niryuu/sni-each-converted huggingface dataset:
Diarrhea is common in young calves and is often caused by Cryptosporidium parvum infection. The aim of this study was to investigate if disinfection of calf pens with hydrated lime would reduce contamination of C. parvum oocysts and improve calf health in herds with C. parvum associated diarrhea problems. Four dairy herds with ongoing C. parvum associated calf diarrhea problems each participated in the study over six to seven months. During the study period, all pens/huts for young calves were cleaned according to the usual farm routine before a new calf entered. Hydrated lime was then used to disinfect half of the pens/huts. Diarrhea incidence was recorded by the farmers and by veterinarians, who clinically examined the calves every second month. In total, 402 calves participated in the study. The farmers detected diarrhea in 214 (53%) calves, with similar proportions in calves kept in lime disinfected and control pens. Age at diarrhea onset was significantly higher in lime disinfected pens than in control pens, 9.0 days and 7.6 days, respectively. There was no difference between the groups regarding duration or severity index recorded by the farmers. The body condition score in 6-8 week old calves was significantly higher in calves that had been kept in lime disinfected pens during their first weeks of life, indicating that calves in disinfected pens/huts were less affected by their infections. Faecal samples from 5 to 21 day old calves, were collected on four occasions at each farm (n = 95). Cryptosporidium positive samples were found at all samplings in all four herds. Cryptosporidium spp. was detected in 79 (83%) samples with no difference between lime disinfected and control pens. C. parvum was the dominant species. Two different C. parvum subtypes were found; IIaA16G1R1b in three herds and IIaA16G1R1b_variant in one herd. Only one subtype was found in each herd. Disinfection of calf pens with slaked lime delayed onset of diarrhea and improved the body condition in the calves, but did not affect diarrhea incidence or duration. Although lime disinfection alone will not be sufficient to control Cryptosporidium associated diarrhea in herds with extensive calf diarrhea problems, these results suggest that it can be a valuable complement to other measures.
Output: Disinfection with hydrated lime may help manage cryptosporidiosis in calves
Oncolytic herpes simplex viruses (HSVs), in clinical trials for the treatment of malignant gliomas, are assumed to be selective for tumor cells because their replication is strongly attenuated in quiescent cells, but not in cycling cells. Oncolytic selectivity is thought to occur because mutations in viral ICP6 (encoding a viral ribonucleotide reductase function) and/or c34.5 function are respectively complemented by mammalian ribonucleotide reductase and GADD34, whose genes are expressed in cycling cells. However, it is estimated that only 5-15% of malignant glioma cells are in mitosis at any one time. Therefore, effective replication of HSV oncolytic viruses might be limited to a subpopulation of tumor cells, since at any one time the majority of tumor cells would not be cycling. However, we report that an HSV with defective ICP6 function replicates in quiescent cultured murine embryonic fibroblasts obtained from mice with homozygous p16 deletions. Furthermore, intracranial inoculation of this virus into the brains of p16À/À mice provides evidence of viral replication that does not occur when the virus is injected into the brains of wild-type mice. These approaches provide in vitro and in vivo evidence that ICP6-negative HSVs are 'molecularly targeted,' because they replicate in quiescent tumor cells carrying specific oncogene deletions, independent of cell cycle status.
Output: Oncolytic herpes virus with defective ICP6 specifically replicates in quiescent cells with homozygous genetic mutations in p16
An enzyme-linked immunosorbent assays (ELISA) based on recombinant nucleocapsid (N) protein generated in Escherichia coli was evaluated for its sensitivity and specificity for diagnosis of porcine epidemic diarrhea (PEDV) infection. The N gene encoding the N protein was cloned and expressed as a fusion protein with His tag protein in E. coli. The recombinant N protein was migrated at 48 kDa and reacted with six histidine tag specific monoclonal antibody by immunoblotting. Recombinant N protein ELISA (rnELISA) demonstrated 98.7% specificities among (80) PEDV-free individuals, and 98% sensitivity ranging among (103) clinical samples with PEDV. On testing 884 field samples, an overall agreement of 88.3% was generated between the SN and rnELISA. Taken together, these results indicated that nucleocapsid protein may be a useful antigen for the seradiagnosis of PEDV and it was also suggested that the ELISA is a highly sensitive and specific test for detecting antibodies to PEDV. #
Output: Development and evaluation of enzyme-linked immunosorbent assay based on recombinant nucleocapsid protein for detection of porcine epidemic diarrhea (PEDV) antibodies
The circRNA is a newly defined noncoding RNA and characterized by its unique splicing reactions to form circles. However, the function of circRNAs during viral infection remains largely unknown. In this study, the circRNA expression profile during porcine endemic diarrhea virus (PEDV) infection in IPEC-J2 cell line was investigated using the next-generation sequencing technology. A total of 26670 circRNA candidates were identified. The functional annotation analysis revealed that the parent genes of differentially expressed circRNAs might be associated with host response to PEDV infection. Further analysis verified the existence of eight selected circRNAs and confirmed that PEDV infection alerted the expression patterns of circRNAs and their linear parent genes in IPEC-J2 cell line. The circRNA-miRNA interaction network was also constructed to elucidate their potential targets. Our results provided not only the first large-scale profile analysis of circRNAs associated with PEDV infection but also a novel direction to elucidate host-PEDV interactions.
Output: Profile analysis of circRNAs induced by porcine endemic diarrhea virus infection in porcine intestinal epithelial cells
In response to the coronavirus disease 2019 (COVID-19) pandemic, 107 countries had implemented national school closures by March 18, 2020. It is unknown whether school measures are effective in coronavirus outbreaks (eg, due to severe acute respiratory syndrome [SARS], Middle East respiratory syndrome, or COVID-19). We undertook a systematic review by searching three electronic databases to identify what is known about the effectiveness of school closures and other school social distancing practices during coronavirus outbreaks. We included 16 of 616 identified articles. School closures were deployed rapidly across mainland China and Hong Kong for COVID-19. However, there are no data on the relative contribution of school closures to transmission control. Data from the SARS outbreak in mainland China, Hong Kong, and Singapore suggest that school closures did not contribute to the control of the epidemic. Modelling studies of SARS produced conflicting results. Recent modelling studies of COVID-19 predict that school closures alone would prevent only 2-4% of deaths, much less than other social distancing interventions. Policy makers need to be aware of the equivocal evidence when considering school closures for COVID-19, and that combinations of social distancing measures should be considered. Other less disruptive social distancing interventions in schools require further consideration if restrictive social distancing policies are implemented for long periods.
Output: Review School closure and management practices during coronavirus outbreaks including COVID-19: a rapid systematic review
Background. Umbilical cord blood transplant (UCBT) is used for patients who do not have a matched donor, but engraftment often takes longer than with a standard allogeneic transplant, likely increasing the risk for infection. We characterized specific infections and outcomes in adults undergoing UCBT at our 2 centers. Methods. All adults who underwent UCBT between January 1, 2006 and December 31, 2015 were included. Infectious episodes from 6 months before to 2 years after UCBT were reviewed. Results. Fifty-seven patients underwent UCBT; 47 had neutrophil engraftment. A total of 179 infectious episodes occurred in 55 patients, 73 (41%) within 30 days post-UCBT. Viruses caused 85 (47%) infections. Cytomegalovirus caused 32 infectious episodes and was most common from day 30 to 100. Human herpesvirus 6 occurred in 28 episodes, was most common within 30 days, and caused 1 death. Bacteria were responsible for 82 (46%) infections, most commonly bacteremias due to Staphylococcus spp, Enterococcus spp, and Enterobacteriaceae. Of 11 invasive fungal infections, 9 were aspergillosis, 4 of which were fatal. Overall mortality was 56% in the first year. Thirteen deaths were from infection; 11 occurred in the first 100 days and 7 in the first 30 days post-UCBT. Of 10 patients who never engrafted, 9 died, 6 from infection, within 100 days post-UCBT. Conclusions. Infectious complications were common after UCBT, especially in the first 30 days. Deaths from viral infections were fewer than expected. Delayed engraftment and nonengraftment continue to convey increased risk for fatal bacterial and fungal infections post-UCBT.
Output: Open Forum Infectious Diseases Infectious Complications After Umbilical Cord Blood Transplantation for Hematological Malignancy
A B S T R A C T Porcine epidemic diarrhea virus (PEDV) is a very contagious swine pathogen that spreads easily via the fecaloral route, notably from contaminated fomites. The present study investigated heated water as a method for rapid thermal inactivation of PEDV. Cell-culture adapted PEDV was treated with water at varying temperatures and viral titers were measured at multiple time points post-treatment. Viable PEDV was not recovered after a ten second or longer treatment with water heated to ≥76°C; however, PEDV nucleic acid was detected in all samples regardless of treatment. Hot water decontamination could be considered in settings where chemical disinfection is impractical.
Output: Inactivation of porcine epidemic diarrhea virus using heated water
and South Africa (BRICS) represent almost half the world's population, and all fi ve national governments recently committed to work nationally, regionally, and globally to ensure that universal health coverage (UHC) is achieved. This analysis reviews national eff orts to achieve UHC. With a broad range of health indicators, life expectancy (ranging from 53 years to 73 years), and mortality rate in children younger than 5 years (ranging from 10·3 to 44·6 deaths per 1000 livebirths), a review of progress in each of the BRICS countries shows that each has some way to go before achieving UHC. The BRICS countries show substantial, and often similar, challenges in moving towards UHC. On the basis of a review of each country, the most pressing problems are: raising insuffi cient public spending; stewarding mixed private and public health systems; ensuring equity; meeting the demands for more human resources; managing changing demographics and disease burdens; and addressing the social determinants of health. Increases in public funding can be used to show how BRICS health ministries could accelerate progress to achieve UHC. Although all the BRICS countries have devoted increased resources to health, the biggest increase has been in China, which was probably facilitated by China's rapid economic growth. However, the BRICS country with the second highest economic growth, India, has had the least improvement in public funding for health. Future research to understand such diff erent levels of prioritisation of the health sector in these countries could be useful. Similarly, the role of strategic purchasing in working with powerful private sectors, the eff ect of federal structures, and the implications of investment in primary health care as a foundation for UHC could be explored. These issues could serve as the basis on which BRICS countries focus their eff orts to share ideas and strategies.
Output: An assessment of progress towards universal health coverage in Brazil, Russia, India, China, and South Africa (BRICS)
Knowing which populations are most at risk for severe outcomes from an emerging infectious disease is crucial in deciding the optimal allocation of resources during an outbreak response. The case fatality ratio (CFR) is the fraction of cases that die after contracting a disease. The relative CFR is the factor by which the case fatality in one group is greater or less than that in a second group. Incomplete reporting of the number of infected individuals, both recovered and dead, can lead to biased estimates of the CFR. We define conditions under which the CFR and the relative CFR are identifiable. Furthermore, we propose an estimator for the relative CFR that controls for time-varying reporting rates. We generalize our methods to account for elapsed time between infection and death. To demonstrate the new methodology, we use data from the 1918 influenza pandemic to estimate relative CFRs between counties in Maryland. A simulation study evaluates the performance of the methods in outbreak scenarios. An R software package makes the methods and data presented here freely available. Our work highlights the limitations and challenges associated with estimating absolute and relative CFRs in practice. However, in certain situations, the methods presented here can help identify vulnerable subpopulations early in an outbreak of an emerging pathogen such as pandemic influenza.
Output: Estimating Absolute and Relative Case Fatality Ratios from Infectious Disease Surveillance Data HHS Public Access
Rapid diagnostics, vaccines and therapeutics are important interventions for the management of the 2019 novel coronavirus (2019-nCoV) outbreak. It is timely to systematically review the potential of these interventions, including those for Middle East respiratory syndrome-Coronavirus (MERS-CoV) and severe acute respiratory syndrome (SARS)-CoV, to guide policymakers globally on their prioritization of resources for research and development. A systematic search was carried out in three major electronic databases (PubMed, Embase and Cochrane Library) to identify published studies in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Supplementary strategies through Google Search and personal communications were used. A total of 27 studies fulfilled the criteria for review. Several laboratory protocols for confirmation of suspected 2019-nCoV cases using real-time reverse transcription polymerase chain reaction (RT-PCR) have been published. A commercial RT-PCR kit developed by the Beijing Genomic Institute is currently widely used in China and likely in Asia. However, serological assays as well as point-of-care testing kits have not been developed but are likely in the near future. Several vaccine candidates are in the pipeline. The likely earliest Phase 1 vaccine trial is a synthetic DNA-based candidate. A number of novel compounds as well as therapeutics licensed for other conditions appear to have in vitro efficacy against the 2019-nCoV. Some are being tested in clinical trials against MERS-CoV and SARS-CoV, while others have been listed for clinical trials against 2019-nCoV. However, there are currently no effective specific antivirals or drug combinations supported by high-level evidence.
Output: Potential Rapid Diagnostics, Vaccine and Therapeutics for 2019 Novel Coronavirus (2019-nCoV): A Systematic Review
Drug Design, Development and Therapy Dovepress submit your manuscript | www.dovepress.com Dovepress 2255 O r i g i n a l r e s e a r c h open access to scientific and medical research Open access Full Text article http://dx. The thiazolidinedione class peroxisome proliferator-activated receptor gamma (PPARγ) agonists are restricted in clinical use as antidiabetic agents because of side effects such as edema, weight gain, and heart failure. The single and selective agonism of PPARγ is the main cause of these side effects. Multitargeted PPARα/γ/δ pan agonist development is the hot topic in the antidiabetic drug research field. In order to identify PPARα/γ/δ pan agonists, a compound database was established by core hopping of rosiglitazone, which was then docked into a PPARα/γ/δ active site to screen out a number of candidate compounds with a higher docking score and better interaction with the active site. Further, absorption, distribution, metabolism, excretion, and toxicity prediction was done to give eight compounds. Molecular dynamics simulation of the representative Cpd#1 showed more favorable binding conformation for PPARs receptor than the original ligand. Cpd#1 could act as a PPARα/γ/δ pan agonist for novel antidiabetic drug research.
Output: Identification of novel multitargeted PPARα/γ/δ pan agonists by core hopping of rosiglitazone
Cellular uptake of therapeutic oligonucleotides and subsequent intracellular trafficking to their target sites represents the major technical hurdle for the biological effectiveness of these potential drugs. Accordingly, laboratories worldwide focus on the development of suitable delivery systems. Among the different available non-viral systems like cationic polymers, cationic liposomes and polymeric nanoparticles, cell-penetrating peptides (CPPs) represent an attractive concept to bypass the problem of poor membrane permeability of these charged macromolecules. While uptake per se in most cases does not represent the main obstacle of nucleic acid delivery in vitro, it becomes increasingly apparent that intracellular trafficking is the bottleneck. As a consequence, in order to optimize a given delivery system, a side-by-side analysis of nucleic acid cargo internalized and the corresponding biological effect is required to determine the overall efficacy. In this review, we will concentrate on peptide-mediated delivery of siRNAs and steric block oligonucleotides and discuss different methods for quantitative assessment of the amount of cargo taken up and how to correlate those numbers with biological effects by applying easy to handle reporter systems. To illustrate current limitations of non-viral nucleic acid delivery systems, we present own data as an example and discuss options of how to enhance trafficking of molecules entrapped in cellular compartments.
Output: Peptide-Mediated Cellular Delivery of Oligonucleotide-Based Therapeutics In Vitro: Quantitative Evaluation of Overall Efficacy Employing Easy to Handle Reporter Systems
Purpose of work The non-structural protein 4 (Nsp4) of porcine reproductive and respiratory syndrome virus (PRRSV) functions as a 3C-like proteinase (3CLpro) and plays a pivotal role in gene expression and replication. We have examined the biochemical properties of PRRSV 3CLpro and identified those amino acid residues involved in its catalytic activity as a prelude to developing anti-PRRSV strategies. The 3C-like proteinase (3CLpro) of porcine reproductive and respiratory syndrome virus (PRRSV) was expressed in Escherichia coli and characterized. The optimal temperature and pH for its proteolytic activity were 8°C and 7.5, respectively. Na ? (1000 mM) and K ? (500 mM) were not inhibitory to its activity but Cu 2? , Zn 2? , PMSF and EDTA were significantly inhibitory. His 39 , Asp 64 and Ser 118 residues were identified to form the catalytic triad of PRRSV 3CLpro by a series of site-directed mutagenesis analysis. Keywords 3C-like proteinase Á Nsp4 Á Porcine reproductive and respiratory syndrome virus
Output: Characterization of the biochemical properties and identification of amino acids forming the catalytic center of 3C-like proteinase of porcine reproductive and respiratory syndrome virus
As the practice of intensive animal production increases, there is a need for affordable treatment technologies that can help manage the large amounts of manure generated. Our approach has been to develop an efficient liquid-solid separation module using polymer technology and integrate this separation module into systems of treatment technologies for both the separated liquid and solids. We describe the progress that has been made in management techniques and new technological alternatives for manure treatment and generation of value added by-products based on the SELCO-Ecopurin â separation technology and experiences during the last five years in 12 livestock farms in Spain, Italy and the USA. High recovery of solids (>90%) makes the use of advanced purification of the liquid a more economical alternative. The liquid can be further treated to reduce N and P and produce effluents virtually free of these nutrients. Production of methane and energy was affected by solids concentration; the anaerobic process was optimised with polymer application rate of 120 ppm during separation and a solids content of 13%.
Output: SELCO-Ecopurin â pig slurry treatment system
publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active. cytochromes P450 isoenzymes. Med Hypotheses 2005;64:802-5. [3] Wiseman A, Goldfarb PS. Oxaliplatin and targeted adjunct chemotherapy for bowel cancer through DNA binding: causal involvement of ROS. J Appl Therapeut Res 2005;5:24-31.
Output: No anti-ACTH autoantibody in serum of SARS patients
Nod-like receptor family, pyrin domain-containing 3 (NLRP3) regulates the secretion of proinflammatory cytokines interleukin 1 beta (IL-1β) and IL-18. We previously showed that influenza virus M2 or encephalomyocarditis virus (EMCV) 2B proteins stimulate IL-1β secretion following activation of the NLRP3 inflammasome. However, the mechanism by which severe acute respiratory syndrome coronavirus (SARS-CoV) activates the NLRP3 inflammasome remains unknown. Here, we provide direct evidence that SARS-CoV 3a protein activates the NLRP3 inflammasome in lipopolysaccharide-primed macrophages. SARS-CoV 3a was sufficient to cause the NLRP3 inflammasome activation. The ion channel activity of the 3a protein was essential for 3a-mediated IL-1β secretion. While cells uninfected or infected with a lentivirus expressing a 3a protein defective in ion channel activity expressed NLRP3 uniformly throughout the cytoplasm, NLRP3 was redistributed to the perinuclear space in cells infected with a lentivirus expressing the 3a protein. K + efflux and mitochondrial reactive oxygen species were important for SARS-CoV 3a-induced NLRP3 inflammasome activation. These results highlight the importance of viroporins, transmembrane pore-forming viral proteins, in virus-induced NLRP3 inflammasome activation.
Output: Severe Acute Respiratory Syndrome Coronavirus Viroporin 3a Activates the NLRP3 Inflammasome
The relationship between air pollution and stock pricing of locally headquartered firms is explored using firm-level data in China. Severe air pollution results in low returns, turnover, volatility, and high illiquidity, mainly through a home bias. The results remain robust after a series of checks. The relation between air pollution and local firm performance is insignificant, implying that the air pollution effects can be attributed to investor mood bias rather than to economic effects. The sensitivity of stock returns to air pollution is significantly large for highgrowth stocks, distressed stocks, and stocks with high volatility.
Output: Air pollution, stock returns, and trading activities in China ☆
The novel coronavirus SARS-CoV-2 is a newly emerging virus. The antibody response in infected patient remains largely unknown, and the clinical values of antibody testing have not been fully demonstrated. A total of 173 patients with confirmed SARS-CoV-2 infection were enrolled. Their serial plasma samples (n = 535) collected during the hospitalization period were tested for total antibodies (Ab), IgM and IgG against SARS-CoV-2 using immunoassays. The dynamics of antibodies with the progress and severity of disease was analyzed. Among 173 patients, the seroconversion rate for Ab, IgM and IgG was 93.1% (161/173), 82.7% (143/173) and 64.7% (112/173), respectively. Twelve patients who had not seroconverted were those only blood samples at the early stage of illness were collected. The seroconversion sequentially appeared for Ab, IgM and then IgG, with a median time of 11, 12 and 14 days, respectively. The presence of antibodies was < 40% among patients in the first 7 days of illness, and then rapidly increased to 100.0%, 94.3% and 79.8% for Ab, IgM and IgG respectively since day 15 after onset. In contrast, the positive rate of RNA decreased from 66.7% (58/87) in samples collected before day 7 to 45.5% (25/55) during days 15 to 39. Combining RNA and antibody detections significantly improved the sensitivity of pathogenic diagnosis for COVID-19 patients (p < 0.001), even in early phase of 1-week since onset (p = 0.007). Moreover, a higher titer of Ab was independently associated with a worse clinical classification (p = 0.006). The antibody detection offers vital clinical information during the course of SARS-CoV-2 infection. The findings provide strong empirical support for the routine application of serological testing in the diagnosis and management of COVID-19 patients.
Output: Title: Antibody responses to SARS-CoV-2 in patients of novel coronavirus disease 2019 Brief Title: Antibody responses in COVID-19 patients Summary Background
Infectious bronchitis (IB) is a highly contagious disease involving mostly upper respiratory tract in chickens, leading to significant economic losses in the poultry industry worldwide. One of the major concerns regarding to IB is the emergence of new types of infectious bronchitis viruses (IBVs). The purpose of this study was to identify the IBVs isolated from Iranian broiler chickens with respiratory symptoms. Twenty-five broiler flocks around Ahwaz (southwest of Iran) were examined for IBV. The specimens including trachea, lung, liver, kidney, and ceacal tonsil, were collected from diseased birds and inoculated into chicken embryonated eggs. Harvested allantoic fluids were subjected to reverse transcription polymerase chain reaction (RT-PCR) using primers in order to amplify spike 1 (S1) gene of IBV. The RT-PCR products of four IBV isolates were sequenced. The results showed that from 25 examined flocks with respiratory disease, 12 flocks (48.00%) were positive for IBV. In phylogenetic analysis, our isolates were closely related to the QX-like viruses such as PCRLab/06/2012 (Iran), QX, HC9, HC10, CK/CH/GX/NN11-1, CK/CH/JS/YC11-1, CK/CH/JS/2010/13, CK/CH/JS/2011/2 (China), QX/SGK-21, QX/SGK-11 (Iraq) with nucleotide homology up to 99.00%. This study indicates the role of IBVs in the respiratory disorders of broiler flocks located in southwest Iran, and also the existence of a variant of IBV, which is distinguishable from the other Iranian variants.
Output: Molecular detection and phylogenetic properties of isolated infectious bronchitis viruses from broilers in Ahvaz, southwest Iran, based on partial sequences of spike gene
The consequences of natural infections by bovine virus diarrhoea virus (BVDV) in a dairy herd comprising approximately 60 cows were studied over a 3 year period. The outcome of 39 pregnancies after artificial insemination or natural service during a 4 month period of risk for contracting BVDV was nine abortions, one mummified foetus, one stillbirth, three calves that died within I week of age, 12 calves persistently infected (PI) with BVDV (11 males and one female) and 13 non-PI calves. Retrospective studies showed that only two of the 13 dams (15.4%) ofnon-PI calves had been inseminated once, which is a significantly (P< 0.001 ) lower rate than for 192 other gestations (66.7%) during the 3 year period. The gestational duration of multiparous cows (but not of heifers ) was longer (P < 0.01 ) for five cows with PI calves (mean + SD 287.6 + 9.5 days) than for 53 other gestations in 35 cows (280.6 + 3.8 days). Five of the 12 dams of the PI calves had not expelled the foetal membranes within 2 days after calving, which is a higher (P<0.001) incidence than the seven cases of retained placenta observed after 198 other calvings. Furthermore, there was a 4.4-fold higher risk (P < 0.01 ) of treatment for enteritis and/or pneumonia in calves and a 6.0-fold higher risk of calf mortality associated with the introduction of BVDV. The mean heart girth of the PI calves was less (P< 0.05) than that of non-PI calves, at both 80 and 180 days of age.
Output: Natural infection with bovine virus diarrhoea virus in a dairy herd: A spectrum of symptoms including early reproductive failure and retained placenta
Interferons (IFNs) are important components in innate immunity involved in the first line of defense to protect host against viral infection. Porcine reproductive and respiratory syndrome virus (PRRSV) leads to severe economic losses for swine industry since being first identified in early 1990s. PRRSV interplays with host IFN production and IFN-activated signaling, which may contribute to the delayed onset and low level of neutralizing antibodies, as well as weak cell-mediated immune response in infected pigs. PRRSV encodes several proteins that act as antagonists for the IFN signaling. In this review, we summarized the various strategies used by PRRSV to antagonize IFN production and thwart IFN-activated antiviral signaling, as well as the variable interference with IFN-mediated immune response by different PRRSV strains. Thorough understanding of the interaction between PRRSV and host innate immune response will facilitate elucidation of PRRSV pathogenesis and development of a better strategy to control PRRS.
Output: Antagonizing Interferon-Mediated Immune Response by Porcine Reproductive and Respiratory Syndrome Virus
The beginning of 2020 brought us information about the novel coronavirus emerging in China. 39 Rapid research resulted in the characterization of the pathogen, which appeared to be a member 40 of the SARS-like cluster, commonly seen in bats. Despite the global and local efforts, the virus 41 escaped the healthcare measures and rapidly spread in China and later globally, officially 42 causing a pandemic and global crisis in March 2020. At present, different scenarios are being 43 written to contain the virus, but the development of novel anticoronavirals for all highly 44 pathogenic coronaviruses remains the major challenge. Here, we describe the antiviral activity 45 of previously developed by us HTCC compound (N-(2-hydroxypropyl)-3-trimethylammonium 46 chitosan chloride), which may be used as potential inhibitor of currently circulating highly 47 pathogenic coronaviruses -SARS-CoV-2 and MERS-CoV. : bioRxiv preprint 65 pneumocytes in human airways, hijacking the angiotensin-converting enzyme 2 (ACE2) to 66 enter the cell, similarly as SARS-CoV and HCoV-NL63. 67 MERS-CoV is related to SARS-CoV-2, but together with some bat viruses forms 68 a separate Merbecovirus subgenus. Bats are believed to serve as an original reservoir also in 69 this case 10 , but camels were identified as the intermediate host 11 . The virus never fully crossed 70 the species border, as the human-to-human transmission is limited, and almost all the cases are 71 associated with animal-to-human transmission. The entry receptor for MERS-CoV is the 72 dipeptidyl peptidase 4 (DPP4) 12,13 . In humans, MERS-CoV causes a respiratory illness with 73 author/funder. All rights reserved. No reuse allowed without permission.
Output: HTCC as a highly effective polymeric inhibitor of SARS-CoV-2 and MERS-CoV 2 3
The emergency department evaluation of the febrile traveler presents the emergency physician with a set of unique and often challenging circumstances. In addition to evaluating and managing the usual array of community-acquired infections, the clinician must be prepared to diagnose and treat a host of uncommon and potentially life-threatening pathogens. This diseases range from widespread tropical diseases such as malaria to the more exotic and lethal viral hemorrhagic fevers. A thoughtful approach guided by geographic patterns of illness offers a reliable method for determining the most likely sources of fever in the returned traveler as well as a focused diagnostic and treatment strategy.
Output: Emergency department evaluation of the febrile traveler
Cowpox virus (CPXV), is a global health threat. The proteasome is essential for poxvirus replication, making the viral components interacting with the ubiquitin-proteasome system attractive antiviral targets. We show that proteasome inhibition impairs CPXV replication by prevention of uncoating, suggesting that uncoating is mediated by proteasomal degradation of viral core proteins. Although Orthopoxvirus particles contain considerable amounts of ubiquitin, distinct modification sites are largely unknown. Therefore, for the first time, we analyzed globally ubiquitination sites in CPXV mature virion proteins using LC-MS/MS. Identification of 137 conserved sites in 54 viral proteins among five CPXV strains revealed extensive ubiquitination of structural core proteins. Moreover, since virions contained primarily K48-linked polyubiquitin, we hypothesized that core proteins are modified accordingly. However, quantitative analysis of ubiquitinated CPXV proteins early in infection showed no proteasomal degradation of core proteins. Instead, our data indicate that the recently suggested proteasomal regulation of the uncoating factor E5 is a prerequisite for uncoating. Expanding our understanding of poxvirus uncoating and elucidating a multitude of novel ubiquitination sites in poxvirus proteins, the present study verifies the major biological significance of ubiquitin in poxvirus infection. The ubiquitin-proteasome system (UPS) is exploited by members of most virus families 1 and is essential for the replication of different virus families, e.g. Pox-2-4 , Reo-5 and Coronaviridae 6 . As a member of the Poxviridae family the genus Orthopoxvirus (OPV) comprises complex enveloped DNA viruses, including the smallpox-causing Variola virus (VARV), Vaccinia virus (VACV), which was used for smallpox eradication 7 , and several animal-borne viruses with zoonotic potential like Cowpox virus (CPXV) 8-10 . Having caused the death of hundreds of millions of people, VARV is the most prominent member of OPV. Although VARV has been eradicated in 1979, it is still a global health threat because of its possible release in the context of a bioterrorist attack and the emergence of VARV-like viruses from circulating OPV by natural evolution 11 . CPXV are well suited to fill the niche that was created by VARV eradication, since it has the largest OPV genome including homologous open reading frames of all VARV genes. Currently, the number of zoonotic infections in Europe caused by CPXV is increasing, illustrating the need for a comprehensive understanding of the virus biology, especially the interaction with the host cell 12,13 .
Output: Global ubiquitination analysis reveals extensive modification and proteasomal degradation of cowpox virus proteins, but preservation of viral cores OPEN
Cooperative interactions play a central role in the regulation of protein functions. Here we show that in multi-site systems like ion channels the application of the Hill formalism could require a combination of different experiments, even involving site-directed mutagenesis, to identify the different sources of cooperativity and to discriminate between genuine and apparent cooperativity. We discuss the implications for the channel function in the bacterial porins PorA (N. meningitidis) and OmpF (E. coli ) and the viroporin SARS-CoV E.
Output: THE EUROPEAN PHYSICAL JOURNAL E On the different sources of cooperativity in pH titrating sites of a membrane protein channel
The anti-inflammatory master regulator IL-10 is critical to protect the host from tissue damage during acute phases of immune responses. This regulatory mechanism, central to T cell homeostasis, can be hijacked by viruses to evade immunity. IL-10 can be produced by virtually all immune cells, and it can also modulate the function of these cells. Understanding the effects of this multifunctional cytokine is therefore a complex task. In the present review we discuss the factors driving IL-10 production and the cellular sources of the cytokine during antiviral immune responses. We particularly focus on the IL-10 regulatory mechanisms that impact antiviral immune responses and how viruses can use this central regulatory pathway to evade immunity and establish chronic/latent infections.
Output: IL-10: A Multifunctional Cytokine in Viral Infections
Highlights d ITZ, an antifungal and anticancer agent, is a broad-spectrum enterovirus inhibitor d OSBP and ORP4 are identified as novel targets of ITZ d ITZ binds OSBP and inhibits OSBP-mediated lipid exchange at membrane contact sites d ITZ also inhibits hepatitis C virus replication SUMMARY Itraconazole (ITZ) is a well-known antifungal agent that also has anticancer activity. In this study, we identify ITZ as a broad-spectrum inhibitor of enteroviruses (e.g., poliovirus, coxsackievirus, enterovirus-71, rhinovirus). We demonstrate that ITZ inhibits viral RNA replication by targeting oxysterol-binding protein (OSBP) and OSBP-related protein 4 (ORP4). Consistently, OSW-1, a specific OSBP/ORP4 antagonist, also inhibits enterovirus replication. Knockdown of OSBP inhibits virus replication, whereas overexpression of OSBP or ORP4 counteracts the antiviral effects of ITZ and OSW-1. ITZ binds OSBP and inhibits its function, i.e., shuttling of cholesterol and phosphatidylinositol-4phosphate between membranes, thereby likely perturbing the virus-induced membrane alterations essential for viral replication organelle formation. ITZ also inhibits hepatitis C virus replication, which also relies on OSBP. Together, these data implicate OSBP/ORP4 as molecular targets of ITZ and point to an essential role of OSBP/ORP4-mediated lipid exchange in virus replication that can be targeted by antiviral drugs.
Output: Itraconazole Inhibits Enterovirus Replication by Targeting the Oxysterol-Binding Protein
Foodborne and waterborne viral infections are increasingly recognized as causes of illness in humans. This increase is partly explained by changes in food processing and consumption patterns that lead to the worldwide availability of high-risk food. As a result, vast outbreaks may occur due to contamination of food by a single foodhandler or at a single source. Although there are numerous fecalô rally transmitted viruses, most reports of foodborne transmission describe infections with Norwalk-like caliciviruses (NLV) and hepatitis A virus (HAV), suggesting that these viruses are associated with the greatest risk of foodborne transmission. NLV and HAV can be transmitted from person to person, or indirectly via food, water, or fomites contaminated with virus-containing feces or vomit. People can be infected without showing symptoms. The high frequency of secondary cases of NLV illness and^to a lesser extent^of hepatitis A following a foodborne outbreak results in amplification of the problem. The burden of illness is highest in the elderly, and therefore is likely to increase due to the aging population. For HAV, the burden of illness may increase following hygienic control measures, due to a decreasing population of naturally immune individuals and a concurrent increase in the population at risk. Recent advances in the research of NLV and HAV have led to the development of molecular methods which can be used for molecular tracing of virus strains. These methods can be and have been used for the detection of common source outbreaks. While traditionally certain foods have been implicated in virus outbreaks, it is clear that almost any food item can be involved, provided it has been handled by an infected person. There are no established methods for detection of viruses in foods other than shellfish. Little information is available on disinfection and preventive measures specifically for these viruses. Studies addressing this issue are hampered by the lack of culture systems. As currently available routine monitoring systems exclusively focus on bacterial pathogens, efforts should be made to combine epidemiological and virological information for a combined laboratory-based rapid detection system for foodborne viruses. With better surveillance, including typing information, outbreaks of foodborne infections could be reported faster to prevent further spread. ß
Output: Foodborne viruses 1
We had earlier proposed a hypothesis to explain the mechanism of perpetuation of immunological memory based on the operation of idiotypic network in the complete absence of antigen. Experimental evidences were provided for memory maintenance through anti-idiotypic antibody (Ab 2 ) carrying the internal image of the antigen. In the present work, we describe a structural basis for such memory perpetuation by molecular modeling and structural analysis studies. A three-dimensional model of Ab 2 was generated and the structure of the antigenic site on the hemagglutinin protein H of Rinderpest virus was modeled using the structural template of hemagglutinin protein of Measles virus. Our results show that a large portion of heavy chain containing the CDR regions of Ab 2 resembles the domain of the hemagglutinin housing the epitope regions. The similarity demonstrates that an internal image of the H antigen is formed in Ab 2 , which provides a structural basis for functional mimicry demonstrated earlier. This work brings out the importance of the structural similarity between a domain of hemagglutinin protein to that of its corresponding Ab 2 . It provides evidence that Ab 2 is indeed capable of functioning as surrogate antigen and provides support to earlier proposed relay hypothesis which has provided a mechanism for the maintenance of immunological memory.
Output: Structural basis for the function of anti-idiotypic antibody in immune memory
The Tasmanian devil (Sarcophilus harrisii), so named for its blood-curdling, nocturnal shrieks and snarls, is the largest of the carnivorous marsupials. Although once widely persecuted, concerted efforts are now being made to save the devil from extinction following the emergence of a fatal transmissible malignancy known as devil facial tumour disease (DFTD). DFTD is unusual in that the infectious agent is the cancer cell itself. This chapter discusses the aetiology and pathogenesis of DFTD as well as the profound impact the spread of DFTD has had on the devil's conservation status. Strategies for managing DFTD and conserving the devil will be explored and the contribution of new sequencing technology to the field of conservation genetics and genomics will be examined with regard to the Tasmanian devil and DFTD.
Output: Devil Facial Tumour Disease (DFTD): Using Genetics and Genomics to Investigate Infectious Disease in an Endangered Marsupial
Recognition of autologous major histocompatibility complex (MHC) antigens by T cells is an essential step in the induction of an immunologic reaction to either endogenous or exogenous antigens. We investigated the ability of murine glial cells of different ages to stimulate clones of allospecific T lymphocytes. We also investigated the effects of supernatants from cultures of activated T cells on the immunologic recognition of MHC antigens on routine glial cells. Lymphocyte clones specific for Class I, Class II and non-MHC, background antigens were obtained from C57B1/6J-anti-DBA/2 mixed lymphocyte cultures. Glial cell cultures were prepared from newborn syngeneic (C57B1/6J) and allogeneic (DBA/2) mouse brains. G1ial cultures 1-4 weeks of age were able to stimulate a-Class I-specific clones. No stimulation of a-Class II or a-background clones was noted. Incubation of glial cells with supernatants from cultures of alloantigen-activated spleen cells (C57B1/6J-anti-DBA/2) resulted in a decreased ability of glial cells to stimulate a-Class I responses. In contrast supernatant-treated cultures acquired the capacity to stimulate a-Class II-specific clones. No responses were noted in clones responsive to non-MHC antigens. The ability to stimulate a-Class II-specific clones was most prominent with bne-week-old glial cultures and was lost by four weeks of culture. The increased susceptibility of younger glial 226 cultures to the modulatory effects of lymphokines from activated T cells may be a factor in the increased susceptibility of the immature central nervous system to persistent viral infections and the development of autoimmune phenomena.
Output: Recognition of Major Histocompatibility Complex Antigens on Murine Glial Ceils
The dynamics of disease transmission strongly depends on the properties of the population contact network. Pair-approximation models and individual-based network simulation have been used extensively to model contact networks with nontrivial properties. In this paper, using a continuous time Markov chain, we start from the exact formulation of a simple epidemic model on an arbitrary contact network and rigorously derive and prove some known results that were previously mainly justified based on some biological hypotheses. The main result of the paper is the illustration of the link between graph automorphisms and the process of lumping whereby the number of equations in a system of linear differential equations can be significantly reduced. The main advantage of lumping is that the simplified lumped system is not an approximation of the original system but rather an exact version of this. For a special class of graphs, we show how the lumped system can be obtained by using graph automorphisms. Finally, we discuss the advantages and possible applications of exact epidemic models and lumping.
Output: Mathematical Biology Exact epidemic models on graphs using graph-automorphism driven lumping
Background: Rhinovirus (RV), a major cause of respiratory infection in humans, imposes an enormous economic burden due to the direct and indirect costs associated with the illness. Accurate and timely diagnosis is crucial for deciding the appropriate clinical approach and minimizing unnecessary prescription of antibiotics. Diagnosis of RV is extremely challenging due to genetic and serological variability among its numerous types and their similarity to enteroviruses. Objective: We sought to develop a rapid nucleic acid test that can be used for the detection of Rhinovirus within both laboratory and near patient settings. Study design: We developed and evaluated a novel isothermal nucleic acid amplification method called Reverse Transcription Strand Invasion-Based Amplification (RT-SIBA) to rapidly detect Rhinovirus from clinical specimens. Result: The method, RT-SIBA, detected RV in clinical specimens with high analytical sensitivity (96%) and specificity (100%). The time to positive result was significantly shorter for the RV RT-SIBA assay than for a reference RV nucleic acid amplification method (RT-qPCR). Conclusion: The rapid detection time of the RV SIBA assay, as well as its compatibility with portable instruments, will facilitate prompt diagnosis of infection and thereby improve patient care.
Output: Detection of human rhinoviruses by reverse transcription strand invasion based amplification method (RT-SIBA)
During the first few months of 2020, the COVID-19 pandemic has reached Europe. Health systems all over the world are trying to control the outbreak in the shortest possible time. Exotic disease outbreaks are not uncommon in animal health and randomised surveillance is frequently used as support for decision-making. This editorial discusses the possibilities of practicing One Health, by using methods from animal health to enhance surveillance for COVID-19 to provide an evidence base fort decision-making in communities and countries.
Output: To appear in: One Health