lower respiratory tract sample analysis and an assumed incubation period of 12 days. Immunosuppression should also be taken into account as a risk factor.
Output: Clinical features and viral diagnosis of two cases of infection with Middle East Respiratory Syndrome coronavirus: a report of nosocomial transmission
Worldwide community-acquired pneumonia (CAP) is one of the most frequent infectious diseases and a leading cause of death. Several studies have shown that a pathogen could be identified only in 50 to 60% of all patients, although in children < 6 month infectious agents can be detected in about 90%. Viral infections are most frequent in children < 2 years (80%), whereas bacterial infections increase with age. RSV, influenzaviruses, rhinoviruses, parainfluenzaviruses and adenoviruses are the most common viruses associated with CAP in children. Among adenoviruses a predominance of adenovirus 7 has been reported in several countries with emergence of highly pathogenic variants with significant lethality in young children. Many childhood respiratory infections are caused by more than one pathogen and up to 30% mixed viral / bacterial infections can be observed. CAP in immunocompetent adults is rare, whereas persons with underlaying diseases have an increased incidence of CAP. In the elderly, RSV, influenzaviruses, parainfluenzaviruses and less frequent adenoviruses are predominant viruses causing pneumonia. Less frequently associated with CAP are the newly discovered human metapneumovirus and the coronaviruses NL63 and HKU1. Hantaviruses, involved in the hantavirus pulmonary syndrome, belong to the emerging pathogens to date in North, Middle and South America. For optimum diagnosis the whole spectrum of potential respiratory viral agents should be included and multiple diagnostic techniques have to be used. In view of the high relevance of influenzavirus for CAP influenza vaccination is highly advisable for prevention of CAP, especially in high-risk groups.
Output: Community-Acquired Pneumonia Viral pathogens and epidemiology, detection, therapy and resistance
Clinical and public health laboratories have experienced unprecedented challenges in the form of demands to comply with revised regulations and economic pressures to be more efficient while preparing to respond to everything from pandemic influenza to bioterrorism. These forces have been an impetus for laboratorians to communicate, cooperate, and collaborate as never before and to seek the common ground where knowledge and resources can be shared to weather the profound economic and political forces at work today. The appearance of newly emerging and reemergent infections caused by agents of foodborne illness, anthrax, smallpox, plague, influenza, and other diseases has fostered cooperative network enterprises between clinical and public health laboratories, allowing the early detection of outbreaks of common and unusual pathogens and the measurement of the effectiveness of public health measures.
Output: Public Health and Clinical Laboratories: Partners in the Age of Emerging Infections
Acute respiratory infection is a frequently transmitted illness of concern to doctors and patients. Considering its airborne transmission, early diagnosis of such disease is particularly important. This study explored respiratory viral infections with influenza virus, parainfluenza virus, respiratory syncytial virus, human metapneumovirus, human bocavirus, coronavirus, and other early diagnostic substances as confirmed by literature resources. This study also used the corresponding monoclonal antibodies that were produced with the use of hybridoma technology, which were fixed on the chip after purification, for further serum detection. Using this method, a new technique to simultaneously detect 6 kinds of febrile respiratory viruses in a protein chip was developed. The accuracy rate of this method can be >99.65%. This product is inexpensive and capable of high-precision and high-throughput screening, which are prominent advantages.
Output: Prospective Evaluation of Rapid Antigen Tests for Diagnosis of Respiratory Viral Pathogens
Frog virus 3 (FV3) is the best characterized member of the family Iridoviridae. FV3 study has provided insights into the replication of other family members, and has served as a model of viral transcription, genome replication, and virus-mediated host-shutoff. Although the broad outlines of FV3 replication have been elucidated, the precise roles of most viral proteins remain unknown. Current studies using knock down (KD) mediated by antisense morpholino oligonucleotides (asMO) and small, interfering RNAs (siRNA), knock out (KO) following replacement of the targeted gene with a selectable marker by homologous recombination, ectopic viral gene expression, and recombinant viral proteins have enabled researchers to systematically ascertain replicativeand virulence-related gene functions. In addition, the application of molecular tools to ecological studies is providing novel ways for field biologists to identify potential pathogens, quantify infections, and trace the evolution of ecologically important viral species. In this review, we summarize current studies using not only FV3, but also other iridoviruses infecting ectotherms. As described below, general principles ascertained using FV3 served as a model for the family, and studies utilizing other ranaviruses and megalocytiviruses have confirmed and extended our understanding of iridovirus replication. Collectively, these and future efforts will elucidate molecular events in viral OPEN ACCESS Viruses 2011, 3 1960 replication, intrinsic and extrinsic factors that contribute to disease outbreaks, and the role of the host immune system in protection from disease.
Output: The Molecular Biology of Frog Virus 3 and other Iridoviruses Infecting Cold-Blooded Vertebrates
Background: Severe acute respiratory syndrome (SARS) is an emerging infection caused by a novel coronavirus known as SARS-CoV, characterized by an over-exuberant immune response with lung lymphomononuclear cells infiltration and proliferation that may account for tissue damage more than the direct effect of viral replication. This study is aimed at investigating the capability of SARS-CoV to activate IFNa and -g expression in lymphomonocytes (PBMC) from healthy donors, evaluating whether viral replication is necessary for this activation. Results: SARS-CoV virus is able to induce both IFN-a and -g mRNA accumulation and protein release in a dose-dependent manner, MOI 10 being the most effective. The time course curve indicated that IFN-a mRNA induction peaked at 24 h.p.i,. whereas IFN-g mRNA was still increasing at 48 h.p.i. Released IFN (both types) reached a plateau after 24 -48 h.p.i. and remained rather stable over a 5-day period. A transient peak of negative strand viral RNA was detected after 1 -2 days of infection, but neither infectious virus progeny yield nor newly produced viral genomic RNA could be evidenced in infected cultures, even after prolonged observation time (up to 13 days). Cocultivation of PBMC with fixed SARS-CoV-infected Vero cells was even more efficient than exposure to live virus in eliciting IFN-a and -g induction. A combination of IFN-a and -g strongly inhibited SARS-CoV replication in Vero cells, while the single cytokines were much less effective. Conclusions: This study provides evidence that SARS-CoV is able to induce in normal PBMC a coordinate induction of IFN-a and -g gene expression. Virus replication is not necessary for IFN induction since efficient IFN expression could be obtained also by the cocultivation of normal PBMC with fixed SARS-CoV-infected cells. Concomitant activation of IFN-a and -g gene expression by SARS-CoV in vivo may be relevant for the pathogenesis of the disease, both for the possible involvement in immunomediated damage of the tissues and for the strong inhibition of SARS-CoV replication as a result of combined cytokine action. D
Output: Coordinate induction of IFN-a and -g by SARS-CoV also in the absence of virus replication
The ongoing coronavirus disease pandemic caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is a global public health concern due to relatively easy person-to-person transmission and the current lack of effective antiviral therapy. However, the exact molecular mechanisms of SARS-CoV-2 pathogenesis remain largely unknown. We exploited an integrated proteomics approach to systematically investigate intra-viral and virus-host interactomes for the identification of unrealized SARS-CoV-2 host targets and participation of cellular proteins in the response to viral infection using peripheral blood mononuclear cells (PBMCs) isolated from COVID-19 patients. Using this approach, we elucidated 251 host proteins targeted by SARS-CoV-2 and more than 200 host proteins that are significantly perturbed in COVID-19 derived PBMCs. From the interactome, we further identified that non-structural protein nsp9 and nsp10 interact with NKRF, a NF-kB repressor, and may precipitate the strong IL-8/IL-6 mediated chemotaxis of neutrophils and overexuberant host inflammatory response observed in COVID-19 patients. Our integrative study not only presents a systematic examination of SARS-CoV-2-induced perturbation of host targets and cellular networks to reflect disease etiology, but also reveals insights into the mechanisms by which SARS-CoV-2 triggers cytokine storms and represents a powerful resource in the quest for therapeutic intervention.
Output: Virus-host interactome and proteomic survey of PMBCs from COVID-19 patients reveal potential virulence factors influencing SARS-CoV-2 pathogenesis
In the immuno-competent adult Ebstein-Barr virus (EBV) infection is a self-limiting disease that resolves spontaneously. Case report We report a case of acute respiratory distress syndrome (ARDS) complicating severe EBV pneumonia and requiring prolonged artificial ventilation. The diagnosis was confirmed by specific serology and estimation of the viral load by PCR. Apart from supportive treatment with artificial ventilation the medical treatment included the use of Acyclovir and polyclonal immunoglobulins in the early phase and corticosteroids in the late phase. Recovery was progressive and complete. Conclusion ARDS can complicate EBV pneumonia in an immuno-competent subject. Its management represents a diagnostic and therapeutic challenge.
Output: Cas clinique SDRA par pneumonie à EBV
To determine the role of CD13 as an adhesion molecule in trafficking of inflammatory cells to the site of injury in vivo and its function in wound healing following myocardial infarction induced by permanent coronary artery occlusion. Seven days post-permanent ligation, hearts from CD13 knockout (CD13 KO ) mice showed significant reductions in cardiac function, suggesting impaired healing in the absence of CD13. Mechanistically, CD13 KO infarcts showed an increase in small, endothelial-lined luminal structures, but no increase in perfusion, arguing against an angiogenic defect in the absence of CD13. Cardiac myocytes of CD13 KO mice showed normal basal contractile function, eliminating myocyte dysfunction as a mechanism of adverse remodelling. Conversely, immunohistochemical and flow cytometric analysis of CD13 KO infarcts demonstrated a dramatic 65% reduction in infiltrating haematopoietic cells, including monocytes, macrophages, dendritic, and T cells, suggesting a critical role for CD13 adhesion in inflammatory trafficking. Accordingly, CD13 KO infarcts also contained fewer myofibroblasts, consistent with attenuation of fibroblast differentiation resulting from the reduced inflammation, leading to adverse remodelling. In the ischaemic heart, while compensatory mechanisms apparently relieve potential angiogenic defects, CD13 is essential for proper trafficking of the inflammatory cells necessary to prime and sustain the reparative response, thus promoting optimal post-infarction healing. ---
Output: CD13 is essential for inflammatory trafficking and infarct healing following permanent coronary artery occlusion in mice
Background: Despite the research importance of rhinovirus detection in asymptomatic healthy infants, the literature remains sparse. Objective: To investigate the prevalence of respiratory syncytial virus (RSV) and rhinovirus (and its species). We conducted a cross-sectional study of 110 healthy, non-hospitalized infants without acute illness at an academic medical center from November 2013 through May 2014. We tested nasal swab specimens by using polymerase chain reaction and genetic sequencing. Results: Overall, the median age was 3.8 months (IQR 2.0-5.1 months), 56 % were male, and 90 % were born >37 weeks. RSV was detected in nasal swabs from infants (1.8 %). By contrast, rhinovirus was detected in nasal swabs from 16 infants (14.5 %). Molecular typing assay revealed rhinovirus species: six rhinovirus-A (5.5 %), one rhinovirus-B (0.9 %), eight rhinovirus-C (7.3 %), and one untypeable (0.9 %). In this cross-sectional study of healthy, community-based infants, RSV was rare (<2 %) in nasal swabs, while rhinovirus was detected in 14.5 % with a predominance of rhinovirus-A and -C. These finding are important for understanding the clinical significance of rhinovirus detection among infants hospitalized for bronchiolitis.
Output: Detection of respiratory syncytial virus and rhinovirus in healthy infants
Mannheimia haemolytica is the most important bacterial agent associated with the bovine respiratory disease complex (BRDC), which causes worldwide economic losses to the cattle industry. M. haemolytica cells initially colonize the tonsillar crypts in the upper respiratory tract of cattle, from where they can subsequently descend into the lungs to cause disease. Many bacteria exist as biofilms inside their hosts. We hypothesize that M. haemolytica colonization of cattle during its commensal state may include biofilm formation. To begin to assess this possibility, we developed an in vitro system to study biofilm formation directly on bovine respiratory epithelial cells. Using fixed primary bovine bronchial epithelial cells, we observed M. haemolytica biofilm formation after a 48 h incubation period at 37 C. Addition of mucin, the main component of mucus present in the upper respiratory tract, decreased M. haemolytica biofilm formation on bovine epithelial cells. We investigated the effects of prior viral infection of the epithelial cells on subsequent biofilm formation by M. haemolytica and found negligible effects. Utilization of this model system will provide new insights into the potential role of biofilm formation by M. haemolytica in the pathogenesis of BRDC.
Output: Mannheimia haemolytica biofilm formation on bovine respiratory epithelial cells
Two full-length porcine reproductive and respiratory syndrome virus (PRRSV) genomes, strain VR-2332 and its cell culture passaged descendent RespPRRS vaccine strain, were compared and analyzed in order to identify possible sites of attenuation. Of the 44 nucleotide changes, 13 resulted in conservative changes and 18 produced non-conservative changes. The results suggest that key amino acids in ORF1 may contribute to the phenotype of RespPRRS, which includes increased growth rate on MA-104 cells and decreased virulence in swine. The results provide a genetic basis for future manipulation of a PRRSV reverse genetics system.
Output: Complete genome comparison of porcine reproductive and respiratory syndrome virus parental and attenuated strains